金玄痔科熏洗散药效物质及其作用机理研究
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摘要
金玄痔科熏洗散是中药六类新药,是马应龙药业集团的独家品种,于09年开始上市销售,临床用于各种痔疮术后肿胀、疼痛、嵌顿痔、混合痔等的治疗,疗效显著,得到了医生和患者的高度认可。该中药复方制剂由金银花、枯矾、玄明粉、马齿苋、荆芥五味中药组方制成,具有清热解毒、祛风燥湿、消肿止痛的功效。但是,虽然临床疗效确切,由于金玄痔科熏洗散为传统生产工艺制备,存在质量控制标准不完善,物质基础不明确等问题,且临床使用剂量大导致生产成本较高。
本论文采用现代科学技术,通过多学科交叉的研究方法,对金玄痔科熏洗散抗炎止痒的药效物质进行了研究,探讨了其抗炎的作用机理,诠释了金玄痔科熏洗散的药效物质基础,即该中药品种是什么物质发挥作用和如何发挥作用,这是中药现代化过程中需要解决的两个关键性问题。本课题的研究结果为金玄痔科熏洗散的临床疗效和市场销售提供了科学依据,可更好的指导临床推广,提高市场销售份额,产生更好的经济效益和社会效益。
在中医药理论指导下,将该中药复方制剂方中三味植物药视为整体,采用中药现代化共性关键技术,即超临界CO2萃取技术和大孔吸附树脂纯化技术,将其提取分离为不同的化学物质部位,即大孔吸附树脂水洗脱物质部位、大孔吸附树脂乙醇洗脱物质部位、超临界CO2萃取物。通过对上述部位进行药理试验筛选,确定了金玄痔科熏洗散有效物质部位群为超临界CO2萃取物和大孔吸附树脂乙醇洗脱物质部位及矿物药。
通过二甲苯所致小鼠耳肿胀,蛋清诱发的大鼠足肿胀和磷酸组织胺所致大鼠致痒阈的药理试验,将有效物质部位按处方生药配伍比例配伍,与金玄痔科熏洗散原制剂进行抗炎止痒的药理比较研究。结果表明,有效物质部位配伍的药效与原制剂药效相似,从而为金玄痔科熏洗散的二次开发,减少处方用量和降低成本提供了理论依据。
采用二甲苯诱导去肾上腺小鼠的耳肿胀模型、CMC所致气囊灌洗液中白细胞游走和角叉菜胶诱导的腹膜炎的炎症模型,对金玄痔科熏洗散药效物质的抗炎作用机理进行了研究。结果表明,金玄痔科熏洗散的药效物质是通过依赖垂体-肾上腺皮质轴、影响PGE2的释放、抑制炎症部位的白细胞数目、降低炎性因子而综合发挥抗炎作用,从而进一步诠释了该中药复方制剂的药效物质基础。
采用气-质联用(GC-MS)分析方法,对该中药复方制剂方中植物药超临界CO2萃取物进行了分离和鉴定；采用电位返滴定法和紫外可见分光光度法,对该中药复方制剂方中植物药提取后,经大孔吸附树脂纯化的有效物质部位中的总皂苷、总黄酮和总有机酸进行了含量测定,建立了可靠性强的含量方法。上述方中植物药的药效物质研究,为阐释该中药复方制剂的药效物质基础提供了依据,并为有效控制金玄痔科熏洗散的质量,完善其质量标准提供了理论依据。
本论文的研究围绕金玄痔科熏洗散抗炎药效物质基础及作用机理展开,为该中药复方制剂的临床疗效提供了科学依据,并为临床推广提供了学术依据,以期提高金玄痔科熏洗散的市场竞争力,创造更好的经济效益和社会效益,同时为其二次开发成创新中药品种奠定了一定基础。
Jinxuan Zhike Xunxi San is New Traditional Chinese MedicineⅥ, which is exclusive species of Mayinglong Pharmaceutical Group Co., LTD and has sold more than a year. In clinical it could be used to cure kinds of hemorrhoid such as external hemorrhoids, incarcerated hemorrhoid, combined hemorrhoid, et al. This preparation is composed of Natrii Sulfas Exsiccatus、Herba Portulacae、Flos Lonicerae Japonicae、Calcine Alumen、Herba Schizonepetae that can clear away heat and toxic material, expel pathogenic wind, swelling, ease pain. But Jinxuan Zhike Xunxi San uses the tradition manufacturing technique, which has many problems, such as the quality control standard is unperfect, the material base of pharmacal efficacy is not explicit and so on. In addition, the oversized dosage leads to high production costs.
The paper applies the research techniques of the multi-disciplinary overlapping, and uses the modern science and technology, has conducted the research to the efficacy substance of anti inflammatory and antipruritic of Jinxuan Zhike Xunxi San, has discussed the mechanism of its anti-inflammatory, has interpreted the material basis for efficacy of Jinxuan Zhike Xunxi San that what the substances play a role are and how to play a role, which are two critical issues that need to be addressed.
Under the guidance of Chinese medicine theory, Three taste plant medicines were regarded as a whole in this traditional Chinese medicine preparation, we used common key technologies in modern Chinese medicine theory, Which are the pocket polymeric adsorbent purification technology and the supercritical CO2 extract technology, its extraction was separated into different chemical substance spot which are the material of supercritical CO2 extract, pocket polymeric adsorbent ethyl alcohol elution spot,and pocket polymeric adsorbent water elution spot.
By pharmacological study of the Wistar rat foot swelling experiments, xylene-induced ear edema in mouse experiments and itching threshold caused by histamine phosphate in the Wistar rat, the results show that the efficacy of the reconstituted effective substance compared with the original preparation is similar, so it provide a reference for reforming the traditional production process of Jinxuan Zhike Xunxi San.
Using tumescent ear model in mice without adrenal induced by xylene, the migration of leukocytes in air chamber because of CMC and the peritonitis inflammation model induced by carrageenan, We studied on the anti-inflammatory mechanism of efficacy substances in Jinxuan Zhike Xunxi San. The results indicats that efficacy substances in Jinxuan Zhike Xunxi San play an anti-inflammatory effects through depending on pituitary-adrenal axis, affecting on the release of PGE2, inhibiting the leukocyte's number of sites of inflammation, reducing inflammatory factors, further interpreting the efficacy material basis of the traditional Chinese medicine.
Anlysising by gas chromatography-mass spectrometry (GC-MS),we isolated and identified chemical compositions of supercritical C02 extractive from Jinxuan Zhike Xunxi San After extracting three herbals in Jinxuan Zhike Xunxi San,we determined flavonoids, saponins and total organic acids purified through macroporous resin in effective fraction by UV-visible spectrophotometry and potential back titration method, and established a reliable method for the determination. Above methods in the study on efficacy substances provide the basis for the material basis in the Chinese herbal compound, and improve the quality standards of Jinxuan Zhike Xunxi San. It provides the basis for effectivly controlling the quality of the traditional Chinese medicine products.
The research findings of this paper interpret Jinxuan Zhike Xunxi San'material basis of anti-inflammatory effecacy and mechanism. They provide a scientific basis for the Chinese herbal compound'clinical effact, and a academic basis for clinical promotion to improve the market competitiveness of Jinxuan Zhike Xunxi San and create a better economic and social benefits. At the meantime, it lays a certain foundation for the secondary development into a variety of innovative raditional Chinese medicines.
本论文采用现代科学技术,通过多学科交叉的研究方法,对金玄痔科熏洗散抗炎止痒的药效物质进行了研究,探讨了其抗炎的作用机理,诠释了金玄痔科熏洗散的药效物质基础,即该中药品种是什么物质发挥作用和如何发挥作用,这是中药现代化过程中需要解决的两个关键性问题。本课题的研究结果为金玄痔科熏洗散的临床疗效和市场销售提供了科学依据,可更好的指导临床推广,提高市场销售份额,产生更好的经济效益和社会效益。
在中医药理论指导下,将该中药复方制剂方中三味植物药视为整体,采用中药现代化共性关键技术,即超临界CO2萃取技术和大孔吸附树脂纯化技术,将其提取分离为不同的化学物质部位,即大孔吸附树脂水洗脱物质部位、大孔吸附树脂乙醇洗脱物质部位、超临界CO2萃取物。通过对上述部位进行药理试验筛选,确定了金玄痔科熏洗散有效物质部位群为超临界CO2萃取物和大孔吸附树脂乙醇洗脱物质部位及矿物药。
通过二甲苯所致小鼠耳肿胀,蛋清诱发的大鼠足肿胀和磷酸组织胺所致大鼠致痒阈的药理试验,将有效物质部位按处方生药配伍比例配伍,与金玄痔科熏洗散原制剂进行抗炎止痒的药理比较研究。结果表明,有效物质部位配伍的药效与原制剂药效相似,从而为金玄痔科熏洗散的二次开发,减少处方用量和降低成本提供了理论依据。
采用二甲苯诱导去肾上腺小鼠的耳肿胀模型、CMC所致气囊灌洗液中白细胞游走和角叉菜胶诱导的腹膜炎的炎症模型,对金玄痔科熏洗散药效物质的抗炎作用机理进行了研究。结果表明,金玄痔科熏洗散的药效物质是通过依赖垂体-肾上腺皮质轴、影响PGE2的释放、抑制炎症部位的白细胞数目、降低炎性因子而综合发挥抗炎作用,从而进一步诠释了该中药复方制剂的药效物质基础。
采用气-质联用(GC-MS)分析方法,对该中药复方制剂方中植物药超临界CO2萃取物进行了分离和鉴定；采用电位返滴定法和紫外可见分光光度法,对该中药复方制剂方中植物药提取后,经大孔吸附树脂纯化的有效物质部位中的总皂苷、总黄酮和总有机酸进行了含量测定,建立了可靠性强的含量方法。上述方中植物药的药效物质研究,为阐释该中药复方制剂的药效物质基础提供了依据,并为有效控制金玄痔科熏洗散的质量,完善其质量标准提供了理论依据。
本论文的研究围绕金玄痔科熏洗散抗炎药效物质基础及作用机理展开,为该中药复方制剂的临床疗效提供了科学依据,并为临床推广提供了学术依据,以期提高金玄痔科熏洗散的市场竞争力,创造更好的经济效益和社会效益,同时为其二次开发成创新中药品种奠定了一定基础。
Jinxuan Zhike Xunxi San is New Traditional Chinese MedicineⅥ, which is exclusive species of Mayinglong Pharmaceutical Group Co., LTD and has sold more than a year. In clinical it could be used to cure kinds of hemorrhoid such as external hemorrhoids, incarcerated hemorrhoid, combined hemorrhoid, et al. This preparation is composed of Natrii Sulfas Exsiccatus、Herba Portulacae、Flos Lonicerae Japonicae、Calcine Alumen、Herba Schizonepetae that can clear away heat and toxic material, expel pathogenic wind, swelling, ease pain. But Jinxuan Zhike Xunxi San uses the tradition manufacturing technique, which has many problems, such as the quality control standard is unperfect, the material base of pharmacal efficacy is not explicit and so on. In addition, the oversized dosage leads to high production costs.
The paper applies the research techniques of the multi-disciplinary overlapping, and uses the modern science and technology, has conducted the research to the efficacy substance of anti inflammatory and antipruritic of Jinxuan Zhike Xunxi San, has discussed the mechanism of its anti-inflammatory, has interpreted the material basis for efficacy of Jinxuan Zhike Xunxi San that what the substances play a role are and how to play a role, which are two critical issues that need to be addressed.
Under the guidance of Chinese medicine theory, Three taste plant medicines were regarded as a whole in this traditional Chinese medicine preparation, we used common key technologies in modern Chinese medicine theory, Which are the pocket polymeric adsorbent purification technology and the supercritical CO2 extract technology, its extraction was separated into different chemical substance spot which are the material of supercritical CO2 extract, pocket polymeric adsorbent ethyl alcohol elution spot,and pocket polymeric adsorbent water elution spot.
By pharmacological study of the Wistar rat foot swelling experiments, xylene-induced ear edema in mouse experiments and itching threshold caused by histamine phosphate in the Wistar rat, the results show that the efficacy of the reconstituted effective substance compared with the original preparation is similar, so it provide a reference for reforming the traditional production process of Jinxuan Zhike Xunxi San.
Using tumescent ear model in mice without adrenal induced by xylene, the migration of leukocytes in air chamber because of CMC and the peritonitis inflammation model induced by carrageenan, We studied on the anti-inflammatory mechanism of efficacy substances in Jinxuan Zhike Xunxi San. The results indicats that efficacy substances in Jinxuan Zhike Xunxi San play an anti-inflammatory effects through depending on pituitary-adrenal axis, affecting on the release of PGE2, inhibiting the leukocyte's number of sites of inflammation, reducing inflammatory factors, further interpreting the efficacy material basis of the traditional Chinese medicine.
Anlysising by gas chromatography-mass spectrometry (GC-MS),we isolated and identified chemical compositions of supercritical C02 extractive from Jinxuan Zhike Xunxi San After extracting three herbals in Jinxuan Zhike Xunxi San,we determined flavonoids, saponins and total organic acids purified through macroporous resin in effective fraction by UV-visible spectrophotometry and potential back titration method, and established a reliable method for the determination. Above methods in the study on efficacy substances provide the basis for the material basis in the Chinese herbal compound, and improve the quality standards of Jinxuan Zhike Xunxi San. It provides the basis for effectivly controlling the quality of the traditional Chinese medicine products.
The research findings of this paper interpret Jinxuan Zhike Xunxi San'material basis of anti-inflammatory effecacy and mechanism. They provide a scientific basis for the Chinese herbal compound'clinical effact, and a academic basis for clinical promotion to improve the market competitiveness of Jinxuan Zhike Xunxi San and create a better economic and social benefits. At the meantime, it lays a certain foundation for the secondary development into a variety of innovative raditional Chinese medicines.
引文
[1]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的药效学作用研究：抗炎作用.
[2]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的药效学作用研究：镇痛作用.
[3]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的药效学作用研究：抑菌作用.
[4]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的药效学作用研究：局部感染试验.
[5]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的药效学作用研究：止血作用.
[6]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的毒理作用研究：急性毒性试验.
[7]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的毒理作用研究：长期毒性试验.
[8]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的毒理作用研究：直肠刺激性试验.
[9]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的毒理作用研究：皮肤刺激性试验.
[10]金玄痔科熏洗散中药新品种申报资料,金玄痔科熏洗散的毒理作用研究：豚鼠皮肤过敏试验.
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