消脂通脉颗粒的研制
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摘要
目的:研制中药复方制剂消脂通脉颗粒。方法与结果:采用超临界CO2萃取技术提取处方中莪术、炒白术、陈皮的有效成分挥发油,用正交试验,以挥发油收率为指标,优选超临界CO2萃取条件为:萃取压力为25Mpa、温度为45℃、时间为2.5h。为了防止挥发油的挥发损失,增加其稳定性,采用饱和水溶液恒温搅拌法,用β-环糊精对所得挥发油进行包合。以挥发油利用率、包合物收率、包合物含油率的综合评分为指标,用L9(34)正交实验考察的最佳包合条件是:挥发油与β-CD的比例为1:8、50℃包合1小时。处方药物的非挥发性有效成分为醇溶性成分,宜用乙醇提取。以醇提干浸膏得率和臣药泽泻中泽泻醇B23-乙酸酯含量的综合评分为指标,用正交实验优选醇提工艺,结果显示:以加8倍生药量的70%乙醇温浸(50℃)60 min作为第一次提取,第二次提取加6倍生药量的70%乙醇温浸(50℃)30 min为最佳。醇提液的回收乙醇、浓缩与干燥采用减压蒸馏与真空干燥。所得干浸膏含水量控制在4%以内,以达制粒要求。制剂成型工艺进行了最佳赋形剂的用量、矫味剂的用量、润湿剂乙醇的浓度的选择实验,确定薏苡仁细粉的用量为干浸膏重的40%,甜菊素为干浸膏重的5%,乙醇以80%为最佳。按照优选出的制备工艺,进行了三批制剂的中试研究,每批制剂投料量为每日处方量的80倍,进一步验证了优选工艺的稳定可行性。进行了制剂质量标准的研究,建立了半夏、大黄、威灵仙、炒白术、莪术的薄层色谱鉴别方法,斑点清晰,阴性无干扰。通过方法学考察试验,用HPLC法测定制剂中泽泻醇B23-乙酸酯和橙皮苷的含量,规定了含量限度。对样品进行了初步稳定性研究,室温条件下储存三个月,按制订的质量标准进行考察,结果都达到了要求,表明制剂稳定性良好。进行了制剂的药效学和毒理学研究,结果能显著降低家兔血清甘油三酯含量,能显著降低高脂血症大鼠的TC、HDL-C、LDL-C值,表明消脂通脉颗粒有显著的降脂作用,急性毒性试验表明本制剂低毒安全。结论:工艺及质量控制方法切实可行,稳定可靠,药效学及毒理学实验为临床应用提供了理论基础。
Objective: The Preparation and Evaluation of the compound Chinese medicine Xiaozhitongmai. Methods: We extracted the volatile oil from Curcuma and Atractylodes macrocephala and Citri reticulatae by the Supercritical CO2 Fluid extraction.Using the yield of volatile oil as index,we selected the Optimum extraction conditions by the orthogonal test, which were 25MPa(the extracting pressure), 45℃(the extracting temperature ) ,2.5hour(the extracting time). Using the ultizision ratio of oil and the oil-beared ratio and the yield of inclusion compound as indexes , we selected the Optimum conditions for inclusion by the orthogonal test ,which were 1:8(w/w) (the ratio of oilβ-CD ), 50℃(the inclusion temperature),1hour(the inclusion time).To find the best condition of extracting the active constituents of Xiaozhitongmai Granule with alcohol, using the yield of alcohol extractive and content of AlisoB23-acetate as the detective indexes,we selected Optimum extracting conditions by The orthogonal text. Experiments showed best condition was Volume ratio of 1:8(w/w) (the ratio of herbs and 70% alcohol), extracting for 2 times(first times 60min,second times 30 min) and water temperature was 50℃.Extracting solution with alcohol was Concentrated by pressure-reduced distillation and dried in Vacuum dry box. and water-content of alcohol extractive was smaller than 4%. in the Preparation Process,Coix lachrymajobi was used as Cppropriate ,Steviosin was used to correct the taste and 80% alcohol was used as moistening agent.We carried out the dctermination methods of Pinellia Ternata、WeiLing- Xian、Rhubarb、Curcuma and Atractylodes macrocephala through TLC,and the speekles were clear and the negative contrast had no interference.The content of AlisoB23-acetate and Hesperidi was determined through HPLC in XiaoZhiTongMai granule.we studied the stability of Xiaozhitongmai granule,The result showed that the product quality keep stable when beening conserved in room temperature for three months. The study of Pharmacodynamics and toxicology indicated that it held obvious Lowering blood lipids effect and had no toxicity .Conclusion: The well-chosen technology was stable and feasible,the quality of the granule of Xiaozhitongmai can be controlled by the established containation testing method. The study on Pharmacodynamics and toxicology of the granule of Xiaozhitongmai offered a foundation to clinical use.
Objective: The Preparation and Evaluation of the compound Chinese medicine Xiaozhitongmai. Methods: We extracted the volatile oil from Curcuma and Atractylodes macrocephala and Citri reticulatae by the Supercritical CO2 Fluid extraction.Using the yield of volatile oil as index,we selected the Optimum extraction conditions by the orthogonal test, which were 25MPa(the extracting pressure), 45℃(the extracting temperature ) ,2.5hour(the extracting time). Using the ultizision ratio of oil and the oil-beared ratio and the yield of inclusion compound as indexes , we selected the Optimum conditions for inclusion by the orthogonal test ,which were 1:8(w/w) (the ratio of oilβ-CD ), 50℃(the inclusion temperature),1hour(the inclusion time).To find the best condition of extracting the active constituents of Xiaozhitongmai Granule with alcohol, using the yield of alcohol extractive and content of AlisoB23-acetate as the detective indexes,we selected Optimum extracting conditions by The orthogonal text. Experiments showed best condition was Volume ratio of 1:8(w/w) (the ratio of herbs and 70% alcohol), extracting for 2 times(first times 60min,second times 30 min) and water temperature was 50℃.Extracting solution with alcohol was Concentrated by pressure-reduced distillation and dried in Vacuum dry box. and water-content of alcohol extractive was smaller than 4%. in the Preparation Process,Coix lachrymajobi was used as Cppropriate ,Steviosin was used to correct the taste and 80% alcohol was used as moistening agent.We carried out the dctermination methods of Pinellia Ternata、WeiLing- Xian、Rhubarb、Curcuma and Atractylodes macrocephala through TLC,and the speekles were clear and the negative contrast had no interference.The content of AlisoB23-acetate and Hesperidi was determined through HPLC in XiaoZhiTongMai granule.we studied the stability of Xiaozhitongmai granule,The result showed that the product quality keep stable when beening conserved in room temperature for three months. The study of Pharmacodynamics and toxicology indicated that it held obvious Lowering blood lipids effect and had no toxicity .Conclusion: The well-chosen technology was stable and feasible,the quality of the granule of Xiaozhitongmai can be controlled by the established containation testing method. The study on Pharmacodynamics and toxicology of the granule of Xiaozhitongmai offered a foundation to clinical use.
引文
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[6]顾勤,周仲瑛,周晓波,等.血脂清胶囊治疗高脂血症的药效学研究.中医药学刊,2003,(21)3:365-366.
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[12]王亚,陈彦.中药威灵仙研究概况.中药材,2006(29)5:513-515.
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[14]胡国臣.现代中药药理手册.中国中医药出版社,1998年10月第1版:350.
[15]范世忠.药食兼用薏苡仁.药膳食疗,2002,21(5):334.
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[17]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:193-195.
[18]杨文革,刘媛,周劲松,等.姜半夏渗漉工艺研究.中成药,2001(23)8:576-577.
[19]曾建红,彭正松,毛子成,等.半夏生物碱最佳提取条件的研究.中药材,2003,(6)5:361-363.
[20]文红梅,彭国,池玉梅,等.泽泻药材的质量标准研究Ⅰ-泽泻中两种泽泻醇的HPLC测定法.药物分析杂志,1998,18(6): 375-377.
[21]段启,龚千峰,王少军,等.中药饮片泽泻的炮制工艺和质量标准研究.陕西中医学院学报,2004,(27)3:51-52.
[22]李艳,胡广利.降血脂中药—泽泻的最佳提取条件研究.海峡药学,2005,(17)2:86-87.
[23]高素琴,朱春林.莪术挥发油提取工艺优化试验研究.时珍国医国药研究,2000,(11)10:46 .
[24]沈雪梅,李勇,何伟.均匀设计法优选莪术挥发油提取工艺的研究.齐鲁药事,2006,(25)4:246-247.
[25]刘红梅,李可意.均匀设计和回归分析优选莪术超临界萃取工艺.中成药,2006(28)3:326-328.
[26]王道平,张雪琴,周欣,等.正交试验研究莪术挥发油的提取工艺.中成药,2005,(27)9:1085-1086.
[27]李瑞明,岑帼英,邝翠仪,等.正交法优选陈皮挥发油提取工艺.制剂技术,2006,(15)1:47.
[28]于莲,焦淑清,李玉环,等.陈皮挥发油超临界CO2萃取工艺研究.黑龙江医药,2005,28(5):5-6.
[29]李行利,郭秋月.陈皮提取工艺研究.中成药,1997,(19)1: 6-8.
[30]周建国,邵青,陈柳蓉.陈皮提取工艺的优化选择.中国现代应用药学杂志,1998,(15)2:17-18.
[31]卢静华,王亚娟,于玲.陈皮中橙皮苷超声提取工艺研究.时珍国医国药研究,2006,(17)4:604.
[32]左锦静,陈复生,姚永志.陈皮中黄酮类化合物的最佳提取工艺.食品研究与开发,2005,(26)3:61-64.
[33]吴素香,吕圭源,杨万里,等.白术超临界CO2萃取工艺及萃取物的化学成分研究.中成药,2005,(27)8:885-887.
[34]刘斌,石任兵,王伟.蒲黄总黄酮提取方法研究.中成药,2002,(24)2:88-89.
[35]傅大煦,王玮,程小卫,等.蒲黄的黄酮类成分提取工艺研究.中成药,2005,(27)5:517-518.
[36]张兆旺.中药药剂学.北京:中国中医药出版社,2003年1月第1版:111.
[37]董方言.现代实用中药新剂型新技术.北京:人民卫生出版社,2001,第一版:568
[38]李丹,许江,夏顺宁,等.β-环糊精包合莪术挥发油的工艺研究.中药材,2004,(27)11:866-867.
[39]蔡溱,吴丽霞,钟贵陵,等.β-环糊精包合陈皮挥发油的工艺研究.中国中药杂志,603-604.
[40]王晓颖,叶梦屏.陈皮挥发油β-环糊精包合工艺研究.福建中医学院学报,2005,15(2):28-29.
[41]熊阳,刘勇,邓凤君.白术、陈皮挥发油的包合工艺研究.浙江中医学院学报,2005(29)5:93-95.
[42]张兆旺.中药药剂学,北京:中国中医药出版社,2003年1月第1版:97.
[43]张兆旺,中药药剂学,北京:中国中医药出版社,2003年1月第1版:397.
[44]傅佳.半夏泻心颗粒的质量标准研究.中国中医药信息杂志,2006,(13)8:9.
[45]中华人民共和国药典委员会.中国药典一部.北京:人民卫生出版社, 2005:17.
[46]中华人民共和国药典委员会.中国药典一部.北京:人民卫生出版社, 2005:175.
[47]中华人民共和国药典委员会.中国药典一部.北京:人民卫生出版社, 2005:68.
[48]刘汉清,刘洪波.戕麟口服液的药剂学研究.中成药,1995,(17)5:6.
[49]李仪奎,中药药理实验方法学,上海科学出版社,1991:397.
[2]玄瑞英,杨光全.高脂血症的病因及证治探析.实用中医内科杂志, 2006, 20(1): 32 .
[3]杨莹.浅谈肾虚和痰瘀与高脂血症的关系.江西中医药, 2006, 37(2): 11.
[4]黄质诚.高脂血症的中医药治疗近况.中国社区医师,2007年第10期:12.
[5]张秋霞,吴明珠.柴泽合剂治疗高脂血症的临床研究.北京中药杂志,2003,(22)3:48-49.
[6]顾勤,周仲瑛,周晓波,等.血脂清胶囊治疗高脂血症的药效学研究.中医药学刊,2003,(21)3:365-366.
[7]刘青云.中药药理学.人民卫生出版社,2002年2月第2版: 200-201.
[8]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:130-131.
[9]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:180-181.
[10]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:150-152.
[11]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:96-99.
[12]王亚,陈彦.中药威灵仙研究概况.中药材,2006(29)5:513-515.
[13]梅全喜,毕焕新.现代中药药理手册.中国中医药出版社,1998年10月第1版:379 .
[14]胡国臣.现代中药药理手册.中国中医药出版社,1998年10月第1版:350.
[15]范世忠.药食兼用薏苡仁.药膳食疗,2002,21(5):334.
[16]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:248.
[17]刘青云.中药药理学.人民卫生出版社,2002年2月第2版:193-195.
[18]杨文革,刘媛,周劲松,等.姜半夏渗漉工艺研究.中成药,2001(23)8:576-577.
[19]曾建红,彭正松,毛子成,等.半夏生物碱最佳提取条件的研究.中药材,2003,(6)5:361-363.
[20]文红梅,彭国,池玉梅,等.泽泻药材的质量标准研究Ⅰ-泽泻中两种泽泻醇的HPLC测定法.药物分析杂志,1998,18(6): 375-377.
[21]段启,龚千峰,王少军,等.中药饮片泽泻的炮制工艺和质量标准研究.陕西中医学院学报,2004,(27)3:51-52.
[22]李艳,胡广利.降血脂中药—泽泻的最佳提取条件研究.海峡药学,2005,(17)2:86-87.
[23]高素琴,朱春林.莪术挥发油提取工艺优化试验研究.时珍国医国药研究,2000,(11)10:46 .
[24]沈雪梅,李勇,何伟.均匀设计法优选莪术挥发油提取工艺的研究.齐鲁药事,2006,(25)4:246-247.
[25]刘红梅,李可意.均匀设计和回归分析优选莪术超临界萃取工艺.中成药,2006(28)3:326-328.
[26]王道平,张雪琴,周欣,等.正交试验研究莪术挥发油的提取工艺.中成药,2005,(27)9:1085-1086.
[27]李瑞明,岑帼英,邝翠仪,等.正交法优选陈皮挥发油提取工艺.制剂技术,2006,(15)1:47.
[28]于莲,焦淑清,李玉环,等.陈皮挥发油超临界CO2萃取工艺研究.黑龙江医药,2005,28(5):5-6.
[29]李行利,郭秋月.陈皮提取工艺研究.中成药,1997,(19)1: 6-8.
[30]周建国,邵青,陈柳蓉.陈皮提取工艺的优化选择.中国现代应用药学杂志,1998,(15)2:17-18.
[31]卢静华,王亚娟,于玲.陈皮中橙皮苷超声提取工艺研究.时珍国医国药研究,2006,(17)4:604.
[32]左锦静,陈复生,姚永志.陈皮中黄酮类化合物的最佳提取工艺.食品研究与开发,2005,(26)3:61-64.
[33]吴素香,吕圭源,杨万里,等.白术超临界CO2萃取工艺及萃取物的化学成分研究.中成药,2005,(27)8:885-887.
[34]刘斌,石任兵,王伟.蒲黄总黄酮提取方法研究.中成药,2002,(24)2:88-89.
[35]傅大煦,王玮,程小卫,等.蒲黄的黄酮类成分提取工艺研究.中成药,2005,(27)5:517-518.
[36]张兆旺.中药药剂学.北京:中国中医药出版社,2003年1月第1版:111.
[37]董方言.现代实用中药新剂型新技术.北京:人民卫生出版社,2001,第一版:568
[38]李丹,许江,夏顺宁,等.β-环糊精包合莪术挥发油的工艺研究.中药材,2004,(27)11:866-867.
[39]蔡溱,吴丽霞,钟贵陵,等.β-环糊精包合陈皮挥发油的工艺研究.中国中药杂志,603-604.
[40]王晓颖,叶梦屏.陈皮挥发油β-环糊精包合工艺研究.福建中医学院学报,2005,15(2):28-29.
[41]熊阳,刘勇,邓凤君.白术、陈皮挥发油的包合工艺研究.浙江中医学院学报,2005(29)5:93-95.
[42]张兆旺.中药药剂学,北京:中国中医药出版社,2003年1月第1版:97.
[43]张兆旺,中药药剂学,北京:中国中医药出版社,2003年1月第1版:397.
[44]傅佳.半夏泻心颗粒的质量标准研究.中国中医药信息杂志,2006,(13)8:9.
[45]中华人民共和国药典委员会.中国药典一部.北京:人民卫生出版社, 2005:17.
[46]中华人民共和国药典委员会.中国药典一部.北京:人民卫生出版社, 2005:175.
[47]中华人民共和国药典委员会.中国药典一部.北京:人民卫生出版社, 2005:68.
[48]刘汉清,刘洪波.戕麟口服液的药剂学研究.中成药,1995,(17)5:6.
[49]李仪奎,中药药理实验方法学,上海科学出版社,1991:397.