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| Study on the Preparation Technology of Injectable Powder of Fusion Protein GGH |
| QIAN Jian ying, XU Zheng hong, DOU Wen fang |
| School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China |
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Abstract Objective:To establish an HPLC method for the determination of content of GGH and its injectable powder. To screen the supplementary materials and pH and study on the stability for 6 months. Methods:The Waters DELTA PAK C18 column was used, and the mobile phase was acetonitrile and water with gradient elution for 20 minutes. The detection wavelength was 280nm. Screened the fillers and pH according to the powder shape, solubility, stability and activity. Results:The calibration curve was linear in the range of 0.2~1.6mg/ml,R2=0.999,which could be used to the content detection of the powder. Four percent mannitol and pH5.5 were selected to prepare the GGH injectable powder with stable quality. Conclusions:The determination of purity and activity, together with the appearance observation method, could be used for the study of preparation technology, which provided references for the application of new drugs.
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Received: 21 July 2016
Published: 25 November 2016
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| [1] Hui H, Zhao X, Perfetti R. Structure and function studies of glucagon-like peptide-1(GLP-1):the designing of a novel pharmacological agent for the treatment of diabetes. Diabetes Metab Res Rev,2005,21(2):313-331.
[2] Drucker D J. Minireview:the glucagon-like peptides. Endocrinology,2001,142(2):521-527.
[3] Kreymann B, Williams G, Ghatei M A,et al. Glucagon-like peptide-17-36:a physiological incretin in man.Lancet,1987,2(8571):1300-1303.
[4] Vahl T P, Paty B W, Fuller B D, et al. Effects of GLP-1-(7-36)NH2, GLP-1-(7-37), and GLP-1-(9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans. Clin Endocrinol Metab,2003,88(4):1772-1779.
[5] Turton M D, O'Shea D, Gunn I, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature,1996,379(6560):69-72.
[6] Deacon C F, Wamberg S, Bie P, et al. Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs. J Endocrinol,2002,172(2):355-362.
[7] Pospisilik J A, Stafford S G, Demuth H U, et al. Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucoseresponsi-veness in VDF (fa/fa) Zucker rats. Diabetes,2002,51(4):943-950.
[8] Deacon C F, Johnsen A H, Holst J J. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab,1995,80(3):952-957.
[9] 窦文芳.长效融合蛋白GGH的构建、表达、纯化及其初步药效学和药代动力学.无锡:江南大学,生物工程学院,2010:1-59. Dou W F. Construction, Expression and Purification of the Long-term Fusion Protein GGH and Its Preliminary Pharmacodynamic and Pharmacokinetics. Wuxi:Jiangnan University,School of Biotechnolog,2010:1-59.
[10] 耿燕,任怡琳,许正宏,等.基于胞内cAMP浓度测定融合蛋白GGH活性的改良方法.中国生物工程杂志,2013,33(11):63-67. Geng Y, Ren Y L, Xu Z H, et al. An improved method to measure bioactivity of the fusion protein GGH based on the intracellular cAMP level. China Biotechnology, 2013,33(11):63-67.
[11] 胡雄伟,宋洪涛.核黄素磷酸钠粉针剂处方及制备工艺研究.解放军药学学报,2011,27(4):314-317. Hu XW, Song H T. A study on the formulation and preparation technology of riboflavin sodium phosphate injectable powder. Pham J Chin PLA, 2011,27(4):314-317.
[12] 那伊,阿凯尔斯.蛋白质药物——开发与生产. 北京:化学工业出版社,2006:35-37. Nail S L, Akers M J.Development and Manufacture of Protein Pharmaceuticals. Beijing, Chemical Industry Press,2006:35-37.
[13] 丁晓丽,张金亮,张慧,等.重组胰高血糖素样肽-1受体激动剂(rExendin-4)原液质量研究. 中国新药杂志,2015,2(12):1358-1363. Ding X L,Zhang J L,Zhang H,et al. Study on the quality of bulk solution of recombinant pancreatic glucagon-like peptide-1 receptor agonist(rExendin-4). Chinese Journal of New Drugs, 2015,2(12):1358-1363.
[14] 徐岩.干扰素α2b-29肽融合蛋白的制剂处方筛选及稳定性研究.哈尔滨:东北农业大学,生命学院,2013:18-20. Xu Y. Formulation and Stability Study of Interferon α2b-endothelial Inhibitory Peptide Fusion Protein. Ha'erbin:Northeast Agricultural University, College of Life Science,2013:18-20.
[15] 于忠喜.重组人生长激素冻干配方筛选和稳定性研究.长春:吉林大学,生命科学学院,2012:34-43. Yu Z X. Screening and Stability Study of Freeze-drying Formula for Recombinant Human Growth Hormone. Changchun:Jilin University,College of Life Science,2012:34-43.
[16] 罗文.rIL2-HSA融合蛋白注射剂型的开发研究.无锡:江南大学,药学院,2012:48-49. Luo W. Research on Injection Formulation of the Fusion Protein of rIL2-HSA. Wuxi:Jiangnan University,School of Pharmaceutical Sciences,2012:48-49.
[17] 田洪斌.注射用艾塞那肽冻干粉针剂的研究. 长春:吉林大学,生命科学学院,2008:33-36. Tian H B. The Study on Exenatide Freeze-dried Powder for Injection. Changchun:Jilin University,College of Life Science,2008:33-36. |
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