TW200942181A - Nutrition composition for inhibiting high blood glucose - Google Patents

Nutrition composition for inhibiting high blood glucose Download PDF

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TW200942181A
TW200942181A TW098103251A TW98103251A TW200942181A TW 200942181 A TW200942181 A TW 200942181A TW 098103251 A TW098103251 A TW 098103251A TW 98103251 A TW98103251 A TW 98103251A TW 200942181 A TW200942181 A TW 200942181A
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nutritional composition
fatty acid
nutritional
composition according
vitamin
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TW098103251A
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TWI439234B (en
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Mio Fujimaki
Satoko Tanisaka
Naoki Hayashi
Itaru Kon
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Ajinomoto Kk
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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    • A23L29/30Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115Fatty acids or derivatives thereof; Fats or oils
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/175Amino acids
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L5/00Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016Disaccharides, e.g. lactose, lactulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/02Nutrients, e.g. vitamins, minerals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P39/06Free radical scavengers or antioxidants
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Obesity (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract

Disclosed is a nutritional composition for preventing hyperglycemia, which comprises a nitrogen source, a lipid and a sugar component, wherein the nitrogen source comprises free isoleucine and/or free leucine, the lipid comprises a middle-chain fatty acid triglyceride, and the sugar component comprises palatinose and/or trehalose. The nutritional composition has an excellent nutritional balance even when the nutritional composition is ingested for a long period, can prevent the development of hyperglycemia after the nutritional composition is administered, and enables the reduction in the amount of insulin to be administered.

Description

200942181 六、發明說明 【發明所屬之技術領域】 本發明有關具有高血糖抑制作用之營養均衡優異之營 養組成物。 【先前技術】 0BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nutritional composition excellent in nutrient balance with a high blood sugar suppressing action. [Prior Art] 0

必須胺基酸除維持人類生命以外,亦爲營造每日生活 愉快舒適所必須之營養要素,但由於對於各種疾病具有治 療效果,因此已使用作爲醫藥品、營養劑或補充品等之有 效成分。 例如,提案有含有亮胺酸、異亮胺酸及纈胺酸之至少 一種之耐糖能異常用藥劑及飲食品(專利文獻1及2)。 該等公報中實際上於實施例中所用者爲僅亮胺酸或亮胺酸 、異亮胺酸及纈胺酸之混合物,並調查將該等對大鼠經口 投與1.5克/公斤之量時血糖値之變化。因此,此耐糖能異 常用藥劑尤其可有效地治療、改善及/或預防於難以使用 以往糖尿病藥之具有肝臟障礙之耐糖能異常。 異麥芽酮糖(palatinose )及海藻糖爲糖質之一種, 提案有使用作爲血糖値控制用營養組成物之必須成分(專 利文獻3)。該發明中規定糖質之能量比率中異麥芽酮糖 及/或海澡糖爲6 0〜100%,又另外,本發明人等對異麥芽 酮糖之血糖値控制效果進行調查之後,確認若未使用佔糖 質之68.5質量%以上之量的異麥芽酮糖,則無法充分發揮 異麥芽酮糖之血糖値上升抑制效果(參見圖1)。 -5- 200942181 另一方面,以提案有含有選自亮胺酸、異亮胺酸及纈 胺酸之一種或兩種以上之分支鏈胺基酸及異麥芽酮糖之肝 障障礙者用之營養組成物(專利文獻4)。該發明之實施 例中,於以糖質之75質量%之量使用異麥芽酮糖之情況, 糖質更緩慢燃燒而具有較佳特性。 即使任一種上述各種營養組成物,雖可發揮血糖値上 升抑制效果,但於長時間攝取後,尤其是糖質之消化吸收 變差,而有營養均衡變大的問題。對於患有高血糖之患者 一般會指導其營養限制,於三大營養素中尤其是作爲能量 基質之利用效率高的糖質由於修正高血糖而受到限制。於 此等情況下,若大量使用由腸管吸收極爲緩慢之上述異麥 芽酮糖及海藻糖,則難以充分供給維持體內蛋白質合成或 生體維持所必要之能量,若長時間持續該種狀態,則說起 來有陷入低營養狀態之情況。因而關於其營養指導,推薦 審慎應對,尤其對高齡者實施飲食療法時,爲不使陷入營 養不良,而推薦提供特別考慮適當能量之營養組成物(非 專利文獻1)。然而,有關營養療法,熱切期望一種當然 可使血糖値降低,且營養均衡優異而可效率良好地供給能 量之營養組成物。 另一方面,伴隨著糖尿病之增加,糖尿病倂發症之糖 尿病性腎病之患者數量亦不斷增加。近幾年來,透析導入 症病例中所佔之糖尿病性腎病之比例超過4成,亦報導於 透析人口中腎失調原疾病亦最多(非專利文獻2),亦期 望一種患有高血糖之腎臟病患者用之營養組成物。 -6 - 200942181 [專利文獻1]特開2003-171271號公報 [專利文獻2]特開2006-28194號公報 [專利文獻3]W〇2003/0 22288號公報 [專利文獻4]特開2005-350371號公報 [非專利文獻1]基於科學根據之糖尿病診療指引,曰 本糖尿病學會編,第21-25頁,2004,南江堂In addition to maintaining human life, amino acids are essential for creating a daily lifestyle that is essential for a pleasant and comfortable life. However, because it has a therapeutic effect on various diseases, it has been used as an effective ingredient in medicines, nutrients or supplements. For example, a drug for preventing sugar abnormality and foods and drinks containing at least one of leucine, isoleucine, and valine are proposed (Patent Documents 1 and 2). In the publications, the only ones used in the examples were leucine or a mixture of leucine, isoleucine and valine, and the rats were orally administered with 1.5 g/kg. Changes in blood glucose levels when measured. Therefore, this sugar-tolerant drug-specific agent is particularly effective for treating, ameliorating, and/or preventing the sugar-resistant abnormality of a liver disorder which is difficult to use in the conventional diabetes drug. Isocetulose (palatinose) and trehalose are one type of saccharide, and are proposed to be used as an essential component of a nutritional composition for controlling blood sugar sputum (Patent Document 3). In the present invention, the isomaltulose and/or sea-thream sugar in the energy ratio of the saccharide is 60 to 100%, and the inventors of the present invention investigate the blood sugar sputum control effect of isomaltulose. It was confirmed that if the amount of isomaltulose which is 68.5 mass% or more of the saccharide is not used, the effect of suppressing the increase in blood sugar 异 of isomaltulose cannot be sufficiently exhibited (see FIG. 1). -5- 200942181 On the other hand, it is proposed to use a liver-defective disorder containing one or more kinds of branched-chain amino acids and isomaltulose which are selected from the group consisting of leucine, isoleucine and valine. Nutritional composition (Patent Document 4). In the embodiment of the present invention, when isomaltulose is used in an amount of 75% by mass of the saccharide, the saccharide is burned more slowly and has better characteristics. Even if any of the above-mentioned various nutrient compositions exhibits an effect of suppressing the blood sugar sputum, the long-term ingestion, in particular, the digestion and absorption of the saccharide is deteriorated, and the nutritional balance becomes large. For patients with hyperglycemia, their nutritional limitations are generally instructed. Among the three major nutrients, especially the highly efficient saccharide as an energy matrix is limited by the correction of hyperglycemia. In such a case, if the above-mentioned isomaltulose and trehalose which are absorbed very slowly by the intestinal tract are used in a large amount, it is difficult to sufficiently supply energy necessary for maintaining protein synthesis or maintenance of the body, and if the state is maintained for a long period of time, It is said that there is a situation of falling into a low nutritional status. Therefore, it is recommended to take a prudent response to the nutrition guidance, and it is recommended to provide a nutrient composition that takes into consideration appropriate energy in order not to cause malnutrition when the diet is administered to an elderly person (Non-Patent Document 1). However, with regard to nutritional therapy, it is eagerly desired to have a nutrient composition which can reduce blood sugar sputum and which is excellent in nutritional balance and can efficiently supply energy. On the other hand, with the increase in diabetes, the number of patients with diabetes mellitus with diabetes mellitus has also increased. In recent years, the proportion of diabetic nephropathy in dialysis patients has exceeded 40%. It is also reported that the kidney disease is also the most common in the dialysis population (Non-Patent Document 2), and a kidney disease with hyperglycemia is also expected. The nutritional composition used by the patient. 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 Bulletin No. 350371 [Non-Patent Document 1] Based on the guidelines for the diagnosis and treatment of diabetes based on science, edited by the Diabetes Society, pp. 21-25, 2004, Nanjiang Hall

[非專利文獻2]日本透析醫學會統計調査委員會,透 析學會誌,41(1) ,1,2008。 【發明內容】 本發明目的在於提供一種即使長時間攝取時營養均衡 性亦優異,且投藥後可抑制高血糖,可減輕胰島素投與量 之營養組成物。 又’本發明目的係提供一種可減低糖質中異麥芽酮糖 及/或海藻糖之含量,進而可減低異麥芽酮糖及/或海藻糖 之絕對含量之營養組成物。 又’本發明之目的係提供一種患有高血糖之腎臟疾病 患者用之營養組成物。 本發明係基於發現若倂用游離異亮胺酸及/或游離亮 胺酸、異麥芽酮糖及/或海藻糖以及中鏈脂肪酸三酸甘油 酯,可獲得優異之高血糖抑制效果且獲得營養均衡優異之 營養組成物,以及可減低糖質中異麥芽酮糖及/或海藻糖 之含量進而可減低異麥芽酮糖及/或海藻糖之絕對含量而 可解決上述課題據此完成者。 200942181 亦即’本發明提供一種高血糖抑制用營養組成物,其 爲含有氮源、脂質及糖質之營養組成物,其特徵爲氮源中 含有游離異亮胺酸及/或游離亮胺酸,脂質含有中鏈脂肪 酸三酸甘油酯,糖質含有異麥芽酮糖及/或海藻糖。 【實施方式】 本發明中使用之游離異亮胺酸及游離亮胺酸可使用L-體、D-體及DL-體之任一者,但較好使用L-體。本發明尤 其較好使用游離異亮胺酸。該等游離異亮胺酸或游離亮胺 酸每lOOkcal營養組成物較好含有0.1~2.0克,進而較好 每lOOkcal營養組成物含有0.3~1.5克。 本發明中,作爲氮源,可倂用異亮胺酸及亮胺酸以外 之游離胺基酸,例如榖胺酸及其鹽、纈胺酸、精胺酸及其 鹽、榖胺醯胺、色胺酸、組胺酸及其鹽、甘胺酸、丙胺酸 等,但較好全氮源中之異亮胺酸及/或亮胺酸之量爲2質 量%〜100質量%,尤其較好爲6質量%〜80質量%,又更好 爲6質量%~40質量%。 本發明中,除上述氮源以外,亦可使用脫脂奶粉或全 脂奶粉、酪蛋白或乳清及其分解物等之乳蛋白質源、膠原 蛋白及其分解物、分離大豆蛋白質或小麥蛋白質及其分解 物等之植物性蛋白質或其水解物(肽)。 又,氮源之比例,營養組成物之固體成分每100質量 份,較好爲12-27質量份。 本發明中,可使用中鏈脂肪酸三酸甘油酯作爲脂質之 -8- 200942181 全部或其一部分。其中,作爲中鏈脂肪酸三酸甘油酯較好 係構成脂肪酸三酸甘油酯之脂肪酸殘基之碳數爲6〜12,尤 其較好是構成脂肪酸三酸甘油酯之脂肪酸殘基之碳數爲8 及/或10。本發明中使用之中鏈脂肪酸三酸甘油酯可爲例 如容易自市面上獲得者。 中鏈脂肪酸三酸甘油酯之能量效率優異,相較於由碳 數16以上之脂肪酸(長鏈脂肪酸三酸甘油酯)所成之紅 0 花油或大豆油等之一般食用油脂,其吸收速度較快速可謂 與糖質相近者。再者於體內組織中,即使沒有如肉鹼之介 質,於粒線體內亦可於體內儘速燃燒,不累積於生體內, 生體能量之產生量非常高。因此,爲不使血糖値升高之較 佳脂肪,但此中鏈脂肪酸三酸甘油酯,除能量產生以外, ' 並非維持生體機能所必要之必須胺基酸,僅其無法維持生 體機能。因此,發明品之特定配合比具重要性。另一方面 ,由於上述一般食用油脂之長鏈脂肪酸三酸甘油酯亦爲脂 ^ 肪,因此卡路里高,雖不使血糖値上升,但於大量長期攝 取時,有高血脂症發病、動脈硬化起因、胰島素抗性增大 之情況,進而促進耐糖能異常。 本發明中,較好總脂質中之1〇~75質量%爲中鏈脂肪 酸三酸甘油酯,尤其較好爲15質量%~60質量%。其他則 使用食用油脂。作爲食用油脂,除可舉例爲棕櫚油、椰子 油、棉籽油、向日葵油、花生油、紫蘇油、杏仁油、油菜 籽油、大豆油、葵花油、橄欖油、米油、玉米油、芝麻油 、可可奶油等植物性油脂、或牛油、豬油、魚油、奶油、 200942181 奶油脂等之動物性油脂以外,亦可舉例有以人造奶油( shortening )等之加工油脂等,可依據用途選擇數種組合 使用。該等油脂,尤其於含水分多的形態,較好使用脂肪 酸單甘油酯或有機酸單甘油酯、聚甘油脂肪酸酯、蔗糖脂 肪酸酯、卵磷脂等之乳化劑,予以乳化處理,成爲適宜乳 液之分散狀態。又較好以使尤其爲必須脂肪酸之ω 6系脂 肪酸/ω3系脂肪酸比成爲0.5〜4.5之方式而決定選擇食用 油脂或乳化劑及使用量。 脂質之比例較好爲營養組成物之固體成分每100質量 份爲9〜27質量份。 本發明中,作爲糖質之一部分,係使用異麥芽酮糖及 /或海藻糖,較好爲異麥芽酮糖。糖質中異麥芽酮糖及/或 海藻糖之含量較好爲50質量%以下,尤其較好爲5~4 0質 量%。又,異麥芽酮糖及/或海藻糖之絕對含量,由營養均 衡而言,較好每lOOkcal營養組成物爲0.5至7.5克。作 爲其以外之糖質源,依據其記載並無特別限制,但其例可 舉例爲購得之消化吸收優異之作爲能量源而加以利用之蛋 白質或其分解物(糊精)、蔗糖、果糖等。 又,本發明中,糖質比例較好爲營養組成物固體成分 每100質量份爲22〜68質量份。 本發明中,異麥芽酮糖及/或海藻糖相對於異亮胺酸 及/或亮胺酸之質量比較好爲1/75〜4/1,更好爲1/50-2/1 〇 本發明中’作爲卡路里源,除蛋白質或肽、胺基酸等 -10- 200942181 之氮源、糖質、脂質以外,亦可使用於生體內作爲能量加 以利用脂各種食品材料。作爲其例舉例有醇、一部分之食 物纖維、寡糖、有機酸及其鹽等。除了配合該等作爲卡路 里源以外,亦可就有關其他營養素之補給、乳化或色調、 流變學等之製劑安定性、風味提高、微生物對策、pH調 整、於生體內之3次機能爲目的,而可因應各種必要性加 以選擇、使用。 如此,藉由含有特定量之游離異亮胺酸及/或游離亮 胺酸、倂用特定量之異麥芽酮糖及/或海藻糖,可觀察到 相較於單獨攝取異麥芽酮糖及/或海藻糖更強之血糖値上 升之抑制作用,進而藉由倂用特定量之中鏈脂肪酸三酸甘 爲 ,用 徵術作 特技之 之前量 物先能 成之給 組目供 養矚地 營受好 此備良 。 而率 果糖效 效血可 制低而 抑降升 之因上 著僅値 顯止糖 更爲血 揮今使 發迄不 可於揮 , 較發 酯相有 油,具。 % 本發明之營養組成物進 礦物質等。作爲食物纖維, 半乳甘露聚糖等之水溶性食 麩或結晶纖維素等之非水溶 例有維他命A、維他命B1、 命B12、維他命C、維他命 葉酸、胡蘿蔔素、泛酸、 物質,舉例有鈣、磷、銅、 、鉀、鎂、碘等。該等除了 而可含有食物纖維、維他命或 舉例有難消化性糊精、果膠、 物纖維、源自大豆或小麥之糠 性食物纖維。作爲維他命,舉 維他命B2、維他命B6、維他 K、維他命D3、菸鹼酸醯胺、 維他命E、生物素等,作爲礦 鋅、錳、鉻、鉬、硒、鐵、鈉 以有機酸鹽或無機酸鹽、化學 -11 - 200942181 合成品等爲代表之食品添加劑以外,亦可調配有自各種食 品萃取之萃取物或酵母等、源自各種食品材料者。再者, 爲使脂質等均一分散’亦可含有乳化劑等之界面活性劑。 本發明之營養組成物進而可調配各種天然或合成甜味劑、 著色劑、香料以及酪蛋白或硫辛酸等之所謂機能性營 養素。 近幾年來’若因糖尿病等糖質代謝異常引起之高血糖 狀態持續’則於生體內誘導因過剩活性氧引起之反應成爲 問題。氧化反應過剩之狀態爲動脈硬化症等糖尿病倂發症 惡化之原因。相對於本發明,若於本發明中調配尤其是維 他命胡蘿蔔素或視黃醇)、維他命Ε(生育酚)、 維他命C或鋅或硒等之具有抗氧化能之維他命或微量元素 則確實較佳。又,若亦倂用其他之具有抗氧化活性之 CoQ 10或兒茶素、花色苷、異黃酮爲代表之多酚等之機能 性營養材料而進而更佳。 本發明藉調整鉀、磷含量,故即使對於伴隨有高血糖 之腎臟病患者,亦可提供降低高血糖之危險性而可適當地 營養管理之營養組成物。如此之伴隨有高血糖之腎臟病患 者用之營養組成物中每lOOkcal之鉀含量較好爲35〜155 毫克,進而最好爲50~130毫克。又,較好爲每lOOkcal 之磷含量爲20~100毫克,更好爲35〜80毫克。 今曰,糖尿病持續增多’加上高齡化之高齡者中糖尿 病患者數變得非常多。於高齡的糖尿病患者對臥床之營養 管理或營養補給亦有使用管對胃中餵入營養組成物。一般 -12- 200942181 高齡者的胃體積小,因此,於該等高齡者之情況,高濃度 之高營養組成物爲較佳。所以,可了解若投與加入有糖質 之綜合營養之高濃度營養物,則高血糖之危險性將提高。 Ο[Non-Patent Document 2] Statistical Research Committee of the Japan Dialysis Medical Association, Research Society, 41(1), 1, 2008. DISCLOSURE OF THE INVENTION An object of the present invention is to provide a nutritional composition which is excellent in nutritional balance even when taken for a long period of time, and which can suppress hyperglycemia after administration, and which can reduce the amount of insulin administered. Further, the object of the present invention is to provide a nutritional composition which can reduce the content of isomaltulose and/or trehalose in the saccharide, thereby reducing the absolute content of isomaltulose and/or trehalose. Further, the object of the present invention is to provide a nutritional composition for a patient suffering from a kidney disease suffering from hyperglycemia. The present invention is based on the discovery that if a free isoleucine and/or free leucine, isomaltulose and/or trehalose, and a medium chain fatty acid triglyceride are used, an excellent hyperglycemic inhibitory effect can be obtained and obtained. The above-mentioned problem can be solved by reducing the nutritional composition of the nutrient composition and reducing the content of isomaltulose and/or trehalose in the saccharide, thereby reducing the absolute content of isomaltulose and/or trehalose. By. 200942181 That is, the present invention provides a nutritional composition for suppressing hyperglycemia, which is a nutrient composition containing a nitrogen source, a lipid and a saccharide, characterized in that the nitrogen source contains free isoleucine and/or free leucine The lipid contains a medium chain fatty acid triglyceride, and the saccharide contains isomaltulose and/or trehalose. [Embodiment] The free isoleucine and the free leucine used in the present invention may be any of an L-form, a D-form and a DL-form, but an L-form is preferably used. In particular, free isoleucine is used in the present invention. The free isoleucine or free leucine preferably contains 0.1 to 2.0 g per 100 kcal of the nutritional composition, and more preferably 0.3 to 1.5 g per 100 kcal of the nutritional composition. In the present invention, as the nitrogen source, free amino acids other than isoleucine and leucine, such as lysine and its salts, valine, arginine and its salts, amidoxime, Tryptophan, histidine and its salts, glycine, alanine, etc., but preferably the amount of isoleucine and/or leucine in the total nitrogen source is from 2% by mass to 100% by mass, especially It is preferably from 6% by mass to 80% by mass, and more preferably from 6% by mass to 40% by mass. In the present invention, in addition to the nitrogen source, a milk protein source such as skim milk powder or whole milk powder, casein or whey and a decomposition product thereof, collagen and a decomposition product thereof, and soybean protein or wheat protein may be used. A vegetable protein such as a decomposition product or a hydrolyzate (peptide) thereof. Further, the ratio of the nitrogen source to the solid content of the nutritional composition is preferably from 12 to 27 parts by mass per 100 parts by mass. In the present invention, a medium chain fatty acid triglyceride can be used as the lipid -8- 200942181, or a part thereof. Wherein, the medium chain fatty acid triglyceride is preferably a fatty acid residue of the fatty acid triglyceride having a carbon number of 6 to 12, particularly preferably the fatty acid residue constituting the fatty acid triglyceride has a carbon number of 8 And / or 10. The medium chain fatty acid triglyceride used in the present invention can be, for example, a commercially available one. The medium chain fatty acid triglyceride is excellent in energy efficiency, and its absorption rate is higher than that of general edible oil such as red scented oil or soybean oil which is formed by a fatty acid having 16 or more carbon atoms (long-chain fatty acid triglyceride). Faster is similar to sugar. Furthermore, in the tissues of the body, even if there is no medium like carnitine, the mitochondria can be burned as soon as possible in the body, and does not accumulate in the living body, and the amount of bio-energy generated is very high. Therefore, in order to prevent blood sugar from rising, the medium-chain fatty acid triglyceride, in addition to energy production, is not an essential amino acid necessary for maintaining the body's function, but it cannot maintain the body function. . Therefore, the specific mix ratio of the invention is important. On the other hand, since the long-chain fatty acid triglyceride of the above-mentioned general edible oil and fat is also fat, the calorie is high, and although the blood sugar is not increased, the cause of hyperlipemia and the cause of arteriosclerosis are caused by a large amount of long-term intake. Insulin resistance increases, which in turn promotes abnormal sugar tolerance. In the present invention, it is preferred that 1 to 75% by mass of the total lipid is medium chain fatty acid triglyceride, and particularly preferably 15% by mass to 60% by mass. Others use edible oils and fats. As edible fats and oils, in addition to palm oil, coconut oil, cottonseed oil, sunflower oil, peanut oil, perilla oil, almond oil, rapeseed oil, soybean oil, sunflower oil, olive oil, rice oil, corn oil, sesame oil, cocoa For example, vegetable oils such as butter, or animal fats such as butter, lard, fish oil, butter, and butter, etc., may be processed, such as margarine (shortening), and may be selected according to the use. use. These oils and fats, especially in the form of a large amount of water, are preferably emulsified by using an emulsifier such as a fatty acid monoglyceride or an organic acid monoglyceride, a polyglycerin fatty acid ester, a sucrose fatty acid ester or a lecithin. The dispersed state of the emulsion. Further, it is preferable to select an edible fat or oil, an emulsifier, and a use amount so that the ratio of the ω 6 -based fatty acid/ω3 fatty acid, which is an essential fatty acid, is 0.5 to 4.5. The proportion of the lipid is preferably from 9 to 27 parts by mass per 100 parts by mass of the solid content of the nutritional composition. In the present invention, as a part of the saccharide, isomaltulose and/or trehalose is used, and isomaltulose is preferred. The content of isomaltulose and/or trehalose in the saccharide is preferably 50% by mass or less, particularly preferably 5 to 40% by mass. Further, the absolute content of isomaltulose and/or trehalose is preferably from 0.5 to 7.5 g per 100 kcal of the nutritional composition in terms of nutritional balance. The saccharide source other than the above is not particularly limited, and examples thereof include commercially available proteins or their decomposition products (dextrin), sucrose, fructose, etc., which are used as an energy source and have excellent digestion and absorption. . Further, in the present invention, the ratio of the saccharide is preferably from 22 to 68 parts by mass per 100 parts by mass of the solid content of the nutritional composition. In the present invention, the mass of isomaltulose and/or trehalose relative to isoleucine and/or leucine is preferably 1/75 to 4/1, more preferably 1/50 to 2/1 〇. In the present invention, as a calorie source, in addition to a nitrogen source, a saccharide or a lipid of a protein, a peptide, an amino acid, etc., such as -10-200942181, it is also possible to use a variety of food materials for use as energy in a living body. Examples thereof include alcohols, a part of dietary fibers, oligosaccharides, organic acids and salts thereof. In addition to the use of these as calorie sources, it is also possible to provide stability, flavor enhancement, microbial countermeasures, pH adjustment, and three functions in the body for the supply of other nutrients, emulsification, color tone, rheology, etc. It can be selected and used according to various needs. Thus, by containing a specific amount of free isoleucine and/or free leucine, a specific amount of isomaltulose and/or trehalose, it can be observed that isomaltulose is separately taken. And/or the inhibition of the increase in blood sugar sputum by trehalose, and then by using a certain amount of medium-chain fatty acid triglyceride, before the sedition is used as a special effect, the first thing can be used to support the group. Be prepared for this. The rate of fructose effect can be low, but the cause of the increase is only 値 止 止 止 止 止 止 止 止 止 止 止 止 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血 血% The nutrient composition of the present invention is a mineral or the like. As a dietary fiber, non-aqueous examples of water-soluble bran or crystalline cellulose such as galactomannan include vitamin A, vitamin B1, life B12, vitamin C, vitamin folic acid, carotene, pantothenic acid, and substances, for example, calcium. , phosphorus, copper, potassium, magnesium, iodine, etc. These may in addition contain dietary fiber, vitamins or examples of indigestible dextrin, pectin, fiber, and dietary fiber derived from soy or wheat. As a vitamin, vitamin B2, vitamin B6, vitamin K, vitamin D3, niacinamide, vitamin E, biotin, etc., as mineral zinc, manganese, chromium, molybdenum, selenium, iron, sodium as an organic acid salt or Inorganic acid salt, chemical -11 - 200942181 In addition to the food additives represented by synthetic products, etc., it is also possible to prepare extracts derived from various foods, yeast, etc., and various food materials. Further, in order to uniformly disperse the lipid or the like, a surfactant such as an emulsifier may be contained. The nutritional composition of the present invention can be further formulated with various natural or synthetic sweeteners, coloring agents, perfumes, and so-called functional auxins such as casein or lipoic acid. In recent years, if the hyperglycemia state caused by abnormal glucose metabolism such as diabetes persists, it is a problem to induce a reaction caused by excess active oxygen in the living body. The state in which the oxidation reaction is excessive is a cause of deterioration of diabetes mellitus such as atherosclerosis. Compared with the present invention, it is preferred to formulate vitamins or trace elements having antioxidant energy, such as vitamin carotene or retinol, vitamin Ε (tocopherol), vitamin C or zinc or selenium, in the present invention. . Further, it is further preferable to use other functional nutrients such as CoQ 10 having an antioxidant activity or polyphenols such as catechins, anthocyanins and isoflavones. According to the present invention, by adjusting the potassium and phosphorus contents, it is possible to provide a nutritional composition which can be appropriately nutritionally managed by reducing the risk of hyperglycemia even in patients with kidney diseases accompanied by hyperglycemia. The potassium content per 100 kcal of the nutrient composition of the kidney disease associated with such high blood sugar is preferably 35 to 155 mg, and more preferably 50 to 130 mg. Further, it is preferred that the phosphorus content per 100 kcal is 20 to 100 mg, more preferably 35 to 80 mg. In the future, diabetes continues to increase. The number of patients with diabetes in the elderly who are aging is increasing. In elderly patients with diabetes, nutritional management or nutritional supplementation in bed is also used to feed the nutrient composition into the stomach. In general, -12-200942181 elderly people have a small stomach volume, and therefore, in the case of such elderly people, a high concentration of a high nutritional composition is preferred. Therefore, it can be understood that the risk of hyperglycemia will increase if a high concentration of nutrients with a comprehensive nutritional supplement is added. Ο

本發明之營養組成物之卡路里濃度若依據患者狀態使 用最佳者,則較好爲自〇.5kcal/毫升開始至1.5kcal/毫升 以上。尤其是對胃體積小的高齡者或伴隨有高血糖之腎臟 病患者,對於可投與、攝取之營養組成物或水分量有其限 制,較好爲1.5kcal/毫升以上。上限並未特別限制,但較 好爲3.Okcal/毫升左右。本發明中,卡路里濃度高、亦爲 高營養價,而不引起高血糖。 本發明中,藉由組合胰島素刺激物質、類胰島素物質 ,則可進而增強有效性。於一例舉例有游離精胺酸。精胺 酸係作用於胰臟/3細胞爲促進胰島素分泌之原因,截至目 前爲止,並不認爲藉由倂用此等物質及游離異亮胺酸及/ 或游離亮胺酸、異麥芽酮糖及/或海藻糖以及中鏈脂肪酸 三酸甘油酯有較佳之相乘效果。所並用之該等物質中,若 以上述精胺酸爲例,較好倂用〇.〇1克〜20克/lOOkcal,更 好0.1克〜10克/lOOkcal。關於調配游離精胺酸,於經口及 經管投與時消化作用非必要之形態,例如係使用游離精胺 酸、精胺酸鹽酸鹽、精胺酸硝酸鹽、精胺酸硫酸鹽、精胺 酸有機酸鹽、精胺酸榖胺酸鹽等、游離精胺酸及其鹽之形 態之原料。 作爲本發明之營養組成物,可爲粉末、顆粒狀、板狀 、條狀、凝膠狀或液狀等之各種形態,但較好爲液狀,尤 -13- 200942181 其是經腸用之流體食物形態較佳。 本發明之營養組成物,對於經口攝取不完 言,可使用投與液狀物之管直接對腸或胃投與 接對胃投與之情況下,有於胃食道營養組成物 肺炎等重症症狀之原因之情況。此時,於本發 成物中添加增黏劑等可自由地調整組成物黏度 好爲 500mPa· s 以上、7,000 mPa. s( 23 °C ) ,爲減低高齡者誤吞嚥之危險,如何增加黏度 據情況將營養組成物調製成高黏度時,亦可藉 或稀釋等降低黏度後使用。 又,於本發明,亦可不添加增黏劑等,而 之選擇、製造步驟之改變、製劑濃度之調! 5-20,000 mPa · s ( 2 3 °C )者而使用。 另一方面,投與營養物後之血糖値異常上 之糖尿病等疾病以外,大多亦在進行外科手術 剛進行外科手術侵襲性大的手術後之時期,荷 化變大,引起高血糖而成爲手術後營養管理之 且,手術前之高血糖未經管理亦無法進行手術 營養組成物爲在該等情況之營養管理下亦可降 具有營養恢復效果之適當組成物。 另外,耐糖能異常者,已知有引起血管障 血管之血流降低,而降低氧氣對末梢組織之供 易引起手術後之縫合不全,且對長期臥床之患 瘡。因此,本發明可再管理血糖的同時適當地 全之患者而 。尤其是直 逆流而成爲 明之營養組 。此情況較 以下。再者 均可。又依 由機械操作 藉由原材料 鋈等,作成 昇,除單純 時所引起。 爾蒙環境變 問題點。而 。本發明之 低血糖且亦 礙尤其是微 給。由此容 者將發生褥 保有營養狀 -14- 200942181 態,而可用於預防或治癒褥瘡、創傷。 於本發明,較好以每次服用至少可攝取0.3克游離異 亮胺酸及/或游離亮胺酸之方式收容於容器中。也就是說 ,若攝取收容於容器中之食品全部,於人體胃中,可產生 至少0.3克游離異亮胺酸及/或游離亮胺酸則較佳》The caloric concentration of the nutritional composition of the present invention is preferably from 5 kcal/ml to more than 1.5 kcal/ml, depending on the state of the patient. In particular, for elderly people with a small stomach volume or kidney disease patients with hyperglycemia, there is a limit to the nutrient composition or water content that can be administered or ingested, and it is preferably 1.5 kcal/ml or more. The upper limit is not particularly limited, but is preferably about 3.Okcal/ml. In the present invention, the calorie concentration is high and also high in nutrient value without causing hyperglycemia. In the present invention, by combining insulin stimulating substances and insulin-like substances, the effectiveness can be further enhanced. An example of free arginine is given as an example. The action of arginine on the pancreas/3 cells promotes insulin secretion. Up to now, it has not been considered that by using these substances and free isoleucine and/or free leucine, isomalt The ketose and/or trehalose and the medium chain fatty acid triglyceride have a better multiplying effect. Among the above-mentioned substances, if the above arginine is used as an example, it is preferably used in an amount of 克1 g to 20 g/lOOkcal, more preferably 0.1 g to 10 g/lOOkcal. Regarding the preparation of free arginine, it is not necessary for digestive action when administered orally or via a tube, for example, using free arginine, arginine hydrochloride, arginine nitrate, arginine sulfate, and fine A raw material in the form of an amino acid organic acid salt, a arginine glutamate, or a free arginine acid and a salt thereof. The nutritional composition of the present invention may be in the form of a powder, a granule, a plate, a strip, a gel or a liquid, but is preferably a liquid, especially 13-200942181 which is used in the intestine. The fluid food form is preferred. The nutrient composition of the present invention can be administered to the intestine or stomach directly by the administration of a liquid-like tube, and is administered to the stomach or the stomach. The cause of the symptoms. In this case, it is possible to adjust the viscosity of the composition to 500 mPa·s or more and 7,000 mPa·s (23 °C) by adding a tackifier or the like to the present invention, thereby reducing the risk of swallowing by the elderly, and how to increase the viscosity. According to the situation, when the nutrient composition is prepared to a high viscosity, it may be used by reducing or decreasing the viscosity. Further, in the present invention, it is also possible to select, to change the manufacturing steps, and to adjust the concentration of the preparation without adding a tackifier or the like! Use for 5-20,000 mPa · s ( 2 3 °C). On the other hand, in addition to diseases such as diabetes mellitus, which are abnormally caused by the blood sugar after the administration of the nutrient, most of the surgery is performed immediately after the surgery is performed, and the surgery becomes large, causing hyperglycemia and becoming surgery. After the nutrition management, the hyperglycemia before the operation is unmanageable and the surgical nutrient composition is not suitable for the nutrient recovery under the nutritional management of the above conditions. In addition, those with abnormal glucose tolerance are known to have reduced blood flow in vascular barrier blood vessels, and to reduce the supply of oxygen to the peripheral tissue, which may cause suture incompleteness after surgery, and to suffer from soreness in long-term bed rest. Therefore, the present invention can re-administer blood glucose while appropriately accommodating the patient. In particular, it is straight backwards and becomes the nutrition group of Ming. This situation is more than the following. Anymore. In addition, it is caused by the mechanical operation, by the raw material, etc., in addition to the simple. Ermen environment has become a problem. And. The hypoglycemia of the present invention is also particularly impeding. As a result, the capsule will occur in the form of nutrients, which can be used to prevent or cure acne and wounds. In the present invention, it is preferred to store in a container in a manner that at least 0.3 g of free isoleucine and/or free leucine is taken per administration. That is to say, if all the foods contained in the container are ingested, at least 0.3 g of free isoleucine and/or free leucine may be produced in the stomach of the human body.

本發明之營養組成物作爲經腸用之流動食物之形態時 ,較好收容於容量爲5 0〜1000毫升之容器中。又本發明營 養組成物相較於於以往已知之高血糖抑制用營養組成物, 由於抑制餐後高血糖之效果更高,因此亦可一次投與較多 量。此情況下,可以用後即丟類型之包裝形態簡便且衛生 地使用,且由於爲大容量於輸送包材成本方面較有利,而 可作成可在便宜環境下保管之製品而提供與消費者。此情 況之每單位之塡充量較好爲 300~600毫升,更好爲 3 00〜4 0 0毫升。於高齡者或孩童之情況下,胃容積亦不大 ’此情況較好地是一次服用較好爲80〜400毫升,更好爲 100〜300毫升。 作爲收容本發明之營養組成物之容器,較好爲易開封 性之容器,又,較好爲獨立性。作爲該種容器舉例有特開 2005-040630號公報 '特開2003-327259號公報等中記載 之容器。 另一方面’本發明之營養組成物中欲含有各種食品材 料時’有於製造時或保存中其一部分引起氧化或分解之可 能性。尤其油脂類容易引起劣化,其中由於大量含有魚油 或紫蘇油、杏仁油等之高度不飽和脂肪酸而更容易氧化, -15- 200942181 導致不適臭味、味道劣化。又,教示有攝取含有過氧化物 之油脂時’對生體而言成爲氧化壓力,而有促進老化或致 癌'成爲生活習慣疾病之一原因。此種氧化或分解可藉由 (i )製造方法或(ii )包裝形態之方法加以極力抑制。具 體而言’可藉由下列而達成:(i)極力抑制製造時於調 / 配液中捲入空氣或在遮光下實施;於調配後藉由脫氣裝置 或充入惰性氣體而除去空氣;避免必要以上之加熱,於調 配結束後殺菌處理之前儘可能保持於低溫狀態;塡充係在 惰性氣體環境氛圍下進行或塡充後置換爲惰性氣體,極力 減少殘留氣體之方式加以密封;(ii )使用阻氣膜例如由 鋁或氧化鋁、氧化矽等構成之蒸鍍薄膜或脫氧包裝材,進 而封入AGELESS等之脫氧劑之包裝形態,進而使用以紫 外線吸收油墨或特殊阻氣性油墨等進行表面印刷之包裝材 ’進而於外包裝材中進行捆包後氣體置換或脫氣處理等。 藉此’亦可抑制因油脂氧化使維他命C或視黃醇、維他命 E等之營養成分殘留率降低、風味惡化等,於本製品中成 爲更佳之形態。 [實施例] 以下以實施例詳細說明本發明,但本發明並不受該等 實施例之限制。 實施例1 如表1中所示之調配比例計量原材料,且進行2,000 -16- 200942181 kcal/2,000ml之裝入時之調配。於3升之不鏽鋼桶中計量 入776克之調配水,且於熱水浴中加溫至70〜80 °C。邊攪 拌邊投入糊精、不溶性食物纖維、含有礦物之酵母、生物 素酵母、葡糖酸鋅、葡糖酸銅、檸檬酸亞鐵鈉並分散。接 著’投入將食用油脂、中鏈脂肪酸三酸甘油酯、胡蘿 蔔素懸浮液、維他命E油及乳化劑於70〜80°C下混合溶解 而成之液體。接著,於其中投入乳蛋白質、異麥芽酮糖、 0 水溶性食物纖維並溶解。 另外,於不鏽鋼容器中注入180克之加溫水(30〜40 °C ),且依序溶解檸檬酸、氫氧化鈣、檸檬酸三鈉、碳酸 鉀、氯化鎂、甘油磷酸鈣、榖胺酸鈉,且將該溶液投入於 3升不鏽鋼容器中之預先調製之溶液中,並經混合。接著 * ,於其中投入異亮胺酸、異抗壞血酸鈉、綜合維他命,且 分散溶解,接著加入香料。最後加入並溶解抗壞血酸鈉且 混合。以調配水使總量成爲2,000ml定量後,攪祥至成均 ^ 勻溶液爲止。以高壓均質機使該溶液乳化(均質壓力: 7 OMPa )。將其塡充於透明直立袋(standing pouch)(包 裝材構成:蒸鍍PET/Ny/CPP )中每一個重量成爲200ml( 214g),在124t下進行高壓蒸煮殺菌處理,於5天後測 定該液體之黏度爲6.4mPa.s(24°C)。又,另外藉由無 菌塡充,塡充於117ml(125g)之袋中。 其中,爲透明直立袋之構成材料之Ny及CPP爲尼龍 及無延伸聚丙烯之簡稱(以下亦相同)。 該等任一種包裝形態中乳化亦爲長期安定。又,該營 -17- 200942181 養組成物爲營養均衡優異者,且可長期持續攝取。其中, 構成使用之中鏈脂肪酸三酸甘油酯之脂肪酸殘基之碳數爲 6~12。另外’ ω6系脂肪酸/ ω3系脂肪酸比係調整成爲 2.7。糖質中之異麥芽酮糖之含有量爲丨6.4質量% ( 39.2/239.2 ) ’本發明品i〇〇kCal中之異麥芽酮糖量爲 1.96克。又,本發明品i〇〇kcai中游離異亮胺酸之量爲When the nutritional composition of the present invention is in the form of a flowing food for enteral use, it is preferably contained in a container having a capacity of 50 to 1000 ml. Further, the nutritional composition of the present invention can be administered in a larger amount at a time than the conventional nutritional composition for suppressing hyperglycemia, which has a higher effect of suppressing postprandial hyperglycemia. In this case, the package type of the disposable type can be used simply and hygienically, and since it is advantageous in terms of the cost of transporting the package material in a large capacity, it can be provided to consumers in a product that can be stored in a cheap environment. In this case, the charge per unit is preferably from 300 to 600 ml, more preferably from 300 to 400 ml. In the case of an elderly person or a child, the stomach volume is also small. This condition is preferably preferably 80 to 400 ml, more preferably 100 to 300 ml. As the container for accommodating the nutritional composition of the present invention, it is preferably a container which is easy to open, and is preferably self-contained. A container described in JP-A-2003-327259, and the like. On the other hand, when the nutrient composition of the present invention is intended to contain various food materials, there is a possibility that a part thereof causes oxidation or decomposition at the time of production or storage. In particular, oils and fats are liable to cause deterioration. Among them, a large amount of highly unsaturated fatty acids such as fish oil or perilla oil and almond oil are more likely to be oxidized, and -15-200942181 causes unpleasant odor and taste deterioration. Further, it has been suggested that when a fat containing a peroxide is ingested, "the oxidative stress is applied to the living body, and the promotion of aging or carcinogenesis" is one of the lifestyle diseases. Such oxidation or decomposition can be suppressed as much as possible by (i) the method of manufacture or (ii) the form of the package. Specifically, it can be achieved by: (i) suppressing the entrapment of air in the conditioning/dispensing solution during production or under shading; after the formulation, removing air by means of a degassing device or by charging an inert gas; Avoid the necessary heating above, and keep it as low as possible before the sterilization treatment after the end of the preparation; the charging is carried out in an inert gas atmosphere or after being replaced with an inert gas, and the residual gas is reduced to seal it; (ii) A gas barrier film, for example, a vapor deposition film or a deoxidizing packaging material made of aluminum, aluminum oxide, cerium oxide or the like, and further encapsulated in a package form of a deoxidizer such as AGEGESS, and further used as an ultraviolet absorbing ink or a special gas barrier ink. The surface-printed packaging material' is further subjected to gas replacement or degassing treatment after being packaged in the outer packaging material. In this way, it is also possible to suppress a decrease in the residual ratio of nutrients such as vitamin C, retinol or vitamin E due to oxidation of fats and oils, deterioration of flavor, and the like, and it is more preferable in the present product. [Examples] Hereinafter, the present invention will be described in detail by way of examples, but the invention should not be construed as limited. Example 1 The raw materials were metered in the proportions shown in Table 1, and the blending was carried out at the loading of 2,000 -16 - 200942181 kcal / 2,000 ml. 765 grams of blended water was metered into a 3 liter stainless steel drum and heated to 70-80 °C in a hot water bath. The mixture was mixed with dextrin, insoluble dietary fiber, mineral-containing yeast, biotin yeast, zinc gluconate, copper gluconate, sodium ferrous citrate and dispersed. Then, a liquid obtained by mixing and dissolving edible fats and oils, medium-chain fatty acid triglyceride, carotenoid suspension, vitamin E oil and emulsifier at 70 to 80 ° C was added. Next, milk protein, isomaltulose, 0 water-soluble dietary fiber was added thereto and dissolved. In addition, 180 grams of warm water (30~40 °C) is injected into the stainless steel container, and citric acid, calcium hydroxide, trisodium citrate, potassium carbonate, magnesium chloride, calcium glycerate, sodium amide are dissolved in sequence. The solution was placed in a pre-conditioned solution in a 3 liter stainless steel container and mixed. Next, *, isoleucine, sodium erythorbate, and vitamins are added thereto, and dispersed and dissolved, followed by addition of a fragrance. Finally, sodium ascorbate is added and dissolved and mixed. After mixing the water to make the total amount 2,000 ml, the mixture was stirred until it was homogeneous. The solution was emulsified by a high pressure homogenizer (homogeneous pressure: 7 OMPa). It was filled in a standing pouch (packaging material composition: vapor-deposited PET/Ny/CPP), and each weight was 200 ml (214 g), and subjected to autoclaving at 124 t, and it was measured after 5 days. The viscosity of the liquid was 6.4 mPa.s (24 ° C). Further, it was further filled with a 117 ml (125 g) bag by sterile filling. Among them, Ny and CPP which are constituent materials of the transparent standing pouch are short for nylon and non-stretched polypropylene (the same applies hereinafter). Emulsification in any of these packaging forms is also long-term stability. In addition, the camp -17- 200942181 is a nutritionally balanced person with long-term continuous intake. Among them, the number of carbon atoms constituting the fatty acid residue using the medium chain fatty acid triglyceride is 6 to 12. In addition, the ratio of the ω6 fatty acid/ω3 fatty acid was adjusted to 2.7. The content of isomaltulose in the saccharide was 6.4% by mass (39.2/239.2). The amount of isomaltulose in the product i〇〇kCal of the present invention was 1.96 g. Further, the amount of free isoleucine in the product i〇〇kcai of the present invention is

〇.5g,游離異亮胺酸/異麥芽酮糖之質量比爲1/3.9 ( 10/39.2)。质量.5g, the mass ratio of free isoleucine/isomaltulose was 1/3.9 (10/39.2).

將增黏劑適度地添加於如此製造之本發明營養組成物 中,使用旋轉式黏度計(BH-80,東機產業)測定黏度後 ,確認爲亦可調整成3 50〜20,OOOmPa. s之安定高黏度組 成物(23°C)。另外,使本發明品之溶液經噴霧乾躁,且 藉由將其造粒,可穩定地製造出粉末及顆粒。進而於加熱 之本發明品中適度的添加洋菜或購得之各種凍膠調製食品 (例如,HERUSHU (註冊商標)凍膠構成物),經溶解 並冷卻,亦可調製成凝膠狀之形態。 -18- 200942181The tackifier was appropriately added to the nutritional composition of the present invention thus produced, and the viscosity was measured using a rotary viscometer (BH-80, Toki Sang), and it was confirmed that it was adjusted to 3 50 to 20, OOO mPa. s. Stabilized high viscosity composition (23 ° C). Further, the solution of the present invention is spray-dried, and by granulating it, the powder and the granules can be stably produced. Further, a moderately added agar or a commercially available jelly-prepared food (for example, a HERUSHU (registered trademark) jelly composition) in the heated product of the present invention can be prepared into a gel form after being dissolved and cooled. . -18- 200942181

表1 實施例1之調配組成(2,000kcal/2,000ml ) 原材料名稱 使用量 單位 乳蛋白質 82.6 克 糊精 200.0 克 異麥芽酮糖 39.2 克 不溶性食物纖維 8.0 克 水溶性食物纖維 27.0 克 食用油脂 42.7 克 中鏈脂肪酸三酸甘油酯 22.6 克 乳化劑 12.5 克 檸檬酸 7.5 克 氫氧化15 1.4 克 檸檬酸三鈉 5.4 克 碳酸鉀 5.6 克 氯化鎂 4.8 克 甘油磷酸鈣 3.2 克 穀胺酸鈉 6.0 克 異亮胺酸 10.0 克 抗壞血酸鈉 1.29 克 異抗壞血酸鈉 0.54 克 檸檬酸亞鐵鈉 180.0 毫克 葡糖酸鋅 230.0 毫克 葡糖酸銅 14.0 毫克 含有硒之酵母 80.0 毫克 含有鉬之酵母 12.0 毫克 含有錳之酵母 180.0 毫克 含有鉻之酵母 52.0 毫克 含碘之酵母 22.0 毫克 生物素酵母 244.0 毫克 維他命E油 167.9 毫克 冷-胡蘿蔔素懸浮液 26.4 毫克 香3 1.6 克 綜 合 維 他 命 維他命A棕櫚酸鹽 36.0 毫克 維他命B1鹽酸鹽 27.1 毫克 核黃素磷酸酯鈉 10.2 毫克 維他命B6鹽酸鹽 17.72 毫克 維他命Β12(0·1%水溶性粉末) 15.0 毫克 維他命D 3 1.8 毫克 菸鹼酸醯胺 49.0 毫克 葉酸(維他命Μ) 1 .7 毫克 泛酸鈣 28.8 毫克 維他命Κ2(0·2%乳化粉末) 22.1 毫克 -19- 200942181 實施例2 如表2中所示之之原材料調配比例計量’且進行 l,000g(2,000kcal)之裝入時之調配。於2升之不鏽鋼桶 中計量入320克之調配水,且於熱水浴中加溫至7〇〜80°C 。接著,在 TK ROBOMIX ( PRIMIX公司)中’於 3 OOOrpm之高速攪伴條件化,依海藻糖、檸檬酸亞鐵鈉、 葡糖酸鋅、葡糖酸銅、檸檬酸鉀、氯化鉀、磷酸鉀、葡糖 酸鈉之順序混合溶解。接著投入於70~80°C下將食用油脂 與中鏈脂肪酸三酸甘油酯、胡蘿蔔素懸浮液、維他命E 油、乳化劑混合溶解而成之液體。隨後,依糊精、乳蛋白 質、不溶性食物纖維、榖胺酸鈉、亮胺酸、含有各種礦物 質之酵母、生物素酵母、香料之順序投入並混合,成爲均 勻之溶解分散溶液後,緩慢投入將水溶性食物纖維、硫酸 鎂、氯化鎂、乳酸鈣溶解於120毫升調配水中而成之液體 。隨後,投入綜合維他命、抗壞血酸鈉、異抗壞血酸鈉, 並分散溶解。邊測定該等之重量邊加水至1,〇〇〇克,且混 合至成均勻狀態爲止。使之以每100ml塡充於附加噴管之 直立帶(袋膜構成:PET/Al/Ny/CPP )中,且在125°C下 進行高壓蒸煮殺菌。其比重爲1.18,該溶液之卡路里濃度 爲2.0kcal/g(2.4kcal/ml)。將該試料儲存於25 °C下,殺 菌處理之隔天,以旋轉式黏度計(BH-80,東機產業), 在3號轉子、12rpm之條件下測定後,約爲4,000mPa· s (2 5 °C )。長期儲存下乳化亦長期穩定。於該液體中加水 可調成500mPa · s ( 25°C )之均質營養組成物,且亦可添 -20- 200942181Table 1 Formulation composition of Example 1 (2,000 kcal / 2,000 ml) Raw material name usage unit milk protein 82.6 g dextrin 200.0 g isomaltulose 39.2 g insoluble dietary fiber 8.0 g water soluble dietary fiber 27.0 g edible fat 42.7 g Medium chain fatty acid triglyceride 22.6 grams emulsifier 12.5 grams citric acid 7.5 grams of hydroxide 15 1.4 grams of trisodium citrate 5.4 grams of potassium carbonate 5.6 grams of magnesium chloride 4.8 grams of calcium glycerophosphate 3.2 grams of sodium glutamate 6.0 grams of isoleucine 10.0 g sodium ascorbate 1.29 g sodium isosodium sulphate 0.54 g sodium ferrous citrate 180.0 mg zinc gluconate 230.0 mg copper gluconate 14.0 mg yeast containing selenium 80.0 mg yeast containing molybdenum 12.0 mg yeast containing manganese 180.0 mg containing chromium Yeast 52.0 mg Iodine-containing yeast 22.0 mg Biotin Yeast 244.0 mg Vitamin E oil 167.9 mg Cold-carotene suspension 26.4 mg Fragrance 3 1.6 g Multivitamin Vitamin A palmitate 36.0 mg Vitamin B1 hydrochloride 27.1 mg Nuclear yellow Sodium phosphate phosphate 10. 2 mg of vitamin B6 hydrochloride 17.72 mg of vitamin Β 12 (0.1% water-soluble powder) 15.0 mg of vitamin D 3 1.8 mg of niacin guanamine 49.0 mg of folic acid (vitamin Μ) 1. 7 mg of calcium pantothenate 28.8 mg of vitamin Κ 2 ( 0·2% emulsified powder) 22.1 mg-19- 200942181 Example 2 The raw material compounding ratio shown in Table 2 was measured and the formulation at the time of loading of 1,000 g (2,000 kcal) was carried out. 320 g of the formulated water was metered into a 2 liter stainless steel drum and heated to 7 〇 to 80 ° C in a hot water bath. Next, in TK ROBOMIX (PRIMIX), the condition was tempered at a high speed of 3 OOO rpm, based on trehalose, sodium ferrous citrate, zinc gluconate, copper gluconate, potassium citrate, potassium chloride, phosphoric acid. The order of potassium and sodium gluconate is mixed and dissolved. Then, the liquid is mixed with a medium-chain fatty acid triglyceride, a carotene suspension, a vitamin E oil, and an emulsifier at 70 to 80 ° C to dissolve the liquid. Subsequently, according to dextrin, milk protein, insoluble dietary fiber, sodium citrate, leucine, yeast containing various minerals, biotin yeast, and spices, the ingredients are put into and mixed to form a uniform dissolved and dispersed solution, and then slowly input. A liquid obtained by dissolving water-soluble dietary fiber, magnesium sulfate, magnesium chloride, and calcium lactate in 120 ml of formulated water. Subsequently, synthetic vitamins, sodium ascorbate, sodium erythorbate were added and dispersed. While measuring the weights, water was added to 1, gram, and mixed until it became homogeneous. This was carried out in an upright belt (bag film composition: PET/Al/Ny/CPP) filled with an additional nozzle per 100 ml, and autoclaved at 125 °C. Its specific gravity was 1.18, and the caloric concentration of the solution was 2.0 kcal/g (2.4 kcal/ml). The sample was stored at 25 ° C, and the next day after the sterilization treatment, it was measured by a rotary viscometer (BH-80, Toki Sangyo Co., Ltd.) under the condition of No. 3 rotor and 12 rpm, and was about 4,000 mPa·s ( 2 5 °C). Emulsification under long-term storage is also stable for a long time Adding water to the liquid can be adjusted to a homogeneous nutrient composition of 500 mPa · s (25 ° C), and can also be added -20- 200942181

加購得之增黏劑調整成7,000mPa . s ( 25°C )之均質高黏 度溶液。又,於加熱之本發明品中適度的添加洋菜或購得 之各種凍膠調製食品(例如,HERUSHU (註冊商標)凍 膠構成物),經溶解並冷卻,亦可調製成凝膠狀之形態。 進而使本發明品之溶液經噴霧乾躁,藉由將其造粒,可穩 定地製造出粉末及顆粒。構成其中使用之中鏈脂肪酸三酸 甘油酯之脂肪酸殘基之碳數爲8~1〇。另外,ω6系脂肪酸 “3系脂肪酸比爲1.5。糖質中之海藻糖之含量爲9.5質 量% ( 18.3/192.8 ),本發明品lOOkcal中之海藻糖量爲 0.92克。又,本發明品100kcal中游離亮胺酸之量爲 〇-27g,游離亮胺酸/海藻糖之質量比爲1/3.4 ( 5.40/18.3) 200942181 表2 實施例2之調配組成(2,000kcal/l,000g) 原材料名稱 使用量 單位 乳蛋白質 99.0 克 糊精 174.5 克 海藻糖 18.3 克 不溶性食物纖維 5.0 克 水溶性食物纖維 25.0 克 食用油脂 58.0 克 中鏈脂肪酸三酸甘油酯 13.7 克 乳化劑 5.3 克 乳酸鈣 3.30 克 檸檬酸鉀 3.10 克 氯化鉀 0.60 克 磷酸鉀 3.30 克 氯化鎂 2.60 克 硫酸鎂 3.80 克 葡糖酸鈉 19.1 克 榖胺酸鈉 4.50 克 亮胺酸 5.40 克 抗壞血酸鈉 1.30 克 異抗壞血酸鈉 2.90 克 檸檬酸亞鐵鈉 180.0 毫克 葡糖酸鋅 2 3 0.0 毫克 葡糖酸銅 14.0 毫克 含有硒之酵母 80.0 毫克 含有鉬之酵母 12.0 毫克 含有錳之酵母 180.0 毫克 含有鉻之酵母 52.0 毫克 含碘之酵母 22.0 毫克 生物素酵母 244.0 毫克 香料 1.0 克 維他命E油 167.9 毫克 β - 胡蘿蔔素懸浮液 26.4 毫克 維他命Α棕櫚酸鹽 36.0 毫克 維他命B 1鹽酸鹽 27.1 毫克 核黃素磷酸酯鈉 10.2 毫克 綜 維他命B6鹽酸鹽 1 7.72 毫克 合 維他命Β12(0·1%水溶性粉末) 15.0 毫克 維 維他命D 3 1.8 毫克 他 菸鹼酸醯胺 49.0 毫克 饰‘ 葉酸(維他命Μ) 1.7 毫克 泛酸鈣 28.8 毫克 維他命Κ2(0·2%乳化粉末) 22.1 毫克 -22- 200942181 實施例3 ΟThe commercially available tackifier was adjusted to a homogenous high viscosity solution of 7,000 mPa.s (25 °C). Further, a moderately added agar or a commercially available jelly-prepared food (for example, a HERUSHU (registered trademark) jelly composition) in the heated product of the present invention may be prepared into a gel after being dissolved and cooled. form. Further, the solution of the present invention is spray-dried, and by granulating it, the powder and the granules can be stably produced. The number of carbon atoms constituting the fatty acid residue in which the medium chain fatty acid triglyceride is used is 8 to 1 Å. Further, the ω6-based fatty acid "3 series fatty acid ratio is 1.5. The trehalose content in the saccharide is 9.5% by mass ( 18.3/192.8), and the amount of trehalose in the present invention 100 kcal is 0.92 g. Further, the present invention 100 kcal The amount of free leucine is 〇-27g, and the mass ratio of free leucine to trehalose is 1/3.4 (5.40/18.3) 200942181 Table 2 Formulation of Example 2 (2,000kcal/l,000g) Usage unit milk protein 99.0 g dextrin 174.5 g trehalose 18.3 g insoluble dietary fiber 5.0 g water soluble dietary fiber 25.0 g edible fat 58.0 g medium chain fatty acid triglyceride 13.7 g emulsifier 5.3 g calcium lactate 3.30 g potassium citrate 3.10 grams of potassium chloride 0.60 grams of potassium phosphate 3.30 grams of magnesium chloride 2.60 grams of magnesium sulfate 3.80 grams of sodium gluconate 19.1 grams of sodium citrate 4.50 grams of leucine 5.40 grams of sodium ascorbate 1.30 grams of sodium erythorbate 2.90 grams of sodium ferrous citrate 180.0 Mg of zinc gluconate 2 3 0.0 mg of copper gluconate 14.0 mg of yeast containing selenium 80.0 mg of yeast containing molybdenum 12.0 mg containing manganese Yeast 180.0 mg Chromium-containing yeast 52.0 mg Iodine-containing yeast 22.0 mg Biotin yeast 244.0 mg Perfume 1.0 G-vitamin E oil 167.9 mg Beta-carotene suspension 26.4 mg Vitamin Α palmitate 36.0 mg Vitamin B 1 hydrochloride 27.1 Mg riboflavin sodium phosphate 10.2 mg Synthetic vitamin B6 hydrochloride 1 7.72 mg of vitamin Β 12 (0·1% water-soluble powder) 15.0 mg of vitamin D 3 1.8 mg of his nicotinic acid guanamine 49.0 mg of 'folate ( Vitamin Μ) 1.7 mg calcium pantothenate 28.8 mg vitamin Κ 2 (0·2% emulsified powder) 22.1 mg-22- 200942181 Example 3 Ο

如表3中所示之調配比例計量原材料,且以與實施例 1相同之方法調製2,000kcal/2,000ml之營養組成物。將其 塡充於透明直立袋中使每個重量爲200g。在124 °C下進行 高壓蒸煮殺菌處理。此時黏度爲6.0mPa.s(24°C)。乳 化爲長期安定。又,該營養組成物爲營養均衡優異者,可 長期持續攝取。構成其中使用之中鏈脂肪酸三酸甘油酯之 脂肪酸殘基之碳數爲6〜12。另外,ω6系脂肪酸/ 03系脂 肪酸比爲4.0。糖質中之異麥芽酮糖之含有量爲16.4質量 % ( 39.2/239.2),本發明品lOOkcal中之異麥芽酮糖量爲 1.96克。又,本發明品lOOkcal中游離異亮胺酸之量爲 〇.5g,游離異亮胺酸/異麥芽酮糖之質量比爲 1/3.9( 10/3 9.2)。又,lOOkcal中之游離精胺酸爲1.5克。 將增黏劑適度添加於如此製造之本發明營養組成物中 ,使用旋轉式黏度計(BH-80,東機產業)測定黏度後, 爲3 50~20,000mPa. s,確認亦可調整成安定高黏度組成物 (23 °C )。另外,於加熱之本發明品中適度的添加洋菜或 購得之各種膠凍調製食品(例如,例如,HERUSHU (註 冊商標)凍膠構成物),經溶解並冷卻,亦可調製成凝膠 狀之形態。另外使本發明品之溶液經噴霧乾躁,藉由將其 造粒,可穩定地製造出粉末及顆粒。 -23- 200942181 表3 實施例3之調配組成( 2,000kcal/2,000ml) 原材料名稱 使用量 單位 乳蛋白質 82.6 克 L-精胺酸L-榖胺酸鹽 2.8 克 糊精 200.0 克 異麥芽酮糖 39.2 克 不溶性食物纖維 8.0 克 水溶性食物纖維 27.0 克 食用油脂 42.7 克 中鏈脂肪酸三酸甘油酯 22.6 克 乳化劑 12.5 克 檸檬酸 7.5 克 氫氧化鈣 1.4 克 檸檬酸三鈉 5.4 克 碳酸鉀 5.6 克 氯化鎂 4.8 克 甘油磷酸鈣 3.2 克 榖胺酸鈉 4.4 克 異亮胺酸 10.0 克 抗壞血酸鈉 1.29 克 異抗壞血酸鈉 0.54 克 檸檬酸亞鐵鈉 180.0 毫克 葡糖酸鋅 23 0.0 毫克 葡糖酸銅 14.0 毫克 含有硒之酵母 80.0 毫克 含有鉬之酵母 12.0 毫克 含有錳之酵母 180.0 毫克 含有鉻之酵母 52.0 毫克 含碘之酵母 22.0 毫克 生物素酵母 244.0 毫克 維他命E油 167.9 毫克 yS -胡蘿蔔素懸浮液 26.4 毫克 香料 1.6 克 維他命A棕櫚酸鹽 36.0 毫克 維他命B1鹽酸鹽 27.1 毫克 核黃素磷酸酯鈉 10.2 毫克 綜 維他命B6鹽酸鹽 17.72 毫克 合 維他命B1 2(0.1 %水溶性粉末) 15.0 毫克 維 維他命D3 1.8 毫克 他 菸鹼酸醯胺 49.0 毫克 口 P 葉酸(維他命M) 1.7 毫克 泛酸鈣 28.8 毫克 維他命Κ2(0·2%乳化粉末) 22.1 毫克 -24- 200942181 實施例4The raw materials were metered in the proportions as shown in Table 3, and 2,000 kcal / 2,000 ml of the nutritional composition was prepared in the same manner as in Example 1. It was filled in a transparent standing pouch so that each weight was 200 g. Autoclaved sterilization at 124 °C. The viscosity at this time was 6.0 mPa.s (24 ° C). The emulsification is long-term stability. Further, the nutritional composition is excellent in nutritional balance and can be continuously ingested for a long time. The number of carbon atoms constituting the fatty acid residue in which the medium chain fatty acid triglyceride is used is 6 to 12. Further, the ratio of the omega 6 fatty acid / 03 fatty acid was 4.0. The content of isomaltulose in the saccharide was 16.4% by mass (39.2/239.2), and the amount of isomaltulose in the 100 kcal of the present invention was 1.96 g. Further, the amount of free isoleucine in the 100 kcal of the present invention is 〇.5 g, and the mass ratio of free isoleucine/isomaltulose is 1/3.9 (10/3 9.2). Further, the free arginine in lOOkcal was 1.5 g. The tackifier is appropriately added to the nutritional composition of the present invention thus produced, and after measuring the viscosity using a rotary viscometer (BH-80, Toki Sang), it is 3 50 to 20,000 mPa·s, and it can be confirmed that it can be adjusted to stability. High viscosity composition (23 °C). Further, a moderately added agar or a commercially available jelly-prepared food (for example, a HERUSHU (registered trademark) jelly composition) in the heated product of the present invention may be prepared into a gel after being dissolved and cooled. Shape. Further, the solution of the present invention is spray-dried, and by granulating it, the powder and the granules can be stably produced. -23- 200942181 Table 3 Formulation composition of Example 3 (2,000kcal/2,000ml) Raw material name Usage unit Milk protein 82.6 g L-arginine L-valerate 2.8 g dextrin 200.0 g isomaltulose 39.2 g insoluble dietary fiber 8.0 g water soluble dietary fiber 27.0 g edible fat 42.7 g medium chain fatty acid triglyceride 22.6 g emulsifier 12.5 g citric acid 7.5 g calcium hydroxide 1.4 g trisodium citrate 5.4 g potassium carbonate 5.6 g magnesium chloride 4.8 g of calcium glycerophosphate 3.2 g of sodium citrate 4.4 g of isoleucine 10.0 g of sodium ascorbate 1.29 g of sodium erythorbate 0.54 g of sodium citrate 180.0 mg of zinc gluconate 23 0.0 mg of copper gluconate 14.0 mg containing selenium Yeast 80.0 mg Molybdenum-containing yeast 12.0 mg Manganese-containing yeast 180.0 mg Chromium-containing yeast 52.0 mg Iodine-containing yeast 22.0 mg Biotin yeast 244.0 mg Vitamin E oil 167.9 mg yS-carotene suspension 26.4 mg flavor 1.6 g of vitamins A palmitate 36.0 mg of vitamin B1 hydrochloride 2 7.1 mg of riboflavin phosphate 10.2 mg of vitamin B6 hydrochloride 17.72 mg of vitamin B1 2 (0.1% water-soluble powder) 15.0 mg of vitamin D3 1.8 mg of nicotinic acid guanamine 49.0 mg of mouth P folic acid (vitamin M ) 1.7 mg calcium pantothenate 28.8 mg vitamin Κ 2 (0.2% emulsified powder) 22.1 mg-24- 200942181 Example 4

以表4中所示之調配比例計量原材料,且進行3000L (lkcal/lml )之裝入時之實機試作。於1號桶中饋入 1 164kg ( 70~8 0°C )之溫水,邊攪拌邊加入糊精、不溶性 食物纖維、含有礦物之酵母、檸檬酸亞鐵鈉。接著,加入 使食用油脂、中鏈脂肪酸三酸甘油酯、;8-胡蘿蔔素懸浮 液、維他命E油及乳化劑於70〜80 °C下混合溶解而成之液 體。接著,於其中投入乳蛋白質、異麥芽酮糖、水溶性食 物纖維,並經溶解。 於另一桶中加入135kg之溫水(30〜40°C ),且依序 溶解檸檬酸、氫氧化鈣、檸檬酸三鈉、碳酸鉀、氯化鎂、 甘油磷酸鈣、榖胺酸鈉,且將該溶液加於預先調製之1號 桶溶液中。經混合,且重複該操作兩次。接著,於其中加 入異亮胺酸、異抗壞血酸鈉、綜合維他命,且分散溶解, 再加入葉酸與香料。使該液體經除氣處理(約20cmHg) 後,以高壓均質機在乳化壓力98MPa下處理,且藉由板冷 卻機使液溫成爲1 (TC以下。貯存於儲液桶中之後,加入抗 壞血酸鈉並使之溶解,且以調配水使總量成爲3 000L定量 ,並攪拌至成均勻液體爲止。將其塡充於附加噴管之透明 薄膜袋(袋膜構成:PET7蒸鑛PET/Ny/CPP)中使每個重 量成爲400ml,塡充後以除氣棒使殘留氣體部分成爲15 毫升以下之狀態下以熱密封加以密封後,在124 °C下進行 高壓蒸煮殺菌處理。 於8天後測定該液體之黏度爲6.3mPa · s ( 24°C )。 -25- 200942181 另外,本發明品lOOkcal中之游離異亮胺酸之量爲 0.5克,游離異亮酸/異麥芽酮糖之質量比爲1/3.9( 15.0/58.8)。 200942181 Ο % 表4實施例4之調配組成 3000L裝入 _„_ 原材料名稱 使用量 單位 乳蛋白質 ~ 123.9 公斤 S"精 3 00.0 公斤 異麥芽酮糖 - 58.8 公斤 不溶性食物纖維 12.0 公斤 水溶性食物纖維 40.5 公斤 食用油脂 97.88 公斤 中錢 1脂肪酸二酸甘油酯 33.9 公斤 乳化劑 18.75 公斤 檸檬酸 11.3 公斤 氫氧化鈣 2.1 公斤 檸檬酸三鈉 8.1 公斤 mmm 8.4 公斤 氯化鎂 7.2 公斤 甘油磷酸鈴 — 4.8 公斤 榖胺酸鈉 9.0 公斤 異亮胺酸 ' 15.0 公斤 抗壞血酸鈉 1.93 公斤 異抗壞血酸鈉 0.8 1 公斤 檸檬酸亞鐵鈉 0.270 公斤 葡糖酸鋅 0.345 公斤 葡糖酸銅 0.02 1 公斤 含有硒之酵母 0.1200 斤 含有鉬之酵母 0.0180 公斤 含有錳之酵母 0.2700 公斤 含有鉻之酵母 0.0780 「公斤 含碘之酵母 0.0330 公斤 生物素酵母 0.3660 公斤 維他命E油 0.2190 公斤 厶-胡蘿蔔素1%水溶性粉末 1.190 公斤 香判 2.4 公斤 維他命A棕櫚酸鹽 54.00 克 維他命B1鹽酸鹽 33.90 克 綜 核黃素磷酸酯鈉 15.30 克 合 維他命B6鹽酸鹽 26.58 克 維 維他命B12 ( 0.1%水溶性粉末) 19.50 克 他 維他命D3 4.05 克 命 菸鹼酸醯胺 86.40 克 葉酸(維他命M) 2.34 克 泛酸鈣 43.20 克 維他命K2 ( 0·2%乳化粉末) 39.00 克 -27- 200942181 試驗例1 對實施例4獲得之試作品,進行在室溫(25 °C前後) 儲存達6個月之長期安定性試驗。且對試驗開始時與在室 溫下靜置6個月時之試作品進行物性値測定與各種評價。 •粒度分佈(中値粒徑) 以雷射散射式粒度分佈測定裝置(LS 1 3 320 (商品名 ),貝克曼·柯達公司製造),使用PIDS (偏光差動散 射)組件,在液體(懸浮液體部分):1.32,試料:實體部 分1.45,虛擬部分0之條件解析射率。The raw materials were measured in the blending ratio shown in Table 4, and a real machine test at the time of loading of 3000 L (lkcal/lml) was carried out. Feed 1 164kg (70~80 °C) of warm water in the No. 1 bucket, add dextrin, insoluble food fiber, mineral-containing yeast, sodium ferrous citrate while stirring. Next, a liquid obtained by mixing and dissolving edible fats and oils, medium-chain fatty acid triglyceride, 8-carotene suspension, vitamin E oil and emulsifier at 70 to 80 °C is added. Next, milk protein, isomaltulose, and water-soluble dietary fiber are put therein and dissolved. Add 135kg of warm water (30~40°C) to another barrel, and dissolve citric acid, calcium hydroxide, trisodium citrate, potassium carbonate, magnesium chloride, calcium glycerate, sodium amide, and This solution was added to a pre-conditioned No. 1 barrel solution. This was mixed and the operation was repeated twice. Next, isoleucine, sodium erythorbate, and vitamins are added thereto, and dispersed and dissolved, and then folic acid and flavor are added. After the liquid was degassed (about 20 cmHg), it was treated with a high pressure homogenizer at an emulsification pressure of 98 MPa, and the liquid temperature was made 1 (TC or less) by a plate cooler. After storage in a liquid storage tank, sodium ascorbate was added. And dissolve it, and mix the water to make the total amount to 3,000 L, and stir until it becomes a uniform liquid. Fill it with a transparent film bag with additional nozzle (bag film composition: PET7 steamed PET/Ny/CPP In each case, the weight is 400 ml, and after the filling, the residual gas portion is sealed to 15 ml or less with a degassing rod, and then sealed with a heat seal, and then subjected to autoclaving at 124 ° C. After 8 days, the measurement is carried out. The viscosity of the liquid is 6.3 mPa · s (24 ° C). -25- 200942181 In addition, the amount of free isoleucine in the 100 kcal of the present invention is 0.5 g, and the mass of free isoleic acid/isomaltulose The ratio is 1/3.9 ( 15.0/58.8). 200942181 Ο % Table 4 Example 4 compounding composition 3000L loading _„_ Raw material name usage unit milk protein ~ 123.9 kg S" fine 3 00.0 kg isomaltulose- 58.8 kg of insoluble dietary fiber 12.0 Pound water soluble dietary fiber 40.5 kg edible fat 97.88 kg medium money 1 fatty acid diglyceride 33.9 kg emulsifier 18.75 kg citric acid 11.3 kg calcium hydroxide 2.1 kg trisodium citrate 8.1 kg mmm 8.4 kg magnesium chloride 7.2 kg glycerol phosphate bell - 4.8 kg sodium citrate 9.0 kg isoleucine '15.0 kg sodium ascorbate 1.93 kg sodium erythorbate 0.8 1 kg sodium ferrous citrate 0.270 kg zinc gluconate 0.345 kg copper gluconate 0.02 1 kg yeast containing selenium 0.1200 Kiln yeast containing molybdenum 0.0180 kg yeast containing manganese 0.2700 kg yeast containing chromium 0.0780 "kg iodine-containing yeast 0.0330 kg biotin yeast 0.3660 kg vitamin E oil 0.2190 kg 厶-carotene 1% water-soluble powder 1.190 kg scent 2.4 Kg Vitamin A Palmitate 54.00 Gram Vitamin B1 Hydrochloride 33.90 g Synthetic Sodium Flavin Phosphate 15.30 Gram Vitamin B6 Hydrochloride 26.58 Kevivitamin B12 (0.1% Water Soluble Powder) 19.50 Gram Vitamin D3 4.05 g Nicotinic acid decylamine 86.40 g of folic acid (vitamin M) 2.34 g of calcium pantothenate 43.20 g of vitamin K2 (0.2% emulsified powder) 39.00 g -27- 200942181 Test Example 1 The test piece obtained in Example 4 was carried out in the room. Temperature (around 25 °C) Long-term stability test stored for 6 months. The physical properties were measured and evaluated for the test pieces at the start of the test and at room temperature for 6 months. • Particle size distribution (midium particle size) Laser scattering type particle size distribution measuring device (LS 1 3 320 (trade name), manufactured by Beckman Kodak Company), using PIDS (polarized differential scattering) component, in liquid (suspended) Liquid part): 1.32, sample: physical part 1.45, virtual part 0 conditional resolution rate.

• pH 以pH計(HM-25R型(商品名),TOA DKK (股) 公司製)測定。 •黏度 以旋轉式黏度計(BH-80 (商品名),東機產業公司 製)’使用10號轉子,在6 0rpm之條件下測定。 •官能評價 針對風味、香味、舌觸感,以剛開始儲存之試作品做 爲標準試料進行比較。 與標準試料比較下,判斷毫無遜色之情況作爲適當。 •色差 測定用小瓶中採取5克試料,且使用分光式色彩計( SE- 2 000 (商品名),日本電色工業(股)公司製)測定 〇 •外觀 -28 - 200942181 觀察隨著乳化狀態之變化產生之乳狀、或不溶性鹽之 形成、色調顯著之變化等目視之狀態。 •管中流動性 將管(JMS營養套組(商品名),JMS公司製)與 5Fr 之導管(SURFI FITTING TUBE (商品名), TERUMO公司製)連接於試料之噴管上,且自lm之高度 使內容液自然滴下,測定每15分鐘滴下之量。連續滴下 hi 直至袋內無液體爲止,求得每單位時間內之平均滴下流量 ,作爲管中流動性。 •耐酸性 採取100毫升之試料於燒杯內,使用攪拌器邊攪拌邊 緩慢添加預先調製之2%鹽酸溶液。2分鐘後,觀察性狀, " 且測定pH。此時,測定至數十個以上之凝乳狀浮游物被 確認爲止(添加鹽酸溶液後產生之凝聚物未消失)之pH 値。 比較例1 針對購得之流動食物(MEDIEFF (註冊商標)袋,味 之素(股)製),進行與試驗例1相同之保存試驗,進行 物性値測定及各種評價。 所得測定結果列於表5。即使於粒度分佈' pH '黏度 、色差,經6個月之儲存均未看到有太大變化,且至少於 6個月之期間顯示製品爲具有充分安定性者。官能性評價 中經時變化亦小’且可維持經口攝取上較佳之形態。又本 -29- 200942181 發明品黏度低流動性良好,因此亦可使用各種營養管或導 管,尤其是內徑小且長之形式亦可使用。另外由於耐酸性 亦優異,因此對導管產生胃酸逆流時不易使流動食物產生 凝固,而不會發生經報告爲凝乳化原因之菌之增殖(非專 利文獻3:外科與代謝、營養,日本外科代謝營養學會會 刊,pp73 ’ 42 ( 3 ) ,2008 ),即使與顯示酸性之藥劑同 時或前後使用,宣稱不會引起管堵塞。由上述,本發明品 於經管營養使用時,.亦具有極佳之形態。 表5實施例1及比較例1之儲存安定性試驗結果 實施例1 比較例1 測定項目 單位 最初 經6個月 最初 經6個月 中値直徑 β m 0.106 0.103 0.103 0.107 pH 6.12 6.06 6.50 6.40 黏度 mPa · s 6.30 6.50 9.60 10.34 官能 • 適宜 適宜 適宜 適宜 色差 ΔΕ* 46.92 49.36 42.11 48.52 外觀 - 無問題 無問題 無問題 無問題 管中流動性 mL/h 139 146 89 84 耐酸性(pH) 5.0 - 5.9 實施例5 如表6中所示之調配比例計量原材料,且進行4500 kcal/4,500ml之裝入時之調配。於5升之不鏽鋼桶中計量 入2000克之調配水,且於熱水浴中加溫至70〜8〇ac。邊攪 拌邊投入糊精、不溶性食物纖維、乳蛋白質、異麥芽酮糖 、水溶性食物纖維、含有礦物之酵母、生物素酵母、葡糖 -30- 200942181 酸鋅、葡糖酸銅、檸檬酸亞鐵鈉、異亮胺酸、榖胺酸鈉並 經分散。接著,投入將食用油脂、中鏈脂肪酸三酸甘油酯 、召-胡蘿蔔素懸浮液、維他命E油及乳化劑於70〜80 t下 混合溶解而成之液體。• The pH was measured by a pH meter (Model HM-25R (trade name), manufactured by TOA DKK Co., Ltd.). • Viscosity was measured by a rotary viscometer (BH-80 (trade name), manufactured by Toki Sangyo Co., Ltd.) using a No. 10 rotor at 60 rpm. • Functional evaluation For the flavor, aroma, and tongue touch, the test pieces that were just started to be stored were compared as standard samples. In comparison with the standard sample, it is appropriate to judge the situation that is not inferior. • 5 g sample was taken from the vial for color difference measurement, and measured using a spectroscopic color meter (SE- 2 000 (trade name), manufactured by Nippon Denshoku Industries Co., Ltd.). • Appearance-28 - 200942181 Observed with emulsified state The state of the visual appearance such as the formation of a milky or insoluble salt and a significant change in color tone. • In the tube, a tube (JMS nutrition kit (trade name), manufactured by JMS) and a 5Fr tube (SURFI FITTING TUBE (product name), manufactured by TERUMO) are connected to the nozzle of the sample, and The contents were allowed to drip naturally, and the amount dropped every 15 minutes was measured. Continuously drip hi until there is no liquid in the bag, and the average dropping flow rate per unit time is obtained as the fluidity in the tube. • Acid resistance Take 100 ml of the sample in a beaker and slowly add a pre-conditioned 2% hydrochloric acid solution while stirring with a stirrer. After 2 minutes, observe the traits, " and measure the pH. At this time, the pH of the condensed milk-like floats after tens of or more was confirmed (the aggregate produced after the addition of the hydrochloric acid solution did not disappear) was measured. Comparative Example 1 The same storage test as in Test Example 1 was carried out for the purchased mobile food (MEDIEFF (registered trademark) bag, manufactured by Ajinomoto Co., Ltd.), and the physical properties were measured and evaluated. The results of the measurements obtained are shown in Table 5. Even in the particle size distribution 'pH' viscosity, chromatic aberration, no significant change was observed after 6 months of storage, and the product was shown to have sufficient stability for at least 6 months. In the evaluation of the functionality, the change over time was also small, and the preferred form of oral ingestion was maintained. Also -29- 200942181 The invention has good viscosity and good fluidity, so various nutrient tubes or tubes can also be used, especially in the form of small inner diameter and long length. In addition, since the acid resistance is also excellent, it is difficult to cause the flow food to coagulate when the gastric acid is reversely flowed to the catheter, and the proliferation of the bacteria which is reported to be the cause of coagulation does not occur (Non-Patent Document 3: Surgical and Metabolic, Nutrition, Japanese Surgical Metabolism) The Journal of the Nutrition Society, pp73 '42 (3), 2008), even if it is used at the same time or before and after the use of acidic agents, it is claimed that it will not cause tube blockage. From the above, the present invention also has an excellent form when used in the management of nutrients. Table 5 Storage stability test results of Example 1 and Comparative Example 1 Example 1 Comparative Example 1 The measurement unit was initially subjected to 6 months in the first 6 months. Diameter β m 0.106 0.103 0.103 0.107 pH 6.12 6.06 6.50 6.40 Viscosity mPa · s 6.30 6.50 9.60 10.34 Functionality Suitable and suitable Suitable color difference ΔΕ* 46.92 49.36 42.11 48.52 Appearance - No problem No problem No problem No problem Tube fluidity mL/h 139 146 89 84 Acid resistance (pH) 5.0 - 5.9 Example 5 The raw materials were metered in the proportions shown in Table 6, and the blending was carried out at 4500 kcal/4,500 ml. Into a 5-liter stainless steel bucket, weigh 2000g of blended water and warm it to 70~8〇ac in a hot water bath. Into the dextrin, insoluble dietary fiber, milk protein, isomaltulose, water-soluble dietary fiber, mineral-containing yeast, biotin yeast, glucose-30- 200942181 zinc acid, copper gluconate, citric acid Sodium ferrous, isoleucine, sodium amide and dispersed. Next, a liquid obtained by mixing and dissolving edible fats and oils, medium-chain fatty acid triglyceride, phyto-carotene suspension, vitamin E oil, and emulsifier at 70 to 80 t is introduced.

另外,於不鏽鋼容器中投入300克之加溫水(30~40 °〇 ),且依序溶解檸檬酸、氫氧化鈣、檸檬酸三鈉、碳酸 鉀、氯化鎂,且將該溶液投入於5升不鏽鋼容器中之預先 調製之溶液中,並經混合。接著,於其中投入磷酸三鈣、 綜合維他命,並經分散溶解,且加入香料。最後加入並溶 解異抗壞血酸鈉、抗壞血酸鈉且混合。以調配水使總量成 爲4,500ml定量之後’攪拌至成均勻溶液爲止。以高壓均 質機使該溶液乳化(均質壓力:70MPa )。將其塡充於附 加噴管之透明膜袋(袋膜構成:PET/蒸著PET/Ny/CPP) 中使每個容量成爲300ml,且在124 °C下進行高壓蒸煮殺 菌處理。本營養品之黏度爲T.OmPa.s^^C),經時儲 存安定性優異,尤其是高溫儲存時(40〜6(TC )亦極少發 生乳狀,且亦認爲沒有源自不溶性磷酸鈣之沉澱物之產生 。風味及管中流動性亦良好。 另外,本發明品l〇〇k cal中之游離異亮胺酸之量爲 〇·5克’游離異亮胺酸/異麥芽酮糖之質量比爲1/3.9( 22.5/88.2 )。 -31 - 200942181 表6 實施例5之調配組成(4,500kCal/4,500ml ) 原材料名稱 使用量 單位 乳蛋白質 185.9 克 糊精 450.0 克 異麥芽酮糖 88.2 克 不溶性食物纖維 18.0 克 水溶性食物纖維 60.8 克 食用油脂 96.2 克 中鏈脂肪酸三酸甘油酯 50.9 克 乳化劑 28.1 克 檸檬酸 12.6 克 氫氧化鈣 1.8 克 檸檬酸三鈉 11.7 克 碳酸鉀 12.6 克 氯化鎂 10.8 克 磷酸三鈣 5.4 克 榖胺酸鈉 13.5 克 異亮胺酸 22.5 克 抗壞血酸鈉 3.29 克 異抗壞血酸鈉 1.96 克 檸檬酸亞鐵鈉 405.0 毫克 葡糖酸鋅 5 17.5 毫克 葡糖酸銅 3 1.5 毫克 含有硒之酵母 180.0 毫克 含有鉬之酵母 27.0 毫克 含有錳之酵母 405.0 毫克 含有鉻之酵母 117.0 毫克 含碘之酵母 49.5 毫克 生物素酵母 549.0 毫克 維他命E油 328.5 毫克 召-胡蘿蔔素懸浮液 74.3 毫克 香料 3.2 克 維他命A棕櫚酸鹽 58.5 毫克 維他命B1鹽酸鹽 67.5 毫克 核黃素磷酸酯鈉 . 23.0 毫克 綜 維他命B6鹽酸鹽 40.1 毫克 合 維他命Β12(0·1%水溶性粉末) 84.2 毫克 維 維他命D 3 3.6 毫克 他 菸鹼酸醯胺 94.5 毫克 口卩 葉酸(維他命Μ) 4.1 毫克 泛酸鈣 64.8 毫克 維他命Κ2(0.2%乳化粉末) 58.5 -^4* -4 · 毫克 -32- 200942181 發明品之營養組成物之效力評價實驗 實驗1 (參考例:僅使用異麥芽酮糖時之效力) 0 % 使用爲使耐糖能異常發病之糖尿病模型鼠之GK鼠( 7週齡雄性,日本SLC (股))進行實驗。使GK鼠禁食 18小時,且分別經口投與將糖質(12克/ lOOkcal )之一部 分置換成〇克、4.4克、8_9克/lOOkcal之異麥芽酮糖之表 7中所示之營養組成物A、B、C(實施例1之營養組成基 礎,其中並未調配游離異亮胺酸)(12kcal/kgB.W.),且 測定血糖値(測定機器:富士 DRYCHEM 5500,富士膠片 (股)製)。 其結果,營養組成物C相較於營養組成物A,在投與 營養組成物15、30、60分鐘後血糖値之上升被有意義地 抑制(15、30分鐘:p<0.01 ’ 60分鐘:ρ<0·05,參數性 D unnet型多重檢定,圖1)。但,營養組成物Β與營養組 成物A相較,並無法抑制血糖値之上升(圖1) ° 由該結果,僅使用異麥芽酮糖,未與游離異亮胺酸倂 用之情況下,若未使用佔有糖質之約70質量%以上之量之 異麥芽酮糖,則判定無法充分發揮異麥芽酮糖之血糖値上 升抑制效果。 -33- 200942181 表7營養組成物A、B、C之調 配組成(2,000kcal/2,000ml) 原材料名稱 單位 組成物A 組成物B 組成物C 乳蛋白質 克 92.6 糊精 克 239.0 150.4 6 1.6 異麥芽酮糖 克 0 88.6 177.4 不溶性食物纖維 克 8.0 水溶性食物纖維 克 27.0 食用油脂 克 42.7 中鏈脂肪酸三酸甘油酯 克 22.6 乳化劑 克 12.5 檸檬酸 克 7.5 氫氧化鈣 克 1.4 檸檬酸三鈉 克 5.4 碳酸鉀 克 5.6 氯化鎂 克 4.8 甘油磷酸鈣 克 3.2 榖胺酸鈉 克 6.0 異亮胺酸 克 抗壞血酸鈉 克 1.29 異抗壞血酸鈉 克 0.54 檸檬酸亞鐵鈉 克 180.0 葡糖酸鋅 毫克 230.0 葡糖酸銅 毫克 14.0 含有硒之酵母 毫克 80.0 含有鉬之酵母 毫克 12.0 含有錳之酵母 毫克 180.0 含有鉻之酵母 毫克 52.0 含碘之酵母 毫克 22.0 生物素酵母 毫克 244.0 維他命E油 毫克 167.9 冷-胡蘿蔔素懸浮液 毫克 26.4 香料 毫克 1.6 維他命A棕櫚酸鹽 毫克 36.0 維他命B1鹽酸鹽 毫克 27.1 核黃素磷酸酯鈉 毫克 10.2 維他命B6鹽酸鹽 毫克 17.72 維他命B12(0_l%水溶性粉末) 毫克 15.0 維他命D3 毫克 1.8 菸鹼酸醯胺 毫克 49.0 葉酸(維他命M) 毫克 1.7 泛酸鈣 毫克 28.8 維他命K2 (0 · 2 %乳化粉末) 毫克 22.1 -34- 200942181 實驗2 對本發明品之血糖上升抑制效果,使用爲呈現耐糖能 異常之糖尿病模型鼠之GK鼠(鼠齡7週之雄性’曰本 SLC (股))進行實驗。對禁食1 8小時之鼠分別投與實施 例1中調製之本發明營養組成物與未調配游離異亮胺酸及 異麥芽酮糖之營養組成物A(12kcal/kgB.W.),且測定血 糖値(測定機器:富士 DRYCHEM 5500,富士膠片(股) Λ 製)。 圖2中顯示之結果,本發明品相較於營養組成物A, 可有意地抑制投與營養組成物60、120分鐘後之血糖値上 升(p<0.05,t檢定,圖2)。由該結果,判定藉由游離異 亮胺酸與異麥芽酮糖之倂用,可發揮極強的血糖上升抑制 ' 效果。異麥芽酮糖之血糖値上升抑制效果在未以糖質之約 70質量%以上之比例調配異麥芽酮糖時無法充分發揮,但 藉由倂用每lOOkcal爲0.5克之游離異亮胺酸時,可將異 麥芽酮糖之量降低至糖質之16質量%。 實驗例3 透過GK老鼠(14週齡之雄鼠,日本SLC (股))之 胃瘻,分別將實施例2中調製之本發明品與營養組成物D 經管投入胃內(l2kcal/kgB.W.),且測定血糖値(測定機 器:富士 DRYCHEM 5500,富士膠片(股)製)。營養組 成物D係依據表8之調配,如實施例2般製造,且該溶液 之卡路里濃度爲2.4kcal/ml ’又使以黏度爲代表之物理性 -35- 200942181 質與實施例2相同。關於油脂,係使ω6系脂肪酸/ α>3系 脂肪酸比成爲1.5之方式調整食用油脂之使用比例。構成 中鏈脂肪酸三酸甘油酯之脂肪酸殘基之碳數爲6〜12。該中 鏈脂肪酸相對於全部脂肪之比例爲1 8重量%。糖質中未含 海藻糖,另外,亦不含游離亮胺酸。 該實驗結果,本發明品相較於營養組成物D,可有意 義地抑制投與15、30、60分鐘後之血醣値上升(ρ<0.05 ,t檢定,圖3)。對照之營養組成物D係將卡路里濃度 調整成2.4kcal/ml (比重1.18)之高卡路里,將其投與糖 尿病模型老鼠時引發高血糖。然而,實施例2之組成即使 以卡路里濃度成爲2.4kcal/ml (比重1.18)投與之情況下 ,亦可抑制血糖上升(圖3)。 高齡糖尿病患者中,本身無法攝取營養,大多存在有 藉由胃瘻直接對胃投與營養組成物之患者。由於~般高齡 者之胃容量較小,故使用之營養組成物較好爲體積小且高 卡路里濃度者,但在投與速度相同之情況下,提高卡路里 濃度明顯的容易引起某程度之高血糖。然而,如結果所示 ,2.4kcal/ml之高卡路里濃度之本發明品確認並不會引起 高血糖。 -36- 200942181In addition, 300 grams of warm water (30 ~ 40 ° 〇) is placed in a stainless steel container, and citric acid, calcium hydroxide, trisodium citrate, potassium carbonate, magnesium chloride are sequentially dissolved, and the solution is put into 5 liters of stainless steel. The pre-conditioned solution in the container is mixed. Next, tricalcium phosphate, a synthetic vitamin, and dissolved in a dispersion are added thereto, and a fragrance is added. Finally, sodium erythorbate, sodium ascorbate is added and dissolved and mixed. The amount of water was adjusted so that the total amount became 4,500 ml, and then the mixture was stirred until it became a homogeneous solution. The solution was emulsified by a high pressure homogenizer (homogeneous pressure: 70 MPa). This was filled in a transparent film bag (bag film structure: PET/vaporized PET/Ny/CPP) with an additional nozzle to make each volume 300 ml, and subjected to autoclaving sterilization at 124 °C. The viscosity of the nutrient is T.OmPa.s^^C), and the storage stability is excellent over time, especially when stored at high temperature (40~6(TC) is also rarely milky, and it is also considered that it is not derived from insoluble phosphoric acid. The production of calcium precipitates. The flavor and the fluidity in the tube are also good. In addition, the amount of free isoleucine in the product l〇〇k cal of the present invention is 〇·5 g 'free isoleucine/iso malt The mass ratio of ketose was 1/3.9 (22.5/88.2). -31 - 200942181 Table 6 Formulation of Example 5 (4,500kCal/4,500ml) Raw material name Usage unit Milk protein 185.9 gdextrin 450.0 g of malt Ketoose 88.2 g Insoluble dietary fiber 18.0 g Water-soluble dietary fiber 60.8 g Edible fat 96.2 g Medium chain fatty acid triglyceride 50.9 g Emulsifier 28.1 g Citric acid 12.6 g Calcium hydroxide 1.8 g Trisodium citrate 11.7 g Potassium carbonate 12.6 Gram magnesium chloride 10.8 g Tricalcium phosphate 5.4 Grams sodium citrate 13.5 g Isoleucine 22.5 g Sodium ascorbate 3.29 Sodium erythorbate 1.96 g Sodium citrate 405.0 mg Zinc gluconate 5 17.5 mg Copper citrate 3 1.5 mg Yeast containing selenium 180.0 mg Yeast containing molybdenum 27.0 mg Yeast containing manganese 405.0 mg Yeast containing chromium 117.0 mg Yeast containing iodine 49.5 mg Biotin yeast 549.0 mg Vitamin E oil 328.5 mg Call-carotene Suspension 74.3 mg of fragrance 3.2 g of vitamin A palmitate 58.5 mg of vitamin B1 hydrochloride 67.5 mg of sodium riboflavin phosphate. 23.0 mg of vitamin B6 hydrochloride 40.1 mg of vitamin Β 12 (0·1% water soluble powder) 84.2 mg of vitamin D 3 3.6 mg of his nicotinic acid decylamine 94.5 mg of phlegonic acid (vitamin Μ) 4.1 mg of calcium pantothenate 64.8 mg of vitamin Κ 2 (0.2% emulsified powder) 58.5 -^4* -4 · mg-32- 200942181 Efficacy Evaluation of the Nutritional Composition of the Invention Product Experiment 1 (Reference Example: Efficacy when only isomaltulose was used) 0 % GK mice (7-week-old males, 7-week-old males) used for diabetic mice with abnormal sugar tolerance SLC (shares)) Experiments. GK rats were fasted for 18 hours and administered orally with glycosides (12 g / lOO) One part of kcal ) was replaced with the nutritional compositions A, B, and C shown in Table 7 of gram, 4.4 g, and 8-9 g/lOOkcal of isomaltulose (the nutrient composition basis of Example 1 in which no formulation was made. Free isoleucine) (12 kcal/kg B.W.), and blood glucose was measured (measurement machine: Fuji DRYCHEM 5500, manufactured by Fujifilm Co., Ltd.). As a result, the nutritional composition C was significantly inhibited from the nutritional composition A after 15, 30, and 60 minutes of administration of the nutritional composition (15, 30 minutes: p < 0.01 ' 60 minutes: ρ <;0·05, parametric D unnet type multi-check, Figure 1). However, the nutrient composition Β compared with the nutrient composition A does not inhibit the rise of blood sugar ( (Fig. 1) ° From the result, only isomaltulose is used, and it is not used with free isoleucinate. When the amount of isomaltulose in an amount of about 70% by mass or more of the saccharide is not used, it is judged that the effect of suppressing the increase in blood sugar 异 of isomaltulose is not sufficiently exhibited. -33- 200942181 Table 7 Composition of nutritional composition A, B, C (2,000 kcal / 2,000 ml) Raw material name Unit composition A Composition B Composition C Milk protein gram 92.6 Dextrin gram 239.0 150.4 6 1.6 Isomalt Ketoose gram 0 88.6 177.4 Insoluble food fiber gram 8.0 Water-soluble dietary fiber gram 27.0 Edible oil gram 42.7 Medium chain fatty acid triglyceride gram 22.6 Emulsifier gram 12.5 Citric acid gram 7.5 Calcium hydroxide gram 1.4 Trisodium citrate 5.4 Carbonic acid Potassium gram 5.6 Magnesium chloride 4.8 Calcium phosphate gram 3.2 Sodium amide sodium 6.0 Isoleucine gram sodium ascorbate 1.28 Sodium oxalate 0.54 Sodium citrate gram 180.0 Zinc gluconate mg 230.0 Copper gluconate mg 14.0 Selenium-containing yeast mg 80.0 Molybdenum-containing yeast mg 12.0 Manganese-containing yeast mg 180.0 Chromium-containing yeast mg 52.0 Iodine-containing yeast mg 22.0 Biotin yeast mg 244.0 Vitamin E oil mg 167.9 Cold-carotene suspension mg 26.4 Fragrance mg 1.6 Vitamin A Palmitate mg 36.0 Vitamins B1 hydrochloride mg 27.1 riboflavin sodium mg 10.2 Vitamin B6 hydrochloride mg 17.72 Vitamin B12 (0_l% water soluble powder) mg 15.0 Vitamin D3 mg 1.8 Nicotinamide mg 49.0 Folic acid (vitamin M) mg 1.7 Calcium pantothenate mg 28.8 Vitamin K2 (0 · 2 % emulsified powder) mg 22.1 -34- 200942181 Experiment 2 The GK mouse of a diabetic model mouse exhibiting an anti-sugar tolerance abnormality is used for the blood glucose increase inhibitor of the present invention (at 7 weeks of age) The male 'Sakamoto SLC (share)) was tested. The nutritional composition of the present invention prepared in Example 1 and the nutritional composition A (12 kcal/kg B.W.) of unisolated free isoleucine and isomaltulose were administered to the rats fasted for 18 hours, respectively. And blood glucose 测定 was measured (measurement machine: Fuji DRYCHEM 5500, Fujifilm (share) system). As shown in Fig. 2, the present invention can intentionally suppress the increase in blood glucose sputum after 60 and 120 minutes of administration of the nutritional composition as compared with the nutritional composition A (p < 0.05, t-test, Fig. 2). From this result, it was judged that the use of free isoleucine and isomaltulose could exert an extremely strong effect of suppressing blood sugar rise. The effect of suppressing the increase in the blood sugar level of isomaltulose is not sufficiently exerted when the isomaltulose is not prepared in a ratio of about 70% by mass or more of the saccharide, but 0.5 g of free isoleucine per 100 kcal is used. At the time, the amount of isomaltulose can be reduced to 16% by mass of the saccharide. Experimental Example 3 The inventive product prepared in Example 2 and the nutritional composition D were respectively administered into the stomach through a gastric fistula of GK mice (14-year-old male rats, Japanese SLC (stock)) (l2 kcal/kg B.W. And the measurement of blood glucose 値 (measurement machine: Fuji DRYCHEM 5500, Fujifilm Co., Ltd.). The nutrient composition D was prepared according to Table 8, and was produced as in Example 2, and the calorie concentration of the solution was 2.4 kcal/ml', and the physical property represented by the viscosity was the same as in Example 2. In the case of fats and oils, the ratio of use of edible fats and oils is adjusted so that the ratio of the omega 6 fatty acid / α > 3 fatty acids is 1.5. The carbon number of the fatty acid residue constituting the medium chain fatty acid triglyceride is 6 to 12. The ratio of the medium chain fatty acid to the total fat was 18% by weight. The saccharide does not contain trehalose, and it does not contain free leucine. As a result of the experiment, the product of the present invention can intentionally suppress the increase in blood glucose 15 after 15, 30, and 60 minutes of administration compared with the nutritional composition D (ρ < 0.05, t test, Fig. 3). The comparative nutrient composition D adjusted the calorie concentration to a high calorie of 2.4 kcal/ml (specific gravity 1.18), and when it was administered to a diabetic model mouse, hyperglycemia was induced. However, the composition of Example 2 can suppress the increase in blood glucose even when the calorie concentration is 2.4 kcal/ml (specific gravity 1.18) (Fig. 3). In elderly patients with diabetes, they are unable to take up their own nutrition. Most patients have a nutritional composition that is directly administered to the stomach by stomach cramps. Because the stomach capacity of the elderly is small, the nutrient composition used is preferably small in size and high in calorie concentration. However, when the administration speed is the same, increasing the calorie concentration is likely to cause a certain degree of high blood sugar. . However, as shown by the results, the present invention of a high calorie concentration of 2.4 kcal/ml confirmed that it did not cause hyperglycemia. -36- 200942181

表8 營養組成物D之調配組成(2,000kcal/l,000g) 原材料名稱 使用量 單位 乳蛋白質 1 04.4 克 糊精 192.8 克 海藻糖 - 克 不溶性食物纖維 5.0 克 水溶性食物纖維 25.0 克 食用油脂 58.0 克 中鏈脂肪酸三酸甘油酯 13.7 克 乳化劑 5.3 克 乳酸鈣 3.30 克 檸檬酸鉀 3.10 克 氯化鉀 0.60 克 磷酸鉀 3.30 克 氯化鎂 2.60 克 硫酸錢 3.80 克 葡糖酸鈉 19.1 克 榖胺酸鈉 4.50 克 亮胺酸 克 抗壞血酸鈉 1.30 克 異抗壞血酸鈉 2.90 克 檸檬酸亞鐵鈉 180.0 毫克 葡糖酸鋅 230.0 毫克 葡糖酸銅 14.0 毫克 含有硒之酵母 80.0 毫克 含有鉬之酵母 12.0 毫克 含有錳之酵母 180.0 毫克 含有鉻之酵母 52.0 毫克 含碘之酵母 22.0 毫克 生物素酵母 244.0 毫克 香料 1.0 毫克 維他命E油 167.9 毫克 点-胡蘿蔔素懸浮液 26.4 毫克 綜 合 維 他 口卩 維他命A棕櫚酸鹽 36.0 毫克 維他命B 1鹽酸鹽 27.1 毫克 核黃素磷酸酯鈉 10.2 毫克 維他命B6鹽酸鹽 17.72 毫克 維他命B1 2(0.1 %水溶性粉末) 15.0 毫克 維他命D3 1.8 毫克 菸鹼酸醯胺 49.0 毫克 葉酸(維他命M) 1.7 毫克 泛酸鈣 28.8 毫克 維他命K2(0.2%乳化粉末) 22.1 毫克 -37- 200942181 實驗4 使用爲使耐糖能異常發病之糖尿病模型鼠之ZDF鼠( 10週齡雄鼠,日本Charles River (股)),驗證本發明 品之血紅蛋白 Ale ( HbAlc )之上升抑制效果。HbAlc爲 反映過去約一個月間血糖値之指標。另外,ZDF鼠爲伴隨 著病態惡化,自10週齡開始HbAlc緩慢上升,爲顯示接 近人類糖尿病惡化過程之狀態之模型。將老鼠以使HbAlc 之平均値相等之方式分爲2組後,分別自由的攝取每營養 組成物lOOkcal含有0.5克游離異亮胺酸與2.0克異麥芽 酮糖之營養組成物E,與未調配游離異亮胺酸及異麥芽酮 糖之營養組成物F,比較4週後之HbAlc (營養組成物調 配組成:表 9,測定機器:DCA2000系統,SIEMENS MEDICAL SOLUTIONS · DIAGNOSTICS (股)製)。營養 組成物E及F之維他命、礦物質之調配係使用老鼠之標準 飼料(AIN-93G維他命混合及 AIN-93G礦物質混合, ORIENTAL酵母工業(股)製造)。 其結果,營養組成物E相較於營養組成物F,判定可 有意義地抑制HbAlc之上升率,每營養組成物lOOkcal組 合0.5克之游離異亮胺酸與2.0克異麥芽酮糖(游離異亮 胺酸/異麥芽酮糖之質量比1/4,糖質中異麥芽酮糖之含量 爲12質量%),對於長期血糖之控制有用,且證明可在自 由經口攝取之條件下抑制血糖上升(p<0.05,t檢定,圖4 -38- 200942181 表9 營養組成物E、F之調配組成(1 00kcal/27g) 原材料名稱 單位 組成物E 組成物F 乳蛋白質 克 4.9 5.4 異亮胺酸 克 0.5 - 玉米澱粉 克 15 17 異麥芽酮糖 克 2.0 - 不溶性食物纖維 克 1.3 食用油脂(中鏈脂肪酸三酸甘 油酯%w/w) 克 1.9(30) 維他命 AIN-93G維他命混合 礦物質 AIN-93G礦物質混合 實驗5 使用使耐糖能異常發病之鏈脲佐菌素(Streptozocin ) (STZ )誘發性糖尿病老鼠,驗證本發明品之HbAlc ' 之上升抑制效果。STZ誘發性糖尿病老鼠之HbAlc在投與 STZ後上升,且顯示與人類糖尿病惡化之過程接近之狀態 之模型。經腹腔內對 SD老鼠(7週齡之雄鼠,曰本 ^ Charles River (股))投與 STZ 60mg/kgB.W.,製作糖尿 病模型鼠。投與STZ 8天後,將老鼠以使HbAlc之平均値 相等之方式分成2組後,分別自由攝取具有實施例1之組 成之粉末狀營養組成物與未調配游離異亮胺酸及異麥芽酮 糖之營養組成物A之粉末狀營養組成物,且比較6週後之 HbAlc (測定機器:DCA2000 系統,SIEMENS MEDICAL SOLUTIONS · DIAGNOSTICS (股)製)。實施例 1 中所 示之本發明營養組成物(未使用調配水)及營養組成物A 之調配組成物係使用萬能混合攪拌機(DALTON (股)製 -39- 200942181 ),將原材料混合製作。 其結果,本發明之營養組成物相較於營養組成物A, 判定可有意義地抑制Hb A 1 c之上升。而且,證明本發明之 營養組成物即使爲粉末狀對於血糖之控制亦有用(p<0.01 ,t檢定,圖5 )。 糖尿病患者及耐糖能異常之情況下營養攝取時急速血 糖値上升之抑制係使用胰島素注射或經口降血糖藥。胰島 素或經口降血糖藥爲抑制血糖上升作用強者,但會伴隨著 低血糖或胃腸受損、浮腫、貧血等副作用。另外,進行胰 島素療法之過半數患者亦有認爲「針刺疼痛」之報告(非 專利文獻4 :加來浩平,實務,22 ( 3 ),240, 2005 ),胰 島素注射會造成大的精神壓力。本發明由於在長期攝取之 情況下亦可抑制投藥期間中之高血糖,因此可減少胰島素 及經口降血糖藥之投藥量,對於藥劑之副作用及針刺之壓 力減輕具有貢獻。 實驗6 使呈現耐糖能異常之糖尿病模型鼠之GK鼠(曰本 SLC (股))落在低營養狀態,且驗證本發明組成物之營 養效果。亦即,對11週齡之GK老鼠投與無蛋白質之老 鼠飼料21天,製作耐糖能異常之低營養狀態之模型鼠。 將該等老鼠依使體重及空腹時血糖値之平均相等之方式分 成2組,藉由剖腹手術透過造設之胃瘻,且使用朝胃內之 泵,在第 〇~1天爲 20kcal/18小時/隻,第 1〜2天爲 -40- 200942181Table 8 Composition of nutritional composition D (2,000kcal/l,000g) Raw material name Usage unit Milk protein 1 04.4 grams of dextrin 192.8 grams of trehalose - grams of insoluble dietary fiber 5.0 grams of water soluble dietary fiber 25.0 grams of edible fat 58.0 grams Medium chain fatty acid triglyceride 13.7 g emulsifier 5.3 g calcium lactate 3.30 g potassium citrate 3.10 g potassium chloride 0.60 g potassium phosphate 3.30 g magnesium chloride 2.60 g sulfuric acid money 3.80 g sodium gluconate 19.1 glysinate 4.50 g Leucine sodium gram ascorbate 1.30 g sodium isoascorbate 2.90 g sodium citrate 180.0 mg zinc gluconate 230.0 mg copper gluconate 14.0 mg yeast containing selenium 80.0 mg yeast containing molybdenum 12.0 mg yeast containing manganese 180.0 mg Chromium-containing yeast 52.0 mg Iodine-containing yeast 22.0 mg Biotin yeast 244.0 mg Perfume 1.0 mg Vitamin E oil 167.9 mg Dot-carotene suspension 26.4 mg Synthetic Vitalin Vitamin A palmitate 36.0 mg Vitamin B 1 Hydrochloric acid Salt 27.1 mg nuclear yellow Sodium phosphate 10.2 mg Vitamin B6 hydrochloride 17.72 mg Vitamin B1 2 (0.1% water soluble powder) 15.0 mg Vitamin D3 1.8 mg Nicotinamide 49.0 mg Folic acid (vitamin M) 1.7 mg Calcium pantothenate 28.8 mg Vitamin K2 (0.2 % emulsified powder) 22.1 mg-37- 200942181 Experiment 4 Verification of the hemoglobin Ale (HbAlc) of the present invention using a ZDF mouse (10-week old male, Charles River, Japan) for the diabetic model of abnormal glucose tolerance ) The rising inhibitory effect. HbAlc is an indicator of blood glucose sputum in the past month or so. In addition, in the ZDF mouse, HbAlc gradually rises from the age of 10 weeks as the disease progresses, and it is a model showing the state of the process of deterioration of human diabetes. The mice were divided into two groups in such a way that the average enthalpy of HbAlc was equalized, and the nutrient composition E containing 0.5 g of free isoleucine and 2.0 g of isomaltulose was taken freely per 100 kcal of each nutrient composition, respectively. The nutrient composition F of free isoleucine and isomaltulose was formulated, and HbAlc was compared after 4 weeks (nutrition composition composition: Table 9, measuring machine: DCA2000 system, SIEMENS MEDICAL SOLUTIONS · DIAGNOSTICS (share) system) . Nutrition Compositions E and F are formulated with vitamins and minerals (AIN-93G Vitamin Blend and AIN-93G Mineral Blend, manufactured by ORIENTAL Yeast Industries). As a result, the nutrient composition E was judged to be more effective in suppressing the increase rate of HbAlc than the nutrient composition F, and each nutrient composition 100 kcal was combined with 0.5 g of free isoleucine and 2.0 g of isomaltulose (free isoprene). Amino acid/isomaltulose has a mass ratio of 1/4, and the content of isomaltulose in the saccharide is 12% by mass), which is useful for the control of long-term blood sugar, and proves to be inhibited under conditions of free oral ingestion. Blood sugar rise (p<0.05, t-test, Figure 4 -38- 200942181 Table 9 Composition of nutrient composition E, F (1 00kcal/27g) Raw material name Unit composition E Composition F Milk protein 4.9 5.4 Isoleucine Acid gram 0.5 - corn starch gram 15 17 isomaltulose gram 2.0 - insoluble food fiber gram 1.3 edible oil (medium chain fatty acid triglyceride% w/w) gram 1.9 (30) vitamin AIN-93G vitamin mixed mineral AIN-93G Mineral Mixing Experiment 5 The anti-hypertensive effect of HbAlc' of the present invention was verified by using Streptozocin (STZ)-induced diabetic mice with abnormal sugar tolerance. STZ-induced diabetic mice HbAlc rises after administration of STZ and shows a model close to the state of progression of human diabetes. SD rats (7-week-old male, Sakamoto ^ Charles River) were administered intraperitoneally to STZ 60 mg/kg B. .W., a diabetic model rat was prepared. After 8 days of STZ administration, the mice were divided into two groups in such a manner that the average enthalpy of HbAlc was equalized, and the powdered nutrient composition having the composition of Example 1 was freely ingested and unmixed, respectively. A powdery nutrient composition of the nutritional composition A of free isoleucine and isomaltulose was measured, and HbAlc was measured after 6 weeks (measurement apparatus: DCA2000 system, manufactured by SIEMENS MEDICAL SOLUTIONS DIAGNOSTICS Co., Ltd.). The blending composition of the nutritional composition of the present invention (unmixed water used) and the nutritional composition A shown in Fig. 1 was prepared by mixing a raw material using a universal mixing mixer (DALTON Co., Ltd. - 39-200942181). The nutritional composition of the present invention determines that the increase in Hb A 1 c can be remarkably suppressed as compared with the nutritional composition A. Moreover, it is proved that the nutritional composition of the present invention is even in powder form for blood sugar. Control is also useful (p < 0.01, t test, Figure 5). In the case of diabetic patients and sugar tolerance, the inhibition of rapid increase in blood glucose sputum during nutritional intake is the use of insulin injection or oral hypoglycemic agents. Insulin or oral hypoglycemic The drug is strong in inhibiting the rise of blood sugar, but it is accompanied by side effects such as hypoglycemia or gastrointestinal damage, edema, and anemia. In addition, more than half of the patients who underwent insulin therapy also reported that they had acupuncture pain (Non-Patent Document 4: Jialai Haoping, Practice, 22 (3), 240, 2005). Insulin injection caused great mental stress. . According to the present invention, since hyperglycemia during administration can be suppressed in the case of long-term ingestion, the administration amount of insulin and oral hypoglycemic agents can be reduced, and the side effects of the drug and the pressure reduction of acupuncture can be contributed. Experiment 6 GK mice (Sakamoto SLC (strand)) which exhibited a diabetic model rat with abnormal glucose tolerance were placed in a low-nutrient state, and the nutritional effects of the composition of the present invention were verified. That is, 11-week-old GK mice were fed a protein-free mouse for 21 days to prepare a model rat with a low nutritional status which was abnormal in sugar tolerance. The mice were divided into two groups according to the average of the body weight and the fasting blood glucose level. The laparotomy was performed through the stomach sputum, and the pump was used in the stomach. The first day was 20kcal/18. Hours/only, the first to the second day is -40- 200942181

45kcal/18小時/隻,第2〜7天爲65kcal/18小時/隻,第7 天以後爲71kcal/20小時/隻之量’對其一群在1〇天內經 管投與實施例1之液狀本發明組成物,另一群在10天內 經管投與據報告可良好地維持糖尿病患者之血糖控制之調 配購得食物纖維·寡糖,糖質·脂質調整液營養食品(「 TABION」(註冊商標),α :以下,T 〇:)(非專利文獻 5 :齋藤Mari,靜脈經腸營養,23 (增刊號),3 1 1, 2008 )。表10中顯示Τα之主要營養組成。 實施該試驗之結果,投與中(投與結束1小時前)之 血糖値爲本發明品組比Τ α更低之値(圖6 )。另外,本 發明品組之體內氮氣良好維持(圖7),於飼育期間變長 之情況營養均衡優異之本發明品組體重成爲高値(圖8) ,有效地驗證本發明品之營養均衡。耐糖能異常者,由於 因代謝異常引起之血管障礙或血流降低,容易引起手術後 之縫合不全或因長期臥床而引起褥瘡。於創傷或褥瘡之治 癒而言營養均衡之營養素不可或缺,因均衡差之營養攝取 引起之營養不良狀態提高該等發病之危險性,導致治癒延 長。本發明之營養組成可抑制攝取後之高血糖且可適當保 持營養狀態’非常有用於創傷、褥瘡之預防或促進治癒。 -41 - 200942181 表10 購得製品Τα之調配組成(200kCal/200ml) 原材料名稱 使用量 單位 乳蛋白質 8.0 克 異亮胺酸 • 克 亮胺酸 克 糖質 22 克 異麥芽酮糖 • 克 海藻糖 . 克 食物纖維 3.6 克 寡糖 1.0 克 食用油脂 9.0 克 中鏈脂肪酸三酸甘油酯 - 克 維他命※ 以日本人飮食攝取基 準(2005年版)爲主 礦物質※ ※豐富調配維他命B1及鉻(上述飮食攝取基準推薦量充 足率之約2倍) 實驗7 使呈現耐糖能異常之糖尿病模型鼠之GK鼠(日本 SLC (股))落在低營養狀態,且驗證本發明組成物之營 養效果。亦即,對5週齡之GK老鼠投與無蛋白質之老鼠 飼料21天,製作耐糖能異常之低營養狀態之模型鼠。將 該等老鼠分成2組,使用投與噴嘴,以第天爲 20kcal/100g B.W·、第 3 天以後爲 25kcal/100g B.W.之量 對一組投與實施例1之液狀本發明組成物且對另一組投與 Τα,共攝取8天。該Τα於糖質中並未調配異麥芽酮糖 、海藻糖或游離異亮胺酸或游離亮胺酸亦未調配中鏈脂肪 酸三酸甘油酯。又,ω6系脂肪酸/ ω3系脂肪酸比爲3.6 -42- 200942181 。實施該試驗之結果,於飼育期間變長之情況營養均衡優 異之本發明品組體重成爲高値(圖9)。而且,確認本發 明品不僅是經管投與時,即使經口攝取時亦爲營養均衡優 異之組成。 實驗845kcal/18 hours/only, 65kcal/18 hours/only on the 2nd to 7th days, 71kcal/20 hours/day after the 7th day', the liquid of Example 1 was administered to a group within 1 day. In the case of the composition of the present invention, the other group purchased the dietary fiber, oligosaccharide, and saccharide/lipid regulating nutrient food ("TABION" (registered) in a 10-day period. Trademark), α: below, T 〇:) (Non-Patent Document 5: Saito Mari, intravenous enteral nutrition, 23 (supple issue), 3 1 1, 2008). The main nutritional composition of Τα is shown in Table 10. As a result of the test, the blood glucose level in the administration (one hour before the end of the administration) was lower than that of the invented group (Fig. 6). Further, the nitrogen in the body of the present invention group was well maintained (Fig. 7), and the body weight of the product group having excellent nutritional balance was high in the case of becoming longer during the breeding period (Fig. 8), and the nutritional balance of the product of the present invention was effectively verified. In patients with abnormal glucose tolerance, vascular disorders or decreased blood flow due to metabolic abnormalities may cause sutures after surgery or acne due to prolonged bed rest. The treatment of trauma or hemorrhoids is indispensable for nutritionally balanced nutrients, and the malnutrition caused by poorly balanced nutrient intake increases the risk of such diseases, leading to prolonged healing. The nutritional composition of the present invention can suppress hyperglycemia after ingestion and can appropriately maintain a nutritional state. It is very useful for prevention of wounds, acne, or promotion of healing. -41 - 200942181 Table 10 Composition of purchased product Τα (200kCal/200ml) Raw material name Usage unit Milk protein 8.0 g of isoleucine • Creramamic acid saccharide 22 g Isomaltulose • Gram trehalose克 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维 纤维About 2 times the sufficiency rate of the foraging intake recommendation recommended amount) Experiment 7 GK rats (Japanese SLC (stock)) exhibiting a diabetic model with abnormal glucose tolerance were placed in a low-nutrient state, and the nutritional effects of the composition of the present invention were verified. That is, a 5-week-old GK mouse was administered with a protein-free mouse for 21 days to prepare a model rat having a low nutritional status against abnormal sugar. The rats were divided into two groups, and the liquid-like composition of Example 1 was administered to a group using a dispensing nozzle of 20 kcal/100 g BW· on the first day and 25 kcal/100 g BW after the third day. Another group was administered Τα for a total of 8 days. The Τα is not formulated with isomaltulose, trehalose or free isoleucine or free leucine in the saccharide, and no medium chain fatty acid triglyceride is formulated. Further, the ratio of the ω6 fatty acid/ω3 fatty acid is 3.6 - 42 to 200942181. As a result of carrying out the test, the weight of the product of the present invention which was excellent in nutritional balance during the period of the breeding period became high (Fig. 9). Further, it was confirmed that the present invention is not only a composition for administration, but also a nutritionally balanced composition even when taken orally. Experiment 8

使用爲使耐糖能異常發病之糖尿病模型鼠之GK鼠( 25週齡雄性,曰本SLC (股))進行實驗。對禁食18小 時之鼠,以8kcal/kg投與實施例1調配之本發明之營養組 成物,以6kcal/kg投與未調配游離異亮胺酸及異麥芽酮糖 之營養組成物 A,並測定血糖(測定機器:富士 DRYCHEM 5 5 00 > 富 士膠片(股)製)。 投與本發明品後之血糖値,於比營養組成物A投與量 多亦無關地顯示同樣的血糖推移(p = 〇.05,t檢定,圖10 )。此結果顯示具有血糖値抑制效果之本發明品,比不考 慮血糖値上升抑制之營養組成物,能攝取更多的能量或營 養素。本結果,於不考慮血糖値上升抑制之營養組成物之 攝取時,相對於具有血糖値上升疑慮而每次僅能攝取225 毫升’本發明品爲顯示可攝取約1.3倍之3 00毫升者。爲 血糖値不會上升之營養均衡優異之營養組成物的本發明品 之攝取量增加,有助於維持、改善糖尿病患者之營養狀態 。其中’對於營養狀態惡化之糖尿病患者,本發明品可投 與營養均衡良好之高卡路里而爲非常有用之組成。 -43- 200942181 【圖式簡單說明】 圖1爲用以確認異麥芽酮糖之效果,而調製營養組成 物A〜C,將該等經口投與後之血糖値推移之圖。 圖2爲顯示以實施例1調配之本發明品與營養組成物 A經口投與後之血糖値推移之圖。 圖3爲顯示以實施例2調配之本發明品與營養組成物 D經口投與後之血糖値推移之圖。 圖4爲顯示營養組成物E及營養組成物F長期經口投 與後之血紅蛋白Ale之變化率之圖。 圖4爲顯示實施例1之粉末狀本發明品及營養組成物 A長期經口投與後之血紅蛋白Ale之變化率之圖。 圖6爲顯示於實施例1調製之本發明品與購得Τα之 經管投與中之血糖値之圖。 圖7爲顯示於實施例1調製之本發明品與購得Τα之 經管投與後之氮產出之圖。 圖8爲顯示於實施例1調製之本發明品與購得Τα之 經管投與後之體重推移之圖。 圖9爲顯示於實施例1調製之本發明品與購得Τα2 經口攝取後之體重增加率之圖。 圖10爲顯示於實施例1調製之本發明品(8kcal/kg B.W.)及營養組成物A(6kcal/kg B.W.)經Q投與後之血 糖値推移之圖。 -44-Experiments were performed using GK mice (25-week-old male, Sakamoto SLC (stock)) in a diabetic model rat with abnormal sugar tolerance. For the fasted 18-hour rat, the nutritional composition of the present invention formulated in Example 1 was administered at 8 kcal/kg, and the nutritional composition A of undistributed free isoleucine and isomaltulose was administered at 6 kcal/kg. And measuring blood sugar (measurement machine: Fuji DRYCHEM 5 5 00 > Fujifilm (share) system). The blood glucose sputum after administration of the present invention showed the same blood glucose shift irrespective of the amount of the nutritional composition A (p = 〇.05, t test, Fig. 10). This result shows that the present invention having a blood sugar sputum inhibitory effect can absorb more energy or nutrients than a nutrient composition which does not take into consideration the increase in blood sugar sputum. In the case of the ingestion of the nutritional composition which is not inhibited by the increase in the blood sugar level, only 225 ml of the present invention can be ingested at a time, which is about 1.3 times that of the present invention. The increase in the intake of the present invention, which is a nutrient composition excellent in nutritional balance, which does not increase blood sugar levels, contributes to maintaining and improving the nutritional status of diabetic patients. Among them, in the case of a diabetic patient whose nutritional status is deteriorated, the present invention is a very useful composition which can be administered with a well-balanced high calorie. -43- 200942181 [Simplified Schematic Description] Fig. 1 is a diagram showing the effect of the isomaltulose to prepare the nutritional compositions A to C, and the blood glucose levels after oral administration. Fig. 2 is a graph showing the transition of blood glucose after oral administration of the present invention and the nutritional composition A formulated in Example 1. Fig. 3 is a graph showing changes in blood glucose after oral administration of the present invention and the nutritional composition D formulated in Example 2. Fig. 4 is a graph showing the rate of change of hemoglobin Ale after long-term oral administration of the nutritional composition E and the nutritional composition F. Fig. 4 is a graph showing the rate of change of hemoglobin Ale after long-term oral administration of the powdery inventive product of Example 1 and nutritional composition A. Fig. 6 is a graph showing blood glucose levels in the administration of the present invention prepared in Example 1 and the purchased Τα. Fig. 7 is a graph showing the nitrogen output of the inventive product prepared in Example 1 and the purchased Τα. Fig. 8 is a graph showing the change in body weight after administration of the inventive product prepared in Example 1 and the purchased Τα. Fig. 9 is a graph showing the rate of increase in body weight of the inventive product prepared in Example 1 after oral ingestion of the commercially available Τα2. Fig. 10 is a graph showing the transition of blood glucose after administration of the present invention (8 kcal/kg B.W.) and nutritional composition A (6 kcal/kg B.W.) prepared in Example 1. -44-

Claims (1)

200942181 七、申請專利範圍 1. 一種高血糖抑制用營養組成物,其爲含有氮源、 脂質及糖質之營養組成物,其特徵爲氮源中含有游離異亮 胺酸及/或游離亮胺酸,脂質含有中鏈脂肪酸三酸甘油酯 ,糖質含有異麥芽酮糖(palatinose)及/或海藻糖》 2. 如申請專利範圍第1項之營養組成物,其相當於 每lOOkcal之營養組成物含有0.05~2.0克之游離異亮胺酸 及/或游離亮胺酸。 3-如申請專利範圍第1或2項之營養組成物,其中 構成中鏈脂肪酸三酸甘油酯之脂肪酸殘基之碳數爲6~12。 4.如申請專利範圍第3項之營養組成物,其中構成 中鏈脂肪酸三酸甘油酯之脂肪酸殘基之碳數爲8及/或10 5.如申請專利範圍第1~4項中任一項之營養組成物 ,其中中鏈脂肪酸三酸甘油酯之含量爲總脂肪中之5~75200942181 VII. Patent application scope 1. A nutritional composition for suppressing hyperglycemia, which is a nutrient composition containing a nitrogen source, a lipid and a saccharide, characterized in that the nitrogen source contains free isoleucine and/or free bright amine. Acid, lipid containing medium chain fatty acid triglyceride, saccharide containing palatinose and/or trehalose 2. The nutritional composition of claim 1 is equivalent to nutrition per 100 kcal The composition contains 0.05 to 2.0 grams of free isoleucine and/or free leucine. The nutritional composition according to claim 1 or 2, wherein the fatty acid residue constituting the medium chain fatty acid triglyceride has a carbon number of 6 to 12. 4. The nutritional composition of claim 3, wherein the carbon number of the fatty acid residue constituting the medium chain fatty acid triglyceride is 8 and/or 10 5. As in any of claims 1 to 4 of the patent application scope The nutritional composition of the item, wherein the content of the medium chain fatty acid triglyceride is 5 to 75 in the total fat 6.如申請專利範圍第1~5項中任一項之營養組成物 ,其中糖質中之異麥芽酮糖及/或海藻糖之含量爲50質量 %以下。 7. 如申請專利範圍第1~6項中任一項之營養組成物 ,其中異麥芽酮糖及/或海藻糖相對於游離異亮胺酸及/或 游離亮胺酸之質量比爲1/75〜4/1。 8. 如申請專利範圍第1〜7項中任一項之營養組成物 ,其係與胰島素分泌刺激物質倂用。 -45- 200942181 9.如申請專利範圍第1〜8項中任—項之營養組成物 ,其中該營養組成物之形態爲粉末、顆粒狀、板狀、桿狀 、凝膠狀或液狀。 1 〇 ·如申請專利範圍第1 ~ 8項中任一項之營養組成物 ,其中該營養組成物爲經腸用之流體食用形態。 11. 如申請專利範圍第1〜8項中任一項之營養組成物 ,其中該營養組成物係收容於容器中。 12. 如申請專利範圍第11項之營養組成物,其中將 3 00〜600毫升之營養組成物收容於容器中。 13. 如申請專利範圍第1~12項中任一項之營養組成 物,其係透過使用於抑制源自光、空氣、加熱而導致內容 物之氧化或分解之經步驟控制的製造步驟而製造營養組成 物,且係收容於儲存時可抑制源自氧或氧及光而導致劣化 之包裝材料所構成之容器中。 14. 如申請專利範圍第1〜13項中任一項之營養組成 物,其中該營養組成物之卡路里濃度爲1.5 kcal/ml以上。 15. 如申請專利範圍第1〜14項中任一項之營養組成 物,其中該營養組成物之黏度爲5 00mPa · s以上。 16. 如申請專利範圍第1~15項中任一項之營養組成 物,其係用於促進褥瘡、創傷之預防及治療。 17. 如申請專利範圍第1〜16項中任一項之營養組成 物,其係用於手術前後之營養管理。 18. 如申請專利範圍第1〜17項中任一項之營養組成 物,其係用於減輕或防止高血糖所引起之氧化壓力。 -46- 200942181 19.如申請專利範圍第1~18項中任一項之營養組成 物,其每lOOkcal含有35〜155毫克鉀、20~100毫克磷而 供伴隨有高血糖之腎臟病患者使用。6. The nutritional composition according to any one of claims 1 to 5, wherein the content of isomaltulose and/or trehalose in the saccharide is 50% by mass or less. 7. The nutritional composition according to any one of claims 1 to 6, wherein the mass ratio of isomaltulose and/or trehalose to free isoleucine and/or free leucine is 1 /75~4/1. 8. The nutritional composition according to any one of claims 1 to 7, which is used in combination with an insulin secretion stimulating substance. The nutrient composition of any one of the first to eighth aspects of the invention, wherein the nutrient composition is in the form of a powder, a granule, a plate, a rod, a gel or a liquid. 1 〇 The nutritional composition according to any one of claims 1 to 8, wherein the nutritional composition is in the form of a fluid for enteral use. 11. The nutritional composition according to any one of claims 1 to 8, wherein the nutritional composition is contained in a container. 12. The nutritional composition of claim 11, wherein the nutritional composition of 300 to 600 ml is contained in a container. 13. The nutritional composition according to any one of claims 1 to 12, which is produced by a step-controlled manufacturing step for suppressing oxidation or decomposition of a content by light, air or heating. The nutrient composition is contained in a container composed of a packaging material capable of suppressing deterioration due to oxygen, oxygen, and light during storage. 14. The nutritional composition according to any one of claims 1 to 13, wherein the nutritional composition has a calorie concentration of 1.5 kcal/ml or more. 15. The nutritional composition according to any one of claims 1 to 14, wherein the nutritional composition has a viscosity of 500 mPa·s or more. 16. A nutritional composition according to any one of claims 1 to 15 for use in the prevention and treatment of acne, wounds. 17. The nutritional composition according to any one of claims 1 to 16, which is used for nutritional management before and after surgery. 18. The nutritional composition according to any one of claims 1 to 17, which is for use in reducing or preventing oxidative stress caused by hyperglycemia. -46- 200942181 19. The nutritional composition according to any one of claims 1 to 18, which contains 35 to 155 mg of potassium and 20 to 100 mg of phosphorus per 100 kcal for use by kidney patients with hyperglycemia . -47--47-
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