TW201039759A - Reduction of risk of obesity - Google Patents
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- TW201039759A TW201039759A TW099110173A TW99110173A TW201039759A TW 201039759 A TW201039759 A TW 201039759A TW 099110173 A TW099110173 A TW 099110173A TW 99110173 A TW99110173 A TW 99110173A TW 201039759 A TW201039759 A TW 201039759A
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Classifications
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- Child & Adolescent Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
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Description
201039759 六、發明說明: 【發明所屬之技術領域】 本發明係關於一種以包括n-6長鏈多不飽和脂肪酸之諸 - 如嬰兒調配物或嬰兒食品之營養組合物於降低嬰兒日後發 展出肥胖及抗胰島素症之風險上之用途。 【先前技術】 為所有嬰兒推薦母乳。然而,於一些情形中,因醫學原 因母乳银養不適當或不成功或不建議,或母親選擇根本不 G 儀養母乳或餵養不超過幾週以上。#於該等情形已發展 出嬰兒調配物。同樣地,在幼兒期之前, 依然具特異性。有時候不能由家庭食品充分心營養= 求。因此,在嬰兒及幼兒時期,根據嬰兒之特定需求而設 计之營養平衡嬰兒食品為最適宜之營養補充來源。 在美國及世界範圍内,在過去3〇年中,成年人、兒童及 月v年之肥胖及超重之普及度已快速增加並持續增加中。 目前全世界有-千八百萬5歲以下兒童受到兒童期超重及 肥胖影響。幾乎3 〇 %美國兒童及青少年、及H)至3 〇 %歐洲 兒童超重或肥胖。 越來越相信,出生後6個月代表出生後人類脂肪質量發 展之其中-個最重要時期,且因此可代表曰後發展出肥胖 之重要時期。此外,人類流行病學數據及動物研究雙實出 生時或嬰兒期間之體重增加係與日後發展出諸如抗姨島素 症候群(亦稱為新陳代謝症候群)、2型糖尿病 韻 之風險相關。 吕問@ 147352.doc 201039759
Massiera等人研究善办^ ^ 長鏈夕不飽和脂肪酸花生四烯酸 C20:4,n-6(ARA)對結腸脂肪前驅細胞分化之影響。其發 現’相對於針對文過氧化物酶體增殖劑活化之受體谷及丫, 或針對飽和單不飽和及η_3多不飽和脂肪酸之特定促效劑 之組合’ ARA大體上促進結腸脂肪前驅細胞分化。他們進 步發現,该效應可被環氧化酶抑制劑阻斷且卡巴環素 —Μη)具有擬似作用,此表示其對前列環素受體有 作用’亚活化環AMP-依賴性途a ’其調節涉及脂肪生成 之⑺趨增強子結合蛋白質β及δ之表現。在-項研究中, 以富含亞油酸(ARA之前驅體)之飲食或含亞油酸及α_亞麻 酉夂混合物之等熱量飲食娘養不同組之授乳期小鼠,發現8 週齡時,接受富含亞油酸之飲食的小鼠斷奶後之體重、脂 肪質置、睪脂肪塾重及脂肪細胞大小均較大。當利用前 列環素受體缺陷型小鼠進行相同實驗時,在組間並未觀察 到差異,此說明冑列環素信號轉導有助於脂肪组織發展。 作者認為其在相對高含量亞油酸之嬰兒調配物中出現顯著 結果’亞油酸係ARA之前驅體。 於WO 2008/0541 92中,其主張:嬰兒之整體脂肪組織質 量並非確定日後疾病風險的良好指標,而應考慮嬰兒早期 ,内臟脂肪質量之累積。已證實:内臟脂肪細胞數主要於 嬰兒時期決定,且若能夠在該時期控制脂肪生成,將會具 重要性。在W0 2008/054192中所建議之可能解決方法中’ 建議投與n·3長鏈多不飽和脂肪酸(二十二碳六烯酸、十八 厌四浠g欠、一十二碳五烯酸及/或二十碳五烯酸)可減少内 147352.doc 201039759 臟脂肪質量累積,同時維持正常生長及發展。然而,其建 議不應包括ARA,因為ARA會抵消n_3長鏈多不飽和脂肪 酸之效應。 、令人驚奇的,本發明者已發現在生命早期階段適度攝取 花生四烯酸會減少日後總脂肪質量累積並改善胰島素敏感 性。 【發明内容】 因此,本發明提供一種以花生四烯酸於製造供投與出生 〇 六個月、一年或三年内之嬰兒之營養組合物上之用途,以 減少日後發展出肥胖及抗胰島素症之風險。本發明特別針 對(但不限於)具有肥胖及抗胰島素症候群傾向之嬰兒。 本發明另外提供一種減少嬰兒日後發展出肥胖及抗胰島 素症之風險的方法,其包括在嬰兒出生當年餵養包含花生 *四烯酸之營養組合物。 該營養組合物較佳包括花生四烯酸,其含量足以提供每 Q 日每公斤5至100 mg之日劑量。就諸如嬰兒調配物之提供 完全營養素之營養組合物而言’以組合物中總脂肪酸含量 百分比表示’其花生四烯酸含量相當於〇 6%(w/w)至 1 ·2%(Λν/\ν) 0 【實施方式】 於本說明書中,以下表達具有如下指定之含意: 「ARA」或「ΑΑ」意指花生四烯酸(C20:4n-6); 「DHA」意指二十二碳六烯酸(C22:6n-3); 「嬰兒」意指12個月以下之兒童,且應相應理解「嬰兒 147352.doc 201039759
J 期 「曰後」意指嬰兒在嬰兒期 /月之後的任一時間點。該時間 點之實例為脂肪組織反彈時齡 卞气年齡,對於人類嬰兒,其通 常發生於五至六歲。 「肥胖素因」包括影響嬰兒或胎兒日後㈣出超重或肥 胖狀態之所有因素。該等因素可包括已顯示會誘發嬰兒或 胎兒發展出超重或肥胖之基因因素、遺傳因素、後天因 素、環境因素、新陳代謝因素、地理、社會及/或經濟因 素。肥胖或超重之定義係基於公認的國際標 體質 量指數)。 「抗騰島素症」係指體内細胞對騰島素沒有反應。其將 隨時間導致高姨島素血症(金液中騰島素過量)。抗姨島素 症”腹巴胖、尚血壓、高三酸甘油賴、低肋[膽固醇相 關。該等病症為稱為「抗胰島素症候群」或「新陳代謝症 候群」之疾病集群之-部份。類似於肥胖之素因,抗姨島 素症之素因為影響發展出抗騰島素症之風險之所有因素。 除非另外指出,否則所有百分比及比例均係重量比。 根據本發明使用之營養組合物可為適於出生—年内之嬰 兒艮用之任—產品。該等產品實例包括嬰兒配方、較大嬰 兒配方、成長奶品、嬰兒穀片、水果蔬菜泥及嬰兒餐,諸 l常主伤食用份量出售之現成可食用肉或魚與蔬菜之 混合物。 、根據本發明使用之營養組合物較佳為完全營養組合物, 亦即提供所有嬰兒營養需求之組合物’諸如嬰兒配方或較 J47352.doc 201039759 大嬰兒配方。該種組合物在每日用量之營養組合物中包括 至V 50 mg ARA,較佳為在每日用量之營養組合物中包括 至少340 mg且最佳500至850 mg之ARA。 在本發明之一項實施例中,本發明營養組合物花生四烯 酸含量可以提供比針對該哺乳動物年齡群組之標準或平均 飲食所提供之平均花生四烯酸含量更多之花生四烯酸。據 乜,該種藉由本發明營養組合物加強提供花生四烯酸給哺 乳動物之方式會誘發所述效應。因此認為該標準飲食遞送 之ARA為每日每公斤哺乳動物〇至34 mg以下。在一些情形 中,標準飲食遞送之ARA為每曰每公斤哺乳動物5至2〇 mg 以下。在該等實施例中,當依所建議之日劑量(取決於年 齡、組合物性質等)食用該組合物時,本發明組合物之 ARA 3畺可比可遞送上述範圍之組合物更多。因此,在一 項實施例中,本發明組合物所遞送之ARA多於由標準飲食 所提供者。 Q 於針對10 kg嬰兒之嬰兒食品之理論實例中:嬰兒在曰 常飲食中之每日ARA攝取量可為5〇 mg/日。根據本發明, 該嬰兒之目標每曰ARA攝取量可為或至少為5〇〇 mg/曰 (5 0 mg/曰/公斤嬰兒)。因此,本發明組合物應每曰提供 450 mg,或至少45〇 mg2ARA。可建議依45〇 g/日之劑量 艮用本發明組合物。因此,於本發明組合物中之濃度 可為至少1 mg ARA/公克組合物。在本發明之其他實施例 中母公克組合物包含0.5 mg ARA至3. mg ARA,較佳為 至2 mg ARA/公克組合物。最佳範圍隨營養組合物類型 147352.doc 201039759 及每日建議食用量而定。針對不同目標嬰兒設計之其他本 發明組合物,每公克組合物包含〇· 1 mg ARA至1.5 mg ARA。可為其他目標考慮極濃縮之本發明組合物,其係每 公克組合物包含5 mg ARA至1 0 mg ARA,較佳6至8 mg ARA/公克組合物。 在本發明之一項實施例中,含於營養組合物中之ARA之 數量為每kcal營養組合物中含0.30 mg至0.85 mg之ARA’ 較佳為0.3 mg至0.7 mg。據信,該等範圍代表在效益、口 味及成本之間之適當平衡,且不顯著影響總熱量。 在本發明之一項實施例中,組合物中之ARA含量為以總 脂肪酸含量占組合物之百分比表示之〇· 1 %至2%之ARA, 更佳為0.6%至1.2%。據信,該等範圍代表效益、口味及成 本之間之適當平衡。 本發明營養組合物中之ARA來源可源自該組合物之成份 及/或可作為獨立單離營養素添加。較佳之組合物包括源 自成份之ARA,並補充單離之ARA,以達到計晝向嬰兒遞 送之目標ARA濃度,或達到組合物中之目標ARA含量。 ARA通常源自真菌生物質,例如培養已熟知且闡述於相 關技術之高山被抱徽(Mortierella alpina)。可藉由添加少 量濃縮ARA油(諸如Martek Biosciences公司以商品名 ARASCO®出售之ARA油),使ARA包括於營養組合物内。 或者,如EP 1239022所述(其内容已以引用的方式併入文 中),利用轉移油自生物質收集,並與轉移油一起併入營 養組合物。 147352.doc 201039759 在本發明之一項實施例中,組合物包括蛋白質源、脂質 源及碳水化合物源。脂質源之花生四烯酸含量可以對每公 斤哺乳動物每日提供5 mg至100 mg之花生四烯酸,較佳35 至85 mg/kg/日,最佳5〇至6〇 mg/kg/日。可考慮目標哺乳 動物之每日飲&及其年齡及體重來調整組合物中之ARA含 量。 在本發明之一項實施例中,考慮來自組合物本身以外其 ◎ 他來源之每日飲食中之ARA來調整組合物中之ARA含 1,且視需要進一步根據年齡及體重調整。其可保證總 ARA每日攝人量維持在各年齡/體重組之允許限度之内, 以免誘發副作用。 在本發明之較佳實施例中,ARA係呈單離化合物(補充 物)併入已包括顯著量脂肪酸(亦即2〇%以上之總能量來自 脂肪酸)之組合物(較佳為固體食品)。 本發明所考慮之哺乳動物較佳為年輕哺乳動物,最佳為 〇 自出生至3歲之人類嬰兒。事實上認為直至該年齡之嬰兒 期為該特定食品對預防肥胖及/或抗胰島素症之影響最有 效之年齡群組。 曰 本發明係關於一種以組合物於製造供投與出生幾個月 内,較佳出生12個月内,最佳6個月内之嬰兒之組合物上 之用途,以降低日後發展出肥胖及/或抗胰島素症之風 險。在—項實施财,本發明組合物最適於斷乳期以前並 包括斷礼期之嬰兒。在_項實施例中’嬰兒組合物為嬰兒 配方、嬰兒補充物、嬰兒穀片、嬰兒成長奶品(gum)或婴 147352.doc 201039759 兒食品(GUM包括以牛奶為基底之供18個月以上、24個月 以上、3歲以上或5歲以上之兒童食用之組合物)。在一項 實施例中’可依連續或不連續之方式投與該組合物直至3 歲、直至5歲。例如,該組合物可作為嬰兒調配物投與較 小年齡(0至6、12或18個月),且隨後在介於3至5歲之不同 階段投與。在一項實施例中,在3歲以後獨立投與該組合 物。 受限於理論,本發明者相信以下所述實驗中所闡述之效 應可應用於人類嬰兒,尤指小嬰兒或學步幼兒。藉由投與 本申e青專利權之組合物,可因此降低日後發展出肥胖或發 展出超重之風險。自實驗數據計算並推算至人類嬰兒,已 付出組合物中之ARA含量值。已考慮源自日常食品之ara 源及般觀察到飲食中不會誘發副作用之最高ARA含量 (估算為約1 〇〇 mg ARA/kg/曰)。 本發明組合物之ARA含量最好能夠遞送比通常由日常飲 食所遞送之ARA更多之ARA。因此,ARA含量最佳調整至 遞送 35 至 85 mg ARA/kg/日或 5〇至 6〇 mg ARA/kg/日。據 信,該數量代表相當高含量之ARA(遞送顯著有益效應)與 保持不會誘發副作用之足夠低數量(尤指嬰兒)之間之適當 平衡。 在本發明之一項實施例中,組合物所遞送之ARA之量稍 大於通常由標準飲食所提供之數量,㈣料在低於已顯 示會誘發副作用之範圍内。在該實施财,該組合物能夠 遞送 35至 55 mg ARA/kg/ 日或 40至 50 mg ARA/kg/ 日。 147352.doc -10- 201039759 特定言之,本發明者所證實之效應係針對具有日後發展 出肥胖素因或變得超重的嬰兒。 發展出肥胖或超重之風險之測定方法為:藉由测定目標 族群之肥胖或超重發生率(與未接受本發明組合物之類似 族群比較)。 ★較佳地,用於本發明之嬰兒配方或較大嬰兒配方之蛋白 '3量j於1.85 g/ι〇〇 kca卜並不認為蛋白質源之具體組 «本發明重要,其限制條件為應滿足必需胺基酸之最低 要求並確保令人滿意的生長。因此,可使用諸如乳清、酿 蛋白及其混合物之以牛奶蛋白質為基底之蛋白質源及以大 豆為基底之蛋白質源。然而,以乳清及絡蛋白蛋白質混合 物較佳。路蛋白:乳清之比例可為70:30至30:70,但以 30:70較佳。 質原中之蛋白質可為完整或經部份水解或可使用 2:及t水解之蛋白質之混合物。若需要滿足必需胺基酸 ◎" 敢氐要求,蛋白質源可另外補充游離胺基酸。該等 要求條件已公開於例如Ec指令2刪/⑷肌中。 上所述較佳蛋白質源為酪蛋白及乳清蛋白質之混合 物。乳清蛋白質可為乳清蛋白質單離物、酸乳清、甜乳; 或已移除路蛋白-糖巨肽之乳清(經改質甜乳清)。然而,乳 m蛋白貝較佳為經改質甜乳清。甜乳清為製造乳酪 得之副產品,B A ™ 且㊉用於製造以牛奶為基底之營養組合物。 然而,甜乳渣台紅 ^ 括一種稱為酪蛋白-糖巨肽(CGMP)之組 分,其包含不期矽+ ^ θ # °' '立之鬲I穌胺酸,且色胺酸含量低。自甜 147352.doc 201039759 乳清移除CGMP ’產生蘇胺酸含量接近人乳之蛋白質。自 甜乳清中移除CGMP之方法闡述於EP 880902中。 若在70%乳清及30%酪蛋白之混合物中使用甜乳清作為 乳清蛋白質’則可對蛋白質源補充數量占總蛋白質含量之 0 _ 2至0 · 5 %的游離組胺酸。 根據本發明使用之完全營養組合物包含碳水化合物源。 較佳之碳水化合物源為乳糖,雖然亦可添加諸如蔗糖、麥 芽糖糊精、及澱粉之其他碳水化合物。營養組合物中之碳 水化合物含量較佳為9至14 g/100 kcal。 根據本發明使用之完全營養組合物含有脂質源。除ara 外,脂質源還可包括任何適用於餵養嬰兒之營養組合物之 脂質或脂肪。較佳脂肪源包括椰子油、低芬酸菜籽油(菜 籽油)、大豆卵磷脂、棕櫚油精、及葵花油。亦可包括必 需多不飽和脂肪酸(亞油酸(C18:2n-6)及α-亞麻酸(C18:3n_ 3))。脂質源中之亞油酸:α-亞麻酸之比例較佳為7.丨以 下。亦可添加少量預製之二十二碳六烯酸(C22:6n_3、 dha)。魚油及單細胞微生物油為二十二碳六烯酸(dha)之 適宜來源。若存在二十二碳六烯酸,則脂質源中之花生四 烯酸:二十二碳六烯酸之比例較佳為2:1至1:1。總體上, 營養組合物中之脂質含量可為4.4至6 g/l〇〇 kcal。 完全營養組合物亦會包括營養上顯著量之所有認為在每 曰飲食中所必需之維生素及礦物質。已確定某些維生素及 礦物質之最低要求。礦物質、維生素及其他視需要存在於 營養組合物中之營養素實例包括維生素A、維生素Βι、維 147352.doc -12- 201039759 生素B2、維生素A、維生素Bu、維生素E、維生素&、維 生素C、維生素D、葉酸、肌醇、菸酸、生物素、泛酸、 膽鹼、鈣、磷、碘、鐵、鎂、鋼、鋅、錳、氯、鉀、鈉、 ” 硒、鉻、鉬、牛磺酸及L-肉鹼。礦物質通常係呈鹽形式添 加0 若必須,營養組合物可含有乳化劑及安定劑,諸如大豆 卵粦月曰、單及一檸檬酸甘油酯、等。若組合物係呈液態提 供,則必須添加。 〇 營養組合物可視需要含有可能具有有益影響之其他物 質,諸如益生菌、纖維素、乳鐵蛋白(lactoferrin)、核苷 酸、核酸等,其數量如同通常於飯養嬰兒之營養組合物中 存在之數量。 了依任適且方式製備該營養組合物。例如,依適宜比 例摻合蛋白質源、碳水化合物源、及脂質源,來製備營養 組合物。若採用,則可在該階段於摻合物中包含乳化劑。 〇 可在此時添加維生素及礦物質,但通常稍後添加,以避免 熱降解。於換合之前,可使任何親脂性維生素乳化劑等 溶解於脂肪源。隨後可混入水(較佳為經過逆滲透之水), - 以形成液態混合物。 • 隨後可熱處理該液態混合物’以減少微生物量。例如, 可將液態混合物快速加熱至約8G°C至約約5秒至約5 分鐘。此步驟可藉由蒸汽注入或藉由熱交換器(例如平板 熱交換器)進行。 隨後可例如藉由快速冷卻將混合物冷卻至約6G°C至約85 147352.doc •13- 201039759 °c。隨後可將液態混合物均質化;例如在兩個階段中,第 一階段為約7 MPa至約40 Mpa,且第二階段為約2 MPa至 約14 MPa。隨後可進一步冷卻該均質化混合物,並可添加 諸如維生素及礦物質之任何熱敏感性組分。通常於此時校 正均質化混合物之pH及固形物含量。 若需要製備粉末狀組合物,將均質化混合物轉移至諸如 噴霧乾燥機或冷凍乾燥機之適宜乾燥裝置,並轉變成粉 末。粉末之水含量應為約5重量%以下。 若需要製備液態組合物,均質化混合物較佳係無菌裝填 入適宜容器。然而,液態組合物亦可於容器中殺菌。適於 進行該種性質之裝填之裝置可自商品購得。液態組合物可 呈固形物含量為約10至約14重量%之即食組合物之形式, 或可呈濃縮形式(固形物含量通常為約20至約26重量%)。 或者,對於諸如六個月至十二個月之較大嬰兒,可例如 在食用諸如嬰兒榖片、較大嬰兒配方及嬰兒餐之嬰兒期所 食用之多種食品中併入適宜數量之ARA,以達到所需曰劑 量之ARA。 本發明將參照以下實例進一步闡述。 實例la 以下出示根據本發明使用之完全營養組合物之組分實 例:(「完全營養組合物」表) 147352.doc -14- 201039759 「完全營養組合物」表 營養素 每 lOOkcal 每公升 能量(kcal) 100 630 蛋白質(g) 1.5 9.45 (脫脂奶粉、經改質甜乳清)游離組胺酸 2.5 15.8 (mg) 酪蛋白:乳清之比例 40:60 40:60 脂肪(g) 5.3 33.4 亞油酸(g) 0.7 4.4 α-亞麻酸(mg) 106 668 DHA(mg) 79 500 ARA(mg) 79 500 亞油酸:α-亞麻酸 6.5 6.5 乳糖(g) 11.6 73.1 礦物質及電解質 Na(mg) 25 158 K(mg) 89 561 Cl(mg) 64 403 Ca(mg) 64 403 P(mg) 32 202 Ca/P 2.0 2.0 Mg(mg) 6.9 43.5 Μη(μβ) 8.0 50.4 維生素及微量元素 維生素A(IU) 350 2205 維生素D(IU) 60 378 維生素E(IU) 1.2 7.6 維生素Κ1(μ§) 8.0 50.4 維生素C(mg) 10 63 維生素Bl(mg) 0.07 0.44 維生素B2(mg) 0.15 0.95 菸鹼(mg) 1.0 6.3 147352.doc •15- 201039759 維生素B6(mg) 0.075 0.47 葉酸(Kg) 12 75.6 泛酸(mg) 0.45 2.83 維生素B12〇ig) 0.3 1.89 生物素(pg) 2.2 13.9 膽驗(mg) 10 63 肌醇(mg) 5.0 31.5 牛石黃酸(mg) 7.0 44.1 肉驗(mg) 1.6 10.1 Fe(mg) 1.2 7.56 Ι(μ8) 15 94.5 Cu(mg) 0.07 0.44 Se(pg) 2.0 12.6 Zn(mg) 0.75 4.72 核苷酸 CMP(mg) 2.3 14.5 UMP(mg) 1.5 9.5 AMP(mg) 0.7 4.4 GMP(mg) 0.3 1.9 該營養組合物可作為餵養出生至4至6個月嬰兒之唯一營 養源,且隨後在引入固態食品直至於約1 2個月完全斷乳期 間作為混合飲食之一部份餵養。 實例lb : 本發明組合物之另一實例為固態嬰兒食品。該食品存在 於玻璃罐中,且其基礎型態係以名稱「3rd FOODS Dinners-Chicken Noodle」在美國出售(未添加ARA,故不 屬於本發明)。下表說明該嬰兒食品之組成。每一容器中 (=每份量)之下述嬰兒食品亦包括60 mg之ARA。其相當於 每kCal嬰兒食品中包括0.5 mg ARA。 147352.doc -16- 201039759 成份:水、胡蘿蔔、雞絞肉、米磨粉、強化蛋麵條(硬 質小麥粗粒麵粉、蛋黃粉、疼驗、硫酸鐵、硫胺素單硝酸 鹽、核黃素、葉酸)、雞脂肪、梨汁濃縮液、洋蔥粉、意 大利黑醋、乾歐芹。 營養素_ 供應份量1罐 每一容器供應量:1份 每份供應量_ 熱量120_
總脂肪:_3g 反式脂肪. 〇g 納:_45 mg 钟:_200 mg 總碳水化合物:_18 g 纖維·‘_2g 糖: 4 g 蛋白質:_4 g 每曰數值百分比 蛋白質:21%_維生素A : 290% 維生素C : 0% 鈣:4%_ 鐵:4% 鋅:15% 實例2 該實例研究向新生天竺鼠幼仔餵養補充或未補充ARA之 飲食對斷乳期後幼仔之總脂肪質量發展之效應。嬰兒期天 竺鼠被認為係研究人類嬰兒發展脂肪質量之良好動物模 型:事實上,類似於新生人類嬰兒,出生時之天竺鼠幼仔 具有相當多體脂肪,而新生大鼠及小鼠幼仔則非常痩。 研究設計: 147352.doc -17- 201039759 將新生雄性天竺鼠分成兩組,使每組有20隻動物。以哺 乳/斷乳飲食餵養各組21天,其中44%之能量係由脂肪供 應。不同飲食均呈等熱量,且不同之處僅在於其ARA含 量。ARA飲食含有占總脂肪酸1.5%之ARA,且對照飲食不 含ARA。於下文及圖示中,接受ARA飲食之組代號為 「ARA飲食」或「+AA」。於下文及圖示中,未接受ARA 之組代號為「對照飲食」或「-AA」。不同飲食之間之亞油 酸及α-亞麻酸濃度維持相當恒定,使得亞油酸對α-亞麻酸 之比例為約35。兩種飲食之脂肪酸組成的進一步細節出示 於表1。 表1 :哺乳/斷乳飲食之脂肪酸組成: 占總脂肪酸之百分比 對照飲食 ARA飲食 C12:0 7.9 6.6 C14:0 3.7 3.3 C16:0 21.8 22.2 C16.1 0.1 0.1 Cl 8:0 3.0 3.4 C18:l 33.3 33.5 C18:2n-6(LA) 28.5 27.9 C18:3n-3(ALA) 0.8 0.8 C20:0 0.0 0.0 C20:l 0.0 0.0 C20:4n-6(ARA) 0.0 1.5 C20:5n-3 0.0 0.0 C22:0 0.0 0.0 C22:5n-3 0.0 0.0 C22:6n-3(DHA) 0.0 0.0 於哺乳/斷乳期結束時(第2 1天),以不含ARA且含適度高 147352.doc -18- 201039759 脂肪含量(35°/。能量來自脂肪)之飲食餵養兩組,直至第136 天。於第21、51 ' 79、107、128及136天記錄體重及脂肪 質量,且於第21天及第136天記錄血漿胰島素濃度。 . 結果: . 如預期,補充ARA之組顯示其血漿磷脂(表2)及三酸甘 油酯(表3)中之ARA濃度高於對照組。
表2 :於第21天之血漿磷脂質中之脂肪酸(Mg/ml)組成。平 均值士SEM 對照飲食 ARA飲食 cio:〇 0.1 ±0.07 0.1 ±0.01 Cl 2:0 0.3 ±0.13 0.2 ±0.01 __ C14:〇 1.1 土 0.17 0.8 ±0.13 C16:0 40.2 ± 3.6. 37.8 ±3.4 一 C17:〇 1.2 士 0.10 1.1 ±0.29 Cl 8:0 68.6 ± 4.2 83.6 ±4.6 C18:l n-9順式+反式 23.2 士 1.9 24.9 ± 1.8 C18:l n-7順式+反式 5.2 ±0.9 4.3 ±0.3 C18:2n-6(LA) 77.0 ±7.5 61.5 ±4.3 _ C18:3n-6(GLA) 0.2 ±0.13 0.1 ±0.04 _ C18:3n-3(ALA) 0.6 ±0.2 0.4 ±0.14 C20:0 0.9 士 0.03 1.0 ±0.05 C20:ln-9 0.6 ±0.1 0.5 ± 0.03 C20:2n-6 1.3 ±0.2 1.0 ±0.05 C20:3n-6 1.0 ±0.07 1.1 ±0.06 C20:4n-6(ARA) 11_7± l.la 40.7±3.2b C20:3n-3 0.1 ±0.03 0.4 ± 0.02 C22:0 1.1±0_2 1.2 ±0.08 C22:ln-9 1.5 士 1.0 0.3 ± 0.02 C20:5n-3(EPA) 0.1 ±0.03 ND C22:2n-6 0.8 士 0.1 0_8 ± 0.06 147352.doc -19- 201039759 C22:4n-6 1.2±〇.2a 2.8 ± 0.1b C24:0 1.9 ±0.4 2.3 ±0.1 C24:ln-9 2.0 ±0.5 1.8 ±0.1 C22:5n-3(DPA) 0.9 ±0.1 0.7 士 0.09 C22:6n-3(DHA) 0.7 ±0.1 0.6 ± 0.06 不同字母說明其在P<0.〇5下具統計學顯著性,nd :不可 測得 表3 :於第21天時之血襞二酸甘油酿之脂肪酸(Pg/ml)組
成。平均值土SEM C10:0 C12:0 C14:0 C16:0 C17:0 C18:0 C18:l n-9 順式 C18:l n-7順式 對照飲食 0.2 士 0.01 ARA飲食 0.2 ± 0.09 0.8 ± 0.3 4.0 ± 2.4 42.2 土 18 0.7 ± 0.09 10·5 ±3.5 63.2 ±18 2.0 ± 0.6 0.8 ±0.1 4.1 ±0.7 57.5 ±3.2 1.0 ±0.1 16.7 土 4·6 88.7 ±16.1 2.7 ±0.5
Cl8:2 n-6(LA) 71.1 ±27.9 87.0 ± 14.5 C18:3n-6(GLA) C18:3n-3(ALA) C20.0 0.5 士 0.1 0.9 ±0.1 2.7 ± 0.2 3.9 ±0.6 0.2 ±0.1 0.7 ±0,1 1.1 土 0.5 C20:ln-9 C20:2n-6 1.6 ±0.8 1_4±0.2 C20:3n-6 0.6 ± 0.09 C20:4n-6(ARA) C20:3n-3 C22:0 C22:ln-9 3.7 土 〇.3a 0.1 ±0.09 0.3 ± 0.02 0.2 ±0.03 13.3± l_2b 0.2 ± 0.07 0.4 ±0.04 0.2 ± 0.04 C20:5n-3 (EPA) 0.1 ±0.08 0.1 ±0.04 C22:2n-6 C22:4n-6 0.2 ± 0.08 0.9 ± 0.2 0.2 ± 0.02 1.8 ±0.26 147352.doc -20· 201039759 C24:0 0.6 ±0.1 0.8 ±0.1 C22:5n-3(DPA) 0.4 ±0.01 0.4 ±0.07 C22:6n-3(DHA) 0.2 ± 0.05 0.2 ±0.1 -----—1 不同字母§兒明其在P<〇 〇5下具統計學顯著性,ND :不可 測得 如圖1可見,於實驗過程中,組間之平均體重並無明顯 差異。 於哺礼/斷乳期結束時(第21天),WNMR所測之 總脂肪質 量在組間並無差異。 〇 、 令人驚奇的,於哺乳/斷乳期結束後,如圖2及3可見, ARA組(代號為「+AA」)之脂肪質量在克數及百分比上皆 低於比對照組(代號為「-AA」)。 於第21天組間之血漿胰島素濃度並無差異。然而,如圖 4所示,於實驗結束時,ARA組所顯示之企漿胰島素濃度 比對照組低約1>6倍。圖5顯示在姨腺姨島素濃度上所觀察 到之類似結果。ARA組所顯示之姨腺姨島素濃度比對照組 〇低約1.6倍。於第21天或第136天,組間之血㈣萄糖i度 並無差異(未出示數據)。 不受限於理論,該實例清楚證實,於嬰兒期银養富含 ARA之飲食對脂肪組織之發展或印記具有重要作用,使得 其日後過度發展之可能性降低。特定言之,該等結果說明 於哺乳/斷乳期適度攝人ARA會減少日後之肥胖及抗跋島 素症。 【圖式簡單說明】 圖1顯示在出生後頭136天期間,銀養不同飲食之兩組天 147352.doc •21· 201039759 竺鼠幼仔之體重變化,· 圖2顯示自第21天至第128天,以公克表示之兩組之脂肪 質量的變化; 圆J顯不於第79日、第1〇7 表不之兩組脂肪質量之變化; 圖4顯示於第天時 及 圖5顯示於第 *、、且的平均血漿胰島素濃度 昂1 3 6天時 > 工/ 之兩組的胰腺胰島素含量。 147352.doc 22-
Claims (1)
- 201039759 七、申請專利範圍: 1. 一種供哺乳動物食用之營養組合物,其包含蛋白質源、 脂質源及碳水化合物源,其中該脂質源包括花生四烯 酸,其含量可對每公斤該哺乳動物每曰提供5至100 mg 之花生四稀酸。 2. 如請求項1之營養組合物,其中該花生四烯酸之含量為 35至 85 mg/kg/ 日。 3. 如前述請求項中任一項之營養組合物,其中該花生四烯 〇 酸之含量為50至60 mg/kg/日。 4·如前述請求項中.任一項之營養組合物,其中該哺乳動物 為自出生至3歲,較佳為自出生至12個月内之人類。 5.如㈤述請求項中任一項之營養組合物,其中以占該組合 物總脂肪酸含量之百分比表示,該組合物包含〇 6% (w/w)至1_2%(W/W)之花生四烯酸。 6. 〇 如前述請求項中任一項之營養組合物,其中該組合物中 母kcal包括0.3 mg至0.7 mg花生四稀酸。 7. 一種以花生四烯酸於製備如前述請求項中任一項之營養 組合物上之用途’其係投與出生後3年内之嬰兒,較佳 出生後12個月内之嬰兒,以降低日後發展肥胖及/或抗胰 島素症之風險。 8.如請求項7之花生四烯酸之用途,其中該嬰兒具有肥胖 之素因及/或抗胰島素症之素因。 147352.doc
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CN (1) | CN102368913A (zh) |
AU (1) | AU2010230362B2 (zh) |
BR (1) | BRPI1014923A2 (zh) |
CA (1) | CA2755077A1 (zh) |
CL (1) | CL2011002405A1 (zh) |
ES (1) | ES2570774T3 (zh) |
MX (1) | MX2011010229A (zh) |
MY (1) | MY161505A (zh) |
PL (1) | PL2413718T3 (zh) |
RU (1) | RU2559646C2 (zh) |
SG (1) | SG173914A1 (zh) |
TW (1) | TW201039759A (zh) |
WO (1) | WO2010112429A1 (zh) |
Cited By (1)
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CN104114043A (zh) * | 2011-12-27 | 2014-10-22 | 雅培制药有限公司 | 含有核苷酸和/或类胡萝卜素的降低卡路里的婴儿配方用于降低生命后期的不利健康影响的用途 |
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EP2514435A1 (en) * | 2011-04-19 | 2012-10-24 | Nestec S.A. | Infant formula for use in the prevention of cardiovascular diseases |
RU2604503C2 (ru) * | 2011-10-18 | 2016-12-10 | Нестек С.А. | Композиция для применения при повышении чувствительности к инсулину и/или снижении инсулинорезистентности |
SG11201405709SA (en) * | 2012-03-14 | 2014-10-30 | Abbott Lab | Nutritional compositions including rrr -alpha tocopherol and polyunsaturated fatty acids |
WO2014159967A1 (en) | 2013-03-13 | 2014-10-02 | Abbott Laboratories | A composition for enhancing newborn infant cognitive, brain and/or cns development and method of using same |
SG11201507210XA (en) | 2013-03-13 | 2015-10-29 | Abbott Lab | Infant nutritional product with rrr alpha-tocopherol |
AU2014356485A1 (en) * | 2013-11-29 | 2016-03-03 | Nestec S.A. | Infant nutrition for improvement in insulin sensitivity later in life |
US20180153951A1 (en) * | 2016-12-05 | 2018-06-07 | Mead Johnson Nutrition Company | Methods for Inducing Adipocyte Browning, Improving Metabolic Flexibility, and Reducing Detrimental White Adipocyte Tissue Deposition and Dysfunction |
BR112019028006A2 (pt) | 2017-06-30 | 2020-07-07 | N.V. Nutricia | composição nutricional, uso de uma combinação de bifidobacterium breve e oligossacarídeos não digeríveis, e método para prevenir e/ou reduzir o risco de ocorrência de hipercolesterolemia e/ou aterosclerose |
EP4159224A1 (en) | 2017-06-30 | 2023-04-05 | N.V. Nutricia | Synbiotic composition for preventing chronic inflammation |
CN116622514B (zh) * | 2023-07-21 | 2023-10-20 | 南京师范大学 | 提高微生物菌体和/或微生物油脂中多不饱和脂肪酸含量的调控方法及应用 |
Family Cites Families (17)
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NZ241359A (en) * | 1991-01-24 | 1994-08-26 | Martek Corp | Supplementation of infant formula by the addition of at least two different polyunsaturated fatty acids obtained from at least two different microbial sources; compositions comprising such oils |
US6200624B1 (en) * | 1996-01-26 | 2001-03-13 | Abbott Laboratories | Enteral formula or nutritional supplement containing arachidonic and docosahexaenoic acids |
US6077828A (en) * | 1996-04-25 | 2000-06-20 | Abbott Laboratories | Method for the prevention and treatment of cachexia and anorexia |
PL343902A1 (en) * | 1997-02-21 | 2001-09-10 | Abbott Lab | Methods of and compositions for reducing enteritis and colitis morbidity rate |
CN1660065A (zh) * | 1997-03-27 | 2005-08-31 | 布里斯托尔-迈尔斯斯奎布公司 | 二十二碳六烯酸和花生四烯酸促进不足月婴儿生长的用途 |
EP0880902A1 (fr) | 1997-05-27 | 1998-12-02 | Nestlé Produkte AG | Procédé de traitement d'une matiére première lactosérique |
DK1239022T3 (da) | 2001-03-09 | 2009-07-20 | Nestle Sa | Olie indeholdende en eller flere langkædede flerumættede fedtsyrer hidrörende fra biomasse, fremgangsmåde til fremstilling, levnedsmiddel, næringsmiddelsammensætning, kosmetisk sammensætning eller farmaceutisk sammensætning indeholdende denne |
US6753350B1 (en) * | 2003-03-24 | 2004-06-22 | Bristol-Myers Squibb Company | Method to reduce the incidence of intraventricular hemorrhage in preterm infants |
EP1622467A1 (en) * | 2003-05-05 | 2006-02-08 | Denofa AS | Fish oils with an altered fatty acid profile, method of producing same and their use |
EP1643862A1 (en) * | 2003-06-24 | 2006-04-12 | University of Kansas Medical Center | Infant formula |
US7759507B2 (en) * | 2003-09-05 | 2010-07-20 | Abbott Laboratories | Lipid system and methods of use |
CA2574360A1 (en) * | 2004-07-19 | 2006-01-26 | N.V. Nutricia | A preparation for use of aspartate for regulating glucose levels in blood |
WO2008054192A1 (en) | 2006-11-02 | 2008-05-08 | N.V. Nutricia | Use of nutritional compositions for preventing disorders |
EP1962617A2 (en) * | 2005-12-23 | 2008-09-03 | N.V. Nutricia | Infant nutritional compositions for preventing obesity |
WO2007100561A2 (en) | 2006-02-28 | 2007-09-07 | Bristol-Myers Squibb Company | Use of dha and ara in the preparation of a composition for preventing or treating obesity |
WO2007100562A2 (en) * | 2006-02-28 | 2007-09-07 | Bristol-Myers Squibb Company | Use of dha and ara in the preparation of a composition for reducing triglyceride levels |
EP1932437A1 (en) * | 2006-12-15 | 2008-06-18 | Nestec S.A. | Infant formula |
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2010
- 2010-03-26 ES ES10711219T patent/ES2570774T3/es active Active
- 2010-03-26 EP EP10711219.5A patent/EP2413718B1/en active Active
- 2010-03-26 US US13/260,842 patent/US9480670B2/en active Active
- 2010-03-26 CN CN2010800147082A patent/CN102368913A/zh active Pending
- 2010-03-26 PL PL10711219T patent/PL2413718T3/pl unknown
- 2010-03-26 WO PCT/EP2010/054025 patent/WO2010112429A1/en active Application Filing
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- 2010-03-26 MY MYPI2011004161A patent/MY161505A/en unknown
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- 2010-03-26 SG SG2011064169A patent/SG173914A1/en unknown
- 2010-04-01 TW TW099110173A patent/TW201039759A/zh unknown
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104114043A (zh) * | 2011-12-27 | 2014-10-22 | 雅培制药有限公司 | 含有核苷酸和/或类胡萝卜素的降低卡路里的婴儿配方用于降低生命后期的不利健康影响的用途 |
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AU2010230362A1 (en) | 2011-10-06 |
EP2413718A1 (en) | 2012-02-08 |
CN102368913A (zh) | 2012-03-07 |
BRPI1014923A2 (pt) | 2015-09-01 |
CL2011002405A1 (es) | 2012-03-23 |
WO2010112429A1 (en) | 2010-10-07 |
CA2755077A1 (en) | 2010-10-07 |
SG173914A1 (en) | 2011-10-28 |
RU2011144102A (ru) | 2013-05-10 |
US9480670B2 (en) | 2016-11-01 |
EP2413718B1 (en) | 2016-03-23 |
US9480671B2 (en) | 2016-11-01 |
ES2570774T3 (es) | 2016-05-20 |
MX2011010229A (es) | 2011-10-11 |
US20120029080A1 (en) | 2012-02-02 |
US20130296428A1 (en) | 2013-11-07 |
AU2010230362B2 (en) | 2015-01-15 |
RU2559646C2 (ru) | 2015-08-10 |
MY161505A (en) | 2017-04-14 |
PL2413718T3 (pl) | 2017-08-31 |
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