机构地区:[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,四川成都611137 [2]四川省中医药科学院,国家中医药管理局中药质量生物评价重点研究室,四川成都610041 [3]大理大学药学与化学学院,云南大理671000 [4]成都永康制药有限公司,四川成都611137 [5]中国人民解放军总医院第五医学中心,全军中医药研究所,北京100039 [6]江西中医药大学,江西南昌330004
出 处:《药学学报》2019年第12期2195-2203,共9页Acta Pharmaceutica Sinica
基 金:国家自然科学基金面上项目(81873232,81573676);成都中医药大学中药学学科特色创新科研团队(CXTD2018006);四川省科技厅应用基础研究项目(2019YJ0640)
摘 要:以中医临床治疗乳腺增生的首选中成药小金丸为例,对比生物活性检定与化学指纹图谱在小金丸整体质量评价中的适宜性与科学性。测定小金丸抗血小板聚集生物效价与环氧化酶2(cyclooxygenase-2,COX-2)抑制率,建立小金丸脂溶性和水溶性双部位指纹图谱,对A、B 2个厂家16个批次市售小金丸进行指纹图谱分析,对比研究小金丸在生物活性和化学分析层面的一致性。本研究动物实验方案已获成都中医药大学附属医院实验动物伦理学委员会批准(批准号:2018BL-002)。结果表明,16个批次小金丸的抗血小板聚集生物效价在0.712~1.278 U·mg^-1,相对标准偏差(RSD)为15.4%;COX-2抑制率在52.07%~68.95%,RSD为8.91%,结果显示生物效应差异较小,生物活性一致性较好。16个批次小金丸指纹图谱相似度差,近一半样品相似度小于0.9,共有峰峰面积在各样品中RSD达32.74%~165.37%,化学一致性差。为探究小金丸生物活性一致性好而化学一致性差的原因,对指纹图谱色谱进行多元统计分析,筛选影响相似度的主要色谱峰,并进行色谱峰药材归属指认。结果显示各批次小金丸的相似度主要受脂溶性指纹图谱中面积较大的17、18、20、23、27号色谱峰,水溶性部分30号峰的影响,经鉴定这些色谱峰属于枫香脂和当归。进一步研究不同浓度枫香脂、当归抗血小板聚集与抑制COX-2活性的作用,结果表明在小金丸组方比例下,枫香脂、当归几乎没有抗血小板聚集和抑制COX-2活性的作用。本研究发现化学指纹图谱用于小金丸质量一致性评价存在一定的局限性,部分丰度高、光谱响应强、活性弱的色谱峰成为影响评价结果的主要因素,选择反映临床功效的生物评价方法能很好弥补化学评价方法的不足,为复杂中成药的整体质量评价提供新思路与方法。Xiaojin pills,the first choice for clinical treatment of breast hyperplasia,were selected to explore the suitability of a bioactivity assay with chemical fingerprinting for the development of an overall quality evaluation assay.The liposoluble and water-soluble fraction fingerprints of Xiaojin pills were established.The ability to inhibit platelet aggregation and the rate of inhibition of cyclooxygenase-2(COX-2)for 16 batches of Xiaojin pills from several manufacturers was analyzed;the chemical fingerprints of these samples were correlated with the bioactivity and chemical analysis.The animal protocol was approved by the Committee on the Ethics of Animal Experiments of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Approval,ID:2018BL-002.Results showed that the antiplatelet aggregation activity of 16 batches was 0.712-1.278 U∙mg^-1,with a relative standard deviation(RSD)of 15.4%.COX-2 inhibition was 52.07%-68.95%and the RSD was 8.91%.The results showed that there was little difference in the biological effects of these samples.However,the chemical fingerprint consistency of these 16 batches of Xiaojin pills was poor,and the similarity of nearly half of the samples was less than 0.9.The total peak area of Xiaojin pills was 32.74%-165.37%across samples,showing very poor chemical consistency.In order to explore the reasons for the poor chemical consistency despite good consistency in the biological assays,the fingerprint chromatogram was analyzed by multivariate statistical analysis.The main chromatographic peaks were identified.The results showed that the similarity of Xiaojin pills was mainly determined by the prominent chromatographic peaks 17,18,20,23 and 27 in the liposoluble fingerprints,which were identified from Liquidambaris resina and Angelica sinensis Radix.However,Liquidambaris resina and Angelicae sinensis Radix had almost no anti-platelet aggregation activity or COX-2 inhibitory effect at the normal prescription ratio.As a result,the ability to utilize chemical fingerprints
关 键 词:小金丸 质量评价 指纹图谱 抗血小板聚集 COX-2抑制率
分 类 号:R917[医药卫生—药物分析学]
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...