Selam J L, Zirinis P, Mellet M, Mirouze J
Diabetes Care. 1987 May-Jun;10(3):343-7. doi: 10.2337/diacare.10.3.343.
The stability of a new insulin formulation (lyophilized U100 insulin, Organon) was investigated in vitro in conditions reproducing those of in vivo implanted devices, i.e., constant horizontal agitation at 37 degrees C for 4 wk in various containers and 8 wk in different solvents. Physical stability was assessed by ultraviolet absorption, chemical stability by HPLC, and biological stability by hypoglycemia tests in mice. Insulin precipitated in glass vials but remained clear and active in polyethylene reservoirs and after passage through catheter and pumps in motion, although only 83-90% of insulin was delivered chemically intact. In acidic solvent, insulin showed a major gradual transformation into deamidized derivatives (up to 78% after 8 wk), although still fully active and clear, as expected from previously published excellent in vivo results with acidic insulins. Heparin addition to neutral insulin solution (500 IU/ml) did not alter the properties of the two compounds and might thus be tried to prevent in vivo catheter obstruction due to fibrin deposition.
在模拟体内植入装置的条件下，对一种新型胰岛素制剂（冻干的U100胰岛素，欧加农公司生产）的稳定性进行了体外研究，即在37℃下于各种容器中持续水平搅拌4周以及在不同溶剂中搅拌8周。通过紫外吸收评估物理稳定性，通过高效液相色谱法评估化学稳定性，通过对小鼠进行低血糖测试评估生物学稳定性。胰岛素在玻璃小瓶中会沉淀，但在聚乙烯储器中以及通过运动中的导管和泵后仍保持澄清且有活性，尽管仅有83 - 90%的胰岛素以化学完整形式递送。在酸性溶剂中，胰岛素显示出主要逐渐转化为脱酰胺衍生物（8周后高达78%），尽管如先前发表的关于酸性胰岛素的出色体内结果所预期的那样，其仍完全有活性且澄清。向中性胰岛素溶液（500 IU/ml）中添加肝素不会改变这两种化合物的性质，因此可尝试用于预防因纤维蛋白沉积导致的体内导管阻塞。
