喷雾干燥技术在蛋白、多肽类药物微球制备中的应用

按照不同的常用载体材料（聚乳酸类和壳聚糖类），分类综述应用喷雾干燥技术制备蛋白、多肽类药物微球的研究进展，主要介绍和比较了溶液，喷雾干燥、乳剂，喷雾干燥、喷雾冷冻干燥、喷雾液中冷冻及低温喷雾提取等制备工艺的特点。     

多柔比星壳聚糖微球的制备及其特性研究

目的 以壳聚糖为载体材料,多柔比星为模型药物, 制备脑内局部给药缓释微球。方法 以液体石蜡为油相,L-抗坏血酸棕榈酸酯为交联剂,司盘-80为乳化剂,采用乳化化学交联技术制备多柔比星脑用微球。用动态透析法检测微球的体外释放特性。结果 多柔比星/壳聚糖的质量比为1：9的载药微球形态良好,粒径分布较为均匀,平均粒径为（9.41±2.43） μm,载药量为（8.49±0.37）%,包封率为（70.56±4.23）%。体外释放具有良好的缓释效果。结论 所优化的制备工艺稳定,适用于多柔比星壳聚糖脑用微球的制备.     

复方黄芩鼻用止血复合涂膜剂的制备及安全性评价

目的:研制一种外用的治疗鼻腔出血的复方中药复合涂膜剂,并对其进行安全性评价。方法:提取黄芩的有效成分,以壳聚糖-羧甲基壳聚糖为基质制备复方黄芩鼻用止血复合涂膜剂;以止血涂膜剂的细胞毒性、刺激性、过敏性实验及纤毛毒性来评价其安全性。结果:复方黄芩鼻用止血复合涂膜剂为棕黄色半透明状黏稠物体,有一定流动性,能在皮肤和黏膜表面形成膜;无细胞毒性,无刺激性和过敏性,对纤毛运动时间几乎无影响。结论:复方黄芩鼻用止血复合涂膜剂是一种新型的中药止血涂膜剂,具有良好的生物安全性。     

复方雌三醇阴道生物黏附膜的制备及质量控制

目的:制备复方雌三醇阴道生物黏附膜并建立其质量控制方法。方法:以雌三醇、盐酸环丙沙星和醋酸地塞米松为主药制备膜剂,采用高效液相色谱法测定其中主药的含量。结果:所制制剂为半透明淡黄色薄膜,鉴别、检查项均符合2005年版《中国药典》中的相关规定;雌三醇、盐酸环丙沙星、醋酸地塞米松检测浓度的线性范围分别为1.56~77.8、15.97~798.4、1.66~83.2μg·mL-1(r=0.9999),平均回收率分别为98.44%(RSD=0.87%)、99.67%(RSD=0.54%)、98.54%(RSD=0.42%)。结论:本制剂制备工艺简便可行,质量稳定可控。     

Specific permeability modulation of intestinal paracellular pathway by chitosan-poly(isobutylcyanoacrylate) core-shell nanoparticles

This work is focused on the evaluation of the in vitro permeation modulation of chitosan and thiolated chitosan (chitosan-TBA) coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles as drug carriers for mucosal administration. Core-corona nanoparticles were obtained by radical emulsion polymerisation of isobutylcyanoacrylate (IBCA) with chitosan of different molecular weights and different proportions of chitosan/chitosan-TBA. In this work, the effect of these nanoparticles on the paracellular permeability of intestinal epithelium was investigated using the Ussing chamber technique, by adding nanoparticle suspensions in the mucosal side of rat intestinal mucosa. Results showed that permeation of the tracer [14C]mannitol and the reduction of transepithelial electrical resistance (TEER) in presence of nanoparticles were more pronounced in those formulations prepared with intermediate amounts of thiolated polymer. This effect was explained thanks to the high diffusion capacity of those nanoparticles through the mucus layer that allowed them to reach the tight junctions in higher extent. It was concluded that, although a first contact between nanoparticles and mucus was a mandatory condition for the development of a permeation enhancement effect, the optimal effect depended on the chitosan/chitosan-TBA balance and the conformational structure of the particles shell.     

Dietary chitosan enhances hepatic CYP7A1 activity and reduces plasma and liver cholesterol concentrations in diet-induced hypercholesterolemia in rats

The present study was performed to elucidate the hypocholesterolemic action of chitosan on the diet-induced hypercholesterolemia in rats. Male Sprague-Dawley rats (n=24) were fed with chitosan-free diet (Control), diets containing 2% or 5% chitosan for 4 weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Body weight gain and food intake of rats did not differ among the groups. The chitosan treated groups showed significant improvement in the plasma concentration of total cholesterol and LDL-cholesterol compared to the control group (p<0.05). Also, the chitosan treated groups decreased the liver concentration of total lipid and total cholesterol compared to the control group (p<0.05). The activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, was increased by 123% and 165% for the 2% or 5% chitosan diets, respectively. These findings suggest that enhancement of hepatic CYP7A1 activity may be a mechanism, which can partially account for the hypocholesterolemic effect of dietary chitosan in cholesterol metabolism.     

壳聚糖结肠靶向释药体系的初步研究

目的:制备壳聚糖作载体的结肠靶向给药制剂,并评价其体外释药性能。方法:将亚甲蓝与壳聚糖形成小丸,再以丙烯酸树脂(Ⅱ)包裹该小丸,以分光光度法测定其体外释放性能。结果:该小丸在pH1.2盐酸溶液及pH6.8磷酸缓冲液中药物累积释放量8h内小于6%,而在人工结肠液中,14h时累积释放度为38%左右。结论:用丙烯酸树脂(Ⅱ)包膜的壳聚糖制剂具有潜在的结肠靶向释药效果。     

几丁糖预防周围神经术后粘连的临床疗效观察

目的：为了解决周围神经损伤手术后神经粘连问题，特别是周围神经断伤吻合术后，解决神经纤维的生长与预防粘连问题。方法：在动物实验成功的基础上，临床在周围神经损伤应用显微外科技术行束问松解或外膜一束膜缝合的基础上应用几丁糖局部注入。于手术后6个月至2年观察神经功能恢复情况。结果：共临床应用102例110条神经，按照分级评定神经功能恢复.结果应用几丁糖者周围神经功能恢复和运动神经传导速度及诱发电位波幅明显优于未应用几丁糖者。周围神经粘连术后恢复优良率达91．5％，周围神经断伤吻合术后优良率达84％，总优良率达86．4％。结论：几丁糖具有明确的预防周围神经术后粘连的作用同时能够促进神经纤维的生长；临床应用疗效确切。并可在周围神经损伤的手术中临床推广应用。     

Experimental study of natural hydroxyapatite/chitosan composite on reconstructing bone defects

Objective:To study the possibility of natural hydroxyapatite/chitosan composite on repairing bone defects. Methods:We developed a natural hydroxyapatite/chitosan composite that could be molded into any desired shape. The powder component consists of natural hydroxyapatite, which is epurated from bone of pigs. The liquid component consists of malic acid and chitosan. Operations were performed on the left tibias of 15 white rabbits to create two square bone defects. One of the defects was reconstructed with the composite, while the other was not repaired and used as a blank control. Three of the animals were killed at the end of 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks respectively and implants were evaluated anatomically and histologically. Results:No apparent rejection reaction was found, except for a mild inflammatory infiltration observed 2 weeks after surgery. Fibrous tissue became thinner 2～8 weeks after surgery and bony connections were detected 12 weeks after surgery. The new bone was the same as the recipient bone by the 16th postoperative week. Conclusion:The hydroxyapatite/chitosan composite has good biocompatibility and osteoconduction. It is a potential repairing material for clinical application.     

Colon delivery of prednisolone based on chitosan coated polysaccharide tablets

Colon drug delivery is advantageous in the treatment of colonic disease and oral delivery of drugs unstable or suceptible to enzymatic degradation in upper GI tract. In this study, multilayer coated system that is resistant to gastric and small intestinal conditions but can be easily degraded by colonic bacterial enzymes was designed to achieve effective colon delivery of prednisolone. Variously coated tablets containing prednisolone were fabricated using chitosan and cellulose acetate phthalate (CAP) as coating materials. Release aspects of prednisolone in simulated gastrointestinal fluid and rat colonic extracts (CERM) were investigated. Also, colonic bacterial degradation study of chitosan was performed in CERM. From these results, a three layer (CAP/Chitosan/CAP) coated system exhibited gastric and small intestinal resistance to the release of prednisolone in vitro most effectively. The rapid increase of prednisolone in CERM was revealed as due to the degradation of the chitosan membrane by bacterial enzymes. The designed system could be used potentially used as a carrier for colon delivery of prednisolone by regulating drug release in stomach and the small intestine.