CN101420933A - 用于胃肠外营养的儿科氨基酸溶液 - Google Patents
用于胃肠外营养的儿科氨基酸溶液 Download PDFInfo
- Publication number
- CN101420933A CN101420933A CNA2007800136921A CN200780013692A CN101420933A CN 101420933 A CN101420933 A CN 101420933A CN A2007800136921 A CNA2007800136921 A CN A2007800136921A CN 200780013692 A CN200780013692 A CN 200780013692A CN 101420933 A CN101420933 A CN 101420933A
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- China
- Prior art keywords
- freamine
- aminoacid
- tyrosine
- glutamine
- amino acid
- 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.)
- Pending
Links
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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Abstract
本发明涉及用于儿科患者胃肠外营养的氨基酸溶液。所述氨基酸溶液突出的特点是谷氨酰胺、酪氨酸、半胱氨酸和牛磺酸浓度增加,而苯丙氨酸和蛋氨酸的浓度则较低。谷氨酰胺和酪氨酸是以寡肽的形式提供的。
Description
技术领域
本发明涉及用于胃肠外营养的氨基酸溶液,其包含根据权利要求1的前序部分的氨基酸。所述溶液特别适于早产儿和新生儿、婴儿和小儿的胃肠外营养,其作为胃肠外补充剂或与其它营养溶液联用作为全胃肠外营养(total parenteral nutrition,TPN)使用。本发明还涉及制备所述氨基酸溶液的方法。
背景技术
如果不能通过口服/肠途径确保完全营养,则需要进行完全或额外的胃肠外营养治疗。在这种情况下,通过静脉内途径摄取食物。尤其当存在胃肠道阻碍时,这是必需的。在早产儿和新生儿、婴儿和小儿中经常发生肠畸形或炎症。其实例有炎性肠病症(比如克罗恩病、溃疡性结肠炎等)、胃肠道瘘、恶性肠病症、短肠综合征(short-bowel syndrome)或出生时肠发育不完全。此外,在围术期、在重症监护患者中、在脓毒症或抗治疗性腹泻的情况下可能需要胃肠外营养。
适于婴儿和小儿的氨基酸溶液在氨基酸模式(pattern)的需求上与用于成人的氨基酸溶液有很大不同。基于体重,小儿需要明显更多的氨基酸。同样,小儿的代谢不同于成人。多种对成人而言被视为非必需的的氨基酸对早产儿和小儿来说则肯定被视为是必需的,因为机体仅在超过一定年龄后才能够自身合成足够量的这些氨基酸。虽然小儿也可合成其它一些氨基酸,但其以相对于成人较慢的速率进行。因此,当给早产儿和新生儿以及小儿施用为成人设计的氨基酸时,有可能出现特定氨基酸缺乏和/或过量的征兆。对于氨基酸谷氨酰胺、酪氨酸、半胱氨酸、牛磺酸、蛋氨酸和苯丙氨酸而言,情况尤其如此。
因为尤其在早产儿和新生儿中氨基酸代谢尚未完全发育,针对任何异常情况的补偿对于年幼机体而言都更加困难,所以混合物的平衡就尤为重要。而且,由于机体尚未建立起其自身的可缓解可能出现的缺乏症状的确定储备,因此精确且连续的胃肠外营养必须被视为对早产儿和新生儿以及小儿来说在需要时是尤为重要的。仅在年龄大于2岁时,儿童的代谢才开始接近成人的水平。虽然本发明的氨基酸溶液特别适合儿科患者的需要,但也可用于由于代谢的病理生理性变化而导致类似缺乏症状的成人。对于肾病或肝病患者来说,情况尤其如此。
因此,考虑到下文中详细描述的多种标准,必须重新定义用于早产儿和新生儿以及小儿的胃肠外营养的氨基酸溶液的氨基酸模式。在此方面,至关重要的不仅是各氨基酸的量,还有施用方式以及所述溶液制备方面良好的工艺转换(technologische Umsetzung);这尤其适用于灭菌条件。
EP 0 148 680 A1描述了适于儿科胃肠外营养要求的氨基酸溶液。氨基酸半胱氨酸、牛磺酸和酪氨酸被定性为半必需氨基酸。
DE 2531201 A1表明了如何可利用胃肠外儿科氨基酸溶液获得合适的氮平衡。还讨论了相比于施用蛋白质水解产物而言施用适量的游离氨基酸的优势。
WO91/16067 A1描述了寡肽用于可应用于儿科目的的胃肠外营养溶液的用途。
寡肽(特别是三肽和二肽)用于作为胃肠外营养的氨基酸溶液的一般用途和与之相关的在溶解度和产品稳定性方面的有益作用在US 5432 160、DE 31 08 079 C2、EP 0 087 751 A1和EP 0 087 750 B1中作了讨论。
上述出版物没有公开有可能利用寡肽提供氨基酸以施用一定量的特定氨基酸,所述氨基酸的水平不同于以前所述的水平,而是更适于新生儿机体的发育。
发明内容
因此,本发明基于的是提供用于胃肠外营养的氨基酸溶液的目的,所述氨基酸溶液具有尤其适合早产儿和新生儿、婴儿和小儿需要的氨基酸模式并提供合适量及比例的所需全部氨基酸。在此方面,应特别注意提供适量的易于代谢形式的氨基酸谷氨酰酸、酪氨酸、半胱氨酸和牛磺酸,以及注意与之相关地减少氨基酸谷氨酸、苯丙氨酸和蛋氨酸。
该目的通过提供权利要求1的用于儿科患者胃肠外营养的氨基酸溶液以及权利要求13的用途来实现。
本发明的另一个目的涉及提供全胃肠外营养,所述全胃肠外营养以合适量及比例提供全部所需的氨基酸。
该目的通过提供权利要求16的药物组合物和权利要求18的用途来实现。
涉及优化本发明溶液的灭菌方法的另一个目的通过权利要求18来实现。
有利的实施方案在从属权利中给出。
取决于早产儿和新生儿的体重和发育状态,胃肠外营养不应超过每天每公斤体重(body weight,BW)100-160ml的体积。一方面,为避免施用的浓度局部过高,另一方面,又要确保与其它成分(比如碳水化合物、脂类、电解质、维生素和微量元素)的可混合性并且不超过体积限度,氨基酸溶液包含3-30%w/w的蛋白质结构单元(building block),优选5-20%w/w的蛋白质结构单元,尤其优选7-15%w/w的蛋白质结构单元。所述蛋白质结构单元优选为游离氨基酸、二肽或三肽的形式,并且链长度>5的肽或蛋白质的含量小于所述蛋白质结构单元的5%,优选小于1%。
用于早产儿和新生儿、婴儿和小儿的胃肠外营养的氨基酸溶液在定量含量和氨基酸模式方面都不同于用于成人胃肠外营养的常见氨基酸溶液。
与其中蛋白质的合成和分解以恒定重量约处于平衡的成人不同,在早产儿和新生儿以及小儿中,由于体重的快速生长,则需要合成明显占优势。由于这一原因,基于体重,在这些患者中氨基酸的日需求明显大于成人。通过氨基酸溶液施用的蛋白质结构单元的日剂量是2-4g/千克体重,优选2.5-3.5g/千克体重,以便满足儿科患者的总日需求。使用3g蛋白质结构单元/千克体重的量用于常规计算。
所有提及的氨基酸都可以以游离形式或者以其前体形式提供。如果要以其前体形式提供氨基酸,则所述氨基酸的标示量仅涉及所述前体的氨基酸部分的量。在所有情况下,都优选使用左旋氨基酸。
除了早产儿和新生儿、以及小儿的增加的日需要以外,其代谢还在特定方面不同于成人的代谢,这是因为多种氨基酸以相比而言较慢的速率形成和/或降解。一些在成人中内源性合成并因此而被视为非必需的氨基酸无法在早产儿和新生儿以及小儿中内源性充足地产生,因此在这些情况下,其被视为必需的或半必需的。因此这些氨基酸的供应尤其重要,这些氨基酸是半胱氨酸、酪氨酸、谷氨酰胺和牛磺酸。早产儿和新生儿以及小儿仅以减慢速率降解其它氨基酸,包括苯丙氨酸和蛋氨酸。
谷氨酰胺是最常见的氨基酸。其大量存在于血浆和肌肉中。谷氨酰胺被看做是必不可少的,尤其是对于高有丝***速率的细胞而言。这些细胞包括例如淋巴细胞和肠细胞。因此,谷氨酰胺的充分供应还特别确保起作用的免疫***。此外,谷氨酰胺对于肌肉的构建和维持而言是必不可少的。由于新生儿机体自身不能产生足量的谷氨酰胺,因此在胃肠外营养中此氨基酸的适当供应尤其重要。这也适用于嘌呤和嘧啶的合成。谷氨酰胺是这些DNA结构单元的前体。因此,谷氨酰胺在早产儿和新生儿以及小儿的正在成长的频繁发生细胞***的身体中特别重要。此外,谷氨酰胺还是谷胱甘肽的前体,后者作为抗氧化剂发挥重要作用。
由于这些原因,本发明的胃肠外组合物包含比例增加的谷氨酰胺,所述谷氨酰胺的量达到每100g氨基酸(AA)中9-30g,优选11-25g,特别优选13-20g。每千克体重所用的谷氨酰胺的日剂量是0.25-0.90g,优选0.3-0.75g,特别优选0.39-0.6g。
另一种被视为成人非必需氨基酸的氨基酸—酪氨酸—必须在某种程度上被看作是早产儿和新生儿以及小儿中的必需氨基酸。新生儿身体由苯丙氨酸合成酪氨酸的能力仅非常有限或者不存在。原因在于负责其合成的酶—苯丙氨酸羟化酶的表达不足。其结果是,相比于成人身体而言苯丙氨酸的降解同时减少。除了作为构建蛋白质的结构单元的一般功能外,酪氨酸还是去甲肾上腺素、多巴胺、甲状腺素和其它激素的前体。因此,酪氨酸的充分供应对于受控的激素平衡和神经***的结构来说非常重要。
由于这些原因,胃肠外组合物包含比例增加的易于代谢的酪氨酸,其量达到每100g氨基酸中1-4g、优选1.2-3g、特别优选1.5-2.5g的酪氨酸。每千克体重所用酪氨酸的日剂量是30-120mg,优选35-90mg,特别优选45-75mg。
酪氨酸和苯丙氨酸彼此竞争其进入组织的转运途径。因此,苯丙氨酸水平的增加将抑制酪氨酸的摄取。一方面由于苯丙氨酸的降解减少,另一方面为保持芳香族氨基酸的总量相对于其它氨基酸(AA)恒定,因此减少了本发明氨基酸溶液中苯丙氨酸的量。芳香族氨基酸的总量不应超过7g/100g AA,优选不超过6g/100g AA,特别优选不超过5.6g/100g AA。
所述胃肠外组合物包含3-5g/100g AA、优选3.3-4g/100g AA、特别优选3.5-3.8g/100g AA的苯丙氨酸。酪氨酸对苯丙氨酸的比例是1:1到1:3,优选1:1.3到1:2.5,特别优选1:1.5到1:2。
由于半胱氨酸亚磺酸脱羧酶和胱硫醚酶的低活性,在早产儿、新生儿和小儿中的转硫作用代谢几乎检测不到。因此,由蛋氨酸合成半胱氨酸以及由半胱氨酸合成牛磺酸仅以极低的速率发生或者根本不发生。因此,半胱氨酸和牛磺酸都被视为早产儿的必需氨基酸。另一方面,牛磺酸尤其是在早产儿和新生儿以及小儿的中枢神经***、消化***、视觉和听觉的发育中,以及一般而言对细胞尤其是神经细胞的钙平衡发挥重要的作用。同样,除了作为蛋白质结构单元的功能外,半胱氨酸还用作在防止氧化应激中发挥重要作用的三肽谷胱甘肽的前体。已表明,即使与迄今为止常规的剂量相比,大量的牛磺酸易于被早产儿身体所接受。
由于这个原因,增加了所述组合物中半胱氨酸和牛磺酸的相对量,而减少了蛋氨酸的量。半胱氨酸、牛磺酸和蛋氨酸的总量不超过5g/100g AA,但至少为2g/100g AA。
所述组合物包含0.3-1.5g半胱氨酸/100g AA,优选0.5-1g半胱氨酸/100g AA。所述组合物还包含0.3-2g牛磺酸/100g AA,优选0.7-1.5g牛磺酸/100g AA。
由于半胱氨酸作为游离氨基酸在水溶液中不稳定,特别是不允许热灭菌,因此半胱氨酸优选以前体N-乙酰基-L-半胱氨酸的形式使用。同样,以其它前体的形式、特别是以寡肽的形式施用也可在本发明的范围之内。
如果不使用稳定且易溶的寡肽,则不可能制备含有适量的谷氨酰胺和酪氨酸的氨基酸溶液。这两种游离氨基酸的溶解度都很低。此外,游离谷氨酰胺的使用不允许进行热灭菌。由于这一原因,过去常使用谷氨酸以替代谷氨酰胺。谷氨酸和谷氨酰胺在机体中处于代谢平衡状态,但其内源性相互转化仅在一定程度上发生。因此,不能将谷氨酸视为完全的谷氨酰胺替代物。已发现施用大量的谷氨酸具有兴奋性作用并导致在刺激神经细胞方面过度活跃,有可能造成细胞死亡[Barinaga(1990)Science 247:20-22]。与之相比,可发现施用增加量的谷氨酰胺是无害的。此外,所需谷氨酸的日剂量当然可通过增加谷氨酰胺摄入来补偿。因此,如果通过适当高剂量的谷氨酰胺而确保基础供应,则也可在完全缺乏谷氨酸的情况下获得合适的胃肠外营养。由于这一原因,本发明组合物中谷氨酰胺的比例用量也明显超过了迄今所使用的量。
通过提供寡肽尤其是三肽或二肽形式的谷氨酰胺解决了稳定性和溶解度问题。三肽的实例是X’-Gln-X,X’-X-Gln和Gln-X’-X。二肽的实例是Gln-X和X-Gln。X和X’是任何天然氨基酸,优选使用丙氨酸和甘氨酸。
同样,游离氨基酸酪氨酸具有低溶解度的缺点。过去,酪氨酸的低溶解度导致在保留同样氨基酸模式的情况下使用游离酪氨酸时,必须以低于理想的约10%w/w蛋白结构单元(7-15%w/w蛋白结构单元)的总浓度制备氨基酸溶液。因此,至今为止用于胃肠外营养的氨基酸溶液中酪氨酸成分常被更易溶的乙酰基酪氨酸替代。然而,乙酰基酪氨酸很难被人体所代谢[Magnusson等(1989)Metabolism 38:957-961],并且对新生儿来说更是如此。
此问题的一个优选的解决方案同样是提供寡肽特别是三肽或二肽形式的酪氨酸。三肽的实例是X’-Tyr-X、X’-X-Tyr和Tyr-X’-X。二肽的实例是Tyr-X和X-Tyr。X和X’是任何天然氨基酸,优选使用丙氨酸和甘氨酸。
以上述可快速代谢的寡肽的形式提供谷氨酰胺和酪氨酸使得可以制备同时具有高稳定性和可储存性的热灭菌的完全氨基酸溶液。
出乎意料地发现,热灭菌可在比通常更高的灭菌温度下(>121℃)进行而具备同样的灭菌效率(通过常数F0值定义)和更好的寡肽稳定性。在此方面灭菌温度优选≥124℃,特别优选≥127℃。pH优选5~6.5。当使用较高温度时,可减少热灭菌的处理时间。在优选的条件下,在灭菌产物中存在显著较少量的降解产物(实施例3)。
对于全胃肠外营养而言,可在与其它胃肠外饮食组分一起施用之前与本发明的氨基酸溶液混合,以得到符合所有全营养要求的组合物。相对于成人,由于处于生长期,在早产儿和新生儿以及小儿中相对于体重的热量需求增加。新生儿身体需要80-190kcal/kg、优选90-120kcal/kg的日剂量,对于年龄大于一岁的小儿来说,此剂量降至75-90kcal/kg,对于更大的儿童来说,低于此范围。在此方面,对于在胃肠外营养治疗中提供的氨基酸而言,优选旨在仅仅用于蛋白质构建和必需的代谢过程,而不作为一般的能量摄入。因此,完全胃肠外营养中以蛋白质结构单元形式仅提供约10-20%的能量,30-60%的能量由碳水化合物(优选葡萄糖)提供,另外30-50%的能量由脂类提供。电解质、维生素和微量元素使胃肠外膳食组合物完整。
已知由于会出现稳定性问题,氨基酸不能与脂类和碳水化合物储存在一起。因此,所述胃肠外营养的这些成分仅在施用前不久在无菌条件下混合在一起。因此,这样的施用前混合特别耗时。通过如EP 1396249实施例中所述的具有可剥离密封的多室袋(multichamber bag),此问题已得到解决。这种***的用途还适于施用根据本发明的Neoven。
通过以下实施例,将对本发明做出更详细的说明。
实施例1:
在下表中显示本发明氨基酸溶液的特性,其基于1000ml体积。给出了量的可能范围、量的优选范围、优选日剂量和量的具体实例。
*以L-丙氨酰-L-谷氨酰胺的形式
**以甘氨酰-L-酪氨酸的形式
AA=氨基酸
EAA=必需氨基酸
BCAA=支链氨基酸
实施例2:
一种用于儿科患者全胃肠外营养的溶液中按每kg体重包含用于历时24小时的日剂量输注的以下成分:
12-35ml | 根据实施例1的氨基酸溶液 |
20-120ml | 5-20%葡萄糖溶液 |
2-15ml | 脂质溶液 |
2-3mmol | 钠 |
2-3mmol | 钾 |
0,1-0,6mmol | 钙 |
0,1-0,8mmol | 镁 |
D,5-15μg | 维生素D |
2-7mg | 维生素E |
10-200μg | 维生素K |
10-80mg | 维生素C |
0,3-1,5mg | 维生素B1 |
0,1-1,5mg | 维生素B2 |
0,1-1,5mg | 维生素B6 |
0,2-1,2μg | 维生素B12 |
4-18mg | 烟酸 |
50-150μg | 叶酸 |
50-500μg | 锌 |
2-3μg | 硒 |
30-200μg | 铁 |
实施例3:
在121℃、124℃和127℃将200g/l丙氨酰-谷氨酰胺的溶液灭菌。pH在pH5、pH5.5和pH6之间变化。改变热灭菌的处理时间从而达到12-12.5的相当的F0值,证实灭菌效率保持在同样水平。F0值描述灭菌效率并对应于121.11℃时的处理时间。对于在较高温度下的灭菌而言,减少处理时间以保持恒定的F0值。灭菌后,检测二肽丙氨酰-谷氨酰胺、环(丙氨酰-谷氨酰胺)(cyclo-alanyl-glutamine)和L-焦丙氨酰-谷氨酰胺的降解产物的量。这些降解产物的较低值直接表明了灭菌过程中所述二肽的稳定性。在较高温度下降解产物的值降低。
灭菌试验的结果示于下表。
PH | Tst | 环(丙氨酰-谷氨酰胺)[%] | 焦谷氨酰-丙氨酸[%] | FO |
5,0 | 121℃ | 1,09 | 0,36 | 12,1 |
5,5 | 121℃ | 1,31 | 0,30 | 12,1 |
6,0 | 121℃ | 1,54 | 0,28 | 12,1 |
5,0 | 124℃ | 0,89 | 0,30 | 12,5 |
5,5 | 124℃ | 1,08 | 0,26 | 12,5 |
6,0 | 124℃ | 1,25 | 0,24 | 12,5 |
5,0 | 127℃ | 0,76 | 0,26 | 12,5 |
5,5 | 127℃ | 0,9 | 0,22 | 12,5 |
6,0 | 127℃ | 1,08 | 0,21 | 12,5 |
实施例4:
在具有可剥离隔板(peelable partition)的两室袋(two-chamberbag)中提供供胃肠外施用的溶液。所述袋的一个室容纳有本发明的氨基酸溶液,另一个室容纳有包含葡萄糖、电解质、维生素和微量元素的营养溶液。所述组合物特别适合一个月到一岁年龄的儿科患者。
组成 | 优选范围 具体实例 |
体积(ml) | 100 100,0 |
氨基酸/g(实施例1) | 2-3 2,4 |
葡萄糖/g | 9-15 12,0 |
Na mmol | 2-3 2,40 |
K mmol | 1,5-2,5 2,00 |
Ca mmol | 1-1,8 1,44 |
Mg mmol | 0,1-0,3 0,20 |
P mmol | 0,9-1,4 1,12 |
容纳有相应组合物的袋可以350ml、500ml和1000ml的体积提供,以便给不同年龄组的患者提供合适的量。
实施例5:
在具有可剥离隔板的三室袋(three-chamber bag)中提供供胃肠外施用的溶液。所述袋的一个室容纳有本发明的氨基酸溶液,一个室容纳有包含葡萄糖、电解质、维生素和微量元素的营养溶液,另一个室包含脂质乳液。所述脂质乳液优选包含来自大豆油、中链脂肪酸(medium-chain fatty acids,MCT)、橄榄油和鱼油的脂类。所述组合物特别适合体重为10-40kg且年龄超过一岁的儿科患者。然而,通常还认为其适合更年幼的患者。
组成 | 优选范围 | 具体实例 |
体积(ml) | 100 | 100 |
总热量 | 60-100 | 80 |
氨基酸/g(实施例1) | 1,5-2,5 | 2 |
葡萄糖/g | 9-15 | 12 |
脂肪/g(SMOF脂质) | 1,5-2,5 | 2 |
Na mmol | 2-2,5 | 2,22 |
K mmol | 2-2,5 | 2,22 |
Ca mmol | 0,4-0,7 | 0,56 |
Mg mmol | 0,05-0,15 | 0,11 |
P mmol | 0,6-1 | 0,78 |
容纳有相应组合物的袋可以1000ml和2000ml的体积提供,以便给不同重量组的患者提供合适的量。
Claims (19)
1.一种用于儿科患者胃肠外营养的氨基酸溶液,其特征在于所述氨基酸溶液包含9-30g谷氨酰胺/100g氨基酸和0.3-2g牛磺酸/100g氨基酸。
2.根据权利要求1的氨基酸溶液,其特征在于所述氨基酸溶液包含1-4g酪氨酸/100g氨基酸、0.3-1.5g半胱氨酸/100g氨基酸、3-5g苯丙氨酸/100g氨基酸和1-3g蛋氨酸/100g氨基酸。
3.根据前述权利要求中任一项的氨基酸溶液,其特征在于谷氨酰胺以寡肽的形式存在。
4.根据权利要求2或权利要求3的氨基酸溶液,其特征在于酪氨酸以链长度为至多5个氨基酸单元的寡肽的形式存在。
5.根据权利要求3或权利要求4的氨基酸溶液,其特征在于所述寡肽是二肽或三肽。
6.根据前述权利要求中任一项的氨基酸溶液,其特征在于谷氨酰胺以丙氨酰谷氨酰胺、甘氨酰谷氨酰胺或其混合物的形式存在。
7.根据权利要求2~6中任一项的氨基酸溶液,其特征在于酪氨酸以甘氨酰酪氨酸、丙氨酰酪氨酸或其混合物的形式存在。
8.根据前述权利要求中任一项的氨基酸溶液,其特征在于所述氨基酸溶液包含至多3g/l的谷氨酸。
9.根据前述权利要求中任一项的氨基酸溶液,其特征在于所述氨基酸溶液包含3-30%w/w的蛋白质结构单元。
10.根据权利要求2~8中任一项的氨基酸溶液,其特征在于酪氨酸和苯丙氨酸的比例为1:1~1:3。
11.根据权利要求2~9中任一项的氨基酸溶液,其特征在于氨基酸半胱氨酸、牛磺酸和蛋氨酸的总量为全部氨基酸的2-5%。
12.根据前述权利要求中任一项的氨基酸溶液,其特征在于所述氨基酸溶液包含的链长度>5个氨基酸单元的蛋白质或肽的量不到1%。
13.权利要求1的氨基酸溶液在制备用于儿科患者胃肠外营养的药物组合物中的用途。
14.权利要求12的用途,其特征在于所述患者患有肠畸形或肠炎。
15.权利要求1的氨基酸溶液在制备用于肾病或肝病患者的胃肠外营养的药物组合物中的用途。
16.一种用于全胃肠外营养的药物组合物,其特征在于其:
a)通过碳水化合物提供30-60%的能量,
b)通过脂类提供30-50%的能量,
c)通过权利要求1的氨基酸溶液提供10-20%的能量。
17.根据权利要求16的药物组合物,其特征在于所述营养组合物还包含电解质、维生素和微量元素。
18.权利要求16的药物组合物在制备用于治疗儿科患者的胃肠外输注溶液中的用途,其特征在于所述输注溶液包含90-180kcal/kg患者体重的日剂量。
19.一种制备用于胃肠外营养的包含7-30g寡肽形式谷氨酰胺/100g氨基酸的无菌氨基酸溶液的方法,其特征在于其至少包括在≥124℃的温度下热灭菌的步骤。
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CN102883729A (zh) * | 2010-01-04 | 2013-01-16 | 潘泰克健康公司 | 营养组合物及其使用方法 |
CN102762115A (zh) * | 2010-02-24 | 2012-10-31 | 美赞臣营养品公司 | 供给营养素的制剂和方法 |
CN104039174A (zh) * | 2012-01-09 | 2014-09-10 | N·V·努特里奇亚 | 用于早产婴儿的富含谷氨酰胺的营养组合物 |
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WO2007121807A1 (de) | 2007-11-01 |
EA200870451A1 (ru) | 2009-04-28 |
KR20090010050A (ko) | 2009-01-28 |
EP2007348B1 (de) | 2014-12-10 |
BRPI0710298A2 (pt) | 2011-08-09 |
JP2009534323A (ja) | 2009-09-24 |
US20090203626A1 (en) | 2009-08-13 |
EP2007348A1 (de) | 2008-12-31 |
AU2007241469A1 (en) | 2007-11-01 |
TWI429405B (zh) | 2014-03-11 |
AU2007241469B2 (en) | 2012-09-20 |
DE102006018293A1 (de) | 2007-10-25 |
US8377876B2 (en) | 2013-02-19 |
EA015709B1 (ru) | 2011-10-31 |
TW200740380A (en) | 2007-11-01 |
ZA200807860B (en) | 2009-08-26 |
CN104524542A (zh) | 2015-04-22 |
MX2008013540A (es) | 2008-10-31 |
CA2647087A1 (en) | 2007-11-01 |
AR060555A1 (es) | 2008-06-25 |
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