重组人生长激素粉针剂在冷链流通断链后的稳定性研究

Study on the stability of recombinant human growth hormone lyophilized power injection after cold chain interruption

关键词:  重组人生长激素粉针剂  冷链  稳定性研究  

Key words:  Recombinant human growth hormone lyophilized power injection  Cold chain  Stability study  

摘要:

目的 考察重组人生长激素(recombinant human growth hormone, rhGH)粉针剂放置在不同温度下的稳定性研究。方法 本研究拟考察rhGH粉针剂在5℃±3℃放置0天、15天和40天的长期稳定性,25℃±2℃放置0天、7天、15天、30天和40天的加速稳定性,40℃±2℃放置0天、1天、3天、5天和7天的高温稳定性,参照《中国药典(2020版)》标准,本研究以人生长激素含量、高分子蛋白和相关蛋白含量作为质量评价指标,采用尺寸排阻高效液相色谱法(size exclusion chromatography-high performance liquid chromatography, SEC-HPLC)测定人生长激素和高分子蛋白含量,采用反相高效液相色谱法(reverse phase- high performance liquid chromatography, RP-HPLC)测定相关蛋白质含量。结果 rhGH粉针剂在5℃±3℃放置40天,在25℃±2℃放置40天,在40℃±2℃放置7天,人生长激素含量在90.0%-110.0%,高分子蛋白含量<6.0%,相关蛋白含量<12.0%,均符合《中国药典(2020版)》的质量标准。结论 rhGH粉针剂在5℃±3℃放置40天、25℃±2℃放置40天、40℃±2℃放置7天,人生长激素含量、高分子蛋白含量和相关蛋白含量变化未见明显异常。

Abstract:

Objective To investigate the stability of recombinant human growth hormone (rhGH) lyophilized power injection under different temperature conditions. Methods This study aimed to evaluate the long-term stability of rhGH lyophilized power injection stored at 5℃±3℃ for 0, 15 and 40 days, accelerated stability at 25℃±2℃ for 0, 7, 15, 30 and 40 days, and high-temperature stability at 40℃±2℃ for 0, 1, 3, 5 and 7 days. Based on the《Chinese Pharmacopoeia (2020 Edition)》standards, quality assessment indicators included human growth hormone content, high molecular proteins and related proteins. The size exclusion chromatography-high performance liquid chromatography (SEC-HPLC) method was used to determine human growth hormone and high molecular protein contents, while the reverse phase-high performance liquid chromatography (RP-HPLC) method was employed to analyze related protein contents. Results After storing the rhGH lyophilized powder injection at 5℃±3℃ for 40 days, 25℃±2℃ for 40 days, and 40℃±2℃ for 7 days, the following results were observed: the content of human growth hormone within the range of 90.0%-110.0%, the content of high molecular proteins and related proteins was less than 6.0% and 12.0%, respectively. These parameters met the quality standards specified in the《Chinese Pharmacopoeia (2020 Edition)》. Conclusions After storing the rhGH lyophilized powder injection at 5℃±3℃ for 40 days, 25℃±2℃ for 40 days, and 40℃±2℃ for 7 days, no significant abnormalities were observed in the content of human growth hormone, high molecular proteins and related proteins.