壳聚糖的止血机理和应用

壳聚糖在医学领域的应用越来越广泛。本简述了壳聚糖止血机理研究的进展，指出它的止血机理不是常规的依赖于血小板和凝血因子的瀑布机制。壳聚糖止血机制中的重要一环是对红细胞作用，使红细胞发生粘附聚集从而使血液凝固。另外，中对壳聚糖在止血剂中的应用也作了简要的介绍。     

甲壳素/壳聚糖止血机理及应用

甲壳素通过蛋白质介导黏附血小板,形成的甲壳素/血小板复合物加速血纤维蛋白单体的聚合并共同形成凝块;另一方面,甲壳素诱导红细胞聚集,刺激血管收缩,最终形成血栓,封合伤口.壳聚糖的止血机理基本类似于甲壳素,但两者对红细胞的聚集程度和对补体的激活程度存在一定差异.甲壳素独特的三次结晶结构(包括α型和β型)赋予甲壳素优良的止血功能;壳聚糖的止血效果则与它的分子量、脱乙酰度、质子化程度和物理形式等有关.本文综述了甲壳素和壳聚糖的止血机理及应用情况.     

壳聚糖醋酸溶液对凝血作用的研究

研究了不同脱乙酰度和不同分子量壳聚糖醋酸溶液的凝血作用。发现壳聚糖醋酸溶液使抗凝血液中红细胞发生了明显的聚集和变形。通过不同分子量和脱乙酰度壳聚糖的促红细胞聚集实验,证明了低脱乙酰度壳聚糖(60%~70%)使红细胞聚集效果更好,分子量在105~106范围内作用不十分明显。对血液的凝血酶时间(TT)、凝血酶原时间(PT)、活化部分促凝血酶原激酶时间(APTT)和纤维蛋白原浓度(FIB)的测定结果验证了壳聚糖醋酸溶液凝血机理不依赖于血小板和常规“瀑布”凝血机制。     

医用生物可吸收止血材料的研究现状与临床应用

背景：目前市场已开发出多种不同组成和不同机制的止血材料,因其不同特性而应用各异。 目的：概述国内外临床常用医用可吸收止血材料,对其组成、止血机制及临床应用进行总结,指导临床医生更加合理有效地应用止血材料。 方法：应用计算机检索CNKI和PubMed数据库中2002-02/2011-05关于止血材料的文章,以“生物材料,止血材料,生物可吸收材料,止血效果,止血机制”或“biomaterial,hemostatic material,bioresorbable material,hemostatic effect,hemostatic mechanism”为中、英文关键词。纳入与生物可吸收止血材料及其应用相关的文章;排除重复研究的内容和与研究目的不相符的文献。 结果与结论：目前国内外主要应用的可吸收止血材料为纤维蛋白胶、氧化纤维素和氧化再生纤维素、α-氰基丙烯酸酯类组织胶、壳聚糖等。壳聚糖的止血性在于壳聚糖带有一定量的电荷,它的分子直接与创面上的红细胞发生交联反应形成血凝块,它的止血过程不依赖于机体凝血因子和血小板。α-氰基丙烯酸酯类黏合剂已应用于血管外科的中小管径血管吻合、神经外科的中硬脑膜修补、各类软组织修补、骨科中骨折的黏合等,并且成为介入栓塞治疗中的首选材料。在骨科领域纤维蛋白胶除了局部止血、防止粘连和渗漏外主要是作为缓释载体,骨材料支架而发挥作用。氧化纤维素和氧化再生纤维素已成功应用于神经外科、耳鼻喉科、肝胆外科等。不同的止血材料其止血机制和止血效果均不同,只有充分了解各种止血材料性能,才能合理、有效应用。      

壳聚糖/鞣花酸/红细胞膜脂止血复合海绵的制备与评价

背景：部分文献报道壳聚糖对严重创伤的止血效果有限,因此以壳聚糖为基础止血剂的促凝血活性还有待进一步增强。 目的：制备一种新型的壳聚糖/鞣花酸/红细胞膜脂复合海绵,评价其促凝血活性和细胞毒性。 方法：通过冻干法制备壳聚糖海绵和壳聚糖乙酸盐海绵,然后再通过静电吸附法制备壳聚糖/鞣花酸/红细胞膜脂复合海绵。血浆复钙时间法观察3种海绵的促凝血活性,并检测3种海绵对SD大鼠肝脏的止血效果及对L929细胞的毒性。 结果与结论：壳聚糖/鞣花酸/红细胞膜脂复合海绵组的血浆复钙时间、出血时间、失血量均显著少于壳聚糖海绵组和壳聚糖乙酸盐海绵组(P < 0.01)。细胞实验显示壳聚糖/鞣花酸/红细胞膜脂复合海绵无细胞毒性。说明壳聚糖/鞣花酸/红细胞膜脂复合海绵具有良好的促凝血活性且无细胞毒性。     

基于壳聚糖的医用可吸收止血贴的研究与应用

几丁质是自然界中合成的产量仅次于纤维素的天然有机化合物,其经过脱乙酰作用生成的壳聚糖具有优良的生物及化学性质;此外通过改变聚合度、脱乙酰度或经过不同官能团的修饰,壳聚糖的理化性质可以发生变化,因此它在生物医药和保健领域的应用倍受重视.本文首先叙述了壳聚糖及其衍生物与止血相关的性质与功能,说明了壳聚糖可作为止血贴主要材料的巨大应用价值,然后阐述了壳聚糖及其止血贴产品的研究现状与生产手段,最后依据目前研究现状,对基于壳聚糖的可吸收止血贴产品的未来发展趋势进行了展望.     

可吸收止血材料的研究现状及临床应用

简要综述了近年国内外主要的可吸收止血材料包括可吸收纤维蛋白胶、氧化纤维素、氧化再生纤维素、壳聚糖、α-氰基丙烯酸酯类组织胶、可吸收性明胶海绵和明胶纤维网、微纤维胶原和胶原纤维网、海藻酸钙纤维的组成、止血机理、止血性能、研究现状及临床应用,展望了可吸收止血材料未来的发展趋势.对医生了解医用可吸收止血材料的止血特性、掌握正确的使用方法、充分发挥其止血效果,提供了一定的参考价值,同时,对医用材料工作者进一步研究止血材料提供了参考.     

壳聚糖结构和分子量对凝血作用的研究

本工作研究了不同脱乙酰度和不同分子量壳聚糖、壳聚糖醋酸生理盐水溶液及羧甲基壳聚糖生理盐水溶液的凝血作用。在壳聚糖醋酸生理盐水溶液作用下，红细胞发生聚集和形变，而且低脱乙酰度现象明显，分子量在10^5～10^6范围内影响不十分明显；羧甲基壳聚糖不能使红细胞在低相对离心力下发生沉降，仅有部分叠连现象；而壳聚糖则不能使红细胞发生聚集和形变。血液凝血酶时间(TT)、凝血酶原时间(PT)、活化部分促凝血酶原激酶时间(APTT)和纤维蛋白原浓度(FIB)验证了壳聚糖、壳聚糖醋酸生理盐水溶液以及羧甲基壳聚糖均不激活凝血因子，且脱乙酰度、分子量以及取代基对这些指标也没有明显地影响。动态凝血实验发现低脱乙酰度壳聚糖能够更好地使血液凝固。     

胶原/壳聚糖止血敷料在外科伤口中的应用

背景：壳聚糖与胶原联合可更有效地止血。 目的：评价胶原/壳聚糖止血敷料的材料学性能及应用于外科伤口的生物相容性。 方法：以“生物材料,止血敷料,纱布,胶原/壳聚糖,生物相容性”为中文关键词,以“biomaterial;hemostatic material;bioresorbable material;hemostasis effect;hemostatic mechanism”为英文关键词,采用计算机检索2000-01/2010-06与生物敷料、胶原/壳聚糖止血材料在伤口或创面止血过程中应用相关的文献。 结果与结论：壳聚糖独特的生物学特性,具有广谱抑菌、促进上皮细胞生长及止血,促进创面愈合的作用,在体内具有良好的生物降解性与组织相容性,可用于指端损伤和肉芽创面的治疗,如制成伤口敷料、可吸收缝线、止血材料、防粘连剂、药物缓释及组织工程支架,用于平战时伤口的处理。     

胶原/壳聚糖复合膜的制备及止血效果的研究

目的以胶原和壳聚糖制备复合膜,检验其止血效果,并探讨其止血原因.材料与方法:以酸解法从牛腱中提取胶原,用甲壳素制得壳聚糖,以胶原和壳聚糖制成复合膜,通过动物实验测不同配比的复合膜对出血创面的止血时间,并与其它止血材料做对比.结果:各种配比的复合膜的止血效果均比明胶等一般止血材料好.结论:胶原/壳聚糖复合膜有良好的止血作用,可望在外科手术上得到广泛应用.     

Should chitosan and tranexamic acid be combined for improved hemostasis after sinus surgery?

Chitosan, a β-1,4-linked polymer of glucosamine with lesser amounts of N-acetylglucosamine, has well-recognized hemostatic properties. Chitosan is also able to open tight cellular junctions, facilitating paracellular drug transport and delivery. Chitosan, through topical application, facilitates the systemic delivery of analgesic drugs. Theoretically this ability could be used to enhance the local delivery of hemostatic drugs, such as tranexamic acid, improving chitosan’s role as a topical dressing. Individually a chitosan–dextran gel and tranexamic acid have been shown to improve hemostasis after endoscopic sinus surgery. A combination of both should lead to improved hemostasis and better postsurgical outcomes. The use of a chitosan/tranexamic acid dressing could have a wide range of potential beneficial applications in a number of other clinical surgical settings. While the initial main application might be as an improved external hemostatic dressing, it should also be useful on a range of internal surgical wounds.     

蝇蛆壳提取壳聚糖的综合评价

目的 壳聚糖具有良好的水溶性、生物相容性、生物降解性、成膜性及止血、愈创、消炎等作用,在医用生物材料应用方面具有广阔前景.蝇蛆的皮中含有大量壳聚糖成分,是获得较纯壳聚糖的方式之一.对蝇蛆提取的壳聚糖创伤敷料进行综合评价.方法 按照国家统一标准对蝇蛆壳聚糖进行理化分析(相对分子质量、脱乙酰度和重金属含量)、抑菌、皮肤致敏、细胞毒性和溶血实验.结果 蝇蛆壳聚糖的相对分子质量为266 ku,脱乙酰度为75％,重金属含量小于10-5,细胞毒性总评级为1级,具有较轻细胞毒性.致敏和溶血实验结果表明,蝇蛆壳聚糖材料不具有致敏反应,材料的溶血率为0.769％,小于5％,即没有溶血现象.此外,蝇蛆壳聚糖还具有抑菌作用.结论 蝇蛆壳聚糖具有较好的综合特性,可以满足生物医药方面的要求.     

Should chitosan and tranexamic acid be combined for improved hemostasis after sinus surgery?

Chitosan, a β-1,4-linked polymer of glucosamine with lesser amounts of N-acetylglucosamine, has well-recognized hemostatic properties. Chitosan is also able to open tight cellular junctions, facilitating paracellular drug transport and delivery. Chitosan, through topical application, facilitates the systemic delivery of analgesic drugs. Theoretically this ability could be used to enhance the local delivery of hemostatic drugs, such as tranexamic acid, improving chitosan’s role as a topical dressing. Individually a chitosan–dextran gel and tranexamic acid have been shown to improve hemostasis after endoscopic sinus surgery. A combination of both should lead to improved hemostasis and better postsurgical outcomes. The use of a chitosan/tranexamic acid dressing could have a wide range of potential beneficial applications in a number of other clinical surgical settings. While the initial main application might be as an improved external hemostatic dressing, it should also be useful on a range of internal surgical wounds.     

几丁糖/海藻酸敷料止血性能的实验研究

目的研究一种新型敷料：几丁糖／海藻酸敷料（本项目组自行研制，已申请国家专利）的止血性能。方法取新西兰兔4只，在背部两侧对称性剪5个直径1cm的圆型创口，分别与创面大小相当的几丁糖／海藻酸敷料和明胶海绵止血，观察与创面的粘附情况，记录出血时间：止血停止后，将几丁糖／海藻酸敷料和明胶海绵放入预先配制好的氰化高铁血红蛋白检测试剂中仔细清洗，用分光光度计在540nm波长处光度比色，测出的Hb光度吸收值表示出血量。结果几丁糖／海藻酸敷料与创面粘附较好，几丁糖／海藻酸敷料、明胶海绵组的出血时间分别为87.7±19.1妙、170.7±22.6妙，Hb光度吸收值分别为1.131±0.44、1.733±0.733，经统计学分析，两组数据都有显著性差异（P〈0.01），几丁糖／海藻酸敷料组明显优于明胶海绵组。结论几丁糖／海藻酸敷料具有较好的止血性能。     

Effect of chitosan and carboxymethyl chitosan on fibrinogen structure and blood coagulation

Chitosan has numerous biomedical applications such as tissue engineering scaffolds, drug/gene delivery systems, hemostasis materials, antibacterial materials, wound dressing, etc. In any case, chitosan administered in vivo would positively or passively contact or enter blood tissue. In this situation, the interaction of chitosan with blood components is critical to determine the efficacy and safety of the polymer. In this study, the effect of chitosan with different molecular weight and its derivative carboxymethyl chitosan (CMC) on the structure and function of clotting-related proteins was studied. Specifically, the structural and conformational change of fibrinogen, an important clotting protein, was studied by using UV, fluorescence, and circular dichroism spectroscopy, respectively. Further, the impact of chitosan and CMC on the clotting function was evaluated with activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen time (FT), and thromboelastography (TEG) assays. These results showed that, chitosan and fibrinogen can form complex mainly by electrostatic attraction. As a result, the structure and conformation of fibrinogen are altered by chitosan and CMC. Additionally, the presence of chitosan and CMC has little impact on the values of APTT, PT and FT, but causes significant abnormality in the clotting process by changing TEG parameters. These results provide important insight into the molecular basis for the biological response to chitosan and other biopolymers.     

壳聚糖膜的降解性研究

用不同性能地壳聚糖为膜材料制备壳聚糖膜，通过体外酸解，酶解试验及动物体内植入试验研究其降解。试验结果表明，壳聚糖是一种可生物降解性膜材料，壳聚糖膜的降解性与其脱乙酰度，介质酸性强弱及溶菌酶等因素有关。壳聚糖膜在动物体内降解比较缓慢，２０天约降解８．２％。     

The potential role of free chitosan in bone trauma and bone cancer management

Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management.     

壳聚糖膜的降解与生物相容性研究

用小鼠作实验动物，研究了壳聚膜的生物降解与生物相容性，结果表明，壳聚糖膜易于生物降解，在植入初期有轻度炎症反应，至１６周后炎症反应基本消失。作为一种新型天然可吸收性生物材料，壳聚糖具有很好的发展应用前景。