【作者】 张巍；

【导师】 付学奇；

【作者基本信息】 吉林大学 ， 生物工程（专业学位）， 2020， 硕士

【摘要】 据统计,不可控的出血是造成交通事故、医疗事故、无法避免的自然灾害等突发性死亡的重要原因之一。每年因大量出血导致的医疗事故屡见不鲜,在外科手术及创口护理的过程中,如何有效的控制创面出血是一大难题。如果采用止血材料在短时间内有效止血,不仅可以提高手术成功率,而且可以降低出血造成的创伤性死亡率。止血材料不但要满足操作方便、止血迅速的要求,同时对产品的安全性提出了更高的要求。因此开发出一种快速止血,安全无副作用的产品不仅能够提高手术效率,缓解医生压力,而且可以有效缓解患者经济压力,让患者的生命安全得到保障。固体材料是止血材料市场的主力军,罕有液体止血材料的报道。羧甲纤维素钠和海藻酸钠都是高分子糖类化合物,具有止血和促进创面愈合的作用。因两种材料都是植物来源,具有来源广泛、生物安全性好、安全无毒副作用等优点。若以羧甲纤维素钠和海藻酸钠为原料,制备出液体止血材料,不仅操作方便,而且能减少术后的并发症,将极大的拓宽医疗市场。本文采用生物共混技术,将羧甲纤维素钠和海藻酸钠进行混合,制备出复合植物液体止血材料——生物止血流体膜,并进一步测试其结构及性能,该共混溶液具有止血、促进创面愈合的功能。生物止血流体膜的微观结构可通过原子力显微镜和红外光谱检测的方法来证明。通过一系列生物安全性试验,对其生物学性能进行评价。得出如下结果:1.采用生物共混技术,将羧甲纤维素钠和海藻酸钠混合,通过采用傅立叶红外光谱对生物止血流体膜内部微观结构进行检测,表明生物止血流体膜中两种大分子在氢键的作用下相互贯穿形成三维网状结构。2.通过原子力显微镜观察生物止血流体膜微观形貌,羧甲纤维素钠和海藻酸钠由于氢键的缔合作用,形成致密的三维网状支架结构,使生物止血流体膜的总厚度增加,生物止血流体膜的厚度约为羧甲纤维素钠和海藻酸钠单独厚度总和的10倍,进一步证实生物止血流体膜由于氢键的作用形成三维网状结构。3.通过一系列生物安全性试验来评价生物止血流体膜的生物安全性,试验结果如下:细胞毒性试验结果表明,生物止血流体膜无细胞毒性,级别为0级;皮肤致敏试验和皮内反应试验结果表明,生物止血流体膜对皮肤及皮内组织均无刺激性,不会引起过敏反应;急性全身毒性试验结果表明,生物止血流体膜无急性全身毒性;热原试验和溶血试验结果显示,生物止血流体膜热原试验及溶血试验均合格;植入试验结果表明,生物止血流体膜植入机体后不会引起机体的免疫排斥反应,生物相容性好,可作为良好的止血产品应用于临床。更多还原

【Abstract】 According to statistics,excessive blood loss is one of the major causes of accidental death such as traffic accidents,medical accidents,and unavoidable natural disasters.Medical accidents caused by a large amount of bleeding are common every year.How to effectively control wound bleeding during surgery and wound care is a major problem.If hemostatic materials are used to effectively stop bleeding in a short period of time,it will not only improve the success rate of surgery,but also reduce the traumatic mortality caused by bleeding.The hemostatic material must not only meet the requirements of convenient operation and rapid hemostasis,but also put forward higher requirements for the safety of the product.Therefore,the development of a product that quickly stops bleeding and is safe and has no side effects can not only improve the efficiency of surgery and relieve the pressure on doctors,but also effectively alleviate the economic pressure on patients and ensure the safety of patients’ lives.At present,the hemostatic materials on the market are mainly solid materials,and there are few reports of liquid hemostatic materials.Carboxymethyl cellulose sodium and sodium alginate are high molecular sugar compounds,which have the effect of stopping bleeding and promoting wound healing.Because both materials are of plant origin,they have the advantages of extensive sources,good biological safety,and safety without toxic and side effects.If carboxymethyl cellulose sodium and sodium alginate are used as raw materials to prepare a liquid hemostatic material,it will not only be convenient to operate,but also reduce postoperative complications,which will greatly expand the medical market.This article uses biological blending technology to mix carboxymethyl cellulose sodium and sodium alginate to prepare a compound plant liquid hemostatic material-biological hemostatic fluid film,and further test its structure and performance.The blended solution has hemostatic,promoting Wound healing function.Infrared spectroscopy and atomic force microscopy were used to test the structure of the biological hemostatic fluid membrane and observe its microscopic morphology.Through a series of biological safety tests,the biological properties were evaluated.The results are as follows:1.Using bio-blending technology,mixing carboxymethyl cellulose sodium and sodium alginate,and using Fourier infrared spectroscopy to measure the internal microstructure of the biological hemostatic fluid membrane,it is shown that the two macromolecules in the biological hemostatic fluid membrane are in hydrogen A three-dimensional network structure is formed through the interaction of bonds.2.Observe the microscopic morphology of the biological hemostatic fluid membrane by atomic force microscope.The carboxymethyl cellulose sodium and sodium alginate form a dense three-dimensional network scaffold structure due to the association of hydrogen bonds,which increases the total thickness of the biological hemostatic fluid membrane.The thickness of the biological hemostatic fluid film was about 10 times the sum of the thicknesses of the carboxymethyl cellulose sodium and sodium alginate alone,further confirming that the biological hemostatic fluid film formed a three-dimensional network structure due to the hydrogen bonding effect.3.A series of biological safety tests were carried out to evaluate the biological safety of the biological hemostatic fluid membrane.The results were as follows: The cytotoxicity test showed that the biological hemostatic fluid membrane had no cytotoxicity and its grade was 0;The results of skin sensitization test and intradermal reaction test showed that the biological hemostatic fluid membrane had no irritation to skin and intradermal tissue and could not cause allergic reaction,the results of pyrogen test and hemolysis test showed that both pyrogen test and hemolysis test of biological hemostatic fluid membrane were qualified,biological hemostatic fluid membrane implanted in the body will not cause the body’s immune rejection,biocompatibility,can be used as a good hemostatic products in clinical.更多还原