Cyclodextrins as stabilizers for the preparation of drug nanocrystals by the emulsion solvent diffusion method

Cyclodextrins (CyDs) were employed as protective stabilizers for the preparation of surfactant-free nanocrystals of indomethacin (IMC) by using the emulsion solvent diffusion method. The effect of changing the type and concentration of CyDs on the formation of IMC nanocrystals was investigated. Dispersions were freeze-dried to characterize the size, shape, nanoparticle yield, crystallinity, and dissolution behavior of the obtained particles. Submicron-sized particles of IMC with average diameters in the range of 300–500 nm were obtained by incorporating -, β-, or γ-CyD in the outer phase of the primary emulsions. Quantitative determination demonstrated that more than 80% of IMC was recovered as fine particles smaller than 0.8 μm. The powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses of the freeze-dried samples confirmed the polymorphic change of IMC to the meta-stable form. A significant enhancement in the dissolution rate of IMC nanocrystals was observed when compared to the commercial powder.     

复乳研究进展

复乳具有多层液体膜结构,是一种复杂的液体分散体系。复乳可作为缓控释给药系统与靶向给药系统的药物载体;亦可作为多肽、蛋白质类药物的载体避免药物口服后受胃肠液的破坏;同时有利于药物进入淋巴系统,因此复乳广泛的应用于药学领域。本文对复乳的定义、分类、特点、制备方法、常见问题及对策等方面进行综述。     

龙掌口含液联合丁硼乳膏治疗牙周炎的临床研究

目的 探讨龙掌口含液联合丁硼乳膏治疗牙周炎的临床疗效。方法 选择2020年4月—2021年4月在沧州市人民医院诊治的86牙周炎患者,根据用药的差别分为对照组和治疗组,每组各43例。对照组给予丁硼乳膏,1 g/次涂抹于患处,5 min后清水漱口,4次/d。在此基础上,治疗组含漱龙掌口含液,10 mL/次,含漱2 min/次,4次/d。两组患者连续治疗7 d。观察两组患者临床疗效,比较治疗前后两组患者牙周指标牙周袋深度（PD）、龈沟出血指数（SBI）、菌斑指数（PLI）、牙龈指数（GI）和附着丧失（AL）,SESS、Barthel、VAS和GOHAI评分,龈沟液细胞因子超敏-C反应蛋白（hs-CRP）、可溶性细胞间黏附分子-1（sICAM-1）、高迁移率族蛋白B1（HMGB1）、前列素E₂（PGE₂）和白细胞介素-23（IL-23）水平。结果 治疗后,对照组临床总有效率为81.40%,明显低于治疗组（97.67%,P＜0.05）。经治疗,两组PD、SBI、PLI、GI、AL均明显降低（P＜0.05）,并以治疗组下降最为明显（P＜0.05）。治疗后,两组患者SESS评分和Barthel评分明显升高,而VAS评分和GOHAI均明显下降（P＜0.05）,并以治疗组评分改善的最为明显（P＜0.05）。经治疗,两组患者龈沟液中hs-CRP、sICAM-1、HMGB1、PGE₂、IL-23水平均明显降低（P＜0.05）,并以治疗组患者下降最为明显（P＜0.05）。结论 龙掌口含液联合丁硼乳膏治疗牙周炎可有效提高口腔自我效能,利于牙周状态改善,降低局部炎症反应。     

乳化溶剂挥发法及在微囊化制剂中的应用

许多方法和技术被用来制备聚合物微粒。制备方法决定微粒的种类和粒径,影响微粒组成物之间的作用力。微囊化制剂不仅可以达到缓释及控释药物的作用,还可以掩盖药物的不良气味及口味,防止药物的降解,减少药物的毒副作用等。聚合物载体被广泛地应用于微粒的制备,可分为生物降解及非降解型。本文主要综述近几年乳化溶剂挥发法的作用特点及其制备的微粒制剂的研究进展。     

白藜芦醇三甲醚乳胶局部外用于兔踝关节后的体内药物浓度研究

目的:比较家兔灌胃给药与踝骨关节局部给药后的血药浓度和关节组织中药物浓度,评价白藜芦醇三甲醚(BTM)乳胶局部用药的可行性。方法:36只家兔随机分成2组即灌胃给药(对照)组与局部给药组,每组18只家兔又随机分成6个时间组,分别于给药后0.5、1、3、6、9、12 h取血样和关节组织样品;采用高效液相色谱-紫外法测定各时间点血浆和关节样品中的药物浓度。结果:家兔局部给药组的血药浓度均低于检测限(9.2 ng.mL-1),对照组0.5 h血药浓度最高((334.6±42.8)ng.mL-1),9 h下降为(17.9±17.0)ng.mL-1;对照组关节组织中药物浓度在0.5 h时大于局部给药组(P<0.05),在1、3 h 2组比较无显著性差异(P>0.05),在6、9、12 h低于局部给药组(P<0.05)。结论:外用BTM乳胶能透过皮肤进入家兔关节局部,与口服灌胃给药后比较,血药浓度更低而关节组织处药物浓度更高,并具有一定缓释作用,且可提高药物治疗的安全性,具有局部用药的可行性。     

反相高效液相色谱法测定O／W型二氢青蒿素脂肪乳剂中二氢青蒿素含量

目的建立测定O／W型二氢青蒿素脂肪乳剂中二氢青蒿素含量的高效液相色谱法。方法采用AgilentHC—C18柱（250mm×4．6mm,5μm）,流动相为乙腈-水（60：40）,流速1．0mL／min,柱温25℃,检测波长216nm。结果该方法试样质量浓度0．002129-2．18g／L范围内与检测峰峰面积呈良好线性关系,平均回收率为95．33％,RSD=1．40％（n=9）。结论该方法简便、精密,回收率高,重现性好,可用于二氢青蒿素脂肪乳剂中二氢青蒿素含量的测定。     

Effect of Oil-in-Water Submicron Emulsion Surface Charge on Oral Absorption of a Poorly Water-Soluble Drug in Rats

The effect of oil-in-water submicron emulsion (SE) droplet surface charge on absolute bioavailability of a poorly water-soluble drug (griseofulvin, as model drug) after oral administration was studied in conscious rat. Positively, negatively, and neutrally charged SE were designed and characterized (size, polydispersity index, zeta potential, and pH). Three emulsion formulations, whose compositions included 40% oil phase and differed only in the nature of the emulsifying agent, were retained. Only the positively charged SE showed a higher area under the plasma concentration–time curve (AUC_{0 → ∞}) in comparison with the tablet and with the other SE.     

Fine Multiple Emulsions Bearing 6-Mercaptopurine: In Vitro and In Vivo Antitumor Studies

Fine multiple emulsions were prepared by a two-step emulsification using the sonication technique. 6-mercaptopurine (6-MP) was encapsulated in the internal aqueous phase. It was coated with a phospholipid derivative of polyethylene glycol (PEG-PC). The coated multiple emulsion was characterized for antitumor activity on the murine leukemia cell line L-1210 in vitro. A decreased uptake and cytotoxicity were observed for PEG-PC-coated multiple emulsion in vitro, compared with uncoated ones. The IC₅₀ (50% inhibitory concentrated) was also decreased 1.64 times. In vivo antitumor activity was recorded as mean survival time (MST) of mice injected intravenously or intraperitoneally with tumor cells or, treated with 6-MP formulations through similar routes. MST was increased upon treatment. The normal peritoneal cells remained unchanged while blood parameters were restored with multiple emulsion treatment to tumor-bearing mice. The efficacy of the formulation was mainly due to the slow release and effective delivery of the drug from the formulation, suggesting its potential use for the treatment of cancer.     

Enzymatic Degradation of Leuprolide in Rat Intestinal Mucosal Homogenates

The purpose of this study was to evaluate in vitro enzymatic degradation and protection of leuprolide acetate in the mucosal homogenates of rat small intestine. When leuprolide was incubated at 37°C with the homogenates, it was degraded quickly. The apparent Michaelis–Menten constant, K_m, and the maximal reaction velocity, V_max, for leuprolide were 898 mM and 3.4 nmol/min/mg protein, respectively. At least four metabolites of leuprolide were observed in HPLC chromatograms, which were related to cleavages by some serine proteases. In the presence of protease inhibitors in the incubation medium, degradation of leuprolide was significantly suppressed by antipain and 3,4-dichloroisocoumarin (DCI), whereas bestatin and p-hydroxymercuribenzoic acid (PCMB) showed weaker protection than antipain and DCI, and α₂-macroglobulin (MG) exhibited no protection. When a w/o/w emulsion formulation was used, rapid degradation of the drug in intestinal homogenates was also inhibited. Therefore, the present study with representative protease inhibitors and a w/o/w formulation revealed that the enzymatic degradation of leuprolide is preventable in the rat intestinal mucosal homogenates.     

鸦胆子油乳对HPV16亚型感染细胞的作用及机制研究

目的研究鸦胆子油乳（bruceajavanicaoilemulsion,BJOE）在体外对人乳头瘤病毒（hu-manpapillomavirus,HPV）16亚型感染细胞的抑制作用及其可能作用机制。方法选择人宫颈鳞状上皮永生化细胞系（Ectl／E6E7）与人宫颈癌CaSki细胞系作为HPV16亚型感染的宫颈癌前病变与宫颈癌体外实验模型。采用MTT法检测5、10、20及40#g／mLBJOE体外分别作用24、48及72h对HPV16感染细胞增殖活性的影响;Hoechst33258细胞核染色荧光显微镜下观察细胞凋亡形态学变化;AnnexinV-FITC／Pl双染色法检测细胞凋亡率;半定量RT．PCR法检测HPV16E6、E7基因mRNA的表达;免疫细胞化学染色（Elivison二步法）检测HPV16E6、E7、p53及Rb基因蛋白的表达。结果（1）5、10、20及40μg,mLBJOE体外分别作用24、48及72h对HPV16感染细胞的增殖具有明显抑制作用,且表现为浓度与时间的依赖性（P〈0．05）。（2）HPV16阳性细胞在BJOE作用后发生了细胞凋亡形态学变化,5、10及20μg／mLBJOE体外作用48h后细胞凋亡率逐渐升高（P〈0．05）。（3）5、10及20μg／mLBJOE体外作用HPV16阳性细胞48h后E6与E7基因mRNA的相对表达量逐渐降低（P〈0．05）。（4）5、10及20μg,mLBJOE作用后,HPV16E6、E7及突变型P53蛋白的表达逐渐减弱（P〈0．05）,而Rb蛋白的表达逐渐增强（P〈0．05）。结论BJOE在体外对HPV16亚型感染细胞具有明显的抑制作用,其作用机制可能与药物下调病毒癌基因E6、E7表达相关。