TW201208583A - Nutritional compositions - Google Patents
Nutritional compositions Download PDFInfo
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- TW201208583A TW201208583A TW100118668A TW100118668A TW201208583A TW 201208583 A TW201208583 A TW 201208583A TW 100118668 A TW100118668 A TW 100118668A TW 100118668 A TW100118668 A TW 100118668A TW 201208583 A TW201208583 A TW 201208583A
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- TW
- Taiwan
- Prior art keywords
- glucan
- nutritional composition
- source
- milk
- nutritional
- Prior art date
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- 235000016709 nutrition Nutrition 0.000 title claims abstract description 118
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- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019143 vitamin K2 Nutrition 0.000 description 1
- 239000011728 vitamin K2 Substances 0.000 description 1
- 235000012711 vitamin K3 Nutrition 0.000 description 1
- 239000011652 vitamin K3 Substances 0.000 description 1
- 235000019195 vitamin supplement Nutrition 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 235000008939 whole milk Nutrition 0.000 description 1
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- 210000005253 yeast cell Anatomy 0.000 description 1
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Abstract
Description
201208583 六、發明說明: 【發明所屬之技術領域】 本揭露內容關於用於兒科個體之營養組成物,諸如以 乳爲基底之營養組成物,諸如嬰兒配方及兒童營養產品。 再者,本揭露內容進一步關於供增進兒科個體之免疫功能 的方法,其包含投予兒科個體有效量之葡聚醣,尤其 是於以乳爲基底之基質中。 【先前技術】 嬰兒及兒童接觸各種病原體,因此傳染病的發病高峰 在生命首4年。新生兒一般都受到出生前通過胎盤所接受 之抗體保護,接著在出生後透過母乳中之抗體保護;但新 生兒沒有成熟的免疫系統,往往不能負擔有效之免疫反應 。事實上,在細胞層級中,嬰兒在必要時集中白血球之能 力是降低的anrf G^neco/ogic Care,201208583 VI. Description of the Invention: [Technical Field of the Invention] The present disclosure relates to nutritional compositions for pediatric individuals, such as milk-based nutritional compositions such as infant formulas and child nutrition products. Furthermore, the present disclosure further relates to a method for enhancing the immune function of a pediatric individual comprising administering to a pediatric individual an effective amount of dextran, especially in a milk-based matrix. [Prior Art] Infants and children are exposed to various pathogens, so the peak incidence of infectious diseases is in the first 4 years of life. Newborns are generally protected by antibodies that are received through the placenta before birth and then protected by antibodies in breast milk after birth; however, newborns do not have a mature immune system and often cannot afford an effective immune response. In fact, at the cell level, the ability of the baby to concentrate white blood cells when necessary is reduced by anrf G^neco/ogic Care,
Jewe/i,Za/ar, j&ch’iion, 470)。因此,新生兒是 無法限制入侵的病原體,因爲其發炎及免疫機制整體功能 低下。如此,改善嬰兒及/或兒童之免疫反應將提供減少 感染發病率及維持或改善兒科個體整體健康的機會。 嬰兒腸道菌叢在出生後的最初幾個星期內迅速建立, 其對嬰兒的免疫系統有很大的影響。此腸道菌落的性質最 初係由宿主早期接觸環境微生物來源及嬰兒的健康所決定 。該嬰兒是餵食母乳或配方奶對腸道菌叢亦有很大的影響 -5- 201208583 人類母乳中包含多種可能有助於嬰兒腸道菌叢生長和 族群的因子。在這些因子中,有一種具有超過130種不同 寡醣之複雜混合物在過渡和成熟乳中之含量達到8-1 2克/升 0 Kunz, et a l., Oligosaccharides in Human Milk: Structure, Functional, and Metabolic Aspects, Ann. Rev. Nutr. 20: 699-722 (2000)。這些寡醣在上消化道對酶催化分解具有 抗性且到達結腸時仍保持完整,然後在結腸作爲結腸醱酵 之受質。 由於牛奶及市售之以牛乳爲底質之嬰兒配方僅提供微 量寡醣,可使用益菌素作爲餵食配方奶之嬰兒的飲食補充 品。益菌素被定義爲不易消化之食物成分,其可藉由選擇 性地刺激結腸中可改良宿主健康之一或有限之數目的細胞 之生長及/或活性而有利地影響宿主。. 由於膳食成分之間及腸道生態系統之菌叢間的二種交 互作用均非常複雜,當益菌素和寡醣這類成分以補充品之 形式提供在餵食配方之嬰兒的飲食中時,嬰兒配方中之基 質或其他兒科營養補充品可能會影響其有效性。此外,配 方基質中所使用之蛋白質的類型和濃度亦可調節腸道菌叢 。 (Boehm et a 1., Structural and Functional Aspects ofJewe/i, Za/ar, j&ch’iion, 470). Therefore, neonates are unable to limit the pathogens of invasion because of their inflammation and overall poor immune function. As such, improving the immune response of infants and/or children will provide an opportunity to reduce the incidence of infection and maintain or improve the overall health of the pediatric individual. Infant gut flora is rapidly established during the first few weeks of life and has a large impact on the baby's immune system. The nature of this intestinal colony is primarily determined by the host's early exposure to environmental microbial sources and the health of the infant. The baby is fed with breast milk or formula and has a great influence on the intestinal flora. -5 - 201208583 Human breast milk contains a variety of factors that may contribute to the growth and ethnicity of the infant's intestinal flora. Among these factors, a complex mixture of more than 130 different oligosaccharides has a content of 8-1 2 g/l in transition and mature milk. Kunz, et al., Oligosaccharides in Human Milk: Structure, Functional, And Metabolic Aspects, Ann. Rev. Nutr. 20: 699-722 (2000). These oligosaccharides are resistant to enzymatic breakdown in the upper digestive tract and remain intact when they reach the colon, and then serve as a substrate for colonic fermentation. Since milk and commercially available milk-based infant formulas only provide micro-oligosaccharides, prebiotics can be used as a dietary supplement for infants fed formula. Prebiotics are defined as non-digestible food ingredients that can beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of cells in the colon that can improve host health. Because the two interactions between dietary components and the flora of the gut ecosystem are very complex, when ingredients such as prebiotics and oligosaccharides are provided as supplements in the diet of infants fed formulas, Substrates or other pediatric nutritional supplements in infant formula may affect their effectiveness. In addition, the type and concentration of the protein used in the formulation matrix can also regulate the intestinal flora. (Boehm et a 1., Structural and Functional Aspects of
Prebiotics Used in Infant Nutrition, The. Journal of Nutrition )。由於人類母乳爲嬰兒營養之較佳來源,能有 效地補充作爲功能性食品成分之益菌素及寡醣以提供模擬 人類母乳之品質的配方基質是有需要的。 因此,提供用於兒科個體之包含能刺激免疫系統的營 -6 - 201208583 品係提供 此外,提 物以增強 係針對一 底之營養 葡聚醣之 -1,3-葡聚 .源爲β -該營養組 長鏈多不 益菌素組 益菌素組 一段延長 物可包括 快之醱酵 此,該寡 系中,該 組成物, 養補充品之營養組成物將是有利的,其中該補充 於不會抑制該補充品之有益作用的配方基質中。 供經由投予兒科個體可被其良好耐受之營養組成 及改善兒科個體之免疫反應的方法將是有利的。 【發明內容】 因此,簡單地說,於一體系中,本揭露內容 種用於兒科個體之營養組成物,尤其是以乳爲基 組成物,其包含脂質或脂肪、蛋白質來源及点-來源。於某些體系中,該/3-葡聚醣之來源爲召 醣之來源。於其他體系中,該/3-葡聚醣之抹 1,3;1,6-葡聚醣之來源。此外,於一些體系中, 成物進一步包含長鏈多不飽和脂肪酸之來源,該 飽和脂肪酸包括二十二碳六烯酸(DHA )及/或 成物,該益菌素組成物包括多種寡醣,如此,該 成物之總體醱酵速率變化形廓可在人體腸道中於 的時間內提供增加之有益細菌叢。該益菌素組成 多種寡醣,如此,該寡醣中至少有一種具有相當 速率且該寡醣之一具有相當緩慢之醱酵速率,據 醣之組合可提供有利之整體醱酵速率。於某些體 益菌素包含半乳糖-寡醣與聚右旋糖之組合。 於一些體系中,本揭露內容係針對一種營養 其包含: a.至多約7克/100千卡之脂肪或脂質,較佳爲約3至 201208583 約7克/100千卡之脂肪或脂質; b·至多約5克/100千卡之蛋白質來源,較佳爲約1至 約5克/100千卡之蛋白質來源; c. 約5至約100毫克/100千卡之包括DHA的長鏈多不飽 和脂肪酸來源,其,較佳爲約10至約50毫克/100千卡之包 括DHA的長鏈多不飽和脂肪酸來源; d. 約1 ·〇至約1 〇·〇克/升(較佳爲約2.0克/升至約 8.0 克/升)之益菌素組成物,該益菌素組成物包含數種寡醣 ’如此’其總體醱酵率變化形廓可在人體腸道中於一段延 長的時間內提供增加之有益細菌叢.;及 e. /3 -葡聚醣之來源。 於某些體系中,該營養組成物包含以乳爲基底之基質》 再於另一體系中,本發明係針對一種具有改善之消化 率的營養組成物,該組成物包含以乳爲基底之基質、脂質 或脂肪、蛋白質來源、包括二十二碳六烯酸(DHA )之長 鏈多不飽和脂肪酸的來源、包含至少20 %之寡醣混合物( 其包含聚右旋糖及半乳-寡醣)的益菌素組成物,以及/3-1,3-葡聚醣之來源。 再於另一體系中,本揭露內容教示經由投予兒科個體 在以乳爲基底之基質中之/5 -葡聚醣來增強兒科個體之免 疫系統功能的方法。 應理解的是,前文之一般描述及下文之詳細描述係呈 現本揭露內容之體系且旨在提供用於了解本揭露內容所主 張之性質和特性的槪觀或框架。該描述係用於解釋所主張 -8 - 201208583 之標的物的原則和操作。熟習本技藝之人士在閱讀以下之 揭露內容後將清楚明白本揭露內容之其他和進一步的特性 及優點。 發明詳細說明 現在將對本揭露內容之體系作出詳細之參考內容,下 文中列出其中之一或多個實例。各實例係用於解釋本揭露 內容之營養組成物而非用於限制之。事實上,熟習本技藝 之人士將清楚明白可對本揭露內容之教示做不同的修改和 變化,而不背離本揭露內容之範圍或精神。例如:所說明 或描述之作爲一種體系之一部分的特性可與另一種體系一 起使用,以再產生另一種體系。 因此,本揭露內容係欲涵蓋在附屬之申請專利範圍及 彼等之同等項內之範圍內的這類修改和變動。本揭露內容 之其他目標、特點及觀點揭示於下文中之詳細描述,或可 從其中顯明。熟習本技藝之人士需理解本討論內容僅爲典 型體系之描述,而非旨在限制本揭露內容之更廣泛的面向Prebiotics Used in Infant Nutrition, The. Journal of Nutrition). Since human breast milk is a better source of nutrition for infants, it is desirable to be able to effectively supplement the probiotics and oligosaccharides as functional food ingredients to provide a formulation matrix that mimics the quality of human breast milk. Therefore, it is provided for the pediatric individual to contain the stimulating immune system bat-6 - 201208583 strain. In addition, the extract is enhanced to the lignin-based glucoside-1,3-glucan. The source is β- The probiotic group of the long-chain multi-benexin group of the probiotic group may include a fast fermentation, in which the nutrient composition of the composition, the supplement may be advantageous, wherein the supplement is It does not inhibit the beneficial effects of the supplement in the formulation matrix. It would be advantageous to provide a nutritional composition that is well tolerated by the pediatric individual and to improve the immune response of the pediatric individual. SUMMARY OF THE INVENTION Accordingly, in one embodiment, the present disclosure is directed to a nutritional composition for a pediatric individual, particularly a milk-based composition comprising a lipid or fat, a protein source, and a point-source. In some systems, the source of the /3-glucan is the source of the sugar. In other systems, the source of the /3-glucan 1,3; 1,6-glucan. Furthermore, in some systems, the product further comprises a source of a long chain polyunsaturated fatty acid comprising docosahexaenoic acid (DHA) and/or a composition comprising a plurality of oligosaccharides Thus, the overall fermentation rate profile of the product provides an increased beneficial bacterial plexus within the time of the human intestinal tract. The prebiotic comprises a plurality of oligosaccharides such that at least one of the oligosaccharides has a comparable rate and one of the oligosaccharides has a relatively slow rate of fermentation, and the combination of sugars provides a favorable overall fermentation rate. Certain probiotics comprise a combination of galactose-oligosaccharide and polydextrose. In some systems, the present disclosure is directed to a nutrient comprising: a. up to about 7 grams per 100 kilocalories of fat or lipid, preferably from about 3 to 201208583 about 7 grams per 100 kilocalories of fat or lipid; a protein source of up to about 5 grams per 100 kilocalories, preferably from about 1 to about 5 grams per 100 kilocalories; c. from about 5 to about 100 milligrams per 100 kilocalories of long chain including DHA a source of saturated fatty acids, preferably from about 10 to about 50 mg/100 kcal of a long chain polyunsaturated fatty acid source comprising DHA; d. from about 1 〇 to about 1 〇·〇克/liter (preferably From about 2.0 g/L to about 8.0 g/L of the probiotic composition, the probiotic composition contains several oligosaccharides 'so that its overall fermentation rate profile can be extended in the human intestinal tract Provides increased beneficial bacterial flora within the time; and e. /3 - the source of glucan. In some systems, the nutritional composition comprises a milk-based substrate. In another system, the present invention is directed to a nutritional composition having improved digestibility, the composition comprising a milk-based substrate , a source of lipids or fats, a source of protein, a long chain polyunsaturated fatty acid comprising docosahexaenoic acid (DHA), a mixture comprising at least 20% of oligosaccharides comprising polydextrose and galacto-oligosaccharides a probiotic composition, and a source of /3-1,3-glucan. In yet another system, the present disclosure teaches a method of enhancing the immune system function of a pediatric individual by administering a pediatric individual's /5-glucan in a milk-based matrix. It is to be understood that the foregoing general description and the following description of the embodiments of the present invention are intended to provide an understanding of the nature and characteristics of the claimed subject matter. This description is intended to explain the principles and operation of the subject matter claimed in -8 - 201208583. Other and further features and advantages of the present disclosure will become apparent to those skilled in the <RTIgt; DETAILED DESCRIPTION OF THE INVENTION A detailed reference will now be made to the system of the present disclosure, one or more of which are listed below. Each example is used to explain the nutritional composition of the present disclosure and is not intended to be limiting. In fact, it will be apparent to those skilled in the art that various modifications and changes can be made to the teachings of the present disclosure without departing from the scope or spirit of the disclosure. For example, the features described or described as part of one system can be used with another system to create another system. Therefore, the disclosure is intended to cover such modifications and variations within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the disclosure are disclosed in the following detailed description. Those skilled in the art will understand that this discussion is only a description of a typical system and is not intended to limit the broader scope of the disclosure.
P “營養組成物”係指滿足至少一部分之個體營養需求的 物質或配方。 “兒科個體”係指小於13歲之人類。於一些體系中,兒 科個體係指小於8歲之人類個體。 “嬰兒”意指年齡在出生到不超過約一歲之範圍內的個 體,包括矯正年齡從0至約12個月的嬰兒。嬰兒一詞包括 -9 - 201208583 低出生體重嬰兒、極低出生體重嬰兒以及早產兒。“矯正 年齡”一詞係指嬰兒之實足年齡減去嬰兒早產的時間量。 因此,若嬰兒已到足月則矯正年齡爲該嬰兒之年齡。 “兒童”意指年齡在約12個月至約13歲之範圍內的個體 。於一些體系中,兒童爲一至十二歲之間的個體。於其他 體系中,“兒童(children ) ”或“兒童(child ) ”係指二、 三、四、五或六歲之個體。於其他體系中,“兒童( children) ”或“兒童(child) ”等詞係指年齡在約12個月至 約13歲之間的任何範圍內。 “兒童之營養產品”係指滿足至少一部分之兒童營養需 求的組成物。 “嬰兒配方”係指滿足至少一部分之嬰兒營養需求的組 成物。在美國,嬰兒配方之內含物係由21 C.F.R.之100、 106和107條款中提出之聯邦法規所規定。這些條款規定巨 營養素、維生素、礦物質及其他成分之含量以盡力模擬人 類母乳之營養及其他性質。 “營養完全型”係指可作爲唯一營養來源之組成物’其 將提供大致上所有每日需要量之維生素、礦物質和/或微 量元素加上蛋白質、碳水化合物及脂質。 “益生菌”係指具有低致病性或無致病性,能發揮對宿 主之健康有益之作用的微生物。 “益菌素”係指一種不易消化之食物成分’其經由選擇 性地刺激消化道中可改良宿主健康之一或有限數目之細菌 的生長及/或活性而有利地影響宿主。 -10- 201208583 “有效量”係指在個體中提供刺激性免疫效果的量。 “;5 -葡聚醣”係指所有/3 -葡聚醣,包括/3 -1,3-葡聚醣 及/3-1,3;1,6-葡聚醣,因其各爲一種葡聚醣之特定類型 。此外,/3-1,3;1,6-葡聚醣爲一種/3-1,3-葡聚醣之類型。 因此,“/3-1,3-葡聚醣”一詞包括;8-1,3;1,6-葡聚醣。 “以乳爲基底之基質”係指包含至少一種從哺乳動物之 乳腺中吸取或萃取之組分的介質。於一些體系中,所揭露 之營養組成物的以乳爲基底之基質包含源自馴養之有蹄類 哺乳動物、反芻動物、人類或彼等之任何組合的乳汁組分 。此外,於一些體系中,該以乳爲基底之基質包含酪蛋白 、乳清蛋白、乳糖或彼等之任何組合。此外,本揭露內容 之以乳爲基底之基質可能包含任何本技藝已知之源自乳或 以乳爲基底之產品。 於一些體系中,本揭露內容描述一種用於個體之營養 組成物,其包含以乳爲基底之基質、碳水化合物之來源、 脂質來源、蛋白質來源及/3-葡聚醣(尤其是/3-1,3;1,6-葡 聚醣)之來源,其中該/3-葡聚醣及該以乳爲基底之基質 提供協同效果,從而刺激兒科個體之免疫系統。 本揭露內容亦描述增強兒科個體之免疫功能的方法, 其包含投服有效量之營養組成物,該營養組成物包含碳水 化合物來源、脂質來源、蛋白質來源及yS-葡聚醣來源。 用於實行本發明之合適的脂肪或脂質來源可包含任何 本技藝中已知之脂質來源,包括,但不限於動物來源,例 如:乳脂、奶油,奶油脂肪、蛋黃脂質;海產來源,諸如 -11 - 201208583 魚油、海產物油、單細胞油;蔬菜及植物油,如玉米油、 菜籽油、葵花子油' 大豆油、棕櫚油精、椰子油、高油酸 葵花籽油、月見草油、菜籽油、橄欖油、亞麻籽(亞麻子 )油、棉籽油、高油酸紅花籽油、棕櫚硬脂、大豆卵磷脂 、棕櫚仁油、小麥胚芽油、中鏈三酸甘油酯。 用於實行本發明之牛乳蛋白之來源包括,但不限於牛 乳蛋白粉、牛乳蛋白濃縮物、牛乳蛋白分離物、脫脂牛乳 固體、脫脂牛乳、脫脂奶粉、乳清蛋白、乳清蛋白分離物 、乳清蛋白濃縮物、甜乳清、酸乳清、酪蛋白、酸性酪蛋 白、酪蛋白酸鹽(如:酪蛋白酸鈉、酪蛋白酸鈉鈣、酪蛋 白酸鈣)及彼等之任意組合。 於一體系中,該蛋白質係以完整的蛋白質形式提供。 於其他體系中,該蛋白質係以完整之蛋白質及經部分水解 之蛋白(水解程度係介於約4%和1 0%之間)二者之組合的 方式提供。於某些其他體系中,該蛋白質被更徹底地水解 。再於另一體系中,該蛋白質來源中可補充含有麩醯胺之 肽類。 於本發明之特殊體系中,該蛋白質來源之乳清:酪蛋 白比係類似於人類母乳中所發現者。於一體系中,該蛋白 質來源包含約40%至約80%之乳清蛋白,以及約20%至約 60%之酪蛋白。 於本揭露內容之某些體系中,該營養組成物可能包含 一或多種益生菌。此體系中可接受本技藝已知之任何益生 菌’惟其該益生菌可取得所欲之結果。於特殊之體系中, -12- 201208583 該益生菌可選自任何乳酸菌種、鼠李糖乳桿菌GG、雙歧 桿菌種、長雙歧桿菌及動物雙歧桿菌乳亞種BB-12或彼等 之組合。 若組成物中包含益生菌,該益生菌之量可在每天每公 斤體重約1〇4至約101°個菌落形成單位(cfu )之間變化。 於另一體系中,該益生菌之量可能在每天每公斤體重約 106至約109 cfu之間變化。再於另一體系中,該益生菌之 量可爲每天每公斤體重至少約106 cfu。 於一體系中,該益生菌可能爲可存活或非存活的。此 處所使用之“存活的”一詞係指活的微生物。“非存活的”或 “非存活之益生菌”係指非存活之益生菌微生物、其細胞組 分及/或代謝物。這類非存活之益生菌可能已經熱滅殺或 以其他方式滅活,但其保留有利地影響宿主之健康的能力 。可用於本發明之益生菌可能爲天然產生、人工合成或透 過有機體之基因操縱而硏發者,無論這類新來源是否爲目 前已知的或後來開發的。 該營養組成物包含一或多種益菌素。此處所使用之“ 益菌素”一詞係指在宿主上施加健康益處之難以消化的食 物成分。這類健康益處可包括,但不限於選擇性地刺激一 或有限數目之有益的腸道細菌之增長及/或活性、刺激攝 入之益生菌微生物增長及/或活性、選擇性地減少腸道致 病菌及有利地影響腸道短鏈脂肪酸之變化形廓。這類益菌 素可能爲天然產生、人工合成或透過基因操縱而硏發之有 機體和/或植物,無論這類新來源是否爲目前已知的或後 -13- 201208583 來開發的。用於本發明之益菌素可包括寡醣類、多醣類及 其他含有果糖、木糖、大豆、半乳糖、葡萄糖及甘露糖的 益菌素。更具體地說,可用於本發明之益菌素可包括聚右 旋糖、聚右旋糖粉、乳果糖 '乳蔗糖、棉子糖、葡萄寡醣 、菊糖、果寡醣、異麥芽寡醣、大豆寡醣、乳蔗糖、木寡 醣、殻寡醣、甘露寡醣、阿拉伯寡醣、唾液寡醣、岩藻寡 醣、半乳寡醣及龍膽寡醣。 於一體系中,存在於該營養組成物中之益菌素的總量 可爲該組成物之約1.0克/升至約10.0克/升。更佳地,存在 於該營養組成物中之益菌素的總量可爲該組成物之約2.0 克/升至約8.0克/升。至少20%之該益菌素可包含半乳寡醣 與聚右旋糖之混合物。於一體系中,該營養組成物中之各 半乳寡醣及聚右旋糖的量可在約1.0克/升至約4.0克/升之 範圍內。 於一體系中,該營養組成物中之半乳寡醣之量可爲約 0.1毫克/100千卡至約1.0毫克/100千卡。於另一體系中, 該營養組成物中之半乳寡醣之量可爲約0.1毫克/100千卡至 約0.5毫克/100千卡。於一體系中,該營養組成物中之聚右 旋糖之量可在約0.1毫克/100千卡至約0.5毫克/100千卡之 範圍內。於另一體系中,該聚右旋糖之量可爲約0.3毫克 /100千卡。於一特殊體系中,半乳寡醣及聚右旋糖係補充 在該營養組成物中,其總量爲至少約〇·2毫克/100千卡且可 爲約0.2毫克/100千卡至約1.5毫克/100千卡。 本發明之營養組成物包含長鏈多不飽和脂肪酸( -14- 201208583 LCPUF As )之來源,該長鏈多不飽和脂肪酸包括二十二碳 六烯酸(DHA )。其他合適之LCPUFAs包括,但不僅限於 α -亞油酸、γ -亞油酸、亞油酸、亞麻酸、二十碳五烯酸( ΕΡΑ )及花生四烯酸(ARA )。 於一體系中,該營養組成物中補充了 DH Α及AR Α二者 。於此體系中,AR A : DHA之重量比可爲約1:3至約9:1。 於本發明之一種體系中,此比例爲釣1:2至約4:1。 較有利地,該營養組成物中之長鏈多不飽和脂肪酸之 量爲至少約5毫克/100千卡,且可在約5毫克/100千卡至約 100毫克/100千卡(更佳爲約10毫克/100千卡至約50毫克 /1〇〇千卡)之間變化。 該營養組成物可使用本技藝已知之標準技術來補充包 含DHA及ARA之油。例如:可以DHA及ARA取代正常存在 於該組成物中之等量的油(諸如高油酸葵花籽油)來將其 添加到該組成物中。另一實例爲可以該包含DH A及ARA之 油類取代等量之通常存在於該不含DH A和AR A之組成物中 的總體脂肪混合物的剩餘部分,以將其添加在該組成物中 〇 若使用時,該DH A和AR A之來源可能爲本技藝中已知 之任何來源,諸如海產油、魚油、單細胞油、蛋黃脂質及 腦脂質。於一些體系中,該DHA和ARA係源於單細胞馬泰 克(Martek)油,DHASCO®或其變體。該DHA和ARA可爲 天然形式,惟其該LCPUFA來源之其餘部分不會對嬰兒造 成任何實質上的有害影響。另外,DHA和ARA可以精製之 -15- 201208583 形式使用。 於本發明之一種體系中,DHA及ARA之來源爲美國專 利案編號5374567; 5550156;及5397591 (其揭露之全部 內容納爲本文之參考)中所教示之單細胞油。然而,本發 明並不僅限於這類油。 如上述,所揭露之營養組成物在其各體系中均包括一 種/5-葡聚醣之來源。葡聚醣爲多醣類,具體地說,爲葡 萄糖之聚合物,其係天然產生且可在細菌、真菌、酵母菌 及植物之細胞壁中找到。乙型-葡聚醣(/5 -葡聚醣)本身 爲葡萄糖聚合物之不同子集,其係由葡萄糖單體鏈所組成 ,該葡萄糖單體鏈係經由yS-型葡萄糖苷鍵連接在一起, 以形成複雜的碳水化合物。 冷-1,3 -葡聚醣爲碳水化合物聚合物之純型,例如:酵 母菌、蘑菇、細菌、藻類或穀物。(Stone BA,Clarke AE. Chemistry and Biology of (1 - 3 ) - B e t a - G 1 ucan s. London: Portland Press Ltd; 1 993 )。該冷-1,3-葡聚醣之化學結構 係取決於該)8-1,3 -葡聚醣之來源。此外,各種物理化學參 數(諸如溶解度、一級結構、分子量及分支)在-1,3-葡 聚醣之生物活性中發揮作用。(Yadomae T.,Structure and biological activities of fungal beta-1 ,3 -glucans. Yakugaku Zasshi. 2000; 120: 413-431) 〇 /3 -1,3-葡聚醣爲帶有或不帶有0 -1,6-葡萄糖側鏈之天 然產生的多醣,其可在多種植物、酵母菌、真菌及細菌之 細胞壁中找到。/9-1,3;1,6-葡聚醣爲那些包含帶有(1,3) -16- 201208583 鏈接之葡萄糖單位的葡聚醣,該具(1,3)鏈接之葡萄糖 單位具有在(1,6)位置處連接之側鏈。yS-l,3;l,6-葡聚醣 爲葡萄糖聚合物之異質群體,這些葡萄糖聚合物分享結構 共通性,包括藉由/3-1,3鍵連接之直鏈葡萄糖單位骨架, 其上具有從此骨架延伸之石-1,6-鏈接之葡萄糖支鏈。雖然 此爲目前描述之/3-葡聚醣類別之基本結構,但可能存在 一些變化。例如,某些酵母菌葡聚醣具有從A ( 1,6) 支鏈分支延伸之額外的/3 (1,3)區,其係,此額外之泠 1,3區進一步爲其各別結構增加複雜性。 源自麵包酵母(釀酒酵母(cerev/hae ))之/3-葡聚醣係由在1和3位置處連接之D -葡萄糖分子 鏈所組成,其具有連接在位置1和6處之葡萄糖側鏈。源自 酵母菌之/3-葡聚醣爲一種不溶性、纖維樣的複合糖,其 一般結構爲具有0-1,3-骨架之直鏈葡萄糖單位,該石-1,3-骨架上穿插著長度通常爲6-8個葡萄糖單位之^ -1,6-側鏈 。更具體地說,源自麵包酵母之/3-葡聚醣爲聚-(1,6)-冷-D-吡喃葡糖基-(1,3) -/S -D-吡喃葡萄糖。 此外,/3-葡聚醣已被發現具有刺激成年人之免疫系 統的能力。事實上,這些多醣類中有多種已顯示出可與單 核細胞、巨噬細胞及嗜中性粒細胞上之Θ -1,3-葡聚醣受體 結合。(Czop,J.K·,& Austen, K.F. (1985). β-glucans activate cellular immunity primarily through macrophages and neutrophils. Properties of glycans that activate the human alternate complement pathway and interact with the -17- 201208583 human monocyte beta g 1 u c a n receptor. J. I m mun o. 135, 3388-3393)。然而,冷-葡聚醣不曾被鑑定爲可提供本揭 露內容之益處且可投予兒科個體的物質。 事實上,眾所周知,嬰兒腸道菌叢之發展不如成人。 雖然成人之菌叢係由超過1〇13個微生物及接近50 0種菌種所 組成,嬰兒之腸道菌叢僅包含那些微生物之一部分(無論 是絕對數量及物種之多樣性)。由於嬰兒或兒童與成人腸 道之間的細菌叢及物種有極大的不同,不能假設對成年人 有益之益菌素物質亦可對嬰兒和/或兒童有所助益。 如上述,葡聚醣爲一種多醣,其屬於一組被描述爲生 物防禦修飾劑之生理活性化合物。/3-1,3;1,6-葡聚醣爲裝 備免疫監督之多醣部分,當其係以本揭露內容之營養組成 物的一部分投服時,其可經由刺激免疫功能來減少兒童或 嬰兒體內之與微生物有關的疾病。此外,葡聚醣可被 良好耐受且不會在兒科個體中產生或引起過多的氣體、腹 部膨脹、胃氣脹或腹瀉。當將/3-葡聚醣與以乳爲基底之 基質同時投服以提供協同、刺激性免疫效果時,A -葡聚 醣作爲免疫系統刺激劑之效力先前並未曾得到證實。 於一些體系中,本揭露內容之營養組成物包含;S-葡 聚醣與以乳爲基底之基質,其中當該兩種成分之組合被納 入營養組成物時,其可提供協同效果。由此產生之營養組 成物對個體之呼吸爆發能力具有刺激作用。更具體地說, 於一些體系中,沒-1,3;1,6-葡聚醣與以乳爲基底之基質的 組合提供增加個體中之中性粒細胞數的效果。 -18- 201208583 當接觸到某些刺激時,吞噬細胞(包括中性粒細胞、 嗜酸性粒細胞及單核吞噬細胞)大大地增加其葡萄糖及氧 氣消耗並開始在一系列稱爲“呼吸爆發”的變化中製造大量 超氧化物(〇2 )及過氧化氫(H2〇2 )。該由呼吸爆發產生 之包含氧氣的化合物在稱爲氧依賴性胞內減殺的過程中殺 死入侵的細菌或病原體。因此,刺激個體中之呼吸爆發可 增強個體之免疫系統。 爲了證明此效果,可在體內實驗中評估當有或無以乳 爲基底之配方存在時/3-葡聚醣之生物活性。可用於實驗 之一種以乳爲基底之配方爲市售之配方Enfagrow® (其可 從美國印第安那州埃文斯維爾,美贊臣公司(Mead Johnson & Company)取得)。/3-葡聚醋可包含 Wellmune WGP® (可從美國明尼蘇達州伊根之Biothera公司取得) 〇 在體內硏究方面,單獨餵食老鼠)S-葡聚醣(1毫克/小 鼠/天)或將其與以乳爲基底之配方混合來餵食老鼠,最 多1 0天。同樣以生理鹽水或單獨之以乳爲基底之配方餵食 小鼠來作爲對照。在小鼠模型中,口服/3 -葡聚醣係經由 小腸之培氏斑(Peyer's patches )攝取。由培氏斑攝取之 顆粒隨後進入系統循環,因爲其係經由巨噬細胞運送。接 著,在巨噬細胞中發生降解,葡聚醣破碎成較小的片 段,此可隨後激活中性粒細胞。全部細胞數係以中性粒細 胞呼吸爆發活性、在巨噬細胞和樹突細胞上之活化標記, 以及細胞因子之血清水準來評估。 -19- 201208583 口服給藥後,分離並計算血細胞。該細胞顯示出與 PBS未經治療之小鼠相比較,以配方基質或/3 -葡聚醣治療 之老鼠在第10天時具有顯著較高之中性粒細胞計數。這些 數據暗示沒-葡聚醣及配方基質可刺激中性粒細胞之動員 且可能在抗菌保護性反應中發揮重要作用。與對照組相比 較,單獨之以乳爲基底之配方、單獨之/3-葡聚醣及兩者 之組合顯著增加中性粒細胞之數量》 第】及2圖顯示中性粒細胞之呼吸爆發,其指出/3-葡 聚醣與以乳爲基底之基質間的協同作用,此協同作用顯著 增加中性粒細胞之呼吸爆發。經由對比的方式,單獨之 冷-葡聚醣及單獨之以乳爲基底之配方的呼吸爆發效果僅 稍高於對照組。事實上,葡聚醣與以乳爲基底之配方 的組合對呼吸爆發能力具協同效應使其明顯高於對照組。 此外,第1及2圖說明葡聚醣及以乳爲基底之基質對促 進中性粒細胞之呼吸爆發具有協同作用。 如第3圖所示,與接受單獨之以乳爲基底之配方的小 鼠相比較,以沒-葡聚醣加配方基質治療之小鼠中的IL-6水 準也顯著升高。第3圖中顯示與接受單獨之以乳爲基底之 配方的小鼠相比較,接受單獨之WGP® /3 -葡聚醣以及接受 /3-葡聚醣與以乳爲基底之配方的小鼠中之IL-6明顯上調。 因此,體內硏究證明口服葡聚醣與以乳爲基底之 配方基質可顯著增加周圍血液中之中性粒細胞計數’並促 進中性粒細胞之呼吸爆發活性。事實上,以乳爲基底之配 方基質與^-1,3;1,6-葡聚醣之間在免疫細胞功能(亦即, -20- 201208583 中性粒細胞之氧化爆發)方面具有協同作用。此外,無論 是否有以乳爲基底之基質存在,葡聚醣在體內均能使 IL-6分泌增加。 因此,在用於兒科個體之以乳爲基底之營養組成物( 諸如嬰兒配方或兒童營養組成物)中添加葡聚醣將可 經由增加對入侵病原體之抗性來改善個體之免疫反應,從 而保持或改善整體健康。A -1,3 ;1,6-葡聚醣可誘導先天免 疫系統細胞之反應。換言之,此可激活適應性免疫。因此 ,yS -1,3;1,6-葡聚醣經由增加中性粒細胞計數及加強呼吸 爆發能力來發動宿主免疫系統之能力可增強個體之免疫反 應。 當經口投服時,yS -1,3-葡聚醣(諸如,例如:泠-1,3; 1,6-葡聚醣)並非直接藉由消化系統之代謝過程吸收 。事實上,攝入酵母菌/3-葡聚醣後並未發生顯著之系統 性暴露;然而,小腸培氏斑攝入少量之不溶性Θ -葡聚醣 顆粒,而這些顆粒隨後進入系統循環,因爲其係經由巨噬 細胞運輸。巨噬細胞吞噬/3-葡聚醣後,攝入之/3-葡聚醣 的小片段從巨噬細胞釋出。這些片段發動中性粒細胞及淋 巴細胞,諸如天然殺手(NK )細胞。此外,点-葡聚醣可 以刺激細胞因子的產生,亦可刺激T淋巴細胞(T細胞)。 此/9-葡聚醣之作用機制可連接先天免疫系統之激活與適 應性免疫力之激活。 因此,於一些體系中係使用Θ-1,3-葡聚醣(或者,更 具體地說/3 _1,3; 1,6-葡聚醣)增強免疫系統之功能。例如 -21 - 201208583 :使用/5-1,3;1,6-葡聚醣可增強對感染之抗性及/或降低炎 症反應。於至少一種體系中,本揭露內容係針對用於增強 兒科個體中之免疫系統功能的方法,其包含投予該個體在 以乳爲基底之基質中的/3-1,3;1,6-葡聚醣來源。於另一體 系中,本揭露內容係針對用於增強兒科個體中對感染之抵 抗力的方法,其包含投予該個體在以乳爲基底之基質中的 /9-1,3;1,6-葡聚醣。再於另一體系中,本揭露內容係針對 用於減少兒科個體中由廣譜細菌及病毒病原體引起之感染 的持續時間和嚴重程度之方法,其包含投予該個體在以乳 爲基底之基質中的/9 -葡聚醣。再於另一體系中,本揭露 內容係針對用於減少兒科個體中伴隨這類感染之炎症反應 的方法,其包含投予該兒科個體在以乳爲基底之基質中的 /8 -葡聚醣。 本揭露內容之營養組成物包含/3 -1,3-葡聚醣。於一些 體系中,該;5 -1,3-葡聚醣爲/3-1,3;1,6-葡聚醣。於一些體 系中,該葡聚醣爲全葡聚醣顆粒狀点-葡聚醣、微粒狀 /3-葡聚醣、?〇0-葡聚醣(聚-1,6-冷-0-吡喃葡糖基-1,3-yS-D-吡喃葡萄糖)或彼等之任何混合物。於其他體系中 ,該營養組成物包含θ-1,3;1,6-葡聚醣,其可能以全葡聚 醣顆粒狀、微粒狀或顯微粒子狀/3-葡聚醣顆粒之形式或 彼等之任何組合提供》 本揭露內容之A -葡聚醣爲一種可抵抗上腸道之消化 作用的寡聚物,此意味其被上腸道之消化酶降解之部分極 少。可從其中萃取合適之)3-1,3;1,6-葡聚醣以用於實行本 -22- 201208583 揭露內容的物種之非限制性實例包括釀酒酵母(麵包酵母 )、香廷(Lentinus edodes )(花链(Shitake mushrooms ))、灰樹花{ Grifola frondosa )(舞茸(Maitake mushrooms)) ' 裂福菌(Sc/iizo_p/ii//wm comwwne)、核 盤菌(、Sclerotium glucanicum ,等。於一些體系中,本揭露內容之/3-1,3;1,6 -葡聚醣係 從酵母菌、蘑菇或其它真菌中分離出。於一體系中,該 /5-葡聚醣係源自麵包酵母,更特別的是,自麵包酵母之 細胞壁中取得之;S-葡聚醣。同樣地,微粒沒-1,3;1,6-葡聚 醣可從釀酒酵母之細胞壁分離出。該從酵母細胞壁中萃取 出之具有/3 -1,6-葡聚醣鍵聯的石-1,3-葡聚醣可作爲非特異 性免疫激活劑。於一些體系中,本揭露內容之營養組成物 包含由沒-1,3葡萄醣之長聚合物(其中約3-6%之骨幹葡萄 糖單位擁有/3 -1,6分支)所組成之Θ -葡聚醣。於其他體系 中,該卢·葡聚醣可爲由美國明尼蘇達州伊根(Eagan )市 之Biothera提供之微粒Wellmune WGP® /3 -葡聚醣。於一 些體系中,該營養組成物包含具有至少一個0-1,6 -分支之 不溶性-1,3-葡聚醣。 於一體系中,本揭露內容之營養組成物包含不溶性 召-葡聚醣。一些天然產生之yS-葡聚醣不溶於水且可能是 具有相當高之分子量的非常大之分子。人類無法消化具有 召-葡萄糖苷鍵聯之碳水化合物聚合物。由於人類無法消 化具有/3-葡萄糖苷鍵聯之碳水化合物聚合物,因而小腸 上皮細胞不會吸收並大量暴露於微粒狀酵母菌葡聚醣 -23- 201208583 。然而,經口投服後確實發生一些全身性暴露且係在小腸 培氏斑中受到調節。然後,經由培氏斑吸收之β -葡聚醣 由巨噬細胞運送至網狀內皮系統。於一些體系中,該營養 組成物之/3 ·葡聚醣可能已經酶處理以降低其粒徑或操控 其分子量。 於一些體系中,該營養組成物之/3-葡聚醣係作爲益 菌素,此益菌素不在人類之胃及小腸中消化,大部分保持 完好地進入結腸,其可在此處進行微生物醱酵。於一些體 系中,該營養組成物中之/3 -葡聚醣可能包含水溶性、低 分子量之葡聚醣。此外,於一些體系中,該營養組成 物可能包含經酶處理之葡聚醣。再於其他體系中,該 營養組成物包含全酵母葡聚醣顆粒。 於一些體系中,本揭露內容之營養組成物可能包含 /3-1,3;1,6-葡聚醣作爲用於兒科個體之營養產品(諸如兒 童產品或嬰兒配方)的一部分。於其他體系中,本揭露內 容之營養組成物可能大致上不含乳糖。 於一體系中,存在於該組成物中之yS-葡聚醣的量係 在每100克組成物中含有約〇.〇 10至約0.050克之間。於一些 體系中,每一份之營養組成物包含約10毫克之石-葡聚醣 。於另一體系中’每一份之營養組成物包含約5至約50毫 克之)S-葡聚醣。於其他體系中,該營養組成物包含足以 提供每天約40毫克之/3-葡聚醣的沒-葡聚醣量。於一些體 系中,可在營養組成物中添加沒-葡聚醣,其添加濃度爲 足夠每天遞送給個體目標約38毫克之/3-葡聚醣。該營養 24 - 201208583 組成物可以複數劑量之形式投遞,以達到在一整天中遞送 目標量之yS-葡聚醣給予個體。 於一些體系中,可投予兒科個體本揭露內容之營養組 成物,其投服量爲足夠每天遞送約0.5毫克至約2 00毫克之 冷-葡聚醣量。於另一體系中,該經由該營養組成物投予 兒科個體之沒-葡聚醣的量可在每天約1毫克至約1〇〇毫克 之範圍內。再於另一體系中,該營養組成物可經配製以每 天遞送約20毫克至約50毫克之yS-葡聚醣給予兒科個體。 再於另一體系中,經由該營養組成物投予兒科個體之/3-葡聚醣的量可爲每天約35毫克。 於另一體系中,該兒童產品爲可重構成之粉末形式的 乳替代品,其可每天供應1至3次,且投予兒童之yS-葡聚 醣的量可爲約25至約50毫克/天之冷-葡聚醣。再於另一體 系中係建議兒科個體每天服用3次營養組成物,3次共遞送 約25至約5 0毫克/天之/3 -葡聚醣。 於一體系中,該包含0-1,3;1,6-葡聚醣之營養組成物 係以營養完全型嬰兒配方之形式提供,其含有合適類型及 量之脂質、碳水化合物、蛋白質、維生素及礦物質。於此 體系中,該碳水化合物之量可在約8至約12克/100千卡之 間變化、蛋白質之量可爲約1至約5克/1 00千卡、脂質或脂 肪之量可爲約3至約7克/100千卡且可補充包含約5至約577 毫克/100千卡之召-1,3;1,6-葡聚醣量。 本揭露內容之營養組成物可爲液態、蒸發、濃縮或乾 燥乳形式之以乳爲基底之營養組成物。於一些體系中,該 -25- 201208583 營養組成物亦可能包括非奶類之液體或固體食品、蛋白質 、香料或味道掩蔽劑、甜味劑及維生素或飲食補充品。 於一些體系中,該營養組成物可爲營養完全型,其含 有合適類型及量之脂質、碳水化合物、蛋白質、維生素及 礦物質,以作爲個體之唯一營養來源。於一體系中,該營 養組成物爲兒童營養產品。於另一體系中,該營養組成物 包含嬰兒配方。再於另一體系中,該營養組成物包含營養 完全型嬰兒配方。再於另一體系中,該營養組成物包含營 養完全型兒童營養產品。 該揭露之營養組成物可以本技藝已知之任何形式提供 ’諸如粉末、凝膠、懸浮液、糊狀物、固體、液體、濃縮 液、可重構成之粉狀奶替代品或即時可用之產品。於某些 體系中,該營養組成物可能包含營養補充品、兒童營養產 品、嬰兒配方、人類母乳營養強化劑、成長奶粉或任何其 他經設計用於兒科個體之營養組成物。本揭露內容之營養 組成物,包括,例如:可口服攝入促進健康之物質,包括 ’例如:咀嚼食物、飮料、片劑、膠囊及粉末。本揭露內 容之營養組成物可經標準化成具特定之卡路里含量,其可 以即時可用之產品或濃縮形式提供。 於提供兒童營養產品之體系中,可添加足量之一或多 種維生素和/或礦物質,以供應1至13歲之兒童的每日營養 需求。本技藝之一般技術人士理解1至13歲之兒童對維生 素及礦物質之需求會有所不同。因此,這些體系並不欲限 制特定年齡組之營養組成物,而是提供一個範圍以適用於 -26- 201208583 1至1 3歲之兒童。 於提供兒童營養組成物之體系中,該組成物可選擇性 地包含,但不限於一或多種下列維生素或其衍生物:維生 素B!(硫胺素、硫胺素焦磷酸鹽、TPP、硫胺素三磷酸鹽 、TTP、硫胺素鹽酸鹽、硫胺素單硝酸鹽)、維生素B2 ( 核黃素、黃素單核苷酸、FMN、黃素腺嘌呤二核苷酸、 FAD、乳黃素、卵黃素)、維生素B3(菸酸(niacin )、 薛鹼酸(nicotinic acid)、薛驗醯胺(nicotinamide)、 蔽醯胺(niacinamide)、薛驗醯胺腺嗓玲二核苷酸、NAD 、菸鹼酸單核苷酸、NicMN、吡啶-3-羧酸)、維生素B3-先質色胺酸、維生素B 6 (吡哆醇、吡哆醛、吡哆胺、吡哆 醇鹽酸鹽)、泛酸(泛酸鈣、泛醇)、葉酸化物(葉酸( folic acid )、葉酸(folacin )、蝶醯麩胺酸)、維生素 B ! 2 (鈷胺素、甲基鈷胺素、去氧基腺苷鈷胺素、氰基鈷 胺素、羥基鈷胺素、腺苷鈷胺素)、生物素、維生素C( 抗壞血酸)、維生素A (視黃醇、醋酸視黃酯、棕櫚酸視 黃酯、具有其他長鏈脂肪酸之視黃酯類、視黃醛、視黃酸 、視黃醇酯)、維生素D (骨化醇、膽骨化醇、維生素D3 、1,2 5-二羥基維生素D)、維生素Ε(α_生育酚' 生育 酚醋酸鹽、α-生育酚琥珀酸鹽、α-生育酚菸鹼酸鹽、r-生育酚)、維生素Κ (維生素反,'葉綠醌、萘醌、維生素 Κ2、甲萘醌-7、維生素κ3、甲萘醌-4、甲萘醌、甲萘醌-8 、甲萘醌- 8Η、甲萘醌-9、甲萘醌-9Η、甲萘醌-10、甲萘 醌-11、甲萘醌-12、甲萘醌-13)、膽鹼、肌醇、/3-胡蘿 -27- 201208583 蔔素及彼等之任何組合。 於提供兒童營養產品之體系中’該組成物可選擇性地 包括,但不限於一或多種下列礦物質或其衍生物:硼、鈣 、醋酸鈣、葡萄糖酸鈣、氯化鈣、乳酸鈣、磷酸鈣、硫酸 鈣、氯化物、鉻、氯化鉻、吡啶甲基鉻、銅、硫酸銅( copper sulfate)、葡萄糖酸銅、硫酸銅(cupric sulfate) 、氟化物、鐵、羰基鐵、三價鐵、富馬酸亞鐵、正磷酸亞 鐵、硏磨鐵、多醣鐵、碘化物、碘、鎂、碳酸鎂、氫氧化 鎂、氧化鎂、硬脂酸鎂、硫酸鎂、錳、鉬、磷、鉀、磷酸 鉀、碘化鉀、氯化鉀、醋酸鉀、硒、硫、鈉、琥珀辛酸鈉 (docusate sodium)、氯化鈉、亞硒酸鈉' 鉬酸鈉、鋅、 氧化鋅、硫酸鋅及彼等之混合物。礦物質化合物之非限制 性示範性衍生物包括任何礦物質化合物之鹽類、鹼鹽類、 酯類及螯合物。 礦物質可以鹽之形式添加在兒童之營養組成物中,諸 如磷酸鈣、甘油磷酸鈣、檸檬酸鈉、氯化鉀、磷酸鉀、磷 酸鎂、硫酸亞鐵、硫酸鋅、硫酸銅、硫酸錳及亞硒酸鈉。 其他維生素和礦物質可依本技所已知者添加。 於一體系中,每一份兒童營養組成物中可包含任何指 定國家對維生素A、C和E、鋅、鐵、碘、硒及膽鹼之最大 膳食建議量的約10至約50%,或國家群組對彼等之平均膳 食建議量的約10至約50%。於另一體系中,每一份兒童營 養組成物可供應之維生素B爲任何指定國家對維生素B之最 大膳食建議量的約10-30%,或爲國家群組對彼等之平均膳 -28- 201208583 食建議量的約10至30%。再於另一體系中’在兒童營養產 品中之維生素D、鈣、鎂、磷及鉀的水準可能與在乳中找 到的平均水準相當。於其他體系中,在每一份兒童營養組 成物中之其他營養物質的存在量可爲任何指定國家對彼等 之最大膳食建議量的約2 0%,或爲國家群組對彼等之平均 膳食建議量的約20%。 本揭露內容之兒童營養組成物可選擇性地包括下列一 或多種調味劑,包括,但不限於:調味之萃取物、揮發性 油類、可可或巧克力調味劑、花生醬調味劑、餅乾碎片、 香草或任何市售之調味劑。有用之調味劑的實例包括,但 不限於:純茴香萃取物、模擬之香蕉萃取物、模擬之櫻桃 萃取物、巧克力萃取物、純檸檬萃取物、純柳橙萃取物、 純薄荷萃取物、蜂蜜、模擬之菠蘿萃取物、模擬之萊姆酒 萃取物、模擬之草莓萃取物或香草精;或揮發性油類,諸 如香膏、月桂油、香檸檬油、雪松油、櫻桃油、肉桂油、 丁香油或薄荷油;花生醬、巧克力調味劑、香草餅乾碎片 、奶油糖果、太妃糖及彼等之混合物。該調味劑之量根據 所使用之調味劑可有很大之變化。調味劑之類型和量可依 本技藝所已知者選擇。 本揭露內容之營養組成物可選擇性地包含一或多種可 添加乳化劑以穩定最終產品。合適之乳化劑的實例包括, 但不限於卵磷脂(例如:來自蛋或大豆)、α乳白蛋白及 /或單和二-甘油酯及彼等之混合物。其它乳化劑對熟習本 技藝之人士而言是顯而易知的且將根據(一部分)該配方 -29- 201208583 及最終產品選擇。 本揭露內容之營養組成物可選擇性地包含一或多種亦 可添加之防腐劑以延長產品之貨架壽命。合適之防腐劑包 括,但不限於山梨酸鉀、山梨酸鈉、苯甲酸鉀、苯甲酸鈉 、乙二胺四醋酸二鈉鈣及彼等之混合物。 本揭露內容之營養組成物可選擇性地包含一或多種安 定劑。用於實行本揭露內容之營養組成物的合適安定劑包 括,但不限於阿拉伯膠、節替膠(ghatti gum)、梧桐膠 (karaya gum)、黃蓍膠、寝脂、紅藻膠(furcellaran) 、瓜爾豆膠(guar gum)、結冷膠(gellan gum)、刺槐 豆膠、果膠、低甲氧基果膠、明膠、微晶型纖維素、CMC (羧甲基纖維素鈉)、羥丙基甲基纖維素、甲基纖維素、 羥丙基纖維素、DATEM (單及二甘油酯之二乙醯酒石酸酯 類)、右旋糖酐、卡拉膠(carrageenans )及彼等之混合 物。 除非另有規定,此處所使用之所有百分比、份數及比 率係以全部配方之重量計算。 本掲露內容之營養組成物可大致上不含任何此處所描 述之可選擇的或選定的成分,惟該剩餘之營養組成物仍包 含所有本文所述之必要成分或特性。在這種情況下,除非 另有規定,“大致上不含”一詞意指該選定之組成物包含之 可選擇的成分可能少於功能量,通常係少於這類可選擇的 或選定之成分的0.1重量% (包括〇重量%)。 除非另有規定或由參考之上下文中明確暗示相違背, -30- 201208583 所有關於本揭露內容之單數特性或限制之引用應包括對應 之複數特性或限制,反之亦然。 除非另有規定或由參考之組合的上下文中明確暗示相 違背,此處所使用之所有方法或過程的步驟之組合可以任 何順序執行。 本揭露內容之方法及組成物(包括其組分)可由此文 所描述之體系的必須要素和限制,以及任何本文所述或可 用於營養組成物中之額外或可選擇之成分、組分或限制所 組成,或大致上由其組成。 本文所使用之“約”一詞應被解釋爲係指所指定之任何 範圍內之數字。提及之任何範圍均應被視爲是替該範圍內 之任意子集提供支持。 下列實例係用於說明本揭露內容之營養組成物的一些 體系,但不應被解釋爲對彼等之任何限制。熟習本技藝之 人士考量本文所揭露之營養組成物或方法的具體說明或操 作後將清楚明白此處之申請專利範圍內的其他體系。該專 利說明書與實例僅欲作爲示範,本揭露內容之範圍及精神 係由接續於實例之後的申請專利範圍所指定。 【實施方式】 表1中提供根據本揭露內容之粉狀營養組成物之示範 體系。於此體系中,當使用替代之寡果糖及/或DHA粉末 來源時’可調整該玉米糖獎固體之重量。此外,表1中所 描述之粉狀營養組成物可以水重構成。 • 31 201208583 表1.用於兒科個體之營養組成物的示範體系之營養變化形廓 說明 每份100.0公斤中之量 酪乳粉 3 1.000公斤 即溶全脂奶粉CODEX (食品法典委員會) 28.000公斤 蔗糖 1 5.000公斤 椰子油稀奶油粉 12.600公斤 玉米糖漿固體 7.519公斤 寡果糖 1.815公斤 菊糖 1.810公斤 磷酸二鈣 0.700公斤 人工香草味 0.582公斤 海洋高DHA高維生素C油粉 0.322公斤 玉米糖漿固體 145.070克 牛磺酸 22.000克 生育酚醋酸鹽,DL-α,50% 16.244 克 (乾燥,S.D.) 菸醯胺 7.130 克 維生素A棕櫚酸鹽,乾燥小珠, 3.738 克 CW可分散的 維生素L,1% 2.546 克 維生素D3粉末 1.524 克 (膽骨化醇) 吡哆醇鹽酸鹽 0.540 克 硫胺素鹽酸鹽 0.534 克 泛酸鈣 0.500 克 核黃素 0.114 克 葉酸 0.060 克 硏磨鐵Y0034 ( 01 ) 0.180公斤 玉米糖漿固體 139.441克 硫酸亞鐵 36.000 克 抗壞血酸WP 4.509 克 硫酸錳 0.050 克 膽鹼酒石酸氫鹽(經調整的,80網孔) 100.000 克 磷酸氫鎂 80.000 克 乳糖乾燥混合物 44.339克 硫酸鋅,單水合物 12.198克 (粉末純化的) 亞硒酸鈉S.D. ( CSS) 2.946 克 玉米糖漿固體大袋DRB 2.931 克 無水亞硒酸鈉 0.015 克 無水硫酸銅,特純 0.295 克 硫酸錳,單水合物 0.222 克 麵包酵母/3葡聚醣 32.000克 -32- 201208583 所有本專利說明書中引用之參考資料,包括,但不限 於所有文件、出版物、專利案、專利申請案、發表文章、 文字、報告、手稿、小冊子、書籍、互聯網張貼、雜誌文 章、期刊,等之全部內容均納爲本專利說明書之參考。本 文中之參考資料的討論僅欲用於總結其作者之主張’並不 作爲承認任何參考資料構成先前技術。申請人保留挑戰引 用之參考文獻之準確性和針對性的權利。 雖然本揭露內容之體系已使用特定術語、設備和方法 來描述,這類描述僅係用於說明。所使用之文字爲描述之 文字,而非用於限制。必須理解,本技藝之一般技術人士 可在不偏離本發明之精神或範圍(其載於以下申請專利範 圍內)下對本發明做一些修改和變化。此外,應理解,各 種不同體系之面向可全部或部分互換。例如,雖然已示範 用於製造根據那些方法製造之市售的無菌液態營養補充品 的方法,其他用途亦可考慮。因此,所附之申請專利範圍 不應只限於其中所包含之變化形式的說明。 【圖式簡單說明】 第1圖說明與未經治療、僅以WGP-葡聚醣治療或僅以 基質治療之小鼠相比較時,該使用以乳爲基底之配方基質 加WGP葡聚醣治療之小鼠中之顯示出粒細胞呼吸爆發增強 的數個樣本之平均螢光強度(MFI)。 第2圖說明與未經治療或以WGP或基質治療之小鼠相 比較時,該使用以乳爲基底之配方基質加WGP葡聚醣治療 -33- 201208583 之小鼠中之顯示出粒細胞呼吸爆發增強之數個樣本的FL1 -Η螢光。 第3圖說明使用WGP葡聚醣加以乳爲基底之基質治療 之小鼠中所提高之IL-6量。 -34-P "Nutrition composition" means a substance or formulation that meets at least a portion of the individual's nutritional needs. "Pediatric individual" means a human being less than 13 years of age. In some systems, a pediatric system refers to a human individual less than 8 years old. "Infant" means an individual who is born within the range of not more than one year old, including infants with a corrected age from 0 to about 12 months. The term infant includes -9 - 201208583 low birth weight infants, very low birth weight infants, and premature infants. The term “corrected age” refers to the age of the baby minus the amount of time the baby is born prematurely. Therefore, if the baby has reached the full term, the corrected age is the age of the baby. "Child" means an individual who is between the ages of about 12 months and about 13 years old. In some systems, children are individuals between the ages of one and twelve. In other systems, "children" or "child" means an individual who is two, three, four, five or six years old. In other systems, the terms "child" or "child" mean any range between the ages of about 12 months and about 13 years. “Children's nutritional products” means those that meet at least a portion of the child's nutritional needs. "Infant Formula" means a composition that meets at least a portion of the nutritional needs of an infant. In the United States, the inclusion of infant formula is 21 C. F. R. The federal regulations set out in clauses 100, 106 and 107. These provisions specify the levels of macronutrients, vitamins, minerals and other ingredients in an effort to mimic the nutritional and other properties of human breast milk. "Nutritionally complete" refers to a composition that can serve as the sole source of nutrients' which will provide substantially all of the daily requirements of vitamins, minerals and/or microelements plus protein, carbohydrates and lipids. "Probiotic" means a microorganism that has low pathogenicity or is non-pathogenic and can exert a beneficial effect on the health of a host. "Probiotic" means a non-digestible food ingredient which advantageously affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the digestive tract which may improve the health of the host. -10- 201208583 "Effective amount" means an amount that provides a stimulatory immune effect in an individual. "5-glucan" refers to all /3-glucans, including /3 -1,3-glucan and /3-1,3; 1,6-glucan, each of which is a A specific type of dextran. Further, /3-1,3; 1,6-glucan is a type of /3-1,3-glucan. Thus, the term "/3-1,3-glucan" includes; 8-1,3; 1,6-glucan. "Milk-based substrate" means a medium comprising at least one component that is aspirated or extracted from the mammary gland of a mammal. In some systems, the milk-based matrix of the disclosed nutritional composition comprises a milk component derived from a domesticated ungulate mammal, a ruminant, a human, or any combination thereof. Moreover, in some systems, the milk-based matrix comprises casein, whey protein, lactose or any combination thereof. In addition, the milk-based substrate of the present disclosure may comprise any milk- or milk-based product known in the art. In some systems, the present disclosure describes a nutritional composition for an individual comprising a milk-based substrate, a source of carbohydrates, a source of lipids, a source of protein, and/or 3-glucan (especially /3- A source of 1,3; 1,6-glucan, wherein the /3-glucan and the milk-based matrix provide a synergistic effect to stimulate the immune system of the pediatric individual. The present disclosure also describes a method of enhancing the immune function of a pediatric individual comprising administering an effective amount of a nutritional composition comprising a carbohydrate source, a lipid source, a protein source, and a yS-glucan source. Suitable fat or lipid sources for practicing the invention may comprise any of the lipid sources known in the art, including, but not limited to, animal sources such as: creams, creams, butter fats, egg yolk lipids; marine sources such as -11 - 201208583 Fish oil, marine oil, single cell oil; vegetable and vegetable oils such as corn oil, rapeseed oil, sunflower oil 'soybean oil, palm olein, coconut oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, Olive oil, flaxseed (linseed) oil, cottonseed oil, high oleic safflower oil, palm stearin, soy lecithin, palm kernel oil, wheat germ oil, medium chain triglyceride. Sources of cow's milk protein for use in the practice of the invention include, but are not limited to, cow's milk protein powder, cow's milk protein concentrate, cow's milk protein isolate, skim milk solids, skim milk, skimmed milk powder, whey protein, whey protein isolate, milk Albumin concentrate, sweet whey, acid whey, casein, acid casein, caseinate (eg sodium caseinate, calcium caseinate, calcium caseinate) and any combination thereof. In a system, the protein is provided as a complete protein. In other systems, the protein is provided as a combination of intact protein and partially hydrolyzed protein (degree of hydrolysis between about 4% and 10%). In some other systems, the protein is more thoroughly hydrolyzed. In another system, the protein source may be supplemented with a peptide containing branamide. In the particular system of the invention, the protein-derived whey:casein ratio is similar to that found in human breast milk. In a system, the protein source comprises from about 40% to about 80% whey protein, and from about 20% to about 60% casein. In certain systems of the present disclosure, the nutritional composition may comprise one or more probiotics. Any probiotic known in the art can be accepted in this system, except that the probiotic can achieve the desired result. In a special system, -12- 201208583 the probiotic may be selected from any lactic acid bacteria, Lactobacillus rhamnosus GG, Bifidobacterium species, Bifidobacterium longum and Bifidobacterium animalis subsp. BB-12 or their The combination. If the composition contains probiotics, the amount of the probiotic may vary from about 1.4 to about 101 colony forming units per kilogram of body weight per day (cfu). In another system, the amount of probiotic may vary from about 106 to about 109 cfu per kilogram of body weight per day. In still another system, the probiotic may be at least about 106 cfu per kilogram of body weight per day. In a system, the probiotic may be viable or non-viable. The term "survival" as used herein refers to a living microorganism. "Non-viable" or "non-viable probiotic" means a non-viable probiotic microorganism, its cellular components and/or metabolites. Such non-viable probiotics may have been heat killed or otherwise inactivated, but retain their ability to beneficially affect the health of the host. The probiotics useful in the present invention may be naturally occurring, synthetically synthesized or transfected by the manipulation of the organism's genes, whether or not such new sources are currently known or later developed. The nutritional composition comprises one or more prebiotics. The term "probiotic" as used herein refers to an indigestible food ingredient that exerts a health benefit on a host. Such health benefits may include, but are not limited to, selectively stimulating the growth and/or activity of one or a limited number of beneficial enteric bacteria, stimulating ingestion of probiotic microbial growth and/or activity, and selectively reducing intestinal tract Pathogenic bacteria and beneficially affect the profile of the short-chain fatty acids in the intestine. Such probiotics may be organisms and/or plants that are naturally occurring, synthetically synthesized or genetically manipulated, whether or not such new sources are currently known or developed from -13 to 201208583. The prebiotics used in the present invention may include oligosaccharides, polysaccharides, and other probiotics containing fructose, xylose, soybean, galactose, glucose, and mannose. More specifically, the probiotics useful in the present invention may include polydextrose, polydextrose powder, lactulose lactose, raffinose, grape oligosaccharide, inulin, fructooligosaccharide, isomalt Oligosaccharide, soybean oligosaccharide, lactulose, xylooligosaccharide, chitooligosaccharide, mannooligosaccharide, arabinooligosaccharide, salivary oligosaccharide, fucooligosaccharide, galactooligosaccharide and gentian oligosaccharide. In a system, the total amount of the prebiotics present in the nutritional composition may be about 1. 0 g / l to about 10. 0 g / liter. More preferably, the total amount of the prebiotics present in the nutritional composition may be about 2. 0 g / l to about 8. 0 g / liter. At least 20% of the prebiotics may comprise a mixture of galactooligosaccharides and polydextrose. In a system, the amount of each galactooligosaccharide and polydextrose in the nutritional composition may be about 1. 0 g / l to about 4. Within the range of 0 g / liter. In a system, the amount of galactooligosaccharide in the nutritional composition may be about 0. 1 mg / 100 kcal to about 1. 0 mg / 100 kcal. In another system, the amount of galactooligosaccharide in the nutritional composition may be about 0. 1 mg / 100 kcal to about 0. 5 mg / 100 kcal. In a system, the amount of polydextrose in the nutritional composition can be about 0. 1 mg / 100 kcal to about 0. Within the range of 5 mg / 100 kcal. In another system, the amount of the polydextrose can be about 0. 3 mg / 100 kcal. In a particular system, the galactooligosaccharide and polydextrose supplements are present in the nutritional composition in a total amount of at least about 2 mg/100 kcal and may be about 0. 2 mg / 100 kcal to about 1. 5 mg / 100 kcal. The nutritional composition of the present invention comprises a source of a long chain polyunsaturated fatty acid (-14-201208583 LCPUF As ) comprising docosahexaenoic acid (DHA). Other suitable LCPUFAs include, but are not limited to, alpha-linoleic acid, gamma-linoleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (indole), and arachidonic acid (ARA). In a system, the nutritional composition is supplemented with both DH AR and AR Α. In this system, the weight ratio of AR A : DHA can be from about 1:3 to about 9:1. In one system of the invention, the ratio is from 1:2 to about 4:1. Advantageously, the amount of long chain polyunsaturated fatty acids in the nutritional composition is at least about 5 mg/100 kcal and may range from about 5 mg/100 kcal to about 100 mg/100 kcal (more preferably A change between about 10 mg / 100 kcal to about 50 mg / 1 〇〇 kcal). The nutritional composition can be supplemented with oils comprising DHA and ARA using standard techniques known in the art. For example, an equivalent amount of oil (such as high oleic sunflower oil) normally present in the composition can be substituted for DHA and ARA to add it to the composition. Another example is that the oil containing DH A and ARA can be substituted for an equivalent amount of the remainder of the total fat mixture normally present in the composition without DH A and AR A to be added to the composition. 〇 If used, the source of the DH A and AR A may be from any source known in the art, such as marine oil, fish oil, single cell oil, egg yolk lipids, and brain lipids. In some systems, the DHA and ARA are derived from single cell Martek oil, DHASCO® or variants thereof. The DHA and ARA may be in their native form, except that the remainder of the LCPUFA source does not have any substantial deleterious effect on the infant. In addition, DHA and ARA can be used in the form of refined -15-201208583. In one system of the invention, the source of DHA and ARA is the single cell oil taught in U.S. Patent No. 5,374,567; 5,550,156; and 5, 359, 907, the entire disclosure of which is incorporated herein by reference. However, the present invention is not limited to such oils. As noted above, the disclosed nutritional compositions include a source of/5-glucan in each of their systems. Glucan is a polysaccharide, specifically a polymer of glucose, which is naturally occurring and can be found in the cell walls of bacteria, fungi, yeasts and plants. Type B-dextran (/5-glucan) itself is a different subset of glucose polymers consisting of a chain of glucose monomers linked together via yS-type glucosidic bonds To form complex carbohydrates. Cold-1,3-glucan is a pure form of a carbohydrate polymer such as yeast, mushroom, bacteria, algae or grain. (Stone BA, Clarke AE. Chemistry and Biology of (1 - 3 ) - B e t a - G 1 ucan s. London: Portland Press Ltd; 1 993 ). The chemical structure of the cold-1,3-glucan is dependent on the source of the 8-1,3-glucan. In addition, various physicochemical parameters such as solubility, primary structure, molecular weight and branching play a role in the biological activity of -1,3-glucan. (Yadomae T. ,Structure and biological activities of fungal beta-1 ,3 -glucans. Yakugaku Zasshi. 2000; 120: 413-431) 〇/3-1,3-glucan is a naturally occurring polysaccharide with or without 0-1,6-glucose side chain, which is available in a variety of plants, yeasts, Found in the cell wall of fungi and bacteria. /9-1,3; 1,6-glucan is a glucan containing a glucose unit with a (1,3) -16-201208583 linkage, the (1,3) linked glucose unit having (1,6) The side chain connected at the position. yS-l,3;l,6-glucan is a heterogeneous population of glucose polymers that share structural commonalities, including linear glucose unit backbones linked by /3-1,3 linkages, A glucose-chain having a -1,6-link extending from the backbone. Although this is the basic structure of the currently described /3-glucan class, there may be some variations. For example, some yeast glucans have an additional /3 (1,3) region extending from the A (1,6) branched branch, which is the additional 泠1,3 region further for its individual structure. Increase complexity. The 3-glucan derived from baker's yeast (cerev/hae) consists of a chain of D-glucose molecules linked at positions 1 and 3 with a glucose side attached at positions 1 and 6. chain. The yeast-derived 3-glucan is an insoluble, fiber-like complex sugar, and its general structure is a linear glucose unit having a 0-1,3-skeleton interspersed with the stone-1,3-framework. The length is usually from 6 to 8 glucose units of the ^ -1,6- side chain. More specifically, the 3-glucan derived from baker's yeast is poly-(1,6)-cold-D-glucopyranosyl-(1,3)-/S-D-glucopyranose. In addition, /3-glucan has been found to have the ability to stimulate the immune system of adults. In fact, many of these polysaccharides have been shown to bind to the Θ-1,3-glucan receptors on monocytes, macrophages, and neutrophils. (Czop, J. K·, & Austen, K. F. (1985). --glucans activate cellular immunity primarily through macrophages and neutrophils. Properties of glycans that activate the human alternate complement pathway and interact with the -17- 201208583 human monocyte beta g 1 u c a n receptor. J. I m mun o. 135, 3388-3393). However, cold-glucan has not been identified as a substance that provides the benefits of the present disclosure and can be administered to a pediatric individual. In fact, it is well known that the development of infantile intestinal flora is not as good as that of adults. Although the adult flora consists of more than one 13 microorganisms and nearly 50 species, the infant's intestinal flora contains only one part of those microorganisms (whether in absolute quantity and species diversity). Because of the vast differences in bacterial flora and species between infants or children and the adult gut, it cannot be assumed that beneficial factors for adults can also benefit infants and/or children. As described above, dextran is a polysaccharide belonging to a group of physiologically active compounds described as biodefense modifiers. /3-1,3;1,6-glucan is a part of the polysaccharide that is equipped with immunological supervision. When it is administered as part of the nutritional composition of the present disclosure, it can reduce the child or infant by stimulating immune function. Microbial-related diseases in the body. In addition, dextran can be well tolerated and does not produce or cause excessive gas, bloating, bloating or diarrhea in pediatric individuals. The efficacy of A-glucan as an immune system stimulator has not previously been demonstrated when /3-glucan is administered concurrently with a milk-based matrix to provide a synergistic, stimulatory immune effect. In some systems, the nutritional composition of the present disclosure comprises: S-dextran and a milk-based matrix, wherein when the combination of the two components is incorporated into the nutritional composition, it provides a synergistic effect. The resulting nutrient composition has a stimulating effect on the individual's ability to breathe out. More specifically, in some systems, the combination of -1,3; 1,6-glucan with a milk-based matrix provides an effect of increasing the number of neutrophils in an individual. -18- 201208583 When exposed to certain stimuli, phagocytic cells (including neutrophils, eosinophils, and mononuclear phagocytic cells) greatly increase their glucose and oxygen consumption and begin in a series called "breathing outbreaks" The change produces a large amount of superoxide (〇2) and hydrogen peroxide (H2〇2). The oxygen-containing compound produced by the respiratory burst kills the invading bacteria or pathogen during a process known as oxygen-dependent intracellular reduction. Therefore, stimulating a respiratory burst in an individual can enhance the individual's immune system. To demonstrate this effect, the biological activity of /3-glucan in the presence or absence of a milk-based formulation can be assessed in in vivo experiments. One milk-based formulation that can be used in the experiment is the commercially available formulation Enfagrow® (available from Mead Johnson & Company, Evansville, IN). /3-Glucan can include Wellmune WGP® (available from Biothera, Inc., Eagan, Minnesota). In vivo, mice are fed with S-glucan (1 mg/mouse/day) or It is mixed with a milk-based formula to feed the mice for up to 10 days. Mice were also fed as a control in either saline or a milk-based formulation. In the mouse model, oral/3-glucan is taken up via Peyer's patches in the small intestine. The particles taken up by the Pein's patches then enter the systemic circulation as they are transported via macrophages. Then, degradation occurs in macrophages, and the glucan breaks into smaller pieces, which can then activate neutrophils. All cell numbers were assessed by neutrophil respiratory burst activity, activation markers on macrophages and dendritic cells, and serum levels of cytokines. -19- 201208583 After oral administration, blood cells are isolated and counted. The cells showed significantly higher neutrophil counts on day 10 compared to mice treated with the formulation matrix or /3-glucan compared to PBS untreated mice. These data suggest that no-glucan and formulation matrices can stimulate neutrophil mobilization and may play an important role in antimicrobial protective responses. Compared with the control group, the milk-based formula alone, /3-glucan alone, and the combination of the two significantly increased the number of neutrophils. Chapters 2 and 2 show respiratory bursts of neutrophils. It indicates a synergy between /3-glucan and a milk-based matrix that synergistically increases respiratory bursts in neutrophils. By contrast, the respiratory burst effect of the separate cold-dextran and milk-based formulations was only slightly higher than the control group. In fact, the combination of dextran and milk-based formulations had a synergistic effect on respiratory bursting ability that was significantly higher than the control group. In addition, Figures 1 and 2 illustrate that dextran and a milk-based matrix have a synergistic effect on promoting respiratory bursts of neutrophils. As shown in Figure 3, IL-6 levels were also significantly elevated in mice treated with the non-dextran plus formulation matrix compared to mice receiving a separate milk-based formulation. Figure 3 shows mice receiving WGP® /3-glucan alone and receiving /3-glucan and milk-based formulations compared to mice receiving a separate milk-based formulation. The IL-6 is significantly up-regulated. Therefore, in vivo studies have demonstrated that oral glucan and a milk-based formulation matrix can significantly increase neutrophil counts in peripheral blood' and promote respiratory burst activity of neutrophils. In fact, a milk-based formulation matrix synergizes with ^-1,3; 1,6-glucan in immune cell function (ie, -20-201208583 oxidative burst of neutrophils) . In addition, glucan can increase IL-6 secretion in vivo regardless of whether a milk-based matrix is present. Therefore, the addition of dextran to a milk-based nutritional composition (such as an infant formula or a child's nutritional composition) for pediatric individuals will improve the individual's immune response by increasing resistance to invading pathogens, thereby maintaining Or improve overall health. A-1,3; 1,6-glucan induces responses in cells of the innate immune system. In other words, this activates adaptive immunity. Therefore, yS-1,3; 1,6-glucan enhances the immune response of an individual by increasing the neutrophil count and enhancing the ability of the respiratory burst to activate the host immune system. When administered orally, yS-1,3-glucan (such as, for example, 泠-1,3; 1,6-glucan) is not directly absorbed by the metabolic processes of the digestive system. In fact, no significant systemic exposure occurred after the intake of yeast/3-glucan; however, small intestinal plaques ingested a small amount of insoluble sputum-glucan particles, which then entered the system cycle because It is transported via macrophages. After macrophages phagocytose/3-glucan, small fractions of the ingested /3-glucan are released from macrophages. These fragments act on neutrophils and lymphocytes, such as natural killer (NK) cells. In addition, dot-glucan can stimulate the production of cytokines and stimulate T lymphocytes (T cells). The mechanism of action of this /9-glucan can be linked to activation of the innate immune system and activation of adaptive immunity. Therefore, in some systems, Θ-1,3-glucan (or, more specifically, /3 _1,3; 1,6-glucan) is used to enhance the function of the immune system. For example -21 - 201208583: Use of /5-1,3; 1,6-glucan enhances resistance to infection and/or reduces inflammatory response. In at least one system, the present disclosure is directed to a method for enhancing immune system function in a pediatric individual comprising administering to the individual /3-1,3;1,6- in a milk-based matrix Glucan source. In another system, the present disclosure is directed to a method for enhancing resistance to infection in a pediatric individual comprising administering to the individual a /9-1,3;1,6 in a milk-based matrix - dextran. In yet another system, the present disclosure is directed to a method for reducing the duration and severity of infections caused by a broad spectrum of bacterial and viral pathogens in a pediatric individual, comprising administering to the individual a milk-based matrix /9-glucan. In yet another system, the present disclosure is directed to a method for reducing an inflammatory response associated with such infections in a pediatric individual comprising administering to the pediatric individual a /8-glucan in a milk-based matrix . The nutritional composition of the present disclosure comprises /3 -1,3-glucan. In some systems, the 5-1,3-glucan is /3-1,3; 1,6-glucan. In some systems, the glucan is a whole glucan granular spot-glucan, particulate/3-glucan, ? 〇0-glucan (poly-1,6-cold-0-glucopyranosyl-1,3-yS-D-glucopyranose) or any mixture thereof. In other systems, the nutritional composition comprises θ-1,3; 1,6-glucan, which may be in the form of whole glucan granules, particulate or microparticulate/3-glucan granules or Any combination of these provides that the A-glucan of the present disclosure is an oligomer which is resistant to the digestion of the upper intestinal tract, which means that it is rarely degraded by the digestive enzymes of the upper intestinal tract. Non-limiting examples of species from which 3-1,3; 1,6-glucan can be extracted for use in the practice of the disclosure of this -22-201208583 include Saccharomyces cerevisiae (Baker's yeast), Lentinus Edodes) (Shitake mushrooms), Grifola frondosa (Maitake mushrooms) 'Sc/iizo_p/ii//wm comwwne), Sclerotinia (Sclerotium glucanicum, Etc. In some systems, the /3-1,3; 1,6-glucan of the present disclosure is isolated from yeast, mushroom or other fungi. In a system, the/5-glucan It is derived from baker's yeast, more specifically, from the cell wall of baker's yeast; S-glucan. Similarly, the microparticles are not -1,3; 1,6-glucan can be separated from the cell wall of Saccharomyces cerevisiae. The stone-1,3-glucan with /3 -1,6-glucan linkage extracted from the yeast cell wall can be used as a non-specific immune activator. In some systems, the disclosure The nutritional composition comprises a long polymer of no -1,3 glucose (of which about 3-6% of the backbone glucose units have /3 -1,6 branches) In the other systems, the dextran may be a particulate Wellmune WGP® /3-glucan supplied by Biothera of Eagan, Minnesota, USA. In some systems, The nutritional composition comprises at least one 0-1,6-branched insoluble-1,3-glucan. In one system, the nutritional composition of the present disclosure comprises insoluble char-glucan. Some naturally occurring yS-glucan is insoluble in water and may be a very large molecule with a relatively high molecular weight. Humans cannot digest carbohydrate polymers with a call-glucoside linkage. Since humans cannot digest with /3-glucoside linkages The carbohydrate polymer, so the intestinal epithelial cells will not be absorbed and exposed to the particulate yeast dextran-23-201208583. However, some systemic exposure does occur after oral administration and is in the small intestinal plaque. It is regulated. Then, the β-glucan absorbed by the Pein's patch is transported by the macrophage to the reticuloendothelial system. In some systems, the nutrient composition of the glucan may have been enzymatically In order to reduce its particle size or manipulate its molecular weight. In some systems, the /3-glucan of the nutritional composition is used as a prebiotic, which is not digested in the stomach and small intestine of humans, and most of them remain intact. Entering the colon where it can be microbially fermented. In some systems, the /3-glucan in the nutritional composition may comprise water-soluble, low molecular weight dextran. In addition, in some systems, The nutritional composition may comprise an enzyme treated glucan. In still other systems, the nutritional composition comprises whole yeast glucan particles. In some systems, the nutritional composition of the present disclosure may comprise /3-1,3; 1,6-glucan as part of a nutritional product for a pediatric individual, such as a child product or an infant formula. In other systems, the nutritional composition of the present disclosure may be substantially free of lactose. In one system, the amount of yS-glucan present in the composition is about 〇 per 100 grams of the composition. 〇 10 to about 0. Between 050 grams. In some systems, each nutrient composition contains about 10 mg of stone-glucan. In another system, each of the nutritional compositions comprises from about 5 to about 50 milligrams of S-glucan. In other systems, the nutritional composition comprises an amount of di-glucan sufficient to provide about 40 mg/3-glucan per day. In some systems, no-glucan may be added to the nutritional composition at a concentration sufficient to deliver about 38 mg/3-glucan per day to an individual. The nutrient 24 - 201208583 composition can be delivered in the form of a plurality of doses to achieve delivery of a target amount of yS-dextran to the individual throughout the day. In some systems, the nutritional composition of the pediatric individual may be administered in an amount sufficient to deliver about 0 per day. Amount of cold-dextran from 5 mg to about 200 mg. In another system, the amount of non-glucan administered to the pediatric individual via the nutritional composition can range from about 1 mg to about 1 mg per day. In yet another system, the nutritional composition can be formulated to deliver from about 20 mg to about 50 mg of yS-glucan per day to a pediatric individual. In still another system, the amount of /3-glucan administered to the pediatric individual via the nutritional composition can be about 35 mg per day. In another system, the child product is a milk substitute in the form of a reconstitutable powder, which can be supplied 1 to 3 times a day, and the amount of yS-glucan administered to the child can range from about 25 to about 50 mg. / Cold of the day - dextran. In another system, it is recommended that the pediatric individual take the nutritional composition three times a day and deliver about 25 to about 50 mg/day of 3-glucan in three times. In a system, the nutritional composition comprising 0-1,3; 1,6-glucan is provided in the form of a nutritionally complete infant formula containing suitable types and amounts of lipids, carbohydrates, proteins, vitamins And minerals. In this system, the amount of the carbohydrate may vary from about 8 to about 12 grams per 100 kilocalories, the amount of protein may range from about 1 to about 5 grams per 100 kilocalories, and the amount of lipid or fat may be From about 3 to about 7 grams per 100 kilocalories and may be supplemented with an amount of from about 5 to about 577 mg per 100 kcal of -1,3; 1,6-glucan. The nutritional composition of the present disclosure may be a milk-based nutritional composition in the form of a liquid, evaporated, concentrated or dried milk. In some systems, the -25-201208583 nutritional composition may also include non-dairy liquid or solid foods, protein, flavor or taste masking agents, sweeteners and vitamins or dietary supplements. In some systems, the nutritional composition may be nutritionally complete, containing suitable types and amounts of lipids, carbohydrates, proteins, vitamins, and minerals as the sole source of nutrition for the individual. In a system, the nutrient composition is a child nutrition product. In another system, the nutritional composition comprises an infant formula. In yet another system, the nutritional composition comprises a nutritionally complete infant formula. In yet another system, the nutritional composition comprises a nutritionally complete child nutrition product. The disclosed nutritional compositions can be provided in any form known in the art, such as powders, gels, suspensions, pastes, solids, liquids, concentrates, reconstitutable powdered milk substitutes, or ready-to-use products. In some systems, the nutritional composition may comprise a nutritional supplement, a child nutritional product, an infant formula, a human breast milk fortifier, a growing milk powder, or any other nutritional composition designed for use in a pediatric individual. The nutritional composition of the present disclosure includes, for example, a substance that can be orally ingested to promote health, including, for example, chewing foods, dips, tablets, capsules, and powders. The nutritional composition of the present disclosure can be standardized to a specific calorie content, which can be provided in ready-to-use products or in concentrated form. One or more vitamins and/or minerals may be added to the system for providing children's nutritional products to provide daily nutritional needs for children between the ages of 1 and 13. The general practitioner of the art understands that children between the ages of 1 and 13 will have different needs for vitamins and minerals. Therefore, these systems are not intended to limit the nutritional composition of a particular age group, but rather to provide a range for children aged -26-201208583 between 1 and 13 years old. In a system for providing a nutritional composition for children, the composition may optionally comprise, but is not limited to, one or more of the following vitamins or derivatives thereof: vitamin B! (thiamine, thiamine pyrophosphate, TPP, sulfur Amine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate), vitamin B2 (riboflavin, flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, Lutein, yolk), vitamin B3 (niacin, nicotinic acid, nicotinamide, niacinamide, serotonin adenine dinucleotide , NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic acid), vitamin B3-precursor tryptophan, vitamin B 6 (pyridoxine, pyridoxal, pyridoxamine, pyridoxine Acid salt), pantothenic acid (calcium pantothenate, panthenol), folic acid (folic acid, folicin, pterin glutamate), vitamin B! 2 (cobalamin, methylcobalamin, go Oxygen adenosine cobalamin, cyanocobalamin, hydroxycobalamin, adenosine cobalamin), biotin, vitamin C (ascorbic acid) Vitamin A (retinol, retinyl acetate, retinyl palmitate, retinyl esters with other long-chain fatty acids, retinal, retinoic acid, retinyl ester), vitamin D (calciferol, Cholecalciferol, vitamin D3, 1,2 5-dihydroxyvitamin D), vitamin Ε (α_tocopherol' tocopherol acetate, alpha-tocopherol succinate, alpha-tocopherol nicotinic acid, r -tocopherol), vitamin Κ (vitamin, 'green leaf 醌, naphthoquinone, vitamin Κ 2, menaquinone-7, vitamin κ3, menaquinone-4, menaquinone, menaquinone-8, menadione 甲- 8Η, menaquinone-9, menaquinone-9Η, menaquinone-10, menaquinone-11, menaquinone-12, menaquinone-13), choline, inositol, /3-hu萝-27- 201208583 素素 and any combination of them. In a system for providing a nutritional product for children, the composition may optionally include, but is not limited to, one or more of the following minerals or derivatives thereof: boron, calcium, calcium acetate, calcium gluconate, calcium chloride, calcium lactate, Calcium phosphate, calcium sulfate, chloride, chromium, chromium chloride, pyridine methyl chromium, copper, copper sulfate, copper gluconate, cupric sulfate, fluoride, iron, carbonyl iron, trivalent Iron, ferrous fumarate, ferrous orthophosphate, honing iron, polysaccharide iron, iodide, iodine, magnesium, magnesium carbonate, magnesium hydroxide, magnesium oxide, magnesium stearate, magnesium sulfate, manganese, molybdenum, phosphorus , potassium, potassium phosphate, potassium iodide, potassium chloride, potassium acetate, selenium, sulfur, sodium, sodium octosanoate (docusate sodium), sodium chloride, sodium selenite, sodium molybdate, zinc, zinc oxide, zinc sulfate and a mixture of them. Non-limiting exemplary derivatives of mineral compounds include salts, base salts, esters and chelates of any mineral compound. Minerals may be added to children's nutritional compositions in the form of salts such as calcium phosphate, calcium glycerophosphate, sodium citrate, potassium chloride, potassium phosphate, magnesium phosphate, ferrous sulfate, zinc sulfate, copper sulfate, manganese sulfate, and Sodium selenite. Other vitamins and minerals may be added as known in the art. In a system, each child's nutritional composition may comprise from about 10 to about 50% of the maximum recommended amount of vitamin A, C and E, zinc, iron, iodine, selenium and choline in any given country, or The national group has about 10 to about 50% of their average dietary recommendation. In another system, the vitamin B available for each child's nutritional composition is about 10-30% of the maximum recommended dietary intake of vitamin B in any given country, or the average diet for the group of countries. - 201208583 About 10 to 30% of the recommended amount. In another system, the levels of vitamin D, calcium, magnesium, phosphorus and potassium in children's nutritional products may be comparable to the average levels found in milk. In other systems, the amount of other nutrients present in each child's nutritional composition may be about 20% of the maximum dietary recommendation for any given country, or the average for the group of countries. About 20% of the recommended amount of meal. The child nutritional composition of the present disclosure may optionally include one or more of the following flavoring agents including, but not limited to, flavored extracts, volatile oils, cocoa or chocolate flavorings, peanut butter flavorings, biscuit chips, vanilla Or any commercially available flavoring agent. Examples of useful flavoring agents include, but are not limited to, pure fennel extract, simulated banana extract, simulated cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure mint extract, honey , simulated pineapple extract, simulated lime extract, simulated strawberry extract or vanilla extract; or volatile oils such as balm, bay oil, bergamot oil, cedar oil, cherry oil, cinnamon oil, Clove oil or peppermint oil; peanut butter, chocolate flavoring, vanilla biscuit chips, butterscotch, toffee and mixtures of them. The amount of the flavoring agent can vary widely depending on the flavoring agent used. The type and amount of flavoring agent can be selected as known to those skilled in the art. The nutritional composition of the present disclosure may optionally comprise one or more additional emulsifiers to stabilize the final product. Examples of suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), alpha lactalbumin and/or mono- and di-glycerides, and mixtures thereof. Other emulsifiers are readily apparent to those skilled in the art and will be selected based on (part of) the formulation -29-201208583 and the final product. The nutritional composition of the present disclosure may optionally comprise one or more preservatives which may also be added to extend the shelf life of the product. Suitable preservatives include, but are not limited to, potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate, calcium disodium edetate, and mixtures thereof. The nutritional composition of the present disclosure may optionally comprise one or more stabilizers. Suitable stabilizers for carrying out the nutritional compositions of the present disclosure include, but are not limited to, gum arabic, ghatti gum, karaya gum, tragacanth, bed fat, red algae (furcellaran) , guar gum, gellan gum, locust bean gum, pectin, low methoxyl pectin, gelatin, microcrystalline cellulose, CMC (carboxymethyl cellulose sodium), Hydroxypropyl methylcellulose, methylcellulose, hydroxypropylcellulose, DATEM (diethyl tartaric acid esters of mono- and diglycerides), dextran, carrageenans and mixtures thereof. All percentages, parts and ratios used herein are by weight of the entire formulation, unless otherwise specified. The nutritional composition of the present disclosure may be substantially free of any of the optional or selected ingredients described herein, but the remaining nutritional composition will still contain all of the essential ingredients or characteristics described herein. In this case, unless otherwise specified, the term "substantially free" means that the selected component may contain less than a functional amount of optional ingredients, usually less than such optional or selected ones. 0. 1% by weight (including 〇% by weight). Unless otherwise stated or clearly contradicted by the context of the reference, all references to the singular characteristics or limitations of the disclosure should include the corresponding plural features or limitations and vice versa. Combinations of steps of all methods or procedures used herein can be performed in any order, unless otherwise specified or the context clearly contradicted by the context of the combination. The methods and compositions of the present disclosure, including components thereof, may be essential elements and limitations of the systems described herein, as well as any additional or optional ingredients, components or compositions described herein or useful in the nutritional compositions. Restrictions consist of, or consist essentially of,. The term "about" as used herein shall be interpreted to mean any number within the range specified. Any reference to the scope should be considered as providing support for any subset of the scope. The following examples are intended to illustrate some of the systems of the nutritional compositions of the present disclosure, but should not be construed as limiting them. Those skilled in the art will be able to clarify other systems within the scope of the patent application herein after considering the specific description or operation of the nutritional compositions or methods disclosed herein. The patent specification and examples are intended to be exemplary only, and the scope and spirit of the disclosure is intended to be [Embodiment] An exemplary system of a powdery nutritional composition according to the present disclosure is provided in Table 1. In this system, the weight of the corn candy solid can be adjusted when an alternative source of oligofructose and/or DHA powder is used. Further, the powdery nutrient composition described in Table 1 can be composed of water. • 31 201208583 Table 1. Nutritional Change Profile for a Demonstration System for Nutritional Compositions in Pediatric Individuals Description 100 per serving. The amount of 0 kg of buttermilk powder 3 1. 000 kg Instant whole milk powder CODEX (Codex Alimentarius Commission) 28. 000 kg sucrose 1 5. 000 kg coconut oil cream powder 12. 600 kg corn syrup solid 7. 519 kg of oligofructose 815 kg inulin 1. 810 kg of dicalcium phosphate 0. 700 kg artificial vanilla 0. 582 kg marine high DHA high vitamin C oil powder 0. 322 kg of corn syrup solids 145. 070 g of taurine 22. 000 g Tocopherol acetate, DL-α, 50% 16. 244 grams (dry, S. D. Nicotinamide 7. 130 g Vitamin A palmitate, dry beads, 3. 738 grams of CW dispersible vitamin L, 1% 2. 546 grams of vitamin D3 powder 1. 524 g (cholecalciferol) pyridoxine hydrochloride 0. 540 g thiamine hydrochloride 0. 534 grams of calcium pantothenate 0. 500 grams of riboflavin 0. 114 grams of folic acid 0. 060 g honing iron Y0034 ( 01 ) 0. 180 kg corn syrup solid 139. 441 grams of ferrous sulfate 36. 000 grams of ascorbic acid WP 4. 509 grams of manganese sulfate 0. 050 grams of choline bitartrate (adjusted, 80 mesh) 100. 000 grams of magnesium hydrogen phosphate 80. 000 g lactose dry mixture 44. 339 g zinc sulfate, monohydrate 12. 198 g (powder-purified) sodium selenite S. D. (CSS) 2. 946 grams of corn syrup solid large bag DRB 2. 931 g anhydrous sodium selenite 0. 015 grams of anhydrous copper sulfate, special purity 0. 295 grams of manganese sulfate, monohydrate 0. 222 grams of baker's yeast / 3 glucan 32. 000g-32- 201208583 All references cited in this patent specification, including, but not limited to, all documents, publications, patents, patent applications, published articles, texts, reports, manuscripts, pamphlets, books, internet postings, The contents of magazine articles, periodicals, etc. are all referenced to this patent specification. The discussion of the references herein is intended to be merely a summary of the claims of the authors' and is not an admission that any reference material constitutes prior art. Applicants reserve the right to the accuracy and pertinence of the references cited in the challenge. Although the system of the present disclosure has been described using specific terms, devices, and methods, such description is for illustrative purposes only. The text used is the text of the description and is not intended to be limiting. It is to be understood that modifications and variations of the present invention may be made by those skilled in the art without departing from the spirit and scope of the invention. In addition, it should be understood that the various aspects of the various systems may be interchanged in whole or in part. For example, while methods have been demonstrated for the manufacture of commercially available sterile liquid nutritional supplements made according to those methods, other uses are contemplated. Therefore, the scope of the appended patent application should not be limited to the description of the variations contained therein. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates the use of a milk-based formulation matrix plus WGP dextran when compared to untreated, WGP-dextran-only or matrix-only mice. The mean fluorescence intensity (MFI) of several samples showing enhanced granulocyte respiratory burst in the mice. Figure 2 is a graph showing granulocyte respiration in mice treated with a milk-based formulation matrix plus WGP dextran-33-201208583 when compared to untreated or WGP or matrix treated mice. The FL1 - Η fluorescent light of several samples of the enhanced explosion. Figure 3 illustrates the increased amount of IL-6 in mice treated with WGP dextran for a milk-based matrix. -34-
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US20140170259A1 (en) * | 2012-12-14 | 2014-06-19 | Mead Johnson Nutrition Company | Nutritional composition for promoting satiety |
US20140255537A1 (en) * | 2013-03-11 | 2014-09-11 | Mead Johnson Nutrition Company | Nutritional Compositions Containing an Enriched Lipid Fraction and Uses Thereof |
US9980506B2 (en) | 2013-03-11 | 2018-05-29 | Mead Johnson Nutrition Co. | Nutritional compositions containing structured fat globules and uses thereof |
US10455854B2 (en) | 2013-03-11 | 2019-10-29 | Mead Johnson Nutrition Company | Nutritional compositions containing structured fat globules and uses thereof |
US9661874B2 (en) | 2013-03-11 | 2017-05-30 | Mead Johnson Nutrition Company | Nutritional compositions containing structured fat globules and uses thereof |
US10709770B2 (en) | 2013-07-31 | 2020-07-14 | Mead Johnson Nutrition Company | Nutritional compositions containing a prebiotic and lactoferrin and uses thereof |
US10582714B2 (en) | 2015-07-10 | 2020-03-10 | Mead Johnson Nutrition Company | Nutritional compositions and methods for promoting cognitive development |
US20170020950A1 (en) * | 2015-07-23 | 2017-01-26 | Mead Johnson Nutrition Company | Methods for modulating kinases |
AU2020295290A1 (en) * | 2019-06-18 | 2022-01-27 | Gamble, Mardelle Helen | Nutritional compositions |
RU2765579C1 (en) * | 2020-12-16 | 2022-02-01 | Общество с ограниченной ответственностью «ЖЕНЕЛ РД» | Concentrate for preparing a non-alcoholic beverage |
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AU661297B2 (en) | 1991-01-24 | 1995-07-20 | Martek Corporation | Microbial oil mixtures and uses thereof |
US5374567A (en) | 1993-05-20 | 1994-12-20 | The United States Of America As Represented By The Secretary Of The Navy | Operational amplifier using bipolar junction transistors in silicon-on-sapphire |
EP1062873A1 (en) * | 1999-12-13 | 2000-12-27 | N.V. Nutricia | Improved infant formula, protein hydrolysate for use in such an infant formula, and method for producing such a hydrolysate |
US20020044988A1 (en) * | 2000-08-22 | 2002-04-18 | Fuchs Eileen C. | Nutritional composition and method for improving protein deposition |
WO2002047612A2 (en) * | 2000-10-27 | 2002-06-20 | Mannatech, Inc. | Dietary supplement compositions |
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NZ546664A (en) * | 2003-10-24 | 2009-04-30 | Nutricia Nv | Synbiotic composition for infants |
EP2248430A3 (en) * | 2005-02-15 | 2011-01-12 | Barry R. Goldin | A food containing a probiotic and an isolated beta-glucan and methods of use thereof |
WO2007035007A1 (en) * | 2005-09-22 | 2007-03-29 | Weon Ho Kim | Barley milk containing beta-glucan |
JP5053558B2 (en) * | 2006-03-24 | 2012-10-17 | 株式会社Adeka | β-glucan composition, health supplement and health food |
FR2912610B1 (en) * | 2007-02-20 | 2009-05-15 | Gervais Danone Sa | SEMI-FLUID FOOD PRODUCT COMPRISING BETA-GLUCAN FIBERS |
US20090321787A1 (en) * | 2007-03-20 | 2009-12-31 | Velox Semiconductor Corporation | High voltage GaN-based heterojunction transistor structure and method of forming same |
WO2008115046A1 (en) * | 2007-03-22 | 2008-09-25 | N.V. Nutricia | Cereal-based infant nutrition with fibre |
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SG183849A1 (en) | 2012-10-30 |
RU2541396C2 (en) | 2015-02-10 |
WO2011150337A1 (en) | 2011-12-01 |
SG10201504748SA (en) | 2015-07-30 |
ECSP12012238A (en) | 2012-11-30 |
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