星点设计-效应面法优化阴道用儿黄散白及胶缓释双层膜的处方
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摘要
目的:以白及胶为主要成膜材料,将临床有效经验方——儿黄散研制开发成阴道用缓释双层膜剂。方法:以羟丙基甲基纤维素(HPMC)和白及胶为黄连明矾药膜层的成膜材料,羧甲基纤维素钠(CMC-Na)和白及胶为儿茶药膜层的成膜材料,甘油为增塑剂,制备儿黄散白及胶缓释双层膜,以外观质量(浆液状态、成膜性、脱膜性、均匀性、黏连性、表面光滑度、柔软性)评分、黏附力和体外累积释放度为考察指标,采用星点设计-效应面法优化该膜剂的处方,并对最优处方进行验证。结果:儿茶药膜层最优处方组成为CMC-Na质量分数1.61%,白及胶质量分数3.81%,甘油用量8.49%;黄连明矾药膜层最优处方组成为HPMC质量分数1.15%,白及胶质量分数3.41%,甘油体积分数10.02%。结论:通过星点设计-效应面法优化的儿黄散白及胶缓释双层膜处方稳定可行,该制剂具有使用方便、药物滞留时间延长等特点,为中医药治疗宫颈癌提供一个可行的现代中药制剂,并为类似中药膜剂的研究积累实验数据。
Objective:With Bletillae Rhizoma gelatin as the main film-forming materials,Erhuangsan was developed into a sustained-release double-layer membrane for vagina.Method:Taking hydroxypropyl methyl cellulose(HPMC) and Bletillae Rhizoma gelatin as the film-forming materials of Coptidis Rhizoma-Alumen membrane layer,sodium carboxymethyl cellulose(CMC-Na) and Bletillae Rhizoma gelatin as the film-forming materials of Catechu membrane layer,glycerol as plasticizer,Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane was prepared.Central composite design-response surface methodology was used to optimize formulation of this preparation with appearance quality score,adhesion force and in vitro cumulative release as indexes.Result:Optimum formulation of Catechu membrane layer was 1.61% of CMC-Na,3.81% of Bletillae Rhizoma gelatin and 8.49% of glycerol;optimum formulation of Coptidis Rhizoma-Alumen membrane layer was 1.15% of HPMC,3.41% of Bletillae Rhizoma gelatin and 10.02% of glycerol.Conclusion:The optimized formulation is stable and feasible.Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane has characteristics of advanced dosage form and convenient use,providing a feasible modern Chinese medicine preparation for treatment of cervical cancer,and accumulating data for the research of Chinese medicine film agent.
Objective:With Bletillae Rhizoma gelatin as the main film-forming materials,Erhuangsan was developed into a sustained-release double-layer membrane for vagina.Method:Taking hydroxypropyl methyl cellulose(HPMC) and Bletillae Rhizoma gelatin as the film-forming materials of Coptidis Rhizoma-Alumen membrane layer,sodium carboxymethyl cellulose(CMC-Na) and Bletillae Rhizoma gelatin as the film-forming materials of Catechu membrane layer,glycerol as plasticizer,Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane was prepared.Central composite design-response surface methodology was used to optimize formulation of this preparation with appearance quality score,adhesion force and in vitro cumulative release as indexes.Result:Optimum formulation of Catechu membrane layer was 1.61% of CMC-Na,3.81% of Bletillae Rhizoma gelatin and 8.49% of glycerol;optimum formulation of Coptidis Rhizoma-Alumen membrane layer was 1.15% of HPMC,3.41% of Bletillae Rhizoma gelatin and 10.02% of glycerol.Conclusion:The optimized formulation is stable and feasible.Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane has characteristics of advanced dosage form and convenient use,providing a feasible modern Chinese medicine preparation for treatment of cervical cancer,and accumulating data for the research of Chinese medicine film agent.
引文
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[20]邢树礼,徐燕平,孙迎东,等.复方阿昔洛韦双层缓释膜剂的制备及质量控制[J].中国医院药学杂志,2013,33(18):1068-1071.
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[23]周昌妮,冯青云,徐如冰,等.星点设计-效应面法优化复方葛黄微孔渗透泵片的处方组成[J].中国实验方剂学杂志,2016,22(10):20-24.
[24]王双双,刘睿,何新.星点设计-效应面法优化桔梗泡腾片的处方[J].中国实验方剂学杂志,2016,22(12):23-27.
[25]彭芬芬,黄开合,杜士明.妇科膜剂的研究概况[J].中国药师,2013,16(12):1921-1923.
[26]刘芳,张浩,青琳森.黄连HPLC数字化指纹图谱研究及7种生物碱含量测定[J].中国中药杂志,2013,21(12):3713-3719.
[27]陈芳,邓雁如,许妍妍,等.双波长HPLC同时测定黄连及金芪降糖片中6种生物碱的含量[J].中国实验方剂学杂志,2013,19(17):60-65.
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[29]谢兴亮,杨明,邱雪兰,等.p H-时滞型愈肠宁结肠靶向片的制备及体外释放评价[J].中国中药杂志,2007,32(13):1280-1284.
[30]陈两绵,王锦玉,仝燕,等.黏膜给药原位凝胶的研究进展[J].中国实验方剂学杂志,2008,14(8):76-80.
[2]谭展望.儿黄散对宫颈上皮内瘤变逆转机理的实验研究[D].哈尔滨:黑龙江中医药大学,2006.
[3]韩凤娟,陈惠铮,姜醒,等.儿黄散对宫颈上皮内瘤变小鼠宫颈组织PCNA、EGFR和bcl-2表达的影响[J].山东中医杂志,2006,25(12):835-837.
[4]王建英.儿黄散对宫颈癌Hela细胞凋亡影响的实验研究及对CIN的临床观察[D].哈尔滨:黑龙江中医药大学,2009.
[5]陈海丽.儿黄散治疗CIN临床观察及其诱导宫颈癌Hela细胞凋亡机制实验研究[D].哈尔滨:黑龙江中医药大学,2010.
[6]马宁,韩凤娟,郭蕊,等.儿黄散促进宫颈柱状上皮异位物理治疗后创面修复的临床观察[J].中国中西医结合杂志,2011,31(12):1601-1603.
[7]陈海丽,韩凤娟,宫艳秋,等.中药复方儿黄散对宫颈癌Hela细胞增殖抑制及Bcl-2蛋白表达的影响[J].现代肿瘤医学,2010,18(11):2102-2104.
[8]宋璟璐.儿黄散治疗宫颈柱状上皮异位合并HPV感染LEEP术后的临床研究[D].哈尔滨:黑龙江中医药大学,2013.
[9]赵永伟,王艳宏.白及多糖的研究进展[J].中国中医药科技,2015,22(4):479-481.
[10]侯绪浩,刘学蔚,彭凤梅,等.天然药物材料白及胶制备生物支架材料的实验研究[J].中草药,2013,44(16):2230-2233.
[11]崔殿波,赵永伟,姜继宗,等.儿黄散缓释双层栓的体外释药特性研究[J].中成药,2014,36(8):1619-1625.
[12]刘莉,李泳怡,潘育方.荔枝核多糖脱蛋白工艺考察[J].中国实验方剂学杂志,2012,18(23):52-55.
[13]李晓强,何荣霞,秦龙,等.复方苦参碱阴道生物黏附性栓的制备及质量控制[J].中国医院药学杂志,2014,36(8):1619-1625.
[14]Arts I C W,Hollman P C H,Feskens E J M,et al.Catech in intake and associated dietary and lifestyle factors in a representative sample of Dutch men and women[J].Eur J Clin Nutr,2001,55(2):76-81.
[15]谭晓华,周殿元,张亚历.神经酰胺在儿茶素诱导Lo Vo细胞凋亡中的作用[J].中国药学杂志,2000,35(8):517-520.
[16]狄晓鸿,高英敏,郭红云.黄连素对人宫颈癌Hela细胞株的体外作用研究[J].中国中医药信息杂志,2008,15(1):30-32.
[17]张瑶,郑欢,曹凤光,等.治疗宫颈癌儿黄散温敏凝胶的制备与质量控制[J].哈尔滨商业大学学报:自然科学版,2013,29(2):148-152.
[18]李锐,陈国彪.儿茶HPLC指纹图谱研究[J].广东药学院学报,2011,27(4):388-391.
[19]曲园,张振秋,张杰,等.HPLC法同时测定儿茶青黛复合膜中4个成分的含量[J].药物分析杂志,2013,33(10):1698-1701.
[20]邢树礼,徐燕平,孙迎东,等.复方阿昔洛韦双层缓释膜剂的制备及质量控制[J].中国医院药学杂志,2013,33(18):1068-1071.
[21]崔日新,张蜀,邓红,等.盐酸利多卡因缓释膜的体外释放度测定[J].广东药学院学报,2015,31(6):701-704.
[22]金玲,王锦玉,仝燕,等.五倍子提取物喷雾膜剂体外释放评价[J].中国实验方剂学杂志,2012,18(6):27-29.
[23]周昌妮,冯青云,徐如冰,等.星点设计-效应面法优化复方葛黄微孔渗透泵片的处方组成[J].中国实验方剂学杂志,2016,22(10):20-24.
[24]王双双,刘睿,何新.星点设计-效应面法优化桔梗泡腾片的处方[J].中国实验方剂学杂志,2016,22(12):23-27.
[25]彭芬芬,黄开合,杜士明.妇科膜剂的研究概况[J].中国药师,2013,16(12):1921-1923.
[26]刘芳,张浩,青琳森.黄连HPLC数字化指纹图谱研究及7种生物碱含量测定[J].中国中药杂志,2013,21(12):3713-3719.
[27]陈芳,邓雁如,许妍妍,等.双波长HPLC同时测定黄连及金芪降糖片中6种生物碱的含量[J].中国实验方剂学杂志,2013,19(17):60-65.
[28]洪军辉,乡世健,曹思玮,等.甘草总黄酮微海绵的制备及体外释放度评价[J].中国实验方剂学杂志,2017,23(14):12-18.
[29]谢兴亮,杨明,邱雪兰,等.p H-时滞型愈肠宁结肠靶向片的制备及体外释放评价[J].中国中药杂志,2007,32(13):1280-1284.
[30]陈两绵,王锦玉,仝燕,等.黏膜给药原位凝胶的研究进展[J].中国实验方剂学杂志,2008,14(8):76-80.