碱性成纤维生长因子鼻腔喷雾剂的质量评价

Quality assessment and stability test of basic fibroblast growth factor nasal spray

目的:对碱性成纤维生长因子(bFGF)鼻腔喷雾剂的质量进行评价,并考察其稳定性。方法:参照中国药典2010年版规定,对bFGF鼻腔喷雾剂的外观、pH值、黏度、含量、最低装量、每瓶总喷次、平均每喷主药含量、生物学活性等进行测定;采用大鼠鼻黏膜纤毛模型考察鼻腔喷雾剂的纤毛毒性;考察高温、光照及加速和长期试验下,bFGF鼻腔喷雾剂的稳定性。结果:制备的3批鼻腔喷雾剂各项质量指标均符合中国药典规定。持续给药7 d后,鼻腔喷雾剂对大鼠鼻黏膜纤毛影响较小,纤毛浓密整齐,基本未见脱落;鼻黏膜上皮细胞排列紧密有序,黏膜下腺体、血管等清晰可见,黏膜层厚度与生理盐水组相近。鼻腔喷雾剂的稳定性受高温影响大,制剂应在4℃、避光保存。加速实验和长期实验结果显示,鼻腔喷雾剂的各项指标均符合规定。结论:制备的bFGF鼻腔喷雾剂质量稳定且具有良好的生理适应性。

OBJECTIVE To evaluate the quality of basic fibroblast growth factor （bFGF） nasal spray and investigate its stability. METHODS According to Chinese Pharmacopoeia （2010 edition）, some indexes of the preparation such as appearance,pH, osmotic pressure, viscosity, content, biological activity, total spray times/bottle, average content/spray were determined. Rat nasal cilia model was used to evaluate the ciliotoxicity of nasal spray. The stability of bFGF nasal spray under high temperature,strong light,accelerated test and long term test was investigated. RESULTS All indexes of nasal spray met its specified requirements. After administration to rats for consecutive 7 days, the nasal spray showed little influence on the morphology of ratnasal mucosa cilia which was thick and intact with no ecclasis. The shape of the epithelium was regular, meanwhile the glandulartissue and capillary in the lamina propria were clearly visible. The thickness of the nasal mucosa was close to that of the negative control. High temperature severely affected the stability of bFGF nasal spray, so the preparation should be stored in 4 C and dark area. Accelerated test and long-term test results revealed that all indexes of preparation met the prescribed qualifications.CONCLUSION The quality of bFGF nasal spray was stable and its physiological flexibility was good.