麝香生物活性物质复合物脂质体的制备工艺研究

S. L. Lyublinskiy, I. N. Lyublinskaya, E. Koloskova, A. Azizov, V. Karkischenko, M. Nesterov, A. Kaptsov, R. Ageldinov, V. N. Gerasimov, D. Grinenko
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引用次数: 1

摘要

为了保存和提高从鹿香中分离的生物活性物质的生物有效性,研究了从鹿香中提取脂质稳定的纳米颗粒物质的工艺。对所得物质的稳定性进行了评价。结果表明,高压均质是提取鹿香生物活性物质的最佳途径。确定了具有预定分散参数(平均粒径250±100 nm,多分散指数0.3±0.1,zeta电位-5 ~ -35 mV)的生物活性物质脂质体的制备模式。结果发现,高压均质机“Donor-5”可以获得符合标准参数的脂质体分散体,麝香生物活性物质的包合度可达60%,同时对磷脂(氧化指数0.3)提供最小的氧化和水解。我们的研究表明,使用国产磷脂酰胆碱在经济上是合理的,并允许获得适当质量的脂质体形式。采用常规分析方法(动态光散射、电镜、凝胶色谱、色谱-质谱等)对所得脂质体物质的质量指标进行表征。根据所获得的结果,制定了含有从麝麝香中分离的生物活性物质复合物的脂质体物质(粉末)的规范草案。所开发的从麝中提取生物活性物质脂质体的技术可以按照GMP要求进行放大。
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Technological Aspects of Obtaining Liposomes Containing of a Complex of Biologically Active Substances Isolated from Deer Musk
In order to preserve and increase the biological effectiveness of biologically active substances isolated from deer musk, we studied technological aspects of obtaining a substance of lipid-stabilized stable nanoparticles from deer musk. The stability of the obtained substance was evaluated. It was found that homogenization under high pressure is an optimal approach to obtaining biologically active substances from deer musk. The modes of preparation of a liposomal form of biologically active substances with predetermined dispersion parameters (average particle diameter 250 ± 100 nm, polydispersity index 0.3 ± 0.1, and zeta potential from -5 to -35 mV) were determined. It was found that the high-pressure homogenizer “Donor-5” makes it possible to obtain liposomal dispersions with standard parameters and the degree of inclusion of musk biologically active substances up to 60%, at the same time as providing minimal oxidation and hydrolysis of phospholipids (oxidation index 0.3). Our studies showed that the use of a domestic phosphatidylcholine is economically justified and allows obtaining liposomal forms of proper quality. The quality indicators of the obtained liposomal substance were characterised by conventional analytical methods (dynamic light scattering, electron microscopy, gel chromatography, chromatography-mass spectrometry, etc.). On the basis of the results obtained, a draft specification was developed for a liposomal substance (powder) containing a complex of biologically active substances isolated from deer musk. The developed technology for obtaining a liposomal form of biologically active substances from deer musk can be scaled up in accordance with GMP requirements.
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