苦茶妇科凝胶的工艺研究及流变学参数考察
|
摘要
目的考察苦茶妇科凝胶的制备工艺,制备出在阴道环境中能够快速发生相变的温度敏感型原位凝胶。方法泊洛沙姆P188、P407为凝胶基质,乳酸、乳酸钠为酸缓冲溶液,采用星点设计法筛选原位凝胶的处方工艺,并测定其胶凝温度、胶凝时间、不同酸缓冲溶液对胶凝温度的影响、凝胶稳定性及相关流变学性质。结果在一定用量范围内,泊洛沙姆P188用量增大胶凝温度逐渐升高,泊洛沙姆P407用量增大胶凝温度逐渐下降,通过星点设计优化处方为泊洛沙姆P188的用量为3.51%,P407的用量为17.16%;在体外实验中,不同缓冲液的加入对凝胶的胶凝温度影响偏差在5%以内,但在阴道液中的影响偏差较大,柠檬酸-柠檬酸钠缓冲液在阴道液中的胶凝温度为68.5℃,乳酸-乳酸钠缓冲溶液在阴道液中的胶凝温度为35.8℃;流变学数据表明凝胶在体内滞留性好。结论苦茶妇科凝胶处方工艺符合星点设计模型,筛选工艺可制备出滞留性好,性质稳定的原位凝胶。
Objective To investigate the preparation process of Kucha gynecological gel and prepare a temperature-sensitive in situ gel capable of rapid phase change in vagina. Methods Poloxamer P188 and Poloxamer P407 were used as gel matrix, Lactic acid and sodium lactate were used as the acid buffer solution. The central composite design was performed to optimize the prescription and technology, and the gelation temperature(GT), gelation time, and the effects of different acid buffer solutions on GT, gel stability, and related rheological properties were determined. Results Within a certain concentration range, the gelation temperature was gradually increased with the increase of poloxamer 188 concentration, and the gelation temperature was gradually decreased with the increase of poloxamer 407 concentration, and the optimized prescription by central composite design was poloxamer P188 with a concentration of 3.51% and poloxamer P407 with a concentration of 17.16%. The addition of different buffers has a deviation of 5% of the gelation temperature of the gel in vitro, but the variation in the vaginal fluid is large. The gelation temperatures of the citric acid-sodium citrate buffer and the lactic acid-sodium lactate buffer solution in the vaginal fluid were 68.5 ℃ and 35.8 ℃, respectively, and the rheological data showed that the gel retained better in vivo. Conclusion The Kucha gynecological gel preparation corresponded with the model employed by central composite design, and the screened process can prepare situ gels with good retention and stable properties.
Objective To investigate the preparation process of Kucha gynecological gel and prepare a temperature-sensitive in situ gel capable of rapid phase change in vagina. Methods Poloxamer P188 and Poloxamer P407 were used as gel matrix, Lactic acid and sodium lactate were used as the acid buffer solution. The central composite design was performed to optimize the prescription and technology, and the gelation temperature(GT), gelation time, and the effects of different acid buffer solutions on GT, gel stability, and related rheological properties were determined. Results Within a certain concentration range, the gelation temperature was gradually increased with the increase of poloxamer 188 concentration, and the gelation temperature was gradually decreased with the increase of poloxamer 407 concentration, and the optimized prescription by central composite design was poloxamer P188 with a concentration of 3.51% and poloxamer P407 with a concentration of 17.16%. The addition of different buffers has a deviation of 5% of the gelation temperature of the gel in vitro, but the variation in the vaginal fluid is large. The gelation temperatures of the citric acid-sodium citrate buffer and the lactic acid-sodium lactate buffer solution in the vaginal fluid were 68.5 ℃ and 35.8 ℃, respectively, and the rheological data showed that the gel retained better in vivo. Conclusion The Kucha gynecological gel preparation corresponded with the model employed by central composite design, and the screened process can prepare situ gels with good retention and stable properties.
引文
[1]傅兰勇,熊正爱.需氧性阴道炎的研究进展[J].中国微生态学杂志,2012,24(12):1143-1145.
[2]张春霞,陈庆华.阴道炎治疗药物及其外用制剂研究进展[J].世界临床药物,2010,31(6):381-384.
[3]Ci L,Huang Z,Liu Y,et al.Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties:Preparation,characterization and application in a vaginal drug delivery system[J].Acta Pharm Sin B,2017,7(5):593-602.
[4]马冬冬,孟庆丽,刘红梅,等.阴道黏膜给药系统的研究进展[J].中国药师,2015,18(4):649-651.
[5]Shabir G A.Method development and validation for the GC-FID assay of p-cymene in tea tree oil formulation[J].J Pharm Biomed Anal,2005,39(3/4):681-684.
[6]娄杰,贾运涛,田睿,等.眼用小檗碱白蛋白纳米粒温敏原位凝胶的制备及性质研究[J].中草药,2013,44(3):277-281.
[7]陈海燕,钟昌勇,黄耀恒.我国天然茶树油的研究现状及发展方向[J].生物质化学工程,2003,37(4):35-36.
[8]柴玲,刘布鸣,林霄,等.互叶白千层花、果与叶挥发油成分的对比分析[J].香料香精化妆品,2014,(6):1-4.
[9]钟昌勇,陈海燕.茶树油的应用及市场前景[J].林产化工通讯,2003,37(5):31-34.
[10]曹维,朱建梅,俞励平,等.河源引种互叶白千层精油抗菌实验研究[J].中药材,2013,36(6):988-991.
[11]钟振声,袁裕泉,樊丽妃.引种互叶白千层茶树油有效抑菌成分辨析[J].中山大学学报:自然科学版,2012,51(5):7-13.
[12]黄戈,翁晓晨,张帆,等.互叶白千层的种植和加工研究进展[J].广东化工,2017,44(4):71-73.
[13]Xu J,Shao X,Li Y,et al.Metabolomic analysis and mode of action of metabolites of tea tree oil involved in the suppression of[J].Microbiol,2017(8):1017-1121.
[14]张军芳,韩飞.苦参碱制剂的临床应用研究进展[J].西部中医药,2012,25(5):107-110.
[15]胡珍真,高妍,张杰.苦参凝胶临床应用研究进展[J].中草药,2014,45(21):3204-3207.
[16]李晓红,王玉红.康妇炎胶囊联合苦参碱栓治疗阴道炎的临床研究[J].现代药物与临床,2016,31(8):1220-1223.
[17]赵宇,王晓波,张治然,等.温敏凝胶的研究与应用进展[J].中国药房,2015,26(1):132-135.
[18]张明发,沈雅琴.苦参碱类生物碱的镇痛作用研究进展[J].药物评价研究,2018,41(5):904-911.
[19]Owen D H,Katz D F.A vaginal fluid stimulant[J].Contraception,1999,59(2):91-95.
[20]马凤余,胡容峰,徐亚静.奥洛他定温度敏感眼用原位凝胶的制备[J].中国医院药学杂志,2012,32(11):858.
[21]Chang J Y,Oh Y K,Choi H G.Rheological evaluation of thermosensitiveand mucoadhesive vaginal gels in physiological conditions[J].Int J Pharm,2002,241(1):155-163.
[22]Chen J,Zhou R,Li L.Mechanical,rheological and releasebehaviors of a poloxamer 407/poloxamer 188/carbopol 940 thermosensitive composite hydrogel[J].Molecules,2013,18(10):12415-12425.
[23]王姗姗,曾慧琳,符旭东.雌二醇阴道用生物黏附性温敏型凝胶的处方筛选及流变学考察[J].中国医院药学杂志,2015,35(17):1563-1567.
[24]李燕,赵利刚,王春艳,等.参黄阴道用温敏原位凝胶的制备及质量评价[J].中国药师,2015,18(4):655-659.
[25]徐伟娜,杨清华,王勤,等.温敏型阴道缓冲原位凝胶的制备与质量评价[J].生物医学工程研究,2017,36(2):164-167.
[26]田芳,王玉柱,杨凯,等.尼非韦罗阴道温敏原位凝胶流变学研究[J].中国新药杂志,2017,22(3):345-349.
[2]张春霞,陈庆华.阴道炎治疗药物及其外用制剂研究进展[J].世界临床药物,2010,31(6):381-384.
[3]Ci L,Huang Z,Liu Y,et al.Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties:Preparation,characterization and application in a vaginal drug delivery system[J].Acta Pharm Sin B,2017,7(5):593-602.
[4]马冬冬,孟庆丽,刘红梅,等.阴道黏膜给药系统的研究进展[J].中国药师,2015,18(4):649-651.
[5]Shabir G A.Method development and validation for the GC-FID assay of p-cymene in tea tree oil formulation[J].J Pharm Biomed Anal,2005,39(3/4):681-684.
[6]娄杰,贾运涛,田睿,等.眼用小檗碱白蛋白纳米粒温敏原位凝胶的制备及性质研究[J].中草药,2013,44(3):277-281.
[7]陈海燕,钟昌勇,黄耀恒.我国天然茶树油的研究现状及发展方向[J].生物质化学工程,2003,37(4):35-36.
[8]柴玲,刘布鸣,林霄,等.互叶白千层花、果与叶挥发油成分的对比分析[J].香料香精化妆品,2014,(6):1-4.
[9]钟昌勇,陈海燕.茶树油的应用及市场前景[J].林产化工通讯,2003,37(5):31-34.
[10]曹维,朱建梅,俞励平,等.河源引种互叶白千层精油抗菌实验研究[J].中药材,2013,36(6):988-991.
[11]钟振声,袁裕泉,樊丽妃.引种互叶白千层茶树油有效抑菌成分辨析[J].中山大学学报:自然科学版,2012,51(5):7-13.
[12]黄戈,翁晓晨,张帆,等.互叶白千层的种植和加工研究进展[J].广东化工,2017,44(4):71-73.
[13]Xu J,Shao X,Li Y,et al.Metabolomic analysis and mode of action of metabolites of tea tree oil involved in the suppression of[J].Microbiol,2017(8):1017-1121.
[14]张军芳,韩飞.苦参碱制剂的临床应用研究进展[J].西部中医药,2012,25(5):107-110.
[15]胡珍真,高妍,张杰.苦参凝胶临床应用研究进展[J].中草药,2014,45(21):3204-3207.
[16]李晓红,王玉红.康妇炎胶囊联合苦参碱栓治疗阴道炎的临床研究[J].现代药物与临床,2016,31(8):1220-1223.
[17]赵宇,王晓波,张治然,等.温敏凝胶的研究与应用进展[J].中国药房,2015,26(1):132-135.
[18]张明发,沈雅琴.苦参碱类生物碱的镇痛作用研究进展[J].药物评价研究,2018,41(5):904-911.
[19]Owen D H,Katz D F.A vaginal fluid stimulant[J].Contraception,1999,59(2):91-95.
[20]马凤余,胡容峰,徐亚静.奥洛他定温度敏感眼用原位凝胶的制备[J].中国医院药学杂志,2012,32(11):858.
[21]Chang J Y,Oh Y K,Choi H G.Rheological evaluation of thermosensitiveand mucoadhesive vaginal gels in physiological conditions[J].Int J Pharm,2002,241(1):155-163.
[22]Chen J,Zhou R,Li L.Mechanical,rheological and releasebehaviors of a poloxamer 407/poloxamer 188/carbopol 940 thermosensitive composite hydrogel[J].Molecules,2013,18(10):12415-12425.
[23]王姗姗,曾慧琳,符旭东.雌二醇阴道用生物黏附性温敏型凝胶的处方筛选及流变学考察[J].中国医院药学杂志,2015,35(17):1563-1567.
[24]李燕,赵利刚,王春艳,等.参黄阴道用温敏原位凝胶的制备及质量评价[J].中国药师,2015,18(4):655-659.
[25]徐伟娜,杨清华,王勤,等.温敏型阴道缓冲原位凝胶的制备与质量评价[J].生物医学工程研究,2017,36(2):164-167.
[26]田芳,王玉柱,杨凯,等.尼非韦罗阴道温敏原位凝胶流变学研究[J].中国新药杂志,2017,22(3):345-349.