复方甘草酸苷治疗儿童复发性丘疹性荨麻疹临床疗效观察

目的观察复方甘草酸苷治疗儿童复发性丘疹性荨麻疹的疗效。方法120例患者随机分为治疗组和对照组,两组均给予扑尔敏片剂0.35mg/kg.d,分3次口服。治疗组同时口服复方甘草酸苷片,15mg/kg,3次/d,7d为一个观察疗程,连用4周。结果治疗组有效率为88.3%,复发2例(4.87%)。对照组有效率为28.3%,复发5例(71.4%)。两组有效率与复发率相比,差异有统计学意义(P0.05)。结论复方甘草酸苷治疗儿童复发性丘疹性荨麻疹疗效显著,副作用少,复发率低。     

Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles

Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs) has been performed in this study. GL-SDC/PL-MMs were produced by a film dispersion method and then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as its physical stability after storage for 10, 20, 30, 60, 90 and 120 days. To verify the theoretical hypothesis, pharmacokinetics and pharmacodynamic studies based on carbon tetrachloride (CCl₄)-induced acute liver injury was investigated. Results showed that a narrow size distributed nanomicelles with a mean particle size of 82.99?±?7.5?nm and a zeta potential of ?32.23?±?1.05 mV was obtained. In the pharmacokinetics, GL-SDC/PL-MMs show a significant superiority in AUC_0–t, C_max and other pharmacokinetic parameters compared with the control group. In the pharmacodynamic studies, compared with the bifendate control group, GL-SDC/PL-MMs showed an equivalent effect in reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST) and improving the pathological changes of liver tissue. These results revealed that SDC/PL-MMs could enhance GL absorption in gastrointestinal tract and pharmacodynamic effect in the treatment of acute liver injury caused by CCl₄, and SDC/PL-MMs might be a good choice for oral delivery of poor bioavailability drug like GL.     

维甲酸和甘草酸联合对人肺癌细胞增殖和侵袭抑制作用的研究

目的　探讨全反式维甲酸和甘草酸单独及联合作用对高转移人肺癌细胞 (PGCL3 )增殖和侵袭的抑制作用。方法　用维甲酸和甘草酸处理PGCL3细胞 ,通过细胞增殖抑制试验、软琼脂集落形成试验、侵袭、运动和黏附试验、以及组织蛋白酶B活性的测定 ,观察PGCL3细胞增殖和侵袭能力的变化。结果　维甲酸和甘草酸可减弱PGCL3细胞增殖能力 ,并呈剂量依赖性 ,半抑制浓度IC50 分别为 12 .6μmol/L和 1.8mmol/L。 2 .5 μmol/L和 5 .0 μmol/L维甲酸、0 .5mmol/L和 1.0mmol/L甘草酸能抑制PGCL3细胞的侵袭能力 (P <0 .0 5和P <0 .0 1) ,且有剂量依赖性。 5 .0 μmol/L维甲酸和 0 .5mmol/L甘草酸联合作用对PGCL3细胞的侵袭抑制率高于两药单独作用之和 ,呈协同作用。上述浓度甘草酸对细胞的运动、黏附、组织蛋白酶B分泌和软琼脂集落形成率均有显著抑制作用 (P <0 .0 1)。结论　维甲酸和甘草酸对PGCL3细胞的增殖和侵袭有抑制作用 ,两药有协同作用 ,甘草酸抗侵袭机理不是对侵袭的某一环节的阻断 ,而是对侵袭各个基本环节都有抑制作用     

Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV)

Glycyrrhizin (GL) achieved a dose-dependent inhibition of the replication of human immunodeficiency virus type 1 (HIV-1) in MOLT-4 (clone No. 8) cells within the concentration range of 0.075 to 0.6 mM. Within this concentration range, GL also effected a dose-dependent reduction in the protein kinase C (PKC) activity of MOLT-4 (clone No. 8) cells. A well-known PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), also proved inhibitory to HIV-1 replication in MOLT-4 (clone No. 8) cells. PKC inhibition may thus be considered as one of the mechanisms by which GL inhibits HIV-1 replication. In addition, GL may also owe its anti-HIV-1 activity, at least in part, to an interference with virus-cell binding, since the compound at 1.2 mM partially inhibited the adsorption of radiolabeled HIV-1 particles to MT-4 cells. At this concentration GL also suppressed giant cell formation induced by co-culturing MOLT-4 (clone No. 8) cells with MOLT-4/HTLV-III_B cells, whereas the PKC inhibitor H-7 failed to do so.     

甘草酸二铵对急性肺损伤大鼠肺组织糖皮质激素受体及核因子κB表达的影响

目的 观察甘草酸二铵(GL)对急性肺损伤(ALI)大鼠肺组织核因子κB(NF-κB)、糖皮质激素受体(GR)表达的调控作用及对血清肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)表达的影响.方法 将24只雄性SD大鼠采用随机数字表法分为生理盐水对照组、ALI模型组和GL干预组,每组8只.ALI模型组、GL干预组分别给予内毒素(LPS)5 mg/kg尾静脉注射;IPS注射前1 h,GL干预组给予GL 20 mg/kg静脉注射.观察4 h后各组大鼠肺组织病理,测定肺湿干比(W/D)、PaO_2,并采用逆转录-PCR反应检测肺组织NF-κB mRNA,GR mRNA的表达,western blot法测定肺组织Nf-κB及GR蛋白的表达,ELISA法测定血清TNF-α,IL-10质量浓度.采用SPSS 13.0软件进行统计学分析,各组间均数比较采用单因素方差分析,均数两两比较采用q检验.结果 (1)ALI模型组TNF-α为(153.68±20.42)ng/L,明显高于生理盐水组(43.96±7.57)ng/L(P<0.01)和GL干预组(87.23±7.52)ng/L(P<0.01).ALI模型组IL-10为(42.48±6.81)ug/L,明显高于生理盐水组(24.72±8.03)ng/L(P<0.01),但低于GL干预组水平(58.33±9.62)ug/L(P<0.05).(2)ALI模型组NF-κBmRNA和蛋白的表达水平[分别为(3.414±0.521),(254.7±16.4)]明显高于生理盐水组[分别为(0.432±0.085),(45.6±7.3)](P<0.01),而GRmRNA和蛋白的表达[分别为(0.152±0.025),(11.5±2.3)]则明显低于生理盐水组[分别为(0.434±0.013),(54.6±6.5)](P<0.01);GL干预组NF-κB mRNA和蛋白的表达水平[分别为(1.894±0.272),(133.5±11.7)]明显低于ALI模型组(P<0.01),GR mRNA和蛋白的表达[分别为(0.308±0.033),(28.2±5.6)]则明显高于ALI模型组(P<0.05,P<0.01).(3)ALI模型组肺组织出现充血、水肿、中性粒细胞浸润,GL干预组肺部炎症较ALI模型组减轻.结论 甘草酸二铵可能通过下调NF-κB的表达,同时提高GR的表达,进而调节炎症因子TNF-α及抗炎介质IL-10的表达,从而起到减轻ALI的作用.     

阿维A胶囊联合美能治疗中、重度银屑病疗效观察

目的:观察阿维A胶囊与美能联合治疗中、重度银屑病临床疗效。方法:将120例银屑病患者分为三组,治疗组用阿维A胶囊联合美能,对照组I单用美能,对照组II单用阿维A胶囊。结果:治疗组与对照组I组、II组治愈率比较P<0.05为差异有统计学意义。结论:阿维A胶囊与美能联合治疗中、重度银屑病临床疗效好。     

Pharmacokinetic profiles of glycyrrhizin in patients with chronic hepatitis

The pharmacokinetics of glycyrrhizin (G) in eight patients with chronic hepatitis receiving chronically i.v. administration of 120 mg dose of G was investigated. The plasma concentration of G in the patients after dosing declined in a monophasic manner. However, the pharmacokinetic profiles varied among patients. The mean elimination half-life (t_1/2) and the total body clearance (CL_tot) were 6.0 h (range 4.3–10.7 h) and 7.9 ml h^?1 kg^?1 (4.5–12.7 ml h^?1 kg^?1), respectively. The variation of the CL_tot for G was closely related to that of aspartate aminotransferase (r = ?0.739, p <0.05) and alanine aminotransferase (r = ?0.783, p <0.05) activities in the plasma.     

Uptake of albumin nanoparticle surface modified with glycyrrhizin by primary cultured rat hepatocytes

AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NP-GL and Cal-BSA-NP by rat hepatocytes was determined by fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of Cal-BSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P<0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL. CONCLUSION: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.     

阿维A与其他药物治疗脓疱型银屑病疗效对比分析

目的 评价阿维A、甲氨蝶呤、复方甘草酸苷注射液治疗脓疱型银屑病的疗效差异.方法 将156例患者随机分成3组,A组75例患者口服阿维A胶囊 10 mg,每日3次；B组45例患者口服甲氨蝶呤2.5 mg,每日1次；C组36例患者用复方甘草酸苷注射液20ml加入5％葡萄糖溶液250 ml静脉滴注,每日1次.3组疗程均为8周.结果 A、B、C3组有效率分别为88.00％、75.56％、66.67％.3种药物治疗脓疱型银屑病的有效率比较,差异有统计学意义(P＜0.01)；不良反应发生率分别为37.33％、64.44％和8.33％,3种药物不良反应发生率比较,差异有统计学意义(P＜0.01)；追踪随访治愈患者3个月,A、B、C3组复发率分别为7.69％、47.62％和10.00％,3种药物治疗脓疱型银屑病的复发率比较差异有统计学意义(P＜0.01).结论 阿维A能更有效地控制脓疱型银屑病的症状,疗效明显,复发率低,值得在临床推广使用.     

糠酸莫米松乳膏联合复方甘草酸苷片治疗慢性湿疹临床近期疗效观察

目的观察糠酸莫米松乳膏联合复方甘草酸苷片治疗慢性湿疹的临床近期疗效。方法将66例慢性湿疹患者,随机分为治疗组36例,对照组30例,疗程均为4周,治疗组用糠酸莫米松乳膏均匀涂于患处,1次／日,并且口服复方甘草酸苷片,3次／日,2片／次,对照组单纯外用糠酸莫米松乳膏均匀涂于患处,1次／日。结果治疗组痊愈22例,痊愈率61．1％,总有效32例,总有效率88．9％;对照组痊愈12例,痊愈率40．0％,总有效17例,总有效率56．7％,治疗组与对照组临床疗效相比差异有统计学意义（Х^2=13．7,P〈0．05）。结论糠酸莫米松乳膏联合复方甘草酸苷片治疗慢性湿疹比单纯外用糠酸莫米松乳膏临床近期疗效好,是治疗慢性湿疹的较好方法之一。