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TW201233331A - Nutritional products including monoglycerides and fatty acids - Google Patents

Nutritional products including monoglycerides and fatty acids Download PDF

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Publication number
TW201233331A
TW201233331A TW100149631A TW100149631A TW201233331A TW 201233331 A TW201233331 A TW 201233331A TW 100149631 A TW100149631 A TW 100149631A TW 100149631 A TW100149631 A TW 100149631A TW 201233331 A TW201233331 A TW 201233331A
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Taiwan
Prior art keywords
fatty acid
fat
weight
oil
nutritional
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TW100149631A
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Chinese (zh)
Inventor
Chron-Si Lai
John B Lasekan
Christopher T Cordle
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Abbott Lab
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Priority claimed from US13/333,949 external-priority patent/US9078846B2/en
Application filed by Abbott Lab filed Critical Abbott Lab
Publication of TW201233331A publication Critical patent/TW201233331A/en

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Abstract

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

Description

201233331 六、發明說明: 【發明所屬之技術領域】 本發明係關於包含預消化脂肪之營養品且係關於使用該 等營養品之方法。更特定而言,本發明係關於包含含有脂 肪酸之單酸甘油酯及/或脂肪酸組分的嬰兒、幼兒及小兒 產aD ’其&供營養益處,包括改善消化、耐受性及營養素 吸收以及減小壞死性小腸結腸炎、腹痛及短腸症之發生 率。 相關申請案之交叉參考 本申凊案主張2010年12月29曰申請之美國臨時申請案第 61/428,168號、2010年12月29日申請之美國臨時申請案第 61/428,173號、2010年12月29日申請之美國臨時申請案第 61/428,176號、2010年12月29日申請之美國臨時申請案第 61/428,177號及2010年12月29日申請之美國臨時申請案第 61/428’185號的權益,其揭示内容以全文引用之方式併入 本文中。 【先前技術】 包含有目標地選擇之營養素的營養液體及粉末(包括嬰 兒及小兒配方)為吾人所熟知且能廣泛獲得,其中一些可 乂供單一之營養來源,而其他可提供補充來源。該等營養 物包括可用水或其他含水液體復原之粉末,以及濃縮型及 即飲型營養液體,諸如基於牛奶或蛋白之乳液。該等營養 液體在與選定營養成分一起調配時尤為適用。 儘官通常認為母乳為新生嬰兒之最佳營養,但並非每位 161217.doc 201233331 母親能成功地以母乳哺育。母乳替代品(婴兒配方)可提供 完整營養,且已證明其能滿足嬰兒正常生長及發育營養需 求。不幸的是,小比例之嬰兒配方餵養新生兒可能會遇到 胃腸道(GI)不耐性問題,包括軟便、脹氣、壞死性小腸結 腸炎、腹痛及其類似問題》 GI不耐性問題可至少部分歸因於嬰兒營養素消化及吸收 不完全。為解決該耐受性問題,一些嬰兒配方排除乳糖作 為成分,而其他以水解蛋白替代完整乳蛋白以減輕嬰兒消 化系統的負擔。 此外,一些配方餵養新生嬰兒之脂肪吸收速率比母乳餵 養嬰兒低得多。此脂肪吸收速率之差異隨嬰兒逐漸成熟而 減小。據推測,新生嬰兒缺乏脂肪酶,且因此其無法與接 受母乳中之脂肪酶的母乳餵養嬰兒同等好地消化及吸收脂 肪。 早產兒之消化系統發育不及足月嬰兒之消化系統,其益 發比足月婴兒需要更多營養素(熱量)來促進生長及發育。 中鏈二酸甘油醋(MCT油)易於消化及吸收,且已包含於早 產兒配方中以改善配方脂肪、蛋白及鈣吸收。然而,中鏈 三酸甘油酷中包含之中鏈脂肪酸不被用於再合成三酸甘油 酯以在MCT油經消化及吸收之後形成乳糜微粒。因為咸信 許多脂溶性營養素(諸如類胡蘿蔔素及維生素A、d、E及 K)在進入全身性循環之前經封裝至乳糜微粒中,因此mct 油對脂溶性營養素吸收提供之益處(其對於生長及發育亦 重要)可能受到更多限制。 1612I7.doc 201233331 儘s過去已嘗試解決GI問題及上文提及之其他問題,但 理想的是提供可提供與母乳類似之營養益處且亦提供非水 溶性疏水性營養素之良好耐受性、消化及吸收以及使諸如 壞死性小腸結腸炎、腹痛及短腸症之病況發生率減小之嬰 兒及小兒配方。此外,若該等配方無穩定劑且特定而言無 角叉菜膠,則將為有益的。 【發明内容】 本發明係關於營養品,且特定而言係關於嬰兒配方,其 包3預消化脂肪,該預消化脂肪包含含有脂肪酸之單酸甘 油酯及/或脂肪酸組分。該等營養組合物可有利地用於改 善營養素(包含非水溶性/脂溶性營養素)耐受性、消化及吸 收’以及用於減小壞死性小腸結腸炎、腹痛及短腸症之發 生率。在某些實施例中,脂肪酸組分可為脂肪酸形式,或 以脂肪酸之鈣鹽或鎂鹽形式提供,由此提供其他營養素之 其他益處。 一個實施例為一種包含脂肪系統之營養品。該脂肪系統 包含至少10 wt%之不飽和游離脂肪酸組分與含有脂肪酸之 單酸甘油酯的滬合物。 另一實施例為一種包含脂肪系統之嬰兒配方。該脂肪系 統包含至少10 wt%之不飽和游離脂肪酸組分與含有脂肪酸 之單酸甘油酯的混合物。 已發現,包含預消化脂肪(諸如如本文所述之單酸甘油 酯及脂肪酸)之營養品(諸如嬰兒、幼兒及小兒配方)可減輕 嬰兒脂肪消化系統之總體負擔以改善嬰兒脂肪消化及吸 161217.doc 201233331 收,包含非水溶性/脂溶性營養素吸收。特定而言’小腸 近端部分中對預消化脂肪之吸收刺激CCK分泌’此促使胰 腺α細胞成熟及消化酶分泌。又,GLP-1及GLP-2分泌受到 刺激,此進一步促使腸道成熟。 令人驚訝地,使用預消化脂肪以及後續分泌CCK及GLP-1 使得GI轉運延遲且刺激胰腺酶分泌以使得營養素消化及吸 收更為完全。進入嬰兒結腸之營養素量的減少導致結腸醱 酵減少,此為脹氣及軟便問題之部分原因。另外,已發現 使用預消化脂肪可減小壞死性小腸結腸炎、腹痛及/或短 腸症之發生率。 此外’已發現預消化脂肪之不飽和脂肪酸組分可與辦或 鎂源反應且所得形成之鹽令人驚訝地為生物可用。除提供 良好鈣或鎂源以外’該等鈣或鎂鹽亦令人驚訝的是,與通 常有苦味且賦予強烈咽喉灼熱感受之脂肪酸相比較為溫 和。此外,已發現脂肪酸鈣鹽或鎂鹽令人驚訝地起到使營 養乳液穩定之作用,此係因為其不會形成在乳液中難以分 散之沈降物,不同於有此傾向之許多不溶性鈣鹽。因此, 在多個實施例中,包含脂肪酸鈣鹽或鎂鹽作為預消化脂肪 之部分可減少對穩定劑(諸如角又菜膠)之需求。 【實施方式】 本文所述之營養品包括預消化脂肪。在多個實施例中 =等產品包含含有脂肪酸之單酸甘油g旨及脂肪酸組分則 得預消化脂肪系統包含兩種組分。藉由減輕嬰兒、幼兒; 孩童消化系統之負擔’在提供穩定的生物可用產品之同: 161217.doc 201233331 實現多種益處。營養品之該等及其他特徵以及多種視情況 存在之變化及加料中之某些在下文中詳細描述。 術語「殺菌釜封裝」及「殺菌釜殺菌」在本文中可互換 使用,且除非另外說明,否則係指以營養液體填充容器 (最一般為金屬罐或其他類似封裝)且隨後使經液體填充之 封裝經觉必要之熱殺菌步驟以形成經殺菌之殺菌釜封裝營 養液體產品的常見操作。 除非另外說明,否則如本文所用之術語「無菌封裝」係 指不依賴於上述殺菌釜封裝步驟製造封裝產品,其中營養 液體及封裝在填充之前分開經過殺菌,且隨後在經殺菌或 無菌加工條件下組合以形成經殺菌、無菌封裝之營養液體 產品。 除非另外說明,否則如本文所用之術語「脂肪」及 「油j可互換使用,係指源自植物或動物或由其加工而得 之月曰質物質》g亥等術語亦包含合成脂質物質,只要該等合 成物質適合人類口服即可。 匕除非另外說明,㈣如本文㈣之術語「存放穩定」係 指在封裝且隨後在18_2代下儲存至少3個月(包含⑽個月 至約24個月’且亦包含約12個月至約18個月)之後仍在商 業上具穩定性之營養品β 如本文所用之術語「營養調配物」或「營養品」或「營 養組合物」可互換使用’且除非另外說明,否則係指液體 及固體(包含半液體及半固體)人乳強化劑、液體及固體早 產兒配方、液體及固體嬰兒配方、液體及固體第二階段配 161217.doc 201233331 方、液體及固體小兒配方以及液體及固體幼兒配方。該等 固體可為可經復原以形成營養液體之粉末,所有該等固體 均包括脂肪、蛋白及碳水化合物中之一或多者且適於人類 經口服用。 除非另外說明,否則如本文所用之術語「營養液體」係 指呈即飲型液體形式、濃縮形式之營養品及藉由在使用之 前使本文所述之營養粉末復原而製得之營養液體。 除非另外說明,否則如本文所用之術語「營養粉末」係 指在服用之前可用水或另一含水液體復原之呈可流動或可 ㈡取形式的營養品,且包含噴霧乾燥及乾混合/乾摻合粉 末。 「嬰兒」係指12 「早產兒」係指 「幼兒」係指〜 除非另外說明,否則如本文所用之術語 個月大或更幼小之人。如本文所用之術語 在懷孕36週之前出生之嬰兒。 除非另外說明,否則如本文所用之術語 歲以上至三歲之人。 除非另外說明,否則如本文所用之術語「孩童」係指三 歲以上至十二歲之人。 除非另外說明’否則如本文所用之術語「預消化脂肪」 係^含有脂肪酸之單酸甘油酯及/或脂肪酸組分。 除非另外說明’否則如本文所用之術語「嬰兒配方」係 才曰適於嬰兒服用作為主要營養源之液體及固體營養品。 除非另外說明’否則如本文所用之術語「早產兒配方」 系才θ適於早產兒服用作為主要營養源之液體及固體營養 161217.Λ 201233331 品。 =非另外說明’ $則如本文所用之術語「人乳強化劑」 系导曰適口與母乳或早產&酉己方或嬰兒配方混合以供早產或 足月嬰兒服用之液體及固體營養品。 。。除非另外說明,否則如本文所用之術語「含有脂肪酸之 早酸甘油si」係指由_個經㈣鍵在甘油分子之㈤⑷、 2(β)或Sn-3(a’)位置之一者處共價鍵結至甘油分子的脂 肪酸鏈組成之甘油酯。 除非另外說明’ $則如本文所用之術語「脂肪酸組分」 系才曰源自其中肉丑缝酸、棕櫚酸及硬脂酸總量小於20%(以 量。i*)之來源的游離脂肪酸或脂肪酸鹽(諸如脂肪酸鈣鹽 或鎂鹽)。 除非另外說明,否則如本文所用之術語「脂溶性營養 素」係指非水溶性營養素,諸如油可溶性(脂溶性)維生素 (例如維生素A、D、£及κ)、類胡蘿蔔素(例如葉黃素、β- 月蘿蔔素、番茄紅素等)、醣脂(神經結醣脂)、固醇及植物 化學品。 無挪疋否明確揭示,如本文所用之數值範圍均意欲包含 彼範圍内之每一數值及數值子集。此外,該等數值範圍應 視為對針對该範圍内任何數值或數值子集之主張提供支 持舉例而言,揭示1至10應理解為支持2至8、3至7、5至 6、1至9、3.6至4.6、3,5至9.9等之範圍。 除非另外說明或在有提及之語境下明確相反暗示,否則 本發明中所有提及之單數特徵或限制均應包含對應之複數 161217.doc 201233331 特徵或限制,且反之亦然。 除非另外說明或在有提及組合之語境下明確相反暗示, 否則如本文利之所有方法或製师驟組合均可 序進行。 本發明營養品之各個實施例亦可實f上無本文所述之任 何視情況存在或選定的成分或特徵,其限制條件為其餘營 養品應仍含有如本文所述之所有所需成分或特徵。在此背 景下,且除非另外說明’否則術語「實質上無」意謂選定 營養品含有小於功能量之視情況存在之成分般小於丄 重量%(包含小於〇.5重量% ’包含小於〇」重量%且亦包含。 重量%)之該視情況存在或選定的成分。 營養品及方法可包括如本文所述之產品要素以及本文所 述或另外適用於營養品及方法應用中之任何其他或視情況 存在之要素,由其組成或基本上由其組成。 產品形式 本發明之含有預消化脂肪的營養品及相關方法可以任何 已知或另外適合之口服產品形式來調配及執行。任何固 體半固體、液體、半液體或粉末形式(包括其組合或變 化形式)在本文中均適用,其限制條件為該等形式允許安 全且有效地向個體經口傳遞亦如本文所定義之各成分。 本發明之營養品包含如本文所述之預消化脂肪。該等產 品可視情況包含含有脂肪酸之單酸甘油酯或脂肪酸組分與 下文所述之其他脂肪來源的組合。 該等產品可包含包括本文所述之成分且口服安全又有效 16l2l7.doc -10- 201233331 之任何產品形式。該等營養品可經調配以僅包含本文所述 之成为,或可用視情況存在之成分改質以形成多種不同之 產品形式。 本發明之營養品較佳經調配為飲食產品形式,其在本文 中定義為以因而含有脂肪、蛋白及碳水化合物中之至少一 者且較佳亦含有維生素、礦物質或其組合之產品形式包括 本發明之成分的彼等實施例。在多個實施例甲,該產品將 包括預消化脂肪與蛋白質、碳水化合物、維生素及礦物質 之組合以產生營養品。 該·#營養品可用足夠種類及量之營養素調配以提供單 一、主要或補充性之營養來源,或提供專用於罹患特定疾 病或病況之個體或具有目標營養益處的營養品。 舉例而言,適合與如本文揭示之預消化脂肪一起使用之 產品形式的特定非限制性實例包含液體及粉末狀人乳強化 劑、液體及粉末狀早產兒配方、液體及粉末狀嬰兒配方、 液體及粉末狀要素及半要素配方、液體及粉末狀小兒配方 以及液體及粉末狀幼兒配方。 營養液艘 營養液體包含濃縮型及即食型營養液體。該等營養液體 最一般地經調配為懸浮液或乳液。 適用之營養乳液可為包含蛋白質、脂肪及碳水化合物之 含水乳液。該等乳液在約1 至約25°C下通常為可流動或 可飲用之液體且一般呈水包油、油包水或複合含水乳液形 式’不過該等乳液最一般為具有連續水相及不連續油相之 1612l7.doc 201233331 水包油乳液形式。 營養乳液可為存放穩定的且一般為存放穩定的。該等營 養乳液以營養乳液之重量計一般含有高達約95重量。/〇之 水’包括約50重量%至約95重量%,亦包括約60重量。/〇至 約90重量% ’且亦包括約7〇重量%至約88重量%之水。營 養乳液可具有各種產品密度,但最一般具有大於約丨〇3 g/ml之松度’包括大於約〗〇4 ,包括大於約丨〇55 g/ml ’包括約1.06 g/mi至約112 g/m丨,且亦包括約1 〇85 g/ml 至約 1.10 g/ml。 營養乳液可具有為符合最終使用者之營養需求而定製之 熱量密度’不過在大多數情況下該等乳液通常包含至少19 kcal/fl oz(660千卡/公升)' 更一般為約2〇 kcai/fi 〇z(675- 680千卡/公升)至約25 kcal/fl oz(820千卡/公升)、甚至更一 般為約 20 kcal/fl OZ(675-680 千卡 /公升)至約 24 kcal/fl oz(800-810千卡/公升)。通常而言,22_24 kcal/fl 〇z(74〇_ 810千卡/公升)配方更普遍用於早產或低出生體重的嬰兒, 且20-21 kcal/fl OZ(675-680至700千卡/公升)配方更常用於 足月嬰兒。在某些實施例中,乳液可具有約! 〇〇千卡/公升 至約660千卡/公升之熱量密度,包括約15〇千卡/公升至約 500千卡/公升。 營養乳液可具有約3.5至約8範圍内之pH值,但最有利地 為約4.5至約7.5範圍内,包括約5.5至約7.3,包括約6.2至 約 7.2。 儘管營養乳液之服用量可視多種變數而變化,但典型之 161217.doc •12- 201233331 服用量通常為至少約2mL ’或甚至至少約5机,或甚至至 少mo mL’或甚至至少約25 mL,包括約2 ‘至約3〇〇 mL範圍内,包括約4 mL至約25〇机,且包括約ι〇社至約 240 mL。 如上所述,營養品亦可為半液體形式,包括特性(諸如 流動特性)介於中間態(在液體與固體之間)之彼等形式。例 示性半液體包括黏稠奶昔及液體凝膠。 營養固體 營養固體可為任何固體形式,但一般為可流動或實質上 可流動的微粒組合物形式,或至少為微粒組合物。尤其適 合之營養固體產品形式包括經喷霧乾燥、聚結或乾摻合之 粉末組合物。該等組合物可容易地用勺子或類似其他裝置 來舀取或量測,其中該等組合物可容易地由預期使用者以 適合之含水液體(一般為水)來復原以形成營養調配物以供 即刻經口或經腸使用。在此背景下,「即刻」使用通常意 吕胃較佳正好在復原後約48小時之内,最一般在約24小時之 内。 營養粉末可在使用之前用水復原至為符合最終使用者之 營養需求而定製之熱量密度,不過在大多數情況下該等粉 末用水復原而形成包含至少19 kcal/fl oz(660千卡/公升)、 更一般為約 20 kcal/fl oz(675-680千卡/公升)至約25 kcal/fl oz(820千卡/公升)、甚至更一般為約20 kcal/fl oz(675-680 千卡/公升)至約24 kcal/fl oz(800-810千卡/公升)之組合 物。通常而言,22-24 kcal/fl οζ(740·810千卡/公升)配方更 I61217.doc 13 201233331 普遍用於早產或低出生體重的嬰兒,且2〇_2l kcal/fi 〇ζ(675·680至700千卡/公升)配方更常用於足月嬰兒。在某 些實施例中,復原粉末可具有約5〇千卡/公升至約66〇千卡/ 公升之熱量密度,包括約1〇〇千卡/公升至約500千卡/公 升。 如上所述,營養品亦可為半固體形式,包括特性(諸如 剛性)介於中間態(在固體與液體之間)之彼等形式。一些半 固體實例包括布丁、明膠及膏團。 預消化脂肪系統 A.含有脂肪酸之單酸甘油醋 在某些實施例中,本發明之營養品包含單獨或與如下文 所述之脂肪酸組分組合的含有脂肪酸之單酸甘油酯,亦稱 作單醯基甘油。單酸甘油酯為在三酸甘油酯及二酸甘油酯 刀解時在體内形成之正常代謝物β正如所述,含有脂肪酸 之單酸甘油酯可與脂肪酸組分(諸如如下文所述之脂肪酸 及/或脂肪酸鹽)組合包含於營養品中,或可在不存在脂肪 酸組分之情況下包含於營養品中。 適合用於營養品中之含有脂肪酸之單酸甘油酯可包含具 有4至22個碳原子之鍵長度的脂肪酸,包括具有丨4至2〇個 碳原子之鏈長度的脂肪酸,且包括棕櫚酸(16個碳原子)。 尤其較佳為單酸甘油酯,其中單酸甘油酯中至少7〇%之脂 肪酸位於Sn-1位置,包括在Sn_ 1位置(亦稱作α位置)處具有 至少約70%之棕櫊酸殘基的單棕櫚酸甘油酯,包括在以] 值置處至少約80°/。,且包括在位置處約85%至約 I61217.doc 14 201233331 100 /ό。此外,在某些實施例中,本文所述營養品中包含 之單酸甘油酯可包括痕量之二酸甘油酯、游離甘油及/或 游離脂肪酸。如本文中所用,術語「痕量」意謂不超過10 wt/ό但更通常小於7.5 wt%之量。 在一個特定實施例中,營養品中之單酸甘油酯(且視情 況為如下文論述之脂肪酸組分)部分地或完全經由使用水 解豬油或水解動物脂來向產品提供。豬油、動物脂及其他 基於動物之產品可添加至營養品中且由胰腺脂肪酶水解為 單酸甘油酿及脂肪酸。或者,豬油或動物脂可經水解之後 併入營養品中以產生單酸甘油酯及脂肪酸,其可引入營養 中。豬油、動物脂或水解豬油或動物脂可提供營養品中 之一部分或所有單酸甘油醋及/或脂肪酸。 在另一實施例中,營養品中之單酸甘油酯部分或完全源 自油類,諸如植物油、水產動物油、魚油、海藻油、真菌 油、樹脂及其組合。舉例而言’適合之植物油包括撖欖 油、芥花籽油(Canola oil)、玉米油、棕櫚油、大豆油 (soybean oil)及其組合。 含有脂肪酸之單酸甘油酷以&技I 0 h <平敗甘油S日以按營養品中包含之脂肪組分 s十至少約1 〇重量%之量存在於營養 包含之脂肪組分計至少約1 5重量% 品中,包括以營養品中 ’包括以營養品中包含 之脂肪組分計至少約20重量0/,句括放 丄 置々a栝以營養品中包含之摧 肪組分計12重量%至45重量%、包括舌旦 I。巴栝15重量%至25重量%卫 包括約10重量%、包括約j 5重量% 里$ /〇包括約20重量%、包 括約25重量%、包括約3〇重量% 里丘進一步包括約35重量 161217.doc -15- 201233331 %、或甚至約40重量%、或甚至約50重量%、或甚至約60 重量%、或甚至約70重量%、或甚至約80重量%、或甚至 約90重量%、或甚至約10〇重量%。 在一個特定實施例中,當營養品為包含約28%(以營養粉 末之重量計)脂肪組分之營養粉末時,含有脂肪酸之單酸 甘油酯以約10%(以脂肪組分之重量計)之含量存在,或每 100公克營養粉末約2.8公克含有脂肪酸之單酸甘油酯。 在另一特定實施例中,當營養品為包含約3.67%(以即食 型營養液體之重量計)脂肪組分之即食型營養液體時,含 有脂肪酸之單酸甘油酯以約10%(以脂肪組分之重量計)之 含量存在’或每100公克即食型營養液體約〇3 67公克含有 脂肪酸之單酸甘油酯。 在另一特定實施例中,當營養品為包含約7 34〇/〇(以濃縮 型營養液體之重量計)脂肪組分之濃縮型營養液體時,含 有脂肪酸之單酸甘油酯以約1 〇%(以脂肪組分之重量計)之 含量存在,或每100公克濃縮型營養液體約〇 734公克含有 脂肪酸之單酸甘油酯。 除k供上文所列之多種益處以外’亦已發現含有脂肪酸 之單酸甘油酯在營養品中具有抗病毒及/或抗細菌活性。 特定而言,已發現營養品中含有脂肪酸之單酸甘油酯之存 在能殺死病原體及/或減緩其複製。 B.脂肪酸组分 除上述含有脂肪酸之單酸甘油酯以外,或替代上述含有 脂肪酸之單酸甘油酯,本發明之營養品可包含含有脂肪酸 161217.doc 16 201233331 之脂肪酸組分作為預消化脂肪系統之一部分。脂肪酸為在 月曰肪(二酸甘油酯、二酸甘油酯、膽固醇酯及某些填脂)分 解時在體内顯著形成之正常代謝物^該脂肪酸組分為獨立 的且不同於上文論述之含有脂肪酸之單酸甘油酯。 在營養品中有益之任何脂肪酸均可作為預消化脂肪系統 之 #分包含於營養品中。在一個實施例中,脂肪酸為不 飽和游離脂肪酸。在包含不飽和游離脂肪酸之某些實施例 中’具有超過14個碳原子之鏈長度的不飽和游離脂肪酸之 總量小於15 wt%。適合包含於本文所述營養品中之例示性 脂肪酸包括(但不限於)花生四烯酸、次亞麻油酸、二十二 碳六烯酸、十八碳四稀酸、油酸、二十碳烯酸、二十碳三 烯酸(mead acid)、芥酸、神經酸以及其混合物及組合。尤 其較佳之脂肪酸包括花生四烯酸、亞麻油酸、次亞麻油 酸、二十二碳六烯酸及油酸。 包含於預消化脂肪系統中之脂肪酸組分包括源自諸如植 物油、水產動物油、魚油、海藻油、真菌油、動物脂肪、 動物脂肪分離物及其組合之油類的彼等脂肪酸組分。舉例 而言,適合之植物油包括撖欖油、芥花籽油、玉米油、大 豆油及其組合。在一個實施例中,當使用動物脂肪時,脂 肪酸係由豬油或動物脂之酶促水解而獲得,且所得脂肪酸 混合物中棕櫚酸及硬脂酸之含量減少至小於總脂肪酸之 20%,包括小於總脂肪酸之2%。在另一實施例中,至少一 些脂肪酸源自大豆油或樹脂。一旦源自油來源,則脂肪酸 實質上不含單酸甘油酯、二酸甘油酯及三酸甘油酯。 161217.doc •17- 201233331 脂肪酸通常將源自含有小於約20%(以重量計)棕櫚酸及/ 或硬脂酸及/或肉豆蔻酸之源油。在某些實施例中,脂肪 酸將源自含有小於約15%(以重量計)、包括小於約1〇%(以 重量計)、包括小於約5°/。(以重量計)且包括小於2%(以重量 計)棕摘酸及/或硬脂酸及/或肉豆蔻酸之源油。 在一個特定實施例中,脂肪酸係源自含有小於約2〇%(以 重量什)’包括約1 〇%(以重量計)至約丨(以重量計)栋棚 酸及/或硬脂酸及/或肉豆蔻酸之源油。在另一特定實施例 中’營養品包含以總脂肪酸計小於約10%(以重量計)之量 的棕櫚酸》 在某些實施例中,營養品可包含呈鹽形式之脂肪酸;亦 即’脂肪酸可以脂肪酸鹽形式添加至營養品中。在一個適 合的實施例中,脂肪酸係以脂肪酸鈣鹽、脂肪酸鎂鹽或其 組合之形式添加至營養品中。 脂肪酸鹽可由熟習此項技術者基於本文之揭示内容來製 備。在一種適合的製程中,包含Cl〇_C24脂肪酸鈣鹽之乳液 可藉由首先藉由使用與至少一種Cl0_C24脂肪酸來源混合之 若干種起始鈣來源製備脂肪酸鹽來製備。更特定而t,在 一種方法中,包含呈三酸甘油酯摻合物形式或游離形式的 C10-C24脂肪酸之起始來源可藉由與氫氧化鈣及/或碳酸鈣 及/或磷酸鈣接觸而形成。在另一種方法中,呈三酸甘油 酯摻合物或游離形式之匕❶名24脂肪酸可藉由與15^1值為6至 約7.5之水合〇&(:12或(:3(八(^0)2接觸而製得。 以上方法可在惰性氛圍下,例如在乂或氬氣下進行。在 161217.doc -18- 201233331 其他實例中,任γ所4 m * μ均可錢錢圍下進行 ',其中不在低氧氛圍下進行反應)。 包含。<24脂肪酸之來源與舞來源可藉由此項技 =之任何方法來混合。「混合」並非意謂暗示特定混合社 果,諸如任何組分溶解至特定程度或形成特定組合物(諸 如均質混合物),不過可I生該等混合物且某些組分可藉 混合而溶解。混合可為劇烈的且可手動或藉由機械裝^ 諸如(但不限於)靜態混合器、磁力授拌器、振堡器 '旋轉 器或旋轉裝置)來進行。混合可藉由迫使氣體通過混合物 或使氣體起泡通過混合物或藉由音波處理來進行。201233331 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to a nutritional product comprising pre-digested fat and to a method of using the nutritional product. More particularly, the present invention relates to infants, young children, and pediatrics comprising fatty acid-containing monoglycerides and/or fatty acid components for a nutritional benefit, including improved digestion, tolerance, and nutrient absorption, and Reduce the incidence of necrotizing enterocolitis, abdominal pain and short bowel disease. CROSS-REFERENCE TO RELATED APPLICATIONS RELATED APPLICATIONS STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT STATEMENT REGARDING RELATED APPLICATIONS, RELATED APPLICATIONS, RELATED APPLICATIONS U.S. Provisional Application No. 61/428,176, filed on Dec. 29, and U.S. Provisional Application No. 61/428,177, filed on December 29, 2010, and U.S. Provisional Application No. 61/, filed on Dec. 29, 2010 The benefit of 428 '185, the disclosure of which is incorporated herein in its entirety by reference. [Prior Art] Nutrient liquids and powders (including infant and pediatric formulas) containing targeted nutrients are well known and widely available, some of which are available for a single source of nutrition, while others provide supplemental sources. Such nutrients include powders that can be reconstituted with water or other aqueous liquids, as well as concentrated and ready-to-drink nutrient liquids, such as milk or protein based emulsions. These nutrient liquids are especially useful when formulated with selected nutrients. It is generally considered that breast milk is the best nutrition for newborn babies, but not every 161217.doc 201233331 Mothers can successfully breastfeed. Breastmilk substitutes (infant formulas) provide complete nutrition and have been shown to meet normal growth and developmental nutritional needs of infants. Unfortunately, a small proportion of infant formula-fed newborns may experience gastrointestinal (GI) intolerance problems, including soft stools, flatulence, necrotizing enterocolitis, abdominal pain, and the like. GI intolerance issues can be at least partially Due to the incomplete digestion and absorption of infant nutrients. To address this tolerance problem, some infant formulas exclude lactose as a component, while others replace hydrolyzed proteins with intact milk proteins to reduce the burden on the infant's digestive system. In addition, some formula-fed newborn babies have a much lower rate of fat absorption than breast-fed babies. This difference in fat absorption rate decreases as the baby matures. It is speculated that newborn babies lack lipase and therefore cannot digest and absorb fat as well as breastfed babies who receive lipase from breast milk. The digestive system of premature infants is less developed than the digestive system of full-term infants, which requires more nutrients (calories) than full-term infants to promote growth and development. Medium chain diglyceride (MCT oil) is easy to digest and absorb and is included in preterm formula to improve formula fat, protein and calcium absorption. However, medium chain triglycerides contain medium chain fatty acids that are not used to re-synthesize triglycerides to form chylomicrons after digestion and absorption of MCT oil. Because many fat-soluble nutrients (such as carotenoids and vitamins A, d, E, and K) are encapsulated into chylomicrons before entering the systemic circulation, the benefits of mct oil for fat-soluble nutrient absorption (for growth) And development is also important) may be subject to more restrictions. 1612I7.doc 201233331 In the past, we have tried to solve the GI problem and other problems mentioned above, but it is desirable to provide good tolerance and digestion that can provide similar nutritional benefits to breast milk and also provide water-insoluble hydrophobic nutrients. And infants and pediatric formulations that absorb and reduce the incidence of conditions such as necrotizing enterocolitis, abdominal pain, and short bowel disease. In addition, it would be beneficial if the formulations were free of stabilizers and in particular no carrageenan. SUMMARY OF THE INVENTION The present invention relates to nutritional products, and in particular to infant formulas, which comprise a pre-digested fat comprising a fatty acid monoglyceride and/or fatty acid component. These nutritional compositions can be advantageously used to improve the tolerance of nutrients (including water-insoluble/fat-soluble nutrients), digestion and absorption, and to reduce the incidence of necrotizing enterocolitis, abdominal pain and short bowel disease. In certain embodiments, the fatty acid component can be in the form of a fatty acid or in the form of a calcium or magnesium salt of a fatty acid, thereby providing other benefits of other nutrients. One embodiment is a nutritional product comprising a fat system. The fat system comprises at least 10% by weight of a mixture of an unsaturated free fatty acid component and a fatty acid-containing monoglyceride. Another embodiment is an infant formula comprising a fat system. The fat system comprises a mixture of at least 10% by weight of an unsaturated free fatty acid component and a fatty acid-containing monoglyceride. It has been found that nutrients (such as infants, toddlers, and pediatric formulas) containing pre-digested fats (such as monoglycerides and fatty acids as described herein) can alleviate the overall burden of the baby's fat digestive system to improve infant fat digestion and absorption 161217 .doc 201233331 Received, containing water-insoluble / fat-soluble nutrient absorption. In particular, the absorption of pre-digested fat in the proximal portion of the small intestine stimulates CCK secretion, which promotes pancreatic alpha-cell maturation and digestive enzyme secretion. In addition, GLP-1 and GLP-2 secretion are stimulated, which further promotes intestinal maturation. Surprisingly, the use of pre-digested fat and subsequent secretion of CCK and GLP-1 delays GI transport and stimulates pancreatic enzyme secretion to allow nutrient digestion and absorption to be more complete. A decrease in the amount of nutrients entering the infant's colon leads to a decrease in colonic fermentation, which is partly responsible for the problem of flatulence and soft stools. In addition, the use of pre-digested fat has been found to reduce the incidence of necrotizing enterocolitis, abdominal pain and/or short bowel disease. Furthermore, it has been found that the pre-digested fat unsaturated fatty acid component can react with the magnesium or magnesium source and the resulting salt is surprisingly bioavailable. In addition to providing a good source of calcium or magnesium, the calcium or magnesium salts are surprisingly milder than fatty acids which generally have a bitter taste and impart a strong burning sensation in the throat. In addition, it has been found that fatty acid calcium or magnesium salts surprisingly act to stabilize the nutritional emulsion because it does not form sediments that are difficult to disperse in the emulsion, unlike many insoluble calcium salts that have this tendency. Thus, in various embodiments, the inclusion of a fatty acid calcium or magnesium salt as part of the pre-digested fat may reduce the need for stabilizers such as keratin. [Embodiment] The nutritional products described herein include pre-digested fat. In various embodiments, the iso-product contains a fatty acid containing monoglyceride g and a fatty acid component such that the pre-digested fat system comprises two components. By reducing the burden on infants and young children; the digestive system of children' is to provide stable bioavailable products: 161217.doc 201233331 Achieve multiple benefits. These and other features of the nutritional product, as well as a variety of variations, as appropriate, and some of the additions are described in detail below. The terms "sterilizer" and "sterilizer" are used interchangeably herein and, unless otherwise stated, are meant to fill a container with a nutrient liquid (most typically a metal can or other similar package) and subsequently fill the liquid. Encapsulating the necessary thermal sterilization steps to form a common operation for sterilizing a sterilized bottling nutrient liquid product. The term "aseptically packaged" as used herein, unless otherwise indicated, refers to the manufacture of a packaged product that does not rely on the above described sterilization step, wherein the nutritional liquid and package are separately sterilized prior to filling and subsequently subjected to sterilization or aseptic processing conditions. Combine to form a sterilized, aseptically packaged nutritional liquid product. The terms "fat" and "oil j" are used interchangeably herein to refer to a plant derived from or derived from a plant or animal, unless otherwise stated, and the terms "g" also include synthetic lipid materials. As long as the synthetic substances are suitable for human oral administration. 四 Unless otherwise stated, (4) The term "storage stable" as used in this document (4) means at least 3 months (including (10) months to about 24 months) after encapsulation and subsequent storage at 18_2 generations. Nutritional products that are still commercially stable after the month 'and also contains from about 12 months to about 18 months'. The terms "nutritional formula" or "nutrition" or "nutritional composition" are used interchangeably. Use 'and unless otherwise stated, refers to liquid and solid (including semi-liquid and semi-solid) human milk fortifiers, liquid and solid preterm formula, liquid and solid infant formula, liquid and solid second stage 161217.doc 201233331 Formulas for formulas for children, liquids and solids, as well as liquid and solid infant formulas. The solids can be a powder that can be reconstituted to form a nutrient liquid, all of which include one or more of fats, proteins, and carbohydrates and are suitable for oral administration to humans. The term "nutritional liquid" as used herein, unless otherwise indicated, refers to a nutrient in a ready-to-drink liquid form, a concentrated form, and a nutritional liquid prepared by reconstituting the nutritional powder described herein prior to use. The term "nutritional powder" as used herein, unless otherwise indicated, refers to a nutrient in a flowable or pharmaceutically acceptable form that can be reconstituted with water or another aqueous liquid prior to administration, and includes spray drying and dry mixing/dry mixing. Powder. "Baby" means 12 "premature baby" means "child" means ~ unless otherwise stated, the term "monthly or younger" as used herein. As used herein, the term infant born before 36 weeks of gestation. The term "from one year old to three years old" as used herein, unless otherwise stated. The term "child" as used herein, unless otherwise indicated, refers to a person between the ages of three and twelve. The term "pre-digested fat" as used herein, unless otherwise stated, is intended to include a fatty acid monoglyceride and/or fatty acid component. The term "infant formula" as used herein, unless otherwise stated, is suitable for infants to take liquid and solid nutritional supplements as a primary source of nutrients. Unless otherwise stated, the term "premature formula" as used herein is suitable for preterm infants to take liquid and solid nutrients as a major source of nutrients 161,217.Λ 201233331. = not otherwise stated ’ $ The term “human milk fortifier” as used herein refers to liquid and solid nutritional supplements that are suitable for preterm or full-term infants by mixing with breast milk or premature & . . The term "early acid glycerol si containing a fatty acid" as used herein, unless otherwise indicated, refers to one of the (f) (4), 2 (β) or Sn-3 (a') positions of the glycerol molecule. A glyceride covalently bonded to a fatty acid chain of a glycerol molecule. The term "fatty acid component" as used herein, unless otherwise stated, is derived from a free fatty acid derived from a source of less than 20% (by mass. i*) of the total amount of meat, palmitic acid and stearic acid. Or a fatty acid salt (such as a fatty acid calcium or magnesium salt). The term "liposoluble nutrient" as used herein, unless otherwise indicated, refers to water-insoluble nutrients such as oil-soluble (fat-soluble) vitamins (eg, vitamins A, D, £ and κ), carotenoids (eg, lutein). , β-moon radish, lycopene, etc.), glycolipids (nerveolipids), sterols and phytochemicals. Nothing is explicitly disclosed, and the numerical ranges used herein are intended to encompass each value and sub-set of the. In addition, the numerical ranges are to be construed as providing support for the claims of any value or subset of values within the range. The disclosures 1 to 10 are understood to support 2 to 8, 3 to 7, 5 to 6, 1 to 9. Ranges from 3.6 to 4.6, 3, 5 to 9.9, etc. All singular features or limitations of the present invention are intended to include the singular 161217.doc 201233331 features or limitations, and vice versa, unless otherwise stated or indicated to the contrary. All methods or master combinations as herein may be performed, unless otherwise stated or clearly indicated to the contrary. The various embodiments of the nutritional products of the present invention may also be free of any optional or selected ingredients or features described herein, with the proviso that the remaining nutritional products should still contain all of the desired ingredients or characteristics as described herein. . In this context, and unless otherwise stated, the term "substantially absent" means that the selected nutrient contains less than 丄% by weight of the component, which is less than 功能.5 wt%, contains less than 〇. % by weight and also included % by weight of the component present or selected as appropriate. The nutraceuticals and methods can comprise, consist of, or consist essentially of, the product elements described herein, as well as any other or optionally existing elements described herein or otherwise applicable to the use of the nutraceutical and method. Product Form The pre-digested fat-containing nutrient of the present invention and related methods can be formulated and executed in any known or otherwise suitable oral product form. Any solid semi-solid, liquid, semi-liquid or powder form, including combinations or variations thereof, is used herein with the proviso that such forms permit safe and effective oral delivery to an individual, as defined herein. ingredient. The nutritional product of the present invention comprises pre-digested fat as described herein. Such products may optionally comprise a combination of a fatty acid containing monoglyceride or fatty acid component with other fat sources as described below. Such products may comprise any of the product forms including the ingredients described herein and which are safe and effective for oral administration, 16l2l7.doc -10- 201233331. The nutritional products may be formulated to include only those described herein, or may be modified with components as appropriate to form a plurality of different product forms. The nutritional product of the present invention is preferably formulated in the form of a dietary product, which is defined herein as a product form comprising at least one of fat, protein and carbohydrate, and preferably also vitamins, minerals or combinations thereof. Examples of the components of the invention. In various embodiments A, the product will include a combination of pre-digested fat with protein, carbohydrates, vitamins and minerals to produce a nutritional product. The ## nutraceuticals can be formulated with sufficient types and amounts of nutrients to provide a single, primary or supplemental source of nutrition, or to provide an individual dedicated to a particular disease or condition or a nutritional product with a targeted nutritional benefit. For example, specific non-limiting examples of product forms suitable for use with the pre-digested fats disclosed herein include liquid and powdered human milk fortifiers, liquid and powdered preterm formulas, liquid and powdered infant formulas, liquids And powdery and semi-element formulas, liquid and powdered pediatric formulas, and liquid and powdered infant formulas. Nutrient fluids Nutritional fluids contain concentrated and ready-to-eat nutrient liquids. These nutrient liquids are most commonly formulated as suspensions or emulsions. Suitable nutritional emulsions can be aqueous emulsions containing proteins, fats and carbohydrates. The emulsions are typically in the form of a flowable or potable liquid at from about 1 to about 25 ° C and are typically in the form of an oil-in-water, water-in-oil or complex aqueous emulsion. However, such emulsions most generally have a continuous aqueous phase and Continuous oil phase in the form of 1612l7.doc 201233331 oil-in-water emulsion. The nutritional emulsion can be stable to storage and generally stable to storage. These nutritional emulsions typically contain up to about 95 weight percent based on the weight of the nutritional emulsion. The water of the crucible includes from about 50% by weight to about 95% by weight, and also includes about 60% by weight. /〇 to about 90% by weight' and also includes from about 7% by weight to about 88% by weight of water. The nutritional emulsion can have a variety of product densities, but most typically has a bulk of greater than about 丨〇3 g/ml 'including greater than about 〇4, including greater than about 丨〇55 g/ml' including from about 1.06 g/mi to about 112. g/m丨, and also includes from about 1 〇85 g/ml to about 1.10 g/ml. The nutritional emulsion can have a caloric density tailored to meet the nutritional needs of the end user's. However, in most cases the emulsions typically contain at least 19 kcal/fl oz (660 kcal/liter)' more typically about 2 inches. Kcai/fi 〇z (675- 680 kcal / liter) to about 25 kcal / fl oz (820 kcal / liter), and even more generally about 20 kcal / fl OZ (675-680 kcal / liter) to about 24 kcal/fl oz (800-810 kcal/litre). In general, 22_24 kcal/fl 〇z (74〇_ 810 kcal/litre) formula is more commonly used in preterm or low birth weight infants, and 20-21 kcal/fl OZ (675-680 to 700 kcal/ Liters) formulas are more commonly used in term infants. In certain embodiments, the emulsion can have about! 〇〇 kcal/litre to a heat density of approximately 660 kcal/litre, including approximately 15 〇 kcal/litre to approximately 500 kcal/litre. The nutritional emulsion may have a pH in the range of from about 3.5 to about 8, but most advantageously in the range of from about 4.5 to about 7.5, including from about 5.5 to about 7.3, including from about 6.2 to about 7.2. Although the amount of nutrient emulsion can vary depending on a variety of variables, typical 161217.doc •12-201233331 is typically administered in an amount of at least about 2 mL' or even at least about 5 machines, or even at least mo mL' or even at least about 25 mL. It includes from about 2' to about 3 〇〇mL, including from about 4 mL to about 25 Torr, and includes from about 1 to about 240 mL. As noted above, the nutritional product may also be in a semi-liquid form, including such forms in which the properties (such as flow characteristics) are intermediate (between the liquid and the solid). Exemplary semi-liquids include viscous shakes and liquid gels. Nutritional Solids The nutritional solids can be in any solid form, but are generally in the form of a flowable or substantially flowable particulate composition, or at least a particulate composition. Particularly suitable nutritional solid product forms include spray dried, coalesced or dry blended powder compositions. The compositions can be easily retrieved or measured using a spoon or similar device, wherein the compositions can be readily reconstituted by a prospective user with a suitable aqueous liquid (typically water) to form a nutritional formulation. For immediate oral or enteral use. In this context, the use of "immediately" is usually within about 48 hours of recovery, most typically within about 24 hours. The nutritional powder can be reconstituted with water prior to use to a caloric density tailored to meet the end user's nutritional needs, but in most cases the powder is reconstituted with water to form at least 19 kcal/fl oz (660 kcal/liter) ), more generally about 20 kcal/fl oz (675-680 kcal / liter) to about 25 kcal / fl oz (820 kcal / liter), and even more generally about 20 kcal / fl oz (675-680 thousand Card/L) to a composition of approximately 24 kcal/fl oz (800-810 kcal/liter). In general, 22-24 kcal/fl οζ (740·810 kcal/litre) formula is more I61217.doc 13 201233331 is commonly used in premature or low birth weight infants, and 2〇_2l kcal/fi 〇ζ (675 · 680 to 700 kcal / liter) formula is more commonly used in term infants. In some embodiments, the reconstituted powder can have a caloric density of from about 5 kcal/liter to about 66 kcal/liter, including from about 1 kcal/liter to about 500 kcal/liter. As noted above, the nutritional product may also be in a semi-solid form, including such forms as properties (such as stiffness) in the intermediate state (between the solid and the liquid). Some semi-solid examples include puddings, gelatin, and creams. Pre-digested fat system A. Monoglyceride containing fatty acid. In certain embodiments, the nutritional product of the present invention comprises a fatty acid-containing monoglyceride, alone or in combination with a fatty acid component as described below, also referred to as Monothiol glycerol. Monoglyceride is a normal metabolite formed in the body when the triglyceride and the diglyceride are cleaved. As described, the fatty acid-containing monoglyceride can be combined with the fatty acid component (such as described below). The fatty acid and/or fatty acid salt combination is included in the nutritional product or may be included in the nutritional product in the absence of the fatty acid component. A fatty acid-containing monoglyceride suitable for use in a nutritional product may comprise a fatty acid having a bond length of 4 to 22 carbon atoms, including a fatty acid having a chain length of from 4 to 2 carbon atoms, and including palmitic acid ( 16 carbon atoms). Particularly preferred is a monoglyceride wherein at least 7% by weight of the fatty acid in the monoglyceride is at the Sn-1 position, including at least about 70% palmitate residue at the Sn-1 position (also referred to as the alpha position). The mono-monopalmitinate is included at a value of at least about 80°/. And includes approximately 85% at the location to approximately I61217.doc 14 201233331 100 /ό. Moreover, in certain embodiments, the monoglycerides included in the nutritional products described herein may include trace amounts of diglycerides, free glycerol, and/or free fatty acids. As used herein, the term "trace" means an amount not exceeding 10 wt/ό but more typically less than 7.5 wt%. In a particular embodiment, the monoglyceride in the nutrient (and, as the case may be, the fatty acid component as discussed below) is provided to the product, either partially or completely via the use of hydrolyzed lard or hydrolyzed animal fat. Lard, tallow and other animal-based products can be added to nutrients and hydrolyzed by pancreatic lipase to monoglycerides and fatty acids. Alternatively, lard or tallow can be incorporated into the nutrient after hydrolysis to produce monoglycerides and fatty acids which can be introduced into the nutrient. Lard, tallow or hydrolyzed lard or tallow may provide some or all of the monoglycerides and/or fatty acids in the nutrient. In another embodiment, the monoglycerides in the nutritional product are partially or completely derived from oils such as vegetable oils, marine animal oils, fish oils, algae oils, fungal oils, resins, and combinations thereof. For example, suitable vegetable oils include eucalyptus oil, canola oil, corn oil, palm oil, soybean oil, and combinations thereof. The monoglyceride containing a fatty acid is present in the nutrient-containing fat component in an amount of at least about 1% by weight of the fat component s contained in the nutrient. At least about 15% by weight of the product, including at least about 20% by weight of the fat component contained in the nutrient, and including the fat-containing group included in the nutrient The fraction is from 12% by weight to 45% by weight, including the tongue I. Barley 15% to 25% by weight includes about 10% by weight, including about j 5% by weight, including about 20% by weight, including about 25% by weight, including about 3% by weight, and further comprising about 35%. Weight 161217.doc -15-201233331%, or even about 40% by weight, or even about 50% by weight, or even about 60% by weight, or even about 70% by weight, or even about 80% by weight, or even about 90% by weight %, or even about 10% by weight. In a particular embodiment, when the nutritional product is a nutritional powder comprising about 28% (by weight of the nutritional powder) of the fat component, the fatty acid-containing monoglyceride is about 10% by weight of the fat component. The amount is present, or about 2.8 grams of fatty acid monoglyceride per 100 grams of nutritional powder. In another specific embodiment, when the nutritional product is a ready-to-feed nutritional liquid comprising about 3.67% (by weight of the ready-to-feed nutritional liquid) of the fat component, the fatty acid-containing monoglyceride is about 10% (by fat) The content of the component is in the presence of 'or a total of about 3,67 grams of a nutrient-containing nutrient liquid per 100 grams of a monoglyceride containing a fatty acid. In another specific embodiment, when the nutritional product is a concentrated nutritional liquid comprising a fat component of about 7 34 〇/〇 (by weight of the concentrated nutritional liquid), the fatty acid-containing monoglyceride is about 1 〇. The content of % (by weight of the fat component) is present, or about 734 grams of concentrated fatty acid monoglyceride per 100 grams of concentrated nutrient liquid. In addition to the various benefits listed above, it has also been found that monoglycerides containing fatty acids have antiviral and/or antibacterial activity in the nutritional product. In particular, it has been found that the presence of fatty acid monoglycerides in the nutritional product kills the pathogen and/or slows its replication. B. Fatty acid component In addition to or in place of the above-mentioned fatty acid-containing monoglyceride, the nutritional product of the present invention may comprise a fatty acid component containing fatty acid 161217.doc 16 201233331 as a pre-digested fat system Part of it. Fatty acid is a normal metabolite that is formed in the body when it is decomposed by oligosaccharides (diglycerides, diglycerides, cholesteryl esters and certain fats). The fatty acid components are independent and different from the above discussion. A monoglyceride containing a fatty acid. Any fatty acid that is beneficial in the nutritional product can be included in the nutritional product as a component of the pre-digested fat system. In one embodiment, the fatty acid is an unsaturated free fatty acid. In certain embodiments comprising unsaturated free fatty acids, the total amount of unsaturated free fatty acids having a chain length of more than 14 carbon atoms is less than 15 wt%. Exemplary fatty acids suitable for inclusion in the nutrients described herein include, but are not limited to, arachidonic acid, linoleic acid, docosahexaenoic acid, octadecaic acid, oleic acid, twenty carbon Alkenoic acid, mead acid, erucic acid, nervonic acid, and mixtures and combinations thereof. Particularly preferred fatty acids include arachidonic acid, linoleic acid, linoleic acid, docosahexaenoic acid and oleic acid. The fatty acid component contained in the pre-digested fat system includes those fatty acid components derived from oils such as vegetable oils, aquatic animal oils, fish oils, seaweed oils, fungal oils, animal fats, animal fat isolates, and combinations thereof. For example, suitable vegetable oils include eucalyptus oil, canola oil, corn oil, soybean oil, and combinations thereof. In one embodiment, when animal fat is used, the fatty acid is obtained by enzymatic hydrolysis of lard or tallow, and the content of palmitic acid and stearic acid in the resulting fatty acid mixture is reduced to less than 20% of the total fatty acid, including Less than 2% of total fatty acids. In another embodiment, at least some of the fatty acids are derived from soybean oil or a resin. Once derived from the oil source, the fatty acid is substantially free of monoglycerides, diglycerides, and triglycerides. 161217.doc • 17- 201233331 Fatty acids will generally be derived from source oils containing less than about 20% by weight palmitic acid and/or stearic acid and/or myristic acid. In certain embodiments, the fatty acid will be derived from less than about 15% by weight, including less than about 1% by weight, including less than about 5°. (by weight) and comprises less than 2% by weight of palm oil and/or source oil of stearic acid and/or myristic acid. In a particular embodiment, the fatty acid is derived from containing less than about 2% by weight of 'comprising from about 1% by weight to about 丨 (by weight) of banolic acid and/or stearic acid. And / or source of myristic acid. In another particular embodiment, the 'nutraceuate comprises palmitic acid in an amount less than about 10% by weight based on total fatty acids." In certain embodiments, the nutritional product can comprise a fatty acid in the form of a salt; The fatty acid can be added to the nutrient in the form of a fatty acid salt. In a suitable embodiment, the fatty acid is added to the nutritional product in the form of a fatty acid calcium salt, a fatty acid magnesium salt, or a combination thereof. Fatty acid salts can be prepared by those skilled in the art based on the disclosure herein. In a suitable process, an emulsion comprising a Cl〇_C24 fatty acid calcium salt can be prepared by first preparing a fatty acid salt by using several starting calcium sources mixed with at least one Cl0-C24 fatty acid source. More specifically, t, in one method, the starting source comprising a C10-C24 fatty acid in the form of a triglyceride blend or in a free form can be contacted by calcium hydroxide and/or calcium carbonate and/or calcium phosphate. And formed. In another method, the triglyceride blend or the free form of the anthracene 24 fatty acid can be obtained by hydrating & (: 12 or (: 3 (eight) with a 15^1 value of 6 to about 7.5. (^0) 2 is prepared by contact. The above method can be carried out under an inert atmosphere, for example, under argon or argon. In other examples, 161217.doc -18- 201233331, any γ 4 m * μ can be money Encircle ', which does not react under a low oxygen atmosphere. Include. <24 The source of the fatty acid and the source of the dance can be mixed by any method of this technique. "Mixed" does not mean to imply a specific mixed fruit. , for example, dissolving any component to a specific extent or forming a particular composition (such as a homogeneous mixture), but such mixtures may be produced and some components may be dissolved by mixing. The mixing may be vigorous and may be manual or by mechanical Loading, such as, but not limited to, a static mixer, a magnetic stirrer, a vibrator, a spinner, or a rotating device. Mixing can be performed by forcing a gas through the mixture or by bubbling a gas through the mixture or by sonication. Come on.

Ci0-C24脂肪酸來源與鈣來源混合可進行至少^分鐘。混 合亦可進行至少卜5、15、20、25、3〇、35 4〇 4/、 5〇、55、60、65、70、75、8〇、85、9〇、95或1〇〇分鐘, 其中任何所述值若適當則均可形成上端或下端端點。 混合可在各種溫度下進行,但該方法一般在高溫下發 生。確切尚溫可取決於C1Q-C24脂肪酸或鈣之特定起始來源 及其用量。可進行所揭示混合所處之適合溫度包括(但不 限於)約4°C至約100°c、約urc至約100〇c、約15C>c至約 l〇(TC、或約 20°c 至約 70°c。 包含C1()-C24脂肪酸或鈣之來源亦可在混合之前經加熱。 該種預熱步驟可在本文所述之任何溫度或溫度範圍下進 行。 在某些實施例中’ ci0-C:24脂肪酸與鈣之混合可在減壓下 進行。適合壓力小於或等於約1托(T〇rr)或小於或等於約 161217.doc -19· 201233331 ο. 1 托。 在一個理想實施例中,C1()-C24脂肪酸鈣鹽係藉由添加游 離C1()-c24不飽和脂肪酸及鈣來源(諸如Ca(OH)2、CaCl2、 CaC03、檸檬酸鈣或該等鹽之混合物)以形成油摻合物來製 備。更特定而言,將脂肪酸溶解於溫熱水溶液(例如,具 有約40°C至約80°C之溫度)中。可使用KOH或NaOH將溶液 之pH值調整至一般為約ι〇·ιι之1?11值。隨後向所溶解之含 脂肪酸的溶液中添加鈣。一般使脂肪酸及鈣靜置丨〇分鐘以 確保月曰肪酸與妈離子之間完全反應。隨後使混合物均質化 以形成油摻合物。 在另一個理想實施例中,製備脂肪酸鈣鹽之混合物(包 括來自魚油、海藻油、真菌油及大豆油(S〇y 〇丨1)之脂肪酸) 作為預消化脂肪系統之一部分。將魚油、海藻油、真菌油 及大豆油混合在一起且在氮氣層下由氩氧化鉀水解。隨後 向混合物中添加鈣來源(諸如氣化鈣)以與脂肪酸反應而產 生不溶性脂肪酸鈣鹽《該等不溶性脂肪酸鹽可藉由過濾分 離,且用水洗滌,然後進行真空乾燥。 已7人驚费地發現,儘管脂肪酸鹽(諸如脂肪酸弼鹽)通 常不溶於營養品中,但其不會在溶液中沈降而形成難以再 刀散之沈降物層。因此,使用脂肪酸鈣鹽及/或脂肪酸鎂 義使得鈣/鎂傳遞更佳,且在多個實施例中可消除對於其 他穩定劑(諸如角又菜膠)之需求,以使得產品可實質上或 完全「無角叉菜膠」。 因此,與使用磷酸鈣或碳酸鈣作為鈣來源之產品相比, 161217.doc •20- 201233331 使用脂肪酸鹽使得鈣及/或鎂及脂肪酸生物可用性得以改 善。 此外,已發現在本發明之營養品中使用脂肪酸鹽提供生 物可用性脂肪酸’諸如花生四烯酸(ARA)及其類似物,其 顯示增強嬰兒生長。使用預消化脂肪亦提供具有經改善之 產品穩定性及較長存放期之乳狀營養品。 營養品通常包含按營養品中包含之脂肪組分計至少約 10°/。(以重量計)之量的脂肪酸或脂肪酸鹽,包括按營養品 中包含之脂肪組分計至少約1 5重量%、包括至少約2〇重量 %、包括約1〇重量%至約60重量%、包括約15重量%至約4〇 重量% ’且包括約15重量%至約35重量%、包括約1〇重量 %、包括約15重量%、包括約2〇重量%、包括約25重量%、 包括約30重量%、包括約35重量%且進一步包括約4〇重量 %、或甚至約50重量%、或甚至約60重量%、或甚至約7〇 重量%、或甚至約80重量❾/〇、或甚至約90重量%、或甚至 約100重量%。 在某些實施例中,營養品包含脂肪酸組分與含有脂肪酸 之單酸甘油酯的混合物。在該等實施例中,營養品含有按 營養品中包含之脂肪組分計至少1〇%(以重量計)之量的混 合物,包括按營養品中包含之脂肪組分計至少約15重量 %、包括至少約20重量%、包括約10重量%至約4〇重量%、 包括約20重量%至約65重量%、包括約25重量%至約5〇重 量/°、包括約15重量。/〇至約30重量〇/0,且包括約15重量%至 約25重量%、包括約1〇重量%、包括約15重量%、包括約 161217.doc -21- 201233331 20重量%、包括約25重量%、包括約30重量%、包括約35 重量%,且進一步包括約40重量%或甚至約50重量%、或 甚至約60重量%、或甚至約70重量%、或甚至約80重量 %、或甚至約90重量%或甚至約1〇〇重量% » 在其他實施例中,營養品包含以營養品中總乾物質計至 少0.2%(以重量計)、包括至少1%(以重量計)、包括至少 2%(以重量計)且包括至少5%(以重量計)之量的脂肪酸組 分、含有脂肪酸之單酸甘油酯或其組合。 常量營養棄(Macronutrient) 儘管脂肪、蛋白及碳水化合物之總濃度或量可視產品類 型(亦即’人乳強化劑、嬰兒配方等產品形式(亦即,營 養固體、粉末、即食型液體或濃縮型液體)及預期使用者 之目標飲食需求而變化’但該等濃度或量最一般在以下具 體範圍之一内’包括如本文所述之任何其他脂肪、蛋白及/ 或碳水化合物成分。 對於液體早產及足月嬰兒配方產品而言,以早產或足月 嬰兒配方之重量計’碳水化合物濃度最一般在約5 %至約 40%、包括約7%至約30%、包括約至約25%之範圍 内,以早產或足月嬰兒配方之重量計,脂肪濃度(包括預 消化脂肪與任何其他脂肪來源)最一般在約1 %至約3〇%、 包括約2%至約15%以及包括約3%至約1〇%之範圍内;且以 早產或足月嬰兒配方之重量計,蛋白濃度最一般在約〇5% 至約30% '包括約1%至約15%以及包括約2〇/。至約1〇%之範 圍内。 161217.doc •22- 201233331 對於液體人乳強化劑產品而言,以人乳強化劑之重量 。十’碳水化合物濃度最一般在約10%至約75%、包括約 10%至約50%、包括約20%至約40%之範圍内;以人乳強化 劑之重量計’脂肪濃度(包括預消化脂肪與任何其他脂肪 來源)最一般在約10%至約4〇?/。、包括約15%至約37%以及 包括約1 8%至約30%之範圍内;且以人乳強化劑之重量 计’蛋白濃度最一般在約5%至約40%、包括約1〇%至約 30%以及包括約15%至約25%之範圍内。 除了如下表所列的營養品中之總熱量百分比以外或作為 其替代’亦表徵液體營養品中碳水化合物、脂肪及/或蛋 白之含量或量。用於本發明液體營養品之該等常量營養素 最一般在下表所述之任何熱量範圍内(實施例A_F)調配(每 一數值之前均有術語「約」)„ 營養素總熱蛩% 實施例A 霄施例B 實施例C 破水化合物 0-98 2-96 10-75 蛋白 0-98 2-96 5-70 脂肪 0-98 2-96 20-85 ~ 實施例D 實施例E 實施例F 破水化合物 30-50 25-50 25-50 — 蛋白 15-35 10-30 5-30 '~~ 脂肪 35-55 1-20 2-20 —— 在一個特定實例中,液體嬰兒配方(即食型與濃縮型液 體)包括彼等實施例,其中蛋白組分可構成配方之約7 5% 至約25%之熱量含量;碳水化合物組分可構成嬰兒配方之 約35%至約50%之總熱量含量;且脂肪組分可構成嬰兒配 方之約30%至約60%之總熱量含量。該等範圍僅作為實例 161217.doc •23- 201233331 提供,且不欲具限制性 數值之前均有術語「約」 下表中列舉其他適合範圍(每一 )° 營養素總熱量% Λ ——____ 碳水化合物: 脂肪: 20-8Γ~~~-- 一5_-70— -- 實施例Η 1δ^6〇 實施例I 35-55 蛋白: ~ ΤΤ5 20-ου Tso --- 一7-40 ' ~ 當營養品為粉末型早產或足月嬰兒配方時,以早產或足 Θ # ^之重4計’蛋白組分以約5%至約35%、包括約 8%至約12%且包括約嶋至約12%之量存在;以早產或足 月4c兒配方之重量计’脂肪組分以約i至、約、包括 約25%至約30%且包括約26%至約28%之量存在;且以早產 或足月各兒配方之重量計,碳水化合物組分以約至約 85%、包括約45%至約60%且包括約5〇%至約55%之量存 在。 對於粉末型人乳強化劑而言,以人乳強化劑之重量計, 蛋白組分以約1%至約55%、包括約1〇%至約5〇%且包括約 10 %至約3 0 /0之量存在;以人乳強化劑之重量計,脂肪組 分以約1%至約30°/❶、包括約1%至約25%且包括約1%至約 20°/。之量存在;且以人乳強化劑之重量計,碳水化合物組 分以約15%至約75%、包括約15%至約60%且包括約20%至 約50%之量存在。 脂肪、碳水化合物及蛋白在本發明粉末型營養品中之總 量或濃度可在相當程度上視所選產品及預期使用者之飲食 或醫學需求而變化。下文列舉常量營養素濃度之其他適合 實例。在此背景下,總量或濃度係指粉末型產品中之所有 161217.doc •24- 201233331 脂肪、碳水化合物及蛋白質來源。對於粉末型營養品而 言’該等總量或濃度最一般且較佳在下表所述之任何具體 範圍内調配(所有數值之前均具有「約。 營養素總熱量% 實施例J 實施例K 實施例L 碳水化合物 1-85 30-60 35-55 脂肪 5-70 20-60 ~~-~~~ 25-50 蛋白 2-75 5.50 - ------ 7-40 脂肪 除預消化脂肪以外,本發明之營養品還可包含其他脂肪 來源(脂肪之總量在本文中稱作營養品之「脂肪組分」或 「脂肪系統」)。適合用於本文之其他脂肪來源包括適合 用於口服營養品且可與該等產品之要素及特徵相容之任何 脂肪或脂肪來源。 適合用於本文所述營養品中之其他脂肪或其來源之非限 制性貫例包括椰子油、分德椰子油、大豆油、玉米油、撖 欖油、紅花籽油、高油酸紅花籽油、油酸(EMERS〇L 63 i 3 油酸)、MCT油(中鍵三酸甘油酯)、向日葵油、高油酸向日 葵油、棕櫚油及棕櫚仁油、棕櫚油精、芥花籽油、水產動 物油、魚油、真菌油、海藻油、棉籽油及其組合。在一個 實施例中’適合之脂肪或其來源包括包含長鏈聚不飽和脂 肪酸(LC-PUFA,較佳為具有四個或四個以上雙鍵之lc-PUFA)之油類及油摻合物。舉例而言,可包含之某些非限 制性特定聚不飽和酸包括二十二碳六烯酸(DiIA)、花生四 稀酸(ARA)、二十碳五烯酸(EPA)及其類似物。 本文所述之預消化脂肪通常與一種、兩種、三種、四種 161217.doc •25- 201233331 或四種以上其他脂肪來源組合包含於營養品中。在一個實 施例中,將單酸甘油酯(理想地為單棕櫊酸甘油酯之形 式)、脂肪酸(理想地為鈣鹽之形式)、高油酸油及椰子油組 合在一起以提供營養品中之脂肪組分。在該實施例中,以 脂肪組分之重量計,單酸甘油酯以約1 %至約40%(包括約 10%至約30%,包括約1〇%、約15%、約20%、約23%及約 25%)之量存在;以脂肪組分之重量計,脂肪酸以約至 約40%(包括約1〇%至約30%,包括約10%、約15%、約20% 及約25%)之量存在;以脂肪組分之重量計,高油酸油以約 1%至約40%(包括約1〇%至約30%,包括約1〇〇/。、約15%、 約20%、約25%及約30%)之量存在;且以脂肪組分之重量 計,椰子油以約1 %至約40%(包括約10%至約30%,包括約 10%、約15%、約17%、約20%及約25%)之量存在。 在另一實施例中,將含有脂肪酸之單酸甘油酯(理想地 為單棕櫚酸甘油酯之形式)、脂肪酸組分(理想地為鈣鹽之 形式)、高油酸紅花籽油及椰子油組合在一起以提供營養 品中之脂肪組分。在該實施例中,以脂肪組分之重量計, 單酸甘油酯以約1%至約40%(包括約10%至約30%,包括約 10%、約15%、約20%、約23%及約25%)之量存在;以脂肪 組分之重量計,脂肪酸以約1%至約4〇%(包括約1〇%至約 30%,包括約1〇%、約丨5%、約20。/。及約25%)之量存在;以 脂肪組分之重量計,高油酸油以約1 %至約4〇%(包括約1 〇〇/〇 至約3〇% ’包括約10%、約1 5%、約20%、約25%及約30%) 之量存在;且以脂肪組分之重量計,椰子油以約1 %至約 161217.doc •26_ 201233331 40%(包括約10%至約30%,包括約10%、約15%、約17%、 約20%及約25%)之量存在。 在另一實施例中,將含有脂肪酸之單酸甘油酯(理想地 為單棕橺酸甘油酯之形式)、脂肪酸組分(理想地為鈣鹽之 形式)、高油酸紅花籽油、椰子油、含DHA油及含ARA油 組合在一起以提供營養品中之脂肪組分。在該實施例中, 以脂肪組分之重量計,單酸甘油酯以約1%至約40%(包括 約10%至約30%,包括約10%、約15%、約20%、約23%及 約25%)之量存在;以脂肪組分之重量計,脂肪酸以約1% 至約40%(包括約10%至約30%,包括約10%、約15%、約 20%及約25%)之量存在;以脂肪組分之重量計,高油酸油 以約1%至約40%(包括約10%至約30%,包括約1〇%、約 15% '約20%、約25%及約30%)之量存在;且以脂肪組分 之重量計,椰子油以約1%至約40%(包括約1〇%至約30%, 包括約10%、約15%、約17% 約20%及約25%)之量存在。 含DHA油以脂肪組分之重量計以約1 %至約1 〇%(包括約5〇/0) 之®存在且含ARA油以脂肪組分之重量計以約1 %至約 1〇%(包括約5%)之量存在。 在另一實施例中,脂肪組分包含約38%(以重量計)高油 酸紅花籽油 '約17%(以重量計)椰子油、約23%(以重量計) 單棕櫚酸甘油酯、約20%(以重量計)脂肪酸辦鹽、約 0.5%(以重量計)含DHA油及約1.0%(以重量計)含ARA油。 蛋白質 除預消化脂肪以外,本發明之營養品還可視情況進一步 161217.doc •27- 201233331 白適用於口服營養品且可與今·箄產+ 徵相容之任付了與該專產。。之要素及特 蛋白質來源均適合與預消化脂肪組合使用。 用於該等營養品中之蛋白或其來源之非限制性實例 ^水解、部分水解或非水解蛋白或蛋白質來源,其可源 何已知或另外適合之來源諸如乳類(例如赂蛋白、 乳清)、動物(例如肉類、魚肉)、縠物(例如水稻、玉米)、 植勿(例如大且)或其組合。該等蛋白之非限制性實例包括 乳類蛋白分離物、如本文所述之乳類蛋白濃縮物、赂蛋白 分離物、廣泛水解之酷蛋白、乳清蛋白、路蛋白納鹽或飼 鹽、全牛乳、部分或完全脫脂乳、大豆蛋白分離物、大豆 蛋白濃縮物等等。 碳水化合物 本發明之營養品可進一步視情況包含適合用於口服營養 品且可與該等產品之要素及特徵相容之任何碳水化合物。 適合用於本文所述營養品中之碳水化合物或其來源之非 限制性實例可包括麥芽糊精、水解或改質澱粉或玉米澱 粉、葡萄糖聚合物、玉米糖漿、玉米糖漿固體、源自水稻 之碳水化合物、源自豌豆之碳水化合物、源自馬鈴薯之碳 水化合物、木薯、兔糖、葡萄糖、果糖 '乳糖、高果糖玉 米糠漿、蜂蜜、糖醇(例如麥芽糖醇、赤藻糖醇、山梨糖 醇)、人造甜味劑(例如蔗糖素(sucral〇se)、乙酿績胺酸 釺、甜菊)及其組合。 其他視情況存在之成分 本發明之營養品可進一步包含其他視情況存在之組分, 161217.doc -28- 201233331 其可改變該等產品之物理、化學、美學或加工特徵,或在 用於目標群體時充當醫藥學或其他營養組分。已知多㈣ 等視情況存在之成分或其另外適用於醫學食品或其:營: 品或醫藥劑型中,且亦可用於本文之組合物中,其限二條 件為該等視情況存在之組分口服安全且可與選定產品形式 之各成分相容。 該等視情況存在之成分之非限制性實例包括防腐劑、抗 氧化劑、乳化劑、緩衝劑、果寡醣'半乳寡醣、益菌助生 質、醫藥活性物、如本文所述之其他營養素、著色劑、調 味劑、增稠劑及穩定劑、乳化劑、潤滑劑等等。 營養品可進一步包含甜味劑,較佳包括至少一種糖醇, 諸如麥芽糖醇、赤藻糖醇、山梨糖醇、木糖醇、甘露糖 醇、異麥芽酮糖醇(isolmalt)及乳糖醇,且亦較佳包括至少 一種人造或高效能甜味劑’諸如乙酿磺胺酸K、阿斯巴甜 糖(aspartame)、蔗糖素、糖精、甜菊及塔格糖(tagat〇se)。 該等甜味劑(尤其呈糖醇與人造甜味劑之組合)尤其適用於 調配本發明的具有理想味道型態之液體飲料實施例。該等 甜味劑組合對於遮蔽有時與液體飲料中所添加植物蛋白相 關之不良味道尤其有效。營養品中視情況存在之糖醇濃度 以營養品之重量計可在至少0.01%,包括〇」%至約1〇〇/〇, 且亦包括約1%至約6%之範圍内。視情況存在之人造甜味 劑濃度以營養品之重量計可在約〇 · 〇 1 %,包括約0 0 5 %至約 5%,亦包括約0.1 %至約1.0%之範圍内。 流動劑或防結塊劑可包含於如本文所述之營養品中以延 161217.doc -29- 201233331 遲粉末隨時間而凝塊或結塊且製得易於自其容器流出之粉 末實施例。已知或另外適用於營養粉末或產品形式之任何 已知流動劑或防結塊劑均適用於本文中,其非限制性實例 包括填酸三弼、石夕酸鹽及其組合。營養品中流動劑或防結 塊劑之濃度視產品形式、其他所選成分、所要流動特性等 等而變化,但以營養品之重量計最常在約01%至約, 包括約0.5%至約2%之範圍内。 穩定劑亦可包含於營養品中。已知或另外適用於營養品 中之任何穩定劑亦適用於本文中,其某些非限制性實例包 括角叉菜膠及膠類(諸如三仙膠)。以營養品之重量計穩 定劑可佔約0.1%至約5.0%,包括約〇.5%至約3%,包括約 0.7%至約 1.5%。 營養品組合物可進一步包含任何各種其他維生素或相 營養素,其非限制性實例包括維生素A、維生素d、維生 素E、維生素K、硫胺素、核黃素、吡D多醇、維生素^、 類胡蘿㈣(例如β-胡㈣素、玉米黃素、葉黃素、番莊紅 維生素C、膽鹼、肌 素)、菸酸、葉酸、泛酸、生物素 醇、其鹽及衍生物以及其組合。 營養品可進-步包含任何各種其他礦物f,其非限制性 實例包括鈣、磷、鎂、鐵、辞、錳、銅、鈉、鉀、鉬、 鉻、氣離子及其組合。此外’在某些實施例中,營養品可 不含角又菜膠。 製造方法 外可有效於製備所 本發明之營養品可藉由任何已知或另 161217.doc •30- 201233331 選產品固體或液體形式之製造技術來製備。已知多種該等 技術可用於任何給定的產品形式(諸如營養液體或粉末), 且可容易地由一般熟習此項技術者應用於本文所述之營養 品0 因此,本發明之營養品可藉由任何各種已知或另外有效 之產品或製造方法來製備。舉例而言,在一種適合之製造 製程中,分開製備至少三種漿料,包括脂肪包蛋白質(PIF) 漿料、碳水化合物_礦物質(CH〇_MIN)漿料及水包蛋白質 (PIW)漿料。PIF漿料係藉由加熱及混合油類(例如單酸甘 油酯及/或脂肪酸、含有脂肪酸之油、芥花籽油、玉米油 等)且隨後伴隨持續加熱及攪拌添加乳化劑(例如卵磷脂)、 脂肪可溶性維生素及一部分總蛋白(例如,乳蛋白濃縮物 等)來形成。CHO-MIN漿料係藉由伴隨加熱攪拌向水中添 加以下各物而形成··礦物質(例如檸檬酸鉀、磷酸二鉀、 擰檬酸鈉等)、痕量及超痕量礦物質(TM/UTM預混物)及/或 增稠劑或懸浮劑(例如晶性纖維素(avicel)、結冷膠 (gellan)、角叉菜膠)。使所得ch〇_Min漿料在持續加熱及 攪拌下保持10分鐘’然後添加其他礦物質(例如氯化鉀、 碳酸鎂、碘化鉀等)及/或碳水化合物(例如果寡醣、薦糖、 玉米糖聚等)。隨後若還有任何剩餘蛋白質,則藉由伴隨 加熱及攪拌混合來形成PIW漿料。 在本發明之一個特定實施例中,可將營養品中包含之所 有或一部分預消化脂肪添加至ch〇_Min漿料中,該漿料含 有小於5%(以CH0-MIN漿料之重量計)的呈三酸甘油醋形式 161217.doc -31 - 201233331 之脂肪。在該實施例中’營養品中存在之總脂肪之至少 50/〇(以重量計)為預消化脂肪形式且被添加至CHO-MIN漿料 中。在某些實施例中,將營養品中包含之至少5%(以重量 §十)、包括至少10%(以重量汁)、包括至少2〇%(以重量 計)、包括至少30%(以重量計)、包括至少40%(以重量 §十)、包括至少50%(以重量計)、包括至少6〇%(以重量 計)、包括至少70%(以重量計)、包括至少8〇%(以重量 計)、包括至少90%(以重量計)且包括1〇〇%(以重量計)之總 預消化脂肪添加至CHO-MIN漿料申。在一個特定實施例 中,在將預消化脂肪添加至CHO-MIN漿料中之前或在製造 CHO-MIN漿料期間將脂溶性營養素(諸如混合類胡蘿萄素 或維生素A、D、E及K)溶解於預消化脂肪中。與piF漿料 形成對比,藉由向CHO-MIN漿料中添加預消化脂肪,最終 營養組合物之穩定性可得以改善。 隨後伴隨加熱攪拌將所得漿料摻合在一起且將pH值調; 至6.6-7.0,此後使組合物經受高溫短時(htst)加工,在』 期間組合物經熱處理、乳化且經均質化,且隨後使其》 却添加水溶性維生素及抗壞血酸,若有必要則將阳值言 整至所要範圍,添加調味劑且添加水以達成所要之總固免 含'。隨後將組合物無菌封裝以形成經無菌封裝之營養孕 ./乳液亦可經填充且隨後經殺菌以形成即食型或濃 3L,體或其可經喷霧乾燥、乾混及/或聚結。 :藉由任何已知或另外適於製備及調配營養粉末之有效 技術集合來製備技益 備S養固體,諸如喷霧乾燥營養粉末或乾混 16I217.doc •32, 201233331 營養粉末。 舉例而言,當營養粉末為喷霧乾燥營養粉末時,喷霧乾 燥步驟可類似地包括已知或另外適用於產生營養粉末之任 何喷霧乾燥技術。已知多種不同喷霧乾燥方法及技術可用 於S養領域,所有均適用於製造本文之喷霧乾燥營養粉 末。 一種製備噴霧乾燥營養粉末之方法包含形成及均質化含 有預消化脂肪且視情況含有蛋白質、碳水化合物及其他脂 肪來源之a水漿料或液體,且隨後喷霧乾燥該漿料或液體 以產生喷霧乾燥營養粉末。該方法可進一步包含喷霧乾 燥、乾混或另外向喷霧乾燥營養粉末中添加其他營養成分 (包括任何一或多種本文所述成分)之步驟。 其他適用於製備營養品之方法例如描述於美國專利 6’365,218(Borschel等人)、美國專利 人)、美國專利6,306,908(Carlson等人)及美國專利申請案 20030118703 Al(Nguyen等人)中,其描述以與其一致之程 度以引用的方式併入本文中。 使用方法 根據本發明且如下文進一步描述,本文所述之營養品可 用於多種目的,例如包括改善消化、改善營養素吸收 '改 善耐受性、減小壞死性小腸結腸炎之發生率、減小腹痛之 發生率及減小短腸症之發生率。使用本文所述的營養品之 個體(嬰兒、幼兒或孩童)實際上可能患有或罹患所述疾病 或病況(亦即,實際上可能具有消化、營養素吸收及/或耐 161217.doc 03- 201233331 受性問題,或實際上可能患有壞死性小腸結腸炎、腹痛或 短腸症)’或可能易於患上該疾病或病況或存在此風險(亦 尸了 實際上尚未患有該疾病或病況,但由於某些條 件、家族史等與—般人群相比患病風險增加)。不管個體 貫際上是否患有該疾病或病況,或是否存在患上該疾病或 病況之風險或易於患上該疾病或病況,該個體在本文中均 刀類為冑要」幫助解決及對抗該疾病或病況。舉例而 言’嬰兒由於早產而實際上可能患有壞死性小腸結腸炎或 可能存在患上壞死性小腸結腸炎(易於患上壞死性小腸結 腸炎)之風險。類似地’在另一實例+,嬰兒由於患有其 他疾病或病況或具有該等問題之家族史而實際上可能具有 耐党性及/或消化及/或營養素吸收問題,或可能存在患上 (易於患上)一或多種該等病況之風險。不管個體是否實際 上患有該疾病或病況’或是否僅存在患上該疾病或病況或 易於患上該疾病或病況之風險,本發明之範疇内包括使用 本文所述之營養品協助該個體。 基於以上内容,由於本發明之某些方法實施例係關於確 定個體之特定子群或子類(亦即,「需要」幫助解決本文所 述之一或多種特定疾病或特定病況之個體的子群或子 類),因此並非所有個體均可受益於本文所述之所有方法 實施例同對於某些疾病或病況而言,並非所有個體均 屬於如本文所述之個體子群或子類。 如本文所述之營養品包含理想地與—或多種其他脂肪來 源組合之預消化脂肪,以為嬰兒、幼兒及孩童提供營養來 161217.doc -34- 201233331 源以用於改善營養素消化及吸收。特定而言,類似於母乳 餵養嬰兒之消化,因為脂肪來源在進入十二指腸之前至少 部分被消化,讓嬰兒有更多時間吸收營養素,尤其在腸 内’且進入嬰兒結腸之營養素減少,因此使得會被潑酵且 產生氣體以致降低產品财受性之營養素減少。因此,藉由 在營養品(諸如嬰兒配方)中使用預消化脂肪來源(諸如單酸 甘油酯及/或脂肪酸),現可能向嬰兒提供更接近地模仿母 乳益處之母乳替代物或補充物。 除如上文所述之營養素吸收改善以外,已發現在營養品 中使用預消化脂肪在與一或多種非水溶性疏水性混合物 (諸如油可溶性(脂溶性)維生素(維生素A、〇、κ)、類 胡蘿g素(例如葉黃素、β_胡蘿萄素、番茄紅素等)、醣脂 (神經結醣脂)、固醇及植物化學品)一起投與時亦有助於微 胞形成。該等微胞之形成使得不溶性疏水性化合物可溶解 於消化物中’此為腸絨毛吸收之步驟。此外,預消化脂肪 將用於再合成三酸甘油酯以形成乳糜微粒。乳糜微粒將非 水溶性疏水性化合物運載至淋以,其巾㈣將不溶性疏 水性化合物輸送至目標器官及/或組織以產生所要生理學 作用。 除上文論述之益處以外, 已發現包含預消化脂肪之營養 刺激十二指腸中之膽囊收縮素(CCK)產生, 生,其刺激胰腺The Ci0-C24 fatty acid source can be mixed with the calcium source for at least ^ minutes. Mixing can also be performed at least 5, 15, 20, 25, 3, 35 4〇4/, 5〇, 55, 60, 65, 70, 75, 8〇, 85, 9〇, 95 or 1 minute Any of the values described above may form an upper or lower end if appropriate. Mixing can be carried out at various temperatures, but the process generally occurs at elevated temperatures. The exact temperature may depend on the specific starting source and amount of C1Q-C24 fatty acid or calcium. Suitable temperatures at which the disclosed mixing can be carried out include, but are not limited to, from about 4 ° C to about 100 ° c, from about urc to about 100 ° C, from about 15 C > c to about 10 ° (TC, or about 20 ° c) Up to about 70° C. Sources comprising C1()-C24 fatty acids or calcium may also be heated prior to mixing.This preheating step can be carried out at any of the temperatures or temperature ranges described herein. In certain embodiments ' ci0-C: Mixing of 24 fatty acids with calcium can be carried out under reduced pressure. Suitable pressure is less than or equal to about 1 Torr (T〇rr) or less than or equal to about 161217.doc -19· 201233331 ο. 1 Torr. In a preferred embodiment, the C1()-C24 fatty acid calcium salt is obtained by adding a free C1()-c24 unsaturated fatty acid and a calcium source such as Ca(OH)2, CaCl2, CaC03, calcium citrate or a mixture of such salts. Prepared to form an oil blend. More specifically, the fatty acid is dissolved in a warm aqueous solution (eg, having a temperature of from about 40 ° C to about 80 ° C.) The pH of the solution can be adjusted using KOH or NaOH. Adjust to a value of 1 to 11 which is generally about ι〇·ιι. Then add calcium to the dissolved fatty acid-containing solution. The acid and calcium are allowed to stand for a few minutes to ensure complete reaction between the fatty acid and the mother ion. The mixture is then homogenized to form an oil blend. In another preferred embodiment, a mixture of fatty acid calcium salts is prepared (including Fatty oils from fish oil, algae oil, fungal oil and soybean oil (S〇y 〇丨1) as part of the pre-digested fat system. Fish oil, algae oil, fungal oil and soybean oil are mixed together and under the nitrogen layer Hydrolysis of potassium argon. A calcium source (such as calcium carbonate) is then added to the mixture to react with the fatty acid to produce an insoluble fatty acid calcium salt. The insoluble fatty acid salts can be separated by filtration and washed with water, followed by vacuum drying. Seven people were surprised to find that although fatty acid salts (such as fatty acid strontium salts) are generally insoluble in nutrients, they do not settle in solution and form a sediment layer that is difficult to re-spray. Therefore, fatty acid calcium salts and/or Or fatty acid magnesium meaning better calcium/magnesium delivery, and in various embodiments eliminates the need for other stabilizers, such as keratin, to This allows the product to be substantially or completely "carrageenan-free." Therefore, compared to products that use calcium phosphate or calcium carbonate as a source of calcium, 161217.doc •20- 201233331 uses fatty acid salts to make calcium and/or magnesium and fatty acids In addition, it has been found that the use of fatty acid salts in the nutritional products of the present invention provides bioavailable fatty acids such as arachidonic acid (ARA) and its analogs, which are shown to enhance infant growth. The use of pre-digested fat is also provided with An improved nutritional stability of the product and a longer shelf life of the dairy nutrient. The nutritional product typically comprises at least about 10°/based on the fat component contained in the nutritional product. The (by weight) amount of fatty acid or fatty acid salt, including at least about 15% by weight, including at least about 2% by weight, including from about 1% by weight to about 60% by weight, based on the fat component contained in the nutritional product. And including from about 15% by weight to about 4% by weight 'and including from about 15% by weight to about 35% by weight, including about 1% by weight, including about 15% by weight, including about 2% by weight, including about 25% by weight Including about 30% by weight, including about 35% by weight and further including about 4,000% by weight, or even about 50% by weight, or even about 60% by weight, or even about 7% by weight, or even about 80% by weight/ 〇, or even about 90% by weight, or even about 100% by weight. In certain embodiments, the nutritional product comprises a mixture of a fatty acid component and a monoglyceride containing a fatty acid. In such embodiments, the nutritional product comprises a mixture of at least 1% by weight, based on the fat component contained in the nutritional product, comprising at least about 15% by weight based on the fat component contained in the nutritional product. And comprising at least about 20% by weight, including from about 10% to about 4% by weight, including from about 20% to about 65% by weight, including from about 25% to about 5% by weight, including about 15 weight. /〇 to about 30 weight 〇 / 0, and including about 15% by weight to about 25% by weight, including about 1% by weight, including about 15% by weight, including about 161217.doc -21 - 201233331 20% by weight, including about 25 wt%, including about 30 wt%, including about 35 wt%, and further including about 40 wt% or even about 50 wt%, or even about 60 wt%, or even about 70 wt%, or even about 80 wt% Or, even up to about 90% by weight or even about 1% by weight » In other embodiments, the nutritional product comprises at least 0.2% by weight, including at least 1% by weight of total dry matter in the nutritional product And a fatty acid component comprising at least 2% by weight and comprising at least 5% by weight, a fatty acid containing monoglyceride or a combination thereof. Macronutrient Although the total concentration or amount of fat, protein and carbohydrate can be determined by the type of product (ie, 'human milk fortifier, infant formula, etc. (ie, nutritive solids, powder, ready-to-feed liquid or concentrated type) The liquid) and the intended user's target dietary needs vary 'but the concentrations or amounts are most generally within one of the following specific ranges' include any other fat, protein and/or carbohydrate component as described herein. And for term infant formula, the carbohydrate concentration is most generally from about 5% to about 40%, including from about 7% to about 30%, including from about 5% to about 25%, based on the weight of the preterm or term infant formula. Within the scope, the fat concentration (including pre-digested fat and any other fat source) is generally from about 1% to about 3%, including from about 2% to about 15%, and includes about the weight of the preterm or term infant formula. Between 3% and about 1%; and the protein concentration is generally from about 5% to about 30% by weight of the preterm or term infant formula' including from about 1% to about 15% and including about 2% /. to about 1 In the range of %. 161217.doc •22- 201233331 For liquid human milk fortifier products, the weight of human milk fortifier. The ten' carbohydrate concentration is most generally from about 10% to about 75%, including about 10%. Up to about 50%, including from about 20% to about 40%; the fat concentration (including pre-digested fat and any other fat source) is generally from about 10% to about 4% by weight of the human milk fortifier? Included in the range of from about 15% to about 37% and including from about 18.8% to about 30%; and the protein concentration is most generally from about 5% to about 40% by weight of the human milk fortifier, including From 1% to about 30% and including from about 15% to about 25%. In addition to or as an alternative to the total caloric percentage in the nutraceuticals listed below, it also characterizes carbohydrates, fats and / or content or amount of protein. The macronutrients used in the liquid nutritional products of the present invention are most generally formulated in any of the calories described in the table below (Example A_F) (each term has the term "about"). Total nutrient enthalpy % Example A 霄 Example B Example C Water-breaking compound 0-98 2-96 10-75 Protein 0-98 2-96 5-70 Fat 0-98 2-96 20-85 ~ Example D Example E Example F Water-breaking compound 30-50 25-50 25-50 - Protein 15-35 10-30 5-30 '~~ Fat 35-55 1-20 2-20 - In a specific example, liquid infant formulas (ie, food forms and concentrated liquids) include such embodiments, The protein component may constitute from about 75% to about 25% of the caloric content of the formula; the carbohydrate component may constitute from about 35% to about 50% of the total caloric content of the infant formula; and the fat component may constitute an infant formula 30% to about 60% of the total calorie content. These ranges are provided only as examples 161217.doc •23- 201233331, and the term “about” is used before the restrictive values are given. Other suitable ranges (each) are listed in the table below. % Total nutrient calories Λ —— ____ Carbon water Compound: Fat: 20-8Γ~~~-- A 5-_70- -- Example Η 1δ^6〇 Example I 35-55 Protein: ~ ΤΤ5 20-ου Tso --- A 7-40 ' ~ When When the nutritional product is a powder type preterm or term infant formula, the protein component is about 5% to about 35%, including about 8% to about 12%, and includes about 嶋 to Approximately 12% by weight; the fat component is present in an amount from about i to, about, including from about 25% to about 30%, and including from about 26% to about 28%, by weight of the preterm or term 4c formula; And the carbohydrate component is present in an amount of from about 85%, including from about 45% to about 60%, and including from about 5% to about 55%, by weight of the preterm or term formula. For powdered human milk fortifiers, the protein component is from about 1% to about 55%, including from about 1% to about 5%, and including from about 10% to about 30% by weight of the human milk fortifier. The amount of /0 is present; the fat component is from about 1% to about 30°/❶, including from about 1% to about 25%, and including from about 1% to about 20°/% by weight of the human milk fortifier. The amount is present; and the carbohydrate component is present in an amount from about 15% to about 75%, including from about 15% to about 60%, and including from about 20% to about 50%, by weight of the human milk fortifier. The total amount or concentration of fats, carbohydrates, and proteins in the powdered nutritional products of the present invention can vary to a considerable extent depending on the selected product and the intended user's dietary or medical needs. Other suitable examples of macronutrient concentrations are listed below. In this context, total or concentration refers to all 161217.doc •24- 201233331 fat, carbohydrate and protein sources in powdered products. For powdered nutritional products, the total amount or concentration is most generally and preferably formulated within any of the specific ranges described in the table below (all values have previously been "about. Total nutrient heat %" Example J Example K Example L Carbohydrate 1-85 30-60 35-55 Fat 5-70 20-60 ~~-~~~ 25-50 Protein 2-75 5.50 - ------ 7-40 Fat In addition to pre-digested fat, The nutritional product of the present invention may also comprise other sources of fat (the total amount of fat referred to herein as the "fat component" or "fat system" of the nutritional product). Other fat sources suitable for use herein include those suitable for oral nutrition. Any fat or fat source that is compatible with the elements and characteristics of the products. Non-limiting examples of other fats or sources thereof suitable for use in the nutritional products described herein include coconut oil, coconut oil, Soybean oil, corn oil, eucalyptus oil, safflower seed oil, high oleic acid safflower seed oil, oleic acid (EMERS〇L 63 i 3 oleic acid), MCT oil (medium bond triglyceride), sunflower oil, high oil Sour sunflower oil, palm oil and palm kernel oil, palm olein, Flower seed oil, aquatic animal oil, fish oil, fungal oil, algae oil, cottonseed oil, and combinations thereof. In one embodiment, 'suitable fat or source thereof includes long-chain polyunsaturated fatty acids (LC-PUFA, preferably having Oils and oil blends of four or more double bonds of lc-PUFA). For example, certain non-limiting specific polyunsaturated acids including docosahexaenoic acid (DiIA) may be included. Peanut tetrabasic acid (ARA), eicosapentaenoic acid (EPA) and its analogues. The pre-digested fats described herein are usually associated with one, two, three, four 161217.doc •25- 201233331 or four A combination of the above other fat sources is included in the nutrient. In one embodiment, monoglyceride (ideally in the form of monopalmitate), fatty acid (ideally in the form of a calcium salt), high oil The sour oil and coconut oil are combined to provide a fat component in the nutrient. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component (including about 10% to About 30%, including about 1%, about 15%, about 20%, about 23% and about 25%) The fatty acid is present in an amount of from about 10%, including from about 1% to about 30%, including about 10%, about 15%, about 20%, and about 25%, by weight of the fat component; The high oleic acid oil is from about 1% to about 40% by weight of the fat component, including from about 1% to about 30%, including about 1%, about 15%, about 20%, about 25%, and About 30%) is present; and from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 17%, Approximately 20% and approximately 25%) are present. In another embodiment, a fatty acid containing monoglyceride (ideally in the form of monopalmitate), a fatty acid component (ideally in the form of a calcium salt), high oleic safflower oil, and coconut oil Combined to provide a fat component in the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23% and about 25%) are present; the fatty acid is from about 1% to about 4% by weight of the fat component, including from about 1% to about 30%, including about 1% to about 5%, about 5% , about 20% and about 25%); the high oleic acid oil is from about 1% to about 4% by weight (including about 1 〇〇/〇 to about 3% by weight) based on the weight of the fat component. Included in an amount of about 10%, about 15%, about 20%, about 25%, and about 30%); and from about 1% to about 161,217.doc of the weight of the fat component. % (including from about 10% to about 30%, including about 10%, about 15%, about 17%, about 20%, and about 25%) is present. In another embodiment, a fatty acid containing monoglyceride (ideally in the form of monopalmitoyl glyceride), a fatty acid component (ideally in the form of a calcium salt), high oleic safflower oil, coconut The oil, DHA-containing oil and ARA-containing oil are combined to provide a fat component in the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23% and about 25%) are present; from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 20% And about 25%); the high oleic acid oil is from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 1%, about 15% 'about 20%, about 25%, and about 30%) is present; and from about 1% to about 40% by weight of the fat component, including from about 1% to about 30%, including about 10%, Approximately 15%, approximately 17%, approximately 20% and approximately 25%) are present. The DHA-containing oil is present in an amount of from about 1% to about 1% by weight (including about 5 Å/0) of the weight of the fat component and the ARA oil is from about 1% to about 1% by weight of the fat component. The amount (including about 5%) exists. In another embodiment, the fat component comprises about 38% by weight high oleic safflower oil 'about 17% by weight coconut oil, about 23% by weight glycerol monopalmitate. About 20% by weight of the fatty acid salt, about 0.5% by weight of the DHA-containing oil and about 1.0% by weight of the ARA-containing oil. Protein In addition to pre-digested fat, the nutritional product of the present invention may be further 161217.doc •27-201233331 White is suitable for oral nutrition and can be compatible with the current product. . The elements and special protein sources are suitable for use in combination with pre-digested fat. Non-limiting examples of proteins or sources thereof for use in such nutraceuticals, hydrolyzed, partially hydrolyzed or non-hydrolyzed protein or protein sources, which may be derived from sources known or otherwise suitable, such as milk (eg, albumin, milk) Qing), animals (such as meat, fish), booties (such as rice, corn), planting (such as large and) or a combination thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates as described herein, albumin isolates, extensively hydrolyzed cool proteins, whey proteins, passin sodium salts or feed salts, all Milk, partially or fully skimmed milk, soy protein isolate, soy protein concentrate, and the like. Carbohydrates The nutritional products of the present invention may further comprise any carbohydrate suitable for oral nutrition and compatible with the elements and characteristics of such products, as appropriate. Non-limiting examples of carbohydrates or sources thereof suitable for use in the nutrients described herein can include maltodextrin, hydrolyzed or modified starch or corn starch, glucose polymer, corn syrup, corn syrup solids, derived from rice Carbohydrates, carbohydrates derived from peas, carbohydrates derived from potatoes, cassava, rabbit sugar, glucose, fructose 'lactose, high fructose corn syrup, honey, sugar alcohols (eg maltitol, erythritol, sorbus) Sugar alcohol), artificial sweeteners (such as sucralose, saponin, stevia) and combinations thereof. Other Ingredients Dependent on the Condition The nutritional product of the present invention may further comprise other components which are optionally present, 161217.doc -28- 201233331 which may alter the physical, chemical, aesthetic or processing characteristics of the products, or may be used in the target The group acts as a medical or other nutrient component. It is known that many (four) isoforms exist or are otherwise suitable for use in a medical food or its medicinal or pharmaceutical dosage form, and can also be used in the compositions herein, the second condition being such a component It is safe for oral administration and is compatible with the ingredients of the selected product form. Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifiers, buffers, fructooligosaccharides 'galactooligosaccharides, probiotics, pharmaceutically actives, other nutrients as described herein , colorants, flavoring agents, thickeners and stabilizers, emulsifiers, lubricants, and the like. The nutritional product may further comprise a sweetener, preferably comprising at least one sugar alcohol such as maltitol, erythritol, sorbitol, xylitol, mannitol, isomalt, and lactitol And preferably also includes at least one artificial or high performance sweetener such as acesulfame K, aspartame, sucralose, saccharin, stevia and tagatose. Such sweeteners, especially in combination with sugar alcohols and artificial sweeteners, are particularly suitable for formulating liquid beverage embodiments of the present invention having a desired taste profile. These sweetener combinations are particularly effective for masking undesirable tastes sometimes associated with vegetable proteins added to liquid beverages. The concentration of sugar alcohol present in the nutrient may be in the range of at least 0.01% by weight of the nutritional product, including 〇"% to about 1 〇〇/〇, and also includes from about 1% to about 6%. The artificial sweetener concentration, as the case may be, may range from about 〇·〇 1% by weight of the nutritional product, including from about 0.05% to about 5%, and also from about 0.1% to about 1.0%. A flow or anti-caking agent can be included in the nutrient as described herein to extend 161217.doc -29-201233331 late powder clot or agglomerate over time and to produce a powder embodiment that readily flows out of its container. Any of the known flow agents or anti-caking agents known or otherwise suitable for use in nutritional powders or product forms are suitable herein, non-limiting examples of which include triterpenoids, oxalates, and combinations thereof. The concentration of the flow agent or anti-caking agent in the nutritional product varies depending on the product form, other selected ingredients, desired flow characteristics, etc., but is most often from about 01% to about, including about 0.5% by weight of the nutritional product. Within about 2%. Stabilizers can also be included in the nutritional product. Any stabilizer known or otherwise suitable for use in the nutritional product is also suitable for use herein, some non-limiting examples of which include carrageenan and gums (such as trisin). The stabilizer may comprise from about 0.1% to about 5.0% by weight of the nutritional product, including from about 5% to about 3%, including from about 0.7% to about 1.5%. The nutritional composition may further comprise any of a variety of other vitamins or phase nutrients, non-limiting examples of which include vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridyl D, vitamins, and Carrot (4) (eg β-hu (tetra), zeaxanthin, lutein, scented red vitamin C, choline, myosin), niacin, folic acid, pantothenic acid, biotin, salts and derivatives thereof and combination. The nutrient may further comprise any of a variety of other minerals f, non-limiting examples of which include calcium, phosphorus, magnesium, iron, manganese, copper, sodium, potassium, molybdenum, chromium, gas ions, and combinations thereof. Further, in some embodiments, the nutritional product may be free of horns and vegetable gums. PRODUCTION METHODS Efficient for the preparation of the present invention The nutritional product of the present invention can be prepared by any of the known or alternative manufacturing techniques of the solid or liquid form of the product 161217.doc • 30-201233331. A variety of such techniques are known to be useful in any given product form (such as a nutritional liquid or powder), and can be readily applied to the nutritional products described herein by those of ordinary skill in the art. Thus, the nutritional products of the present invention can be It is prepared by any of various known or otherwise effective products or methods of manufacture. For example, in a suitable manufacturing process, at least three types of slurry are separately prepared, including a fat-packed protein (PIF) slurry, a carbohydrate-mineral (CH〇_MIN) slurry, and a water-packed protein (PIW) slurry. material. PIF paste is prepared by heating and mixing oils (such as monoglycerides and / or fatty acids, fatty acid-containing oils, canola oil, corn oil, etc.) and then adding emulsifiers (such as lecithin) with continuous heating and stirring. ), fat soluble vitamins and a portion of total protein (eg, milk protein concentrate, etc.) to form. The CHO-MIN slurry is formed by adding the following substances to the water with heating and stirring to form minerals (such as potassium citrate, dipotassium phosphate, sodium citrate, etc.), traces and ultra-trace minerals (TM). /UTM premix) and / or thickeners or suspending agents (such as avicel, gellan, carrageenan). Allow the resulting ch〇_Min slurry to be kept under constant heating and stirring for 10 minutes' then add other minerals (such as potassium chloride, magnesium carbonate, potassium iodide, etc.) and/or carbohydrates (eg oligosaccharides, sugar, corn) Sugar gathering, etc.). Then, if there is any remaining protein, the PIW slurry is formed by mixing with heating and stirring. In a particular embodiment of the invention, all or a portion of the pre-digested fat contained in the nutritional product may be added to the ch〇_Min slurry, the slurry containing less than 5% (based on the weight of the CH0-MIN slurry) The fat in the form of triglyceride vinegar 161217.doc -31 - 201233331. At least 50/〇 (by weight) of the total fat present in the nutrient in this example is in the form of pre-digested fat and is added to the CHO-MIN slurry. In certain embodiments, at least 5% (by weight § 10), including at least 10% (by weight of juice), including at least 2% (by weight), including at least 30%, are included in the nutritional product (in terms of Weight, including at least 40% (by weight § ten), including at least 50% (by weight), including at least 6% by weight, including at least 70% by weight, including at least 8 〇 % (by weight), including at least 90% by weight and including 1% by weight of total pre-digested fat, is added to the CHO-MIN slurry. In a particular embodiment, the fat-soluble nutrients (such as mixed cauliflower or vitamins A, D, E, and prior to the addition of pre-digested fat to the CHO-MIN slurry or during the manufacture of the CHO-MIN slurry K) Dissolved in pre-digested fat. In contrast to the piF slurry, the stability of the final nutritional composition can be improved by adding pre-digested fat to the CHO-MIN slurry. The resulting slurry is then blended together with heating and the pH is adjusted; to 6.6-7.0, after which the composition is subjected to high temperature short-term (htst) processing, during which the composition is heat treated, emulsified and homogenized, And then make it add water-soluble vitamins and ascorbic acid, if necessary, the positive value to the desired range, add flavoring and add water to achieve the desired total solid content. The composition is then aseptically packaged to form a sterile encapsulated nutrient. The emulsion may also be filled and subsequently sterilized to form a ready-to-eat or concentrated 3L body which may be spray dried, dry blended and/or coalesced. : Preparing a S-solid, such as a spray-dried nutrient powder or dry blend, by any effective technique set known or otherwise suitable for the preparation and formulation of a nutritional powder. 16I217.doc • 32, 201233331 Nutritional powder. For example, when the nutritional powder is a spray dried nutritional powder, the spray drying step can similarly include any spray drying technique known or otherwise suitable for producing a nutritional powder. A variety of different spray drying methods and techniques are known for use in the field of S nutrition, all of which are suitable for use in the manufacture of spray dried nutritional powders herein. A method of preparing a spray-dried nutritional powder comprises forming and homogenizing a water slurry or liquid containing pre-digested fat and optionally protein, carbohydrate and other fat sources, and then spray drying the slurry or liquid to produce a spray Dry nutrition powder in fog. The method may further comprise the step of spray drying, dry blending or otherwise adding other nutrients, including any one or more of the ingredients described herein, to the spray dried nutritional powder. Other suitable methods for preparing a nutritional product are described, for example, in U.S. Patent No. 6, 365, 218 (Borschel et al.), U.S. Patent., U.S. Patent No. 6,306,908 (Carlson et al), and U.S. Patent Application No. 20030118703 Al (Nguyen et al.). The description is incorporated herein by reference to the extent of the same. Methods of Use In accordance with the present invention and as further described below, the nutritional products described herein can be used for a variety of purposes including, for example, improving digestion, improving nutrient absorption, improving tolerance, reducing the incidence of necrotizing enterocolitis, and reducing abdominal pain. The incidence and the incidence of short bowel disease. Individuals (infants, young children, or children) who use the nutritional products described herein may actually have or suffer from the disease or condition (ie, may actually have digestion, nutrient absorption, and/or resistance 161217.doc 03-201233331 Suffering from sexual problems, or may actually have necrotizing enterocolitis, abdominal pain or short bowel disease' or may be prone to the disease or condition or the risk (also the corpse actually does not have the disease or condition) However, due to certain conditions, family history, etc., the risk of illness increases compared with the general population. Regardless of whether the individual has the disease or condition consistently, or whether there is a risk of developing the disease or condition, or is prone to develop the disease or condition, the individual has a knives in this article to help solve and counter the disease. Disease or condition. For example, an infant may actually have necrotizing enterocolitis due to premature birth or may be at risk of developing necrotizing enterocolitis (prone to necrotizing enterocolitis). Similarly, 'in another example, an infant may actually have resistance to party and/or digestion and/or nutrient absorption problems due to other diseases or conditions or family history with such problems, or may be afflicted (easy Suffering from the risk of one or more of these conditions. Whether the individual is actually afflicted with the disease or condition' or whether there is only a risk of developing the disease or condition or is prone to develop the disease or condition, it is within the scope of the invention to assist the individual using the nutritional products described herein. Based on the above, certain method embodiments of the present invention are directed to determining a particular subgroup or subcategory of an individual (i.e., a subset of individuals who "need" to help resolve one or more specific diseases or specific conditions described herein. Or subclasses, and thus not all individuals may benefit from all of the method embodiments described herein. As with certain diseases or conditions, not all individuals belong to a subgroup or subclass of individuals as described herein. The nutritional product as described herein comprises pre-digested fat which is ideally combined with - or a plurality of other fat sources to provide nutrition to infants, young children and children. 161217.doc -34- 201233331 Source for improving nutrient digestion and absorption. In particular, it is similar to the digestion of breastfed babies, because the fat source is at least partially digested before entering the duodenum, giving the baby more time to absorb nutrients, especially in the intestines' and the nutrients entering the baby's colon are reduced, thus making it Nutrients that are germinated and produce gas to reduce the financial properties of the product. Thus, by using pre-digested fat sources (such as monoglycerides and/or fatty acids) in nutraceuticals, such as infant formulas, it is now possible to provide infants with breast milk substitutes or supplements that more closely mimic the benefits of breast milk. In addition to improved nutrient absorption as described above, it has been found that the use of pre-digested fats in nutrients with one or more water-insoluble hydrophobic mixtures (such as oil-soluble (fat-soluble) vitamins (vitamin A, sputum, κ), Ciliary glucan (such as lutein, β-cafrucin, lycopene, etc.), glycolipids (neurolipids), sterols and phytochemicals form. The formation of such micelles allows the insoluble hydrophobic compound to be dissolved in the digest. This is the step of intestinal villus absorption. In addition, pre-digested fat will be used to re-synthesize triglycerides to form chylomicrons. The chylomicrons carry the water-insoluble hydrophobic compound to the surface, and the towel (4) delivers the insoluble hydrophobic compound to the target organ and/or tissue to produce the desired physiological effect. In addition to the benefits discussed above, it has been found that nutrients containing pre-digested fat stimulate the production of cholecystokinin (CCK) in the duodenum, which stimulates the pancreas

申使用預消化脂肪可減少進入許 步消化營養素且減少上部胃 用於吸收。因此,在營養品 結腸且會被醱酵並產生氣體 161217.doc -35· 201233331 及發脹感受之營養素總量。因此,在營養品中使用預消化 脂肪可藉由改善營養素消化及吸收(具有較少脹氣)來改善 耐受性。此對於嬰兒可尤為重要,因為耐受性可能為某些 嬰兒中存在之問題。 除刺激CCK產生以外,已發現預消化脂肪亦誘發腸生長 激素(姨高血糖素樣肽-2,GLP-2)之分泌》GLP-2可增強嬰 兒腸道成熟,其使得消化及營養素吸收更佳。 已進一步發現’如本文所述之包含預消化脂肪之營養品 可用於為嬰兒、幼兒或孩童提供營養來源,此可減小壞死 性小腸結腸炎(NEC)、腹痛及/或短腸症之發生率。 另外’在與脂肪漿料中之蛋白形成對比,藉由向碳水化 合物-礦物質漿料中添加至少一部分預消化脂肪(或在某些 實施例中為所有預消化脂肪)之方法製造營養品的實施例 中,營養品(通常為營養乳液形式)之所得穩定性可得以改 善。 實例 以下實例說明本發明營養品之特定實施例及/或特徵。 該等實例僅出於說明目的而給出且不應理解為對本發明之 限制,因為在不偏離本發明之精神及範疇下可能存在其多 種變化形式。除非另外說明’否則所有例示量均為基於組 合物總重量計之重量百分比。 例示組合物為根據本文所述之製造方法製備的存放穩定 性營養品,以使得除非另外說明,否則每—例示產品均包 括經無菌加工之實施例及經殺菌釜封裝之實施例。 161217.doc -36- 201233331 營養液體實施例為封裝於240 ml塑膠容器中且在調配/封 裝之後在1-25°C範圍内之儲存溫度下在12-18個月内維持物 理穩定性之水包油含水乳液。 實例1_4 . 實例1-4說明本發明之不含乳糖的嬰兒營養乳液,其成 分列舉於下表中。除非另外說明,否則所有成分量均以每 10 0 0公斤批次產品之公斤數列出。 成分 實例1 實例2 實例3 實例4 水 足量 足量 足量 足量 麥芽糊精 53 43.3 50 60 蔗糖 16.5 25 19.2 16.38 乳蛋白分離物 15.65 1.5.65 15.65 15.65 玉米油 12 12 12 12 高油酸紅花籽油 10 10 10 10 單棕櫚酸甘油酯 10 9 8 7 c10-c24脂肪酸鈣鹽 6.0 7 8 9 椰子油 2 2 2 2 真菌油 0.3 0.3 0.3 0.3 卵磷脂 0.1 0.1 0.1 0.1 填酸氫二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.150 0.150 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 破化鉀 0.00022 0.00022 0.00022 0.00022 氣化鉻 0.000217 0.000217 0.000217 0.000217 實例5-8 實例5-8說明本發明之基於乳糖之營養乳液,其成分列 舉於下表中。除非另外說明,否則所有成分量均以每1000 kg批次產品之kg數列出。 161217.doc -37- 201233331 I成分 實例5 實例6 實例7 實例8 | 水 足量 足量 足量 足量 乳糖 58 66 71 63 非脂肪乾乳 25 10 0 16 乳清蛋白濃縮物 6.4 13 18 10.5 高油酸紅花籽油 14 14 14 14 椰子油 6.2 6.2 6.2 6.2 單棕櫊酸甘油酯 10 8 6 4 C10-C24脂肪酸 5.5 7.5 9.5 11.5 果寡醣/半乳寡醣 9 9 9 9 真菌油 0.3 0.3 0.3 0.3 磷酸氫二鉀 0.96 0.96 0.96 0.96 氫氧化的 0.78 1.07 1.36 1.64 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.150 0.150 0.150 0.150 氩氧化斜 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 硪化鉀 0.00022 0.00022 0.00022 0.00022 氣化鉻 0.000217 0.000217 0.000217 0.000217 實例9-12 實例9-12說明本發明之基於大豆之嬰兒營養乳液,其成 分列舉於下表中。除非另外說明,否則所有成分量均以每 1000公斤批次產品之公斤數列出。 成分 實例9 實例10 實例11 實例12 水 足量 足量 足量 足量 玉米糖漿固體 53 43.3 50 60 蔗糖 16.5 25 19.2 16.38 大豆蛋白分離物 19.5 19.5 19.5 19.5 玉米油 12 12 12 12 高油酸紅花軒油 10 10 10 10 單棕櫊酸甘油酯 10 9 8 7 c10-c24脂肪酸 6.0 7 8.0 9 真菌油 0.3 0.3 0.3 0.3 L-胱胺酸 2.3 2.3 2.3 2.3 161217.doc •38· 201233331 L-酪胺酸 1.1 1,1 1.1 1.1 | 氫氧化在丐 0.09 1,0 1.1 1.2 L-色胺酸 0.66 0.66 0.66 0.66 碌酸氫二钟 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.150 0.150 0.0 0.0 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 嶼化舒 0.00022 0.00022 0.00022 0.00022 實例13-16 實例13-16說明本發明之基於水解蛋白之嬰兒營養乳 液,其成分列舉於下表中。除非另外說明,否則所有成分 量均以每1 000公斤批次產品之公斤數列出。 成分 實例13 實例14 實例15 實例16 水 足量 足量 足量 足量 蔗糖 42 42 42 42 澱粉 21.8 21.8 21.8 21.8 水解蛋白 22.2 22.2 22.2 22.2 高油酸紅花籽油 13.7 13.7 13.7 13.7 MCT油 6 6 6 6 單棕櫊酸甘油酯 10 9 8 7 Ch)-C24脂肪酸 11 9.5 8 6.5 揶子油 5 7.5 9 11.5 真菌油 0.3 0.3 0.3 0.3 氫氧化妈 1.6 L29 1.1 0.93 L-蛋胺酸 0.3 0.3 0.3 0.3 磷酸氫二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.0 0.0 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 蛾化斜 0.00022 0.00022 0.00022 0.00022 161217.doc -39- 201233331 實例17 在該實例中’評估大鼠對c10-c24脂肪酸鈣鹽之吸收及相 關生物可用性。 對三十隻大鼠隨機指定三種含有不同蛋白及脂肪之飲食 (飲食1、飲食2及飲食3)之-^飲食1-3與八〇人(:方法906.48 中所用者相同,不同之處在於飲食1_3具有較高脂肪含量 且包含麥芽糊精作為碳水化合物來源。飲食1含有1〇 wt% 蛋白可用作酸酪蛋白且含有23.6 wt%脂肪可用作含有30 wt0/。椰子油、30 wt%大豆油及40 wt%高油酸紅花籽油 (HOSO)之油摻合物。飲食2及3之營養型態與飲食1之營養 型態相同’除了蛋白質、脂肪、碳水化合物及礦物質被混 合、均質化且喷霧乾燥以外。飲食3與飲食2之不同之處僅 在於以尚油酸紅花籽油脂肪酸鈣鹽替代H〇s〇油且以磷酸 鉀替代磷酸三鈣,以使得飲食2飲食3之總體營養及礦物質 型態相同。HOSO脂肪酸鈣鹽提供1〇〇%之飲食鈣。 對大鼠餵飼飲食1、飲食2或飲食3之一持續4週時期。使 用餵飼試驗結束時之飼料/蛋白攝取及體重增加來計算飼 料轉化(體重增加公克數/飼料攝取公克數)及蛋白效率比 (體重增加公克數/蛋白攝人公克數)(pER卜若由於不良吸 收HOSO月曰肪酸妈鹽之熱量值(亦#,熱量/物質公克數) 量值’則預期飲食3之大鼠將增加較少 體重或服用更多飼料以維持其生長,#兩者均導致較低之 飼料轉化及PER。 下表中所tf之結果顯*,飲食3之大鼠與對照組具有相 161217.doc 201233331 同之飼料轉化或per,顯示HOSO脂肪酸鈣鹽之熱量值並 非不同於HOSO油。因此,顯示HOSO脂肪酸鈣鹽具高度生 物可用性。 蛋白效率比 飼料轉化 飲食1(對照組1) 2.83 +/- 0.28* 0.29 +/- 0.03 飲食2(對照组2J 3.16+/-0.17 0.31+/-0.02 飲食3(脂肪酸約鹽) 3.32 +/- 0.27 0.37 +/- 0.03 *標準偏差(n=l 〇) 實例18 在該實例中,分析10天大之豬對大豆脂肪酸鹽之吸收。 將16隻乳豬隨機分為兩組且個別地圈養於代謝籠中且經 訓練以在30分鐘内自盆中獲取營養乳液。在用市售即食型 基於水解蛋白之配方訓練一週之後,對該等豬餵飼包含碳 酸三鈣及碳酸鈣作為鈣來源之市售基於水解蛋白之配方粉 末(對照組)或包含大豆脂肪酸鈣鹽作為鈣來源之乳液(實驗 乳液)。對於對照組及實驗乳液而言,蛋白質來源及含 量、脂肪含量及礦物質型態相同。然而,實驗乳液包含大 豆脂肪酸替代對照組中之大豆油,且包含氫氧化鈣作為妈 礦物質系統之一部分以中和大豆脂肪酸。調整實驗乳液之 填酸鉀含量以與對照組之峨含量相匹配。大豆脂肪酸約提 供實驗乳液中100%之鈣。 在餵飼兩週之後,基於下式計算表觀脂肪及鈣消化率: 表觀脂肪消化率=((脂肪攝取·糞便脂肪)/脂肪攝取)*丨〇〇 表觀药消化率=((鈣攝取_糞便鈣)/鈣攝取)*1〇〇 乾物質消化率=((乾物質攝取-糞便乾物質)/乾物質攝取)*1〇〇 161217.doc 201233331 實驗乳液減少之飼料轉化(重量/飼料攝取)及減少之脂 肪、辦及乾物質消化率將顯示實驗乳液之大豆脂肪酸釣鹽 吸收不良,且因此顯示對於實驗乳液而言鈣之熱量值及 生物可用性低於對照組。 如下表中所示,實驗乳液之飼料轉化、脂肪消化率及乾 物質消化率顯著不同於對照組,顯示對於初生豬而言,實 驗乳液之大豆脂肪酸鈣鹽被高度吸收且具生物可用性。此 外’下文所示之表觀鈣消化率資料顯示實驗乳液之大豆脂 肪酸詞鹽比對照組中包含之辦(亦即,碟酸三|弓及碳酸辦) 更具生物可用性。 表觀脂肪 消化率 飼料轉化 (體重增加公克數/ 飼料(乾物質) 公克數) 表觀舞消化率 表觀乾物質 消化率 對照組 97.6+/-1.0 0.82+/- 0.14* 81.8+/-7.2 97.8 +/- 0.7 實驗乳液 97.6+/-1.4 0.80+/-0.15 91.3+/-3.3 98.0+/-1.0 *標準偏差(n=10) 實例19 在該實例中,分析脂肪酸鈣鹽之乳化特性。 藉由使用桌上型高剪切混合器用500 ml水剪切! 8 g 13(TF含有單棕棚酸甘油酯(油之5重量%)之大豆油及430 mg Ca(磷酸三鈣形式)來製備第一乳液(對照乳液作為對 照乳液的含有相同含量之鈣及脂肪(12 g大豆油加上6 豆脂肪酸)之第二乳液(脂肪酸鈣乳液)係藉由以下來製備: (1) 在約130°F之溫度下將大豆脂肪酸油溶液分散於水中; (2) 添加430 mg氯化鈣形式之Ca ; (3)使用KOH將溶液 161217.doc •42· 201233331 調整至約7.0 ;及(4)使用桌上型高剪切混合物剪切混合物。 使對照乳液及脂肪酸鈣乳液靜置三週時期以分析乳液分 離。在經過一夜之後,對照乳液在乳液頂部出現包含乳狀 層之可見相分離。(參見圖1A)。相比而言,儲存三週之 後’脂肪酸約乳液在乳液頂部僅出現輕微可彳貞測(但並非 清楚可見)之齊皂層,而乳液仍保持一相^在脂肪酸飼乳 液底部無可見之鈣沈降(參見圖1B)。 該專結果顯示脂肪酸弼鹽為有效乳化劑且能夠為實質上 不會自溶液沈降之營養乳液提供鈣來源。此使得乳液產品 具有改善之穩定性及較長之存放期。 實例20 在該實例中,量測10天大豬對兩種獨立測試調配物及對 照調配物之脂肪吸收量及約吸收量》 第一測試調配物(調配物1)在脂肪系統中包含標禍油精 油,第二測試調配物(調配物2)在脂肪系統中包含預消化脂 肪,且對照調配物(調配物3)在脂肪系統中包含低棕橺酸 油。三種調配物之脂肪系統組分列舉於下表中。 營養素(公克) 調配物1 (栋櫚油精油調配物) 調配物2 (預消化脂肪調配物> 調配物3 (包含低棕櫚酸油 之對照調配物) 椰子油 37.2 0 84.1 高油酸紅花籽油 62.8 108 111.9 又豆脂肪酸 0 563 ~ 0 ARA油 3.03 3.03 3.03 DHA油 1.52 L52 ~ 1.52 ΐ椋櫊酸甘油酯 0 65Α ~ 0 卵磷脂 1.12 1.12 "" 1.12 棕櫊油精 122.7 0 0 大豆油 57.1 0 83.8 161217.doc •43- 201233331 製備三種具有幾乎相同的營養素及礦物質型態之調配 物°調配物1及2之脂肪酸型態模仿母乳脂肪酸型態。調配 物2中包含氫氧化鈣(足以螯合所有游離脂肪酸之量)作為弼 來源’其與大豆脂肪酸反應以形成不溶性脂肪酸鈣鹽。該 反應消除游離脂肪酸所產生之苦味及咽喉燒灼感受。另 外,升高調配物2中磷酸鉀之含量以與調配物1及3中之磷 含量相匹配。調配物1及3中所用之鈣鹽為磷酸鈣。 使60隻10天大豬(加或減兩天)隨機分組接受調配物1、 調配物2或調配物3。使豬個別圈養於代謝籠中且在訓練及 適應4天之後’每天餵飼五次持續三週。收集第2天至第18 天之糞便物質且分析鈣吸收及脂肪吸收。以糞便物質中之 鈣量除以飲食中之鈣量再乘以1 〇〇,計算鈣吸收。以糞便 物質中之脂肪量除以飲食中之脂肪量再乘以1〇〇,計算脂 肪吸收。結果展示於下表中。 脂肪吸收(%) 鈣吸收(%) 調配物1(標櫊油精) 92.3 ± 3.9 88.9 + 4.7 調配物2(預消化脂肪) 98.2 ± 0.7 93.1+2.4 調配物3(對照:低棕櫊酸脂肪系統) 98.0+1.4 90.7 ±3.5 如上表中之結果所顯示,使用預消化脂肪系統使得嬰兒 配方可模仿母乳脂肪酸型態’不會出現如使用棕櫚油精油 脂肪系統時所經歷對鈣及脂肪吸收之不利影響,配方2(預 消化脂肪調配物)之脂肪及弼吸收速率至少與低栋棚酸配 方之脂肪及弼吸收速率同等良好。該等發現說明大豆脂肪 酸鈣鹽在初生豬中具高度生物可用性。 實例21 161217.doc 201233331 在該實例中,評估實例20之豬的CCK產生(AUC)及腸動 素產生(AUC)之餐後增加量。 在實例20中所述之脂肪及鈣吸收分析之結論中,使經投 與調配物2(預消化脂肪調配物)或調配物3(包括低棕櫚酸之 對照調配物)之豬禁食12小時,且抽取禁食血液以分離血 清。使豬恢復兩小時且隨後給予250 mL調配物2或調配物 3。在餵飼後30及60分鐘時抽取餐後血液樣本且測試CCK 及腸動素。計算CCK(曲線下面積)及腸動素(AUC)之餐後 增加量。結果展示於下表中。 調配物2 (預消化脂肪調配物) (pg/mL*min) 調配物3 (對照:低棕櫊酸調配物) (pg/mL*mm) CCK分泌之餐後增加量 (曲線下面積) 1935 ±1464 1046 + 754 腸動素AUC(餐後增加量) 483+253 839+403 上表中之資料顯示以預消化脂肪(單棕櫊酸甘油醋加大 豆脂肪酸)替代三酸甘油酯會刺激餐後CCK分泌,其已顯 示刺激胰腺消化酶分泌、增強膽囊收縮且延遲口腔至盲腸 之輸送。因此,具有預消化脂肪之調配物可刺激更多可消 化酶分泌且減緩GI輸送,以允許更多營養素消化及吸收。 因此,包含預消化脂肪之調配物可改善配方耐受性,因為 未消化之營養素可導致過度結腸醱酵而導致脹氣、腹瀉及 胃脹。 另外,上表中之資料顯示,以預消化脂肪(單棕橺酸甘 油酯加大豆脂肪酸)替代三酸甘油酯可減少餐後腸動素分 161217.doc -45- 201233331 泌。已顯示,患腹痛之嬰兒具有較低之餐後CCK含量,但 具有較高之餐後腸動素含量。餐後腸道激素之間的此種不 平衡導致嬰兒GI收縮,其導致腹痛。上表中之資料顯示, 包含預消化脂肪可增加嬰兒之餐後CCK含量,但減少腸動 素含量,由此減小激素不平衡以緩解GI收縮、腹痛及腹 痛。 實例22 在該實例中,使用實例20之豬來研究各種脂肪系統對乳 糜微粒三酸甘油酯棕櫚酸及Sn-2棕櫚酸含量之影響。 自每隻豬抽取1小時餐後血液樣本且分離血漿,以液氮 冷凍且儲存在-80°C之冷凍器中。使用Folch溶劑萃取總血 毁脂質。藉由薄層層析分離三酸甘油醋。下表顯示調配物 1 (棕櫊油精調配物)及調配物2(預消化脂肪調配物)之血漿 三酸甘油酯棕櫚酸及Sn-2棕櫚酸。表中亦展示餵飼該兩種 調配物之豬的乳糜微粒三酸甘油酯及Sn-2棕櫚酸。 調配物1 : (棕櫊油精) 餵飼調配物1 之緒的血聚 三酸甘油酯 調配物2 : (預消化脂肪) 餵飼調配物2之 諸的血聚 三酸甘油酯 餵飼母乳之人類 嬰兒的血漿三酸 甘油酯 三酸 甘油醋 Sn-2 三酸 甘油醋 Sn-2 三酸 甘油醋 Sn-2 三酸 甘油酯 Sn-2 三酸 甘油酯 Sn-2 棕櫊酸 含量 (%) 23.3 5.8 18.3 10.6 21.4 5.2 18.5 14.4 25 25.5 如上表中所示,餵飼預消化脂肪配方之豬的血漿三酸甘 油酯及Sn-2棕櫚酸含量顯著高於餵飼棕櫚油精配方之豬。 調配物1及調配物2之血漿三酸甘油酯棕櫚酸/Sn-2棕櫚酸比 率分別為約1.7及1.3,且已知母乳餵飼嬰兒之該比率為約 16l217.doc -46- 201233331 1.1。因此,該資料顯示預消化脂肪調配物比掠摘油精脂 肪調配物能更佳地模仿母乳。 實例23 在該實例中’使用實例2G之緒來研究各種脂肪系統對血 液葉黃素含量之影響。 使用氣仿與甲醇之溶劑(比率為2:1)萃取來自每隻豬之丄 小時餐後血液樣本的血漿。移除溶劑且彙集所得脂質且使 用1去方法刀析葉黃素。下表展示傲飼調配物1 (棕橺油精 調配物)' 調配物2(預消化脂肪調配物)及調配物3(低棕櫚 酸調配物)之豬的葉黃素含量,以每mg脂質之葉黃素叫數 表示。 調配物1 : 調配物2 : 調配 (椋櫊油精) (預消化脂肪) (低棕櫊酸、 葉黃素含量 N/A* 0.765 μβ 0.539 μα *調配物1之葉黃素含量過低而難以量測。 如上表中所示’餵飼包含預消化脂肪之調配物之豬與儀 飼包含棕櫚油精或低棕櫚酸之調配物之豬相比具有增加之 葉黃素吸收。 實例24 在該實例中,使用實例20之調配物2(預消化脂肪調配 物)及調配物3(低棕櫚酸調配物)來研究各種脂肪系統對微 胞葉黃素含量之影響。 使調配物2及調配物3用水復原(每1 ·〇 L水133 g粉末狀調 配物),且添加HC1將復原調配物之pH值調整至4.5。藉由 161217.doc -47- 201233331 向40 ml復原調配物中添加1.00 ml USP胃蛋白酶(56 mg/ml) 使復原調配物在室溫下消化1小時。在胃蛋白酶消化之後 將復原調配物之pH值調整至7.0,且隨後向經胃蛋白酶消 化之調配物中添加28 mg USP胰澱粉酶/蛋白酶、28 mg USP姨酶脂肪酶與108 mg膽汁萃取物之混合物。使調配物 在室溫下進一步消化2小時且離心(31,000 g,在201下,3 小時)。經消化之調配物形成油/乳脂凝塊、含水相及沈降 層。抽取含水相以用於微胞之葉黃素分析,該等微胞在含 水内腔中吸收葉黃素期間充當載體。下表展示每kg消化調 配物之微胞葉黃素的含量。 消化調配物2 : (預消化脂肪) 消化調配物3 : (低棕櫊酸) 微跑紫黃素(pg) 0.598 με 0.246 ue 如上表中所示,在包含預消化脂肪之消化調配物中發現 之微胞葉黃素的量為在包含低棕櫊酸之消化調配物中發現 的微胞葉黃素之量的兩倍多,由此顯示使用預消化脂肪可 增加葉黃素吸收。 實例25 在該實例中,分析預消化脂肪減小軟便發生率之能力。 對30隻斷乳大鼠餵飼基於水解蛋白之粉末嬰兒配方(包 含MCT油作為30 wt%之脂肪來源),持續四天適應期。在 適應期結束時’將大鼠隨機分為兩組且餵飼對照調配物 (貝低棕櫚酸粉末嬰兒配方)或測試調配物(含有預消化脂肪之 嬰兒配方)^對照調配物與測試調配物之營養素型態相 16l2l7.doc -48- 201233331 同。使大鼠可自由獲取飼料及水達五天,且每天記錄攝入 之飼料量及體重。 儘管兩組之間的飼料攝取或體重增加無顯著差異彳曰大 便堅實度存在顯著差異。在餵飼之最後兩天期間,使用〇_ 5點系統對大鼠之大便堅實度評分。評分係基於黏結至籠 底吸取薄片之大便的嚴重度及堅實度。〇評分值指示正常 大便且5評分值指示水樣腹瀉。如圖2中所示,餵飼對照調 配物(含有MCT油)之大鼠比餵飼測試調配物(含有預消化脂 肪)之大鼠產生較稀之大便。 實例26 在該實例中’分析預消化脂肪減小壞死性小腸結腸炎 (NEC)發生率之能力。 將經由剖腹產分娩之早產豬(92%孕期)即刻轉移至充氧 培育器(37°C )中且在臍動脈中置放一血管導管。在第一個 24小時期間經由血管導管對該等豬注射三次(4、6及7 mL/kg體重)母體▲聚。以每小時4-6 mL/kg之速率提供完 全胃腸外營養(Total parenteral nutrition,TPN)持續 24 小 時。隨後使該等諸經由口胃管(or〇gastric tube)以每小時5 mL/kg之速率隨機分組接受對照調配物或pdf調配物。除 其中之脂肪系統以外’對照調配物與PDF調配物相同。特 定而言’對照調配物中之脂肪系統包含植物油,且PDF調 配物中之脂肪系統包含30 wt°/〇單棕櫚酸甘油酯、20 wt%大 豆脂肪酸、26 wt%高油酸紅花籽油、i 4 wt%椰子油及1 〇 wt%甘油三丁酸酯。對照調配物與PDF調配物兩者每公升 161217.doc -49- 201233331 調配物中均包含100 g蛋白質、47 g脂肪及5〇 g玉米糖漿。 在經腸餵飼36小時之後使該等豬安樂死且進行屍檢以使用 1·5評分系統評估NEC病變之嚴重程度,其中丨評分值指示 無NEC跡象。結果展示於下表中。 區塊1 區後2 對照調配物 (n=5) PDF調配物 (n=3) 對照調配物 (n=5) PDF調配物 (n=3) 早期NEC死亡 2 0 3~~ 1 屍檢時偵測之NEC 2 1 0 0 總NEC 4 1 3 1 如上表中所示,傲飼對照調配物之1 〇隻豬中有5隻(5〇%) 在腸餵飼期結束之前即死於NEC,但餵飼PDF調配物之6隻 豬中僅有1隻(16.7%)在腸傲飼期結束之前先於NEC。另 外,餵飼對照調配物之1 〇隻豬中有7隻(70%)在腸餵飼期結 束之前經測定即患有NEC,而餵飼PDF調配物之6隻豬中僅 有2隻(33°/。)在腸餵飼期結束之前經測定患有NEC。因此可 得出結論,藉由以包含預消化脂肪之脂肪系統替代植物油 脂肪系統可減小NEC之發生率。 【圖式簡單說明】 圖1A及圖1B展示如實例19中製備之對照乳液及實驗乳 液的圖示。 圖2為展示飲食對糞便堅實度之影響的圖。 161217.doc •50·The use of pre-digested fat reduces the amount of digestive nutrients and reduces the upper stomach for absorption. Therefore, in the colon of the nutrient, it will be fermented and produce gas 161217.doc -35· 201233331 and the total amount of nutrients. Therefore, the use of pre-digested fat in nutrients can improve tolerance by improving nutrient digestion and absorption (with less flatulence). This is especially important for babies because tolerance may be a problem in some babies. In addition to stimulating CCK production, it has been found that pre-digested fat also induces secretion of intestinal growth hormone (glucagon-like peptide-2, GLP-2). GLP-2 enhances intestinal maturation in infants, which allows digestion and nutrient absorption. good. It has further been found that 'pre-digested fat containing nutrients as described herein can be used to provide a source of nutrition for infants, toddlers or children, which can reduce the incidence of necrotizing enterocolitis (NEC), abdominal pain and/or short bowel disease. rate. In addition, 'in the comparison with the protein in the fat slurry, the nutritional product is produced by adding at least a portion of the pre-digested fat (or in some embodiments all pre-digested fat) to the carbohydrate-mineral slurry. In the examples, the resulting stability of the nutritional product (usually in the form of a nutritional emulsion) can be improved. EXAMPLES The following examples illustrate specific embodiments and/or features of the nutritional products of the present invention. The examples are given for illustrative purposes only and are not to be construed as limiting the invention, as many variations are possible without departing from the spirit and scope of the invention. All exemplified amounts are by weight based on the total weight of the composition unless otherwise stated. The exemplified compositions are storage stable nutritional products prepared according to the manufacturing methods described herein such that, unless otherwise stated, each of the exemplified products includes aseptically processed embodiments and autoclaved encapsulated embodiments. 161217.doc -36- 201233331 Examples of nutrient liquids are water that is physically stable in 12-18 months at a storage temperature in the range of 1-25 ° C after being packaged in a 240 ml plastic container. An oil-in-water emulsion. Examples 1-4. Examples 1-4 illustrate lactose-free infant nutritional emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredient amounts are listed in kilograms per 100 kg batch of product. Ingredient Example 1 Example 2 Example 3 Example 4 Water sufficient amount sufficient amount sufficient amount of maltodextrin 53 43.3 50 60 sucrose 16.5 25 19.2 16.38 milk protein isolate 15.65 1.5.65 15.65 15.65 corn oil 12 12 12 12 high oleic acid Safflower oil 10 10 10 10 monopalmitate 10 9 8 7 c10-c24 fatty acid calcium salt 6.0 7 8 9 coconut oil 2 2 2 2 fungal oil 0.3 0.3 0.3 0.3 lecithin 0.1 0.1 0.1 0.1 dipotassium hydrogenate 0.96 0.96 0.96 0.96 Calcium Oxide 0.3 0.3 0.3 0.3 Ascorbic Acid 0.235 0.235 0.235 0.235 Carrageenan 0.150 0.150 0.150 0.150 Potassium Hydroxide 0.136 0.136 0.136 0.136 TM/UTM Premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E Premix 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Broken potassium 0.00022 0.00022 0.00022 0.00022 Calcined chromium 0.000217 0.000217 0.000217 0.000217 Examples 5-8 Examples 5-8 illustrate the lactose-based nutritional emulsion of the present invention, the ingredients of which are listed below In the table. Unless otherwise stated, all ingredient amounts are listed in kg per 1000 kg batch of product. 161217.doc -37- 201233331 I component example 5 Example 6 Example 7 Example 8 | Water sufficient amount sufficient amount sufficient lactose 58 66 71 63 non-fat dry milk 25 10 0 16 whey protein concentrate 6.4 13 18 10.5 high Oleic acid safflower oil 14 14 14 14 Coconut oil 6.2 6.2 6.2 6.2 Monopalmitate 10 8 6 4 C10-C24 fatty acid 5.5 7.5 9.5 11.5 Fructooligosaccharide/galactooligosaccharide 9 9 9 9 Fungal oil 0.3 0.3 0.3 0.3 dipotassium hydrogen phosphate 0.96 0.96 0.96 0.96 0.78 1.07 1.36 1.36 1.64 potassium sulphate 0.3 0.3 0.2 0.3 ascorbic acid 0.235 0.235 0.235 0.235 carrageenan 0.150 0.150 0.150 0.150 argon oxidation 0.136 0.136 0.136 0.136 TM / UTM premix 0.1684 0.1684 0.1684 0.1684 Premix of vitamins A, D and E 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Potassium sulphate 0.00022 0.00022 0.00022 0.00022 Chromium oxide 0.000217 0.000217 0.000217 0.000217 Example 9-12 Example 9-12 The soy-based infant nutritional emulsion of the invention is listed in the table below. Unless otherwise stated, all ingredient amounts are listed in kilograms per 1000 kg batch of product. Ingredient Example 9 Example 10 Example 11 Example 12 Water sufficient amount sufficient amount sufficient amount of corn syrup solids 53 43.3 50 60 sucrose 16.5 25 19.2 16.38 soy protein isolate 19.5 19.5 19.5 19.5 corn oil 12 12 12 12 high oleic acid safflower oil 10 10 10 10 Monopalmitate 10 9 8 7 c10-c24 fatty acid 6.0 7 8.0 9 Fungal oil 0.3 0.3 0.3 0.3 L-cystamic acid 2.3 2.3 2.3 2.3 161217.doc •38· 201233331 L-tyrosine 1.1 1,1 1.1 1.1 | Hydroxide in 丐0.09 1,0 1.1 1.2 L-tryptophan 0.66 0.66 0.66 0.66 hydrogen hydride two clock 0.96 0.96 0.96 0.96 vaporized potassium 0.3 0.3 0.3 0.3 ascorbic acid 0.235 0.235 0.235 0.235 carrageenan 0.150 0.150 0.0 0.0 Potassium hydroxide 0.136 0.136 0.136 0.136 TM/UTM premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E premix 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 Yuhua Shu 0.00022 0.00022 0.00022 0.00022 Examples 13-16 Examples 13-16 illustrate hydrolyzed protein-based infant nutritional emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredients are listed in kilograms per 1,000 kilograms of batch product. Ingredient Example 13 Example 14 Example 15 Example 16 Water sufficient amount sufficient amount sufficient sucrose 42 42 42 42 starch 21.8 21.8 21.8 21.8 hydrolyzed protein 22.2 22.2 22.2 22.2 high oleic acid safflower oil 13.7 13.7 13.7 13.7 MCT oil 6 6 6 6 Monopalmitate 10 9 8 7 Ch)-C24 fatty acid 11 9.5 8 6.5 Hazelnut oil 5 7.5 9 11.5 Fungal oil 0.3 0.3 0.3 0.3 Oxide mother 1.6 L29 1.1 0.93 L-methionine 0.3 0.3 0.3 0.3 Hydrogen phosphate Dipotassium 0.96 0.96 0.96 0.96 Calcium Oxide 0.3 0.3 0.3 0.3 Ascorbic acid 0.235 0.235 0.235 0.235 Carrageenan 0.0 0.0 0.150 0.150 Potassium hydroxide 0.136 0.136 0.136 0.136 TM/UTM premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E Pre Mixture 0.0758 0.0758 0.0758 0.0758 Water-soluble vitamin premix 0.0728 0.0728 0.0728 0.0728 mothification 0.00022 0.00022 0.00022 0.00022 161217.doc -39- 201233331 Example 17 In this example, 'evaluate the absorption of c10-c24 fatty acid calcium salt in rats and Relevant biological availability. Thirty rats were randomly assigned to three diets containing different protein and fat (diet 1, diet 2 and diet 3) -^ diet 1-3 and gossip (: method 906.48 used in the same, the difference is Diet 1_3 has a higher fat content and contains maltodextrin as a carbohydrate source. Diet 1 contains 1% by weight of protein for acid casein and 23.6% by weight of fat can be used to contain 30 wt% of coconut oil, 30 Oil blend of wt% soybean oil and 40 wt% high oleic safflower seed oil (HOSO). The nutritional forms of diets 2 and 3 are the same as those of diet 1 'except protein, fat, carbohydrates and minerals It is mixed, homogenized and spray-dried. Diet 3 differs from diet 2 only in that it replaces H〇s eucalyptus with oleic acid safflower fatty acid calcium salt and replaces tricalcium phosphate with potassium phosphate to make a diet. 2 The overall nutrition and mineral form of Diet 3 is the same. HOSO fatty acid calcium salt provides 1% of dietary calcium. Rats are fed diet 1, diet 2 or diet 3 for 4 weeks. Feeding test Calculation of feed/protein intake and weight gain at the end Feed conversion (weight gain grams / feed intake grams) and protein efficiency ratio (weight gain grams / protein intake grams) (pER Bu if due to poor absorption HOSO month fat fatty salt salt value of heat (also #, Calorie/substance grams) The value of 'rats' diet 3 rats will increase less weight or take more feed to maintain their growth, # both lead to lower feed conversion and PER. The results were *, the rats in diet 3 and the control group had phase 161217.doc 201233331 with feed conversion or per, indicating that the caloric value of HOSO fatty acid calcium salt is not different from HOSO oil. Therefore, it shows that HOSO fatty acid calcium salt is highly bioavailable. Protein efficiency compared to feed conversion diet 1 (control group 1) 2.83 +/- 0.28* 0.29 +/- 0.03 diet 2 (control group 2J 3.16 +/- 0.17 0.31 +/- 0.02 diet 3 (fatty acid salt) 3.32 +/ - 0.27 0.37 +/- 0.03 * standard deviation (n = l 〇) Example 18 In this example, the absorption of soybean fatty acid salt by a 10-day-old pig was analyzed. 16 suckling pigs were randomly divided into two groups and individually housed. In a metabolic cage and trained to self-contain within 30 minutes Obtaining a nutritional emulsion. After training for one week with a commercially available ready-to-eat hydrolyzed protein-based formulation, the pigs were fed a commercially available hydrolyzed protein-based formula powder (control) containing tricalcium carbonate and calcium carbonate as a source of calcium or Contains soy fatty acid calcium salt as a calcium source emulsion (experimental emulsion). For the control and experimental emulsions, the protein source and content, fat content and mineral form are the same. However, the experimental emulsion contains soybean fatty acid instead of the control group. Soybean oil, and contains calcium hydroxide as part of the mom mineral system to neutralize soy fatty acids. The potassium acetate content of the experimental emulsion was adjusted to match the strontium content of the control group. Soybean fatty acids provide about 100% calcium in the experimental emulsion. After two weeks of feeding, the apparent fat and calcium digestibility is calculated based on the following formula: Apparent fat digestibility = ((fat intake / fecal fat) / fat intake) * 丨〇〇 apparent drug digestibility = ((calcium) Intake _ fecal calcium) / calcium intake) *1 〇〇 dry matter digestibility = ((dry matter intake - fecal dry matter) / dry matter intake) * 1 〇〇 161217.doc 201233331 Experimental emulsion reduced feed conversion (weight / Feed intake) and reduced fat, dry and dry matter digestibility will show poor absorption of the soy fatty acid salt of the experimental emulsion, and thus show that the caloric value and bioavailability of calcium for the experimental emulsion is lower than the control. As shown in the table below, the feed conversion, fat digestibility and dry matter digestibility of the experimental emulsions were significantly different from those of the control group, indicating that for newborn pigs, the soy fatty acid calcium salt of the experimental emulsion was highly absorbed and bioavailable. Further, the apparent calcium digestibility data shown below shows that the soy fatty acid salt of the experimental emulsion is more bioavailable than the one contained in the control group (i.e., the dish of the acid and the carbonated water). Apparent fat digestibility feed conversion (weight gain grams / feed (dry matter) grams) apparent dance digestibility apparent dry matter digestibility control group 97.6+/-1.0 0.82+/- 0.14* 81.8+/-7.2 97.8 +/- 0.7 Experimental emulsion 97.6 +/- 1.4 0.80 +/- 0.15 91.3 +/- 3.3 98.0 +/- 1.0 * Standard deviation (n = 10) Example 19 In this example, the emulsification characteristics of the fatty acid calcium salt were analyzed. Cut with 500 ml of water using a tabletop high shear mixer! 8 g 13 (TF containing succinyl glyceride (5 wt% oil) of soybean oil and 430 mg Ca (tricalcium phosphate form) to prepare the first emulsion (control emulsion as a control emulsion containing the same amount of calcium and The second emulsion (fatty acid calcium emulsion) of fat (12 g soybean oil plus 6 soybean fatty acid) is prepared by: (1) dispersing the soybean fatty acid oil solution in water at a temperature of about 130 °F; Adding 430 mg of Ca in the form of calcium chloride; (3) adjusting the solution 161217.doc •42·201233331 to about 7.0 using KOH; and (4) shearing the mixture using a tabletop high shear mixture. The fatty acid calcium emulsion was allowed to stand for three weeks to analyze the emulsion separation. After one night, the control emulsion showed a visible phase separation containing a milky layer on top of the emulsion (see Figure 1A). In comparison, after three weeks of storage, the fatty acid The emulsion showed only a slightly detectable (but not clearly visible) layer of soap on top of the emulsion, while the emulsion remained in one phase without visible calcium deposition at the bottom of the fatty acid feed emulsion (see Figure 1B). Fatty acid strontium salt An effective emulsifier and capable of providing a calcium source for a nutritional emulsion that does not substantially settle out of solution. This results in improved stability and long shelf life of the emulsion product. Example 20 In this example, a 10-day large pig pair was measured. Fat Absorption and Approximate Absorption of Two Independent Test Formulations and Control Formulations The first test formulation (Formulation 1) contained the essential oils in the fat system and the second test formulation (Formulation 2) The fat system contains pre-digested fat, and the control formulation (Formulation 3) contains low palmitic acid oil in the fat system. The fat system components of the three formulations are listed in the table below. Nutrients (grams) Formulation 1 ( Formulation of essential oil formula) Formulation 2 (pre-digested fat formulation> Formulation 3 (control formulation containing low palmitic acid oil) Coconut oil 37.2 0 84.1 High oleic acid safflower oil 62.8 108 111.9 Bean fatty acid 0 563 ~ 0 ARA oil 3.03 3.03 3.03 DHA oil 1.52 L52 ~ 1.52 glyceride citrate 0 65 Α ~ 0 lecithin 1.12 1.12 "" 1.12 palm eucalyptus oil 122.7 0 0 soybean oil 57.1 0 83.8 161217.d Oc •43- 201233331 Preparation of three formulations with nearly identical nutrients and mineral forms ° The fatty acid forms of Formulations 1 and 2 mimic the fatty acid profile of the breast. Formulation 2 contains calcium hydroxide (sufficient to chelate all free) The amount of fatty acid is used as a source of hydrazine to react with soybean fatty acids to form an insoluble fatty acid calcium salt. This reaction eliminates the bitter taste and throat burning sensation produced by free fatty acids. In addition, the amount of potassium phosphate in Formulation 2 was raised to match the phosphorus content of Formulations 1 and 3. The calcium salt used in Formulations 1 and 3 is calcium phosphate. Sixty 10 day old pigs (plus or minus two days) were randomized to receive Formulation 1, Formulation 2 or Formulation 3. Pigs were individually housed in metabolic cages and fed four times a day for three weeks after training and adaptation for four days. Fecal material from day 2 to day 18 was collected and analyzed for calcium absorption and fat absorption. Calcium absorption was calculated by dividing the amount of calcium in the fecal material by the amount of calcium in the diet and multiplying by 1 〇〇. The fat absorption was calculated by dividing the amount of fat in the fecal material by the amount of fat in the diet and multiplying by 1 〇〇. The results are shown in the table below. Fat Absorption (%) Calcium Absorption (%) Formulation 1 (Standard Oil) 92.3 ± 3.9 88.9 + 4.7 Formulation 2 (pre-digested fat) 98.2 ± 0.7 93.1+2.4 Formulation 3 (Control: low palmitic acid fat) System) 98.0+1.4 90.7 ±3.5 As shown in the results in the table above, the use of a pre-digested fat system allows the infant formula to mimic the formula of the fatty acid of the breast milk' without the absorption of calcium and fat as experienced in the palm oil essential oil system. Adversely, the fat and sputum absorption rate of Formulation 2 (pre-digested fat formulation) is at least as good as the fat and sputum absorption rate of the low shed acid formula. These findings indicate that soy fatty acid calcium salts are highly bioavailable in newborn pigs. Example 21 161217.doc 201233331 In this example, the post-prandial increase in CCK production (AUC) and enterokin production (AUC) of pigs of Example 20 was evaluated. In the conclusion of the fat and calcium absorption analysis described in Example 20, pigs administered Formulation 2 (pre-digested fat formulation) or Formulation 3 (including low palmitic acid control formulation) were fasted for 12 hours. And fasting blood is drawn to separate the serum. The pigs were allowed to recover for two hours and then 250 mL of Formulation 2 or Formulation 3 was administered. Postprandial blood samples were taken at 30 and 60 minutes after feeding and CCK and enterin were tested. The post-prandial increase in CCK (area under the curve) and enterin (AUC) was calculated. The results are shown in the table below. Formulation 2 (pre-digested fat formulation) (pg/mL*min) Formulation 3 (control: low palmitic acid formulation) (pg/mL*mm) Post-prandial increase in CCK secretion (area under the curve) 1935 ±1464 1046 + 754 Enterin AUC (post-meal increase) 483+253 839+403 The data in the above table shows that replacing the triglyceride with pre-digested fat (single palmitic acid glycerin plus soy fatty acid) will stimulate the meal. Post-CCK secretion, which has been shown to stimulate pancreatic digestive enzyme secretion, enhance gallbladder contraction, and delay oral to cecal delivery. Thus, formulations with pre-digested fat stimulate more secretion of digestive enzymes and slow GI delivery to allow for more nutrient digestion and absorption. Therefore, formulations containing pre-digested fat can improve formulation tolerance because undigested nutrients can cause excessive colonic fermentation leading to flatulence, diarrhea, and bloating. In addition, the data in the above table shows that the replacement of triglyceride with pre-digested fat (mono-glycolate plus soy fatty acid) can reduce postprandal enterotropin 161217.doc -45- 201233331 secretion. Infants with abdominal pain have been shown to have lower post-prandial CCK levels but higher post-prandial enterin levels. This imbalance between postprandial gut hormones causes the baby to contract GI, which causes abdominal pain. The data in the above table shows that the inclusion of pre-digested fat can increase the CCK content of the baby after a meal, but reduce the intestinal motility, thereby reducing the hormone imbalance to relieve GI contraction, abdominal pain and abdominal pain. Example 22 In this example, the pig of Example 20 was used to study the effect of various fat systems on the content of chylomicron triglyceride palmitate and Sn-2 palmitic acid. One hour postprandial blood samples were taken from each pig and plasma was separated, frozen in liquid nitrogen and stored in a freezer at -80 °C. Total blood lipids were extracted using Folch solvent. The triglyceride was separated by thin layer chromatography. The table below shows the plasma triglyceride palmitic acid and Sn-2 palmitic acid in Formulation 1 (palm oil blending formulation) and Formulation 2 (pre-digested fat formulation). The table also shows chylomicron triglycerides and Sn-2 palmitic acid in pigs fed the two formulations. Formulation 1: (Brown olein) Feeding Triglyceride Formulation 2 of the Formulation 1 : (Pre-digested fat) Feeding the blood polytriglyceride of the Formulation 2 Human baby's plasma triglyceride triglyceride vinegar Sn-2 triglyceride vinegar Sn-2 triglyceride vinegar Sn-2 triglyceride Sn-2 triglyceride Sn-2 palmitic acid content (% 23.3 5.8 18.3 10.6 21.4 5.2 18.5 14.4 25 25.5 As shown in the above table, the plasma triglyceride and Sn-2 palmitic acid content of the pigs fed the pre-digested fat formula was significantly higher than that of the pigs fed the palm olein formula. The ratio of plasma triglyceride palmitate/Sn-2 palmitic acid of Formulation 1 and Formulation 2 was about 1.7 and 1.3, respectively, and the ratio of known breast-fed infants was about 16l217.doc -46 - 201233331 1.1. Therefore, this data shows that pre-digested fat formulations mimic breast milk better than swept oil extracts. Example 23 In this example, the effect of various fat systems on blood lutein content was investigated using Example 2G. Plasma from a post-prandial blood sample from each pig was extracted using a solvent of methanol and methanol (ratio 2:1). The solvent was removed and the resulting lipids were pooled and the lutein was resolved using the 1 method. The table below shows the lutein content of pigs in the arbitrage formulation 1 (palm oil extract) 'Formulation 2 (pre-digested fat formulation) and Formulation 3 (low palmitic acid formulation) per mg of lipid The lutein is called a number. Formulation 1: Formulation 2: Formulation (Oyster Extract) (Pre-digested fat) (Low palmitic acid, lutein content N/A* 0.765 μβ 0.539 μα * Formulation 1 has too low a lutein content Difficult to measure. As shown in the table above, 'pigs fed a formulation containing pre-digested fat have increased lutein absorption compared to pigs containing a formulation containing palm olein or low palmitic acid. Example 24 In the example, Formulation 2 (pre-digested fat formulation) and Formulation 3 (low palmitic acid formulation) of Example 20 were used to study the effect of various fat systems on the lutein content of the microcells. Formulation 2 and Formulations 3Recover with water (133 g powder formulation per 1 · L water), and add HC1 to adjust the pH of the reconstituted formulation to 4.5. Add 1.00 to 40 ml reconstituted formulation by 161217.doc -47- 201233331 Ml USP pepsin (56 mg/ml) The reconstituted formulation was digested for 1 hour at room temperature. The pH of the reconstituted formulation was adjusted to 7.0 after pepsin digestion and subsequently added to the pepsin-digested formulation. 28 mg USP Trypsin/Protease, 28 mg USP姨 Enzyme a mixture of lipase and 108 mg of bile extract. The formulation was further digested at room temperature for 2 hours and centrifuged (31,000 g at 201 for 3 hours). The digested formulation formed an oil/creamt clot, Aqueous phase and sedimentation layer. The aqueous phase is extracted for lutein analysis of the micelles, which serve as carriers during the absorption of lutein in the aqueous cavity. The following table shows the micronutrient yellow per kg of digestion formulation. Digestion Formulation 2 : (Pre-digested fat) Digestion Formulation 3 : (Low palmitic acid) Micro-running Violaxanthin (pg) 0.598 με 0.246 ue As shown in the table above, in the digestion containing pre-digested fat The amount of lutein found in the formulation was more than twice the amount of lutein found in the digestive formulation containing low palmitic acid, thus indicating that the use of pre-digested fat increased lutein absorption. Example 25 In this example, the ability of pre-digested fat to reduce the incidence of soft stool was analyzed. 30 weaned rats were fed a hydrolyzed protein-based powdered infant formula (containing MCT oil as a 30 wt% fat source) for four Adaptation period At the time of the bundle, the rats were randomly divided into two groups and fed a control formulation (bean palmitic acid powder infant formula) or a test formulation (infant formula containing pre-digested fat). The control formulation and the nutrient type of the test formulation. The phase is 16l2l7.doc -48- 201233331. The rats are given free access to feed and water for five days, and the amount of feed and body weight are recorded daily. Although there is no significant difference in feed intake or weight gain between the two groups. There is a significant difference in the firmness of stool. During the last two days of feeding, the stool consistency of the rats was scored using the 〇 5 point system. The score is based on the severity and firmness of the stool that is bonded to the bottom of the cage to absorb the sheet. The 〇 score value indicates normal stool and the 5 score indicates watery diarrhea. As shown in Figure 2, rats fed a control formulation (containing MCT oil) produced a leaner stool than the rats fed the test formulation (containing pre-digested fat). Example 26 In this example 'analysis of the ability of pre-digested fat to reduce the incidence of necrotizing enterocolitis (NEC). Preterm pigs (92% of gestation) delivered via caesarean section were immediately transferred to an oxygenation incubator (37 ° C) and a vascular catheter was placed in the umbilical artery. The pigs were injected three times (4, 6 and 7 mL/kg body weight) into the porcine via the vascular catheter during the first 24 hours. Total parenteral nutrition (TPN) is provided at a rate of 4-6 mL/kg per hour for 24 hours. The control formulations or pdf formulations were then randomized via a orgastric tube at a rate of 5 mL/kg per hour. The control formulation was identical to the PDF formulation except for the fat system therein. In particular, the fat system in the control formulation comprises vegetable oil, and the fat system in the PDF formulation comprises 30 wt / 〇 monopalmitin, 20 wt % soy fatty acid, 26 wt% high oleic safflower oil, i 4 wt% coconut oil and 1 〇 wt% glyceryl tributyrate. Both the control formulation and the PDF formulation per liter 161217.doc -49- 201233331 The formulation contained 100 g protein, 47 g fat and 5 g g corn syrup. The pigs were euthanized 36 hours after enteral feeding and autopsied to assess the severity of NEC lesions using a 1.5 scoring system, where the sputum score indicated no NEC signs. The results are shown in the table below. Block 1 Region 2 Control Formulations (n=5) PDF Formulations (n=3) Control Formulations (n=5) PDF Formulations (n=3) Early NEC Deaths 2 0 3~~ 1 Autopsy NEC 2 1 0 0 Total NEC 4 1 3 1 As shown in the above table, 5 out of 5 pigs (5〇%) of the cockroach control formulation died of NEC before the end of the enteral feeding period, but Only 1 of the 6 pigs fed the PDF formulation (16.7%) preceded NEC before the end of the bowel feeding period. In addition, 7 of the 1 pigs fed the control formulation (70%) had NEC measured before the end of the feeding period, while only 2 of the 6 pigs fed the PDF formulation ( 33°/.) NEC was determined before the end of the enteral feeding period. It can therefore be concluded that the incidence of NEC can be reduced by replacing the vegetable oil fat system with a fat system containing pre-digested fat. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A and 1B show graphical representations of a control emulsion and an experimental emulsion prepared as in Example 19. Figure 2 is a graph showing the effect of diet on fecal firmness. 161217.doc •50·

Claims (1)

201233331 七、申請專利範園: 1. 一種包含脂肪系統之營養品,其中該脂肪系統包含至少 10 wt°/〇之不飽和游離脂肪酸組分與含有脂肪酸之單酸甘 油酯的混合物β 2. 如請求項1之營養品,其中該脂肪系統包含約20 wt0/〇至 約65 wt%之該不飽和游離脂肪酸組分與含有脂肪酸之單 酸甘油酯的該混合物。 3·如請求項1之營養品,其中該脂肪系統包含約25 wt〇/0至 約50 wt%之該不飽和游離脂肪酸組分與含有脂肪酸之單 酸甘油酯的該混合物。 4·如請求項1之營養品,其中該等含有脂肪酸之單酸甘油 酯為單棕橺酸甘油酯。 5. 如請求項1之營養品,其中該不飽和游離脂肪酸組分呈選 自由脂肪酸鈣鹽、脂肪酸鎂鹽及其組合組成之群的形式。 6. 如吻求項1之營養品,其中該不飽和游離脂肪酸組分包 含小於15 wt%之具有超過14個碳原子之鏈長度的飽和游 離脂肪酸。 7·如凊求項1之營養品,其中該不飽和游離脂肪酸組分係 源自植物油。 8. 如凊求項7之營養品,其中該植物油係選自由橄欖油、 芥花籽油、玉米油、大豆油及其組合組成之群。 9. 如吻求項8之營養品,其中該植物油為大豆油。 月求項1之營養品,其中該不飽和游離脂肪酸組分係 源自樹脂。 161217.doc 201233331 11. 如明求項1之營養品,其中該不飽和游離脂肪酸組分係 自動物脂肪分離而得。 12. 如清求項1之營養品,其中該不飽和游離脂肪酸組分係 源自其中肉豆蔻酸、棕櫚酸及硬脂酸總量小於20%(以重 量計)之動物脂肪分離物。 13. 如請求項1之營養品,其中該等含有脂肪酸之單酸甘油 酯係由豬油、動物脂或其組合之酶促水解而獲得。 14. 如請求項1之營養品,其中該營養品不含角叉菜膠。 15. —種包含脂肪系統之嬰兒配方,其中該脂肪系統包含至 少10 wt%之不飽和游離脂肪酸組分與含有脂肪酸之單酸 甘油酯的混合物。 161217.doc201233331 VII. Application for Patent Park: 1. A nutrient containing a fat system, wherein the fat system comprises a mixture of an unsaturated free fatty acid component of at least 10 wt/min and a monoglyceride containing a fatty acid. The nutraceutical of claim 1, wherein the fat system comprises from about 20 wt0/〇 to about 65 wt% of the mixture of the unsaturated free fatty acid component and the fatty acid-containing monoglyceride. 3. The nutraceutical of claim 1, wherein the fat system comprises from about 25 wt%/0 to about 50 wt% of the mixture of the unsaturated free fatty acid component and the fatty acid-containing monoglyceride. 4. The nutritional product of claim 1, wherein the fatty acid-containing monoglyceride is glyceryl monopalmitate. 5. The nutraceutical of claim 1, wherein the unsaturated free fatty acid component is in the form of a group consisting of a free fatty acid calcium salt, a fatty acid magnesium salt, and combinations thereof. 6. The nutraceutical of claim 1, wherein the unsaturated free fatty acid component comprises less than 15% by weight of a saturated free fatty acid having a chain length of more than 14 carbon atoms. 7. The nutritional product of claim 1, wherein the unsaturated free fatty acid component is derived from a vegetable oil. 8. The nutrient of claim 7, wherein the vegetable oil is selected from the group consisting of olive oil, canola oil, corn oil, soybean oil, and combinations thereof. 9. The nutritional product of claim 8, wherein the vegetable oil is soybean oil. The nutrient of claim 1, wherein the unsaturated free fatty acid component is derived from a resin. 161217.doc 201233331 11. The nutrient of claim 1, wherein the unsaturated free fatty acid component is obtained by separating an animal fat. 12. The nutrient of claim 1, wherein the unsaturated free fatty acid component is derived from an animal fat isolate wherein the total amount of myristic acid, palmitic acid, and stearic acid is less than 20% by weight. 13. The nutraceutical of claim 1, wherein the fatty acid-containing monoglyceride is obtained by enzymatic hydrolysis of lard, tallow or a combination thereof. 14. The nutritional product of claim 1 wherein the nutrient is free of carrageenan. 15. An infant formula comprising a fat system, wherein the fat system comprises a mixture of at least 10% by weight of an unsaturated free fatty acid component and a fatty acid-containing monoglyceride. 161217.doc
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