高压电场低温萃取法制备生物可降解骨架的胰岛素缓释微球

目的:探索一种新型的胰岛素缓释微球制备方法.方法:采用高压电场低温萃取法,以生物可降解高分子材料聚乳酸乙醇酸共聚物(PLGA)为骨架材料,制备胰岛素缓释微球.结果:当药物与骨架材料的质量比为1:9时,可制得胰岛素载药微球其粒径＜200μm,载药量为8.82%,包封率为83.2%,缓释达7d.结论:高压电场低温萃取法是一种工艺可行的新方法,为PLGA生物可降解型微球的制备提供了新方法.     

胶原/PLLA纳米粒子复合海绵的制备及其生物相容性评价

通过紫外和自由基聚合在PLLA上接枝聚丙烯酸（PAA）,制备了平均粒径316nm,zeta电位-39.88mV的表面亲水性PLLA纳米粒子,与胶原溶液混合通过冷冻干燥法制备了胶原/PLLA纳米粒子复合多孔支架。复合支架材料的孔隙率与纯胶原支架相近,而密度、湿态压缩模量有明显提高,降解率降低显著。随着复合支架中PLLA纳米粒子的增加,L929细胞在材料中的播种效率和增殖有明显提高,表明胶原/PLLA纳米粒子复合多孔支架是一种理想的组织工程支架材料。     

聚乳酸-乙醇酸微球的生物降解性和生物相容性研究

目的 考察基因重组人干扰素α-聚乳酸乙醇酸微球的生物降解性和生物相容性.方法 以缓冲液为介质,通过光学显微镜观察聚乳酸乙醇酸微球的体外降解;以Wistar大鼠为研究对象,观察给药部位的病理切片,评价微球的体内生物降解和生物相容性.结果 聚乳酸乙醇酸微球在体外,6周降解百分率超过80%,在体内6周可降解完全;给药部位病理切片观察,仅见轻微炎症反应,未见病理变化.结论 聚乳酸乙醇酸微球具有良好的生物降解性和生物相容性.     

雌二醇生物可降解缓释微球的制备四氢呋喃的加入对微球性质的影响

目的　在本实验中 ,以生物可降解和生物相容性良好的聚乳酸 (PLA)或乳酸 -乙醇酸共聚物 (PLGA)为载体材料制备含有雌二醇药物的缓释微球 ,考察在制备过程中水溶性更强的四氢呋喃的加入对微球性质的影响。方法　以乙酸乙酯和四氢呋喃为有机溶剂、采用乳化 -溶剂萃取法制备含药微球 ,分别从成球性、粒径、包封率和体外释药等方面 ,进行制备工艺研究以及微球相关性质的研究。结果　在乙酸乙酯中加入四氢呋喃 ,使包封率降低 ,但在乙酸乙酯体积比大于 5 0 %时 ,增加四氢呋喃的用量对包封率无明显影响。相同条件下 ,在考察范围内 ,粒径随四氢呋喃用量比例的增大而增大 ,而载体的性质和微球含药量是影响微球释药的主要因素。结论　尽管在制备过程中的油相中加入了水溶性更强的四氢呋喃 ,但是通过控制制备工艺和条件 ,仍然可以得到球形态好、有适当粒径分布范围、载药量高并且突释程度小的雌二醇生物可降解缓释微球     

西罗莫司纳米粒子的制备及脱细胞生物血管材料内应用的实验研究

目的制备包载西罗莫司(SRL)的纳米粒子,并将其应用于脱细胞生物血管材料。方法以生物可降解高分子材料聚乙酸-聚乙醇共聚物(PLGA)为载药基质,采用界面沉淀法制备SRL-PLGA-纳米粒子(SRL-PLGA-NPs)。使用激光粒度仪及扫描电镜对纳米粒子的粒径、形态进行测定,采用高效液相色谱法(HPLC)测定纳米粒子的载药量、包封率,双室扩散池行纳米粒子的体外释放实验。脱细胞联合肝素处理犬颈动脉制备生物人工血管材料,采用血管腔内局部灌注的方法将纳米粒子结合于血管材料,根据灌注时间的不同分为4组,120 s(A组)、240 s(B组)、360 s(C组)和480 s(D组)。定期测定各组血管组织内的药物浓度。结果成功制备了SRL-PLGA-NPs,粒径为227~303 nm,平均粒径为(265±24)nm,包封率为81.53%,平均载药量为18.96%。SRLPLGA-NPs在30 d内能够一直持续释放药物,2周后释放药物量约75%,30 d后释放量约90%。经SRL-PLGANPs腔内灌注后的脱细胞血管在21 d后,血管组织内仍可检测到西罗莫司,呈逐渐降低趋势。A组的药物浓度在给药后即刻和1 d低于其他3组(P<0.05),而在3、7、14、21 d后,4组的药物浓度差异无统计学意义(P>0.05)。结论界面沉淀法制备SRL-PLGA-NPs方法稳定可靠,对脱细胞生物血管行局部灌注处理,效果满意。     

PLGA与明胶膜支架材料对神经干细胞生长、分化影响的体外研究

目的：探讨PLGA作为中枢神经组织工程支架材料的可行性。方法：从胎龄14～16d的Wistar大鼠分离培养获得神经干细胞，以10^8/L密度种植于PLGA膜、明胶膜和PLGA／明胶膜表面，置37℃、5％CO2培养箱中共培养，观察神经干细胞在PLGA膜、明胶膜和PLGA／明胶膜表面的生长、分化和PLGA的降解情况。结果：培养获得的神经干细胞表现具有自我更新和多相分化能力，能分化为神经元和胶质细胞。在观察期内PLGA膜无降解，神经干细胞在PLGA膜表面无贴附，但可在PLGA／明胶膜和明胶膜表面贴附、生长和分化。结论：PLGA可作为中枢神经组织工程支架材料。     

组织工程细胞支架与种子细胞复合培养的研究进展

组织工程的核心是建立由生物材料与细胞结合的三维空间复合体,即以合适的生物材料构建与所需要修复的组织或器官结构相同或类似的支架并复合特定细胞,用以对病损组织进行形态、结构和功能的重建而达到永久性替代[1].支架材料是组织工程的基础,它既要为细胞提供生长的空间又要被植入体内,故材料的性质会对细胞的生长、繁殖、分化和宿主内环境产生重要影响.因此,选择具有良好的生物相容性及细胞亲和性好的支架材料尤为重要.另外,要构建细胞支架复合体,又必须考虑种子细胞黏附于支架的问题,支架材料、种子细胞以及复合体的构建在组织工程中被称为三大基本要素.     

胰岛素生长因子-1与血小板衍生因子复合聚乳酸/羟基乙酸共聚物支架促进兔下颌骨缺损愈合的实验研究

<正>聚乳酸/羟基乙酸共聚物(PLGA)支架是由乳酸以及羟基乙酸聚合而成,可被人体正常代谢,最终降解产物是对人体无害的H2O和CO2。PLGA具有良好的生物相容性和可降解性,是美国食品药品管理局(FDA)批准的可用于人体的生物材料,已经被广泛应用于科研研究。胰岛素生长因子-1(IGF-1)和血小板衍生因子(PDGF)都是重要的促有丝分裂因子,可以促进成骨细胞、成纤维细胞和     

Transmyocardial Laser Revascularization

Transmyocardial laser revascularization (TMR or TMLR) is a surgical therapy developed to treat patients with debilitating, medically refractory angina pectoris due to epicardial coronary artery disease that is not amenable to treatment using the traditional methods of percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). This technique can also be applied percutaneously [percutaneous myocardial revascularization (PMR) or direct myocardial revascularization (DMR)]. The original hypotheses which motivated development of TMR were that: (i) oxygenated blood could flow directly from the left ventricle and perfuse the myocardium; and (ii) such artificially created channels would remain patent. However, experimental data have refuted both hypotheses. In the face of early reports of marked clinical benefits in terms of relief of anginal symptoms, alternate hypotheses to explain the mechanism have been pursued, including TMR-associated neoangiogenesis and cardiac denervation. Clinically, numerous reports of reduction in frequency and severity of anginal symptoms, improved exercise tolerance and improved quality of life have appeared from nonblind registry-type studies as well as nonblind randomized clinical trials of TMR or PMR versus continued medical therapy. TMR was not associated with a significant improvement in survival compared with medical therapy alone in randomized trials. For example, the prospective, randomized Angina Treatments-Lasers and Normal Therapies in Comparison (ATLANTIC) trial found a 1-year mortality of 5% in 92 TMR-treated patients and 10% in 90 patients treated with medication only. No proof of improved myocardial blood flow in hearts of treated patients is currently available. The first randomized study of PMR was the Potential Angina Class Improvement From Intramyocardial Channels (PACIFIC) trial which found significantly greater improvements in anginal symptoms and exercise tolerance with PMR plus medical therapy, compared with medical therapy alone. The preliminary results of two double-blind studies with PMR/DMR have been presented but have not yet been published in full. Whereas PMR-treated patients did significantly better than sham-treated control groups after 6 months in the Blinded Evaluation of Laser Intervention Electively For angina pectoris (BELIEF) trial, there was no difference after 1 year between DMR-treated patients and those treated with medication only in the DMR In Regeneration of Endomyocardial Channels Trial (DIRECT). Different devices used for revascularization in these two trials may explain the disparity in the results, and therefore the efficacy and tolerability of each device should be judged upon data collected with that particular device.     

经皮跨心肌激光血管成型对晚期冠心病影响

目的观察CO2激光跨心肌血管成型术(PTMR)对晚期冠心病心肌灌注的影响。方法病人共计42人,男女性别配对,分为激光治疗组和药物治疗组。激光治疗组,男,18例,女3例,年龄51-67(58±8)岁,陈旧性心肌梗死16例,糖尿病合并顽固性心绞疼5例。LVEF35-47(38±13)%,冠状动脉造影示三支血管病变,不适宜做PCI和CABG手术。药物治疗组,男,16例,女5例,年龄53-71(59±10)岁,陈旧性心肌梗死15例,糖尿病合并顽固性心绞疼6例。LVEF36-47(38±14)%,冠状动脉造影示三支血管病变,不适宜做PCI和CABG手术。激光仪:CO2激光。用99锝测定TMLR术后3、6、12个月心肌再灌注的变化(ECT),用超声心动图检测左室射血分数(LVEF)、左室舒张末期容量(LVEDV)。结果21例病人,17例手术顺利,住院期间无死亡。4例病人在术中,因激光击穿出现心包填塞,而行急诊冠状动脉搭桥术(CABG)。3月后,运动和静息ECT显示TMLR病人,运动缺血积分分别为(0.172±0.003和0.161±0.003,P<0.01),静息为(0.170±0.003和0.158±0.003,P<0.01)。6个月缺血积分运动状态PTMR病人为0.176±0.003,对照组为0.162±0.003(P<0.01),静息状态下无区别。12个月时,静息和运动状态下,两组病人无区别。激光区缺血严重程度积分明显比对照组高,3,6,12个月P值前壁均小于0.01,心尖为P<0.01,P<0     

载透明质酸-甲基胶原-三元共聚物/多柔比星复合膜的钽支架的制备及处方优化

目的:制备载透明质酸-甲基胶原-三元共聚物(甲基丙烯酸羟乙酯-甲基丙烯酸甲酯-甲基丙烯酸)/多柔比星复合膜的钽支架,并优化处方。方法:以金属钽支架为载体,透明质酸、甲基胶原、三元共聚物为辅料,利用静电自组装反应制备复合膜。以1、30 d的累积释放度为指标,采用正交设计优化透明质酸、甲基胶原、三元共聚物的质量浓度并验证;考察其体外释药行为。结果:最优处方为透明质酸1 mg/ml、甲基胶原4.5 mg/ml、三元共聚物100 mg/ml;所制钽支架1、30 d的累积释放度分别为7.57%、84.14%,RSD分别为2.3%、2.1%(n=3),20 d后近似呈零级速率释药。结论:成功制得具有缓释功能的载透明质酸-甲基胶原-三元共聚物/多柔比星复合膜的钽支架。     

肝素缓释可降解支架在心肌血运重建中的应用研究

目的:探讨肝素缓释支架在急性心肌梗死后心肌血运重建中的作用.方法:通过结扎前降支冠状动脉制作猪急性心肌梗死模型,然后随机分为3组,A组(6只)为对照组,B组(6只)为心肌打孔组,C组(6只)为心肌打孔+支架植入组.在B组和C组中,于心肌梗死区采用自制高速钻孔器由心外膜打2个直径为3.5mm透壁孔道,C组每个孔道内植入1枚肝素缓释支架.分别于治疗前和治疗后6周观察组织学改变、新生血管密度、心肌灌注及心功能变化.结果:治疗后6周,B组孔道完全闭塞,C组孔道仍然开放,内壁被一层内皮细胞覆盖.C组中新生血管密度较A组和B组明显增加(均P<0.001);治疗前后C组灌注质量缺损百分率的差值(△MDP)较A组和B组明显改善(均P<0.001);C组存活心肌面积较A组和B组明显增加(均P<0.01);C组左室射血分数为较A组和B组明显提高(均P<0.05).结论:肝素缓释支架可以维持穿心肌孔道开放,促进心肌梗死后血管再生,增加心肌灌注,提高心肌存活,改善心功能,可能成为心肌梗死后再血管化的有效方法.     

生物可降解聚合物微球的制备设备概况

概述了制备生物可降解微球的工艺设备及工作原理,如基于乳化法的改进方法、基于射流激发、电压驱动或"切割"成型的设备.     

生物降解微球的制备工艺及释药特性研究进展

综述了近年来生物降解微球在制备工艺、聚合物降解机理、药物释放等方面的研究进展。     

Preparation of Biodegradable Insulin Nanocapsules from Biocompatible Microemulsions

Purpose. To prepare poly(ethyl 2-cyanoacrylate) nanocapsulescontaining insulin by interfacial polymerization of spontaneously forming,biocompatible microemulsions. Methods. A pseudo-ternary phase diagram of a mixture of mediumchain glycerides (caprylic/capric triglycerides and mono-/diglycerides),a mixture of surfactants (polysorbate 80 and sorbitan mono-oleate) andwater was constructed. Polarizing light microscopy was used to identifycombinations forming microemulsions. Microemulsions werecharacterized by conductivity and viscosity to select systems suitable for thepreparation of poly(ethyl 2-cyanoacrylate) nanocapsules by interfacialpolymerization. Nanocapsules were prepared by addition of 100 mgof ethyl 2-cyanoacrylate to a stirred water-in-oil microemulsioncontaining 1 g of water, 7.6 g of oil, and 1.4 g of surfactant. Thenanocapsules formed were characterized by photon correlation spectroscopy,freeze fracture transmission and scanning electron microscopy. Insulinnanocapsules were prepared by using an aqueous solution of insulin(100 units/ml) as the dispersed phase of the microemulsion. Theentrapment and the release of insulin from the nanocapsules were determined. Results. Three regions were identified in the pseudo-ternary phasediagram; a microemulsion region, a region in which liquid crystallinestructures were present and a coarse emulsion region. All systems inthe microemulsion region were water-in-oil dispersions.Poly(ethyl 2-cyanoacrylate) nanocapsules having a mean particle size of 150.9 nmwere formed upon interfacial polymerization of the microemulsion.Nanocapsules were found to have a central cavity surrounded by apolymer wall. In excess of 80;pc of the insulin present in themicroemulsion was encapsulated upon interfacial polymerization. Conclusions. Interfacial polymerization of spontaneously formingwater-in-oil microemulsions represents a convenient method for thepreparation of poly(alkylcyanoacrylate) nanocapsules suitable for theentrapment of bioactive peptides.     

利培酮生物可降解注射型植入剂的制备及体外释放特性的研究

目的:制备利培酮生物可降解注射型植入剂并考察其体外释放特性。方法:选用聚乳酸乙醇酸共聚物(PLGA)为载体和N-甲基吡咯烷酮(NMP)为溶剂,制备利培酮生物可降解注射型植入剂。考察制剂在30d内累积释药率、PLGA在降解过程中分子量的变化情况以及固体聚合物在降解过程表面孔径的变化情况。结果:所制制剂30d内释药曲线平稳,累积释药率为89.01%,前24h突释量较小,为13.8%。聚合物降解30d后分子量从43000减少到10000左右,表面孔径逐渐变大。结论:利培酮生物可降解注射型植入剂可在体外30d持续稳定释药。     

Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties

Abstract— Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(d, l -lactide) (PDLLA) and poly(d, l -lactide-co-∈-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(d, l -lactide-co-∈-caprolactone), low mol. wt poly(d, l -lactide), and a mixture of d, l -lactic acid oligomer and high mol. wt poly(d, l -lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110°C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0·2, 0·4, 0·7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients. Cephazolin and benzylpenicillin were found to be unsuitable for sustained release longer than 300 h due to the hydrolytic instability of the drugs in water.     

Parametric Optimization of 3D Printed Hydrogel-Based Cardiovascular Stent

Pharmaceutical Research - This study aimed to develop personalized biodegradable stent (BDS) for the treatment of coronary heart disease. Three-dimensional (3D) printing technique has offered easy...