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The clinical value of Chinese patent medicine is the core direction of the development of the traditional Chinese medicine industry. The precise clinical positioning determines the way to prove the value of the drug， and is a key link to highlight the clinical value. This paper presented a case study of clinical positioning for Chinese patent medicine， namely Qizhi Tongluo capsules， and the key technical framework of precise clinical positioning of Chinese patent medicine， which was manifested as a comparison of prescription target spectral effect， discovery of core value of prescription， and confirmation of clinical positioning trial. The technical framework was designed to address a range of issues in the realm of precise clinical positioning. Before the clinical positioning trial， based on the multi-component， multi-target， and multi-phenotype data of prescription and clinical indication， the multi-omics network analysis technology was used to identify the core value of the traditional Chinese medicine varieties and predict the potential clinical advantages. Then， based on the predicted clinical advantages， reasonable efficacy indicators were selected， and the clinical efficacy was judged and verified by dynamic and flexible innovative clinical trials to improve the success rate of clinical positioning. This research paradigm integrates "omics technology" with "evidence-based" principles and follows the "precise evidence-based" concept. This research aims to provide a new strategy and method for the precise medication and positioning of Chinese patent medicine with traditional Chinese medicine characteristics after being put into the market and provide more technical thinking for traditional Chinese medicine to move towards precise medicine.
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ObjectiveTo carry out the clinical comprehensive evaluation of Biantong capsules and Biantong tablets in the treatment of constipation guided by the clinical value of drugs， and to provide a scientific basis for the rational pricing， rational use， and cataloging of Biantong capsules/tablets. MethodThe available evidence and survey data were used for the clinical comprehensive evaluation of Biantong capsules/tablets and three control drugs in the treatment of constipation in terms of the six dimensions including effectiveness， safety， economics， innovation， suitability， and accessibility. ResultIn terms of effectiveness， Biantong capsules/tablets can improve the response rate， with clear pharmacological mechanism. In terms of safety， the absence of toxic reaction， the mild adverse reactions， and the favorable prognosis indicate high safety. In terms of economics， the average daily cost of Biantong capsules/tablets is the lowest among the tested drugs， which indicates a cost-effectiveness advantage. In terms of innovation， Biantong capsules/tablets have been authorized patents in China and listed as members in the third category of new drugs of traditional Chinese medicine/ninth new drugs of traditional Chinese medicine. In terms of suitability， Biantong capsules/tablets are convenient to store and take and have good suitability in terms of drug technical characteristics and drug usage. In terms of accessibility， Biantong capsules/tablets have a wide coverage in hospitals， sufficient capacity， low patient burden， extensive drug catalogue coverage， and no major environmental risk for long-term application. The comprehensive values of the tested drugs follow a descending order of control drug B （84.27 score）， Biantong capsules/tablets （82.47 score）， control drug A （70.47 score）， and control drug C （59.46 score）. The recommendations of the expert panel are Class A （18/18）， which can be directly converted into decision-making. ConclusionBiantong capsules/tablets demonstrate a high clinical comprehensive value in the treatment of constipation， providing a reference for the rational pricing， rational use， and cataloging of drugs.
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ObjectiveThrough a randomized， double-blind， double-simulation， positive-control， multicenter design， this study aimed to analyze the relationship between the dosage， efficacy， and safety of Pudilan anti-inflammatory oral liquid in treating acute pharyngitis/tonsillitis in adults caused by bacterial infection and validate the regulatory effect of Pudilan anti-inflammatory oral liquid on inflammatory markers such as serum amyloid A （SAA）， C-reactive protein （CRP）， white blood cells （WBC）， neutrophil percentage （NE%）， and erythrocyte sedimentation rate （ESR）， thereby exploring the feasibility of using Pudilan anti-inflammatory oral liquid as a substitute for antibiotics in the treatment of infectious diseases and providing a basis for rational clinical medication. MethodUsing a stratified randomized， double-blind， double-simulation， positive-control， multicenter design， 220 participants were enrolled from nine centers. The participants were randomly divided into three groups at 1∶1∶1 — a Pudilan anti-inflammatory oral liquid 20 mL group （73 cases）， a Pudilan anti-inflammatory oral liquid 10 mL group （73 cases）， and a control group （amoxicillin group， 74 cases）. The treatment course was 7 days. The study observed parameters including the total effective rate of sore throat， onset and disappearance time of sore throat， health status score， treatment time， and inflammation markers. Result①Dataset division： The 211 cases were included in the full analysis dataset （FAS）， 208 cases were included in the per-protocol dataset （PPS）， and 218 cases were included in the safety dataset （SS）. ② Efficacy evaluation： There were statistically significant differences （P<0.05） in the comparison of the three groups regarding the total effective rate of sore throat， disappearance time of sore throat， and health status. Both the 20 mL and 10 mL groups were non-inferior to the control group， and there was a statistically significant difference between the 20 mL and 10 mL dosage groups （P<0.05）. There was no statistically significant difference in the comparison of onset time of sore throat among the groups. CRP， WBC， and NE% of patients in all three groups significantly decreased on the 7th day of treatment compared with those before treatment （P<0.01）. ③Safety evaluation： Adverse events mainly occurred in various examination indicators. There were no statistically significant differences in the comparison between groups， and no adverse reactions or serious adverse events occurred. ④Economic evaluation： The increased cost of the 10 mL and 20 mL dosage groups was entirely justified as compared with that in the control group. When comparing the 10 mL and 20 mL dosage groups， the 10 mL dosage group was deemed less advantageous. ConclusionPudilan anti-inflammatory oral liquid can be used alone as an alternative to antibiotics in the treatment of acute pharyngitis/tonsillitis caused by bacterial infection. It demonstrates good safety and can lower inflammation markers such as CRP， WBC， and NE%， suggesting its potential to reduce the body's inflammatory response. Its mechanism of action may be related to its multi-target regulatory mechanism.
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ObjectiveTo evaluate the clinical safety of Naoxintong （NXT） capsules after marketing， find out the potential risk factors of the drug as soon as possible， and reveal the incidence， nature， and clinical manifestations of the adverse events （ADE） and adverse reactions （ADR） of NXT capsules， so as to provide a basis for safe use of the drug in clinical practice. MethodA prospective， large-sample， multi-center observational cohort study was conducted to monitor all the 7 345 inpatients and outpatients orally taking NXT in 14 hospitals in China from January to December in 2018， with at least one follow-up. The demographic characteristics， disease type， NXT medication， ADR occurrence， characteristics， and prognosis of the patients were collected. SPSS 23.0 was used for single-factor and multivariate logistic regression to predict the influencing factors of ADR. ResultThe male and female patients accounted for similar proportions. There were 5 081 patients （79.40%） aged ≥60 years and 3 153 patients （49.27%） with body mass index （BMI） exceeding the normal standard. There were 344 （5.38%） patients with a history of allergy to medicines and food， 9 （0.14%） patients with a family history of allergy， and 52 （0.81%） patients with a history of allergic diseases. The ADRs associated with NXT occurred in 22 patients， with the incidence of 0.34%. The clinical manifestations of ADR appeared in 31 cases， involving 10 organs/systems， of which gastrointestinal system damage was the most common （17， 54.84%）. All ADRs were mild or moderate. Most ADRs （19， 86.36%） occurred within 4 weeks after administration. The patients with alleviated NXT-associated ADRs accounted for 81.82%. No indicators related to significant increases in ADR risks were found. ConclusionNXT is well tolerated in the general population. The hospital centralized monitoring for the clinical safety of oral Chinese patent drugs based on HIS data and Web tracking and follow-up system is an essential means for the post-market research on the safety of drugs.
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Gynecological inflammatory disease refers to female reproductive system inflammatory disease, which has a direct impact on the female conception and reproductive health. Kangfuyan capsule is a classic traditional Chinese medicine preparation of the Miao nationality, which has the functions of promoting blood circulation, removing blood stasis, and clearing away heat and dampness. It is mainly used to treat pelvic inflammation, vaginitis, and chronic cervicitis caused by the accumulation of heat and dampness. In this paper, the basic research and clinical application of the Kangfuyan capsule in gynecological inflammatory diseases were reviewed to provide a reference for the development of drug for gynecological inflammation diseases.
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ObjectiveTo comprehensively evaluate the clinical value of Jintiange Capsules （JCs） in the treatment of osteoporosis （OP） and clarify the intrinsic advantages and clinical treatment characteristics of JCs， providing references for relevant departments of national health and medicine decision-making and the basis and clues for clinical and basic in-depth research. MethodBased on evidence-based medical evidence， this study integrated quantitative and qualitative methods and combined with questionnaires， official website data， human experience， pharmacoeconomic evaluation， and other research methods. From the effectiveness， safety， economy， innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics of the '6+1' dimension， the clinical evidence and value of JCs in the treatment of OP were comprehensively evaluated， forming the 'clinical evidence and value evaluation index'. The comprehensive evaluation of clinical value was based on the multi-criteria decision analysis framework. The expert meeting method was used to empower each dimension and value index. The clinical evidence and value evaluation software of Chinese patent medicine （CSC v2.0） was used to calculate the total value score， and the clinical advantages of JCs were comprehensively evaluated. ResultBased on randomized controlled clinical studies and systematic review， data analysis of spontaneous reporting system （SRS）， case reports， non-clinical safety studies， etc.， serious adverse drug reactions （ADRs） were reported after the launch of this product monitored by SRS， mainly involving abnormal liver function and adverse reactions of cardiovascular system. Therefore， the safety evidence adequacy of this product should be further improved， and the safety evaluation was Grade B. Meta-analysis showed that JCs were superior to the control group in improving the total clinical effective rate， improving bone mineral density， reducing visual analogue scale （VAS） score， and shortening fracture healing time. Combined with Grading of Recommendations Assessment， Development and Evaluation （GRADE） evidence evaluation， the comprehensive evaluation of effectiveness was Grade A. Pharmacoeconomic evaluation showed that JCs combined with calcium carbonate D3 tablets were more cost-effective than calcium carbonate D3 tablets alone in patients with OP. Compared with Gushukang capsules， JCs had more cost-effectiveness advantages， but the sample size included in the study was small， and the results needed to be verified by further studies. Combined with the results of the Comparative Assessment of Structure Prediction （CASP） evaluation list， the comprehensive economic evaluation was Grade B. JCs were the only bionic medicine of tiger bone in China with all intellectual property rights， with 3 national invention patents. Its process preparation and fingerprint detection had obvious technical advantages. It had innovative advantages in the supply base equipment， medicine resource management， production technology， and other aspects. Thus， its innovative comprehensive evaluation was Grade A. JCs were in capsule dosage form， which was relatively convenient for storage and transportation. The dosage form was suitable for indications， and the usage was easy for patients to grasp and accept. The statutory information and non-statutory information met the national standards. The comprehensive evaluation of suitability was Grade A. JCs did not contain toxic ingredients， had no restrictions on origin and prescription， and had abundant resources of original medicinal materials. The affordability of JCs in the treatment of OP was good in urban areas （14.97%） but not in rural areas （39.76%）. The price was higher than that of similar Chinese patent medicines， and the comprehensive evaluation of availability was Grade B. JCs had a reasonable proportion of natural animal bones， and their composition was basically the same as that of natural tiger bones. After marketing， more than 2 000 cases of real-world clinical research evidence was accumulated， and the comprehensive evaluation of TCM characteristics was Grade B. CSC v2.0 software was used for quantitative synthesis of the '6+1' dimension， and the comprehensive clinical value of JCs in the treatment of OP was Grade A. ConclusionJCs have good clinical value in the treatment of OP， and the TCM characteristics are prominent. It is suggested that JCs can be directly transformed into the related policy results of basic clinical drug management according to procedures.
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OBJECTIVE To study the effects of Ganbao capsules on intestinal mucosal barrier and gut microbiota in rats with non-alcoholic fatty liver disease （NAFLD）， and to explore its mechanism of prevention and treatment of NAFLD. METHODS Eight of 26 SD rats were randomly selected as blank group and fed with ordinary diet， and the remaining 18 rats were fed with high diet to establish NAFLD model （2 for modeling inspection）； after successful modeling， they were divided into model group and Ganbao group， with 8 rats in each group. Ganbao group were given Ganbao capsules solution （1 440 mg/kg） intragastrically， and the blank group and model group were given the constant volume of distilled water intragastrically， once a day， for consecutive 5 weeks. The contents of alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and triglyceride （TG） in serum of rats were detected by automatic analyzer； the contents of lipopolysaccharide， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum of rats were detected by enzyme-linked immunosorbent assay. The pathological morphology of liver and ileum tissues were observed by HE staining， the expressions of Occludin and zonula occludens-1 （ZO-1） were detected by immunohistochemistry method， and the intestinal flora were detected by 16S ribosomal RNA gene sequencing technology. RESULTS Compared with the model group， the serum contents of ALT， AST， TG， lipopolysaccharide， TNF-α， IL-6 and IL-1β in Ganbao group were decreased significantly （P＜0.01）， the pathological changes of liver and ileum tissues were improved 262 significantly， and the expressions of Occludin and ZO-1 were increased significantly （P＜0.01）. Intestinal microbiotaanalysis revealed that compared with the model group， Ganbao capsules could recover the abundance and diversity of the gut E-mail：hdf8833@126.com microbiota in rats. At the phylum level， Ganbao capsules could significantly increase the relative abundance of Bacteroidetes， and significantly reduce the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes （P＜0.01）. At the genus level， Ganbao capsules could significantly increase the relative abundance of Lactobacillus， Blautia， Bacteroides and Akkermansia， and significantly reduce the relative abundance of Prevotella， Turicibacter， Weissella， SMB53 and Desulfovibrio （P＜0.05 or P＜0.01）. There were different species among the gut microbiota of rats in each group. CONCLUSIONS Ganbao capsules may improve NAFLD by protecting intestinal mucosal barrier function and regulating gut probiotics/harmful bacteria structure.
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ObjectiveTo explore the comprehensive clinical value of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat stasis syndrome， and to provide evidence for the decision-making of clinical basic drug management. MethodBased on the "Guidelines for Comprehensive Clinical Evaluation of Drugs （Trial Version 2021）"， this study systematically reviewed the existing research on the treatment of chronic prostatitis with damp-heat stasis syndrome by Qianlieping capsules. Based on evidence-based medicine， clinical epidemiology， clinical medicine， evidence-based pharmacy， pharmacoeconomics， health statistics， health technology assessment， and other disciplines， the multi-criteria decision analysis model （MCDA） and CSC 2.0 software were used. The six dimensions of safety， effectiveness， economy， innovation， suitability， and accessibility of drugs， as well as traditional Chinese medicine（TCM） characteristics， were comprehensively evaluated qualitatively and quantitatively. ResultIn terms of safety， based on the spontaneous reporting system （SRS） of the National Center for ADR Monitoring， safety literature analysis， pharmacological and toxicological experiment report， and other evidence， the safety grade of Qianlieping capsules was evaluated as grade A， with good safety. In terms of effectiveness， based on the results of pharmacological and pharmacodynamic studies and Meta-analysis， and combined with the value and quality of the evidence for efficacy， the final efficacy grade of Qianlieping capsules was rated as B. In terms of economy， Qianlieping capsules was a class B drug of national medical insurance. Compared with those of similar Chinese patent medicines， the average daily cost of Qianlieping capsules was moderate， and there was no related cost increase during the administration process. Economic research showed that Qianlieping capsules combined with α-receptor blockers were more economical than α-receptor blockers alone. Based on the quality evaluation of economic evidence and the value evaluation of economic evidence， the economic grade of Qianlieping capsules was rated as B. In terms of innovation， Qianlieping capsules were a combination of cold and warm drugs， focusing on clearing heat， detoxifying， removing blood stasis， and relieving pain， with non-toxic medicinal materials. They obtained a number of invention patents. The enterprise service system was perfect， and the quality standard was higher than the international and Chinese standards. The innovation grade of Qianlieping capsules was rated as B. In terms of suitability， the results of the questionnaire survey showed that it had relatively good suitability for clinicians， nurses， pharmacists， and patients who used Qianlieping capsules. The information on Chinese patent medicines was complete and met the requirements of national standards. The suitability grade of Qianlieping capsules was rated as A. In terms of accessibility， Qianlieping capsules were moderately priced and affordable， with sufficient resources of medicinal materials， no shortage of medicinal materials， and good availability. The accessibility grade of Qianlieping capsules was rated as B. In terms of TCM medicine characteristics， the prescription of Qianlieping capsules was derived from Danshen Huoxue Decoction. The original prescription was used for the treatment of chronic prostatitis with blood stasis syndrome. The whole formula was recorded in The Complete Compendium of Fine Formulas （《良方大全》） published by Beijing Publishing Group Co.， Ltd. in 1991 and has been used for more than 30 years. The formula was a combination of warm and cold drugs， attacking pathogens without hurting healthy Qi. The grade of TCM characteristics of Qianlieping capsules was rated as B. ConclusionBased on the above "6+1" dimensions， the comprehensive evaluation result of Qianlieping capsules in the treatment of chronic prostatitis with damp-heat and blood stasis syndrome is grade B， and it is recommended to convert it into the relevant policy results of basic clinical drug management according to the conditions.
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ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis （RA） due to spleen deficiency and dampness exuberance. MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method， with 51 cases in each group. All patients were treated with methotrexate tablets， while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score （DAS28）， visual analogue scale （VAS） scores， morning stiffness time， erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide （anti-CCP） antibody， vascular endothelial growth factor （VEGF）， and serum amyloid A （SAA） of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP， ESR， RF， SAA， VEGF， and anti-CCP. ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment， the total effective rate in the observation group was 90.19% （46/51）， which was higher than 74.51% （38/51） in the control group （χ2＝4.320，P<0.05）. DAS28， VAS score， and morning stiffness time in the observation group were improved compared with those in the control group （P<0.05）. Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF， ESR， hs-CRP， SAA， and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP， ESR， RF， SAA， and VEGF in the observation group were all better than those of the control group， and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP， ESR， RF， SAA， and VEGF in the observation group was superior to that of the control group （P<0.05）. The incidence of adverse reactions in the observation group was lower than in the control group （χ2＝4.057，P<0.05）. ConclusionOn the basis of the treatment with methotrexate tablets， Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.
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Objective:To explore the effects of Bifidobacterium triple viable capsules combined with Berberine tablets on blood lipid and intestinal flora in patients with hyperlipidemia.Methods:A total of 420 hyperlipidemia patients admitted to the Second Medical Center of PLA General Hospital & National Clinical Research Center for Geriatric Diseases from January 2019 to December 2020 were selected and divided into the observation group and the control group according to the random number table method, with 210 cases in each group. Both groups were routinely given lipid-lowering drugs, the control group was also given Bifidobacterium triple viable capsules orally, and the observation group was combined with Berberine tablets orally on the basis of the control group. The levels of serum inflammatory factor, blood lipid, apolipoprotein and the number of intestinal flora before and after treatment were compared between the two groups. The incidence of adverse reactions was compared between the two groups during the treatment.Results:After treatment, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP) in the observation group were significantly lower than those in the control group: (26.78 ± 5.63) ng/L vs. (30.06 ± 5.79) ng/L, (12.88 ± 4.76) ng/L vs. (15.45 ± 5.32) ng/L, (8.22 ± 2.80) mg/L vs. (10.26 ± 3.71) mg/L, there were statistical differences ( P<0.05). After treatment, the levels of blood lipid in the observation group were improve better than those in the control group, the levels of apolipoprotein AⅠ in the observation group was higher than that in the control group: (2.00 ± 0.45) g/L vs. (1.72 ± 0.39) g/L; and the levels of apolipoprotein B and apolipoprotein E in the observation group were lower than those in the control group: (1.08 ± 0.18) g/L vs. (1.20 ± 0.22) g/L, (4.80 ± 0.68) g/L vs. (5.12 ± 0.62) g/L, there were statistical differences ( P<0.05). After treatment, the numbers of Bifidobacterium and Lactic acid bacteria in the observation group were higher than those in the control group: (8.80 ± 0.80) lg CFU/g vs. (8.30 ± 0.75) lg cfu/g, (8.85 ± 0.64) lg cfu/g vs. (8.45 ± 0.68) lg cfu/g; and the numbers of Colon bacillus and Enterococcus faecalis in the observation group were lower than those in the control group: (8.20 ± 0.55) lg cfu/g vs. (8.52 ± 0.50) lg cfu/g, (6.42 ± 0.60) lg cfu/g vs.(6.84 ± 0.65) lg cfu/g, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Bifidobacterium triple viable capsules combined with Berberine tablets in treatment of patients with hyperlipidemia can effectively reduce the level of blood lipid and regulate intestinal flora, with good safety.
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Objective:To evaluate the clinical efficacy rate, vascular endothelial relaxation factor NO and safety of five different Chinese patent medicines combined with western medicine in the treatment of coronary microvascular disease (CMVD).Methods:Randomized controlled trials (RCTs) of Shexiang Baoxin Pills, Tongxinluo Capsules, Compound Danshen Dripping Pills, Yindan Xinnaotong Soft Capsules, and Xinkeshu Tablets combined with conventional western medicine therapy in the treatment of CMVD were retrieved from China National Knowledge Infrastructure (CNKI), China Academic Journal Database (Wanfang Data), Chinese Science and Technology Journal Database (Chongqing VIP), China Biomedical Literature Service System (SinoMed), PubMed, Cochrance Library and Embase databases from the establishment of the database to June 2022. The literature was imported and screened by EndNote software, and the risk quality of literature bias was evaluated by Revman 5.4 software. StataSE16 (64-bit) software was used for reticular meta analysis to compare the differences in clinical efficacy and drug safety of five proprietary Chinese medicines combined with western medicine.Results:A total of 24 RCT studies were included, 24 of which were double-arm studies, and five kinds of proprietary Chinese medicine combined with western medicine were compared. The results of reticular meta analysis: in terms of improving the clinical effective rate, the order of the five proprietary Chinese medicine combination groups was as follows: Yindan Xinnaotong Soft Capsules group > Shexiang Baoxin Pills group > Tongxinluo Capsules group > Xinkeshu Tablets group > Compound Danshen Dripping Pills group. In terms of regulating vasodilation factor NO, the order of the four proprietary Chinese medicine combination groups is as follows: Yindan Xinnaotong Soft Capsules group > Compound Danshen Dripping Pills group > Tongxinluo Capsules group > Shexiang Baoxin Pills group. In terms of safety, there were 3 reports of adverse reactions in the research literature of the five proprietary Chinese medicines.Conclusions:The clinical efficacy rate of five kinds of proprietary Chinese medicine combined with western medicine routine regimen is better than that of western medicine routine regimen alone, and the combination group of four kinds of proprietary Chinese medicine is superior to western medicine in regulating vasodilation factor NO, and Yindan Xinnaotong Soft Capsules group is superior in clinical efficacy rate and regulation of vasodilation factor NO. However, the quality and samples of this study are different, and the comparison of the curative effect of the combined group of proprietary Chinese medicine still needs a large sample and high-quality RCT study to demonstrate.
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Objective:To analyze the molecular mechanism of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS by network pharmacology method and molecular docking technology.Methods:The active components and targets of Zhenqi Fuzheng Capsules were obtained through TCMSP, and the AIDS-related targets were obtained through GeneCards, OMIM and DrugBank databases. The intersection target PPI network was constructed through STRING 11.5 database, and Cytoscape 3.9.1 software was used for network topology analysis; Metascape database was used for GO function and KEGG pathway enrichment analysis of core targets; Cytoscape 3.9.1 was used to construct Zhenqi Fuzheng Capsules component-target-pathway network; Autodock Tools software was used to carry out molecular docking of core targets and active components.Results:Totally 31 active components and 180 targets of Zhenqi Fuzheng Capsules were screened out. TNF, IL6, AKT1, IL1B, TP53, VEGFA, RELA, EGFR and CASP3 were identified as the core targets. GO functional enrichment analysis obtained 1 436 biological processes, 53 cellular components, and 117 molecular functions. KEGG pathway enrichment analysis obtained 167 pathways, which were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, and IL-17 signaling pathway was closely related. Molecular docking results showed that core targets such as AKT1 and TNF had good binding activity to quercetin, kaempferol, and luteolin.Conclusion:The main active components of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS are quercetin, kaempferol and luteolin, which may treat AIDS through the IL-17 signaling pathway.
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Objective:To explore the effect of Quercus Salicina Extract Capsulese on preventing the formation of adherent stones on ureteral stent tube after percutaneous nephrolithotomy (PCNL).Methods:The clinical data of 186 patients who underwent PCNL due to unilateral renal stone in the Affiliated Hospital of Xuzhou Medical University from October 2018 to April 2020 were retrospectively analyzed. All of the patients were indwelling 6 F ureteral stent tube during operation. After postoperative reexamination of kidneys, ureters and bladder, it was confirmed that the postoperative residual stones were clinically meaningless stones (maximum diameter ≤ 4 mm). According to postoperative medication, they were divided into drug group ( n=62) and control group ( n=124). Patients in the drug group were given oral Quercus Salicina Extract Capsules, while patients in the control group did not take the drug. Both groups received the same health education and dietary guidance after operation. The formation of adherent stones on ureteral stent tube was observed when the ureteral stent tube was removed 6 weeks after PCNL. Meanwhile, the adverse reaction, complication and treatment satisfaction of the patients were recorded during the period of taking the drug. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; the Chi-square test was used to compare the count data between groups. Results:When the ureteral stent tube was removed 6 weeks after PCNL, the weight of adherent stones on ureteral stent tube in the drug group was (334.20±26.65) mg for male, and (336.00±25.64) mg for female. In the control group, the weight of adherent stones on ureteral stent tube was (374.11±42.28) mg for male, (374.42±42.44) mg for female. The weight of adherent stones on ureteral stent tube in the drug group was significantly lighter than that in the control group, and the difference was statistically significant ( P<0.01). The drug group had no obvious serious adverse reaction during the period of taking the drug. At the same time, the complications of the drug group during the intubation period were significantly less than the control group, and the difference was statistically significant ( P=0.040). The satisfaction of patients in the drug group was 93.5%, and that in the control group was 82.3%. The difference was statistically significant between the two groups ( P=0.036). Conclusion:Quercus Salicina Extract Capsules can effectively prevent the occurrence of adherent stones on ureteral stent tube after PCNL, and there are no serious adverse reaction, which is worthy of clinical promotion.
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OBJECTIVE To establish methods to identify the chemical components of Gantaishu capsule， and determine the contents of 6 index components including glycyrrhizic acid. METHODS The chemical components of Gantaishu capsule were determined by HPLC-TOF/MS； the contents of 6 index components including glycyrrhizic acid were determined by UPLC-MS/MS. RESULTS A total of 41 chemical components were identified in Gantaishu capsules. The linear ranges of glycyrrhizic acid， mangiferin， luteolin， costunolide， oleanolic acid and berberine were 200-10 000 ng/mL（r were all greater than 0.999）. The limits of quantification were 200， 20， 10， 1， 10， 0.5 ng/mL， and the limits of detection were 100， 10， 5， 0.5， 5， 0.25 ng/mL， respectively； RSDs of precision， stability （24 h） and reproducibility tests were all less than 5.0% （n＝6 or n＝3）； the recoveries were 99.05%-101.08% （RSD were all less than 2.0%， n＝6）. The contents of them were 2.42-2.66， 0.85-1.16， 0.35-0.46， 6.18- 6.46， 0.99-1.29， 5.22-5.56 mg/g. CONCLUSIONS The established methods for identification and content determination are rapid and simple， and can be used for the identification of chemical components and the content determination of index components in Gantaishu capsule.
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Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.
Subject(s)
Network Pharmacology , Capsules , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Drugs, Chinese Herbal/pharmacologyABSTRACT
ObjectiveTo study the effect of Bazi Bushen capsules on delaying the aging process of naturally aging mice and its mechanism. MethodThe mice were randomly divided into four groups according to their body weight， namely， aging group， low-dose Bazi Bushen capsules group （1 g·kg-1）， high-dose Bazi Bushen capsules group （2 g·kg-1）， and rapamycin group （0.002 g·kg-1）. The debilitating signs were detected by behavioral tests and the weakness index was measured. The percentages of spleen T and B lymphocytes， effector T cells （TE）， memory T cells （TM）， naive T cells （TN）， helper T cells （Th）， cytotoxic T cells （Tc） ，Th1 cells， Th2 cells， and regulatory T cells （Treg） were determined by flow cytometry. Cell proliferation and the cell counting kit-8 （CCK-8） assay was used to detect the proliferation of lymphocytes in mice. The hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the mouse spleen. The expression of cyclin-dependent kinase inhibitor 2A （p16） and cyclin-dependent kinase inhibitor 1A （p21） was detected by immunohistochemistry （IHC）. The mRNA expression of senescence-related proteins p16 and p21 was determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the inflammatory cytokines， including tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin （IL）-1β， IL-2， IL-4， IL-10， and IL-12 p70， in peripheral blood of mice were detected by Luminex. ResultAs compared with the aging group， mice in the Bazi Bushen capsules and rapamycin groups showed significantly improved debilitating signs and reduced weakness index scores （P<0.05， P<0.01）， increased proportions of T cells， TN cells， Tc cells， Th2 cells， and Treg cells in the spleen， decreased proportions of TE cells， TM cells， Th cells， Th1 cells （P<0.05， P<0.01）， and increased proliferation of splenic lymphocytes （P<0.05， P<0.01）. In the Bazi Bushen capsules and rapamycin groups， clear structure of the red and white marrow marginal zone was observed in the spleen of mice， the area of the white marrow was increased， and the area of the red marrow was correspondingly decreased. The protein and mRNA expression of aging-related proteins p16 and p21 in the spleen was decreased （P<0.01）， the levels of serum pro-inflammatory cytokines IL-1β， IL-2， IL-12 p70， IFN-γ， and TNF-α levels were decreased， and the levels of IL-4 and IL-10 were increased （P<0.05， P<0.01） in the Bazi Bushen capsules and rapamycin groups as compared with the aging group. ConclusionBazi Bushen capsules have the effect of regulating the debilitating signs of natural aging mice， regulating the immune homeostasis and inflammation level of the body， and reducing cell aging.
ABSTRACT
Obesity is a global public health problem that imposes a heavy economic burden on society. The current main strategies for treating obesity include lifestyle interventions, pharmacological treatments, endoscopic treatments and metabolic surgery. With the development of medical technology, weight reduction by intragastric occupancy devices represented by intragastric balloons and intragastric capsules are gradually emerging. Intragastric balloons are used to reduce weight by occupying the volume of the stomach with balloons filled with different volumes of gas or liquid, among which ReShape, Orbera, Obalon, Elipse and Spatz balloons are gradually used in patients with mild to moderate obesity due to their non-invasive, high safety and reusable advantages. Intragastric capsules are recommended in overweight and obese patients for weight loss through hydrogels with transient superabsorbent swelling properties and completely noninvasive. Both approaches achieve weight loss by limiting gastric volume, increasing satiety and reducing food intake. Despite the presence of adverse gastrointestinal events associated with nausea, vomiting, and abdominal distention, they offer new ideas for the non-invasive clinical treatment of obesity.
Subject(s)
Humans , Capsules , Weight Loss , Obesity/surgery , Overweight , Stomach/surgeryABSTRACT
UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.
Subject(s)
Animals , Tumor Necrosis Factor-alpha/genetics , Network Pharmacology , Capsules , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Reproducibility of Results , Tandem Mass SpectrometryABSTRACT
Fracture is one of the common diseases in the department of orthopaedics and traumatology. Jiegu Qili Tablets(Capsules) are a Chinese patent medicine commonly used to treat fractures in clinical practice, which has been included in the Class A drugs of the catalog of medicines covered by the National Medical Insurance System. However, no consensus or guideline has yet been developed to guide clinicians based on an evidence-based approach in detail, which has severely limited the clinical value of this drug. According to the guiding principle of evidence as the key, consensus as the supplement, and experience as the reference, a consensus was developed in strict accordance with the steps stipulated in the expert consensus on clinical applications of proprietary Chinese medicines. Based on literature review and questionnaire survey, the consensus was a timely summary of the existing clinical evidence on the treatment of fractures with Jiegu Qili Tablets(Capsules), and incorporated the treatment experience of a number of clinical experts. The preparation process took more than a year and the consensus(GS/CACM 293-2021) was officially released by the China Association of Chinese Medicine in September 2021, with the participation of multidisciplinary experts from 27 organizations of Chinese and Western medicine and research institutions. This article introduces the background and objectives of the consensus in detail, and describes the main process of proposal, drafting, expert consensus, and consultation. In particular, 5 consensus recommendations and 12 consensus suggestions are formed with regard to the key issues of indications, treatment timing, dose, duration, and safety in the clinical application of Jiegu Qili Tablets(Capsules) for the treatment of fractures, which guide and standardize the rational use by clinicians and improve the accuracy and safety of drugs.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Capsules , Medicine, Chinese Traditional , Consensus , Tablets , ChinaABSTRACT
Abstract The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42-NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient's compliance.