促红细胞生成素双层微条的处方筛选与工艺优化研究

目的 对促红细胞生成素（EPO）胶原蛋白双层微条的处方及工艺进行筛选优化。方法 采用正交试验，以偏离度为评价指标，得到胶原蛋白与EPO含量比、硫酸软骨素钠（CS）含量、喷嘴外管内径和微条长度4个因素的最佳取值。结果 筛选得到胶原蛋白与EPO含量比为1000：1，CS含量为1％，喷嘴外管内径为1．4mm，微条长度为15mm。结论 根据得到的最优处方制备的双层微条释放缓慢、平稳。     

促红细胞生成素胶原蛋白双层微条的处方筛选与工艺优化

目的:对促红细胞生成素胶原蛋白双层微条(EPO-DLMP)的处方及工艺进行筛选优化。方法:采用正交试验,以偏离度为评价指标,优选胶原蛋白与促红细胞生成素的含量比、硫酸软骨素钠的含量、喷嘴外管内径和微条的长度4个因素的最佳取值,并进行验证试验。结果:筛选得到上述4种因素的最佳取值分别为1000∶1、1%、1.4mm、15mm,偏离度值为7.59。结论:采用最优处方制备的EPO-DLMP经验证其释放较平稳,能够达到试验要求。     

重组人红细胞生成素胶原蛋白双层微条的制备及含量测定

目的:制备重组人红细胞生成素(rhEPO)胶原蛋白双层微条并建立其含量测定方法。方法:以胶原蛋白为包裹材料,以硫酸软骨素钠为释放调节剂,采用凝胶加压成型的方法制备双层微条;采用反相高效液相色谱法测定双层微条中rhEPO的含量。结果:rhEPO检测浓度线性范围为0 .25～20μg/ml(r=0 9998) ,平均回收率为96 .2% ,日内、日间精密度分别为0. 9%、2 .6%(n=3)。结论:rhEPO胶原蛋白双层微条制备方法简单可行,含量测定方法准确、可靠。     

硫酸软骨素眼用温敏凝胶的制备与质量考察

摘要：目的:制备硫酸软骨素眼用温敏凝胶,并考察其体外释放度和房水动力学。方法:选用泊洛沙姆407(P407)、泊洛沙姆188(P188)和聚卡波菲为凝胶基质,正交试验L9(34)确定处方组成,通过含量测定、胶凝温度(T1)、人工泪液稀释后的胶凝温度(T2)、凝胶黏度(P)、眼部刺激性试验考察其质量,体外释放度和房水动力学考察其体内疗效。结果:最佳处方组成为硫酸软骨素3%,P407 16%,P188 3%,聚卡波菲1%。凝胶制剂的T1为27.38℃,T2为34.28℃,P为740 cpa,眼部刺激性符合要求,体外释放度和房水动力学均优于溶液剂。结论:所制备的硫酸软骨素眼用温敏凝胶各项质量指标符合要求。     

红细胞生成素双层微条的体外释放研究

目的：对红细胞生成素胶原蛋白双层微条的体外释放特性进行研究。方法：采用浸泡释放法，用HPLC法测定释放液中红细胞生成素的量，计算不同时间点的累积释放百分率。结果：单层微条和双层微条中的红细胞生成素分别在第4天和第7天完全释放。结论：双层微条的释放平稳，具有显著的缓释效果。     

熔融高速搅拌法制备双氯芬酸钠缓释胶囊的研究

目的研究熔融高速搅拌法制备双氯芬酸钠缓释胶囊及其体外释药行为。方法采用KJZ-10型熔融高速搅拌制粒机制备含药微丸,以微丸体外释放度为指标,考察处方工艺因素对微丸体外释放度的影响,通过释放度曲线药动力学拟合确定微丸缓释机制。结果双氯芬酸钠微丸体外释放行为符合Higuchi方程Y=35.43t1/2-16.1523（r=0.9988）,释药机制主要是骨架溶蚀和扩散释放。结论该技术制备的双氯芬酸钠缓释微丸具有较好的释药性能及良好的缓释效果。     

熔融高速搅拌法制备双氯芬酸钠缓释胶囊的研究

目的 研究熔融高速搅拌法制备双氯芬酸钠缓释胶囊及其体外释药行为。方法 采用KJZ-10型熔融高速搅拌制粒机制备含药微丸,以微丸体外释放度为指标,考察处方工艺因素对微丸体外释放度的影响,通过释放度曲线药动力学拟合确定微丸缓释机制。结果 双氯芬酸钠微丸体外释放行为符合Higuchi方程 Y=35.43t_1/2-16.152 3(r=0.998 8),释药机制主要是骨架溶蚀和扩散释放。结论 该技术制备的双氯芬酸钠缓释微丸具有较好的释药性能及良好的缓释效果。     

四乙酰基葛根素固体自微乳化双层片的研究

目的:探索固体自微乳化释药系统,制备四乙酰基葛根素固体自微乳化双层片。方法:考察各吸附材料对自微乳化液的吸附能力;以片剂外观、硬度、崩解时限等为指标筛选速释层处方;采用相似因子(f2)法评价双层片释药曲线的相似性,通过单因素考察,确定影响药物释放的主要因素;利用中心复合设计法对双层片处方进行优化,以HPMC K100LV和PEO400用量的各水平分别进行多元线性回归和二项式方程拟合,用效应面法预测最佳处方。结果:速释层的最佳处方为10%四乙酰基葛根素,30%自微乳化液,15%微粉硅胶,15%微晶纤维素,30%交联聚维酮,粘合剂为20%淀粉浆。缓释层中HPMC K100LV用量是影响药物释放的主要因素。中心复合设计优化处方的体外释放度预测值与实验值很接近。结论:中心复合设计法优化的固体自乳化双层片处方良好,双层片体外释放度达到了设计要求。     

盐酸坦洛新肠溶缓释微丸的制备及其体内外评价

目的:制备盐酸坦洛新肠溶缓释微丸,并与参比制剂进行体内外一致性评价。方法:分别以乙基纤维素和羟丙甲纤维素为缓释包衣材料,以聚丙烯酸树脂为肠溶性包衣材料,采用流化床底喷包衣技术对载药微丸包衣,制备肠溶缓释微丸;考察释放度主要影响因素;采用多条释放曲线对比考察受试制剂与参比制剂体外一致性;双周期交叉试验设计,考察Beagle犬口服单剂量受试制剂与参比制剂后血浆中的药物浓度,评价受试制剂与参比制剂的体内一致性;考察受试制剂的体内外相关性。结果:确定了影响盐酸坦洛新释放的主要处方工艺因素;多条释放曲线测定结果表明,所制备的微丸与参比制剂体外一致性较好;Beagle犬体内药动学研究结果表明,受试制剂与参比制剂生物等效且体内外相关性良好。结论:成功制备了盐酸坦洛新肠溶缓释微丸,且与参比制剂体内外一致性良好。     

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 ,其最终确定有赖于体内试验     

Controlled release of rhBMP-2 from collagen minipellet and the relationship between release profile and ectopic bone formation

The purpose of this study was to examine the effects of various additives on the profiles of rhBMP-2 release from minipellet, which is a sustained release formulation for protein drugs using collagen as a carrier, and to examine the influence of varying release profiles on ectopic bone formation. When the amount of rhBMP-2 remaining in the preparation after subcutaneous implantation to mice was examined, it was found that the addition of sucrose, glucose, PEG4000, alanine (Ala) or acacia in a concentration of 20% (w/w) to the minipellet with 5% (w/w) of rhBMP-2 did not accelerate the drug release in a noticeable manner, while the addition of sodium chondroitin sulfate, glutamic acid (Glu) or citric acid accelerated the release of rhBMP-2 markedly. When two types of minipellets (a fast release type added with 20% Glu and 20% Ala and a slow release type without additives) containing varying amounts of rhBMP-2 were implanted subcutaneously to mice, the soft X-ray observation, histological examination and measurement of calcium formation 3 weeks after implantation revealed extensive ectopic bone formation in mice implanted with the fast release type preparation. Ectopic bone formation was dose-dependent. The result of this study exhibited that the effects of controlled release formulation of rhBMP-2 on bone formation vary depending on their release profiles, and suggested that combination of initial burst and sustained release was effective for bone formation. It was also shown that minipellet is useful as a controlled release formulation which can release rhBMP-2 to areas around the implanted site with various release profiles.     

Effect of dextran derivatives on arginine amidase activities released from isolated rabbit arteries

In the present research we examined the levels and types of arginine amidase activities that were released from isolated rabbit arteries treated with heparin or chondroitin sulfate. Heparin accelerated the release of arginine amidase activity from the isolated rabbit ear artery, the induction was not significant; a slight increase in activity was observed in the level of arginine amidase released from isolated rabbit aorta, but no significant difference was observed. On the other hand, it was revealed that the addition of chondroitin sulfate, accelerated this release from isolated rabbit ear artery with 5% significant differences. After the addition of chondroitin sulfate, the arginine amidase activity released from isolated rabbit arteries was analyzed using various affinity adsorption methods. This analysis confirmed the presence of two types of fibrinolytic enzymes: plasminogen/plasmin activity and plasminogen activators, but no thrombin was detected.     

白术黄连微丸结肠靶向胶囊的制备及体外释放研究

目的 将中药"白术黄连方"制备成以胃溶微丸和肠溶微丸为基础的结肠靶向胶囊,优化其处方组成和制备工艺,考察其体外释放特性.方法 采用单因素实验和正交实验法优化微丸的处方组成和工艺参数.用挤出-滚圆技术制备素丸,流化床底喷方式进行包衣,考察隔离衣增重、肠溶衣中聚合物比例、增塑剂用量和包衣增重对肠溶微丸释放行为的影响,并对其...     

含玻璃酸钠的复方硫酸软骨素滴眼液中硫酸软骨素的含量测定

目的建立含玻璃酸钠(SH)的复方硫酸软骨素滴眼液中硫酸软骨素(CS)的含量测定方法。方法通过醋酸钠调节样品的酸碱度和离子强度,氯化十六烷基吡啶(CPC)可选择性地沉淀CS,采用咔唑法测定CS的含量,而不受SH的影响。结果优化的样品预处理条件为:醋酸钠的浓度为16%,CPC的浓度为0.8%,充分搅拌后,静置2 h,20μm滤膜过滤;滤饼经8%氯化钠溶液超声解离后,用于CS的含量测定,回收率为100.2%,RSD为1.17%。结论此法简便,快速,结果准确,可作为含SH的复方硫酸软骨素滴眼液中CS的含量测定方法。     

聚N-异丙基丙烯酰胺类温敏凝胶的制备及其对萘普生钠的缓释作用

目的：制备聚N-异丙基丙烯酰胺类的两种温敏凝胶：聚N-异丙基丙烯酰胺均聚水凝胶和N-异丙基丙烯酰胺-甲基丙烯酰胺共聚水凝胶，并考察其性质和对萘普生钠的缓释作用。方法：在氮气保护下制备两种水凝胶，测定和比较交联剂和甲基丙烯酰胺含量对凝胶溶胀度及临界相转变温度的影响。并以两种水凝胶为载体，在模拟人体肠液环境下进行萘普生钠的体外释放实验。结果和结论：交联剂用量增大时，凝胶溶胀度下降；甲基丙烯酰胺含量增加时，共聚水凝胶溶胀度增加，临界相转变温度提高。亲水性共聚水凝胶对药物的释放稳定持久，释药量大，具缓释作用。     

Role of chondroitin sulfate C in the action of anthrax toxin

Anthrax toxin is produced by Bacillus anthracis, the causative agent of anthrax, and is responsible for the majority of disease symptoms. The toxin consists of 3 proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF), which combine to form lethal and edema toxin. Glycosaminoglycans, which are present on the surface of cells, were investigated with regard to their role in toxicity resulting from anthrax toxin exposure. Lethal toxin-induced cytotoxicity of the RAW 264.7 cells was significantly inhibited by the addition of chondroitin sulfate C as determined by the MTT assay. By contrast, several other glycosaminoglycans, including heparin, heparan sulfate, and dermatan sulfate did not show significant levels of inhibition. Studies utilizing fluorescence-labeled PA demonstrated decreased PA binding to RAW 264.7 cells with the addition of chondroitin sulfate C. Formation of PA oligomers at the surface of cells after binding was also inhibited by chondroitin sulfate C. Interestingly, enzymatic degradation of endogenous chondroitin sulfate C from the cell surface with chondroitinase ABC was accompanied by increased sensitivity to the toxin. These findings were further confirmed by pretreating cells with sodium chlorate to reduce the degree of cell surface glycosaminoglycans sulfation. In addition, chondroitin sulfate C effectively inhibits edema toxin-induced cAMP accumulation in cells. Our results indicate that chondroitin sulfate C may play an important role in the toxicity of anthrax toxin.