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Objective To observe the effect of tiopronin combined with glutathione on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT),blood fat and laminin (LN) in patients with non-alcoholic fatty liver. Methods A total of 84 non-alcoholic fatty liver patients admitted to our hospital from March 2018 to September 2019 were selected and randomly divided into control group and observation group, with 42 cases in each group. The control group was treated with tiopronin, and the observation group was treated with glutathione and tiopronin. The levels of ALT, AST, GGT and blood fat were recorded and compared before and after treatment. Results After treatment, the levels of ALT, AST and GGT in the two groups were significantly lower than before treatment (P<0.05). After treatment, the levels of ALT, AST, and GGT in the observation group were different from those in the control group, which was statistically significant (P<0.05). Before treatment, there was no difference in serum TC, TG, and LDL levels between the two groups, which was not statistically significant (P>0.05). The above-mentioned serum levels of the observation group after treatment were lower than those in the control group, and there was a difference, which was statistically significant (P<0.05); the levels of PCⅢ, PCⅣ, and LN in the treatment group after treatment were significantly lower than those of the control group. The difference was statistically significant (P<0.05). Conclusion The application of tiopronin combined with glutathione in the treatment of non-alcoholic fatty liver can promote the recovery of liver function and reduce the concentrations of TC, TG and LDL, which is worthy of clinical promotion.
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@#In this paper, a novel and simple RP-HPLC method for the determination of related substances of tiopronin for injection was described. The RP-HPLC analysis was performed on a C18 column, with acetonitrile-0. 1% phosphoric acid(8 ∶92), mobile phase in isocratic mode at a rate of 1. 0 mL/min. The photodiode array detector was set at 210 nm. Seven related substances were detected and the structures were characterized by mass spectrometry. The method showed great suitability, specificity and excellent linearity over the concentration range of 0. 3 to 50 μg/mL(r≥0. 999), and the limits of detection and quantitation were found to be 0. 10 and 0. 31 μg/mL, respectively. The accuracy of the method determined by the entire mean recovery ranged from 98. 7% to 103. 7%. The intra-and inter-day precision was satisfactory(RSD≤4. 4%)and robust(RSD≤6. 4%). And this method was successfully applied for the determination of related substances of tiopronin for injection, which revealed the retention of sulfhydryl compounds and glycine analogues on the RP-HPLC and the effect of the pH value of the mobile phase on the chromatographic behavior of the analytes.
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Objective To evaluate the application of multiattribute utility theory(MAUT) in pharmacoeco-nomic evaluation of anti - inflammatory and hepatoprotective therapy for chronic hepatitis B ( CHB). Methods During year 2014 - 2016,214 patients with mild to moderate CHB were selected. The patients were divided into three groups: A,B and C according to the therapeutic regimen,and they were given compound glycyrrhizin,tiopronin and polyene phosphatidylcholine to prevent inflammation and protect liver. MAUT model was constructed,the evaluation factors were determined and appropriate weight was given to each element parameter,the specific utility values for each factor were calculated,and by calculating the total utility value of final results quantitatively demonstrated the three regimens in the treatment of chronic hepatitis B. Results The total effective rates of A,B,C three groups were 78. 38％ ,69. 44％ ,79. 41％ ,respectively,the difference was statistically significant( χ2 = 5. 559,P < 0. 05). The incidence rates of adverse reaction of A,B,C three groups were 16. 22％ ,8. 33％ ,5. 88％ ,respectively. As to direct cost,group B(1430. 45 yuan) was better than group C(1494. 04 yuan) and group A (1515. 92 yuan). The hospital days of A,B,C three groups were (11. 3 ± 4. 8) d,(10. 9 ± 10. 6) d,(12. 5 ± 6. 4) d,respectively. The results of MAUT comprehensive evaluation showed that the total score value in polyene phosphatidylcholine group was the highest,and was the optimal treatment in the study. Conclusion Application of MAUT in the study of pharmacoeco-nomics is comprehensive,intuitive and flexible.
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Objective To investigate the effects and its possible mechanisms of tiopronin (TIP) on interleukin-2 (IL-2) immunotherapy of human leukemia KG-1 cells transplanted in nude mice.Methods KG-1 cells (1 x 107/ml) in logarithmic growth phase were injected subcutaneously into the groin of the left hind leg of the 45 5-week-old nude mice.When the subcutaneous tumor diameter was about 8 mm,nude mice were randomly divided into three groups (n =15):Control group (intraperitoneal injection of phosphate buffer),IL-2 group (hypodermic injection of IL-2),IL-2 + TIP group (hypodermic injection of IL-2 and intraperitoneal injection of TIP).The therapeutic effect of TIP combined with IL-2 on human leukemia KG-1 cells transplanted in nude mice was observed.The number of nature killer (NK) cells in peripheral blood of nude mice was detected by flow cytometry.Nitrate reductase assay was used to detect reactive nitric metabolite (RNM) levels in peripheral blood of nude mice.Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-β (TNF-β) and interferon-γ (IFN-γ) in peripheral blood of nude mice.Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay was used to analyze apoptosis.Results Both IL-2 and IL-2 + TIP could inhibit the growth of transplanted tumor.Compared with IL-2 group [(54.32 ± 4.32) ％],the tumor inhibition rate of IL-2 + TIP group was (90.15 ± 3.75)％,and its inhibition of tumor growth was more obvious (t =11.893,P ＜ 0.001).The tumor weights of Control group,IL-2 group and IL-2 + TIP group were (0.95 ± 0.05)g,(0.58 ± 0.03)g and (0.27 ± 0.07)g,and there was statistically significant difference among the three groups (F =52.716,P ＜ 0.001).Compared with IL-2 group,the tumor weight of IL-2 + TIP group was significantly reduced (P =0.008).The number of NK cells in IL-2 + TIP group was (0.658 ±0.157)/L,which was significantly higher than (0.452 ±0.124)/L of IL-2 group (P =0.021).The concentration of RNM in IL-2 + TIP group was (42.92 ± 4.68)μmol/ml,which was significantly lower than (163.38 ± 5.49)μmol/ml in IL-2 group (P =0.007).The concentrations of TNF-β and IFN-γin IL-2 + TIP group were (247.68 ± 8.24) pg/ml and (185.61 ±7.58) pg/ml,which were significantly higher than (97.48 ± 7.28)pg/ml (P =0.021) and (70.62 ± 8.47)pg/ml (P =0.015) in IL-2 group.The apoptotic rate of tumor cells in IL-2 + TIP group was (47.38±4.25)％,which was significantly higher than (21.41 ±2.79)％ in IL-2 group (P ＜0.001).Conclusion TIP can increase the sensitivity of leukemia cells to IL-2 immunothe-rapy by removing RNM,promoting NK cells activity and increasing NK cells-induced tumor cell apoptosis.
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OBJECTIVE:To observe the clinical efficacy of metadoxine combined with tiopronin in the treatment of alcoholic liver disease.METHODS:In retrospective study,70 patients with alcoholic liver disease were selected from Shanxi Provincial People's Hospital and Taiyuan Third People's Hospital during Oct.2013-Dec.2015,and then divided into treatment group and control group with 35 cases in each group according to therapy plan.Control group was additionally given Tiopronin enteric-coated tablet 0.2 g,po,tid,based on routine treatment;treatment groups was additionally Metadoxine tablet 1.0 g,po,bid,on the basis of control group.Both groups received treatment for 6 weeks.Serum indicators as ALT,AST,γ-GT,TBIL,TC,TG and A/G and serum hepatic fibrosis indicators as Ⅳ-C,HA and Ln were observed in 2 groups before and after treatment as well as the diameters of MPV and SPV,spleen thickness and clinical efficacy.The occurrence of ADR was recorded.RESULTS:The serum levels of ALT,AST,y-GT,TBIL,TC and TG were decreased significantly in 2 groups,while A/G level was increased significantly;above indicators of treatment group were more significant than those of control group,with statistical significance (P＜0.05).Serum levels of Ⅳ-C,HA,Ln,MPV,SPV and spleen thickness in treatment group were significantly decreased and lower than in control group,with statistical significance (P＜0.05).Total response rate of treatment group (94.29％) was significantly higher than that of control group (62.86％),with statistical significance (P＜0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Metadoxine combined with tiopronin shows good therapeutic efficacy for alcoholic liver disease with good safety.
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OBJECTIVE:To investigate clinical efficacy and safety of tiopronin combined with lamivudine in the treatment of pulmonary tuberculosis complicated with chronic hepatitis B. METHODS:150 cases diagnosed as pulmonary tuberculosis with chronic hepatitis B were randomly divided into group A(drug combination group),group B(lamivudine group)and the group C (control group),with 50 cases in each group. 3 groups were given isoniazid+rifapentine+ethambutol+levofloxacin(2HTELfx/4HT) anti-TB treatment and liver protection treatment,etc. Group B was additionally given Lamivudine tablet orally,0.1 g,qd;group A was additionally given Tiopronin tablet 0.3 g,tid,on the basis of group B. The treatment course of 3 groups lasted for 6 months. Liver damage,serum fibrosis indexes of 3 groups were observed in 3 groups before and after treatment as well as hepatitis B virolo-gy indexes,clinical efficacy and the occurrence of ADR after treatment. RESULTS:After treatment,serum levels of ALT,AST and TBIL weresignificantly increased in group C,significantly decreased in group A,with statistical significance(P0.05). Serum levels of ALT,AST and TBIL after the treatment:group A0.05). Serum fibrosis indexes of group A and B decreased significantly compared to before treatment,with statistical significance (P0.05). CONCLUSIONS:Tiopronin combined with lamivudine can significantly reduce liver function damage caused by an-ti-TB drugs. It is conducive to the smooth progress of tuberculosis chemotherapy with fewer adverse reactions.
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Objective To compare the effects of glutathione and tiopronin in chemo -induced liver injury respectively.Methods 122 patients with gastrointestinal cancer who were diagnosed with chemo -induced liver injure were chosen.According to random number table,they were divided into treatment group(63 cases)and control group(59 cases).The control group were given glutathione 1.8g/d intravenously,while the treatment group were given tiopronin 0.2g/d.Both treatments lasted a week.Liver function indexes before /after the treatment were observed respectively,as well as the symptoms of every patient.The adverse drug reactions of both treatments were also observed.Results The remission ratio of the treatment group and the control group was 90.48% and 81.35%, respectively,the difference of the two groups was statistically significant(χ2 =7.65,P 0.05);after both treatment the indexes were significantly improved,and ALT,TBIL,AST and ALP between the two groups were significantly different(t =4.67,6.13,4.76,6.90,all P 0.05),and no severe adverse drug reactions were observed in our research.Conclusion Tiopronin is more effective in treating chemo -induced liver injure caused by capetcitabine /5-FU and oxaliplatin,when compared with glutathione.And no severe adverse drug reaction were observed in our research.
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Objective:To explore the influence of infusion drop speed on the efficacy of tiopronin for injection combined with sol-vents in the treatment of abnormal liver function. Methods:Totally 74 patients were randomly divided into the observation group and the control group with 37 ones in each. The infusion drop speed was 60-65 drops per minute in the observation group, and that was 30-35 drops per minute in the control group, and the infusion time was controlled in 1h in the observation group and 2h in the control group. The clinical effect and the improvement of liver function were compared between the two groups after a treatment course of 4 weeks. Results:The total effective rate of the observation group(83. 78%) was obviously higher than that in the control group(56. 76%) (P<0. 05) after the treatment, and ALT, AST and TBIL of liver function indices were improved obviously except for ALB in the two group, and the difference was statistically significant between the two groups(P<0. 05). Conclusion:Tiopronin for injection can effectively improve the clinical effect by strictly controlling the time and drop speed of infusion.
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OBJECTIVE: To establish a Raman spectroscopy method for the determination of tiopronin injection. METHODS: Based on Raman scattering theory, the light intensity of the laser Raman peak is in proportional to the concentration of tiopronin samples in aqueous solution. A quantitative method for determination of tiopronin injection using Raman spectroscopy was established by selecting the Raman peak of tiopronin sulfhydryl group (S-H[2580 cm-1]) as quantitative peak. RESULTS: The calibration curve was linear over the range of 10 - 100 mg · mL-1 (r = 0.9999, n =6), and the average recovery was 101.98% with RSD of 2.09% (n = 9). CONCLUSION: The method is convenient and rapid. It is expected to be used in the quality control of tiopronin injection. Copyright 2012 by the Chinese Pharmaceutical Association.
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OBJECTIVE: To establish a near infrared spectroscopy method for the determination of the concentration of tiopronin for injection. METHODS: By using optical fiber probes and 1 mm sampling accessories, the near infrared transmission reflectance spectra of tiopronin for injection from seven pharmaceutical factories were obtained. The partial least square method was applied to establish the model with HPLC as the reference method. RESULTS: The model had a good prediction performance. The value of the correlation coefficient (r2) was 99.0%, the mean difference of prediction for test sets was 1.30%, and the root mean square error of prediction (RMSEP) was 0.982%. CONCLUSION: NIR is a rapid, reliable and powerful method for the quantitation of tiopronin for injection, and can be applied to rapid drug determination on the spot and stability study. Copyright 2012 by the Chinese Pharmaceutical Association.
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AIM To evaluate the prevention and treatment of N-(2-mercaptopropionyl)-glycine sodium (MPG-Na) and tiopronin (MPG) on acute liver injury. METHODS The experimental mouse model of hepatotoxicity induced by D-galactosamine (Gal) was applied to investigate preventive and remedial effects. In the preventive experiment, the mice were ip administered with MPG-Na or MPG 37.5，75 and 150 mg·kg~(-1), respectively, for 7 d. Gal 800 mg·kg~(-1) was ip given into the mice 30 min after the last administration. In the remedial experiment, the mice were ip given Gal 800 mg·kg~(-1) and 30 min later followed by MPG-Na or MPG 37.5, 75 and 150 mg·kg~(-1) , respectively, for 2 d. The mice were euthanized and serum was prepared 24 h (pre-treatment) or 48 h (post-treatment) after Gal injection. The activities of serum glutamyl pyruvic transaminase (GPT) and glutamyl oxaloacetic transaminase (GOT), the contents of total protein (TP) and albumin (Alb), and the Alb/globulin (A/G) ratio were determined. The liver tissues were collected for histopathological assessment (HE staining) under light microscope. RESULTS Compared with normal control group, the activities of serum GPT and GOT in model group were significantly increased. The injuries such as fatty degeneration and liver cell necrosis were observed. Compared with model group, the activities of GPT and GOT in pre-treatment groups were obviously decreased in MPG-Na 150 mg·kg~(-1) group. In post-treatment groups, the activity of GPT decreased in 3 MPG-Na groups. The contents of TP, Alb and A/G ratio had little change. In addition, MPG-Na alleviated the injuries such as fatty degeneration and liver cell necrosis obviously. Compared with MPG, MPG-Na showed similar effect. CONCLUSION MPG-Na has an obvious protective effect against Gal-induced acute liver injury in mice and the efficiency is equivalent as MPG.
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Aim:To develop a rapid high-performance liquid chromatography-mass spectrometry (HPLC-MS) method for the quantification of tiopronin in human plasma.Methods:Cysteine was chosen as antioxidant and firstly added into the whole blood firstly.After adding mycophenolic acid as internal standard (IS) and 1 mol/L HCl into the plasma,the samples were extracted with acetic ether and then determined by HPLC-MS.The chromatographic separation was performed on a Shim-pack VP-ODS C18 column (250 mm×2.0 mm,5 μm) using methanol-0.1% acetic acid (70∶30) as mobile phase with a flow rate of 0.2 mL/min.Results:The assay exhibited a linear range of tiopronin between 30～4 000 ng/mL.The precisions for intra- and inter-batch were all within 8.5%.The extraction recoveries were more than 70%.The total HPLC-MS analysis time was within 7.5 min per a run.The fully validated method was successfully applied to quantify tiopronin in human plasma for a bioavailability study.Conclusion:The assay proved to be accurate,sensitive,selective and convenient.The fully validated method can be applied to study the pharmacokinetics and bioavailability of tiopronin and tiopronin formulations in human.
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Objective To observe the efficacy and safety of tiopronin supplemented with chemotherapy in treating advanced breast cancer.Methods Sixty patients with advanced breast cancer were randomly divided into two groups:treatment group(n = 28) and control group (n = 32).Two groups were treated the same of NVB + DDP,the treatment group was supplemented with tiopronin,given for 10 days.Efficacy,toxicity in two groups were compared.Results The effective rate in the treatment group and the control group were 46.4% and 46.9% respectively, with no significant difference between the two groups ,P > 0.05.But the improved quality of life of patients in the treatment group was higher than that in the control group, P < 0.05.The rate of adverse reaction in liver function damaged (9.4%)and leucocyte lassitude(46.4%) were apparent lower than those in the control group(31.2% ,81.2% ),with significant difference between the two groups(P < 0.05, P < 0.01).Conclusion Tiopronin supplemented with chemotherapy show apparent effect in decreasing the adverse reaction of chemotherapy,improving the quality of life and not influence efficacy in advanced breast cancer.So tiopronln may act as protective drug for chemotherapy and deserve further testing in the clinic.
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OBJECTIVE:To explore the effect of tiopronin on the expression of cytochrome P4502E1(CYP2E1)in liver of rats with alcoholic fatty liver.METHODS:30 Wistar rats were randomly divided into 3 groups:group A(blank control group),group B(model group)and group C(tiopronin group).Group B and group C were given 50% alcohol intragastrically to establish alcoholic fatty liver model,while group C were intervened with tiopronin(0.15 g?kg-1?d-1 administered at 1 hour after alcohol administration)for 5 consecutive weeks.Then all the rats were sacrificed with AST and ALT levels in serum determined.The CYP2E1 expression was detected by RT-PCR;and the pathologic changes of the liver tissues were observed.RESULTS:In group B compared with group A,serum levels of AST,ALT and CYP2E1 expression were significantly higher(P
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OBJECTIVE:To observe the clinical efficacy of Tiopronin in treating non-alcoholic fatty liver disease.METHODS:104 patients with non-alcoholic fatty liver disease were randomly divided into therapy group and control group:52 patients in therapy group were treated with Tiopronin for 3 months,and 52 in control group with Hugan tablets(liver-protection tablets)for 3 months.Serum transaminase,blood lipid levels and other parameters in the two groups were detected before and after treatment.RESULTS:The therapy group was superior to the control group in lowering ALT,AST,TC and TG(P
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Objective To study the effects of Tiopronin(MPO)combine Penicillamine(PCA)on the copper metabolism and function of liver in rats model with hepatolenticular degeneration.Methods To copy hepatolenticular degeneration model rats with copper overloaded diet.Divide the models into groups HLD control,MPO,PCA and MPO+PCA,and interfere with the propotional drugs.To investigate the concentration changes of the lalanine aminotransferase(ALT),spartate amino transferase(AST),total protein(TP),albumin(ALB),liver copper and 24 h urine copper in each group.Results The concentrations of liver copper and 24 h urine copper in HLD control group and each group with drugs intervention were significantly higher than those in normal control group(all P
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OBJECTIVE:To establish an HPLC method for the determination of tiopronin in Tiopronin/glucose injection.METHODS:The separation was performed on Diamonsil-C18 column with flow rate of 1 mL?min-1.The mobile phase composed of 0.07 mol?L-1 NaH2PO4.The detection wavelength was 210 nm.RESULTS:Tiopronin showed good linearity within range of 24.17～56.39 ?g?mL-1(r=0.999 6).The average recovery was 99.06% (RSD=0.7%).CONCLUSION:The method is simple,rapid,accurate and specific for the determination of tiopronin in Tiopronin/glucose injection.