姜黄挥发油羟丙基-β-环糊精包合物的制备、稳定性及其抗真菌活性
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摘要
目的制备姜黄挥发油羟丙基-β-环糊精(HP-β-CD)包合物,并对包合物进行稳定性及抗真菌活性研究。方法以包合物收率和姜黄挥发油包合率为综合评价指标,筛选出姜黄挥发油HP-β-CD包合物的最佳制备方法,并采用正交实验优化该制备方法的工艺参数。采用紫外光谱、红外光谱、薄层鉴别、显微鉴别对包合物进行表征分析,并考察包合物在光照、高温、高湿条件下的稳定性,同时对姜黄挥发油及其包合物的抗真菌活性进行研究。结果研磨法为最佳制备方法,其最优包合工艺参数为HP-β-CD与姜黄挥发油比例8∶1 (g·m L~(-1)), HP-β-CD与水比例4∶1 (g·m L~(-1)),研磨时间60 min。包合物收率为95.2%(RSD=1.37%, n=3),姜黄挥发油包合率为85.6%(RSD=1.20%, n=3); 4种表征实验均表明包合物已生成,且具有一定的稳定性;姜黄挥发油及其包合物对红色毛癣菌、絮状表皮癣菌、石膏样小孢子菌和黄曲霉的最小抑菌浓度(MIC)分别为0.8μL·m L~(-1)和0.4μL·m L~(-1)。结论将姜黄挥发油制备成HP-β-CD包合物,工艺稳定可行,且具有较强的抗真菌活性,该研究为其医院制剂开发及临床应用提供了实验基础。
AIM To prepare Curcuma longa volatile oil/hydroxypropyl-β-cyclodextrin( HP-β-CD inclusion compound and investigate its stability and antifungal activity. METHODS Using the yield of inclusion compound and the inclusion rate of volatile oil as comprehensive evaluation index, the best preparation method of volatile oil/HP-β-CD inclusion compound was screened out, and its process parameters were optimized by the orthogonal experiment. The stability of inclusion compound was studied under conditions of strong light, high temperature and high humidity, which was characterized using UV, IR, TLC identification and microscopic identification. Antifungal activity of volatile oil and its inclusion compound were investigated. RESULTS Grinding method was the best preparation method, and its optimum inclusion process parameters were as follows: the ratio of HP-β-CD to volatile oil was 8 ∶ 1(g·mL~(~(-1))), the ratio of HP-β-CD to water was 4 ∶ 1(g·m L~(~(-1))) and the grinding time was 60 mins. The yield of inclusion compound was 95.2%(RSD = 1.37%, n = 3)and inclusion rate of volatile oil was 85.6%(RSD = 1.20%, n = 3). Four kinds of characterization experiments indicated that inclusion compound with certain stability had been formed. Minimum inhibitory concentration( MIC) of volatile oil and its inclusion compound against Trichophyton rubrum, Epidermophyton floccosum,Microsporum gypseum and Aspergillus flavus were 0.8 μL·mL~(~(-1)) and 0.4 μL·mL~(~(-1)), respectively. CONCLUSION The optimal inclusion process of Curcuma longa volatile oil/HP-β-CD was stable and feasible, and inclusion compound had stronger antifungal activity than volatile oil. This study provided an experimental basis for the development of the hospital preparation and clinical application of Curcuma longa volatile oil.
AIM To prepare Curcuma longa volatile oil/hydroxypropyl-β-cyclodextrin( HP-β-CD inclusion compound and investigate its stability and antifungal activity. METHODS Using the yield of inclusion compound and the inclusion rate of volatile oil as comprehensive evaluation index, the best preparation method of volatile oil/HP-β-CD inclusion compound was screened out, and its process parameters were optimized by the orthogonal experiment. The stability of inclusion compound was studied under conditions of strong light, high temperature and high humidity, which was characterized using UV, IR, TLC identification and microscopic identification. Antifungal activity of volatile oil and its inclusion compound were investigated. RESULTS Grinding method was the best preparation method, and its optimum inclusion process parameters were as follows: the ratio of HP-β-CD to volatile oil was 8 ∶ 1(g·mL~(~(-1))), the ratio of HP-β-CD to water was 4 ∶ 1(g·m L~(~(-1))) and the grinding time was 60 mins. The yield of inclusion compound was 95.2%(RSD = 1.37%, n = 3)and inclusion rate of volatile oil was 85.6%(RSD = 1.20%, n = 3). Four kinds of characterization experiments indicated that inclusion compound with certain stability had been formed. Minimum inhibitory concentration( MIC) of volatile oil and its inclusion compound against Trichophyton rubrum, Epidermophyton floccosum,Microsporum gypseum and Aspergillus flavus were 0.8 μL·mL~(~(-1)) and 0.4 μL·mL~(~(-1)), respectively. CONCLUSION The optimal inclusion process of Curcuma longa volatile oil/HP-β-CD was stable and feasible, and inclusion compound had stronger antifungal activity than volatile oil. This study provided an experimental basis for the development of the hospital preparation and clinical application of Curcuma longa volatile oil.
引文
[1]国家药典委员会.中华人民共和国药典:2015年版.一部[M].北京:中国医药科技出版社, 2015:264-265.
[2] PINO JA, FON-FAY FM, PEREZ JC, et al. Chemical composition and biological activities of essential oil from turmeric(Curcuma longa L.)rhizomes grown in Amazonian Ecuador[J]. Revista CENIC Ciencias Quimicas, 2018, 49:1-8.
[3] AGGARWAL BB, HARIKUMAR KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic,autoimmune and neoplastic diseases[J]. Int J Biochem Cell B,2009, 41(1):40-59.
[4] KIM TH, JIANG HH, YOUN YS, et al. Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity[J]. Int J Pharm,2011, 403(1-2):285-291.
[5] SURWASE VS, LADDHA KS, KALE RV, et al. Extraction and isolation of turmerone from turmeric[J]. J Agr Food Chem, 2011,10(5):2173-2179.
[6]钱江,邓俊,李勤妹,等.姜黄挥发油乳膏治疗糠秕孢子菌性囊炎疗效观察[J].中医学报, 2013, 28(B08):11.
[7]吴洲.复方姜黄浸剂治疗皮肤癣菌病疗效观察[J].中华现代皮肤科学杂志, 2005, 2(1):72-73.
[8]杜青云,胡永狮.复方姜黄挥发油中空栓的制备和临床疗效观察[J].药学实践杂志, 2002, 20(4):204-206.
[9]马娟,陈树和,朱田密,等.荷泽颗粒中苍术、枳实挥发油的提取及β-环糊精包合工艺研究[J].中国药房, 2016, 27(13):1839-1841.
[10]陈积,胡姗姗,钱英,等.复方莪术油β-环糊精包合物的制备工艺及稳定性研究[J].辽宁中医杂志, 2018, 45(1):131-134.
[11]李明玥,倪健,尹兴斌.改善中药口服生物利用度的制剂技术研究进展[J].中华中医药学刊, 2016, 34(2):307-311.
[12]张超,韩丽,欧小群,等.姜黄挥发油β-环糊精包合物的制备与验证及稳定性考察[J].中药与临床, 2015, 6(3):10-13.
[13] DESHMUKH MM, BARTOLOTTI LJ, GADRE SR. Intramolecular hydrogen bond energy and cooperative interactions inα-,β-,andγ-cyclodextrin conformers[J]. J Comput Chem, 2011, 32(14):2996-3004.
[14]郑德俊,潘娅.马钱子碱羟丙基-β-环糊精包合前后对佐剂性关节炎大鼠足跖肿胀度的作用比较[J].中国实验方剂学杂志, 2015, 21(1):174-177.
[15] LIAO Y, ZHANG X, LI C, et al. Inclusion complexes of HP-β-cyclodextrin with agomelatine:preparation, characterization,mechanism study and in vivo evaluation[J]. Carbohydr Polym,2016, 147:415-425.
[2] PINO JA, FON-FAY FM, PEREZ JC, et al. Chemical composition and biological activities of essential oil from turmeric(Curcuma longa L.)rhizomes grown in Amazonian Ecuador[J]. Revista CENIC Ciencias Quimicas, 2018, 49:1-8.
[3] AGGARWAL BB, HARIKUMAR KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic,autoimmune and neoplastic diseases[J]. Int J Biochem Cell B,2009, 41(1):40-59.
[4] KIM TH, JIANG HH, YOUN YS, et al. Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity[J]. Int J Pharm,2011, 403(1-2):285-291.
[5] SURWASE VS, LADDHA KS, KALE RV, et al. Extraction and isolation of turmerone from turmeric[J]. J Agr Food Chem, 2011,10(5):2173-2179.
[6]钱江,邓俊,李勤妹,等.姜黄挥发油乳膏治疗糠秕孢子菌性囊炎疗效观察[J].中医学报, 2013, 28(B08):11.
[7]吴洲.复方姜黄浸剂治疗皮肤癣菌病疗效观察[J].中华现代皮肤科学杂志, 2005, 2(1):72-73.
[8]杜青云,胡永狮.复方姜黄挥发油中空栓的制备和临床疗效观察[J].药学实践杂志, 2002, 20(4):204-206.
[9]马娟,陈树和,朱田密,等.荷泽颗粒中苍术、枳实挥发油的提取及β-环糊精包合工艺研究[J].中国药房, 2016, 27(13):1839-1841.
[10]陈积,胡姗姗,钱英,等.复方莪术油β-环糊精包合物的制备工艺及稳定性研究[J].辽宁中医杂志, 2018, 45(1):131-134.
[11]李明玥,倪健,尹兴斌.改善中药口服生物利用度的制剂技术研究进展[J].中华中医药学刊, 2016, 34(2):307-311.
[12]张超,韩丽,欧小群,等.姜黄挥发油β-环糊精包合物的制备与验证及稳定性考察[J].中药与临床, 2015, 6(3):10-13.
[13] DESHMUKH MM, BARTOLOTTI LJ, GADRE SR. Intramolecular hydrogen bond energy and cooperative interactions inα-,β-,andγ-cyclodextrin conformers[J]. J Comput Chem, 2011, 32(14):2996-3004.
[14]郑德俊,潘娅.马钱子碱羟丙基-β-环糊精包合前后对佐剂性关节炎大鼠足跖肿胀度的作用比较[J].中国实验方剂学杂志, 2015, 21(1):174-177.
[15] LIAO Y, ZHANG X, LI C, et al. Inclusion complexes of HP-β-cyclodextrin with agomelatine:preparation, characterization,mechanism study and in vivo evaluation[J]. Carbohydr Polym,2016, 147:415-425.