發(fā)布時間：2023-03-09 16:12

  本文選題：威麥寧膠囊　切入點：原花青素B2　出處：《南京中醫(yī)藥大學》2014年碩士論文　論文類型：學位論文

【摘要】：威麥寧膠囊為金蕎麥干燥根莖中含有的抗癌活性成份,經(jīng)醇提水沉方法提取后制得的國家二類中藥新藥保護品種。具有清熱解毒、活血化瘀、驅(qū)邪扶正等作用。臨床上主要用于不適宜放、化療肺癌患者的治療,可增加患者的免疫力。 由于威麥寧膠囊是剛上市藥品,臨床研究相對較少。但已經(jīng)有相關(guān)的文獻報道了從金蕎麥的根莖中能夠提取出抗癌活性物質(zhì),且含量較高。威麥寧膠囊又是從金蕎麥根莖中提取制成的抗癌藥物,中國藥典中已將表兒茶素的含量作為金蕎麥的質(zhì)量標準,因此本課題選擇根莖中含量較高的抗癌活性成份原花青素B2和表兒茶素作為研究對象進行研究,為威麥寧膠囊臨床用藥,以及后期的科研研究提供一些數(shù)據(jù)支持。 為了測定威麥寧膠囊中原花青素B2、表兒茶素的含量,采用高效液相色譜法,ZorbaxSB-C18色譜柱,乙腈-0.04%磷酸水溶液為流動相,1.0mL/min的流速,檢測波長為280nm,柱溫30℃,進樣量10μL,由于原花青素B2和表兒茶素極性相近,所以采用梯度洗脫,使兩峰拉開。結(jié)果顯示,原花青素B2和表兒茶素的標準曲線分別為A原花青素B2=7047.3C-1066(r=0.9998),A表兒茶素=7321.9C-601.43(r=0.9999),加樣回收率分別為93.56%(RSD4.36%)、99.34%(RSD4.14%)。威麥寧膠囊3個批次中原花青素B2、表兒茶素的平均含量分別為1.44mg/粒、0.96mg/粒。因此,威麥寧膠囊三個批次中原花青素B2和表兒茶素的含量相近。該方法簡便、準確、重復性好,可為威麥寧膠囊提供質(zhì)量控制方法,為后期實驗提供含量的數(shù)據(jù)。 采用高效液相色譜法檢測原花青素B2和表兒茶素藥物濃度測定方法,并通過平衡透析法測定二者在體外血漿蛋白結(jié)合率。結(jié)果顯示,在低、中、高3個濃度下,原花青素B2在人和大鼠體外血漿中的蛋白結(jié)合率分別為(44.21±2.80)%、(52.60±1.92)%、(48.11±3.09)%和(82.88±3.24)%、(80.19±2.53)%、(79.95±3.19)%。表兒茶素在人和大鼠體外的血漿中的蛋白結(jié)合率分別為(47.12±2.85)%、(55.03±2.47)%、(43.69±1.53)%和(74.74±4.28)%、(75.63±3.25)%、(73.82±3.63)%。HPLC法簡便、可靠、穩(wěn)定。原花青素B2和表兒茶素在大鼠、人體外血漿屬中等結(jié)合型藥物,無明顯的濃度依賴性,但原花青素B2和表兒茶素與大鼠的血漿蛋白結(jié)合率高于人的血漿蛋白結(jié)合率,說明存在種屬差異性。 采用Cocktail探針藥物法探討了威麥寧膠囊對大鼠體內(nèi)六種CYP450酶活性的影響,為威麥寧膠囊臨床可能聯(lián)合用藥時相互作用提供依據(jù)。分別選用甲苯磺丁脲(CYP2C6)、氯唑沙宗(CYP2E1)、茶堿(CYP1A2)、瞇達唑侖(CYP3A2)、奧美拉唑(CYP2D1)、右美沙芬(CYP2D2)作為六個亞型酶的探針底物。每日早晨灌胃臨床等劑量的威麥寧膠囊,采用液質(zhì)聯(lián)用色譜法(LC-MS/MS)測定給藥前后大鼠體內(nèi)六種混合探針的血藥濃度,計算藥動學參數(shù)。結(jié)果顯示,威麥寧膠囊連續(xù)給藥2周后,與給藥前相比,奧美拉唑、咪達唑侖(p0.05)和右美沙芬代謝明顯減慢,茶堿、甲苯磺丁脲、氯唑沙宗的代謝無顯著性差異。因此,威麥寧膠囊對大鼠體內(nèi)CYP2D1、CYP3A2、CYP2D2(相對應(yīng)的人體內(nèi)的CYP2C19、CYP3A4、CYP2D6)三個亞型酶有抑制作用,對CYP1A2、CYP2C6、CYP2E1(相對應(yīng)人體內(nèi)的CYP1A2、CYP2C9、CYP2E1)三個亞型酶的活性無顯著影響。 為了研究威麥寧膠囊對多潘立酮藥動學的影響。選用8只大鼠連續(xù)10天灌胃威麥寧膠囊(1.6g/kg),并在給威麥寧膠囊前一天和最后一天灌胃多潘立酮片(4mg/kg),用液質(zhì)聯(lián)用色譜法(LC-MS/MS)測定大鼠體內(nèi)多潘立酮的血藥濃度,計算藥動學參數(shù),并比較大鼠給藥前后主要藥動學參數(shù)的差異性。結(jié)果顯示,威麥寧膠囊給藥后,多潘立酮的Tmax、 Cmax、AUC0-t值較沒有給威麥寧膠囊時有明顯的增高(P0.05),其他藥動學參數(shù)無顯著性差異。因此,威麥寧膠囊連續(xù)給藥后,致使多潘立酮的血藥濃度增加,可能會導致多潘立酮在體內(nèi)的藥物蓄積,從而加重多潘立酮對心臟等毒副作用,同時也驗證了威麥寧膠囊對大鼠CYP3A2酶(人的CYP3A4酶)有影響。

【學位級別】：碩士

[Abstract]:Weimaining capsules containing gold buckwheat dried rhizome of the active ingredients of anticancer, by ethanol extraction method after prepared two kind of national medicine to protect species. With detoxification, blood stasis, etc. Clinical Fuzheng evil is mainly used for the treatment of patients with lung cancer, chemotherapy, patients can increase immunity.
Because of weimaining capsules are just listed drugs, clinical research is relatively small. But there have been reports from the golden buckwheat rhizome can extract anti-cancer active substances, and the content is high. Weimaining capsules and anticancer drugs made from buckwheat rhizome extract in the Chinese Pharmacopoeia has content epicatechin as the quality standard of F.cymosum, so the high content of active ingredients in the roots of anticancer procyanidin B2 and epicatechin as the research object, for the clinical use of weimaining capsules, and later the scientific research to provide some data support.
For the determination of weimaining capsules of procyanidin B2, content of epicatechin, HPLC, ZorbaxSB-C18 column, acetonitrile -0.04% phosphoric acid solution as the mobile phase, the flow rate of 1.0mL/min, the detection wavelength was 280nm, the column temperature of 30 DEG C, sample volume 10 L, because the original anthocyanin and B2 epicatechin is eluted by gradient Their natures are much the same., so, the two peak opened. The results showed that procyanidin B2 and epicatechin standard curve were A B2=7047.3C-1066 (r=0.9998), procyanidin A epicatechin (r=0.9999 =7321.9C-601.43), the recoveries were 93.56% (RSD4.36%), 99.34% (RSD4.14%) weimaining capsules. 3 batches of procyanidin B2, the average content of epicatechin were 1.44mg/ particles, 0.96mg/ particles. Therefore, weimaining capsules three batches of procyanidin B2 and epicatechin content are similar. The method is simple, accurate, reproducible and can be weimaining The capsule provides the quality control method and provides the data for the later experiment.
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本文編號：1594623