胰淀素
胰高血糖素
胰岛素
激素
化学
糖尿病
内科学
药代动力学
内分泌学
聚乙二醇
血糖性
医学
药理学
生物化学
小岛
作者
Caitlin L. Maikawa,Anders Smith,Lei Zou,Gillie A. Roth,Emily C. Gale,Lyndsay M. Stapleton,Sam W. Baker,Jay D. Mann,Anthony C. Yu,Santiago Correa,Abigail K. Grosskopf,Celine S. Liong,Catherine M. Meis,Doreen Chan,Megan L. Troxell,David M. Maahs,Bruce A. Buckingham,Matthew J. Webber,Eric A. Appel
标识
DOI:10.1038/s41551-020-0555-4
摘要
Treatment of patients with diabetes with insulin and pramlintide (an amylin analogue) is more effective than treatment with insulin only. However, because mixtures of insulin and pramlintide are unstable and have to be injected separately, amylin analogues are only used by 1.5% of people with diabetes needing rapid-acting insulin. Here, we show that the supramolecular modification of insulin and pramlintide with cucurbit[7]uril-conjugated polyethylene glycol improves the pharmacokinetics of the dual-hormone therapy and enhances postprandial glucagon suppression in diabetic pigs. The co-formulation is stable for over 100 h at 37 °C under continuous agitation, whereas commercial formulations of insulin analogues aggregate after 10 h under similar conditions. In diabetic rats, the administration of the stabilized co-formulation increased the area-of-overlap ratio of the pharmacokinetic curves of pramlintide and insulin from 0.4 ± 0.2 to 0.7 ± 0.1 (mean ± s.d.) for the separate administration of the hormones. The co-administration of supramolecularly stabilized insulin and pramlintide better mimics the endogenous kinetics of co-secreted insulin and amylin, and holds promise as a dual-hormone replacement therapy. The co-administration of insulin and pramlintide stabilized with cucurbit[7]uril-conjugated polyethylene glycol in diabetic pigs improves the mealtime suppression of glucagon over the separate administration of the two hormones.
科研通智能强力驱动
Strongly Powered by AbleSci AI