仿制药一致性评价及其评价过程的质量管理

目的 探讨仿制药一致性评价过程的质量管理,为中国制药企业高效开展一致性评价工作提供参考。方法 阐述一致性评价的基本概念,对仿制药一致性评价的发展阶段和关键步骤进行梳理,提出PDCA循环管理模式在一致性评价过程中的应用。结果 运用PDCA循环管理模式对评价过程进行全面质量管理,可以制定出一致性评价的科学程序。QbD设计管理理念和cGMP生产管理理念的应用,可以保证产品从研发到生产全过程的一致性。结论 以QbD和cGMP理念为重点的PDCA循环管理模式可在中国制药企业一致性评价过程中加以应用,从而加强仿制药一致性评价过程的质量管理。     

Chitosan green tea polyphenol complex as a released control compound for wound healing

Objective： In recent years, oxidative stress has been implicated in a variety of degenerative process and diseases, including acute and chronic inflammatory conditions such as wound healing. Green tea polyphenols have shown anti-oxidant property. The present study discussed the application of chitosan green tea polyphenol complex on the wound healing. Methods： The wound healing effect ofchitosan green tea polyphenol complex was studied in tenweek-old healthy male Sherman rats weighing 150-180 g by two wound models. The rats were randomly chosen and divided into four groups （n=5）, administered with distilled water in Group A as control group, epigallocatechin-3-gallate （EGCG） in Group B, chitosan-EGCG complex in Group C and chitosan-green tea polyphenols complex in Group D, respectively. In rats＇incision wound model, two straight paravertebral incisions were made and skin tensile strength was measured using continuous water flow technology on the 10th day. In rats＇excision wound model, wound contraction and period of epithelization were measured. The polyphenols release from the complex was continuously monitored by an elution technique in aqueous solution at different pH values （pH=4, 5, 6, 7）. Results： The treatment groups showed significantly enhanced the breaking strength in incision wound （328±14.5） g and 021±18.5） g compared with control （264±16.7） g. In the excision wound model, the wound contraction percentage in treatment groups was relatively increased during the recovery period. Respectively, the percentage of wound contraction ranged from 47.60%±2.15% on day 4 to 107.98% ± 1.26% on day 16 compared with control group （8.46%±5.42% to 59.80%±4.47%）. The complex demonstrated a gradual increase in the release rate from the initial stage and slow increase at different pH values. The release rate approximated 0.6-0.7 in the complex and remained stable 6 hours after injury, which may be the end of the release process. Conclusions： In our study, chitosan polyphenol complex has enhanced the healing of incision wounds by increasing the breaking strength of the wounds. In excision wound model, the complex hastens the period of epithelialization. The study on the optimal release of complex among various pH values could be applied in the wound test, which can lead to a gradually active substance （polyphenols） release and efficient coverage of epithelial layers found in the healing of incision and excision wound.