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TW201233329A - Nutritional products including a novel fat system including monoglycerides - Google Patents

Nutritional products including a novel fat system including monoglycerides Download PDF

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Publication number
TW201233329A
TW201233329A TW100149623A TW100149623A TW201233329A TW 201233329 A TW201233329 A TW 201233329A TW 100149623 A TW100149623 A TW 100149623A TW 100149623 A TW100149623 A TW 100149623A TW 201233329 A TW201233329 A TW 201233329A
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Taiwan
Prior art keywords
fat
fatty acid
weight
oil
nutritional
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TW100149623A
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Chinese (zh)
Inventor
Chron-Si Lai
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Abbott Lab
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Priority claimed from US13/333,957 external-priority patent/US9078847B2/en
Application filed by Abbott Lab filed Critical Abbott Lab
Publication of TW201233329A publication Critical patent/TW201233329A/en

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Abstract

Disclosed are nutritional formulations including predigested fats that can be administered to preterm infants, infants, toddlers, and children for improving tolerance, digestion, and absorption of nutrients and for reducing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome. The predigested fats include fatty acid-containing monoglycerides and/or a fatty acid component.

Description

201233329 六、發明說明: 【發明所屬之技術領域】 本發明係關於包含預消化脂肪之營養品且係關於使用該 等營養品之方法。更特定而言,本發明係關於包含含有脂 . 肪酸之單酸甘油酯及/或脂肪酸組分的嬰兒、幼兒及小兒 . 產品,其提供營養益處’包括改善消化、耐受性及營養素 吸收以及減小壞死性小腸結腸炎、腹痛及短腸症之發生 率。 相關申請案之交叉參考 本申請案主張2010年12月29曰申請之美國臨時申請案第 61/428,168號、2010年12月29日申請之美國臨時申請案第 6W42M73號、2010年12月29日申請之美國臨時申請案第 6W42M76號、謂年12月29日中請之美國臨時中請案第 61/428,177號及2010年12月29日申請之美國臨時申請案第 61/428,185號的權益’其揭示内容以全文引用之方式併入 本文中。 【先前技術】 包含有目標地選擇之營養素的營養液體及粉末(包括 兒及小兒配方)為吾人所熟知且能廣泛獲得,立中一些 提供單-之營養來源,而其他可提供補充來源。該料 物包括可用水或其他含水液體復原之粉末,以及濃縮型 即飲型營養液體’諸如基於牛奶或蛋白之乳液。 液體在與選定營養成分-起調配時尤為適用。 儘官通常認為母乳為新生嬰兒之最佳營養’但並非每 161215.doc 201233329 母親能成功地以母乳哺育。母乳替代品(嬰兒配方)可提供 70整營養’且已證明其能滿足嬰兒正常生長及發育營養需 求。不幸的是,小比例之嬰兒配方餵養新生兒可能會遇到 胃腸道(GI)不耐性問題,包括軟便、脹氣、壞死性小腸結 腸炎、腹痛及其類似問題。 GI不耐性問題可至少部分歸因於嬰兒營養素消化及吸收 不完全。為解決該耐受性問題,一些嬰兒配方排除乳糖作 為成分,而其他以水解蛋白替代完整乳蛋白以減輕嬰兒消 化系統的負擔。 此外’ 一些配方銀養新生嬰兒之脂肪吸收速率比母乳傲 養嬰兒低得多。此脂肪吸收速率之差異隨嬰兒逐漸成熟而 減小。據推測’新生嬰兒缺乏脂肪酶,且因此其無法與接 受母乳中之脂肪酶的母乳餵養嬰兒同等好地消化及吸收脂 肪。 早產兒之消化系統發育不及足月嬰兒之消化系統,其益 發比足月嬰兒需要更多營養素(熱量)來促進生長及發育。 中鏈二酸甘油S旨(MCT油)易於消化及吸收,且已包含於早 產兒配方中以改善配方脂肪、蛋白及鈣吸收。然而,中鏈 三酸甘油醋中包含之中鏈脂肪酸不被用於再合成三酸甘油 酯以在MCT油經消化及吸收之後形成乳糜微粒。因為咸信 许多脂溶性營養素(諸如類胡蘿蔔素及維生素A、d、Ε及 K)在進入全身性循環之前經封裝至乳糜微粒中,因此mct 油對脂溶性營養素吸收提供之益處(其對於生長及發育亦 重要)可能受到更多限制。 161215.doc 201233329 儘管過去已嘗試解決GI問題及上文提及之其他問題,但 理想的疋提供可提供與母乳類似之營養益處且亦提供非水 容性疏水性營養素之良好耐受性、消化及吸收以及使諸如 壞死性小腸結腸炎、腹痛及短腸症之病況發生率減小之嬰 . 兒及小兒配方。此外,若該等配方無穩定劑且特定而言無 • 角叉菜膠’則將為有益的。 【發明内容】 本發明係關於營養品,且特定而言係關於嬰兒配方,其 包含預消化脂肪,該預消化脂肪包含含有脂肪酸之單酸甘 油酯及/或脂肪酸組分。該等營養組合物可有利地用於改 善營養素(包含非水溶性/脂溶性營養素)耐受性、消化及吸 收,以及用於減小壞死性小腸結腸炎 '腹痛及短腸症之發 生率。在某些貫施例中’脂肪酸組分可為脂肪酸形式,或 以脂肪酸之鈣鹽或鎂鹽形式提供,由此提供其他營養素之 其他益處。 一個實施例為一種營養品脂肪系統,其包含至少1〇 wt% 的3有月曰肪自文之早酸甘油醋。單酸甘油醋中至少7 〇 %之脂 肪酸處於Sn-Ι位置。 另一實施例為一種嬰兒配方脂肪系統,其包含至少1〇 wt% 的3有月曰肪之早酸甘油g旨。單酸甘油S旨中至少7 0 %之脂 肪酸處於Sn-Ι位置。 已發現,包含預消化脂肪(諸如如本文所述之單酸甘油 酯及脂肪酸)之營養品(諸如嬰兒、幼兒及小兒配方)可減輕 嬰兒月曰肪消化糸統之總體負擔以改善嬰兒脂肪消化及吸 161215.doc 201233329 收,包含非水溶性/脂溶性營養素吸收。特定而言,小腸 近端部分中對預消化脂肪之吸收刺激CCK分泌,此促使胰 腺α細胞成熟及消化酶分泌。又,GLP-1及GLP-2分泌受到 刺激’此進一步促使腸道成熟。 令人驚If地,使用預消化脂肪以及後續分泌CCK及GLP-1 使得GI轉運延遲且刺激胰腺酶分泌以使得營養素消化及吸 收更為完全。進入嬰兒結腸之營養素量的減少導致結腸醱 酵減少,此為脹氣及軟便問題之部分原因。另外,已發現 使用預消化脂肪可減小壞死性小腸結腸炎、腹痛及/或短 腸症之發生率。 此外,已發現預消化脂肪之不飽和脂肪酸組分可與鈣或 鎂源反應且所得形成之鹽令人㈣地為生物可p除提供 良好弼或㈣以外,該料或鎂鹽亦令人驚㈣是,與通 常有苦味且K予強烈咽喉灼熱感受之脂肪酸相比較為溫 和。此外’已發現脂肪㈣鹽或鎮鹽令人驚對地起到使營 養乳液穩定之作用,此你田生# 係因為其不會形成在乳液中難以分 散之沈=物,$同於有此傾向之許多不溶性弼鹽。因此, 在多個實施例中’包含脂肪料鹽或鎂鹽作為預消化脂肪 之部分可減少對穩定劑(諸如角又菜膠)之需求。 【實施方式】 j文所述之營養品包括預消化脂肪。在多個實施例中, β亥等產品包含含有脂肪酸 得預消化脂肪系统包含兩種Γ “脂肪酸組分以使 以包含兩種組分。藉由減 孩童消化系統之負擔,X幼兒或 供穩疋的生物可用產品之同時 16I215.doc 201233329 實現多種益處。營表〇 s養。^之該專及其他特徵以及 存在之變化及加料中之军此/T 裡规滑况 之某些在下文中詳細描述。 術語「殺菌爸封» Γ Μ 4* 困謂裝」及「殺菌|殺菌」在本文中可 使用,且除非另外均ΒΒ τ . = 5 ,否則係指以營養液體填充容5|201233329 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to a nutritional product comprising pre-digested fat and to a method of using the nutritional product. More particularly, the present invention relates to infants, infants, and pediatrics comprising a fatty acid monoglyceride and/or fatty acid component. The product provides nutritional benefits including improved digestion, tolerance, and nutrient absorption. And reduce the incidence of necrotizing enterocolitis, abdominal pain and short bowel disease. CROSS-REFERENCE TO RELATED APPLICATIONS RELATED APPLICATIONS RELATED APPLICATIONS RELATED APPLICATIONS STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT U.S. Provisional Application No. 6W42M76, the US Provisional Application No. 61/428,177, which was filed on December 29, and the US Provisional Application No. 61/428,185, which was filed on December 29, 2010 The disclosure of the 'intention' is incorporated herein by reference in its entirety. [Prior Art] Nutrient liquids and powders (including pediatric and pediatric formulas) containing targeted nutrients are well known and widely available, and some provide a single source of nutrients, while others provide supplemental sources. The material comprises a powder that can be reconstituted with water or other aqueous liquid, and a concentrated ready-to-drink nutrient liquid such as a milk or protein based emulsion. Liquids are especially useful when blended with selected nutrients. It is generally considered that breast milk is the best nutrition for newborn babies, but not every 161,215.doc 201233329 mothers can successfully breastfeed. Breastmilk substitutes (infant formulas) provide 70 whole nutrients and have been shown to meet normal growth and developmental nutritional needs of infants. Unfortunately, a small proportion of infant formula-fed newborns may experience gastrointestinal (GI) intolerance problems, including soft stools, flatulence, necrotizing enterocolitis, abdominal pain, and the like. The problem of GI intolerance can be attributed, at least in part, to incomplete digestion and absorption of nutrients by infants. To address this tolerance problem, some infant formulas exclude lactose as a component, while others replace hydrolyzed proteins with intact milk proteins to reduce the burden on the infant's digestive system. In addition, some formula silver newborn babies have a much lower rate of fat absorption than breast-fed babies. This difference in fat absorption rate decreases as the baby matures. It is speculated that newborn babies lack lipase and therefore cannot digest and absorb fat as well as breast-fed babies who receive lipase from breast milk. The digestive system of premature infants is less developed than the digestive system of full-term infants, which requires more nutrients (calories) than full-term infants to promote growth and development. Medium chain diglyceride S (MCT oil) is easy to digest and absorb and is included in preterm formula to improve formula fat, protein and calcium absorption. However, medium chain fatty acids in medium chain triglycerides are not used to re-synthesize triglycerides to form chylomicrons after digestion and absorption of MCT oil. Because many of the fat-soluble nutrients (such as carotenoids and vitamins A, d, Ε, and K) are encapsulated into chylomicrons before entering the systemic circulation, the benefits of mct oil for fat-soluble nutrient absorption (for growth) And development is also important) may be subject to more restrictions. 161215.doc 201233329 Despite attempts to address the GI problem and other issues mentioned above in the past, it is desirable to provide nutritional benefits similar to breast milk and also provide good tolerance and digestion of non-aqueous hydrophobic nutrients. And infants and pediatric formulations that absorb and reduce the incidence of conditions such as necrotizing enterocolitis, abdominal pain and short bowel disease. In addition, it would be beneficial if the formulations were free of stabilizers and in particular no carrageenan'. SUMMARY OF THE INVENTION The present invention relates to nutritional products, and in particular to infant formulas, which comprise pre-digested fats comprising a monoglyceride and/or fatty acid component comprising a fatty acid. These nutritional compositions can be advantageously used to improve the tolerance, digestion and absorption of nutrients (including water-insoluble/fat-soluble nutrients), and to reduce the incidence of diarrhea enterocolitis 'abdominal pain and short bowel disease. In certain embodiments, the fatty acid component can be in the form of a fatty acid or in the form of a calcium or magnesium salt of a fatty acid, thereby providing other benefits of other nutrients. One embodiment is a nutrient fat system comprising at least 1% by weight of 3 months old instant glycerin. At least 7 % of the fatty acid in the monoglyceride is in the Sn-Ι position. Another embodiment is an infant formula fat system comprising at least 1% wt% of 3 months old fat acid glycerol. At least 70% of the fatty acid in the monoglyceride S is in the Sn-Ι position. It has been found that nutrients (such as infants, toddlers, and pediatric formulas) comprising pre-digested fats (such as the monoglycerides and fatty acids as described herein) can reduce the overall burden of infants' digestive system to improve infant fat digestion. And absorb 161215.doc 201233329, containing water-insoluble / fat-soluble nutrient absorption. In particular, the absorption of pre-digested fat in the proximal part of the small intestine stimulates CCK secretion, which promotes pancreatic alpha-cell maturation and digestive enzyme secretion. In addition, GLP-1 and GLP-2 secretion are stimulated. This further promotes intestinal maturation. Surprisingly, the use of pre-digested fat and subsequent secretion of CCK and GLP-1 delays GI transport and stimulates pancreatic enzyme secretion to allow nutrient digestion and absorption to be more complete. A decrease in the amount of nutrients entering the infant's colon leads to a decrease in colonic fermentation, which is partly responsible for the problem of flatulence and soft stools. In addition, the use of pre-digested fat has been found to reduce the incidence of necrotizing enterocolitis, abdominal pain and/or short bowel disease. In addition, it has been found that the unsaturated fatty acid component of the pre-digested fat can react with the calcium or magnesium source and the resulting salt (4) provides good enthalpy for bio-p-removal or (d), and the material or magnesium salt is also surprising. (d) is milder than fatty acids that usually have a bitter taste and K is strongly irritated by the throat. In addition, it has been found that fat (tetra) salt or salt is surprisingly effective in stabilizing the nutritional emulsion. This is because you will not form a sinking substance that is difficult to disperse in the emulsion. Many insoluble strontium salts tend to be. Thus, the inclusion of a fatty salt or magnesium salt as part of the pre-digested fat in various embodiments may reduce the need for stabilizers such as keratin. [Embodiment] The nutrient described in the article includes pre-digested fat. In various embodiments, the product such as β Hai contains a fatty acid-containing pre-digested fat system comprising two hydrazine fatty acid components to contain two components. By reducing the burden on the child's digestive system, X infants or stable疋's bio-available products at the same time 16I215.doc 201233329 achieves a variety of benefits. The characteristics of the special and other features and changes in the presence of the military / T in the feed some of the details below are detailed below Description: The term "sterilization dad seal» Γ Μ 4* sleepy pack" and "sterilization|sterilization" can be used in this article, and unless otherwise ΒΒ τ . = 5, it means filling the nutrient liquid 5 |

(最一般為金屬罐或i : # W 、他類似封裝)且隨後使經液體填 封裝經受必要之埶殺结半 ' & *、、、杈鹵步驟Μ形成經殺菌之殺菌釜封 養液體產品的常見操作。 、呂 除非另外說明,否則如本文所用之術語「無菌封裝」係 指不依賴於上述殺菌爸封裝步驟製造封裝產品,其中技基 液體及封裝在填充之前分開經過殺菌,且隨後在經殺二或 無菌加工條件下組合以形成經殺菌、無菌封裝之營養液體 產品。 除非另外說明’否則如本文所用之術語「脂肪」及 「油」可互換使用’係指源自植物或動物或由其加 之脂質物質。該等術語亦包含合成脂質物質,只要該等合 成物質適合人類口服即可。 除非另外說明,否則如本文所用之術語「存放穩定」係 指在封裝且隨後在18_24t下儲存至少3個月(包含約6個月 至約24個月,且亦包含約12個月至㈣個月)之後仍在商 業上具穩定性之營養品。 如本文所用之術語「營養調配物」或「營養品」或厂營 養組合物」可互換使用,且除非另外說明,否則係指液= 及固體(包含半液體及半固體)人乳強化劑、液體及固體早 產兒配方、液體及固體嬰兒配方、液體及固體第二階段配 161215.doc 201233329 方、液體及固體小兒配方以及液體及㈣幼兒配方。該等 固體可為可經復原以形成營養液體之粉末,所有該等固體 均包括脂肪、蛋白及碳水化合物中之一或多者且適於人類 經口服用。 除非另外說明’否則如本文所用之術語「營養液體」係 指呈即飲型液體形式、濃縮形式之營養品及藉由在使用之 前使本文所述之營養粉末復原而製得之營養液體。 除非另外說明,否則如本文$ ^ p β 又所用之術語「營養粉末」係 指在服用之前可用水或另 一 〆 3水液體復原之呈可流動或可 舀取形式的營養品,且包含哈 、霧乾燥及乾混合/乾摻合粉 末。 之術語 之術語 嬰兒」係指12 早產兒」係指 除非另外說明,否則如本文所用 個月大或更幼小之人。如本文所用 在懷孕36週之前出生之嬰兒。 除非另外說明, 歲以上至三歲之人 否則如本文所用 之術語「幼兒」係指— π人所用之術語 歲以上至十二歲之人。 除非另外說明,否則如本 ^ 令又所用之術語「預消化脂欣 係指含有脂肪酸之單酸 ㈣化月曰肪」 除非另外說明,否則如本^㈣㈣。 指適於嬰兒服用作為主 所用之術語「嬰兒配方」令 除非另外說明,否則源之液體及固體營養品。(most commonly a metal can or i: #W, he is similarly packaged) and then subject the liquid-filled package to the necessary smashing halved ' & *,, 杈 杈 Μ Μ Μ Μ Μ Μ Μ Μ Μ Μ Μ Μ Μ Μ Common operations of the product. Unless otherwise stated, the term "aseptically packaged" as used herein means that the packaged product is manufactured independently of the sterilization step described above, wherein the technical base liquid and the package are separately sterilized prior to filling, and then killed or killed. The sterile processing conditions are combined to form a sterilized, aseptically packaged nutritional liquid product. The terms "fat" and "oil" as used herein, unless otherwise indicated, are used interchangeably to mean a plant or animal derived from or added to a lipid material. These terms also encompass synthetic lipid materials as long as the synthetic materials are suitable for oral administration to humans. The term "storage stable" as used herein, unless otherwise indicated, means that it is packaged and subsequently stored at 18_24t for at least 3 months (including from about 6 months to about 24 months, and also from about 12 months to (four) Commercially stable nutritional products after the month). The terms "nutritional formulation" or "nutraceutical" or plant nutritional composition as used herein are used interchangeably and, unless otherwise indicated, refer to liquids and solids (including semi-liquid and semi-solid) human milk fortifiers, Liquid and solid preterm formula, liquid and solid infant formula, liquid and solid phase II 161215.doc 201233329 Formula, liquid and solid pediatric formula and liquid and (4) infant formula. The solids can be a powder that can be reconstituted to form a nutrient liquid, all of which include one or more of fats, proteins, and carbohydrates and are suitable for oral administration to humans. The term "nutritional liquid" as used herein, unless otherwise indicated, means a nutrient in a ready-to-drink liquid form, a concentrated form, and a nutritional liquid prepared by reconstituting the nutritional powder described herein prior to use. Unless otherwise stated, the term "nutritional powder" as used in the context of $^pβ herein refers to a nutrient in a flowable or extractable form that can be reconstituted with water or another hydrazine 3 liquid prior to administration, and includes , mist drying and dry mixing / dry blending powder. The term "baby" means 12 premature baby means a person who is older or younger as used herein unless otherwise stated. An infant born before 36 weeks of gestation as used herein. Unless otherwise stated, persons over the age of three to three years of age, as used herein, the term "young child" means the term used by π people to be over the age of twelve. Unless otherwise stated, the term "pre-digested lipids" as used in this instruction refers to mono-acids containing fatty acids (IV). Unless otherwise stated, it is as follows (4) (4). Refers to the term "infant formula" used by the infant as the primary source of liquid and solid nutritional supplements unless otherwise stated.

J 指適於早產兒服用作為主早產兒配方 呂養源之液體及固體營養品 i612l5.doc 201233329 非另外說明則如本文所用之術語「人乳強化劑」 係礼適口與母乳或早產兒配方或嬰兒配方混合以供早產或 足月嬰兒服用之液體及固體營養品。 ”。” Μ外說明’否則如本文所用之術語「含有脂肪酸之 早&甘油s旨」係指由_個經由酿鍵在甘油分子之⑷、 〜2(β)或Sn_3(ai)位置之一者處共價鍵結至甘油分子的脂 肪酸鏈組成之甘油酯。 ^非另外e兒明’ $則如本文所用之術語「脂肪酸組分」 源自其中肉丑蔻酸、棕搁酸及硬脂酸總量小於游〇(以 θ十)之來源的游離脂肪酸或脂肪酸鹽(諸如脂肪酸鈣鹽 或鎂鹽)。 除非另外說明,否則如本文所用之術語「脂溶性營養 素」係指非水溶性營養素,諸如油可溶性(脂溶性)維生素 (例如維生素A、D、£及Κ)、類胡蘿蔔素(例如葉黃素、β- 月蘿蔔素、番加紅素等)、醣脂(神經結醣脂)、固醇及植物 化學品。 無,疋否明確揭示,如本文所用之數值範圍均意欲包含 彼範圍内之每—數值及數值子集n該等數值範圍應 視為對針對該範圍内任何數值或數值子集之主張提供支 持。舉例而言,揭示2至10應理解為支持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。 除非另外說明或在有提及之語境下明確相反暗示,否則 本發明中所有提及之單數特徵或限制均應包含對應之複數 特徵或限制,且反之亦然。 161215.doc 201233329 除非另外說明或在有提及組合之語境下明確相反暗示, 否則如本文所用之所有方法或製程步驟組合均可以任何·欠 序進行。 ~ 本發明營養品之各個實施例亦可實質上無本文所述之住 何視情況存在或選定的成分或特徵,其限制條件為其餘營 養品應仍含有如本文所述之所有所需成分或特徵。在此背 景下,且除非另外說明’否則術語「實質上無」意謂選定 營養品含有小於功能量之視情況存在之成分,—般小於ι 重量%(包含小於0.5重量%,包含小於〇.丨重量%且亦包含〇 重量%)之該視情況存在或選定的成分。 營養品及方法可包括如本文所述之產品要素以及本文所 述或另外適用於營養品及方法應用中之任何其他或視情況 存在之要素,由其組成或基本上由其組成。 產品形式 本發明之含有預消化脂肪的營養品及相關方法可以任何 已知或另外適合之口服產品形式來調配及執行。任何固 體、半固體、液體、半液體或粉末形式(包括其組合或變 化形式)在本文中均適用,其限制條件為該等形式允許安 全且有效地向個體經口傳遞亦如本文所定義之各成分。 本發明之營養品包含如本文所述之預消化脂肪。該等產 品可視情況包含含有脂肪酸之單酸甘油酯或脂肪酸組分與 下文所述之其他脂肪來源的組合。 該等產品可包含包括本文所述之成分且口服安全又有效 之任何產品形式。該等營養品可經調配以僅包含本文所述 161215.doc -10· 201233329 之成分,或可用視情況存在之成八 于隹又或分改質以形成多種不同之 產品形式。 本發明之營養品較佳經調配為飲食產品形式,其在本文 中定義為以因而含有脂肪、蛋白及碳水化合物中之至少一 者且較佳亦含有維生素、礦物質或其組合之產品形式包括 本發明之成分的彼等實施例。在多個實施例中,該產品將 包括預消化脂肪與蛋白質、碳水化合物、維生素及礦物質 之組合以產生營養品。 該等營養品可用足夠種類及量之營養素調配以提供單 一、主要或補充性之營養來源,或提供專用於罹患特定疾 病或病況之個體或具有目標營養益處的營養品。 、 舉例而吕,合與如本文揭示之預消化脂肪一起使用之 產品形式的特定非限制性實例包含液體及粉末狀人乳強化 劑、液體及粉末狀早產絲方、液體及粉末狀嬰兒配方、 液體及粉末狀要素及半要素配方、液體及㈣狀小兒配方 以及液體及粉末狀幼兒配方。 營養液體 營養液體包含濃縮型及即食型營養液體。該等營養液體 最一般地經調配為懸浮液或乳液。 適用之營養乳液可為包含蛋白質、脂肪及碳水化合物之 含水乳液。該等乳液在約!它至約25〇c下通常為可流動戋 可飲用之液體且一般呈水包油、油包水或複合含水乳液形 式,不過該等乳液最一般為具有連續水相及不連續油相之 水包油乳液形式。 1612l5.doc -11 · 201233329 營養乳液可為存放穩定的且一般為存放穩定的。該等營 養乳液以營養乳液之重量計一般含有高達約95重量%之 水,包括約50重量%至約95重量%,亦包括約6〇重量%至 約90重量%,且亦包括約7〇重量%至約88重量%之水。營 養乳液可具有各種產品密度,但最一般具有大於約丨〇3 g/ml之社、度,包括大於約丨〇4 g/mi,包括大於約丨〇55 g/ml,包括約1.06 g/ml至約1.12 g/ml,且亦包括約1.085 g/ml至約 1.10 g/ml。 營養乳液可具有為符合最終使用者之營養需求而定製之 熱量密度’不過在大多數情況下該等乳液通常包含至少19 kcal/fl oz(660千卡/公升)、更一般為約2〇 kcai/fi 〇z(675_ 680千卡/公升)至約25 kcal/fl 〇z(820千卡/公升)、甚至更一 般為約 20 kcal/fl 〇z(675-680 千卡 /公升)至約 24 kcal/fl oz(800-810千卡/公升)。通常而言,22_24 kcal/fl 〇z(74〇_ 810千卡/公升)配方更普遍用於早產或低出生體重的嬰兒, 且20-21 kcal/fl OZ(675-680至700千卡/公升)配方更常用於 足月嬰兒。在某些實施例中,乳液可具有約i 〇〇千卡/公升 至約660千卡/公升之熱量密度,包括約15〇千卡/公升至約 500千卡/公升。 營養乳液可具有約3.5至約8範圍内之pH值,但最有利地 為約4.5至約7.5範圍内’包括約5.5至約7.3,包括約6.2至 約 7.2。 儘管營養乳液之服用量可視多種變數而變化,但典型之 服用量通常為至少約2 mL,或甚至至少約5 mL,或甚至至 161215.doc 12 201233329 包括約2 mL至約300 mL ,且包括約ίο mL·至約J refers to liquid and solid nutrients suitable for preterm infants to be used as the main preterm formula. i612l5.doc 201233329 The term "human milk fortifier" as used herein, unless otherwise stated, is a palatable and breast or premature formula or infant formula. Liquid and solid nutritional supplements for preterm or full-term infants. ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” One is a glyceride covalently bonded to a fatty acid chain of a glycerol molecule. ^非其他儿明' $ The term "fatty acid component" as used herein is derived from free fatty acids in which the total amount of meat ugly acid, palmitic acid and stearic acid is less than that of the free (at θ) source. A fatty acid salt (such as a fatty acid calcium or magnesium salt). The term "liposoluble nutrient" as used herein, unless otherwise indicated, refers to water-insoluble nutrients such as oil-soluble (fat-soluble) vitamins (eg, vitamins A, D, £ and strontium), carotenoids (eg, lutein). , β-moon radish, ruthenium, etc.), glycolipids (neurolipids), sterols and phytochemicals. Nothing is explicitly disclosed, and the numerical ranges used herein are intended to include each of the numerical and numerical sub-sets within the range. n. The numerical ranges should be construed as supporting the claim of any value or subset of values within the range. . For example, the disclosures 2 to 10 should be understood to support ranges 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. All singular features or limitations of the present invention are intended to include the corresponding singular features or limitations, and vice versa, unless otherwise stated or indicated to the contrary. 161215.doc 201233329 All methods or combinations of process steps as used herein may be performed in any order, unless otherwise stated or implicitly stated to the contrary. ~ Each embodiment of the nutritional product of the present invention may also be substantially free of any components or features present or selected as described herein, with the proviso that the remaining nutritional products should still contain all of the desired ingredients as described herein or feature. In this context, and unless otherwise stated, the term "substantially absent" means that the selected nutrient contains less than a functional amount of the component, as opposed to 1% by weight (including less than 0.5% by weight, including less than 〇. The % by weight and also the % by weight of the component present or selected as appropriate. The nutraceuticals and methods can comprise, consist of, or consist essentially of, the product elements described herein, as well as any other or optionally existing elements described herein or otherwise applicable to the use of the nutraceutical and method. Product Form The pre-digested fat-containing nutrient of the present invention and related methods can be formulated and executed in any known or otherwise suitable oral product form. Any solid, semi-solid, liquid, semi-liquid or powder form, including combinations or variations thereof, is used herein with the proviso that such forms permit safe and effective oral delivery to an individual as also defined herein. Each component. The nutritional product of the present invention comprises pre-digested fat as described herein. Such products may optionally comprise a combination of a fatty acid containing monoglyceride or fatty acid component with other fat sources as described below. Such products may comprise any of the product forms including the ingredients described herein and which are safe and effective for oral administration. The nutraceuticals may be formulated to contain only the ingredients of 161215.doc -10· 201233329 as described herein, or may be modified as appropriate to form a plurality of different product forms. The nutritional product of the present invention is preferably formulated in the form of a dietary product, which is defined herein as a product form comprising at least one of fat, protein and carbohydrate, and preferably also vitamins, minerals or combinations thereof. Examples of the components of the invention. In various embodiments, the product will include a combination of pre-digested fat with protein, carbohydrates, vitamins and minerals to produce a nutritional product. These nutrients may be formulated with sufficient types and amounts of nutrients to provide a single, primary or supplemental source of nutrition, or to provide an individual dedicated to a particular disease or condition or a nutritional product having a targeted nutritional benefit. Specific non-limiting examples of product forms for use with pre-digested fats as disclosed herein include liquid and powdered human milk fortifiers, liquid and powdered premature silk, liquid and powdered infant formulas, Liquid and powdered ingredients and semi-element formulas, liquid and (iv) pediatric formulas, and liquid and powdered infant formulas. Nutrient Liquids Nutrient liquids contain concentrated and ready-to-eat nutrient liquids. These nutrient liquids are most commonly formulated as suspensions or emulsions. Suitable nutritional emulsions can be aqueous emulsions containing proteins, fats and carbohydrates. These lotions are around! It is typically a flowable, drinkable liquid at about 25 ° C and is typically in the form of an oil-in-water, water-in-oil or composite aqueous emulsion, although the emulsions are most generally water with a continuous aqueous phase and a discontinuous oil phase. In the form of an oil-in-water emulsion. 1612l5.doc -11 · 201233329 Nutritional emulsions are stable to storage and generally stable to storage. The nutritional emulsions generally comprise up to about 95% by weight water, including from about 50% to about 95% by weight, and also from about 6% to about 90% by weight, and also about 7 Å, by weight of the nutritional emulsion. From % by weight to about 88% by weight of water. The nutritional emulsions can have a variety of product densities, but most typically have a regimen of greater than about 丨〇3 g/ml, including greater than about 丨〇4 g/mi, including greater than about 丨〇55 g/ml, including about 1.06 g/ Ml to about 1.12 g/ml, and also includes from about 1.085 g/ml to about 1.10 g/ml. The nutritional emulsion can have a caloric density tailored to meet the nutritional needs of the end user's. However, in most cases the emulsions typically comprise at least 19 kcal/fl oz (660 kcal/liter), more typically about 2 〇. Kcai/fi 〇z (675_ 680 kcal / liter) to about 25 kcal / fl 〇 z (820 kcal / liter), and even more generally about 20 kcal / fl 〇 z (675-680 kcal / liter) to Approximately 24 kcal/fl oz (800-810 kcal/litre). In general, 22_24 kcal/fl 〇z (74〇_ 810 kcal/litre) formula is more commonly used in preterm or low birth weight infants, and 20-21 kcal/fl OZ (675-680 to 700 kcal/ Liters) formulas are more commonly used in term infants. In certain embodiments, the emulsion can have a caloric density of from about 1 kilocalyptus per liter to about 660 kilocalories per liter, including from about 15 kilocalories per liter to about 500 kilocalories per liter. The nutritional emulsion can have a pH in the range of from about 3.5 to about 8, but most advantageously in the range of from about 4.5 to about 7.5' including from about 5.5 to about 7.3, including from about 6.2 to about 7.2. Although the amount of nutrient emulsion can vary depending on a variety of variables, typical dosages are typically at least about 2 mL, or even at least about 5 mL, or even up to 161215.doc 12 201233329 includes from about 2 mL to about 300 mL, and includes About ίο mL·to about

少約10 mL ’或甚至至少約25 llU, 範圍内,包括約4 mL至約250 mL 240 mL。 如上所述,營養品亦可為半液體形式,包括特性(諸如 流動特性)介於中間態(在液體與固體之間)之彼等形式。例 不性半液體包括黏稠奶昔及液體凝膠。 營養固趙 營養固體可為任何固體形式,但—般為可流動或實質上 可流動的微粒組合物形式,或至少為微粒組合物。尤其適 合之營養固體產品形式包括經喷霧乾燥、聚結或乾摻合之 粉末組合物。該等組合物可容易地用勺子或類似其他裝置 來备取或量測,其中該等組合物可容易地由預期使用者以 適合之含水液體(一般為水)來復原以形成營養調配物以供 即刻經口或經腸使用。在此背景下,「即刻」使用通常意 謂較佳正好在復原後約48小時之内,最一般在約24小時之 内。 營養粉末可在使用之前用水復原至為符合最終使用者之 營養需求而定製之熱量密度,不過在大多數情況下該等粉 末用水復原而形成包含至少19 kcal/fl oz(660千卡/公升)、 更一般為約 20 kcal/fl oz(675-680千卡/公升)至約 25 kcal/fl oz(820千卡/公升)、甚至更一般為約20 kcal/fl oz(675-680 千卡/公升)至約24 kcal/fl oz(800-810千卡/公升)之組合 物。通常而言,22-24 kcal/fl oz(740-810千卡/公升)配方更 普遍用於早產或低出生體重的嬰兒,且20-21 kcal/fl 161215.doc -13- 201233329 M675-680至700千卡/公升)配方更常用於足月嬰兒。在某 些實施例中,復原粉末可具有約5〇千卡/公升至約66〇千卡 公升之熱量密度,包括約100千卡/公升至約5〇〇千卡/公 升。 如上所述,營養品亦可為半固體形式,包括特性(諸如 剛性)介於中間態(在固體與液體之間)之彼等形式。—些半 固體實例包括布丁、明膠及膏團。 預消化脂肪系統 Α.含有脂肪酸之單睃甘油醋 在某些實施例中,本發明之營養品包含單獨或與如下文 所述之脂肪酸組分組合的含有脂肪酸之單酸甘油酯,亦稱 作單醯基甘油。單酸甘油酯為在三酸甘油酯及二酸甘油醋 分解時在體内形成之正常代謝物。正如所述,含有脂肪酸 之單酸甘油酯可與脂肪酸組分(諸如如下文所述之脂肪酸 及/或脂肪酸鹽)組合包含於營養品中,或可在不存在脂肪 酸組分之情況下包含於營養品中。 適合用於營養品中之含有脂肪酸之單酸甘油酯可包含具 有4至22個碳原子之鏈長度的脂肪酸,包括具有14至20個 碳原子之鏈長度的脂肪酸,且包括棕櫚酸(16個碳原子)。 尤其較佳為單酸甘油酯,其中單酸甘油酯中至少70%之脂 肪酸位於Sn-1位置(亦稱作α位置),包括在Sn-1位置處具有 至少約70%之棕櫚酸殘基的單棕櫚酸甘油酯’包括在Sn-1 位置處至少約80%,且包括在Sn-1位置處約85%至約 10 0 %。此外,在某些實施例中,本文所述營養品中包含 161215.doc •14- 201233329 之單酸甘油酯可包括痕量之二酸甘油酯、游離甘油及/或 游離脂肪酸。如本文中所用,術語「痕量」意謂不超過1〇 Wt%,但更通常小於7 5 wt%之量。 在一個特定實施例中,營養品中之單酸甘油酯(且視情 況為如下文論述之脂肪酸組分)部分地或完全經由使用水 解緒油或水解動物脂來向產品提供。豬油、動物脂及其他 基於動物之產品可添加至營養品中且由胰腺脂肪酶水解為 單酸甘油酯及脂肪酸◊或者,豬油或動物脂可經水解之後 併入營養品中以產生單酸甘油酯及脂肪酸,其可引入營養 品中。豬油、動物脂或水解豬油或動物脂可提供營養品中 之一部分或所有單酸甘油酯及/或脂肪酸。 在另一實施例中,營養品中之單酸甘油酯部分或完全源 自油《員’諸如植物油、水產動物油、魚油、海藻油、真菌 油、樹脂及其組合。舉例而言,適合之植物油包括撖欖 油、芥花籽油(canola oil)、玉米油、棕摘油' 大豆油 (soybean oil)及其組合。 ;含有脂肪酸之單酸甘油酯以按營養品中包含之脂肪組分 十至八ί] 1G重里%之量存在於營養品+,包括以營養品中 包=之脂肪組分計至少約15重量%,包括以營養品中包含 之月曰肪組^至少約2G重量%,包括以營養品中包含之脂 肪組分計12重量%至45重量%、包括15重量_重量%且 包括約1〇重量%、包括約15重量。/。、包括約20重量%、包 :約25重量%、包括約3〇重量%且進一步包括㈣重量 。或甚至相重1 %、或甚至約5〇重量。/。、或甚至約的 161215.doc -15· 201233329 重量%、或甚至約70重量%、或甚至約80重量%、或甚至 約90重量%、或甚至約1〇〇重量%。 在一個特定實施例中’當營養品為包含約28%(以營養粉 末之重量計)脂肪組分之營養粉末時,含有脂肪酸之單酸 甘油酯以約1 〇 %(以脂肪組分之重量計)之含量存在,或每 10 0公克營養粉末約2.8公克含有脂肪酸之單酸甘油|旨。 在另—特定實施例中,當營養品為包含約3·67%(以即食 型營養液體之重量計)脂肪組分之即食型營養液體時,含 有脂肪酸之單酸甘油酯以約1 〇 %(以脂肪組分之重量計)之 含量存在’或每100公克即食型營養液體約〇 367公克含有 月曰肪酸之早酸甘油醋。 在另一特定實施例中,當營養品為包含約7 34%(以濃縮 型營養液體之重量計)脂肪組分之濃縮型營養液體時,含 有脂肪酸之單酸甘油酯以約1 0 %(以脂肪組分之重量計)之 含量存在’或每100公克濃縮型營養液體約〇 734公克含有 月曰肪酸之早酸甘油酷。 除提供上文所列之多種益處以外,亦已發現含有脂肪酸 之單酸甘油酯在營養品中具有抗病毒及/或抗細菌活性。 特定而言,已發現營養品中含有脂肪酸之單酸甘油酯之存 在能殺死病原體及/或減緩其複製。 B.脂肪酸組分 除上述含有脂肪酸之單酸甘油酯以外,或替代上述含有 月曰肪酸之單酸甘油酯,本發明之營養品可包含含有脂肪酸 之脂肪酸組分作為預消化脂肪系統之一部分。脂肪酸為在 I612l5.doc -16- 201233329 脂肪(三酸甘油酯、二酸甘油酯、膽固醇酯及某些磷脂)分 解時在體内!頁著形成之正常代謝物。f亥脂肪酸組分為獨立 的且不同於上文論述之含有脂肪酸之單酸甘油酯。 在營養品中有益之任何脂肪酸均可作為預消化脂肪系統 之一部分包含於營養品中。在一個實施例中,脂肪酸為不 飽和游離脂肪酸。在包含不飽和游離脂肪酸之某些實施例 中,具有超過14個碳原子之鏈長度的不飽和游離脂肪酸之 總量小於15 wt%。適合包含於本文所述營養品中之例示性 脂肪酸包括(但不限於)花生四烯酸、次亞麻油酸、二十二 石反六稀酸、十八碳四烯酸、油酸、二十碳烯酸、二十礙三 烯酸(mead acid)、芥酸、神經酸以及其混合物及組合。尤 其較佳之脂肪酸包括花生四烯酸、亞麻油酸、次亞麻油 酸、二十二碳六烯酸及油酸。 包含於預消化脂肪系統中之脂肪酸組分包括源自諸如植 物油、水產動物油、魚油、海藻油、真菌油、動物脂肪、 動物脂肪分離物及其組合之油類的彼等脂肪酸組分。舉例 而言,適合之植物油包括橄欖油、芥花籽油、玉米油、大 豆油及其組合。在一個實施例中’當使用動物脂肪時,脂 肪酸係由豬油或動物脂之酶促水解而獲得,且所得脂肪酸 混合物中棕摘酸及硬脂酸之含量減少至小於總脂肪酸之 20%,包括小於總脂肪酸之2%。在另一實施例中,至少〆 些脂肪酸源自大豆油或樹脂。一旦源自油來源,則脂肪酸 實質上不含單酸甘油酯、二酸甘油酯及三酸甘油酯。 脂肪酸通常將源自含有小於約20%(以重量計)棕櫚酸及/ 161215.doc 17 201233329 或硬脂酸及/或肉豆蔻酸之源油。在某些實施例中,脂肪 酸將源自含有小於約15%(以重量計)、包括小於約10%(以 重量計)、包括小於約5%(以重量計)且包括小於2%(以重量 叶)掠橺酸及/或硬脂酸及/或肉豆蔬酸之源油。 在一個特定實施例中,脂肪酸係源自含有小於約20%(以 重量計)’包括約10%(以重量計)至約15%(以重量計)棕櫚 酸及/或硬脂酸及/或肉豆蔻酸之源油。在另一特定實施例 中’營養品包含以總脂肪酸計小於約10%(以重量計)之量 的掠摘酸。 在某些實施例中’營養品可包含呈鹽形式之脂肪酸;亦 即’脂肪酸可以脂肪酸鹽形式添加至營養品中。在一個適 合的實施例中’脂肪酸係以脂肪酸鈣鹽、脂肪酸鎂鹽或其 組合之形式添加至營養品中。 脂肪酸鹽可由熟習此項技術者基於本文之揭示内容來製 備。在一種適合的製程中,包含c10_C24脂肪酸鈣鹽之乳液 可藉由首先藉由使用與至少一種c】Q _ C 2 4脂肪酸來源混合之 右干種起始鈣來源製備脂肪酸鹽來製備。更特定而言,在 種方法中,包含呈三酸甘油酯摻合物形式或游離形式的 C〗〇-C24脂肪酸之起始來源可藉由與氫氧化鈣及/或碳酸鈣 或磷酸鈣接觸而形成。在另—種方法中,呈三酸甘油 -曰夂。物或游離形式之CicrC24脂肪酸可藉由與口^^值為6至 約7.5之水合(:3(:12或(:^(八(:〇)2接觸而製得。 1 X上方法可在惰性氛圍下,例如在N2或氬氣下進行。在 其他貫例中’任何所揭示之方法均可在環境氛圍下進行 1612l5.d -18· 201233329 (例如,其中不在低氧氛圍下進行反應)。 包含C1Q-C24脂肪酸之來源與鈣來源可藉由此· 知之任何方法來混合。「混合」並非意謂暗示特定 果’諸如任何組分溶解至特定程度或形成特定組八 ° 如均質混合物)’不過可產生該等混合物且 (諸 木二組分可藉 由混合而溶解。混合可為劇烈的且可手動或 曰 4稭由機械裝置 (諸如(但不限於)靜態混合器、磁力攪拌器、 π 俯置器、旋轉 器或旋轉裝置)來進行。混合可藉由迫使氣體通過混合物 或使氣體起泡通過混合物或藉由音波處理來進行。 c1〇-c24脂肪酸來源與飼來源混合可進行至幻分鐘。混 合亦可進行至少1、5、15、20、25、30、35、 w 40 、 45 、 5〇、55、60、65、70、75、8〇、85、9〇、95或1〇〇 分鐘, 其中任何所述值若適當則均可形成上端或下端端點。 混合可在各種溫度下進行,但該方法—般在高溫下發 生。確切高溫可取決於C〗G_C24脂肪酸或鈣之特定起始來源 及其用量。可進行所揭示混合所處之適合溫度包括(但不 限於)約4°C至約l〇(TC、約1〇。(:至約i〇〇°c、約15〇c至約 100°C、或約20°C 至約70°C。 包含C1G-C24脂肪酸或鈣之來源亦可在混合之前經加熱。該 種預熱步驟可在本文所述之任何溫度或溫度範圍下進行。 在某些實施例中,C10-C24脂肪酸與鈣之混合可在減壓下 進行。適合壓力小於或等於約i托(Torr)或小於或等於約 0.1托。 在一個理想實施例中,CI0-C24脂肪酸鈣鹽係藉由添加游 161215.doc 19 201233329 離(:1()-〇:24不飽和脂肪酸及鈣來源(諸如Ca(〇H)2、丨2、Less than 10 mL' or even at least about 25 llU, including about 4 mL to about 250 mL 240 mL. As noted above, the nutritional product may also be in a semi-liquid form, including such forms in which the properties (such as flow characteristics) are intermediate (between the liquid and the solid). Examples of non-volatile semi-liquids include viscous shakes and liquid gels. The nutritional solid can be in any solid form, but is generally in the form of a flowable or substantially flowable particulate composition, or at least a particulate composition. Particularly suitable nutritional solid product forms include spray dried, coalesced or dry blended powder compositions. The compositions can be readily prepared or measured with a spoon or similar device, wherein the compositions can be readily reconstituted by a prospective user with a suitable aqueous liquid (typically water) to form a nutritional formulation. For immediate oral or enteral use. In this context, "immediate" use generally means that it is preferably within about 48 hours of recovery, most typically within about 24 hours. The nutritional powder can be reconstituted with water prior to use to a caloric density tailored to meet the end user's nutritional needs, but in most cases the powder is reconstituted with water to form at least 19 kcal/fl oz (660 kcal/liter) ), more generally about 20 kcal/fl oz (675-680 kcal / liter) to about 25 kcal / fl oz (820 kcal / liter), and even more generally about 20 kcal / fl oz (675-680 thousand Card/L) to a composition of approximately 24 kcal/fl oz (800-810 kcal/liter). In general, 22-24 kcal/fl oz (740-810 kcal/litre) formula is more commonly used in preterm or low birth weight infants, and 20-21 kcal/fl 161215.doc -13- 201233329 M675-680 Formulas up to 700 kcal/litre are more commonly used for term infants. In some embodiments, the reconstituted powder can have a caloric density of from about 5 kcal/liter to about 66 kcal, including from about 100 kcal/liter to about 5 kcal/liter. As noted above, the nutritional product may also be in a semi-solid form, including such forms as properties (such as stiffness) in the intermediate state (between the solid and the liquid). Some semi-solid examples include puddings, gelatin and creams. Pre-digested fat system Α. Monoglyceride containing glycerin in certain embodiments. In certain embodiments, the nutritional product of the present invention comprises a fatty acid-containing monoglyceride, alone or in combination with a fatty acid component as described below, also referred to as Monothiol glycerol. Monoglyceride is a normal metabolite formed in the body when triglyceride and diglyceride are decomposed. As stated, the fatty acid-containing monoglyceride may be included in the nutrient in combination with a fatty acid component such as a fatty acid and/or a fatty acid salt as described below, or may be included in the absence of the fatty acid component. In the nutrition. A fatty acid-containing monoglyceride suitable for use in a nutritional product may comprise a fatty acid having a chain length of 4 to 22 carbon atoms, including a fatty acid having a chain length of 14 to 20 carbon atoms, and including palmitic acid (16 carbon atom). Particularly preferred is a monoglyceride wherein at least 70% of the fatty acids in the monoglyceride are at the Sn-1 position (also referred to as the alpha position), including at least about 70% palmitic acid residues at the Sn-1 position. The monopalmitate 'includes at least about 80% at the Sn-1 position and includes from about 85% to about 100% at the Sn-1 position. Moreover, in certain embodiments, the monoglycerides comprising 161215.doc • 14 to 201233329 in the nutritional products described herein may include trace amounts of diglycerides, free glycerol, and/or free fatty acids. As used herein, the term "trace" means no more than 1 〇 Wt%, but more typically less than 7.5 wt%. In a particular embodiment, the monoglyceride in the nutrient (and, as the case may be, the fatty acid component as discussed below) is provided to the product, either partially or completely via the use of hydrolysate or hydrolyzed animal fat. Lard, tallow and other animal-based products can be added to the nutrient and hydrolyzed by pancreatic lipase to monoglycerides and fatty acids. Alternatively, lard or tallow can be hydrolyzed and incorporated into the nutrient to produce a single Acid glycerides and fatty acids, which can be incorporated into nutrients. Lard, tallow or hydrolyzed lard or tallow may provide some or all of the monoglycerides and/or fatty acids in the nutrient. In another embodiment, the monoglyceride in the nutritional product is partially or completely derived from an oil such as vegetable oil, aquatic animal oil, fish oil, algae oil, fungal oil, resin, and combinations thereof. For example, suitable vegetable oils include eucalyptus oil, canola oil, corn oil, palm oil, soybean oil, and combinations thereof. The fatty acid-containing monoglyceride is present in the nutritional product + in an amount of 10% by weight of the fat component contained in the nutrient, including at least about 15 weights in the fat component of the nutritional product. %, including at least about 2 G weight% of the monthly fat group included in the nutrient, including 12% by weight to 45% by weight, including 15% by weight and including about 1%, based on the fat component contained in the nutrient. % by weight, including about 15% by weight. /. Including about 20% by weight, package: about 25% by weight, including about 3% by weight and further including (iv) by weight. Or even a weight of 1%, or even about 5 inches. /. Or even about 161215.doc -15· 201233329 wt%, or even about 70 wt%, or even about 80 wt%, or even about 90 wt%, or even about 1 wt%. In a particular embodiment, 'when the nutritional product is a nutritional powder comprising about 28% (by weight of the nutritional powder) of the fat component, the fatty acid-containing monoglyceride is about 1% by weight (by weight of the fat component) The content of the compound is present, or about 2.8 grams of fatty acid monoglyceride per 100 grams of nutritional powder. In another specific embodiment, when the nutritional product is a ready-to-feed nutritional liquid comprising about 3.67% (by weight of the ready-to-feed nutritional liquid) fat component, the fatty acid-containing monoglyceride is about 1% The content (based on the weight of the fat component) is present or 'about 367 grams per 100 grams of ready-to-feed nutritional liquid, pre-acid glycerin containing tartaric acid. In another specific embodiment, when the nutritional product is a concentrated nutritional liquid comprising about 734% (by weight of the concentrated nutritional liquid) of the fat component, the fatty acid-containing monoglyceride is about 10% ( The content of the weight of the fat component is present or 'about 734 grams per 100 grams of concentrated nutrient liquid, which contains the early acid glycerin of the fatty acid. In addition to providing the various benefits listed above, it has also been found that monoglycerides containing fatty acids have antiviral and/or antibacterial activity in the nutritional product. In particular, it has been found that the presence of fatty acid monoglycerides in the nutritional product kills the pathogen and/or slows its replication. B. Fatty acid component In addition to or in place of the above-mentioned monoglyceride containing fatty acid, the nutritional product of the present invention may comprise a fatty acid component containing a fatty acid as part of a pre-digested fat system. . Fatty acids are in the body when they are decomposed in I612l5.doc -16- 201233329 fats (triglycerides, diglycerides, cholesterol esters and certain phospholipids)! The normal metabolite formed by the page. The f-fatty acid component is independent and distinct from the fatty acid-containing monoglyceride discussed above. Any fatty acid that is beneficial in the nutritional product can be included in the nutritional product as part of the pre-digested fat system. In one embodiment, the fatty acid is an unsaturated free fatty acid. In certain embodiments comprising an unsaturated free fatty acid, the total amount of unsaturated free fatty acids having a chain length of more than 14 carbon atoms is less than 15 wt%. Exemplary fatty acids suitable for inclusion in the nutrients described herein include, but are not limited to, arachidonic acid, linoleic acid, docosalic acid, stearidonic acid, oleic acid, twenty Carboxenoic acid, mead acid, erucic acid, nervonic acid, and mixtures and combinations thereof. Particularly preferred fatty acids include arachidonic acid, linoleic acid, linoleic acid, docosahexaenoic acid and oleic acid. The fatty acid component contained in the pre-digested fat system includes those fatty acid components derived from oils such as vegetable oils, aquatic animal oils, fish oils, seaweed oils, fungal oils, animal fats, animal fat isolates, and combinations thereof. For example, suitable vegetable oils include olive oil, canola oil, corn oil, soybean oil, and combinations thereof. In one embodiment, 'when animal fat is used, the fatty acid is obtained by enzymatic hydrolysis of lard or tallow, and the content of palmitic acid and stearic acid in the resulting fatty acid mixture is reduced to less than 20% of the total fatty acid. Includes less than 2% of total fatty acids. In another embodiment, at least some of the fatty acids are derived from soybean oil or a resin. Once derived from the oil source, the fatty acid is substantially free of monoglycerides, diglycerides, and triglycerides. The fatty acid will typically be derived from a source oil containing less than about 20% by weight palmitic acid and /161215.doc 17 201233329 or stearic acid and/or myristic acid. In certain embodiments, the fatty acid will be derived from containing less than about 15% by weight, including less than about 10% by weight, including less than about 5% by weight, and including less than 2% (in terms of Weight leaf) The source oil of citric acid and / or stearic acid and / or meat and vegetable acid. In a particular embodiment, the fatty acid is derived from less than about 20% by weight 'comprising from about 10% by weight to about 15% by weight of palmitic acid and/or stearic acid and/or Or the source of myristic acid. In another particular embodiment the 'nutrient comprises plucking acid in an amount of less than about 10% by weight based on total fatty acids. In certain embodiments the 'nutrient may comprise a fatty acid in the form of a salt; i.e., the fatty acid may be added to the nutrient as a fatty acid salt. In a suitable embodiment, the fatty acid is added to the nutritional product in the form of a fatty acid calcium salt, a fatty acid magnesium salt, or a combination thereof. Fatty acid salts can be prepared by those skilled in the art based on the disclosure herein. In a suitable process, an emulsion comprising a c10_C24 fatty acid calcium salt can be prepared by first preparing a fatty acid salt by using a right stem starting calcium source mixed with at least one c]Q _ C 2 4 fatty acid source. More specifically, in the method, the starting source comprising the C 〇-C24 fatty acid in the form of a triglyceride blend or in a free form can be contacted by calcium hydroxide and/or calcium carbonate or calcium phosphate. And formed. In another method, it is triglyceride-oxime. The Citr C24 fatty acid in free form or in free form can be obtained by hydration with a mouth value of 6 to about 7.5 (: 3 (: 12 or (: ^ (eight (: 〇) 2). In an inert atmosphere, for example under N2 or argon. In any other example, 'any of the disclosed methods can be carried out under ambient conditions 1612l5.d -18· 201233329 (eg, where the reaction is not carried out under a low oxygen atmosphere) Sources containing C1Q-C24 fatty acids and calcium sources can be mixed by any means known to this. "Mixing" does not mean implying that a particular fruit 'such as any component dissolves to a certain extent or forms a specific group of eight° such as a homogeneous mixture) 'However, such mixtures can be produced and (the two components of the wood can be dissolved by mixing. The mixing can be vigorous and can be manually or smashed by mechanical means such as (but not limited to) static mixers, magnetic stirrers , π decanter, rotator or rotating device). Mixing can be carried out by forcing the gas through the mixture or by bubbling the gas through the mixture or by sonication. The c1〇-c24 fatty acid source can be mixed with the feed source. to Minutes. Mixing can also be performed at least 1, 5, 15, 20, 25, 30, 35, w 40 , 45 , 5 〇, 55, 60, 65, 70, 75, 8 〇, 85, 9 〇, 95 or 1 〇〇 minutes, any of which may form an upper or lower end if appropriate. Mixing can be carried out at various temperatures, but the method generally occurs at elevated temperatures. The exact high temperature can depend on C gram G_C24 fatty acid or calcium Specific starting sources and amounts thereof. Suitable temperatures at which the disclosed mixing can be carried out include, but are not limited to, from about 4 ° C to about 1 Torr (TC, about 1 Torr. (: to about i 〇〇 ° c, From about 15 ° C to about 100 ° C, or from about 20 ° C to about 70 ° C. Sources containing C1G-C24 fatty acids or calcium may also be heated prior to mixing. This preheating step can be any of those described herein. The temperature or temperature range is carried out. In certain embodiments, the mixing of the C10-C24 fatty acid with calcium can be carried out under reduced pressure. Suitable pressures are less than or equal to about 1 Torr or less than or equal to about 0.1 Torr. In a preferred embodiment, the CI0-C24 fatty acid calcium salt is separated from (:1()-〇:24 unsaturated fat by adding 161215.doc 19 201233329 Acid and calcium source (such as Ca (〇H) 2, Shu 2,

CaC〇3、檸檬酸鈣或該等鹽之混合物)以形成油摻合物來2製 備。更特定而言,將脂肪酸溶解於溫熱水溶液(例如,具 有約40C至約80 C之溫度)中。可使用K〇H4Na〇H將溶液 之pH值調整至一般為約1〇_kp·。隨後向所溶解之含 脂肪酸的溶液中添加辦…般使脂肪酸及弼靜置分鐘以 確保脂肪酸與.㈣子之間完全反應。隨後使混合物均質化 以形成油捧合物。 在另個理想實施丫列中,製備脂肪酸妈鹽之混合物(包 括來自魚油、海薄油、真菌油及大豆油(卿。⑴之脂肪酸) 作為預消化脂肪系統之一部分。將魚油、海藻油、真菌油 及大豆油混合在一起且在氮氣層下由氫氧化鉀水解。隨後 向混&物令添加約來源(諸如氣化妈)以與脂肪酸反應而產 生不溶性脂肪酸鈣鹽^該等不溶性脂肪酸鹽可藉由過濾分 離,且用水洗滌,然後進行真空乾燥。 已令人驚訝地發現,儘管脂肪酸鹽(諸如脂肪酸鈣鹽)通 *不/合於營養品中,但其不會在溶液中沈降而形成難以再 分散之沈降物層。因此,使用脂肪酸鈣鹽及/或脂肪酸鎂 鹽使付鈣/鎂傳遞更佳,且在多個實施例中可消除對於其 他穩定劑(諸如角又菜膠)之需求,以使得產品可實質上或 完全「無角叉菜膠」。 因此,與使用磷酸鈣或碳酸鈣作為鈣來源之產品相比,使 用脂肪酸鹽使得鈣及/或鎂及脂肪酸生物可用性得以改善。 此外,已發現在本發明之營養品中使用脂肪酸鹽提供生 161215.doc -20- 201233329 物可用性脂肪酸’諸如花生四烯酸(ara)及其類似物,其 顯示增強嬰兒生長。使用預消化脂肪亦提供具有經改善之 產品穩定性及較長存放期之乳狀營養品。 營養品通常包含按營養品令包含之脂肪組分計至少約 10%(以重量計)之量的脂肪酸或脂肪酸鹽,包括按營養品 _包含之脂肪組分計至少約丨5重量%、包括至少約2〇重量 %、包括約10重量%至約60重量%、包括約15重量%至約40 重量%,且包括約15重量%至約35重量%、包括約1〇重量 %、包括約15重量%、包括約20重量%、包括約25重量%、 包括約30重量%、包括約35重量%且進一步包括約4〇重量 A、或甚至約50重量%、或甚至約6〇重量%、或甚至約7〇 重量%、或甚至約80重量%、或甚至約9〇重量%、或甚至 約100重量%。 在某些實施例中,#養品包含脂肪酸組分與含有脂肪酸 甘油㈣混合物。在該等實施例中,營養品含有按 二養。α中包含之脂肪組分計至少1〇%(以重量計)之量的混 。合物’包括按營養品中包含之脂肪組分計至少約Η重量 /〇、包括至少約20重量%、包括約10重量%至約40重量%、 ^括約20重量%至約65重量%、包括約25重量%至約5〇重 篁%、包^約15重量%至約3〇重量%,且包括約Μ重量%至 約25 ^里/〇、包括約10重量%、包括約15重量%、包括約 20重里。〆。、包括約25重量%、包括約3〇重量%、包括約35 重量 %,η *ζ*. 且進一步包括約40重量%或甚至約5〇重量%、或 甚至約6°重量%、或甚至約70重量%、或甚至約80重量 161215.doc 21 201233329 %、或甚至約90重量%或甚至約1 〇〇重量%。 在其他實施例_,營養品包含以營養品中總乾物質計至 少0.2%(以重量計)、包括至少1%(以重量計)、包括至少 2%(以重量計)且包括至少5%(以重量計)之量的脂肪酸組 分、含有脂肪酸之單酸甘油酯或其組合。 常量營養素(Macronutrient) 儘管脂肪、蛋白及碳水化合物之總濃度或量可視產品類 型(亦即’人乳強化劑、嬰兒配方等)、產品形式(亦即,營 養固體、粉末、即食型液體或濃縮型液體)及預期使用者 之目標飲食需求而變化’但該等濃度或量最一般在以下具 體範圍之一内,包括如本文所述之任何其他脂肪、蛋白及/ 或碳水化合物成分。 對於液體早產及足月嬰兒配方產品而言,以早產或足月 嬰兒配方之重量計,碳水化合物濃度最一般在約至約 40%、包括約7%至約30%、包括約1〇〇/。至約25%之範圍 内,以早產或足月嬰兒配方之重量計,脂肪濃度(包括預 消化脂肪與任何其他脂肪來源)最一般在約1%至約3〇%、 包括約2%至約15%以及包括約3%至約丨〇%之範圍内;且以 早產或足月嬰兒配方之重量計,蛋白濃度最_般在約〇 5% 至約30 /〇、包括約1%至約15%以及包括約2%至約1〇%之範 圍内。 對於液體人乳強化劑產品而言,以人乳強化劑之重量 計,碳水化合物濃度最一般在約1〇%至約75%、包括約 贈。至約50%、包括約2G%至約㈣之範μ ;以人乳強化 161215.doc -22- 201233329 劑之重量計’脂肪濃度(包括預消化脂肪與任何其他脂肪 來源)最一般在約10%至約40%、包括約15%至約37%以及 包括約18%至約30%之範圍内;且以人乳強化劑之重量 計’蛋白濃度最一般在約5%至約40%、包括約1〇%至約 30%以及包括約15%至約25%之範圍内。 除了如下表所列的營養品中之總熱量百分比以外或作為 其替代,亦表徵液體營養品中碳水化合物、脂肪及/或蛋 白之含量或量。用於本發明液體營養品之該等常量營養素 最一般在下表所述之任何熱量範圍内(實施例A_F)調配(每 一數值之前均有術語「約」)。 營養素總熱量。/。 實施例A 實施例B 實施例C 竣水化合物 0-98 2-96 10-75 蛋白 0-98 2-96 ~ 5-70 脂肪 0-98 2-96 10^5~~" 實施例F 實施例D 實施例E 碳水化合物 , ------- 卜 30-50 25-50 ~~ 「25-50 5-30 蛋白 15-35 10-30 脂肪 35-55 1-20 _ T20 在一個特定實例中,液體嬰兒配方(即食型與濃縮型液 體)包括彼等實施例,其中蛋白組分可構成配方之約7.5% 至約25%之熱量含量;碳水化合物組分可構成嬰兒配方之 約35%至約50%之總熱量含量;且脂肪組分可構成嬰兒配 方之約30%至約60%之總熱量含量。該等範圍僅作為實例 提供,且不欲具限制性。下表中列舉其他適合範圍(每一 數值之前均有術語「約」)。 161215.doc •23· 201233329 營養素總熱量% 實施例G 實施例Η 實施例I 碳水化合物: 20-85 30-60 35-55 脂肪: 5-70 20-60 25-50 蛋白: 2-75 5-50 7-40 當營養品為粉末型早產或足月嬰兒配方時,以早產或足 月嬰兒配方之重量計,蛋白組分以約5%至約35%、包括約 8%至約12%且包括約1〇%至約12%之量存在;以早產或足 月嬰兒配方之重量計,脂肪組分以約1 〇%至約35◦/〇、包括 約25%至約30%且包括約26〇/〇至約28%之量存在;且以早產 或足月嬰兒配方之重量計,碳水化合物組分以約30%至約 85%、包括約45%至約60%且包括約50%至約55%之量存在。 對於粉末型人乳強化劑而言,以人乳強化劑之重量計, 蛋白組分以約1%至約55%、包括約10%至約50%且包括約 10 %至約3 0 %之量存在;以人乳強化劑之重量計,脂肪組 分以約1 %至約3 0 °/〇、包括約1 〇/q至約2 5 %且包括約1 %至約 20%之量存在;且以人乳強化劑之重量計,碳水化合物組 分以約15%至約75%、包括約15%至約60%且包括約2〇%至 約50%之量存在。 脂肪、碳水化合物及蛋白在本發明粉末型營養品中之總 量或濃度可在相當程度上視所選產品及預期使用者之飲食 或醫學需求而變化。下文列舉常量營養素濃度之其他適合 實例。在此背景下,總量或濃度係指粉末型產品中之所有 脂肪、碳水化合物及蛋白質來源。對於粉末型營養品而 言,該等總量或濃度最一般且較佳在下表所述之任何具體 範圍内調配(所有數值之前均具有「約」)。 161215.doc -24- 201233329CaC〇3, calcium citrate or a mixture of such salts) is prepared to form an oil blend. More specifically, the fatty acid is dissolved in a warm aqueous solution (e.g., having a temperature of from about 40 C to about 80 C). The pH of the solution can be adjusted to generally about 1 〇 _kp· using K 〇 H4Na〇H. The fatty acid and hydrazine are then added to the dissolved fatty acid-containing solution to allow for a complete reaction between the fatty acid and the (tetra). The mixture is then homogenized to form an oil cocktail. In another ideal implementation list, a mixture of fatty acid salts (including fish oil, sea oil, fungal oil, and soybean oil (Q1, (1) fatty acids) is prepared as part of the pre-digested fat system. Fish oil, algae oil, The fungal oil and the soybean oil are mixed together and hydrolyzed by potassium hydroxide under a nitrogen blanket. Then, about a source (such as a gasification mother) is added to the mixture to react with the fatty acid to produce an insoluble fatty acid calcium salt. The salt can be separated by filtration and washed with water and then dried under vacuum. It has been surprisingly found that although fatty acid salts (such as fatty acid calcium salts) are not/in combination with nutrients, they do not settle in solution. Forming a sediment layer that is difficult to redisperse. Thus, the use of fatty acid calcium salts and/or fatty acid magnesium salts provides better calcium/magnesium delivery and, in various embodiments, eliminates other stabilizers (such as horn gum The need to make the product substantially or completely "carrageenan". Therefore, compared to products that use calcium phosphate or calcium carbonate as a source of calcium. The fatty acid salt improves the bioavailability of calcium and/or magnesium and fatty acids. Furthermore, it has been found that the use of fatty acid salts in the nutritional products of the present invention provides 161215.doc -20-201233329 availability of fatty acids such as arachidonic acid (ara) And its analogues, which are shown to enhance the growth of infants. The use of pre-digested fat also provides milky nutritional supplements with improved product stability and long shelf life. Nutritional products usually include fat components included in the nutritional supplements. At least about 10% by weight of the fatty acid or fatty acid salt, including at least about 5% by weight, including at least about 2% by weight, including about 10% by weight to about 8% by weight of the nutritional component. 60% by weight, including about 15% to about 40% by weight, and including about 15% to about 35% by weight, including about 1% by weight, including about 15% by weight, including about 20% by weight, including about 25 weight %, including about 30% by weight, including about 35% by weight and further including about 4% by weight A, or even about 50% by weight, or even about 6% by weight, or even about 7% by weight, or even about 80 weight %, or even about 9% by weight, or even about 100% by weight. In certain embodiments, the #养品 comprises a mixture of a fatty acid component and a fatty acid containing glycerol (tetra). In these embodiments, the nutritional product contains two The compound comprising 'at least 1% by weight (by weight) of the fat component contained in the alpha comprises at least about Η weight/〇, including at least about 20 weights, based on the fat component contained in the nutritional product. %, including from about 10% by weight to about 40% by weight, including from about 20% by weight to about 65% by weight, including from about 25% by weight to about 5% by weight, from about 15% by weight to about 3% by weight And comprising from about 5% by weight to about 25 mils/inch, including about 10% by weight, including about 15% by weight, including about 20 mils, including about 25% by weight, including about 3% by weight, including about 35 wt%, η *ζ*. and further comprising about 40% by weight or even about 5% by weight, or even about 6% by weight, or even about 70% by weight, or even about 80% 161215.doc 21 201233329 % Or even about 90% by weight or even about 1% by weight. In other embodiments, the nutritional product comprises at least 0.2% by weight, including at least 1% by weight, including at least 2% by weight, and including at least 5%, by total dry matter in the nutritional product. A fatty acid component (by weight), a fatty acid-containing monoglyceride, or a combination thereof. Macronutrient Although the total concentration or amount of fat, protein and carbohydrate can be determined by product type (ie 'human milk fortifier, infant formula, etc.), product form (ie nutrient solids, powder, ready-to-feed liquid or concentrated) The type of liquid) and the intended user's target dietary requirements vary, but such concentrations or amounts are most generally within one of the following specific ranges, including any other fat, protein, and/or carbohydrate component as described herein. For liquid preterm and term infant formulas, the carbohydrate concentration is most generally from about 40%, including from about 7% to about 30%, including about 1% by weight of the preterm or term infant formula. . To a range of about 25%, the fat concentration (including pre-digested fat and any other fat source) is generally from about 1% to about 3%, including about 2% to about the weight of the preterm or term infant formula. 15% and including from about 3% to about 丨〇%; and the protein concentration is most preferably from about 5% to about 30%, including about 1% to about the weight of the preterm or term infant formula. 15% and include from about 2% to about 1%. For liquid human milk fortifier products, the carbohydrate concentration is most typically from about 1% to about 75% by weight of the human milk fortifier, including the bonus. To about 50%, including about 2G% to about (4), the ratio of the weight of the human milk to 161215.doc -22-201233329, the fat concentration (including pre-digested fat and any other fat source) is most generally about 10 % to about 40%, including from about 15% to about 37%, and including from about 18% to about 30%; and the protein concentration is most generally from about 5% to about 40% by weight of the human milk fortifier, It includes from about 1% to about 30% and includes from about 15% to about 25%. In addition to or as an alternative to the percentage of total calories in the nutritional products listed in the following table, the amount or amount of carbohydrate, fat and/or protein in the liquid nutritional product is also characterized. The macronutrients used in the liquid nutritional products of the present invention are most generally formulated in any of the calories described in the following table (Example A_F) (the term "about" is used before each value). The total calories of nutrients. /. EXAMPLES Example B Example C Hydrophobic Compound 0-98 2-96 10-75 Protein 0-98 2-96 ~ 5-70 Fat 0-98 2-96 10^5~~" Example F Implementation Example D Example E Carbohydrate, ------- Bu 30-50 25-50 ~~ "25-50 5-30 Protein 15-35 10-30 Fat 35-55 1-20 _ T20 in a specific In the examples, liquid infant formulas (ie, ready-to-serve and concentrated liquids) include embodiments in which the protein component can comprise from about 7.5% to about 25% of the caloric content of the formulation; the carbohydrate component can comprise about 35 percent of the infant formula. % to about 50% of the total caloric content; and the fat component may constitute from about 30% to about 60% of the total caloric content of the infant formula. These ranges are provided by way of example only and are not intended to be limiting. Other suitable ranges (each term has the term "about"). 161215.doc •23· 201233329 Total nutrient calories % Example G Example 碳水化合物 Carbohydrate: 20-85 30-60 35-55 Fat: 5-70 20-60 25-50 Protein: 2-75 5- 50 7-40 When the nutritional product is a powdered preterm or term infant formula, the protein component is from about 5% to about 35%, including from about 8% to about 12%, by weight of the preterm or term infant formula. Included in an amount from about 1% to about 12%; the fat component is from about 1% to about 35%, including from about 25% to about 30% by weight of the preterm or term infant formula, and includes about 26 〇 / 〇 to about 28% of the amount; and the carbohydrate component is from about 30% to about 85%, including from about 45% to about 60% and including about 50% by weight of the preterm or term infant formula It is present in an amount of about 55%. For powdered human milk fortifiers, the protein component is from about 1% to about 55%, including from about 10% to about 50%, and including from about 10% to about 30%, by weight of the human milk fortifier. The amount is present; the fat component is present in an amount of from about 1% to about 30 °/〇, including from about 1 〇/q to about 25 %, and including from about 1% to about 20% by weight of the human milk fortifier And the carbohydrate component is present in an amount from about 15% to about 75%, including from about 15% to about 60%, and including from about 2% to about 50%, by weight of the human milk fortifier. The total amount or concentration of fats, carbohydrates, and proteins in the powdered nutritional products of the present invention can vary to a considerable extent depending on the selected product and the intended user's dietary or medical needs. Other suitable examples of macronutrient concentrations are listed below. In this context, total or concentration refers to all sources of fat, carbohydrate and protein in a powdered product. For powdered nutritional supplements, these totals or concentrations are most generally and preferably formulated within any of the specific ranges set forth in the table below (all values have "about" before). 161215.doc -24- 201233329

除預消化脂肪以外,本發明之營養品還可包含其他脂肪 來源(脂肪之總量在本文中稱作營養品之「脂肪組分」或 「脂肪系統」)。適合用於本文之其他脂肪來源包括適合 用於口服營養品且可與該等產品之要素及特徵相容之任何 脂肪或脂肪來源。 適合用於本文所述營#品中之其他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、橄 欖油、紅花籽油、高油酸紅花籽油、油酸(emers〇l 6313 油酸)、MCT油(中鏈三酸甘油酯)、向日葵油、高油酸向日 葵油、棕櫚油及棕搁仁油、棕橺油精、芬花籽油、水產動 物油、魚油、真菌油、海藻油、棉籽油及其組合。在一個 實施例中,適合之脂肪或其來源包括包含長鏈聚不飽和脂 肪酸(LC-PUFA ’較佳為具有四個或四個以上雙鍵之LC_ PUFA)之油類及油換合物。舉例而言,可包含之某些非限 制性特定聚不飽和酸包括二十二碳六烯酸(DHA)、花生四 烯酸(ARA)、二十碳五烯酸(EPA)及其類似物。 本文所述之預消化脂肪通常與一種、兩種、三種、四種 或四種以上其他脂肪來源組合包含於營養品中。在一個實 施例中’將單酸甘油醋(理想地為單棕搁酸甘油醋之形 式)、脂肪酸(理想地為鈣鹽之形式)、高油酸油及椰子油組 161215.doc -25· 201233329 合在一起以提供營養品中之脂肪組分。在該實施例中,以 脂肪組分之重量計,單酸甘油酯以約1 %至約4〇%(包括約 10%至約30%,包括約1〇%、約15%、約20%、約23%及約 25%)之量存在;以脂肪組分之重量計,脂肪酸以約1%至 約40°/。(包括約1〇%至約3〇%,包括約10%、約15%、約2〇% 及約2 5 %)之量存在;以脂肪組分之重量計’高油酸油以約 1%至約40%(包括約1〇%至約30%,包括約10%、約15〇/〇、 約20%、約25%及約30%)之量存在;且以脂肪組分之重量 計,椰子油以約1%至約40%(包括約10%至約30%,包括約 10%、約15%、約17%、約20%及約25%)之量存在。 在另一實施例中,將含有脂肪酸之單酸甘油酯(理想地 為單棕櫚酸甘油酯之形式)、脂肪酸組分(理想地為的鹽之 形式)、高油酸紅花籽油及椰子油組合在一起以提供營養 品中之脂肪組分。在該實施例中,以脂肪組分之重量計, 單酸甘油酯以約1 %至約40%(包括約1 〇%至約30%,包括約 10%、約15%、約20%、約23%及約25%)之量存在;以脂肪 組分之重量計,脂肪酸以約1%至約40%(包括約1〇%至約 30%,包括約10%、約15%、約20%及約25%)之量存在;以 脂肪組分之重量計,高油酸油以約1〇/。至約4〇%(包括約ι〇〇/0 至約30%,包括約10% '約1 5%、約20%、約25%及約30%) 之里存在,且以脂肪組分之重量計,挪子油以約1 %至約 4〇%(包括約10%至約30%,包括約10%、約15%、約π%、 約20%及約25%)之量存在。 在另一實施例中’將含有脂肪酸之單酸甘油酯(理想地 161215.doc -26· 201233329 為單棕櫚酸甘油酯之形式)、脂肪酸組分(理想地為鈣鹽之 形式)、高油酸紅花籽油、椰子油、含DHA油及含ARA油 組合在一起以提供營養品中之脂肪組分。在該實施例中, 以脂肪組分之重量計,單酸甘油酯以約1 %至約40%(包括 約10%至約30%,包括約10%、約15%、約20%、約23%及 約25%)之量存在;以脂肪組分之重量計,脂肪酸以約1 % 至約40%(包括約10%至約30%,包括約10%、約15%、約 20%及約25%)之量存在;以脂肪組分之重量計,高油酸油 以約1。/。至約40%(包括約10%至約30%,包括約10%、約 15%、約20%、約25%及約30%)之量存在;且以脂肪組分 之重量計,椰子油以約1%至約40%(包括約10%至約3〇〇/0, 包括約10%、約15%、約17%、約20%及約25%)之量存在。 含DHA油以脂肪組分之重量計以約1 %至約丨〇%(包括約$0/〇) 之量存在且含ARA油以脂肪組分之重量計以約ι%至約 1〇%(包括約5%)之量存在。 在另一實施例中,脂肪組分包含約38%(以重量計)高油 酸紅花籽油、約17%(以重量計)椰子油、約23%(以重量計) 單棕橺酸甘油酯、約20%(以重量計)脂肪酸舞鹽、約 0.5%(以重量計)含DHA油及約].〇%(以重量計)含ara油。 蛋白質 / 除預消化脂肪以外,本發明之營養品還可視情況進一牛 包含蛋白。適用於口服營養品且可與該等產品之要素及^ 徵相容之任何蛋白質來源均適合與預消化脂肪組合使用。寺 適合用於該等營養品中之蛋白或其來源之非限制性實例 161215.doc -27· 201233329 包括水解、部分水解或非水解蛋白或蛋白質來源,其可源 自任何已知或另外適合之來源’諸如乳類(例如酪蛋白、 乳清)、動物(例如肉類、魚肉)、縠物(例如水稻、玉米)、 植物(例如大豆)或其組合《該等蛋白之非限制性實例包括 乳類蛋白分離物、如本文所述之乳類蛋白濃縮物、路蛋白 分離物、廣泛水解之酪蛋白、乳清蛋白、酪蛋白鈉鹽或鈣 鹽、全牛乳、部分或完全脫脂乳、大豆蛋白分離物、大豆 蛋白濃縮物等等。 碳水化合物 本發明之營養品可進一步視情況包含適合用於口服營養 且可與該等產品之要素及特徵相容之任何碳水化合物。In addition to pre-digested fat, the nutritional products of the present invention may also contain other sources of fat (the total amount of fat referred to herein as the "fat component" or "fat system" of the nutritional product). Other fat sources suitable for use herein include any fat or fat source suitable for oral nutrition and compatible with the elements and characteristics of such products. Non-limiting examples of other fats or sources thereof suitable for use in the products described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, olive oil, safflower oil, high oleic safflower oil, oil Acid (emers〇l 6313 oleic acid), MCT oil (medium chain triglyceride), sunflower oil, high oleic sunflower oil, palm oil and palm oil, palm oil, fennel seed oil, aquatic animal oil , fish oil, fungal oil, algae oil, cottonseed oil and combinations thereof. In one embodiment, suitable fats or sources thereof include oils and oil combinations comprising long chain polyunsaturated fatty acids (LC-PUFA' preferably LC_PUFA having four or more double bonds). For example, certain non-limiting specific polyunsaturated acids that may be included include docosahexaenoic acid (DHA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and the like. . The pre-digested fats described herein are typically included in the nutritional product in combination with one, two, three, four or more other fat sources. In one embodiment 'single monoglyceride (ideally in the form of a single palm glycerol), a fatty acid (ideally in the form of a calcium salt), a high oleic oil and a coconut oil group 161215.doc -25· 201233329 Together to provide the fat component of the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 4% by weight, including from about 10% to about 30%, including about 1%, about 15%, about 20% by weight of the fat component. , about 23% and about 25%) are present; the fatty acid is from about 1% to about 40° by weight of the fat component. (inclusive of from about 1% to about 3%, including about 10%, about 15%, about 2%, and about 25%); based on the weight of the fat component, 'high oleic acid oil is about 1 % to about 40% (including about 1% to about 30%, including about 10%, about 15%/〇, about 20%, about 25%, and about 30%); and the weight of the fat component The coconut oil is present in an amount from about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 17%, about 20%, and about 25%. In another embodiment, a fatty acid containing monoglyceride (ideally in the form of monopalmitate), a fatty acid component (ideally in the form of a salt), high oleic safflower oil, and coconut oil Combined to provide a fat component in the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component, including from about 1% to about 30%, including about 10%, about 15%, about 20%, Approximately 23% and about 25%) are present; from about 1% to about 40% by weight of the fat component, including from about 1% to about 30%, including about 10%, about 15%, about The amount of 20% and about 25%) is present; the high oleic acid oil is about 1 〇/ by weight of the fat component. Up to about 4% (including about ι〇〇/0 to about 30%, including about 10% 'about 1 5%, about 20%, about 25%, and about 30%), and The oil is present in an amount of from about 1% to about 4% by weight, including from about 10% to about 30%, including about 10%, about 15%, about π%, about 20%, and about 25% by weight. In another embodiment, 'a fatty acid-containing monoglyceride (ideally 161215.doc -26·201233329 in the form of monopalmitic acid glyceride), a fatty acid component (ideally in the form of a calcium salt), high oil Saffron seed oil, coconut oil, DHA-containing oil, and ARA-containing oil are combined to provide a fat component in the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23% and about 25%) are present; from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 20% And about 25%) is present; the high oleic acid oil is about 1 by weight of the fat component. /. Up to about 40% (including about 10% to about 30%, including about 10%, about 15%, about 20%, about 25%, and about 30%); and by weight of the fat component, coconut oil It is present in an amount from about 1% to about 40%, including from about 10% to about 3%/0, including about 10%, about 15%, about 17%, about 20%, and about 25%. The DHA-containing oil is present in an amount from about 1% to about 丨〇% (including about $0/〇) by weight of the fat component and the ARA-containing oil is from about 1% to about 1% by weight of the fat component ( Including about 5%). In another embodiment, the fat component comprises about 38% by weight high oleic safflower oil, about 17% by weight coconut oil, and about 23% by weight monopalmitoyl glycerol. Ester, about 20% by weight fatty acid salt, about 0.5% by weight of DHA-containing oil and about 〇% by weight of ara oil. Protein / In addition to pre-digested fat, the nutritional product of the present invention may optionally contain a protein. Any protein source suitable for oral nutrition and compatible with the elements and ingredients of these products is suitable for use in combination with pre-digested fat. Non-limiting examples of a protein suitable for use in such nutraceuticals or sources thereof 161215.doc -27· 201233329 includes hydrolyzed, partially hydrolyzed or non-hydrolyzed protein or protein sources, which may be derived from any known or otherwise suitable Sources such as milk (eg casein, whey), animals (eg meat, fish), booties (eg rice, corn), plants (eg soybean) or combinations thereof. Non-limiting examples of such proteins include milk Protein-like isolates, milk protein concentrates as described herein, road protein isolates, extensively hydrolyzed casein, whey proteins, casein sodium or calcium salts, whole milk, partially or fully skimmed milk, soy protein Isolates, soy protein concentrates, and the like. Carbohydrates The nutritional products of the present invention may further comprise any carbohydrate suitable for oral nutrition and compatible with the elements and characteristics of such products, as appropriate.

鉀、甜菊)及其組合。 其他視情況存在之成分Potassium, stevia) and combinations thereof. Other ingredients that exist as the case may be

等視情況存在之成分或其另外適用於 營香組分。已知多種該 於醫學食品或其他營養 16l215.doc -28- 201233329 品或醫藥劑型中,且亦可用於本文之組合物中,其限制條 件為該等視情況存在之組分口服安全且可與選定產品形式 之各成分相容。 該等視情況存在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、果募醣、半乳募醣、益菌助生 質、醫藥活性物、如本文所述之其他營養素、著色劑、調 味劑、增稠劑及穩定劑、乳化劑、潤滑劑等等。 營養品可進一步包含甜味劑,較佳包括至少一種糖醇, 諸如麥芽糖醇、赤藻糖醇、山梨糖醇、木糖醇、甘露糖 醇、異麥芽酮糖醇(isolmalt)及乳糖醇,且亦較佳包括至少 一種人造或高效能甜味劑,諸如乙醯磺胺酸κ、阿斯巴甜 糖(aspartame)、蔗糖素、糖精、甜菊及塔格糖(tagat〇se)。 該等甜味劑(尤其呈糖醇與人造甜味劑之組合)尤其適用於 調配本發明的具有理想味道型態之液體飲料實施例。該等 甜味劑組合對於遮蔽有時與液體飲料中所添加植物蛋白相 關之不良味道尤其有效。營養品中視情況存在之糖醇濃度 以營養品之重量計可在至少0.01%,包括〇 1%至約1〇%, 且亦包括約1%至約6〇/。之範圍内。視情況存在之人造甜味 劑濃度以營養品之重量計可在約0 01%,包括約〇 〇5%至約 5% ’亦包括約0.1 %至約1.0%之範圍内。 流動劑或防結塊劑可包含於如本文所述之營養品中以延 遲粉末隨時間而凝塊或結塊且製得易於自其容器流出之粉 末實施例。已知或另外適用於營養粉末或產品形式之任何 已知流動劑或防結塊劑均適用於本文中,其非限制性實例 161215.doc -29- 201233329 包括填酸三釣、石夕酸鹽及其組合《營養品中流動劑或防結 塊劑之濃度視產品形式、其他所選成分、所要流動特性等 等而變化,但以營養品之重量計最常在約〇 1%至約4〇/。, 包括約0.5%至約2%之範圍内。 穩定劑亦可包含於營養品中。已知或另外適用於營養品 中之任何穩定劑亦適用於本文中,其某些非限制性實例Z 括角又菜膠及膠類(諸如三仙膠以營養品之重量計,穩 定劑可佔約0_丨%至約5_〇%,包括約〇5%至約3%,包括^ 0.7% 至約 1.5%。 ^ 營養品組合物可進一步包含任何各種其他維生素或相關 營養素,其非限制性實例包括維生素A、維生素D、唯生An ingredient that is present as appropriate or otherwise suitable for use in a camping component. A variety of such products are known to be used in medical foods or other nutraceuticals, or in pharmaceutical compositions, and may also be used in the compositions herein, with the proviso that the components present in such conditions are orally safe and compatible. The ingredients of the selected product form are compatible. Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifiers, buffers, fruit sugars, galactoses, probiotics, pharmaceutically actives, other nutrients as described herein. , colorants, flavoring agents, thickeners and stabilizers, emulsifiers, lubricants, and the like. The nutritional product may further comprise a sweetener, preferably comprising at least one sugar alcohol such as maltitol, erythritol, sorbitol, xylitol, mannitol, isomalt, and lactitol And preferably also includes at least one artificial or high potency sweetener such as acesulfame κ, aspartame, sucralose, saccharin, stevia and tagatose. Such sweeteners, especially in combination with sugar alcohols and artificial sweeteners, are particularly suitable for formulating liquid beverage embodiments of the present invention having a desired taste profile. These sweetener combinations are particularly effective for masking undesirable tastes sometimes associated with vegetable proteins added to liquid beverages. The concentration of sugar alcohol present in the nutritional product may be at least 0.01% by weight of the nutritional product, including from 1% to about 1%, and also including from about 1% to about 6%. Within the scope. The artificial sweetener concentration, as the case may be, may range from about 0.01% by weight of the nutritional product, including from about 5% to about 5%, and also from about 0.1% to about 1.0%. A flow or anti-caking agent can be included in the nutrient as described herein to delay the agglomeration or agglomeration of the powder over time and to produce a powder embodiment that readily flows out of its container. Any known flow or anti-caking agent known or otherwise suitable for use in nutritional powders or product forms is suitable for use herein, non-limiting examples of which are 161215.doc -29-201233329 including acid-filled three-fish, lycopene And combinations thereof. The concentration of the flow agent or anti-caking agent in the nutritional product varies depending on the product form, other selected ingredients, desired flow characteristics, etc., but is usually from about 1% to about 4 by weight of the nutritional product. 〇/. , including from about 0.5% to about 2%. Stabilizers can also be included in the nutritional product. Any stabilizer known or otherwise suitable for use in a nutraceutical is also suitable for use herein, some non-limiting examples of which include a mixture of vegetable gums and gums (such as Sanxian gum, based on the weight of the nutritional product, the stabilizer may From about 0% to about 5%, including from about 5% to about 3%, including from about 0.7% to about 1.5%. ^ The nutritional composition may further comprise any of a variety of other vitamins or related nutrients, Restricted examples include vitamin A, vitamin D, and only life

素£、維生素κ、疏胺素、核黃素、吼。多醇、維生素I :胡蘿萄素(例如β-胡蘿勤素、玉米黃素、葉黃素、番蘇紅 素)、於酸、葉酸、泛酸、生物素、維生素C、膽驗、肌 醇、其鹽及衍生物以及其組合。 —營養品可進—步包含任何各種其他礦物質,其非限制性 貫例包括弼、鱗、鎖、鐵、鋅、猛、銅、納、鉀、_、 子及其組合。此外,在某些實施射,營養品可 不含角又菜夥。 製造方法 :發明之營養品可藉由任何已知或另外可有 :產品固體或液體形式之製造技術來製備。 :可:於任何給定的產品形式(諸如營養繼 谷易地由-般熟習此項技術者應用於本文所述之營養品。 I612I5.doc 201233329 因此’本發明之營養品可藉由任何各種已知或另外有效 之產品或製造方法來製備。舉例而言,在一種適合之製造 製程中’分開製備至少三種躁料’包括脂肪包蛋白質(piF) 漿料、碳水化合物·礦物質(CH〇_MIN)漿料及水包蛋白質 (piwm料。PIF㈣係藉由加熱及混合油類(例如單酸甘 油醋及/或脂肪酸、含有月旨肪酸之油、芬花軒油、玉米油 等)且隨後伴隨持續加熱及攪拌添加乳化劑(例如卵磷脂)、 月曰肪可’合性維生素及一部分總蛋白(例如,乳蛋白濃縮物 等)來形成。CHO-Mmt料係藉由伴隨加熱攪拌向水中添 加以下各物而形成:礦物質(例如擰檬酸鉀、磷酸二鉀、 摔檬酸鈉等)、痕量及超痕量礦物質(TM/UTM預混物)及/或 增稠劑或懸浮劑(例如晶性纖維素(avicel)'結冷膠 (geHan)、角叉菜膠)。使所得(:η〇_μιν漿料在持續加熱及 攪拌下保持10分鐘,然後添加其他礦物質(例如氣化鉀、 碳酸鎂、碘化鉀等)及/或碳水化合物(例如果寡醣、斧糖、 玉米糖㈣)。隨後若還有任何剩餘蛋白f,則藉由伴隨 加熱及攪拌混合來形成PIW漿料。 在本發明之一個特定實施例中,可將營養品中包含之所 有或一部分預消化脂肪添加至CH〇_MIN漿料中,該聚料含 有小於5。/。(以CH0-MIN衆料之重量計)的呈三酸甘油醋形式 之脂肪。在該實施例中,營養品中存在之總脂肪之至少 5%(以重量計)為予員消化脂肪形式且被添加至ch〇_min漿料 中。在某些實施例中’將營養品令包含之至少5%(以重量 計)、包括至少10%(以重量計)、包括至少2〇%(以重量 J61215.doc 31 201233329 計)、包括至少30%(以重量計)、包括至少4〇%(以重量 計)、包括至少50%(以重量計)、包括至少6〇%(以重量 計)、包括至少70%(以重量計)、包括至少8〇%(以重量 計)、包括至少90%(以重量計)且包括1〇〇%(以重量計)之總 預消化脂肪添加至⑽捕㈣料中。在—個特定實施例 中,在將預消化脂肪添加至CH0.MIN激料中之前或在製造 CHO-Mm漿料期間將脂溶性營養素(諸如混合類胡蘿㈣ 或維生素A、D、EAK)溶解於預消化脂肪甲。與阳聚料 形成對比,藉由向CH0_MINMt添加㈣化㈣,最終 營養組合物之穩定性可得以改善。 隨後伴隨加熱搜拌將所得漿料摻合在-起且將pH值調』 至6.6-7.0,此後使組合物經受高溫短時(htst)加工,在仏 期間組合物經熱處理、乳化且經均質化,且隨後使其〆 部。添加水溶性維生素及抗壞血 ’ 整至所耍銘!!! u 右有必要則將pH值朝 =所:範圍’添加調味劑且添加水以達成所要之 二隨後將組合物無菌封裝以形成經無菌封裝 液。该乳液亦可經填充且隨後 型液體,左杀又函以形成即食型或濃縮 液姐或其可經噴霧乾燥、乾混及/或聚结。 可藉由任何已知或另外適於製備及調配營 技術集合來製備營養固體, 有效 營養粉末。 噴霧乾燥營養粉末或乾混 舉例而言,當營養粉末為喷霧乾燥營 燥步驟可類似地包括已知或〃,噴霧乾 何噴霧乾燥技術。已知多種 於產生營養粉末之任 夕種不同喷霧乾燥方法及技術可用 1612l5.doc •32- 201233329 於營養領域’所有均適用於製造本文之喷霧乾燥營養粉 一種製備喷霧乾燥營養粉末之方法包含形成及均質化含 有預消化脂肪且視情況含有蛋白f、碳水化合物及其他月3旨 肪來源之含水㈣或液體,且隨後㈣乾燥該㈣或液體 以產生噴霧乾燥營養粉末。該方法可進一步包含噴霧蓼 燥、乾混或另外向嗔霧乾燥營養粉末甲添加其他營養成= (包括任何一或多種本文所述成分)之步驟。 其他適用於製備營養品之方法例如描述於美國專利 6,365,218(B〇rschel 等人)、美國專利 6 589 576(B〇rschei 等 人)、美國專利6,306,908(Carlson等人)及美國專利申請案 2〇〇3〇1187〇3 Al(Nguyen等人)中,其描述以與其一致之程 度以引用的方式併入本文中。 使用方法 根據本發明且如下文進一步描述,本文所述之營養品可 用於多種目的’例如包括改善消化、改善營養素吸收、改 善耐受性、減小壞死性小腸結腸炎之發生率、減小腹痛之 發生率及減小短腸症之發生率。使用本文所述的營養品之 個體(嬰兒、幼兒或孩童)實際上可能患有或罹患所述疾病 或病況(亦即,實際上可能具有消化、營養素吸收及/或耐 又ί門題或實際上可能患有壞死性小腸結腸炎、腹痛或 短腸症), 或可能易於患 即, 件、 可3b貫際上尚未患有該疾 家族史等,與一般人群相 上該疾病或病況或存在此風險(亦 病或病況,但由於某些條 比患病風險增加)。不管個 161215.doc •33- 201233329 體實際上是否患有該疾病或病況,或是否存在患上該疾病 或病況之風險或易於患上該疾病或病況,該個體在本文中 均分類為「需要」幫助解決及對抗該疾病或病況。舉例而 言’嬰兒由於早產而實際上可能患有壞死性小腸結腸炎或 可能存在患上壞死性小腸結腸炎(易於患上壞死性小腸結 腸炎)之風險。類似地,在另一實例中,#兒由於患有其 他疾病或病況或具有該等問題之家族史而實際上可能具有 耐受性及/或消化及/或營養素吸收問題’或可能存在患上 (易於患上)一或多種該等病況之風險。不管個體是否實際 上患有該疾病或病況’或是否僅存在患上該疾病或病況或 易於患上該疾病或病況之風險’本發明之範嘴内包括使用 本文所述之營養品協助該個體。 基於以上内容,由於本發明之某些方法實施例係關於確 定個體之特定子群或子類(亦即,「需要」幫助解決本文所 述之或多種特定疾病或特定病況之個體的子群或子 類)’因此並非所有個體均可受益於本文所述之所有方法 實施例,如同對於某些疾病或病況而t,並非所有個體均 屬於如本文所述之個體子群或子類。 W〜六 我夕種其他用 源組合之㈣化脂肪,以為嬰兒、幼兒及孩童提供毫 源,用於改善營養素消化及吸收。特定而言,類似= 餵養嬰兒之消化,因為脂肪來源在進入 — <曰賜之別 部分被消化,讓嬰兒有更多時間吸收營養素,尤其 内’且進人嬰兒結腸之營養素減少,因此使得會㈣ 161215.doc -34- 201233329 產生氣體以致降低產品耐受性之營養素減少。因此,藉由 在營養品(諸如嬰兒配方)中使用預消化脂肪來源(諸如單酸 甘油酯及/或脂肪酸),現可能向嬰兒提供更接近地模仿母 乳益處之母乳替代物或補充物。 除如上文所述之營養素吸收改善以外,已發現在營養品 中使用預消化脂肪在與一或多種非水溶性疏水性混合物 (諸如油可溶性(脂溶性)維生素(維生素A、D、£及κ广類 胡蘿蔔素(例如葉黃素、卜胡蘿蔔素、番茄紅素等)、醣脂 (神經結醣脂)、固醇及植物化學品)一起投與時亦有助於微 胞形成。該等微胞之形成使得不溶性疏水性化合物可溶解 於消化物中,此為腸絨毛吸收之步驟。此外,預消化脂肪 將用於再合成三酸甘油酯以形成乳糜微粒^乳糜微粒將非 水溶性疏水性化合物運載至淋巴中,其中循環將不溶性疏 水性化合物輸送至目標器官及/或組織以產生所要生理學 作用。 除上文論述之益處以外,已發現包含預消化脂肪之營養 品刺激十二指腸中之膽囊收縮素(CCK)產生,其刺激胰腺 脂肪酶產生。此產生導致進一步消化營養素且減少上部胃 腸道收縮,其使得有更多時間用於吸收。因此,在營養σ 中使用預消化脂肪可減少進入結腸且會被醱酵並產生氣體 及發脹感受之營養素總量。因此,在營養品中使用預消化 脂肪可藉由改善營養素消化及吸收(具有較少脹氣)來改盖 耐受性。此對於嬰兒可尤為重要,因為耐受性可能為某此 嬰兒中存在之問題。 161215.doc -35- 201233329 除刺激CCK產生以外’已發現預消化脂肪亦誘發腸生長 激素(姨高也糖素樣肽-2 ’ GLP-2)之分泌。GLP-2可增強嬰 兒腸道成熟,其使得消化及營養素吸收更佳。 已進一步發現,如本文所述之包含預消化脂肪之營養品 可用於為嬰兒、幼兒或孩童提供營養來源,此可減小壞死 性小腸結腸炎(NEC)、腹痛及/或短腸症之發生率。 另外,在與脂肪漿料中之蛋白形成對比,藉由向碳水化 合物-礦物質漿料中添加至少一部分預消化脂肪(或在某些 實施例中為所有預消化脂肪)之方法製造營養品的實施例 中,營養品(通常為營養乳液形式)之所得穩定性可得以改 善。 實例 以下實例說明本發明營養品之特定實施例及/或特徵。 該等實例僅出於說明目的而給出且不應理解為對本發明之 限制,因為在不偏離本發明之精神及範疇下可能存在其多 種變化形式。除非另外說明’否則所有例示量均為基於組 合物總重量計之重量百分比。 例不組合物為根據本文所述之製造方法製備的存放穩定 性營養品’以使得除非另外說明,否則每一例示產品均包 括經無菌加工之實施例及經殺菌釜封裝之實施例。 營養液體實施例為封裝於240 ml塑膠容器中且在調配/封 裝之後在1-25。。範圍内之儲存溫度下在以…個月内維持物 理穩定性之水包油含水乳液。 實例1-4 161215.doc • 36 - 201233329 實例1 -4說明本發明之不含乳糖的嬰兒營養乳液,其成 分列舉於下表中。除非另外說明,否則所有成分量均以每 1000公斤批次產品之公斤數列出。 成分 實例1 實例2 實例3 實例4 水 足量 足量 足量 足量 麥芽糊精 53 43.3 50 60 蔗糖 16.5 25 19.2 16.38 乳蛋白分離物 15.65 15.65 15.65 15.65 玉米油 12 12 12 12 高油酸紅花籽油 10 10 10 10 單棕櫚酸甘油S旨 10 9 8 7 c10-c24脂肪酸妈鹽 6.0 7 8 9 椰子油 2 2 2 2 真菌油 0.3 0.3 0.3 0.3 卵填脂 0.1 0.1 0.1 0.1 磷酸氫二鉀 0.96 0.96 0.96 0.96 氯化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角又菜膠 0.150 0.150 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 蜗化鉀 0.00022 0.00022 0.00022 0.00022 氯化鉻 0.000217 0.000217 0.000217 0.000217 實例f;-8 實例5-8說明本發明之基於乳糖之營養乳液,其成分列 舉於下表中。除非另外說明,否則所有成分量均以每1000 kg 批次產品之kg數列出。 成分 實例5 實例6 實例7 實例8 水 足量 足量 足量 足量 乳糖 58 66 71 63 非脂肪乾乳 25 10 0 16 乳清蛋白濃縮物 6.4 13 18 10.5 高油酸紅花籽油 14 14 14 14 161215.doc -37- 201233329 椰子油 6.2 6.2 6.2 6.2 單棕櫊酸甘油酯 10 8 6 4 C10-C24脂肪酸 5.5 7.5 9.5 11.5 果寡酿/半乳寡醣 9 9 9 9 真菌油 0.3 0.3 0.3 0.3 磷酸氫二鉀 0.96 0.96 0.96 0.96 氫氧化在弓 0.78 1.07 1.36 1.64 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.150 0.150 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 蛾化斜 0.00022 0.00022 0.00022 0.00022 氣化鉻 0.000217 0.000217 0.000217 0.000217 實例9-12 實例9-12說明本發明之基於大豆之嬰兒營養乳液,其成 分列舉於下表中。除非另外說明,否則所有成分量均以每 1000公斤批次產品之公斤數列出。 成分 實例9 實例10 實例11 實例12 水 足量 足量 足量 足量 玉米糖漿固體 53 43.3 50 60 蔗糖 16.5 25 19.2 16.38 大豆蛋白分離物 19.5 19.5 19.5 19.5 玉米油 12 12 12 12 高油酸紅花籽油 10 10 10 10 單棕櫊酸甘油酯 10 9 8 7 c10-c24脂肪酸 6.0 7 8.0 9 真菌油 0.3 0.3 0.3 0.3 L-胱胺酸 2.3 2.3 2.3 2.3 L-酪胺酸 1.1 1.1 1.1 1.1 氫氧化妈 0.09 1.0 1.1 1.2 L-色胺酸 0.66 0.66 0.66 0.66 磷酸氫二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角又菜膠 0.150 0.150 0.0 0.0 161215.doc •38· 201233329 |氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 碘化鉀 0.00022 0.00022 0.00022 0.00022 實例13-16 實例13-16說明本發明之基於水解蛋白之嬰兒營養乳 液,其成分列舉於下表中。除非另外說明,否則所有成分 量均以每1000公斤批次產品之公斤數列出。 成分 實例13 實例14 實例15 實例16 水 足量 足量 足量 足量 蔗糖 42 42 42 42 澱粉 21.8 21.8 21.8 21.8 水解蛋白 22.2 22.2 22.2 22.2 高油酸紅花籽油 13.7 13.7 13.7 13.7 MCT油 6 6 6 6 單棕櫚酸甘油酯 10 9 8 7 c10-c24脂肪酸 11 9.5 8 6.5 椰子油 5 7.5 9 11.5 真菌油 0.3 0.3 0.3 0.3 氫氧化妈 1.6 1.29 1.1 0.93 L-蛋胺酸 0.3 0.3 0.3 0.3 磷酸氫二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.0 0.0 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 碘化鉀 0.00022 0.00022 0.00022 0.00022 實例17 在該實例中,評估大鼠對c1()-c24脂肪酸鈣鹽之吸收及相 關生物可用性。 161215.doc 39- 201233329 對三十隻大鼠隨機指定三種含有不同蛋白及脂肪之飲食 (飲食1、飲食2及飲食3)之一。飲食1-3與AOAC方法906.48 中所用者相同’不同之處在於飲食1_3具有較高脂肪含量 且包含麥芽糊精作為碳水化合物來源。飲食1含有1〇 wt% 蛋白可用作酸路蛋白且含有23.6 wt%脂肪可用作含有3〇 wt%椰子油' 30 wt%大豆油及40 wt%高油酸紅花籽油 (HOSO)之油摻合物。飲食2及3之營養型態與飲食i之營養 型態相同,除了蛋白質、脂肪、碳水化合物及礦物質被混 合 '均質化且喷霧乾燥以外。飲食3與飲食2之不同之處僅 在於以高油酸紅花籽油脂肪酸鈣鹽替RH〇s〇油且以磷酸 鉀替代磷酸二鈣,以使得飲食2飲食3之總體營養及礦物質 型態相同。HOSO脂肪酸鈣鹽提供1〇〇%之飲食鈣。 對大鼠餵飼飲食1、飲食2或飲食3之一持續4週時期。使 用餵飼試驗結束時之飼料/蛋白攝取及體重增加來計算飼 料轉化(體重增加公克數/飼料攝取公克數)及蛋白效率比 (體重增加公克數/蛋白攝人公克數)(pER)。若㈣不良吸 收,HOSO脂肪酸㉝鹽之熱量值(亦即,熱量/物質公克數) 顯著低於HOSO之熱量值,則預期飲食3之大鼠將增加較少 體重或服用更多飼料以維持其生長,其兩者均導致較低之 飼料轉化及PER。 下表中所示之結果顯示’飲食3之大鼠與對照組具有相 同之飼料轉化或PER,表示H〇s〇脂肪酸詞鹽之熱量值並 非不同於HOSO油。因此,顯示恥_肪㈣鹽具高度生 16I2l5.doc -40. 201233329 蛋白效毕比 飼料轉化 飲食1(對照組1) 2.83 +/- 0.28* 0.29 +/- 0.03 飲食2(對照組2) 3.16+/-0.17 0.31 +/-0.02 飲食3(脂肪酸詞鹽) 3.32+/-0.27 0.37 +/- 0.03 *標準偏差(n=10) 實例18 在該實例中’分析1 0天大之豬對大豆脂肪酸鹽之吸收。 將1 6隻乳豬隨機分為兩組且個別圈養於代謝籠中,且經 訓練以在30分鐘内自盆中獲取營養乳液。在用市售即食型 基於水解蛋白之配方訓練一週之後,對該等豬餵飼包含磷 酸二#5及碳酸約作為約來源之市售基於水解蛋白之配方粉 末(對照組)或包含大豆脂肪酸鈣鹽作為鈣來源之乳液(實驗 乳液)。對於對照組及實驗乳液而言,蛋白質來源及含 量、脂肪含量及礦物質型態相同。然而,實驗乳液包含大 豆脂㈣替代對照組中之大豆油’且包含氫氧化約作為妈 礦物質系統之一部分,以中和大豆脂肪酸。調整實驗乳液 之磷酸鉀含量以與對照組之磷含量相匹配。大豆脂肪酸鈣 提供實驗乳液中100〇/〇之的。 在餵飼兩週之後,基於下式計算表觀脂肪及鈣消化率: 表觀脂肪消化率=((脂肪攝取-糞便脂肪)/脂肪攝取)*丨00 表觀辦消化率=((鈣攝取-糞便鈣)/鈣攝取)*100 乾物質消化率=((乾㈣攝取-糞便乾物質)/乾物質攝取)* 1〇〇 實驗乳液減少之飼料轉化(重量/飼料攝取)及減少之脂 肪' 的及乾物質消化率將顯示實驗乳液之大豆脂肪酸轉鹽 吸收不良’且因此顯示對於實驗乳液而言,鈣之熱量值及 16U15.doc -41 · 201233329 生物可用性低於對照組。 下表中所不’實驗乳液之飼料轉化、脂肪消化率及乾 物質消化率顯著不同於對照組’顯示對於初生豬而言實 驗乳液之大豆脂肪賴鹽被高度吸收且具生物可用性。此 外,下文所示之表賴消化率資料顯示實驗乳液之大豆脂 肪酸辦鹽比對,昭*中肖合 、、、、 之約(亦即,磷酸三鈣及碳酸鈣) 更具生物可用性。 對照組 實驗乳液_ 表觀脂肪 消化率 97.6+/- 1.0 97.6+/- 1.4 :標準偏差(n=10) 0.82+/-0.14* 0.80+/-0.15 飼料-(趙重增加公克數/ 飼料(乾物質) 公克數) 表觀鈣消化率 表觀乾物質 消化率 81.8+/-7.2 97.8 +/- 0.7 91.3 +/-3.3 98.0 +/- 1 .〇 實例19 在該實例中,分析脂肪酸約鹽之乳化特性。 藉由使用桌上型咼剪切混合器用5〇〇 mi水剪切1 8 § 13 0°F含有單棕橺酸甘油酯(油之5重量之大豆油及43〇 mg Ca(磷酸三鈣形式)來製備第一乳液(對照乳液)。作為對 照乳液的含有相同含量之鈣及脂肪(12 g大豆油加上6 g大 豆脂肪酸)之第二乳液(脂肪酸鈣乳液)係藉由以下來製備: (1) 在約13 0 °F之溫度下將大豆脂肪酸油溶液分散於水中; (2) 添加430 mg氯化鈣形式之Ca; (3)使用KOH將溶液阳值 調整至約7.0 ’·及(4)使用桌上型高剪切混合物剪切;昆人 物。 161215.doc •42· 201233329 使對照乳液及脂肪酸鈣乳液靜置三週時期,以分析乳液 分離。在經過一夜之後’對照乳液在乳液頂部出現包含乳 狀層之可見相分離。(參見圖1A)。相比而言,儲存三週之 後’脂肪酸#5乳液在乳液頂部僅出現輕微可彳貞測(但並非 β楚可見)之約皁層’而乳液仍保持一相。在脂肪酸約乳 液底部無可見之妈沈降(參見圖1Β)。 該等結果顯示脂肪酸鈣鹽為有效乳化劑且能夠為實質上 不會自溶液沈降之營養乳液提供鈣來源。此使得乳液產品 具有改善之穩定性及較長之存放期。 實例20 在該貫例中,量測1 〇天大豬對兩種獨立測試調配物及對 照調配物之脂肪吸收量及妈吸收量。 第一測試調配物(調配物1)在脂肪系統中包含棕櫊油精 油’第二測試調配物(調配物2)在脂肪系統中包含預消化脂 肪’且對照調配物(調配物3)在脂肪系統中包含低棕櫚酸 油。二種調配物之脂肪系統組分列舉於下表中。 %素(公克)— Γ——- 碉配物1 (棕櫚油精油 逆己物) 調配物2 (預消化脂肪 調配物) 調配物3 (包含低掠櫚酸油之 對照調配物) 椰子油 " ~3Z2 0 84.1 鬲油酸紅花軒油 脂肪酸 — ()2.8 *〇---- 108 ~56^9 一 111.9 0 Δ Ό A ·、丄 'Ί •Λ-ΚΑ m Τ〇3 ------- 3.03 3.03 |dha^ '~~~~ _早棕櫚酸甘油S旨 1.52 "7:----- 1.52 1.52 0 65.4 0 9P竭曰 此日·、1-小*- ""**"*" 1.12 1.12 1.12 %獨/由精 大豆油 '^ J22?7~- 0 0 J7T 0 83.8 --1 161215.doc -43· 201233329 製備三種具有幾乎相同的營養素及礦物質型態之調配 物。調配物1及2之脂肪酸型態模仿母乳脂肪酸型態。調配 物2中包含氫氧化鈣(足以螯合所有游離脂肪酸之量)作為辦 來源,其與大豆脂肪酸反應以形成不溶性脂肪酸鈣鹽。該 反應消除游離脂肪酸所產生之苦味及咽喉燒灼感受。另 外,升高調配物2中磷酸鉀之含量以與調配物1及3中之碟 含量相匹配。調配物1及3中所用之鈣鹽為磷酸鈣。 使60隻10天大豬(加或減兩天)隨機分組接受調配物!、 調配物2或調配物3 »使豬個別地圈養於代謝籠中且在訓練 及適應4天之後每天餵飼五次持續三週。收集第2天至第18 天之糞便物質且分析鈣吸收及脂肪吸收。以糞便物質中之 鈣量除以飲食中之鈣量再乘以1 〇〇計算鈣吸收。以糞便物 質中之脂肪量除以飲食中之脂肪量再乘以1 〇〇計算脂肪吸 收。結果展示於下表中。 脂肪吸收(%) 鈣吸收(%) 調配物1(棕櫊油精) 92.3 ±3.9 88.9 ±4_7 調配物2(預消化脂肪) 98‘2±0.7 93,1 ±2.4 調配物3(對照:低棕櫚酸脂肪系統) 98.0 ± 1.4 90.7 ±3_5 如上表中之結果所顯示,使用預消化脂肪系統使得嬰兒 配方可模仿母乳脂肪酸型態不會出現如使用棕櫚油精油脂 肪系統時所經歷對鈣及脂肪吸收之不利影響。配方2(預消 化脂肪調配物)之脂肪及鈣吸收速率至少與低棕櫊酸配方 之脂肪及鈣吸收速率同等良好。該等發現說明大豆脂肪酸 I弓鹽在初生豬中具高度生物可用性。 實例21 I6I215.doc -44- 201233329 在該實例中,評估實例20之豬的CCK產生(AUC)及腸動 素產生(AUC)之餐後增加量。 在實例20中所述之脂肪及鈣吸收分析之結論中,使經投 與調配物2(預消化脂肪調配物)或調配物3 (包括低棕櫚酸之 對照調配物)之豬禁食12小時,且抽取禁食血液以分離血 清。使豬恢復兩小時且隨後給予250 mL調配物2或調配物 3。在餵飼後30及60分鐘時抽取餐後血液樣本且測試CCK 及腸動素。計算CCK(曲線下面積)及腸動素(AUC)之餐後 增加量。結果展示於下表中。 調配物2 (預消化脂肪調配物) (pg/mL^min) 調配物3 (對照:低棕櫚酸調配物) (pg/mL*min) CCK分泌之餐後增加量(曲線下面積) 1935 ± 1464 1046 ±754 腸動素AUC(餐後增加量) 483 ± 253 839 ± 403 上表中之資料顯示以預消化脂肪(單棕櫚酸甘油酯加大 豆脂肪酸)替代三酸甘油酯會刺激餐後CCK分泌,其已顯 示刺激胰腺消化酶分泌、增強膽囊收縮且延遲口腔至盲腸 之輸送。因此,具有預消化脂肪之調配物可刺激更多可消 化酶分泌且減缓GI輸送以允許更多營養素消化及吸收。因 此,包含預消化脂肪之調配物可改善配方耐受性,因為未 消化之營養素可導致過度結腸醱酵而導致脹氣、腹瀉及胃 另外,上表中之資料顯示以預消化脂肪(單棕櫚酸甘油 酯加大豆脂肪酸)替代二酸甘油酯可減少餐後腸動素分 泌。已顯示,患腹痛之嬰兒具有較低之餐後CCK含量,但 161215.doc •45- 201233329 具有較咼之餐後腸動素含量。餐後腸道激素之間的此種不 平衡導致嬰兒GI收縮,其導致腹痛。上表中之資料顯示包 含預消化脂肪可增加嬰兒之餐後CCK含量,但減少腸動素 含量’由此減小激素不平衡以緩解GI收縮、腹痛及腹痛。 實例22 在該實例中’使用實例20之豬來研究各種脂肪系統對乳 糜微粒三酸甘油酯棕橺酸及Sn-2棕橺酸含量之影響。 自每隻豬抽取1小時餐後也液樣本且分離血漿,以液氮 冷凍且儲存在-80°C之冷凍器中。使用Folch溶劑萃取總血 漿脂質。藉由薄層層析分離三酸甘油酯。下表顯示調配物 1 (棕櫚油精調配物)及調配物2(預消化脂肪調配物)之血聚 三酸甘油酯棕櫚酸及Sn-2棕櫚酸。表中亦展示餵飼該兩種 調配物之豬的乳糜微粒三酸甘油酯及Sn-2棕櫚酸。 調配物1 (棕櫊油4 秀) 餵飼調配物1 之豬的血漿 三酸甘油酯 調配物2 : (預消化脂肪) 飯飼調配物2 之豬的血漿 三酸甘油酯 乳之人 類嬰兒的it漿 三後甘油酯 三酸 甘油酯 Sn-2 三酸 甘油酯 Sn-2 三酸 甘油酯 Sn-2 三酸 甘油酯 Sn-2 三酸 甘油醋 Sn-2 棕櫊酸 含量 (%) 23.3 5.8 18.3 10.6 21.4 5.2 18.5 14.4 25 25.5 如上表中所示,餵飼預消化脂肪配方之豬的血漿三酸甘 油酯及Sn-2棕櫚酸含量顯著高於餵飼棕櫚油精配方之緒。 調配物1及調配物2之血漿三酸甘油酯棕櫚酸/Sn-2棕櫚酸比 率分別為約1.7及1 ·3,且已知母乳餵飼嬰兒之該比率為約 1 _ 1。因此’該資料顯示預消化脂肪調配物比棕搁油精脂 肪§周配物此更佳地模仿母乳。 16l215.doc -46- 201233329 實例23 在5亥實例中,使用實例20之豬來研究各種脂肪系統對血 液葉黃素含量之影響。 使用氯仿與甲醇之溶劑(比率為2:1)萃取來自每隻豬之1 小時餐後jk液樣本的血漿。移除溶劑且彙集所得脂質且使 用習知方法分析葉黃素。下表展示餵飼調配物1 (棕櫚油精 調配物)、調配物2(預消化脂肪調配物)及調配物3(低棕櫚 酸調配物)之豬的葉黃素含量,以每mg脂質之葉黃素叫數 表示。 調配物1 : (椋櫚油精) 調配物2 : (預消化脂肪) 調配物3 : (低棕櫚酸) 葉黃素含置 N/A* 0.765 pg 0.539 μβ *調配物1之葉黃素含量過低而難以量測。 如上表令所示,餵飼包含預消化脂肪之調配物之豬與餵 飼包含棕櫚油精或低棕櫚酸之調配物之豬相比具有增加之 葉黃素吸收。 實例24 在該實例中,使用實例20之調配物2(預消化脂肪調配 物)及調配物3(低棕櫚酸調配物)來研究各種脂肪系統對微 胞葉黃素含量之影響。 使調配物2及調配物3用水復原(每1.0 L水133 g粉末狀調 配物),且添加HC1將復原調配物之pH值調整至4.5。藉由 向40 ml復原調配物中添加i·00 ml USP胃蛋白酶(56 mg/ml) 使復原調配物在室溫下消化1小時。在胃蛋白酶消化之後 161215.doc -47· 201233329 將復原調配物之PH值調整至7.0,且隨後向經胃蛋白酶消 化之調配物中添加28 mg USP胰澱粉酶/蛋白酶、28 mg USP胰酶脂肪酶與1 mg膽汁萃取物之混合物。使調配物 在室溫下進一步消化2小時且離心(31,0〇〇§,在20°(:下,3 小時)。經消化之調配物形成油/乳脂凝塊、含水相及沈降 層。抽取含水相以用於微胞之葉黃素分析,該等微胞在含 水内腔中吸收葉黃素期間充當載體。下表展示每kg消化調 配物之微胞葉黃素的含量。 消化調配物2 : (預消化脂肪) 消化調配物3 : (低棕櫊酸) 微胞葉黃素(pg) 0.598 μβ 0.246 pg 如上表中所示,在包含預消化脂肪之消化調配物中發現 之微胞葉黃素的量為在包含低棕櫚酸之消化調配物中發現 的微胞葉黃素之量的兩倍多,由此顯示使用預消化脂肪可 增加葉黃素吸收。 實例25 在該實例中,分析預消化脂肪減小軟便發生率之能力。 對30隻斷乳大鼠餵飼基於水解蛋白之粉末嬰兒配方(包 含MCT油作為30 wt%之脂肪來源),持續四天適應期。在 適應期結束時,將大鼠隨機分為兩組且傲飼對照調配物 (低棕櫚酸粉末嬰兒配方)或測試調配物(含有預消化脂肪之 嬰兒配方)。對照調配物與測試調配物之營養素型態相 同。使大鼠可自由獲取飼料及水達五天,且每天記錄攝入 之飼料量及體重。 161215.doc -48 * 201233329 儘管兩組之間的飼料攝取或體重增加無顯著差異,彳曰大^ 便堅實度存在顯著差異。在餵飼之最後兩天期間,使用〇 5點系統對大鼠之大便堅實度評分。評分係基於黏纟士至籠 底吸取薄片之大便的嚴重度及堅實度。〇評分值指示正常 大便且5評分值指示水樣腹瀉。如圖2中所示,飯飼對照調 配物(含有MCT油)之大鼠比餵飼測試調配物(含有預消化月匕 肪)之大鼠產生較稀之大便。 實例26 在該實例中’分析預消化脂肪減小壞死性小腸結腸炎 (NEC)發生率之能力。 將經由剖腹產分娩之早產豬(92%孕期)即刻轉移至充氧 培育器(37°C )中且在臍動脈中置放一血管導管。在第一個 24小時期間經由血管導管對該等豬注射三次(4、6及7 mL/kg體重)母體血衆。以每小時心6 mL/kg之速率提供完 全月% 外營養(Total parenteral nutrition,TPN)持續 24 小 時。隨後使該等豬經由口胃管(or〇gastric tube)以每小時5 mL/kg之速率隨機分組接受對照調配物或pDF調配物。除 其中之脂肪系統以外,對照調配物與pDF調配物相同。特 定而言,對瑪調配物中之脂肪系統包含植物油,且pDF調 配物中之脂肪系統包含3〇 wt〇/0單棕櫚酸甘油酯、2〇 ^%大 豆脂肪酸、26 wt%高油酸紅花籽油、14 wt%椰子油及1〇 wt%甘油三丁酸酯。對照調配物與pDF調配物兩者每公升 調配物中均包含1〇〇 g蛋白質、47 g脂肪及5〇 g玉米糖漿。 在經腸儀飼36小時之後使該等豬安樂死且進行屍檢以使用 I61215.doc -49- 201233329 1-5評分系統評估NEC病變之嚴重程度,其中1評分值指示 無NEC跡象。結果展示於下表中。 區塊1 區塊2 對照調配物 (n=5) PDF調配物 (n=3) 對照調配物 (n=5) PDF調配物 (π=3) 早期NEC死亡 2 0 3 1 屍檢時偵測之NEC 2 1 0 0 總NEC 4 1 3 1 如上表中所示,餵飼對照調配物之10隻豬中有5隻(50%) 在腸餵飼期結束之前即死於NEC,但餵飼PDF調配物之6隻 豬中僅有1隻(16.7%)在腸餵飼期結束之前死於NEC。另 外,餵飼對照調配物之10隻豬中有7隻(70%)在腸餵飼期結 束之前經測定即患有NEC,而餵飼PDF調配物之6隻豬中僅 有2隻(33%)在腸餵飼期結束之前經測定患有NEC。因此可 得出結論,藉由以包含預消化脂肪之脂肪系統替代植物油 脂肪系統可減小NEC之發生率。 【圖式簡單說明】 圖1A及圖1B展示如實例19中製備之對照乳液及實驗乳 液的圖示。 圖2為展示飲食對糞便堅實度之影響的圖。 161215.doc •50·Prime, vitamin κ, serotonin, riboflavin, sputum. Polyol, vitamin I: carotenoid (such as β-caroline, zeaxanthin, lutein, sulphonin), acid, folic acid, pantothenic acid, biotin, vitamin C, gallbladder, inositol, Its salts and derivatives and combinations thereof. - Nutritional products may include any of a variety of other minerals, non-limiting examples of which include strontium, scale, lock, iron, zinc, turmeric, copper, sodium, potassium, s, and combinations thereof. In addition, in some implementations, the nutritional products can be free of horns and dishes. Method of Manufacture: The nutritional product of the invention can be prepared by any manufacturing technique known or otherwise available in the form of a solid or liquid product. : can be applied to the nutritional products described herein in any given product form (such as nutrition, etc.). I612I5.doc 201233329 Therefore, the nutritional product of the present invention can be used by any of various Prepared by known or otherwise effective products or manufacturing methods. For example, 'prepare at least three types of dips separately' in a suitable manufacturing process, including fat-packed protein (piF) slurries, carbohydrates/minerals (CH〇) _MIN) Slurry and water-packed protein (piwm material. PIF (4) is by heating and mixing oils (such as monoglyceride and/or fatty acids, oils containing yoghurt, fensyl oil, corn oil, etc.) And then, with continuous heating and stirring, an emulsifier (such as lecithin), a tamarind vitamin, and a part of total protein (for example, milk protein concentrate, etc.) are added to form. The CHO-Mmt system is stirred by heating. It is formed by adding the following substances to water: minerals (such as potassium citrate, dipotassium phosphate, sodium citrate, etc.), traces and ultra-trace minerals (TM/UTM premix) and/or thickening Agent or suspending agent (such as crystal Cellulose (avicel) gelatin (geHan), carrageenan. The resulting (:η〇_μιν slurry is kept under constant heating and stirring for 10 minutes, then other minerals (such as potassium carbonate, Magnesium carbonate, potassium iodide, etc.) and/or carbohydrates (for example, oligosaccharides, arachis, corn sugar (4)). If any residual protein f is present, the PIW slurry is formed by mixing with heating and stirring. In a particular embodiment of the invention, all or a portion of the pre-digested fat contained in the nutritional product may be added to the CH〇_MIN slurry, which contains less than 5% by weight of the CH0-MIN mass. a fat in the form of triglyceride vinegar. In this embodiment, at least 5% (by weight) of the total fat present in the nutrient is in the form of a digested fat and is added to the ch〇_min slurry. In certain embodiments, the nutritional product comprises at least 5% by weight, including at least 10% by weight, including at least 2% by weight (by weight J61215.doc 31 201233329), including At least 30% by weight, including at least 4% by weight, Including at least 50% by weight, including at least 6% by weight, including at least 70% by weight, including at least 8% by weight, including at least 90% by weight And including 1% by weight (by weight) of total pre-digested fat added to the (10) capture (four) feed. In a particular embodiment, before the pre-digested fat is added to the CH0.MIN stimuli or during manufacture During the CHO-Mm slurry, fat-soluble nutrients (such as mixed caroten (four) or vitamins A, D, EAK) are dissolved in pre-digested fat nails. In contrast to the agglomerates, by adding (four) to the CH0_MINMt (four), the final nutrition The stability of the composition can be improved. The resulting slurry is then blended with heating and the pH is adjusted to 6.6-7.0, after which the composition is subjected to high temperature short-term (htst) processing during which the composition is heat treated, emulsified and homogenized. And then make it chop. Add water-soluble vitamins and anti-spleen ‘ !! u Right, add the flavor to the pH: range' and add water to achieve the desired two. The composition is then aseptically packaged to form a sterile package. The emulsion may also be filled and subsequently liquid-type, left-handed to form a ready-to-eat or concentrate solution or it may be spray dried, dry blended and/or coalesced. The nutritive solids can be prepared by any known or otherwise suitable preparation and blending technology collection, effective nutrient powder. Spray-dried nutritional powder or dry blending For example, when the nutritional powder is a spray-drying drying step, it may similarly include known or spray drying techniques. Various spray drying methods and techniques are known to be used in the production of nutritional powders. 1612l5.doc •32-201233329 In the field of nutrition 'all spray-dried nutritional powders suitable for the manufacture of a spray-dried nutritional powder The method comprises forming and homogenizing an aqueous (tetra) or liquid comprising pre-digested fat and optionally protein f, carbohydrate and other sources of fat, and subsequently (d) drying the (iv) or liquid to produce a spray-dried nutritional powder. The method may further comprise the steps of spray drying, dry blending or otherwise adding additional nutrients to the haze dry nutritional powder (including any one or more of the ingredients described herein). Other suitable methods for preparing nutritional products are described, for example, in U.S. Patent No. 6,365,218 (B〇rschel et al.), U.S. Patent No. 6,589,576 (B., et al.), U.S. Patent No. 6,306,908 (Carlson et al), and U.S. Patent Application Serial No. In 〇3〇1187〇3 Al (Nguyen et al.), the description thereof is incorporated herein by reference. Methods of Use In accordance with the present invention and as further described below, the nutritional products described herein can be used for a variety of purposes including, for example, improving digestion, improving nutrient absorption, improving tolerance, reducing the incidence of necrotizing enterocolitis, and reducing abdominal pain. The incidence and the incidence of short bowel disease. Individuals (babies, toddlers, or children) who use the nutritional products described herein may actually have or suffer from the disease or condition (ie, may actually have digestive, nutrient absorption, and/or resistance or May have necrotizing enterocolitis, abdominal pain or short bowel disease, or may be prone to suffering from illness, may not have a family history of the disease, etc., and the disease or condition or presence in the general population This risk (also disease or condition, but due to the increased risk of certain strips than the disease). Regardless of whether the body actually has the disease or condition, or whether there is a risk of developing the disease or condition, or is prone to develop the disease or condition, the individual is classified as "needed" in this article. Help solve and fight the disease or condition. For example, an infant may actually have necrotizing enterocolitis due to premature birth or may be at risk of developing necrotizing enterocolitis (prone to necrotizing enterocolitis). Similarly, in another example, #儿 may actually have tolerance and/or digestive and/or nutrient absorption problems due to other diseases or conditions or family history with such problems' or may be present (easy to suffer) the risk of one or more of these conditions. Regardless of whether the individual actually has the disease or condition 'or whether there is only a risk of developing the disease or condition or is prone to develop the disease or condition', the invention includes assisting the individual with the nutritional products described herein. . Based on the above, certain method embodiments of the present invention are directed to determining a particular subgroup or subclass of an individual (ie, a subset of individuals that "need" to help resolve a particular disease or particular condition described herein or Subclass) 'Thus not all individuals may benefit from all of the method embodiments described herein, as for certain diseases or conditions, and not all individuals belong to a subgroup or subclass of individuals as described herein. W~6 I use a combination of other sources (4) to provide a source of fat for infants, toddlers and children to improve nutrient digestion and absorption. In particular, similar to = feeding the baby's digestion, because the fat source is in the intake - < 曰 之 之 被 被 被 被 , , , , , , , , , , , , , , , 被 被 被 被 被 被 被 被 , , , , , , , , , , (iv) 161215.doc -34- 201233329 Reduced nutrients that produce gas to reduce product tolerance. Thus, by using pre-digested fat sources (such as monoglycerides and/or fatty acids) in nutraceuticals, such as infant formulas, it is now possible to provide infants with breast milk substitutes or supplements that more closely mimic the benefits of breast milk. In addition to improved nutrient absorption as described above, it has been found that the use of pre-digested fats in nutrients with one or more water-insoluble hydrophobic mixtures (such as oil-soluble (fat-soluble) vitamins (vitamins A, D, £ and κ) When carotenoids (such as lutein, carotenoids, lycopene, etc.), glycolipids (neurolipids), sterols, and phytochemicals are added together, they also contribute to the formation of micelles. The formation of the microcells allows the insoluble hydrophobic compound to be dissolved in the digest, which is a step of intestinal villus absorption. In addition, the pre-digested fat will be used to re-synthesize triglyceride to form chylomicrons. The chylomicrons will be water-insoluble and hydrophobic. The compound is carried into the lymph, wherein the circulation delivers the insoluble hydrophobic compound to the target organ and/or tissue to produce the desired physiological effect. In addition to the benefits discussed above, it has been found that nutrients comprising pre-digested fat stimulate the duodenum Cholecystokinin (CCK) is produced, which stimulates the production of pancreatic lipase. This produces further digestion of nutrients and reduces upper gastrointestinal tract. Shrinkage, which allows more time for absorption. Therefore, the use of pre-digested fat in nutrient σ reduces the total amount of nutrients that enter the colon and are fermented and produce gas and swell. Therefore, use in nutrients Pre-digested fat can be modified to improve tolerance by improving nutrient digestion and absorption (with less flatulence). This is especially important for infants because tolerance may be a problem in some infants. 161215.doc -35 - 201233329 In addition to stimulating CCK production, 'pre-digested fat has also been found to induce secretion of intestinal growth hormone (glycoside-like peptide-2 'GLP-2). GLP-2 enhances intestinal maturation in infants, which allows digestion and Better absorption of nutrients. It has been further discovered that a nutrient containing pre-digested fat as described herein can be used to provide a source of nutrition for infants, young children or children, which can reduce necrotizing enterocolitis (NEC), abdominal pain and/or The incidence of short bowel disease. In addition, in contrast to the protein in the fat slurry, by adding at least a portion of the pre-digested fat to the carbohydrate-mineral slurry (or in some In the examples of the method of making nutrients for all methods of pre-digesting fat, the resulting stability of the nutritional product (usually in the form of a nutritional emulsion) can be improved. EXAMPLES The following examples illustrate specific embodiments of the nutritional products of the present invention and/or The examples are given for illustrative purposes only and are not to be construed as limiting the invention, as many variations may be present without departing from the spirit and scope of the invention. % by weight based on the total weight of the composition. Examples of compositions are storage stability nutritional products prepared according to the manufacturing methods described herein such that, unless otherwise stated, each exemplary product includes aseptically processed examples. And examples of sterilized autoclave encapsulation. The nutrient liquid example is packaged in a 240 ml plastic container and is 1-25 after compounding/packaging. . An oil-in-water aqueous emulsion that maintains physical stability within a period of ... at storage temperatures within the range. Examples 1-4 161215.doc • 36 - 201233329 Examples 1-4 illustrate lactose-free infant nutritional emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredient amounts are listed in kilograms per 1000 kg batch of product. Ingredient Example 1 Example 2 Example 3 Example 4 Water sufficient amount sufficient amount sufficient amount of maltodextrin 53 43.3 50 60 sucrose 16.5 25 19.2 16.38 Milk protein isolate 15.65 15.65 15.65 15.65 Corn oil 12 12 12 12 High oleic acid safflower seeds Oil 10 10 10 10 Monopalmitic acid glycerol S 10 9 8 7 c10-c24 fatty acid mother salt 6.0 7 8 9 coconut oil 2 2 2 2 fungal oil 0.3 0.3 0.3 0.3 egg fat 0.1 0.1 0.1 0.1 dipotassium hydrogen phosphate 0.96 0.96 0.96 0.96 Potassium chloride 0.3 0.3 0.3 0.3 Ascorbic acid 0.235 0.235 0.235 0.235 Angular vegetable gum 0.150 0.150 0.150 0.150 Potassium hydroxide 0.136 0.136 0.136 0.136 TM/UTM premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E premix 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Potassium sulphate 0.00022 0.00022 0.00022 0.00022 Chromium chloride 0.000217 0.000217 0.000217 0.000217 Example f; -8 Examples 5-8 illustrate the lactose-based nutritional emulsion of the present invention, the ingredients of which are listed below In the table. Unless otherwise stated, all ingredient quantities are listed in kg per 1000 kg batch of product. Ingredient Example 5 Example 6 Example 7 Example 8 Water sufficient amount sufficient amount sufficient lactose 58 66 71 63 non-fat dry milk 25 10 0 16 whey protein concentrate 6.4 13 18 10.5 high oleic acid safflower oil 14 14 14 14 161215.doc -37- 201233329 Coconut oil 6.2 6.2 6.2 6.2 Monopalmitate 10 8 6 4 C10-C24 fatty acid 5.5 7.5 9.5 11.5 Fruit oligosaccharide / galactooligosaccharide 9 9 9 9 Fungal oil 0.3 0.3 0.3 0.3 Phosphoric acid Dihydrogen potassium 0.96 0.96 0.96 0.96 Hydrogen hydroxide in the bow 0.78 1.07 1.36 1.64 Calcium oxide 0.3 0.3 0.3 0.3 Ascorbic acid 0.235 0.235 0.235 0.235 Carrageenan 0.150 0.150 0.150 0.150 Potassium hydroxide 0.136 0.136 0.136 0.136 TM/UTM premix 0.1684 0.1684 0.1684 0.1684 Premix of vitamin A, D, E 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Mothing oblique 0.00022 0.00022 0.00022 0.00022 Calcined chromium 0.000217 0.000217 0.000217 0.000217 Examples 9-12 Examples 9-12 illustrate the invention Soy-based infant nutritional emulsions, the ingredients of which are listed in the table below. Unless otherwise stated, all ingredient amounts are listed in kilograms per 1000 kg batch of product. Ingredient Example 9 Example 10 Example 11 Example 12 Water sufficient amount sufficient amount sufficient amount of corn syrup solids 53 43.3 50 60 sucrose 16.5 25 19.2 16.38 soy protein isolate 19.5 19.5 19.5 19.5 corn oil 12 12 12 12 high oleic acid safflower seed oil 10 10 10 10 Monopalmitate 10 9 8 7 c10-c24 fatty acid 6.0 7 8.0 9 Fungal oil 0.3 0.3 0.3 0.3 L-cystamic acid 2.3 2.3 2.3 2.3 L-tyrosine 1.1 1.1 1.1 1.1 Hydrogen peroxide 0.09 1.0 1.1 1.2 L-tryptophan 0.66 0.66 0.66 0.66 Dipotassium hydrogen phosphate 0.96 0.96 0.96 0.96 Calcium oxide 0.3 0.3 0.3 0.3 Ascorbic acid 0.235 0.235 0.235 0.235 Angular vegetable 0.150 0.150 0.0 0.0 161215.doc •38· 201233329 | Potassium 0.136 0.136 0.136 0.136 TM/UTM premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E premix 0.0758 0.0758 0.0758 0.0758 Water soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Potassium iodide 0.00022 0.00022 0.00022 0.00022 Example 13-16 Example 13- 16 illustrates a hydrolyzed protein-based infant nutritional emulsion of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredients are listed in kilograms per 1000 kg batch. Ingredient Example 13 Example 14 Example 15 Example 16 Water sufficient amount sufficient amount sufficient sucrose 42 42 42 42 starch 21.8 21.8 21.8 21.8 hydrolyzed protein 22.2 22.2 22.2 22.2 high oleic acid safflower oil 13.7 13.7 13.7 13.7 MCT oil 6 6 6 6 Monopalmitin 10 9 8 7 c10-c24 fatty acid 11 9.5 8 6.5 Coconut oil 5 7.5 9 11.5 Fungal oil 0.3 0.3 0.3 0.3 Oxide mother 1.6 1.29 1.1 0.93 L-methionine 0.3 0.3 0.3 0.3 Dipotassium hydrogen phosphate 0.96 0.96 0.96 0.96 Calcium Oxide 0.3 0.3 0.3 0.3 Ascorbic Acid 0.235 0.235 0.235 0.235 Carrageenan 0.0 0.0 0.150 0.150 Potassium Hydroxide 0.136 0.136 0.136 0.136 TM/UTM Premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E Premix 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Potassium iodide 0.00022 0.00022 0.00022 0.00022 Example 17 In this example, the absorption of c1()-c24 fatty acid calcium salt and related bioavailability in rats was assessed. 161215.doc 39- 201233329 Thirty rats were randomly assigned to one of three diets containing different protein and fat (diet 1, diet 2 and diet 3). Diets 1-3 are the same as those used in AOAC Method 906.48. The difference is that Diet 1_3 has a higher fat content and contains maltodextrin as a carbohydrate source. Diet 1 contains 1% by weight of protein for acid path protein and 23.6 wt% of fat can be used as containing 3% by weight of coconut oil '30 wt% soybean oil and 40 wt% high oleic safflower seed oil (HOSO) Oil blend. The nutritional forms of diets 2 and 3 are the same as those of diet i, except that proteins, fats, carbohydrates, and minerals are mixed 'homogeneized and spray dried. Diet 3 differs from diet 2 only in that it uses high oleic acid safflower oil fatty acid calcium salt for RH〇s eucalyptus oil and potassium phosphate instead of dicalcium phosphate to make the overall nutrition and mineral form of diet 2 diet 3. the same. HOSO fatty acid calcium salt provides 1% of dietary calcium. The rats were fed diet 1, diet 2 or diet 3 for a period of 4 weeks. Feed conversion (grams of weight gain/kg of feed intake) and protein efficiency ratio (kg of weight gain/gram of protein ingested) (pER) were calculated using feed/protein intake and weight gain at the end of the feeding trial. If (4) bad absorption, the caloric value of HOSO fatty acid 33 salt (ie, calories per kilogram) is significantly lower than the caloric value of HOSO, then it is expected that rats of diet 3 will increase their body weight or take more feed to maintain their Growth, both of which result in lower feed conversion and PER. The results shown in the table below show that rats in diet 3 have the same feed conversion or PER as the control group, indicating that the caloric value of the H〇s〇 fatty acid salt is not different from HOSO oil. Therefore, it is shown that the shame-fat (four) salt has a high birth rate of 16I2l5.doc -40. 201233329 protein effect Bibby feed conversion diet 1 (control group 1) 2.83 +/- 0.28* 0.29 +/- 0.03 diet 2 (control group 2) 3.16 +/-0.17 0.31 +/-0.02 Diet 3 (fatty acid salt) 3.32+/-0.27 0.37 +/- 0.03 *standard deviation (n=10) Example 18 In this example 'analysis of 10 days of pigs versus soybeans Absorption of fatty acid salts. Sixteen suckling pigs were randomly divided into two groups and individually housed in metabolic cages and trained to obtain a nutritional emulsion from the pot within 30 minutes. After one week of training with a commercially available ready-to-eat hydrolyzed protein-based formulation, the pigs were fed a commercially available hydrolyzed protein-based formula powder (control) containing phosphoric acid #5 and carbonic acid as an approximate source or containing soy fatty acid calcium. Salt is used as a calcium source emulsion (experimental emulsion). For the control and experimental emulsions, the protein source and content, fat content and mineral form were the same. However, the experimental emulsion contained soybean oil (iv) in place of soybean oil in the control group and contained hydroxide as part of the mom mineral system to neutralize the soybean fatty acid. The potassium phosphate content of the experimental emulsion was adjusted to match the phosphorus content of the control. Soy fatty acid calcium provides 100 〇/〇 in the experimental emulsion. After two weeks of feeding, the apparent fat and calcium digestibility were calculated based on the following formula: Apparent fat digestibility = ((fat intake - fecal fat) / fat intake) * 丨 00 Apparent digestibility = ((calcium intake) - fecal calcium) / calcium intake) * 100 dry matter digestibility = ((dry (four) intake - fecal dry matter) / dry matter intake) * 1 〇〇 experimental emulsion reduced feed conversion (weight / feed intake) and reduced fat 'The dry matter digestibility will show the poor absorption of soy fatty acid salt in the experimental emulsion' and thus shows that for the experimental emulsion, the calorific value of calcium and the bioavailability of 16U15.doc -41 · 201233329 are lower than the control group. The feed conversion, fat digestibility and dry matter digestibility of the experimental emulsions in the table below were significantly different from those of the control group, which showed that the soybean fat lysate of the experimental emulsion for the nascent pig was highly absorbed and bioavailable. In addition, the digestibility data shown below shows that the experimental emulsion has a more bioavailability than the soy fatty acid salt of the experimental emulsion, which is about (i.e., tricalcium phosphate and calcium carbonate). Control group experimental emulsion _ apparent fat digestibility 97.6+/- 1.0 97.6+/- 1.4 : standard deviation (n=10) 0.82+/-0.14* 0.80+/-0.15 feed-(Zhao weight increase grams / feed ( Dry matter) grams) Apparent calcium digestibility Apparent dry matter digestibility 81.8 +/- 7.2 97.8 +/- 0.7 91.3 +/- 3.3 98.0 +/- 1 . Example 19 In this example, the fatty acid salt was analyzed. Emulsifying properties. Cut with 5 〇〇mi water using a tabletop 咼 shear mixer 1 8 § 13 0°F containing glyceryl monopalmitate (5 parts by weight of soybean oil and 43 〇 mg Ca (tricalcium phosphate form) To prepare a first emulsion (control emulsion). A second emulsion (calcium fatty acid emulsion) containing the same amount of calcium and fat (12 g of soybean oil plus 6 g of soy fatty acid) as a control emulsion was prepared by: (1) Dispersing the soybean fatty acid oil solution in water at a temperature of about 130 °F; (2) adding 430 mg of Ca in the form of calcium chloride; (3) adjusting the positive value of the solution to about 7.0 ' using KOH. (4) Shearing with a tabletop high shear mixture; Kun character. 161215.doc •42· 201233329 The control emulsion and the fatty acid calcium emulsion were allowed to stand for three weeks to analyze the emulsion separation. After one night, the 'control emulsion was A visible phase separation containing a milky layer appeared on top of the emulsion (see Figure 1A). In contrast, the fatty acid #5 emulsion showed only slight speculation at the top of the emulsion after three weeks of storage (but not beta). About the soap layer' while the emulsion remains in one phase. In fat There is no visible mother sediment at the bottom of the emulsion (see Figure 1Β). These results show that the fatty acid calcium salt is an effective emulsifier and can provide a calcium source for the nutritional emulsion that does not substantially settle from the solution. This makes the emulsion product have improved stability. Sexuality and longer shelf life. Example 20 In this example, the fat uptake and maternal absorption of 1 independent test formulation and control formulation were measured for 1 day old pig. 1) contains palm oil essential oil in the fat system 'The second test formulation (Formulation 2) contains pre-digested fat in the fat system' and the control formulation (Formulation 3) contains low palmitic acid in the fat system The fat system components of the two formulations are listed in the following table: % (g) - Γ - - 碉 ligand 1 (palm oil essential oil) Formulation 2 (pre-digested fat formula) 3 (Contrast formulation containing low-pumped palm acid oil) Coconut oil " ~3Z2 0 84.1 oleic acid safflower oil fatty acid - () 2.8 * 〇---- 108 ~ 56 ^ 9 - 111.9 0 Δ Ό A · ,丄'Ί •Λ-ΚΑ m Τ〇3 ------- 3.03 3.03 |dha^ '~~~~ _ early palmitic acid glycerin S 1.52 "7:----- 1.52 1.52 0 65.4 0 9P exhausted this day ·, 1 small *- ""** "*" 1.12 1.12 1.12 % exclusive/yield soybean oil '^ J22?7~- 0 0 J7T 0 83.8 --1 161215.doc -43· 201233329 Prepare three kinds of nutrients and mineral types with almost the same Formulation. The fatty acid form of Formulations 1 and 2 mimics the fatty acid form of the breast milk. Formulation 2 contains calcium hydroxide (amount sufficient to sequester all free fatty acids) as a source which reacts with the soy fatty acid to form an insoluble fatty acid calcium salt. This reaction eliminates the bitter taste and throat burning sensation produced by free fatty acids. In addition, the amount of potassium phosphate in Formulation 2 was raised to match the dish content in Formulations 1 and 3. The calcium salt used in Formulations 1 and 3 is calcium phosphate. Allow 60 10-day large pigs (plus or minus two days) to be randomly assigned to receive the formulation! , Formulation 2 or Formulation 3 » The pigs were individually housed in metabolic cages and fed five times a day for three weeks after training and adaptation for 4 days. Fecal material from day 2 to day 18 was collected and analyzed for calcium absorption and fat absorption. Calcium absorption is calculated by dividing the amount of calcium in the fecal material by the amount of calcium in the diet and multiplying by 1 〇〇. The fat absorption is calculated by dividing the amount of fat in the fecal material by the amount of fat in the diet and multiplying by 1 〇〇. The results are shown in the table below. Fat Absorption (%) Calcium Absorption (%) Formulation 1 (Brown Oil) 92.3 ± 3.9 88.9 ± 4_7 Formulation 2 (pre-digested fat) 98'2 ± 0.7 93, 1 ± 2.4 Formulation 3 (Control: Low Palmitic Fat System) 98.0 ± 1.4 90.7 ±3_5 As shown in the results above, the use of a pre-digested fat system allows the infant formula to mimic the fatty acid profile of the breast without the appearance of calcium and fat as experienced in the palm oil essential oil system. Adverse effects of absorption. Formulation 2 (pre-digested fat formulation) has a fat and calcium absorption rate that is at least as good as the fat and calcium absorption rate of the low palmitic acid formulation. These findings indicate that soy fatty acid I bow salts are highly bioavailable in newborn pigs. Example 21 I6I215.doc -44- 201233329 In this example, the post-prandial increase in CCK production (AUC) and enterokin production (AUC) of the pig of Example 20 was evaluated. In the conclusion of the fat and calcium absorption analysis described in Example 20, pigs administered Formulation 2 (pre-digested fat formulation) or Formulation 3 (including low palmitic acid control formulation) were fasted for 12 hours. And fasting blood is drawn to separate the serum. The pigs were allowed to recover for two hours and then 250 mL of Formulation 2 or Formulation 3 was administered. Postprandial blood samples were taken at 30 and 60 minutes after feeding and CCK and enterin were tested. The post-prandial increase in CCK (area under the curve) and enterin (AUC) was calculated. The results are shown in the table below. Formulation 2 (pre-digested fat formulation) (pg/mL^min) Formulation 3 (control: low palmitic acid formulation) (pg/mL*min) Post-prandial increase in CCK secretion (area under the curve) 1935 ± 1464 1046 ±754 Enterin AUC (post-prandial increase) 483 ± 253 839 ± 403 The data in the above table shows that replacing pre-digested fat (monopalmitin plus soy fatty acid) with triglyceride stimulates postprandial CCK Secretion, which has been shown to stimulate pancreatic digestive enzyme secretion, enhance gallbladder contraction, and delay oral to cecal delivery. Thus, formulations with pre-digested fat stimulate more secretion of digestible enzymes and slow GI delivery to allow for more nutrient digestion and absorption. Therefore, formulations containing pre-digested fat can improve formulation tolerance, as undigested nutrients can cause excessive colonic fermentation to cause flatulence, diarrhea, and stomach. In addition, the data in the above table shows pre-digested fat (monopalmitic acid). Substituting diglycerides with glycerides plus soy fatty acids reduces postprandial intestinal motility. Infants with abdominal pain have been shown to have a lower post-prandial CCK content, but 161215.doc •45-201233329 has a mild postprandial enterin content. This imbalance between postprandial gut hormones causes the baby to contract GI, which causes abdominal pain. The data in the above table shows that the inclusion of pre-digested fat can increase the CCK content of the baby after a meal, but reduce the intestinal motility content, thereby reducing the hormone imbalance to relieve GI contraction, abdominal pain and abdominal pain. Example 22 In this example, pigs of Example 20 were used to study the effect of various fat systems on the contents of chylomicron triglyceride palmitate and Sn-2 palmitic acid. A sample was also taken from each pig after 1 hour of meal and plasma was separated, frozen in liquid nitrogen and stored in a freezer at -80 °C. Total plasma lipids were extracted using Folch solvent. The triglyceride was separated by thin layer chromatography. The table below shows the blood polytriglyceride palmitic acid and Sn-2 palmitic acid in Formulation 1 (palm oil blend formulation) and Formulation 2 (pre-digested fat formulation). The table also shows chylomicron triglycerides and Sn-2 palmitic acid in pigs fed the two formulations. Formulation 1 (Brown Oil 4 Show) Pigs' Triglyceride Formulation 2 for Feeding Formulation 1 : (Pre-digested Fat) Rice Feed Formulation 2 Pig's Plasma Triglyceride Milk for Human Infant It is a post-triglyceride triglyceride Sn-2 triglyceride Sn-2 triglyceride Sn-2 triglyceride Sn-2 triglyceride vinegar Sn-2 palmitic acid content (%) 23.3 5.8 18.3 10.6 21.4 5.2 18.5 14.4 25 25.5 As shown in the table above, the plasma triglyceride and Sn-2 palmitic acid levels of pigs fed the pre-digested fat formula were significantly higher than those of the palm oil formula. The ratio of plasma triglyceride palmitic acid/Sn-2 palmitic acid of Formulation 1 and Formulation 2 was about 1.7 and 1.3, respectively, and the ratio of known breast-fed infants was about 1 _1. Therefore, this data shows that the pre-digested fat formulation mimics breast milk better than the palm oil-based fat § week. 16l215.doc -46- 201233329 Example 23 In the 5 hai example, the pig of Example 20 was used to study the effect of various fat systems on the blood lutein content. Plasma from a 1 hour postprandial jk fluid sample from each pig was extracted using a solvent of chloroform and methanol (ratio 2:1). The solvent was removed and the resulting lipids were pooled and analyzed for lutein using conventional methods. The following table shows the lutein content of pigs fed with Formulation 1 (palm oily formulation), Formulation 2 (pre-digested fat formulation), and Formulation 3 (low palmitic acid formulation), per mg of lipid Lutein is called a number. Formulation 1: (Peach Palm Oil) Formulation 2: (Pre-digested fat) Formulation 3: (Low palmitic acid) Lutein contains N/A* 0.765 pg 0.539 μβ * Formulation 1 lutein content Too low to measure. As indicated in the above table, pigs fed a formulation containing pre-digested fat had increased lutein absorption compared to pigs fed a formulation containing palm olein or low palmitic acid. Example 24 In this example, Formulation 2 (pre-digested fat formulation) and Formulation 3 (low palmitic acid formulation) of Example 20 were used to study the effect of various fat systems on the lutein content of the cells. Formulation 2 and Formulation 3 were reconstituted with water (133 g of powdered formulation per 1.0 L of water), and the pH of the reconstituted formulation was adjusted to 4.5 by the addition of HC1. The reconstituted formulation was digested for 1 hour at room temperature by adding i.00 ml USP pepsin (56 mg/ml) to 40 ml of the reconstituted formulation. After pepsin digestion 161215.doc -47· 201233329 Adjust the pH of the reconstituted formulation to 7.0, and then add 28 mg USP trypsin/protease, 28 mg USP trypsin fat to the pepsin-digested formulation. A mixture of enzyme and 1 mg of bile extract. The formulation was further digested for 2 hours at room temperature and centrifuged (31,0 〇〇§ at 20° (:3 hours). The digested formulation formed an oil/creamt clot, an aqueous phase, and a sedimentation layer. The aqueous phase was extracted for lutein analysis of the micelles which served as a carrier during the absorption of lutein in the aqueous lumen. The following table shows the content of lutein in the microcapsule per kg of the digested formulation. 2: (pre-digested fat) Digested Formulation 3 : (Low palmitic acid) Microcytophyllin (pg) 0.598 μβ 0.246 pg As shown in the table above, the micro-discovery contained in the digested formulation containing pre-digested fat The amount of lutein was more than twice the amount of lutein found in the digested formulation containing low palmitic acid, thus showing that the use of pre-digested fat increased lutein absorption. Example 25 In this example, Analysis of the ability of pre-digested fat to reduce the incidence of soft stools. 30 weaned rats were fed a hydrolyzed protein-based infant formula (containing MCT oil as a 30 wt% fat source) for a four-day acclimation period. At the end, the rats were randomly divided into two groups. Promising control formulation (low palmitic acid powder infant formula) or test formulation (infant formula containing pre-digested fat). The control formulation is the same as the nutrient form of the test formulation. The rats are given free access to feed and water. For five days, the amount and weight of the ingested feed were recorded daily. 161215.doc -48 * 201233329 Although there was no significant difference in feed intake or weight gain between the two groups, there was a significant difference in the firmness of the sputum. During the last two days, the rat's stool firmness score was scored using the 〇5 point system. The score was based on the severity and firmness of the stool from the sticky gentleman to the bottom of the cage. The 〇 score value indicates normal stool and 5 scores. Watery diarrhea was indicated. As shown in Figure 2, rats fed a control formulation (containing MCT oil) produced a thin stool compared to the test test formulation (containing pre-digested monthly fat). In this example 'analyze the ability of pre-digested fat to reduce the incidence of necrotizing enterocolitis (NEC). Premature pigs (92% of pregnancy) delivered via caesarean section are immediately transferred to an oxygenated incubator (37) And a vascular catheter was placed in the umbilical artery. The pigs were injected three times (4, 6 and 7 mL/kg body weight) through the vascular catheter during the first 24 hours. Total parenteral nutrition (TPN) was provided at a rate of 6 mL/kg for 24 hours. The pigs were then randomized to receive at a rate of 5 mL/kg per hour via an orgastric tube. Control formulation or pDF formulation. In addition to the fat system therein, the control formulation is the same as the pDF formulation. In particular, the fat system in the formulation contains vegetable oil and the fat system in the pDF formulation contains 3〇 Wt 〇 / 0 monopalmitin, 2 〇 ^ % soybean fatty acid, 26 wt% high oleic safflower oil, 14 wt% coconut oil and 1 〇 wt% glyceryl tributyrate. Both the control formulation and the pDF formulation contained 1 g protein, 47 g fat, and 5 g g corn syrup per liter of the formulation. The pigs were euthanized and subjected to autopsy for 36 hours after enteral feeding to assess the severity of NEC lesions using the I61215.doc -49 - 201233329 1-5 scoring system, with a score of 1 indicating no signs of NEC. The results are shown in the table below. Block 1 Block 2 Control Formulation (n=5) PDF Formulation (n=3) Control Formulation (n=5) PDF Formulation (π=3) Early NEC Death 2 0 3 1 Detection at Autopsy NEC 2 1 0 0 Total NEC 4 1 3 1 As shown in the table above, 5 of the 10 pigs fed the control formulation (50%) died of NEC before the end of the enteral feeding period, but fed the PDF blending Only 1 out of 6 pigs (16.7%) died of NEC before the end of the enteral feeding period. In addition, 7 of the 10 pigs fed the control formulation (70%) had NEC measured before the end of the enteral feeding period, while only 2 of the 6 pigs fed the PDF formulation (33) %) NEC was determined before the end of the enteral feeding period. It can therefore be concluded that the incidence of NEC can be reduced by replacing the vegetable oil fat system with a fat system containing pre-digested fat. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A and 1B show graphical representations of a control emulsion and an experimental emulsion prepared as in Example 19. Figure 2 is a graph showing the effect of diet on fecal firmness. 161215.doc •50·

Claims (1)

201233329 七、申請專利範圍: 1 · 種營養品脂肪系統,該脂肪系統包含至少1 〇 wt%的含 有脂肪酸之單酸甘油酯,其中該等單酸甘油酯中至少 70 Λ之该等脂肪酸處於位置。 2.如請求項1之脂肪系統,其中該等單酸甘油酯為單棕櫚 酸甘油自旨。 3·如請求項1之脂肪系統,其中至少80%之該等脂肪酸處於 該Sn-Ι位置。 4·如請求項1之脂肪系統,其令該脂肪系統包含至少i 5 wt 的含有脂肪酸之單酸甘油酯。 5·如請求項1之脂肪系統,其中該脂肪系統包含約12 wt% 至約45 wt%的含有脂肪酸之單酸甘油酯。 6·如明求項1之脂肪系統’其中該脂肪系統包含約丨5 wt% 至約25 wt%的含有脂肪酸之單酸甘油酯。 7.如β青求項1之脂肪系統,其中該等含有脂肪酸之單酸甘 油酯係由豬油、動物脂或其組合之酶促水解而獲得。 8· —種嬰兒配方脂肪系統,該脂肪系統包含至少1〇 wt%的 含有脂肪酸之單酸甘油酯,其中該等單酸甘油酯中至少 70%之該等脂肪酸處於Sn]位置。 9. 如吻求項8之脂肪系統,其中該等單酸甘油酯為單棕櫊 酸甘油酯。 10. 如請求項8之脂肪系統,其中至少80%之該等脂肪酸處於 該Sn-1位置。 11. 如请求項8之脂肪系統,其中該脂肪系統包含至少b 161215.doc 201233329 wt%的含有脂肪酸之單酸甘油略。 12. 如請求項8之脂肪系統,其中 肪系統包含約12 wt% 至約45 wt%的含有脂肪酸之單酸甘油自t。 13. 如請求項8之脂肪系統,其中 茨月日肪系統包含約15 wt〇/〇 至約25 wt%的含有脂肪酸之單酸甘油酯。 14. 如請求項8之脂肪系統,其 ,、T忒孚含有脂肪酸之單酸甘 ::::由豬油、動物脂或其組合之酶促水解而獲得。 .之脂肪系統’其中約85%至約亀之該等脂 肪I處於該Sn-Ι位置。 161215.doc201233329 VII. Patent application scope: 1 · A nutrient fat system containing at least 1% by weight of a fatty acid-containing monoglyceride, wherein at least 70 of the fatty acids in the monoglyceride are in position . 2. The fat system of claim 1 wherein the monoglycerides are monopalmitoyl glycerol. 3. The fat system of claim 1, wherein at least 80% of the fatty acids are in the Sn-Ι position. 4. The fat system of claim 1 which comprises the fat system comprising at least i 5 wt of a fatty acid containing monoglyceride. 5. The fat system of claim 1, wherein the fat system comprises from about 12% to about 45% by weight of a monoglyceride containing a fatty acid. 6. The fat system of claim 1, wherein the fat system comprises from about 5 wt% to about 25 wt% of a monoglyceride containing a fatty acid. 7. The fat system of claim 1, wherein the fatty acid-containing monoglyceride is obtained by enzymatic hydrolysis of lard, tallow or a combination thereof. 8. An infant formula fat system comprising at least 1% by weight of a fatty acid-containing monoglyceride, wherein at least 70% of the fatty acids in the monoglyceride are in the Sn] position. 9. The fat system of claim 8, wherein the monoglyceride is glyceryl monopalmitate. 10. The fat system of claim 8 wherein at least 80% of the fatty acids are in the Sn-1 position. 11. The fat system of claim 8, wherein the fat system comprises at least b 161215.doc 201233329 wt% of a monoglyceride containing a fatty acid. 12. The fat system of claim 8, wherein the fat system comprises from about 12 wt% to about 45 wt% of the fatty acid-containing monoglyceride from t. 13. The fat system of claim 8, wherein the stagnation system comprises from about 15 wt〇/〇 to about 25 wt% of the fatty acid-containing monoglyceride. 14. The fat system of claim 8, wherein the T-fusin contains a fatty acid monosaccharide::: obtained by enzymatic hydrolysis of lard, tallow or a combination thereof. The fat system of about 85% to about 亀 of the fat I is in the Sn-Ι position. 161215.doc
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TW100149627A TW201233330A (en) 2010-12-29 2011-12-29 Nutritional products including a novel fat system including fatty acids
TW100149623A TW201233329A (en) 2010-12-29 2011-12-29 Nutritional products including a novel fat system including monoglycerides
TW100149631A TW201233331A (en) 2010-12-29 2011-12-29 Nutritional products including monoglycerides and fatty acids
TW100149621A TW201233342A (en) 2010-12-29 2011-12-29 Methods for decreasing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome in an infant, toddler, or child

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TW100149621A TW201233342A (en) 2010-12-29 2011-12-29 Methods for decreasing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome in an infant, toddler, or child

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TW201233330A (en) 2012-08-16
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