CN1045922A - 营养组合物 - Google Patents
营养组合物 Download PDFInfo
- Publication number
- CN1045922A CN1045922A CN89104657A CN89104657A CN1045922A CN 1045922 A CN1045922 A CN 1045922A CN 89104657 A CN89104657 A CN 89104657A CN 89104657 A CN89104657 A CN 89104657A CN 1045922 A CN1045922 A CN 1045922A
- Authority
- CN
- China
- Prior art keywords
- glutaminate
- glutamy
- alimentation composition
- dipeptides
- glutamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
本发明涉及含L-谷氨酰-L-谷氨酰胺的哺乳动物用营养组合物。
Description
本发明涉及一种用于哺乳动物的营养组合物,更具体地说涉及一种含有L-谷氨酰基-L-谷氨酰胺的营养组合物。
人类及其他哺乳动物为了维持生命活动,必须经常摄取蛋白质。蛋白质在消化***被转变为氨基酸,从而在体内被用于生长、生育、繁殖及同化作用。
但是,在使消化道机能变低的手术后以及由于厌食症、饥饿等造成的营养失调的情况下,补充营养是必要的,但通常的食物形式的养分往往难以吸收。另外,在激烈的体力劳动和运动过程中或之后,由于代谢机能旺盛,出汗造成的氮损耗非常多,所以也有必要补充营养。在这样情况下,必须以易吸收的形式摄取大量的蛋白质和氨基酸,以尽量减小消化器官负担。
以往的营养补充方法,是用氨基酸静脉注射和点滴,以及将含有肉提取物、酪蛋白、蛋清等优质蛋白质或者氨基酸、肽等的营养组合物经口或经肠投与。
但是,有些氨基酸由于其溶解度低及不稳定等原因,而限制了它们的使用。特别是L-谷氨酰胺更是如此,处于手术后非正常状态下的患者的肌肉中的L-谷氨酰胺显著变低,因而认为必须对此进行补充,但是由于L-谷氨酰胺在溶液状态下不稳定,且其热稳定性低,因此不能使加热灭菌调制的公知营养组合物中含有L-谷氨酰胺类物质。
为了使在溶液状态下不稳定的L-谷氨酰胺作为哺乳动物用营养组合物来供给。已知的方法有将L-谷氨酰胺二肽化,使其以α-L-天冬氨酰-L-谷氨酰胺形式存在的营养组合物(特开昭62-151156),以及以甘氨酰-L-谷氨酰胺形式存在的L-谷氨酰胺营养组合物(特开昭56-140923)等。
另外,在(Clinical Science)75,463(1988)上刊载了关于L-丙氨酰-L-谷氨酰胺在血浆中的作用及向内脏器官中的渗透的报告。
虽然含有α-L-天冬氨酰-L-谷氨酰胺及甘氨酰-L-谷氨酰胺的营养组合物对L-谷氨酰胺的不稳定性有了很大的改进,但是在灭菌条件下的稳定性及在生体内的吸收和用效率等方面还有许多必须改善的地方。
另外,不是摄取L-谷氨酰胺,而是摄取含L-谷氨酰胺的二肽的情况下,在生物体内需将这些二肽水解为氨基酸。以往用的二肽,虽然改进了L-谷氨酰胺的热不稳定性,但是在生物体内吸收、利用效率方面还有待进一步改进。
本发明人发现使用L-谷氨酰-L-谷氨酰胺来代替以往使用的含L-谷氨酰胺的二肽,与以往的营养组合物相比,改善了在生物体内的吸收、利用效率等,因此完成了本发明。
本发明提供了一种含有L-谷氨酰-L-谷氨酰胺的营养组合物。
以下将对本发明进行详细说明。
含有L-谷氨酰-L-谷氨酰胺的营养组合物主要作为口服或内服营养给物来使用。
在口服投与的情况下,为了获得营养平衡,可以配合易消化的碳水化合物、脂肪、维生素、矿物质等营养性添加物,另外为了改善口服用时的风味还可以配合加味料、增甜料、香料、色素等调味剂、除臭剂以及外观改善剂等。具体的营养性添加物的例子为淀粉、糊精、葡萄糖、麦芽糖、乳糖、脱脂乳、卵黄粉末、卵黄油、麦芽抽出物、中等链长脂肪酸、维生素A、硫胺素、核黄素、维生素B6、菸酸、泛酸、维生素B12、L-抗坏血酸、维生素E、食盐、氯化钾、氯化钙、乳酸铁等。
将以上各成分进行混合、加水、分散、并以液状、糊状密封在防湿性袋、瓶、缸中,加热灭菌后保存或流通使用。还可以将各成分进行充分混合,以粉末状保存、运输,使用时再加水分散。现在,由于L-谷氨酰-L-谷氨酰胺热稳定性高,且可以溶液状态下长期稳定存在,因此可以随便进行加热调理、灭菌等操作。
对于补充谷氨酰胺,最好的营养组合物的一例是含有0.0005~30%(重)的L-谷氨酰-L-谷氨酰胺、并含有氨基酸或蛋白质的水解物及上述营养性添加物的组合物(如氨基酸输液、营养补充用口服营养剂、冻胶状的营养制剂等)。
作为含有L-谷氨酰酰-L-谷氨酰胺的氨基酸输液的成分,可具体例举以下。单位为mg/dl。
L-异亮氨酸 160~1070
L-亮氨酸 180~1720
L-赖氨酸盐酸盐 180~2400
L-苯基丙氨酸 130~1400
L-蛋氨酸 50~1200
L-苏氨酸 80~720
L-色氨酸 30~350
L-缬氨酸 70~1130
L-精氨酸盐酸盐 120~1500
L-组氨酸盐酸盐 50~900
谷氨酸 200~2500
L-丙氨酸 70~1130
L-天氨氨酸钠 0~1300
L-巯基丙氨酸 0~150
L-谷氨酸钠 0~1300
L-谷氨酰-L-谷氨酰胺 1~5000
L-脯氨酸 90~1080
L-丝氨酸 60~820
L-酪氨酸 3~90
L-谷氨酰-L-谷氨酰胺有α和γ型,但最好使用γ型。
γ-L-谷氨酰-L-谷氨酰胺与L-谷氨酰胺相比,不仅热稳定性高,而且是γ-谷氨酰-转移酶和γ-谷氨酰-环转移酶[(J.Biol.Chem.)vol.253 No.6]的有效的基质,所以可推测它在生物体内能被有效利用。
将L-谷氨酰-L-谷氨酰胺作为营养组合物使用时,需在生物体内水解成氨基酸。
Mattews.Adibi曾经指出,由二或三肽生成的氨基酸的吸收速度比同样组成的氨基酸混合物的吸收速度要快[Gut,vol.9,p425,(1968)、Clinical Research,vol.16,p446,(1968)]。如上所述,由于生物体内存在γ-谷氨酰-转移酶及γ-谷氨酰-环转移酶,且γ-L-谷氨酰-L-谷氨酰胺是其有效基质所以可以认为它在生物体内易于被水解及吸收。因此,在需要急速营养补充的生理性或病理性状态下,例如激烈的体力劳动、运动后体力大量消耗的时候或者手术后等需要早期体力恢复的情况下,γ-L-谷氨酰-L-谷氨酰胺就可以作为速效营养补充剂使用。
下面,对γ-L-谷氨酰-L-谷氨酰胺及各种含L-谷氨酰胺的二肽在人及鼠血浆中的消长(标准系)、在有γ-谷氨酰-转移酶(γ-GTP)存在下的稳定性、投给鼠时其在血中的消长及对内脏器官中的谷氨酰胺水平的影响进行说明。
1.二肽在人血浆中的水解
分别向由人体采出,调制的0.75ml血浆中,加入下述表1所示的二肽以便使其达到10mM,并使其在37℃下反应30分钟。反应终了后的二肽的残余率列于表1中。
表1
二肽 残余率%
γ-L-谷氨酰-L-谷氨酰胺 99
L-丙氨酰-L-谷氨酰胺 74
L-天冬氨酰-L-谷氨酰胺 58
甘氨酰-L-谷氨酰胺 84
与先有技术采用的二肽相比,γ-L-谷氨酰-L-谷氨酰胺在人血浆中几乎不分解,表示出高稳定性。
2.由γ-GTP造成的二肽的水解
在Tris-HCl缓冲液(50mM PH7.0)中分别将5mM的表1所列的二肽溶解,然后加入由猪肾制备的γ-GTP,在37℃下反应120分钟。γ-L-谷氨酰-L-谷氨酰胺几乎是100%分解,而其它的二肽则完全没有分解。
3.二肽在鼠血浆中的水解
分别在从CH/He鼠(6周龄、雄性、体重20g)提取,制备的血浆中(0.05ml)加入表2所列的二肽,以便使其达到3.13mM,在37℃下分别反应2分钟、5分钟、10分钟、20分钟。反应终了后的二肽残余率列于表2。实验使用了5只鼠,结果为平均值。
表2
残余率(%)
二肽
2 5 10 20分
γ-L-谷氨酰- 100 100 100 100
L-谷氨酰胺
L-丙氨酰-L- 87 62 24 11
谷氨酰胺
与先有技术的二肽相比,γ-L-谷氨酰-L-谷氨酰胺在鼠血浆中完全不分解,表现出了高稳定性。
4.投与鼠时,谷氨酰在血中的变化
通过C3H/He鼠(6周龄,雄性,体重20g)的尾静脉投与γ-L-谷氨酰-L-谷氨酰胺或者L-丙氨酰-L-谷氨酰胺(250μmol/1kg体重),定时采血。将血中二肽及谷氨酰胺随时间的变化表示于图1中。另外,一组实验用了5只鼠,结果用平均值±平均标准误差表示。
L-丙氨酰-L-谷氨酰胺在投与后极迅速地消失,与此同时可观察到血中的急剧的谷氨酰放出,但是,在L-谷氨酰-L-谷氨酰胺投与组中,该二肽的消失和谷氨酰胺的放出都是缓慢的。这说明这两种二肽在血中的变化有很大差异。
5.投与二肽对肾脏谷氨酰水平的影响
从C3H/He鼠(6周龄,雄性,体重20g)的尾静脉投与γ-L-谷氨酰-L-谷氨酰胺及L-丙氨酰-L-谷氨酰胺(250μmol/1kg体重),20分钟后摘出肾脏。将该内脏器官中的谷氨酰胺水平与投与二肽前比较,列于表3中。一组实验用了5只鼠,其结果用平均值±平均标准误差表示。γ-L-谷氨酰-L-谷氨酰胺投与组表现出更高的肾脏谷氨酰胺水平,这表明该二肽进入了肾脏并在此处被有效利用。
表3
二肽 谷氨酰胺浓度(μmol/g湿重量)
投与前 1.07±0.08
γ-L-谷氨酰-
L-谷氨酰胺 1.57±0.12
L-丙氨酰-
L-谷氨酰肮 1.14±0.09
γ-L-谷氨酰-L-谷氨酰胺与其它的二肽比较,具有在血浆中几乎不分解,而可通过γ-GTP进行特殊分解的特征。γ-GTP广泛分布于肾脏、小肠、肝脏等生物组织中,所以将γ-L-谷氨酰-L-谷氨酰胺投与在血中的情况下,它与先有技术的含有L-谷氨酰胺的二肽不同,在血中不分解,而是在肾脏或肝脏中被利用。另外,将γ-L-谷氨酰-L-谷氨酰胺口服投与时,可被小肠上皮细胞的γ-GTP分解,从而被肠有效利用。
溶液状态的L-谷氨酰胺(如10mM:PH6.5)在110℃、60°分的灭菌条件下60%被分解,但是γ-L-谷氨酰-L-谷氨酰胺却完全没有分解(表4)。在40℃、30天的保存稳定实验中,溶液态的L-谷氨酰胺29%被分解,但γ-L-谷氨酰-L-谷氨酰胺完全没有被分解(表5)。这表示γ-L-谷氨酰-L-谷氨酰胺对热具有高稳定性。
表4
灭菌后的残存率%
γ-L-谷氨酰-L-谷氨酰胺 100
L-谷氨酰胺 40
表5
40℃,30日后残存率%
γ-L-谷氨酰-L-谷氨酰胺 100
L-谷氨酰胺 71
图1表示了从投与了γ-L-谷氨酰-L-谷氨酰胺或L-丙氨酰-L-谷氨酰胺的鼠的尾静脉中定时采出的血中的二肽及谷氨酰胺的浓度随时间的变化。实线代表γ-L-谷氨酰-L-谷氨酰胺,虚线表示L-丙氨酰-L-谷氨酰胺。
以下通过实施例来说明本发明。
实施例1
在下述的氨基酸组合物中,加入1升注射用蒸馏水并溶解,用NaOH溶液调节到PH6.5。用米利波阿过滤器过滤该溶液,每200ml装入一个玻璃瓶中,用无菌氮气吹扫30秒。密封后,110℃、60分钟消毒灭菌,使其调制成氨基酸输液。
L-异亮氨酸 4.6g
L-亮氨酸 7.7g
L-赖氨酸盐酸盐 5.0g
L-苯基丙氨酸 4.3g
L-蛋氨酸 2.1g
L-苏氨酸 2.9g
L-色氨酸 1.0g
L-缬氨酸 4.9g
L-精氨酸盐酸盐 6.1g
L-组氨酸盐酸盐 2.6g
谷氨酸 3.4g
L-丙氨酸 4.6g
L-天氨氨酸钠 0.3g
L-巯基丙氨酸 0.3g
L-谷氨酸钠 0.3g
L-谷氨酰-L-谷氨酰胺 3.0g
L-脯氨酸 3.9g
L-丝氨酸 2.3g
L-酪氨酸 0.3g
实施例2
酪蛋白水解物 10g
明胶 8g
γ-L-谷氨酰-
L-谷氨酰胺 2.5g
糊精 20g
还原麦芽糖 20g
水 300ml
将上述成分在100℃下加热30分,分散后冷却,制得冻胶状营养制剂。γ-L-谷氨酰-L-谷氨酰胺在该灭菌条件下可保持稳定。
实施例3
酪蛋白水解物 10g
γ-L-谷氨酰
L-谷氨酰胺 2.5g
环糊精 6.3g
肌苷酸 0.11g
柠檬酸 16g
还原麦芽糖 6.8g
桔子精 0.07ml
水 500ml
将上述充分混合、分散,并在110℃下加热灭菌60分钟,制得口服营养剂。γ-L-谷氨酰-L-谷氨酰胺在该灭菌条件下保持稳定。
Claims (5)
1、含有L-谷氨酰-L-谷氨酰胺的营养组合物。
2、权利要求1的营养组合物,其中含有0.0005~30%(重)的L-谷氨酰-L-谷氨酰胺。
3、权利要求1或2的营养组合物,其中该组合物用于哺乳动物。
4、权利要求1~3中任何一项的营养组合物,其中该营养组合物是氨基酸输液。
5、权利要求4的营养组合物,其中的氨基酸输液含有下列成分。
L-异亮氨酸 160~1070(mg/dl)
L-亮氨酸 180~1720
L-赖氨酸盐酸盐 180~2400
L-苯基丙氨酸 130~1400
L-蛋氨酸 50~1200
L-苏氨酸 80~720
L-色氨酸 30~350
L-缬氨酸 70~1130
L-精氨酸盐酸盐 120~1500
L-组氨酸盐酸盐 50~900
谷氨酸 200~2500
L-丙氨酸 70~1130
L-天氨氨酸钠 0~1300
L-巯基丙氨酸 0~150
L-谷氨酸钠 0~1300
L-谷氨酰-L-谷氨酰胺 1~5000
L-脯氨酸 90~1080
L-丝氨酸 60~820
L-酪氨酸 3~90
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JP (1) | JP2683129B2 (zh) |
KR (1) | KR920003165B1 (zh) |
CN (1) | CN1036837C (zh) |
DE (1) | DE68910126T2 (zh) |
WO (1) | WO1990011024A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN112654362A (zh) * | 2018-08-01 | 2021-04-13 | 凯塞尔德国有限公司 | 用于优化营养补充的β-二肽和氨基酸的组合 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5206220A (en) * | 1990-04-23 | 1993-04-27 | Research Corporation Technologies, Inc. | Soluble and stable sources of tyrosine, cysteine and glutamine for total parenteral nutrition |
JPH06227974A (ja) * | 1993-01-29 | 1994-08-16 | Kyowa Hakko Kogyo Co Ltd | 栄養組成物 |
US5799607A (en) * | 1996-08-06 | 1998-09-01 | The United States Of America As Represented By The Secretary Of Agriculture | Culture medium for parasitic and predaceous insects |
US8519008B2 (en) | 2003-01-22 | 2013-08-27 | Purina Animal Nutrition Llc | Method and composition for improving the health of young monogastric mammals |
US20050279655A1 (en) * | 2004-06-16 | 2005-12-22 | Chen Sabrina P | Holder for SIM card |
US8445536B2 (en) * | 2005-03-31 | 2013-05-21 | Ajinomoto Co., Inc. | Arginine-containing compositions and methods for increasing blood flow using same |
EP2077110A4 (en) * | 2006-09-29 | 2012-06-27 | Ajinomoto Kk | GLUTAMINE-CONTAINING COMPOSITION FOR INCREASING BLOOD FLOW |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB882163A (en) * | 1959-08-06 | 1961-11-15 | Stamicarbon | Process for preparing food-stuffs of improved taste and increased nutritional value |
CH589047A5 (zh) * | 1972-10-23 | 1977-06-30 | Degussa | |
US4024286A (en) * | 1976-05-17 | 1977-05-17 | Miles Laboratories, Inc. | Fortification of foodstuffs with C-terminal amino acid substituted methionine dipeptides |
US4340592A (en) * | 1980-03-14 | 1982-07-20 | Adibi Siamak A | Nutrient compositions and method of administering the same |
US4452888A (en) * | 1980-07-10 | 1984-06-05 | Terumo Corporation | Process for producing a low-molecular weight peptide composition and nutrient agent containing the same |
DE3206784C2 (de) * | 1982-02-25 | 1985-05-09 | Pfrimmer & Co Pharmazeutische Werke Erlangen Gmbh, 8520 Erlangen | Glutaminhaltige Zubereitungen für orale oder intravenöse Applikation |
JPH0773479B2 (ja) * | 1984-11-19 | 1995-08-09 | ザ モンテフイオル ホスピタル アソシエ−シヨン オブ ウエスタ−ン ペンシルバニア | 栄養素組成物 |
US4786493A (en) * | 1985-11-22 | 1988-11-22 | Estee Lauder Inc. | Hair protection composition |
-
1989
- 1989-06-29 WO PCT/JP1989/000651 patent/WO1990011024A1/ja active IP Right Grant
- 1989-06-29 DE DE89907831T patent/DE68910126T2/de not_active Expired - Fee Related
- 1989-06-29 EP EP89907831A patent/EP0416108B1/en not_active Expired - Lifetime
- 1989-06-29 JP JP1507264A patent/JP2683129B2/ja not_active Expired - Lifetime
- 1989-07-08 KR KR1019890009762A patent/KR920003165B1/ko not_active IP Right Cessation
- 1989-07-10 CN CN89104657A patent/CN1036837C/zh not_active Expired - Fee Related
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1990
- 1990-05-22 US US07/613,687 patent/US5134125A/en not_active Expired - Lifetime
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112654362A (zh) * | 2018-08-01 | 2021-04-13 | 凯塞尔德国有限公司 | 用于优化营养补充的β-二肽和氨基酸的组合 |
Also Published As
Publication number | Publication date |
---|---|
EP0416108B1 (en) | 1993-10-20 |
WO1990011024A1 (en) | 1990-10-04 |
KR900013872A (ko) | 1990-10-22 |
DE68910126D1 (de) | 1993-11-25 |
DE68910126T2 (de) | 1994-03-31 |
EP0416108A1 (en) | 1991-03-13 |
JP2683129B2 (ja) | 1997-11-26 |
CN1036837C (zh) | 1997-12-31 |
KR920003165B1 (ko) | 1992-04-23 |
EP0416108A4 (en) | 1992-01-29 |
US5134125A (en) | 1992-07-28 |
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