Three new maleate compounds have been synthesized and studied by infrared,25Mg NMR(Nuclear Magnetic Resonance)Spectroscopy and UV(Ultraviolet)-visible spectroscopies.The suggested structures for the three complexes ar...Three new maleate compounds have been synthesized and studied by infrared,25Mg NMR(Nuclear Magnetic Resonance)Spectroscopy and UV(Ultraviolet)-visible spectroscopies.The suggested structures for the three complexes are discrete with NH-Cl hydrogen bonds.The maleate anion is monochelating(compound 1 and 2)and bichelating(compound 3).The environment tin(IV)and magnesium center are octahedral and the zinc center environment is tetrahedral.In all the suggested structures,when extra hydrogen bonds are considered,supramolecular architectures are obtained.展开更多
AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized t...AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM(group I) or rabeprazole plus placebo(group P).The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease(FSSG) and the short form(SF)-36 quality of life questionnaires after four weeks of treatment.We also assessed whether patients with NERD with minimal changes(grade M) had different responses to the therapies compared with patients who did not have minimal changes(grade N).RESULTS:Group I and group P showed significant improvements in their FSSG scores after the treatment(from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P.Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N(modified Los Angeles classification)(7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041).The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.CONCLUSION:The addition of IM to rabeprazole significantly improves gastroesophageal reflux diseasesymptoms and the quality of the lives of patients with NERD grade N.展开更多
BACKGROUND： The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral inf...BACKGROUND： The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral infarction to decrease blood viscosity by integrated Chinese and western medicine. OBJECTIVE： To investigate the influence and clinical therapeutic effects of cinepazide maleate combined with tanshinone Ⅱ A sodium sulfonate on the hemorrheologic indexes and blood lipids of patients with acute cerebral infarction, and compare the results with those of simple cinepazide maleate treatment. DESIGN： A non-randomized case-controlled observation. SETTINGS： Hebei North University; the Second Affiliated Hospitals of Hebei North University; the Third Affiliated Hospitals of Hebei North University, PARTICIPANTS： Eighty-six inpatients with cerebral infarction were selected from the infirmary, the Second and Third Affiliated Hospitals of Hebei North University from September 2004 to October 2006. They were all diagnosed to have acute cerebral infarction by CT or MRI, and accorded with the diagnostic standards for acute cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995. Meanwhile, 40 teachers and medical staff of voluntary physical examinees were selected as the control group. Informed contents were obtained from all the patients and their relatives. METHODS： The patients were divided into combined treatment group （n=43） and simple treatment group （n=3）. In the combined treatment group, the patients were administrated with 160 mg cinepazide maleate injection （Beijing Four-ring Pharmaceutical, Co.,Ltd, No. H200220125; 80 mg/2 mL） added in 5% glucose, and 40 mg tanshinone Ⅱ sodium sulfonate （Shanghai No.1 Biochemical ＆ Pharmaceutical Co.,Ltd., No. H31022558, 10 mg/2 mL） added in 250 mL normal saline. In the simple treatment group, the patients were only administrated with cinepazide maleate 320 mg added in 5% glucose or 250 mL normal saline. They were treated for 1 or 2 courses, once a day, and 14 days as a course. The patients were detected before treatment and at 14 and 28 days after treatment respectively. ① Determination of hemorrheologic indexes： Whole blood viscosity was determined with LBY-N6B automatic hemorrheologic meter; Plasma viscosity with LBY-F200B automatic plasma viscosity meter; Volume of fibrinogen was determined by the method of 12.5% sodium nitrate depositing biuret reaction. ② Determination of blood lipids： The serum levels of total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） were determined. ③ Severity of neurological deficit： The total score of neurological deficit score （NDS） ranged from 0 to 45 points, 0 - 15 points was taken as mild, 16 - 30 points as moderate and 31 - 45 points as severe.④ Evaluation of curative effects： Generally cured： NDS decreased by 91% - 100%, and disabled severity of grade 0; Significantly improved： NDS decreased by 46% - 90%, and disabled severity of grades 1 - 3; Improved： NDS decreased by 18% - 45%; No change： NDS decreased by less than 18%; Aggravated： NDS increased by more than 18%. Generally cured and significant improved were taken as significant effect. ⑤ The adverse events and side effects after medication were observed. MAIN OUTCOME MEASURES： ① Results of hemorrheologic indexes and blood lipids; ② NDS results in the combined treatment group and simple treatment group; ③ Therapeutic effects and adverse events. RESULTS： All the 86 patients with cerebral infarction and 40 healthy controls were involved in the analysis of results. ① Results of hemorrheologic indexes and blood lipids： The hemorrheologic indexes and blood lipids before treatment were manifested as abnormalities to different extents in both the combined treatment group and simple treatment group; The hemorrheologic indexes after treatment were obviously improved in both groups. But the hemorrheologic indexes were improved more obviously in the combined treatment group as compared with those in the simple treatment group （P 〈 0.05）; The levels of TC, TG and LDL-C after treatment in the combined treatment group were obviously lowered （P 〈 0.05）, whereas those in the simple treatment group were not significantly changed （P 〉 0.05）. ② NDS results： The NDS scores at 14 and 28 days after treatment in the combined treatment group [（6.23±2.34）, （4.27± 1.83） points] were obviously lower than those in the simple treatment group [（8.76±3.41）, （6.65±2.49） points, P 〈 0.05]. ③ Therapeutic effects and side effects： The total significant effective rates in the combined treatment group and simple treatment group were 93% and 81% respectively. In the combined treatment group, 1 case suffered from palpitation, dizziness and agrypnia. In the simple treatment group, 1 case suffered from palpitation, dizziness and agrypnia, 1 case had itch of skin. All the above symptoms disappeared gradually after the transfusing speed was adjusted to be slower. No drug withdrawal occurred in the patients due to the adverse events. CONCLUSION： Cinepazide maleate combined with tanshinon can obviously improve the abnormalities of hemorrheologic indexes and blood lipids and nerve function in patients with acute cerebral infarction, and its curative effect is faster than that of simple cinepazide maleate treatment.展开更多
The cycloaddition reaction of rosin and maleic anhydride under ultrasonic irradiation has been investigated. The results show that both isomerization and Diels-Alder cycloaddition reactions were accelerated remarkably...The cycloaddition reaction of rosin and maleic anhydride under ultrasonic irradiation has been investigated. The results show that both isomerization and Diels-Alder cycloaddition reactions were accelerated remarkably. The sonochemical reaction reached equilibrium in 5-10 min at 110℃, comparing with regular synthesis of 4-5 h over 180℃.展开更多
In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were inves...In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and inter- leukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swell- ing (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflam- matory response after ischemia-reperfusion in this model.展开更多
Near infrared chemical imaging(NIR-CI)combines conventional near infrared(NIR)spectros-copy with chemical imaging,thus provides spectral and spatial information simult aneously.It could be utilized to visualize the sp...Near infrared chemical imaging(NIR-CI)combines conventional near infrared(NIR)spectros-copy with chemical imaging,thus provides spectral and spatial information simult aneously.It could be utilized to visualize the spatial distribution of the ingredients in a sample.The data acquired using NIR CI instrument are hyperspectral data cube(hypercube)containing thousands of spectra.Chemometric methodologies are necessary to transform spectral information into chemical information.Partial least squares(PLS)method was performed to extract chemical information of chlorpheniramine maleate in pharmaceutical formulations.A series of samples which consisted of different CPM concentrations(w/w)were compressed and hypercube data were measured.The spectra extracted from the hypercube were used to establish the PLS model of CPM.The results of the model were R^(2)_(val)0.981,RMSEC 0.384%,RMSECV 0.483%,RMSEP 0.631%,indicating that this model was reliable.展开更多
Flupirtine maleate, a pharmaceutical compound for treating psychotic disease in clinics, has seven polymorphs. Form A, with better crystal stability and bioavailability, has been widely used as the pharmaceutical crys...Flupirtine maleate, a pharmaceutical compound for treating psychotic disease in clinics, has seven polymorphs. Form A, with better crystal stability and bioavailability, has been widely used as the pharmaceutical crystal form. Unfortunately, it is usually found in a polymorphic mixture with form B. In this study, pure crystal forms of A and B were prepared and characterized by X-ray powder diffraction （XRPD）, Fourier transform infrared spectroscopy （FT-IR） and thermal analysis. An XRPD-based method for the quantitative determination of the amount of the flupirtine maleate polymorphs form A and form B was also established through a systematic optimization of instrumental parameters. The results of the analytical methodology validation showed that the XPRD method had a broad quantitative range of 0- 100% （w/w）, good linear relationship, with R2= 0.999, excellent repeatability and precision and low limits of detection （LoD） of 0.15% （w/w） and quantification （LoQ） of 0.5% （w/w）. The results also showed that the single-peak method was not as good as the whole pattern in reducing the influence of the preferred orientation, but this can be compensated for by a systematic optimization of instrumental parameters and validating the analytical methodology to reduce errors and obtain a good, repeatable, sensitive, and accurate method. This XRPD method can be used to analyze mixtures of flupirtine maleate polymorphs （forms A and B） quantitatively and control the quality of the bulk drug.展开更多
A new polymeric cobalt complex [Co(-male)(py)(H2O)]n (male = maleate; py = pyridine) 1 was prepared by cobalt chloride hexahydrate with disodium maleate and pyridine in an alcohol-aqueous solution. Single-crystal X-ra...A new polymeric cobalt complex [Co(-male)(py)(H2O)]n (male = maleate; py = pyridine) 1 was prepared by cobalt chloride hexahydrate with disodium maleate and pyridine in an alcohol-aqueous solution. Single-crystal X-ray analysis has revealed that 1 crystallizes in the orthor- hombic system, space group Pnma with a = 18.001(1), b = 7.6001(6), c = 7.4731(6) ? V = 1022.4(1) 3, Z = 4, C9H9CoNO5, Mr = 270.10, Dc = 1.755 g/cm3, F(000) = 548, m(MoK? = 1.683 mm-1, S = 1.002, the final R = 0.0280 and wR = 0.0746 for 883 observed reflections with I > 2s(I). The structure analysis shows an approximate octahedral coordination environment of metal center. The Co(II) ions are bridged by maleic anions in a rare tetradentate coordination fashion with a syn-anti coplanar con- formation of the carboxyl group, forming a two-dimensional corrugated 2-D structure which is further attached into a three-dimensional framework via non-classical CH…O interactions between adjacent layers.展开更多
BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety...BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical Trials.gov number,NCT-01926288)at weeks 48,96,and 144.AIM To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C.METHODS In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 wk.Then,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49.The primary efficacy endpoint was the reduction in HBV DNA levels from baseline.Secondary endpoints included the proportion of patients with undetectable HBV DNA(<20 IU/m L),serologic response,serum alanine aminotransferase(ALT)normalization and development of resistance mutations.RESULTS Two hundred eighteen patients who were hepatitis B e antigen(HBe Ag)positive and 57 who were HBe Ag negative were analyzed and predominantly presented with genotype B(49.82%)or C(48.73%).For the HBe Ag-positive CHB patients,the mean HBV DNA level decrease(6.61 Log10 IU/m L vs 6.69 Log10 IU/m L,P>0.05),viral suppression with HBV DNA<20 IU/m L(83.33%vs 79.17%,P>0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week 192.However,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P<0.05).For the HBe Ag-negative CHB patients,no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline(6.05 Log10 IU/m L vs 6.03 Log10 IU/m L,P>0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normalization(95.65%vs 100.00%,P>0.05).Safety and adverse event profiles were similar between Groups A and B.Two HBe Ag-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV.CONCLUSION Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.展开更多
The alternating copolymerization of hydroxyalkyl vinyl ethers and dialkyl maleates is investigated by conventional radical polymerization and reversible addition-fragmentation chain transfer polymerization(RAFT).The i...The alternating copolymerization of hydroxyalkyl vinyl ethers and dialkyl maleates is investigated by conventional radical polymerization and reversible addition-fragmentation chain transfer polymerization(RAFT).The influence of comonomer structure,comonomer feeding ratios,and monomer concentrations on the copolymerization and the copolymer structure have been investigated systematically.With 2-hydroxyethyl vinyl ether(HEVE)and dimethyl maleates(DMM)as comonomers,a well-defined alternating copolymer is prepared with M_(n)=3400 and M_(w)/M_(n)=1.93 up to 71.6% monomer.The alternating sequential chain structure of the copolymers has been proved by both NMR and matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The experimental reactivity ratios and theoretical calculated highest occupied molecular orbital and the lowest unoccupied molecular orbital of vinyl ethers and alkyl maleates support that these monomer pairs have tendency to form alternating copolymers.With 2-cyanopropan-2-yl N-methyl-N-(pyridin-4-yl)carbamodithioate as the RAFT agent,the molecular weight of HEVE and DMM copolymer increases with the monomer conversion,demonstrating a controlled radical polymerization feature with well-controlled molecular weight and relatively narrower molecular weight distribution.With alternating copolymer of HEVE and DMM as macro-CTA(M_(n)=5200 and M_(w)/M_(n)=1.46),both the chain extension with HEVE and DMM(M_(n)=10400 and M_(w)/M_(n)=1.72)and block copolymerization with vinyl acetate have been successfully achieved(M_(n)=8500 and M_(w)/M_(n)=1.52).展开更多
Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.
The electrochemical behavior of N,N-diethyl-p-nitroso aniline was carried out using SWV （square wave voltammetric） at HMDE. A well defined reduction peak was observed at （-0.214） volt versus the reference electro...The electrochemical behavior of N,N-diethyl-p-nitroso aniline was carried out using SWV （square wave voltammetric） at HMDE. A well defined reduction peak was observed at （-0.214） volt versus the reference electrode （Ag/AgC1/sat. KCI）, calibration curve was constructed in phosphate buffer （pH = 7.0）, the relationship is linear within the concentration range 1.283 × 10.5 M - 3.66 × 10.5 M with the correlation （R = 0.9923）. The serial addition ofCPM （chlorpheniramine maleate） leads to the decrease in the reduction current peak （Ip）, quantitatively, the plot of Alp （Ip - Ip） where, Ip： Peak current of N, N-diethyl-p-nitroso aniline alone, lp： peak current of N,N-diethyl-p-nitroso aniline in the presence of CPM, versus concentration is linear within the concentration range 0.984 × 10-6 M - 9.756 × 10-6 M, the correlation coefficient was 0.9954. The method was successfully applied to determine CPM in different types of pharmaceutical formulations, and compared with standard method from British Pharmacopeia [1].展开更多
Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇...Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇-（trifluoromethyl-phenyl） valerophenone as a key intermediate. However, the methods in literatures have some disadvantages, such as the use of expensive materials, heavy pollution of environment, long reaction time and low yield of the product （only 30-40% overall yield）. We herein report an environmentally friendly synthetic method of fluvoxamine maleate, which used 4-（trifluoromethyl） benzoic acid and tetrahydrofuran as starting materials and FeCI3 as catalyst for the coupling of acid chloride with Grignard reagent. The fluvoxamine maleate was synthesized in 46% overall yield, through the oximation, etheration and salification of the intermediate successively.This method has some advantages, such as the use of commercially available materials, low cost, short production period （12-14 h）, high yield and light pollution.展开更多
Cu/SiO2 catalysts prepared by different methods have been investigated focusing on the influence of Cu^＋on the catalytic performance.The composition,structure and copper valence state were characterized by means of B...Cu/SiO2 catalysts prepared by different methods have been investigated focusing on the influence of Cu^＋on the catalytic performance.The composition,structure and copper valence state were characterized by means of BET,XRD,XPS,FTIR,N2O-titration.It was found that the Cu/SiO2 prepared by ammoniaevaporation（AE） method had much higher TOF value than that prepared by wetness-impregnation（WI）with the same THF selectivity.The higher TOF value was attributed to the coexistence of Cu^＋ and Cu^0species in the activated AE-Cu/SiO2.while only Cu° species existing in the activated Wl-Cu/SiO2.Researches suggest that Cu^＋ can adsorb and polarize the C=0 bond of DMM.It is concluded that Cu°could be the main active site and the synergistic effect between Cu^0 and Cu^＋ could contribute to hydrogenation of DMM to THF.展开更多
This study aimed at validating an analytical method, using the accuracy profile approach, for the assay of chlorphenamine maleate by capillary electrophoresis. The validation was done using concentrations ranging betw...This study aimed at validating an analytical method, using the accuracy profile approach, for the assay of chlorphenamine maleate by capillary electrophoresis. The validation was done using concentrations ranging between 75% and 125% of the target concentration of 600 mg/ml. Validation standards were prepared separately in triplicate for each series. Studied validation criteria were selectivity, linearity, trueness, precision (repeatability and intermediate precision), accuracy and limits of detection and quantification. The method was selective, with recoveries ranging between 99.55% and 99.84%. The relative standard deviations of repeatability and intermediate precision were <5%. The accuracy profile confirmed the performance of the assay method between 75% and 100% of the target concentration of 600 mg/ml. The detection and quantification limits were 5 mg/l and 15 mg/l respectively. This ecological and economical method was applied to identify and quantify chlorphenamine maleate in 3 samples of chlorphenamine maleate-based drugs provided by the Senegalese National Medicines Control Laboratory. All analyzed samples were in accordance with official standards.展开更多
Objective:To explore the effect of cinepazide maleate combined with promethazine hydrochloride in the treatment of emergency vertigo.Methods:48 cases of emergency vertigo patients in our hospital from November 2017 to...Objective:To explore the effect of cinepazide maleate combined with promethazine hydrochloride in the treatment of emergency vertigo.Methods:48 cases of emergency vertigo patients in our hospital from November 2017 to November 2019 were divided into experimental group(24 cases,treated with cinepazide maleate combined with promethazine hydrochloride)and control group (24 cases,treated with cinepazide maleate).The clinical efficacy,symptom relief time,adverse reactions and quality of life were compared.Results:The total effective rate of the experimental group(95.83%,23/24)was higher than that of the control group(75.00%),The remission time of nausea and vomiting(1.75±0.22)d,vertigo(3.54±0.63)d,deafiiess and tinnitus(3.47±0.58)d,night sweats(3.05±0.33)d in the experimental group were shorter than those in the control group,P<0.05;the incidence of adverse reactions in the experimental group(8.33%,2/24)was lower than that in the control group(33.33%),The scores of social function,material life attitude,physical health and psychological function in the experimental group were 59.14±7.23,54.05±8.04,53.58±0.86 and 60.11±8.44 respectively,P<0.05.Conclusion:In the process of clinical treatment of emergency vertigo patients,the combined application of cinepazide maleate and promethazine hydrochloride has definite curative effect,can relieve clinical symptoms in a short time,has less adverse reactions,and improves the quality of life of patients to a certain extent,which is worthy of promotion.展开更多
Proniosomes are drug-encapsulated,nanoscale vesicular structures that generate multilamellar niosomal dispersions upon hydration.This study aimed to develop enalapril maleate nanoproniosomal gels and assess their effe...Proniosomes are drug-encapsulated,nanoscale vesicular structures that generate multilamellar niosomal dispersions upon hydration.This study aimed to develop enalapril maleate nanoproniosomal gels and assess their effectiveness in experimental hypertensive rat models.The gels were synthesized based on the coacervation phase separation method,using lecithin,cholesterol,and various nonionic surfactants as formulation components,along with the drug.The developed gels were then subjected to various analyses,such as pH,viscosity,rate of spontaneity,entrapment efficiency,vesicle size,ex vivo permeation,skin irritation,scanning electron microscopy,stability,in vivo bio-availability,in vivo antihypertensive activity,and in vitro-in vivo correlation studies.Results revealed that all synthesized gel formulations maintained good physical characteristics,within permissible limits.The results of the ex vivo skin permeation analysis revealed non-Fickian release kinetics and zero-order penetration behaviors of the drug formulations with diffusion,achieving a cumulative permeation rate of 58.75%-89.72%through albino rat skin over 24 h.Moreover,skin irritation tests revealed that the topical application of the drug formulations did not cause any signs of irritation,indicating their safety.Furthermore,in vivo bio-availability studies revealed that one particular formulation,EMNP7,demonstrated an approximately 188.99-fold greater bio-availability compared to the Vasotec tablet.Additionally,in vivo antihypertensive analysis revealed that this formulation effectively restored elevated rat blood pressures to the normal range.Furthermore,the in vitro-in vivo correlation analysis suggested that the ex vivo(in vitro)data could accurately replicate in vivo physiological conditions.Overall,our findings indicate that enalapril maleate encapsulated within nanoproniosomal gels can effectively function as controlled drug delivery systems,releasing the drug once per day for effective hypertension management.展开更多
Fluvoxamine(FXM)is a well-known selective serotonin reuptake inhibitor(SSRI)for treating depression and has recently been repurposed for efficacious treatment of coronavirus disease 2019.Although cyclodextrin(CD)encap...Fluvoxamine(FXM)is a well-known selective serotonin reuptake inhibitor(SSRI)for treating depression and has recently been repurposed for efficacious treatment of coronavirus disease 2019.Although cyclodextrin(CD)encapsulation effectively improves the physicochemical properties of structurally diverse SSRIs,the molecular understanding of their associations is deficient.This comprehensive study used single-crystal X-ray diffraction integrated with density functional theory(DFT)calculation to provide deep insights into the conformationally flexible FXM and its inclusion complexation withβ-CD.Xray analysis revealed the first crystallographic evidence of the uncomplexed 3FXM-H^(+)·3maleate-(1).Three FXM-H^(+)ions are counter-balanced by three planar maleate-ions to form a thin layer stabilized by infinite fused H-bond rings R_(4)^(4)(12)and R_(6)^(4)(16)and the interplay ofπ…π,CF…πand F…F interactions.For 2β-CD·2FXM-H^(+)·maleate^(2-)·23·2H_(2)O(2),the tail-to-tailβ-CD dimer encapsulates two FXM-H^(+)4-(trifluoromethyl)phenyl moieties,which are charge-balanced by the rare non-planar maleate2and stabilized by N…OH…O H-bonds and F…F interactions.This is a hostevip recognition pattern uniquely observed for allβ-CD complexes with halogen(X)-bearing SSRIs,indicating the essence of X…X interactions and the shielding of X-containing moieties in the wall of theβ-CD dimer.DFT calculations unveiled that the monomeric and dimericβ-CD-FXM complexes and FXM isomers are energetically stable,which alleviates the numbness and bitterness of the orally administered drug as previously patented.Additionally,an insightful conformational analysis of FXM emphasizes the importance of drug structural adaptation in pharmacological functions.展开更多
文摘Three new maleate compounds have been synthesized and studied by infrared,25Mg NMR(Nuclear Magnetic Resonance)Spectroscopy and UV(Ultraviolet)-visible spectroscopies.The suggested structures for the three complexes are discrete with NH-Cl hydrogen bonds.The maleate anion is monochelating(compound 1 and 2)and bichelating(compound 3).The environment tin(IV)and magnesium center are octahedral and the zinc center environment is tetrahedral.In all the suggested structures,when extra hydrogen bonds are considered,supramolecular architectures are obtained.
文摘AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM(group I) or rabeprazole plus placebo(group P).The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease(FSSG) and the short form(SF)-36 quality of life questionnaires after four weeks of treatment.We also assessed whether patients with NERD with minimal changes(grade M) had different responses to the therapies compared with patients who did not have minimal changes(grade N).RESULTS:Group I and group P showed significant improvements in their FSSG scores after the treatment(from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P.Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N(modified Los Angeles classification)(7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041).The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.CONCLUSION:The addition of IM to rabeprazole significantly improves gastroesophageal reflux diseasesymptoms and the quality of the lives of patients with NERD grade N.
基金a grant from Zhangjiakou Bureau of Technology,No. 060132
文摘BACKGROUND： The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral infarction to decrease blood viscosity by integrated Chinese and western medicine. OBJECTIVE： To investigate the influence and clinical therapeutic effects of cinepazide maleate combined with tanshinone Ⅱ A sodium sulfonate on the hemorrheologic indexes and blood lipids of patients with acute cerebral infarction, and compare the results with those of simple cinepazide maleate treatment. DESIGN： A non-randomized case-controlled observation. SETTINGS： Hebei North University; the Second Affiliated Hospitals of Hebei North University; the Third Affiliated Hospitals of Hebei North University, PARTICIPANTS： Eighty-six inpatients with cerebral infarction were selected from the infirmary, the Second and Third Affiliated Hospitals of Hebei North University from September 2004 to October 2006. They were all diagnosed to have acute cerebral infarction by CT or MRI, and accorded with the diagnostic standards for acute cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995. Meanwhile, 40 teachers and medical staff of voluntary physical examinees were selected as the control group. Informed contents were obtained from all the patients and their relatives. METHODS： The patients were divided into combined treatment group （n=43） and simple treatment group （n=3）. In the combined treatment group, the patients were administrated with 160 mg cinepazide maleate injection （Beijing Four-ring Pharmaceutical, Co.,Ltd, No. H200220125; 80 mg/2 mL） added in 5% glucose, and 40 mg tanshinone Ⅱ sodium sulfonate （Shanghai No.1 Biochemical ＆ Pharmaceutical Co.,Ltd., No. H31022558, 10 mg/2 mL） added in 250 mL normal saline. In the simple treatment group, the patients were only administrated with cinepazide maleate 320 mg added in 5% glucose or 250 mL normal saline. They were treated for 1 or 2 courses, once a day, and 14 days as a course. The patients were detected before treatment and at 14 and 28 days after treatment respectively. ① Determination of hemorrheologic indexes： Whole blood viscosity was determined with LBY-N6B automatic hemorrheologic meter; Plasma viscosity with LBY-F200B automatic plasma viscosity meter; Volume of fibrinogen was determined by the method of 12.5% sodium nitrate depositing biuret reaction. ② Determination of blood lipids： The serum levels of total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） were determined. ③ Severity of neurological deficit： The total score of neurological deficit score （NDS） ranged from 0 to 45 points, 0 - 15 points was taken as mild, 16 - 30 points as moderate and 31 - 45 points as severe.④ Evaluation of curative effects： Generally cured： NDS decreased by 91% - 100%, and disabled severity of grade 0; Significantly improved： NDS decreased by 46% - 90%, and disabled severity of grades 1 - 3; Improved： NDS decreased by 18% - 45%; No change： NDS decreased by less than 18%; Aggravated： NDS increased by more than 18%. Generally cured and significant improved were taken as significant effect. ⑤ The adverse events and side effects after medication were observed. MAIN OUTCOME MEASURES： ① Results of hemorrheologic indexes and blood lipids; ② NDS results in the combined treatment group and simple treatment group; ③ Therapeutic effects and adverse events. RESULTS： All the 86 patients with cerebral infarction and 40 healthy controls were involved in the analysis of results. ① Results of hemorrheologic indexes and blood lipids： The hemorrheologic indexes and blood lipids before treatment were manifested as abnormalities to different extents in both the combined treatment group and simple treatment group; The hemorrheologic indexes after treatment were obviously improved in both groups. But the hemorrheologic indexes were improved more obviously in the combined treatment group as compared with those in the simple treatment group （P 〈 0.05）; The levels of TC, TG and LDL-C after treatment in the combined treatment group were obviously lowered （P 〈 0.05）, whereas those in the simple treatment group were not significantly changed （P 〉 0.05）. ② NDS results： The NDS scores at 14 and 28 days after treatment in the combined treatment group [（6.23±2.34）, （4.27± 1.83） points] were obviously lower than those in the simple treatment group [（8.76±3.41）, （6.65±2.49） points, P 〈 0.05]. ③ Therapeutic effects and side effects： The total significant effective rates in the combined treatment group and simple treatment group were 93% and 81% respectively. In the combined treatment group, 1 case suffered from palpitation, dizziness and agrypnia. In the simple treatment group, 1 case suffered from palpitation, dizziness and agrypnia, 1 case had itch of skin. All the above symptoms disappeared gradually after the transfusing speed was adjusted to be slower. No drug withdrawal occurred in the patients due to the adverse events. CONCLUSION： Cinepazide maleate combined with tanshinon can obviously improve the abnormalities of hemorrheologic indexes and blood lipids and nerve function in patients with acute cerebral infarction, and its curative effect is faster than that of simple cinepazide maleate treatment.
基金Supported by the Natural Science Foundation of Guangxi Province （0448020）, the Scientific Research Foundation for the Returned Overseas Chinese Scholars of State Education Ministry （2005-383）, and the Guangxi Talent Highland Program.
文摘The cycloaddition reaction of rosin and maleic anhydride under ultrasonic irradiation has been investigated. The results show that both isomerization and Diels-Alder cycloaddition reactions were accelerated remarkably. The sonochemical reaction reached equilibrium in 5-10 min at 110℃, comparing with regular synthesis of 4-5 h over 180℃.
文摘In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and inter- leukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swell- ing (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflam- matory response after ischemia-reperfusion in this model.
基金supported from Beijing Municipal Government for the university a±liated with the Party Central Committee(Prof.Shi)National Natural Science Foundation of China(81303218)+1 种基金Doctoral Fund of Ministry of Education of China(20130013120006)Special Fund of Beijing University of Chinese Medicine(Manfei Xu).
文摘Near infrared chemical imaging(NIR-CI)combines conventional near infrared(NIR)spectros-copy with chemical imaging,thus provides spectral and spatial information simult aneously.It could be utilized to visualize the spatial distribution of the ingredients in a sample.The data acquired using NIR CI instrument are hyperspectral data cube(hypercube)containing thousands of spectra.Chemometric methodologies are necessary to transform spectral information into chemical information.Partial least squares(PLS)method was performed to extract chemical information of chlorpheniramine maleate in pharmaceutical formulations.A series of samples which consisted of different CPM concentrations(w/w)were compressed and hypercube data were measured.The spectra extracted from the hypercube were used to establish the PLS model of CPM.The results of the model were R^(2)_(val)0.981,RMSEC 0.384%,RMSECV 0.483%,RMSEP 0.631%,indicating that this model was reliable.
基金supported by the Major Program of Ministry of Science and Technology of China(No:2015ZX09J15104-003002)
文摘Flupirtine maleate, a pharmaceutical compound for treating psychotic disease in clinics, has seven polymorphs. Form A, with better crystal stability and bioavailability, has been widely used as the pharmaceutical crystal form. Unfortunately, it is usually found in a polymorphic mixture with form B. In this study, pure crystal forms of A and B were prepared and characterized by X-ray powder diffraction （XRPD）, Fourier transform infrared spectroscopy （FT-IR） and thermal analysis. An XRPD-based method for the quantitative determination of the amount of the flupirtine maleate polymorphs form A and form B was also established through a systematic optimization of instrumental parameters. The results of the analytical methodology validation showed that the XPRD method had a broad quantitative range of 0- 100% （w/w）, good linear relationship, with R2= 0.999, excellent repeatability and precision and low limits of detection （LoD） of 0.15% （w/w） and quantification （LoQ） of 0.5% （w/w）. The results also showed that the single-peak method was not as good as the whole pattern in reducing the influence of the preferred orientation, but this can be compensated for by a systematic optimization of instrumental parameters and validating the analytical methodology to reduce errors and obtain a good, repeatable, sensitive, and accurate method. This XRPD method can be used to analyze mixtures of flupirtine maleate polymorphs （forms A and B） quantitatively and control the quality of the bulk drug.
基金This work was supported by the National Natural Science Foundation of China (No. 20272058) and the Program of Science and Technique Plan of Fujian province
文摘A new polymeric cobalt complex [Co(-male)(py)(H2O)]n (male = maleate; py = pyridine) 1 was prepared by cobalt chloride hexahydrate with disodium maleate and pyridine in an alcohol-aqueous solution. Single-crystal X-ray analysis has revealed that 1 crystallizes in the orthor- hombic system, space group Pnma with a = 18.001(1), b = 7.6001(6), c = 7.4731(6) ? V = 1022.4(1) 3, Z = 4, C9H9CoNO5, Mr = 270.10, Dc = 1.755 g/cm3, F(000) = 548, m(MoK? = 1.683 mm-1, S = 1.002, the final R = 0.0280 and wR = 0.0746 for 883 observed reflections with I > 2s(I). The structure analysis shows an approximate octahedral coordination environment of metal center. The Co(II) ions are bridged by maleic anions in a rare tetradentate coordination fashion with a syn-anti coplanar con- formation of the carboxyl group, forming a two-dimensional corrugated 2-D structure which is further attached into a three-dimensional framework via non-classical CH…O interactions between adjacent layers.
文摘BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical Trials.gov number,NCT-01926288)at weeks 48,96,and 144.AIM To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C.METHODS In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 wk.Then,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49.The primary efficacy endpoint was the reduction in HBV DNA levels from baseline.Secondary endpoints included the proportion of patients with undetectable HBV DNA(<20 IU/m L),serologic response,serum alanine aminotransferase(ALT)normalization and development of resistance mutations.RESULTS Two hundred eighteen patients who were hepatitis B e antigen(HBe Ag)positive and 57 who were HBe Ag negative were analyzed and predominantly presented with genotype B(49.82%)or C(48.73%).For the HBe Ag-positive CHB patients,the mean HBV DNA level decrease(6.61 Log10 IU/m L vs 6.69 Log10 IU/m L,P>0.05),viral suppression with HBV DNA<20 IU/m L(83.33%vs 79.17%,P>0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week 192.However,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P<0.05).For the HBe Ag-negative CHB patients,no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline(6.05 Log10 IU/m L vs 6.03 Log10 IU/m L,P>0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normalization(95.65%vs 100.00%,P>0.05).Safety and adverse event profiles were similar between Groups A and B.Two HBe Ag-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV.CONCLUSION Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.
基金financially supported by the National Natural Science Foundation of China(No.22171017).
文摘The alternating copolymerization of hydroxyalkyl vinyl ethers and dialkyl maleates is investigated by conventional radical polymerization and reversible addition-fragmentation chain transfer polymerization(RAFT).The influence of comonomer structure,comonomer feeding ratios,and monomer concentrations on the copolymerization and the copolymer structure have been investigated systematically.With 2-hydroxyethyl vinyl ether(HEVE)and dimethyl maleates(DMM)as comonomers,a well-defined alternating copolymer is prepared with M_(n)=3400 and M_(w)/M_(n)=1.93 up to 71.6% monomer.The alternating sequential chain structure of the copolymers has been proved by both NMR and matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The experimental reactivity ratios and theoretical calculated highest occupied molecular orbital and the lowest unoccupied molecular orbital of vinyl ethers and alkyl maleates support that these monomer pairs have tendency to form alternating copolymers.With 2-cyanopropan-2-yl N-methyl-N-(pyridin-4-yl)carbamodithioate as the RAFT agent,the molecular weight of HEVE and DMM copolymer increases with the monomer conversion,demonstrating a controlled radical polymerization feature with well-controlled molecular weight and relatively narrower molecular weight distribution.With alternating copolymer of HEVE and DMM as macro-CTA(M_(n)=5200 and M_(w)/M_(n)=1.46),both the chain extension with HEVE and DMM(M_(n)=10400 and M_(w)/M_(n)=1.72)and block copolymerization with vinyl acetate have been successfully achieved(M_(n)=8500 and M_(w)/M_(n)=1.52).
文摘Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.
文摘The electrochemical behavior of N,N-diethyl-p-nitroso aniline was carried out using SWV （square wave voltammetric） at HMDE. A well defined reduction peak was observed at （-0.214） volt versus the reference electrode （Ag/AgC1/sat. KCI）, calibration curve was constructed in phosphate buffer （pH = 7.0）, the relationship is linear within the concentration range 1.283 × 10.5 M - 3.66 × 10.5 M with the correlation （R = 0.9923）. The serial addition ofCPM （chlorpheniramine maleate） leads to the decrease in the reduction current peak （Ip）, quantitatively, the plot of Alp （Ip - Ip） where, Ip： Peak current of N, N-diethyl-p-nitroso aniline alone, lp： peak current of N,N-diethyl-p-nitroso aniline in the presence of CPM, versus concentration is linear within the concentration range 0.984 × 10-6 M - 9.756 × 10-6 M, the correlation coefficient was 0.9954. The method was successfully applied to determine CPM in different types of pharmaceutical formulations, and compared with standard method from British Pharmacopeia [1].
文摘Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇-（trifluoromethyl-phenyl） valerophenone as a key intermediate. However, the methods in literatures have some disadvantages, such as the use of expensive materials, heavy pollution of environment, long reaction time and low yield of the product （only 30-40% overall yield）. We herein report an environmentally friendly synthetic method of fluvoxamine maleate, which used 4-（trifluoromethyl） benzoic acid and tetrahydrofuran as starting materials and FeCI3 as catalyst for the coupling of acid chloride with Grignard reagent. The fluvoxamine maleate was synthesized in 46% overall yield, through the oximation, etheration and salification of the intermediate successively.This method has some advantages, such as the use of commercially available materials, low cost, short production period （12-14 h）, high yield and light pollution.
基金Funding for the present study from the National Key Basic Research Program of China(973 Program,No.2011CB710800)National Natural Science Foundation of China(No.NSFC21406199)
文摘Cu/SiO2 catalysts prepared by different methods have been investigated focusing on the influence of Cu^＋on the catalytic performance.The composition,structure and copper valence state were characterized by means of BET,XRD,XPS,FTIR,N2O-titration.It was found that the Cu/SiO2 prepared by ammoniaevaporation（AE） method had much higher TOF value than that prepared by wetness-impregnation（WI）with the same THF selectivity.The higher TOF value was attributed to the coexistence of Cu^＋ and Cu^0species in the activated AE-Cu/SiO2.while only Cu° species existing in the activated Wl-Cu/SiO2.Researches suggest that Cu^＋ can adsorb and polarize the C=0 bond of DMM.It is concluded that Cu°could be the main active site and the synergistic effect between Cu^0 and Cu^＋ could contribute to hydrogenation of DMM to THF.
文摘This study aimed at validating an analytical method, using the accuracy profile approach, for the assay of chlorphenamine maleate by capillary electrophoresis. The validation was done using concentrations ranging between 75% and 125% of the target concentration of 600 mg/ml. Validation standards were prepared separately in triplicate for each series. Studied validation criteria were selectivity, linearity, trueness, precision (repeatability and intermediate precision), accuracy and limits of detection and quantification. The method was selective, with recoveries ranging between 99.55% and 99.84%. The relative standard deviations of repeatability and intermediate precision were <5%. The accuracy profile confirmed the performance of the assay method between 75% and 100% of the target concentration of 600 mg/ml. The detection and quantification limits were 5 mg/l and 15 mg/l respectively. This ecological and economical method was applied to identify and quantify chlorphenamine maleate in 3 samples of chlorphenamine maleate-based drugs provided by the Senegalese National Medicines Control Laboratory. All analyzed samples were in accordance with official standards.
文摘Objective:To explore the effect of cinepazide maleate combined with promethazine hydrochloride in the treatment of emergency vertigo.Methods:48 cases of emergency vertigo patients in our hospital from November 2017 to November 2019 were divided into experimental group(24 cases,treated with cinepazide maleate combined with promethazine hydrochloride)and control group (24 cases,treated with cinepazide maleate).The clinical efficacy,symptom relief time,adverse reactions and quality of life were compared.Results:The total effective rate of the experimental group(95.83%,23/24)was higher than that of the control group(75.00%),The remission time of nausea and vomiting(1.75±0.22)d,vertigo(3.54±0.63)d,deafiiess and tinnitus(3.47±0.58)d,night sweats(3.05±0.33)d in the experimental group were shorter than those in the control group,P<0.05;the incidence of adverse reactions in the experimental group(8.33%,2/24)was lower than that in the control group(33.33%),The scores of social function,material life attitude,physical health and psychological function in the experimental group were 59.14±7.23,54.05±8.04,53.58±0.86 and 60.11±8.44 respectively,P<0.05.Conclusion:In the process of clinical treatment of emergency vertigo patients,the combined application of cinepazide maleate and promethazine hydrochloride has definite curative effect,can relieve clinical symptoms in a short time,has less adverse reactions,and improves the quality of life of patients to a certain extent,which is worthy of promotion.
文摘Proniosomes are drug-encapsulated,nanoscale vesicular structures that generate multilamellar niosomal dispersions upon hydration.This study aimed to develop enalapril maleate nanoproniosomal gels and assess their effectiveness in experimental hypertensive rat models.The gels were synthesized based on the coacervation phase separation method,using lecithin,cholesterol,and various nonionic surfactants as formulation components,along with the drug.The developed gels were then subjected to various analyses,such as pH,viscosity,rate of spontaneity,entrapment efficiency,vesicle size,ex vivo permeation,skin irritation,scanning electron microscopy,stability,in vivo bio-availability,in vivo antihypertensive activity,and in vitro-in vivo correlation studies.Results revealed that all synthesized gel formulations maintained good physical characteristics,within permissible limits.The results of the ex vivo skin permeation analysis revealed non-Fickian release kinetics and zero-order penetration behaviors of the drug formulations with diffusion,achieving a cumulative permeation rate of 58.75%-89.72%through albino rat skin over 24 h.Moreover,skin irritation tests revealed that the topical application of the drug formulations did not cause any signs of irritation,indicating their safety.Furthermore,in vivo bio-availability studies revealed that one particular formulation,EMNP7,demonstrated an approximately 188.99-fold greater bio-availability compared to the Vasotec tablet.Additionally,in vivo antihypertensive analysis revealed that this formulation effectively restored elevated rat blood pressures to the normal range.Furthermore,the in vitro-in vivo correlation analysis suggested that the ex vivo(in vitro)data could accurately replicate in vivo physiological conditions.Overall,our findings indicate that enalapril maleate encapsulated within nanoproniosomal gels can effectively function as controlled drug delivery systems,releasing the drug once per day for effective hypertension management.
基金supported by the Ratchadapisek Sompoch Endowment Fund,Chulalongkorn University,Thailand(Grant No.:RCU_67_023_010).
文摘Fluvoxamine(FXM)is a well-known selective serotonin reuptake inhibitor(SSRI)for treating depression and has recently been repurposed for efficacious treatment of coronavirus disease 2019.Although cyclodextrin(CD)encapsulation effectively improves the physicochemical properties of structurally diverse SSRIs,the molecular understanding of their associations is deficient.This comprehensive study used single-crystal X-ray diffraction integrated with density functional theory(DFT)calculation to provide deep insights into the conformationally flexible FXM and its inclusion complexation withβ-CD.Xray analysis revealed the first crystallographic evidence of the uncomplexed 3FXM-H^(+)·3maleate-(1).Three FXM-H^(+)ions are counter-balanced by three planar maleate-ions to form a thin layer stabilized by infinite fused H-bond rings R_(4)^(4)(12)and R_(6)^(4)(16)and the interplay ofπ…π,CF…πand F…F interactions.For 2β-CD·2FXM-H^(+)·maleate^(2-)·23·2H_(2)O(2),the tail-to-tailβ-CD dimer encapsulates two FXM-H^(+)4-(trifluoromethyl)phenyl moieties,which are charge-balanced by the rare non-planar maleate2and stabilized by N…OH…O H-bonds and F…F interactions.This is a hostevip recognition pattern uniquely observed for allβ-CD complexes with halogen(X)-bearing SSRIs,indicating the essence of X…X interactions and the shielding of X-containing moieties in the wall of theβ-CD dimer.DFT calculations unveiled that the monomeric and dimericβ-CD-FXM complexes and FXM isomers are energetically stable,which alleviates the numbness and bitterness of the orally administered drug as previously patented.Additionally,an insightful conformational analysis of FXM emphasizes the importance of drug structural adaptation in pharmacological functions.
