Protected graft copolymer (PGC) basal formulation of insulin as potentially safer alternative to Lantus® (insulin-glargine): a streptozotocin-induced, diabetic Sprague Dawley rats study.
Protected graft copolymer (PGC) basal formulation of insulin as potentially safer alternative to Lantus® (insulin-glargine): a streptozotocin-induced, diabetic Sprague Dawley rats study.
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受保护的接枝共聚物 (PGC) 胰岛素基础制剂作为来得时®（甘精胰岛素）的潜在更安全替代品：链脲佐菌素诱导的糖尿病 Sprague Dawley 大鼠研究。
DOI：
10.1007/s11095-011-0646-8
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发表时间：
2012
影响因子：
3.7
通讯作者：
Bolotin,ElijahM
中科院分区：
文献类型：
--
作者：
Reichstetter,Sandra;Castillo,GerardoM;Lai,ManShun;Nishimoto-Ashfield,Akiko;Banerjee,Aryamitra;Bogdanov,Alexei;Lyubimov,AlexanderV;Bolotin,ElijahM
PurposeTo develop a long-acting formulation of native human insulin with a similar pharmacodynamics (PD) profile as the insulin analogue insulin glargine (Lantus®, Sanofi-Aventis) with the expectation of retaining native human insulin’s superior safety profile as insulin glargine is able to activate the insulin-like growth factor 1 (IGF-1) receptor and is linked to a number of malignancies at a higher rate than regular human insulin.MethodsDevelopment of protected graft copolymer (PGC) excipients that bind native human insulin non-covalently and testing blood glucose control obtained with these formulations in streptozotocin-induced diabetic Sprague Dawley rats compared to equally dosed insulin glargine.ResultsPGC-formulations of native human insulin are able to control blood glucose to the same extent and for the same amount of time after s.c. injection as the insulin analogue insulin glargine. No biochemical changes were made to the insulin that would change receptor binding and activation with their possible negative effects on the safety of the insulin.ConclusionFormulation with the PGC excipient offers a viable alternative to biochemically changing insulin or other receptor binding peptides to improve PD properties.FigureBlood glucose development in STZ-diabetic Sprague Dawley rats after s.c. injection of 1 mg/kg regular human insulin formulated with formulations 605c, 421a, and 421b, or an equivalent dose of insulin glargine.
