WO2022215619A1 - Glp-1分泌促進用組成物 - Google Patents
Glp-1分泌促進用組成物 Download PDFInfo
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- WO2022215619A1 WO2022215619A1 PCT/JP2022/015872 JP2022015872W WO2022215619A1 WO 2022215619 A1 WO2022215619 A1 WO 2022215619A1 JP 2022015872 W JP2022015872 W JP 2022015872W WO 2022215619 A1 WO2022215619 A1 WO 2022215619A1
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- A—HUMAN NECESSITIES
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
- C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
- C12G3/05—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides
Definitions
- Endocrine cells are scattered in the intestinal epithelium, and it is known that gastrointestinal hormones secreted from these intestinal endocrine cells regulate the functions of other organs. Some of the gastrointestinal hormones secreted from endocrine cells, also called incretins, are secreted into the blood with meal intake and act on ⁇ cells of the islets of Langerhans in the pancreas (hereinafter referred to as “pancreatic ⁇ cells”) to produce insulin. Promotes secretion.
- component (A) glycosylnaringenin
- component (B) ⁇ -pinene, ⁇ -pinene, sabinene, camphene, valencene, ⁇ -caryophyllene, ⁇ -ionone, methyl anthranilate, methyl N-methylanthranilate, thymol and nootkatone as an active ingredient.
- component (A) and component (B) which are active ingredients of the composition of the present invention, will be described in order.
- Typical compounds included in the term "glycosyl naringenin” as used herein include “naringin ” (chemical formula 2 below), and “3′′- ⁇ -monoglucosyl naringin” (chemical formula 3 below) having a structure in which glucose is ⁇ -bonded to the 3-position (3′′) OH group of the glucose residue in neohesperidose of naringin. etc.
- Naringin for example, is contained in immature peels of citrus fruits and is a substance having an antioxidant effect. In addition to physiological actions such as strengthening capillaries, preventing bleeding, regulating blood pressure and lowering cholesterol, it maintains the homeostasis of the body. It has also been found to have TNF inducing activity.
- the dosage, administration route, administration interval, intake amount, or intake interval of the composition for promoting GLP-1 secretion of the present invention are appropriately set according to the body weight, sex, age, condition, or other factors of the subject of administration or intake.
- the intake or dosage is, for example, 0.1 to 500 mg, preferably 1 to 300 mg, more preferably 2 to 200 mg as glycosylnaringenin per day for an adult (body weight 60 kg). , more preferably 5 to 150 mg.
- Acidulants include, for example, benzoic acid, adipic acid, sorbic acid, citric acid, trisodium citrate, gluconodeltalactone, gluconic acid, potassium gluconate, sodium gluconate, succinic acid, monosodium succinate, Disodium succinate, sodium acetate, DL-tartaric acid, L-tartaric acid, DL-sodium tartrate, sodium L-tartrate, lactic acid, sodium lactate, acetic acid, fumaric acid, monosodium fumarate, DL-malic acid, DL-malic acid Examples include sodium, phosphoric acid, malic acid, itaconic acid, ⁇ -ketoglutaric acid, phytic acid, disodium dihydrogen pyrophosphate, sodium metaphosphate, vinegar and fruit juice.
- Examples of food flavors include citrus flavors such as orange, lemon, lime, grapefruit, mandarin, and tangerine, shikuwasha, yuzu, mandarin orange, citrus, bergamot, iyokan, kabosu, bitter orange, buntan, kumquat, sudachi, and ponkan; apple , banana, cherry, grape, melon, peach, pineapple, plum, cranberry, and strawberry; Beans flavors, such as vanilla, coffee, cocoa, and chocolate; mint flavors, such as peppermint, spearmint, and horsemint Flavors; Spicy flavors such as allspice, cinnamon, and nutmeg; Nut flavors such as almonds, peanuts, and walnuts; Seafood flavors such as crab, shrimp, and other seafood; Other vegetables, grains, seaweed, etc. Various flavors of can be exemplified.
- xanthan gum e.g., locust bean gum, guar gum, tara gum, etc.
- galactomannans e.g., locust bean gum, guar gum, tara gum, etc.
- psyllium seed gum e.g., locust bean gum, guar gum, tara gum, etc.
- psyllium seed gum e.g., psyllium seed gum, wormwood seed gum, sesbania gum, tamarind seed gum, gellan gum, deacylated gellan gum, native gellan gum, carrageenan, glucomannan, Konjac powder, macrohomopsis gum, arabinogalactan, elemi resin, karaya gum, dammar resin, tragacanth gum, peach resin, amaseed gum, cassia gum, tricanthus gum, agar, gelatin, pectin (e.g.
- reaction solution containing ⁇ -glycosylnaringin.
- this reaction solution is adjusted to pH 4.5, 100 units of glucoamylase (trade name: Glucozyme (manufactured by Amano Enzyme Co., Ltd.)) is added per 1 g of dextrin, and the mixture is reacted at 55°C for 24 hours to obtain ⁇ - alpha-glucosylnaringin was produced from glycosylnaringin.
- glucoamylase trade name: Glucozyme (manufactured by Amano Enzyme Co., Ltd.)
- ⁇ Energy drink> As an amino acid mixture, 4 parts by mass of isoleucine, 6 parts by mass of leucine, 8 parts by mass of lysine, 8 parts by mass of phenylalanine, 1 part by mass of tyrosine, 12 parts by mass of tryptophan, 8 parts by mass of valine, 1 part by mass of aspartic acid, 1 part by mass of serine, A mixture of 8 parts by weight of aminoacetic acid, 8 parts by weight of alanine, 2 parts by weight of histidine, 8 parts by weight of arginine, 2 parts by weight of threonine, and 1 part by weight of methionine was prepared and dissolved in water to prepare a 2% solution of the mixture.
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Abstract
Description
(1)成分(A)グリコシルナリンゲニンと共に、成分(B)α-ピネン、β-ピネン、サビネン、カンフェン、バレンセン、β-カリオフィレン、β-イオノン、アントラニル酸メチル、N-メチルアントラニル酸メチル、チモール、及びヌートカトンからなる群より選択される少なくとも1種を有効成分として含むGLP-1分泌促進用組成物。
(2)前記成分(A)が、3″-α-モノグルコシルナリンジンである上記(1)記載のGLP-1分泌促進用組成物。
(3)前記成分(B)が、チモール及び/又はヌートカトンである、上記(1)又は(2)記載のGLP-1分泌促進用組成物。
(4)前記成分(A)と前記成分(B)を、モル比で10000:1~1:10の比率で含む上記(1)乃至(3)のいずれかに記載のGLP-1分泌促進用組成物。
(5)前記成分(A)を0.0001質量%以上含む上記(1)乃至(4)のいずれかに記載のGLP-1分泌促進用組成物。
(6)肥満、糖尿病、及び食後高血糖の予防又は改善、血糖上昇抑制、グルカゴン分泌抑制、胃排泄や胃酸分泌の抑制、食欲抑制、摂食抑制、満腹感の誘導作用から選択される少なくとも1つのために用いられる、上記(1)乃至(5)のいずれかに記載のGLP-1分泌促進用組成物。
(7)成分(A)グリコシルナリンゲニンと共に、成分(B)α-ピネン、β-ピネン、サビネン、カンフェン、バレンセン、β-カリオフィレン、β-イオノン、アントラニル酸メチル、N-メチルアントラニル酸メチル、チモール、及びヌートカトンからなる群より選択される少なくとも1種を含む組成物。
(8)前記成分(A)と前記成分(B)のモル比が10000:1~1:10の比率である上記(7)記載の組成物。
(9)前記成分(A)が、3″-α-モノグルコシルナリンジンである上記(7)又は(8)記載の組成物。
(10)前記成分(B)が、チモール及び/又はヌートカトンである、上記(7)乃至(9)のいずれかに記載のGLP-1分泌促進用組成物。
(11)前記成分(A)を0.0001質量%以上含む上記(7)乃至(10)のいずれかに記載の組成物。
(12)上記(1)乃至(11)のいずれかに記載の組成物を含む飲食品。
(13)上記(1)乃至(11)のいずれかに記載の組成物を含むサプリメント。
(14)上記(1)乃至(11)のいずれかに記載の組成物を含む香料。
(15)上記(1)乃至(11)のいずれかに記載の組成物を含む医薬品又は医薬部外品。
(16)上記(1)乃至(11)のいずれかに記載の組成物を含む飼料。
(17)液体状、流動状、ゲル状、半固形状、固形状又は粉末状の形態である上記(12)に記載の飲食品。
(18)液体状、ゲル状、ペースト状、錠剤状、丸状、カプセル状、粉末状、顆粒状、細粒状又はトローチ状の形態である上記(13)に記載のサプリメント。
(19)水溶性香料、油溶性香料、乳化香料又は粉末香料の形態である上記(14)に記載の香料。
(20)液体状、流動状、ゲル状、半固形状、固形状、錠剤状、丸状、カプセル状、粉末状、顆粒状、細粒状又はトローチ状の形態である上記(15)に記載の医薬品又は医薬部外品。
(21)液体状、粉末状、ペレット状、フレーク状又はマッシュ状の形態である上記(16)に記載の飼料。
本発明の組成物に用いられ得る、ピネン(Pinene)とは、分子式C10H16で表されるモノテルペンの一種であり、例えば、テレビン油などに見出される。ピネンには、α-ピネン及びβ-ピネンが含まれ、α-ピネン及びβ-ピネンには、それぞれd体、l体が存在する。本発明の組成物に用いられ得るピネンは、これらのいずれであっても良く、また、混合物であっても良い。
サビネン(Sabinene)とは、分子式C10H16で表されるモノテルペンの1種であり、例えば、杜松油などに見出される。サビネンには、d体、l体が存在する。本発明の組成物に用いられ得るサビネンは、これらのいずれであっても良く、また、混合物であっても良い。
カンフェン(Camphene)とは、分子式C10H16で表されるモノテルペンの1種であり、例えば、ローズマリー油、吉草油などに見出される。カンフェンには、d体、l体が存在する。本発明の組成物に用いられ得るカンフェンは、これらのいずれであっても良く、また、混合物であっても良い。
バレンセン(Valencene)とは、分子式C15H24で表されるセスキテルペンの1種であり、例えば、グレープフルーツやバレンシアオレンジなど、柑橘類の植物に見出される。
β-カリオフィレン(β-Caryophyllene)とは、分子式C15H24で表されるセスキテルペンの1種であり、例えば、フトモモ科の植物の精油、チョウジ油、シナモン油などに見出される。
β-イオノン(β-Ionone)とは、化学式C13H20Oで表され、別名β-ヨノンとも呼ばれる。β-イオノンは、例えば、ミカン科の植物の精油などに見出される。また、シトラールとアセトンを縮合し、これに酸を作用させることによって化学合成することもできる。
アントラニル酸メチル(Methyl anthranilate)とは、分子式C8H9NO2で表される含窒素化合物であり、別名2-アミノ安息香酸メチルとも呼ばれる。アントラニル酸メチルは、例えば、ジャスミンやブドウなどに含まれることが知られており、また、アントラニル酸とメタノールを脱水縮合させることによって化学合成することもできる。
N-メチルアントラニル酸メチル(Methyl N-methyl anthranilate)とは、分子式C9H11NO2で表される含窒素化合物であり、別名N-メチル-2-アミノ安息香酸メチルとも呼ばれる。N-メチルアントラニル酸メチルは、例えば、シナミカン油中に存在することが知られており、また、N-メチルアントラニル酸とメタノールを脱水縮合させることによって化学合成することもできる。
一方、成分(B)に、α-ピネン、β-ピネン、サビネン、カンフェン、バレンセン、β-カリオフィレン、β-イオノン、アントラニル酸メチル、及びN-メチルアントラニル酸メチルからなる群より選択される1種又は2種以上が含まれる場合には、その摂取量乃至投与量は、成人1人(体重60kg)に対して1日あたり、α-ピネン、β-ピネン、サビネン、カンフェン、バレンセン、β-カリオフィレン、β-イオノン、アントラニル酸メチル、又はN-メチルアントラニル酸メチルとして、例えば、0.0001~10mg、好ましくは、0.0005~5mg、より好ましくは、0.001~2mg、更に好ましくは0.01~1mgである。
また、成分(B)にチモールが含まれる場合には、その摂取量乃至投与量は、成人1人(体重60kg)に対して1日あたり、チモールとして、例えば、0.001~10mg、好ましくは、0.05~5mg、より好ましくは0.01~2mg、更に好ましくは0.01~1mgである。
更に、成分(B)にヌートカトンが含まれる場合には、その摂取量乃至投与量は、通常、成人1人(体重60kg)に対して1日あたり、ヌートカトンとして、例えば、1~2000mg、より好ましくは2~1000mg、更に好ましくは5~500mgである。
本発明では斯かる量を1日に1回~複数回、好ましくは1日に1回で投与又は摂取するのが好ましい。
同様に、本発明の組成物を含有する飲食品におけるサビネン、バレンセン、β-イオノン、N-メチルアントラニル酸メチル、又はチモールの含有量に特段の制限はなく、その使用形態により適宜の含有量とすることができる。その下限に特段の制限はないが、好ましくは0.001ppm以上であり、より好ましくは0.01ppm以上、更に好ましくは0.1ppm以上である。また、その上限にも特段の制限はないが、好ましくは100ppm以下であり、より好ましくは、10ppm以下、更に好ましくは5ppm以下である。
また、本発明の組成物を含有する飲食品におけるα-ピネン、β-ピネン、カンフェン、β-カリオフィレン、アントラニル酸メチル、又はヌートカトンの含有量に特段の制限はなく、その使用形態により適宜の含有量とすることができる。その下限に特段の制限はないが、好ましくは0.001ppm以上であり、より好ましくは0.01ppm以上、更に好ましくは0.1ppm以上であり、より更に好ましくは0.5ppm以上である。また、その上限にも特段の制限はないが、好ましくは50000ppm以下、より好ましくは500ppm以下、更に好ましくは50ppm以下、より更に好ましくは30ppm以下である。
また、本発明の組成物を含有するサプリメントにおけるサビネン、バレンセン、β-イオノン、N-メチルアントラニル酸メチル、又はチモールの含有量に特段の制限はなく、その使用形態により適宜の含有量とすることができる。その下限に特段の制限はないが、好ましくは0.001ppm以上であり、より好ましくは0.01ppm以上、更に好ましくは0.05ppm以上、より更に好ましくは1ppm以上である。一方、その上限にも特段の制限はないが、好ましくは10質量%以下であり、より好ましくは5質量%以下、更に好ましくは1質量%以下、より更に好ましくは0.1質量%以下である。
また、本発明の組成物を含有するサプリメントにおけるα-ピネン、β-ピネン、カンフェン、β-カリオフィレン、アントラニル酸メチル、又はヌートカトンの含有量に特段の制限はなく、その使用形態により適宜の含有量とすることができる。その下限に特段の制限はないが、好ましくは0.001ppm以上であり、より好ましくは0.01ppm以上、更に好ましくは0.05ppm以上、より更に好ましくは1ppm以上である。一方、その上限にも特段の制限はないが、好ましくは10質量%以下であり、より好ましくは5質量%以下、更に好ましくは1質量%以下、より更に好ましくは0.1質量%以下である。
香料におけるサビネン、バレンセン、β-イオノン、N-メチルアントラニル酸メチル、又はチモールの含有量の下限に特段の制限はないが、好ましくは0.01ppm以上であり、より好ましくは0.1ppm以上、更に好ましくは、1ppm以上、より更に好ましくは、3ppm以上である。また、香料におけるサビネン、バレンセン、β-イオノン、N-メチルアントラニル酸メチル、又はチモールの含有量の上限にも特段の制限はないが、好ましくは10質量%以下であり、より好ましくは5質量%以下、更に好ましくは1質量%以下、より更に好ましくは0.3質量%以下である。
香料におけるα-ピネン、β-ピネン、カンフェン、β-カリオフィレン、アントラニル酸メチル、又はヌートカトンの含有量の下限に特段の制限はないが、好ましくは0.01ppm以上であり、より好ましくは0.1ppm以上、更に好ましくは1ppm以上、より更に好ましくは2ppm以上である。また、香料におけるα-ピネン、β-ピネン、カンフェン、β-カリオフィレン、アントラニル酸メチル、又はヌートカトンの含有量の上限にも特段の制限はないが、好ましくは10質量%以下であり、より好ましくは5質量%以下、更に好ましくは3質量%以下、より更に好ましくは1質量%以下である。
グリコシルナリンゲニンとして、3″-α-モノグルコシルナリンジン含有組成物を用い、各種香気成分を含有する組成物を調製し、調製した組成物をヒト腸管由来細胞に作用させた場合のGLP-1分泌量を確認した。
特開2002-199896号公報中の実施例1に記載の方法に準じてグリコシルナリンゲニンを調製した。すなわち、ナリンジン50gとDE8のデキストリン200gを500mLの水に加熱溶解し、2N水酸化ナトリウム水溶液でpH7.0に調整し、バチルス・ステアロサーモフィルス由来のシクロデキストリングルカノトランスフェラーゼ(株式会社林原製)をデキストリン1g当たり15単位加えて、68℃で48時間反応させた。反応終了後、酵素を加熱失活させてから濾過して、α-グリコシルナリンジン含有反応液を得た。次いで、この反応液を、pH4.5に調整し、グルコアミラーゼ(商品名:グルコチーム(天野エンザイム株式会社製))をデキストリン1g当り100単位加えて、55℃で24時間反応させることにより、α-グリコシルナリンジンからα-グルコシルナリンジンを生成させた。生成したα-グルコシルナリンジンは、特開2002-199896号公報に示されているように、3″-α-モノグルコシルナリンジンと未反応のナリンジンに加え、その他の配糖体として、3″,4´-α-ジグルコシルナリンジンと4´-α-モノグルコシルナリンジンを含むものであった。そこで、組成物中の3″-α-モノグルコシルナリンジンとナリンジンの含量を高めるべく、α-グルコシダーゼ(商品名:トランスグルコシダーゼL<アマノ>(天野エンザイム株式会社製))をα-グリコシルナリンジン1g当り1mL加えて、55℃で24時間反応させることにより、3″,4´-α-ジグルコシルナリンジンおよび4´-α-モノグルコシルナリンジンをそれぞれ分解し、3″-α-モノグルコシルナリンジンとナリンジンを含む組成物を生成させた。反応終了後、酵素を加熱失活させてから反応液を濾過し、得られた濾液を多孔性合成吸着剤を充填したカラムにSV(空間速度)が2となるように通液することにより溶液中の3″-α-モノグルコシルナリンジンとナリンジンとをカラムに吸着させ、カラムを水で洗浄することによりカラムに吸着しないグルコース、塩類などを除去した。次いで、エタノール濃度を段階的に高めたエタノール水溶液をカラムに通液することにより、3″-α-モノグルコシルナリンジンとナリンジンを溶出させ、溶出液を減圧濃縮し、噴霧乾燥により粉末化して、3″-α-モノグルコシルナリンジン組成物を得た。HPLC分析した結果、その組成(ナリンゲニン比(モル比))は、3″-α-モノグルコシルナリンジンが70%であり、ナリンジンが30%であった。なお、HPLC分析は、以下の条件で実施した。
カラム:『CAPCELL PAK C18 UG 120』(株式会社資生堂製)
溶離液:水/アセトニトリル/酢酸=80/20/0.01(v/v/v)
検出:UV280nm
温度:40℃
流速:0.8mL/分
実験1-1で得た3″-α-モノグルコシルナリンジン組成物を水/アセトニトリル/酢酸混合液(80/20/0.01(v/v/v))に溶解し、前記HPLC分析条件に準じた方法を用い、検出器としては紫外線吸光光度計(UV280nm)を用いて、C18カラムに通液することにより、3″-α-モノグルコシルナリンジンとナリンジンを分離し、3″-α-モノグルコシルナリンジン画分を採取した。その後、該画分を減圧濃縮し、噴霧乾燥により粉末化して、粉末状の高純度3″-α-モノグルコシルナリンジン精製標品を得た。HPLC分析した結果、得られた精製標品の3″-α-モノグルコシルナリンジンの純度は、99.0%であった。
GLP-1分泌促進作用を、NCI-H716細胞(ヒト腸管由来細胞株;ATCC社より購入)を用い、次法により評価した。
実験1-3において、被験物質として、以下の化合物を使用した。
<試験サンプル>
実験1-2の方法で得た高純度3″-α-モノグルコシルナリンジン精製標品(以下、mGN)、及び、香気成分として、シトラール、カンフェン(以上全てシグマ社製)、シトロネラール(Combi-blocks社製)、アントラニル酸メチル、N-メチルアントラニル酸メチル、、ヌートカトン(以上、全て東京化成工業株式会社製)、α-ピネン、β-ピネン、β-イオノン、β-カリオフィレン、チモール(以上、富士フィルム和光純薬株式会社製)、サビネン(Tronto Reserch Chemicals社製)、バレンセン(Cayman社製)を用いた。
相乗効果:理論値<実測値
理論値=(A/D-1)×100+(B/D-1)×100
実測値=(C/D-1)×100
A:mGN単独添加によるGLP-1分泌量
B:各種香気成分添加によるGLP-1分泌量
C:mGNと各種香気成分の併用によるGLP-1分泌量
D:対照群(無添加サンプル)のGLP-1分泌量
実験1-3において、特に優れたGLP-1分泌促進効果が得られたmGNとチモール、又はmGNとヌートカトンの併用によるGLP-1分泌促進効果のうち、まずは、mGNとチモールの併用によるGLP-1分泌促進効果について、更に詳細に検討した。すなわち、チモール0.25mMに対し、mGNを種々のモル比となるように混合した組成物を調製し、GLP-1分泌に対する作用を検討した。実験は、表2に示す試験サンプルを用いた以外は、実験1-3と同様の方法で行い、N数は3とした。
次に、表2に示す結果より、最もGLP-1分泌促進効果の高かった試験No.2-4を基準として、mGN25mMに対し、チモールを種々のモル比となるように混合した組成物を調製し、GLP-1分泌に対する作用を検討した。実験は、表3に示す試験サンプルを用いた以外は、実験1-3と同様の方法で行い、N数は3とした。なお、相乗効果の判断は、実験2と同様の方法で判断した。評価結果を表3に示す。
実験2及び実験3の結果を併せ考えると、本発明の組成物がグリコシルナリンゲニンとチモールとを含む場合、グリコシルナリンゲニンとチモールの配合比に特段の制限はないが、相乗的なGLP-1分泌促進効果を得るという観点から、グリコシルナリンゲニン及びチモールを、グリコシルナリンゲニンとチモールのモル比で4000:1~1:10の比率で含むことが好ましく、より好ましくは3731:1~1:10の比率で含むことが好ましく、200:1~1:1の比率で含むことが更に好ましいと判断された。また、試料No.2-2、2-3、2-4においては、特に、相乗効果の度合いが極めて大きいことから、グリコシルナリンゲニンとチモールのモル比で100:1~1:1の比率でグリコシルナリンゲニン及びチモールを含むことがよりさらに好ましいと判断された。
次に、実験1-3において、特に優れたGLP-1分泌促進効果が得られたmGNとチモール、又はmGNとヌートカトンの併用によるGLP-1分泌促進効果のうち、mGNとヌートカトンの併用によるGLP-1分泌促進効果について、更に詳細に検討した。すなわち、mGNとヌートカトンを種々のモル比で混合した組成物を調製し、GLP-1分泌に対する作用を検討した。実験は、表4に示す試験サンプルを用いた以外は、実験1-3と同様の方法で行い、N数は3とした。なお、相乗効果の判断は、実験2と同様の方法で判断した。評価結果を表4に示す。
以上の結果から、本発明の組成物がグリコシルナリンゲニンとヌートカトンとを含む場合には、相乗的なGLP-1分泌促進効果を得るという観点からは、グリコシルナリンゲニンとヌートカトンをモル比で1000:1~1:5の比率で含むことが好ましく、10:1~1:1の比率で含むことがより好ましいと判断された。
mGNとチモール及びヌートカトンの三成分の併用効果について検討するため、mGNと、チモール及びヌートカトンをモル比で1:1で混合した混合物(以下、「チモール及びヌートカトン1:1混合物」という。)を種々のモル比で混合した組成物を調製し、GLP-1分泌に対する作用を検討した。実験は、表5に示す試験サンプルを用いた以外は、実験1-3と同様の方法で行い、N数は3とした。相乗効果の判断は、実験2と同様の方法で判断した。評価結果を表5に示す。なお、表5において、チモール及びヌートカトン1:1混合物のモル濃度は、該混合物中に含まれるチモールのモル濃度とヌートカトンのモル濃度の合計値であり、mGNと混合物のモル比も当該合計値に基づいて算出したものである。
表5に示すとおり、mGNと、チモール及びヌートカトン1:1混合物の配合比がモル比で1000:1~1:10の範囲にある試験No.5-1乃至5―3の全てについてmGNと、チモール及びヌートカトン1:1混合物の併用による相乗効果が認められ、特に、mGNとチモールをモル比で1:10で含む試験No.5-1において、より相乗効果が顕著であった。
mGNと、チモール及びヌートカトンをモル比で1:2で混合した混合物(以下、「チモール及びヌートカトン1:2混合物」という)を種々のモル比で混合した組成物を調製し、GLP-1分泌に対する作用を検討した。実験は、表6に示す試験サンプルを用いた以外は、実験1-3と同様の方法で行い、N数は3とした。なお、相乗効果の判断は、実験2と同様の方法で判断した。評価結果を表6に示す。
表6に示すとおり、mGNと、チモール及びヌートカトン1:2混合物の配合比が、モル比で1000:1~1:10の範囲にある試験No.6-1乃至6―3の全てについてmGNと、チモール及びヌートカトン1:2混合物の併用による相乗効果が認められ、特に、mGNと、チモール及びヌートカトン1:2混合物をモル比で1000:1~600:1で含む試験No.6-2及びNo.6-3において、より相乗効果が顕著であった。
実験5及び実験6の結果を併せ考えると、本発明の組成物がグリコシルナリンゲニンと、チモール及びヌートカトンを含む場合、チモール及びヌートカトンの配合比に特段の制限はないが、相乗的なGLP-1分泌促進効果を得るという観点から、グリコシルナリンゲニンと、チモール及びヌートカトン混合物を、グリコシルナリンゲニンと、チモール及びヌートカトン混合物のモル比で1000:1~1:10の比率で含むことが好ましいと判断された。
実験1-1で得た3″-α-モノグルコシルナリンジン組成物を0.015質量部、還元水飴30質量部、グラニュー糖30質量部、はちみつ3質量部、アセスルファムカリウム0.07質量部、スクラロース0.03質量部、ビタミンC0.3質量部、クエン酸3質量部、クエン酸ナトリウム1質量部、レモン香料1質量部、ユズ香料1質量部、チモール0.00003質量部 、ヌートカトン0.001質量部を加え、よく攪拌した後に、水を加えて計1000質量部とした。その後、90℃で、30秒間殺菌を行った。得られたレモン風味飲料は、甘味の後キレがよく、トップのフレッシュ感とほろ苦いピール感が感じられた。また、得られたレモン風味飲料を40℃で、4週間保存したところ、保存後もレモン香がよく維持され、好ましくない劣化臭の発生も抑制されていた。本品は、GLP-1分泌促進、血糖上昇抑制のための飲料として有利に利用できる。
果糖ぶどう糖液糖20質量部、アセスルファムカリウムを0.1質量部、スクラロースを0.02質量部、クエン酸を2質量部、クエン酸ナトリウムを0.5質量部、実験1-1で得た3″-α-モノグルコシルナリンジン組成物を0.015質量部、を、水197質量部と混合し、溶解するまでよくかき混ぜた。そこへ適量のレモン香料とチモール0.0001質量部、ヌートカトン0.0001質量部を加え、よく攪拌した後に、炭酸水750質量部を加え、炭酸飲料を得た。得られた炭酸飲料は、適度な苦味が付与され、甘味の後キレがよく、すっきりとした飲みごたえであり、レモン風味がよく維持されていた。本品は、GLP-1分泌促進、血糖上昇抑制のための飲料として有利に利用できる。
果糖ぶどう糖液糖100質量部、オレンジ濃縮果汁(1/5濃縮果汁)22質量部、クエン酸8質量部、ビタミンC1質量部、ステビア0.04質量部、実験1-1で得た3″-α-モノグルコシルナリンジン組成物を0.03質量部、オレンジ香料1質量部、ヌートカトン0.002質量部、チモール0.00001質量部を混合し、水を加えて計1000質量部とし、果汁飲料を調製した。得られた果汁飲料は、オレンジの果汁感が増すとともに、ヌートカトン及びチモールを配合していることから、さらに果実由来の果汁感が増強され、香り立ち良く、グレープフルーツ様の風味、苦味が加わり、好ましい飲料となった。さらに、高甘味度甘味料配合による後キレも抑制され、すっきりとした果汁飲料とすることができた。本品は、GLP-1分泌促進、血糖上昇抑制のための飲料として有利に利用できる。
実験1-1で調製した3″-α-モノグルコシルナリンジン組成物0.05質量部、アセスルファムカリウム0.1質量部、スクラロース0.02質量部、クエン酸4質量部、クエン酸ナトリウム1質量部を、アルコール濃度50%(v/v)のウォッカ(ニッカウヰスキー社 ウヰルキンソン・ウォッカ50゜)133質量部と混合し、溶解するまでよくかき混ぜた。そこへ、適量のレモン香料、チモール0.0001質量部、ヌートカトン0.0001質量部を加え、良く攪拌した後に、炭酸水にて計1000質量部とし、チューハイを得た。得られたチューハイは、アルコール6%であるが、アルコール感が増強され、フレッシュなレモンらしさと、雑味のない、すっきりとした甘味の飲みやすいチューハイであった。
実験1-1で調製した3″-α-モノグルコシルナリンジン組成物0.05質量部、α,α-トレハロース2質量部、麦芽エキス2質量部、及びホップエキス(イソ-α酸として)0.02質量部、チモール0.00005質量部、ヌートカトン0.001質量部を精製水に溶解し、計1000質量部とした後、1時間煮沸し、冷却後、蒸発分の水を補充し、ビールフレーバー適量を添加し、珪藻土濾過及びフィルター濾過により清澄化処理を施した。
得られたビールテイスト飲料は、色調、風味、ボディ感、苦味のキレ、のど越し感のいずれの点においても良好なビールテイスト飲料であった。
緑茶の茶葉25gに70℃の脱イオン水800gを添加して6分間、茶の成分を抽出した後、濾過により茶葉の残渣を除去して、700mlの抽出液を得た。得られた抽出液を脱イオン水で3倍に希釈して、L-アスコルビン酸を50ppmとなるように添加し、炭酸水素ナトリウムにより、pHを6.2に調整した。次いで、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物を10ppm、チモールを0.003ppmとなるように添加後、耐熱性ガラス容器に350mlずつ分注・密閉し、121℃で10分間の殺菌を行って茶飲料とした。
得られた緑茶飲料は、適度な苦味及が付与され、茶の香りの優れた飲料であった。本品は、GLP-1分泌促進、血糖上昇抑制のための飲料として有利に利用できる。
常法により、紅茶葉に熱水を加えて抽出し、紅茶抽出液を得た。この抽出液320質量部、砂糖70質量部、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物0.015質量部、香料としてベルガモット香料0.1質量部、チモール0.00002質量部、ヌートカトン0.00026質量部を加えて混合した後に、脱イオン水で希釈し、重曹にてpH5.8に調整し、計1000質量部の紅茶飲料を調製した。これを350mlずつ缶充填後、レトルト殺菌(120℃、4分)した。得られた紅茶飲料は、適度な苦味と渋味が付与され、紅茶風味と果汁感の感じられる紅茶飲料であった。本品は、GLP-1分泌促進、血糖上昇抑制のための飲料として有利に利用できる。
L値(色差計で測定した、コーヒー豆の明度)が22となるよう焙煎したアラビカ種のコーヒー豆100質量部を粉砕し、熱湯で抽出した。コーヒー豆抽出液をBrix2となるように調整したコーヒー抽出液500質量部に対し、水200質量部、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物を10ppm、チモール0.011ppm、ヌートカトン0.14ppmとなるように添加し、pH調整を行った後に缶に容器詰めを行い、レトルト殺菌し、缶入りコーヒーを得た。得られた缶入りコーヒーは、コーヒーの苦味とも調和し、さらに異味異臭の抑えられた飲みやすい缶入りコーヒーであった。本品は、GLP-1分泌促進、血糖上昇抑制のための飲料として有利に利用できる。
砂糖200質量部、κカラギーナン2.5質量部、ロストビーンガム2.5質量部、クエン酸ナトリウム2.5質量部、塩化カリウム1質量部、アセスルファムカリウム0.2質量部をよく混ぜ、水650質量部を入れた鍋に、ダマにならないように加えた。そこへ、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物0.01質量部を加えた後に、煮詰め、質量が800質量部となるように水分を蒸発させた。その後、70℃程度まで冷却し、オレンジ濃縮果汁(1/5濃縮果汁)35質量部、適量のオレンジ香料、チモール0.00003質量部、ヌートカトン0.001質量を加え、pHが3.2~4.0の範囲内に収まるように、50%クエン酸水溶液を用いてpHを調整した。この溶液を、ゼリーカップに充填し、冷蔵庫で固まるまで静置し、オレンジゼリーを得た。得られたオレンジゼリーは、オレンジの果汁感とフレッシュ感が増し、さらに甘味料由来の嫌味を感じにくいゼリーであった。本品は、GLP-1分泌促進、血糖上昇抑制のための食品として有利に利用できる。
グレープフルーツ果汁300質量部、水350質量部に対して、砂糖30質量部、α,α-トレハロース20質量部、グレープフルーツ香料0.1質量部、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物0.015質量部、チモール0.000005質量部、ヌートカトン0.001質量部を完全に溶解させ、混合液をソルベチュール(シャーベット作成機)で冷凍しながら撹拌し、グレープフルーツ風味のシャーベットを製造した後、プラスチック製のカップに充填して-20℃の冷凍庫で保管した。また、3″-α-モノグルコシルナリンジン組成物を配合しない点以外は、上記と同様の方法で得た氷菓を対照とした。本発明の氷菓は、固形分及び糖質含量が少ないことから、スッキリした低甘味で、対照に比べて、グレープフルーツの果汁感が増し、風味良好であった。
砂糖170質量部、麦芽糖水あめ(商品名『マルトラップ』、株式会社林原製)250質量部、ゼラチン24質量部、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物0.1質量部、水48質量部、50質量%クエン酸水溶液12質量部、グレープフルーツ香料0.6質量部と、着色料の適量、チモール0.0001質量部、ヌートカトン0.0001質量部を、常法に従い、混合する。スターチモールドに充填し、1日乾燥させた後、成型して、グミを得た。
本発明の組成物は水溶性に優れているため、得られたグミは透明で、ほのかな苦味を有し、グレープフルーツのフレッシュ感が引き立つグミであった。
果糖ブドウ糖液糖240質量部、麦芽糖水あめ(商品名『マルトラップ』、株式会社林原製)220質量部、水80質量部を混合し、150℃まで煮詰めた。いったん、120℃以下まで冷却して実験1-1で調製した3″-α-モノグルコシルナリンジン組成物を0.01質量部、ペパーミントオイル0.8質量部、メントール1.1質量部、チモール0.005質量部、ヌートカトン0.00025質量部、着色料 適量を添加し成型してキャンディーを製造した。得られたハードキャンディーは、ミント風味が増強され、清涼感が増したハードキャンディーであった。また、3″-α-モノグルコシルナリンジン組成物、チモールを含有することから、口腔内、喉の荒れや炎症、痛みなどを軽減する作用や抗菌作用を有し、口腔の健康の維持・増進を目的に使用することができるハードキャンディーである。
アミノ酸混合物として、イソロイシン4質量部、ロイシン6質量部、リジン8質量部、フェニルアラニン8質量部、チロシン1質量部、トリプトファン12質量部、バリン8質量部、アスパラギン酸1質量部、セリン1質量部、アミノ酢酸8質量部、アラニン8質量部、ヒスチジン2質量部、アルギニン8質量部、スレオニン2質量部、メチオニン1質量部の混合物を調製し、水に溶解して混合物の2%溶液を調製した。この溶液50質量部に、アスコルビン酸を0.5質量部、ニコチン酸アミドを0.01質量部、ビタミンB1を0.01質量部、ビタミンB2を0.01質量部ビタミンB6を0.01質量部、グレープフルーツ濃縮果汁(1/5濃縮果汁)を1.8質量部、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物を0.01質量部、チモールを0.0003質量部、ヌートカトンを0.003質量部添加し、水にて合計100質量部とした栄養ドリンクを調製した。本品は、GLP-1分泌促進、血糖上昇抑制のため好適であり、長期間保存しても、褐変や異臭の発生もなく、アミノ酸自体の異味が低減され、嗜好性が改善された、風味のよい栄養ドリンクである。
酢酸カルシウム・一水塩10質量部、L-乳酸マグネシウム・三水塩50質量部、マルトース60質量部、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物30質量部、チモール0.1質量部、ヌートカトン0.06質量部を均一に混合し、顆粒成型機にかけて顆粒とした後、常法に従って、ゼラチンカプセルに封入して、1カプセル150mg入のカプセル製剤のサプリメントを製造した。本品は、本品は、GLP-1分泌促進、血糖上昇抑制のため、また健康増進のための経口摂取物として好適である。
常法に従って、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物5質量部、マルトース68質量部、α,α-トレハロース15質量部、プルラン含有粉末5質量部、チモール0.12質量部、グレープフルーツ香料0.1質量部を均一に混合した後、混合物を打錠して錠剤(200mg/1錠)を得た。
本品は、適度な強度を有すると共に、風味、呈味が良好であり、GLP-1分泌促進、血糖上昇抑制のための錠剤として好適である。また、チモールを含有しているため、血流を改善・維持し、冷え性の予防あるいは改善など健康増進のための経口摂取物としても好適である。
レモンオイルと、65w/w%の含水エタノールを混合し、攪拌後、低温下で放置し、含水エタノール中に水溶性の香気成分を含有した水層(エッセンス層)と水不溶性成分を含有する油相に分液し、水層を抽出してレモンエッセンスを得た。得られたレモンエッセンス98質量部に対して実験1-1で調製した3″-α-モノグルコシルナリンジン組成物2質量部、チモール0.01質量部、ヌートカトン0.05質量部を混合して、水溶性のレモン香料を得た。得られたレモン香料は、長期保存による劣化臭が抑制され、良好な香気香味を保持していた。また、本発明の組成物は水溶性に優れるため、安定性の高い水溶性の液体香料とすることができ、本品は、通常飲食品へ0.01~1%の範囲で添加することにより、香味の発現性及び持続性の高められたものとすることができる。また、GLP-1分泌促進、血糖上昇抑制のため、また健康増進のための経口摂取物として好適なものとすることができる。
水100gにHLB15のショ糖脂肪酸エステル5g、実験1-1で調製した3″-α-モノグルコシルナリンジン組成物2gを加えて溶解し、85~90℃で15分間加熱殺菌した。この溶液を約40℃に冷却後ホモミキサーで撹拌しながら、レモンオイル10g、チモール0.001g、ヌートカトン0.5gを混合して乳化香料を得た。本品は、さらに、噴霧乾燥などの方法で乾燥することにより、容易に粉末香料とすることができる。得られた粉末香料は、いずれも長期保存による劣化臭の発生がなく良好な香気香味を保持していた。
本品は、通常飲食品へ0.1~3%の範囲で添加することにより、GLP-1分泌促進、血糖上昇抑制のため、また健康増進のための経口摂取物として好適なものとすることができる。
Claims (21)
- 成分(A)グリコシルナリンゲニンと共に、成分(B)α-ピネン、β-ピネン、サビネン、カンフェン、バレンセン、β-カリオフィレン、β-イオノン、アントラニル酸メチル、N-メチルアントラニル酸メチル、チモール、及びヌートカトンからなる群より選択される少なくとも1種を有効成分として含むGLP-1分泌促進用組成物。
- 前記成分(A)が、3″-α-モノグルコシルナリンジンである請求項1記載のGLP-1分泌促進用組成物。
- 前記成分(B)が、チモール及び/又はヌートカトンである、請求項1又は2記載のGLP-1分泌促進用組成物。
- 前記成分(A)と前記成分(B)を、モル比で10000:1~1:10の比率で含む請求項1乃至3のいずれかに記載のGLP-1分泌促進用組成物。
- 前記成分(A)を0.0001質量%以上含む請求項1乃至4のいずれかに記載のGLP-1分泌促進用組成物。
- 肥満、糖尿病、及び食後高血糖の予防又は改善、血糖上昇抑制、グルカゴン分泌抑制、胃排泄や胃酸分泌の抑制、食欲抑制、摂食抑制、満腹感の誘導作用から選択される少なくとも1つのために用いられる、請求項1乃至5のいずれかに記載のGLP-1分泌促進用組成物。
- 成分(A)グリコシルナリンゲニンと共に、成分(B)α-ピネン、β-ピネン、サビネン、カンフェン、バレンセン、β-カリオフィレン、β-イオノン、アントラニル酸メチル、N-メチルアントラニル酸メチル、チモール、及びヌートカトンからなる群より選択される少なくとも1種を含む組成物。
- 前記成分(A)と前記成分(B)のモル比が10000:1~1:10の比率である請求項7記載の組成物。
- 前記成分(A)が、3″-α-モノグルコシルナリンジンである請求項7又は8記載の組成物。
- 前記成分(B)が、チモール及び/又はヌートカトンである、請求項7乃至9のいずれかに記載の組成物。
- 前記成分(A)を0.0001質量%以上含む請求項7乃至10のいずれかに記載の組成物。
- 請求項1乃至11のいずれかに記載の組成物を含む飲食品。
- 請求項1乃至11のいずれかに記載の組成物を含むサプリメント。
- 請求項1乃至11のいずれかに記載の組成物を含む香料。
- 請求項1乃至11のいずれかに記載の組成物を含む医薬品又は医薬部外品。
- 請求項1乃至11のいずれかに記載の組成物を含む飼料。
- 液体状、流動状、ゲル状、半固形状、固形状又は粉末状の形態である請求項12に記載の飲食品。
- 液体状、ゲル状、ペースト状、錠剤状、丸状、カプセル状、粉末状、顆粒状、細粒状又はトローチ状の形態である請求項13に記載のサプリメント。
- 水溶性香料、油溶性香料、乳化香料又は粉末香料の形態である請求項14に記載の香料。
- 液体状、流動状、ゲル状、半固形状、固形状、錠剤状、丸状、カプセル状、粉末状、顆粒状、細粒状又はトローチ状の形態である請求項15に記載の医薬品又は医薬部外品。
- 液体状、粉末状、ペレット状、フレーク状又はマッシュ状の形態である請求項16に記載の飼料。
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 380, 2009, pages 44 - 49 |
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TW202304312A (zh) | 2023-02-01 |
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US20240139226A1 (en) | 2024-05-02 |
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