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OBJECTIVE To systema tically evaluate the effectiveness and safety of gen eric and original drugs of atorvastatin ， and to provide the latest evidence-based reference for drug selection in clinic. METHODS Retrieved from PubMed ，Cochrane Library，Embase，CNKI，VIP and Wanfang database ，intervention trials and observational studies about generic and original drugs of atorvastatin were collected during the inception to Apr. 2021. After data extraction of literatures met inclusion criteria ，the Cochrane risk bias evaluation tool 5.1.0 was used to evaluate the quality of intervention trials ；Newcastle-Ottawa Scale （NOS）was used to evaluate the quality of observational studies. RevMan 5.4 software was used to conduct meta-analysis ，and descrptive analysis was performed at the same time. RESULTS A total of 24 studies were included ，involving 21 randomized controlled trials （RCTs）and 3 retrospective cohort studies （RCSs），with 20 001 patients involved. Meta-analysis results of RCT showed there was no statistically significant difference between the two groups in reducing low-density lipoprotein cholesterol （LDL-C）levels [MD ＝ － 0.05，95％ CI（－ 0.12，0.02），P＝0.16] and increasing Δ 基金项目：国家重点研发计划项目（No.2017YFC0910004）；山 东省重点研发计划项目（No.2020RKB14165） high-density lipoprotein cholesterol （HDL-C）levels [MD ＝ ＊硕士研究生 。研究方向：临床药学。E-mail：1677032023@qq. － 0.00，95％ CI（－ 0.02，0.01），P＝0.52]；the degree of com reducing total cholesterol （TC）level [MD ＝－0.11，95％CI # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药事 （ － 0.17，－ 0.06），P＜0.000 1] and triglyceride （TG） 管理。电话：0351-89268349。E-mail：13791120711@126.com level [MD ＝－0.05，95％CI（－0.09， －0.01），P＝0.02] in ·358· China Pharmacy 2022Vol. 33 No. 3 中国药房 2022年第33卷第3期 generic drug group was lower than orig inal drug group ，with statistical significance difference. There was no statistical significance difference in total incidence of adverse drug reaction （ADR）[OR＝1.08，95％ CI（0.85，1.37），P＝0.55] and the incidence of other ADR（P＞0.05）. The results of subgroup analysis showed that the reductions of TC and TG of generic drugs produced by Beijing Jialin Pharmaceutical Enterprise （hereinafter refer to Jialin generic drugs ）were less than those of the original drug ，and the difference was statistically significant ；compared with original drugs ，there was no significant difference in other indexes or all indexes of the generic drugs from other manufacturers. Compared with original drugs ，the reductions of TC and TG in 20 mg/d group of Jialin generic drugs were less than original drug group ；the degree of TC reduction at 12 and 24 weeks of follow-up and TG reduction at 24 weeks of follow-up were less than those of the original drugs ，the difference was statistically significant ；there was no significant difference in other indexes. The qualitative description of RCS showed that for elderly patients with death/acute coronary syndrome ，there was no statistical difference between the two groups in terms of cardiovascular events or serious side effects. For the adult patients who switched from original drugs to generic drugs ，the effect of generic drugs instead of original drugs would not be reduced ，but the increase of HDL-C was less than that of original drug. CONCLUSIONS In terms of effectiveness，generic drugs of atorvastatin can replace original drugs and caution should be taken on the levels of HDL-C ，TC and TG for long time use ；in terms of safety ，generic drugs are similar to the original drugs.
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OBJECTIVE To compare the efficacy ，safety and immunogenicity of bevacizumab biosimilars and original drugs for non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical use. METHODS PubMed，Embase， Web of Science ，Cochrane Library ，CBM，CNKI，VIP，Wanfang database ，ClinicalTrials.gov，and Clinical Trial Center of China were searched from the establishment of the database to September 25，2021，randomized controlled trials （RCTs）about bevacizumab biosimilars（trial group ）versus bevacizumab original drugs （control group ）for NSCLC were collected. After literature screening ， data extraction and quality evaluation of included RCTs with bias risk assessment tool recommended by Cochrane Handbook 5.1.0， meta-analysis，sensitivity analysis and publication bias analysis were performed by using RevMan 5.3 software. RESULTS A total of 11 RCTs were included ，involving 6 596 patients in total. Meta-analysis showed that there was no statistical significance in the difference of overall response rate [RR＝0.97，95％CI（0.92，1.02），P＝0.22]，the total incidence of adverse reaction [RR＝1.00， 95％CI（0.99，1.01），P＝0.79]，the incidence of severe adverse reaction [RR＝1.04，95％CI（0.96，1.13），P＝0.38]，positive rate of anti-drug antibody [RR ＝1.10，95％CI（0.88，1.36，P＝0.41] and the incidence of common adverse reactions （except for vomiting）among 2 groups（P＞0.05）. The sensitivity analysis results showed that the obtained results were robust. The results of publication bias analysis showed that there was little possibility of publication bias. CONCLUSIONS The efficacy ，safety and immunogenicity of bevacizumab biosimilars used for NSCLC are equivalent to those of bevacizumab original drugs.
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OBJECTIVE：To provide reference for constructing a patent linking system in line with international standards and balancing the interest conflict between original drug enterprises and generic drug enterprises. METHODS ：The relevant supporting systems of patent link in the United States were introduced ；combined with the development status and relevant systems of drug patent protection at home and abroad ，the existing problems of China ’s drug patent management system were analyzed to put forward suggestions for improvement. RESULTS & CONCLUSIONS ：The United States patent linking system included Orange book system ，generic drug patent declaration system ，generic drug approval waiting period and market monopoly period system of the first generic drug. The innovation and accessibility in the field of pharmaceutical products were facing the dilemma of “commons tragedy ”and“anti commons tragedy ”. There were many problems in China ’s drug patent protection ，such as insufficient R&D and innovation ability inhibited the development of the pharmaceutical industry ，imperfect laws and regulations were not conducive to the settlement of medical professional disputes. It is suggested to establish a digital information database of patented drugs ，standardize the existing generic drug patent declaration system ，promote the coordination between patent litigation cycle and approval waiting period ，increase the independent innovation ability of the pharmaceutical industry ，promote the coordination between pharmaceutical innovation and drug accessibility ，and jointly promote the improvement of intellectual property legislation and the development of medical and health undertakings.
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OBJECTIVE： To investigate the similarity of in vitro dissolution curve between the generic drugs and the reference preparation （original drugs） of the domestic Cyclosporine soft capsules in 6 dissolution mediums. METHODS： The dissolution test was performed with paddle method. 2％ SDS water solution， 2％ SDS pH 1.2 hydrochloric acid solution， 2％ SDS water solution， 2％ SDS pH 4.5 acetate buffer solution， 2％ SDS pH 5.5 acetate buffer solution， 2％ SDS pH 6.8 phosphate buffer solution and 2％ SDS simulated gastric fluid were used as the dissolution medium， and the rotation speed was 50 r /min. HPLC method was used. The determination was performed on Agilent Eclipse XDB-C18 column with mobile phase consisted of acetonitrile phosphate solution （73 ∶ 27 ∶ 0.25，V/V/V），the flow rate was 1.0 mL/min. The detection wavelength was set at 226 nm， the column temperature was 60 ℃， and sample size was 20 μL. The dissolution curves in 6 medium were drawn and the similarity factor （f2） was used to investigate the similarity between the samples from 3 domestic manufacturers （5 batches） and a batch of original drugs. RESULTS： The linear range of cyclosporine was 5-250 μg/mL （r＝0.999 6-0.999 9）； RSDs of precision， stability （12 h） and reproducibility tests were lower than 2.0％ （n＝6 or 7）； the recoveries were 98.4％-99.7％ （RSD＜2.0％， n＝9）. The cumulative dissolution of 6 batches of samples within 15 min reached 85％ in 2％ SDS pH 1.2 hydrochloric acid solution and 2％ SDS simulated gastric juice. f2 of the dissolution curve of 5 batches of generic and original drugs of Cyclosporine soft capsules were 75， 45， 57， 42， 83 in 2％ SDS water solution and 44， 76， 38， 32， 76 in 2％ SDS pH 4.5 acetate buffer solution 76， 47， 49， 40， 79 in 2％ SDS pH 5.5 acetate buffer solution and 52， 49， 55， 48， 80 in 2％ SDS pH 6.8 phosphate buffer solution， respectively. CONCLUSIONS： There have differences in the similarity of the dissolution curve between the domestic generic and the original drugs of 5 batches of Cyclosporin soft capsule from 3 domestic manufacturers.
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Diabetes, so-called “emaciation-thirst disease” in traditional Chinese medicine(TCM), is a prevalent chronic disease with complicated etiology, incurable and multiple complications, as well as extremely high morbidity and mortality. TCM pays attention to tackling the problem in the treatment of emaciation-thirst disease, and many prescriptions are single animal medicine or contain animal-original drug; animal-original drugs possess stasis and other unique characteristics and therapeutic effects. Based on the current anti-diabetic drugs, the review gives an in-depth summary and analysis on the single animal-original drugs derived from the complexes of TCM in the treatment of diabetes according to their mechanism of action, with the aim to provide reference for developing new animal-original drugs to treat diabetes.
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Diabetes,so-called“emaciation-thirst disease”in traditional Chinese medicine(TCM),is a prevalent chronic dis?ease with complicated etiology,incurable and multiple complications,as well as extremely high morbidity and mortality. TCM pays at?tention to tackling the problem in the treatment of emaciation-thirst disease,and many prescriptions are single animal medicine or con?tain animal-original drug;animal-original drugs possess stasis and other unique characteristics and therapeutic effects. Based on the current anti-diabetic drugs,the review gives an in-depth summary and analysis on the single animal-original drugs derived from the complexes of TCM in the treatment of diabetes according to their mechanism of action,with the aim to provide reference for developing new animal-original drugs to treat diabetes.
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We compare the bioequivalence of selected original and generic drugs which were dispensed in Siriraj Hospital in 1994. The 14 items which consist of 7 local and 7 original drugs were chosen on the basis of volume of consumption and price differentials. The in vitro equivalence studies used were assay, weight variation, content uniformity, dissolution test and/or disintregration test. Tested samples of the two groups were Sorbitrate vs. Isotrat 20 mg, Lopid vs. Hidil 300 mg, Nolvades-D vs. Tamoplex 20 mg, Sibilium vs. Flunazine 5 mg, Adalat vs. Nelapine 5 mg, Herbesser vs. Dilatam 30 mg and Tarivid vs. Occidal 100 mg. This study demonstrated no difference of the in vitro test of local and original drugs, suggesting comparable quality of generics to originals.