成骨生长肽鼻喷剂的研制

张望刚, 叶小弟, 郑高利*, 陈国神

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (3) : 210-215.

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PDF(1148 KB)
中国药学杂志 ›› 2014, Vol. 49 ›› Issue (3) : 210-215. DOI: 10.11669/cpj.2014.03.011
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成骨生长肽鼻喷剂的研制

  • 张望刚, 叶小弟, 郑高利*, 陈国神
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Preparation of Osteogenic Growth Peptide Nasal Spray

  • ZHANG Wang-gang, YE Xiao-di, ZHENG Gao-li*, CHEN Guo-shen
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摘要

目的 研制成骨生长肽(OGP)鼻喷剂并考察其吸收特性。 方法 采用大鼠鼻腔灌流模型, 以成骨生长肽在大鼠鼻腔的下降量为指标, 运用正交试验, 筛选吸收促进剂;优化蛋白酶抑制剂及其剂量, 考察并验证最佳处方及其稳定性。并采用扫描电镜观察经成骨生长肽鼻喷剂灌流4 h后大鼠鼻黏膜纤毛形态的改变, 进行局部安全性评价。 结果 成骨生长肽鼻喷剂的最佳处方为含成骨生长肽0.2 mg·mL-1、枸橼酸5 mg·mL-1、羟丙基-β-环糊精10 mg·mL-1、聚山梨酯-80 30 mg·mL-1及杆菌肽锌 5 mg·mL-1的pH3邻苯二甲酸氢钾缓冲溶液;该鼻喷剂对鼻黏膜刺激性较小。 结论 成骨生长肽鼻喷剂在大鼠鼻腔具有良好的吸收、质量稳定。

Abstract

OBJECTIVE To prepare osteogenic growth peptide(OGP) nasal spray and investigate the absorption characteristics. METHODS The absorption enhancer was selected by orthogonal experiment, using the declining quantity of osteogenic growth peptide in rat nose as evalution index with rat nasal perfusion model, and further the dose of protease inhibitor was selected. Finally, the acceletated and long term test were made to investigate the stability of osteogenic growth peptide nasal spray according to Chinese Pharmacopoeia 2010. The rat nasal mucosal shape were inspected by electron microscope after perfusion of osteogenic growth peptide nasal spray.RESULTS The optimal prescription of osteogenic growth peptide nasal spray is composed of osteogenic growth peptide 2 mg, citric acid 50 mg, HP-β-CD 100 mg, Tween-80 300 mg, and bacitracin zinc 50 mg in 10 mL patossium hydrogen phthalate buffer (pH 3.0). Osteogenic growth peptide nasal spray is much lower irritation to the nasal mucosa cilium. CONCLUSION The stablity of osteogenic growth peptide nasal spray was good, safe and had very good absorption in rat nose.

关键词

成骨生长肽 / 鼻喷剂 / 正交试验 / 吸收促进剂 / 蛋白酶抑制剂 / 刺激性

Key words

osteogenic growth peptide / nasal spray / orthogonal experiment / absorption enhacer / protease inhibitor / irritation

引用本文

导出引用
张望刚, 叶小弟, 郑高利*, 陈国神. 成骨生长肽鼻喷剂的研制[J]. 中国药学杂志, 2014, 49(3): 210-215 https://doi.org/10.11669/cpj.2014.03.011
ZHANG Wang-gang, YE Xiao-di, ZHENG Gao-li*, CHEN Guo-shen. Preparation of Osteogenic Growth Peptide Nasal Spray[J]. Chinese Pharmaceutical Journal, 2014, 49(3): 210-215 https://doi.org/10.11669/cpj.2014.03.011
中图分类号: R944   

参考文献

BAB I, GAZIT D, CHOREV M, et al. Histone H4-related osteogenic growth peptide(OGP): A novel circulating stimulator of osteoblastic activity. EMBO J, 1992, 11(5):1867-1873. FEI Q M, CUI D F, CHEN T Y, et al. Synthetic osteogenic growth peptide stimulates osteoblast osteogenic activity and enhances fracture healing in rabbits. Acta Biochim Biophy Sin(生物化学与生物物理学报), 2001, 33(4):415-420. ROBINSON D, BAB I, NEVP Z. Osteogenic growth peptide regulates proliferation and osteogenic maturation of human and rabbit bone marrow stromal cells. J Bone Miner Res, 1995, 10(5):690. RAO H M, WANG Z X, LI Q, et al. Effect of osteogenic growth peptide on osteoblast-like cultured in vitro. Chin J Traumatol(中华创伤杂志), 2001, 17(11):675-678. CHEN X, LUO B E, SU J C. Research progress of osteogenic effects of osteogenic growth peptide. J Shanghai Jaotong Univ(上海交通大学学报), 2010, 30(12):1565-1568. DU Y J, TIAN G T. The research process of peptide and protein drugs by nasal administration. Chin Pharm J(中国药学杂志), 2005, 40(5): 321-324. LI M, BI D Z. Preparation of freeze-dried nimodipine liposomes for intranasal administration and nasal absorption in rats. Chin J Pharm(中国医药工业杂志), 2006, 37(8):543-547. ZHANG W G, YE X D, CHEN A Y, et al. Determination the content of osteogenic growth peptide nasal spray by RP-HPLC. Chin J Mod Appl Pharm(中国现代应用药学), 2009, 26(6):489-491.

基金

浙江省科技厅重大科技项目(2005F11011)
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