Combination of Diclofenac Potassium and Propolis in the Therapy of Oral Aphthosis: A Randomized, Clinical, Double-Blind, Placebo-Controlled Study

Background: Oral aphthosis has a negative impact on oral health. This study aimed to assess the effectiveness of gel formulation including diclofenac and propolis in the treatment of oral ulcers. Methods: Participants included 100 normal individuals with aphthous, excluding those having allergies to any ingredient in the diclofenac formulation. Patients were randomly assigned into two groups: one group received treatment with a combination of diclofenac potassium 3% (10 mg/g, 60 g) and propolis 5% gel (Group II), and the other group received a placebo (Group 1). The patient was evaluated using standard digital photographs and chronic oral mucosal questionnaires on days 1, 3, 5, and 7 after healing. Utilizing the Mann-Whitney U test, the two groups were compared. Each group’s changes were examined using Friedman’s test. Results: There was a statistically dramatic change over time in Group II. After one day, the median total score dropped statistically significantly, and from one to three days with effect size (d) 2.485, Group II demonstrated 48% complete healing and 52% partial healing, while Group I demonstrated 4% partial healing and 96% no change. Effect size (V): 0.995. Conclusions: The combination of diclofenac and propolis provided instant relief and an affordable new regimen for treating oral aphthosis.

Preparation of highly stable diclofenac potassium pellet with microcrystalline cellulose by extrusionespheronization

The main purpose of this study is to prepare highly stable diclofenac potassium(DP)pellet with microcrystalline cellulose(MCC)by extrusionespheronization.Using MCC,DP pellets were prepared and the stability was investigated.Related compounds of DP pellets were analyzed by High Pressure Liquid Chromatography(HPLC).After stability test of 60℃/75%RH for 10 d,the values of two main related compounds were 0.94%and 2.17%,respectively.Compatibility tests show that instability of DP was mainly caused by MCC.To improve the stability of DP in presence of MCC,different kinds of stabilizers were investigated.Upon addition of 1.5%(w/w)sodium hydroxide,the primary related compound of pellets was reduced to be 0.159%after stability test of 60℃/75%RH for 50 d.This study demonstrated that MCC induced decomposition of DP upon exposure to moisture could be prohibited by addition of sodium hydroxide.The mechanisms were discussed and residual hydroxyl free radicals in excipients were responsible for decomposition of DP.Finally,this formulation of DP is highly stable with sustained-release behavior.

Process optimization for the enhanced stability of diclofenac potassium granules and capsules

This study aimed to investigate the effects of different process parameters on the physical properties, in vitro dissolution rate, and short and long-term stability of diclofenac potassium（DFP） granules and capsules. DFP granules exhibited low total amounts of impurities when prepared through the wet granulation method using a granulating solvent with a low water/ethanol ratio. The impurities of the wet DFP mass dried at 70 ℃ were higher than those dried at 50 ℃ or 60 ℃. DFP granules were stable under strong light exposure during preparation. DFP granules prepared using a granulating solvent with a 1：4 water/ethanol ratio had a relatively smaller particle size and higher angle of repose than those prepared using granulating solvents with other water/ethanol ratios. The dissolution rate of DFP capsules prepared using four different water/ethanol ratios was less than 2% after 10 min of dissolution and increased to 95% within 30 min of dissolution. The total amount of drug impurities of DFP capsules prepared using a granulating solvent with 1：4 water/ethanol ratio was considerably lower than those of DFP capsules prepared using a granulating solvent with a 1：0 water/ethanol solvent ratio. Regardless of the water/ethanol ratio, the capsules showed poor stability when exposed to high temperature（60 ℃） and strong light（4500±500 Lux） for 10 days, but were relatively stable at high humidity（92.5% RH）. The results of the long-term stability（25±2 ℃ and 60%±10% relative humidity） study showed that DFP granules were more stable than DFP capsules, and were stable for 12 months. The type of encapsulating material did not affect the 2-month stability of DFP. DFP granules are sensitive to granulating solvent and drying temperature and DFP capsules should be stored away from high temperature and strong light.

Comparison of bioavailability and pharmacokinetics of diclofenac sodium and diclofenac potassium in normal and dehydrated rabbits

Two different salts of diclofenac,diclofenac sodium and diclofenac potassium,in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study.Biochemical and physiological parameters were also measured in both normal and dehydrated states.Diclofenac levels in plasma were determined using a validated reversed phase HPLC method.Primary kinetic parameters i.e.AUC0-∞,Cmax,Tmax and other disposition kinetics were obtained with non-compartmental procedure.Biochemical parameters i.e.packed cell volume,plasma glucose and total lipid concentration in dehydrated rabbits increased significantly.Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits.In comparison,diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.

双氯芬酸钾缓释片的研制及释药特性的探讨

目的 :研制凝胶骨架型双氯芬酸钾缓释片 ,考察缓释片体外释药特性。方法 :以羟丙基甲基纤维素为主要凝胶材料 ,辅以疏水性阻滞剂以调节释放度 ,根据设计的体外释药速率 ,筛选处方。结果 :药物释放系扩散机理控制 ,释药速率受pH环境影响 ,不受压片压力的影响 ,受机械搅动影响较小。结论 :本文研制的双氯芬酸钾缓释片成型性好 ,具工艺重现性 。

口服双氯酚酸钾胶囊剂药代动力学及其生物利用度研究

１０名志愿者自身交叉对照，口服单剂量双氯酚酸钾（ＤＫ）胶囊剂或片剂５０ｍｇ，１周后自身交叉服用。用反相ＨＰＬＣ法测得血浆中双氯酚酸胶囊剂和片剂的药代动力学参数Ｔｍａｘ为０．６３±０．５７ｈ和１．２２±１．１０ｈ，Ｃｍａｘ为２０２８．９±１０２０．８μｇ·Ｌ－１和１９３１．１±９１１．６μｇ·Ｌ－１，Ｔ１／２为２．２６±０．５８ｈ和２．１５±０．４４ｈ，血药浓度曲线下的面积（ＡＵＣ）分别为３７７８．４±４９２．９μｇ·ｈ·Ｌ－１和３６９６．６±６７３．１μｇ·ｈ·Ｌ－１，胶囊剂相对于片剂的生物利用度为１０３．１２±８．５５％。其药代动力学参数和ＡＵＣ值经配对Ｔ检验Ｐ＞０．０５，均无显著性差异。ＡＵＣ和ｌｎ（ＡＵＣ）用ＮＤＳＴ程序作等效性检验具有生物等效性。

双氯芬酸钾用于预防放置宫内节育器疼痛的临床研究

目的:观察双氯芬酸钾用于预防放置宫内节育器(IUD)所致疼痛的效果。方法:随机选取经剖宫产分娩后和阴道分娩后的两组妇女各100例,两组分别放置宫铜200IUD和TCu380IUD:剖宫产分娩后放置宫铜200IUD的妇女49例(观察组24例,对照组25例),放置TCu380IUD的妇女51例(观察组26例,对照组25例)。阴道分娩后放置宫铜200IUD的妇女50例(观察组和对照组各25例),放置TCu380IUD的妇女50例(观察组和对照组各25例)。观察双氯芬酸钾在置器术中、术后30min、术后6h、术后当晚睡前及术后第3日晚睡前预防疼痛的效果及服药的副反应等。结果:阴道分娩后置器的妇女,观察组和对照组在术中、术后30min、术后6h、术后当晚睡前及术后第3日晚睡前的疼痛分级差异均无统计学意义(P>0.05)。剖宫产分娩后放置宫铜200IUD的妇女,观察组和对照组比较,在术中及术后第3日晚睡前疼痛分级差异有统计学意义(P<0.05);放置TCu380IUD的妇女,观察组和对照组术后30min的疼痛分级差异有统计学意义(P<0.05)。结论:双氯芬酸钾用于预防剖宫产分娩后放置IUD所致疼痛有一定的效果,但未发现其能预防阴道分娩后放置IUD所致的疼痛。

双氯芬酸钾胶囊人体药代动力学与相对生物利用度研究

目的 :研究双氯芬酸钾胶囊在正常人体内的药代动力学与相对生物利用度。方法 :采用HPLC法测定10名健康男性志愿者随机自身交叉单剂量口服50mg 双氯芬酸钾胶囊和进口双氯芬酸钾片后的血药浓度 ,计算两者的药代动力学参数及相对生物利用度 ,并以AUC(0～6) 、Tmax 、Cmax 为指标 ,用配对t检验法分析国产胶囊与进口片的生物等效性。结果 :国产与进口双氯芬酸钾制剂的药 -时曲线符合口服吸收一房室模型。AUC(0～6 ) 分别为 (1834 52±711 06) μg/(h·L)、(1891 19±859 08) μg/(h·L) ;Tmax 分别为 (1 15±0 77)h、(1 30±0 97)h ;Cmax 分别为 (1522 29±1063 87)ng/ml、(1508 54±892 44)ng/ml。配对t检验结果表明 ,AUC(0～6) Tmax、Cmax 均无显著性差异 (P>0 05)。结论 :国产双氯芬酸钾胶囊对进口片的相对生物利用度为 (100 80±16 59) % 。

双氯芬酸钾的药效研究

目的:用小鼠和大鼠对双氯芬酸钾(DK)原粉进行镇痛、抗炎的药效作用及急性毒性评价。方法 角叉菜胶致大鼠足跖肿胀法,二甲苯致小鼠耳廓肿胀法,热板法及扭体法。结果:抗炎试验结果显示,单次口服DK5.0～20.0mg·kg-1对角叉菜胶所致大鼠足跖肿胀的抑制作用显著(P<0.05或,P<0.01),镇痛试验结果显示,单次口服DK2.5～10.0mg·kg-1对小鼠热板法和扭体法呈显著或非常显著性镇痛作用(P<0.05或P<0.01),其抗炎和镇痛作用均明显强于阳性对照药扑炎痛。同时,对DK原粉的急性毒性试验结果显示,给予小鼠灌胃的LD50为(160.04±43.49)mg·kg-1,与腹腔注射途径所得LD50(182.58±30.64)mg·kg-1无显著差异。

双氯芬酸钾凝胶含量的HPLC测定

建立了双氯芬酸钾凝胶含量的 HPL C测定法。采用 YWG- C1 8柱 ,以甲醇 - 5 %醋酸水溶液为流动相 ,检测波长2 75 nm。方法平均回收率为 99.5 5 % ,RSD为 1.2 2 %。

双氯酚酸钾双层片体外释放及其影响因素

目的 :考察双氯酚酸钾双层片的体外释放特征及其影响因素。方法 :采用紫外分光光度法 ,按照《中国药典》的转篮法测定体外释放度。采用Higuchi方程模拟体外释药行为 ,对主要释药参数进行统计学分析。结果 :双层片溶出参数T0 3=0 10h ,Td=3 30h ,T0 9=9 19h。压力对体外释放度速率无显著性影响 ;不同转速对双层片的早期释药行为有显著性影响 ,对中、后期释药行为无显著性影响 ;溶出介质的 pH对体外释放度有极显著性影响。结论 :双层片在体外具有良好的缓释和速释特征 ,适宜的溶出介质是体外释放度试验的关键 。

双氯芬酸钾脂质体制剂的大鼠体内透皮研究

目的 研究双氯芬酸钾 (DP)脂质体制剂体内经皮吸收和药物分布特点。方法 用SPE HPLC方法 ,研究在体条件下局部外用脂质体制剂和传统凝胶制剂后 ,DP在深层和浅层肌肉、血清、肝、胃等不同组织中的分布情况。结果 脂质体外用制剂于浅层肌肉、深层肌肉中的浓度峰值分别为 3 2 0 2 82ng g和 14 65 79ng g ,较凝胶外用制剂高 (P <0 0 1) ,且药物浓度维持时间长。结论 脂质体包封的双氯芬酸钾制剂能有效地渗透皮肤到达皮下组织 ,持续发挥局部药物作用 。

双氯芬酸钾脂质体制剂的制备及大鼠体外透皮研究

目的 研究双氯芬酸钾 (DP)脂质体制剂的制备及体外的经皮吸收特点。方法 采用改良均质法制备DP钾脂质体制剂 ;采用改良Franz扩散池 ,研究DP脂质体制剂与上市凝胶制剂大鼠皮肤的体外透皮吸收差异。结果 改良均质法制备的DP脂质体 ,平均粒径为 3 45nm ,粒径分布比较均匀 ,包封率为 87 3 %。体外透皮实验中 ,DP脂质体制剂较凝胶制剂的透皮能力高 (P <0 0 5 )。结论 脂质体包封的双氯芬酸钾制剂质地均一 ,稳定 。

毛细管电泳法检测中药制剂舒骨宁中非法添加的双氯芬酸钾

目的：采用毛细管电泳的方法检测中药制剂舒骨宁中非法添加的西药双氯芬酸钾。方法：毛细管电泳法，贝克曼未涂层石英毛细管柱75μm×50em，以25mM的磷酸氢二钠（磷酸调节pH6．50±0．02）为缓冲液，0．5psi、5s压力进样，检测波长275mm，柱温为25℃，分离电压25kV。结果：双氯芬酸钾的含量在0．010～0．200g／L的范围内线性关系良好，r=0．9984，平均回收率为100．6％，RSD为3．01％。结论：该方法简便、快速、可靠，溶剂用量少，可有效检测出中药制剂舒骨宁中非法添加的西药双氯芬酸钾。

双氯芬酸钾喷雾剂抗炎镇痛的药效学研究

目的 观察双氯芬酸钾喷雾剂的抗炎镇痛作用。方法 采用二甲苯致小鼠耳肿胀、角叉菜胶致大鼠足肿胀和小鼠热板法模型观察双氯芬酸钾喷雾剂的抗炎、镇痛作用。结果 双氯芬酸钾喷雾剂对二甲苯致小鼠耳肿胀和角叉菜胶致大鼠足肿胀均有明显的抑制作用 ,并能增加热刺激小鼠的痛阈。结论 双氯芬酸钾喷雾剂具有明显的抗炎、镇痛作用 。

双氯酚酸钾颗粒与双氯酚酸钾片的人体生物等效性研究

目的 :进行双氯酚酸钾颗粒与双氯酚酸钾片单剂双交叉生物等效性研究。方法 :男性健康志愿者18名自身交叉单剂量口服双氯酚酸钾颗粒与双氯酚酸钾片50mg ,采用高效液相色谱法测定双氯酚酸钾经 -时血药浓度 ,计算其药代动力学参数与相对生物利用度。结果 :双氯酚酸钾颗粒与双氯酚酸钾片主要药代动力学参数T1/2( β) 分别为 (3 022±0 698)h和 (2 980±0 744)h ,Tpeak 分别为 (0 972±0 188)h和 (1 000±0 000)h ,Cmax 分别为 (1 57±0 211) μg/ml和 (1 664±0 243) μg/ml,AUC0～12 分别为 (4 115±0 422) μg/(ml·h)和 (4 217±0 293) μg/(ml·h) ,AUC0～∞分别为 (4 59±0 330) μg/(ml·h)和 (4 639±0 383) μg/(ml·h)。两药各药代动力学参数间均无统计学差异 ,双氯酚酸钾颗粒相对生物利用度 (F)为 (99 47±9 79) %。结论

外用双氯芬酸钾凝胶治疗局部风湿性疼痛综合征

目的 比较研究双氯芬酸钾凝胶（ＤＰＧ）和双氯芬酸钠凝胶（ＤＳＧ）治疗局部风湿性疼痛综合征的疗效和安全性。方法 试验设计为多中心、随机对照、单盲、平行性的比较研究。试验组 ６０例，１％ＤＰＧ外用，每日３－４次，每次２－４ｇ，日总量不超过２０ｇ，疗程２周；对照组４５例，１％ＤＳＧ外用，使用方法同ＤＰＧ。结果 ２周时ＤＰＧ的总有效率为 ８８％，ＤＳＧ总有效率为８７％，ＤＰＧ组疗效明显高于 ＤＳＧ组（Ｐ＜０．０５）。两药均能显著改善病人的临床症状和体征（Ｐ＜０．０５～０．００１），两组相比ＤＰＧ对关节肿胀数的改善优于ＤＳＧ组（Ｐ＜０．０５），对其他各指标的改善两组间差异无显著性（Ｐ＞０．０５）． ＤＰＧ的耐受性良好，无１例病人发生不良反应；ＤＳＧ组的不良反应发生率为２％，两组间差异无显著性（Ｐ＞０．０５）．结论ＤＰＧ治疗局部风湿性疼痛综合征的疗效优于ＤＳＧ，且耐受性好，无明显不良反应。

中药热熨Ⅰ号方治疗阳虚寒凝型膝关节骨性关节炎的临床疗效观察

目的观察中药热熨Ⅰ号方治疗阳虚寒凝型膝关节骨性关节炎的临床疗效。方法将符合入选标准的门诊患者89例随机分为治疗组和对照组,其中治疗组46例以中药热熨Ⅰ号方于膝关节局部熨敷患膝,对照组43例应用双氯芬酸钠乳膏外用涂擦患处进行治疗。在治疗后第2、4周对患者症状、体征积分、关节炎影响指数和安全性指标进行评估。结果 2组治疗后4周总疗效比较,治疗组总有效率为86.7%,对照组总有效率为90.7%,2组间差别无统计学意义(P>0.05)。2组治疗后2、4周症状、体征、关节炎影响指数以及单症状、单体征等积分自身比较,差别均有统计学意义(P<0.05)。结论热熨Ⅰ号方可明显缓解和改善膝关节骨性关节炎患者的症状和体征,改善关节功能,从而促进和提高患者的日常活动以及生活质量,但其作用机制及远期疗效尚有待于通过进一步动物实验研究和临床观察来验证和阐明。

双氯芬酸钾乳胶剂的抗炎镇痛作用研究

目的考查自制的双氯芬酸钾乳胶剂的抗炎镇痛作用及有效性.方法采用小鼠二甲苯致耳肿胀实验、皮肤毛细血管通透性实验及小鼠扭体反应实验3种模型比较自制的双氯芬酸钾乳胶剂和市售扶他林乳胶的抗炎作用和镇痛作用的区别.结果与空白组比较,双氯芬酸钾乳胶剂与扶他林均具有显著的抗炎镇痛作用.自制的双氯芬酸钾乳胶剂的耳肿胀抑制率和疼痛抑制率高于阳性药扶他林,但双氯芬酸钾乳胶剂的小鼠腹部皮肤毛细血管通透性抑制率低于阳性药扶他林.结论自制双氯芬酸钾乳胶剂与扶他林比较具有较强的全身抗炎镇痛作用.

因子设计-重叠等高线图法优化双氯芬酸钾口腔黏附片处方

目的优化双氯芬酸钾口腔黏附片处方。方法采用32满因子设计试验考察因素A(卡波姆和羟丙甲基纤维素的总量在处方中所占的比例)和因素B(卡波姆与羟丙甲基纤维素的质量比)对黏附时间和体外30、180、480 m in的累积释放度的影响,试验数据分别采用线性方程和二次多项式拟合,根据最佳数学模型绘制效应面和等高线图,通过重叠等高线图确定最优处方。结果2个影响因素和4个评价指标之间存在定量关系,最优处方:卡波姆和羟丙甲基纤维素的总量在处方中占30%,卡波姆与羟丙甲基纤维素的质量比为0.75∶1。优化处方各指标的预测值和目标值较接近。结论采用因子设计-重叠等高线图法完成了双氯芬酸钾口腔黏附片的多目标同步优化。