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具有改善吸收特性的胰岛素类似物。

Insulin analogues with improved absorption characteristics.

作者信息

Brange J, Hansen J F, Langkjaer L, Markussen J, Ribel U, Sørensen A R

机构信息

Novo Research Institute, Bagsvaerd, Denmark.

出版信息

Horm Metab Res Suppl. 1992;26:125-30.

PMID:1490679
Abstract

The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

摘要

目前可用的胰岛素制剂并不适合作为治疗药物,因为皮下注射无法提供生理性的胰岛素分布。为了改善吸收特性,人们利用重组DNA技术设计出了具有改变的物理化学特性、从而改变皮下吸收动力学的新型胰岛素分子。等电点从5.4提高到约7的可溶性长效人胰岛素类似物吸收非常缓慢,与目前的长效制剂相比,能提供更稳定的基础胰岛素输注,且每日变化更小。此外,它们具有更好的储存稳定性。自我缔合大幅降低的速效人胰岛素类似物从皮下组织的吸收速度比目前的常规胰岛素快得多,因此更适合推注给药。这些类似物的吸收动力学能够解释剂量对胰岛素吸收速率影响背后的机制。

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