Structure based release kinetics analysis of doxazosin mesylate sustained-release tablets using micro-computed tomography

The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping test.With their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release kinetics.The structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic structures.Furthermore,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic preparations.Moreover,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%ethanol.In conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia:A Prospective,Randomized,Open,Parallel Controlled and Multicenter Clinical Study

Objective This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia.Methods A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups.Patients in the control group were treated with polysaccharide-iron complex,and those in the experimental group were administered Jianpi Shengxue tablet.After 8 weeks of continuous treatment,the therapeutic outcomes regarding anemia were compared between the two groups.Results After treatment,the red blood cell(RBC)count,hematocrit(HCT),reticulocyte percentage(RET),ferritin(SF),serum iron(SI),transferrin saturation(TSAT),and serum albumin(ALB)all increased(P<0.01),and the clinical symptom score and total iron binding capacity decreased(P<0.01)in the experimental group.Moreover,the improvements in RBC,HCT,RET,SF,SI,TAST,ALB,and clinical symptoms(fatigue,anorexia,dull skin complexion,numbness of hands and feet)in the experimental group were significantly greater than those in the control group(P<0.05).The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group(P<0.01).Conclusion The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia,leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

Clinical Effect of Ilaprazole Enteric-Coated Tablets in Patients with Peptic Ulcer

Objective: To discuss the actual effect of ilaprazole enteric-coated tablets in the treatment of peptic ulcer patients. Methods: 200 peptic ulcer patients who received treatment from January to December 2023 were selected as the study sample, and all patients were randomly and evenly divided into the study group (n = 100) and the control group (n = 100), and the serum inflammatory factors and the disappearance time of symptoms were compared. Results: After treatment, the serum inflammatory factors in the observation group were better than those in the control group, and the time of belching and burning sensation in the observation group was shorter than that in the control group, all of which were statistically significant (P Conclusion: Ilaprazole enteric-coated tablets in the treatment of peptic ulcer have a good effect and can effectively improve the symptoms of patients with clinical signs, with reference significance.

Efficacy and safety of Yangxinshi tablet for chronic heart failure:A systematic review and meta-analysis

BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(P<0.00001),left ventricular ejection fraction by 6.69%[mean difference(MD)=6.69,95%CI:4.42-8.95,P<0.00001]and 6-min walk test by 49.82 m(MD=49.82,95%C:38.84-60.80,P<0.00001),and reduced N-terminal pro-Btype natriuretic peptide by 1.03 ng/L[standardized MD(SMD)=-1.03,95%CI:-1.32 to-0.74,P<0.00001],brain natriuretic peptide by 80.95 ng/L(MD=-80.95,95%CI:-143.31 to-18.59,P=0.01),left ventricular end-diastolic diameter by 3.92 mm(MD=-3.92,95%CI:-5.06 to-2.78,P<0.00001),and left ventricular endsystolic diameter by 4.34 mm(MD=-4.34,95%CI:-6.22 to-2.47,P<0.00001).Regarding safety,neither group reported any serious adverse events during treatment(RR=0.54,95%CI:0.15-1.90,P=0.33).In addition,Egger's test results indicated no significant publication bias(P=0.557).CONCLUSION YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Evaluation of the Clinical Efficacy of Chuzhi Shengfa Tablets and Finasteride in the Treatment of Androgenetic Alopecia

Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admitted to our Department of Dermatology between January 2022 and January 2024 were randomly divided into two groups,with 30 patients in each group.The control group was treated with finasteride,while the observation group received a combination of Chuzhi Shengfa tablets and finasteride.The clinical efficacy and adverse reactions in both groups were compared.Results:The overall effectiveness rate in the observation group was 93.33%(28/30),significantly higher than the control group’s 73.33%(22/30),with a statistically significant difference(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The combination of Chuzhi Shengfa tablets and finasteride shows good clinical efficacy in treating male androgenetic alopecia.Additionally,Chuzhi Shengfa tablets are convenient to administer and effectively improve efficacy,significantly improving patients’conditions,and demonstrating good clinical application value.

Analysis of the Therapeutic Effect of Clopidogrel Bisulfate Tablets + Aspirin Enteric-Coated Tablets on Acute Myocardial Infarction

Objective:To investigate and analyze the clinical effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on acute myocardial infarction(AMI)patients.Methods:The study period was from January 2020 to December 2023,the sample source was 82 AMI patients admitted to our hospital,grouped into an observation group(n=41)and a control group(n=41)by the numerical table method.The patients in the control group were treated with aspirin enteric-coated tablets,and the patients in the observation group were treated with aspirin enteric-coated tablets combined with clopidogrel bisulfate.The clinical efficacy,coagulation indexes,and the incidence of cardiovascular adverse events between the two groups were compared.Results:The clinical efficacy of the observation group was higher than that of the control group(P<0.05);the platelet aggregation rate(PAR)of the observation group was lower than that of the con-trol group after treatment(P<0.05),and there was no significant difference in the prothrombin time(PT)and activated partial thromboplastin time(APTT)between the two groups(P>0.05).The incidence of cardiovascular adverse events in the observation group was lower than that of the control group(P<0.05).Conclusion:The treatment effect of clopidogrel bisulfate tablets combined with aspirin enteric-coated tablets on AMI patients is remarkable.It reduces the PAR and the incidence of cardiovascular adverse events,so this treatment method should be popularized.

Effectiveness of Chuzhi Shengfa Tablets Combined with Ketoconazole Shampoo and Chuzhi Shengfa Tablets Combined with 5%Minoxidil Foam in the Treatment of Male Androgenetic Alopecia

Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic alopecia.Methods:From July 2022 to July 2023,120 male patients with androgenetic alopecia were selected from our Department of Dermatology and randomly divided into Control Group 1,Control Group 2,Observation Group 1,and Observation Group 2,with 30 patients in each group.Control Group 1 was treated with ketoconazole shampoo,Control Group 2 with 5%minoxidil foam,Observation Group 1 with ketoconazole shampoo combined with Chuzhi Shengfa Tablets,and Observation Group 2 with 5%minoxidil foam combined with Chuzhi Shengfa Tablets.Hair density,hair diameter,scalp oil secretion(using oil secretion scoring),and adverse reactions were compared before and after treatment across the four groups.Results:After treatment,hair density and hair diameter significantly increased in all four groups compared to before treatment,while scalp oil secretion scores significantly decreased(P<0.05).The improvements in Observation Groups 1 and 2 were significantly better than those in Control Groups 1 and 2(P<0.05).No significant differences in the incidence of adverse reactions were observed among the four groups(P>0.05).Conclusion:Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam are both effective and safe for treating male androgenetic alopecia.These combinations can significantly improve hair growth and are worthy of clinical promotion.

清代功牌、功劄的演变与多元军制文化的交融

清朝军功凭证有功牌和功劄之分,前者颁给八旗、蒙古军,后者则颁给绿营军和有功义士。功牌源于满洲旧制,功劄承自明朝旧制,而到清中后期二者逐渐走向合流。乾隆年间改木质功牌为纸质功牌,改功劄加衔为功劄授职。清后期,八旗和绿营的战斗力下降,团练、水师和新军兴起,清廷适时改革军功凭证,从而出现结合功牌与功劄为一体的顶戴功牌。这是满汉两种叙功制度不断融合的结果,体现了晚清不同军制文化元素的交融进程。

辅酶Q10片辅助美托洛尔治疗高血压合并室性心律失常的效果

目的 探究辅酶Q10片辅助美托洛尔在高血压合并室性心律失常患者中的应用效果。方法 采用回顾性研究,收集2021年1月至2023年12月医院接受美托洛尔治疗的52例高血压合并室性心律失常患者病历资料,纳入对照组;收集医院同期接受辅酶Q10片辅助美托洛尔治疗的52例高血压合并室性心律失常患者病历资料,纳入观察组,全部患者临床资料均保存完整。查阅患者病历资料,比较两组治疗效果,治疗前后血压指标、心率指标及心电图指标、心肌损伤指标,以及用药不良反应发生情况。结果 观察组总有效率为96.15%,高于对照组总有效率84.62%,差异有统计学意义(P<0.05);治疗后,两组舒张压与收缩压均降低,且观察组低于对照组,差异有统计学意义(P<0.05);治疗后,两组心率、窦性心律失常频次、QT间期离散度(QTd)、QT校正离散度(QTcd)均下降,且观察组低于对照组,差异有统计学意义(P<0.05);治疗后,两组心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、肌红蛋白(Myo)均降低,且观察组低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 辅酶Q10片辅助美托洛尔治疗高血压合并室性心律失常患者的临床效果显著,可以有效降低患者血压,改善心律失常症状,促进心肌细胞修复,且安全性好。

Simultaneous Determination of Baicalin, Berberine and Rhein by HPLC in Traditional Chinese Patent Medicine Sanhuang Tablets

Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.

Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers

Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.

Pharmacokinetics and Absolute Bioavailability of the Sublingual Naloxone Hydrochloride Tablet in Dogs

The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.

High Resolution Determination of Ondansetron in Human Plasma by HPLC and Pharmacokinetics of Orally Disintegrating Tablets

Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.

Simultaneous determination of four active compounds in Dangguilonghui tablet by high-performance liquid chromatography

A high-performance liquid chromatography （HPLC） method has been developed for the first time to simultaneously quantify the four active ingredients, namely aloha, baicalein, aloe-emodin and wogonin, in Dangguilonghui tablet. The marker compotmds were separated on the Diamonsil C18 column at a flow rate of 1.0 mL/min with a mobile phase of methanol-acetonitrile-0.3% aqueous phosphoric acid （220： 4： 200, v/v/v） and while the detection wavelength was set at 225 nm. The assay was linear over the range of 1.450 - 29.00 ug/mL （r = 0.9992） for aloin, 0.4050 - 8.100ug/mL （r = 0.9994） for baicalein, 0.1100 - 2.200 ug/mL （r = 0.9997） for aloe-emodin, 0.2160 - 4.320 ug/mL （r = 0.9991） for wogonin, respectively. The average sample recoveries at three concentration levels were 100.7% （RSD = 0.88%）, 101.0% （RSD = 0.89%）, 100.0% （RSD = 1.3%） and 100.1% （RSD = 1.1%） for these constituents, respectively. This method is suitable for the quality control of Dangguilonghui tablet.

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

季德胜蛇药片治疗急性痛风性关节炎大鼠的机制研究

目的探究季德胜蛇药片治疗急性痛风性关节炎(AGA)大鼠的可能机制。方法2022年10月至2023年2月,选取60只雄性SD大鼠为研究对象,采用随机数字表法分为空白对照组、模型组、季德胜蛇药片组和依托考昔组,除空白对照组外其他大鼠均通过关节腔注射尿酸钠溶液构建AGA大鼠模型,造模成功后12 h,季德胜蛇药片组灌胃季德胜蛇药片2.4 g·kg^(−1)·d^(-1),依托考昔组灌胃依托考昔3.125 mg·kg^(−1)·d^(-1),均持续干预7 d,测量各组大鼠关节肿胀程度、步态行为学分级,并于末次干预12 h后腹主动脉取血采用酶联免疫吸附法测量血清白细胞介素-1β(IL-1β)、IL-6、IL-10及肿瘤坏死因子(TNF-α)水平;麻醉处死大鼠后分离踝关节滑膜组织固定后制成切片HE染色观察病理形态学特征,蛋白质印迹法检测滑膜组织中核转录因子-κB p65(NF-κB p65)、IL-1β、IL-6、IL-10、TNF-α蛋白表达水平。结果与空白对照组比较,模型组造模后1、2、3 d时关节肿胀度均升高,且步态行为学分级程度也升高(P<0.05),与模型组比较,季德胜蛇药片组与依托考昔组大鼠关节肿胀度均降低,步态行为学分级程度也有改善(P<0.05)。HE染色结果显示,模型组大鼠可见明显滑膜组织增生,充血水肿并伴有大量中性粒细胞及单核细胞等炎症细胞浸润,季德胜蛇药片干预后滑膜层细胞基本正常,轻微充血水肿,炎症细胞浸润程度降低,与依托考昔干预后情况基本一致。模型组大鼠血清IL-1β、IL-6、TNF-α水平[(45.15±8.76)ng/L、(54.26±8.29)ng/L、(229.54±31.18)ng/L]均高于空白对照组大鼠[(10.41±3.25)ng/L、(16.52±4.13)ng/L、(108.94±21.26)ng/L,P<0.05],滑膜组织中p-NF-κB p65/NF-κB p65、IL-1β、IL-6、TNF-α蛋白表达(1.98±0.32、1.34±0.12、1.20±0.18、1.30±0.11)均高于空白对照组大鼠(0.32±0.07、0.18±0.03、0.28±0.05、0.24±0.04,P<0.05),血清、滑膜组织IL-10水平和蛋白表达[(21.06±4.39)ng/L、0.72±0.09]均低于空白对照组大鼠[(43.15±7.24)ng/L、1.45±0.12,P<0.05]。与模型组大鼠比较,季德胜蛇药片组、依托考昔组大鼠血清IL-1β、IL-6、TNF-α水平[季德胜蛇药片组分别为(21.62±3.95)ng/L、(24.37±5.26)ng/L、(135.31±22.47)ng/L,依托考昔组分别为(22.42±4.39)ng/L、(26.08±5.41)ng/L、(139.42±21.35)ng/L]及滑膜组织中p-NF-κB p65/NF-κB p65、IL-1β、IL-6、TNF-α蛋白表达均降低(季德胜蛇药片组分别为0.72±0.14、0.64±0.09、0.73±0.10、0.56±0.07,依托考昔组分别为0.69±0.13、0.57±0.07、0.68±0.13、0.58±0.08,均P<0.05),血清IL-10水平和滑膜组织IL-10蛋白表达升高[季德胜蛇药片组分别为(38.15±5.25)ng/L、1.08±0.11,依托考昔组分别为(36.97±6.12)ng/L、1.10±0.13,均P<0.05],季德胜蛇药片组与依托考昔组上述指标比较差异无统计学意义(P>0.05)。结论季德胜蛇药片能够明显改善急性痛风性大鼠关节症状,下调关节炎症反应,可能与抑制NF-κB信号通路活化有关。

Compound Metformin/Glipizide Bilayer Extended Release Tablets: Development and in Vitro Release

Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose （HPMC） by wet granulation technique in order to tackle the problems associated with the muhidrug therapy of non-insulin dependent diabetes mellitus. Me^ls High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.

栝蒌瞿麦方加味联合地诺孕素片治疗痰湿瘀结型子宫腺肌症临床研究

目的:观察栝蒌瞿麦方加味联合地诺孕素片治疗痰湿瘀结型子宫腺肌症(AM)的临床疗效。方法:选取2021年8月—2024年2月在郑州市第二人民医院就诊的86例痰湿瘀结型AM患者,按随机数字表法分为对照组、研究组各43例。对照组给予地诺孕素片治疗,研究组给予栝蒌瞿麦方加味联合地诺孕素片治疗,2组均治疗6个月经周期。比较2组临床疗效、视觉模拟评分法(VAS)评分、月经失血图(PBAC)评分、子宫体积、子宫内膜厚度、性激素[雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)]、血管生成因子[前列腺素F2α(PGF2α)、血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)]、氧化应激指标[丙二醛(MDA)、沉默信号调节蛋白6(Sirt6)、超氧化物歧化酶(SOD)]及不良反应发生率。结果:治疗后,总有效率研究组83.72%(36/43),高于对照组65.12%(28/43),差异有统计学意义(P<0.05)。2组VAS、PBAC评分均较治疗前降低,子宫体积均较治疗前缩小,子宫内膜厚度均较治疗前变薄,差异均有统计学意义(P<0.05);研究组VAS、PBAC评分均低于对照组,子宫体积小于对照组,子宫内膜厚度薄于对照组,差异均有统计学意义(P<0.05)。2组LH、FSH、PGF2α、VEGF、Ang-2、MDA水平均较治疗前降低,E2、Sirt6、SOD水平均较治疗前升高,差异均有统计学意义(P<0.05);研究组LH、FSH、PGF2α、VEGF、Ang-2、MDA水平均低于对照组,E2、Sirt6、SOD水平均高于对照组,差异均有统计学意义(P<0.05)。不良反应发生率研究组4.65%(2/43),对照组9.30%(4/43),2组比较,差异无统计学意义(P>0.05)。结论:与仅使用地诺孕素片治疗比较,栝蒌瞿麦方加味联合地诺孕素片治疗痰湿瘀结型AM可提高临床疗效,有效调节性激素水平、减轻机体氧化应激反应,促使子宫内膜厚度变薄,抑制血管新生,改善痛经等临床症状,安全性高。