技术领域technical field
本实验发明涉及一种生物可降解医用止血纸及其制备方法，属于生物医用材料领域。The experimental invention relates to a biodegradable medical hemostatic paper and a preparation method thereof, belonging to the field of biomedical materials.
背景技术Background technique
本发明涉及一种可降解且具有优异止血功能的生物止血贴。具体来说是使用一些天然医用高分子交联之后，进行冷冻干燥，挤压制成，可用于外科和创伤病人的局部止血。The invention relates to a degradable biological hemostatic patch with excellent hemostatic function. Specifically, it is made by cross-linking some natural medical polymers, freeze-dried, and extruded, which can be used for local hemostasis of surgical and trauma patients.
在临床和实际生活中对局部止血有很大的要求，及时的止血有助于我们避免细菌，病毒感染等情况。临床外科上，有助于减少病人输血从而减少感染的机会。目前临床和实际生活中已经有一些商品化产品投入使用。传统的的一些止血材料有较多缺点，比如，纤维蛋白胶止血作用良好，但是配置较为复杂且炎症明显。胶原海绵材料由异种蛋白制成，局部炎症反应也特别明显。理想的止血材料应满足多项要求：首先对人体无毒性，无刺激作用以及良好的生物相容性。同时要有良好的生物可吸收性，便于加工，具有一定的力学性能。In clinical and practical life, there is a great requirement for local hemostasis. Timely hemostasis helps us avoid bacterial and viral infections. In clinical surgery, it helps to reduce the chance of infection by reducing blood transfusion for patients. At present, some commercial products have been put into use in clinical and practical life. Some traditional hemostatic materials have many disadvantages. For example, fibrin glue has a good hemostatic effect, but the configuration is relatively complicated and inflammation is obvious. The collagen sponge material is made of foreign proteins, and the local inflammatory response is also particularly obvious. An ideal hemostatic material should meet multiple requirements: first, it is non-toxic to the human body, has no stimulating effect, and has good biocompatibility. At the same time, it must have good bioabsorbability, be easy to process, and have certain mechanical properties.
羟甲基纤维素是一种纤维素分子经醚化反应引入羟甲基而得到的水溶性衍生物。羟甲基的引入改善了纤维素分子的水溶性，同时其有良好的成膜性，生物相容性，无毒无害，被广泛用于医药领域。明胶是动物的胶原蛋白经部分水解得到的高分子多肽的高聚化合物，胶原蛋白一般可从动物的皮，骨，软骨，韧带，肌膜等中提取。其凝胶性、持水性、成膜性、生物相容性均非常优异，已经广泛应用于食品、医学、化工等行业。2015年，刘勇等人公开了一种壳聚糖医用生物抗菌敷料的制备方法(专利号：CN201310463753.1)，首先将壳聚糖溶于酸液和羧甲基壳聚糖溶于水配制成壳聚糖溶液和羧甲基壳聚糖溶液，之后加入戊二醛等醛类交联剂使上述溶液各自交联，最后通过涂覆，冷冻干燥制备出生物相容性高，可以有效抑制细菌生长的医用敷料。但是交联剂采用戊二醛等醛类交联剂，对人体有一定毒性，存在安全隐患，不符合绿色环保理念。本专利使用氧化海藻酸钠，海藻酸钠经高碘酸钠氧化后制得的氧化海藻酸钠不仅可以改善海藻酸钠的溶解性能，同时氧化海藻酸钠得到的双醛基可以与明胶上的氨基发生Schiff碱反应，形成化学交联结构，从而代替了甲醛，戊二醛等有毒的醛类交联剂。Hydroxymethyl cellulose is a water-soluble derivative obtained by introducing hydroxymethyl groups into cellulose molecules through an etherification reaction. The introduction of hydroxymethyl groups improves the water solubility of cellulose molecules, and at the same time, it has good film-forming properties, biocompatibility, non-toxic and harmless, and is widely used in the field of medicine. Gelatin is a high-polymer compound of high-molecular polypeptide obtained by partial hydrolysis of animal collagen. Collagen can generally be extracted from animal skin, bone, cartilage, ligament, and sarcolemma. It has excellent gel properties, water holding properties, film-forming properties and biocompatibility, and has been widely used in food, medicine, chemical and other industries. In 2015, Liu Yong and others disclosed a preparation method of chitosan medical biological antibacterial dressing (patent number: CN201310463753.1), first dissolving chitosan in acid solution and carboxymethyl chitosan in water to prepare Form chitosan solution and carboxymethyl chitosan solution, then add glutaraldehyde and other aldehyde cross-linking agents to cross-link the above solutions, and finally prepare biocompatibility by coating and freeze-drying, which can effectively inhibit Bacterial growth in medical dressings. However, the cross-linking agent adopts aldehyde cross-linking agents such as glutaraldehyde, which has certain toxicity to the human body, has potential safety hazards, and does not conform to the concept of green environmental protection. This patent uses oxidized sodium alginate. The oxidized sodium alginate obtained after the sodium alginate is oxidized by sodium periodate can not only improve the solubility of sodium alginate, but also the dialdehyde group obtained by oxidizing sodium alginate can be combined with the dialdehyde group on gelatin. The amino group undergoes Schiff base reaction to form a chemical cross-linking structure, thereby replacing toxic aldehyde cross-linking agents such as formaldehyde and glutaraldehyde.
本发明将上述物质适度交联。足够的凝胶强度和适宜的交联密度保证了成品的吸水性和力学强度。冷冻干燥技术的使用保证了凝胶的多孔性。成品加工包装后制成止血贴，具有较好的力学强度。The present invention moderately crosslinks the aforementioned materials. Sufficient gel strength and suitable cross-linking density ensure the water absorption and mechanical strength of the finished product. The use of freeze-drying technique ensures the porosity of the gel. After the finished product is processed and packaged, it is made into a hemostatic patch, which has good mechanical strength.
发明内容Contents of the invention
本发明的目的是得到一种生物可降解的水凝胶敷料，同时使其达到一定得强度，具有较好的吸水性和耐水性，在去离子水中浸泡不改变其结构，同时具有止血功效。所述的生物可降解水凝胶材料，以部分氧化海藻酸钠/海藻酸钠/明胶/羟甲基纤维素为基体。为实现上述目标，采用如下技术方案：The purpose of the present invention is to obtain a biodegradable hydrogel dressing, which can reach a certain strength, has good water absorption and water resistance, soaks in deionized water without changing its structure, and has hemostatic effect. The biodegradable hydrogel material is based on partially oxidized sodium alginate/sodium alginate/gelatin/hydroxymethyl cellulose. In order to achieve the above goals, the following technical solutions are adopted:
(1)部分氧化海藻酸钠制备。将海藻酸钠配制成1wt％～5wt％的溶液，再加入高碘酸钠固体避光反应24～48h，加入乙二醇、NaCl停止反应，沉析，在30～60℃下过滤烘干；(1) Preparation of partially oxidized sodium alginate. Prepare sodium alginate into a solution of 1wt%-5wt%, then add solid sodium periodate to avoid light for 24-48 hours, add ethylene glycol and NaCl to stop the reaction, precipitate, filter and dry at 30-60°C;
(2)海藻酸钠/羟甲基纤维素/明胶共混溶液的制备：称取海藻酸钠1.0wt％～5.0wt％，明胶1.0wt％～5.0wt％，羟甲基纤维素1.0wt％～5.0wt％。加入去离子水中，磁力搅拌，在20℃～60℃下溶解。(2) Preparation of sodium alginate/hydroxymethylcellulose/gelatin blend solution: weigh 1.0wt% to 5.0wt% sodium alginate, 1.0wt% to 5.0wt% gelatin, and 1.0wt% hydroxymethylcellulose ~5.0 wt%. Add in deionized water, stir magnetically, and dissolve at 20°C to 60°C.
(3)总共称取增韧剂1,2-丙二醇与丙三醇6wt％～12wt％。加入(2)溶解好的溶液中，磁力搅拌，常温溶解即可。(3) Weigh 6wt%-12wt% of the toughening agents 1,2-propanediol and glycerol in total. Add (2) to the dissolved solution, stir magnetically, and dissolve at room temperature.
(4)称取步骤(1)制备的部分氧化海藻酸钠0.5wt％～3wt％加入步骤(3)所述体系中，磁力搅拌，直至部分氧化海藻酸钠溶解，过滤，消除气泡。之后用氯化钙稀溶液喷淋3～4次，静置一段时间。(4) Weigh 0.5wt%-3wt% of the partially oxidized sodium alginate prepared in step (1) and add it to the system described in step (3), stir magnetically until the partially oxidized sodium alginate dissolves, filter to eliminate air bubbles. After that, spray 3 to 4 times with dilute calcium chloride solution and let it stand for a period of time.
(5)上述步骤制成的胶体在均质器中制成均匀胶浆。倒入模具，在-10℃～-40℃冰箱中预冷冻6～24h。之后用冷冻干燥机冷冻干燥.最后以适当的压力压实成纸片状固体。消毒，包装。即为所得生物止血贴。(5) The colloid made in the above steps is made into a uniform glue in a homogenizer. Pour into molds, and pre-freeze in -10℃～-40℃ refrigerator for 6～24h. Then freeze-dry with a freeze dryer. Finally, compact it into a paper-like solid with an appropriate pressure. Sterilize, pack. That is the obtained biological hemostatic patch.
具体地，海藻酸钠的分子量为20000～200000g/mol，羟甲基纤维素的分子量为20000～200000g/mol，明胶分子量为20000～200000g/mol。Specifically, the molecular weight of sodium alginate is 20,000-200,000 g/mol, the molecular weight of hydroxymethyl cellulose is 20,000-200,000 g/mol, and the molecular weight of gelatin is 20,000-200,000 g/mol.
具体地，海藻酸钠与氧化剂高碘酸钠与摩尔比为1:1～2。Specifically, the molar ratio of sodium alginate to oxidant sodium periodate is 1:1-2.
具体地，1,2丙二醇与丙三醇的质量比为1:1～5。Specifically, the mass ratio of 1,2-propanediol to glycerol is 1:1-5.
具体地，氯化钙溶液浓度为1wt％～5wt％。Specifically, the calcium chloride solution has a concentration of 1 wt% to 5 wt%.
具体地。冷冻干燥机冻干参数为-40℃～80℃，冷冻时间12～48h，1～10×10-3MBr。specifically. The freeze-drying parameters of the freeze dryer are -40°C~80°C, the freezing time is 12~48h, and 1~10×10-3 MBr.
实施实例Implementation example
本发明可用下列事例说明，但不局限于下列实例。The present invention is illustrated by, but not limited to, the following examples.
实施实例1Implementation example 1
(1)用天平称取海藻酸钠1.9g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.9g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠1.5g、羟甲基纤维素1.5g、明胶3.0g加入到85.5g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 1.5 g of sodium alginate, 1.5 g of hydroxymethyl cellulose, and 3.0 g of gelatin into 85.5 g of deionized water with a balance, and stir magnetically at 40°C until completely dissolved.
(3)称取1.70g1,2-丙二醇和5.30g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取1.5g步骤(2)所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 1.70g of 1,2-propanediol and 5.30g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 1.5 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在-30℃冰箱中预冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, pre-freeze in a -30°C refrigerator and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例2Implementation example 2
(1)用天平称取海藻酸钠1.9g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.9g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠0.6g、羟甲基纤维素2.4g、明胶1.2g加入到82.6g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 0.6 g of sodium alginate, 2.4 g of hydroxymethyl cellulose, and 1.2 g of gelatin into 82.6 g of deionized water with a balance, and stir magnetically at 40° C. until completely dissolved.
(3)称取3.0g1,2-丙二醇和9.0g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取1.2g步骤(2)所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 3.0 g of 1,2-propanediol and 9.0 g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 1.2 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system is free of stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在-30℃冰箱中预冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, pre-freeze in a -30°C refrigerator and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例3Implementation example 3
(1)用天平称取海藻酸钠1.9g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.9g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠0.8g、羟甲基纤维素2.1g、明胶2.1g加入到83.6g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 0.8 g of sodium alginate, 2.1 g of hydroxymethyl cellulose, and 2.1 g of gelatin into 83.6 g of deionized water, and stir magnetically at 40°C until completely dissolved.
(3)称取1.75g1,2-丙二醇和7.84g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取1.8g步骤(2)所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 1.75g of 1,2-propanediol and 7.84g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 1.8 g of the partially oxidized sodium alginate produced in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system is free of stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在-30℃冰箱中预冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, pre-freeze in a -30°C refrigerator and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例4Implementation example 4
(1)用天平称取海藻酸钠1.9g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.9g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠1.2g、羟甲基纤维素2.4g、明胶2.4g加入到84.5g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 1.2 g of sodium alginate, 2.4 g of hydroxymethyl cellulose, and 2.4 g of gelatin into 84.5 g of deionized water with a balance, and stir magnetically at 40° C. until completely dissolved.
(3)称取1.60g1,2-丙二醇和6.40g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取1.5g步骤(2)所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 1.60g of 1,2-propanediol and 6.40g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 1.5 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在-30℃冰箱中预冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, pre-freeze in a -30°C refrigerator and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally press molding with proper pressure. Sterilized with cobalt-60, packaged.
实施实例5Implementation Example 5
(1)用天平称取海藻酸钠1.9g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.9g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠1.2g、羟甲基纤维素2.4g、明胶2.4g加入到81.6g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 1.2 g of sodium alginate, 2.4 g of hydroxymethyl cellulose, and 2.4 g of gelatin into 81.6 g of deionized water with a balance, and stir magnetically at 40° C. until completely dissolved.
(3)称取2.0g1,2-丙二醇和8.0g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取2.4g步骤(2)所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 2.0 g of 1,2-propanediol and 8.0 g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 2.4 g of the partially oxidized sodium alginate produced in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在-30℃冰箱中预冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, pre-freeze in a -30°C refrigerator and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例6Implementation Example 6
(1)用天平称取海藻酸钠1.9g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.9g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠0.6g、羟甲基纤维素1.8g、明胶1.8g加入到84.4g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 0.6 g of sodium alginate, 1.8 g of hydroxymethyl cellulose, and 1.8 g of gelatin into 84.4 g of deionized water with a balance, and stir magnetically at 40° C. until completely dissolved.
(3)称取1.75g1,2-丙二醇和7.85g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取1.8g步骤(2)所制的部分氧化海藻酸钠和3.0g聚乙二醇二甲基丙烯酸酯，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 1.75g of 1,2-propanediol and 7.85g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 1.8 g of partially oxidized sodium alginate and 3.0 g of polyethylene glycol dimethacrylate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system is free of stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在-30℃冰箱中冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, freeze in a freezer at -30°C and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例7Implementation example 7
(1)用天平称取海藻酸钠1.90g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.90g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠1.5g、羟甲基纤维素3g、明胶3g加入到79.5g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 1.5 g of sodium alginate, 3 g of hydroxymethyl cellulose, and 3 g of gelatin into 79.5 g of deionized water, and stir magnetically at 40° C. until completely dissolved.
(3)称取2.0g1,2-丙二醇和8.0g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取3.0g步骤⑵所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 2.0 g of 1,2-propanediol and 8.0 g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 3.0 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在—30℃冰箱中冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, freeze in a refrigerator at -30°C, and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例8Implementation example 8
(1)用天平称取海藻酸钠1.90g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.90g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠1.5g、羟甲基纤维素3g、明胶3g加入到77.5g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 1.5 g of sodium alginate, 3 g of hydroxymethyl cellulose, and 3 g of gelatin into 77.5 g of deionized water with a balance, and stir magnetically at 40° C. until completely dissolved.
(3)称取3.0g1,2-丙二醇和9.0g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取3.0g步骤⑵所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 3.0 g of 1,2-propanediol and 9.0 g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 3.0 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在—30℃冰箱中冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, freeze in a refrigerator at -30°C, and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例9Implementation example 9
(1)用天平称取海藻酸钠1.90g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.90g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠1.5g、羟甲基纤维素3g、明胶3g加入到78.4g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 1.5 g of sodium alginate, 3 g of hydroxymethyl cellulose, and 3 g of gelatin into 78.4 g of deionized water, and stir magnetically at 40° C. until completely dissolved.
(3)称取3.0g1,2-丙二醇和9.0g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取2.1g步骤⑵所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 3.0 g of 1,2-propanediol and 9.0 g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 2.1 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在—30℃冰箱中冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片型。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, freeze in a refrigerator at -30°C, and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally, it is pressed into a paper shape with an appropriate pressure. Sterilized with cobalt-60, packaged.
实施实例10Implementation example 10
(1)用天平称取海藻酸钠1.90g加入到150g去离子水中，在30℃下磁力搅拌溶解完全，加入1.76g高碘酸钠固体，避光反应48h，温度不高于30℃，加入0.41g乙二醇终止反应，加入150g乙醇，3.0g氯化钠，静止分层，抽滤，放入40℃的真空烘箱中干燥48h。制得氧化海藻酸钠。(1) Use a balance to weigh 1.90g of sodium alginate and add it to 150g of deionized water, stir it with a magnetic force at 30°C to dissolve completely, add 1.76g of sodium periodate solid, and react in the dark for 48 hours, the temperature is not higher than 30°C, add 0.41g of ethylene glycol was used to terminate the reaction, 150g of ethanol and 3.0g of sodium chloride were added, the layers were statically separated, filtered with suction, and dried in a vacuum oven at 40°C for 48h. Oxidized sodium alginate was obtained.
(2)天平量取海藻酸钠0.6g、羟甲基纤维素1.8g、明胶1.8g加入到84.0g去离子水中，在40℃下磁力搅拌，直至完全溶解。(2) Add 0.6 g of sodium alginate, 1.8 g of hydroxymethyl cellulose, and 1.8 g of gelatin into 84.0 g of deionized water with a balance, and stir magnetically at 40° C. until completely dissolved.
(3)称取3.0g1,2-丙二醇和9.0g丙三醇，加入步骤(2)得到的体系，搅拌完全溶解。称取0.8g步骤⑵所制的部分氧化海藻酸钠，常温磁力搅拌直至部分氧化海藻酸钠完全溶解且体系无分层。消除气泡后，用2wt％的氯化钙稀溶液喷淋3到4次上述体系，放置4h，制成水凝胶。(3) Weigh 3.0 g of 1,2-propanediol and 9.0 g of glycerol, add the system obtained in step (2), and stir to dissolve completely. Weigh 0.8 g of the partially oxidized sodium alginate prepared in step (2), and stir magnetically at room temperature until the partially oxidized sodium alginate is completely dissolved and the system has no stratification. After eliminating air bubbles, spray the above-mentioned system with 2wt% calcium chloride dilute solution for 3 to 4 times, and leave it for 4 hours to make a hydrogel.
(4)均质器中制成均匀胶浆。倒入模具，在—30℃冰箱中冷冻之后用冷冻干燥机在-50℃冷冻48h得到海绵状固体。最后以适当的压力加压成纸片状。用钴-60灭菌消毒，包装。(4) Make uniform glue in the homogenizer. Pour into a mold, freeze in a refrigerator at -30°C, and freeze at -50°C for 48 hours with a freeze dryer to obtain a spongy solid. Finally press it into a paper sheet with appropriate pressure. Sterilized with cobalt-60, packaged.
| Application Number | Priority Date | Filing Date | Title |
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| CN201710662857.3ACN107376005A (en) | 2017-08-04 | 2017-08-04 | A kind of biodegradable medical hemostatic paper and preparation method thereof |
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| CN201710662857.3ACN107376005A (en) | 2017-08-04 | 2017-08-04 | A kind of biodegradable medical hemostatic paper and preparation method thereof |
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| CN107376005Atrue CN107376005A (en) | 2017-11-24 |
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| CN201710662857.3APendingCN107376005A (en) | 2017-08-04 | 2017-08-04 | A kind of biodegradable medical hemostatic paper and preparation method thereof |
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| RJ01 | Rejection of invention patent application after publication | Application publication date:20171124 |