蛋白質類製劑及其安定性研究

因蛋白質特有的物化性質，使得其於純化、分離、儲存及運輸過程中顯得困難。蛋白質的分解途徑可為化學的不安定性及物理的不安定性二類。化學不安定性包括β－移除反應、斷裂反應、脫醯胺反應、氧化反應、雙硫鏈交換反應、蛋白質水解反應、光解反應、寡合反應、架橋反應及消旋反應。物理不安定性常論及蛋白質或胜肽之高級次結構的完整性，一般先進行變性應，隨後則進行表面吸附，聚集及沈澱反應。加入藥物添加物、使用不同的介質、部位突變及化學修飾等方法，常被採用為增進蛋白質安定性的方法。蛋白質會因受光照射、加熱、冷卻、冰凍、加入致變性物質，賦型劑、酸度及介質面造成變質。因此蛋白質製劑之配方設計與，小分子量的有機物在設計方法上有很大的差異。冷凍乾燥製劑一般為好的劑型。在研究蛋白質製劑安定性時，其安定性試驗之分析方法，需要多種分析方法合併使用，才能瞭解蛋白質之分解途徑。

關鍵字

蛋白質製劑；化學不安定性；物理不安定性；配方設計；冷凍乾燥法；安定性試驗之分析方法

並列摘要

Proteins possess chemical and physical properties which present unique difficulties in purification, separation, storage, and delivery of these materials. The degradation pathways of protein can be separated into chemical instability and physical instability. The chemical instability involves β-elimination, fragmentation, deamidation, oxidation, disulfide exchange, protolysis, photolysis, oligomerization, crosslinking, and racemization. The physical instability refers to the integrity of the higher order structure of proteins and peptides. After protein denaturation, the surface adsorption, aggregation and precipitation will be followed. Additives, media, site-directed mutagenesis, chemical modification etc. are the methods of improving protein stability. Proteins degradation can be caused by radiation, heating, cooling, freezing, denaturants, excipients, pHs, and media. Therefore, formulation of proteins differ greatly from that of small organic molecules. Lyophilized products will be the better dosage form for protein pharmaceuticals. In studying the stability of protein pharmaceuticals, a combination of different stability indicating methods is needed to characterize pathways of protein degradation.

並列關鍵字

Protein pharmaceuticals ； Chemical instability ； Physical instability ； Formulation ； Lyophilization ； Stability indicating method

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蛋白質類製劑及其安定性研究

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