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.

中文翻译：

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超分子稳定胰岛素和普兰林肽的复合制剂可增强糖尿病猪进餐时胰高血糖素的抑制。

使用胰岛素和普兰林肽（胰淀素类似物）治疗糖尿病患者比仅使用胰岛素治疗更有效。然而，由于胰岛素和普兰林肽的混合物不稳定并且必须单独注射，因此只有 1.5% 需要速效胰岛素的糖尿病患者使用胰淀素类似物。在这里，我们证明用葫芦[7]脲结合的聚乙二醇对胰岛素和普兰林肽进行超分子修饰可改善双激素疗法的药代动力学，并增强糖尿病猪的餐后胰高血糖素抑制。复合制剂在 37°C 和连续搅拌下可稳定稳定超过 100 小时，而胰岛素类似物的商业制剂在类似条件下 10 小时后会聚集。在糖尿病大鼠中，单独施用激素时，稳定复合制剂的施用使普兰林肽和胰岛素的药代动力学曲线的重叠面积比从0.4±0.2增加到0.7±0.1（平均值±标准差）。超分子稳定胰岛素和普兰林肽的共同给药更好地模拟了共同分泌的胰岛素和胰淀素的内源动力学，并有望成为双激素替代疗法。