Pinaverium Research Articles

Efficacy of the Combination of Pinaverium Bromide 100 mg Plus Simethicone 300 mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial.

Goals:We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS).Background:IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials.Materials and Methods:IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, double-blind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores.Results:A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events.Conclusions:PB+S was superior to placebo in improving abdominal pain and bloating in patients with active IBS. The effect on the frequency of stool consistency was particularly significant in IBS-C and IBS-M.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Clinical Effects and Safety of Tongxieyaofang on Diarrhea Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized Trails.

Background. Tongxieyaofang (TXYF), a prescription originated from traditional Chinese medicine (TCM), has been widely used on treating Diarrhea Predominant Irritable Bowel Syndrome (IBS-D). The purpose of this meta-analysis was to investigate whether TXYF was effective and safe for IBS-D. Methods. We searched seven electronic databases including CENTRAL, MEDLINE, PubMed, CNKI, VIP, CBM, and Wanfang Data up to 26 July 2017. Randomized controlled trails (RCTs) were eligible, regardless of blinding. Risk of bias of included trials was evaluated according to the Cochrane Handbook. Results. The total number of participants analyzed in the meta-analysis was 3062, of which 1556 received TXYF, while 1506 received ordinary treatment. The primary outcome was clinical effective rate. Compared with conventional medication which included probiotics, pinaverium bromide, trimebutine, and Oryzanol, TXYF significantly improved the clinical effective rate (n=37, OR: 4.61; 95% CI: 3.67–5.78; P < 0.00001) and decreased the adverse events (n=10, OR: 0.26; 95% CI: 0.08–0.86; P = 0.03). There was not significant association with the score of abdominal pain, defecating frequency, fecal property, and total symptom. Conclusions. We suggested a moderate recommendation for TXYF on IBS-D, due to the fact that the risk of bias of the finally included trails was not high. Considering that all identified studies were not of high qualities and large samples, further rigorously designed and large scale RCTs were necessary to improve the applicability of our study results.

Efficacy and safety of pinaverium bromide combined with flupentixol-melitracen for diarrhea-type irritable bowel syndrome: A systematic review and meta-analysis.

Background:There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D), but the sample sizes are small, and the research conclusions are inconsistent. Thus, a meta-analysis was performed, aiming to evaluate the efficacy and safety of this combination therapy in patients with IBS-D.Methods:A systematic literature search was conducted in 7 databases covering the period up to July 2018 to identify randomized controlled trials (RCTs) of PB combined with FM versus PB alone for IBS-D. The primary outcome was the total symptom relief rate. The other outcomes were the adverse events rate, HAMA/SAS score, and HAMD/SDS score. The methodological quality of the RCTs was assessed independently using 6 criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.3.Results:Fifteen RCTs with 1487 participants were identified from 2005 to 2018. Compared with PB alone, 15 RCTs showed significant effects of PB plus FM in terms of improved symptom relief in patients with IBS-D (n = 1487, OR = 5.17, 95%CI, 3.79–7.07, P < .00001). Eleven RCTs reported adverse effects in both the PB plus FM and PB groups, there was no statistically significant difference in the adverse events rate between the 2 groups (n = 1207, OR = 2.91, 95%CI, 0.91–9.28, P = 0.07). Two RCTs and 3 RCTs reported HAMA and HAMD scores respectively, and 3 RCTs reported both SAS and SDS scores. After treatment, the above scores in the PB plus FM group were significantly lower than the PB group (all P < .01). However, the trials were deemed to have a medium risk of bias.Conclusions:The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS-D, and it is safe for clinical use. However, the conclusions still need to be verified by conducting more large-scale and high-quality RCTs.

Acupuncture and related therapies for treating irritable bowel syndrome: overview of systematic reviews and network meta-analysis.

Background:An overview of systematic reviews (SRs) and a network meta-analysis (NMA) were conducted to evaluate the comparative effectiveness of acupuncture and related therapies used either alone, or as an add-on to other irritable bowel syndrome (IBS) treatments.Methods:A total of eight international and Chinese databases were searched for SRs of randomized controlled trials (RCTs). The methodological quality of SRs was appraised using the AMSTAR instrument. From the included SRs, data from RCTs were extracted for the random-effect pairwise meta-analyses. An NMA was used to evaluate the comparative effectiveness of different treatment options. The risk of bias among included RCTs was assessed using the Cochrane risk of bias tool.Results:From 15 SRs of mediocre quality, 27 eligible RCTs (n = 2141) were included but none performed proper blinding. Results from pairwise meta-analysis showed that both needle acupuncture and electroacupuncture were superior in improving global IBS symptoms when compared with pinaverium bromide. NMA results showed needle acupuncture plus Geshanxiaoyao formula had the highest probability of being the best option for improving global IBS symptoms among 14 included treatment options, but a slight inconsistency exists.Conclusion:The risk of bias and NMA inconsistency among included trials limited the trustworthiness of the conclusion. Patients who did not respond well to first-line conventional therapies or antidepressants may consider acupuncture as an alternative. Future trials should investigate the potential of (1) acupuncture as an add-on to antidepressants and (2) the combined effect of Chinese herbs and acupuncture, which is the norm of routine Chinese medicine practice.

Acupuncture with Du’s heat-reinforcing method for diarrhea-predominant irritable bowel syndrome: a randomized controlled trial

To compare the clinical efficacy of Du’s heat-reinforcing method and Western medication in treating diarrheapredominant irritable bowel syndrome (IBS-D). Sixty-five IBS-D patients were randomized into two groups by the random number table. Thirty-three cases in the treatment group were intervened by acupuncture with Du’s heat-reinforcing method, while thirty-two cases in the control group were given oral administration of pinaverium bromide tablets. The intervention lasted 4 weeks for both groups. The IBS symptom severity score (IBS-SSS), IBS-quality of life (IBS-QOL) and hospital anxiety and depression scale (HAD) were adopted to evaluate the therapeutic efficacy. The two groups each had two dropout cases. The clinical recovery rate was 38.7% and the total effective rate was 90.3% in the treatment group versus 13.3% and 66.7% in the control group. The treatment group was superior to the control group in both clinical recovery rate and total effective rate (both P<0.05). After 1-week and 4-week treatment, respectively, the IBS-SSS scores were lower compared with the baseline in both groups, and the intra-group differences were statistically significant (both P<0.05); the score in the treatment group was lower than that in the control group, and the between-group difference was statistically significant (both P<0.05). After 4-week treatment, the component scores of IBS-QOL showed improvements in both groups, and the treatment group was superior to the control group in the improvements of dysphoria, interference with activity, health worry and food avoidance (all P<0.05). The anxiety and depression scales of HAD (HAD-a, HAD-d) in the treatment group and the HAD-a in the control group obtained significant improvements (all P<0.05); the scores of HAD-a and HAD-d in the treatment group were significantly better than those in the control group (both P<0.05). Acupuncture with Du’s heat-reinforcing method can effectively ease the symptoms of IBS-D, improve the quality of life and the state of anxiety and depression. It can produce a more significant efficacy than oral administration of pinaverium bromide tablets.

Gut microbiota was modulated by moxibustion stimulation in rats with irritable bowel syndrome

BackgroundThe pathogenesis of irritable bowel syndrome (IBS) is closely related to intestinal dysbacteriosis and can be controlled by moxibustion treatment. However, the mechanism underlying the therapeutic value of moxibustion in IBS treatment remains unknown.MethodsAn IBS rat model was established by colorectal distention (CRD) stimulus and mustard oil clyster. Sixty-five male rats were randomly divided into six groups: normal, IBS model, moxibustion, electroacupuncture (EA), Bifid-triple Viable Capsule (BTVC) and Pinaverium Bromide (PB) groups. The moxibustion group was treated with mild moxibustion at the bilateral Tianshu (ST25) and Shangjuxu (ST37) for 10 min/day for 7 days, the EA group was given EA at ST25 and ST37 once daily for 7 days, while the BTVC group and PB groups received Bifid-triple Viable Capsule and Pinaverium Bromide solution (at the proportion of 1:0.018) respectively by gavage once daily for 7 days. After the treatment, abdominal withdrawal reflex (AWR) scores were determined based on CRD stimulus, gut microbiota profiling was conducted by 16S rRNA high-throughput sequencing.ResultsIrritable bowel syndrome model rats had significantly increased AWR scores at all intensities (20, 40, 60 and 80 mmHg) compared with the normal group. Moxibustion treatment significantly reduced AWR scores compared with the IBS model group at all intensities. Across all groups the most abundant phyla were Bacteroidetes and Firmicutes followed by Proteobacteria and Candidatus Saccharibacteria. At genus level IBS model rats had a higher abundance of Prevotella, Bacteroides and Clostridium XI and a lower abundance of Lactobacillus and Clostridium XIVa compared with normal rats. These changes in microbiota profiles could however be reversed by moxibustion treatment. Alpha diversity was decreased in IBS model rats compared with normal rats, yet significantly increased in moxibustion- and PB-treated rats compared with IBS rats.ConclusionOur findings suggest that moxibustion treats IBS by modulating the gut microbiota.

Electroacupuncture Relieves Visceral Hypersensitivity by Down-regulating Mast Cell Number，PAR-2/TRPV 1 Signaling, etc. in Colonic Tissue of Rats with Irritable Bowel Syndrome

To observe the effect of electroacupuncture (EA) stimulation of "Shangjuxu" (ST 37, Lower Confluent point) and "Tianshu" (ST 25, Front-Mu point) on visceral pain and expression of colonic tryptase(Try), proteinase-activated receptor 2(PAR-2)，transient receptor potential channel vanilloid subfamily member 1 (TPRV 1)，substance P (SP) and calcitonin gene-related peptide (CGRP) in rats with irritable bowel syndrome (IBS), so as to explore its mechanisms underlying improvement of IBS. Forty male Sprague Dawley rats were equally randomized into normal control (control), model, medication and EA groups (n＝10 in each). The IBS model was established by chronic acute combining stress (CACS, water deprivation, fasting, tail clamping, forced swimming in ice water, restraint, etc.) for 21 days. Rats of the medication group were treated by gavage of Pinaverium Bromide (1 mg/mL, 15 mg/kg), once daily for 14 d. EA (10 Hz/50 Hz, 0.2－0.3 mA) was applied to bilateral ST 37 and ST 25 for 30 min, once daily for 14 d. The muscular withdrawal reflex (AWR) of both abdomen and buttock was detected by colorectal distension (CRD) with a water-filled balloon for examining the visceral hypersensitivity. The number of mast cells in the colonic tissue was counted after toluidine blue stain. The immunoactivity of colonic Try was determined by immunochemistry and the expression of colonic PAR-2, TRVP 1, SP and CGRP proteins detected by Western blot. After modeling, the body weight was significantly decreased in IBS rats of the model, medication and EA groups compared with their own individual pre-treatment and with the control group (P<0.01), and markedly higher in both medication and EA groups than in the model group (P<0.05, P<0.01). The intra-colonic volume thresholds for inducing abdominal and hip AWR were significantly lower in the model group than in the normal control group (P<0.01), and obviously higher in both medication and EA groups than in the model group (P<0.05，P<0.01). The AWR scores of intra-colorectal balloon at volumes of 0.5, 1.0 and 1.5 mL of water were significantly higher in the model group than in the control group (P<0.01), and considerably lower in the EA and medication groups than in the model group (P<0.01). The number of colonic MC and the expression levels of colonic Try, PAR-2, TRPV 1, SP and CGRP proteins were significantly higher in the model group than in the control group (P<0.01), and obviously decreased in both medication and EA groups relevant to the model group (P<0.01). Comparison between the medication and EA groups showed that the decreased expression levels of colonic PAR-2, TRPV 1, SP and CGRP proteins were significantly lower in the EA group than in the medication group (P<0.05), but no significant differences were found between the two groups in intra-colonic volumes for inducing AWR, AWR scores, body weight, and colonic MC number and Try immunoactivity levels (P>0.05)．. EA of ST 37 and ST 25 can relieve visceral hypersensitivity in IBS rats, which may be associated with its effects in down-regulating the number of MC and the expression of PAR-2, TRVP 1, SP, CGRP and Try proteins in the colonic tissue.

Effects of Fengliao-Changweikang in Diarrhea-predominant Irritable Bowel Syndrome Rats and Its Mechanism Involving Colonic Motility.

Background/AimsThis study was designed to investigate the effect of Fengliao-Changweikang (FLCWK) in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its underlying mechanisms.MethodsIBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). In in vivo experiments, the model rats were randomly divided into 5 groups: NMS + RS, FLCWK (low dose, middle dose, and high dose), and pinaverium bromide. The normal control (no handling) rats were classified as the NH group. The therapeutic effect of FLCWK was evaluated by fecal characteristics, electromyographic response and abdominal withdrawal reflex scores. In in vitro experiments, the model rats were randomly divided into 2 groups: NMS + RS, FLCWK (middle dose), and no handling rats were used as the NH group. The differences in basic tension and ACh-induced tension of isolated colonic longitudinal smooth muscle strips (CLSMs) among the 3 groups were observed. In addition, different inhibitors (nifedipine, TMB-8, L-NAME, methylene blue, and 4-AP) were pretreated to explore the underlying mechanisms.ResultsIn in vivo experiments, fecal characteristics, electromyographic response, and abdominal withdrawal reflex scores significantly improved in the FLCWK group, compared with the NMS + RS group. In in vitro experiments, the basic tension and ACh-induced tension of CLSMs in IBS-D rats were significantly inhibited by FLCWK. After pre-treatment with different inhibitors, the ACh-induced tension of CLSMs in each group showed no significant difference.ConclusionsFLCWK manifested curative effect in IBS-D rats by inhibiting colonic contraction. The underlying mechanisms may be related to regulatory pathway of nitric oxide/cGMP/Ca2+ and specific potassium channels.

Analysis of assortment and availability indicators of spasmolytic drugs for gastrointestinal tract functional disorders in Ukraine

Gastrointestinal tract (GIT) functional disorders are one of the most urgent problems in modern gastroenterology, which is due to the widespread nature of this pathology and the problems associated with it. They form a group of heterogeneous (different in nature and origin) clinical states, manifested by various symptoms and disorders of gastrointestinal tract functions, and are not accompanied by structural, metabolic or systemic changes. According to the results of numerous epidemiological studies, up to 50-60 % of adults and up to 30-40 % of children who apply to gastroenterologists suffer from various functional disorders in the digestive system. The World Health Organization (WHO) states: over the past 60 years, the incidence of these disorders has increased 24-fold. Aim. To analyze the range, prices and availability indicator Ca.s. of anesthetic drugs in Ukraine during 2014-2016, and to determine the dynamics of these characteristics for the study period. Results. In 2016 there were 9 INN on the Ukrainian pharmaceutical market , 69 trade names (TN) of drugs were detected. The structural analysis of antispasmodics assortment (2016) showed the largest TN assortment is characteristic of INN: Drotaverin – 30 TN; Simethicone – 16 TN; Papaverine – 10 TN. Medicines are presented on the market in a wide assortment and in an affordable price range, which enables the physician to choose a drug based on its effectiveness and safety. Spasmolytics are presented in a variety of forms: tablets, capsules, syrups, rectal suppositories, oral drops (in the form of emulsions), and solutions / suspensions for the preparation of injections. The most common form of release in this pharmacological group is the pill. In the process of analysis the antispasmodics drugs assortment during the period of 2014-2016, a tendency was observed in the decreased number of foreign manufactured medicines, but there was a slight increase in domestic drug production. By the indicator of economic availability, most generic drugs used for treatment functional disorders in gastrointestinal tract, are highly available. In most cases, imported medicines are in average availability. Conclusions. During the three years studies, the number of domestic generic drugs increased, which are more accessible to Ukrainian consumers, and the number of imported medicines is slightly decreased. The range of prices varied from low to high, and this gave the opportunity to individually choose drugs based on the active ingredients, dosage forms and prices. It ranged from 4.35 to 266.31 UAH, and within the limits of one INN Drotaverin. The study of antispasmodic drugs availability allowed us to establish the vast majority of SLS is represented by highly available medicines, and only some of the INNs are mediated by spasmolytic action medications of mebeverine, drotaverin and pinaverium bromide.

Acupuncture for Diarrhoea-Predominant Irritable Bowel Syndrome: A Network Meta-Analysis.

Background The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture, and drugs in the treatment of diarrhoea-predominant irritable bowel syndrome. Methods Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and CBM) up to December 2017. Additional references were obtained from review articles. With document quality evaluations and data extraction, Network Meta-Analysis was performed using a random-effects model under a frequentist framework. Results A total of 29 studies (n = 9369) were included; 19 were high-quality studies, and 10 were low-quality studies. NMA showed the following: (1) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome is acupuncture, sham acupuncture, pinaverium bromide, alosetron = eluxadoline, ramosetron, and rifaximin; (2) the ranking of treatments in terms of severity of side effects in diarrhoea-predominant irritable bowel syndrome is rifaximin, alosetron, ramosetron = pinaverium bromide, sham acupuncture, and acupuncture; and (3) the treatment of diarrhoea-predominant irritable bowel syndrome includes common acupoints such as ST25, ST36, ST37, SP6, GV20, and EX-HN3. Conclusion Acupuncture may improve diarrhoea-predominant irritable bowel syndrome better than drugs and has the fewest side effects. Sham acupuncture may have curative effect except for placebo effect. In the future, it is necessary to perform highly qualified research to prove this result. Pinaverium bromide also has good curative effects with fewer side effects than other drugs.

The evaluation of the effectiveness of pinaverium bromide therapy for abdominal pain in the patients presenting with ulcerative colitis in remission

The evaluation of the effectiveness of pinaverium bromide therapy for abdominal pain in the patients presenting with ulcerative colitis in remission

Clinical effect of abdominal acupuncture for diarrhea irritable bowel syndrome

To compare the efficacy differences between abdominal acupuncture and western medication for diarrhea irritable bowel syndrome (IBS-D). Sixty-one patients with IBS-D were randomly assigned into an acupuncture group (30 cases after 1 dropping) and a western medication group (28 cases after 2 dropping). Acupuncture was used at Yinqiguiyuan points [Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanyuan (CV 4)], Fusiguan points [bilateral Huaroumen (ST 24), Wailing (ST 26)], Tiaopiqi point [bilateral Daheng (SP 15)], once every other day, 3 times a week. Pinaverium bromide tablet was used orally in the western medication group, 50 mg a time, 3 times a day. All the treatment was given for 4 weeks in the two groups. IBS symptom severity score (IBS-SSS) and clinical symptom scores for abdominal pain and distension, diarrhea, poor stool output, defecation urgency and stool abnormality were observed before and after the treatment as well as 3 months after treatment. Adverse reactions were recorded and the effects were evaluated. ①After treatment and at follow-up, the IBS-SSS scores of the two groups were lower than those before treatment (all P<0.01). Compared with the western medication group, the scores and the improvements between the two time points and before treatment were better in the acupuncture group (P<0.05, P<0.01). ②The symptom scores in the two groups after treatment were lower than those before treatment including abdominal pain, abdominal distension, diarrhea, poor stool output, defecation urgency and stool abnormality (P<0.05, P<0.01), and the scores of abdominal pain, abdominal distension, diarrhea, poor stool output and stool abnormality in the acupuncture group were lower than those in the western medication group (P<0.05, P<0.01). ③The total effective rate and the cured and remarkable effective rate of the acupuncture group were higher than those of the western medication group [(86.7% (26/30) vs 64.3% (18/28), P<0.05; 70.0% (21/30) vs 35.7% (10/28), P<0.01)], and the therapeutic efficacy of the acupuncture group was better than that of the western medication group (P<0.05). There was no adverse reaction. Abdominal acupuncture is more effective for IBS-D than western medication and can relieve abdominal pain, abdominal distension, diarrhea, poor stool output, stool abnormality, with long-term effect.

Wuji Wan Formula Ameliorates Diarrhea and Disordered Colonic Motility in Post-inflammation Irritable Bowel Syndrome Rats by Modulating the Gut Microbiota.

Emerging evidence suggests that gut microbiota contribute to the treatment of post-inflammatory irritable bowel syndrome (PI-IBS). Our previous studies have demonstrated that a Chinese formula, Wuji Wan, has the ability to mitigate abdominal pain and diarrhea in PI-IBS rats. However, little is known about the underlying mechanism and whether the gut microbiota mediate the effect of Wuji Wan on PI-IBS. Thus, the aim of this study was to determine whether Wuji Wan mitigated PI-IBS by modifying the gut microbiota. PI-IBS was induced in Sprague-Dawley rats by enema using 4% acetic acid and restraint stress. Rats were fed water, Wuji Wan extract (630 mg/kg) or pinaverium bromide (13.5 mg/kg). Our data showed that Wuji Wan effectively ameliorated abdominal pain, colonic motility abnormality and visceral hypersensitivity. Analysis of the fecal microbiota showed that Wuji Wan could reverse the reduction in richness of the gut microbiota and significantly increase the relative abundances of Akkermansia, Bacteroides, and Parasutterella; however, Lactobacillus and Prevotella were markedly decreased in the PI-IBS rats. Moreover, Wuji Wan promoted goblet cell proliferation in the colonic mucosa by increasing the release of mucin, up-regulating the distribution of tight junction proteins Occludin and ZO-1 and down-regulating the expression of MLCK in colonic epithelial cells. These findings suggest that Wuji Wan may remit IBS by modulating the gut microbiota and stabilizing the gut mucosal barrier, indicating that the use of a classical formula of Traditional Chinese Medicine (TCM) that exhibits a prebiotic effect may be a promising strategy for PI-IBS treatment.

Pinaverium Bromide: Development and Validation of Spectrophotometric Methods for Assay and Dissolution Studies.

This study presents the development and validation of UV spectrophotometric methods for the determination of pinaverium bromide (PB) in tablet assay and dissolution studies. The methods were satisfactorily validated according to International Conference on Harmonization guidelines. The response was linear (r2 > 0.99) in the concentration ranges of 2-14 μg/mL at 213 nm and 10-70 μg/mL at 243 nm. The LOD and LOQ were 0.39 and 1.31 μg/mL, respectively, at 213 nm. For the 243 nm method, the LOD and LOQ were 2.93 and 9.77 μg/mL, respectively. Precision was evaluated by RSD, and the obtained results were lower than 2%. Adequate accuracy was also obtained. The methods proved to be robust using a full factorial design evaluation. For PB dissolution studies, the best conditions were achieved using a United States Pharmacopeia Dissolution Apparatus 2 (paddle) at 50 rpm and with 900 mL 0.1 M hydrochloric acid as the dissolution medium, presenting satisfactory results during the validation tests. In addition, the kinetic parameters of drug release were investigated using model-dependent methods, and the dissolution profiles were best described by the first-order model. Therefore, the proposed methods were successfully applied for the assay and dissolution analysis of PB in commercial tablets.

DETERMINATION OF PINAVERIUM BROMIDE IN PHARMACEUTICAL DOSAGE FORMS BY A VALIDATED STABILITY-INDICATING LC METHOD

A reversed-phase liquid chromatography (LC) method is validated for the determination of pinaverium bromide (PB) in pharmaceutical dosage forms. The LC method is carried out on a reversed-phase monolithic C18 column (100 x 4.6 mm i.d.), maintained at 45 ºC. The mobile phase consisted of acetonitrile and a solution of triethylamine 0.3% pH 5.0 (50:50; v/v), run at a flow rate of 2.0 mL/min, with photodiode array detector set at 213 nm. The chromatographic separation is obtained with PB retention time of 3.4 min, and it is linear in the range of 5-100 μg/mL (r2 = 0.9991). The limits of detection and quantitation are 1.41 and 4.70 μg/mL, respectively. The specificity and stability-indicating capability of the method are proven through degradation studies, which also showed that there is no interference of the formulation excipients, showing that peak is free from any coeluting peak. The method showed adequate precision, with a relative standard deviation values lower than 1.38%. Excellent values of accuracy were also obtained, with a mean value of 100.68%. Experimental design is used during validation to calculate and prove method robustness. The proposed LC method is applied for the analysis of the PB pharmaceutical dosage forms, contributing to improve the quality control and to assure the therapeutic efficacy.

Clinical effect of traditional Chinese spinal orthopedic manipulation in treatment of Functional Abdominal Pain Syndrome

ObjectiveTo evaluate the clinical effect of Traditional Chinese Spinal Orthopedic Manipulation (TCSOM) in treating Functional Abdominal Pain Syndrome (FAPS) in comparison with Pinaverium Bromide (Dicetel, PBD), and to assess a possible cause for FAPS. Methods60 cases of FAPS patients were randomly assigned to the TCSOM group and PBD group according to the random number table method. The TCSOM group was treated with thumb pressing manipulation, every other day in the first week, and once every three days in the second week, for 5 times treatments. Patients in the PBD group were instructed to take 50mg 3 times a day, consistently for 2 weeks. The symptoms of pre-treatment and post-treatment were assessed on a visual analog scale (VAS) pain score. A symptom improvement rating (SIR) was implemented in order to evaluate the effects of the treatments, and to statistically compare the two groups. ResultsThe symptoms of 21 patients of the TCSOM group were resolved soon after the first spinal manipulation treatment and 4 cases were significantly improved. The VAS pain scores in the TCSOM group were significantly lower than those in the PBD group after 2 weeks treatment. According to the SIR based on VAS, the TCSOM research group included 20 cases with excellent results, 8 cases with good, and 2 cases with poor. There were no side effects in the TCSOM group after treatment. Based on VAS, the PBD research group reported 6 cases with excellent results, 8 cases with good and 16 cases with poor. All cases were statistically analyzed, revealing a significant difference (P<0.001) between the two groups. ConclusionTCSOM group performed much better than PBD group for relief of the symptoms of FAPS. Thumb pressing manipulation on the thoracic and/or lumbar region can correct the displacement of inter-vertebral discs and/or vertebra, resolving the stimuli caused by pressure exerting on the nerves and vessels around the spine. Treatmentwith thumb pressing manipulation on the Back-Shu acupoints, the Jiaji (EX-B2) and the governor vessel acupoint had a very good clinical effect for abdominal pain indicating that it is an effective treatment for FAPS.

Improvement of Quality of Nonanesthetic Colonoscopy by Preoperative Administration of Pinaverium Bromide.

Background:Nonanesthetic colonoscopy is popular in clinical practice in China. However, intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rate, and failure to complete the procedure clinically. Therefore, exploring alternative approaches that can reduce the pain in patients during colonoscopy is of utmost importance, and finding the optimal preoperative administration to improve the quality of nonanesthetic colonoscopy is also necessary. This study aimed to investigate the effects of the prophylactic administration of pinaverium bromide before colonoscopy and the effects of pinaverium bromide alone at different time points or combined with scopolamine butylbromide.Methods:A randomized controlled trial was performed on a cohort of 1000 patients who underwent colonoscopy in outpatient clinic of Wuhan Union Hospital. The patients were randomly assigned to the following groups: Group A, given oral pinaverium bromide (100 mg, three times a day) one day before examination combined with intramuscular injection of scopolamine butylbromide (20 mg) 10 min before colonoscopy; Group B0, given pinaverium bromide alone on the day of colonoscopy (100 mg, three times a day); Group B1, given pinaverium bromide alone (100 mg, three times a day) one day before colonoscopy; Group B2, given pinaverium bromide alone (100 mg, three times a day) two days before colonoscopy; and Group C, given scopolamine butylbromide alone (20 mg) before colonoscopy. The successful rate of colonoscopy, procedure time, degree of abdominal pain, and polyp detection rate were recorded and compared among all groups.Results:The successful rate of colonoscopy in Group B1 (82.0%) and Group B2 (83.0%) was significantly higher than that in Group B0 (62.0%, all P < 0.01). The time to reach the ileocecal region in Group B1 and Group B2 were lower than those in Group B0 (all P < 0.05). However, no significant differences were observed in polyp detection rate between Group B1 (24.0%) or Group B2 (26.0%), and Group B0 (22.4%, all P > 0.05). Furthermore, there were no significant differences in the various parameters examined between Group B1 and Group B2 (P > 0.05). The successful rate of colonoscopy in Group A (92.0%) was significantly higher than that in Group B1 (82.0%) and Group C (80.0%; both P < 0.05). Moreover, the time for the colonoscope to reach the ileocecal region in Group A were markedly shorter as compared to those in Group B1 and Group C (P < 0.05). The polyp detection rate in Group A was 32.0%, significantly higher than that in Group B1 (24.0%, P < 0.05) and Group C (24.2%, P < 0.05).Conclusion:Administration of pinaverium bromide alone one day before examination was beneficial to relieve symptoms of abdominal pain during nonanesthetic colonoscopy. In addition, therapeutic effects were improved when pinaverium bromide administration was combined with intramuscular injection of scopolamine butylbromide. Therefore, the combined use of pinaverium bromide with scopolamine butylbromide might have great application value to improve the quality of nonanesthetic colonoscopy in the preoperative preparation.

Acupuncture with regulating mind and spleen for diarrhea irritable bowel syndrome and sleep quality:a randomized controlled trial

To compare the effects between acupuncture with regulating mind and spleen and wes-tern medication for diarrhea irritable bowel syndrome (IBS-D). Eighty-one patients were randomly at the ratio of 2 to 1 assigned into an acupuncture group (54 cases) and a western medication group (27 cases). Acupuncture with regulating mind and spleen was applied in the acupuncture group for 6 weeks at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37), Sanyinjiao (SP 6), and Taichong (LR 3), once every other day, 3 times a week. Pinaverium bromide tablet was used orally in the western medication group for 6 weeks, 50 mg a time, 3 times a day. IBS symptom severity score (IBS-SSS) were observed before and after 1-week, 6-week treatment. Pittsburgh sleep quality index (PSQI) was applied before and after 6-week treatment. Also, clinical efficacy was evaluated in the two groups. Three patients dropped out in the acupuncture group, and 1 in the western medication group. Except abdominal distension score after 1-week treatment in the western medication group, single scores and total scores of IBS-SSS apparently reduced in the two groups after 1-week and 6-week treatment (P<0.01, P<0.05). After 1-week treatment, the abdominal pain score of the acupuncture group was obviously lower than that of the western medication group (P<0.05). After 6-week treatment, with abdominal pain relief advantage, other results including the number of pain days, defecation satisfaction,life disturbance degree and total score of the acupuncture group were obviously lower than those of the wes-tern medication group (P<0.01,P<0.05). After 6-week treatment, the PSQI score and its change before and after treatment in the acupuncture group were superior to those in the western medication group (both P<0.05). The relief rate and relief plus obvious effective rate in the acupuncture group were higher than those in the western medication group[51.0% (26/51) vs 19.2% (5/26), P<0.01; 64.7% (33/51) vs 34.6% (9/26), P<0.05]. Acupuncture with regulating mind and spleen for diarrhea irritable bowel syndrome can more effectively relieve abdominal pain than pinaverium bromide tablet at the early stage. Its total effect and single effects are better at the later stage on abdominal pain, seizure frequency, defecation satisfaction, life disturbance, and sleep quality.

Effects of baldrinal of Valeriana jatamansi on expression of CRF, TPH1 mRNA and 5-HT in rats with irritable bowel syndrome

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.