Flakozid治疗病毒性肝炎的实验与临床研究回顾性分析

Q3 Pharmacology, Toxicology and Pharmaceutics
V. V. Karabaeva, L. Krepkova, A. N. Babenko, V. Bortnikova, T. V. Fateeva, P. G. Mizina, N. S. Mikheeva, O. Karabaeva
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The AGMK cell culture (BS-C-1 line) and the hepatitis A virus strain HM 175 adapted to it were used in the work. The studies were conducted in two series of experiments using different concentrations of the drug, which was introduced into cultures simultaneously with the infection of HAV. Experimental study of the effect of flakozid on viral hepatitis C (HCV). In the present experiments, a virus-containing culture fluid collected from infected cultures of chicken embryo fibroblasts containing 7,0 lg TCD50/ml of infectious HCV (genotype 1b) was used. The cytotoxic, viricidal and antiviral activity of flakozid was studied using transplanted cultures of pig embryo kidney cells (SPEV) obtained from the collection of cell lines of the D. I. Ivanovsky Research institute of virology of the Ministry of Health of the Russian Federation. In the experiments, a one-day monolayer of cells grown in 96-well plastic culture panels was used. ID50 – the concentration of the drug \"Flacozid\", which inhibits the development of the virus in the monolayer by 50 %, and CD50 – its minimum concentration, which causes cytotoxic destruction of 50 % of the cells of the monolayer, as well as the CTI – chemotherapeutic index, calculated as the ratio of CD50 to ID50, were determined. A well – known domestic antiviral agent, \"Ribavirin\", was used as a comparison drug. Clinical studies of flakozid in viral hepatitis A. The results of clinical studies of the antiviral drug \"Flakozid\" (0,1 g tablets) were analyzed in 258 patients with viral hepatitis A. \"Flakozid\" was prescribed to patients with a moderate course of the disease, 0,1 g 3 times a day for 20 days against the background of basic therapy: diet, alkaline drinking, Enterodes®. The therapeutic effect was assessed by clinical (weakness, decreased appetite, nausea, vomiting) and biochemical parameters (the level of direct bilirubin, transaminase activity), as well as by the severity of hepatolienal syndrome. Clinical studies of flakozid in viral hepatitis В. The results of clinical studies of the antiviral drug \"Flakozid\"(0,1 g tablets) were analyzed in 410 patients with acute viral hepatitis B, which was regarded as moderate. \"Flakozid\" was prescribed against the background of basic therapy: diet and detoxification therapy: 5 % glucose solution, 5 % ascorbic acid solution, \"Hemodesi\", at a daily dose of 0,3–0,8 g for up to 38 days. The comparison group received the same basic therapy without flakozid. The dynamics of clinical symptoms (general weakness, headache, sleep disorders, dizziness, nausea, vomiting, impaired appetite, itchy skin, pain in the right hypochondrium, jaundice, etc.), data from laboratory examination methods were evaluated, markers of hepatitis B – HBeAg and Australian antigen (HBsAg) were determined every 10 days and indicators of cellular immunity before the appointment and after 21 days of treatment; the absolute number of lymphocytes, the total number of T-lymphocytes, as well as theophylline-resistant and theophylline-sensitive cells.Results and discussion. The results of experimental studies revealed the antiviral effect of flakozid against the hepatitis A virus, confirmed during clinical studies in adult patients. Treatment with flakozid in patients with viral hepatitis A against the background of basic therapy at a daily dose of 0,3 g for 20 days led to a significant reduction in the symptoms of intoxication, a reduction in the jaundice period, normalization of the size of the liver and spleen. Treatment with flakozid as part of complex therapy of patients with acute viral hepatitis B (AHVB) of moderate severity in daily doses of 0,3–0,8 g for 38 days showed its high effectiveness, contributing to a faster disappearance of clinical symptoms of the disease (improvement of the general condition of patients, reduction of the severity and disappearance of clinical symptoms of intoxication, reducing of the jaundice period), normalization of biochemical parameters (reducing the level of bilirubin and transaminase activity), as well as elimination of HBsAg from the blood, stimulation of cellular immunity. \"Flakozid\" was well tolerated, did not cause allergic reactions. Based on the results of clinical studies, \"Flakozid\" is approved for medical use as an antiviral agent (registration number 90/248/7). The high antiviral activity of flakozid against the hepatitis C virus in cell cultures was established. In terms of the severity of the therapeutic effect, \"Flakozid\" was not inferior to ribavirin, and in terms of CTI it was noticeably superior.Conclusion. Treatment with flakozid in patients with viral hepatitis A and B showed its high efficiency, contributed to a faster disappearance of clinical symptoms of the disease, normalization of biochemical parameters, elimination of HCV from the blood, good tolerability. \"Flakozid\" is recommended in clinical practice in the complex treatment of hepatitis A and B. 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Viral hepatitis (HV) by its socio-economic significance occupies one of the leading places in human infectious pathology, therefore, the development of fundamentally new methods of prevention, diagnosis and treatment, as well as the creation of new antiviral drugs remain relevant. An antiviral herbal drug \\\"Flakozid\\\" has been created in VILAR, which is presented in a dosage form – 0,1 g tablets for oral administration.Аim. To analyze the experimental and clinical efficacy and safety of flakozid therapy in viral hepatitis.Materials and methods. Experimental study of the effect of flakozid on viral hepatitis A (HAV). The AGMK cell culture (BS-C-1 line) and the hepatitis A virus strain HM 175 adapted to it were used in the work. The studies were conducted in two series of experiments using different concentrations of the drug, which was introduced into cultures simultaneously with the infection of HAV. Experimental study of the effect of flakozid on viral hepatitis C (HCV). In the present experiments, a virus-containing culture fluid collected from infected cultures of chicken embryo fibroblasts containing 7,0 lg TCD50/ml of infectious HCV (genotype 1b) was used. The cytotoxic, viricidal and antiviral activity of flakozid was studied using transplanted cultures of pig embryo kidney cells (SPEV) obtained from the collection of cell lines of the D. I. Ivanovsky Research institute of virology of the Ministry of Health of the Russian Federation. In the experiments, a one-day monolayer of cells grown in 96-well plastic culture panels was used. ID50 – the concentration of the drug \\\"Flacozid\\\", which inhibits the development of the virus in the monolayer by 50 %, and CD50 – its minimum concentration, which causes cytotoxic destruction of 50 % of the cells of the monolayer, as well as the CTI – chemotherapeutic index, calculated as the ratio of CD50 to ID50, were determined. 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The dynamics of clinical symptoms (general weakness, headache, sleep disorders, dizziness, nausea, vomiting, impaired appetite, itchy skin, pain in the right hypochondrium, jaundice, etc.), data from laboratory examination methods were evaluated, markers of hepatitis B – HBeAg and Australian antigen (HBsAg) were determined every 10 days and indicators of cellular immunity before the appointment and after 21 days of treatment; the absolute number of lymphocytes, the total number of T-lymphocytes, as well as theophylline-resistant and theophylline-sensitive cells.Results and discussion. The results of experimental studies revealed the antiviral effect of flakozid against the hepatitis A virus, confirmed during clinical studies in adult patients. 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引用次数: 7

摘要

介绍。病毒性肝炎(HV)因其社会经济意义在人类感染病理学中占据主导地位,因此,开发新的预防、诊断和治疗方法以及开发新的抗病毒药物仍然具有重要意义。VILAR已研制出一种抗病毒草药“Flakozid”,其剂型为0.1 g口服片剂administration.Аim。目的:分析氟科齐治疗病毒性肝炎的实验和临床疗效及安全性。材料和方法。flakozid治疗病毒性甲型肝炎(HAV)的实验研究。实验采用AGMK细胞培养物(BS-C-1系)和与之相适应的甲型肝炎病毒hm175株。研究是在两个系列实验中进行的,使用不同浓度的药物,在感染甲肝病毒的同时将其引入培养物中。flakozid治疗病毒性丙型肝炎(HCV)的实验研究。本实验采用鸡胚成纤维细胞感染培养物中含有7,0 lg TCD50/ml感染性HCV(基因型1b)的含病毒培养液。利用俄罗斯联邦卫生部D. I. Ivanovsky病毒学研究所收集的猪胚肾细胞(SPEV)移植培养物,研究了flakozid的细胞毒、杀病毒和抗病毒活性。在实验中,使用96孔塑料培养板中培养的单层细胞。测定了药物“Flacozid”的浓度ID50和最低浓度CD50,前者可抑制50%的病毒在单层中的生长,后者可对50%的单层细胞造成细胞毒性破坏,并计算了CTI -化疗指数(CD50与ID50之比)。采用国内知名的抗病毒药物“利巴韦林”作为对照药物。分析了抗病毒药物“flakozid”(0.1 g片剂)在258例病毒性甲型肝炎患者中的临床研究结果。“Flakozid”被开给病程中等的患者,在基础治疗的背景下,每天0.1 g 3次,持续20天:饮食、碱性饮料、Enterodes®。通过临床表现(虚弱、食欲下降、恶心、呕吐)、生化指标(直接胆红素水平、转氨酶活性)以及肝胆综合征的严重程度来评估治疗效果。flakozid治疗病毒性肝炎的临床研究В。对410例急性乙型病毒性肝炎患者使用抗病毒药物“Flakozid”(0.1 g片剂)的临床研究结果进行分析,判定其为中度。“Flakozid”是在基础治疗的背景下开出的:饮食和排毒治疗:5%葡萄糖溶液,5%抗坏血酸溶液,“止血”,每日剂量为0,3 - 0,8 g,长达38天。对照组给予相同的基础治疗,不加氟科齐。评估临床症状(全身无力、头痛、睡眠障碍、头晕、恶心、呕吐、食欲减退、皮肤瘙痒、右肋部疼痛、黄疸等)的动态,评估实验室检查方法的数据,每10天检测一次乙型肝炎- HBeAg和澳大利亚抗原(HBsAg)标志物,并在预约前和治疗21天后检测细胞免疫指标;淋巴细胞的绝对数量,t淋巴细胞的总数,以及茶碱抗性和茶碱敏感细胞的数量。结果和讨论。实验研究结果揭示了flakozid对甲型肝炎病毒的抗病毒作用,在成人患者的临床研究中得到证实。在基础治疗的背景下,用flakozid治疗病毒性甲型肝炎患者,每日剂量0.3 g,持续20天,导致中毒症状显著减轻,黄疸期减少,肝脏和脾脏大小正常化。flakozid作为中度急性病毒性乙型肝炎(AHVB)患者综合治疗的一部分,每日剂量为0,3 - 0,8 g,持续38天,显示其高效,有助于疾病临床症状更快消失(改善患者一般状况,减轻中毒临床症状的严重程度和消失,减少黄疸期)。生化参数的正常化(降低胆红素水平和转氨酶活性),以及从血液中消除HBsAg,刺激细胞免疫。“Flakozid”耐受性良好,未引起过敏反应。根据临床研究结果,"Flakozid"被批准作为抗病毒药物在医疗上使用(注册号为90/248/7)。 在细胞培养中证实了flakozid对丙型肝炎病毒的高抗病毒活性。就治疗效果的严重程度而言,“Flakozid”不逊于利巴韦林,而在CTI方面,“Flakozid”明显优于利巴韦林。flakozid治疗病毒性甲型肝炎和乙型肝炎疗效显著,临床症状消失较快,生化指标恢复正常,血液中HCV消除,耐受性好。“Flakozid”在临床实践中被推荐用于甲型和乙型肝炎的综合治疗。体外实验证实,Flakozid对丙型肝炎病毒具有较高的抗病毒活性,这证明了该药物在病毒性丙型肝炎患者中进行临床研究的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Retrospective Analysis of Experimental and Clinical Studies of Flakozid in Viral Hepatitis
Introduction. Viral hepatitis (HV) by its socio-economic significance occupies one of the leading places in human infectious pathology, therefore, the development of fundamentally new methods of prevention, diagnosis and treatment, as well as the creation of new antiviral drugs remain relevant. An antiviral herbal drug "Flakozid" has been created in VILAR, which is presented in a dosage form – 0,1 g tablets for oral administration.Аim. To analyze the experimental and clinical efficacy and safety of flakozid therapy in viral hepatitis.Materials and methods. Experimental study of the effect of flakozid on viral hepatitis A (HAV). The AGMK cell culture (BS-C-1 line) and the hepatitis A virus strain HM 175 adapted to it were used in the work. The studies were conducted in two series of experiments using different concentrations of the drug, which was introduced into cultures simultaneously with the infection of HAV. Experimental study of the effect of flakozid on viral hepatitis C (HCV). In the present experiments, a virus-containing culture fluid collected from infected cultures of chicken embryo fibroblasts containing 7,0 lg TCD50/ml of infectious HCV (genotype 1b) was used. The cytotoxic, viricidal and antiviral activity of flakozid was studied using transplanted cultures of pig embryo kidney cells (SPEV) obtained from the collection of cell lines of the D. I. Ivanovsky Research institute of virology of the Ministry of Health of the Russian Federation. In the experiments, a one-day monolayer of cells grown in 96-well plastic culture panels was used. ID50 – the concentration of the drug "Flacozid", which inhibits the development of the virus in the monolayer by 50 %, and CD50 – its minimum concentration, which causes cytotoxic destruction of 50 % of the cells of the monolayer, as well as the CTI – chemotherapeutic index, calculated as the ratio of CD50 to ID50, were determined. A well – known domestic antiviral agent, "Ribavirin", was used as a comparison drug. Clinical studies of flakozid in viral hepatitis A. The results of clinical studies of the antiviral drug "Flakozid" (0,1 g tablets) were analyzed in 258 patients with viral hepatitis A. "Flakozid" was prescribed to patients with a moderate course of the disease, 0,1 g 3 times a day for 20 days against the background of basic therapy: diet, alkaline drinking, Enterodes®. The therapeutic effect was assessed by clinical (weakness, decreased appetite, nausea, vomiting) and biochemical parameters (the level of direct bilirubin, transaminase activity), as well as by the severity of hepatolienal syndrome. Clinical studies of flakozid in viral hepatitis В. The results of clinical studies of the antiviral drug "Flakozid"(0,1 g tablets) were analyzed in 410 patients with acute viral hepatitis B, which was regarded as moderate. "Flakozid" was prescribed against the background of basic therapy: diet and detoxification therapy: 5 % glucose solution, 5 % ascorbic acid solution, "Hemodesi", at a daily dose of 0,3–0,8 g for up to 38 days. The comparison group received the same basic therapy without flakozid. The dynamics of clinical symptoms (general weakness, headache, sleep disorders, dizziness, nausea, vomiting, impaired appetite, itchy skin, pain in the right hypochondrium, jaundice, etc.), data from laboratory examination methods were evaluated, markers of hepatitis B – HBeAg and Australian antigen (HBsAg) were determined every 10 days and indicators of cellular immunity before the appointment and after 21 days of treatment; the absolute number of lymphocytes, the total number of T-lymphocytes, as well as theophylline-resistant and theophylline-sensitive cells.Results and discussion. The results of experimental studies revealed the antiviral effect of flakozid against the hepatitis A virus, confirmed during clinical studies in adult patients. Treatment with flakozid in patients with viral hepatitis A against the background of basic therapy at a daily dose of 0,3 g for 20 days led to a significant reduction in the symptoms of intoxication, a reduction in the jaundice period, normalization of the size of the liver and spleen. Treatment with flakozid as part of complex therapy of patients with acute viral hepatitis B (AHVB) of moderate severity in daily doses of 0,3–0,8 g for 38 days showed its high effectiveness, contributing to a faster disappearance of clinical symptoms of the disease (improvement of the general condition of patients, reduction of the severity and disappearance of clinical symptoms of intoxication, reducing of the jaundice period), normalization of biochemical parameters (reducing the level of bilirubin and transaminase activity), as well as elimination of HBsAg from the blood, stimulation of cellular immunity. "Flakozid" was well tolerated, did not cause allergic reactions. Based on the results of clinical studies, "Flakozid" is approved for medical use as an antiviral agent (registration number 90/248/7). The high antiviral activity of flakozid against the hepatitis C virus in cell cultures was established. In terms of the severity of the therapeutic effect, "Flakozid" was not inferior to ribavirin, and in terms of CTI it was noticeably superior.Conclusion. Treatment with flakozid in patients with viral hepatitis A and B showed its high efficiency, contributed to a faster disappearance of clinical symptoms of the disease, normalization of biochemical parameters, elimination of HCV from the blood, good tolerability. "Flakozid" is recommended in clinical practice in the complex treatment of hepatitis A and B. In vitro experiments have established a high antiviral activity of flakozid against the hepatitis C virus, which justifies the possibility of conducting clinical studies of the drug in patients with the viral hepatitis C.
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来源期刊
Drug Development and Registration
Drug Development and Registration Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
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审稿时长
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