TWI403276B - 用於創傷癒合之營養組合物 - Google Patents
用於創傷癒合之營養組合物 Download PDFInfo
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- TWI403276B TWI403276B TW093139499A TW93139499A TWI403276B TW I403276 B TWI403276 B TW I403276B TW 093139499 A TW093139499 A TW 093139499A TW 93139499 A TW93139499 A TW 93139499A TW I403276 B TWI403276 B TW I403276B
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Description
本發明係關於一種用於促進創傷癒合(尤其是促進諸如壓瘡(褥瘡)之慢性創傷癒合)之營養組合物。
在正常創傷癒合中,存有某程度上交迭之三個階段。簡而言之,第一期為炎症期,其中血凝塊形成,阻止血管出血,接著單核血細胞會滲出,其清潔了創傷且除去了碎屑。下一期為肉芽形成期,其中纖維母細胞會增生且聚集在創傷處,並產生膠原蛋白幫助傷口閉合,此一時期的特徵是具有高代謝活動。最後,上皮細胞開始覆蓋傷口。
創傷癒合延遲或受損對醫療專業人員和病人來講是一個問題,因為其會導致延長治療時間和在醫療院所中逗留之時間並增加病人痛苦。上述任一時期因諸如感染或營養不良等因素會阻斷創傷癒合之過程。常折磨老年人和臥床病人之壓瘡特別令人關注,且此類病人常被發現身受營養不良之苦。實際上,所有患有急性或慢性創傷之病人與未受此等代謝壓力之苦之個體相比,其營養需求增加,呈現出需要較高營養和熱量之需求。如果此等病人在遭受創傷之前就營養不良,則該創傷可能完全不能癒合。
近年來,許多注意力集中於精胺酸在創傷癒合中之作用。舉例而言,此在美國專利5,053,387中討論,該專利揭示一種腸道營養調配物,其中較佳地是1%至3%之總熱量攝取量係由精胺酸提供。同樣地,歐洲專利960 572 A揭示了
一種適於治療和預防壓瘡之營養組合物,其包含精胺酸和大量維生素C及E。在美國專利5,733,884中也討論了精胺酸之作用,該專利揭示一種利用一組合物提供患有急性或慢性創傷病人營養物之方法,其中至少2%之熱量係由精胺酸提供,脯胺酸亦提供等量之熱量。該專利假設精胺酸和脯胺酸在促進創傷癒合中具有協同效應。商業上,有大量適於促進創傷癒合之產品出售,包括CUBITAN®及ARGINAID®,其基礎為含有高含量之精胺酸。
足量供應精胺酸與創傷癒合過程明顯相關。然而,精胺酸亦為形成一氧化氮之前體,一氧化氮作用為血管擴張劑且可促進生長激素分泌。重病個體不應暴露於高量的一氧化氮下,但如果該個體接受了含有高含量精胺酸之營養補充品,這將不可避免地會發生-例如,見L.Cynober,Curr Opin Clin Nutr Metab Care.6:189-93 2003。另外,極可能有高比例面臨發生褥瘡危險之老年、臥床或重病病人也身受不宜採用高含量精胺酸之病狀之苦(J.Takala等,N Engl J Med 341:785-792 1999)。
在第一方面中,本發明提供一種用於促進創傷癒合之營養組合物,其包括一蛋白質來源、一脂類來源和一碳水化合物來源,其中不高於該組合物總熱量之1.8%係源自精胺酸,且其中該蛋白質來源包含至少3%該組合物總熱量之脯胺酸含量。
在第二方面中,本發明提供一種供應患有急性或慢性創
傷病人營養支持之方法,其包括投予一治療有效劑量之營養組合物之步驟,該組合物包括一蛋白質來源、一脂類來源和一碳水化合物來源,其中不高於該組合物總熱量之1.8%係源自精胺酸,且其中該蛋白質來源包含至少3%該組合物總熱量之脯胺酸含量。
在第三方面中,本發明提供一蛋白質來源、一脂類來源和一碳水化合物來源之用途,其係用於生產促進創傷癒合之治療性調配物,其中不高於該組合物總熱量之1.8%係源自精胺酸,且其中該蛋白質來源包含至少3%該調配物總熱量之脯胺酸含量。
儘管上述創傷癒合過程之炎症期是關鍵階段,但本發明者認為以治療/營養方法調控該時期是具有高度風險,而肉芽形成期則為營養干涉提供更好的潛能。在此期中,新的結締組織被合成,且該組織超過80%係由膠原蛋白組成。膠原蛋白中富含脯胺酸(約22%)和甘胺酸(約33%),且此等胺基酸之存在係膠原蛋白形成之速率限制(步驟),換言之,如果無法獲得足量之胺基酸則不能有效形成膠原蛋白。然而,正常飲食中僅含總計為約3%之此等胺基酸,且應瞭解身受創傷之個體可能吸收的更少,尤其是一般不被認為是飲食必需胺基酸之脯胺酸。對於無論任何原因遭受營養不良之個體,此等缺乏現象尤為顯著。因此本發明組合物補充了足夠量之脯胺酸,以促進膠原蛋白合成作用。其尤適用於改善壓瘡,但亦可用於處理包含手術前及手術後之急
性創傷。
本發明組合物不需要補充精胺酸-當然某些精胺酸的存在可能係來自該蛋白質來源之組成部分。然而,咸信精胺酸也會在創傷癒合之炎症期起作用,且由於此原因,較佳地本發明組合物可補充少量精胺酸,通常要求精胺酸量必須不高於該組合物總熱量之1.8%。
本發明組合物含有蛋白質、脂類和碳水化合物來源,可經口或經腸投藥。該組合物較佳地係提供約1.25千卡/毫升。
蛋白質對於癒合是必要的,因為組織損傷會導致一種異化反應,其包括所需要蛋白質占總熱量之比例比一般人更大。研究顯示藉由採用大量蛋白質之經腸營養強化作用可以加速內臟蛋白質之合成作用,因此本發明蛋白質來源較佳地組成至少25%該組合物總熱量,更佳地為至少28%。
可採用各種不同蛋白質來源,其包含完整蛋白質來源,諸如,酪蛋白或乳清及水解蛋白質、游離胺基酸和甚至完整及水解蛋白質和/或游離胺基酸之混合物,在每一情況中都補充游離脯胺酸,且視需要補充游離精胺酸。較佳地的是,選擇本發明蛋白質來源以產生在蛋白質中具有最高量之脯胺酸,從而使所加入之作為游離胺基酸之含量最少。
較佳地,脯胺酸組成至少3.5%本發明組合物之熱量。以提供總熱量之此種含量而言,該組合物需要補充約3.0%(以該蛋白質來源重量計)之脯胺酸。
本發明組合物之總熱量/氮的克數較佳約160:1。非蛋白之總熱量/氮的克數較佳約110:1。
本發明組合物亦包含一脂類來源。脂類或脂肪是體內儲存熱量之主要來源,且來自脂肪代謝之熱量用於所有正常細胞功能中。就創傷癒合為令人所關注者而言,脂肪代謝會導致前列腺素及其他炎症過程調節子之形成。用於本發明脂類來源較佳地組成約20%該組合物總熱量。在該20%中,較佳地約8%係由單或二脂肪酸甘油酯組成。n-6至n-3脂肪酸之比率較佳為4:1至10:1,更佳為約7:1。
本發明組合物亦包含一碳水化合物來源。葡萄糖為許多組織細胞代謝之主要燃料,包括白細胞、巨噬細胞及纖維母細胞,所有這些細胞都與創傷癒合過程有關。葡萄糖需要符合創傷癒合之特殊代謝要求。本發明所用之碳水化合物來源較佳地組成約50%該組合物之總熱量。適宜之碳水化合物來源為糊精-麥芽糖複合物和蔗糖。較佳地,該碳水化合物來源實質上不含有乳糖。
維生素、礦物質和微量元素在創傷癒合過程中也是重要的。較佳地本發明組合物應至少遵守用於特殊醫療目的之食物之組合標準(於1999/21/EC指令中提出)中關於此等微量營養素之規定。然而,某些微量營養素對創傷癒合尤其重要,因此本發明組合物較佳地含有高於最低建議量之維生素C和E、錳、鋅和硒。
現以實例說明一種根據本發明之即用型液體組合物:
如從先前描述中所瞭解,該組合物亦含有符合EC指令1999/21/EC之腸內組合物中慣常發現類型之其他微量營養素、及腸內組合物中慣常發現之調味劑(諸如咖啡或香草、乳化劑、稠化劑和穩定劑)。
該營養組合物可以慣用方法製備。舉例而言,該蛋白質
來源和該脂類來源可溶解於水中形成液體混合物,其中較佳的是水經過逆滲透處理。如果需要乳化劑,在混合前可溶解在該脂類來源中。較佳的是採用源自蔬菜來源之食品級乳化劑。
水溫合宜地為約50℃至約80℃以幫助各成分分散。市售液化劑可用以形成液體混合物。較佳地,係用食品級氫氧化物將該液體混合物之pH調整至約6.3至7。
製備該液體混合物後,該碳水化合物來源與其他易溶解成份(包含,例如維生素、礦物質、調味劑和著色劑)一起加入。
然後,熱處理該液體混合物以減少(用巴氏滅菌法)細菌孳生。此步驟可以蒸汽注入法或熱交換器來進行,例如板式熱交換器。
如果需要常溫下穩定之液體組合物,則較佳地係在預熱至50-85℃後進行超高溫處理(UHT)。舉例而言,可在管式熱交換器中以140-155℃持續5-8秒來進行間接UHT處理。然後將該液體混合物冷卻至約60℃至約85℃;例如藉由閃蒸冷卻。然後將該液體混合物均質化,並將所得均質化乳狀液體在無菌條件下裝入至適宜容器中,諸如200毫升經口餵食用之杯子。可以冷卻該液體混合物來進行該容器之無菌填裝。
如果需要的是粉狀、可復水之調配物,則可蒸發該均質混合物,並乾燥成粉末,例如藉由噴霧乾燥法。可採用慣用的方法。
正常人纖維母細胞經胰蛋白酶處理,然後以10,000個細胞/立方公分之密度接種於12孔盤中。當長滿後,將細胞轉移至儘可能模擬人血清胺基酸分布與濃度之培養基中。將該細胞培養物分成兩類,一為對照培養物(其中該培養基含有0.201 mM之脯胺酸),及一試驗樣品(其中該培養基含有0.592 mM之脯胺酸)。24小時後收集纖維母細胞之條件化培養基,該培養基含有100微克/毫升β-胺基丙基腈,以阻止膠原蛋白分子在培養物中交聯。該條件化培養基以斑點法轉漬至硝基纖維膜上,並以多株免疫吸附抗體來測定I型膠原蛋白含量。補充脯胺酸之樣品所顯示之數值是相對於設置在100%之對照數值。
該實驗實例顯示人類纖維母細胞對補充脯胺酸有反應,膠原蛋白合成作用可增加50%。在該補充脯胺酸之培養基中,膠原蛋白合成作用之增加與添加生長因子或其他刺激膠原轉錄之介質無關,其顯示出針對有效膠原蛋白合成作用之所增加基質需求。
Claims (11)
- 一種用於促進創傷癒合之營養組合物,其包括一蛋白質來源、一脂類來源和一碳水化合物來源,其中不高於該組合物總熱量之1.8%係源自精胺酸,且其中該蛋白質來源包含至少3%該組合物總熱量之脯胺酸含量。
- 如請求項1之營養組合物,其中至少3.5%之該組合物總熱量係源自脯胺酸。
- 如請求項1或2之營養組合物,其中1.5%之該組合物總熱量係源自精胺酸。
- 如請求項1或2之營養組合物,其中該蛋白質來源組成至少28%之該組合物總熱量。
- 如請求項1或2之營養組合物,該組合物具有約1.25千卡/毫升之熱量密度。
- 一種提供患有急性或慢性創傷病人營養支持之方法,其包括投予一營養組合物之步驟,該組合物包括一蛋白質來源、一脂類來源和一碳水化合物來源,其中不高於該組合物總熱量之1.8%係源自精胺酸,且其中該蛋白質來源包含至少3%該組合物總熱量之脯胺酸含量。
- 如請求項6之方法,其中至少3.5%之該組合物總熱量係源自脯胺酸。
- 如請求項6或7之方法,其中1.5%之該組合物總熱量係源自精胺酸。
- 一種蛋白質來源、脂類來源和碳水化合物來源之用途,其係用於製備促進創傷癒合之治療性調配物,其中不高 於該組合物總熱量之1.8%係源自精胺酸,且其中該蛋白質來源包含至少3%之該組合物總熱量之脯胺酸含量。
- 如請求項9之用途,其中至少3.5%之該組合物總熱量係源自脯胺酸。
- 如請求項9或10之用途,其中1.5%之該組合物總熱量係源自精胺酸。
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- 2003-12-20 ES ES03029505.9T patent/ES2550608T3/es not_active Expired - Lifetime
- 2003-12-20 DK DK03029505.9T patent/DK1543735T3/en active
- 2003-12-20 EP EP03029505.9A patent/EP1543735B1/en not_active Expired - Lifetime
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2004
- 2004-12-03 CN CN2004800371701A patent/CN1893839B/zh not_active Expired - Fee Related
- 2004-12-03 JP JP2006544267A patent/JP2007515417A/ja active Pending
- 2004-12-03 CA CA002546472A patent/CA2546472A1/en not_active Abandoned
- 2004-12-03 WO PCT/EP2004/013787 patent/WO2005060768A1/en active Application Filing
- 2004-12-03 US US10/596,159 patent/US20070087035A1/en not_active Abandoned
- 2004-12-03 BR BRPI0417875-0A patent/BRPI0417875A/pt active Search and Examination
- 2004-12-17 TW TW093139499A patent/TWI403276B/zh not_active IP Right Cessation
- 2004-12-20 AR ARP040104799A patent/AR046969A1/es unknown
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2006
- 2006-05-08 IL IL175478A patent/IL175478A0/en unknown
- 2006-07-19 ZA ZA200605983A patent/ZA200605983B/xx unknown
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2011
- 2011-05-26 US US13/116,827 patent/US20110230400A1/en not_active Abandoned
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2014
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5714472A (en) * | 1993-12-23 | 1998-02-03 | Nestec Ltd. | Enternal formulation designed for optimized nutrient absorption and wound healing |
US6194379B1 (en) * | 1998-05-01 | 2001-02-27 | Abbott Laboratories | Elemental enteral formula |
Also Published As
Publication number | Publication date |
---|---|
WO2005060768A1 (en) | 2005-07-07 |
JP2007515417A (ja) | 2007-06-14 |
IL175478A0 (en) | 2006-09-05 |
CN1893839B (zh) | 2010-06-09 |
CN1893839A (zh) | 2007-01-10 |
US20110230400A1 (en) | 2011-09-22 |
EP1543735A1 (en) | 2005-06-22 |
TW200528035A (en) | 2005-09-01 |
BRPI0417875A (pt) | 2007-04-27 |
EP1543735B1 (en) | 2015-10-07 |
DK1543735T3 (en) | 2015-11-02 |
CA2546472A1 (en) | 2005-07-07 |
ES2550608T3 (es) | 2015-11-11 |
US20070087035A1 (en) | 2007-04-19 |
US20140357553A1 (en) | 2014-12-04 |
ZA200605983B (en) | 2007-12-27 |
AR046969A1 (es) | 2006-01-04 |
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