[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

TW201233328A - Reduced buffering capacity of a low calorie infant formula - Google Patents

Reduced buffering capacity of a low calorie infant formula Download PDF

Info

Publication number
TW201233328A
TW201233328A TW100149844A TW100149844A TW201233328A TW 201233328 A TW201233328 A TW 201233328A TW 100149844 A TW100149844 A TW 100149844A TW 100149844 A TW100149844 A TW 100149844A TW 201233328 A TW201233328 A TW 201233328A
Authority
TW
Taiwan
Prior art keywords
formula
infant
infant formula
micronutrient
formulation
Prior art date
Application number
TW100149844A
Other languages
Chinese (zh)
Inventor
Christine L Clinger
Barbara J Marriage
Paul W Johns
Original Assignee
Abbott Lab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbott Lab filed Critical Abbott Lab
Publication of TW201233328A publication Critical patent/TW201233328A/en

Links

Landscapes

  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

The present disclosure is directed to low calorie infant formulas, and in particular, low calorie infant formulas that have a low buffering capacity, exhibit an increased rate of protein hydrolysis and digestion, and have an improved tolerance, as compared to full calorie infant formulas. Also disclosed are low calorie liquid infant formulas that have a reduced (i.e., ''low'') micronutrient content on a per volume basis, and exhibit an overall improvement in the physical properties of the formula, as compared to low calorie liquid infant formulas having a higher micronutrient content.

Description

201233328 六、發明說明： 【發明所屬之技術領域】 本發明係關於低熱量嬰兒配方，且詳言之，與全熱量嬰 兒配方相比具有低緩衝能力、呈現增加之蛋白質水解及消 化率且具有改良之耐受性之低熱量嬰兒配方。亦揭示與具 有較高微量營養素含量之低熱量液體嬰兒配方相比具有降 低（亦即「低」）之以單位體積計之微量營養素含量且配方 之物理性質呈現整體改良（包括顏色較淺及穩定性改良）之 低熱量液體嬰兒配方。 【先前技術】 存在多種類型之熟知且廣泛可用之嬰兒營養配方。該等 嬰兒配方包含多種經設計以滿足嬰兒生長之營養需要的營 養物’且通常包括脂肪、碳水化合物、蛋白質、維生素、 礦物質及其他有助於最佳化嬰兒生長及發育之營養物。 然而，通常認為母乳為新生兒之最佳營養源。已知人類 母礼向母乳餵養嬰兒提供優良免疫學利益。因此大部分 嬰兒配方經設計以在組成及功能方面與母乳更接近。 亦已知人類母乳之組成在嬰兒分娩後最初數週内發生變 化。人類母乳在出生後最初5天期間稱為初乳，在出生後 第6天至第14天期間稱為過渡乳且隨後稱為成熟乳。在各 泌乳階段期間，相應人類母乳組成顯著不同。舉例而言， 初乳及過渡乳與成熟乳相比具有較低熱量密度以及較高蛋 白質及較低碳水化合物濃度。三種定義之人乳分組中之維 生素及礦物質濃度亦不同。 161198.doc 201233328 一些市售嬰兒配方在組成上與成熟人類母乳類似但不相 同’且用於新生兒以及較大嬰兒。先前已公認新生兒之餵 養應以促進嬰兒生長為重點進行，且可藉由用具有與成熟 乳類似之營養物及能量含量之市售嬰兒配方餵養嬰兒來最 佳地實現該生長。 近來’已嘗試調配用於新生兒之具有較低能量含量且因 此與用習知全熱量嬰兒配方餵養提供之熱量相比在生命之 最初數週或數月期間提供較少熱量之嬰兒配方。先前對調 配具有低能量含量之嬰兒配方之嘗試涉及以單位體積計降 低一或多種常量營養素（例如蛋白質、脂肪、碳水化合物） 之含量同時保持微量營養素含量與可見於全熱量嬰兒配方 中之含量類似。然而，常量營養素減少與高微量營養素之 組合可產生具有弱物理屬性之配方。舉例而言，該等配方 通常顏色較深，沈降問題增加且與全熱量配方相比在存放 期期間更易於分離。 此外"头·兒配方银養之新生兒可經歷腸胃道（GI)不 f又[生問4包括軟便、放屁及咳吐。GI不耐受性問題可 至少部分地歸因於嬰兒之營養物（例Μ白質）消化及吸收 不全。為解決此不耐受性問題一些嬰兒配方排除乳糖作 為成分’而其他嬰兒配方則用水解蛋白置換完整乳蛋白以 減輕嬰兒消化系統負擔。 些配 之嬰兒與母乳餵養嬰兒相比亦可能經歷更 多的腸胃道感染事件。對此現象之—種解釋可為人類母乳 之緩衝能力較低。已知人類母乳與牛乳及以牛乳為基礎之 161198.doc 201233328 嬰兒配方相比具有較低酸緩衝性質。人類母乳之低緩衝能 力可使嬰兒之天然胃液酸度更有效使經口攝取之病原體失 活》 因此需要提供與先前已知的低熱量嬰兒配方相比具有改 良之物理屬性（諸如顏色較淺及穩定性改良）之低熱量液體 嬰兒配方。亦需要提供具有低緩衝能力（與母乳類似）且亦 具有增加之蛋白質水解及消化率及優良耐受性以提供嬰兒 其他利益之嬰兒配方。 【發明内容】 本發明係關於具有改良之物理屬性之低熱量液體嬰兒配 方。該等配方與具有較高微量營養素含量之低熱量液體嬰 兒配方相比具有降低（亦即「低」）之以單位體積計之微量 營養素含量且產品之物理性質呈現整體改良（包括顏色較 淺及穩定性改良）。亦揭示與習知全熱量嬰兒配方相比具 有低緩衝能力，呈現增加之蛋白質水解及消化率及/或具 有改良之配方耐受性的低熱量液體及粉末嬰兒配方。本發 明之低熱量配方在生命之最初數週期間投與新生兒時提供 充足的用於新生兒生長及發育之營養。 因此在一個實施例中，本發明係關於增加嬰兒中胃液酸 度之方法。該方法包含投與嬰兒能量含量為約2〇〇至約5〇〇 千卡/公升配方之嬰兒配方。 在另一實施例中’本發明係關於增加嬰兒中胃液酸度之 方法。該方法包含投與嬰兒包含微量營養素及至少一種選 自由蛋白質、碳水化合物及脂肪組成之群之常量營養素的 161198.doc 201233328 低微量營養素嬰兒配方。嬰兒配方之能量密度為約2〇〇至 小於600千卡/公升’其中以單位體積計，至少65%微量營 養素以習知相應微量營養素量之約3〇%至約8〇%之量包括 於嬰兒配方中。 在另一實施例中’本發明係關於增加嬰兒中胃液酸度之 方法。該方法包含投與嬰兒低微量營養素嬰兒配方，其包 含微量營養素及至少一種選自由蛋白質、碳水化合物及脂 肪及其組合組成之群之常量營養素且具有約2〇〇至約36〇千 卡/公升配方之能量含量^以單位體積計，至少45%微量營 養素以習知相應微量營養素量之約3〇%至約65%之量包括 於嬰兒配方中。 在另一實施例中，本發明係關於增加嬰兒中胃液酸度之 方法。該方法包含投與嬰兒低微量營養素嬰兒配方，其包 含微量營養素及至少-種選自由蛋白f、碳水化合物及脂 肪及其組合組成之群之常量營養素且具有約36〇至小於6〇〇 千卡/公升配方之能量含量。以單位體積計，至少3〇%微量 營養素以習知相應微量營養素量之約55%至約8〇%之量包 括於嬰兒配方中。 在另實施例中，本發明係關於調節嬰兒中腸胃菌叢生 長之方法。該方法包含投與嬰兒低微量營養素嬰兒配方， 其包含微量營養素及至少—種選自由蛋白f、碳水化合物 及脂肪及其組合組成之群之常量營養素且具有約2〇〇至小 於600千卡/公升配方之能量含量。以單位體積計，至少 65 /。微量營養素以習知相應微量營養素量之約％%至約 161198.doc 201233328 80%之量包括於嬰兒配方中β 罗 一 &例中’本發明係關於調節嬰兒中腸胃菌叢生 :二：。該方法包含投與嬰兒低微量營養素嬰兒配方， 其包含微量螯表去 及r肪及盆種選自由蛋白質、碳水化合物 及月日肪及其組合組成 , 成*之群之吊量營養素且具有約200至約 360千卡/公升配方之能量 料旦Α甚主 乂皁位體積计，至少45〇/〇 ^里呂養素以習知相應微量營養素量之約规至約咖之 釦包括於嬰兒配方中。 貫Μ列中’本發明係關於調節嬰兒中腸胃菌叢生 長之方法。該方法包含投與嬰兒低微量營養素嬰兒配方， 其包含微量營養素及至少一種選自由蛋白質、碳水化合物 及脂肪及其組合組成之群之常量營養素且具有約⑽至小 於6〇0千卡/公升时之能量含量》以單位體積計，至少 3〇%微量營養素以習知相應微量營養素量之約55%至約 80。/〇之量包括於嬰兒配方中。 現意外發現若低熱量配方中足夠量的—或多種微量營養 素以每千卡計轉以單位體積計與全熱量配方巾之微量營 養素大體上匹配.，則可調配具有改良之物理屬性之低熱^ 液體嬰兒配方。因此該等配方與具有較高微量營養素含量 之低熱量液體嬰兒配方相比具有降低（亦即「低」）之以單 位體積計之微量營養素含量且產品之物理性質呈現整體改 良（包括顏色較淺及穩定性改良）。 亦發現低熱量液體或粉末嬰兒配方與習知全熱量嬰兒配 方相比具有較低緩衝能力，且在一些實施例中，其緩衝能 161198.doc 201233328 力低於人乳。因此本發明之低熱量嬰兒配方可用於調節嬰 兒之胃液酸度、減少嬰兒腸胃道中病原微生物生長及促進 有益微生物生長。亦發現本發明之低熱量嬰兒配方與習知 全熱量嬰兒配方相比呈現增加之蛋白質水解及消化率，且 因此具有改良之配方耐受性。 【實施方式】 本文中揭示之低熱量液體嬰兒配方與具有較高微量營養 素含量之習知嬰兒配方相比可具有低微量營養素含量（以 單位體積計）及改良之物理屬性。此外，本發明之方法利 用低熱量液體及粉末嬰兒配方調節嬰兒之胃液酸度，減少 嬰兒腸胃道中病原微生物生長且促進有益微生物生長，提 高蛋白質水解及消化率且改良配方对受性。下文中詳細描 述本發明之嬰兒配方及方法之該專及其他及視情況可選特 徵以及一些多種其他視情況可選變化及添加。 本文中術語「殺菌釜（retort)」與「殺菌釜滅菌（ret〇rt stedlized)」可互換使用，且除非另有說明，否則係指用 營養液體（諸如液體嬰兒配方）填充容器（最通常為金屬罐或 其他類似封裝）且接著使填充有液體之封裝經歷必要加熱 滅菌步驟以形成殺菌釜滅菌之營養液體產品之常用操作。 本文中術語「無菌（aseptic)」與「無菌滅菌㈨邛以 sterilized)」可互換使用，且除非另有說明，否則係指不 依靠上述殺菌釜滅菌封裝步驟製造封裝產品，其中在填充 之月〗獨立地對營養液體及封裝進行滅菌’且接著在滅菌或 無菌加工條件下組合以形成經滅菌、無菌封裝之營養液體 161198.doc 201233328 產品。 如本文中所用術語 営養配方」或「營養產品 養組合物」可互換㈣且除非另有說明，否則羞營 體、營養半液體、營養固體、營養半固體、營養=液 養補充物及此項技術中已知的任何其他營養食品袭營 末可經復原以形成營養液體，其均包含脂肪、蛋白i , 水化。物中之一或多者，且適於由人類口服 方可包括嬰兒配方。 s養配 除非另有說明，否則如本文令所用術語「營養液體 指呈即飲型液體形式、濃縮形式之營養產品及藉由在使用 前復原本文中所描述之營養粉末產生之營養液體。 除非另有說明，否則如本文中所用術語「營養粉末」係 指呈可流動或可自取形式之營養產品，其可在食用前= 或另一種水性液體復原且包括喷霧乾燥及乾燥混人 摻合粉末。 σ乾燥 除非另有說明’否則如本文中所用術語「營養半液體」 係才曰性質（諸如流動性質）介於液體與固體之間的形式，其 實例包括奶昔（thick shakes)及液體凝膠。 除非另有說明，否則如本文中所用術語「營養半固體」 係指性質（諸如剛性）介於固體與液體之間的形式，其實例 包括布丁、明膠及麵團。 除非另有說明，否則如本文中所用術語「嬰兒」係指12 月齡或12月齡以下的孩子。如本文中所用術語「早產兒」 係指在36週妊娠期之前出生之嬰兒。如本文中所用術語 16H98.doc 201233328 足月兒」係指在36週妊娠期時或36週妊娠期後出生之嬰 兒。 除非另有說明，否則如本文中所用術語「新生兒」係指 年7】於約3個月之嬰兒，包括年齡為零至約2週之嬰兒。 新生兒可為足月兒或早產兒。 除非另有說明，否則如本文中所用術語「嬰兒配方」係 指適於由嬰兒食用之液體及固體營養產品。除非本文中另 有說明，否則術語「嬰兒配方」意欲涵蓋足月兒配方及早 產兒配方。 除非另有說明，否則如本文中所用術語「早產兒配方」 係指適於由早產兒食用之液體及固體營養產品。 如本文中所用術語「微量營養素」係指生物體所需之少 量必要物質。非限制性實例包括維生素、礦物質及其類似 物。 如本文中所用術語「全熱量嬰兒配方」係指其中配方之 熱量密度或能量含量與嬰兒配方中習知包括之熱量密度或 能量含量相比未減少之嬰兒配方。通常，全熱量嬰兒配方 之能量含量將為至少600 kcal/L，或甚至至少66〇 kcal/L， 且更通常為至少676 kcal/L ’包括600 kcal/L至800 kcal/L。 如本文中所用術語「低熱量嬰兒配方」係指以單位體積 計之能量含量低於全熱量嬰兒配方之嬰兒配方。 _參考4c兒配方之微量營養素含量時，術語「高微量營 養素」或「高微量營養素含量」意謂嬰兒配方中至少8〇% 161198.doc 201233328 :量S養素以與嬰兒配方中習知包括之微量營養素量幾 =同之量（對於大部分微量營養素，m常在約㈣内）存 除非另有說明’否則如本文中所用之所有百分比' ^比率均以組合物總重量計。除非另有說明，否則所有該 等重量(當其係關於所列舉成分時)均基於活性物含量且因 此不包括市售物質中可能包括之溶劑或副產物。 無响疋否特定揭示’如本文中所用之數值範圍均意欲包 括該範圍内之每—數值及數值子集。此外，該等數值範圍 應視為對針對該範Μ任何數值缝值子#之主張提供支 持。舉例而言，說明丨至⑺應視為支持2至8、3至7、5至 6、1至9、3.6至4.6、3,5至9.9等之範圍。 除非另有說明或與產生參考之上下文明顯矛盾，否則所 有對本發明之單數特徵或限制之參考均應包括相應複數特 徵或限制，且反之亦然。 除非另有說明或與產生參考組合之上下文明顯矛盾，否 則可以任何次序進行如本文中所用之方法或過程步驟之所 有組合。 本發明之嬰兒配方及方法之多種實施例亦可實質上不含 任何本文中所描述之視情況選用或所選成分或特徵，限制 條件為其餘嬰兒配方仍含有本文中所描述之所有所需成分 或特徵《在此情形下且除非另有說明，否則術語「實質上 不含」意謂所選嬰兒配方含有小於功能性量之視情況選用 之成分，通常為小於1重量％(包括小於0.5重量％，包括小 161198.doc 201233328 於o.i重量°/。且亦包括〇重量％)該視情況選用或所選成分。 本發明之嬰兒配方及方法可包含本文中所描述之產品及 方法之要素以及本文中所描述或以其他方式適用於營養嬰 兒配方應用之任何其他或視情況選用之要素、由本文中所 描述之產品及方法之要素以及本文中所描述或以其他方式 適用於營養嬰兒配方應用之任何其他或視情況選用之要素 組成或基本上由本文中所描述之產品及方法之要素以及本 文中所描述或以其他方式適用於營養嬰兒配方應用之任何 其他或視情況選用之要素組成。 產品形式 本發明之嬰兒配方可以任何已知或其他適當口服產品形 式調配及投與。任何固體、半固體、液體、半液體或粉末 形式（包括其組合或變化）均適用於本發明，限制條件為該 等形式可安全及有效經口傳遞亦於本文中定義之必要成分 至個體。 適用於本文中揭示之產品及方法之產品形式之特定非限 制性實例包括例如液體及粉末早產兒配方、液體及粉末足 月兒配方以及液體及粉末元素及半元素配方。 本發明之嬰兒配方較佳調配為膳食產品形式，其於本文 中定義為包含本發明之必要成分且呈含有脂肪、蛋白質及 碳水化合物中之至少一者之產品形式之實施例。 可用足夠種類及數量營養物調配嬰兒配方以提供唯一、 主要或附加營養源，或提供用於罹患特定疾病或病狀之嬰 兒之特定營養產品或提供目標營養效益。 161198.doc -12- 201233328 本發明之嬰兒配方需要經調配以用於新生兒，包括足月 新生兒及早產新生兒。嬰兒配方較佳經調配以用於在出生 後最初數週内餵養新生兒’且更佳用於餵養0至2週齡之新 生兒。在一個實施例中’嬰兒配方經調配以用於在出生後 頭兩天餵養新生兒。本文中將該配方稱為「第1_2天配 方」或「第1 -2天嬰兒配方」。在其他實施例中，嬰兒配方 經調配以用於在出生後第3_9天期間餵養新生兒。本文中 將該配方稱為「第3-9天配方」或「第3-9天嬰兒配方」。應 理解投與本發明之第1_2天嬰兒配方不限於僅在出生後頭 兩天期間投與，而在一些實施例中亦可投與較大嬰兒。類 似地，投與第3·9天嬰兒配方不限於僅在出生後第3_9天期 間投與’而在一些實施例中亦可投與其他年齡之嬰兒。 營養液體 營養液體包括濃縮營養液體及即食型營養液體。該等營 養液體最通常調配為懸浮液、乳液或澄清或實質上澄清液 體。 適用營養乳液可為包含蛋白質、脂肪及碳水化合物之水 性礼液。該等乳液通常在約rc至約25<t下為可流動或可 仅用液體且通常呈水包油、油包水或複合物水性乳液形 式，但該等乳液最通常呈具有連續水相及不連續油相之水 包油乳液形式。 '營養液體可為輯常為可穩定儲存。營養液體通常含有 :液體重量計至多約95重量。水，約5〇重量％至約％ 重量％，亦包括約60重量％至約9〇重量％，且亦包括約7〇 161198.doc .13· 201233328 重量％至約85重量％水，液體可具有多種產品密度， 但其密度最通常大於約U3 g/mL，包括大於約丄〇4 g/mL，包括大於約g/mL，包括約1〇6 g/mL至約} μ g/mL，且亦包括約丨〇85 g/mL至約丨1〇以爪乙。 營養液體之pH值可在約3.5至約8範圍内’但最佳在約 4.5至約7.5範圍内’包括在約5.5至約73範圍内，包括在約 6.2至約7.2範圍内。 儘管營養液體之食用量可視多種變數而不同但典型食 用量通常為至少約2毫升，或甚至至少約5毫升，或甚至至 少約10 mL，或甚至至少約25 mL，包括約2 mL至約3〇〇 mL之範圍’包括約1〇〇 mL至約300 mL、約4 mL至約250 mL、約 150 mL至約 250 mL、約 10 mL至約 240 mL及約 190 mL至約 240 mL。 營養粉末 營養粉末呈可流動或實質上可流動顆粒組合物形式，或 至少呈顆粒組合物形式。尤其合適營養粉末形式包括喷霧 乾燥、聚結或乾燥摻合粉末組合物或其組合，或由其他合 適方法製備之粉末》組合物可易於用匙子或其他類似裝置 舀取及量測，其中組合物可易於用合適水性液體（通常為 水）復原以形成營養液體（諸如嬰兒配方）以用於即刻經口或 經腸使用。在此情形下，「即刻」使用通常意謂在復原後 約48小時内使用，最通常在約24小時内使用’較佳在復原 後立即使用或在復原後20分鐘内使用。 能量含量 161198.doc -14- 201233328 本發明之嬰兒配方與習知足月及早產兒配方相比具有低 能量含量（在本文中可與術語「熱量密度」互換使用）。明 確言之，本發明之嬰兒配方提供約200 kcal/L至小於600 kcal/L(包括約200 kcal/L至約500 kcal/L，且更特定言之約 250 kcal/L至約500 kcal/L)之熱量密度或能量含量。本發明 之第1-2天嬰兒配方提供約200 kcal/L至約360 kcal/L(包括 約 200 kcal/L至約 350 kcal/L，亦包括約 250 kcal/L至約 350 kcal/L、約250 kcal/L至約3 10 kcal/L，且更特定言之約250 kcal/L或約270 kcal/L)之熱量密度或能量含量。本發明之 第3-9天嬰兒配方提供約360 kcal/L至小於600 kcal/L(包括 約370 kcal/L至小於600 kcal/L，亦包括約360 kcal/L至約 500 kcal/L、約 390 kcal/L 至約 470 kcal/L，且更特定言之 約406 kcal/L或約410 kcal/L)之熱量密度或能量含量。與本 發明之嬰兒配方相比，習知足月及早產兒配方（本文中亦 稱為「全熱量嬰兒配方」）之熱量密度或能量含量顯著較 高，通常在600 kcal/L至880 kcal/L範圍内。 當本發明之嬰兒配方呈粉末形式時，則意欲在使用前對 粉末進行復原以獲得上述熱量密度及本文中所描述之其他 營養需求量。同樣地，當本發明之嬰兒配方呈濃縮液體形 式時，則意欲在使用之前稀釋濃縮物以獲得所需熱量密度 及營養需求量。嬰兒配方亦可調配為已具有所需熱量密度 及營養需求量之即食型液體。 本發明之嬰兒配方需要根據本文中詳細描述之方法投與 嬰兒，且詳言之新生兒。該等方法可包括根據本文中所描 161198.doc 15 201233328 述之每日配方攝取量餵食嬰兒配方。 嬰兒配方之能量組分最通常由脂肪、蛋白質及碳水化合 物營養物之組合提供。蛋白質可包含約4%至約40%總熱 量，包括約10%以約30%，亦包括約15%至約25% ;碳水化 合物可包含小於40%總熱量，包括約5%至約37%，亦包括 小於約36°/。，且亦包括約20%至約33% ;且脂肪可包含其 餘配方熱量，最通常小於約60%熱量，包括約3〇%至約 60%。其他例示性量闡述於下文中。 微量營養素 在一些實施例中，除低能量含量外’本發明之嬰兒配方 亦由低微量營養素含量（以單位體積計）表徵。 如本文中所描述，先前對調配具有低能量含量之嬰兒配 方之嘗試涉及降低一或多種常量營養素（例如蛋白質、脂 肪、碳水化合物）之含量同時保持微量營養素含量與可見 於全熱量嬰兒配方中之含量近似（以單位體積計）。舉例而 言’與1公升全熱量配方相比，1公升該低熱量配方中之一 或多種常量營養素量降低，但其微量營養素量與可見於1 公升全熱量配方中者大致相同（對於大部分微量營養素， 通常在至少約82%内）。然而，常量營養素減少與高微量營 養素之組合可產生具有弱物理屬性之配方。舉例而言，該 等配方通常顏色較深，沈降問題增加且與全熱量配方相比 在產品存放期期間更易於分離。 現意外發現若低熱量配方中之微量營養素量以每千卡 (kcal)計而非以單位體積計而大體上可符合全熱量配方中 161198.doc •16- 201233328 者時’則可調配具有改良之物理屬性之低熱量液體嬰兒配 方。舉例而言，1 〇〇 kcal低熱量配方將包含與可見於1〇〇 lccal全熱量配方中者大致相同量（對於大部分微量營養素， 通常在約80%内）之微量營養素。在此實例中，將以1〇〇 kCal計調配低熱量配方之微量營養素含量。以每kcal計調 配之低熱量液體嬰兒配方具有降低（亦即「低」）之微量營 養素含量（以單位體積計，亦即與相同體積全熱量配方相 比），且配方之物理外觀呈現整體改良，包括顏色較淺及 穩定性改良。 因此，在一些實施例中，本發明係關於低熱量、低微量 營養素嬰兒配方。如本文中所用，當提及嬰兒配方時，術 語「低微量營養素」或「低微量營養素含量」意謂嬰兒配 方中所包括之至少一部分微量營養素量低於嬰兒配方中習 知包括之相應微量營養素量（以單位體積計）。應理解，嬰 兒配方中所包括之所有微量營養素之量不—^均需低於習 4相應微#營養素量（以單位體積計）即可達成嬰兒配方視 為低微量營養素嬰兒配方之目的。與習知料位體積計之 量^減少嬰兒配方中—部分微量營養素即足夠。 、曰兒配方中I知包括之」微量營養素量或「習知量」 #里營養素係指f界認可之嬰兒配方中包含之用於實現嬰 兒之適當+ i S 2欠+ ^ 發月所需之標準微量營養素量（以單位體 0〇 可匕括於嬰兒配方中之習知所選微量營養素量（以 ill積計)閣述於以下表A(即食型配方)及表B(復原粉末 S丨己万）中。 I61198.doc 17· 201233328 表A :即食型配方 微量營養素 最小量 (每公升） 最大量 (每公升） 殺菌釜滅菌配 方之典型量 (每公升） 無菌滅菌配方 之典型量 (每公升） 維生素A(IU) 2030 4400 3110 3890 維生素D(IU) 406 642 526 506 維生素E(IU) 10.2 15.0 13.3 11.8 維生素K(ng) 54.1 410 125 106 維生素Bl(pg) 676 4060 1220 1420 維生素B2 (Riboflavin)hg) 1010 4000 2500 2590 維生素B6(pg) 406 556 476 495 維生素B12(pg) 1.69 14.0 4.7 5.4 终酸(με) 7100 21000 9730 9680 葉酸㈣） 101 600 193 212 泛酸㈣） 3040 14400 6220 6710 生物素(pg) 29.7 169 56.1 67.2 維生素C(mg) 60.8 800 416 352 膽驗(mg) 109 203 127 120 肌醇(mg) 31.8 130 39.8 39.9 釣(mg) 528 620 585 581 碟(mg) 284 398 349 341 鎂(mg) 40.6 71.5 55.7 55.0 鐵(mg) 12.2 15.6 13.4 13.7 辞(mg) 5.07 14.0 6.46 6.67 ^(με) 33.8 235 84.4 87.8 銅(pg) 609 1484 676 728 碘㈣） 40.2 474 118 140 鈉(mg) 163 245 190 189 鉀(mg) 710 1196 946 942 氣化物(mg) 440 551 474 504 氟化物(μβ) — — 168 143 硒㈣ 12.3 36.1 24.9 24.3 161198.doc -18- 201233328 表B :復原粉末配方 微量營養素 最小量 (每公升） 最大量 (每公升） 典型量 (每公升） 維生素A(IU) 2030 4820 3583 維生素D(IU) 406 642 563 維生素E(IU) 10.1 15.0 12.6 維生素Κ(μ8) 54.1 410 137 維生素Bl(pg) 676 4060 1560 維生素B2(pg) 1010 4000 1500 維生素B6(pg) 406 556 467 維生素B12(pg) 1.69 14.0 5.85 菸酸hg) 7100 21000 9400 葉酸(pg) 101 600 209 泛酸㈣ 3040 14400 6750 生物素(pg) 29.7 169 63.8 維生素C(mg) 60.8 670 170 膽鹼(mg) 108 203 123 肌醇(mg) 31.8 130 41.0 鈣(mg) 536 637 580 碟(mg) 289 408 332 鎂(mg) 40.6 73.3 53.7 鐵(mg) 12.4 16.1 13.9 辞(mg) 5.15 14.4 6.69 猛㈣） 34.3 148 89.7 銅(με) 618 1519 720 碘(με) 41.0 489 126 鈉(mg) 165 251 201 鉀(mg) 721 1235 1039 氣化物(mg) 446 565 486 氟化物(pg) — • 116 硒㈣ 12.4 37.0 25.6 可包括於習知嬰兒配方中之例示性非限制性微量營養素 包括維生素A、維生素D、維生素E、維生素K、維生素 B1、維生素B2、維生素B6、維生素B12、菸酸、葉酸、泛 161198.doc •19- 201233328 酸、生物素、維生素c、膽鹼、肌醇、鈣、磷、鎂、鐵、 鋅、錳、銅、碘、鈉、鉀、氣化物、氟化物、硒及其組 合。一些例不性習知嬰兒配方可包括銅、磷、鐵、鈣及鋅 之組合。一些其他例示性習知嬰兒配方可包括銅、鐵及磷 之組合。 在一個特定實施例中，銅、磷、鐵、鈣及鋅中之至少兩 者以比以上表A及B中闡述之量小約5%、或甚至小約 10%，或甚至小約20% ,或甚至小約3〇%，或甚至小約 5〇/〇或甚至小約75%，或甚至小約80%，或甚至小約900/〇 的量存在於低微量營養素配方中。在另一特定實施例中， 鐵及銅以比以上表八及B中闡述之量小約5%、或甚至小約 10/。，或甚至小約20%，或甚至小約3〇%，或甚至小約 50 /。，或甚至小約75。/❶，或甚至小約8〇%，或甚至小約9〇% 的量存在於低微量營養素配方中。 應理解，表A及B不含本發明之嬰兒配方中可包括之合 適微量營養素之完全清單。此外，本發明之低微量營養素 嬰兒配方無需包含表A及B中列舉之每一微量營養素。本 發明涵蓋包含表A及B中列舉之微量營養素及/或此項技術 中已知適於包含於嬰兒配方中之其他微量營養素中之一或 多者之任何組合的嬰兒配方。可容易地參考歐洲及/或美 國嬰兒配方規則及標準確定該等及其他微量營養素之標準 或習知含量（以每1〇〇 kcal計）。 备判疋嬰兒配方中之微量營養素含量（以單位體積計）與 習知含量相比是否較低時，應比較「相應微量營養素」之 161198.doc -20- 201233328 量。在此情況下，「相應微量營養素」係指所評估之嬰兒 配方中存在之相同微量營養素。舉例而言若嬰兒配方包 含微量營養素鈣、磷及鎂，則應分別比較嬰兒配方中該等 微量營養素之量與嬰兒配方中習知包括之鈣、磷及鎂之量 以判定嬰兒配方中該等微量營養素之量是否較「低」。 本發明之低微量營養素嬰兒配方中所包括之微量營養素 量可表示為以單位體積計之習知相應微量營養素量百分 比。舉例而言，在本發明之_些實施例中，提供低微量營 養素嬰兒配方，其中微量營養素以習知相應微量營養素量 之約30%至約80%之量包括於嬰兒配方中（以單位體積 «十），包括習知相應微量營養素量之約3〇%至約65%、約 55%至約80%、約40%至約7〇%、約4〇%至約5〇%及約6〇% 至約70%(均以單位體積計）。通常，本發明之低微量營養 素嬰兒配方中至少65%微量營養素，包括至少75%、至少 80%、至少90%及1〇〇%微量營養素以習知相應微量營養素 1之約30%至約80%之量包括於嬰兒配方中（以單位體積 計）。 在一些實施例令，提供低微量營養素嬰兒配方，其中微 置營養素以習知相應微量營養素量之約3〇%至約65%之量 包括於嬰兒配方中（以單位體積計），包括習知相應微量營 養素量之約35%至約60%、約4〇%至約5〇%、約4〇%至約 45〇/。且尤其約40%(均以單位體積計在該等實施例中’ 低微量營養素嬰兒配方中通常至少45%微量營養素，包括 至少50%、至少60%、至少75%、至少8〇%、至少9〇%及 161198.doc -21· 201233328 100%微量營養素以習知相應微量營養素量之約3 5%至約 60%之量包括於嬰兒配方中（以單位體積計）》在其他實施 例中，低微量營養素嬰兒配方中至少1 〇%微量營養素，包 括至少25%、至少50%、至少60%、至少75%及至少80%微 量營養素以習知相應微量營養素量之約40%至約50%之量 包括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰 兒配方可包括例如第1-2天嬰兒配方。 在其他實施例中，提供低微量營卷素嬰兒配方，其中微 量營養素以習知相應微量營養素量之約55%至約80%之量 包括於嬰兒配方中（以單位體積計），包括習知相應微量營 養素量之約60%至約75%、約60%至約70%、約60%至約 65。/。且尤其約6〇%(均以單位體積計）。在該等實施例中， 低微量營養素嬰兒配方中通常至少30%微量營養素，包括 至少50。/。、至少6〇%、至少75%、至少8〇%、至少9〇%及 1 〇〇%微量營養素以習知相應微量營養素量之約55%至約 80%之量包括於嬰兒配方中（以單位體積計在其他實施 例中’低微量營養素嬰兒配方中至少10%微量營養素，包 括至少25%、至少50%、至少60%、至少75%及至少80%微 量營養素以習知相應微量營養素量之約60%至約70%之量 包括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰 兒配方可包括例如第3-9天嬰兒配方。 在其中微量營養素包括礦物質之一些實施例中，礦物質 以&知相應礦物質的量之約30%至約80%之量包括於低微 *營養素嬰兒配方中（以單位體積計），包括習知相應礦物 161198.doc •22· 201233328 質的量之約30%至約65%、約55%至約80%、約40%至約 70〇/〇、約40%至約5〇%及約6〇%至約7〇%(均以單位體積 計）°通常’本發明之低微量營養素嬰兒配方中至少1〇%， 包括至少45。/〇、至少50%、至少60%、至少70%、至少 75¼、至少80%、至少90%及1〇〇%礦物質以習知相應礦物 質的量之約30。/。至約80%之量包括於嬰兒配方中（以單位體 積計）。 在其他實施例中，礦物質以習知相應礦物質的量之約 30%至約65°/。之量包括於低微量營養素嬰兒配方中（以單位 體積計）’包括習知相應礦物質的量之約35%至約60。/。、約 40%至約50%、約40%至約45%且尤其約40%(均以單位體積 計）。在該等實施例中，低微量營養素嬰兒配方中通常至 少1 0°/。礦物質’包括至少25%、至少50%、至少60%、至少 75%、至少80%、至少90%及100%礦物質以習知相應礦物 質的量之約30%至約65%之量包括於嬰兒配方中（以單位體 積計）。在其他實施例中，低微量營養素嬰兒配方中至少 10°/。’包括至少25%、至少50%、至少60%、至少75%、至 少80%、至少90%及100%礦物質以習知相應礦物質的量之 約40%至約50%之量包括於嬰兒配方中（以單位體積計）。 該等低微量營養素嬰兒配方可包括例如第1 -2天嬰兒配 方。 在其他實施例中，礦物質以習知相應礦物質的量之約 5 50/。至約80%之量包括於低微量營養素嬰兒配方中（以單位 體積計），包括習知相應礦物質的量之約60%至約75%、約 161I98.doc -23- 201233328 600/。至約70°/。、約60%至約65%且尤其約60%(均以單位體積 計）。在該等實施例中，低微量營養素嬰兒配方中通常至 少10°/。’包括至少25%、至少50。/〇、至少60%、至少75%、 至少80%、至少90%及1〇〇%礦物質以習知相應礦物質的量 之約55°/〇至約80%之量包括於嬰兒配方中（以單位體積 計）。在其他實施例中，低微量營養素嬰兒配方中至少 10% ’包括至少25%、至少50%、至少60%、至少75%、至 少80°/〇、至少90%及100%礦物質以習知相應礦物質的量之 約60°/〇至約70%之量包括於嬰兒配方中（以單位體積計）。 該等低微量營養素嬰兒配方可包括例如第3-9天嬰兒配 方。 在其中微量營養素包括維生素之一些實施例中，維生素 以習知相應維生素量之約30%至約80%之量包括於低微量 營養素嬰兒配方中（以單位體積計），包括習知相應維生素 量之約30%至約65%、約55%至約80%、約40%至約70%、 約40%至約50%及約60%至約70%(均以單位體積計）。通 常，本發明之低微量營養素嬰兒配方中至少45%，包括至 少50%、至少60%、至少70%、至少80%、至少85%、至少 90%及100%維生素以習知相應維生素量之約30%至約80〇/〇 之量包括於嬰兒配方中（以單位體積計）。 在其他實施例中，維生素以習知相應維生素量之約30% 至約65 %之量包括於低微量營養素嬰兒配方中（以單位體積 計），包括習知相應維生素量之約35%至約60%、約40%至 約50%、約40%至約45%且尤其約40%(均以單位體積計）。 161198.doc •24- 201233328 在該等實施例中，低微量營養素嬰兒配方中通常至少ιοο/〇 維生素，包括至少25%、至少50%、至少60%、至少75%、 至少80%、至少90%及100%維生素以習知相應維生素量之 約30%至約65%之量包括於嬰兒配方中（以單位體積計）。 • 在其他實施例中，低微量營養素嬰兒配方中至少10%維生 . 素，包括至少25%、至少50%、至少60%、至少75%及至少 80%維生素以習知相應維生素量之約4〇%至約5〇0/。之量包 括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰兒 配方可包括例如第1_2天嬰兒配方。 在其他實施例中’維生素以習知相應維生素量之約55〇/〇 至約80%之量包括於低微量營養素嬰兒配方中（以單位體積 計）’包括習知相應維生素量之約6〇%至約75%、約6〇%至 約70%、約60%至約65°/。且尤其約60%(均以單位體積計）。 在該等實施例中’低微量營養素嬰兒配方中通常至少 10%，包括至少25%、至少50%、至少6〇。/0、至少75❶/〇、至 少80%、至少90%及1〇〇。/。維生素以習知相應維生素量之約 55%至約80%之量包括於嬰兒配方中（以單位體積計）。在 其他實施例中，低微量營養素嬰兒配方中至少1〇%，包括 至少25%、至少5〇〇/0、至少6〇%、至少75%、至少8〇%及至 . > 9〇 /l>維生素以習知相應維生素量之約60%至約70°/。之量 包括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰 兒配方可包括例如第3_9天嬰兒配方。 可包3於本發明之嬰兒配方中之合適微量營養素包括維 生素或相關營養物、礦物質及其組合。合適維生素之非限 161198.doc -25· 201233328 制性實例包括維生素A、維生素D、維生素E、維生素κ、 維生素Β1、維生素Β2、吡哆醇、維生素Β5、維生素Β6、 維生素Β12、於酸、葉酸、泛酸、生物素、維生素c、膽 驗、肌醇、抗壞血酸、其鹽及衍生物以及其組合。 可包括於本發明之嬰兒配方中之合適礦物質之非限制性 實例包括鈣、磷、鎂、鐵、鋅、錳、銅 '碘、鈉、鉀、 銷、鉻、氣化物、氟化物、硒及其組合。 任何嬰兒配方均可經調配具有本文中揭示之低微量營養 素含量，包括殺菌釜滅菌及無菌滅菌即食型營養液體、濃 縮營養液體及營養粉末。 常量營養素 除本文中所描述之微量營養素外，本發明之嬰兒配方亦 可包含一或多種常量營養素。常量營養素包括蛋白質、脂 肪、碳水化合物及其組合。適用於本文中之常量營養素包 括任何已知或以其他方式適用於口服營養產品中之蛋白 質、脂肪、碳水化合物或其來源，限制條件為常量營養素 可安全且有效經口投與嬰兒Μ其他方式與嬰兒配方中其 他成分相容。 儘管蛋白質、脂肪及碳水化合物之總濃度或量可視產 形式（例如粉末或即食型液體）及所欲使用者之目標膳食 要不同，但該等濃度或量通常屬於下表中描述之具體範 中之-者内（各數值前均加上術語「約」），包括本文中 描述之任何其他必需脂肪、}白質及/或碳水化合^ /刀。對於粉末實施例，下表中之含量為粉末復原後之/ 16I198.doc -26- 201233328 量。 表c 營養物(g/l〇〇 mL) 實例A 實例Β 蛋白質 0·5 至 1.0 0.6 至 0.9 脂肪 1.25.2.5 1.4 至 2.3 碳水化合物 2.75.6.5 3.1 至 6.1 蛋白質、脂肪及碳水化合物之總濃度或量亦可視嬰兒配 方是為第1-2天配方還是為第3-9天配方而不同。第1-2天配 方及第3-9天配方中蛋白質、脂肪及碳水化合物之濃度最 通常經調配屬於下表中描述之具體範圍中之任一者内（各 數值前均加上術語「約」），包括本文中所描述之任何其 他必需脂肪、蛋白質及/或碳水化合物成分。對於粉末實 施例，下表中之含量為復原後之含量。201233328 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a low-calorie infant formula, and in particular, has a low buffering capacity, exhibits increased protein hydrolysis and digestibility, and is improved compared to a full-calorie infant formula. Tolerant low calorie infant formula. It also reveals a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and an overall improvement in the physical properties of the formulation (including lighter color and stability) Sexual improvement) low calorie liquid infant formula. [Prior Art] There are many types of well-known and widely available infant nutrition formulas. These infant formulas contain a variety of nutrients designed to meet the nutritional needs of infant growth' and typically include fats, carbohydrates, proteins, vitamins, minerals, and other nutrients that help optimize the growth and development of the baby. However, breast milk is generally considered to be the best source of nutrition for newborns. Human mothers are known to provide excellent immunological benefits to breastfed babies. Therefore, most infant formulas are designed to be closer to breast milk in terms of composition and function. It is also known that the composition of human breast milk changes during the first few weeks after delivery of the baby. Human breast milk is called colostrum during the first 5 days after birth and is called transitional milk during the 6th to 14th day after birth and is subsequently referred to as mature milk. The corresponding human breast milk composition is significantly different during each lactation phase. For example, colostrum and transition milk have lower caloric density and higher protein and lower carbohydrate concentrations than mature milk. The vitamins and mineral concentrations in the three defined human milk groups are also different. 161198.doc 201233328 Some commercially available infant formulas are similar in composition but not identical to mature human breast milk and are used in newborns as well as larger infants. It has previously been recognized that feeding of newborns should be focused on promoting infant growth and that growth can be best achieved by feeding the infant with a commercial infant formula having nutrient and energy content similar to mature milk. Recently, it has been attempted to formulate infant formulas for newborns that have lower energy content and therefore provide less calories during the first weeks or months of life compared to the calories provided by conventional full calorie infant formula feeding. Previous attempts to formulate infant formulas with low energy content involved reducing the content of one or more macronutrients (eg, protein, fat, carbohydrates) per unit volume while maintaining micronutrient levels similar to those found in whole calorie infant formulas. . However, the combination of macronutrient reduction and high micronutrients produces a formulation with weak physical properties. For example, such formulations are generally darker in color, have increased settling problems and are easier to separate during the shelf life than full calorie formulations. In addition, the newborns of the head and children formula can experience gastrointestinal tract (GI) and f. [Life 4 includes soft stools, fart and cough. The problem of GI intolerance can be attributed, at least in part, to the digestion and absorption of nutrients (e.g., white matter) in infants. To address this intolerance problem, some infant formulas exclude lactose as a component' while other infant formulas replace the whole milk protein with hydrolyzed proteins to reduce the burden on the baby's digestive system. Some infants may also experience more gastrointestinal infections than breastfed infants. An explanation for this phenomenon is that the buffering capacity of human breast milk is low. It is known that human breast milk has a lower acid buffering property than cow's milk and milk based 161198.doc 201233328 infant formula. The low buffering capacity of human breast milk allows the infant's natural gastric acidity to be more effective in inactivating pathogenic ingested pathogens. It is therefore desirable to provide improved physical properties (such as lighter color and stability) than previously known low calorie infant formulas. Sexual improvement) low calorie liquid infant formula. It is also desirable to provide infant formulas that have low buffering capacity (similar to breast milk) and that also have increased protein hydrolysis and digestibility and excellent tolerance to provide other benefits to the infant. SUMMARY OF THE INVENTION The present invention is directed to a low calorie liquid infant formula having improved physical properties. These formulations have a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and the overall physical properties of the product are improved (including lighter colors and Stability improvement). It also discloses low calorie liquid and powder infant formulas that have low buffering capacity, exhibit increased protein hydrolysis and digestibility, and/or improved formulation tolerance compared to conventional full calorie infant formulas. The low calorie formula of the present invention provides sufficient nutrients for neonatal growth and development when administered to a newborn during the first few weeks of life. Thus in one embodiment, the invention relates to a method of increasing the acidity of gastric juice in an infant. The method comprises administering an infant formula having an infant energy content of from about 2 inches to about 5 kilocalories per liter. In another embodiment, the invention relates to a method of increasing the acidity of gastric juice in an infant. The method comprises administering to a baby a micronutrient and at least one macronutrient selected from the group consisting of free protein, carbohydrates and fats. 161198.doc 201233328 Low micronutrient infant formula. The infant formula has an energy density of from about 2 Å to less than 600 kcal / liter, wherein at least 65% of the micronutrient is included in an amount of from about 3% to about 8% by weight of the conventional micronutrient amount per unit volume. In the infant formula. In another embodiment, the invention relates to a method of increasing the acidity of gastric juice in an infant. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having from about 2 to about 36 kilocalories per liter Energy content of the formulation ^ At least 45% of the micronutrient is included in the infant formula in an amount of from about 3% to about 65% by weight of the conventional micronutrient. In another embodiment, the invention is directed to a method of increasing the acidity of gastric juice in an infant. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of protein f, carbohydrates and fats, and combinations thereof, and having from about 36 〇 to less than 6 〇〇 kcal / liter formula energy content. At least 3% by weight of the micronutrients per unit volume are included in the infant formula in amounts of from about 55% to about 8% by weight of the corresponding micronutrient. In another embodiment, the invention relates to a method of regulating the growth of gastrointestinal flora in an infant. The method comprises administering to a baby low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of protein f, carbohydrates and fats, and combinations thereof, and having from about 2 to less than 600 kcal/ The energy content of the liter formula. At least 65 / per unit volume. The micronutrient is about 5% of the amount of the corresponding micronutrient to about 161,198.doc 201233328 80% of the amount is included in the infant formula. The invention relates to the regulation of gastrointestinal tract in infants: II:. The method comprises administering an infant low-micronutrient infant formula comprising a micro-chelating agent and a fertilization and a potting species selected from the group consisting of protein, carbohydrate and moon-day fat and a combination thereof, and the group of nutrients of the group 200 to about 360 kcal / liter of formula energy 料 Α 乂 乂 Α 乂 , , , , , , , , 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少 至少. The present invention relates to a method for regulating the growth of gastrointestinal flora in infants. The method comprises administering an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having a ratio of from about (10) to less than 6,000 kcal/liter The energy content" is at least 3% by weight of the micronutrient per unit volume, from about 55% to about 80 of the conventional micronutrient amount. The amount of 〇 is included in the infant formula. It has been unexpectedly found that if a sufficient amount of the low-calorie formula, or a plurality of micronutrients, is substantially matched to the micronutrient of the full-calorie formula per unit of calories per kilocalorie, the low-heating with improved physical properties can be adjusted^ Liquid infant formula. Therefore, these formulations have a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and the overall physical properties of the product are improved (including lighter colors) And stability improvement). It has also been found that low calorie liquid or powder infant formulas have lower buffering capacity than conventional full calorie infant formula, and in some embodiments, have a buffering capacity of 161198.doc 201233328 which is lower than human milk. Thus, the low calorie infant formula of the present invention can be used to adjust the gastric acidity of infants, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of infants, and promote the growth of beneficial microorganisms. It has also been found that the low calorie infant formula of the present invention exhibits increased protein hydrolysis and digestibility as compared to conventional full calorie infant formula, and thus has improved formulation tolerance. [Embodiment] The low calorie liquid infant formula disclosed herein has a low micronutrient content (in terms of unit volume) and improved physical properties as compared to conventional infant formulas having higher micronutrient content. In addition, the method of the present invention utilizes a low-calorie liquid and a powdered infant formula to adjust the gastric acidity of the infant, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of the infant and promote the growth of beneficial microorganisms, improve protein hydrolysis and digestibility, and improve formulation compatibility. The specific and other optional features of the infant formula and method of the present invention, as well as a variety of other optional variations and additions, are described in detail below. The term "retort" and "ret〇rt stedlized" are used interchangeably herein and, unless otherwise indicated, are meant to fill a container with a nutrient liquid (such as a liquid infant formula) (most commonly A metal can or other similar package) and then subjecting the liquid-filled package to the necessary heat sterilization step to form a common operation of the sterilization-sterilized nutrient liquid product. The terms "aseptic" and "sterilely sterilized" are used interchangeably herein and, unless otherwise indicated, mean that the packaged product is manufactured without relying on the sterilization sterilization step described above, wherein in the month of filling The nutritional liquids and packages are independently sterilized' and then combined under sterile or aseptic processing conditions to form a sterilized, aseptically packaged nutritional liquid 161198.doc 201233328 product. The term "foster formula" or "nutraceutical composition" as used herein is interchangeable (iv) and unless otherwise stated, shy, nutrient semi-liquid, nutrient solids, nutrient semi-solids, nutrients = liquid supplements and Any other nutraceutical food known in the art can be reconstituted to form a nutritional liquid, which all contains fat, protein i, and hydration. One or more of the items, and suitable for oral administration by humans, may include an infant formula. s Fostering Unless otherwise stated, the term "nutritional liquid" as used herein means a ready-to-drink liquid form, a concentrated form of a nutritional product, and a nutrient liquid produced by restoring the nutritional powder described herein prior to use. Further, otherwise, the term "nutritional powder" as used herein refers to a nutritional product in a flowable or self-contained form that can be reconstituted before consumption = or another aqueous liquid and includes spray drying and dry mixing. Powder. σ Drying Unless otherwise stated 'otherwise the term "nutrient semi-liquid" as used herein is a form in which the properties (such as flow properties) are between liquid and solid, examples of which include thick shakes and liquid gels. . The term "nutritional semi-solid" as used herein, unless otherwise indicated, refers to a form in which the properties (such as rigidity) are between a solid and a liquid, examples of which include pudding, gelatin, and dough. The term "infant" as used herein, unless otherwise indicated, refers to a child 12 months of age or younger than 12 months of age. The term "preterm infant" as used herein refers to an infant born before the 36-week gestation period. As used herein, the term 16H98.doc 201233328 term infant refers to an infant born at 36 weeks of gestation or after 36 weeks of gestation. The term "neonatal" as used herein, unless otherwise indicated, refers to an infant of about 3 months, including infants from zero to about two weeks old. Newborns can be term infants or premature babies. The term "infant formula" as used herein, unless otherwise indicated, refers to liquid and solid nutritional products suitable for consumption by infants. Unless otherwise stated herein, the term "infant formula" is intended to cover both full term formula and preterm formula. The term "preterm formula" as used herein, unless otherwise indicated, refers to liquid and solid nutritional products suitable for consumption by preterm infants. The term "micronutrient" as used herein refers to a small amount of essential material required by an organism. Non-limiting examples include vitamins, minerals, and the like. The term "full calorie infant formula" as used herein refers to an infant formula in which the caloric density or energy content of the formulation is not reduced compared to the heat density or energy content conventionally included in infant formulas. Typically, the full calorie infant formula will have an energy content of at least 600 kcal/L, or even at least 66 〇 kcal/L, and more typically at least 676 kcal/L ' including 600 kcal/L to 800 kcal/L. The term "low calorie infant formula" as used herein refers to an infant formula that has a lower energy content per unit volume than a full calorie infant formula. _Refer to the micronutrient content of the 4c formula, the term "high micronutrient" or "high micronutrient content" means at least 8 % of the infant formula. 161198.doc 201233328: The amount of S nutrient is well known in the infant formula The amount of micronutrients is the same amount (for most micronutrients, m is often within about (four)) unless otherwise stated 'otherwise all percentages' used herein are based on the total weight of the composition. All such weights, when referring to the recited ingredients, are based on the active level and therefore do not include solvents or by-products that may be included in the commercially available materials, unless otherwise stated. No particular disclosure is intended to encompass a range of values and values in the range. In addition, the numerical ranges should be construed as supporting the claim that any numerical value of the value of the value is #. For example, the description 丨 to (7) should be considered to support the range of 2 to 8, 3 to 7, 5 to 6, 1 to 9, 3.6 to 4.6, 3, 5 to 9.9, and the like. References to singular features or limitations of the invention are intended to include the corresponding plural features or limitations, and vice versa, unless otherwise indicated. All combinations of methods or process steps as used herein may be performed in any order, unless otherwise indicated or clearly contradicted by the context in which the reference combination is made. The various embodiments of the infant formulas and methods of the present invention may also be substantially free of any optional ingredients or features selected as described herein, with the proviso that the remaining infant formula still contains all of the desired ingredients described herein. Or characteristic "In this case and unless otherwise stated, the term "substantially free" means that the selected infant formula contains less than 1% by weight (including less than 0.5 weight), optionally as a component of the functional amount. %, including small 161198.doc 201233328 at oi weight ° / and also includes 〇 weight %) depending on the selected or selected ingredients. The infant formula and method of the present invention may comprise the elements of the products and methods described herein as well as any other or optionally selected elements described herein or otherwise suitable for use in a nutritional infant formula application, as described herein. The elements of the products and methods, as well as any other or optional elements described herein or otherwise suitable for use in a nutritional infant formula application, consist essentially of or consist essentially of the elements of the products and methods described herein and or described herein or Any other or optional element that is otherwise suitable for use in nutritional infant formula applications. Product Form The infant formula of the present invention can be formulated and administered in the form of any known or other suitable oral product. Any solid, semi-solid, liquid, semi-liquid or powder form, including combinations or variations thereof, is suitable for use in the present invention, provided that such forms are safe and effective for oral delivery of the essential ingredients as defined herein to the individual. Specific non-limiting examples of product forms suitable for use in the products and methods disclosed herein include, for example, liquid and powder preterm formulas, liquid and powder term formulas, and liquid and powder elements and semi-element formulations. The infant formula of the present invention is preferably formulated in the form of a dietary product, which is defined herein as an embodiment comprising the essential ingredients of the present invention and in the form of a product comprising at least one of a fat, a protein and a carbohydrate. Infant formula can be formulated with sufficient types and amounts of nutrients to provide a unique, primary or additional source of nutrients, or to provide specific nutritional products for infants suffering from a particular disease or condition or to provide targeted nutritional benefits. 161198.doc -12- 201233328 The infant formula of the present invention needs to be formulated for use in newborns, including term newborns and premature newborns. Infant formulas are preferably formulated for feeding newborns within the first few weeks of life' and are better for feeding newborns between 0 and 2 weeks of age. In one embodiment, the infant formula is formulated for feeding the newborn in the first two days after birth. This formula is referred to herein as "Day 1 - 2 Formulation" or "Day 1 - 2 Infant Formulation". In other embodiments, the infant formula is formulated for feeding the newborn during the 3rd to 9th day after birth. This formula is referred to herein as "Day 3-9 Formulation" or "Day 3-9 Infant Formulation". It is to be understood that the Formula 1-2-day infant formula for administration of the present invention is not limited to administration only during the first two days after birth, and in some embodiments, larger infants may also be administered. Similarly, administration of the 3rd-9th infant formula is not limited to administration only during the 3rd-9th day after birth' and in some embodiments infants of other ages may also be administered. Nutrient Liquids Nutrient liquids include concentrated nutrient liquids and ready-to-eat nutrient liquids. These nutrient liquids are most often formulated as suspensions, emulsions or as clear or substantially clear liquids. Suitable nutritional emulsions can be aqueous liquids containing protein, fat and carbohydrates. The emulsions typically range from about rc to about 25 <t is a flowable or liquid-only form and is typically in the form of an oil-in-water, water-in-oil or composite aqueous emulsion, but such emulsions are most often in the form of oil-in-water emulsions with a continuous aqueous phase and a discontinuous oil phase. form. 'Nutritional liquids can often be stored stably. The nutritional liquid typically contains up to about 95 weights by weight of the liquid. Water, from about 5% by weight to about 3% by weight, also including from about 60% by weight to about 9% by weight, and also including about 7 〇 161,198.doc.13·201233328% by weight to about 85% by weight of water, liquid Having a variety of product densities, but the density is most typically greater than about U3 g/mL, including greater than about 丄〇4 g/mL, including greater than about g/mL, including from about 1〇6 g/mL to about} μg/mL, It also includes about 85 g/mL to about 〇1〇 to the claw B. The pH of the nutritional liquid may range from about 3.5 to about 8 'but preferably from about 4.5 to about 7.5', including from about 5.5 to about 73, including from about 6.2 to about 7.2. Although the amount of nutrient liquid to be consumed may vary depending on a variety of variables, typical consumption levels are typically at least about 2 milliliters, or even at least about 5 milliliters, or even at least about 10 milliliters, or even at least about 25 milliliters, including from about 2 mL to about 3 The range of 〇〇mL' includes from about 1 mL to about 300 mL, from about 4 mL to about 250 mL, from about 150 mL to about 250 mL, from about 10 mL to about 240 mL, and from about 190 mL to about 240 mL. Nutritional Powder The nutritional powder is in the form of a flowable or substantially flowable particulate composition, or at least in the form of a particulate composition. Particularly suitable nutritional powder forms include spray-dried, coalesced or dry-blended powder compositions or combinations thereof, or powders prepared by other suitable methods. The compositions can be easily taken and measured with a spoon or other similar device, where The article can be readily reconstituted with a suitable aqueous liquid (usually water) to form a nutritional liquid, such as an infant formula, for immediate oral or enteral use. In this case, "immediate" use generally means use within about 48 hours of recovery, most commonly within about 24 hours of use, preferably immediately after recovery or within 20 minutes of recovery. Energy content 161198.doc -14- 201233328 The infant formula of the present invention has a low energy content compared to conventional full-term and preterm formulas (as used herein interchangeably with the term "caloric density"). In particular, the infant formula of the present invention provides from about 200 kcal/L to less than 600 kcal/L (including from about 200 kcal/L to about 500 kcal/L, and more specifically from about 250 kcal/L to about 500 kcal/ L) The heat density or energy content. The infant formula of Days 1-2 of the present invention provides from about 200 kcal/L to about 360 kcal/L (including from about 200 kcal/L to about 350 kcal/L, also including from about 250 kcal/L to about 350 kcal/L, A heat density or energy content of from about 250 kcal/L to about 3 10 kcal/L, and more specifically about 250 kcal/L or about 270 kcal/L. The 3-9 day infant formula of the present invention provides from about 360 kcal/L to less than 600 kcal/L (including from about 370 kcal/L to less than 600 kcal/L, also including from about 360 kcal/L to about 500 kcal/L, A heat density or energy content of from about 390 kcal/L to about 470 kcal/L, and more specifically about 406 kcal/L or about 410 kcal/L. Compared to the infant formula of the present invention, the conventional full-term and preterm formula (also referred to herein as "full calorie infant formula") has a significantly higher caloric density or energy content, typically in the range of 600 kcal/L to 880 kcal/L. Inside. When the infant formula of the present invention is in powder form, it is intended to restore the powder prior to use to achieve the above described caloric density and other nutritional requirements as described herein. Similarly, when the infant formula of the present invention is in the form of a concentrated liquid, it is intended to dilute the concentrate prior to use to achieve the desired caloric density and nutritional requirements. Infant formulas can also be formulated as ready-to-feed liquids that have the required caloric density and nutritional requirements. The infant formula of the present invention needs to be administered to the infant according to the methods described in detail herein, and in detail the newborn. The methods can include feeding the infant formula according to the daily formula intake described in 161198.doc 15 201233328. The energy component of an infant formula is most often provided by a combination of fat, protein and carbohydrate nutrients. The protein may comprise from about 4% to about 40% total calories, including from about 10% to about 30%, and also from about 15% to about 25%; the carbohydrate may comprise less than 40% total calories, including from about 5% to about 37% Also included is less than about 36°/. And also includes from about 20% to about 33%; and the fat may comprise the remainder of the formula, most typically less than about 60%, including from about 3% to about 60%. Other illustrative amounts are set forth below. Micronutrients In some embodiments, in addition to low energy content, the infant formula of the present invention is also characterized by a low micronutrient content (in terms of unit volume). As previously described, previous attempts to formulate infant formulas with low energy content have involved reducing the levels of one or more macronutrients (eg, protein, fat, carbohydrates) while maintaining micronutrient content and being found in a full calorie infant formula. The content is approximate (in terms of unit volume). For example, one liter of one or more macronutrients in a 1 liter lower calorie formula is reduced compared to a one liter full calorie formula, but the amount of micronutrients is roughly the same as that found in a 1 liter full calorie formula (for most Micronutrients, usually at least about 82%). However, the combination of macronutrient reduction and high micronutrients produces a formulation with weak physical properties. For example, such formulations are generally darker in color, have increased settling problems and are easier to separate during the product shelf life than the full calorie formulation. It has been unexpectedly found that if the amount of micronutrients in a low-calorie formula is generally in kilocalories rather than unit volume, it can generally meet the full-calorie formula of 161198.doc •16-201233328. The low-calorie liquid infant formula with physical properties. For example, a 1 〇〇 kcal low calorie formula will contain micronutrients in approximately the same amount (for most micronutrients, typically within about 80%) as found in the 1 lccal all-calorie formulation. In this example, the micronutrient content of the low calorie formula will be formulated in 1 〇〇 kCal. The low calorie liquid infant formula formulated per kcal has a reduced (ie "low") micronutrient content (in terms of unit volume, ie compared to the same volume full calorie formula), and the overall physical appearance of the formulation is improved overall , including lighter color and improved stability. Thus, in some embodiments, the present invention is directed to low calorie, low micronutrient infant formulas. As used herein, the term "low micronutrient" or "low micronutrient content" when referring to an infant formula means that the amount of at least a portion of the micronutrient included in the infant formula is lower than the corresponding micronutrient conventionally included in the infant formula. Quantity (in unit volume). It should be understood that the amount of all micronutrients included in the infant formula is not lower than that of the corresponding micronutrient (in terms of unit volume) to achieve the infant formula as a low micronutrient infant formula. It is sufficient to reduce the amount of micronutrients in the infant formula by the amount of the known material volume. The amount of micronutrients or "negative amount" included in the formula of the formula is the appropriate for the infant to be used in the infant formula approved by the f-environment. The standard amount of micronutrients (the amount of micronutrients selected in the formula for the unit body in infant formula (in ill) is described in Table A below (ie diet formula) and Table B (recovery powder S) I61198.doc 17· 201233328 Table A: Minimum amount of ready-to-serve formula micronutrients (per liter) Maximum amount (per liter) Typical amount of sterilization kit (per liter) Typical amount of sterile sterilization formula ( Per liter) Vitamin A (IU) 2030 4400 3110 3890 Vitamin D (IU) 406 642 526 506 Vitamin E (IU) 10.2 15.0 13.3 11.8 Vitamin K (ng) 54.1 410 125 106 Vitamin Bl (pg) 676 4060 1220 1420 Vitamin B2 (Riboflavin)hg) 1010 4000 2500 2590 Vitamin B6(pg) 406 556 476 495 Vitamin B12(pg) 1.69 14.0 4.7 5.4 Final acid (με) 7100 21000 9730 9680 Folic acid (iv) 101 600 193 212 Pantothenic acid (iv) 3040 14400 6220 6710 Biotin (pg) 29.7 169 56.1 67.2 Vitamin C (mg) 60.8 800 416 352 Biliary test (mg) 109 203 127 120 Inositol (mg) 31.8 130 39.8 39.9 Fishing (mg) 528 620 585 581 Dish (mg) 284 398 349 341 Magnesium (mg) 40.6 71.5 55.7 55.0 Iron (mg) 12.2 15.6 13.4 13.7 (mg) 5.07 14.0 6.46 6.67 ^(με) 33.8 235 84.4 87.8 Copper (pg) 609 1484 676 728 Iodine (4)) 40.2 474 118 140 Sodium (mg) 163 245 190 189 Potassium (mg) 710 1196 946 942 Vapor (mg) 440 551 474 504 Fluoride (μβ) — — 168 143 Selenium (4) 12.3 36.1 24.9 24.3 161198.doc -18- 201233328 Table B: Minimum amount of micronutrients in reconstituted powder formula (per liter) Maximum amount (per liter) Typical amount (per liter) Vitamin A (IU) 2030 4820 3583 Vitamin D (IU) 406 642 563 Vitamin E (IU) 10.1 15.0 12.6 Vitamin Κ (μ8) 54.1 410 137 Vitamin Bl (pg) 676 4060 1560 Vitamin B2 (pg) 1010 4000 1500 Vitamin B6 (pg) 406 556 467 Vitamin B12 (pg) 1.69 14.0 5.85 Nicotinic acid hg) 7100 21000 9400 Folic acid (pg) 101 600 209 Pantothenic acid (iv) 3040 14400 6750 Prime (pg) 29.7 169 63.8 Vitamin C (mg) 60.8 670 170 Choline (mg 108 203 123 Inositol (mg) 31.8 130 41.0 Calcium (mg) 536 637 580 Dish (mg) 289 408 332 Magnesium (mg) 40.6 73.3 53.7 Iron (mg) 12.4 16.1 13.9 (mg) 5.15 14.4 6.69 Meng (4) 34.3 148 89.7 Copper (με) 618 1519 720 Iodine (με) 41.0 489 126 Sodium (mg) 165 251 201 Potassium (mg) 721 1235 1039 Vapor (mg) 446 565 486 Fluoride (pg) — • 116 Selenium (4) 12.4 37.0 25.6 Exemplary non-limiting micronutrients that may be included in conventional infant formulas include vitamin A, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pan 161198 .doc •19- 201233328 Acid, biotin, vitamin C, choline, inositol, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, sodium, potassium, vapor, fluoride, selenium and combinations thereof . Some examples of infant formulas may include combinations of copper, phosphorus, iron, calcium, and zinc. Some other exemplary conventional infant formulas may include a combination of copper, iron, and phosphorus. In a particular embodiment, at least two of copper, phosphorus, iron, calcium, and zinc are about 5% less, or even about 10% smaller, or even about 20% smaller than the amounts set forth in Tables A and B above. , or even about 3 % by weight, or even about 5 〇 / 〇 or even about 75%, or even about 80%, or even about 900 / 小 is present in low micronutrient formulations. In another particular embodiment, the iron and copper are about 5% less, or even less than about 10% less than the amounts set forth in Tables 8 and B above. , or even about 20% smaller, or even about 3〇%, or even about 50%. , or even about 75. /❶, or even about 8〇%, or even about 9〇% of the amount is present in low micronutrient formulations. It should be understood that Tables A and B do not contain a complete list of suitable micronutrients that may be included in the infant formula of the present invention. In addition, the low micronutrient infant formula of the present invention need not include each of the micronutrients listed in Tables A and B. The present invention encompasses infant formulas comprising any of the micronutrients listed in Tables A and B and/or any combination of one or more of the other micronutrients known in the art to be included in an infant formula. Standards or known levels of these and other micronutrients (in terms of 1 kcal) can be readily determined by reference to European and/or US infant formula rules and standards. When the micronutrient content (in terms of unit volume) in the infant formula is lower than the conventional content, the amount of the corresponding micronutrients should be compared to 161198.doc -20- 201233328. In this case, "corresponding micronutrient" means the same micronutrients present in the infant formula being evaluated. For example, if the infant formula contains micronutrients such as calcium, phosphorus and magnesium, the amount of such micronutrients in the infant formula and the amount of calcium, phosphorus and magnesium conventionally included in the infant formula should be compared to determine the infant formula. Is the amount of micronutrients relatively low? The micronutrient amount included in the low micronutrient infant formula of the present invention can be expressed as a percentage of the conventional corresponding micronutrient amount per unit volume. For example, in some embodiments of the invention, a low micronutrient infant formula is provided wherein the micronutrient is included in the infant formula in an amount of from about 30% to about 80% of the amount of the corresponding micronutrient (in unit volume) «Ten", including from about 3% to about 65%, from about 55% to about 80%, from about 40% to about 7%, from about 4% to about 5%, and about 6 parts of the corresponding micronutrient amount. 〇% to about 70% (both in unit volume). Typically, at least 65% of the micronutrients in the low micronutrient infant formula of the present invention comprise at least 75%, at least 80%, at least 90% and 1% micronutrient, from about 30% to about 80% of the corresponding micronutrient 1 The amount of % is included in the infant formula (in unit volume). In some embodiments, a low micronutrient infant formula is provided, wherein the micronutrients are included in the infant formula (in unit volume) in an amount from about 3% to about 65% of the amount of the corresponding micronutrient, including conventional The amount of the corresponding micronutrient is from about 35% to about 60%, from about 4% to about 5%, from about 4% to about 45%. And especially about 40% (both in terms of unit volume in the examples of low micronutrient infant formulas typically at least 45% micronutrient, including at least 50%, at least 60%, at least 75%, at least 8%, at least 9〇% and 161198.doc -21· 201233328 100% micronutrients are included in the infant formula (in unit volume) in an amount from about 35% to about 60% of the amount of the corresponding micronutrient (in other embodiments) , at least 1% micronutrient in the low micronutrient infant formula, including at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% micronutrient, from about 40% to about 50% of the corresponding micronutrient amount. The amount of % is included in the infant formula (in unit volume). The low micronutrient infant formula may include, for example, the infant formula on Days 1-2. In other embodiments, a low micro-bubble infant formula is provided, wherein Nutrients are included in the infant formula (in unit volume) in an amount from about 55% to about 80% by weight of the corresponding micronutrient, including from about 60% to about 75%, about 60% of the conventional micronutrient amount. About 70%, about 60% to about 65. / And especially about 6% (both in unit volume). In these embodiments, the low micronutrient infant formula typically comprises at least 30% micronutrients, including at least 50%, at least 6%, at least 75%, At least 8%, at least 9%, and 1% by weight of the micronutrient is included in the infant formula in an amount from about 55% to about 80% of the amount of the corresponding micronutrient (in other embodiments, in the other embodiments, 'low At least 10% of the micronutrients in the micronutrient infant formula, including at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% of the micronutrients in an amount of from about 60% to about 70% of the conventional micronutrient amount Included in infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 3-9 infant formula. In some embodiments where micronutrients include minerals, minerals are & Amounts from about 30% to about 80% of the minerals are included in the low micronutrient infant formula (in terms of unit volume), including about 30% to about 30% of the amount of the corresponding mineral 161198.doc •22·201233328 65%, about 55% to about 80%, about 40 % to about 70 〇 / 〇, about 40% to about 5%, and about 6% to about 7% by weight per unit volume. Generally, at least 1% of the low micronutrient infant formula of the present invention, Included at least 45%, at least 50%, at least 60%, at least 70%, at least 751⁄4, at least 80%, at least 90%, and 1% by weight of the minerals are about 30% of the amount of the corresponding mineral. Up to about 80% of the amount is included in the infant formula (in unit volume).In other embodiments, the mineral is from about 30% to about 65°/ of the amount of the corresponding mineral. The amount is included in the low micronutrient infant formula (in terms of unit volume)' comprising from about 35% to about 60 of the amount of the corresponding mineral. /. From about 40% to about 50%, from about 40% to about 45%, and especially about 40% (both in unit volume). In these embodiments, the low micronutrient infant formula typically has at least 10°/. The mineral 'comprises at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% of the minerals in an amount from about 30% to about 65% of the amount of the corresponding minerals. Included in infant formula (in unit volume). In other embodiments, the low micronutrient infant formula is at least 10°/. 'Include at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% minerals, including from about 40% to about 50% of the amount of the corresponding minerals, In infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 1-2 baby formula. In other embodiments, the mineral is about 5 50/ of the amount of the corresponding mineral. Up to about 80% of the amount is included in the low micronutrient infant formula (in unit volume), including from about 60% to about 75% of the amount of the corresponding mineral, from about 161I98.doc -23 to 201233328 600/. Up to about 70°/. From about 60% to about 65% and especially about 60% (both in unit volume). In these embodiments, the low micronutrient infant formula is typically at least 10°/. 'includes at least 25%, at least 50. /〇, at least 60%, at least 75%, at least 80%, at least 90%, and 1% by weight of the mineral is included in the infant formula in an amount from about 55°/〇 to about 80% of the amount of the corresponding mineral. (in unit volume). In other embodiments, at least 10% of the low micronutrient infant formula comprises at least 25%, at least 50%, at least 60%, at least 75%, at least 80°/〇, at least 90%, and 100% minerals by conventional means. An amount of from about 60°/〇 to about 70% of the amount of the corresponding mineral is included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 3-9 infant formula. In some embodiments wherein the micronutrient comprises a vitamin, the vitamin is included in the low micronutrient infant formula (in unit volume) in an amount from about 30% to about 80% of the conventional vitamin amount, including the conventional vitamin amount. From about 30% to about 65%, from about 55% to about 80%, from about 40% to about 70%, from about 40% to about 50%, and from about 60% to about 70% (both in unit volume). Typically, at least 45%, including at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, and 100% of the vitamins of the low micronutrient infant formula of the present invention are conventionally known as vitamins. Amounts from about 30% to about 80 〇/〇 are included in the infant formula (in unit volume). In other embodiments, the vitamin is included in the low micronutrient infant formula (in unit volume) in an amount from about 30% to about 65% of the conventional vitamin amount, including about 35% to about 10% of the conventional vitamin amount. 60%, from about 40% to about 50%, from about 40% to about 45% and especially about 40% (both in unit volume). 161198.doc • 24-201233328 In such embodiments, the low micronutrient infant formula typically comprises at least ιοο/〇 vitamins, including at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90 The % and 100% vitamins are included in the infant formula (in unit volume) in amounts from about 30% to about 65% of the conventional vitamin amount. • In other embodiments, at least 10% of the vitamins in the low micronutrient infant formula comprise at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% of the vitamins in a conventional amount of vitamins. 4〇% to about 5〇0/. The amount is included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 1_2 infant formula. In other embodiments, 'vitamins are included in low micronutrient infant formula (in terms of unit volume) in amounts of from about 55 〇/〇 to about 80% of the conventional vitamin amount, including about 6 习 of the corresponding vitamin amount. From about 75%, from about 6% to about 70%, from about 60% to about 65°/. And especially about 60% (both in unit volume). In such embodiments, the 'low micronutrient infant formula is typically at least 10%, including at least 25%, at least 50%, at least 6 inches. /0, at least 75 ❶ / 〇, at least 80%, at least 90% and 1 〇〇. /. The vitamin is included in the infant formula (in unit volume) in an amount from about 55% to about 80% of the conventional vitamin amount. In other embodiments, the low micronutrient infant formula comprises at least 1%, including at least 25%, at least 5〇〇/0, at least 6%, at least 75%, at least 8%, and to. > 9〇/l&gt The vitamin is about 60% to about 70°/ of the conventional vitamin amount. The amount is included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 3-9 infant formula. Suitable micronutrients that may be included in the infant formula of the present invention include vitamins or related nutrients, minerals, and combinations thereof. Non-limiting vitamins 161198.doc -25· 201233328 Examples of the system include vitamin A, vitamin D, vitamin E, vitamin κ, vitamin Β 1, vitamin Β 2, pyridoxine, vitamin Β 5, vitamin Β 6, vitamin Β 12, acid, Folic acid, pantothenic acid, biotin, vitamin C, gallstones, inositol, ascorbic acid, salts and derivatives thereof, and combinations thereof. Non-limiting examples of suitable minerals that may be included in the infant formula of the present invention include calcium, phosphorus, magnesium, iron, zinc, manganese, copper 'iodine, sodium, potassium, pin, chromium, vapor, fluoride, selenium And their combinations. Any infant formula can be formulated with the low micronutrient content disclosed herein, including autoclave sterilization and aseptic sterilization of ready-to-eat nutrient liquids, concentrated nutrient liquids, and nutritional powders. Macronutrients In addition to the micronutrients described herein, the infant formula of the present invention may also comprise one or more macronutrients. Macronutrients include proteins, fats, carbohydrates, and combinations thereof. The macronutrients suitable for use herein include any protein, fat, carbohydrate or source thereof known or otherwise suitable for use in an oral nutritional product, the restriction being that the macronutrient can be safely and effectively administered orally to the infant. The other ingredients in the infant formula are compatible. Although the total concentration or amount of protein, fat and carbohydrate may vary depending on the form of production (eg, powder or ready-to-feed liquid) and the intended diet of the intended user, such concentrations or amounts generally fall within the specific ranges described in the table below. Within - all values are preceded by the term "about", including any other essential fats, white matter and/or carbohydrates described in this article. For the powder examples, the amounts in the table below are the amount of /16I198.doc -26- 201233328 after the powder is recovered. Table c Nutrients (g/l〇〇mL) Example A Example 蛋白质 Protein 0·5 to 1.0 0.6 to 0.9 Fat 1.25.2.5 1.4 to 2.3 Carbohydrate 2.75.6.5 3.1 to 6.1 Total concentration of protein, fat and carbohydrate or The amount may also vary depending on whether the infant formula is a 1-2 day formula or a 3-9 day formula. The concentrations of protein, fat and carbohydrate in Formulations 1-2 and Days 3-9 are most often formulated in any of the specific ranges described in the table below (the terms are added before each value) "), including any other essential fat, protein and/or carbohydrate ingredients described herein. For the powder embodiment, the content in the table below is the amount after recovery.

表D 第1-2天配方 第3-9天配方 營養物(g/l〇〇mL) 實例C 實例D 實例E 實例F 蛋白質 0.50 至 0.75 0_58 至 0.72 0.76 至 1_0 0.85 至 0.98 脂肪 1.2 至 1.7 1.4 至 1.6 1.8 至 2.5 2.0 至 2.2 碳水化合物 2.7 至 4.0 2.9 至 3.6 4.1 至 6.5 4.9 至 6.3 或者或另外，嬰兒配方（無論粉末配方或即食型液體或 濃縮液體）中碳水化合物、脂肪及蛋白質之含量或量亦可 表徵為嬰兒配方中之總熱量百分比。本發明之嬰兒配方中 之該等常量營養素最通常經調配屬於下表中描述熱量範圍 中之任一者内（各數值前均加上術語「約」）。 161198.doc •27· 201233328 表E 營養物(總熱量％) 實例G 實例Η 實例I 破水化合物 2至96 10 至 75 30 至 50 蛋白質 2至96 5至70 15 至 35 脂肪 2至96 20 至 85 35 至 55 實例J 實例Κ 實例L 碳水化合物 25 至 50 25 至 50 35 至 50 蛋白質 10 至 30 5至30 7.5 至 25 脂肪 1至20 2至20 30 至 60 蛋白質 除本文中所描述之微量營養素外，本發明之嬰兒配方亦 可包含蛋白質。本發明之嬰兒配方中可包括任何已知或其 他適用之蛋白質或蛋白質源，限制條件為該等蛋白質適用 於餵養嬰兒且尤其為新生兒。 用於嬰兒配方中之合適蛋白質或其來源之非限制性實例 包括水解、部分水解或非水解蛋白質或蛋白質源，其可來 源於任何已知或其他合適來源，諸如乳（例如酪蛋白、乳 清）、動物（例如肉、魚）、榖類（例如稻、玉蜀黍）、植物（例 如大豆）或其組合。該等蛋白質之非限制性實例包括如本 文中所描述之乳蛋白分離物、乳蛋白濃縮物、酪蛋白分離 物、高度水解酷蛋白、乳清蛋白、酷蛋白納或赂蛋白的、 全脂牛乳、部分或完全脫脂乳、大豆蛋白分離物、大豆蛋 白濃縮物等。本文中使用之蛋白質亦可包括已知用於營養 產品中之游離胺基酸或完全或部分地由已知用於營養產品 中之游離胺基酸替代，該等游離胺基酸之非限制性實例包 括L-丙胺酸、L-天冬胺酸、L-麩胺酸、甘胺酸、L-組胺 酸、L-異白胺酸、L-白胺酸、L-苯丙胺酸、L-脯胺酸、L- 161198.doc -28 - 201233328 絲胺酸、L-蘇胺酸、L-纈胺酸、L-色胺酸、L-麩醯胺酸、 L-路胺酸、L-甲硫胺酸、L-半胱胺酸、牛橫酸、L-精胺 酸、L-肉鹼及其組合。 脂肪 除本文中所描述之微量營養素外，本發明之嬰兒配方亦 可包含脂肪源。用於本文中揭示之嬰兒配方中之合適脂肪 源包括任何適用於口服營養產品中且與該等產品之要素及 特徵相容之脂肪或脂肪源’限制條件為該等脂肪適用於餵 養嬰兒。 用於本文中所描述之嬰兒配方中之合適脂肪或其來源之 非限制性實例包括椰子油、分餾椰子油、大豆油、玉米 油、撖欖油、紅花子油、高油酸紅花子油、高GLA紅花子 油、油酸、MCT油（中鏈三酸甘油酯）、葵花籽油、高油酸 葵祀籽油、結構化三酸甘油酯、棕櫚油及棕櫊仁油、棕櫚 油精（palm olein)、菜籽油、亞麻籽油、琉璃苣籽油、月見 草油、黑醋栗籽油、轉殖基因油來源、水產油（例如金搶 魚、沙丁魚）、魚油、真菌油、海藻油、棉籽油及其組 合。在一個實施例中，合適脂肪或其來源包括油及油摻合 物，包括長鏈多不飽和脂肪酸（LC_puFA)。可包含之一些 非限制性特定多不飽和酸包括例如二十二碳六烯酸 (DHA)、二十碳四烯酸（ARA)、二十碳五烯酸（EpA)、亞麻 油酸（LA)及其類似物。非限制性二十碳四烯酸及二十二碳 六烯酸之來源包括水產油、來源於蛋類之油、真菌油、海 藻油及其組合。 161198.doc -29- 201233328 碳水化合物 本發明之嬰兒配方可包含任何適用於口服營養產品（諸 如4c兒配方)中且與該等產品之要素及特徵相容之碳水化 合物 適用於本文中所描述之嬰兒配方中之碳水化合物或其來 源之非限制性實例可包括麥芽糊精；水解完整或改質之 澱粉或玉米澱粉；㈣糖聚合物；玉米糖漿；玉米糖漿固 體；來源於稻米之碳水化合物；稻米糖漿；來源於豌豆之 故水化合物，來源於馬铃薯之碳水化合物；木薯；嚴糖； 葡萄糖；果糖；乳糖；高果糖玉米糖浆；蜂蜜；糖醇（例 如麥芽糖醇、赤藻糖醇、山梨糖醇)；人工甜味劑(例如蔗 糖素、乙酿續胺酸_、甜菊）；㈣化寡醣，諸如果寡膽 (FOS) ’及其組合。在一個實施例中，碳水化合物可包括 DE值小於2〇之麥芽糊精。 其他視情況可選成分 本發明之嬰兒配方亦可進一步包含可改良產品之物理、 化學、美學或加工特徵或在用於目標群體時充當醫藥或其 他營養組分之其他視情況選用之成分。多種該等視情況選 用之成分為已知或以其他方式適用於醫藥食品或其他營養 產品或醫藥劑型中且亦可用於本文中之組合物中，限制條 牛為該等視隋況選用之成分可安全經口投與且與所選產品 形式中之必需及其他成分相容。 '•亥等視情況選用之成分之非限制性實例包括防腐劑、抗 氧化劑、乳化劑、緩衝劑、果寡醣、半乳寡醣、人乳寡醣 161198.doc 201233328 及其他益菌助生質（Prebiotic)、醫藥活性物、本文中所描 述之其他營養物、著色劑、香料、增稠劑及穩定劑、乳化 劑潤'月劑、類胡蘿萄素（例如β-胡蘿蔔素、玉米黃素、葉 黃素、番茄紅素）等及其組合。 本文中所描述之粉末嬰兒配方可包括流動劑或抗結塊劑 以延緩粉末隨時間推移而凝塊或結塊且使粉末實施例易於 自其容器流動。任何已知或以其他方式適用於營養粉末或 產品形式中之流動劑或抗結塊劑均可適用於本文中，其非 限制實例包括磷酸三鈣、矽酸鹽及其組合。營養產品中流 勒劑或抗結塊劑之濃度視產品形式、其他所選成分、所需 流動性質等不同’但最通常在營養產品之約〇.1重量％至約 4重量％範圍内，包括約0.5重量。/〇至約2重量。/0。 嬰兒配方中亦可包括穩定劑。任何已知或以其他方式適 用：營養產品中之穩定劑亦適用於本文中，其一些非限制 性實例包括_ ’諸如三仙膠H劑可占嬰兒配方之約 0·1重量％至約5.0重量％，包括約〇.5重量。/。至約3重量％， 包括約0.7重量。/。至約2 5重量0/〇。 穩定性 』本：”：低熱量、低微量營養素液體嬰兒配方與低熱 i :微里營養素配方相比有利地呈現物理屬性改良，包 括穩定性改良。液體嬰兒配方之物理穩定性問題通常在配 力於使用前長期儲存時出現。在此㈣，配方之組分(例 如腊肪）通常與水性組分分離。嬰兒配方之組分亦可能自 懸淨液沈降，從而在配方容器底部形成沈降物。儘管可藉 161198.doc •31 - 201233328 由搖動配方以再混合配方組分來矯正此相分離及沈降，但 該相分離及沈降通常引起消費者對產品之接受度極大降 低。 現發現低熱量液體嬰兒配方之微量營養素含量可影響嬰 兒配方之穩定性。詳言之’本發明之低熱量、低微量營養 素液體嬰兒配方與低熱量、高微量營養素配方相比在配方 存放期期間有利地呈現較少沈降及較少分離。 蛋白質負載 可使用多種量測法驗證液體嬰兒配方之穩定性。舉例而 言’一種方法為可藉由量測蛋白質負載量來測定液體嬰兒 配方之穩定性。蛋白質負載量可表示為對嬰兒配方進行高 速離心後形成之乳油層之蛋白質百分比（每1〇〇公克乳膏劑 層中蛋白質公克數）。適用於測定蛋白質負載量之技術詳 細描述於本揭示案之實例中。 液體嬰兒配方乳液之穩定性通常隨蛋白質負載量增加而 增加°現發現低熱量、低微量營養素殺菌爸滅菌液體嬰兒 配方與低熱量、高微量營養素殺菌釜滅菌液體嬰兒配方相 比具有較高蛋白質負載量。在第1-2天殺菌爸滅菌嬰兒配 方及第3-9天殺菌釜滅菌嬰兒配方中均發現此情況。 因此’在一個態樣中’本發明係關於低熱量、低微量營 養素液體嬰兒配方，其與低熱量、高微量營養素嬰兒配方 相比蛋白質負載量增加。低熱量、低微量營養素液體嬰兒 配方較佳為殺菌爸滅菌之即食型（RTF)配方。在其中低熱 量、低微量營養素液體嬰兒配方為第1_2天嬰兒配方之實 161198.doc -32- 201233328 施例中，嬰兒配方之蛋白質負載量將通常為至少約5 〇%， 包括約5.0%至約7.0%、約5 5%至約6 5%、約$ 7%至°約 6_ 1 %且尤其為約5 9%。 在其中低熱量、低微量營養素液體嬰兒配方為第天 . 嬰兒配方之實施例中，嬰兒配方之蛋白質負載值將通常為 至少約6·0%，包括約6.0。/。至約8.0%、約6 5%至約7 5% : 約6.7%至約7.1%且尤其為約6 9%。低熱量、低微量營養素 液體嬰兒配方較佳經殺菌釜滅菌。 ” 粒徑 另一種可用於驗證液體嬰兒配方之穩定性的量測法為存 在於嬰兒配方中顆粒之粒徑分佈及平均粒徑。可使用此項 技術中已知的任何技術測定粒徑分佈及平均粒徑。本揭示 案之實例中描述之一種技術涉及使用光散射機器（例如 Beckman Couiter LS i3 32〇)，其使用多波長光源量測懸浮 於液體嬰兒配方樣品中之顆粒之粒徑分佈。亦可使用其他 合適技術。 液體嬰兒配方乳液之穩定性通常隨粒徑減小而增加。現 發現本發明之低熱量、低微量營養素第丨_2天殺菌爸滅菌 液體嬰兒配方與低熱量、高微量營養素第1_2天殺菌釜滅 .菌液體嬰兒配方相比具有更多數目的小顆粒且存在於配方 中顆粒之平均粒徑較小。 因此，在一個態樣中，本發明係關於低熱量、低微量營 養素液體嬰兒配方，其與低熱量、高微量營養素液體嬰兒 配方相比存在於配方中顆粒之平均粒徑較小。低熱量、低 161193.doc •33- 201233328 微量營養素液體嬰兒配方較佳為殺菌釜滅菌RTF配方，且 更佳為第1-2天殺菌蚤滅菌液體嬰兒配方。在其中低熱 量、低微量營養素液體嬰兒配方為第1-2天嬰兒配方之實 施例中，存在於嬰兒配方中顆粒之平均粒徑將通常為約 〇.1 μηι 至約 1.〇 μπΊ，包括約 0.15 μιη 至約 〇·8 μηι 及約 0.15 μιη至約 0.7 μιη。 通常’對於本發明之低熱量、低微量營養素第1-2天液 體嬰兒配方’存在於嬰兒配方中之至少約5〇%(包括約5〇% 至約100%及約50%至約70%)顆粒之粒徑（直徑）將為約oj 5 μιη至約 0.8 μηι。 乳油分離速度（Creaming Velocity) 另一種可用於驗證液體嬰兒配方之穩定性的量測法為乳 油分離速度。乳油分離速度量測液體樣品（在此情況下， 兒配方）中顆粒移動之速率且可預示嬰兒配方在長期靜 置或離心後形成乳油層之能力。可使用以下方程式計算乳 油分離速度： ^ cream 2 Pfluid PparticleTable D Day 1-2 Formulation Day 3-9 Formula Nutrients (g/l〇〇mL) Example C Example D Example E Example F Protein 0.50 to 0.75 0_58 to 0.72 0.76 to 1_0 0.85 to 0.98 Fat 1.2 to 1.7 1.4 To 1.6 1.8 to 2.5 2.0 to 2.2 Carbohydrates 2.7 to 4.0 2.9 to 3.6 4.1 to 6.5 4.9 to 6.3 or alternatively, the amount of carbohydrates, fats and proteins in infant formula (whether in powder formula or ready-to-feed liquid or concentrated liquid) or The amount can also be characterized as the percentage of total calories in the infant formula. The macronutrients in the infant formula of the present invention are most often formulated in any of the ranges of calories described in the table below (each term is preceded by the term "about"). 161198.doc •27· 201233328 Table E Nutrients (% of total calories) Example G Example 实例 Example I Water-breaking compound 2 to 96 10 to 75 30 to 50 Protein 2 to 96 5 to 70 15 to 35 Fat 2 to 96 20 to 85 35 to 55 Example J Example 实例 Example L Carbohydrate 25 to 50 25 to 50 35 to 50 Protein 10 to 30 5 to 30 7.5 to 25 Fat 1 to 20 2 to 20 30 to 60 Proteins In addition to the micronutrients described herein The infant formula of the invention may also comprise a protein. Any known or otherwise suitable source of protein or protein may be included in the infant formula of the present invention with the proviso that the proteins are suitable for feeding infants and especially newborns. Non-limiting examples of suitable proteins or sources thereof for use in an infant formula include hydrolyzed, partially hydrolyzed or non-hydrolyzed protein or protein sources, which may be derived from any known or other suitable source, such as milk (eg, casein, whey) ), animals (eg, meat, fish), mites (eg, rice, maize), plants (eg, soybeans), or combinations thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates, casein isolates, highly hydrolyzed proteins, whey proteins, whey protein or gluten, as described herein, whole milk , partially or completely skim milk, soy protein isolate, soy protein concentrate, and the like. The protein used herein may also include free amino acids known for use in nutritional products or may be replaced, in whole or in part, by free amino acids known for use in nutritional products, such non-limiting free amino acids. Examples include L-alanine, L-aspartic acid, L-glutamic acid, glycine, L-histamine, L-isoleucine, L-leucine, L-phenylalanine, L- Proline, L-161198.doc -28 - 201233328 Serine, L-threonine, L-proline, L-tryptophan, L-glutamic acid, L-Litanic acid, L- Methionine, L-cysteine, erucic acid, L-arginine, L-carnitine, and combinations thereof. Fat In addition to the micronutrients described herein, the infant formula of the present invention may also comprise a source of fat. Suitable fat sources for use in the infant formula disclosed herein include any fat or fat source suitable for use in oral nutritional products and compatible with the elements and characteristics of such products. The limitation is that the fats are suitable for feeding infants. Non-limiting examples of suitable fats or sources thereof for use in the infant formulas described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, eucalyptus oil, safflower oil, high oleic safflower oil, High GLA safflower oil, oleic acid, MCT oil (medium chain triglyceride), sunflower oil, high oleic sunflower seed oil, structured triglyceride, palm oil and palm kernel oil, palm olein (palm olein), rapeseed oil, linseed oil, borage seed oil, evening primrose oil, blackcurrant seed oil, source of genetic oil, aquatic oil (eg gold fish, sardines), fish oil, fungal oil, seaweed Oil, cottonseed oil and combinations thereof. In one embodiment, suitable fats or sources thereof include oils and oil blends, including long chain polyunsaturated fatty acids (LC_puFA). Some non-limiting specific polyunsaturated acids that may be included include, for example, docosahexaenoic acid (DHA), arachidonic acid (ARA), eicosapentaenoic acid (EpA), linoleic acid (LA). ) and its analogues. Sources of non-limiting eicosatetraenoic acid and docosahexaenoic acid include aquatic oils, oils derived from eggs, fungal oils, algae oils, and combinations thereof. 161198.doc -29- 201233328 Carbohydrates The infant formula of the present invention may comprise any carbohydrate suitable for use in an oral nutritional product, such as a 4c formulation, and compatible with the elements and characteristics of such products, as described herein. Non-limiting examples of carbohydrates or sources thereof in an infant formula may include maltodextrin; hydrolyzed whole or modified starch or corn starch; (iv) sugar polymer; corn syrup; corn syrup solids; Rice syrup; water compound derived from pea, derived from potato carbohydrate; cassava; strict sugar; glucose; fructose; lactose; high fructose corn syrup; honey; sugar alcohol (eg maltitol, erythritol) , sorbitol); artificial sweeteners (such as sucralose, ethanoic acid, stevia); (iv) oligosaccharides, if oligobiliary (FOS) 'and combinations thereof. In one embodiment, the carbohydrate may comprise maltodextrin having a DE value of less than 2 Torr. Other Optional Ingredients The infant formula of the present invention may further comprise other optional ingredients which modify the physical, chemical, aesthetic or processing characteristics of the product or act as a pharmaceutical or other nutrient component when used in the target population. A variety of such optional ingredients are known or otherwise suitable for use in pharmaceutical foods or other nutritional products or pharmaceutical dosage forms and can also be used in the compositions herein, limiting the ingredients selected by the cattle for such visual conditions. It can be safely administered orally and is compatible with the essential and other ingredients in the selected product form. Non-limiting examples of ingredients selected in the following cases include preservatives, antioxidants, emulsifiers, buffers, fructooligosaccharides, galactooligosaccharides, human milk oligosaccharides 161198.doc 201233328 and other beneficial bacteria (Prebiotic), medicinal actives, other nutrients, colorants, fragrances, thickeners and stabilizers described herein, emulsifiers, emollients, guacamera (eg beta-carotene, zeaxanthin) , lutein, lycopene, etc. and combinations thereof. The powdered infant formula described herein can include a flow or anti-caking agent to delay the agglomeration or agglomeration of the powder over time and to facilitate the flow of the powder embodiment from its container. Any flow or anti-caking agent known or otherwise suitable for use in a nutritional powder or product form may be suitable for use herein, non-limiting examples of which include tricalcium phosphate, citrate, and combinations thereof. The concentration of the fluid or anti-caking agent in the nutritional product varies depending on the product form, other selected ingredients, the desired flow properties, etc., but is most typically in the range of from about 1% by weight to about 4% by weight of the nutritional product, including About 0.5 weight. /〇 to about 2 weights. /0. Stabilizers may also be included in the infant formula. Any known or otherwise applicable: Stabilizers in nutritional products are also suitable for use herein, some non-limiting examples of which include _ 'such as Sanxian gum H agent may comprise from about 0.1% by weight to about 5.0 of the infant formula % by weight, including about 〇.5 by weight. /. Up to about 3% by weight, including about 0.7% by weight. /. To about 25 weight 0 / 〇. Stability: Ben:": Low-calorie, low-micronutrient liquid infant formula is beneficially improved in physical properties compared to low-heat i: micro-nutrient formula, including stability improvement. The physical stability problem of liquid infant formula is usually in stamina It occurs during long-term storage before use. In this (4), the components of the formula (such as fat) are usually separated from the aqueous component. The components of the infant formula may also settle from the suspension to form a sediment at the bottom of the formulation container. Although this phase separation and sinking can be corrected by shaking the formulation to remix the formulation components by 161198.doc • 31 - 201233328, the phase separation and sinking usually cause a great reduction in consumer acceptance of the product. The micronutrient content of the infant formula can affect the stability of the infant formula. In particular, the low calorie, low micronutrient liquid infant formula of the present invention advantageously exhibits less during the formulation storage period than the low calorie, high micronutrient formulation. Settling and less separation. Protein loading can be used to verify the stability of liquid infant formulas using a variety of measurements For example, one method is to measure the stability of a liquid infant formula by measuring the protein load. The protein load can be expressed as the percentage of protein in the cream layer formed by high-speed centrifugation of the infant formula (per 1 gram) The number of grams of protein in the cream layer. The technique applicable to the determination of protein loading is described in detail in the examples of this disclosure. The stability of liquid infant formula emulsions generally increases with increasing protein loading. Low heat, low traces are now found. Nutrient sterilizing dad sterilized liquid infant formula has higher protein loading than low calorie and high micronutrient sterilizing liquid sterilized liquid infant formula. On day 1-2, sterilized dad sterilized infant formula and 3-9 day sterilized sterilized infant This is the case in the formulation. Therefore, 'in one aspect' the present invention relates to a low calorie, low micronutrient liquid infant formula which has an increased protein loading compared to a low calorie, high micronutrient infant formula. Low calorie, low The micronutrient liquid infant formula is preferably a ready-to-eat type (RTF) for sterilizing dad sterilization. In the case where the low-calorie, low-micronutrient liquid infant formula is the 1st-day infant formula 161198.doc -32-201233328, the infant formula will typically have a protein loading of at least about 5%, including about 5.0. % to about 7.0%, about 55% to about 65%, about $7% to about 6% to about 1% and especially about 5.9%. In which the low-calorie, low-micronutrient liquid infant formula is the first day. In an embodiment of the formulation, the infant formula will typically have a protein loading value of at least about 0.001%, including from about 6.0% to about 8.0%, from about 5% to about 75%, from about 6.7% to about 7.1%. And especially about 6 9%. Low-calorie, low-micronutrient liquid infant formula is preferably sterilized by autoclave.” Particle size Another measure that can be used to verify the stability of liquid infant formula is the presence of particles in infant formula. Particle size distribution and average particle size. The particle size distribution and average particle size can be determined using any technique known in the art. One technique described in the examples of the present disclosure involves the use of a light scattering machine (e.g., Beckman Couiter LS i3 32®) that uses a multi-wavelength source to measure the particle size distribution of particles suspended in a liquid infant formula sample. Other suitable techniques can also be used. The stability of liquid infant formula emulsions generally increases with decreasing particle size. It has been found that the low-calorie, low-micronutrient 丨2 day sterilized dad sterilized liquid infant formula of the present invention has a larger number of small particles than the low-calorie, high-micronutrient 1st-day sterilizing kettle. The average particle size of the particles present in the formulation is small. Thus, in one aspect, the present invention is directed to a low calorie, low micronutrient liquid infant formula that has a smaller average particle size in the formulation than a low calorie, high micronutrient liquid infant formula. Low calorie, low 161193.doc •33- 201233328 The micronutrient liquid infant formula is preferably a sterilization autoclave RTF formulation, and more preferably a 1-2 day sterilization and sterilization liquid infant formula. In embodiments wherein the low calorie, low micronutrient liquid infant formula is the 1-2 day infant formula, the average particle size of the particles present in the infant formula will typically range from about 0.1 μm to about 1. 〇μπΊ, including From about 0.15 μηη to about 〇·8 μηι and from about 0.15 μηη to about 0.7 μιη. Typically, the 'lower calorie, low micronutrient 1-2 day liquid infant formula' of the present invention is present in at least about 5% (including from about 5% to about 100% and from about 50% to about 70%) of the infant formula. The particle size (diameter) of the particles will range from about oj 5 μιη to about 0.8 μηι. Creaming Velocity Another measure that can be used to verify the stability of a liquid infant formula is the rate of cream separation. The emulsification speed measures the rate at which the particles move in the liquid sample (in this case, the formula) and predicts the ability of the infant formula to form a cream layer after prolonged standing or centrifugation. The separation rate can be calculated using the following equation: ^ cream 2 Pfluid Pparticle

gR2 其中：gR2 where:

Vcream為乳油分離速度 Pfluid為配方密度 Ppartic丨e為顆粒密度 η為配方黏度 R為平均粒徑 g為重力加速度。 161198.doc -34· 201233328 液體嬰兒配方乳液之穩定性通常隨乳油分離速度降低而 増加。現發現本發明之低熱量、低微量營養素第1-2天殺 菌釜滅菌液體嬰兒配方與低熱量、高微量營養素第1-2天 殺菌爸滅菌液體嬰兒配方相比具有較低乳油分離速度。 因此’在一個態樣中，本發明係關於低熱量、低微量營 養素液體嬰兒配方，其與低熱量、高微量營養素嬰兒配方 相比具有低乳油分離速度。低熱量、低微量營養素液體嬰 兒配方較佳為殺菌釜滅菌RTF配方，且更佳為第1-2天殺菌 签滅菌液體嬰兒配方。在其中低熱量、低微量營養素液體 嬰兒配方為第1 -2天嬰兒配方之實施例中，嬰兒配方之乳 油分離速度將通常為約5.0公分/天或5.0公分/天以下，包括 約1.0公分/天至約5 ·0公分/天、約3.0公分/天至約3.5公分/ 天且尤其為約3.2公分/天。 顏色 本發明之低熱量、低微量營養素液體嬰兒配方與低熱 量、高微量營養素配方相比亦有利地呈現顏色改良。 液體嬰兒配方含有多種營養物，其在調配、加工及儲存 期間可能相互作用。該等相互作用可使配方顏色扭曲為灰 色、米色或其他類似變色。該等變色通常引起消費者對產 品之接受度極大降低，消費者通常偏愛光亮、發白色的產 品。 一種可用於評估嬰兒配方之顏色特徵之技術為艾格壯顏 色计分（Agtron color score)。本文中所用艾格壯計分係使 用 Agtron 45分光光度計（可自 Agtron Inc.，Reno，Nevada獲 161193.doc -35- 201233328 得）藉由習知技術量測。艾格壯計分為自各嬰兒配方之表 面反射之能量（光）百分比之量測值。配方表面顏色反射性 越強或越亮’則艾格壯計分越高。該等計分在0(黑色）至 100(白色）範圍内。 現發現低熱量液體嬰兒配方之微量營養素含量可影響配 方顏色。詳言之，本發明之低熱量、低微量營養素液體嬰 兒配方與低熱量、高微量營養素配方相比具有更亮、更白 的顏色C如由艾格壯計分定義）。在殺菌釜滅菌及無菌滅菌 低熱量、低微量營養素液體配方中均發現此情況。亦不僅 在剛調配後，且亦在長時間後（在一些情況下，產品調配 後至少9個月）觀測到低熱量、低微量營養素液體嬰兒配方 之顏色改良。 因此’在一個態樣中’本發明係關於低熱量、低微量營 養素第1-2天液體嬰兒配方，其調配後（調配後丨天内）之艾 格壯計分為至少約45，包括約45至約60及約47至約55。配 方較佳為殺菌釜滅菌RTF配方。在其他實施例中，配方在 調配後兩個月之艾格壯計分為至少約4〇 ’包括約4〇至約 5 0，在調配後四個月之艾格壯計分為至少約3 7，包括約利 至約50 ;在調配後六個月之艾格壯計分為至少約37，包括 約37至約50 ;且在調配後九個月之艾格壯計分為至少約 35，包括約35至約45。 在另一態樣中’本發明係關於低熱量、低微量營養素第 3-9天液體殺菌爸滅菌嬰兒配方’其調配後之艾格壯計分 為至少約42，包括約42至約55及約45至約52。在其他實施 161198.doc -36· 201233328 例中，配方在調配後三個月之艾格壯計分為至少約40，包 括約4 0至約5 0 ;且在調配後六個月.之艾格壯計分為至少約 4〇，包括約40至約50。 在另一態樣中’·本發明係關於低熱量、低微量營養素第 3-9天液體無菌滅菌嬰兒配方，其調配後之艾格壯計分為 至少約58 ’包括約58至約65及約60至約62 ^在其他實施例 中，配方在調配後兩個月之艾格壯計分為至少約5 $，包括 約55至約62 ;在調配後六個月之艾格壯計分為至少約55， 包括約55至約60 ;且在調配後九個月之艾格壯計分為至少 約52，包括約52至約55。 緩衝能力 本發明之低熱量嬰兒配方（具有高或低微量營養素含量） 與全熱量配方相比亦有利地呈現改良之緩衝能力。 咸信人類母乳含有某些促進有利腸細菌群落（明確言 之，雙又桿菌發育之因子，雙又桿菌可 阻止病原微生物增殖。咸信嬰兒腸道中雙又桿菌之生長係 兩人類母乳之物理化學性質（尤其其高乳糖含量（其為雙叉 才干菌之受質）、其低蛋白含量及其低緩衝能力）促進。此 外，人乳之低緩衝能力可使嬰兒腸胃道（GI)中之天然酸度 更有效地使經口攝取之病原體失活。在一些情況下，嬰兒 配方可具有相對較高缓衝能力，其可能不完全有利於雙叉 桿菌之生長且可能潛在影響嬰兒腸胃道之天然酸度。因 此，一些配方餵養之嬰兒與母乳餵養嬰兒相比可能經歷更 多的腸胃道感染事件。 161198.doc •37· 201233328 現發現嬰兒配方之緩衝能力與配方之能量含量有關。明 確言之，已發現嬰兒配方之緩衝能力隨能量含量降低而降 低。因此本發明之低熱量嬰兒配方與全熱量嬰兒配方相比 有利地具有改良（亦即較低）之緩衝能力，且在一些實施例 中’其緩衝能力低於人乳。因此，本發明之低熱量嬰兒配 方可用於調節嬰兒且尤其新生兒之胃液酸度，減少嬰兒腸 胃道中病原微生物生長、促進有益微生物（諸如雙叉桿菌） 生長且提高使經口攝取之病原體失活之有效性。 緩衝能力通常係指液體抵抗pH值變化之能力。用於表示 本發明嬰兒配方之緩衝能力的量度有很多種。舉例而言， 嬰兒配方之緩衝能力可表示為在向嬰兒配方（或向粉末嬰 兒配方實施例之復原配方）中添加鹽酸（HC1)後氫離子濃度 ([H+])之增加量。明確言之，緩衝能力係以向1〇〇 配方 中添加5 mmo丨HC1後[H+]之增加量表示，或以向1〇〇 „^配 方中添加5.50 mm〇l HC1(或向50 mL配方中添加2.75 mmol HC1)後[H+]之增加量表示。 本發明之低熱量嬰兒配方之緩衝能力（以向1〇〇 mL配方 中添加5 mmol HC1後之[H+]表示）可為至少約2,〇 mM，包 括至少約5.G mM、至少約7·〇 mM、至少約lo.o mM、至少Vcream is the separation speed of the cream. Pfluid is the formula density. Ppartic丨e is the particle density. η is the formula viscosity. R is the average particle size. g is the gravitational acceleration. 161198.doc -34· 201233328 The stability of liquid infant formula emulsions is usually accompanied by a decrease in the rate of separation of the cream. It has been found that the low-calorie, low-micronutrient of the present invention has a lower emulsion separation rate than the low-calorie, high-micronutrient 1-2 days of the sterilized dad-sterilized liquid infant formula. Thus, in one aspect, the present invention is directed to a low calorie, low micronutrient liquid infant formula that has a low cream separation rate compared to a low calorie, high micronutrient infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilized autoclaved RTF formulation, and more preferably a 1-2 day sterilization-sterilized liquid infant formula. In embodiments in which the low calorie, low micronutrient liquid infant formula is a 1-2 day infant formula, the infant formula will typically have a cream separation rate of about 5.0 cm/day or less than 5.0 cm/day, including about 1.0 cm/ The day is about 5 · 0 cm / day, about 3.0 cm / day to about 3.5 cm / day and especially about 3.2 cm / day. Color The low calorie, low micronutrient liquid infant formula of the present invention also advantageously exhibits color improvement as compared to low heat, high micronutrient formulations. Liquid infant formulas contain a variety of nutrients that may interact during formulation, processing, and storage. These interactions can distort the color of the formula to gray, beige or other similar discoloration. These discolorations often cause consumer acceptance of the product to be greatly reduced, and consumers generally prefer bright, white products. One technique that can be used to assess the color characteristics of an infant formula is the Agtron color score. The Aeghen scoring system used herein was measured by a conventional technique using an Agtron 45 spectrophotometer (available from Agtron Inc., Reno, Nevada, 161193. doc-35-201233328). Aegis is divided into measurements of the percentage of energy (light) reflected from the surface of each infant formula. The stronger or brighter the color of the surface of the formula is, the higher the score is. These scores range from 0 (black) to 100 (white). It has been found that the micronutrient content of low calorie liquid infant formulas can affect the formula color. In particular, the low calorie, low micronutrient liquid infant formula of the present invention has a brighter, whiter color C than the low calorie, high micronutrient formulation as defined by the Aegean score. This was observed in both sterilized and sterile sterilized low-calorie, low-micronutrient liquid formulations. Not only after the blending, but also after a long period of time (in some cases, at least 9 months after the product was formulated), the color improvement of the low calorie, low micronutrient liquid infant formula was observed. Therefore, 'in one aspect', the present invention relates to a low-calorie, low-micronutrient 1-2 day liquid infant formula, and after the blending (within days after blending), the Aegean score is at least about 45, including about 45 to About 60 and about 47 to about 55. The formulation is preferably a sterilization autoclave RTF formulation. In other embodiments, the formulation is divided into at least about 4 〇 ' including about 4 〇 to about 50 两个 after two months of formulation, and at least about 3 7 after four months of blending. Including about a profit of about 50; six months after the blending, the Aegis is divided into at least about 37, including about 37 to about 50; and nine months after the blending, the Aegean score is at least about 35, including about 35. To about 45. In another aspect, the present invention relates to a low calorie, low micronutrient 3-9 day liquid sterilized dad sterilized infant formula, which is formulated to have at least about 42, including about 42 to about 55 and about 45 to about 52. In other implementations, 161198.doc -36·201233328, the formula is divided into at least about 40, including about 40 to about 50, for three months after the formulation; and six months after the blending. The score is at least about 4 inches, including about 40 to about 50. In another aspect, the present invention relates to a low-calorie, low-micronutrient 3-9 day liquid aseptically sterilized infant formula, which is formulated to have an Aegis score of at least about 58' including from about 58 to about 65 and about 60 to about 62 ^ In other embodiments, the formula is divided into at least about 5 $, including about 55 to about 62, for two months after the formulation; the Eiger is divided into at least about six months after the blending. 55, including from about 55 to about 60; and nine months after the blending, the Eiger is divided into at least about 52, including about 52 to about 55. Buffering Capacity The low calorie infant formula of the present invention (having high or low micronutrient content) also advantageously exhibits improved cushioning capacity as compared to a full calorie formulation. Salty human breast milk contains certain enzymes that promote beneficial intestinal bacteria (clearly speaking, the factor of Bifidobacterium development, Bifidobacterium can prevent the proliferation of pathogenic microorganisms. The growth of Bifidobacterium in the intestinal tract of the baby is the physical chemistry of two human breast milk. The nature (especially its high lactose content, which is the quality of the bifurcated bacteria), its low protein content and its low buffering capacity). In addition, the low buffering capacity of human milk can make the natural intestines (GI) of infants. Acidity more effectively inactivates orally ingested pathogens. In some cases, infant formulas may have a relatively high buffering capacity, which may not fully benefit the growth of the bifidobacteria and may potentially affect the natural acidity of the infant's gastrointestinal tract. Therefore, some formula-fed infants may experience more gastrointestinal infections than breast-fed infants. 161198.doc •37· 201233328 It has been found that the buffering capacity of infant formula is related to the energy content of the formula. It was found that the buffering capacity of the infant formula decreased as the energy content decreased. Therefore, the low calorie infant formula and total calories of the present invention The infant formula advantageously has an improved (i.e., lower) buffering capacity and, in some embodiments, has a lower buffering capacity than human milk. Thus, the low calorie infant formula of the present invention can be used to regulate infants and especially newborns. The acidity of the gastric juice reduces the growth of pathogenic microorganisms in the gastrointestinal tract of the infant, promotes the growth of beneficial microorganisms such as Bifidobacterium, and increases the effectiveness of inactivation of pathogens that are orally ingested. Buffering capacity generally refers to the ability of a liquid to resist changes in pH. There are many variations on the buffering capacity of the infant formula of the present invention. For example, the buffering capacity of the infant formula can be expressed as the addition of hydrochloric acid (HC1) to the infant formula (or to the formula of the powder infant formula). The increase in hydrogen ion concentration ([H+]). Specifically, the buffering capacity is expressed as the increase in [H+] after adding 5 mmo丨HC1 to the 1〇〇 formula, or in the formula of 1〇〇„^ Addition of 5.50 mm〇l HC1 (or 2.75 mmol of HC1 to a 50 mL formulation) is indicated by the increase in [H+]. The buffering capacity of the low calorie infant formula of the present invention (to 1〇〇) The [H+] after addition of 5 mmol of HC1 in the mL formulation may be at least about 2, mM mM, including at least about 5. G mM, at least about 7 〇 mM, at least about lo. o mM, at least

約13.0 mM及至少約17 〇 mM 及/或約2.〇 mM至約25.0About 13.0 mM and at least about 17 mM mM and/or about 2. 〇 mM to about 25.0

福’包括約5.〇祕至約21〇福及約ι〇 〇蝴至約μ 續。嬰兒配方可為復原粉末配方(殺菌爸滅菌或無菌滅 ^且可為第1_2天或第3·9天配方。在一個實施例中，低熱 置嬰兒配方為第3_9天配方且其緩衝能力（表示為向⑽W 162198.doc -38. 201233328 配方中添加5 mmol HC1後之[H+])為至少約2〇 mM，包括 至少約5_0 mM、至少約7.0 mM及至少約9.〇 mM，及/或約 2.0 mM至約13.0 mM，包括約8.0 mM至約11.0 mMe在另 一實施例中，低熱量嬰兒配方為第i_2天配方且其緩衝能 力（表不為向100 mL配方中添加5 mmol HC1後之[H+])為至 少約8.0 mM ’包括至少約1〇.〇 mM、至少約ΐ3·〇 mM、至 少約17.0 mM及至少約20.0 mM，及/或約8.0 mM至約25.0 mM，包括約 8.0 mM至約 21.0 mM，約 13.0 mM至約 20.0 mM及約 17.0 mM至約 20.0 mM » 或者，嬰兒配方之緩衝能力可表示為在向嬰兒配方（或 向粉末嬰兒配方實施例之復原配方）中添加HC1後配方之pH 值之降低。明確言之’緩衝能力可表示為向1〇〇 mL配方中 添加 5.50 mmol HC1(或向 50 mL配方中添加 2.75 mmol HC1) 後之pH值之降低。 因此，在一個實施例中’本發明之低熱量嬰兒配方為粉 末嬰兒配方且其在復原後之緩衝能力（表示為向丨〇〇 mL復 原配方中添加5.50 mmol HC1後配方之pH值之降低）為至少 約4.20，包括至少約4.50及至少約4.80。在其中低熱量嬰 兒配方為殺菌爸滅菌RTF配方之另一實施例中，緩衝能力 (表示為向50 mL配方中添加2.75 mmol HC1後配方之pH值 之降低）為至少約4.20，包括至少約4.30。在其中低熱量嬰 兒配方為無菌滅菌RTF配方之又一實施例中，緩衝能力（表 示為向100 mL配方中添加5.50 mmol HC1後配方之pH值之 降低）為至少約4.60，包括至少約4.70。 161198.doc -39- 201233328 緩衝能力之另一量度為緩衝劑強度。除非另有說明，否 則本發明之嬰兒配方之緩衝強度可表示為使5〇 mL配方（或 粉末嬰兒配方實施例之復原配方）之pH值自起始pH值（例如 6.0)降至pH 3.0所需之oj μ HC1之體積。如本文中所用， 術語「低緩衝強度」係指緩衝強度為約丨8 mL或1 8 mL以 下°緩衝強度（當指示時）在本文中亦表示為使1〇〇 mL配方 之pH值自6.0降至3.0所需之HC1之毫莫耳量及使50 mL配方 之pH值自6.0降至3.0所需之HC1之毫莫耳量。 本發明之低熱量嬰兒配方之緩衝強度（表示為使5〇 mL配 方（或粉末嬰兒配方實施例之復原配方）之pH值自起始pH值 降至pH 3.0所需之0.1 M HC1之毫升量）為約18 mL或18 mL 以下’包括約14 mL或14 mL以下，及/或包括約9 mL至約 18 mL，包括約1〇 mL至約14 mL及約14 mL至約18 mL。在 一個實施例中’低熱量嬰兒配方為第3-9天配方且其緩衝 強度為約18 mL或18 mL以下，包括約14 mL至約18 mL及 約16 mL至約17 mL。在另一實施例中’低熱量嬰兒配方為 第1-2天配方且其緩衝強度為約14 mL或14 mL以下，包括 約9 mL至約14 mL及約10 mL至約11 mL。人乳之緩衝強度 通常在9 mL至18 mL範圍内。本發明之低熱量嬰兒配方有 利地具有與人乳相當或低於人乳之緩衝強度。 蛋白質水解及消化 本發明之低熱量嬰兒配方（具有高或低微量營養素含量） 與全熱量配方相比亦有利地呈現較快蛋白質水解及消化 率 〇 161198.doc • 40· 201233328 確定食品蛋白質之營養品質之兩種因素為消化率及生物 可用性。通常，嬰兒配方之蛋白質含量高於可見於母乳中 之蛋白質含量。嬰兒配方通常製備為具有較高蛋白質含量 以解決假定的蛋白質消化率較低問題。 此外，在-些情況下，嬰兒配方製備期間使用之方法可 能在營養方面造成潛在影響，諸如使配方中蛋白質之溶解 度及/或消化率降低。舉例而言，在一些情況下，一些用 於製備濃縮液體及即食型嬰兒配方之長時間熱處理可能潛 在地降低蛋白質消化率。由於暴露於熱，蛋白質變性或聚 集，在-些情況下可能改變其消化率。在高溫下處理乳品 亦可能增加胺基酸與糖之反應，稱為梅納反應(MaiUard reaction)。在一些情況下，該等反應可因限制蛋白分解酶 接近而降低胺基酸之生物可用性。因此，一些配方餵養之 嬰兒可能經歷一些營養物（且尤其為蛋白質）吸收不全。因 此，具有改良之蛋白質消化之嬰兒配方將對已知消化酶 (諸如胃蛋白酶及腸胰酶）含量低於較大嬰兒及成年人之新 生兒尤其有益。 現已發現嬰兒配方中蛋白質之消化（本文中可與術語 「水解」互換使用）之程度（本文中可與術語「速率」互換 使用）與配方之能量含量有關。明確言之，已發現存在於 嬰兒配方中之蛋白質之消化率隨配方之能量含量降低而增 加。本發明之低熱量嬰兒配方與全熱量嬰兒配方相比有利 地具有改良（例如更快）之蛋白質消化率。此可改良嬰兒對 嬰兒配方之耐受性及改良營養物（且尤其為蛋白質）之吸 I61198.doc 201233328 收。 用於表不蛋白質〉肖化率或程度之量度有許多種。舉例而 2 ’本發明之嬰兒配方中蛋白質之消化率或程度係以使用 胃蛋白酶及騰酶（殿粉酶/蛋白酶/脂肪酶）進行活體外腸胃 消化或活體外胰酶消化後蛋白質之中值分子量(mw)表 示。蛋白質MW中值降低表示消化率較快及消化程度增 加。用於該等消化之程序闡述於實例中。 在二實施例中，本發明之低熱量嬰兒配方之蛋白質消 化率或程度（表示為在如本文中所描述進行活體外腸胃消 化後之蛋白質河冒中值）為約95〇道爾頓（Da)或95〇道爾頓以 下，包括約925 Da或925 Da以下、約850 !^或85() 〇&以 下、約800 Da或800 Da以下及約790 !^或79() Da以下。對 於本發明之第3·9天配方，蛋白質消化率或程度（表示為在 如本文中所描述進行活體外腸胃消化後之蛋白質MW中值） 通常為約700 Da至約950 Da 對於第1-2天配方，蛋白質消 化率或程度（表示為在如本文中所描述進行活體外腸胃消 化後之蛋白質MW中值）通常為約825 Da或825 Da以下，包 括約800 Da或800 Da以下、約780 Da或780 Da以下、約750 Da或750 Da以下及約720 Da或720 Da以下。第i_2天配方 之蛋白質消化率或程度通常為約700 Da至約800 Da。 對於第3-9天配方’本發明之低熱量嬰兒配方之蛋白質 ’肖化率或程度（表示為在如本文中所描述進行71分鐘活體 外姨酶消化後之蛋白質MW中值）為約800 Da或800 Da以 下’包括約775 Da或775 Da以下及約750 Da或750 Da以 161198.doc •42· 201233328 下’且尤其為約725 Da至約775 Da。對於第1-2天配方’蛋 白質消化率或程度（表示為在如本文中所描述進行71分鐘 活體外胰酶消化後之蛋白質MW中值）通常為約75〇 〇&或 750 Da以下，包括約725以或725 Da以下、約7〇〇叫或· Da以下及約690 Da或690 Da以下，且尤其為約675 〇3或 675 Da以下至約700 Da或700 Da以下。 本發明之低熱量嬰兒配方之蛋白質消化率或程度（表示 為在如本文中所描述進行60分鐘活體外胰酶消化後之蛋白 質MW中值）為約1000 Da或1〇〇〇 Da以下，包括約95〇 Da或 950 Da 以下、約 900 Da 或 9〇〇 Da 以下、約 85〇 〇&或85〇 以下、約825 Da或825 Da以下及約810 0&或81〇 Da以下， 且尤其為約775 Da至約825 Da。 蛋白質消化率或程度亦可表示為在本文中所描述之活體 外腸胃消化或活體外胰酶消化後河1大於5〇〇〇 Da之總蛋白 f分比。百分比較小表示消化率較快及消化程度增加。對 於粉末配方，本發明之低熱量嬰兒配方之蛋白質消化率或 程度（表不為在如本文中所描述進行活體外腸胃消化後Mw 大於5000 Da之總蛋白百分比）為約13 5%或13 5%以下包 括約12.0%或12.0%以下、約u 〇%以下、約9 〇% 或9.0%以下及約6·0%或6.0%以下，且尤其為約5〇%至約 13.5%。在其中嬰兒配方經殺菌釜滅菌之實施例中，蛋白 質消化率或程度（表示為在如本文中所描述進行活體外腸 4消化後MW大於5000 Da之總蛋白百分比）為約8 〇0/〇或 8.0%以下’包括約7·0%%或7〇%以下、約6〇%或6〇%以 161198.doc -43- 201233328 下、約5.0〇/〇或5·0%以下、約4〇%或4〇%以下及約或 3.0/。以下，且進一步包括約2 〇%至約6 〇%。在其中嬰兒配 方經無菌滅菌之實施例卜蛋白質消化率或程度(表示為 在如本文中所描述進行活體外腸胃消化後MW大於5000 Da 之總蛋白百分比）為約9〇%或9〇%以下，包括約7〇%%或 7_〇%以下、約6.0%或6.〇%以下、約5.0%或5.0%以下、約 3.0%或3.0%以下，且進一步包括約2 〇%至約5 〇%。 蛋白質消化率或程度亦可由在如本文中所描述進行活體 外腸胃消化後存在於嬰兒配方中之不可溶蛋白質的量表 不。用於測定不可溶蛋白質含量之技術闡述於本發明之實 例中。不可溶蛋白質量較小表示消化率較快及消化程度增 加。 本發明之低熱量嬰兒配方之蛋白質消化率或程度（表示 為在如本文中所描述進行活體外腸胃消化後存在於配方中 之不可溶蛋白質的量）為約15〇 mg/L或15〇 mg/L以下，包括 約 110 mg/L或 11〇 mg/L以下、約75 mg/L或 75 mg/L以下、 約50 mg/L或50 mg/L以下及約25 mg/L或25 mg/L以下，且 尤其為約20 mg/L至約11 〇 mg/L。 如本文中所論述’加工嬰兒配方且尤其在高溫下處理乳 產品可增加胺基酸與糖之反應，稱為梅納反應。該等反應 藉由限制蛋白分解酶之可接近性來降低胺基酸之生物可用 性。現已發現與全熱量配方相比，本發明之低熱量嬰兒配 方中梅納反應進行程度較低。此可由測定消化後嬰兒配方 中梅納反應標記物含量說明。明確言之，已發現在如本文 161198.doc • 44 - 201233328 + m #述進行活體外腸胃消化後，本發明之低熱量嬰兒配 方之梅納反應標記物糠胺酸之含壹低於全熱量配方。 因此在一個態樣中，本發明提供嬰兒配方，其在如本 文中所描述進行活體外腸胃消化後包含約2.5或2.5以下， 包括約1,5或h5以下，約1.0或1.0以下及約0.90或0.90以下 尤其為、0·7至約1 .〇之量（毫克/1 〇〇公克產品）的梅納反應 標記物糠胺酸。 製備方法 可由任何已知或其他有效用於製備所選產品固體或液體 形式之製備技術製備本發明之嬰兒配方。已知多種該等技 術用於任何既疋產品形式（諸如營養液體或粉末）且可由一 般良、S此項技術者容易地應用於本文中所描述之嬰兒配 方0 】因此本發明之嬰兒配方可由多種已知或其他有效調配或 備方法中之任一種製備。舉例而言，在一種合適製備方 法中’製備至少兩種獨立漿料，隨後將其摻合在—起，進 行熱處理’標準化且最終經滅菌以形成殺菌爸滅菌嬰兒配 方或經無g處理且填充以形成無菌滅菌嬰兒配方。或者， 漿料可摻合在-起，經熱處理，標準化，第二次熱處理， 蒸發以移除水a噴霧乾燥以形成粉末嬰兒配方。 所形成漿料可包括碳水化合物_礦物質（CHO_MIN)裝料 及油包蛋白質（prc^ein.i㈣u/助）漿料。最初，藉由使所 選碳水化合物（例如浦、半乳寡料）錢拌下溶解於敎 水中，接著添加礦物質(例如檸檬酸鉀、氯化鎂、氣化 16I198.doc -45- 201233328 鉀、氣化鈉、氣化膽鹼等）來形成CH〇_MIN。所得cH〇_ min漿料保持在持續加熱及適度攪拌下直至其隨後與其他 製備之漿料摻合在一起。 藉由加熱及混合油（例如高油酸紅花子油、大豆油、椰 子油、單甘油酸酯等）及乳化劑（例如大豆卵構脂），且接著 在持續加熱及攪拌下添加油溶性維生素、混合類胡蘿蔔 素、蛋白質（例如乳蛋白濃縮物、乳蛋白水解產物等）、角 叉菜膠（若存在）、碳酸鈣或磷酸三鈣（若存在）以及ARA油 及DHA油（在一些實施例中）來形成ρι〇漿料。所得ρι〇漿料 保持在持續加熱及適度攪拌下直至其隨後與其他製備之漿 料摻合在一起。 加熱水且接著在充分攪拌下與CH0_MIN漿料、脫脂乳 (若存在）及PIO漿料合併。調節所得摻合物之pH值至6 6_ 7.〇，且摻合物保持在適度加熱攪拌下。在一些實施例 中’在此階段下添加ARA油及DHA油。 接著組合物經高溫短時（HTST)加工，其間組合物經熱處 理，乳化及均質化，且接著冷卻。添加水溶性維生素及抗 壞血酸，必要時調節PH值至所需範圍，添加香料（若存在） 且添加水以獲得所需總固體含量。對於無菌滅菌嬰兒配 方，乳液經無菌處理器接受第二次熱處理，冷卻且接著無 菌封裝入合適容器中。對於殺菌釜滅菌嬰兒配方，乳液封 裝入合適容器中且最終滅菌。在一些實施例中，乳液可視 情況進一步經稀釋，熱處理’且封裝以形成所需即食型或 濃縮液體，或可經熱處理且接著處理且封裝為可復原粉末 161198.doc -46- 201233328 (例如喷霧乾燥、乾燥混合、聚結）。 可藉由適用於製備及調配營養粉末之任何已知或其他有 效技術集合製備噴霧乾燥粉末嬰兒配方或乾燥混合粉末嬰 兒配方。舉例而言，當时嬰兒配方為喷霧乾燥營養粉末 時，喷霧乾燥步驟可類似地包括任何已知或以其他方式適 用於製備營養粉末之喷霧乾燥技術。已知多種不同喷霧乾 燥方法及技術詩營養學領域巾，其均適詩製備本文中 之喷霧乾燥粉末嬰兒配方^在乾職，成品粉末可封裝入 合適容器中。 使用方法 本發明之低熱量嬰兒配方可經口投與嬰兒，包括足月 兒、早產兒及/或新生兒。低熱量嬰兒配方可投與早產 兒足月兒及/或新生兒作為嬰兒營養源及/或可用於解決 ，或多種本文中所論述之疾病或病狀，或可用於提供一或 〆種本文中所描述之效此群組中之任―者可能實際羅 患=病或病狀，或可能具有羅患疾病或録之風險（歸因 t豕族史等）’可對疾病或病狀敏感，或可能需要治療小 制/減輕某一疾病或病狀。將通常以適用於嬰兒年齡之^ 取量每曰投與嬰兒配方。因&，因為本文中揭示之-些方 法實施例係關於嬰兒之某些子群或子類（例如需要治療砸 制/減輕疾病或病狀之嬰兒）且通常並非係關於標準嬰兒群 體’因此並非所有嬰兒均可自本文中揭示之所有方 例獲益。 舉例而言，本發明之方^包括以本文中所描述之平均 161198.doc 201233328 攝取量投與嬰兒-或多種本發明之低熱量配方。在一些實 施例中’在生命最初數週期間提供新生兒遞增之配方量。 該等量最通常在生命之約第一天期間在平均至多約⑽毫 升/天㈣新生兒料期之其餘時間期間為 平均至夕約200至約7〇〇毫升/天，包括約2〇〇至約6〇〇毫升/ 天且亦包括約250至約500毫升/天。然而應理解，該等量 可視特疋新生兒及其在生命最初數週或數月期間的獨特營 養需要以及所投與嬰兒配方之特定營養物及熱量密度而顯 著不同》 在一些實施例中，本發明之方法可針對生命最初數週或 數月期間（較佳為生命之至少第一週期間，更佳為生命之 至少最初兩週期間且包括生命之至多約3個月）之新生兒。 此後，嬰兒可轉為食用習知嬰兒配方（單獨或與人乳組 合）。 本文中所描述之方法可包含投與嬰兒兩種或兩種以上不 同嬰兒配方。舉例而言，可在出生後頭兩天投與嬰兒低熱 量第1-2天嬰兒配方且接著可在出生後第3_9天投與低熱量 第3-9天嬰兒配方。可視情況在出生後第9天過後投與第3 9 天嬰兒配方’或可在出生後第10天開始投與較高熱量配方 (包括全熱量配方）。 除非另有說明’否則本文中所描述之方法中所用嬰兒配 方為營養配方且可呈任何產品形式’包括即食型液體、濃 縮液體、復原粉末及其類似物。在嬰兒配方呈粉末形式之 實施例中，該方法可進一步包含用水性媒劑（最通常為水 161198.doc -48· 201233328 或人乳）復原粉末以形成所需熱量密度，接著經口或經腸 餵養嬰兒。用足量水或其他合適流體（諸如人乳）復原粉末 配方以產生所需熱量密度及適用於餵養一名嬰兒之所需餵 食量。亦可在使用之前經殺菌釜滅菌或無菌滅菌手段對嬰 兒配方進行滅菌。 下文更詳細地描述其他實施例。 營養 在一個態樣中，本發明係關於提供嬰兒營養之方法。該 方法包含投與嬰兒任一或多種本發明之低熱量、低微量營 養素嬰兒配方。該等方法可包括每曰投與嬰兒配方，包括 以如上文所描述之每日攝取量投與。在一些實施例中，嬰 兒為新生兒。 如上所述，本發明之任何低熱量、低微量營養素嬰兒配 方均可用於此方法。明確言之，低微量營養素嬰兒配方包 含微量營養素及至少一種選自由蛋白質、碳水化合物、脂 肪及其組合組成之群的常量營養素。在一個實施例中，低 微量營養素嬰兒配方之能量含量為約200 keal/L至小於6〇〇 kcal/L，其中至少65%微量營養素以習知相應微量營養素 量之約30%至約80%之量包括於嬰兒配方中（以單位體積 3十）。在另一貫施例中，低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45。/〇微量營養 素以習知相應微量營養素量之約3〇%至約65%之量包括於 嬰兒配方中（以單位體積計）。在另一實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcal/L至小於600 I61198.doc • 49· 201233328 kcal/L，#中至少鄕微量營養素以習知相應微量營養素 量之約55%至約80%之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰兒配方可為帛卜2天配方及/或帛W天配 方。 該方法亦可進一 #包含㈣嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約2〇〇 kcal/L至約36〇。“虬之低熱 量嬰兒配方（具有高或低微量營養素含量）（例如第丨_2天配 方）’且接著在出生後第3天至第9天投與能量含量為約36〇 kcal/L至小於600 kcai/L之低熱量嬰兒配方（具有高或低微 量營養素含量）（例如第3-9天配方）。可視情況在出生後第9 天過後投與第3-9天嬰兒配方，或可在出生後第1〇天開始 投與較高熱量配方（包括全熱量配方）。 緩衝能力 已發現嬰兒配方之緩衝能力與配方之能量含量有關。明 確s之，已發現嬰兒配方之緩衝能力隨能量含量降低而降 低。因此本發明之低熱量嬰兒配方與全熱量嬰兒配方相比 有利地具有改良（亦即較低）之緩衝能力，且在一些實施例 中，其緩衝能力低於人類母乳。因此本發明之低熱量嬰兒 配方可用於增加嬰兒且尤其新生兒之胃液酸度及調節嬰兒 之腸胃菌叢生i，包括控制（例如降低）嬰兒腸胃道中病原 微生物生長促進嬰兒腸胃道中有益微生物生長及增加使 經口攝取之病原體失活的有效性。 不希望文任何特定理論約束，咸信與全熱量配方餵養嬰 I6im.doc •50· 201233328 兒相比’母乳傲養嬰兒之腸胃道中pH值酸性更強，從而有 =於經π攝取之病原體之失活且提供更適宜天然存在之有 皿腸月菌叢生長之環境。咸信此至少部分地歸因於人類母 乳之低緩衝能力。因為本發明之低熱量嬰兒配方之緩衝能 力與人類母乳相當或低於人類母乳，因此本文中揭示之低 熱量嬰兒S&枝養之嬰兒之胃液酸度將更接近地類似於母 乳餵養嬰兒中可見者。 因此，在一個態樣中，本發明係關於使嬰兒之胃液酸度 增加（例如藉由降低胃液pH值）至與母乳餵養嬰兒約相同程 度之方法。該方法包含鑑別胃液酸度降低之嬰兒且對該嬰 兒投與任何本發明之低熱量嬰兒配方。嬰兒較佳為新生 兒。 術語「胃液酸度」係指胃中酸性程度且可使用pH值量 測。舉例而言，胃液酸度隨胃内含物之pH值降低而增加。 如本文中所用，術語「胃液酸度降低」意謂嬰兒之胃液酸 度低於母乳餵養嬰兒中通常可見之胃液酸度。胃液酸度降 低之嬰兒可鑑別為腸道中病原菌群落形成速率降低或較 低。在投與本發明之低熱量嬰兒配方後，嬰兒之胃液酸度 增加至通常可見於母乳餵養嬰兒中之程度。 如上所述’任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中’可具有高微量營養素含量，且可為第1 _2天配 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約 200 kcal/L至約 500 kcal/L。 161198.doc 51 201233328 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方’且接著在出生後第3至9天投與能量含量為約36〇 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3_9天嬰兒配方，或可在出生後第1〇天 開始投與較高熱量配方（包括全熱量配方）。投與嬰兒之配 方將通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於提高嬰兒之胃液酸度之方 法’其包含投與嬰兒任何本發明之低微量營養素嬰兒配 方。嬰兒較佳為新生兒β低微量營養素嬰兒配方包含微量 營養素及至少一種選自由蛋白質、碳水化合物、脂肪及其 組合組成之群的常量營養素。在一個實施例中，低微量營 養素嬰兒配方之能量含量為約200 kcal/L至小於6〇〇 kcal/L，其中至少65%微量營養素以習知相應微量營養素 量之約30%至約80%之量包括於嬰兒配方中（以單位體積 計）。在另一實施例中，低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45〇/〇微量營養 素以s知相應微量營養素量之約至約之量包括於 嬰兒配方中（以單位體積計）。在另—實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcal/L至小於6〇〇 kcal/L，其中至少30%微量營養素以習知相應微量營養素 量之約55%至約_之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰絲方可為第^天配方及/或第3_9天配 161198.doc -52- 201233328 方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而，在—個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約36〇 kcai/L之低 熱量嬰兒配方（具有高或低微量營養素含量例如第丨_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 3 60 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第弘9天配方）。可視情況在出生後 第9天過後投與第3-9天嬰兒配方，或可在出生後第1〇天開 始投與較高熱量配方（包括全熱量配方）β在埶 方具有低微量營養素含量之實施例中，配方中；包= 量營養素量可為任-上述含量。&與嬰兒之配方將通常以 如上述攝取量每日投與。 在另貫施例中，本發明係關於調節嬰兒中有益腸胃菌 叢生長之方法。該方法包含鑑別腸胃菌叢生長不平衡之嬰 兒且對該嬰兒投與任何本發明之低熱量嬰兒配方。嬰兒較 佳為新生兒。 為達成本發明目的，可藉由促進有益於GI健康之微生物 生長及/或控制病原微生物生長來調節腸胃菌叢生長。可 I曰由制止抑制、殺滅、失活、破壞或以其他方式妨礙病 原微生物生長使得該等微生物之生長速率減緩或停止來控 制病原微生物生長。GI菌叢生長不平衡之嬰兒包括嬰兒腸 胃道中一或多種病原微生物含量高於通常可見於母乳餵養 嬰兒中之含量及/或嬰兒腸胃道中一或多種有益微生物含 161198.doc •53· 201233328 量低於通常可見於母乳傲養嬰兒中之含量的嬰兒^該等嬰 兒可由腸道中病原菌群落形成速率較低鑑別。在投與本發 明之低熱量嬰兒配方後，嬰兒之胃液酸度增加至與通常可 見於母乳餵養嬰兒中類似之程度，從而產生促進有益微生 物生長及控制病原微生物生長之GI環境。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中，可具有高微量營養素含量，且可為第1_2天配 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約200 kcal/L配方至約500 kcal/L配方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方’且接著在出生後第3至9天投與能量含量為約360 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3-9天嬰兒配方，或可在出生後第1〇天 開始投與較高熱量配方（包括全熱量配方）。投與嬰兒之配 方抑通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於調節嬰兒之腸胃菌叢生長 之方法，其包含投與嬰兒任何本發明之低微量營養素嬰兒 配方。嬰兒較佳為新生兒。低微量營養素嬰兒配方可為任 一上述配方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 161198.doc _ 54 · 201233328 期間投與嬰兒能量含量為約200 kcal/L至約36〇 kcai/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第丨_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3_9天配方）。可視情況在出生後 第9天過後投與第3_9天嬰兒配方，或可在出生後第ι〇天開 始投與較高熱量配方（包括全熱量配方）。在低熱量嬰兒配 方具有低微量營養素含量之實施例中，配方中所包括之微 量營養素量可為任一上述含量。投與嬰兒之配方將通常以 如上述攝取量每日投與。 有益微生物係指保持腸胃道之微生物生態學且展示生理 學、免疫調節及/或抗微生物作用，使得發現其存在可預 防及治療GI疾病及/或病症之微生物。有益微生物之非限 制性實例包括以下微生物中之任一或多者：乳桿菌屬 (genus ’ 包括嗜酸乳桿菌（[.acw〇pA"MS)、 食澱粉乳桿菌（I. am少/ovorMi)、短乳桿菌（HaWi)、保加 利亞乳桿菌（Z. 、乾酪乳桿菌乾酪亞種（Z caiez· SPP，Ca·^·)、乾酪乳桿菌鼠李糖亞種（Ζ· casei spp. A/mmwoswi)、捲曲乳桿菌（i. cr/jpaiws)、德氏乳桿菌乳亞 種（L. up. 、醱酵乳桿菌（尤 /awewiww)、瑞士 乳桿菌（ζ· /ze/vaiz.cw)、約氏乳桿菌（I· _/〇/2則〇«/〇、副乾酪乳桿菌（I. ⑽以）、戊糖乳桿菌 /ieniosws)、胚芽乳桿菌（Z. p/awarMm)、洛德乳桿菌 rewieh)及清酒乳桿菌（乙wk);雙叉桿菌屬（genus 161198.doc -55- 201233328 ，包括動物雙叉桿菌（5. 、雙歧 雙叉桿菌（5. 、短型雙叉桿菌（5.心eve)、嬰兒雙叉 桿菌（5· 及龍根雙叉桿菌（5. /〇«gwm);小球菌屬 (genus Pdz’ococcw·?) ’ 包括乳酸小球菌（/>· acW/flcih·);丙 酸桿菌屬（genus Pro；7i_omlacieriwm)，包括丙酸丙酸桿菌 (P. acidipropionici)、負氏丙藏辑蛰(J>· freudenreichif)、龜 氏丙酸桿菌（户· y'ewe«⑴及塞氏丙酸桿菌（/>. ;及鍵 球菌屬（genus 々repiococcw)，包括乳酪鏈球菌（& cremoris) >乳鏈球菌（51· /如心）及嗜熱鏈球菌（& thermophilus) ·，反矣紙合。 可由本文中揭示之方法控制生長之病原微生物之非限制 性實例包括以下病原微生物中之任一或多者：細菌，諸如 梭菌屬（genus Clostridum)，包括難養芽胞梭菌（c difficile)，大綠辑逢（Escherichia coli/E. coif).，私壤凰 (mrio ίρ·),沙門氏菌屬（5^/抑似心);志賀桿菌屬 (»S7nge//a sp·)，曲桿菌屬（Cawp/j少/〇5ac⑽印）；產氣單胞 菌屬（Arom⑽似π.);葡萄球菌屬（汾印紗/〇c〇ccw π ); 假單胞菌屬（八π.);及寄生物，諸如梨形鞭毛 Α 屬（Giardia sP.);反隱胞子 AM(Crypt〇sp〇ridium 邛）， 及其組合。 蛋白質消化及水解 已發現嬰兒配方中蛋白質之消化率及程度與配方之能量 含量有1明4言之，6發現嬰兒配〇之蛋白f之消化 率隨配方之能量含量降低而增加。因此本發明之低熱量嬰 161198.doc -56- 201233328 兒配方與全熱量嬰兒配方相比有利地具有改良（例如更快） 之消化率。因此本發明之低熱量嬰兒配方可用於改良嬰兒 且尤其新生兒之配方耐受性、蛋白質消化及營養物（且尤 其蛋白質）吸收。 因此，在一個態樣中，本發明係關於改良嬰兒之蛋白質 消化之方法。該方法包含鑑別經歷蛋白質消化不全之嬰兒 且對該嬰兒投與任何本發明之低熱量嬰兒配方。嬰兒較佳 為新生兒。 如本文中所用，術語「改良蛋白質消化」包括提高存在 嬰兒配方中蛋白質之消化（或水解）率及/或增加嬰兒配方中 蛋白質與消化酶接觸時的消化程度。此蛋白質消化改良可 使用任何本文中所描述之量度測定，包括（例如）消化後蛋 a質中值重量、消化後分子量大於5000道爾頓之佔總蛋白 質百分比及/或消化後存在於配方中之不可溶蛋白質的 量。 如本文中所用，術語「蛋白質消化不全」意謂存在於嬰 兒食用之營養產品中的蛋白質實際消化之量低於母乳餵養 嬰兒通常消化之蛋白質的量。經歷蛋白質消化不全之嬰兒 可能展示配方不耐受性跡象且可因此使用任何本文中所描 述之配方不耐受性症狀鑑別。亦可由腹瀉、軟便、放屁及 /或氣脹鑑別經歷蛋白質消化不全之嬰兒。在投與本發明 之低熱量嬰兒配方後，蛋白質消化率及程度得到改良。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 161198.doc •57· 201233328 貫施例中’可具有高微量營養素含量，且可為第1 -2天配 方及/或第3-9天配方》在一個實施例中，嬰兒配方之能量 含量為約2〇〇 kcal/L配方至小於600 kcal/L配方》 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方’且接著在出生後第3至9天投與能量含量為約360 kcal/L至小於600 kcai/L之第3_9天配方。可視情況在出生 後第9天過後投與第3_9天配方，或可在出生後第1〇天開始 投與較南熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中’本發明係關於改良嬰兒之蛋白質消化之 方法’其包含投與嬰兒任何本發明之低微量營養素嬰兒配 方嬰兒較佳為新生兒。低微量營養素嬰兒配方包含微量 營養素及至少一種選自由蛋白質、碳水化合物、脂肪及其 組合組成之群的常量營養素。在一個實施例中，低微量營 養素嬰兒配方之能量含量為約2〇〇 kcai/L至小於600 kcal/L ’其中至少65%微量營養素以習知相應微量營養素 量之約30%至約80%之量包括於嬰兒配方中（以單位體積 计）。在另一實施例中’低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45%微量營養 素以習知相應微量營養素量之約3〇%至約65%之量包括於 嬰兒配方中（以單位體積計）。在另一實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcai/L至小於600 161198.doc • 58 · 201233328 kcal/L，其中至少30%微量營養素以習知相應微量營養素 量之約55%至約80%之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰兒配方可為第丨_2天配方及/或第3·9天配 方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約36〇 kcai/L之低 熱量4c兒配方（具有咼或低微量營養素含量）（例如第1_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3-9天配方）。可視情況在出生後 第9天過後投與第3-9天配方，或可在出生後第1〇天開始投 與較高熱量配方（包括全熱量配方）。在低熱量嬰兒配方具 有低微量營養素含量之實施例中’配方中所包括之微量營 養素量可為任一上述含量。投與嬰兒之配方將通常以如上 述攝取量每日投與。 在另一實施例中，本發明係關於改良嬰兒之蛋白質吸收 之方法。該方法包含鑑別經歷蛋白質吸收不全之嬰兒；及 對該嬰兒投與任何本發明之低熱量嬰兒配方。可使用本文 中所描述用於鑑別經歷蛋白質消化不全之嬰兒之準則中之 任一者鑑別經歷蛋白質吸收不全之嬰兒。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中’可具有高微量營養素含量，且可為第1 _2天配 161198.doc •59- 201233328 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約200 kcal/L配方至小於600 kcal/L配方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方’且接著在出生後第3至9天投與能量含量為約360 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3-9天配方，或可在出生後第1〇天開始 投與較高熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於改良嬰兒之蛋白質吸收之 方法，其包含投與嬰兒任何本發明之低微量營養素嬰兒配 方。嬰兒較佳為新生兒。低微量營養素嬰兒配方可為任一 上述配方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第1·2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 3 60 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3_9天配方）。可視情況在出生後 第9天過後投與第3-9天嬰兒配方，或可在出生後第1〇天開 始投與較高熱量配方（包括全熱量配方在低熱量嬰兒配 方具有低微量營養素含量之實施例中，配方中所包括之微 161I98.doc -60- 201233328 里營養素量可為任一上述含量。投與嬰兒之配方將通常以 如上述攝取量每日投與。 耐受性 本發明亦係關於改良嬰兒之嬰兒配方耐受性之方法。嬰 兒配方不耐受性為非免疫性系統相關反應，其可由行為或 糞便或進食型態變化所證實，諸如咳吐或嘔吐增加、排便 次數增加、水狀便較多、黑色糞便及哭鬧增加。嬰兒配方 不耐文性最通常與腸胃症狀（例如糞便形態、放屁、咳吐） 以及行為特徵（例如配方接受度、哭鬧及喊叫）有關。罹患 配方不耐受性之嬰兒亦可能經歷胃食道逆流。 現意外發現嬰兒對具有低能量含量之嬰兒配方之耐受性 大於全熱量配方。明確言之，已發現與全熱量配方相比， 低熱量嬰兒配方顯示較快蛋白質水解及消化率、在食用後 產生較少梅納反應產物（其無法分解及吸收）且具有較快胃 排空速率》胃排空較快時，可減少胃食道逆流及改良配方 耐受^生。 因此本發明之低熱量嬰兒配方可用於減少嬰兒放屁及/ 或咳吐發生頻率。本發明之低熱量嬰兒配方與全熱量嬰兒 配方相比亦可用於提高嬰兒之胃排空速率及降低由食用配 方所產生之梅納反應產物量。 低熱量嬰兒配方可投與任何嬰兒（早產兒或足月兒）且尤 其任何可自接受具有低能量含量且亦具有高耐受性之嬰兒 配方獲益之嬰兒。在一些實施例中’對新生兒投與本發明 之低熱量嬰兒配方。 161198.doc -61 - 201233328 因此’在-個態樣中’本發明亦係關於改良嬰兒之嬰 配方财受性之方法。該方法包含鑑別罹患嬰兒配方不耐受 性之嬰兒及對該嬰兒投與任__或多種本發明之低熱量嬰兒 配方。罹患嬰兒配方不耐受性之嬰兒可包括具有配方不耐 受性之任-或多種症狀之嬰兒。該等症狀包括（但不限於） 糞便或進食型態變化，諸如咳吐㈣吐增加；排便次數增 加；水狀便較多；黑色糞便；哭鬧、喊叫、放屁增加；: 不願食用酉己方。纟投與本發明之低熱量嬰力配方後，可減 少或消除一些或所有配方不耐受性症狀。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中’可具有高微量營養素含量，且可為第1_2天配 方或第3-9天配方。在一個實施例中，低熱量嬰兒配方之 能量含量為約200至約600千卡/公升配方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中’在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方，且接著在出生後第3至9天投與能量含量為約360 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3_9天配方，或可在出生後第1〇天開始 投與較高熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於改良嬰兒之嬰兒配方耐受 性之方法，其包含投與嬰兒任何本發明之低微量營養素嬰 161198.doc -62- 201233328 兒配方。嬰兒較佳為新生兒。低微量營養素嬰兒配方包含 微量營養素及至少一種選自由蛋白質、碳水化合物、脂肪 及其組合組成之群的常量營養素。在一個實施例中，低微 量營養素嬰兒配方之能量含量為約200 kcai/L至小於6〇〇 kcal/L，其令至少65%微量營養素以習知相應微量營養素 量之約30%至約80%之量包括於嬰兒配方中（以單位體積 計）。在另一實施例中，低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45%微量營養 素以習知相應微量營養素量之約30%至約65%之量包括於 嬰兒配方中（以單位體積計）。在另一實施例中，低微量營 養素嬰兒配方之能量含量為約360 kcal/L至小於6〇〇 kcal/L ’其中至少30%微量營養素以習知相應微量營養素 量之約5 5°/。至約80%之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰兒配方可為第1_2天配方及/或第3_9天配 方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第1_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 3 60 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3-9天配方）。可視情況在出生後 第9天過後投與第3 -9天配方’或可在出生後第1 〇天開始投 與較高熱量配方（包括全熱量配方在低熱量嬰兒配方具 161198.doc -63- 201233328 有低微量營養素含量之實施例中，配方中所包括之微量營 養素量可為任一上述含量。投與嬰兒之配方將通常以如上 述攝取量每日投與。 在另一實施例中，本發明係關於抑制嬰兒胃食道逆流之 方法。該方法包含鑑別罹患胃食道逆流之嬰兒及對該嬰兒 投與任一或多種本發明之低熱量嬰兒配方。嬰兒較佳為新 生兒。 ▲發生胃食道逆流（GER)時’胃含物逆流入食道中且自 口中流出，引起反胃、咳吐及/或嘔吐。GER症狀包括咳 吐、°區吐、咳漱、煩躁、進食不良、血便及其組合。當發 生GER時，嬰兒亦可能咳嗽、喊叫或緊張。為達成本發明 之目的，術語「抑制胃食道逆流」意欲包括治療、預防 GER及/或其至少一種症狀及/或降低其發生率。不希望受 任何特疋理淪約束，咸信本發明之低熱量嬰兒配方與全熱 量配方相比具有較快胃排空速率（亦即内含物穿過胃之速 率）’其引起胃食道逆流減少。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中，可具有高微量營養素含量，且可為第丨_2天配 方或第3·9天配方。在—個實施例t，嬰兒配方之能量含 量為約200 kcal/L配方至小於600 kcai/L配方。Fu' includes about 5. Secret to about 21 〇 及 and about ι 〇 〇 至 to about μ continue. The infant formula may be a reconstituted powder formulation (sterilized dad sterilization or sterile) and may be formulated on Days 1 - 2 or Day 3. In one embodiment, the low heat infant formula is the 3rd - 9th day formula and its buffering capacity (represented) For (10)W 162198. Doc -38.  The [H+] after the addition of 5 mmol of HC1 in the formulation of 201233328 is at least about 2 mM, including at least about 5_0 mM, at least about 7. 0 mM and at least about 9. 〇 mM, and / or about 2. 0 mM to about 13. 0 mM, including about 8. 0 mM to about 11. 0 mMe In another embodiment, the low calorie infant formula is the i_2 day formulation and its buffering capacity (not [H+] after adding 5 mmol of HC1 to the 100 mL formulation) is at least about 8. 0 mM 'includes at least about 1 〇. 〇 mM, at least about 〇3·〇 mM, at least about 17. 0 mM and at least about 20. 0 mM, and / or about 8. 0 mM to about 25. 0 mM, including approximately 8. 0 mM to approximately 21. 0 mM, about 13. 0 mM to approximately 20. 0 mM and about 17. 0 mM to approximately 20. 0 mM » Alternatively, the buffering capacity of the infant formula can be expressed as a decrease in the pH of the formula after the addition of HC1 to the infant formula (or to the reconstituted formula of the powder infant formula embodiment). Specifically, the buffer capacity can be expressed as a addition to a 1 〇〇 mL formulation. 50 mmol HC1 (or add to the 50 mL formula 2. A decrease in pH after 75 mmol of HC1). Thus, in one embodiment, the low calorie infant formula of the present invention is a powdered infant formula and its cushioning capacity after reconstitution (expressed as adding to the 丨〇〇 mL reconstitution formula. The pH of the formulation after 50 mmol of HC1 is reduced by at least about 4. 20, including at least about 4. 50 and at least about 4. 80. In another embodiment in which the low-calorie infant formula is a sterilized dad-sterilized RTF formulation, the buffering capacity (expressed as adding to the 50 mL formulation). The pH of the formulation after 75 mmol of HC1 is reduced by at least about 4. 20, including at least about 4. 30. In yet another embodiment in which the low calorie infant formula is a sterile sterilized RTF formulation, the buffering capacity (represented by adding 5. to the 100 mL formulation). The pH of the formulation after 50 mmol of HC1 is reduced by at least about 4. 60, including at least about 4. 70. 161198. Doc -39- 201233328 Another measure of buffer capacity is buffer strength. Unless otherwise stated, the buffer strength of the infant formula of the present invention can be expressed as the pH of the 5 〇 mL formulation (or the reconstituted formulation of the powdered infant formula embodiment) from the initial pH (e.g., 6. 0) down to pH 3. 0 required oj μ HC1 volume. As used herein, the term "low buffer strength" means that the buffer strength is about mL8 mL or less than 18 mL. The buffer strength (when indicated) is also expressed herein as the pH of the 1 〇〇mL formulation from 6 . 0 dropped to 3. 0 The amount of milligrams of HC1 required and the pH of the 50 mL formulation are from 6. 0 dropped to 3. 0 The amount of milligrams of HC1 required. The buffer strength of the low calorie infant formula of the present invention (expressed to reduce the pH of the 5 〇 mL formula (or the reconstituted formula of the powder infant formula) from the initial pH to pH 3. 0 required 0. 1 M HC1 in milliliters) is about 18 mL or less than 18 mL 'includes about 14 mL or less, and/or includes about 9 mL to about 18 mL, including about 1 mL to about 14 mL and about 14 mL. Up to about 18 mL. In one embodiment, the 'low calorie infant formula is a Day 3-9 formulation with a buffer strength of about 18 mL or less, including from about 14 mL to about 18 mL and from about 16 mL to about 17 mL. In another embodiment, the low calorie infant formula is formulated on Day 1-2 and has a buffer strength of about 14 mL or less, including from about 9 mL to about 14 mL and from about 10 mL to about 11 mL. The buffer strength of human milk is usually in the range of 9 mL to 18 mL. The low calorie infant formula of the present invention advantageously has a buffer strength comparable to or lower than that of human milk. Protein Hydrolysis and Digestion The low calorie infant formula of the present invention (having high or low micronutrient content) also advantageously exhibits faster protein hydrolysis and digestibility compared to the full calorie formulation 〇 161198. Doc • 40· 201233328 Two factors that determine the nutritional quality of food proteins are digestibility and bioavailability. Generally, the infant formula has a higher protein content than the protein content found in breast milk. Infant formulas are usually prepared with higher protein content to address the problem of hypothetical protein digestibility. In addition, in some cases, the methods used during infant formula preparation may have potential nutritional effects, such as reducing the solubility and/or digestibility of the protein in the formulation. For example, in some cases, some prolonged heat treatments for preparing concentrated liquids and ready-to-eat infant formulas may potentially reduce protein digestibility. Due to exposure to heat, proteins are denatured or aggregated, which may change their digestibility in some cases. Treatment of dairy products at elevated temperatures may also increase the reaction of the amino acid with the sugar, known as the MaiUard reaction. In some cases, such reactions may reduce the bioavailability of the amino acid by limiting the proximity of the proteolytic enzyme. Therefore, some formula-fed babies may experience some absorption of nutrients (and especially proteins). Therefore, infant formulas with improved protein digestion will be particularly beneficial for newborns with known levels of digestive enzymes (such as pepsin and entero-trypsin) that are lower than older infants and adults. It has been found that the degree of protein digestion in infant formula (which may be used interchangeably herein with the term "hydrolysis") (which may be used interchangeably herein with the term "rate") is related to the energy content of the formulation. Specifically, it has been found that the digestibility of proteins present in infant formula increases as the energy content of the formula decreases. The low calorie infant formula of the present invention advantageously has improved (e. g., faster) protein digestibility compared to a full calorie infant formula. This improves the infant's tolerance to infant formula and improves the absorption of nutrients (and especially protein) I61198. Doc 201233328 Received. There are many kinds of measures for expressing the rate or degree of proteinization. For example, 2 'the digestibility or degree of protein in the infant formula of the present invention is the median value of protein digestion by in vitro digestion or in vitro digestion using pepsin and Tengase (house enzyme/protease/lipase). The molecular weight (mw) is expressed. A decrease in the median MW of the protein indicates a faster digestibility and an increased degree of digestion. The procedure for such digestion is illustrated in the examples. In two embodiments, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median value of the protein river after in vitro gastrointestinal digestion as described herein) is about 95 Daltons (Da ) or 95 〇 Dalton below, including about 925 Da or 925 Da, about 850 !^ or 85 () 〇 & below, about 800 Da or 800 Da below and about 790 !^ or 79 () Da or less. For the 3.9% formulation of the present invention, the protein digestibility or extent (expressed as the median MW of the protein after in vitro gastrointestinal digestion as described herein) is typically from about 700 Da to about 950 Da for the first A 2-day formulation, protein digestibility or degree (expressed as the median MW of protein after in vitro gastrointestinal digestion as described herein) is typically about 825 Da or less than 825 Da, including about 800 Da or less, about 800 Da or less. Below 780 Da or 780 Da, below 750 Da or 750 Da and below 720 Da or 720 Da. The protein digestibility or degree of the i2-day formula is usually from about 700 Da to about 800 Da. For the Days 3-9 formulation 'protein of the low calorie infant formula of the invention' rate or degree (expressed as the median MW of protein after 71 minutes of in vitro chymase digestion as described herein) is about 800 Da or 800 Da below 'includes approximately 775 Da or 775 Da below and approximately 750 Da or 750 Da to 161198. Doc •42· 201233328 under 'and especially from about 725 Da to about 775 Da. For the day 1-2, the formula 'protein digestibility or degree (expressed as the median MW protein value after 71 minutes of in vitro trypsinization as described herein) is typically about 75 〇〇 & or 750 Da or less, Included is about 725 or less 725 Da, about 7 〇〇 or Da Da and about 690 Da or 690 Da or less, and especially about 675 〇 3 or 675 Da or less to about 700 Da or less. The protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median MW of protein after 60 minutes of in vitro trypsinization as described herein) is about 1000 Da or less, including About 95 〇 Da or 950 Da or less, about 900 Da or 9 〇〇 Da, about 85 〇〇 & or 85 〇 or less, about 825 Da or 825 Da or less and about 810 0& or 81 〇 Da, and especially It is about 775 Da to about 825 Da. The protein digestibility or extent can also be expressed as the total protein f ratio of river 1 greater than 5 〇〇〇 Da after parenteral digestion or in vitro trypsinization as described herein. A smaller percentage means faster digestibility and increased digestion. For powder formulations, the protein digestibility or extent of the low calorie infant formula of the present invention (not shown as a percentage of total protein with Mw greater than 5000 Da after in vitro gastrointestinal digestion as described herein) is about 13 5% or 13 5 % below includes approximately 12. 0% or 12. 0% or less, about u 〇% or less, about 9 〇% or 9. 0% or less and about 6.00% or 6. 0% or less, and especially about 5% to about 13. 5%. In an embodiment wherein the infant formula is sterilized by autoclave, the protein digestibility or extent (expressed as a percentage of total protein having a MW greater than 5000 Da after in vitro intestinal 4 digestion as described herein) is about 8 〇0/〇 Or 8. 0% or less 'includes about 7·0%% or less, about 6〇% or 6〇% to 161198. Doc -43- 201233328 Next, about 5. 0〇/〇 or 5·0% or less, about 4〇% or less, and about or 3. 0/. Hereinafter, and further comprising from about 2% to about 6%. The protein digestibility or degree (indicated as the percentage of total protein having a MW greater than 5000 Da after in vitro gastrointestinal digestion as described herein) is about 9% or less in the case where the infant formula is aseptically sterilized. , including about 7〇%% or 7_〇% or less, about 6. 0% or 6. 〇% below, about 5. 0% or 5. 0% or less, about 3. 0% or 3. Below 0%, and further including from about 2% to about 5%. The protein digestibility or extent can also be expressed by the amount of insoluble protein present in the infant formula after parenteral digestion as described herein. Techniques for determining the insoluble protein content are set forth in the examples of the present invention. A smaller amount of insoluble protein indicates a faster digestibility and an increased degree of digestion. The protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the amount of insoluble protein present in the formulation after in vitro parenteral digestion as described herein) is about 15 mg/L or 15 mg. Below /L, including below about 110 mg/L or 11 〇mg/L, below about 75 mg/L or 75 mg/L, below about 50 mg/L or 50 mg/L, and about 25 mg/L or 25 mg Below /L, and especially from about 20 mg/L to about 11 〇mg/L. Processing the infant formula as discussed herein and treating the dairy product especially at elevated temperatures can increase the reaction of the amino acid with the sugar, known as the Mena reaction. These reactions reduce the bioavailability of the amino acid by limiting the accessibility of the proteolytic enzyme. It has now been found that the Mena reaction in the low calorie infant formula of the present invention is less advanced than the full calorie formulation. This can be illustrated by determining the content of the Mena reaction marker in the infant formula after digestion. Clearly stated, it has been found in this article 161198. Doc • 44 - 201233328 + m # After the in vitro gastrointestinal digestion, the sputum of the melanine reaction label methionine of the low calorie infant formula of the present invention is lower than the total calorie formula. Thus, in one aspect, the invention provides an infant formula comprising about 2. after in vitro gastrointestinal digestion as described herein. 5 or 2. 5 or less, including about 1, 5 or below, about 1. 0 or 1. Below 0 and about 0. 90 or 0. Below 90, especially, from 0. 7 to about 1. The amount of sputum (mg / 1 gram of product) of the Mena reaction marker lysine. Method of Preparation The infant formula of the present invention can be prepared by any of the known or other preparative techniques effective for preparing the solid or liquid form of the selected product. A variety of such techniques are known for use in any of the product forms (such as nutritional liquids or powders) and can be readily applied to the infant formula described herein by the general practitioner of the art. Thus, the infant formula of the present invention can be It is prepared by any of a variety of known or other effective formulation or preparation methods. For example, in a suitable preparation method, at least two separate slurries are prepared, which are subsequently blended, heat treated 'normalized and finally sterilized to form a sterilized dad sterilized infant formula or g-treated and filled To form a sterile sterile infant formula. Alternatively, the slurry can be blended, heat treated, normalized, second heat treated, evaporated to remove water a spray dried to form a powdered infant formula. The resulting slurry may include carbohydrate-mineral (CHO_MIN) charge and oil-packed protein (prc^ein. i (four) u / help) slurry. Initially, by mixing the selected carbohydrates (such as Pu, galacto), it is dissolved in hydrazine, followed by the addition of minerals (such as potassium citrate, magnesium chloride, gasification 16I198. Doc -45- 201233328 Potassium, vaporized sodium, gasified choline, etc.) to form CH〇_MIN. The resulting cH〇_min slurry was maintained under continuous heating and moderate agitation until it was subsequently blended with the other prepared slurry. By heating and mixing oils (such as high oleic acid safflower oil, soybean oil, coconut oil, monoglycerides, etc.) and emulsifiers (such as soy egg fat), and then adding oil-soluble vitamins under continuous heating and stirring Mixed carotenoids, proteins (eg milk protein concentrates, milk protein hydrolysates, etc.), carrageenan (if present), calcium carbonate or tricalcium phosphate (if present), and ARA oil and DHA oil (in some implementations) In the example) to form a ρι slurry. The resulting ρι slurry was kept under continuous heating and moderate agitation until it was subsequently blended with other prepared slurries. The water is heated and then combined with CH0_MIN slurry, skim milk (if present) and PIO slurry with sufficient agitation. Adjust the pH of the resulting blend to 6 6_ 7. 〇, and the blend is kept under moderate heating and stirring. In some embodiments 'ARA oil and DHA oil are added at this stage. The composition is then processed by high temperature short time (HTST) during which the composition is heat treated, emulsified and homogenized, and then cooled. Water-soluble vitamins and ascorbic acid are added, pH is adjusted to the desired range if necessary, perfume (if present) is added and water is added to obtain the desired total solids content. For aseptically sterilized infant formula, the emulsion is subjected to a second heat treatment via a sterile processor, cooled and then inoculated into a suitable container. For sterilized infant formula, the emulsion is sealed in a suitable container and finally sterilized. In some embodiments, the emulsion may optionally be further diluted, heat treated' and packaged to form the desired ready-to-eat or concentrated liquid, or may be heat treated and then processed and packaged as a recoverable powder 161198. Doc -46- 201233328 (eg spray drying, dry mixing, coalescence). Spray-dried powder infant formulas or dry blended powder infant formulas can be prepared by any known or other effective technique set suitable for the preparation and formulation of nutritional powders. For example, when the infant formula is a spray dried nutritional powder, the spray drying step can similarly include any spray drying technique known or otherwise suitable for preparing nutritional powders. A variety of different spray drying methods and technical poetry nutrition field towels are known, which are suitable for preparing the spray-dried powder infant formula herein. In the dry position, the finished powder can be packaged in a suitable container. Method of Use The low calorie infant formula of the present invention can be administered orally to infants, including term infants, premature infants, and/or newborns. A low-calorie infant formula can be administered to a preterm infant, as a source of infant nutrition and/or as a nutritional source for infants and/or can be used to solve, or a variety of diseases or conditions as discussed herein, or can be used to provide one or more The person described in this group may actually be suffering from a disease or condition, or may have a disease or a risk of recording (attributed to the history of the family, etc.), which may be sensitive to the disease or condition. Or may need to treat a small system / reduce a disease or condition. The infant formula will usually be administered in an amount appropriate to the age of the infant. Because & because some of the method embodiments disclosed herein pertain to certain subgroups or subclasses of infants (eg, infants in need of treatment for palliative/mitigating diseases or conditions) and are generally not related to standard infant populations' Not all infants benefit from all the examples disclosed in this article. For example, the invention of the invention includes an average of 161,198 as described herein. Doc 201233328 Intake is administered to infants - or a variety of low calorie formulations of the invention. In some embodiments, the amount of formula in which the newborn is increasing is provided during the first few weeks of life. The equivalent amount is most typically from about 200 to about 7 〇〇 ml/day, including about 2 平均, during the remainder of the first day of life, at an average of up to about (10) ml/day (iv) of the newborn's feed period. Up to about 6 ml/day and also from about 250 to about 500 ml/day. It should be understood, however, that the same amount of visible amnesty newborns and their unique nutritional needs during the first weeks or months of life and the particular nutrient and caloric density of the infant formula being administered are significantly different. In some embodiments, The method of the present invention may be directed to a newborn during the first few weeks or months of life (preferably during at least the first week of life, more preferably during at least the first two weeks of life and including up to about 3 months of life). Thereafter, the infant can be converted to a conventional infant formula (alone or in combination with human milk). The methods described herein can include administering two or more different infant formulas to an infant. For example, infants with low calorie 1-2 days of infant formula can be administered on the first two days after birth and then low calorie infant formula 3-9 can be administered on day 3-9 of birth. A 3rd day infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. Unless otherwise stated, otherwise the infant formula used in the methods described herein is a nutritional formula and can be in any product form' including ready-to-feed liquids, concentrated liquids, reconstituted powders, and the like. In embodiments where the infant formula is in powder form, the method may further comprise an aqueous vehicle (most commonly water 161198. Doc -48· 201233328 or human milk) reconstitutes the powder to form the desired caloric density, followed by oral or enteral feeding of the infant. The powder formulation is reconstituted with sufficient water or other suitable fluid, such as human milk, to produce the desired caloric density and the amount of feed required to feed a baby. The infant formula can also be sterilized by sterilization or sterilization prior to use. Other embodiments are described in more detail below. Nutrition In one aspect, the invention relates to a method of providing nutritional nutrition to an infant. The method comprises administering to the infant one or more of the low calorie, low micronutrient infant formulas of the invention. The methods can include administering an infant formula per meal, including administration in a daily intake as described above. In some embodiments, the infant is a newborn. As noted above, any low calorie, low micronutrient infant formula of the present invention can be used in this method. Specifically, the low micronutrient infant formula contains micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 keal/L to less than 6 〇〇 kcal/L, wherein at least 65% of the micronutrient is from about 30% to about 80% of the conventional micronutrient amount. The amount is included in the infant formula (at a unit volume of 30). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, of which at least 45. The micronutrient is included in the infant formula (in unit volume) in an amount from about 3% to about 65% of the amount of the corresponding micronutrient. In another embodiment, the low micronutrient infant formula has an energy content of from about 36 〇 kcal/L to less than 600 I61198. Doc • 49· 201233328 kcal/L,# At least 鄕 micronutrients are included in the infant formula (in unit volume) in amounts ranging from about 55% to about 80% of the corresponding micronutrient. The low-calorie infant formula can be formulated as a 2-day formula and/or a W-day formula. The method can also be carried out to include (four) infants with two or more different infant formulas. For example, in one embodiment, the infant is administered an energy level of from about 2 〇〇 kcal/L to about 36 在 during the first two days of life. "A low-calorie infant formula (with high or low micronutrient content) (eg, Day 丨_2 formula) and then administered an energy content of about 36〇kcal/L from day 3 to day 9 after birth to Low calorie infant formula (with high or low micronutrient content) of less than 600 kcai/L (eg, Formula 3-9). May be administered to Day 3-9 infant formula after the 9th day after birth, or The higher calorie formula (including the full calorie formula) was started on the first day after birth. Buffering ability It has been found that the buffering capacity of the infant formula is related to the energy content of the formula. It is clear that the buffering capacity of the infant formula has been found with energy. The reduced calorie size of the present invention thus advantageously has an improved (i.e., lower) buffering capacity compared to a full calorie infant formula, and in some embodiments, has a lower buffering capacity than human breast milk. The low-calorie infant formula of the present invention can be used to increase the acidity of the stomach of infants and especially newborns and to regulate the gastrointestinal flora of infants, including controlling (eg, reducing) pathogens in the gastrointestinal tract of infants. Biological growth promoting infant gastrointestinal tract beneficial microbial growth and increase the oral ingestion of the pathogen inactivation validity does not want the text to any particular theory, it is believed that feeding and infant and I6im full-calorie recipes. Doc •50· 201233328 The pH of the gastrointestinal tract is stronger than that of the breast-fed infants, so that there is an inactivation of the pathogens that are ingested by π and provide a more suitable environment for the growth of the intestinal flora. . This is due, at least in part, to the low buffering capacity of human breast milk. Because the buffering capacity of the low-calorie infant formula of the present invention is comparable to or lower than that of human breast milk, the gastric acidity of the infants of the low-calorie infants described in this article will be more similar to those seen in breast-fed infants. . Thus, in one aspect, the present invention is directed to increasing the acidity of the gastric juice of an infant (e.g., by lowering the pH of the gastric juice) to about the same extent as breastfed infants. The method comprises identifying an infant whose gastric acid is reduced in acidity and administering to the infant any of the low calorie infant formulas of the present invention. The baby is preferably a newborn. The term "gastric acidity" refers to the degree of acidity in the stomach and can be measured using pH. For example, gastric acidity increases as the pH of the stomach contents decreases. As used herein, the term "lower gastric acidity" means that the gastric acidity of an infant is lower than the gastric acidity normally seen in breastfed infants. Infants with reduced gastric acidity can be identified as having a reduced or lower rate of pathogen community formation in the gut. After administration of the low calorie infant formula of the present invention, the gastric acidity of the infant is increased to the extent typically found in breastfed infants. As described above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content, or in some embodiments ' may have a high micronutrient content and may be a 1st - 2 day formulation or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L to about 500 kcal/L. 161198. Doc 51 201233328 The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation of the first 1-2 days of the infant's energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days after birth and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 36 〇 kcal/L to less than 600 kcal/L. The 3rd-9th day infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 1st day after birth. Formulations for infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of increasing the acidity of gastric juice in an infant' which comprises administering to the infant any of the low micronutrient infant formulas of the invention. Preferably, the infant is a neonatal beta low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 6 〇〇 kcal/L, wherein at least 65% of the micronutrients are from about 30% to about 80% of the conventional micronutrient amount. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45 〇/〇 of the micronutrient is included in an amount to about the amount of the corresponding micronutrient. In infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 36 〇 kcal/L to less than 6 〇〇 kcal/L, wherein at least 30% of the micronutrient is from about 55% to about 55% of the corresponding micronutrient amount. The amount of _ is included in the infant formula (in unit volume). Low-calorie baby can be formulated for the first day and/or for the third day. Doc -52- 201233328 side. The methods may further comprise administering two or more different infant formulas to the infant. By way of example, in one embodiment, a low calorie infant formula having an infant energy content of from about 200 kcal/L to about 36 〇 kcai/L during the first two days of life (having a high or low micronutrient content such as Dijon) is administered during the first two days of life. _2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 3 60 kcal/L to less than 600 kcal/L can be administered on the 3rd to 9th day after birth (eg, the 9th day formula) . May be administered to the 3rd-9th infant formula after the 9th day after birth, or may be given a higher calorie formula (including the full calorie formula) on the 1st day after birth. β has low micronutrient content in the prescription. In the examples, in the formula; the amount of the package = amount of nutrient may be any - the above content. & and infant formulas will usually be administered daily as described above. In a further embodiment, the invention relates to a method of modulating the growth of a beneficial gastrointestinal flora in an infant. The method comprises identifying an infant with an imbalance in gastrointestinal flora growth and administering to the infant any of the low calorie infant formulas of the invention. Babies are better for newborns. For the purposes of the present invention, gastrointestinal flora growth can be modulated by promoting the growth of microorganisms that are beneficial to GI health and/or controlling the growth of pathogenic microorganisms. The growth of pathogenic microorganisms can be controlled by inhibiting the inhibition, killing, inactivation, destruction or otherwise impeding the growth of pathogenic microorganisms such that the growth rate of such microorganisms is slowed or stopped. Infants with unbalanced GI flora growth include one or more pathogenic microorganisms in the infant's gut, higher levels than those normally found in breastfed infants and/or one or more beneficial microorganisms in the infant's gastrointestinal tract. Doc •53· 201233328 The amount of infants below the levels normally found in breast-fed infants can be identified by a lower rate of pathogen community formation in the gut. After administration of the low calorie infant formula of the present invention, the gastric acidity of the infant is increased to a similar extent as is generally seen in breastfed infants, resulting in a GI environment that promotes the growth of beneficial microbes and controls the growth of pathogenic microorganisms. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1st or 2nd day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to about 500 kcal/L formulation. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation of the first 1-2 days of the infant's energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days after birth and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 1st day after birth. The formula for administration to infants is usually administered daily as in the above intake. In another aspect, the invention relates to a method of modulating the growth of a gastrointestinal flora of an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, the first two days after birth 161,198. Doc _ 54 · 201233328 A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 200 kcal/L to about 36 〇 kcai/L (eg 丨_2 day formula). A low calorie infant formula (with high or low micronutrient content) (e.g., day 3-9 formulation) with an infant energy content of from about 360 kcal/L to less than 600 kcal/L can then be administered on days 3-9 after birth. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the first day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrient included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested above. Beneficial microorganisms are microorganisms that maintain the gastrointestinal tract and exhibit physiological, immunomodulatory and/or antimicrobial effects such that they are found to be capable of preventing and treating GI diseases and/or conditions. Non-limiting examples of beneficial microorganisms include any one or more of the following microorganisms: Lactobacillus (genus' including Lactobacillus acidophilus ([. acw〇pA"MS), Lactobacillus amylovorum (I.  Am less / ovorMi), Lactobacillus brevis (HaWi), Lactobacillus bulgaricus (Z.  , Lactobacillus casei subsp. (Z caiez· SPP, Ca·^·), Lactobacillus casei rhamnosperm subsp. (Ζ· casei spp.  A/mmwoswi), Lactobacillus crispus (i.  Cr/jpaiws), Lactobacillus delbrueckia subsp. lactis (L.  Up.  Lactobacillus brevis (U/Awewiww), Lactobacillus swiss (ζ· /ze/vaiz. Cw), Lactobacillus johnsonii (I· _ / 〇 / 2 〇 « / 〇, Lactobacillus paracasei (I.  (10) to, Lactobacillus pentosus / ieniosws), Lactobacillus plantarum (Z.  p/awarMm), Lactobacillus reedii rewieh) and Lactobacillus sakei (Bw); genus genus 161198. Doc -55- 201233328, including animal bifidobacteria (5.  Bifidobacterium bifidum (5.  Short Bifidobacterium (5. Heart eve), Bifidobacterium infantis (5· and B. rhizogenes (5.  /〇«gwm); genus Pdz'ococcw·? 'includes lactic acid bacteria (/>· acW/flcih·); Propionibacterium (genus Pro; 7i_omlacieriwm), including Propionibacterium propioni (P.  Acidipropionici), negative C. sinensis (J>· freudenreichif), Propionibacterium turdus (H. y'ewe«(1) and Propionibacterium citrate (/>.  And genus genus (repiococcw), including Streptococcus mutans (& cremoris) > Streptococcus lactis (51·/如心) and Streptococcus thermophilus (& thermophilus), 矣 paper. Non-limiting examples of pathogenic microorganisms that can be grown by the methods disclosed herein include any one or more of the following pathogenic microorganisms: bacteria, such as genus Clostridum, including c difficile, Big Green Collection (Escherichia coli/E.  Coif). , private phoenix (mrio ίρ·), Salmonella (5^/ suppressing heart); Shigella (»S7nge//a sp·), Aspergillus (Cawp/j less / 〇5ac (10) India); gas production Amonium (Arom (10) like π. ); Staphylococcus (汾 纱 / 〇c〇ccw π ); Pseudomonas (eight π. And parasites, such as the pear-shaped flagellum (Giardia sP. ); anti-cryptive AM (Crypt〇sp〇ridium 邛), and combinations thereof. Protein Digestion and Hydrolysis It has been found that the digestibility and extent of protein in infant formula are consistent with the energy content of the formula. 6 It is found that the digestibility of protein f in infants increases with the energy content of the formula. Therefore, the low-calorie infant of the present invention 161198. The doc-56-201233328 pediatric formulation advantageously has improved (e.g., faster) digestibility compared to a full calorie infant formula. Thus, the low calorie infant formula of the present invention can be used to improve formulation tolerance, protein digestion, and nutrient (and especially protein) absorption in infants and especially newborns. Thus, in one aspect, the invention relates to a method of improving protein digestion in infants. The method comprises identifying an infant undergoing protein insufficiency and administering to the infant any of the low calorie infant formulas of the invention. The baby is preferably a newborn. As used herein, the term "modified protein digestion" includes increasing the rate of digestion (or hydrolysis) of a protein present in an infant formula and/or increasing the degree of digestion of the protein in the infant formula when contacted with a digestive enzyme. This protein digestion modification can be determined using any of the metrics described herein, including, for example, the median weight of the egg after digestion, the percentage of total protein in the molecular weight greater than 5000 Daltons after digestion, and/or the presence in the formulation after digestion. The amount of insoluble protein. As used herein, the term "protein insufficiency" means that the amount of protein actually present in the nutritional product consumed by the infant is less than the amount of protein normally digested by the breastfed infant. Infants undergoing protein insufficiency may exhibit signs of formulation intolerance and may therefore be identified using any of the formulation intolerance symptoms described herein. Infants who experience protein insufficiency can also be identified by diarrhea, soft stools, fart and/or bloating. The protein digestibility and extent are improved upon administration of the low calorie infant formula of the present invention. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. Low calorie infant formula can have low micronutrient content, or in some 161198. Doc •57· 201233328 In the example, 'can have a high micronutrient content, and can be a 1-2 day formula and/or a 3-9 day formula. In one embodiment, the infant formula has an energy content of about 2 〇〇kcal/L formula to less than 600 kcal/L formula. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation of the first 1-2 days of the infant's energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days after birth and then 3 to 9 after birth. The 3rd and 9th day formulas with an energy content of about 360 kcal/L to less than 600 kcai/L. The formula may be administered on the 3rd to 9th day after the 9th day after birth, or may be administered to the southerly formula (including the full calorie formula) on the 1st day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method for improving protein digestion in infants, which comprises administering to a baby any of the low micronutrient infant formula infants of the invention is preferably a neonate. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 2 〇〇 kcai/L to less than 600 kcal/L 'where at least 65% of the micronutrient is from about 30% to about 80% of the conventional micronutrient amount. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrients are from about 3% to about 65% of the conventional micronutrient amount. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 36 〇 kcai/L to less than 600 161198. Doc • 58 · 201233328 kcal/L, wherein at least 30% of the micronutrients are included in the infant formula (in unit volume) in amounts ranging from about 55% to about 80% of the corresponding micronutrient. The low calorie infant formula can be formulated on Day 丨_2 and/or on Day 3.9. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie 4c formulation (having a sputum or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 36 〇 kcai/L is administered during the first two days of life ( For example, the 1st day formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . Formulations may be administered on days 3-9 after the 9th day after birth, or higher calorie formulas (including full calorie formulas) may be administered on the first day after birth. In the examples where the low calorie infant formula has a low micronutrient content, the amount of micronutrient included in the formulation may be any of the above amounts. Formulations for infants will usually be administered daily as described above. In another embodiment, the invention is directed to a method of improving protein absorption in an infant. The method comprises identifying an infant experiencing protein insufficiency; and administering to the infant any of the low calorie infant formulas of the invention. An infant undergoing protein insufficiency can be identified using any of the criteria described herein for identifying infants undergoing protein insufficiency. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content, or in some embodiments ' may have a high micronutrient content and may be 161198 for the first 1-2 days. Doc •59- 201233328 Formula or Day 3-9 Formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a formulation of the first 1-2 days of the infant's energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days after birth and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 1st day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of improving protein absorption in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1 · 2 days formula). A low-calorie infant formula (having a high or low micronutrient content) with an infant energy content of about 3 60 kcal/L to less than 600 kcal/L can then be administered on days 3 to 9 after birth (eg, Day 3-9 formulation). Infants may be given a 3-9 day infant formula after the 9th day after birth, or may be given a higher calorie formula on the 1st day after birth (including a full calorie formula with low micronutrient content in a low calorie infant formula) In the embodiment, the micro 161I98 included in the formula. The amount of nutrients in doc -60- 201233328 can be any of the above. Formulations for administration to infants will usually be administered daily as ingested above. Tolerance The present invention is also directed to methods for improving the tolerance of infant formulas in infants. Infant formulation intolerance is a non-immune system-related response that can be confirmed by behavioral or fecal or eating patterns, such as increased cough or vomiting, increased frequency of bowel movements, more watery stools, increased black stools and crying . Infant Formulas Insufficiency is most often associated with gastrointestinal symptoms (eg, fecal morphology, fart, cough) and behavioral characteristics (eg, formula acceptance, crying, and shouting). Infants with formulation intolerance may also experience gastroesophageal reflux. It has been unexpectedly found that infants are more tolerant of infant formulas with lower energy content than full calorie formulas. Specifically, it has been found that low-calorie infant formulas exhibit faster protein hydrolysis and digestibility, produce less Mena reaction products (which cannot be broken down and absorbed) and have faster gastric emptying compared to the full-calorie formula. When the gastric emptying is faster, it can reduce the gastroesophageal reflux and improve the formulation tolerance. Thus, the low calorie infant formula of the present invention can be used to reduce the frequency of infant fart and/or cough. The low calorie infant formula of the present invention can also be used to increase the gastric emptying rate of an infant and to reduce the amount of the Mena reaction product produced by the food formulation as compared to the whole calorie infant formula. A low-calorie infant formula can be administered to any infant (preterm or term) and in particular any infant who can benefit from an infant formula that has low energy content and is highly tolerant. In some embodiments, the low calorie infant formula of the present invention is administered to a newborn. 161198. Doc -61 - 201233328 Therefore, the present invention is also directed to a method for improving the financial acceptability of an infant's infant formula. The method comprises identifying an infant suffering from infant formula intolerance and administering to the infant any of the low calorie infant formulas of the invention. Infants with infant formula intolerance may include infants with any or all of the symptoms of formulation intolerance. These symptoms include (but are not limited to) fecal or eating patterns, such as cough (four) increased vomiting; increased frequency of bowel movements; more watery stools; black stools; crying, shouting, fart increase;: unwilling to eat . After administration of the low calorie infant formula of the present invention, some or all of the formulation intolerance symptoms may be reduced or eliminated. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1st or 2nd day formulation. In one embodiment, the low calorie infant formula has an energy content of from about 200 to about 600 kcal/liter of formula. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, the formulation of the first 1-2 days of the infant's energy content from about 200 kcal/L to about 360 kcal/L is administered during the first two days after birth, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. The formula may be administered on Day 3-9 after the ninth day after birth, or may be administered on a higher calorie formula (including a full calorie formula) on the first day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of improving infant formula tolerance in an infant comprising administering to the infant any of the low micronutrient infants of the invention 161198. Doc -62- 201233328 Formula for children. The baby is preferably a newborn. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcai/L to less than 6 〇〇 kcal/L, which causes at least 65% of the micronutrients to be from about 30% to about 80% of the corresponding micronutrient amount. The amount of % is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 30% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 360 kcal/L to less than 6 〇〇 kcal/L' wherein at least 30% of the micronutrient is about 55 °/ of the corresponding micronutrient. Up to about 80% of the amount is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1_2 and/or Formulated on Day 3-9. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1_2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 3 60 kcal/L to less than 600 kcal/L can then be administered on days 3 to 9 after birth (eg, Days 3-9) ). Subject to the 3rd-9th day after the 9th day after birth, or may be given a higher calorie formula (including the full calorie formula in the low calorie infant formula 161198. Doc-63-201233328 In the examples having a low micronutrient content, the amount of the micronutrient included in the formulation may be any of the above contents. Formulations for infants will usually be administered daily as described above. In another embodiment, the invention is directed to a method of inhibiting gastric esophageal reflux in a baby. The method comprises identifying an infant suffering from a gastroesophageal reflux and administering to the infant any one or more of the low calorie infant formulas of the invention. The baby is preferably a new child. ▲ When gastroesophageal reflux (GER) occurs, the stomach contents flow back into the esophagus and flow out of the mouth, causing nausea, cough and/or vomiting. Symptoms of GER include cough, ° vomiting, coughing, irritability, poor eating, bloody stools, and combinations thereof. When a GER occurs, the baby may also cough, shout or be nervous. For the purposes of the present invention, the term "inhibiting gastroesophageal reflux" is intended to include treating, preventing, and/or reducing the incidence of GER and/or at least one of its symptoms. Without wishing to be bound by any particularity, the low-calorie infant formula of the present invention has a faster gastric emptying rate (i.e., the rate at which the contents pass through the stomach) compared to the all-calorie formulation, which causes gastroesophageal reflux. cut back. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 2-1 day formulation or a 3.9 day formulation. In an embodiment t, the infant formula has an energy content of from about 200 kcal/L to less than 600 kcai/L.

該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在—個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約2〇〇 kcal/L至約36〇 kcai/L之第U 161198.doc -64 - 201233328 天配方，且接著在出生後第3至9天投與能量含量為約36〇 kcal/L至小於600 kcal/L之第3·9天配方。可視情況在出生 後第9天過後投與第3-9天配方，或可在出生後第1〇天開始 投與較高熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中’本發明係關於抑制嬰兒胃食道逆流之方 法，其包含投與嬰兒任一或多種本發明之低微量營養素嬰 兒配方°嬰兒較佳為新生兒》低微量營養素嬰兒配方可為 任一上述配方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約2〇〇 kcal/L至約36〇 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第丨_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcai/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3_9天配方）。可視情況在出生後 第9天過後投與第3_9天配方，或可在出生後第1〇天開始投 與較而熱量配方（包括全熱量配方）。在低熱量嬰兒配方具 有低微量營養素含量之實施例中，配方中所包括之微量營 養素量可為任一上述含量。投與嬰兒之配方將通常以如上 述攝取量每日投與。 在另一態樣中’本發明係關於提高嬰兒之胃排空速率之 力法’其包含投與嬰兒任一或多種本發明之低微量營養素 婴兒配方。嬰兒較佳為新生兒。低微量營養素嬰兒配方可 16119S.doc •65· 201233328 為任一上述配方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言’在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第1_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3-9天配方）^可視情況在出生後 第9天過後投與第3-9天配方，或可在出生後第1〇天開始投 與較高熱量配方（包括全熱量配方配方中所包括之微量 營養素量可為任一上述含量。投與嬰兒之配方將通常以如 上述攝取量每日投與。 套組 此外本發明提供包含兩種或兩種以上本發明之低熱』 嬰兒配方之套組。 舉例而言，在-些實施例中，套組可包含至少一種第】 -己方及至少種第3·9天配方。套組較佳將包含足量纪 第1 2天配方以在出生後頭兩天期間提供嬰兒充分營養， 的第^天配方以在出生後至少第W天提供嬰兒充 套、且中包括之嬰兒配方可呈任何合適形式，包括 括歹低Γ1食型液體、濃縮液體、粉末或其組合。套組可包 =，、低微量營養素配方及/或低熱量、高微量營養 套組可視情況進—步包含套組使用說明書。舉例而言， 161198.doc -66 - 201233328 說明書可描述如何使用配方’例如可指示應在出生後頭兩 天投與第卜2天配方且應在出生後第3-9天投與第3_9天配 方；可描述配方之每日投藥時程；及/或可描述如何實踐 任何本揭示案中描述之方法。說明書可進一步視情況描述 如何復原套組中所包括之任何粉末嬰兒配方。 除嬰兒配方及視情況選用之說明書外，套組亦可包括其 他組分，諸如一或多個各種大小之奶瓶（baby b〇uie)、一 或夕個各種大小之奶瓶襯墊、奶瓶奶嘴及其類似物。 實例 以下實例說明本發明之嬰兒配方及方法之特定實施例及/ 或特徵^實例係僅出於說明目的提供且不應視為限制本發 月可在不偏離本發明之精神及範疇的情況下對其做出多 種良化。除非另有說明’否則所有例示量均為以組合物之 總重量計之重量百分比。 除非另有說明，否則根據本文中所描述之製備方法製備 〜殺菌爸滅菌及無菌滅菌配方為即食型液體配方。 實例1-8 在該等實例中，製備2盘司具有高或低微量營養素含量 •^第1-2天嬰兒配方及第3_9天嬰兒配方。用於製備配方之 成分闞述於以下表丨及2中。 I61198.doc •67· 201233328 表1 :第1-2天配方 單位 配方1 (第1-2天） 配方2 (第1-2天） 配方3 (第1-2天） 配方4 (第1-2天） 能量 Kcal/L 270 270 250 250 微量營養素含量 低 低 尚 向 成分(每1000 Kg批 次含量） 水 kg 適量 適量 適量 適量 乳糖 kg 23.2 23.1 15.5 15.2 脫脂乳粉 kg 11.0 11.0 11.0 11.3 半乳寡醣 kg 4.40 4.40 4.40 4.40 高油酸紅花子油 kg 5.34 5.35 5.33 5.37 大豆油 kg 4.00 4.00 3.99 4.00 挪子油 kg 3.82 3.82 3.81 3.84 乳清蛋白濃縮物 kg 2.70 2.70 2.70 2.86 1 NKOH g 1340 1.40 1340 1340 氫氧化鉀 g 67.0 70.0 67.0 67.0 磷酸氫鈣 g 327.1 249.8 1090 770.2 檸檬酸鉀 g 3.10 1.24 1370 1240 檸檬酸鈣 g 351.0 578.8 752.6 768.9 抗壞血酸 g 727.5 727.5 727.5 727.5 ARA油 g 367.9 367.9 367.9 367.9 核苷酸-膽鹼預混 物 g 328.5 328.5 328.5 328.5 磷酸二鈣 g … --- --- 氯化鎂 g 16.8 102.6 460.9 450.7 氯化鈉 g 45.7 28.5 325.8 186.7 大豆卵鱗脂 g 143.0 143.0 143.0 143.0 蒸餾後的單酸甘 油酯 g 143.0 143.0 143.0 143.0 維生素/礦物質/牛 磺酸預混物 g 31.4 57.1 157.0 157.0 牛磺酸 g 9.60 17.5 48.0 48.0 m-肌醇 g 6.97 12.7 34.85 34.85 硫酸鋅 g 3.21 5.85 16.07 16.07 菸鹼醯胺 g 2.05 3.73 10.24 10.24 泛酸鈣 g 1.23 2.23 6.14 6.14 硫酸亞鐵 g 1.07 1.95 5.37 5.37 硫酸銅 mg 377 686 1890 1890 鹽酸維生素B1 mg 318 578 1590 1590 維生素B2 mg 140 255 701 701 鹽酸維生素B6 mg 128 234 642 642 16ll98.doc •68· 201233328 單位 配方1 (第1-2天） 配方2 (第1-2天） 配方3 (第1-2天） 配方4 (第1-2天） 葉酸 mg 43.2 78.5 216 216 硫酸猛 mg 36.6 66.5 183 183 生物素 mg 12.4 22.6 62.0 62.0 硒酸鈉 mg 7.44 13.5 37 37 氰鈷胺素 mg 0.990 1.8 4.95 4.95 DHA油 g 137.9 137.9 137.9 137.9 氣化鉀 g 46.3 52.4 視需要 60.7 氣化膽鹼 g 58.9 21.5 88.9 54.0 硫酸亞鐵 g 5.80 23.20 60.9 60.9 角叉菜膠 g 175.0 175.0 175.0 175.0 維生素A、D3、 E、K1 g 22.8 19.0 47.5 47.5 RRR乙酸α-生育 酚 g 4.61 3.84 9.6 9.6 棕櫚酸維生素A mg 867 721.5 1800 1800 維生素K1 mg 50.2 41.8 104.5 104.5 維生素D3 mg 6.08 5.06 12.65 12.65 檸樣酸 g 29.8 29.8 29.8 29.8 混合類胡蘿S素預 混物 g 23.8 23.8 23.8 23.8 番茄紅素 mg 119 119 119 119 葉黃素 mg 50 50 50 50 β-胡蘿蔔素 mg 26.2 26.2 26.2 26.2 肌醇 g 33.1 6.6 12.9 12.9 L-肉驗 g 6.38 1.31 6.38 3.28 維生素Β2 mg … 466.0 882 882 表2 :第3-9天配方 單位 配方5 (第3-9天） 配方6 (第3-9天） 配方7 (第3-9天） 配方8 (第3-9天） 能量 Kcal/L 406 406 406 410 微量營養素含量 低 低 低 高 成分(每1000 Kg批 次含量） 水 kg 適量 適量 適量 適量 乳糖 kg 37.0 37.2 37.5 35.50 脫脂乳粉 kg 16.3 16.2 16.2 16.30 半乳寡醣 kg 8.63 8.63 8.63 8.63 高油酸紅花子油 kg 7.72 7.72 7.72 7.72 大豆油 kg 5.78 5.78 5.78 5.78 椰子油 kg 5.52 5.52 5.52 5.51 161198.doc -69· 201233328 單位 配方5 (第3-9天） 配方6 (第3-9天） 配方7 (第3-9天） 配方8 (第3-9天） 乳清蛋白濃縮物 kg 4.00 4.00 4.00 4.00 1 ΝΚΟΗ kg 1.34 1.34 0.8035 1.34 氫氧化鉀 g 67.0 67.0 40.2 67.0 磷酸氫鈣 kg 0.309 — — … 檸檬酸鉀 kg 0.00186 0.00186 0.00186 1.06 檸檬酸鈣 g 687.6 583.5 583.5 261.1 抗壞血酸 g 727.5 727.5 436.5 727.5 ARA油 g 378.2 378.2 378.2 378.2 核苷酸-膽鹼預混物 g 319.7 319.7 319.7 319.7 超微細磷酸三鈣 g … 226.8 226.8 1470 氣化鎂 g 122.5 147.7 147.7 288.1 氣化納 g … … 235.8 大豆卵磷脂 g 206.0 206.0 206.0 206.0 殺菌釜蒸餾後的單 酸甘油醋 g 206.0 206.0 206.0 206.0 維生素/礦物質/牛磺 酸預混物 g 85.6 115.7 115.7 142.7 牛磺酸 g 26.2 35.4 35.4 43.6 m-肌醇 g 19.0 25.7 25.7 31.7 硫酸鋅 g 8.76 11.8 11.8 14.61 菸鹼醯胺 g 5.59 7.55 7.55 9.31 泛酸鈣 g 3.35 4.53 4.53 5.58 硫酸亞鐵 g 2.93 3.96 3.96 4.88 硫酸銅 g 1.03 1.39 1.39 1.71 鹽酸維生素B1 g 0.8667 1.17 1.17 1.44 維生素B2 mg 382.2 516.6 516.6 637 鹽酸維生素B6 mg 350.1 473.2 473.2 584 葉酸 mg 117.7 159.1 159.1 196 硫酸猛 mg 99.7 134.7 134.7 166 生物素 mg 33.8 45.7 45.7 56.0 硒酸鈉 mg 20.3 27.4 27.4 34 氰鈷胺素 mg 2.7 3.64 3.64 4.5 DHA油 g 137.9 137.9 137.9 137.9 氣化鉀 g 108.7 111.3 111.3 129.5 氣化膽驗 g 32.4 32.4 32.4 88.9 硫酸亞鐵 g 34.8 37.5 37.5 60.9 角叉菜膠 g 175.0 175.0 175.0 175.0 維生素A、D3、E、 K1 g 28.5 30.2 30.2 44.8 RRR乙酸α-生育酚 g 5.8 6.11 6.11 9.1 棕櫊酸維生素A g 1.08 1.15 1.15 1.7 維生素K1 mg 62.7 66.4 66.4 98.5 161198.doc ·70· 201233328 單位 配方5 (第3-9天） 配方6 (第3-9天） 配方7 (第3-9天） 配方8 (第3-9天） 維生素D3 mg 7.6 8.04 8.04 11.9 檸檬酸 8 29.8 29.8 29.8 29.8 混合類胡蘿蔔素預 混物 g 23.8 23.8 23.8 23.8 番茄紅素 mg 119 卜119 119 119 葉黃素 mg 50 50 50 50 β-胡蘿蔔素 mg ^ 26.2 26.2 26.2 26.2 肌醇 8 ~— — _·— ΪΖ9~' L-肉驗 g 1.97 2.31 2.31 5.51 ~ 維生素Β2 S 0.70 0.699 0.699 1.50 維生素A mg … 770 770 780 — 棕櫊酸維生素A mg 420 420 425 放酸銅 mg --- … … 391 — 藉由製備至少兩種獨立漿料，接著使其摻合在一起，熱 處理，標準化且最終滅菌來製備配方。最初，藉由使所選 碳水化合物（例如乳糖、半乳寡醣）在74^ _79t：下溶解於水 中，接著添加擰檬酸、氯化鎮、氯化卸、檸檬酸卸、氯化 膽鹼及氣化鈉來製備碳水化合物_礦物質漿料。所得漿料 在49°C -60°C下保持在適度攪拌下直至其隨後與其他製備 之衆料推合在一起。 藉由在攪拌下合併高油酸紅花子油、椰子油、單甘油酸 酯及大豆卵磷脂且加熱至66。〇-79〇c來製備油包蛋白質漿 料。靜置10-15分鐘時間後，接著向漿料中添加大豆油、 油溶性維生素預混物、混合類胡蘿蔔素預混物、角叉菜 膠、維生素A、檸檬酸鈣、磷酸二鈣、ara油、DHA油及 乳清蛋白濃縮物。所得油漿料在49°c _6〇它下保持在適度 攪拌下直至其隨後與其他製備之漿料摻合在一起。 水加熱至4 9 °C · 6 0 °C且接著在充分攪拌下與碳水化合物_ 礦物質漿料、脫脂乳及油包蛋白質漿料合併。用氫氧化鉀 161198.doc -7卜 201233328 調節所得摻合物之PH值。該掺合物在49°C -60°C下保持在 適度攪拌下。 加熱所得摻合物至74t_79t:,經單階段均質器乳化至 9⑼-1100 psig且接著加熱至144〇c_147t：保持約5秒。加熱 之推〇物通過快速冷卻器以使溫度降至88它_93它，且接 著通過板式冷卻器以使溫度進一步降至74。(：-85°C。接著 冷卻之摻合物在2900-3100/400_600 psig下均質化，保持在 74 C 85 C下16秒且接著冷卻至2。(： -7°C ^獲取用於分析測 試之樣品。混合物在2〇c_7<t下保持在攪拌下。 獨立製備水溶性維生素（WSV)溶液及抗壞血酸溶液且添 加至經處理之摻合漿料中。藉由在攪摔下向水中添加以下 成分來製備維生素溶液：檸檬酸鉀、硫酸亞鐵、wsv預混 物、L-肉鹼、硫酸銅、維生素”、肌醇及核苷酸_膽鹼預 混物。藉由將氫氧化鉀及抗壞血酸添加至足以溶解該等成 分之量的水中來製備抗壞血酸溶液。接著用氫氧化鉀調節 抗壞血酸溶液pH值至5-9。 用氫氧化鉀調節摻合物pH值至指定？1|值範圍7卜7 6(視 產物而不同）以獲得最佳產品穩定性。接著將成品填充入 合適容器中且最終滅菌。 實例9-11 在該等實例中，製備32盎司具有高或低微量營養素含量 之無菌滅菌第3-9天嬰兒配方。用於製備配方之成分闡述 於以下表3中。 161198.doc •72- 201233328 表3 單位 配方9 (第3-9天） 配方10 (第3-9天） 配方11 (第3-9天） 能量 Kcal/L 406 410 410 微量營養素含量 低 南 兩 成分 tlOOO kg批次含J t 水 kg 適量 適量 適量 乳糖 kg 37.0 33.7 34.03 脫脂乳粉 kg 16.3 17.0 16.47 半乳寡醣 kg 8.63 8.63 8.63 高油酸紅花子油 kg 7.72 7.83 7.72 大豆油 kg 5.78 5.87 5.78 挪子油 kg 5.52 5.60 5.51 乳清蛋白濃縮物 kg 4.00 4.19 4.05 1NKOH kg 1.85 1.85 1.85 氫氧化鉀 g 92.5 92.5 92.5 檸檬酸鈣 g 675.0 716.8 993.9 磷酸氫鈣 g 577.4 1170 1390 抗壞血酸 g 431.7 431.7 431.7 ARA油 g 378.2 378.2 378.2 核苷酸-膽鹼預混物 g 319.7 319.7 319.7 大豆卵磷脂 g 206.0 206.0 206.0 蒸餾後的單酸甘油酯 g 206.0 206.0 206.0 角叉菜膠 g 200.0 240.0 200.0 DHA油 g 137.9 137.9 137.9 氣化鎂 g 128.9 279.3 285.9 氯化斜 g 118.5 213.9 122.4 氣化膽鹼 g 88.9 54.0 88.9 維生素/礦物質/牛磺 酸預混物 g 41.4 142.7 142.7 牛磺酸 g 12.7 43.6 43.6 m-肌醇 g 9.19 31.7 31.7 硫酸鋅 g 4.24 14.61 14.61 於驗龜胺 g 2.70 9.31 9.31 泛酸鈣 g 1.62 5.58 5.58 硫酸亞鐵 g 1.42 4.88 4.88 硫酸銅 mg 497 1710 1710 鹽酸維生素B1 mg 419 1440 1440 維生素B2 mg 185 637 637 鹽酸維生素B6 mg 169 584 584 葉酸 mg 56.9 196 196 硫酸猛· mg 48.2 166 166 161198.doc -73- 201233328 單位 配方9 (第3-9天） 配方10 (第3-9天） 配方11 (第3-9天） 生物素 mg 16.4 56.0 56.0 砸酸納 mg 9.81 34 34 氰鈷胺素 mg 1.3 4.5 4.5 氣化納 g 32.1 65.4 231.9 維生素A、D3、E、 K1 g 30.9 44.8 44.8 RRR乙酸α-生育酚 g 6.24 9.1 9.1 棕櫚酸維生素A g 1.17 1.7 1.7 維生素K1 mg 67.9 98.5 98.5 維生素D3 mg 8.22 11.9 11.9 檸檬酸 g 29.8 29.8 29.8 肌醇 g 25.8 12.9 12.9 混合類胡蘿節素預 混物 g 23.8 23.8 23.8 番茄紅素 mg 119 119 119 葉黃素 mg 50 50 50 β·胡蘿蔔素 mg 26.2 26.2 26.2 硫酸亞鐵 g 16.2 60.9 60.9 L-肉驗 g 5.51 3.28 5.51 檸檬酸鉀 g 3.10 895.0 1060 維生素Β2 mg 599 1500 1500 維生素A mg --- 780 780 棕櫊酸維生素A mg --- 425 425 硫酸銅 mg --- 391 藉由製備至少兩種獨立漿料，接著使其摻合在一起，熱 處理，標準化且接著進行無菌處理及填充來製備配方。最 初，藉由使所選碳水化合物（例如乳糖、半乳寡醣）在74°C -79°C下溶解於水中，接著添加檸檬酸、氣化鎂、氣化鉀、 檸檬酸鉀、氣化膽鹼及氯化鈉（礦物質視調配物而不同）來 製備碳水化合物-礦物質漿料。所得漿料在49°C -60°C下保 持在適度攪拌下直至其隨後與其他製備之漿料摻合在一 起。 藉由在授拌下合併高油酸紅花子油、椰子油、單甘油酸 酯及大豆卵磷脂且加熱至66°C -79°C來製備油包蛋白質漿 161198.doc -74- 201233328 料°靜置10-15分鐘時間後，接著向漿料中添加大豆油、 油溶性維生素預混物、混合類胡蘿g素預混物 '角又菜 膠、檸檬酸鈣、磷酸氫鈣、ARA油、DHA油及乳清蛋白濃 縮物。所得油漿料在49。(： -6〇t下保持在適度攪拌下直至 其隨後與其他製備之漿料摻合在一起。 水加熱至49K0°C且接著在充分攪拌下與碳水化合物_ 礦物質漿料、脫脂乳及油包蛋白質漿料合併。用氫氧化鉀 調節所得摻合物之pH值。該摻合物在49。(： -60°C下保持在 適度攪拌下。 加熱所得摻合物至74eC-79t：，經單階段均質器乳化至 900-1100 psig且接著加熱至144t_147t保持約5秒。加熱 之摻合物通過快速冷卻器以使溫度降至88<t ，且接 者通過板式冷卻器以使溫度進一步降至74〇c _85它。接著 冷卻之摻合物在2900·3100/400_600 psig下均質化保持在 7代-85。(：下16秒且接著冷卻至2。(：_7。。。獲取用於分析測 試之樣品。混合物在下保持在攪拌下。 獨立製備水溶性維生素（WSV)溶液及抗壞錢溶液且添 加至經處理之摻合漿料中。藉由在難下向水中添加以下 成分來製備維生素溶液：檸檬酸卸、硫酸亞鐵、刪預混 物、L·肉驗、維生㈣、肌醇及㈣酸_膽鹼預混物。藉 由將氫氧化鉀及抗壞▲酸添加至足轉解該等成分之量的 水中來製備抗壞錢溶液。接著用氫氧化鉀 溶液pH值至5-9。 用氫氧化鉀調節摻合物pH值 至pH值範圍6.8-7.0以獲得 161198.doc •75· 201233328 最佳產品穩定性。接著標準化摻合物經無菌處理器接受第 二次熱處理。摻合物預加熱至63°C-74°C且在200 psig下均 質化。摻合物進一步加熱至141 °C -144°C且通過固持管。 冷卻加熱之摻合物以使溫度降至74°C -85°C且接著在 1200/200 psig下均質化。進一步冷卻摻合物至16°C -27°C且 接著在21 °C下無菌填充入合適容器中。 實例12-15 在該等實例中，製備具有高或低微量營養素含量之粉末 第1-2天嬰兒配方及第3-9天嬰兒配方。用於製備配方之成 分闡述於以下表4中。 表4 配方12 (第1-2天） 配方13 (第1-2天） 配方14 (第3-9天） 配方15 (第3-9天） Kcal/L 270 250 406 420 營養物含量 低 向 低 向 成分 單位 每1000 kg批次含量 乳糖 kg 376.90 288.6 406.4 380.4 脫脂乳粉 kg 223.00 223.1 201.1 201.1 高油酸紅花子油 kg 109.30 108.5 97.69 97.7 半乳寡醣 kg 81.70 84.7 104.1 104.10 大豆油 kg 81.70 82.4 74.21 74.2 揶子油 kg 75.30 75.9 68.36 68.4 乳清蛋白濃縮物 kg 48.80 54.9 49.50 49.5 檸檬酸鉀 kg 8.52 42.6 11.12 22.0 ARA油 kg 7.20 7.43 4.643 4.57 乳清蛋白水解產物 kg 6.80 … — … 碳酸鈣 kg 3.76 --- 2.839 1.5 磷酸三鈣 kg 24.1 2.638 10.9 DHA油 kg 2.70 2.8 1.752 1.7 抗壞血酸 kg 2.03 3.20 2.006 2.0 核苷酸·膽鹼預混物 kg 2.01 5.9 2.346 3.6 氣化鉀 kg 1.154 --- 1.219 … 維生素/礦物質/牛磺 酸預混物 kg 1.116 2.8 1.116 1.7 161198.doc -76- 201233328 配方12 (第1-2天） 配方13 (第1-2天） 配方14 (第3-9天） 配方15 (第3-9天） 牛磺酸 g 341 859.9 341 528.9 肌醇 g 248 624.3 248 384.0 硫酸辞 g 114 287.9 114 177.1 菸鹼醯胺 g 72.8 183.5 72.8 112.9 泛酸鈣 g 43.7 110 43.7 67.7 硫酸亞鐵 g 38.2 96.3 38.2 59.2 硫酸銅 g 13.4 33.8 13.4 20.8 鹽酸維生素Β1 g 11.3 28.5 11.3 17.5 維生素Β2 g 4.98 12.60 4.98 7.72 鹽酸維生素Β6 g 4.58 11.5 4.58 7.07 葉酸 g 1.53 3.9 1.53 2.4 硫酸猛 g 1.3 3.27 1.3 2.01 生物素 mg 441 1100 441 683 硒酸鈉 mg 264 666.1 264 410 氰鈷胺素 mg 35.1 88.6 35.1 54.5 大豆卵碟脂 kg 1.120 1.1 1.112 1.1 氣化鎂 kg 0.839 6.6 1.437 3.4 氯化鉀 kg --- 2.6 … 2.3 棕櫊酸抗壞血酸酯 g 459.25 348.1 313.5 313.6 類胡蘿蔔素預混物 g 454.02 463.0 286.6 286.6 番茄紅素 g 2.27 2.27 1.43 1.41 葉黃素 mg 953 953 602 589.9 β-胡蘿蔔素 mg 499 499 315 308.9 硫酸亞鐵 g 453.5 1100 453.6 703.1 氣化膽鹼 g 432.1 1100 432.1 670.2 氣化納 g 388.0 7100 1138 2900 維生素A、D3、Ε、 K1 g 385.24 914.5 327.3 568.8 RRR乙酸α-生育酚 g 77.9 184.9 66.2 115.0 棕櫊酸維生素A g 14.63 34.7 12.4 21.6 維生素K1 mg 847 2000 720 1250 維生素D3 mg 102.3 243.5 87.1 151.4 混合生育酚 g 246.3 153.4 138.2 138.2 L-肉臉 g 26.3 66.3 23.3 40.8 維生素B2 g 3.2 8.0 3.2 4.9 1 N氫氧化鉀 視需要 視需要 視需要 視需要 藉由製備至少兩種獨立漿料，接著使其摻合在一起，熱 處理，標準化，第二次熱處理，蒸發以移除水且最終喷霧 乾燥來製備配方。最初，藉由使所選碳水化合物（例如乳 161198.doc -77- 201233328 糖、半乳寡釀）在60°C-71°C下溶解於水中，接著添加氣化 鎂、氣化鉀、檸檬酸鉀、氣化膽鹼及氣化鈉（礦物質視調 配物而不同）來製備碳水化合物-礦物質漿料。所得衆料在 49°C -60°C下保持在適度攪拌下直至其隨後與其他製備之 漿料摻合在一起。 藉由在4 9 C - 6 0 C下合併南油酸紅花子油、大豆油及挪 子油’接著添加棕搁酸抗壞血酸酯、混合生育紛、大豆印 磷脂、油溶性維生素預混物、乳清蛋白濃縮物、乳清蛋白 水解產物（在一些情況下）、類胡蘿萄素預混物及碳酸鈣（及/ 或磷酸三鈣）來製備油包蛋白質漿料。所得油漿料在38^ _ 49 °C下保持在適度攪拌下直至其隨後與其他製備之漿料摻 合在一起。 在充分攪拌下合併水、碳水化合物_礦物質漿料、脫脂 乳及油包蛋白質漿料。用氫氧化鉀調節所得摻合物之pH 值。該摻合物在49*t-60t下保持在適度攪拌下。在15^1值 調節後且加工之前添加ARA油及DHA油。 加熱所得摻合物至71 t-77°C，經單階段均質器乳化至 最高值300 psig且接著加熱至82〇c_88t：保持約5秒。加熱 之摻合物通過快速冷卻器以使溫度降至77<t _82<t，且接 著通過板式冷卻器以使溫度進一步降至71艺_77艽^接著 冷卻之摻合物在2400-2600/400-600 psig下均質化，保持在 74t-85。。下16秒且接著冷卻至2t-rc。獲取用於分析測 試之樣品。混合物在2。〇-7。(：下保持在攪拌下。 獨立製備水溶性維生素（WSV)溶液及抗壞血酸溶液且添 16I198.doc •78· 201233328 加至經處理之摻合漿料中。藉由在攪拌下向水中添加以下 成分來製備維生素溶液：檸檬酸鉀、硫酸亞鐵、wsv預混 物L肉驗、維生素B2及核苷酸_膽驗預混物（特定成分視 調配物而不同）。藉由將氫氧化鉀及抗壞血酸添加至足以 溶解該等成分之量的水中來製備抗壞血酸溶液。接著用氮 氧化鉀調節抗壞血酸溶液pH值至5-9。 用氫氧化鉀調節摻合物pH值至pH值範圍6 6〇_6 9〇以獲 得最佳產品穩定性。接著標準化摻合物接受第二次熱處 理。最初加熱摻合物至66°C_82t：，且接著進一步加熱至 ].18°C-124°C保持約5秒。接著加熱之摻合物通過快速冷卻 器以使溫度降至7rc-82t。在熱處理後，摻合物蒸：降 至密度 1.15-1.17 g/mL。 蒸發之摻合物通過喷霧乾燥器以達成成品粉末中水分含 量為2.5%之目#。接著成品粉末與水一起聚結為黏合劑溶 液。接著將成品封裝入合適容器中。 實例16 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定本發明之多種第卜2天嬰 兒配方及第3-9天嬰兒配方之緩衝能力及緩衝強度且與市 售粉末對照嬰兒配方、市售即食型2盘司殺菌釜滅菌對照 嬰兒配方、市售即食型32盘司無菌滅菌對照嬰兒配方及人 乳之緩衝能力及緩衝強度進行比較。用於製備對照配方之 成分闡述於以下表5中。 161198.doc -79· 201233328 表5 對照配方1 (粉末） 對照配方2 (殺菌釜滅菌） 對照配方3 (無菌滅菌） Kcal/L 676 676 676 成分 單位 每1000 kg批次含3 水 kg … Q.S. Q.S. 濃縮脫脂乳 kg 698.5 83.61 86.64 乳糖 kg 386.0 54.88 54.7 高油酸紅花子油 kg 114.4 14.07 14.0 大豆油 kg 85.51 10.54 10.5 挪子油 kg 78.76 10.05 10.0 半乳寡醣 kg 69.50 8.630 8.60 乳清蛋白濃縮物 kg 51.08 6.120 6.52 檸檬酸鉀 g 9168 518.3 418.07 碳酸鈣 g 4054 508.5 477.16 ARA油 g 2949 355.6 378.16 核苷酸-膽鹼預混物 g 2347 293.2 293.26 氣化_ g 1295 208.5 282.24 角叉菜膠 g — 175.0 240.00 抗壞血酸 G 1275 727.5 582.12 大豆卵磷脂 G 1120 534.6 356.11 穩定劑 G --- 534.6 356.11 維生素/破物質/牛磺 酸預混物 G 1116 142.8 142.77 牛磺酸 G 340.5 43.66 43.654 m_肌醇 G 247.9 31.70 31.695 硫酸鋅 G 114.2 14.62 14.617 菸鹼醯胺 G 72.78 9.323 9.3157 泛酸鈣 G 44.16 5.587 5.5860 硫酸亞鐵 G 39.24 4.880 4.8870 硫酸銅 G 13.68 1.714 1.7143 鹽酸維生素B1 G 11.30 1.445 1.4456 維生素B2 Mg 4985 637.6 637.47 鹽酸維生素B6 Mg 4572 584.1 583.96 葉酸 Mg 1535 196.4 215.72 硫酸猛 Mg 1306 166.3 166.25 生物素 Mg 441.0 56.41 56.390 础酸鈉 Mg 261.8 33.82 33.820 氰鈷胺素 Mg 35.17 4.493 4.500 DHA油 G 1113 135.4 130.01 氣化鎂 G 1038 141.5 140.46 氣化納 G 579.4 視需要 視需要 161198.doc -80- 201233328 對照配方1 (粉末） 對照配方2 (殺菌釜滅菌） 對照配方3 (無菌滅菌） 硫酸亞鐵 G 453.6 58.02 58.03 氣化膽鹼 G 432.1 54.02 50.02 維生素A、D3、Ε、 K1 G 377.2 47.50 44.76 RRR乙酸α-生育酚 G 76.23 9.604 9.0507 棕櫚酸維生素A G 14.32 1.803 1.6998 維生素K1 Mg 829.3 104.5 98.47 維生素D3 Mg 100.4 12.65 11.92 檸檬酸 G — 29.80 29.77 棕櫚酸抗壞血酸酯 G 361.3 … — 類胡蘿蔔素預混物 G 350.1 23.80 42.91 番茄紅素 Mg 1720 119.0 214.55 葉黃素 Mg 735 49.98 90.11 β-胡蘿蔔素 Mg 385 26.18 47.201 混合生育酚 G 159.2 — 一一 混合生育酚 G 111.4 --- … L-肉驗 G 26.30 3.285 3.28 維生素Β2 G 3.181 1.166 1.4994 磷酸三鈣 G 0-5230 12.5 41.89 磷酸二氫鉀 G … 11.01 36.60 棕櫊酸維生素A Mg … … 776.16 棕櫚酸維生素A Mg --- 427.19 α生育紛 Mg --- 7.760 磷酸氫二鉀 Kg 0-5.23 … — 1ΝΚΟΗ Kg 視需要 1.583 視需要 氫氧化鉀 G 視需要 79.15 視需要 如上文實例12-15中所描述製備對照配方1 ;如上文實例 1-8中所描述製備對照配方2且如上文實例9-11中所描述製 備對照配方3。 測定多種第1-2天即食型（RTF)殺菌釜滅菌或復原粉末配 方及第3-9天RTF殺菌釜滅菌、RTF無菌滅菌或復原粉末配 方之緩衝能力及緩衝強度且與對照配方1-3及人乳之緩衝 能力及緩衝強度進行比較。明確言之，藉由以1分鐘時間 間隔向50 mL各配方（或在粉末配方情況下為復原配方）中 添加0.5 mL 0.10 M HC1之等分試樣來測定配方（或人乳）之 161198.doc -81 - 201233328 緩衝強度。在添加各等分試樣後量測各配方之pH值。緩衝 強度報導為使50 mL配方之pH值降至3.0所需之0.10 M HC1 毫升量。藉由向100 mL各配方（或在粉末配方情況下為復 原配方）中添加5.00 mmol HC1來測定配方（或人乳）之緩衝 能力。緩衝能力報導為添加HC1後[H+]之增加量。結果展 示於以下表6以及圖1及2中。 表6The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a U 161198.doc -64 - 201233328 day formulation having an infant energy content of from about 2 〇〇 kcal/L to about 36 〇 kcai/L is administered during the first two days of life. Then, a 3rd-9th day formulation having an energy content of about 36〇kcal/L to less than 600 kcal/L is administered on the 3rd to 9th day after birth. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 1st day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method for inhibiting reflux of the stomach and esophagus of a baby, comprising administering to the infant any one or more of the low micronutrient infant formula of the invention, wherein the infant is preferably a newborn, the low micronutrient infant formula can be For any of the above formulations. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having a high or low micronutrient content) having an infant energy content of from about 2 〇〇 kcal/L to about 36 〇 kcal/L is administered during the first two days of life. (eg the second day of the formula). A low-calorie infant formula (with high or low micronutrient content) (eg, day 3_9 formula) with an infant energy content of about 360 kcal/L to less than 600 kcai/L can then be administered on days 3-9 after birth. The formula may be administered on the 3rd to 9th day after the 9th day after birth, or the calorie formula (including the full calorie formula) may be administered on the 1st day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formula can be any of the above levels. Formulations for infants will usually be administered daily as described above. In another aspect, the invention relates to a method for increasing the rate of gastric emptying in an infant' which comprises administering to the infant any one or more of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. Low micronutrient infant formula can be 16119S.doc •65· 201233328 for any of the above formulations. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having a high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1_2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) ^ May be administered on Days 3-9 after the 9th day after birth, or may be administered on a higher calorie formula on the first day after birth (including the amount of micronutrients included in the full calorie formula) Any of the above contents. Formulations for administration to infants will usually be administered daily as ingested as above. Kits Further, the present invention provides kits comprising two or more of the low calorie infant formulas of the present invention. In some embodiments, the kit may comprise at least one of the first-party and at least the third-ninth-day formula. The kit preferably will contain a sufficient amount of the 12th day formula to provide the baby during the first two days of life. The fully nutritious, day-to-day formula provides a baby filling at least W days after birth, and the infant formula included therein may be in any suitable form, including a parenteral low-grade 1 food liquid, a concentrated liquid, a powder, or a combination thereof. Set can be packaged =, low Nutrient formula and / or low-calorie, high-micro nutrient kits can be included in the kit. For example, 161198.doc -66 - 201233328 instructions can describe how to use the formula 'for example, the first two should be indicated after birth. Tiantou and Dib Day Formulations should be administered on Days 3-9 on the 3rd to 9th day after birth; the daily dosing schedule of the formula can be described; and/or how to describe any of the methods described in this disclosure can be described The instructions may further describe how to restore any powder infant formula included in the kit as appropriate. In addition to the infant formula and optionally instructions, the kit may also include other components, such as one or more bottles of various sizes ( Baby b〇uie), one or a variety of bottle liners, bottle nipples and the like. Examples The following examples illustrate specific embodiments and/or features of the infant formula and method of the present invention. The purpose of providing and not to be construed as limiting the present invention may be varied and varied without departing from the spirit and scope of the invention. The amounts are by weight based on the total weight of the composition. Unless otherwise stated, the preparations prepared according to the methods described herein are prepared as ready-to-eat liquid formulations. Examples 1-8 In the examples, the preparation of the two plates has high or low micronutrient content • The 1-2 day infant formula and the 3rd-9 day infant formula. The ingredients used to prepare the formulation are described in the following Tables and 2. I61198.doc •67· 201233328 Table 1: Formula 1-2 Formulation Unit Formula 1 (Day 1-2) Formula 2 (Day 1-2) Formula 3 (Day 1-2) Formula 4 (Day 1-2) Energy Kcal/L 270 270 250 250 Micronutrient content low and low content component (per 1000 Kg batch content) Water kg Appropriate amount of proper amount of lactose kg 23.2 23.1 15.5 15.2 Skim milk powder kg 11.0 11.0 11.0 11.3 galacto-oligosaccharide kg 4.40 4.40 4.40 4.40 High oleic acid safflower oil kg 5.34 5.35 5.33 5.37 Soybean oil kg 4.00 4.00 3.99 4.00 Nvwa oil kg 3.82 3.82 3.81 3.84 Whey protein concentrate kg 2.70 2.70 2.70 2.86 1 NKOH g 1340 1.40 1340 1340 Potassium hydroxide g 67 .0 70.0 67.0 67.0 Calcium hydrogen phosphate g 327.1 249.8 1090 770.2 Potassium citrate g 3.10 1.24 1370 1240 Calcium citrate g 351.0 578.8 752.6 768.9 Ascorbic acid g 727.5 727.5 727.5 727.5 ARA oil g 367.9 367.9 367.9 367.9 Nucleotide-choline premix Material g 328.5 328.5 328.5 328.5 Dicalcium phosphate g ... --- --- Magnesium chloride g 16.8 102.6 460.9 450.7 Sodium chloride g 45.7 28.5 325.8 186.7 Soybean egg fat g 143.0 143.0 143.0 143.0 Distilled monoglyceride g 143.0 143.0 143.0 143.0 Vitamin/Mineral/Taurine Premix g 31.4 57.1 157.0 157.0 Taurine g 9.60 17.5 48.0 48.0 m-inositol g 6.97 12.7 34.85 34.85 Zinc sulfate g 3.21 5.85 16.07 16.07 Nicotine guanamine g 2.05 3.73 10.24 10.24 Calcium pantothenate g 1.23 2.23 6.14 6.14 Ferrous sulfate g 1.07 1.95 5.37 5.37 Copper sulfate mg 377 686 1890 1890 Vitamin B1 mg 318 578 1590 1590 Vitamin B2 mg 140 255 701 701 Vitamin B6 mg 128 234 642 642 16ll98.doc • 68· 201233328 Unit Formula 1 (Day 1-2) Formula 2 (Day 1-2) Formula 3 (Day 1-2) Formula 4 (Day 1-2) Folic acid mg 43.2 78.5 216 216 Sulfuric acid mg 36.6 66.5 183 183 Biotin mg 12.4 22.6 62.0 62.0 Sodium selenate mg 7.44 13.5 37 37 Cyanocobalamin mg 0.990 1.8 4.95 4.95 DHA oil g 137.9 137.9 137.9 137.9 Gasification potassium g 46.3 52.4 60.7 gas choline g 58.9 21.5 88.9 54.0 ferrous sulfate g 5.80 23.20 60.9 60.9 carrageenan g 175.0 175.0 175.0 175.0 Vitamin A, D3, E, K1 g 22.8 19.0 47.5 47.5 RRR A-tocopherol g 4.61 3.84 9.6 9.6 Palmitic acid vitamin A mg 867 721.5 1800 1800 vitamin K1 mg 50.2 41.8 104.5 104.5 vitamin D3 mg 6.08 5.06 12.65 12.65 lemon acid g 29.8 29.8 29.8 29.8 mixed carotenoid S premix g 23.8 23.8 23.8 23.8 tomato red Prime mg 119 119 119 119 Lutein mg 50 50 50 50 β-carotene mg 26.2 26.2 26.2 26.2 Inositol g 33.1 6.6 12.9 12.9 L-meat test g 6.38 1.31 6.38 3.28 Vitamin Β 2 mg ... 466.0 882 882 Table 2: 3-9 Day Formulation Unit Formula 5 (Days 3-9) Formulation 6 (Days 3-9) Formulation 7 (Days 3-9) Formulation 8 (Days 3-9) Energy Kcal/L 406 406 406 410 Micro-battalion Low and low nutrient content (per 1000 Kg batch content) Water kg Appropriate amount appropriate amount of lactose kg 37.0 37.2 37.5 35.50 skim milk powder kg 16.3 16.2 16.2 16.30 galacto-oligosaccharide kg 8.63 8.63 8.63 8.63 high oleic acid safflower Oil kg 7.72 7.72 7.72 7.72 Soybean oil kg 5.78 5.78 5.78 5.78 Coconut oil kg 5.52 5.52 5.52 5.51 161198.doc -69· 201233328 Unit formula 5 (days 3-9) Formula 6 (days 9-9) Formulation 7 (No. 3-9 days) Formulation 8 (days 3-9) Whey protein concentrate kg 4.00 4.00 4.00 4.00 1 ΝΚΟΗ kg 1.34 1.34 0.8035 1.34 Potassium hydroxide g 67.0 67.0 40.2 67.0 Calcium hydrogen phosphate kg 0.309 — — ... Potassium citrate Kg 0.00186 0.00186 0.00186 1.06 Calcium citrate g 687.6 583.5 583.5 261.1 Ascorbic acid g 727.5 727.5 436.5 727.5 ARA oil g 378.2 378.2 378.2 378.2 Nucleotide-choline premix g 319.7 319.7 319.7 319.7 Ultrafine tricalcium phosphate g ... 226.8 226.8 1470 Magnesium gas g 122.5 147.7 147.7 288.1 Gasification nano g ... 235.8 Soy lecithin g 206.0 206.0 206.0 206.0 Sterilization of single acid after sterilization Vinegar g 206.0 206.0 206.0 206.0 Vitamin/Mineral/Taurine Premix g 85.6 115.7 115.7 142.7 Taurine g 26.2 35.4 35.4 43.6 m-inositol g 19.0 25.7 25.7 31.7 Zinc sulfate g 8.76 11.8 11.8 14.61 Nicotinamide g 5.59 7.55 7.55 9.31 Calcium pantothenate g 3.35 4.53 4.53 5.58 Ferrous sulfate g 2.93 3.96 3.96 4.88 Copper sulfate g 1.03 1.39 1.39 1.71 Hydrochloric acid vitamin B1 g 0.8667 1.17 1.17 1.44 Vitamin B2 mg 382.2 516.6 516.6 637 Vitamin B6 mg 350.1 473.2 473.2 584 Folic acid mg 117.7 159.1 159.1 196 Sulfuric acid ng mg 99.7 134.7 134.7 166 Biotin mg 33.8 45.7 45.7 56.0 Sodium selenate mg 20.3 27.4 27.4 34 Cyanocobalamin mg 2.7 3.64 3.64 4.5 DHA oil g 137.9 137.9 137.9 137.9 Gasification potassium g 108.7 111.3 111.3 129.5 Gasification and bile test g 32.4 32.4 32.4 88.9 Ferrous sulfate g 34.8 37.5 37.5 60.9 Carrageenan g 175.0 175.0 175.0 175.0 Vitamin A, D3, E, K1 g 28.5 30.2 30.2 44.8 RRR A-tocopherol g 5.8 6.11 6.11 9.1 Palmitic acid vitamin A g 1.08 1.15 1.15 1.7 Vitamin K1 mg 62.7 66.4 66.4 98.5 161198.doc ·70· 201233328 Unit Formula 5 (Days 3-9) Formula 6 (Days 3-9) Formulation 7 (Days 3-9) Formulation 8 (Days 3-9) Vitamin D3 mg 7.6 8.04 8.04 11.9 Citric Acid 8 29.8 29.8 29.8 29.8 Mixed carotenoid premix g 23.8 23.8 23.8 23.8 Lycopene mg 119 Bu 119 119 119 Lutein mg 50 50 50 50 β-carotene mg ^ 26.2 26.2 26.2 26.2 Inositol 8 ~- _ _ ΪΖ9~' L-meat test g 1.97 2.31 2.31 5.51 ~ Vitamin Β2 S 0.70 0.699 0.699 1.50 Vitamin A mg ... 770 770 780 — Palmitic acid A mg 420 420 425 Acid-dissolved copper mg --- ... 391 — by At least two separate slurries are prepared, which are then blended together, heat treated, standardized, and finally sterilized to prepare a formulation. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides) in water at 74^_79t: followed by addition of citric acid, chlorination, chlorination, citric acid unloading, choline chloride And gasification of sodium to prepare a carbohydrate-mineral slurry. The resulting slurry was maintained under moderate agitation at 49 ° C - 60 ° C until it was subsequently pushed together with other prepared ingredients. High oleic safflower oil, coconut oil, monoglyceride and soy lecithin were combined by stirring and heated to 66. 〇-79〇c was used to prepare a protein-packed protein slurry. After standing for 10-15 minutes, add soybean oil, oil-soluble vitamin premix, mixed carotenoid premix, carrageenan, vitamin A, calcium citrate, dicalcium phosphate, ara to the slurry. Oil, DHA oil and whey protein concentrate. The resulting oil slurry was kept under moderate agitation at 49 ° C -6 ° until it was subsequently blended with the other prepared slurry. The water is heated to 49 ° C · 60 ° C and then combined with the carbohydrate_mineral slurry, skim milk and oil-in-oil slurry with sufficient agitation. The pH of the resulting blend was adjusted with potassium hydroxide 161198.doc -7b 201233328. The blend was maintained under moderate agitation at 49 °C - 60 °C. The resulting blend was heated to 74t-79t: emulsified to 9(9)-1100 psig via a single stage homogenizer and then heated to 144 〇c_147t: held for about 5 seconds. The heated pusher passes through the flash cooler to bring the temperature down to 88 it, and then passes through the plate cooler to further reduce the temperature to 74. (: -85 ° C. The cooled blend was then homogenized at 2900-3100/400-600 psig, held at 74 C 85 C for 16 seconds and then cooled to 2. (: -7 ° C ^ obtained for analysis The sample tested. The mixture was kept under stirring at 2 〇 c_7 < t. A water-soluble vitamin (WSV) solution and an ascorbic acid solution were separately prepared and added to the treated blended slurry. The following ingredients are used to prepare vitamin solutions: potassium citrate, ferrous sulfate, wsv premix, L-carnitine, copper sulfate, vitamins, inositol and nucleotide-choline premix. And ascorbic acid is added to the amount of water sufficient to dissolve the components to prepare the ascorbic acid solution. Then adjust the pH of the ascorbic acid solution to 5-9 with potassium hydroxide. Adjust the pH of the blend to the specified ?1 value range with potassium hydroxide. 7b 7 6 (depending on the product) for optimum product stability. The finished product is then filled into a suitable container and finally sterilized. Examples 9-11 In these examples, 32 ounces were prepared with high or low micronutrient content. Sterile sterilization 3-9 days baby The ingredients used to prepare the formulation are set out in Table 3. 161198.doc •72- 201233328 Table 3 Unit Formulation 9 (Days 3-9) Formulation 10 (Days 3-9) Formulation 11 (Days 3-9) ) Energy Kcal/L 406 410 410 Low nutrient content low South two components tlOOO kg batch containing J t water kg appropriate amount appropriate amount of lactose kg 37.0 33.7 34.03 skim milk powder kg 16.3 17.0 16.47 galacto-oligosaccharide kg 8.63 8.63 8.63 high oleic acid Safflower oil kg 7.72 7.83 7.72 Soybean oil kg 5.78 5.87 5.78 Oyster oil kg 5.52 5.60 5.51 Whey protein concentrate kg 4.00 4.19 4.05 1NKOH kg 1.85 1.85 1.85 Potassium hydroxide g 92.5 92.5 92.5 Calcium citrate g 675.0 716.8 993.9 Hydrogen phosphate Calcium g 577.4 1170 1390 Ascorbic acid g 431.7 431.7 431.7 ARA oil g 378.2 378.2 378.2 Nucleotide-choline premix g 319.7 319.7 319.7 Soy lecithin g 206.0 206.0 206.0 Distilled monoglyceride g 206.0 206.0 206.0 Carrageen Glue 200.0 240.0 200.0 DHA oil g 137.9 137.9 137.9 Magnesium sulfide g 128.9 279.3 285.9 Chlorination oblique g 118.5 213.9 122.4 Gasification choline g 88.9 54.0 88.9 Dimensions Prime/Mineral/Taurine Premix g 41.4 142.7 142.7 Taurine g 12.7 43.6 43.6 m-inositol g 9.19 31.7 31.7 Zinc sulfate g 4.24 14.61 14.61 Tested toramine g 2.70 9.31 9.31 Calcium pantotheate g 1.62 5.58 5.58 Ferrous sulfate g 1.42 4.88 4.88 Copper sulfate mg 497 1710 1710 Hydrochloric acid vitamin B1 mg 419 1440 1440 Vitamin B2 mg 185 637 637 Hydrochloric acid vitamin B6 mg 169 584 584 Folic acid mg 56.9 196 196 Sulfuric acid violent mg 48.2 166 166 161198.doc -73 - 201233328 Unit Formulation 9 (Days 3-9) Formulation 10 (Days 3-9) Formulation 11 (Days 3-9) Biotin mg 16.4 56.0 56.0 Sodium citrate mg 9.81 34 34 Cyanocobalamin mg 1.3 4.5 4.5 Gasification nano g 32.1 65.4 231.9 Vitamin A, D3, E, K1 g 30.9 44.8 44.8 RRR A-tocopherol g 6.24 9.1 9.1 Vitamin A g palmitate 1.17 1.7 1.7 Vitamin K1 mg 67.9 98.5 98.5 Vitamin D3 mg 8.22 11.9 11.9 Citric acid g 29.8 29.8 29.8 Inositol g 25.8 12.9 12.9 Mixed carotenoid premix g 23.8 23.8 23.8 Lycopene mg 119 119 119 Lutein mg 50 50 50 β carotene mg 26.2 26.2 26.2 Sulfuric acid Iron g 16.2 60.9 60.9 L-meat test g 5.51 3.28 5.51 potassium citrate g 3.10 895.0 1060 vitamin Β 2 mg 599 1500 1500 vitamin A mg --- 780 780 palmitate vitamin A mg --- 425 425 copper sulfate mg -- - 391 Formulations were prepared by preparing at least two separate slurries, then blending them together, heat treating, normalizing, and then performing aseptic processing and filling. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides) in water at 74 ° C -79 ° C, followed by the addition of citric acid, magnesium hydride, potassium hydride, potassium citrate, gasification Choline and sodium chloride (minerals vary depending on the formulation) to prepare a carbohydrate-mineral slurry. The resulting slurry was maintained at 49 ° C - 60 ° C with moderate agitation until it was subsequently blended with other prepared slurries. Preparation of oil-packed protein slurry by mixing high oleic safflower oil, coconut oil, monoglyceride and soy lecithin under heating and heating to 66 ° C -79 ° C 161198.doc -74 - 201233328 After standing for 10-15 minutes, the soybean oil, the oil-soluble vitamin premix, the mixed carotenoid premix, the carrageenan, the calcium citrate, the calcium hydrogen phosphate, the ARA oil are added to the slurry. , DHA oil and whey protein concentrate. The resulting oil slurry was at 49. (: -6 〇t kept under moderate agitation until it is subsequently blended with other prepared slurries. The water is heated to 49K0 ° C and then with sufficient agitation with carbohydrates _ mineral slurry, skim milk and The oil-in-oil slurry was combined. The pH of the resulting blend was adjusted with potassium hydroxide. The blend was maintained at 49 ° C. at -60 ° C. The resulting blend was heated to 74eC-79t: Emulsified to 900-1100 psig via a single stage homogenizer and then heated to 144t_147t for about 5 seconds. The heated blend is passed through a flash cooler to bring the temperature down to 88<t and the temperature is passed through the plate cooler to bring the temperature It was further reduced to 74 〇 c _85. The cooled blend was then homogenized at 2900·3100/400-600 psig and maintained at 7 to 85. (: 16 seconds and then cooled to 2. (: _7. The sample used for the analysis test. The mixture was kept under stirring. The water-soluble vitamin (WSV) solution and the anti-bad money solution were separately prepared and added to the treated blended slurry. The following ingredients were added to the water by difficulty. To prepare vitamin solution: citric acid unloading, sulfur Ferrous acid, premix, L. meat test, vitamin (4), inositol and (iv) acid-choline premix. By adding potassium hydroxide and anti-bad ▲ acid to the foot to transfer the ingredients The amount of water was used to prepare a solution of the bad money. Then the pH of the solution was adjusted to 5-9 with potassium hydroxide solution. The pH of the blend was adjusted to pH range 6.8-7.0 with potassium hydroxide to obtain 161198.doc •75·201233328 Good product stability. The standardized blend is then subjected to a second heat treatment by a sterile processor. The blend is preheated to 63 ° C - 74 ° C and homogenized at 200 psig. The blend is further heated to 141 ° C. -144 ° C and passed through the holding tube. Cool the heated blend to lower the temperature to 74 ° C -85 ° C and then homogenize at 1200 / 200 psig. Further cool the blend to 16 ° C -27 ° C and then aseptically filled into a suitable container at 21 ° C. Examples 12-15 In these examples, powders with high or low micronutrient content were prepared for Day 1-2 infant formula and Day 3-9 infant formula The ingredients used to prepare the formulation are set forth in Table 4 below. Table 4 Formulation 12 (Day 1-2) Formulation 13 (Day 1-2) Formulation 14 (Sections 3-9) Formulation 15 (Days 3-9) Kcal/L 270 250 406 420 Low nutrient content to low component unit per 1000 kg batch content Lactose kg 376.90 288.6 406.4 380.4 Skim milk powder kg 223.00 223.1 201.1 201.1 High oleic acid safflower Sub-oil kg 109.30 108.5 97.69 97.7 galacto-oligosaccharide kg 81.70 84.7 104.1 104.10 Soybean oil kg 81.70 82.4 74.21 74.2 Hazelnut oil kg 75.30 75.9 68.36 68.4 Whey protein concentrate kg 48.80 54.9 49.50 49.5 Potassium citrate kg 8.52 42.6 11.12 22.0 ARA Oil kg 7.20 7.43 4.643 4.57 Whey protein hydrolysate kg 6.80 ... — ... Calcium carbonate kg 3.76 --- 2.839 1.5 Tricalcium phosphate kg 24.1 2.638 10.9 DHA oil kg 2.70 2.8 1.752 1.7 Ascorbic acid kg 2.03 3.20 2.006 2.0 Nucleotide · Gallbladder Alkali premix kg 2.01 5.9 2.346 3.6 Calcium carbonate kg 1.154 --- 1.219 ... Vitamin/Mineral/Taurine premix kg 1.116 2.8 1.116 1.7 161198.doc -76- 201233328 Formula 12 (Day 1-2 Formulation 13 (Day 1-2) Formulation 14 (Days 3-9) Formulation 15 (Days 3-9) Taurine g 341 859.9 341 528.9 Inositol g 248 624.3 248 384.0 Sulfur辞 g 114 287.9 114 177.1 Nicotinamide gg 72.8 183.5 72.8 112.9 Calcium pantothenate g 43.7 110 43.7 67.7 Ferrous sulfate g 38.2 96.3 38.2 59.2 Copper sulfate g 13.4 33.8 13.4 20.8 Hydrochloric acid hydrochloride 1 g 11.3 28.5 11.3 17.5 Vitamin Β 2 g 4.98 12.60 4.98 7.72 Hydroquinone hydrochloride 6 g 4.58 11.5 4.58 7.07 Folic acid g 1.53 3.9 1.53 2.4 Sulfuric acid g 1.3 3.27 1.3 2.01 Biotin mg 441 1100 441 683 Sodium selenate mg 264 666.1 264 410 Cyanocobalamin mg 35.1 88.6 35.1 54.5 Soybean egg dish Grease kg 1.120 1.1 1.112 1.1 Magnesium sulfide kg 0.839 6.6 1.437 3.4 Potassium chloride kg --- 2.6 ... 2.3 Ascorbyl palmitate g 459.25 348.1 313.5 313.6 Carotenoid premix g 454.02 463.0 286.6 286.6 Lycopene g 2.27 2.27 1.43 1.41 Lutein mg 953 953 602 589.9 β-carotene mg 499 499 315 308.9 Ferrous sulfate g 453.5 1100 453.6 703.1 Gas choline g 432.1 1100 432.1 670.2 Gasification nano g 388.0 7100 1138 2900 Vitamin A, D3, Ε, K1 g 385.24 914.5 327.3 568.8 RRR A-tocopherol acetate 77.9 184.9 66.2 115.0 Palmitic acid vitamin A g 1 4.63 34.7 12.4 21.6 Vitamin K1 mg 847 2000 720 1250 Vitamin D3 mg 102.3 243.5 87.1 151.4 Mixed tocopherol g 246.3 153.4 138.2 138.2 L-Flesh g 26.3 66.3 23.3 40.8 Vitamin B2 g 3.2 8.0 3.2 4.9 1 N Potassium hydroxide as needed The formulation may be prepared as needed by preparing at least two separate slurries, then blending them together, heat treating, normalizing, second heat treating, evaporating to remove water, and finally spray drying. Initially, by dissolving selected carbohydrates (eg, milk 161198.doc -77-201233328 sugar, galacto-oligosaccharides) in water at 60 ° C - 71 ° C, followed by the addition of magnesium sulfate, potassium carbonate, lemon The potassium carbonate, the gasified choline, and the sodium carbonate (different minerals depending on the formulation) are used to prepare a carbohydrate-mineral slurry. The resulting batch was kept under moderate agitation at 49 ° C - 60 ° C until it was subsequently blended with the other prepared slurries. By combining linoleic acid safflower oil, soybean oil and raisin oil at 4 9 C - 60 C, then adding palmitic acid ascorbate, mixed fertility, soy-printed phospholipids, oil-soluble vitamin premix, milk The proteinaceous protein slurry is prepared by clear protein concentrate, whey protein hydrolysate (in some cases), carotenoid premix, and calcium carbonate (and/or tricalcium phosphate). The resulting oil slurry was kept under moderate agitation at 38 ° - 49 ° C until it was subsequently blended with other prepared slurries. The water, carbohydrate-mineral slurry, skim milk and oil-in-oil slurry were combined with sufficient agitation. The pH of the resulting blend was adjusted with potassium hydroxide. The blend was maintained under moderate agitation at 49*t-60t. ARA oil and DHA oil were added after the 15^1 value was adjusted and before processing. The resulting blend was heated to 71 t-77 ° C, emulsified to a maximum of 300 psig via a single stage homogenizer and then heated to 82 〇 c_88 t: held for about 5 seconds. The heated blend was passed through a flash cooler to bring the temperature down to 77 < t _82 < t, and then passed through a plate cooler to further reduce the temperature to 71 _ 77 艽 ^ and then the cooled blend at 2400-2600 / Homogenized at 400-600 psig, maintained at 74t-85. . The next 16 seconds and then cooled to 2t-rc. Obtain samples for analytical testing. The mixture is at 2. 〇-7. (: Keep under stirring. Separately prepare water-soluble vitamin (WSV) solution and ascorbic acid solution and add 16I198.doc •78· 201233328 to the treated blending slurry. Add the following ingredients to the water by stirring To prepare vitamin solutions: potassium citrate, ferrous sulfate, wsv premix L meat test, vitamin B2 and nucleotide _ biliary test premix (specific components vary depending on the formulation). By using potassium hydroxide and The ascorbic acid solution is prepared by adding ascorbic acid to the amount of water sufficient to dissolve the components. The pH of the ascorbic acid solution is then adjusted to 5-9 with potassium oxynitride. The pH of the blend is adjusted to a pH range of 6 6 用 with potassium hydroxide. 6 9 〇 to obtain the best product stability. Then the standardized blend is subjected to a second heat treatment. The blend is initially heated to 66 ° C _82t:, and then further heated to ~ 18 ° C - 124 ° C to maintain about 5 The second heated mixture was passed through a flash cooler to reduce the temperature to 7 rc-82 t. After the heat treatment, the blend was steamed: to a density of 1.15 - 1.17 g / mL. The evaporated blend passed through a spray dryer To achieve water in the finished powder The content is 2.5% of the mesh #. The finished powder is then coalesced together with water into a binder solution. The finished product is then packaged into a suitable container. Example 16 In this example, the energy content is evaluated for buffering capacity and cushioning strength of the infant formula. Effects. Specifically, the buffering capacity and buffering strength of the various Day 2 infant formulas of the present invention and the infant formulas of Days 3-9 are determined and sterilized with a commercially available powdered infant formula, a commercially available ready-to-serve type 2 tray. The control infant formula, the commercially available ready-to-eat 32-plate aseptically sterilized control infant formula, and the buffering capacity and buffer strength of the human milk were compared. The ingredients used to prepare the control formulation are set forth in Table 5 below. 161198.doc -79· 201233328 Table 5 Control Formula 1 (Powder) Control Formula 2 (Sterilization Sterilization) Control Formula 3 (sterile sterilization) Kcal/L 676 676 676 Ingredient unit contains 3 water kg per 1000 kg batch... QSQS Concentrated skim milk kg 698.5 83.61 86.64 Lactose kg 386.0 54.88 54.7 High oleic acid safflower oil kg 114.4 14.07 14.0 Soybean oil kg 85.51 10.54 10.5 Norse oil kg 78.76 10.05 10.0 galacto-oligosaccharide Kg 69.50 8.630 8.60 Whey protein concentrate kg 51.08 6.120 6.52 Potassium citrate g 9168 518.3 418.07 Calcium carbonate g 4054 508.5 477.16 ARA oil g 2949 355.6 378.16 Nucleotide-choline premix g 2347 293.2 293.26 Gasification _ g 1295 208.5 282.24 Carrageenan g — 175.0 240.00 Ascorbic acid G 1275 727.5 582.12 Soy lecithin G 1120 534.6 356.11 Stabilizer G --- 534.6 356.11 Vitamin / breaking substance / taurine premix G 1116 142.8 142.77 Taurine G 340.5 43.66 43.654 m_inositol G 247.9 31.70 31.695 Zinc sulfate G 114.2 14.62 14.617 Nicotinamide G 72.78 9.323 9.3157 Calcium pantothenate G 44.16 5.587 5.5860 Ferrous sulfate G 39.24 4.880 4.8870 Copper sulfate G 13.68 1.714 1.7143 Vitamin B1 G 11.30 1.445 1.4456 Vitamin B2 Mg 4985 637.6 637.47 Vitamin B6 Hydrochloric acid B6 Mg 4572 584.1 583.96 Folic acid Mg 1535 196.4 215.72 Sulfuric acid Meng 1306 166.3 166.25 Biotin Mg 441.0 56.41 56.390 Sodium citrate Mg 261.8 33.82 33.820 Cyanocobalamin Mg 35.17 4.493 4.500 DHA oil G 1113 135.4 130.01 Magnesium hydride G 1038 141.5 140.46 Gasification G 579.4 As needed 161198.doc -80- 201233328 Control Formula 1 (Powder) Control Formula 2 (Sterilization Sterilization) Control Formula 3 (sterile sterilization) Ferrous Sulfate G 453.6 58.02 58.03 Gasified Choline G 432.1 54.02 50.02 Vitamins A, D3, Ε, K1 G 377.2 47.50 44.76 RRR A-tocopherol G 76.23 9.604 9.0507 Vitamin E palmitate AG 14.32 1.803 1.6998 Vitamin K1 Mg 829.3 104.5 98.47 Vitamin D3 Mg 100.4 12.65 11.92 Citric acid G — 29.80 29.77 Ascorbyl palmitate G 361.3 ... — Carotenoid premix G 350.1 23.80 42.91 Lycopene Mg 1720 119.0 214.55 Lutein Mg 735 49.98 90.11 Beta-carotene Mg 385 26.18 47.201 Mixed tocopherol G 159.2 — one mixed tocopherol G 111.4 - -- ... L-meat test G 26.30 3.285 3.28 Vitamin Β 2 G 3.181 1.166 1.4994 Tricalcium phosphate G 0-5230 12.5 41.89 Potassium dihydrogen phosphate G ... 11.01 36.60 Palmitic acid vitamin A Mg ... 776.16 Palmitic acid vitamin A Mg -- - 427.19 α Fertility Mg --- 7.760 Dipotassium hydrogen phosphate Kg 0-5.23 ... — 1ΝΚΟΗ Kg As needed 1. 583 Potassium hydroxide G as needed 79.15 Prepare Control Formulation 1 as described in Examples 12-15 above; Prepare Control Formulation 2 as described in Examples 1-8 above and prepare as described in Examples 9-11 above Control Formula 3. Determination of the buffering capacity and buffering strength of a variety of Day 1-2 ready-to-eat (RTF) Sterilization Sterilization or Reconstituted Powder Formulations and Day 3-9 RTF Sterilization, RTF Sterile or Reconstituted Powder Formulations and Control Formulations 1-3 And the buffer capacity and buffer strength of human milk are compared. Specifically, formula (or human milk) 161198 was determined by adding 0.5 mL of an aliquot of 0.10 M HCl to 50 mL of each formulation (or a reconstituted formulation in the case of a powder formulation) at 1 minute intervals. Doc -81 - 201233328 Buffer strength. The pH of each formulation was measured after each aliquot was added. Buffer strength is reported as the amount of 0.10 M HC1 mL required to reduce the pH of the 50 mL formulation to 3.0. The buffering capacity of the formulation (or human milk) was determined by adding 5.00 mmol of HCl to 100 mL of each formulation (or a reconstituted formulation in the case of a powder formulation). The buffering capacity is reported as the increase in [H+] after the addition of HC1. The results are shown in Table 6 below and Figures 1 and 2. Table 6

配方 能量(kcal/L) 形式 緩衝強度d 緩衝能 對照配方1 676 粉末a 25.8 0.776 mM 配方14(第3-9天） 406 粉末b 17.1 9.55 mM 配方14(第3-9天)c 406 粉末b 17.0 9.33 mM 配方12(第1-2天） 270 粉末b 11.4 20.0 mM 對照配方2 676 殺菌釜滅菌 25.1 0.977 mM 配方5(第3-9天） 406 殺菌釜滅菌 16.8 7.94 mM 配方5(第3-9天)c 406 殺菌釜滅菌 16.2 9.12 mM 配方2(第1-2天） 270 殺菌釜滅菌 13.2 13.2 mM 配方2(第I-2天)e 270 殺菌釜滅菌 11.9 17.8 mM 配方1(第1-2天） 270 殺菌釜滅菌 10.8 18.6 mM 對照配方3 676 無菌滅菌 23.3 1.86 mM 配方9(第3-9天） 406 無菌滅菌 16.1 10.5 mM 人乳 11.6 14.1 mM a在測定緩衝能力及緩衝強度前，使用35.0 g配方加240 mL水復原對照配方1。 b在測定緩衝能力及緩衝強度前，分別使用12.2 g配方及 2 1.4 g配方，加240 mL水復原配方12及14。 ^配方2、5及14測試兩次。 d使50 mL配方之pH值降至3.0所需之0.10 M HC1毫升量。 e向10〇1111^配方中添加5.0〇111111〇111(31後[11+]之增加量。 161198.doc •82· 201233328 如可自該等結果可見，調配物之緩衝能力隨能量含量降 低而降低。能量含量為270 kcal/L之第1-2天配方之緩衝能 力在所有測試配方中最低。已報導人乳之緩衝強度在9.0 至18.0範圍内，平均為13.5。如可自表6以及圖1及2中闡述 之結果可見，第1 -2天配方之緩衝強度與所測試人乳之緩 衝強度相當或低於所測試人乳之緩衝強度。 本發明之配方，且尤其第1-2天配方之降低之緩衝能力 及緩衝強度可向嬰兒提供生理學效益。詳言之，緩衝能力 及強度降低可幫助貪現更有利的腸道微生物群落分佈且可 增加使經口攝取之腸病原體失活之有效性。 實例17 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定本發明之第1 -2天（配方13) 及第3-9天（配方15)粉末嬰兒配方在復原後之緩衝能力及緩 衝強度且與市售粉末對照嬰兒配方（對照配方i )在復原後之 緩衝能力及緩衝強度進行比較。 使用12,2 g配方加240 mL水復原配方13，使用21.4 g配 方加240 mL水復原配方15且使用35.0 g配方加240 mL水復 原對照配方1。測定各配方之緩衝能力及緩衝強度。明確 言之，藉由以1分鐘時間間隔向1 〇〇 mL復原配方中添加 1.00 mL 0.500 M HC1之等分試樣來測定配方之緩衝強度。 在添加各等分試樣後量測各配方之pH值。緩衝強度報導為 使100 mL復原配方之pH值自6.00降至3.00所需HC1之毫莫 耳量。藉由向100 mL各復原配方中添加5.50 mmol HC1來 161198.doc -83- 201233328 測定配方之緩衝能力。缓衝能力報導為添加HC1後[H+]之 增加量及添加HC1後pH值降低量。結果展示於以下表7以 及圖3 - 6中。 表7Formula Energy (kcal/L) Form Buffer Strength d Buffer can be compared to Formula 1 676 Powder a 25.8 0.776 mM Formulation 14 (Days 3-9) 406 Powder b 17.1 9.55 mM Formulation 14 (Days 9-9) c 406 Powder b 17.0 9.33 mM Formulation 12 (Day 1-2) 270 Powder b 11.4 20.0 mM Control Formulation 2 676 Sterilization Sterilization 25.1 0.977 mM Formulation 5 (Days 3-9) 406 Sterilization Sterilization 16.8 7.94 mM Formula 5 (Part 3 9 days) c 406 Sterilization Sterilization 16.2 9.12 mM Formulation 2 (Day 1-2) 270 Sterilization Sterilization 13.2 13.2 mM Formulation 2 (Day I-2) e 270 Sterilization Sterilization 11.9 17.8 mM Formulation 1 (Part 1 2 days) 270 Sterilization Sterilization 10.8 18.6 mM Control Formulation 3 676 Sterile Sterilization 23.3 1.86 mM Formulation 9 (Days 3-9) 406 Sterile Sterilization 16.1 10.5 mM Human Milk 11.6 14.1 mM a Before measuring buffer capacity and buffer strength, use A 35.0 g formula plus 240 mL water was used to restore Control Formula 1. b Before formulating buffer capacity and buffer strength, use 12.2 g formula and 2 1.4 g formula, and add 240 mL water to restore formulas 12 and 14. ^ Recipe 2, 5 and 14 were tested twice. d Reduce the pH of the 50 mL formulation to the amount of 0.10 M HC1 mL required for 3.0. e Add 5.0〇111111〇111 to the 10〇1111^ formula (after 31 [11+] increase. 161198.doc •82· 201233328 As can be seen from these results, the buffering capacity of the formulation decreases with energy content. Reduced. The buffer capacity of the first 1-2 days of the energy content of 270 kcal / L is the lowest in all test formulations. The buffer strength of human milk has been reported to be in the range of 9.0 to 18.0 with an average of 13.5. As can be seen from the results illustrated in Figures 1 and 2, the buffer strength of the first 1-2 day formulation is comparable to or lower than the buffer strength of the human milk tested. The formulation of the present invention, and especially the first 1-2 The reduced buffering capacity and cushioning strength of the formula can provide physiological benefits to the infant. In particular, the reduction in buffering capacity and strength can help to promote a more favorable distribution of intestinal microflora and increase the loss of intestinal pathogens for oral ingestion. The effectiveness of the activity. Example 17 In this example, the effect of energy content on the buffering capacity and buffer strength of the infant formula was evaluated. Specifically, the first 1-2 days (Formulation 13) and Days 3-9 of the present invention were determined. (Formulation 15) Powder Baby The buffer capacity and buffer strength after recovery were compared with the buffered capacity and buffer strength of the commercially available powder control infant formula (control formula i). Formulation 13 was used to restore formula 13 using 12,2 g formula plus 240 mL water. 21.4 g of formula plus 240 mL of water to reconstitute Formulation 15 and use 35.0 g of formula plus 240 mL of water to restore Control Formulation 1. Determine the buffering capacity and buffering strength of each formulation. Clearly, by 1 minute at 1 minute intervals An aliquot of 1.00 mL of 0.500 M HC1 was added to the reconstituted formula to determine the buffer strength of the formulation. The pH of each formulation was measured after each aliquot was added. The buffer strength was reported as the pH of the 100 mL recovery formulation. The millimolar amount of HC1 required for 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 5.50 mmol of HC1 to 100 mL of each reconstituted formula. 161198.doc -83 - 201233328 The buffering capacity was reported after the addition of HC1 [H+ The amount of increase and the decrease in pH after the addition of HC1. The results are shown in Table 7 below and in Figure 3-6.

配方13(第1-2天） 配方15(第3-9天） 對照配方1 Kcal/L 250 420 676 緩衝強度(mmol) 3.41 3.81 4.56 緩衝能力-pH降低量 4.84 4.52 4.02 緩衝能力·丨H+】增加量 6.17 mM 4.17 mM 1.20 mM 如可自表7及圖3-6中闡述之結果可見，第1-2天配方及 第3-9天配方之緩衝強度及緩衝能力（如由pH值降低量及 [H+]增加量量測）均顯著低於對照配方之緩衝強度及緩衝 能力。能量含量為250 kcal/L之第1-2天配方在所有測試配 方中緩衝能力及緩衝強度最低，表示緩衝強度及緩衝能力 隨能量含量降低而降低。 實例18 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定2盘司本發明之殺菌釜滅 菌第1-2天嬰兒配方（配方3)之緩衝能力及緩衝強度且與2盘 司市售殺菌釜滅菌對照嬰兒配方（對照配方2)之緩衝能力及 緩衝強度進行比較。 測定各配方之緩衝能力及緩衝強度。明確言之，藉由以 1分鐘時間間隔向50 mL各配方中添加0.50 mL 0.500 M HC1 之等分試樣來測定配方之緩衝強度。在添加各等分試樣後 量測各配方之pH值。緩衝強度報導為使50 mL配方之ΡΗ值 自6.00降至3.00所需Ηα之毫莫耳量。藉由向mL各配方 161198.doc •84- 201233328 中添加2.75 mmol HC1來測定配方之緩衝能力。緩衝能力 報導為添加HC1後[H+]增加量及添加HC1後pH值降低量。 結果展示於以下表8中。 表8Formulation 13 (Day 1-2) Formulation 15 (Days 3-9) Control Formula 1 Kcal/L 250 420 676 Buffer Strength (mmol) 3.41 3.81 4.56 Buffer Capacity - pH Reduction 4.84 4.52 4.02 Buffer Capacity · 丨H+ Increasing amount 6.17 mM 4.17 mM 1.20 mM As can be seen from the results described in Table 7 and Figure 3-6, the buffer strength and buffering capacity of the formulation on Days 1-2 and Days 3-9 (eg, by pH reduction) And [H+] increase measurement) were significantly lower than the buffer strength and buffer capacity of the control formulation. Formulations 1-2 days with an energy content of 250 kcal/L have the lowest buffering capacity and buffer strength in all test formulations, indicating that buffer strength and buffer capacity decrease with decreasing energy content. Example 18 In this example, the effect of energy content on the buffering capacity and buffer strength of an infant formula was evaluated. Specifically, the buffer capacity and buffer strength of the infant formula (Formulation 3) of the 1-2 days of sterilization of the sterilization machine of the present invention were measured, and the infant formula (control formula 2) was sterilized with 2 trays. Buffering capacity and buffering strength were compared. The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 0.50 mL of an aliquot of 0.500 M HC1 to 50 mL of each formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the millimolar amount of Ηα required to reduce the enthalpy of the 50 mL formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 2.75 mmol of HC1 to each of the mL formulations 161198.doc •84-201233328. The buffering capacity is reported as the amount of [H+] increase after the addition of HC1 and the decrease in pH after the addition of HC1. The results are shown in Table 8 below. Table 8

配方3(第1-2天） 對照配方2 Kcal/L 250 676 緩衝強度(mmol) 1.53 2.28 緩衝能力-pH降低《量 4.34 4.13 緩衝能力-[H+]增加量 10.7 mM 3.72 mM 如可自表8中闡述之結果可見，第1-2天配方之緩衝強度 及緩衝能力（如由pH值降低量及增加量量測）均顯著低於對 照配方之緩衝強度及緩衝能力，顯示本發明之低熱量第1-2天殺菌釜滅菌配方之緩衝強度及緩衝能力低於習知全熱 量嬰兒配方之緩衝強度及緩衝能力。 實例19 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定32盎司本發明之無菌滅菌 第3-9天嬰兒配方（配方11)之緩衝能力及緩衝強度且與32盎 司市售無菌滅菌對照嬰兒配方（對照配方3)之緩衝能力及緩 衝強度進行比較。 測定各配方之緩衝能力及緩衝強度。明確言之，藉由以 1分鐘時間間隔向100 mL各配方中添加1.00 mL 0_500 Μ HC1之等分試樣來測定配方之緩衝強度。在添加各等分試 樣後量測各配方之pH值。缓衝強度報導為使100 mL配方 之pH值自6.00降至3.00所需HC1之毫莫耳量。藉由向100 mL各配方中添加5.50 mmol HC1來測定配方之緩衝能力。 161198.doc • 85 · 201233328 緩衝能力報導為添加HC1後[H+]增加量及添加HC1後pH值 降低量。結果展示於以下表9中。 表9Formula 3 (Day 1-2) Control Formula 2 Kcal/L 250 676 Buffer Strength (mmol) 1.53 2.28 Buffer Capacity - pH Reduction "Quantity 4.34 4.13 Buffer Capacity - [H+] Increase 10.7 mM 3.72 mM As shown in Table 8 As can be seen from the results, the buffer strength and buffering capacity of the formulation on Day 1-2 (as measured by pH reduction and increase) are significantly lower than the buffer strength and buffering capacity of the control formulation, indicating the low heat of the present invention. The buffer strength and buffering capacity of the Sterilization Sterilization Formulation on Day 1-2 are lower than the buffer strength and buffering capacity of the conventional full calorie infant formula. Example 19 In this example, the effect of energy content on the buffering capacity and buffer strength of an infant formula was evaluated. Specifically, the buffer capacity and buffer strength of 32 ounces of the Aseptic Sterilization Day 3-9 infant formula (Formulation 11) of the present invention were determined and buffered and buffered with 32 ounces of commercially available sterile sterile control infant formula (Control Formula 3). The strength is compared. The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 1.00 mL of an aliquot of 0_500 Μ HC1 to 100 mL of each formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the millimolar amount of HC1 required to reduce the pH of the 100 mL formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 5.50 mmol of HCl to 100 mL of each formulation. 161198.doc • 85 · 201233328 The buffer capacity is reported as the increase in [H+] after the addition of HC1 and the decrease in pH after the addition of HC1. The results are shown in Table 9 below. Table 9

配方11(第3-9天） 對照配方3 Kcal/L 410 676 緩衝強度(mmol) 3.46 3.84 緩衝能力-pH降低量 4.78 4.54 緩衝能力·丨H+]增加量 8.51 mM 5.50 mM 如可自表9中闡述之結果可見，第3-9天配方之緩衝強度 及緩衝能力（如由pH值降低量及增加量量測）均顯著低於對 照配方之緩衝強度及緩衝能力，顯示本發明之低熱量第3_ 9天無菌滅菌配方之緩衝強度及緩衝能力低於習知全熱量 嬰兒配方之緩衝強度及緩衝能力。 實例20 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定復原之本發明之第1 _2 天粉末嬰兒配方（配方13)及復原之本發明之第3-9天粉末嬰 兒配方（配方15)在活體外腸胃消化後之蛋白質水解程度， 且與復原之粉末對照嬰兒配方（對照配方1)之蛋白質水解程 度進行比較。 使用12.2 g配方加240 mL水復原配方13，使用21.4 g配 方加240 mL水復原配方15且使用35.0 g配方加240 mL水復 原對照配方1。藉由使復原配方經活體外腸胃消化來製備 消化物。明確言之，使用6 M HC1調節40 mL各復原配方之 pH值至4.5。1.00 mL USP胃蛋白酶（於水中以56 „^/111[製 備）添加至配方中且在室溫下攪拌所得混合物1小時。使用 161198.doc -86 - 201233328 10 N NaOH調節混合物之pH值至7.2。接著添加4.00 mL USP胰酶澱粉酶/蛋白酶（於水中以6.94 mg/mL製備）加USP 胰酶脂肪酶（於水中以6.94 mg/mL製備）且在室溫下攪拌混 合物2小時。所得消化物在20°C下以31，000xg離心4小時。 使用Superdex®肽10/3 00 GL凝膠過濾管柱（Amersham Biosciences)藉由HPLC分析上清液。明確言之，5 mg上清 液添加至1 mL移動相溶液（700 mL Milli-Q®水、300 mL乙 腈、1.00 mL TFA)中且所得溶液在環境溫度下運行於 Superdex®管柱上（流動速率：0.4毫升/分鐘；彳貞測：205 nm下UV ;注射：10 μί ;運行時間：80分鐘）以測定消化 物中蛋白質之分子量中值及消化物中分子量大於5000道爾 頓之蛋白質量（佔總蛋白質百分比）。該等測定值為蛋白質 消化程度之指標。亦使用習知方法使用酸水解/胺基酸概 況測試消化物離心後產生之集結塊中不可溶蛋白質之存 在。結果展示於以下表10以及圖7-9中。 表10 配方13 (第1-2天） 配方15 (第3-9天） 對照配方1 Kcal/L 250 420 676 蛋白質MW中值(Da) 777 925 1022 蛋白質>5000 Da(佔總蛋 白質百分比） 8.4% 13.4% 14.0% 不可溶蛋白質a(mg/L) 24 59 156 消化物高速離心後集結塊中之總蛋白質 如可自該等結果可見，與對照配方相比，第1-2天配方 及第3-9天配方中之蛋白質水解更廣泛。此外，所有三種 消化指標（蛋白質MW中值、大於5000 Da之蛋白質量及不 161198.doc • 87 · 201233328 可溶蛋白質量）均隨能量含量降低而降低。該等結果顯示 蛋白質消化率與能量含量反相關。 實例21 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定2盎司本發明之殺菌爸 滅菌第1-2天嬰兒配方（配方3)在活體外腸胃消化後之蛋白 質水解程度且與2盘司市售殺菌爸滅菌對照嬰兒配方（對照 配方2)之蛋白質水解程度進行比較。 使用實例20中闡述之程序藉由使配方經活體外腸胃消化 來製備消化物。消化物在20°C下以31,000xg離心4小時。 使用以上實例20中闡述之程序使用Superdex®肽 10/3 00 GL凝 膠過渡管柱（Amersham Biosciences)藉由HPLC分析上清液， 且測定消化物中蛋白質之分子量中值及消化物中分子量大 於5000道爾頓之蛋白質量（佔總蛋白質百分比）。亦使用實例 20中描述之酸水解/胺基酸型態分析測試消化物離心後產生 之集結塊中不可溶蛋白質之存在。結果展示於以下表11中。 亦使用酸水解及HPLC測試消化物中梅納反應標記物糠 胺酸之存在。該等結果亦展示於以下表11中。 表11 配方3(第1-2天） 對照配方2 Kcal/L 250 676 蛋白質MW中值(Da) 789 992 蛋白質>5000 Da(佔總蛋白質百分比） 3.77% 8.81% 不可溶蛋白質a(mg/L) 48 471 糠胺酸(佔總離胺酸莫耳百分比） 0.84% 2.61% 消化物高速離心後集結塊中之總蛋白質 161198.doc -88 * 201233328 如可自該等結果可見，與對照配方相比，第1 -2天配方 中之蛋白質水解更廣泛。所有三種消化指標（蛋白質MW中 值、大於5000 Da之蛋白質量及不可溶蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。此外，第1 -2天配方之梅納反應標記物糠胺酸含 量低於對照配方。該等結果顯示與習知全熱量嬰兒配方相 比’本發明之低熱量第1 ·2天殺菌釜滅菌配方對梅納反應 之敏感度較低。 實例22 在此實例中’評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定32盎司本發明之無菌滅 菌第3-9天嬰兒配方（配方11)在活體外腸胃消化後之蛋白質 水解程度且與3 2盎司市售無菌滅菌對照嬰兒配方（對照配 方3)之蛋白質水解程度進行比較。Formulation 11 (Days 3-9) Control Formula 3 Kcal/L 410 676 Buffer Strength (mmol) 3.46 3.84 Buffer Capacity - pH Reduction 4.78 4.54 Buffer Capacity · 丨H+] Increase 8.51 mM 5.50 mM As shown in Table 9 As can be seen from the results, the buffer strength and buffering capacity of the formulation on days 3-9 (such as the decrease in pH and the amount of increase) are significantly lower than the buffer strength and buffering capacity of the control formulation, indicating the low calorie content of the present invention. The buffer strength and buffering capacity of the 3_ 9-day aseptic sterilization formula is lower than that of the conventional full-calorie infant formula. Example 20 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, the degree of protein hydrolysis of the reconstituted first 1-2 day powder infant formula (Formulation 13) of the present invention and the reconstituted 3-9 day powder infant formula of the present invention (Formulation 15) after intestine digestion in vitro, And compared to the degree of protein hydrolysis of the reconstituted powder control infant formula (Control Formula 1). Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of Formulation plus 240 mL of water and Formulation 1 was reconstituted using 35.0 g of Formula plus 240 mL of water. The digest is prepared by in vitro digestion of the reconstituted formula. Specifically, use 6 M HC1 to adjust the pH of each 40 mL recovery formula to 4.5. 1.00 mL USP pepsin (added to the formulation at 56 „^/111 [preparation] in water and stir the resulting mixture at room temperature 1 Hour. Use 161198.doc -86 - 201233328 10 N NaOH to adjust the pH of the mixture to 7.2. Then add 4.00 mL USP trypsin amylase / protease (prepared in water at 6.94 mg / mL) plus USP trypsin lipase (in The mixture was prepared at 6.94 mg/mL in water and the mixture was stirred at room temperature for 2 hours. The resulting digest was centrifuged at 31,000 xg for 4 hours at 20 ° C. Superdex® peptide 10/3 00 GL gel filtration column (Amersham) Biosciences) The supernatant was analyzed by HPLC. Specifically, 5 mg of the supernatant was added to 1 mL of mobile phase solution (700 mL Milli-Q® water, 300 mL acetonitrile, 1.00 mL TFA) and the resulting solution was at ambient temperature. Run on a Superdex® column (flow rate: 0.4 ml/min; speculation: UV at 205 nm; injection: 10 μί; run time: 80 minutes) to determine the molecular weight of the protein in the digest and digest The amount of protein with a molecular weight greater than 5000 Daltons (accounting for Total protein percentage. These measurements are indicators of the degree of protein digestion. The presence of insoluble proteins in the agglomerates produced by centrifugation of the digests was also tested using acid hydrolysis/amino acid profiles using conventional methods. The results are shown in the table below. 10 and Figure 7-9. Table 10 Formulation 13 (Day 1-2) Formulation 15 (Days 3-9) Control Formula 1 Kcal/L 250 420 676 Protein MW Median (Da) 777 925 1022 Protein > 5000 Da (% of total protein) 8.4% 13.4% 14.0% Insoluble protein a (mg/L) 24 59 156 Total protein in the agglomerate after high-speed centrifugation of the digestible can be seen from these results, compared with the control formula The protein hydrolysis in Formulation 1-2 and Formula 3-9 is more extensive. In addition, all three digestion indicators (median MW protein, protein amount greater than 5000 Da and not 161198.doc • 87 · 201233328 soluble) Protein quality) decreased with decreasing energy content. These results showed that protein digestibility was inversely related to energy content.Example 21 In this example, the energy content of infant formula was evaluated for the rate and extent of protein hydrolysis. Specifically, the degree of protein hydrolysis of the 2 ounce infant formula (Formulation 3) of the sterilized dad sterilization of the present invention after intestine digestion in vitro was determined and compared with the 2 infants marketed sterilization dad sterilization control infant formula (control) The degree of protein hydrolysis of Formulation 2) was compared. The digest was prepared using the procedure set forth in Example 20 by digesting the formulation in vitro and in vivo. The digest was centrifuged at 31,000 xg for 4 hours at 20 °C. The supernatant was analyzed by HPLC using a Superdex® Peptide 10/3 00 GL Gel Transition Column (Amersham Biosciences) using the procedure set forth in Example 20 above, and the median molecular weight of the protein in the digest and the molecular weight in the digest were determined to be greater than A protein content of 5000 daltons (% of total protein). The acid hydrolysis/amino acid type analysis described in Example 20 was also used to test for the presence of insoluble proteins in the agglomerates produced after centrifugation of the digest. The results are shown in Table 11 below. The presence of the Mena reaction label guanamine in the digest was also tested using acid hydrolysis and HPLC. These results are also shown in Table 11 below. Table 11 Formulation 3 (Day 1-2) Control Formula 2 Kcal/L 250 676 Protein MW Median (Da) 789 992 Protein > 5000 Da (% of total protein) 3.77% 8.81% Insoluble Protein a (mg/ L) 48 471 Proline (% of total oleic acid molars) 0.84% 2.61% Total protein in agglomerates after high-speed centrifugation of digested 161198.doc -88 * 201233328 As can be seen from these results, and control formula In contrast, protein hydrolysis in the first 1-2 day formulation is more extensive. All three digestion indicators (median MW protein, protein content greater than 5000 Da, and insoluble protein) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. In addition, the Maya reaction label methionine content of the first 1-2 day formulation was lower than the control formulation. These results show that the low calorie day 1 day sterilization autoclave formulation of the present invention is less sensitive to the Mena reaction than the conventional full calorie infant formula. Example 22 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was evaluated. Specifically, the degree of protein hydrolysis of 32 ounces of the sterile sterile 3-9 day infant formula of the present invention (Formulation 11) after parenteral digestion in vitro was compared to 32 ounces of commercially available sterile sterile control infant formula (Control Formula 3). The degree of protein hydrolysis is compared.

使用實例20中闡述之程序藉由使配方經活體外腸胃消化 來製備消化物。消化物在20°C下以3 1，000xg離心4小時。 使用以上實例20中闡述之程序使用Superdex®肽10/300 GL 凝膠過濾管柱（Amersham Biosciences)藉由HPLC分析上清 液’且測定消化物中蛋白質之分子量（MW)中值及消化物 中分子量大於5000道爾頓之蛋白質量（佔總蛋白質百分 比）。亦使用實例20中描述之酸水解/胺基酸型態分析測試 消化物離心後產生之集結塊中不可溶蛋白質之存在。結果 展示於以下表12中。 I61l98.doc •89- 201233328 表12The digest was prepared using the procedure set forth in Example 20 by digesting the formulation in vitro and in vivo. The digest was centrifuged at 31,000 xg for 4 hours at 20 °C. The supernatant was analyzed by HPLC using a Superdex® Peptide 10/300 GL Gel Filtration Column (Amersham Biosciences) using the procedure set forth in Example 20 above and the median molecular weight (MW) of the protein in the digest and the digest were determined. The amount of protein with a molecular weight greater than 5000 Daltons (% of total protein). The acid hydrolysis/amino acid type analysis described in Example 20 was also used to test for the presence of insoluble proteins in the agglomerates produced after centrifugation of the digest. The results are shown in Table 12 below. I61l98.doc •89- 201233328 Table 12

Kcal/L 配方11(第3-9天1 ^方 3 蛋白質MW中值(Da) 410 799 ~___676 978 蛋白質>5000 Da(佔總蛋白質百分比> 2.5% 9.5% 不可溶蛋白質a(me/L) 110 4〇〇 消化物高速離心後集結塊中之總蛋白質 如可自該等結果可見’與對照配方相比，第3_9天配方 中之蛋白質水解更廣泛。所有三種消化指標（蛋白質MW中 值、大於5000 Da之蛋白質量及不可溶蛋白質量）均隨能量 3量降低而降低。該專結果顯不蛋白質消化率與能量含量 反相關。 實例23 在此實例中’評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定復原之本發明之第1·2 天粉末嬰兒配方（配方13)及復原之本發明之第3-9天粉末嬰 兒配方（配方1 5)在胰酶消化後之蛋白質水解程度，且與復 原之市售粉末對照嬰兒配方（對照配方丨）在胰酶消化後之蛋 白質水解程度進行比較。 使用12.2 g配方加240 mL水復原配方13，使用21.4 g配 方加240 mL水復原配方15且使用35.0 g配方加240 mL水復 原對照配方1。藉由使復原配方經胰酶消化來製備消化 物。明確言之，在20 mL小瓶中，9.00 mL 0.05 Μ NaH2P〇4(pH 7.5)添加至9.00 mL各配方中。2.00 mL豬胰酶 (於pH 7.5緩衝劑中以4.0 g/L製備）添加至配方中且小瓶置 I61198.doc -90- 201233328 放於37°C水浴中71分鐘。71分鐘後，1.5 mL混合物等分試 樣轉移入HPLC自動取樣器小瓶中且捲曲密封小瓶。密封 小瓶置放於1 〇〇°C加熱模組中5分鐘以終止胰酶消化。用 1.00 mL 8.30/6.00 /0.02(v/v)水/乙腈/三氟乙酸稀釋 0.400 mL所得消化物。稀釋之消化物在室溫下以14,000xg離心5 分鐘。使用以上實例20中闡述之程序使用Superdex®肽 10/300 GL凝膝過濾管柱（Amersham Biosciences).藉由 HPLC 分析上清液，且測定消化物中蛋白質之分子量（MW)中值 及消化物中分子量大於5000道爾頓之蛋白質量（佔總蛋白 質百分比）。結果展示於以下表13以及圖10及11中。 表13 配方13(第1-2天） 配方15(第3-9天） 對照配方1 Kcal/L 250 420 676 蛋白質MW中值(Da) 680 748 853 蛋白質>5000 Da(佔總蛋 白質百分比） 2.15% 2.54% 3.03% 如可自該等結果可見，與對照配方相比，第1 -2天配方 及第3-9天配方中之蛋白質水解更廣泛。此外，兩種消化 指標（蛋白質MW中值、大於5000 Da之蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。 實例24 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定2盎司本發明之殺菌釜 滅菌第1-2天嬰兒配方（配方3)在胰酶消化之前及之後的蛋 白質水解程度且與2盎司市售殺菌釜滅菌對照嬰兒配方（對 161198.doc -91 - 201233328 照配方2)在姨麵消化之前及之後的蛋白質水解程度進行比 較。 除嬰兒配方/胰酶混合物保持在37。(：水浴中僅60分鐘 外’使用與實例23中所闡述相同之程序藉由使配方經胰酶 消化來製備消化物。稀釋之消化物在室溫下以14,〇〇〇%離 心5分鐘。使用Superdex®肽10/300 GL凝膠過遽管柱 (Amersham Biosciences)使用以上實例2〇中所闡述之程序 藉由HPLC分析消化之前的上清液以及嬰兒配方之樣品， 且測定消化之前嬰兒配方中蛋白質之分子量中值及6〇分鐘 胰酶消化後蛋白質之中值分子量。結果展示於以下表14 中。 表14 配方3(第1-2天） 對照配方2 Kcal/L 250 676 /月1〇抓贫曰買MW宁值(Da) 14,774 19,120 分鐘消化後查白質MW中信 801 1128 ~—-------' , 如可自該等結果可見，與對照配方相比，低熱量第卜2 天配方中之蛋白質水解速率較快。此外，⑼分鐘騰酶消化 後之MW中值與嬰兒配方之熱量密度成正比，顯示蛋白質 消化率與能量含量反相關。 實例25 在此實例中，5平估嬰兒配方之能量♦量對蛋白質水解速 率及程度之影響。明確言之，測定復原之本發明之第卜2 天粉末嬰兒配方(配方12)或第3_9天粉末嬰兒配方(配方 )盎司本發明之第1-2天殺菌蚤滅菌嬰兒配方（西己方α 161198.doc -92- 201233328 2)或第3-9天殺菌釜滅菌嬰兒配方（配方5)及32盎司本發明 之第3-9天無菌滅菌嬰兒配方（配方9)在胰酶消化（粉末）或 活體外GI消化（液體）後之蛋白質水解程度且與復原之市售 粉末對照嬰兒配方（對照配方1)、2盎司市售殺菌釜滅菌對 照嬰兒配方（對照配方2)及32盎司市售無菌滅菌對照配方 (對照配方3)之蛋白質水解程度進行比較。 使用12.2 g配方加240 mL水復原配方12，使用21.4 g配 方加240 mL水復原配方14且使用35.0 g配方加240 mL水復 原對照配方1。使用與上文所闡述相同之程序藉由使配方 (或復原配方）經胰酶消化來製備消化物。使用以上實例20 中闡述之程序使用Superdex®肽10/300 GL凝膠過濾管柱 (Amersham Biosciences)藉由HPLC分析上清液，且測定消 化物中蛋白質之分子量（MW)中值及消化物中分子量大於 ί;000道爾頓之蛋白質量（佔總蛋白質百分比）。結果展示於 以下表15中。 表15 配方 能量 (kcal/L) 形式 蛋白質MW> 5000 Da (佔總蛋白質百分比） 蛋白質MW 中值(Da) 對照配方1 676 粉末 17.9% 1050 配方14(第3-9天)a 406 粉末 10.9% 846 配方14(第3-9天） 406 粉末 8.4% 812 配方Π(第1-2天） 270 粉末 5.2% 717 對照配方2 676 殺菌釜滅菌 13.7% 988 配方S(第3-9天） 406 殺菌釜滅菌 5.3% 789 配方1(第1-2天） 270 殺菌釜滅菌 3.9% 730 配方2(第1-2天） 270 殺菌釜滅菌 2.9% 707 對照配方3 676 無菌滅菌 10.2% 963 配方9(第3-9天） 406 無菌滅菌 4.1% 801 配方14測試2次。 161198.doc -93- 201233328 如可自該等結果可見’與對照配方相比，第1 _2天配方 及第3-9天配方中之蛋白質水解更廣泛。此外，兩種消化 指標（蛋白質中值MW、大於5000 Da之蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。 實例26 此實例中，評估微量營養素含量對第1-2天殺菌釜滅菌 嬰兒配方及第3-9天無菌滅菌嬰兒配方之乳液穩定性之影 響。明確§之，比較32盘司具有高（配方η)或低（配方9)微 量營養素含量之第3-9天無菌滅菌嬰兒配方之乳液穩定性 及2盎司具有高（配方3)或低（配方丨）微量營養素含量之第卜 2天殺菌爸滅菌嬰兒配方之乳液穩定性。 使用蛋白質負載量（表示為配方高速離心後形成之乳油 層之蛋白質百分比）測定乳液穩定性。各配方之蛋白質負 載量係藉由將36-38公克配方傾入配衡之5〇 mL離心管中且 封蓋離心管來測定。接著將封蓋之離心管置放於JA_2〇定 角旋轉器（Beckman Coulter ’ p/N 334831)中且旋轉器置放 於 Beckman J2-HS 離心機（Beckman c〇uher)中。樣品在 2〇°C下以31，_xg離心8小時。離心後，#品上形成乳油 層◊乳油層轉移入配衡燒杯中且記錄其重量。上清液傾入 獨立燒杯中且再次稱重離心管以測定集結塊重量。 使用酸水解/胺基酸測定技術測定乳油層中之蛋白質 量。結果闡述於以下表16中。 161198.doc •94· 201233328 表16 配方 能量(kcal/L) 微量營養 素含量 形式 乳油層中蛋白質 百分比(重量/重量 百分比近似值） 配方11(第3-9天） 410 無菌滅菌 5.1% 配方9(第3-9天） 406 無菌滅菌 4.7% 配方3(第1-2天） 250 殺菌蚤滅菌 4.6% 配方1(第1-2天） 270 殺菌爸滅菌 5.9% 平均值(η=4) ------- 5.1%±0.6% 蛋白質負載值為乳液穩定性指標。明確言之，乳液穩定 性通常隨蛋白質負載值增加而增加。如可自以上結果可 見，具有低微量營養素含量之第丨_2天殺菌釜滅菌配方（亦 即配方υ中之蛋白質負載值高於具有高微量營養素含量之 苐1-2天殺菌爸滅菌配方（亦即配方3)中之蛋白質負載值。 該等結果顯示，與可比較之具有高微量營養素含量之配方 相比，具有低微量營養素含量之第丨_2天殺菌釜滅菌配方 中之乳液穩定性增加。未發現高微量營養素含量無菌滅菌 配方與低微量營養素含量無菌滅菌配方之間存在蛋白質負 載之顯著差異》 實例27 此實例中，評估微量營養素含量對第3_9天殺菌釜滅菌 配方之乳液穩定性之影響《明確言之，比較2盎司具有高 (配方8)或低（配方6)微量營養素含量之第3_9天殺菌爸滅菌 嬰兒配方之乳液穩定性。 使用蛋白質負載量（表示為配方高速離心後形成之乳油 層之蛋白質百分比）測定乳液穩定性。使用實例26中闡述 之程序測疋各配方之蛋白質負載置。亦計算乳油層量（以 161I98.doc •95· 201233328 全部產品重量計)及乳油層中之蛋白質量(以全部產品重量 計）。結果闡述於以下表17中。 表17 配方 能量 (kcal/L) 微量營 - 含量 乳油層中蛋白質 百分比(w/w) 全部產品之乳油層 蛋白質百分比(w/w、 配乃弟j-9天） 406 6.9% 0.35% 配方8(第3-9天） 410 _高 5.1% 0.22% 等結果可見’具有低微量營養素含量之配方6 中之蛋白質負載值高於高微量營養素配方（亦即配方8)中之 蛋白質負載值。與配方8相比，西己方6亦形成較大的乳油層 且乳油層中之蛋白質百分比（以全部產品重量計）較高《該 等結果顯示’與可比較之具有高微量營養素含量之配方相 比，具有低微量營養素含量之第3_9天殺菌釜滅菌配方中 之乳液穩定性增加。與低微量營養素含量第1-2天殺菌釜 滅菌配方（參見配方1，實例26)相比，低微量營養素含量第 3 9天叙菌爸滅菌配方（亦即配方6)亦具有較高蛋白質負載 值且因此乳液穩定性增加。 實例28 此實例中，評估微量營養素含量對第1-2天及第3_9天殺 菌釜滅菌配方及第3-9天無菌滅菌配方之顏色之影響。 使用艾格壯顏色法評估配方之顏色品質。艾格壯顏色法 使用分光光度計以〇(黑色）至】〇〇(白色）等級量測自樣品反 射之光之百分比。亮色嬰兒配方（其通常受消費者偏愛）具 有較咼艾格壯顏色計分，而深色配方具有較低計分。在多 個時間週期量測之本發明之低及高微量營養素含量殺菌釜 161198.doc -96· 201233328 滅菌及無菌滅菌配方之艾格壯顏色計分闡述於以下表 18(殺菌釜滅菌配方）及表19(第3-9天無菌滅菌配方）中。 表18 ··殺菌釜滅菌配方 配方 能量(kcal/L) 微量營養素含量 時間間隔 艾格壯顏色計分(％)a 配方3 (第1-2天） 250 0天 39.3 1個月 … 2個月 33.3 4個月 30.2 9個月 28.5 12個月 28.2 配方4 (第1-2天） 250 0天 44.1 1個月 3個月 37.5 6個月 35.4 9個月 33.4 12個月 33.0 配方1 (第1-2天） 270 低 0天 47.9 2個月 43.7 4個月 42.2 6個月 40.3 9個月 38.6 配方2 (第1-2天） 270 低 0天 54.4 3個月 49.7 6個月 47.8 配方8 (第3-9天） 410 尚 0天 39.4 配方5 (第3-9天） 406 低 0天 51.1 3個月 48.8 6個月 46.0 配方6 (第3-9天） 406 低 0天 45.3 配方7 (第3-9天） 406 低. 0天 46.2 (—)意謂未測試 a對於所有量測，均使用Agtron M-45分光光度計（藍色濾光 片-43 6 nm)測定艾格壯顏色計分。 161198.doc -97- 201233328 表19 :第3-9天無菌滅菌配方 配方 能量(kcal/L) 微量營養素含量 時間間隔 艾格壯顏色計分(％)a 配方11 410 南 0天 53.1 1個月 49.7 2個月 — 4個月 —- 12個月 46.2 配方10 410 南 0天 56.5 1個月 … 3個月 51.7 6個月 53.1 9個月 51.4 12個月 47.6 配方9 406 低 0天 61.5 1個月 … 2個月 60.0 6個月 56.9 9個月 53.8 (---)意謂未測試 a對於所有量測，均使用Agtron M-45分光光度計（藍色濾光 片-43 6 nm)測定艾格壯顏色計分。 如可自該等結果可見，與具有高微量營養素含量之殺菌 釜滅菌第1-2天嬰兒配方相比，具有低微量營養素含量之 殺菌釜滅菌第1-2天嬰兒配方具有較高艾格壯顏色計分且 因此具有較亮的顏色外觀。在第3-9天殺菌釜滅菌配方及 第3-9天無菌滅菌配方下獲得類似結果，其中低微量營養 素含量配方之艾格壯顏色計分高於可比較之具有高微量營 養素含量之配方。甚至在長時間後（在一些情況下，在產 品調配後多達9個月）亦觀測到低微量營養素配方相比於可 比較之高微量營養素配方之顏色改良。該等結果顯示本發 明之具有低微量營養素含量之嬰兒配方與具有高微量營養 161198.doc •98· 201233328 素含量之可比較之配方相比具有較亮且較淡的顏色外觀。 實例29 此實例中，評估微量營養素含量對殺菌爸滅菌第1-2天 配方之粒徑分佈及乳油分離速度之影響。 明確言之，使用Beckman Coulter LS 13 320光散射機器 測定2盘司具有高微量營養素含量（配方3)或低微量營養素 含量（配方1)之殺菌爸滅菌第1 _2天配方之粒徑分佈。結果 展示於圖12中。 如可自圖12中可見’低微量營養素第ι_2天殺菌釜滅菌 配方（配方1)中之大部分顆粒之尺寸介於約〇1 μηι與約〇.8 μπι之間，少部分顆粒介於約i μιη與約8 μιη之間。相比之 下，高微量營養素第丨_2天殺菌爸滅菌配方（配方3)之粒徑 必佈更平均地在約〇 1 至約7 μηι範圍内。 由粒徑分佈測定各配方之平均粒徑且用於計算各配方之 乳油分離速度。明確言之’使用以下方程式計算乳油分離 速度： 其中：Kcal/L Formula 11 (Day 3-9 1 ^ square 3 Protein MW Median (Da) 410 799 ~___676 978 Protein > 5000 Da (% of total protein) 2.5% 9.5% Insoluble protein a (me/ L) 110 4〇〇 The total protein in the agglomerate after high-speed centrifugation can be seen from the results. 'Compared with the control formula, the protein hydrolysis in the 3rd-9th formula is more extensive. All three digestion indicators (protein MW The value, the amount of protein greater than 5000 Da and the amount of insoluble protein) decreased with the decrease of energy 3. The specific result showed that the protein digestibility was inversely related to the energy content. Example 23 In this example, the energy content of the infant formula was evaluated. Effect on the rate and extent of protein hydrolysis. Specifically, the 1st and 2nd day powder infant formula (Formulation 13) of the present invention and the 3-9 day powder infant formula of the present invention (Formulation 15) were determined. The degree of protein hydrolysis after trypsinization was compared to the degree of protein hydrolysis after trypsinization in a reconstituted commercial powder control infant formula (control formula). Use 12.2 g formula plus 240 mL water to reconstitute 13. Reconstitute Formulation 15 using 21.4 g of Formula plus 240 mL of Water and Restore Control Formulation 1 using 35.0 g of Formulation plus 240 mL of Water. Digestion was prepared by trypsinization of the reconstituted formula. Clearly, in a 20 mL vial 9.00 mL 0.05 Μ NaH2P〇4 (pH 7.5) was added to 9.00 mL of each formulation. 2.00 mL of porcine pancreatin (prepared at 4.0 g/L in pH 7.5 buffer) was added to the formulation and the vial was placed I61198.doc - 90-201233328 Placed in a 37 ° C water bath for 71 minutes. After 71 minutes, 1.5 mL mixture aliquots were transferred to a HPLC autosampler vial and crimped vials. Sealed vials were placed in a 1 °C heating module The trypsin digestion was stopped for 5 minutes. 0.400 mL of the digest was diluted with 1.00 mL of 8.30/6.00 /0.02 (v/v) water/acetonitrile/trifluoroacetic acid. The diluted digest was centrifuged at 14,000 x g for 5 minutes at room temperature. Superdex® peptide 10/300 GL gel filtration column (Amersham Biosciences) was used using the procedure set forth in Example 20 above. The supernatant was analyzed by HPLC and the molecular weight (MW) of the protein in the digest was determined and digested. The amount of protein with a molecular weight greater than 5000 Daltons (accounting for Protein percentage). The results are shown in Table 13 below and Figures 10 and 11. Table 13 Formulation 13 (Day 1-2) Formulation 15 (Days 3-9) Control Formula 1 Kcal/L 250 420 676 Protein MW Median (Da) 680 748 853 Protein > 5000 Da (% of total protein) 2.15% 2.54% 3.03% As can be seen from these results, the first 1-2 day formula and the 3rd-9th formula are compared to the control formula. The protein is more widely hydrolyzed. In addition, both digestion indices (median protein MW, protein content greater than 5000 Da) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. Example 24 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, determine the degree of protein hydrolysis of the 2 ounce infant formula (Formulation 3) of the sterilization of the 1-2 days of the present invention before and after trypsin digestion and compare the infant formula with 2 ounces of commercially available sterilization kettle sterilization (pair 161198) .doc -91 - 201233328 Compare the degree of protein hydrolysis before and after digestive digestion according to Formulation 2). The infant formula/pancreatin mixture was maintained at 37. (: Only 60 minutes in the water bath' The digest was prepared by trypsinizing the formulation using the same procedure as described in Example 23. The diluted digest was centrifuged at room temperature for 14 minutes at room temperature. The supernatant before digestion and the sample of the infant formula were analyzed by HPLC using a Superdex® Peptide 10/300 GL gel column (Amersham Biosciences) using the procedure set forth in Example 2 above, and the infant before digestion was determined. The median molecular weight of the protein in the formulation and the median molecular weight of the protein after 6 minutes of trypsin digestion. The results are shown in Table 14. Table 14 Formulation 3 (Day 1-2) Control Formula 2 Kcal/L 250 676 / month 1 〇 曰 曰 MW MW MW 14, 14, 14, 14, 14, 14, 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 774 801 801 801 801 801 801 801 801 801 The protein hydrolysis rate was faster in the formulation of the second day. In addition, the median MW of the (9) minute digestive enzyme digestion was directly proportional to the caloric density of the infant formula, indicating that the protein digestibility was inversely related to the energy content. Example 25 In this example , 5 flat assessment of infant formula The effect of the amount of energy ♦ on the rate and extent of proteolysis. Specifically, the reconstituted second day powder infant formula (Formulation 12) or the 3rd-9th powder infant formula (formulation) ounce of the present invention is determined to be the first 2-day sterilized sterilized infant formula (Xifangfang α 161198.doc -92- 201233328 2) or Day 3-9 Sterilization sterilized infant formula (Formulation 5) and 32 ounces of the 3-9th sterile sterilized infant formula of the present invention (Formulation 9) Degree of protein hydrolysis after trypsinization (powder) or in vitro GI digestion (liquid) and in comparison with the reconstituted commercial powder control infant formula (Control Formula 1), 2 ounces of commercial sterilization sterilization control infant formula (Comparative Formulation 2) and 32 ounces of commercially available sterile sterile control formulation (Control Formulation 3) were compared for protein hydrolysis. Formulation 12 was reconstituted using 12.2 g of formula plus 240 mL of water, and Formulation 14 was reconstituted using 21.4 g of Formula plus 240 mL of water and Control Formulation 1 was reconstituted using a 35.0 g formulation plus 240 mL of water. The digest was prepared by trypsinizing the formulation (or reconstituted formulation) using the same procedure as described above. Use the example 20 above. The supernatant was analyzed by HPLC using a Superdex® peptide 10/300 GL gel filtration column (Amersham Biosciences), and the median molecular weight (MW) of the protein in the digest and the molecular weight in the digest were determined to be greater than ί; The amount of protein (% of total protein). The results are shown in Table 15. Table 15 Formula Energy (kcal/L) Form Protein MW> 5000 Da (% of total protein) Protein MW Median (Da) Control Formula 1 676 Powder 17.9% 1050 Formula 14 (Days 3-9) a 406 Powder 10.9% 846 Formula 14 (Days 3-9) 406 Powder 8.4% 812 Formula Π (Day 1-2) 270 Powder 5.2% 717 Control Formulation 2 676 Sterilization Sterilization 13.7% 988 Formulation S (Days 3-9) 406 Sterilization Sterilization 5.3% 789 Formulation 1 (Day 1-2) 270 Sterilization Sterilization 3.9% 730 Formulation 2 (Day 1-2) 270 Sterilization Sterilization 2.9% 707 Control Formulation 3 676 Sterile Sterilization 10.2% 963 Formulation 9 (Days 3-9) 406 Sterile Sterilization 4.1% 801 Formulation 14 was tested twice. 161198.doc -93- 201233328 As can be seen from these results, protein hydrolysis in Formula 1 and Day 2-3 formulations is more extensive than in the control formulation. In addition, both digestion indices (protein median MW, protein content greater than 5000 Da) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. Example 26 In this example, the effect of micronutrient content on the stability of the emulsion on the 1-2 day sterilization autoclave formulation and the 3-9 day sterile sterile infant formula was evaluated. Clearly § compare the emulsion stability of the 3-9 day sterile sterilized infant formula with high (formulation η) or low (formulation 9) micronutrient content and 2 ounces with high (formulation 3) or low (formulation)丨) The micronutrient content of the second day of sterilization of the dad sterilized infant formula emulsion stability. The emulsion stability was determined using the protein loading (expressed as the percentage of protein in the emulsifiable layer formed after high speed centrifugation of the formulation). The protein loading of each formulation was determined by pouring a 36-38 gram formulation into a tared 5 〇 mL centrifuge tube and capping the centrifuge tube. The capped centrifuge tube was then placed in a JA 2 角 angle rotator (Beckman Coulter ' p/N 334831) and the rotator was placed in a Beckman J2-HS centrifuge (Beckman c〇uher). The sample was centrifuged at 31, _xg for 8 hours at 2 °C. After centrifugation, the cream layer formed on the ## layer was transferred into a tared beaker and its weight recorded. The supernatant was poured into a separate beaker and the centrifuge tube was weighed again to determine the aggregate weight. The amount of protein in the cream layer was determined using an acid hydrolysis/amino acid assay technique. The results are set forth in Table 16 below. 161198.doc •94· 201233328 Table 16 Formulation energy (kcal/L) Micronutrient content form Percentage of protein in the cream layer (approximate weight/weight percentage) Formulation 11 (days 3-9) 410 Sterile sterilization 5.1% Formulation 9 (No. 3-9 days) 406 Sterile Sterilization 4.7% Formulation 3 (Day 1-2) 250 Sterilization 蚤 Sterilization 4.6% Formulation 1 (Day 1-2) 270 Sterilization Dad Sterilization 5.9% Average (η=4) --- ---- 5.1% ± 0.6% Protein loading value is the indicator of emulsion stability. Specifically, emulsion stability generally increases with increasing protein loading. As can be seen from the above results, the 丨_2 day sterilization kettle sterilization formula with low micronutrient content (that is, the protein load value in the formula 高于 is higher than the 1-2 day sterilization sterilized formula with high micronutrient content ( That is, the protein loading value in Formulation 3). These results show that the emulsion stability in the Di-2-day sterilization autoclave formulation with low micronutrient content compared to the comparable formula with high micronutrient content Increased. No significant differences in protein loading between aseptically sterilized formulations of high micronutrient content and aseptically sterilized formulations with low micronutrient content. Example 27 In this example, the emulsion stability of the micronutrient content on the 3rd-9th sterilizer formulation was evaluated. Impact “Confirmally, compare the emulsion stability of the 2nd ounce sterilized dad sterilized infant formula with 2 ounces of high (Formulation 8) or low (Formulation 6) micronutrient content. Use protein loading (expressed as formula after high speed centrifugation) The percentage of protein in the formed cream layer) was determined for emulsion stability. The procedure described in Example 26 was used. The protein loading of each formulation was also calculated. The amount of cream layer (based on the weight of all products of 161I98.doc • 95·201233328) and the amount of protein in the cream layer (based on the total weight of the product) were also calculated. The results are set forth in Table 17 below. Table 17 Formulation energy (kcal/L) Micro-battalion - Percentage of protein in the emulsion layer (w/w) Percentage of protein in the cream layer of all products (w/w, with a pair of j-9 days) 406 6.9% 0.35% Formulation 8 (Days 3-9) 410 _ high 5.1% 0.22% The results showed that the protein load value in Formulation 6 with low micronutrient content was higher than that in the high micronutrient formulation (ie Formulation 8). Compared to Formulation 8, Xijifang 6 also formed a larger cream layer and the percentage of protein in the cream layer (by weight of the total product) was higher. "These results show that compared to comparable formulations with high micronutrient content. The emulsion stability in the sterilization solution of the 3rd-9th day with low micronutrient content increased. Compared with the low micronutrient content 1-2 days sterilization kettle sterilization formula (see Formula 1, Example 26), low trace The content of the nutrient content on the 39th day of the bactericidal formula (also known as formula 6) also has a higher protein loading value and therefore increased emulsion stability. Example 28 In this example, the evaluation of micronutrient content on days 1-2 and Effect of 3_9 days sterilization pot sterilization formula and the color of the 3-9 day sterile sterilization formula. The color quality of the formula was evaluated using the Aegis color method. The Aegis color method uses a spectrophotometer to 〇 (black) to 〇〇 (white) The rating is measured as a percentage of the light reflected from the sample. Bright color infant formula (which is usually preferred by the consumer) has a better score than the Eiger color, while the dark formula has a lower score. It is measured over multiple time periods. The low and high micronutrient content sterilization kettle of the present invention 161198.doc -96· 201233328 The Aegean color score of the sterilization and aseptic sterilization formula is described in the following Table 18 (sterilization kettle sterilization formula) and Table 19 (3-9 days sterility) Sterilization formula). Table 18 ·· Sterilization Sterilization Formulation Formula Energy (kcal/L) Micronutrient Content Time Interval Egson Color Score (%) a Formula 3 (Day 1-2) 250 0 days 39.3 1 month... 2 months 33.3 4 months 30.2 9 months 28.5 12 months 28.2 Formulation 4 (Day 1-2) 250 0 days 44.1 1 month 3 months 37.5 6 months 35.4 9 months 33.4 12 months 33.0 Formula 1 (Part 1 2 days) 270 low 0 days 47.9 2 months 43.7 4 months 42.2 6 months 40.3 9 months 38.6 Formula 2 (Day 1-2) 270 Low 0 days 54.4 3 months 49.7 6 months 47.8 Formula 8 (No. 3-9 days) 410 0 days 39.4 Formula 5 (Days 3-9) 406 Low 0 days 51.1 3 months 48.8 6 months 46.0 Formula 6 (Days 3-9) 406 Low 0 days 45.3 Formula 7 (No. 3-9 days) 406 low. 0 days 46.2 (-) means untested a For all measurements, the Agron M-45 spectrophotometer (blue filter -43 6 nm) was used to determine the Aegean color score. . 161198.doc -97- 201233328 Table 19: Day 3-9 Sterile Sterilization Formulation Energy (kcal/L) Micronutrient Content Time Interval Egson Color Score (%) a Formula 11 410 South 0 Days 53.1 1 Month 49.7 2 months - 4 months - 12 months 46.2 Formula 10 410 South 0 days 56.5 1 month... 3 months 51.7 6 months 53.1 9 months 51.4 12 months 47.6 Formula 9 406 Low 0 days 61.5 1 month ... 2 months 60.0 6 months 56.9 9 months 53.8 (---) means untested a For all measurements, Agger M-45 spectrophotometer (blue filter -43 6 nm) was used to determine Iger Strong color scores. As can be seen from these results, the 1-2 day infant formula with low micronutrient content has a higher Aegis color than the 1-2 day infant formula with high micronutrient content. Score and therefore have a brighter color appearance. Similar results were obtained on the 3-9th Sterilization Sterilization Formulation and the 3-9th Sterile Sterilization Formula, where the low micronutrient content formulation had a higher Egson color score than the comparable formula with high micronutrient content. Even after prolonged periods of time (in some cases up to 9 months after product formulation), color improvements in low micronutrient formulations compared to comparable high micronutrient formulations were observed. These results show that the infant formula with low micronutrient content of the present invention has a brighter and lighter color appearance than a comparable formula with a high micronutrient content of 161198.doc • 98·201233328. Example 29 In this example, the effect of micronutrient content on the particle size distribution and the separation rate of the cream on the first 1-2 days of sterilized dad sterilization was evaluated. Specifically, the Beckman Coulter LS 13 320 light scattering machine was used to determine the particle size distribution of the 2nd 1-2 day formulation of the 2nd plate with high micronutrient content (Formulation 3) or low micronutrient content (Formulation 1). The results are shown in Figure 12. As can be seen from Figure 12, the size of most of the particles in the low micronutrient Day 1st Sterilization Sterilization Formula (Formulation 1) is between about μ1 μηιη and about 〇.8 μπι, with a small amount of particles in between Between i μηη and about 8 μιη. In contrast, the particle size of the high-micronutrient 丨_2 day sterilization dad sterilization formula (Formulation 3) must be more evenly in the range of about 〇 1 to about 7 μηι. The average particle size of each formulation was determined from the particle size distribution and used to calculate the cream separation speed for each formulation. Specifically, use the following equation to calculate the separation rate of the cream:

Vcream 為乳油分離速度 Pfluid為配方密度 Pparticle為顆粒密度 η為配方黏度 R.為平均粒徑 161198.doc -99- 201233328 g為重力加速度。 藉由使用Beckman Coulter LS 13 320光散射機器量測單 位樣品（100 mL)中顆粒之總表面積來計算顆粒（例如油滴） 之密度。接者使用超離心法量測附著於油滴表面之蛋白質 之體積。接著用蛋白質體積除以油滴總表面積得到塗於各 油滴上之蛋白質層之平均厚度β接著使用蛋白質密度丨41 (Fischer等人，Protein Science (2004),第 13 (10)卷，第 2825-2828頁）計算平均顆粒密度。 各配方之R2值及乳油分離速度展示於表2〇中。 表20:第1-2天殺菌釜滅菌配方之粒徑及乳油分離速度 能量 (kcal/L) 微量營養 素含量 平均粒徑之平方(R2) (μ®2) 乳油分離速度 (公分/天） 配方1 270 低 1.8 3.2 配方3 250 1¾ 3.5 6.3 如可自此表可見’低微量營養素第1_2天殺菌爸滅菌配 方（配方1)之平均粒徑小於高微量營養素第〖_2天殺菌爸滅 菌配方（配方3)之平均粒徑。因為較小粒徑可表示產品穩定 性’因此該等結果顯示本發明之低微量營養素第1·2天殺 菌釜滅菌配方之產品穩定性大於可比較之具有高微量營養 素含量之配方。 乳油分離速度量測顆粒（例如液滴）移動穿過液體樣品（在 此情況下’嬰兒配方）之速率且預示嬰兒配方形成乳油層 之能力。如可自表20中可見’低微量營養素含量第υ天 殺菌爸滅菌配方之乳油分離速度小於高微量營養素含量第 1 -2天殺菌爸滅菌配方之乳油分離速度。該等結果顯示本 161198.doc -100· 201233328 發日月之低微量營養素含量第1-2天殺菌釜滅菌配方與可比 & < w微量營養素配方相比形成乳油層之能力降低且因此 物理穩定性改良。 【圖式簡單說明】 圖1為展示如實例16中所論述，與對照全熱量配方及人 礼相比’多種低熱量第1-2天及第3-9天嬰兒配方之緩衝強 度之圖表》 圖2為展示如實例丨6中所論述，與對照全熱量配方及人 乳相比’多種低熱量第1-2天及第3-9天嬰兒配方之緩衝能 力之圖表。 圖3為展示如實例丨7中所論述，與對照全熱量配方相 比，添加HC1對低熱量第i_2天及第3-9天復原粉末嬰兒配 方之pH值之影響之圖表。 圖4為展示如實例丨7中所論述，與對照全熱量配方相 比’低熱量第1 -2天及第3-9天復原粉末嬰兒配方之緩衝強 度之圖表。 圖5為展示如實例17中所論述’與對照全熱量配方相 比，低熱量第1 -2天及第3-9天復原粉末嬰兒配方之緩衝能 力（如在向100 mL配方中添加5.50毫莫耳HC1後藉由pH值降 低量測）之圖表。 圖6為展示如實例17中所論述’與對照全熱量配方相 比’低熱1第1-2天及第3-9天復原粉末嬰兒配方之緩衝能 力（如在向1〇〇11^配方中添加5.50毫莫耳11(：1後藉由旧+.]增 加量測）之圖表。 161193.doc -101 - 201233328 圖7為展示如實例20中所論述，與對照全熱量配方相 比’在活體外腸胃消化後，低熱量第1-2天及第3-9天復原 粉末嬰兒配方之蛋白質分子量（MW)中值之圖表。 圖8為展示如實例20中所論述，與對照全熱量配方相 比，在活體外腸胃消化後，低熱量第1-2天及第3-9天復原 粉末嬰兒配方中MW大於5000 Da之佔總蛋白質百分比之圖 表。 圖9為展示如實例20中所論述，與對照全熱量配方相 比’在活體外腸胃消化後，低熱量第1-2天及第3-9天復原 粉末嬰兒配方在高速離心後蛋白質顆粒中不可溶（難消化） 蛋白質量之圖表。 圖10為展示如實例23中所論述，與對照全熱量配方相 比’在胰酶消化71分鐘後，低熱量第1-2天及第3-9天復原 粉末嬰兒配方之蛋白質MW中值之圖表。 圖11為展示如實例23中所論述，與對照全熱量配方相 比，在胰酶消化71分鐘後，低熱量第1-2天及第3-9天復原 粉末嬰兒配方中MW大於5000 Da之佔總蛋白質百分比之圖 表。 圖12為展示如實例29中所論述，經殺菌釜滅菌之具有高 微量營養素含量（配方3)或低微量營養素含量（配方丨）之第 1-2天配方之粒徑分佈之圖表。 161198.doc •102-Vcream is the separation speed of the cream. Pfluid is the formula density. Pparticle is the particle density. η is the formula viscosity. R. is the average particle size. 161198.doc -99- 201233328 g is the acceleration of gravity. The density of particles (e.g., oil droplets) was calculated by measuring the total surface area of the particles in a single sample (100 mL) using a Beckman Coulter LS 13 320 light scattering machine. The receiver used ultracentrifugation to measure the volume of protein attached to the surface of the oil droplets. The protein volume is then divided by the total surface area of the oil droplets to obtain the average thickness of the protein layer applied to each oil droplet, followed by the protein density 丨41 (Fischer et al., Protein Science (2004), Vol. 13 (10), pp. 2825 - page 2828) Calculate the average particle density. The R2 values of each formulation and the separation rate of the cream are shown in Table 2〇. Table 20: Particle size and cream separation speed energy (kcal/L) of the sterilization solution on the first 1-2 days. The square root of the average particle size of the micronutrient content (R2) (μ®2) Separation speed of the cream (cm/day) Formulation 1 270 Low 1.8 3.2 Formulation 3 250 13⁄4 3.5 6.3 As can be seen from this table, 'low micronutrient 1st day 2D sterilization dad sterilization formula (Formulation 1) average particle size is less than high micronutrients 〖_2 days sterilization dad sterilization formula (formulation 3) Average particle size. Since the smaller particle size can indicate product stability', these results show that the low micronutrient of the present invention has a product stability greater than that of a comparable high micronutrient content. The cream separation rate measures the rate at which particles (e.g., droplets) move through the liquid sample (in this case ' infant formula) and predicts the ability of the infant formula to form a cream layer. As can be seen from Table 20, 'low micronutrient content υ天 sterilized dad sterilization formula emulsifiable oil separation speed is less than high micronutrient content 1-2 days sterilized dad sterilization formula emulsifiable oil separation speed. These results show that the low micronutrient content of the 161198.doc -100· 201233328 day and month is the 1-2 day sterilization kettle sterilization formula and the ability to form a cream layer is reduced compared to the comparable &< w micronutrient formula and therefore physical Improved stability. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a graph showing the buffer strength of a variety of low calorie 1-2 and 3-9 infant formulas as compared to a control full calorie formula and a gift as discussed in Example 16. Figure 2 is a graph showing the buffering capacity of a variety of low calorie 1-2 day and 3-9 day infant formulas as compared to the control full calorie formula and human milk as discussed in Example 丨6. Figure 3 is a graph showing the effect of the addition of HC1 on the pH of the low calorie i-day and day 3-9 reconstituted powder infant formula as compared to the control full calorie formulation as discussed in Example 丨7. Figure 4 is a graph showing the buffer strength of the low calorie 1-2 days and 3-9 day reconstituted powder infant formula as compared to the control total calorie formulation as discussed in Example 丨7. Figure 5 is a graph showing the buffering capacity of a low calorie 1-2 day and 3-9 day reconstituted powder infant formula as discussed in Example 17 (e.g., adding 5.50 milligrams to a 100 mL formulation compared to a control full calorie formulation) A graph of the measurement of pH reduction after Mol HC1. Figure 6 is a graph showing the buffering capacity of the Reconstituted Powder Infant Formula for Low Heat 1 Days 1-2 and Days 3-9 as described in Example 17 (as compared to the control full calorie formula) (e.g., in the formulation to 1〇〇11^ Add a graph of 5.50 millimoles 11 (:1 and then increase by the old +.) 161193.doc -101 - 201233328 Figure 7 is a graph showing the comparison with the control full calorie formula as discussed in Example 20. A graph of the median molecular weight (MW) median of the powdered infant formula after low-calorie 1-2 days and days 3-9 after in vitro parenteral digestion. Figure 8 is a graph showing the full calorie formula as discussed in Example 20. A graph comparing the percentage of total protein with a MW greater than 5000 Da in the low-calorie 1-2 days and 3-9 days of reconstituted powdered infant formula after in vitro gastrointestinal digestion. Figure 9 is a graph showing the effect as discussed in Example 20. , compared with the control total calorie formula, the graph of insoluble (indigestible) protein mass in protein granules after high-speed centrifugation in low-calorie 1-2 days and 3-9 days after intestine digestion in vitro Figure 10 is a graph showing the full calorie formulation as compared to the control as discussed in Example 23. A graph of the median MW of the protein of the powdered infant formula reconstituted after 71 minutes of trypsin digestion, low calorie days 1-2 and days 3-9. Figure 11 is a graph showing the total calories as compared to the control as discussed in Example 23. A graph comparing the percentage of total protein with a MW greater than 5000 Da in the infant formula of hypothermia on days 1-2 and days 3-9 after pancreatin digestion for 71 minutes. Figure 12 is shown in Example 29. A graph of the particle size distribution of the 1-2 day formulation with high micronutrient content (Formulation 3) or low micronutrient content (Formulation 丨) sterilized by autoclave. 161198.doc •102-

Claims (1)

201233328 七、申請專利範圍： l種增加嬰兒之胃液酸度之方法，該方法包含對該嬰兒 投/、肖b量含量為約2〇〇至約5〇〇千卡/公升配方之嬰兒配 方。 2·如凊求項1之方法，其中該嬰兒配方之能量含量為約200 至約360千卡/公升配方。 3. 如凊求項丨之方法，其中該嬰兒配方之能量含量為約 至約500千卡/公升配方。 4. 如咕求項1之方法，其中該嬰兒配方之緩衝強度為約1 8 mL或18 mL以下。 5. 如呀求項1之方法，其中該嬰兒配方之緩衝強度為約18 mL或18 mL以下。 6. 如研求項5之方法，其中該嬰兒配方為能量含量為約2〇〇 至約360千卡/公升配方之第1-2天嬰兒配方。 7·如凊求項6之方法，其進一步包含在出生後頭兩天期間 對該新生兒投與該丨_2天嬰兒配方，及在出生後第3至9天 對该新生兒投與能量含量為約360至小於600千卡/公升配 方之第3-9天嬰兒配方。 .8.如請求項7之方法，其中該第1-2天嬰兒配方之缓衝強度 . 為約9 mL至約14 mL。 9·如請求項7之方法，其中該第3_9天嬰兒配方之緩衝強度 為約14 mL至約18 mL。 10· —種增加嬰兒之胃液酸度之方法，該方法包含對該嬰兒 投與低微量營養素嬰兒配方，其包含微量營養素及至少 16119S.doc 201233328 一種選自由蛋白質、碳水化合物、脂肪及其組合組成之 群的常量營養素且具有約200至小於600千卡/公升配方之 能量含量’其中以單位體積計，至少65%該等微量營養 素以習知相應微量營養素量之約3〇%至約8〇%之量包括 於該嬰兒配方中。 11. 如請求項1〇之方法，其中該嬰兒配方之緩衝強度為約18 mL或1 8 mL以下。 12. —種增加嬰兒之胃液酸度之方法，該方法包含：對該嬰 兒投與低微量營養素嬰兒配方，其包含微量營養素及至 少一種選自由蛋白質、碳水化合物、脂肪及其組合組成 之群的常量營養素且具有約2〇〇至約360千卡/公升配方之 此量含量，其中以單位體積計，至少45%該等微量營養 素以習知相應微量營養素量之約3〇%至約65%之量包括 於該嬰兒配方中。 13. 如請求項12之方法，其中該嬰兒配方為第^2天嬰兒配 方。 14·如明求項13之方法，其進一步包含在出生後頭兩天期間 對該嬰兒投與該1-2天嬰兒配方及在出生後第3至9天對該 嬰兒投與能量含量為約360至小於6〇〇千卡/公升配方之第 3-9天嬰兒配方。 15. —種增加嬰兒之胃液酸度之方法，該方法包含：對該嬰 兒投與低微量營養素嬰兒配方，其包含微量營養素及至 少一種選自由蛋白質、碳水化合物、脂肪及其組合組成 之群的常量營養素且具有約3 6〇至小於6〇〇千卡/公升配方 161198.doc 201233328 之能量含量，其中以單位體積計，至少3〇%該等微量營 養素以習知相應微量營養素量之約55%至約8〇%之量： 括於該嬰兒配方中。 匕 16. 之方法，該方法包含 500千卡/公升配方之 一種調節嬰兒中有益腸胃菌叢生長 對該嬰兒投與能量含量為約2〇〇至約 嬰兒配方。 17.如請求項16之方法，其中該嬰兒配方之能量含量為約 200至約400千卡/公升配方。 18· 一種調節嬰兒中腸胃菌叢生長之方法，該方法包含··對 該嬰兒投與低微量營養素嬰兒配方，其包含微量營養素 及至少一種選自丨蛋白#、碳水化合物、脂肪及其組合 組成之群的常量營養素且具有約200至小於600千卡/公升 配方之能量含量’其中以單位體積計，至少65%該等微 量吕養素以^知相應微量營養素量之約30%至約80。/〇之 量包括於該嬰兒配方中。 19· 一種調節嬰兒中腸胃菌叢生長之方法，該方法包含：對 該嬰兒投與低微量營養素嬰兒配方，其包含微量營養素 及至少一種選自由蛋白質、碳水化合物、脂肪及其組合 組成之群的常量營養素且具有約200至約360千卡/公升配 方之能量含量，其中以單位體積計，至少45%該等微量 營養素以習知相應微量營養素量之約30%至約65%之量 包括於該嬰兒配方中。 20. —種調節嬰兒中腸胃菌叢生長之方法，該方法包含對該 嬰兒投與低微量營養素嬰兒配方，其包含微量營養素及 161193.doc 201233328 至少一種選自由蛋白質、碳水化合物、脂肪及其組合組 成之群的常量營養素且具有約360至小於600千卡/公升配 方之能量含量，其中以單位體積計，至少30%該等微量 營養素以習知相應微量營養素量之約55%至約80%之量 包括於該嬰兒配方中。 161198.doc201233328 VII. Scope of application: l A method for increasing the acidity of the gastric juice of an infant. The method comprises the infant formula of the infant having a dosage of about 2 〇〇 to about 5 〇〇 kcal/liter. 2. The method of claim 1, wherein the infant formula has an energy content of from about 200 to about 360 kcal/liter of formula. 3. A method of claiming wherein the infant formula has an energy content of from about 500 kcal/liter to the formula. 4. The method of claim 1, wherein the infant formula has a buffer strength of about 18 mL or less. 5. The method of claim 1, wherein the infant formula has a buffer strength of about 18 mL or less. 6. The method of claim 5, wherein the infant formula is an infant formula of the first 1-2 days of an energy content of from about 2 约 to about 360 kcal/liter. 7. The method of claim 6, further comprising administering the neonatal 1-2 day infant formula to the newborn during the first two days after birth, and administering the energy content to the newborn on the 3rd to 9th day after birth A 3-9 day infant formula for a formula of about 360 to less than 600 kcal/liter. 8. The method of claim 7, wherein the buffer strength of the infant formula on day 1-2 is from about 9 mL to about 14 mL. 9. The method of claim 7, wherein the 3rd-9th infant formula has a buffer strength of from about 14 mL to about 18 mL. 10. A method of increasing the acidity of a gastric juice of an infant, the method comprising administering to the infant a low micronutrient infant formula comprising micronutrients and at least 16119 S. doc 201233328 one selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof a group of macronutrients and having an energy content of from about 200 to less than 600 kcal/liter of formula 'of which at least 65% of the micronutrient is from about 3% to about 8% by weight of the conventional micronutrient amount per unit volume The amount is included in the infant formula. 11. The method of claim 1, wherein the infant formula has a buffer strength of about 18 mL or less. 12. A method of increasing the acidity of a gastric acid in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising a micronutrient and at least one constant selected from the group consisting of protein, carbohydrate, fat, and combinations thereof Nutrients and having an amount of from about 2 Torr to about 360 kcal/liter of formula, wherein at least 45% of the micronutrient per unit volume is from about 3% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula. 13. The method of claim 12, wherein the infant formula is a second day baby formula. 14. The method of claim 13, further comprising administering the infant to the infant for 1-2 days during the first two days of life and administering an energy content of about 360 to the infant on days 3 to 9 after birth. To the 3rd-9th infant formula of less than 6〇〇 kcal/litre formula. 15. A method of increasing the acidity of a gastric acid in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising a micronutrient and at least one constant selected from the group consisting of protein, carbohydrate, fat, and combinations thereof Nutrient and having an energy content of from about 36 〇 to less than 6 〇〇 kcal/liter formula 161198.doc 201233328, wherein at least 3% by weight of the micronutrient per unit volume is about 55% of the amount of the corresponding micronutrient Up to about 8% of the amount: included in the infant formula.匕 16. The method comprising a 500 kcal/liter formula for regulating growth of a beneficial gastrointestinal flora in an infant. The infant is administered an energy content of from about 2 Torr to about an infant formula. 17. The method of claim 16, wherein the infant formula has an energy content of from about 200 to about 400 kcal/liter of formula. 18. A method of regulating growth of a gastrointestinal flora in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of prion protein #, carbohydrates, fats, and combinations thereof The group of macronutrients and having an energy content of from about 200 to less than 600 kcal/liter of formula 'of which at least 65% of the microulonol per unit volume is from about 30% to about 80 of the amount of the corresponding micronutrient. The amount of 〇/包括 is included in the infant formula. 19. A method of regulating growth of a gastrointestinal flora in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof a macronutrient having an energy content of from about 200 to about 360 kcal/liter of formula, wherein at least 45% of the micronutrient is included in an amount of from about 30% to about 65% by weight of a conventional micronutrient, per unit volume In the infant formula. 20. A method of regulating growth of a gastrointestinal flora in an infant, the method comprising administering to the infant a low micronutrient infant formula comprising micronutrients and 161193.doc 201233328 at least one selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof a group of macronutrients and having an energy content of from about 360 to less than 600 kcal/liter of formula, wherein at least 30% of the micronutrient per unit volume is from about 55% to about 80% of the conventional micronutrient amount The amount is included in the infant formula. 161198.doc
TW100149844A 2010-12-30 2011-12-30 Reduced buffering capacity of a low calorie infant formula TW201233328A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US42882410P 2010-12-30 2010-12-30

Publications (1)

Publication Number Publication Date
TW201233328A true TW201233328A (en) 2012-08-16

Family

ID=47069879

Family Applications (1)

Application Number Title Priority Date Filing Date
TW100149844A TW201233328A (en) 2010-12-30 2011-12-30 Reduced buffering capacity of a low calorie infant formula

Country Status (1)

Country Link
TW (1) TW201233328A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105007758A (en) * 2013-03-15 2015-10-28 Mjn美国控股有限责任公司 Low-buffer nutritional compositions and uses thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105007758A (en) * 2013-03-15 2015-10-28 Mjn美国控股有限责任公司 Low-buffer nutritional compositions and uses thereof
CN109259225A (en) * 2013-03-15 2019-01-25 Mjn 美国控股有限责任公司 Low-buffer alimentation composition and application thereof

Similar Documents

Publication Publication Date Title
TWI436740B (en) Acidified liquid human milk supplement
JP6857175B2 (en) Liquid nutritional composition containing micelle casein and hydrolyzed whey protein
JP5892948B2 (en) Nutritional emulsion containing calcium HMB
TW201026232A (en) Modulation of infant fat mass
AU2011210683A1 (en) Nutritional powders comprising spray dried HMB
TW201039759A (en) Reduction of risk of obesity
US20140010912A1 (en) Low calorie infant formula with improved physical attributes
US20160213040A1 (en) Nutritional composition for pregnant women with a beneficial glucose and insulin profile
TW201223460A (en) Stable concentrated liquid human milk fortifier
JP2016512686A (en) Nutritional composition comprising calcium β-hydroxy-β-methylbutyrate, casein phosphopeptide and protein
CN104394714A (en) Dietary management of celiac disease and food allergy
EP2797431A1 (en) Reduced calorie infant formulas containing specific whey to casein ratios
JP5384333B2 (en) Liquid nutritional composition containing whey protein at high concentration and method for producing the same
CN104768383B (en) Method for preparing a protein and lipid containing composition with reduced digestive coagulation
EP2708146A1 (en) Nutritional composition for pregnant women with a beneficial glucose and insulin profile
TW201332555A (en) Use of specific carbohydrate systems during pregnancy for reducing adverse health effects later in life in offspring
TWI492744B (en) Methods of modulating inflammation in preterm infants using carotenoids
TW201233328A (en) Reduced buffering capacity of a low calorie infant formula
Falcão et al. Infant Formulas: A Long Story
WO2012092082A1 (en) Reduced buffering capacity of a low calorie infant formula
TW201306753A (en) Improved rate of protein digestion in a low calorie infant formula
US20140010913A1 (en) Tolerance in a low calorie infant formula
TW201233333A (en) Improved tolerance in a low calorie infant formula
TW201233332A (en) Low calorie infant formula with improved physical attributes
JP2023069186A (en) Nutritive composition, manufacturing method of nutritive composition, and evaluation method of bioavailability of copper in nutritive composition