目的 筛选晒后修复乳剂的最佳处方,并对其进行质量评价.方法 采用单因素、Box-Behnken中心组合设计原理和响应面分析法对晒后修复乳剂的处方进行优化,通过考察乳剂外观性状及稳定性,确定最佳的处方配比,最后对乳剂保湿性、抗氧化性和安全性进行评价.结果 晒后修复乳剂最佳处方为单硬脂酸甘油酯4.0％、白凡士林3.0％、二甲基硅油5.0％、硬脂酸3.0％、三乙醇胺0.4％、十二烷基硫酸钠0.2％、透明质酸钠0.1％、尼泊金乙酯0.1％、青刺果油3.0％、金缕梅提取液8.0％.该处方所得基质均匀细腻,离心及加速试验未见分层,易于涂抹、安全温和、质量稳定;当青刺果油加入量为3.0％时,乳剂具有很好的稳定性、保湿性和抗氧化性.结论 所制晒后修复乳剂质量稳定、安全温和,有望开发成一种新型晒后修复乳剂.

WangShiBaoChiWan(WSBCW)is a traditional Chinese medicine with a recorded administration history of more than 180 years.In the present study,the preclinical safety of WSBCW was evaluated the preclinical safety of WSBCW using a toxicity test,which consisted of an administration period of 28 d and a recovery period of 15 d.During the test,male and female SD rats were administered the medicine once a day by oral gavage,at a dose of 60 mg/kg/day,600 mg/kg/day,or 1500 mg/kg/day.As a reference medicine,mosapride citrate was administered at a dose of 37.5 mg/kg/day,which was clinically equivalent to the high-dosage treatment of WSBCW.With all the dosage groups,statistically,no adverse effect was observed in terms of clinical observation,food intake,body weights,organ coefficient,blood biochemistry,and histopathology examination.No intestinal melanosis was observed in the rats.When the data were examined animal by animal,test substance-related adverse effects were found with the high-dosage rats in hematology assay.The deranged,however,reversible changes suggested a compromised intestinal barrier,which was also observed with in mosapride citrate-treated rats.In addition to the histopathology assay,molecular toxicology was explored using high-throughput gene sequencing.No evident toxicity was revealed.In summary,administration of WSBCW was well tolerated within a treatment of 28 d.

目的:观察健肾颗粒大鼠经口给药可能出现的急性毒性、长期毒性反应,评价临床前安全性.方法:急性毒性试验:经口ig给药,空白对照组给予去离子水、受试物组给予健肾颗粒混悬液(24 g· kg-1·d-1),给药体积为30 mL·kg-1·次-1,24 h内给药2次(分上、下午给予),给药后观察14d,通过临床观察体重变化和病理大体解剖等确定急性毒性反应.长期毒性试验:经口ig给药,溶剂对照组给予超纯水,低、中、高剂量组给予0.025,0.100和0.300 g·mL-1的健肾颗粒混悬液.试验给药26周,给药频率为bid,给药体积12 mL·kg-1·次-1,恢复期4周.检查项目包括临床观察、体重、摄食量、血液学、生物化学和尿液分析检测、组织病理学检查等.结果:急毒试验:24 g·kg-1健肾颗粒ig给予SD大鼠无明显急性毒性,最小致死剂量(MLD) ＞24 g·kg-1.长毒试验:SD大鼠ig给予健肾颗粒重复给药26周,未观察到临床不良反应的剂量水平为2.4 g·kg-1.高剂量组潜在毒性靶器官为肝脏和肾脏,主要毒性作用表现为7.2 g·kg-1剂量对肝细胞空泡变性、肝细胞肥大和肾脏的肾小管玻璃小滴有促进作用,肾小管玻璃小滴恢复期未恢复.结论:健肾颗粒对受试动物在拟临床使用剂量范围内未见有明显的急性毒性和长期毒性作用.

目的 制备并表征载苦参碱泊洛沙姆水凝胶,探究其对小鼠皮肤慢性湿疹的治疗作用.方法 以泊洛沙姆407、188为基质制备苦参凝胶,采用流变仪表征苦参凝胶黏弹性质.通过检测耳部肿胀度、质量差,血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量,以及通过对小鼠耳部组织病理切片、蛋白酶活化受体-2(PAR-2)免疫组织化学切片的观察,考察苦参凝胶对小鼠皮肤慢性湿疹的治疗作用.结果 苦参凝胶流动性、铺展性良好,在皮肤表面可快速形成透明、有黏性的均一凝胶制剂.与正常组相比,模型组小鼠在慢性湿疹模型建立后的3、5和10 d耳部质量差、肿胀度明显增高(P<0.05);与模型组相比,苦参凝胶组小鼠慢性湿疹导致的耳部质量差、肿胀度明显降低(P<0.01),血清中促炎因子TNF-α、IL-6的水平明显降低(P<0.01),慢性湿疹组织中PAR-2的表达也明显降低(P<0.01,P<0.05).结论 苦参凝胶对慢性湿疹所致的表皮层损伤、真皮层炎性浸润均有一定的治疗作用,有望成为一种良好的治疗皮肤慢性湿疹的外用凝胶制剂.

目的 研究复方茜草增色液定性定量方法,建立其质量控制标准.方法 采用薄层色谱(TLC)法对茜草、马齿苋、苏木、虎杖、独活进行定性鉴别.HPLC法测定制剂中羟基茜草素、大叶茜草素的含量,采用Agilent ZORBAX-SB C18色谱柱(250 mm×4.6 mm,5μm),流动相为甲醇-乙腈-0.2％磷酸(25∶50∶25);流速:1.0ml/min;检测波长:250 nm;柱温:30℃.结果 TLC法能定性鉴别茜草、马齿苋、苏木、虎杖、独活.羟基茜草素、大叶茜草素分别在0.8～5.6 μg/ml(r2=0.9999)、2～14 μg/ml(r2=0.9999)范围内线性关系良好.平均加样回收率分别为101.09％(RSD为1.44％)、101.56％(RSD为1.59％).结论 该制剂制备方法简便易行,主要成分含量分析方法专属性好、重复性和准确度高,操作方便,该标准可作为本制剂的质量控制标准.

目的 优化清热止痒颗粒(QRZYG)原料药的粉碎工艺,以期提高QRZYG的溶出和混悬稳定性.方法 以颗粒复溶后的混悬液沉降比,混悬液粒径D90,分散指数(Span),胆红素、甘草苷、甘草酸的溶出量为考察指标,采用析因设计考察QRZYG中3味药人工牛黄、琥珀、甘草浸膏的粉碎目数.结果 以人工牛黄和甘草浸膏粉碎120目、琥珀粉碎200目制得的QRZYG复溶后的混悬液稳定性较好、D90约降低66％,胆红素、甘草苷、甘草酸在60 min的体外溶出量分别为35.70％、93.44％、84.68％,明显高于旧工艺QRZYG的溶出量(23.59％、54.41％、47.11％) (P＜0.05).结论 采用析因设计优化QRZYG的粉碎工艺是有效、可行的,优化后QRZYG具有较好的溶出和混悬稳定性.

目的 评价假升麻提取物对大鼠皮肤创伤的作用.方法 从性状鉴别、DNA分子鉴别两个方面对药材进行种属鉴定;采用打孔法考察假升麻提取物的体外抑菌效果;建立SD大鼠创伤感染模型,大鼠给予假升麻提取物治疗16d后,以创面形态、创面愈合率、组织病理学、免疫组化为指标评价其治疗效果.结果 鉴定药材基原植物为蔷薇科(Rosaceae)假升麻属(Aruncus)植物假升麻(Aruncus sylvester Kostel.);假升麻提取物对金黄色葡萄球菌、铜绿假单胞菌、大肠杆菌均具有一定的体外抑菌作用;动物创伤感染实验发现,大鼠创面感染治疗第12天,给药组伤口结痂完全脱落,伤口边缘处可见粉嫩的新生皮肤,模型组伤口表面干燥,给药组伤口表面脓状物明显少于模型组.治疗第16天,给药组创伤基本愈合,创面愈合率＞95％,模型组创面愈合率仍未达愈合标准.组织病理分析表明给药组角质层、表皮层、真皮层规则有序排列,模型组存在严重的表皮增生现象.给药组组织中有明显的血管内皮生长因子的表达,表明有大量的新生血管生成.结论 假升麻提取物对细菌感染性皮肤创伤具有一定的促伤口愈合能力,有可能用于治疗皮肤创伤.

目的 优选复方盐酸特比萘芬凝胶的处方,并建立含量测定方法.方法 以外观性状、涂展性、pH值、黏度值及低温实验结果为考察指标,进行处方筛选,并以高效液相法(HPLC)测定盐酸特比萘芬和糠酸莫米松的含量.结果 处方中95％乙醇用量为30％,水为27.3％,聚山梨酯80为4％,二甲基亚砜为5％时凝胶性状良好,处方稳定;盐酸特比萘芬与糠酸莫米松含量测定专属性良好,精密度RSD分别为0.08％、0.07％,盐酸特比萘芬在40～280 μg/ml浓度范围内,线性关系良好(r=0.9999);糠酸莫米松在4～28 μg/ml浓度范围内,线性关系良好(r=0.9999).加速实验6个月稳定.结论 复方盐酸特比萘芬凝胶制备工艺简单,优化处方稳定可行,检测方法准确可靠,可用于生产过程的质量控制.

目的 制备健肾颗粒剂并建立质量控制标准.方法 原药材经水提,低温浓缩干燥,湿法制粒,检查成品颗粒的粒度、水分、溶化性、干燥失重、装量差异、装量和微生物限度,TLC法对山茱萸、黄芪、丹参、当归与川芎、大黄6味药进行鉴别;HPLC法同时测定莫诺苷、马钱苷、毛蕊异黄酮葡萄糖苷的含量.结果 颗粒剂的粒度、水分、溶化性、干燥失重符合规定.TLC法能定性检出山茱萸、黄芪、丹参、当归与川芎、大黄.HPLC法精密度、稳定性、重复性、准确性良好,莫诺苷、马钱苷、毛蕊异黄酮葡萄糖苷分别在0.054～1.080 μg(r =0.9999)、0.039～0.780 μg(r =0.9999)、0.011～0.220 μg(r=1.0000)范围内线性关系良好.平均加样回收率分别为98.37％(RSD为1.75％)、99.69％(RSD为1.77％)、99.27％(RSD为1.79％)(n=6).结论 制备工艺合理,定性、定量方法准确可靠,可作为健肾颗粒的质量控制标准.

Objective To assess the anti-inflammatory and anti-fungal efficacy of compound terbinafine hydrochloride gel as a topical antifungal drug for common dermatophytosis by pathological methods.Methods Guinea pig skin was infected by Trichophyton mentagrophytes to establish animal model.Treated them with four topical preparations and then investigated the recovery of their affected skin,comparing the therapeutic effect of compound terbinafine hydrochloride gel with other three formulations.Results In terms of curing guinea pig skin infected by Trichophyton mentagrophytes,compound terbinafine hydrochloride gel was more effective than terbinafine hydrochloride gel (P ＜ 0.05),triamcinolone acetonide,econazole nitrate cream (P＜0.01) and mometasone furoate gel (P＜0.01).Conclusions Compound terbinafine hydrochloride gel had better effect in the treatment and relapse prevention of guinea pig skin infection of Trichophyton mentagrophytes.

Objective To establish an HPLC method for the determination of psoralen and isopsoralen in Baiban cream.Methods The quantitative analysis was performed on a Kromasil 100-5C18 column (250 mm× 4.6 mm,5 μm) with a mobile phase of acetonitrile-water (38 ∶ 62).The column temperature was maintained at 25 ℃,the flow rate Was 0.8 ml ·min-1 and the detection wavelength was set at 246 nm.Results The linear range of psoralen and isopsoralen was 1.62-32.48 ng (r =1.0000) and 1.62-32.34 ng (r =0.9999),respectively.The recovery was 99.06％ (psoralen) and 96.41％ (isopsoralen) respectively,and their RSD was 1.75％ (psoralen) and 1.31％ (isopsoralen),respectively.Conclusion This method is simple,accurate and stable,which can be used for the determination of psoralen and isopsoralen in Baiban cream.

The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 versus 3.80 ± 0.66 mg/L) and AUC0 - t (193.61 ± 16.30 versus 91.92 ± 17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.

Objective To prepare and evaluate the targeted paclitaxel nanoparticles with biodegradable materials of lactic acid-glycolic acid copolymer modified by folic acid (PLGA-PEG-FOL)as the carrier.Methods The emulsification-dispersion method was used to prepare nanoparticles.The optimum prescription and preparation technology were determined by investigating the influence of the dosage of emulsifiers,the species of organic phase,the proportion of water phase and organic phase,molecular weight of polymer,the proportion of drug particle size and the entrapment efficiency.The nanoparticles were evaluated in terms of the morphology of nanoparticles,particle size,Zeta potential,entrapment efficiency and drug-loading rate.Results PLGA-PEG-FOL was successfully synthesized.The targeted nanoparticle was uniform spherical particle.The particle size was (88.2 ±6.7)nm,Zeta potential was (56.5 ±4.2)mV,the entrap-ment efficiency was (92.9 ±3.2)%,and the drug-loading rate was (4.8 ±1.3)%.Conclusions The preparation method of nanopar-ticles was simple and reproducible.The particle size of nanoparticles was uniform with a narrow size distribution.The entrapment effi-ciency and drug loadings were high.

目的:建立高效液相色谱梯度洗脱法测定埃索美拉唑镁肠溶片的有关物质。方法:采用venusil XBP C18色谱柱（250×4.6 mm,5μm）,以乙腈-磷酸盐缓冲液（pH7.6）-水（10∶10∶80）为流动相A,以乙腈-磷酸盐缓冲液（pH7.6）-水（80∶1∶19）为流动相B进行梯度洗脱,流速为1 mL·min -1 ,柱温为25℃,检测波长为302 nm。结果:埃索美拉唑镁与杂质分离良好,埃索美拉唑镁、杂质D分别在0.50~5.02,0.50~4.96μg·mL -1 浓度范围内线性关系良好,检测限分别为1.25,2.50 ng·mL -1 ,定量限分别为5.00,6.25 ng·mL -1 ,埃索美拉唑镁与杂质D的平均回收率分别为99.91%,100.10%（n=9）。结论:该方法简便、准确、灵敏,专属性强,适用于埃索美拉唑镁肠溶片有关物质的测定。

The generation of dental structures depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin and enamel. Five different types of dental stem cells have been isolated from dental soft tissues: dental pulp, apical papilla, dental follicle and periodontal ligament. The characteristic features of these cells have been explored. They express various arrays of biomarkers including those specific for mesenchymal and/or embryonic stem cells. In vitro and in vivo studies have revealed that these stem cells varied in their proliferation and differentiation potential. Recent studies have demonstrated their wide range of plasticity and their potential use for regenerative medicine and dentistry. This review focuses on the different sources of dental stem cells and discusses their potential use in regenerative medicine. Nevertheless, the development of biological approaches for dental reconstruction using stem cells is promising and remains one of the greatest challenges in the dental field for the years to come. Published by www.inter-use.com. Available online Dec, 10 Vol. 4 Iss. 5, Page 50-54.

目的 以叶酸修饰的生物可降解材料乳酸-羟基乙酸共聚物(PLGA-PEG-FA)为载体,构建叶酸偶联紫杉醇纳米粒[PLGA-PEG-FA (PTX)-NPs]并进行评价.研究其对MCF-7细胞的效应并初步探讨其靶向作用机制.方法 乳化分散法制备PLGA-PEG-FA(PTX)-NPs,并对纳米粒的形态、粒径、Zeta电位、包封率及载药量进行评价;同法制备无叶酸偶联的紫杉醇纳米粒[PLGA-PEG (PTX)-NPs],分别用荧光物质FITC标记,应用荧光显微镜观察其对MCF-7细胞和A549细胞的靶向作用,以及游离叶酸对PLGA-PEG-FA(PTX)-NPs的干扰作用;MTT法观察PLGA-PEG-FA(PTX)-NPs、PLGA-PEG(PTX)-NPs对MCF-7细胞的生长抑制作用;流式细胞术检测细胞凋亡率.结果 制备的PLGA-PEG-FA(PTX)-NPs为均匀球形粒子,粒径为(88.2±6.7) nm,Zeta电位为(56.5±4.2) mV,包封率为(92.96±0.16)％,载药量为(4.84±0.10)％.与PLGA-PEG(PTX)-NPs相比,PLGA-PEG-FA(PTX)-NPs能更有效的被MCF-7细胞吞噬(P＜0.05);PLGA-PEG-FA(PTX)-NPs、PLGA-PEG(PTX)-NPs对A549细胞无明显靶向作用;培养基中加入游离叶酸干扰了PLGA-PEG-FA(PTX)-NPs的靶向性.MTT法测得PLGA-PEG-FA(PTX)-NPs抑制MCF-7细胞生长的IC50值(10.72 μg·ml-1)明显低于PLGA-PEG(PTX)-NPs组(17.41 μg·ml-1,P＜0.05),紫杉醇浓度在1～15 μg·ml-1时,PLGA-PEG-FA(PTX)-NPs组的生长抑制率在24 h明显高于PLGA-PEG(PTX)-NPs组(P＜0.05),紫杉醇浓度达到20μg·ml-1时,两组无显著性差异.PLGA-PEG(PTX)-NPs组的48 h细胞凋亡率(87.04％)明显高于PLGA-PEG(PTX)-NPs组(64.14％).结论 制备的PLGA-PEG-FA(PTX)-NPs能够靶向抑制MCF-7细胞增殖并促进其凋亡,其靶向性可能是由叶酸受体介导的.

目的 探讨瑞舒伐他汀钙片制备过程中相关因素对其质量的影响,以确定最佳生产工艺.方法 采用空白颗粒制粒法,对黏合剂种类、崩解剂加入方式等因素进行考察,并测定其溶出度变化情况.结果 制粒的最佳工艺选用50％的乙醇为黏合剂,内外加法崩解的方式加入崩解剂.结论 最终确定的瑞舒伐他汀钙片生产工艺可行,质量可控,适用于工业化大生产.

目的:制备埃索美拉唑镁肠溶微丸片,并建立其质量控制方法.方法:采用流化床包衣法制备埃索美拉唑镁肠溶微丸,然后压制成微丸片,采用HPLC法对肠溶微丸及微丸片进行含量、有关物质、耐酸力及溶出度的测定.结果:自制3批埃索美拉唑镁肠溶微丸及微丸片含量平均值分别为100.88％和100.69％,在pH 1.2盐酸中2h累积释放率均＜10％,在pH 6.8磷酸盐缓冲液中45 min累积释放率均＞75％,主峰和杂质峰分离良好,杂质含量分别为0.22％和0.25％.结论:制备的肠溶微丸及微丸片在人工胃液中耐酸力良好,在人工肠液中溶出迅速且完全,主药和杂质含量符合要求,该处方工艺稳定可靠.

Objective To study the release rate of metformin hydrochloride sustained-release tablets in vitro by different manufacturers, in order to provide the basis for clinical rational drug use.Methods According to the standard of metformin hydrochloride sustained-release tablets (imported drug registration standard JX2001 0451 )and related references,the stripping device of rotating basket method was adopted for the release experiment in vitro.Phosphate buffer solution 1 000 mL with pH 6.8 was used as medium,at 1 00 rpm rota-tion speed,and the temperature was at (37 ±0.5 )℃.The content was determined by UV spectrophotometry.In vitro release tests of metformin hydrochloride sustained-release tablets of different manufacturers were taken and the cumulative release percentage,drawing stripping curve and f2 similarity factor were calculated.Results The f2 similarity factor of two kinds of imported preparation was 93.54.The f2 similarity factors of the domestic preparation and Bristol-Myers Squibb formulation were 47.80,48.1 0,49.67,66.27, 47.65,70.53,67.05,respectively;and the f2 similarity factors of the domestic preparation and BIOVAIL formulation are 49.21 , 49.49,51 .25,67.00,49.05,68.22,67.21 ,respectively.Conclusions The domestic and imported preparations have significant differ-ences in drug release behavior in vitro.

目的:制备单硝酸异山梨酯缓释微丸胶囊并建立其质量控制方法.方法:采用湿法制粒及挤出滚圆制粒制得速释微丸;使用流化床包衣制得缓释微丸;用高效液相色谱法对其制备的微丸胶囊进行含量、有关物质及释放度检测.结果:最佳处方工艺条件为单硝酸异山梨酯60 g、微晶纤维素PH101 120 g、羟丙基纤维素HPC-LS 20 g,加入适量黏合剂,制得速释微丸;缓释微丸包衣增重为15％,制得缓释微丸;所制备的缓释微丸胶囊为速释微丸与缓释微丸混合组成(3∶7,w/w).其3批样品平均释放度分别为1 h(28.07±2.15)％,2 h(40.01±1.12)％,4 h(63.28±0.76)％,6 h(72.38 ±0.94)％,8 h(73.55±1.37)％,3批含量测定分别为97.34％,96.99％,97.10％,平均含量97.14％,RSD为0.18％.杂质测定未出现硝酸异山梨酯与2-单硝酸异山梨酯杂质峰.结论:制剂工艺简单,缓释效果理想,稳定性好,质量可控.