CN107050502B - 一种超吸水性高分子水凝胶干胶海绵及其制备方法和用途 - Google Patents
一种超吸水性高分子水凝胶干胶海绵及其制备方法和用途 Download PDFInfo
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Abstract
一种超吸水性高分子水凝胶干胶海绵及其制备方法和用途。该海绵是由壳聚糖作为骨架,超吸水聚合物作为支链,具有柔性结构的大分子或聚合物作为交联剂的立体网状多孔海绵。该海绵可通过一锅法制备完成。产物呈多孔道结构,并具有超吸水性特征,且吸水后仍保持整体结构和一定的机械强度。该材料可用于较大动静脉出血的急救止血,效果优于市场现有材料。本发明的超吸水水凝胶干胶海绵制备工艺简单、成本低廉而止血效果突出,且安全性好,不产热不残留,具有显著的医用价值和产业化潜力。
Description
技术领域
本发明涉及一种急救止血用生物材料,具体涉及一种急救止血用超吸水性高分子水凝胶干胶海绵。
背景技术
止血是紧急医疗救治的重要环节,特别是在恶劣的战争环境和复杂突发事件造成的战、创伤急救时,实现快速有效的止血尤为重要。急救止血剂不同于平时应用于临床的一般止血剂,其应用时机更为紧迫,而操作者往往并非专业救护人士,因而对于其便携性、易用性,乃至保存等方面的要求更为苛刻。一种理想的急救止血剂应当同时满足以下几个条件:①在2min内迅速达到对大动脉和静脉的止血效果。②随时随地方便使用,不需要在使用前进行混合或其他特殊的准备。③简单易用,不需要特殊培训,方便在复杂突发事件中的战、创伤人员和急救队进行自救、互救。④轻便耐用,保存时间长。⑤在常温下保存达2年以上,在一些特殊的环境条件下(-10℃-55℃)应能保存数周或更长的时间。⑥使用安全,不会对组织或细胞产生毒性,不会对局部组织产生继发损伤,不会引起身体远端血管栓塞,也不会引发细菌或病毒感染。⑦生产成本低廉,便于大批量生产。[E.M.Acheson,B.S.Kheirabadi,R.Deguzman,E.J.Jr Dick,J.B.Holcomb.J.Trauma.2005,59(4),865-74.]
目前市场上的止血材料主要有纤维蛋白胶、胶原蛋白(如明胶海绵)、多微孔类无机材料(如沸石)、淀粉(如Trauma DEX)、羧甲基纤维素(如可溶性止血纱布)、α-氰基丙烯酸酯类组织胶等。它们在医院内使用时止血效果尚可,但应用于自救和互救还有明显的不足之处:如纤维蛋白胶源自血液,成本较高,且易传染疾病;胶原蛋白单纯依赖激活血小板止血,止血效果有限,且机械强度和组织黏附性较差;多孔沸石和Trauma DEX在吸收血液水分后会释放大量热能,进而导致组织烧伤;羧甲基纤维素可溶性纱布无法在创面降解,止血能力有限。
壳聚糖是由甲壳素经脱乙酰化后制得的天然聚阳离子多糖,具有凝血、抑菌、促进创伤愈合、抑制瘢痕形成等多种作用,它是一种生物相容性好、无免疫原性、无刺激性的多功能材料,2001年被美国FDA确认属于GRAS(通常公认为是安全的)物质。壳聚糖基快速止血剂是指通过对壳聚糖及其衍生物进行理化改性提高其止血作用,并在此基础上与其他功能材料进行复合制得的一系列新型多效止血材料。近年来,以壳聚糖及其衍生物作为主要止血材料的快速止血剂在止血领域应用日益广泛,但是这些止血材料仍然存在一些不足。如美国HemCon公司生产的HemCon壳聚糖止血海绵(HC)可以显著增加肝脏v级损伤动物的存活率,并降低出血量,但是在股动脉损伤模型中,HC并未能如人们期待的那样表现出持续、完全的止血作用;Celox止血粉的主要成分是从虾壳中提取出来的一种名为Celox的颗粒状混合物,其中包含有壳聚糖。其止血效果虽然显著,但是其颗粒状物体会粘附在创伤表面,为后期创面的处理增加难度。
近年研究发现,吸水浓缩作用可迅速启动凝血,并显著促进凝血过程。血液中的水分被材料吸收后,导致红细胞、血小板、凝血因子等浓度升高,启动凝血过程。如沸石止血颗粒即通过分子筛作用将血液中的水分吸收到材料孔隙中从而达到凝血的目的。进一步地,将壳聚糖的电荷吸附作用与聚丙烯酸等富含羧基的大分子的分子筛作用结合,也是开发新型止血材料的新思路。国内窦桂芳等制备的聚丙烯酸钠止血粉(ZL 03153260.8)和羧甲基纤维素接枝聚丙烯酸(ZL 200410096825.4)即通过超吸水高分子材料吸收血液中的水分浓缩血液来达到凝血的目的;郭希民等将聚丙烯酸钠接枝壳聚糖与明胶、壳聚糖复合制备止血海绵也显示出较好的止血效果(ZL 201110044474.2)。这些发明均意识到了简单的吸水浓缩作用所带来的显著的凝血作用,但受限于工艺、剂型等因素限制,并未能发挥出理想的止血效果。专利ZL 03153260.8和专利ZL 200410096825.4披露的材料,由于聚丙烯酸钠或聚丙烯酰胺类超吸水分子不具有生物可降解性,制备成粉剂针对出血较迅猛的动脉或静脉损伤时容易被血流冲开且吸水性被迅速饱和,止血效果受限,且使用后难于清理;专利ZL201110044474.2披露的材料中具有超吸水性的聚丙烯酸钠接枝壳聚糖成分仅是材料中的一个组分,使材料整体的吸水效果大打折扣。以上专利披露的超吸水聚合物改性大分子均未能解决剂型问题,制备的材料为粉剂形式或粉剂掺杂形式,既限制了材料作为整体发挥作用,又带来清理困难和体内残留问题。
发明内容
针对现有急救止血产品的不足,本发明设计了一种柔性分子交联、超吸水性聚合物分子改性的壳聚糖止血海绵——超吸水性高分子水凝胶干胶海绵。该海绵可采用便于规模化生产的“一锅法”制备,且材料具有良好的整体性和柔韧性,吸水后能通过化学键锁住水分,并且在压力下仍能保持整体性。该材料通过快速而强大的吸水能力,可使血液在材料表面与血管破损处快速形成稳定的血凝块,从而达到快速止血的目的。
为实现上述目的,本发明包括如下技术方案:
一种超吸水性高分子水凝胶干胶海绵,其是由壳聚糖作为骨架,超吸水聚合物作为支链,具有柔性结构的大分子或聚合物作为交联剂的立体网状多孔海绵;其中,超吸水聚合物为聚丙烯酸钠、聚丙烯酰胺、甲基丙烯酸甲酯和/或聚乙烯醇;交联剂为N′N-二甲基丙烯酰胺、甲基丙烯酸酐封端的聚乙二醇、丙烯酸酐封端的聚乙二醇、马来酸酐封端的聚乙二醇、衣康酸酐封端的聚乙二醇、甲醛和戊二醛中的一种或几种。
如上所述的超吸水性高分子水凝胶干胶海绵,优选地,所述壳聚糖占海绵总质量的1~10%;所述超吸水聚合物占海绵总质量的85~98%;所述交联剂占海绵总质量的0.5~5%。
如上所述的超吸水性高分子水凝胶干胶海绵,优选地,所述海绵还包括增塑剂、乳化剂和/或抗氧化剂。
如上所述的超吸水性高分子水凝胶干胶海绵,优选地,所述增塑剂选自丙二醇、甘油、山梨醇、司班、吐温、聚乙二醇和/或脂肪酸钠。
另一方面,本发明提供一种超吸水性高分子水凝胶干胶海绵的制备方法,该方法包括:将壳聚糖、超吸水聚合物单体、交联剂、过硫酸铵和制孔剂混合,通过自由基聚合反应得到多孔海绵;其中,
超吸水聚合物单体为聚丙烯酸钠、聚丙烯酰胺、聚甲基丙烯酸甲酯和/或聚乙烯醇;
交联剂为N′N-二甲基丙烯酰胺、甲基丙烯酸酐封端的聚乙二醇、丙烯酸酐封端的聚乙二醇、马来酸酐封端的聚乙二醇、衣康酸酐封端的聚乙二醇、甲醛和戊二醛中的一种或几种;
制孔剂为Na2CO3或NaHCO3;
壳聚糖、超吸水聚合物、交联剂、过硫酸铵与制孔剂的质量比为1∶(100~300)∶(0.5~5)∶(0.5~5)∶(10~20)。
如上所述的制备方法,优选地,所述壳聚糖为经过甲基丙烯酸酐修饰的甲基丙烯酸酐封端壳聚糖、经过丙烯酸酐修饰的丙烯酸酐封端壳聚糖、经过马来酸酐修饰的马来酸酐封端壳聚糖、经过甲基丙烯酸酐修饰的甲基丙烯酸酐封端壳聚糖和经过衣康酸酐修饰的衣康酸酐封端壳聚糖中的一种或几种。
如上所述的制备方法,优选地,所述方法包括如下步骤:室温下,向浓度为(70-99)v%的所述超吸水聚合物单体水溶液中加入所述交联剂和浓度为1%-30%(g/ml)的所述壳聚糖溶液,搅拌,随后加入所述过硫酸铵,搅拌后加入浓度为1%-20%(g/ml)的所述制孔剂,搅拌;于50~100℃反应30~60分钟,得到多孔海绵。
如上所述的制备方法,优选地,在所述多孔海绵中加入增塑剂,增塑剂为浓度为1wt%-10wt%的甘油、1wt%-5wt%的丙二醇或1wt%-5wt%的山梨醇。
如上所述的制备方法,优选地,在所述发泡反应体系中加入乳化剂,乳化剂为浓度为1wt%-10wt%的司班、1wt%-10wt%的吐温或1wt%-10wt%的SDS溶液。
又一方面,本发明提供一种超吸水性高分子水凝胶干胶海绵,其是采用如上所述方法制备的。
再一方面,本发明提供上述的超吸水性高分子水凝胶干胶海绵在急救止血、填塞止血、伤道堵漏中作为止血海绵的应用。
如上所述的超吸水性高分子水凝胶干胶海绵及其制备方法,优选地,所述聚乙二醇选自PEG-400,PEG-600,PEG-1500,PEG-4000,PEG-6000,PEG-20000中的一种或几种。
本发明的止血海绵是由壳聚糖作为骨架,超吸水聚合物作为支链,具有柔性结构的大分子或聚合物作为交联剂,Na2CO3或NaHCO3作为制孔剂形成的一种空间立体网状多孔海绵,其孔径为500nm-20μm。本发明的有益效果在于以下几个方面:
(1)本发明制备的水凝胶干胶海绵具有瞬时超吸水特性。其吸水倍率为自重60-600倍,遇水后瞬时吸收。海绵通过富含的羟基以氢键与水分子结合,因而具有分子内锁水特性,通过外力不能将吸收的水分挤出。
(2)海绵中与壳聚糖接枝的聚丙烯酸钠具有超亲水作用,当血液与其接触时,该吸水作用一方面使材料自身溶胀,孔道变窄,降低血流速度;另一方面,使血液中的血小板、凝血酶、纤维蛋白等止血成分高度浓缩,从而加速和加强血凝块的形成。
(3)壳聚糖在凝血过程通过所携带的正电荷对带负电荷的红细胞有聚集(凝集)作用,介导黏附血小板,形成的壳聚糖/血小板复合物可加速血纤维蛋白单体的聚合并共同形成凝块,壳聚糖还能刺激血小板吸附,使血小板由静止相转变为机能相,聚集在壳聚糖上的血小板迅速形成血栓,封闭伤口,达到止血目的。另外,当壳聚糖与血液接触时,能吸收大量血清蛋白,吸附在壳聚糖表面的蛋白质的变性和活化将启动外源性凝血途径,同时壳聚糖具有抑制体内溶解纤维蛋白活性、降低巨噬细胞分泌溶纤酶原激活剂的能力,可减少血纤维蛋白的溶解,提高止血效果。
(4)应用聚乙二醇作为交联剂,可显著改善材料的力学性状,使得止血海绵柔软有弹性,吸水后变成凝胶状,能保持整体性和机械强度,便于外力施压。
(5)该止血海绵可与创面紧密贴合,封闭创面,阻隔环境中的细菌和有害微粒接触创面,但透气透水,且不会与创面组织粘连。
(6)本发明制备的水凝胶干胶海绵可用于急救止血,特别是较大的动脉、静脉损伤引起的出血。由于本发明的干胶海绵具有显著的吸水膨胀作用,因而还可用于局限空间出血的填塞止血,如鼻出血、弹道伤止血。该止血海绵还具有组织黏附特性,因而还可用于伤道堵漏,如胃、胰腺、膀胱、子宫、肝、肾等破裂。
(7)本发明的止血海绵可采用一锅法制备,中间无须分离纯化过程,既节约成本,方便质控,又利于大规模生产。
附图说明
图1超吸水性高分子水凝胶干胶海绵结构。
图2超吸水性高分子水凝胶干胶海绵的吸水性。
图3家兔股动脉止血效果图。
具体实施方式
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。
实施例1超吸水性高分子水凝胶干胶海绵样品1的制备
以甲基丙烯酸酐(MAA)修饰的聚乙二醇(PEG)为交联剂,聚丙烯酸钠作为吸水聚合物,与MAA封端的壳聚糖(MAACTS)反应,制备聚丙烯酸钠改性壳聚糖,其合成工艺流程图如下:
步骤1:在质量/体积分数(g/ml)为3%的壳聚糖(CTS)溶液100ml中加入甲基丙烯酸酐(MAA)3ml,机械搅拌60min,搅拌速度为1200r/min,获得甲基丙烯酸酐封端的壳聚糖(MAACTS)。
步骤2:将1g PEG-6000加入到50ml氯仿中,磁力搅拌3h,加入甲基丙烯酸酐1ml,磁力搅拌6h,挥发掉氯仿,得到甲基丙烯酸封端的PEG-6000白色粉末。
步骤3:在盐冰浴中将100g NaOH加入到300ml去离子水中,机械搅拌。当NaOH溶液降到0℃时,加入200ml丙烯酸(AA)溶液,溶液温度控制在80℃。当溶液温度降至室温,加入步骤1所得溶液,加入步骤2所得到的白色粉末,机械搅拌4h。
步骤4:将步骤3混合液体中加入过硫酸铵6g,机械搅拌30min,加入10%NaHCO3100ml,机械搅拌得到白色乳液,加入聚四氟乙烯磨具中,80℃反应120min,得到白色多孔海绵。
步骤5:将步骤4中获得的海绵依次在60%、70%和80%的乙醇溶液中洗涤4次,然后挥发掉乙醇,得到白色弹性海绵,包装,裁切,钴60辐照灭菌。
实施例2超吸水性高分子水凝胶干胶海绵样品2的制备
步骤1:在质量/体积分数(g/ml)为3%的壳聚糖溶液100ml中加入甲基丙烯酸酐3ml,机械搅拌60min,搅拌速度为1200r/min,获得甲基丙烯酸酐封端的壳聚糖。
步骤2:将1gPEG-20000加入50ml氯仿中,磁力搅拌3h,加入马来酸酐1g,磁力搅拌6h。将溶液滴加到过量乙醚中得到白色粉末,真空干燥36h。将干燥好的白色粉末在氯仿/乙醚共沉淀体系提纯4次,真空干燥36h,得到马来酸酐封端的PEG-20000白色粉末。
步骤3:在盐冰浴中将50g NaOH加入到150ml去离子水中,机械搅拌。当NaOH溶液降到0℃时,加入100ml丙烯酸溶液,溶液温度控制在80℃。当溶液温度降至室温,加入50g丙烯酰胺,加入步骤1所得溶液和步骤2所得到的白色粉末,机械搅拌4h。
步骤4:将步骤3混合液体中加入过硫酸铵6g,机械搅拌30min,加入10%NaHCO3100ml,机械搅拌得到白色乳液,加入聚四氟乙烯磨具中,80℃反应120min,依次在60%、70%和80%的乙醇溶液中洗涤4次,挥发掉乙醇,得到白色多孔海绵,包装,裁切,钴60辐照灭菌。
实施例3超吸水性高分子水凝胶干胶海绵样品3的制备
步骤1:在质量/体积分数(g/ml)为3%的壳聚糖溶液100ml中加入甲基丙烯酸酐3ml,机械搅拌60min,搅拌速度为1200r/min,获得甲基丙烯酸酐封端的壳聚糖。
步骤2:将1g PEG-20000加入到50ml氯仿中,磁力搅拌3h,加入衣康酸酐1g,磁力搅拌6h。将溶液滴加到过量乙醚中得到白色粉末,真空干燥36h。将干燥好的白色粉末在氯仿/乙醚共沉淀体系提纯4次,真空干燥36h,得到衣康酸酐封端的PEG-20000白色粉末。
步骤3:在盐冰浴中将50g NaOH加入到150ml去离子水中,机械搅拌。当NaOH溶液降到0℃,加入100ml丙烯酸溶液,溶液温度控制在80℃。当溶液温度降至室温,加入50g丙烯酰胺,加入50ml甲基丙烯酸甲酯溶液,加入步骤1所得溶液和步骤2所得到的白色粉末,机械搅拌4h。
步骤4:将步骤3混合液体中加入过硫酸铵6g,机械搅拌30min,加入10%NaHCO3100ml,机械搅拌得到白色乳液,加入聚四氟乙烯磨具中,80℃反应120min,得到白色多孔海绵。
步骤5:将步骤4中获得的海绵依次在60%、70%和80%的乙醇溶液中洗涤4次,挥发掉乙醇,得到白色弹性海绵,包装,裁切,钴60辐照灭菌。
实施例4超吸水性高分子水凝胶干胶海绵样品4的制备
步骤1:在质量/体积分数(g/ml)为3%的壳聚糖溶液100ml中加入甲基丙烯酸酐3ml,机械搅拌60min,搅拌速度为1200r/min,获得甲基丙烯酸酐封端的壳聚糖。
步骤2:将1g PEG-6000加入到50ml氯仿中,磁力搅拌3h,加入甲基丙烯酸酐1ml,磁力搅拌6h,挥发掉氯仿,得到甲基丙烯酸封端的PEG-6000白色粉末。
步骤3:在盐冰浴中将50g NaOH加入到150ml去离子水中,机械搅拌。当NaOH溶液降到0℃,加入100ml丙烯酸溶液,溶液温度控制在80℃。当溶液温度降至室温,加入50g丙烯酰胺,加入50ml聚乙烯醇溶液,加入50ml甲基丙烯酸甲酯溶液,加入步骤1所得溶液和步骤2所得到的白色粉末,机械搅拌4h。
步骤4:将步骤3混合液体中加入过硫酸铵6g,机械搅拌30min,加入10%NaHCO3100ml,机械搅拌得到白色乳液,加入聚四氟乙烯磨具中,80℃反应120min,得到白色多孔海绵。
步骤5:将步骤4中获得的海绵依次在60%、70%和80%的乙醇溶液中洗涤4次,挥发掉乙醇,得到白色弹性海绵,包装,裁切,钴60辐照灭菌。
实施例5物理和结构表征
实施例1-4中获得的急救止血海绵材料呈多孔海绵样结构,孔隙率在40%-80%之间,孔径大小在100um-2mm之间,孔间存在广泛的交通。与血液接触后其孔隙结构迅速将血液吸入孔内,并迅速浓缩,一方面使得孔道壁吸水后增厚并凝胶化,管腔变窄,管壁粘弹性增加,形成对血流的缓冲;另一方面血液高度浓缩,迅速形成启动凝血,形成血凝块,并通过持续的吸水作用使血凝块更加牢固,从而达到快速有力的止血作用
将实施例1-4所制备的超吸水性高分子水凝胶干胶海绵样品在与血液接触前和揭除后进行大体结构观察,并采用扫描电镜进行微观结构检查。以样品1为代表,如图1所示,样品皆为柔软的多孔海绵状,有弹性,可卷曲,无异味(图1A)。电镜下显示相互连通的多孔道结构(图1B)。与血液接触后(图1C),孔道壁迅速吸水膨胀,孔道变窄直至封闭(图1D),血液因快速浓缩而凝固(图1E)。
实施例6吸水性表征
吸水性是本发明的重要特征。准确称取试样0.100g,置于尼龙布袋中,再将其浸于蒸馏水(pH=7.0,温度25℃)中,室温下自然吸水溶胀,于10秒、20秒、30秒、45秒、1分钟、2分钟、4分钟、8分钟、16分钟和32分钟分别取出布袋,吸去布袋表面水分,称取试样吸液后质量。计算每个时间点的吸水倍率,绘制吸水倍率与时间关系曲线。
吸水倍率Q计算公式如下:Q=(m2-m1)/ml。式中:Q为吸水(盐水)倍率,g/g;ml为吸液前试样质量,g;m2为吸液后试样质量,g。
结果如图2所示,样品1-4表现出相近的吸水性,在3分钟内达到最大吸水倍率约165倍,最大吸盐水倍率约72倍。
实施例7体外凝血能力
将实施例1所制备的急救用止血海绵进行体外凝血试验,并采用胶原止血纤维(Avitene)作为对照组与本发明材料进行对照。血样采自健康献血者(n=3),实验过程及结果如下:
体外凝血试验效果分析:
利用血球弹力仪(TEG)检测急救用止血海绵的体外凝血能力(表1所示)。实验结果显示,与阴性对照组比较各组样品R-time和K-time均有显著性减小(p<0.05),Angle deg和MA值有显著增加;与阳性对照组比较,R-time、K-time、Angle deg和MA无显著性差异(p>0.05),表明各组样品实验材料具有与对照的胶原纤维(Avitene)相等强度的启动血液内源性凝血机制能力。
表1 TEG分析
a 阴性对照组是不添加止血材料,血液自然凝固。
b 阳性对照组是胶原海绵(Avitene),是内源性凝血的强触发剂。
c R:凝血酶原被激活的时间,即在血液中刚刚出现血凝块的时间。
d K:形成稳定凝血块所需要的时间。
e Angle deg:检测纤维蛋白织网的速度,从而评价形成血凝块的速率。
f MA:纤维蛋白血凝块的强度。
实施例8兔股动脉止血试验
健康雄性家兔,体重在2.5-3.1kg,1%戊巴比妥钠耳缘静脉给药麻醉,右后肢腹股沟处备皮,剪开皮肤和皮下组织,在距离腹股沟2cm处用分离股动脉,16G针头穿刺透过对侧血管壁,松开动脉夹,自然喷血5秒钟,然后,用纱布擦去血液,,立即给予止血。以32层普通纱布作为阴性对照,QuikClot Combat Gauze(Z-Medica,美国,美军装备部队)作为阳性对照。每组10只动物。局部按压1分钟,观察是否止血,如无出血5分钟后小心揭除材料,观察有无出血,结果如表2所示。
在止血过程中,阴性对照组没有有效止血,动物全部死亡。QuikClot CombatGauze组去除压力后,7只动物仍有不同程度出血,只有3只动物达到止血,但在5分钟揭除后均再次出血。本发明的4种配方的吸水性高分子水凝胶干胶海绵在兔股动脉止血过程中全部成功达到止血效果(图3)。压力去除后5分钟内所有实验组动物均无出血,将止血海绵从创面移除时,其与创面组织紧密贴附,显示出极佳的创面封闭性,移除后创面整洁,无继发性出血,无血块残留,动物出血量也远远少于对照组(p<0.01)。
表2家兔股动脉止血
a对照1是32层普通纱布
b对照2是QuikClot Combat Gauze
c对照3是Celox
d撤去压力后无出血视为达到成功止血
e撤去压力后无出血,但在随后的5分钟内有出血视为继发出血。
Claims (10)
1.一种超吸水性高分子水凝胶干胶海绵,其特征在于,其是由壳聚糖作为骨架,超吸水聚合物作为支链,具有柔性结构的大分子或聚合物作为交联剂的立体网状多孔海绵;其中,超吸水聚合物为聚丙烯酸钠、聚丙烯酰胺、甲基丙烯酸甲酯和/或聚乙烯醇;交联剂为甲基丙烯酸酐封端的聚乙二醇、丙烯酸酐封端的聚乙二醇、马来酸酐封端的聚乙二醇和衣康酸酐封端的聚乙二醇中的一种或几种。
2.如权利要求1所述的超吸水性高分子水凝胶干胶海绵,其特征在于,所述壳聚糖占海绵总质量的1~10%;所述超吸水聚合物占海绵总质量的85~98%;所述交联剂占海绵总质量的0.5~5%。
3.如权利要求1或2所述的超吸水性高分子水凝胶干胶海绵,其特征在于,所述壳聚糖为经过甲基丙烯酸酐修饰的甲基丙烯酸酐封端壳聚糖、经过丙烯酸酐修饰的丙烯酸酐封端壳聚糖、经过马来酸酐修饰的马来酸酐封端壳聚糖、经过甲基丙烯酸酐修饰的甲基丙烯酸酐封端壳聚糖和经过衣康酸酐修饰的衣康酸酐封端壳聚糖中的一种或几种。
4.如权利要求3所述的超吸水性高分子水凝胶干胶海绵,其特征在于,所述海绵还包括增塑剂、乳化剂和/或抗氧化剂。
5.如权利要求4所述的超吸水性高分子水凝胶干胶海绵,其特征在于,所述增塑剂选自丙二醇、甘油、山梨醇、司班、吐温、聚乙二醇和/或脂肪酸钠。
6.一种超吸水性高分子水凝胶干胶海绵的制备方法,其特征在于,该方法包括:将壳聚糖、超吸水聚合物单体、交联剂、过硫酸铵和制孔剂混合,通过自由基聚合反应得到多孔海绵;其中,
超吸水聚合物单体为聚丙烯酸钠、聚丙烯酰胺、聚甲基丙烯酸甲酯和/或聚乙烯醇;
交联剂为甲基丙烯酸酐封端的聚乙二醇、丙烯酸酐封端的聚乙二醇、马来酸酐封端的聚乙二醇和衣康酸酐封端的聚乙二醇中的一种或几种;
制孔剂为Na2CO3或NaHCO3;
壳聚糖、超吸水聚合物、交联剂、过硫酸铵与制孔剂的质量比为1∶(100~300)∶(0.5~5)∶(0.5~5)∶(10~20)。
7.如权利要求6所述的制备方法,其特征在于,所述壳聚糖为经过甲基丙烯酸酐修饰的甲基丙烯酸酐封端壳聚糖、经过丙烯酸酐修饰的丙烯酸酐封端壳聚糖、经过马来酸酐修饰的马来酸酐封端壳聚糖、经过甲基丙烯酸酐修饰的甲基丙烯酸酐封端壳聚糖和经过衣康酸酐修饰的衣康酸酐封端壳聚糖中的一种或几种。
8.如权利要求6或7所述的制备方法,其特征在于,所述方法包括如下步骤:室温下,向浓度为70-99v%的所述超吸水聚合物单体水溶液中加入所述交联剂和浓度为1%-30%的所述壳聚糖溶液,浓度单位为g/ml,搅拌,随后加入所述过硫酸铵,搅拌后加入浓度为1%-20%的所述制孔剂,浓度单位为g/ml,搅拌;于50~100℃反应30~60分钟,得到多孔海绵。
9.一种超吸水性高分子水凝胶干胶海绵,其特征在于,其是采用权利要求6-8中任一项所述方法制备的。
10.如权利要求1-5或9中任一项所述的超吸水性高分子水凝胶干胶海绵在制备作为急救止血、填塞止血、伤道堵漏的止血海绵中的应用。
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US16/471,508 US20190388580A1 (en) | 2016-12-20 | 2017-04-18 | A superabsorbent polymer hydrogel xerogel sponge and preparation method and application thereof |
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CN110090317B (zh) * | 2019-04-26 | 2020-07-03 | 非零和(北京)投资管理有限公司 | 一种超吸水性高分子水凝胶抗菌海绵及其制备方法和用途 |
CN110152051B (zh) * | 2019-04-26 | 2021-10-08 | 非零和(北京)投资管理有限公司 | 一种吸水烧创伤抗菌敷料及其制备方法和用途 |
CN113398321B (zh) * | 2020-03-17 | 2022-04-12 | 天津大学 | 一种具有高吸液率和高回弹性的多孔止血海绵及其制备方法和应用 |
CN111450308B (zh) * | 2020-06-09 | 2021-07-13 | 北京化工大学 | 一种多功能止血海绵及其制备方法与应用 |
US11739166B2 (en) | 2020-07-02 | 2023-08-29 | Davol Inc. | Reactive polysaccharide-based hemostatic agent |
CN111991611B (zh) * | 2020-08-12 | 2021-10-19 | 山东百多安医疗器械股份有限公司 | 一种可粘附自修复止血海绵及其制备方法 |
CN112494714A (zh) * | 2020-12-02 | 2021-03-16 | 郭芳芳 | 一种纳米抗菌凝胶材料及其制备方法 |
CN112979377A (zh) * | 2021-03-18 | 2021-06-18 | 深圳市华创汇能技术有限公司 | 一种保水-缓释肥的双功能化复合水凝胶的制法和应用 |
CN113616842B (zh) * | 2021-09-02 | 2022-05-03 | 中国人民解放军总医院京北医疗区 | 一种用于外伤急救止血材料的制备方法 |
CN113929819B (zh) * | 2021-11-11 | 2024-01-09 | 军事科学院军事医学研究院环境医学与作业医学研究所 | 壳聚糖聚丙烯酰胺复合多孔水凝胶、金属离子检测试剂及其制备方法和应用 |
CN114272431A (zh) * | 2021-11-15 | 2022-04-05 | 欣乐加生物科技温州有限公司 | 表面富集钙离子的止血海绵及制备方法 |
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CN115887738B (zh) * | 2022-12-16 | 2024-05-10 | 湖南师范大学 | 一种聚丙烯酰胺-壳聚糖/高岭土多孔材料及其制备方法 |
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