双环醇片治疗慢性肝炎高转氨酶血症的疗效观察

目的：观察双环醇片治疗慢性肝炎高转氨酶血症的临床疗效。方法：选择住院或门诊慢性肝炎高转氨酶血症患者280例,随机分为治疗组和对照组,治疗组141例,对照组139例。治疗组在常规保肝治疗的基础上加用双环醇片25m每日3次口服,对照组在常规保肝治疗的基础上加用甘利欣胶囊150mg每日3次口服。疗程均为4周。治疗前后每周详细记录患者症状、体征、肝功能、肾功能、电解质、及血尿常规,同时记录治疗过程中的不良反应及停药后随访3个月。结果：两组均有显著疗效,肝功能生化指标与治疗前相比有显著性差异（治疗组P〈0.01,对照组P〈0.05）,治疗组明显优于对照组（P〈0.05）,且治疗组出现的不良反应明显少于对照组。结论：双环醇片治疗慢性肝炎高转氨酶血症疗效好,不良反应较少,值得临床推广。     

Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its mechanism of action

The aim was to investigate the suppressive effect of bicyclol on hepatic fibrosis induced by dimethylnitrosamine (DMN) in mice and the mechanism of its action. Hepatic fibrosis was established by intraperitoneal injection of 8 mg kg(-1) day(-1) on three consecutive days of each week for 4 or 5 weeks. In the prophylactic experiment, bicyclol (100 and 200mg.kg(-1)) was administered by gavage in association with DMN injection. For the therapeutic experiment, mice were firstly injected with DMN for 5 weeks as in the prophylactic experiment, and then the mice in drug groups were orally administered bicyclol (100 and 200mg.kg(-1)) once daily for 5 weeks. As a result, the levels of alanine aminotransferase (ALT), total bilirubin, hydroxyproline (Hyp), prolidase, tumor necrosis factor-alpha (TNFalpha), transforming growth factor beta-1 (TGFbeta(1)), type I collagen in serum and the score of liver fibrosis all significantly increased in the hepatic fibrosis model group in comparison with those in control group. The treatment with bicyclol markedly reduced all the above criteria. Bicyclol also attenuated the decrease of body weight of mice, serum total protein and albumin. In addition, bicyclol treatment inhibited liver TGFbeta(1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA expression in the prophylactic experiment. Similarly, bicyclol reduced TIMP-1 levels in liver and serum and increased collagenase activity in the liver in the therapeutic experiment. The result suggest that bicyclol attenuates DMN-induced hepatic fibrosis in mice. Its mechanisms of action may be related to the hepatoprotective and anti-inflammation properties, the down-regulation of liver TGFbeta(1) and TIMP-1 expression and the increase of net collagenase activity in liver.     

Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice

Heat shock proteins (HSPs) are the best-known endogenous factors that protect against cell injury under various pathological conditions and that can be induced by various physical, chemical, and biological stressors. New research seeks to discover a compound that is clinically safe and can induce the accumulation of HSPs in patients. This paper reports that the oral administration of three doses of bicyclol, a novel antihepatitis drug, induced hepatic HSP27 and HSP70 expression in a time- and dose-dependent manner, and that bicyclol treatment stimulated heat shock factor 1 (HSF1) activation in mice. The inducing effects of bicyclol on HSP27, HSP70 and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/70 induced by bicyclol against hepatotoxicity of acetaminophen (AP) was assessed in mice. The prior administration of bicyclol markedly suppressed AP-induced liver injury as indicated by the reduction in the elevation of serum alanine aminotransferase and aspartate aminotransferase, in liver necrosis, in the release of cytochrome c and apoptosis-inducing factor from mitochondria, as well as in hepatic deoxyribonucleic acid fragmentation in mice. However, all the above actions of bicyclol against AP-induced mouse liver injuries were significantly attenuated by quercetin. This is the first report to show that bicyclol induces hepatic HSP27/70 expression via activation of HSF1 and that the cytoprotective action of bicyclol against liver injury is mediated by its induction of HSP27/70. These results provide new evidence for elucidating the mechanism of the hepatoprotective action of bicyclol in animals and patients.     

Determination of bicyclol in dog plasma using liquid chromatography–tandem mass spectrometry

A sensitive and accurate method for determination of bicyclol in dog plasma was developed. Thermo Scientific TSQ Quantum triple quadrupole system with multiple ion monitoring (MIM) positive scanning mode was applied. Bicyclol and DDB (IS) sodium adduct molecular ions were monitored at m/z 413 and m/z 441 in both Q1 and Q3, respectively. The collision energy in Q2 was set to 15 eV. Precipitation method was employed in the extraction of bicyclol and DDB from the biological matrix. The method was validated over 1–500 ng/mL for bicyclol. The recovery was 96.5–109.5%, and the limit of quantitation (LOQ) detection was 1 ng/mL for bicyclol. The intra- and inter-day precision of the method at three concentrations was 3.3–14.3% with accuracy of 99.9–109.0%. The method was successfully applied to bioequivalence studies of bicyclol controlled-release formulation to obtain the pharmacokinetic parameters.     

富马酸替诺福韦二吡呋酯片联合双环醇在治疗慢性乙型病毒性肝炎方面的研究

目的:研究探讨富马酸替诺福韦二吡呋酯片(tenofovir dipivoxil fumarate tablets,TDF)联合双环醇在治疗慢性乙型病毒性肝炎方面的临床效果。方法:选取2017年1月-2020年1月中国人民解放军陆军第七十三集团军医院疾病预防控制科感染病区收治的80例慢性乙型病毒性肝炎患者,随机将其分为两组,对照组40例,给予TDF治疗,研究组40例,给予TDF联合双环醇治疗,观察两组治疗后的疗效及不良反应率,检测两组治疗前后血清乙型肝炎病毒DNA(Deoxyribonucleic acid)的水平及血清丙氨酸氨基转移酶(ALT)的水平。结果:治疗后,研究组总有效率95.0%,显著高于对照组总有效率75.0%(P<0.05);研究组血清乙型肝炎病毒DNA的水平<500 cps/mL的有32例,占80.0%,对照组<500 cps/mL的有14例,占35.0%,对比有统计学意义(P<0.05);两组血清ALT的水平明显降低,且研究组低于对照组(P<0.05)。研究组不良反应总发生率2.5%明显低于对照组25.0%(P<0.05)。结论:富马酸替诺福韦二吡呋酯片(TDF)联合双环醇治疗慢性乙型病毒性肝炎疗效显著,能使患者体内血清乙型肝炎病毒DNA的水平显著的降低,且安全可靠,值得临床推广和应用。     

双环醇片治疗慢性肝炎高转氨酶血症的疗效观察

目的:观察双环醇片治疗慢性肝炎高转氨酶血症的临床疗效。方法:选择住院或门诊慢性肝炎高转氨酶血症患者280例,随机分为治疗组和对照组,治疗组141例,对照组139例。治疗组在常规保肝治疗的基础上加用双环醇片25m每日3次口服,对照组在常规保肝治疗的基础上加用甘利欣胶囊150mg每日3次口服。疗程均为4周。治疗前后每周详细记录患者症状、体征、肝功能、肾功能、电解质、及血尿常规,同时记录治疗过程中的不良反应及停药后随访3个月。结果:两组均有显著疗效,肝功能生化指标与治疗前相比有显著性差异(治疗组P<0.01,对照组P<0.05),治疗组明显优于对照组(P<0.05),且治疗组出现的不良反应明显少于对照组。结论:双环醇片治疗慢性肝炎高转氨酶血症疗效好,不良反应较少,值得临床推广。