【摘要】：熱敏性蛋白藥物胰島素的熱穩(wěn)定性較差,極易受制備方式和保存條件等影響而失活。故本研究分別利用高效液相色譜(HPLC)測定凍干樣品中胰島素的效價和差示掃描量熱儀(DSC)測定凍干樣品的玻璃化轉(zhuǎn)變溫度等重要參數(shù),來研究胚胎發(fā)育晚期富集蛋白特征片段(LEA-motif,LEAM)和海藻糖凍干保護(hù)劑對胰島素凍干保護(hù)效果的影響。凍干實(shí)驗表明,兩種保護(hù)劑均對胰島素的活性具有保護(hù)效果,且LEAM的活性保護(hù)效果優(yōu)于海藻糖。在效價和熱穩(wěn)定性方面,LEAM保護(hù)的胰島素凍干品均高于海藻糖保護(hù)的胰島素凍干樣品。更為重要的是,兩種保護(hù)劑協(xié)同保護(hù)時,少量海藻糖對于LEAM的保護(hù)特性具有增效作用。在凍干過程中,可有效提升藥物玻璃態(tài)的穩(wěn)定性,防止熱致變性失活。由此可見,這種LEAM和海藻糖保護(hù)劑復(fù)合保護(hù)方法有望也可以應(yīng)用在熱敏性蛋白藥物凍干粉針制備過程以保護(hù)藥物活性。
[Abstract]:The thermal stability of heat sensitive protein drug insulin is poor, and it is easily inactivated due to the influence of preparation methods and preservation conditions. In this study, the titer of insulin in freeze-dried samples was determined by high performance liquid chromatography (HPLC) and the glass transition temperature of freeze-dried samples was determined by differential scanning calorimeter (DSC). To study the effects of LEA-motif,LEAM and trehalose lyophilization protectant on the protective effect of insulin freeze-drying. The freeze-drying experiments showed that both of the two protective agents had protective effects on the activity of insulin, and the protective effect of LEAM was better than that of trehalose. In terms of titer and thermal stability, LEAM protected insulin freeze-dried products were higher than trehalose protected insulin freeze-dried samples. More importantly, a small amount of trehalose has a synergistic effect on the protective properties of LEAM. In the freeze-drying process, the stability of the glass state of the drug can be improved effectively, and the thermal denaturation and inactivation can be prevented. Therefore, the composite protection method of LEAM and trehalose protectant may also be used in the preparation of freeze dried powder for thermosensitive protein drugs to protect the drug activity.
【作者單位】： 上海理工大學(xué)生物系統(tǒng)熱科學(xué)研究所;上海東富龍科技股份有限公司;
【基金】：國家自然科學(xué)基金(51076108)資助項目 上海市“創(chuàng)新行動計劃”國際科技合作項目(12430702000) 上海市重點(diǎn)學(xué)科項目(T0503和P0502) 上海市自然科學(xué)基金(12ZR1420400) 上海市教委科研創(chuàng)新項目(14YZ092) 上海市聯(lián)盟計劃項目資助~~
【分類號】：R943

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