当前位置:主页 > 医学论文 > 生物医学论文 >

可吸收壳聚糖材料止血性能及其生物相容性研究

发布时间:2018-08-08 10:35
【摘要】:壳聚糖是甲壳素部分脱乙酰的产物,具有止血、抗菌、促进伤口愈合和生物相容性好等优点,广泛应用于血管支架、创伤修复等组织工程领域。目前壳聚糖基止血材料取得巨大成功,其优秀的促凝血效果在军事和民用领域得到验证。然而,FDA批准的现有壳聚糖基止血材料的应用领域仅仅是外用,还不能作为可吸收止血材料长期体内植入。研究表明,现有壳聚糖基止血材料存在以下两个问题:(1)大都呈酸性,在动物体内植入后会导致急性炎症反应和慢性炎症,影响创伤的愈合;(2)降解较缓慢,由此产生组织粘连、纤维囊肿等副作用,并形成严重的疤痕组织。要使壳聚糖材料作为可吸收止血材料体内植入,必须解决这两个存在的缺陷。 (1)通过系统性研究壳聚糖分子量和脱乙酰度对壳聚糖降解速度的调控行为,采用均相氧化降解和非均相氧化降解法制备得到了重均分子量在36537-529652的系列小分子量的壳聚糖,采用甲壳素脱乙酰法和壳聚糖乙酰化法制备脱乙酰度在39.6%~59.6%的系列低脱乙酰度壳聚糖(酸碱滴定)。体外溶菌酶降解壳聚糖实验结果表明,脱乙酰度为39.6%的壳聚糖酶降解速度最快,比明胶海绵快。 (2)创新性的提出了仿手工抄纸工艺,从壳聚糖水凝胶悬浮液出发,利用壳聚糖水凝胶颗粒之间的毛细作用和形成的氢键作用,使用高温烘制或一次冷冻干燥成型,制备了壳聚糖多孔膜和多孔海绵材料。制得的壳聚糖多孔膜形状规整、柔顺性好并能够与创面良好贴敷;壳聚糖多孔海绵具有高孔隙率和高表面粗糙度,这种高孔隙率和高表面粗糙度有利于促进血液凝固。 (3)采用体外动态凝血法测定了不同脱乙酰度纯壳聚糖促凝血性能,其中M0D3(D.D=48.07%,红外)促凝效果最好。通过血小板吸附、红细胞吸附、APTT和TT测试等方法初步研究可壳聚糖的促凝血机理。壳聚糖主要通过对血小板及红细胞的吸附促进血液凝固; (4)将脱乙酰度分别为39.6%,48.07%和93.6%的新型壳聚糖海绵进行大鼠肝脏创伤止血实验,结果显示自制壳聚糖海绵在动物体内也有止血效力,所有壳聚糖海绵止血效果都比明胶海绵好,总出血量都小于明胶海绵组,其中脱乙酰度为48.3%的壳聚糖止血效果最好。 (5)将脱乙酰度分别为39.6%,48.07%和93.6%(酸碱滴定)的新型壳聚糖海绵和明胶海绵植入大鼠肝脏创伤部位,在1周、4周、8周和24周时分别取各组大鼠的肝脏组织标本,做HE.Masson's染色以及免疫组化染色(TGF-β1和IL-1p),检查各种材料的吸收、炎症、创伤愈合情况。结果表明,脱乙酰度39.6%的壳聚糖在第8周时完全被吸收;明胶海绵完全吸收的时间则大于8周,在24周时完全吸收;而脱乙酰度为48.07%和93.6%的壳聚糖在24周还未完全吸收。病理切片和IL-1β染色结果表明,脱乙酰度39.6%的壳聚糖体内炎症反应最弱;,脱乙酰度39.6%的壳聚糖TGF-β1分泌水平低,胶原生成量适中,不形成疤痕性愈合;,脱乙酰度39.6%的壳聚糖,减少其他组织的粘连的几率。
[Abstract]:Chitosan is a product of chitin partial deacetylation. It has many advantages, such as hemostasis, antibacterial, wound healing and good biocompatibility. It is widely used in the tissue engineering fields such as vascular scaffold and wound repair. At present, chitosan based hemostat has been a great success, and its excellent coagulation effect is verified in military and civil fields. However, FD The application of the existing chitosan based hemostat approved by A is only external and can not be implanted in the body for a long time as an absorbable hemostat. Research shows that the existing chitosan based hemostat has two problems: (1) most of them are acidic, and they can lead to acute inflammatory reaction and chronic inflammation after implantation in animals and affect the trauma. Healing; (2) slow degradation, resulting in tissue adhesions, fibrous cysts and other side effects, and forming severe scar tissue. To make the chitosan material as an absorbable hemostatic material to be implanted in the body, these two existing defects must be solved.
(1) by systematic study of the regulation of chitosan molecular weight and deacetylation degree on the degradation rate of chitosan, a series of small molecular weight chitosan with a heavy average molecular weight of 36537-529652 was prepared by means of homogeneous oxidation degradation and heterogeneous oxidation degradation. The deacetylation degree of chitosan was prepared by chitin deacetylation and chitosan acetylation. A series of low deacetylation degree chitosan (acid-base titration) from 39.6% to 59.6%. The results of in vitro lysozyme degradation of chitosan showed that the degradation rate of chitosan was 39.6% faster than that of gelatin sponge.
(2) an innovative handmade papermaking process was proposed. Starting from the chitosan hydrogel suspension, using the capillary action and the hydrogen bond between the chitosan hydrogel particles, the chitosan porous membrane and the porous sponge were prepared by high temperature drying or one freeze drying. The chitosan porous membrane was formed in shape and soft. The chitosan porous sponge has high porosity and high surface roughness. This high porosity and high surface roughness can help to promote blood coagulation.
(3) the procoagulant properties of pure chitosan with different deacetylation degree were measured by dynamic coagulation in vitro, in which the effect of M0D3 (D.D=48.07%, IR) was the best. The coagulation mechanism of chitosan was preliminarily studied by means of platelet adsorption, red cell adsorption, APTT and TT test. Chitosan was mainly used to promote the adsorption of platelets and red blood cells. Blood coagulation;
(4) a new chitosan sponge with a degree of deacetylation of 39.6%, 48.07% and 93.6% was carried out in the rat liver trauma test. The results showed that the self-made chitosan sponge had hemostatic effect in the animal body. All chitosan sponges had better hemostatic effect than gelatin sponge. The total amount of bleeding was less than that of Gelfoam group, and the degree of deacetylation of the chitosan sponge was 48.3%. The hemostatic effect of chitosan is the best.
(5) the deacetylation degree was 39.6%, 48.07% and 93.6% (acid-base titration), the new chitosan sponge and gelatin sponge were implanted in the rat liver trauma site. The liver tissue specimens of rats were collected at 1 weeks, 4 weeks, 8 weeks and 24 weeks respectively. HE.Masson's staining and immunohistochemical staining (TGF- beta 1 and IL-1p) were used to examine the absorption and inflammation of various materials. The results showed that the chitosan was completely absorbed at eighth weeks when the degree of deacetylation was 39.6%; the total absorption time of the gelatin sponge was more than 8 weeks and completely absorbed at 24 weeks. The chitosan with deacetylation of 48.07% and 93.6% was not completely absorbed at 24 weeks. Pathological section and IL-1 beta staining showed that the degree of deacetylation was 39.6% of the shell. The inflammatory reaction was the weakest in the body, and the degree of deacetylation of chitosan TGF- beta 1 was low, the amount of collagen production was moderate, and no scar healing was formed; and the degree of deacetylation of chitosan was 39.6%, reducing the risk of adhesion of other tissues.
【学位授予单位】:浙江大学
【学位级别】:博士
【学位授予年份】:2013
【分类号】:O636.1;R318.08

【共引文献】

相关期刊论文 前10条

1 郎笑梅,董学锋,樊敏,赵湘,戚世伟,周永列;高血压病患者血小板活化分子的变化及意义[J];中医药临床杂志;2004年02期

2 杨小玮;肾挫伤非手术治疗患者并发深静脉血栓的原因分析与预防护理[J];安徽医药;2005年02期

3 李勇,夏翠英,吕明安;胃萎汤对气虚血瘀证大鼠血液流变学指标的影响[J];安徽中医学院学报;2005年01期

4 梁桦;杨承祥;李恒;刘洪珍;王汉兵;;术前急性超容血液稀释对结肠癌患者高凝状态的影响[J];癌症;2006年10期

5 李家增;恶性肿瘤与止血障碍[J];癌症进展;2005年02期

6 高翔,冯燕娴,孙宝玲,阳海红;低分子肝素钙在急性心肌梗死溶栓前的应用[J];蚌埠医学院学报;2001年06期

7 司春强;;兔深静脉血栓形成后内皮细胞凋亡变化[J];蚌埠医学院学报;2007年05期

8 王东;王亿平;;P-选择素与肾脏疾病[J];浙江中医药大学学报;2008年04期

9 赵莹,蒋淑方,袁敏;主动和被动活动下肢对老年前列腺术后患者股静脉血流速度的影响[J];滨州医学院学报;2004年01期

10 钱盛伟;高宝山;金点石;常庆勇;张继志;黄坤;曲凯;;神经外科领域的静脉血栓栓塞症[J];中华神经医学杂志;2006年07期

相关会议论文 前7条

1 李国贤;鄢毅;;多病同治——血栓病的诊治进展[A];江西省第八次中西医结合活血化瘀学术研讨会暨心脑血管病培训班论文集[C];2009年

2 蒋德玉;王燕;邱有贤;周婷;郑小美;;髋关节置换术后预防下肢深静脉血栓形成的护理[A];2006年贵州省医学会骨科学分会学术年会论文汇编[C];2006年

3 周晓菊;王淑琴;;骨科术后下肢深静脉血栓形成的危险因素及干预对策[A];宁夏医学会骨科学分会第三届学术会议论文汇编[C];2005年

4 王晓凤;;人工膝、髋关节置换术后预防下肢深静脉血栓形成的整体护理[A];第二届第二次中医护理学术交流会议论文汇编[C];2007年

5 王鹂;魏陵博;彭敏;丁书文;戎冬梅;;解毒通络法对血栓形成大鼠AT-Ⅲ活性、D二聚体含量的影响[A];中华中医药学会血栓病分会成立大会暨首届血栓病学术研讨会论文集[C];2007年

6 杨春仙;;剖宫产术后下肢深静脉血栓形成的相关因素与护理[A];第三届浙江中西部科技论坛论文集(第八卷 护理分卷)[C];2006年

7 王爱霞;;循证护理在预防脑梗死患者下肢深静脉血栓形成中的应用[A];2012年河南省外科创伤及灾难救治专科知识学术会议论文集[C];2012年

相关博士学位论文 前10条

1 阎亮;桃红四物汤对THR术后血液高凝状态的影响及DVT预防的实验和临床研究[D];广州中医药大学;2011年

2 徐传毅;生脉成骨胶囊治疗激素性股骨头坏死的骨修复机理研究[D];广州中医药大学;2001年

3 徐丽荣;清开灵有效组分干预缺血性中风细胞粘附机制的研究[D];北京中医药大学;2005年

4 高永红;清开灵有效组分对大鼠脑微血管内皮细胞缺血再灌注损伤炎症反应的影响[D];北京中医药大学;2005年

5 谢露;广西海带多糖LO1提取纯化与抗血栓作用机制研究[D];广西医科大学;2005年

6 王兵;大鼠急性创伤性深静脉血栓模型建立及股静脉基因表达研究[D];昆明医学院;2005年

7 黄河;创伤性股静脉血栓基因表达变化及低分子肝素干预研究[D];昆明医学院;2007年

8 刘彦琴;加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D];辽宁中医药大学;2007年

9 唐丽琴;IL-1α对佐剂性关节炎大鼠滑膜细胞前列腺素受体脱敏的影响及木瓜苷和儿茶素的作用[D];安徽医科大学;2007年

10 黎渊弘;短尾蝮蛇毒磷脂结合抗凝蛋白的生物化学、药理学和分子生物学的研究[D];广西医科大学;2007年

相关硕士学位论文 前10条

1 窦宁;肝郁血瘀型宫环出血病蛋白标志物的建立及出血机理研究[D];湖南中医药大学;2010年

2 郑伟;月舒方治疗气滞血瘀型原发性痛经的临床研究[D];山东中医药大学;2010年

3 易小民;全蝎纯化液对凝血酶诱导血管内皮细胞释放作用的影响[D];湖南中医药大学;2011年

4 赖海峰;加味苇茎汤对AECOPD患者血TNF-α及凝血功能的影响[D];广州中医药大学;2011年

5 古力努尔·依明;合并糖耐量减低的急性冠脉综合症患者血浆D-二聚体水平的变化[D];新疆医科大学;2011年

6 李雪姣;坏死性小肠结肠炎血小板活化因子的表达及纳洛酮干预的研究[D];天津医科大学;2011年

7 杨海娜;血栓弹力图(TEG)在冠状动脉介入治疗患者抗血小板治疗监测中的应用[D];天津医科大学;2011年

8 刘德君;高渗盐晶胶复合液预扩容对剖宫产患者相关生理功能的影响[D];郑州大学;2011年

9 艾明瑞;康脉Ⅱ号胶囊治疗下肢深静脉血栓形成的临床观察[D];黑龙江中医药大学;2007年

10 成慧中;单环刺嚑纤溶酶UFE Ⅰ的酶学性质和初步药效学及安全性评价[D];中国海洋大学;2011年



本文编号:2171519

资料下载
论文发表

本文链接:https://www.wllwen.com/yixuelunwen/swyx/2171519.html


Copyright(c)文论论文网All Rights Reserved | 网站地图 |

版权申明:资料由用户63b26***提供,本站仅收录摘要或目录,作者需要删除请E-mail邮箱bigeng88@qq.com