bFGF复合膜对同种异体肌腱移植的作用的实验研究

目的　用bFGF复合膜 ,包裹在腱移植处 ,探讨腱内部再生是否快于腱周结缔组织增生 ,从而达到防止或减轻腱粘连的目的。方法　用 - 80℃冰箱冷存 10天的同种异体跟腱缝接 30只兔左肢跟腱缺损 2 .0cm处 ,分两组 :A组在腱移植处包裹bFGF复合非降解膜 (药膜 )为实验组 ,B组在腱移植处包裹无药的非解降解膜 (无药膜 )为对照组 ,术后不同时间 ,切取腱移植部位 ,常规制成光、电镜标本 ,再行镜下观察 ,图像分析仪测定和腱周粘连定量测定。结果　包药膜腱移植段内部的成纤维细胞和胶原纤维明显较无药膜的多 (<0 0 1) ,包无药膜腱周结缔组织的成纤维细胞和胶原纤维明显较包膜的多 (<0 0 1) ,包药膜腱移植段内部的成纤维细胞和胶原纤维明显较腱周结缔组织的多 (<0 1) ,无药膜的明显较腱周的少 (<0 0 1)。结论　bFGF复合膜有增强腱内部再生和减轻或防止腱粘连的作用     

治疗溃疡膜材料和载药膜材料的检测指标

背景：口腔溃疡是由多种原因引起的口腔黏膜常见病,常以局部用药的治疗为主,口腔溃疡膜的应用可以将药物直接作用于溃疡创面,溃疡膜的缓释设计延长了药物的作用时间,使局部的药物浓度明显增高,有利于药效的发挥。 目的：探讨口腔溃疡膜材料及口腔溃疡载药膜材料的制备方法以及检测指标。 方法：口腔溃疡膜可以通过持续的黏附于溃疡创面,阻隔口腔唾液及口腔菌群对溃疡创面的侵蚀,起到阻碍细菌及保护创面的作用。口腔溃疡载药膜材料可分为合成高分子成膜材料和天然高分子聚合物成膜材料。常用于制备口腔溃疡膜的材料有聚乙烯醇、羟丙基甲基纤维素、羧甲基纤维素等。 结果与结论：壳聚糖口腔溃疡膜具有抗菌、抗氧化的作用,同时可以止血、消炎,促进溃疡组织愈合的作用。壳聚糖和中药载药膜材料可以使溃疡面积明显缩小,壳聚糖膜在治疗有效率方面明显高于抗生素膜。口腔溃疡载药膜制备的过程中,常用高效液相色谱法测定药物浓度,通过线性关系、回收率试验、黏附力和黏附时间的测量,分析溃疡载药膜材料作用后局部的药物浓度、作用时间以及黏附情况。     

硫酸长春新碱缓释药膜的制备及稳定性初步研究

目的制备出载硫酸长春新碱微球的胶原-壳聚糖缓释药膜,并考察该制剂的稳定性。方法采用W/O/O溶剂挥发法制备载硫酸长春新碱的聚乳酸/聚羟基乙酸共聚物(PLGA)微球,后把微球与壳聚糖、胶原溶液共混及二次冻干,制备出载硫酸长春新碱微球的胶原-壳聚糖药膜。对微球和药膜表面形态进行了电镜观察,测定了微球和药膜的包封率、载药量及药物释放,药物含量采用高效液相法检测。此外,还初步考察了缓释药膜的稳定性。结果制备的微球包封率达到79.0%±1.0%,微球药物的突释为27.2%±1.2%,制备成药膜后降低到18.0%±1.1%,采用该工艺流程制备出来的缓释药膜,药物突释明显减少。稳定性实验显示,该药膜在40℃条件下放置3个月药物含量下降到97.9%±0.1%,而高湿度或光照环境下放置10 d药物含量下降到91.4%±0.3%和91.2%±0.4%。结论药物包囊制成微球后与胶原、壳聚糖共混制备出的缓释药膜具有较好的释放特性和稳定性,有望成为一种实用的新型缓释抗肿瘤制剂。     

胶原-壳聚糖载硫酸长春新碱微球缓释药膜的研究

目的本研究制备载硫酸长春新碱(vincristinesulfate,VCR)微球的胶原-壳聚糖缓释药膜。并考察加入壳聚糖对药膜性质的影响。选定适当的胶原壳聚糖比例制备药膜。方法采用W/O/O溶剂挥发法制备VCR的聚乳酸-羟基乙酸(poly(lactic-co-glycolicacid),PLGA)微球,并对微球性质表征,采用二次冻干法制备载VCR微球的胶原-壳聚糖药膜,对药膜的表面形态、降解性质、热力学性质及释放性质进行表征,并与释放2周后的药膜进行比较。采用高效液相法分析药物含量。结果VCR制成PLGA微球后再制备成药膜,可达到双重缓释的作用,明显减少药物突释,并延缓药物释放。添加了壳聚糖的药膜降解速度明显小于单纯的胶原药膜。在体外释放实验中,微球突释为(27.2±1.2)%,而胶原药膜的突释为(20.4±1.9)%,胶原与壳聚糖比例为9∶1、4∶1、3∶2的药膜突释分别为(20.2±2.1)%、(18.0±1.1)%和(16.3±1.8)%。结论胶原壳聚糖载VCR的缓释药膜能不同程度减少药物的突释,使药物释放更加平稳缓慢,优于单纯的胶原药膜。     

胶原/纤维蛋白胶复合药膜的性质及其体外抑瘤效应初步研究

目的 制备载硫酸长春新碱（VCR）微球的胶原/纤维蛋白胶的缓释药膜并研究其性质,考察京尼平的交联浓度（0、0.05、0.1、0.2 mol/ml）对药膜性质的影响.方法 冷冻干燥和京尼平交联法制备多孔胶原膜,将VCR微球混合纤维蛋白胶后加入多孔胶原膜中制备胶原/纤维蛋白胶复合药膜,考察药膜的表面形态、机械性能、降解性质和体外释药行为,并用CCK-8法检测药膜对3种肿瘤细胞（人肺癌细胞株A549、人乳腺癌细胞株MCF-7和人宫颈癌细胞株HeLa）的体外抑瘤率.结果 随着交联剂京尼平浓度的增加,药膜机械强度增加,而断裂伸长率降低.VCR微球与纤维蛋白胶及胶原复合制备成药膜,可达到双重缓释的作用,减少药物突释,并延缓药物释放.未交联的F0药膜药物24h突释为（41.8±3.4）％,京尼平交联后的F0.05、F0.1和F0.2药膜的药物突释分别为（38.4±4.1）％、（35.2±3.6）％和（34.3±3.7）％.未载药的F0.1药膜无显著细胞毒效应,而载药的F0.1药膜在不同时间释放的药液对3种肿瘤细胞株均有显著的抑制作用,且对各细胞株敏感度不同.结论 F0.1药膜能不同程度减少药物的突释,使药物释放更加平稳缓慢,有望用作抗肿瘤药物载体.     

温春制药厂生产的罗红霉素颗粒剂上市

由黑龙江省牡丹江温春制药厂最新研制开发的罗红霉素颗粒剂，已批量生产并投放市场。罗红霉素是目前国际上应用最广的三大抗生素之一。该厂生产的罗红霉素颗粒剂采用高科技的颗粒包衣工艺，将罗红霉素制成无味颗粒，既能使药物正常溶出吸收，保证药物疗效，又减少了服用过...     

罗红霉素对小鼠腹腔巨噬细胞产生TNF-α的影响

罗红霉素(Roxithromycin，Rox)是常用的抗生素。20世纪70年代,Itkin等在临床观察中发现红霉素等大环内酯类抗生素可能具有糖皮质激素相近的作用。近年来，发现以红霉素、罗红霉素、克拉霉素为代表的大环内酯类抗生素具有免疫调节和抗炎作用。一种新型大环内酯类抗生素——他克莫司(tacrolimus)，可作为免疫抑制药物，其免疫抑制作用比环抱菌素A(CyA)强数十倍，对排斥反应有预防和治疗作用．临床应用于器官移植和自身免疫性疾病。     

可降解缓释药膜对大鼠牙周炎的治疗作用

实验选用Wistar大鼠对其下齿作了连续结扎及机械创伤刺激,配合高糖低蛋白饲料饲养,在六周左右大鼠出现了牙周炎症状。可吸收缓释药膜一次性放入患牙的牙周袋内作局部缓释药物治疗。五天后观察牙周炎症状。比较治疗前后牙周炎症状指数改变及组织病理变化。实验结果:1.大鼠实验性牙周炎经可吸收缓释药膜局部治疗后牙龈红肿明显减轻或消失;牙周病症状指数—牙龈指数(GI)及龈沟出血指数(SBI)明显下降;P<0.01;2。牙周组织的病理诊断,治疗后上皮组织少量的淋巴细胞浸润、纤维组织增生、修复明显。这说明可降解缓释药膜用于牙周炎的治疗有明显的治疗效果。     

透明质酸膜在防粘连领域的研究进展

阐述了以透明质酸(Hyaluronic Acid,HA)及其衍生物为主要成分的膜在防粘连领域的研究进展。分类阐述单交联、多重交联的HA防粘连膜;交联HA与多糖分子以及包含药物或功能性金属离子的膜在防粘连领域的应用。交联HA及其衍生物膜用于防粘连领域,不但能弥补HA凝胶和溶液易流动的不足,而且具有适宜的体内存留时间及稳定性。同时HA作为一种良好的药物载体有望在防粘连领域发挥更大的作用。     

植入型表阿霉素缓释药膜的制备及体内抑瘤活性

制备用于实体肿瘤局部治疗的植入型表阿霉素缓释药膜.采用复乳.溶剂挥发法制备聚乳酸载表阿霉素缓释微球,用交联复合法制备含载药微球的植入型胶原药膜;用扫描、透射电镜、共聚焦及粒度仪等考察微球和药膜的形貌、结构、粒径及体外释放;用H22肝癌荷瘤动物模型评价其体内抑瘤效果.结果:载药微球粒径分布均匀,外观圆整,平均粒径为5.8μm;微球的载药量4.39%,包裹率为37.2%;10h内载药微球在模拟体液中的累积释放率为35%;腹腔注射载药微球与瘤体局部植入胶原药膜对H22肝癌均有明显的抑瘤效果;微球注射与药膜植入两种不同给药方式对H22肝癌抑瘤效果也存在显著性差异(P<0.05).植入型载表阿霉素缓释胶原膜具有良好的药物局部缓释特性,在肿瘤的术后局部治疗方面具有良好的临床应用前景.     

Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions

Peritendinous adhesions, as a major problem in hand surgery, may be due to the proliferation of fibroblasts and excessive collagen synthesis, in which ERK1/2 and SMAD2/3 plays crucial roles. In this study, we hypothesized that the complication progression could be inhibited by down-regulating ERK1/2 and SMAD2/3 phosphorylation of exogenous fibroblasts with celecoxib. Celecoxib was incorporated in poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes via electrospinning. Results of an in vitro drug release study showed celecoxib-loaded membrane had excellent continuous drug release capability. It was found that celecoxib-loaded PELA membranes were not favorable for the rabbit fibroblast and tenocyte adhesion and proliferation. In a rabbit tendon repair model, we first identified ERK1/2 and SMAD2/3 phosphorylation as a critical driver of early adhesion formation progression. Celecoxib released from PELA membrane was found to down-regulate ERK1/2 and SMAD2/3 phosphorylation, leading to reduced collagen I and collagen Ⅲ expression, inflammation reaction, and fibroblast proliferation. Importantly, the celecoxib-loaded PELA membranes successfully prevented tissue adhesion compared with control treatment and unloaded membranes treatment. This approach offers a novel barrier strategy to block tendon adhesion through targeted down-regulating of ERK1/2 and SMAD2/3 phosphorylation directly within peritendinous adhesion tissue.     

魔芋葡甘聚糖/透明质酸共混膜的体外细胞生物相容性

背景：高分子材料透明质酸与魔芋葡甘聚糖均可用于防治术后粘连。 目的：观察兔骨髓间充质干细胞与魔芋葡甘聚糖-透明质酸共混膜复合培养的生物相容性。 方法：取第3代兔骨髓间充质干细胞与魔芋葡甘聚糖-透明质酸共混膜体外复合培养,倒置显微镜和扫描电镜观察复合程度,MTT法检测细胞增殖。体外定向外诱导魔芋葡甘聚糖-透明质酸共混膜上的骨髓间充质干细胞向脂肪细胞分化,油红O染色检测其分化效果。 结果与结论：骨髓间充质干细胞与魔芋葡甘聚糖-透明质酸共混膜修复材料复合良好,倒置显微镜和扫面电镜观察均可见细胞在共混膜上良好黏附与增殖;体外定向诱导魔芋葡甘聚糖-透明质酸共混膜上的骨髓间充质干细胞可向脂肪细胞分化,具有成脂潜能。说明魔芋葡甘聚糖-透明质酸共混膜与骨髓间充质干细胞具有良好的生物相容性。     

Improved blood compatibility by sustained release of heparin-deoxycholic acid conjugates in a PCL-PEG multiblock copolymer matrix

The heparin and deoxycholic acid conjugate (heparin-DOCA) synthesized in this study has an amphiphilic property and could be completely dissolved in a co-solvent made of 1,4-dioxane (50 v/v%), n-propanol (25 v/v%), and water (25 v/v%). A polycaprolacton (PCL)-polyethylene glycol (PEG) multiblock copolymer was used as the coating matrix; this polymer also dissolved readily in the same co-solvent. Heparin-DOCA and the PCL-PEG multiblock copolymer were mixed well to produce a transparent coated film on an angio-catheter. The bioactivity of the released heparin-DOCA was determined by evaluating platelet adhesion and fibrin formation on the coated surfaces. The release rate could be controlled by the loading amount of the drug and drug release was maintained for 12 h. The released heparin-DOCA significantly prevented platelet adhesion and fibrin formation at the surfaces, as well as in the bulk in the plasma.     

胶原/透明质酸膜与明胶海绵支架材料力学及组织相容性的比较

背景：课题组前期实验证明胶原/透明质酸膜具有良好的力学性能和组织相容性。 目的：观察复合材料胶原/透明质酸膜及明胶海绵的生物学性能。 方法：应用材料复合交联的实验方法构建胶原/透明质酸膜并测定胶原/透明质酸膜、明胶海绵支架的力学性能。将支架材料种植于兔皮下,按照2,4,6,8,12周不同时间点评价材料在体内的降解情况和组织相容性。 结果与结论：①成功制备了胶原/透明质酸膜。②胶原/透明质酸膜具有较好的韧性和抗张强度,明胶海绵的力学性能不够理想。③两种材料在体内的降解均符合生物材料的组织反应过程,胶原/透明质酸膜在体内12周可完全降解,明胶海绵约6周完全降解。④胶原/透明质酸膜与平滑肌细胞的黏附率高,细胞的增殖和代谢状况较好,而明胶海绵的细胞黏黏附和增殖率相对较低。说明胶原/透明质酸膜具有较好的生物学性能。     

Use of polylactic acid/polytrimethylene carbonate blends membrane to prevent postoperative adhesions

The objective of the study was to evaluate the effect of a novel biodegradable membrane on the prevention of postoperative adhesion formation. The membrane was prepared by blending 50% PLA (polylactic acid) with 50% PTMC (polytrimethylene carbonate). The prepared blends polymer membrane was more flexible than pure PLA membrane, as measured by glass-transition temperature and tensile study. Cytotoxicity study revealed that PLA/PTMC blends membrane showed good biocompatibility. The membrane elicited slight tissue reaction based on the results of histological study. Thirty adult Japanese rabbits were used for the intestine adhesion model. The treatment group had PLA/PTMC membrane, the control group had chitosan, and the blank control group was not operated. The animals were housed for two weeks and sacrificed to investigate adhesion of intestine. Compared with the blank control group, the treatment group and the control group lowered the extent of adhesions (p < 0.01), but the treatment group was better than the control group (p < 0.05). The in-vivo studies confirmed that PLA/PTMC blends membrane could prevent postoperative adhesions.     

Layer-by-layer assembly of chitosan and platelet monoclonal antibody to improve biocompatibility and release character of PLLA coated stent

The aim of this study is to construct a biocompatible coating of a drug-eluting stent through the incorporation of chitosan with monoclonal antibody (mAb) to a platelet glycoprotein (GP) IIIa receptor, by electrostatic layer-by-layer (LBL) adsorption of oppositely charged polyelectrolytes and proteins. The platelet maximum aggregation rate and aggregation inhibition rate tests confirm the bioactivity of mAb in different pH assembly environments. The fluorescence spectra test and confocal laser scanning microscopy observation were used to monitor the LBL assembly process of the mAb/chitosan multilayer on the surface of the aminolyzed Poly-L-lactic acid (PLLA) membrane, when using Rhodamine B isothiocyanate-labeled mAb and Fluorescein isothiocyanate-labeled chitosan. The in vitro platelet adhesion experiment demonstrated the amicable blood compatibility of the mAb/chitosan multilayer. The endothelial cell adhesion and migration test revealed that the multilayer could improve the cytocompatibility of the PLLA matrix in terms of cell attachment, proliferation, and migration. An in vitro perfusion circuit was designed to evaluate the release rates measured by a radioisotope technique with 12?I-labeled GP IIIa mAb. The different eluting curves of the mAb/chitosan-assembled stent and mAb physically absorbed stent showed the improvement of mAb's release character when using LBL self-assembly technology. Our method to prepare a biocompatible stent surface with mAb/chitosan multilayers has proved to be favorable and effective in vitro, thus justifying further evaluation to improve the biocompatibility in an animal model test.     

血管组织工程支架材料的细胞相容性

背景：胶原与透明质酸均有利于组织培养中细胞的黏附、增殖和分化。 目的：观察血管内皮细胞、平滑肌细胞与胶原/透明质酸膜、明胶海绵的细胞相容性,并筛选最佳种植方法。 方法：将第3-5代兔血管平滑肌细胞种植在胶原/透明质酸膜(或明胶海绵)材料上,连续培养2周后将兔内皮细胞接种在平滑肌细胞-胶原/透明质酸膜(或明胶海绵)复合体上,并设置单纯平滑肌细胞与内皮细胞共同接种组。 结果与结论：①光镜和扫描电镜观察：细胞在两种材料上均随着培养时间,接种次数增加而生长加快,其中在胶原/透明质酸膜上的细胞生长更好,细胞连接更致密。②WST-1法检测：胶原/透明质酸膜组平滑肌细胞的黏附率及增殖率均高于明胶海绵组(P < 0.05),且细胞在材料上的生长随着接种次数的增加有不同程度提高。③³H-TDR掺入法检测DNA合成率：在胶原/透明质酸膜上的细胞DNA合成最高,明胶海绵上的较差。表明胶原/透明质酸膜具有较理想的细胞相容性,采用适当间隔、反复接种的方法可提高细胞的黏附和增殖。     

Deposition of PLA/CDHA composite coating via electrospraying

Composite coatings composed of carbonated calcium deficient hydroxyapatite (CDHA) and polylactic acid (PLA) were deposited on a PLA substrate surface via electrospraying. The operation parameters, structural properties, bioactivity, cell adhesion, and growth capability of as-fabricated PLA/CDHA coatings were investigated. The composite coating showed good biocompatibility and bioactivity. The deposited coating was also applied as a carrier to assist alendronate sodium (AS) local release. AS, an approved bisphosphonate drug used for the treatment of osteoporosis, was incorporated into a composite coating matrix via coelectrospraying. Its release behavior showed a long-term sustained release. This approach can be a potential coating technique for the surface modification of biopolymer implants.     

Enhanced transport in a therapeutic transdermal system

Ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. A variety of control membrane laminates were examined for swelling and adhesion strength following equilibration with ethanolic solutions to identify a mechanically stable control membrane laminate. In vitro skin permeation analysis of the control membrane laminate showed that ethanol flux was linearly related to the ethanol volume fraction. A reservoir-type therapeutic transdermal system incorporating ethanol was developed to provide constant release of drug and ethanol through skin for 24 h. In vitro ethanol skin permeation rates were constant for 24 h and adhesion was stable over 16 wk at 40°C using a transdermal reservoir device.     

Influence of poly(ethylene glycol)-alpha-cyclodextrin complexes on stabilization and transdermal permeation of ascorbic acid

The present study was conducted to investigate the effect of poly(ethylene glycol)-alpha-cyclodextrin (alpha-CD) complexes on stabilization and cutaneous permeation of ascorbic acid from specially prepared transdermal patches. Poly(ethylene glycol) citrate (6-armPEG) and its inclusion complex with alpha-CD were prepared and used for preparation of the transdermal patches. Duro-Tak 87-2979 was taken as an adhesive matrix in combination with ascorbic acid. A diffusion cell with an artificial membrane was used to evaluate the absorption of ascorbic acid from the patches. The influence of drug release of alpha-CD and two types of its PEG complexes (as the novel permeation enhancers) was tested. The 6-armPEG-alpha-CD complex consisting of a PEG-citric acid ester at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for ascorbic acid during UV assay. The release studies showed that the type of enhancer is important in diffusion of the drug across membrane. Furthermore, the diffusion of ascorbic acid was considerably enhanced in the presence of 6-armPEG-alpha-CD complex. Inclusion complexes of 6-armPEG with alpha-CD at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for UV method of assay. The present data suggest that 6-armPEG-alpha-CD complex is also useful in enhancing the release of ascorbic acid from the acrylic type pressure sensitive adhesives.