The role of N-acetyl-methioninate as a new stabilizer for albumin products
The role of N-acetyl-methioninate as a new stabilizer for albumin products
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DOI：
10.1016/j.ijpharm.2006.08.014
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发表时间：
2007-02-01
影响因子：
5.8
通讯作者：
Otagiri, Masaki
中科院分区：
文献类型：
--
作者：
Anraku, Makoto;Kouno, Yousuke;Otagiri, Masaki
辛酸钠（Oct）和N - 乙酰 - L - 色氨酸盐（N - AcTrp）在白蛋白制品的巴氏消毒过程中被广泛用作稳定剂。然而，N - AcTrp可能有引发脑部疾病的副作用。为了提供安全无风险的白蛋白制品，我们验证了N - 乙酰甲硫氨酸盐（N - AcMet）可作为白蛋白制品的一种新型稳定剂。使用2,2'-偶氮二（2 - 脒基丙烷）二盐酸盐（AAPH）作为氧化剂，检测了N - AcMet对氧化的影响。在N - AcMet存在的情况下，羰基含量以及在24小时后N - AcTrp存在时的羰基含量（Anraku等人，2004年）都显著降低。还通过高效液相色谱法（HPLC）研究了AAPH对人血清白蛋白中34 - 半胱氨酸氧化状态的影响。结果发现，N - AcMet和N - AcTrp在1小时后对巯基都有很大的保护作用。此外，使用1,1'-二苯基 - 2 - 苦基肼基（DPPH）自由基发现，N - AcMet是比N - AcTrp更优的自由基清除剂。通过差示扫描量热法（DSC）测定，N - AcMet的热稳定作用表现为变性温度和量热焓的升高。在本研究中，我们认为在白蛋白制剂中使用N - AcMet是安全的，且无副作用风险。（c）2006爱思唯尔公司。版权所有。
Sodium octanoate (Oct) and N-acetyl-L-tryptophanate (N-AcTrp) are widely used as stabilizers during the pasteurization of albumin products. However, N-AcTrp has a possible side effect of intracerebral disease. To provide safe and risk-free albumin products, we validated N-acetylmethioninate (N-AcMet) as a new stabilizer for albumin products. The effect of N-AcMet on oxidation was examined using 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as an oxidizing agent. Carbonyl content in the presence of N-AcMet, as well as that in the presence of N-AcTrp after 24 h (Anraku et al., 2004), was significantly decreased. The effect of AAPH on the oxidative status of 34-Cys on human serum albumin was also studied by HPLC. It was found that N-AcMet as well as N-AcTrp, has a large protective effect on the sulfhydryl group after 1 h. Further, N-AcMet was found to be a superior radical scavenger to N-AcTrp using 1, 1'-diphenyl-2-picrylhydrazyl (DPPH) radicals. The thermal stabilizing role of N-AcMet manifested as an increase in denaturation temperature and calorimetric enthalpy, as determined by differential scanning calod metry (DSQ. In the present study, we suggest that use of N-AcMet in albumin preparation is safe and free of risk of side effects. (c) 2006 Elsevier B.V. All rights reserved.