Maleate Group Research Articles

Chemical Bonds Formed in Solid Wood by Reaction with Maleic Anhydride and Sodium Hypophosphite

The reaction of wood with maleic anhydride (MA) and sodium hypophosphite (SHP) has been identified as a viable modification method, with macroscopical properties indicating formation of cross-linking to explain the results. However, the chemical reaction between wood and the modification reagents has not been studied yet. To resolve this, the reaction was studied with solid-state 13C cross-polarization magic-angle-spinning (CP-MAS) and 31P MAS nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) to reveal the formation of bonds between wood components, MA and SHP during the treatments to explain the formation of cross-linking and the possible fixation of phosphorus in wood. XPS, solid state 13C and 31P MAS NMR revealed the maleation of wood in the absence of SHP, whilst its presence led to forming a succinic adduct observed through the C-P bond formation, as evidenced by the loss of the maleate C=C bonds at around 130 ppm and the upfield shift of the peak at 165–175 ppm, which was also significantly smoothed, as well as the increase in a peak at 26 ppm due to the reaction between the maleate group and SHP; however, the C-P-C bond could not be unambiguously rationalized from the obtained data. On the other hand, a resonance line at 16 ppm in 31P MAS NMR and the peaks in the XPS P 2p spectrum suggested the formation of a cross-linked structure at low concentrations of SHP, which was more likely to be phosphonate (C-P-O) than organophosphinic acid (C-P-C). The results herein provide a greater fundamental understanding of the mechanisms involved in the reaction of wood, MA and SHP, providing further scope for improved treatment systems in the future.

Effect of Trimebutine and Rifaximin on Breath Hydrogen and Methane by Glucose Breath Test in Patients With Functional Bloating: A Randomized Double-blind Clinical Trial.

Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2)-methane (CH4) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment. The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2/CH4.

A New Method for Quantifying Aluminum in Antiperspirant Lotion Using a Differential Refractometer and an HPLC Column Containing a Maleate Functional Group Kumarswamy Ummiti1*, Narayana Reddy Godi2 , Hanimi Reddy Bapatu2

Aluminum chlorohydrate is a chemical substance employed as an agent to reduce perspiration. As an active antiperspirant agent, it is present in over-the-counter hygiene products at a concentration of up to 25%. The concentration of aluminum chrohydrate will be estimated indirectly by measuring the concentration of free aluminum ions. Various methodological approaches, including atomic absorption spectroscopy, ion chromatography, and titration, can be employed for the estimation of aluminum. In this study, a novel reverse-phase isocratic liquid chromatography approach was created. The method utilized a differential refractometer, a column packed with a maleate group, and an eluent consisting of 2.0% v/v formic acid. The suggested methodology demonstrates a high degree of precision in quantifying the presence of aluminum in Aldry lotion. According to studies testing accuracy, linearity, and precision, the disclosed analytical technique for quantifying aluminum has a range of 0.125 mg/mL to 0.375 mg/mL. The proposed methodology has a significantly reduced execution time of 10 minutes and is characterized by its cost-effectiveness.

L-carnitine promotes liver regeneration after hepatectomy by enhancing lipid metabolism

BackgroundLipid metabolism plays an important role in liver regeneration, but its regulation still requires further research. In this study, lipid metabolites involved in mouse liver regeneration at different time points were sequenced and analyzed to study their influence on liver regeneration and its mechanism.MethodsOur experiment was divided into two parts. The first part examined lipid metabolites during liver regeneration in mice. In this part, lipid metabolites were sequentially analyzed in the livers of 70% mouse hepatectomy models at 0, 1, 3and 7 days after operation to find the changes of lipid metabolites in the process of liver regeneration. We screened L-carnitine as our research object through metabolite detection. Therefore, in the second part, we analyzed the effects of carnitine on mouse liver regeneration and lipid metabolism during liver regeneration. We divided the mouse into four groups: control group (70% hepatectomy group); L-carnitine group (before operation) (L-carnitine were given before operation); L-carnitine group (after operation)(L-carnitine were given after operation) and L-carnitine + perhexiline maleate (before operation) group. Weighing was performed at 24 h, 36 and 48 h in each group, and oil red staining, HE staining and MPO staining were performed. Tunnel fluorescence staining, Ki67 staining and serological examination.ResultsSequencing analysis of lipid metabolites in 70% of mouse livers at different time points after hepatectomy showed significant changes in carnitine metabolites. The results showed that, compared with the control group the mouse in L-carnitine group (before operation) at 3 time points, the number of fat drops in oil red staining was decreased, the number of Ki67 positive cells was increased, the number of MPO positive cells was decreased, the number of Tunnel fluorescence positive cells was decreased, and the liver weight was increased. Serum enzymes were decreased. Compared with control group, L-carnitine group (after operation) showed similar trends in all indexes at 36 and 48 h as L-carnitine group (before operation). L-carnitine + perhexiline maleate (before operation) group compared with control group, the number of fat drops increased, the number of Ki67 positive cells decreased, and the number of MPO positive cells increased at 3 time points. The number of Tunnel fluorescent positive cells increased and serum enzyme increased. However, both liver weights increased.ConclusionL-carnitine can promote liver cell regeneration by promoting lipid metabolism and reduce aseptic inflammation caused by excessive lipid accumulation.

Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Acupuncture for Adults with Diarrhea-Predominant Irritable Bowel Syndrome or Functional Diarrhea: A Systematic Review and Meta-Analysis.

Objective. To evaluate the clinical effectiveness and safety of acupuncture therapy in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) or functional diarrhea (FD) in adults. Method. Five electronic databases—PubMed, EMBASE, CNKI, VIP, and Wanfang—were searched, respectively, until June 8, 2020. The literature of clinical randomized controlled trials of acupuncture for the treatment of IBS-D or FD in adults were collected. Meta-analysis was conducted by Using Stata 16.0 software, the quality of the included studies was assessed by the RevMan ROB summary and graph, and the results were graded by GRADE. Result. Thirty-one studies with 3234 patients were included. Most of the studies were evaluated as low risk of bias related to selection bias, attrition bias, and reporting bias. Nevertheless, seven studies showed the high risk of bias due to incomplete outcome data. GRADE's assessments were either moderate certainty or low certainty. Compared with loperamide, acupuncture showed more effectiveness in weekly defecation (SMD = −0.29, 95% CI [-0.49, -0.08]), but no significant improvement in the result of the Bristol stool form (SMD = −0.28, 95% CI [-0.68, 0.12]). In terms of the drop-off rate, although the acupuncture group was higher than the bacillus licheniformis plus beanxit group (RR = 2.57, 95% CI [0.24, 27.65]), loperamide group (RR = 1.11, 95% CI [0.57, 2.15]), and trimebutine maleate group (RR = 1.19, 95% CI [0.31, 4.53]), respectively, it was lower than the dicetel group (RR = 0.83, 95% CI [0.56, 1.23]) and affected the overall trend (RR = 0.93, 95% CI [0.67, 1.29]). Besides, acupuncture produced more significant effect than dicetel related to the total symptom score (SMD = −1.17, 95% CI [-1.42, -0.93]), IBS quality of life (SMD = 2.37, 95% CI [1.94, 2.80]), recurrence rate (RR = 0.43, 95% CI [0.28, 0.66]), and IBS Symptom Severity Scale (SMD = −0.75, 95% CI [-1.04, -0.47]). Compared to dicetel (RR = 1.25, 95% CI [1.18, 1.32]) and trimebutine maleate (RR = 1.35, 95% CI [1.13, 1.61]), acupuncture also showed more effective at total efficiency. The more adverse effect occurred in the acupuncture group when comparing with the dicetel group (RR = 11.86, 95% CI [1.58, 89.07]) and loperamide group (RR = 4.42, 95% CI [0.57, 33.97]), but most of the adverse reactions were mild hypodermic hemorrhage. Conclusion. Acupuncture treatment can improve the clinical effectiveness of IBS-D or FD, with great safety, but the above conclusions need to be further verified through the higher quality of evidence.

Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundIschemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke.MethodsPatients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram.ResultsIn total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups.ConclusionsThe results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported.Trial registrationChinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827. Retrospectively registered June 13, 2019.

Michael Addition of Thiol Compounds on ω-Maleate Poly(ethylene oxide)s: Model Study for the “Site-Specific” Modification of Proteins

In this study, we successfully synthesized ω-maleate poly(ethylene oxide)s (PEOs) as the modifier for proteins through the thiol-ene Michael addition reaction. Both α-azido-ω-maleate PEO and α-t-butoxy-ω-maleate PEO were obtained from the reaction of ‘living’ polymeric alkoxides with maleic anhydride (over 98 mol%). To examine their availability as one of basic matrices for the thiol-ene Michael addition, model compounds as the precursors of protein carrying the thiol group such as thioacetic acid, cysteamine, and cysteine were employed. Their addition on the maleate group was over 98 mol% under sonication or ultraviolet (UV) irradiation. The acidic condition appeared to affect to yield a diastereomeric mixture. All the PEOs carrying the ω-maleate group appeared to be applied for the efficient modifiers in the “site-specific” PEGylation of peptides or proteins. All the functionalized PEOs including ω-succinate PEO were characterized by a combination of size exclusion chromatographic (SEC), 1H nuclear magnetic resonance (NMR), and Fourier transform-infrared (FT-IR) spectroscopic analyses.

Effects and mechanisms of Shenkang injection promoting extracellular matrix degradation via regulating ERK1/2/MMPs signaling pathway in renal failure rats

This study aimed to clarify preliminarily the effects and mechanisms of Shenkang injection (SKI) promoting extracellular matrix(ECM)degradation via regulating extracellular-signal regulated protein kinase(ERK)1/2/matrix metalloproteinases(MMPs)signaling pathway in renal failure rats. Twenty rats were randomly divided into 4 groups：the Sham group,the Model group,the SKI group and the Enalapril maleate(EM)group. The model rats with renal failure were induced by intragastric administration of adenine and unilateral ureteral obstruction(UUO). After modeling, the rats in SKI group and EM group were intervened by intraperitoneal injection of SKI or intragastric administration of the EM suspension,while the rats in Sham group and Model group were administrated with distilled water respectively for 3 weeks. The 24 h urinary protein excretion(Upro)and urinary N-acety1-β-D-glucosaminidase(UNAG)in all rats were tested after drug administration. All rats were sacrificed after drug administration for 3 weeks,blood and kidney were collected,renal morphological characteristics were observed. Furthermore,serum biochemical indices and the protein expressions of collagen type IV(CIV),MMP-2,MMP-9,tissue inhibitors of metalloproteinase(TIMP)-1,ERK1/2 and phosphorylated-ERK1/2(p-ERK1/2)in the kidney were evaluated respectively. The results indicated that,after the intervention of SKI,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),albumin(Alb),Upro,UNAG and renal morphological change in model rats were improved at different levels,respectively. Moreover,these actions were similar to EM. In addition to these,SKI adjusted the protein expressions of MMP-2,MMP-9 and TIMP-1,and down-regulated the protein expressions of p-ERK1/2 in the kidney. Moreover,these actions were different from EM. In conclusion,SKI promotes ECM degradation and delays the progression of renal failure possibly through regulating ERK1/2 signaling pathway activation in the kidney and intervening MMPs/TIMP-1 expressions in vivo.

Analysis of a randomized, double-blind, double-dummy, controlled, multicenter study confirmed the similar therapeutic efficacies of entecavir maleate and entecavir for treatment of HBeAg-positive chronic hepatitis B

To evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB). The patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded. As in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05). Performing analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.

Effects of traditional Chinese medicine on rats with Type II diabetes induced by high-fat diet and streptozotocin: A urine metabonomic study

Type II diabetes has become a serious threat to human health in recent years. Among adults above 20 years old in China, the prevalence rate of diabetes is 9.7%. Thus, it is imperative to study the mechanisms underlying type II diabetes to develop effective therapeutic treatments. To examine metabolic changes in a rat model of type II diabetes and explore mechanisms underlying the beneficial effects of traditional Chinese medicine (TCM) in this model. 120 rats were divided into four groups, including a control group, a high-fat diet group (high-fat diet and streptozotocin injection), a TCM group (high-fat diet, streptozotocin injection, followed by TCM administration), and a rosiglitazone maleate group (high-fat diet, streptozotocin injection, followed by rosiglitazone maleate administration). Metabolites in urine samples from 1-3 weeks (time point 1) and 4-6 weeks (time point 2) of drug administration were compared by gas chromatography-mass spectrometry (GC-MS). Our results showed that in the high-fat diet group, at time point 2, the levels of dihydroxybenzoic acid, L-ascorbic acid, D-gluconic acid, octadecanoic acid, and glutaric acid in urine were significantly higher than at time point 1. In the TCM group, at time point 2, the urine levels of L-ascorbic acid were markedly lower than at time point 1. Our studies demonstrated that examining urine metabolic changes provided important insights into the mechanisms underlying type II diabetes as well as the therapeutic effects of TCM.

The Incidence of Irritable Bowel Syndrome in Children Using the Rome III Criteria and the Effect of Trimebutine Treatment

Background/AimsIrritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and when compared to the vast knowledge pertaining to adults with IBS, very little is known about IBS in children and adolescents. We aimed to explore the prevalence of IBS, identify symptoms and contributing factors and also to examine the efficacy of trimebutine maleate in children and adolescents.MethodsThe study involved 345 children and adolescents (4-18 years) and parents were requested to fill in a questionnaire, Rome III criteria was used to diagnose IBS. To exclude organic disease, all patients underwent medical investigations. Half of the randomly selected IBS patients were treated with trimebutine maleate while the rest of IBS patients were not. The IBS patients were reevaluated at the end of 3 weeks.ResultsThe prevalence of IBS according to Rome III criteria in children and adolescents was 22.6% and IBS with constipation was the predominant subtype. Back pain (OR, 6.68), headache (OR, 4.72) and chronic fatigue (OR, 3.74) were significantly higher in IBS group. The prevalence of IBS in both parents and depression in mothers was greater for the patient group than the healthy controls (P < 0.0001). The prevalence of functional dyspepsia in IBS group was 80.8% and was significantly higher than control group. Clinical recovery was seen in 94.9% of the trimebutine maleate group versus spontaneous recovery in 20.5% of the non-medicated group. The difference was significant (P < 0.0001).ConclusionsIBS is a common disorder in children and adolescents. IBS is closely associated with somatic and familial factors. Trimebutine maleate is effective for pediatric IBS patients.

Alpha 2A-adrenoreceptor blockade improves sepsis-induced acute lung injury accompanied with depressed high mobility group box-1 levels in rats

PurposeTo investigate the effects of α2A-adrenoreceptor blockade on acute lung injury (ALI) and high mobility group box-1 protein (HMGB1) expression in a rat model of sepsis. MethodsSepsis was induced in male rats by cecal ligation and puncture (CLP). Thirty adult male Sprague-Dawley rats were equally randomized to the Sham group, the CLP group, and the CLP+maleate group. Five hours after CLP, rats received an intraperitoneal injection of BRL-44408 maleate or the same volume of vehicle. Serum levels of TNF-α, IL-6, IL-10, HMGB1, and norepinephrine were measured at baseline, 6, 18, and 24h after CLP. Lung TNF-α, IL-6, IL-10, immunohistochemical and western blotting analysis of HMGB1, nuclear factor (NF)-κB activation, myeloperoxidase (MPO) activity, histological scores, and wet-to-dry weight ratio were determined 24h after CLP. In additional CLP and CLP+maleate groups, the 7day survival rate was evaluated. ResultsCompared with the CLP group, serum TNF-α at 6h, HMGB1 at 18 and 24h, and norepinephrine at 6 and 18h after CLP decreased in the CLP+maleate group. Lung TNF-α, IL-6, and HMGB1 expressions decreased at 24h after CLP. NF-κB activation, MPO activity, histological scores, and wet-to-dry weight ratio were lower in the CLP+maleate group than the CLP group. There was no significant difference in 7day survival rate between the CLP and CLP+maleate groups. ConclusionsThe α2A-adrenoreceptor blockade by a specific antagonist maleate improves sepsis-induced acute lung injury accompanied with depressed HMGB1 expression in rats. The mechanism seemed to be mediated partly through downregulation of the signal transductions of the NF-κB pathway.

Synthesis, Characterization, and Thermostability of Four Novel Cadmium(II) Coordination Polymers with Mixed Ligands

Abstract Four novel mixed‐ligand complexes were obtained from the reaction of maleic acid, diimine chelating ligands and Cd(OH)2 or CdO in a mixed solvent of water and methanol. The complexes were characterized by IR spectroscopy, elemental analysis, and single‐crystal X‐ray diffraction. The results show that all the four complexes are coordination polymers. [Cd(phen)(H2O)(male)]n·2nH2O (1) and [Cd(bipy)(H2O)(male)]n·2nH2O (2) (male = maleate; phen = 1, 10‐phenanthroline, bipy = 2, 2′‐bipyridine) are isomorphic, and the asymmetric unit is constructed by one CdII atom, a maleate group, a diimine ligand and two crystal water molecules. Each maleate group links two CdII atoms in a bis(bidentate) chelating mode, resulting in a 1D helical chain. Within [Cd(phen)(H2O)2(male)]n·2nH2O (3), the maleate group bridges two CdII atoms in a bis(monodentate) chelating mode into a 1D helical chain along the [100] direction. The helical chain is decorated by phen groups alternatively at the two sides, and each phen plane of one chain is inserted in the void space between two adjacent phen ligands from an adjacent chain, resulting in a double zipper‐like chain. The asymmetric unit of [Cd2(phen)2(male)2]n (4) contains a CdII cation, one phen molecule, and a maleate group, and one bridging maleate group links three CdII atoms resulting in a 2D layer extending in [011] plane. The 2D networks are constructed by four kinds of rings formed by the central metal atom and maleate dianion. The thermostabilities of the four complexes were investigated.

Clinical trial: irsogladine maleate, a mucosal protective drug, accelerates gastric ulcer healing after treatment for eradication of Helicobacter pylori infection – the results of a multicentre, double‐blind, randomized clinical trial (IMPACT study)

Helicobacter pylori eradication therapy alone is not sufficient to heal all gastric ulcers. To verify the efficacy of treatment with irsogladine maleate between the termination and assessment of treatment for eradicating H. pylori in a double-blind study. Three hundred and twenty-two patients with a single H. pylori-positive gastric ulcer were given eradication treatment, then assigned randomly to a treatment group [given 4 mg/day irsogladine maleate (n = 150)] or a control group [given a placebo (n = 161)]. The gastric ulcer healing rates were compared after 7 weeks of treatment. The healing rate was significantly higher in the irsogladine maleate group (83.0%) than in the placebo group (72.2%; chi2 test, P = 0.0276). In the subgroup analysis of cases of eradication failure, the gastric ulcer healing rate was significantly higher in the irsogladine maleate group (57.9%) than in the placebo group (26.1%; chi2 test, P = 0.0366). Irsogladine maleate was effective for treating gastric ulcer after H. pylori eradication. The high healing rates observed in patients with or without successful eradication demonstrate the usefulness of irsogladine maleate treatment regardless of the outcome of eradication.

Starch Acetate‐Maleate Mixed Ester Synthesis and Characterization

ABSTRACTA new starch acetate‐maleate mixed ester with different degrees of substitution (DS) for each ester group was prepared. High‐amylose (70%) corn starch was first reacted at 123°C with ≈4.5 equivalents of acetic anhydride for different times, and then the intermediate products were further reacted at 80°C with 0.27–1.1 equivalents of maleic anhydride for a fixed time. 1H NMR and alkaline saponification were used to determine DS values of acetyl and maleate groups. Increasing the reaction time from 60 to 120 min for starch and acetic anhydride increased DS of the acetyl group, while DS of the maleate group increased with increasing amounts of maleic anhydride. There was a good agreement between the two methods for DS determination. The reaction efficiency of acetylation increased from ≈30 to 50% with reaction time, and maleation decreased from ≈30 to 20% with increasing amounts of maleic anhydride. The mixed esters were characterized by 1H NMR, 13C NMR, FTIR, DSC, and TGA. Characteristic peaks in 1H NMR, 13C NMR, and FTIR spectra indicated the presence of acetyl and maleate groups in starch molecules. The exothermic peak in the DSC curve and the increase in thermal stability from the TGA curve were attributed to thermal cross‐linking of the double bond of the maleate group.

Results of a multicenter, 8-week, parallel-group, randomized,double-blind, double-dummy, phase III clinical trial to evaluate the efficacy and tolerability of amlodipine maleate versus amlodipine besylate in Korean patients with mild to moderate hypertension

Background: Recently, amlodipine maleate was developed and tested in preclinical and Phase I clinical trials in Korea. The studies found pharmacokinetics and pharmacodynamics similar to those of amlodipine besylate. Objective: The aim of this study was to compare the efficacy and tolerability of amlodipine maleate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. Methods: This was a multicenter, 8-week, parallel-group, randomized, double-blind, double-dummy, Phase III clinical trial. Eligible patients were Korean, aged 18 to 75 years, had hypertension, and were either taking antihypertensive medications or had a documented sitting diastolic blood pressure of 90 to 109 mm Hg. After a washout period of 2 weeks, patients were randomized to amlodipine maleate or amlodipine besylate for 8 weeks. In both groups, the medications were initiated at 5 mg QD. At day 29, the medication dose was increased to 10 mg QD if sitting diastolic blood pressure (SiDBP) was ≥90 mm Hg. Results: One hundred eighteen patients were enrolled. Fifty-seven patients received amlodipine maleate (29 men, 28 women; mean [SD] age, 49.0 [11.4] years) and 61 received amlodipine besylate (35 men, 26 women; mean [SD] age, 51.6 [9.4] years). Baseline mean (SD) values for sitting systolic blood pressure and SiDBP were 152.0 (12.2) mm Hg and 98.1 (5.6) mm Hg, respectively, for the amlodipine maleate group and 153.4 (14.0) mm Hg and 98.1 (5.5) mm Hg, respectively, for the amlodipine besylate group. In this population, amlodipine maleate was not inferior to amlodipine besylate: the lower limit of the 2-sided 95% CI for the treatment difference in SiDBP was greater than −4 mm Hg. The between-group difference in SiDBP response rate (the proportion of patients who experienced adequate SiDBP reductions) did not reach statistical significance: 85.7% (42/49) for the amlodipine maleate group and 91.8% (45/49) for the amlodipine besylate group. Compliance rates were similar between groups, with mean (SD) compliance rates of 97.4% (2.8%) and 97.1% (3.6%) in the amlodipine maleate and amlodipine besylate groups, respectively. Also, there were no significant differences in the incidences of drug-related clinical and laboratory adverse events; the most common were headache, flushing, facial edema, and paresthesia. Conclusion: In this population, the efficacy and tolerability observed with amlodipine maleate were similar to those seen with amlodipine besylate.

Efficacy of latanoprost and timolol maleate in black and white patients

The purpose of this study was to assess the efficacy of latanoprost 0.005% and timolol maleate 0.5% in black and white patients with elevated intraocular pressure (IOP). This double-masked, randomized, 2-period crossover study included 39 eyes in 22 patients with primary open-angle glaucoma or ocular hypertension. After a 2- to 4-week washout period, patients were randomly assigned to receive either vehicle placebo in the morning and latanoprost in the evening or timolol maleate twice daily for 6 weeks. Then, after a 4-week washout period, patients received the opposing treatment for 6 weeks. Both latanoprost and timolol maleate significantly lowered IOP from baseline in both black and white patients. Latanoprost treatment was associated with lower mean IOP compared with timolol treatment in black patients (P = .013 at 8 AM, P = .19 at 10 AM). At 10 AM at the end of the treatment period, the mean +/- SD change from baseline IOP in black patients receiving latanoprost was significantly greater than that of white patients (-10.2 +/- 7.0 and -5.9 +/- 2.5 mm Hg, respectively; P = .042). The mean +/- SD change from baseline IOPs in black patients was not significantly different from that in white patients at 8 AM at the end of the treatment period for the latanoprost group and at 8 AM and 10 AM at the end of the treatment period for the timolol maleate group. In white patients, the change from baseline IOP in light (grade 1) irises was not significantly different from dark (grade 5) irises after treatment with either latanoprost or timolol maleate. In summary, intraocular pressure after treatment with latanoprost was lower than that after timolol treatment in black patients with primary open-angle glaucoma or ocular hypertension, and at 1 of 2 timepoints, latanoprost caused a significantly greater reduction of IOP in black patients than in white patients.

Dimethyl α-(2-benzyl-1-methyl-4-phenylsulfonylpyrrolo[3,4-b]indol-3-yl)maleate

The title molecule, C 30 H 26 N 2 O 6 S, consists of a methyl-pyrrolo[3,4-b]indole ring with a phenylsulfonyl, a phenyl and a dimethyl maleate group as exocyclic substituents. The pyrrolo[3,4-b]indole ring system is planar. The S atom has distorted tetrahedral geometry. The dihedral angle between the pyrrolo[3,4-b]indole and the phenylsulfonyl group is 65.2 (4) and it is 75.69 (1)° with the phenyl group. The sum of angles at the indole-N atom is 341.7°, while the second pyrrole ring N atom adopts sp 2 hybridization. The packing is stabilized by weak C-H...O hydrogen bonds.

Reactive surfactants in heterophase polymerization. XXIV. Emulsion polymerization of styrene with maleate- and succinate-containing cationic surfactants

A series of alkyl pyridinium bromide maleate and succinate diester surfactants has been used as stabilizers in the free radical emulsion polymerization of styrene. High conversions of styrene were achieved readily with the maleate surfactants, but the succinates gave rise to varying levels of retardation. In two of the latter cases, use of the surfactant at a concentration below its crucial micelle concentration appears to be a key factor, but the other retardations are difficult to account for. Little difference in reactivity and latex properties was found with the maleate surfactants despite the position of the maleate group being very different in the series of molecules examined. Chemical incorporation of the maleate surfmers into the polymer particles appears to occur early on in the polymerizations, but a sufficiently high proportion of groups is on the surface to yield stable latex emulsions. The surface tensions of the final latices produced with both the maleate and succinate surfactants are high, suggesting a large proportion of succinate species are also surface adsorbed. However, the surface tensions of these latices are a little lower than those of latices produced with the maleates, suggesting the proportion of solubilized succinate surfactant is a little higher. This seems to be important in terms of the robustness of the stability of the latices to the addition of electrolytes, the succinate-stabilized species being consistently more tolerant. This suggests that while chemically bound surfactants can improve some of the properties of latices, e.g. the hydrophobicity of films, this might be at the expense of latex stability.