Preventive effect of ecabet sodium on low-dose aspirin-induced small intestinal mucosal injury: a randomized, double-blind, pilot study.

BACKGROUND: We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers. METHODS: Healthy volunteers were enrolled randomly into one of two groups with the following drug regimens for 2 weeks: group A, low-dose aspirin once per day and group B, low-dose aspirin and 4.0 g of ecabet sodium. Small bowel capsule endoscopy was performed before and 2 weeks after low-dose aspirin administration. RESULTS: A significant difference was found in the median number [range] of small intestinal lesions between baseline and two weeks after low-dose aspirin administration in group A (baseline: 1 [0-5], after: 5 [1-11]; p = 0.0059) but not in group B (baseline: 0.5 [0-9], after: 3 [0-23]; p = 0.0586). In group B, although the median number [range] of lesions in the first tertile of the small intestine did not increase two weeks after low-dose aspirin administration (baseline: 0 [0-4], after: 1.5 [0-8]; p = 0.2969), the number of lesions in the second and third tertiles of the small intestine increased significantly (baseline: 0 [0-5], after: 2 [0-15]; p = 0.0469). CONCLUSIONS: Ecabet sodium had a preventive effect on low-dose aspirin-induced small intestinal mucosal injury in the upper part of the small intestine. TRIAL REGISTRATION: ISRCTN 99322160 , 01/10/2018.

[The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen].

Background/Aims: Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. Methods: We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). Results: The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00-12.32; p=0.05). Conclusions: Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.

The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen / 대한소화기학회지

BACKGROUND/AIMS: Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. METHODS: We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). RESULTS: The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00–12.32; p=0.05). CONCLUSIONS: Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.

Efficacy of Ecabet Sodium for Helicobacter pylori Eradication with Sequential Therapy

BACKGROUND/AIMS: We aimed to compare the outcomes of Helicobacter pylori eradication in patients receiving sequential therapy (ST) depending on the use of ecabet sodium (ES). MATERIALS AND METHODS: Between January to December 2015, 176 patients randomly received either ST alone (n=72) or 10-day ES therapy combined with ST (n=104). After applying the exclusion criteria, 56 patients were finally assigned to the ST-only group and 84 to the ST with ES group. We retrospectively reviewed and analyzed the H. pylori eradication rate and adverse events between the two groups. RESULTS: Among the 140 patients, 121 (86.4%) achieved successful H. pylori eradication and 24 (17.1%) had adverse events. Eradication was achieved in 50 patients (89.3%) in the ST-only group and in 71 patients (84.5%) in the ST with ES group (P=0.420). No significant difference in the incidence of adverse events was found between the ST-only and ST with ES groups (12.5% vs. 20.2%, respectively; P=0.234). However, the ST with ES group tended to have a higher prevalence of nausea or vomiting than the ST-only group (11.9% vs. 1.8%; P=0.050). CONCLUSIONS: ST showed a good H. pylori eradication rate without deteriorating the adverse events regardless of adding ES.

Determination of potential genotoxic impurity in ecabet sodium active pharma-ceutical ingredient by HPLC-MS/MS / 中国药科大学学报

To develop a sensitive analytical method for the determination of the genotoxic impurity mono ethyl ester of ecabet (Imp-I),an HPLC-MS/MS technique was employed. Imp-I was synthesized according to the previ-ous literatures. MS/MS and NMR were used to confirm the structure of Imp-I. A Thermo C18column was used for chromatographic separations. The mobile phase consisting of A:5 mmol/L ammonium acetate (pH adjusted to 3. 0 with formic acid)and B:acetonitrile,with a gradient program:0 min 50%B,4 min 50%B,12 min 80%B,16 min 80%B,16. 1 min 50%B and 20 min 50%B. The column was maintained at 40 °C throughout the analysis.All measurements were carried out with the mass spectrometer operated under the negative ESI mode. The selective reaction monitor (SRM)transition was used. Good linearity was obtained for Imp-I over the concentration range of 4 150 ng/mL with the coefficient of determination (r)of 0. 999. And the LOQ was 4 ng/mL. A rapid and sensi-tive HPLC-ESI-MS/MS method was developed for quantitative analysis of Imp-I in ecabet sodium APIs. This method can be of used for quality assurance of ecabet sodium in bulk commercial drugs.

The impact of inflammatory cytokines and therapy effect of ecabet sodium quadruple therapy for patients with duodenal ulcer / 中国生化药物杂志

Objective To study the effect of inflammatory cytokines and therapy effect of ecabet sodium quadruple therapy for patients with duodenal ulcer.Methods80 cases patients with H.pylori-positive ulcer duodenal in In our hospital In our hospital April 2015 to December 2016 were randomLy divided into observation group 42 cases and control group 38 cases, the observation group were treated with ecabet sodium quadruple therapy, the control group were treated with colloidal bismuth pectin quadruple therapy.Then therapy effect, H.pylori eradication rate, inflammatory cytokines, adverse reactions were compared between two groups.ResultsUlcer healing: the observation group total effective rate 97.62% was significantly higher than the control group 78.95% (χ2=6.966, P<0.05);Hp eradicate rate: the observation group Hp eradicate rate 95.24% was significantly higher than that of control group 76.32%(χ2=6.023, P<0.05);Serum inflammatory factors: observation group serum TNF-α, IL-6, IL-8 levels were significantly lower than the control group(t =4.272, 7.584, 3.095, P<0.05);Adverse reaction: observation group adverse reactions 7.14% was significantly lower than the control group 23.68%(χ2=4.281, P<0.05).ConclusionEcabet sodium quadruple therapy helps to reduce serum inflammatory factor expression level, then improve therapy effect and reduce adverse reactions.

Ecabet sodium alleviates neomycin-induced hair cell damage.

Ecabet sodium (ES) is currently applied to some clinical gastrointestinal disease primarily by the inhibition of the ROS production. In this study, the protective role of ES was evaluated against the neomycin-induced hair cell loss using zebrafish experimental animal model. Zebrafish larvae (5-7 dpf), were treated with each of the following concentrations of ES: 5, 10, 20, 40, and 80 µg/mL for 1 h, followed by 125 µM neomycin for 1h. The positive control group was established by 125 µM neomycin-only treatment (1h) and the negative control group with no additional chemicals was also established. Hair cells inside four neuromasts ( SO1, SO2, O1, OC1) were assessed using fluorescence microscopy (n = 10). Hair cell survival was calculated as the mean number of viable hair cells for each group. Apoptosis and mitochondrial damage were investigated using special staining (TUNEL and DASPEI assay, respectively), and compared among groups. Ultrastructural changes were evaluated using scanning electron microscopy. Pre-treatment group with ES increased the mean number of viable hair cells as a dose-dependent manner achieving almost same number of viable hair cells with 40 µM/ml ES treatment (12.98 ± 2.59 cells) comparing to that of the negative control group (14.15 ± 1.39 cells, p = 0.72) and significantly more number of viable hair cells than that of the positive control group (7.45 ± 0.91 cells, p < 0.01). The production of reactive oxygen species significantly increased by 183% with 125 µM neomycin treatment than the negative control group and significantly decreased down to 105% with the pre-treatment with 40 µM/ml ES (n = 40, p = 0.04). A significantly less number of TUNEL-positive cells (reflecting apoptosis, p < 0.01) and a significantly increased DASPEI reactivity (reflecting viable mitochondria, p < 0.01) were observed in 40 µM/ml ES pre-treatment group. Our data suggest that ES could protect against neomycin-induced hair cell loss possibly by reducing apoptosis, mitochondrial damages, and the ROS generation.

The effect of sequential therapy with lansoprazole and ecabet sodium in treating iatrogenic gastric ulcer after endoscopic submucosal dissection: a randomized prospective study.

OBJECTIVE: Ecabet sodium (ES) is a new non-systemic anti-ulcer agent belonging to the category of gastroprotective agents. In this study we aimed to compare the efficacy of a combination therapy with lansoprazole (LS) followed by ES with LS alone in treating endoscopic submucosal dissection (ESD)-induced iatrogenic gastric ulcers. METHODS: Patients diagnosed with gastric adenomas or early gastric cancer were randomly divided into either the LS group (30 mg once daily for 4 weeks; n = 45) or the LS + ES group (LS 30 mg once daily for one week followed by ES 1500 mg twice daily for 3 weeks; n = 45). Four weeks after ESD, a follow-up endoscopy was conducted to evaluate the proportions of ulcer reduction and ulcer stages in the two groups. RESULTS: In all, 79 patients were included in the final analyses. Both treatment modalities were well-tolerated in most patients, with a drug compliance of over 80%. There were no significant differences between the two groups in terms of the proportions of ulcer reduction (0.9503 ± 0.1215 in the LS group vs 0.9192 ± 0.0700 in the LS + ES group, P = 0.169) or ulcer stage (P = 0.446). The prevalence of adverse events related to drugs and bleeding were also similar between the two groups. CONCLUSION: Sequential therapy with LS + ES is as effective as LS alone against ESD-induced gastric ulcers.

Determination of Residual of 4 Kinds Organic Solvents in Ecabet Sodium Crude Drug by Capillary GC / 中国药房

OBJECTIVE:To establish a method for the determination of residuals of petroleum ether,ethanol,xylene and ace-tic acid in ecabet sodium crude drug. METHODS:Capillary GC was performed on the column of PGE-20M capillary column at the flow rate of 1.7 ml/min,detector was hydrogen flame ionization detector,carrier gas was nitrogen with high purity,column temper-ature was 45 ℃,maintaining 4 min,it increased to 80 ℃ with rate of 10 ℃/min,then increased to 135 ℃ with rate of 30 ℃/min,maintaining 3 min,the injection mode was direct injection,inlet temperature was 250 ℃,and the volume injection was 1.0 μl. RESULTS:The mass concentration was 0.050-1.952 g/L for petroleum ether,0.050-1.941 g/L for ethanol,0.024-0.948 g/L for xy-lene and 0.050-1.947g/L for acetic acid(r=0.999 1-0.999 7);RSDs of precision,stability and reproducibility tests were no more than 1.7%;recoveries were 99.3%-101.0%(RSD=0.7%,n=9),102.3%-103.7%(RSD=0.4%,n=9),101.2%-102.1%(RSD=0.3%,n=9) and 100.3%-102.2%(RSD=0.6%,n=9),respectively. CONCLUSIONS:The method is simple and accurate,and can be used for the control of residual of organic solvents in ecabet sodium crude drug.

Efficacy and safety of ecabet sodium as an adjuvant therapy for Helicobacter pylori eradication: a systematic review and meta-analysis.

BACKGROUND: Several studies have reported that the application of ecabet sodium during the eradication of Helicobacter pylori can improve the eradication rate and reduce therapy-associated side effects. However, the efficacy and safety of this therapy are controversial. OBJECTIVES: To determine whether ecabet sodium improves the eradication rate of H. pylori and examine treatment safety by conducting a meta-analysis based on randomized controlled trials (RCTs). METHODS: Literature searches were conducted in the following databases: PubMed, Embase, the Cochrane Library, the Science Citation Index, the China National Knowledge Infrastructure Database, and the Wanfang Database. A meta-analysis of all RCTs comparing ecabet sodium supplementation with nonecabet sodium-containing therapy was performed. RESULTS: Thirteen RCTs that included a total of 1808 patients were assessed. The meta-analysis showed that the eradication rate in the ecabet sodium-containing quadruple therapy group was higher than that in the standard triple therapy group (84.5% vs 74.55%, OR 1.757 (95%CI: 1.307 to 2.362), p < .001). The analysis also showed that the eradication rate in the ecabet sodium-containing triple therapy group was significantly higher than that in the PPI plus amoxicillin or clarithromycin therapy group (74.6% vs 43.9%,OR 3.727 (95%CI: 2.320 to 5.988), p < .001)(ITT), (74.6% vs 43.9%,OR 3.863 (95%CI: 2.369 to 6.298), p < .001) (PP). Furthermore, our meta-analysis suggested that the occurrence of side effects did not significantly differ between patients receiving ecabet sodium-containing therapy and patients receiving nonecabet sodium-containing therapy (14.0% vs 13.3%, OR 1.055 (95%CI: 0.632 to 1.759), p = .839). CONCLUSION: Supplementation with ecabet sodium during H. pylori eradication therapy improves the eradication rate. The use of ecabet sodium does not increase the side effects based on our meta-analysis.

Efficacy of Ecabet Sodium for Helicobacter pylori Eradication, Combined with Lansoprazole-Based Triple Regimen: A Prospective Study / 대한내과학회지

BACKGROUND/AIMS: Ecabet sodium is used for treating gastric ulcers and gastritis. It exhibits a bactericidal effect against Helicobacter pylori by inhibiting bacterial urease activity. Thus, ecabet sodium has been suggested to improve the efficacy of the H. pylori eradication in patients with peptic ulcers. The aim of this study was to compare the H. pylori eradication rate of lansoprazole-based triple therapy versus lansoprazole-based triple therapy plus ecabet sodium. METHODS: The subjects consisted of 363 H. pylori-positive patients who had undergone eradication therapy from February 2007 to February 2010. In total, 363 patients with H. pylori-positive peptic ulcer disease or symptomatic erosive gastritis received LAC (lansprazole 30 mg b.i.d., amoxicillin 1.0 g b.i.d., clarithromycin 500 mg b.i.d.) or LACE (lansoprazole 30 mg b.i.d., amoxicillin 1.0 g b.i.d., clarithromycin 500 mg b.i.d., ecabet sodium 1 g b.i.d.) for 1 week. Successful eradication was defined as a negative 13Curea breath test 4-5 weeks after treatment completion. RESULTS: H. pylori eradication rates were 81.4% (166/204) in the LAC group and 86.2% (137/159) in the LACE group (p = 0.159). No significant difference in eradication was observed. No significant difference was observed in the side effects experienced by the patients in the two treatment groups. CONCLUSIONS: Our results suggest that adding ecabet sodium did not improve the H. pylori eradication rate significantly in standard lansoprazole-based triple therapy for H. pylori.

Effect of Additional Ecabet Sodium on Conventional Triple Therapy for Helicobacter pylori Eradication in Korea / 대한소화기내시경학회지

BACKGROUND/AIMS: Ecabet sodium is known for its bactericidal effect against H. pylori. It was reported that a supplement of ecabet sodium to conventional triple therapy showed good results in Asia. The Aim of this study was to ascertain the efficacy of additional ecabet sodium on conventional triple therapy for eradication of H. pylori. METHODS: We reviewed the cases of 111 patients (Group A) with H. pylori infection who received ecabet sodium with triple therapy (20 mg of rabeprazole, 1 g of amoxicillin, 500 mg of clarithromycin and 1 g of ecabet sodium, twice daily for 7 days). Another 186 patients (Group B) received PPI-based triple therapy (same as the above, except without the ecabet sodium). Eradication was evaluated 4 weeks later after completion of treatment by 13C-UBT. RESULTS: Eradication rates were 74.8% (83/111) in group A and 70.4% (131/186) in group B by intention-to-treat analysis (p=0.420), and 75.2% (82/109) in group A and 70.7% (128/181) in group B by per protocol analysis (p=0.405). CONCLUSIONS: The addition of ecabet sodium to conventional triple therapy did not increase the eradication rate of H. pylori in this study. These findings imply that ecabet sodium as an additional agent cannot overcome antibiotic resistance, which is the most important cause of failure of triple therapy.

Efficacy of ecabet sodium enema on intractable rectal ulcer after piecemeal endoscopic mucosal resection for rectal tumor.

We describe a case with rectal bleeding from a rectal ulcer after endoscopic mucosal resection (EMR), successfully treated with an ecabet sodium (ES) enema. A 44-year-old woman with a laterally spreading rectal tumor of a granular type, 60 mm in diameter, underwent piecemeal EMR. After the EMR, she suffered from rectal bleeding on several occasions over a period of 1 month. Although she was repeatedly treated with thermocoagulation by a heater probe to stop the bleeding, a rectal ulcer with visible vessels still remained at the resected site. Because the rectal ulcer was considered to be intractable, an ES enema was used twice a day (1.5 g) for 2 weeks, which improved rectal bleeding. Colonoscopic findings revealed that the ulcer improved with mucosal healing after the ES enema treatment. This represents the first report of an ES enema treatment in a patient with a rectal ulcer after EMR. Further studies are needed to determine the effectiveness and safety of using an ES enema in patients with EMR-related refractory colorectal ulcers.

Prospective multi-center trial for the efficacy of ecabet sodium on the relief of dyspepsia in korean patients with chronic gastritis.

Anti-peptic and anti-inflammatory actions of ecabet sodium might be beneficial in either improving gastritis or relieving dyspeptic symptoms. This study was designed to evaluate the clinical efficacy of ecabet sodium on dyspeptic symptoms and to elucidate the molecular mechanism attributable to symptom relief in patients with chronic gastritis. Two hundred and sixty eight chronic gastritis patients with persistent dyspepsia received ecabet sodium 1 g b.i.d. for 2 weeks, after which dyspeptic symptoms were reassessed with a questionnaires as before. The changes of interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), prostaglandin E(2) (PGE(2)), and vascular endothelial growth factor (VEGF) levels in gastric juices were measured by ELISA. The changes of nitrotyrosine in gastric mucosa were measured by immunohistochemical staining. The most common dyspeptic symptom in Korean patients with chronic gastritis was epigastric soreness (76.8%), which was improved significantly after ecabet sodium treatment (81.7%, p<0.001). Ecabet sodium was more effective in patients with epigastric pain than vague abdominal discomfort (p = 0.02), especially in patients with old age. Complete relief of discomfort was more highly achieved in patients with positive Helicobacter pylori than without (p = 0.01). In spite of clear tendency that the decreased levels of IL-8, iNOS, and PGE(2) and increased levels of VEGF were measured in gastric juices after ecabet sodium treatment, no statistical significance was noted, which might be due to high inter-individual variations. The nitrotyrosine expressions were significantly decreased after ecabet sodium treatment than before (p<0.01). In conclusion, ecabet sodium treatment was very useful for the relief of dyspeptic symptoms in chronic gastritis, to which both attenuated inflammatory and enhanced regenerative mechanisms were contributive.

The effects of ecabet sodium on nuclear factor-kappa B activation and chemokine gene expression in Helicobacter pylori-infected human gastric epithelial cells / 대한내과학회지

BACKGROUND: Helicobacter pylori stimulates nuclear factor-kappa B (NF-kappa B) activation and chemokine expression of gastric epithelial cells. Although ecabet sodium (ecabet), a locally acting anti-ulcer drug, is known to have an anti-H. pylori activity, there is little known how ecabet acts anti-inflammatory effects in gastric epithelial cells infected with H. pylori. We investigated the effects of ecabet on chemokine gene expression and NF-kappa B activation of human gastric epithelial cells infected with H. pylori. METHODS: After the infection of Hs746T and MKN-45 gastric epithelial cell lines with cagA+cytotoxin+ H. pylori in the presence of ecabet, mRNA expression of chemokine such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) was assessed by quantitative RT-PCR, and chemokine secretion was measured by ELISA. NF-kappa B signals were assayed by electrophoretic mobility shift assay. The activation of NF-kappa B and IL-8 reporter genes was measured by luciferase assay. RESULTS: The treatment of ecabet (5 microgram/mL) decreased the transcription and secretion of chemokine IL-8 and MCP-1 from the gastric epithelial cells infected with H. pylori in a dose-dependent manner. In addition, ecabet inhibited NF-kappa B activation of gastric epithelial cells induced by H. pylori infection. Moreover, the inhibited NF-kappa B signal by ecabet was comprised of heterodimers of p65/p50 predominantly. CONCLUSION: These results suggest that ecabet can inhibit H. pylori-induced IL-8 and MCP-1 gene transcription via suppression of NF-kappa B signal.