康体多复方甘草酸铵注射液福建省皮肤病性病防治院%程波

康体多的临床应用,福建医科大学附属第一医院福建省皮肤病性病防治院 程波,甘草酸铵的药理作用,康体多在皮肤科的应用,目 录,一、甘草的主要有效成分,甘草含有多种化学成分，主要成分有甘草酸、黄酮、生物碱等，大量研究表明，甘草酸（甘草甜素）和黄酮类物质是甘草中最重要的生理活性物质，主要存在于甘草根部。,二、甘草酸的药理作用,Marianecci C, Rinaldi F, Di Marzio L,et al. Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models. Int J Nanomedicine. 2014 Jan 24;9:635-51.,1、抗过敏作用,复方甘草酸铵能够多靶点抑制抗体产生，降低血清中IgE和IgG的水平。复方甘草酸铵抑制肥大细胞释放组胺、乙酰胆碱等过敏介质，也能抑制慢性炎症介质（白三烯）的合成。,甘草酸的抗过敏作用,GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p0.02), and decreased IL-4 (p0.05), IL-5 (p0.05) and eosinophils (p0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p0.01) and prevented the reduction of total IgG(2a) (p0.01) in serum. We have also showed that it has no effect on serum cortisol levels.,Ram A1,Mabalirajan U,Das M,Glycyrrhizinalleviates experimental allergic asthma in mice. Int Immunopharmacol.2006 Sep;6(9):1468-77.,2、抗炎作用,1、 抑制细胞核因子NF-kB的活化，从而抑制许多炎症因子的合成和释放。 2、抑制磷脂酶A2（phospholipase A2）和脂氧合酶（lipoxygenase）的活性，从而抑制炎性介质（前列腺素、白三烯、血栓素A2等）的合成。 3、抑制补体系统，抑制血清总补体活性，从而抑制变态疾病中补体参与的膜攻击复合物对组织的损伤。,3、皮质激素（类固醇）样作用,康体多中的甘草酸铵分解的甘草次酸与类固醇结构相似具有肾上腺皮质激素样作用，激素样副作用少。,组织中11羟基类固醇脱氢酶(11- HSD)有HSD1和HSD2两种亚型，它们催化GC的C11位的氧化和还原反应。HSD1具有还原酶的功能，通过结构修饰增强GC的活性。HSD2则为氧化酶，降低GC的活性。,皮质激素代谢的关键酶,The kinetic analysis associated with the loss of 11alpha-2H during the conversion of cortisol-13C4,2H1 to cortisone-13C4 by 11beta-HSD2 clearly indicated reduced 11beta-HSD2activitywith glycyrrhetinicacidingestion, as observed by an increase in the elimination half-life of cortisol-13C4,2H1. The elimination half-life of cortisol-13C4,2H1 provided sensitive in vivo measures of 11beta-HSD2activityand was more sensitive for detecting changes in renal 11beta-HSD2activitythan the measurement of the urinary ratio of free cortisol and free cortisone .,Kasuya Y1,Yokokawa A,Takashima S,Use of 11alpha-deuterium labeled cortisol as a tracer for assessing reduced 11beta-HSD2activityin vivo following glycyrrhetinicacidingestion in a human subject. Steroids.2005 Feb;70(2):117-25.,甘草酸能减低11beta-HSD2的活性,甘草酸能增强激素的抗炎作用,Upon incubation of MP with the cecal contents, MP disappeared, and this was delayed by addition of GCZ. In addition, more MP produced from MPS in the cecal contents accumulated in the presence of GCZ. Consistent with these results, upon oral administration of MPS/GCZ, MPS or MP, MP was detected at a greater level in the large intestine for MPS/GCZ. MPS/GCZ ameliorated TNBS-induced colitis of rats, and this therapeutic effect was superior to that of MPS and MP. Moreover, MPS/GCZ decreased the plasma levels of corticosterone and ACTH to a greater extent than MPS, but less than MP.Co-administration of GCZ, a reduction inhibitor, may be a plausible strategy to reduce the therapeutic loss of MP produced from MPS in the large intestine, thus improving the therapeutic property of the prodrug againstinflammatorybowel disease.,Lee Y1,Jeong S,Kim W,Glycyrrhizinenhances therapeuticactivityof a colon-specific methylprednisolone prodrug against experimental colitis. Dig Dis Sci.2013 May;58(5):1226-34.,糖皮质激素治疗皮肤病的缺陷,禁忌症糖尿病高血压病毒性肝炎结核消化性溃疡慢性感染,副作用反跳现象及停药症状 心绞痛库欣综合症 急性胰腺炎肾上腺皮质功能不全 类固醇肌病神经症状：激动、失眠 肺动脉栓塞抗感染能力低下 精神异常股骨头缺血坏死 胆道出血,3、免疫调节作用,甘草酸的免疫机制非常复杂，具有非特异性免疫调节作用，主要通过：1、主要是增强细胞免疫作用，增强吞噬细胞的吞噬功能，可选择性地增强辅助性T淋巴细胞的增殖能力和活性，使CD4+细胞增加，CD8+细胞减少。2、可促进淋巴细胞产生IL-2、IFN-r，抑制lL-4或IL-10的生成。3、增强自然杀伤细胞的杀伤力。所以不能单纯地把甘草酸归为免疫抑制剂或免疫增强剂，实际上它是具有“双向”调节作用的免疫制剂。,免疫调节作用：,4、抗病毒作用,甘草酸可明显减轻肝细胞脂肪变性和坏死，减轻肝细胞间质炎症反应，抑制肝细胞纤维增生以及促肝细胞再生等。因此是治疗乙型病毒性肝炎值得重视和推广的药物。因此认为甘草酸有直接抗HBV活性及改善肝功能障碍的作用。甘草酸的抗病毒作用机制大致可分为两种类型：一是抑制病毒DNA复制而产生抗病毒作用。二是可抑制黄曲霉素-B在细胞内的活性，从而降低其在肝细胞中的毒性。,甘草酸的广谱抗病毒活性,Animal studies demonstrated a reduction of mortality and viral activity inherpessimplex virus encephalitis and influenza A virus pneumonia. . The compound was also effective against HSV-1 with a 50% inhibitory concentration of 0.5 mM Glycyrrhiza glabra derived compound glycyrrhizinand its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In vitro studies revealed antiviral activity against HIV-1, SARS, vaccinia virus . 作用机制：1、减少病毒通过细胞膜转运（HBV、HIV-1和HSV）；2、减少病毒抗原的表达（HBVsurface antigen）；3、诱导T-cells 表达interferon gamma 等。,Fiore C1,Eisenhut M,Krausse R,Antiviral effects of Glycyrrhiza species. Phytother Res.2008 Feb;22(2):141-8.,甘草的药理作用,康体多在皮肤科的应用,目 录,复方甘草酸铵注射液（康体多注射液）：由西安迪赛生物药业有限责任公司生产，是以中药甘草的有效成分-型甘草酸铵为主药，配以L-半胱氨酸、甘氨酸等多种成分制成的复方制剂。,康体多的皮肤科临床应用,1、荨麻疹类皮肤病：急慢性荨麻疹、人工性荨麻疹、丘疹性荨麻疹、寒冷性荨麻疹2、湿疹：急性、亚急性、慢性湿疹3、皮炎：异位性皮炎、接触性皮炎4、药疹5、神经障碍性皮肤病：神经性皮炎、皮肤瘙痒症、痒疹6、血管炎皮肤病：过敏性紫癜7、物理性皮肤病：日光性皮炎（日光疹）8、病毒性皮肤病：带状疱疹、扁平疣、带状疱疹后遗神经痛9、红斑鳞屑性皮肤病：银屑病、玫瑰糠疹,1、康体多治疗慢性荨麻疹,对照组30例,单独服用咪唑斯汀片10mg,1次/d,连续714d.治疗组32例,同上+康体多针2040mL加入5%GS中静脉滴注,1次/d, 每周连续5d.结果：治疗后7、14d治疗组总有效率均比对照组高;停药后4周随访,治疗组复发率较对照组明显偏低。结论：康体多联合咪唑斯汀治疗慢性荨麻疹较单一服用咪唑斯汀疗效优势明显.,药物与临床 2012 32,2、康体多治疗皮炎湿疹,对照组30例,口服西替利嗪10mg,1次/日.治疗组46例,同上+康体多20ml加入5%GS250ml静脉点滴,1次/日.疗程：接触性皮炎1周,特应性皮炎神经性皮炎泛发性湿疹2周,皮肤病与性病2008 ：30（4）,De Waure C, Cadeddu C, Venditti A, et al.Non steroid treatment foreczema: results from a controlled and randomized study.Ital Dermatol Venereol. 2013 Oct;148(5):471-7,3、康体多治疗面部激素依赖性皮炎,对照组84例、维丁胶钙+左西替利嗪治疗组82例,康体多+左西替利嗪观察两组治疗2周和4周后的疗效。,医学信息09 2011,4、复方甘草酸铵注射液治疗带状疱疹,52例带状疱疹患者按就诊顺序分成2组。对照组:阿昔洛韦0.5g,每1次/日，静脉滴注,治疗组:同上+康体多40ml, 1次/日,静脉滴注.两组都外用聚维酮碘溶液(艾利克),均治疗6d。第12d、21d、28d,各随访一次。结果治疗组、对照组：3d疼痛减轻者分别为58%、42%；6d分别为42%、39%；6d疼痛基本消失者分别为42%、23%；12d分别为50%、46%；后遗神经痛者分别为0%、8%。结论：治疗组比对照组的疗效好,可以缩短病程、减轻炎症和疼痛、减少后遗神经痛。,临床和实验医学杂志2007年11月 第6卷 第11期,5、康体多治疗寻常型银屑病,对照组30例, 点滴状17例,斑块状13例,进行期19例,静止期