CN103028135B - Method for preparing hemostatic sponge for dressing - Google Patents

Method for preparing hemostatic sponge for dressing Download PDF

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CN103028135B
CN103028135B CN 201210545888 CN201210545888A CN103028135B CN 103028135 B CN103028135 B CN 103028135B CN 201210545888 CN201210545888 CN 201210545888 CN 201210545888 A CN201210545888 A CN 201210545888A CN 103028135 B CN103028135 B CN 103028135B
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chitosan
temperature
step
sponge
process
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CN 201210545888
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CN103028135A (en )
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吴斌
孙云
张锐
朱思洁
张静
颜斯
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武汉奥绿新生物科技有限公司
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Abstract

本发明提供了一种用于敷料的止血海绵的制备方法,其特征在于包括以下步骤:(1)制备壳聚糖水溶液;(2)将所制备的壳聚糖水溶液注入模具中;(3)对模具中的壳聚糖水溶液进行冷冻;(4)将冷冻材料进行冻干;(5) 将壳聚糖海绵进行后处理。 The present invention provides a method for preparing a hemostatic sponge for dressing, comprising the steps of: (1) preparing an aqueous chitosan solution; (2) an aqueous solution of chitosan prepared into a mold; (3) chitosan solution in the mold freeze; (4) freeze-drying the frozen material; (5) after processing chitosan sponge. 本发明方法采用壳聚糖水溶液为原料制备用于敷料的止血海绵,并且经过冷冻、冻干以及后处理等工序,使得生产出来的海绵不仅吸水能力强,即湿态稳定性好,而且也更加的安全可靠,止血效果也很明显,吸附能力强,适用范围更加广泛。 The method of the present invention is employed as an aqueous solution of chitosan hemostatic sponge dressing for the preparation of starting materials, and after freezing, freeze-drying and post-treatment processes, such produced water absorption capacity of not only sponge, i.e., good wet stability, but also more safe and reliable, hemostatic effect is obvious, strong adsorption capacity, broader scope.

Description

一种用于敷料的止血海绵的制备方法 The method of preparation for a hemostatic sponge dressing

技术领域 FIELD

[0001] 本发明提供了一种海绵的制备方法,特别是一种用于敷料的止血海绵的制备方法。 [0001] The present invention provides a method for producing a sponge, in particular a method for preparing hemostatic sponge for dressing.

背景技术 Background technique

[0002] 外伤是危害人类健康的严重问题,据世界卫生组织创伤治疗指南报道,全球每天有16000人因外伤致死,而且因为外伤导致医疗费用是高达所有全球医疗支出的16%,其中创伤者中有1/3是因失血以及失血相关的多脏器衰竭而致死。 [0002] Trauma is a serious problem hazard to human health, according to the World Health Organization trauma treatment guidelines reported around the world every day 16,000 people due to trauma of death, but because of trauma resulting in medical costs is as high as 16% of all global health spending, which traumatized in 1/3 is due to blood loss and blood loss associated with multiple organ failure and death. 如果能及时有效地止血,对挽救伤员生命,稳定伤情,为后续治疗创造条件十分重要。 If a timely and effective manner to stop bleeding, to save the wounded lives, stabilize the condition is very important to create the conditions for follow-up treatment. 而敷料作为止血材料,是指盖在伤口上、有保护作用的覆盖物,可以协助控制出血,防止感染并吸收分泌物,止血敷料对于及时止血有着重要的意义。 The dressing as a hemostatic material refers to cover the wound, covering a protective effect, can help control bleeding, prevent infection and absorb secretions, hemostatic dressings to stop the bleeding is significant. 同时,止血对术中减少失血、保持术野清晰、防止重要组织损伤、保证手术安全以及术后创口愈合等均具有重要意义。 At the same time, bleeding reduce blood loss and maintain a clear surgical field, to prevent tissue damage is important to ensure the safety of operation and postoperative wound healing will have great significance.

[0003] 壳聚糖,化学名称为2-氨基-β -1,4-葡聚糖,是由自然界广泛存在的几丁质经过脱乙酰作用得到的一种天然阳离子多糖。 [0003] Chitosan, chemical name is 2-amino-dextran -β -1,4-, is a natural cationic polysaccharide chitin is a widespread in nature obtained through deacetylation. 自1859年被首次合成以来,由于其具有的可降解性、良好的成膜性、血液相容性、良好的生物相容性及一定的抗菌和抗肿瘤等优异性能,这种天然高分子的被广泛用于医药、食品、化工、环保等行业,素有万能多糖的美誉。 Since was first synthesized in 1859, because it has excellent properties of biodegradability, good film-forming properties, blood compatibility, good biocompatibility and certain anti-bacterial and anti-tumor, this natural polymer It is widely used in medicine, food, chemical, environmental protection and other industries, known as universal reputation as polysaccharides.

[0004] 市场上的止血敷料一般是通过加入生物活性分子,如凝血酶和纤维原蛋白,来提高敷料的止血性能,但是这类敷料的成本较高,而且保持该类生物活性分子的活性比较困难。 [0004] The haemostatic dressings on the market typically by adding a biologically active molecule, such as proteins thrombin and fibroblasts, to increase hemostatic properties of the dressing, but the high cost of such a dressing, but also to maintain the activity of the biologically active molecule such comparison difficult. 现有的壳聚糖止血材料是一种聚丙烯酸改性后的壳聚糖衍生物,主要性能为吸水性非常优异,但是聚丙烯酸的生物安全性至今未得到认可,美国食品安全管理局至今未批准任何一款含聚丙烯酸的相关医疗产品,还有一种壳聚糖止血海绵是以壳聚糖与明胶为主要成分的多孔海绵,其湿态稳定性很差,易于在大量血液渗出的伤口溶解,无法发挥凝血性能。 Chitosan hemostatic material existing after the chitosan derivative is an acid-modified polypropylene, mainly water-absorbing performance is excellent, but the biological safety of polyacrylic acid has not been recognized by the United States Food Safety Authority has not approve any related medical products containing a polyacrylic acid, there is a hemostatic sponge is chitosan and chitosan gelatin as a main component a porous sponge, which wet poor stability, easiness of oozing wounds dissolution, can not play clotting properties.

发明内容 SUMMARY

[0005] 为了解决现有技术的不足,本发明提供了一种用于敷料的止血海绵的制备方法,制得的止血海绵安全可靠、湿态稳定性好、止血效果强且粘附能力强。 [0005] In order to solve the deficiencies of the prior art, the present invention provides a method for dressing a hemostatic sponge was prepared hemostatic sponge safe, good wet stability, strong adhesion and hemostasis.

[0006] 本发明解决其技术问题所采用的技术方案是: [0006] aspect of the present invention to solve the technical problem are:

[0007] 一种用于敷料的止血海绵的制备方法,包括以下步骤: Preparation [0007] A method for dressing a hemostatic sponge, comprising the steps of:

[0008] (I)制备壳聚糖水溶液:选取分子量为150〜300千道尔的壳聚糖,壳聚糖的脱乙酰度为75%〜97%,壳聚糖水溶液的制备过程中加入酸性物质,酸性物质选取谷氨酸、乳酸、盐酸、乙酸以及乙醇酸中的任意一种,制得的壳聚糖水溶液中酸性物质的浓度为0.8 %〜4%,壳聚糖的浓度为0.1%〜2.7% ; [0008] (I) preparing an aqueous chitosan solution: selecting a molecular weight of one thousand 150~300 Seoul chitosan, degree of deacetylation of chitosan is 75% ~97%, preparation of an acidic aqueous solution of chitosan was added substance, an acidic substance selected arbitrarily acid, lactic acid, hydrochloric acid, acetic acid and glycolic acid in a concentration of aqueous solution of chitosan prepared in the acidic substance is 0.8% ~ 4%, the chitosan concentration was 0.1% ~2.7%;

[0009] (2)将所制备的壳聚糖水溶液注入模具中:用于壳聚糖水溶液注模的模具的长度为60〜70cm,宽度为9〜21cm,所述模具具有3个腔室,腔室的高度为0.05〜0.2cm,宽度为2〜6cm ; [0009] (2) an aqueous solution of chitosan is poured into a mold prepared: length of the mold for injection molding of an aqueous solution of chitosan 60~70cm, width 9~21cm, the mold having three chambers, the height of the chamber is 0.05~0.2cm, width 2~6cm;

[0010] (3)对模具中的壳聚糖水溶液进行冷冻:将模具置入冻干机冻干室,所述冷冻过程包含有四个步骤,第一步为温度平衡过程,温度平衡过程中温度为20-25°C,平衡时间为2-5h ;第二步为降温过程,以0.3〜1.(TC /min的降温速率降温至2〜10°C,并保持2〜10°C的温度20〜60min ;第三步为降温延迟过程,以0.3〜1.(TC /min的降温速率继续降温,当降温温度达到_5°C时,需要保持短暂的回温阶段,回温温度为-3〜0°C,保持时间为3-5min ;第四步为继续降温过程,以0.3〜1.(TC /min的降温速率继续降温至_40°C,并在-40°C冷冻30〜60min。冷冻完成后,得到冷冻材料; [0010] (3) an aqueous solution of chitosan freezing mold: the mold was placed into the lyophilization chamber lyophilizer, the freezing process comprises four steps, the first step of the process of temperature equilibration, the temperature equilibrium during temperature of 20-25 ° C, equilibration time is 2-5h;. the second step is a cooling process, to 0.3~1 (TC / min cooling rate of 2~10 ° C to cool, and the holding 2~10 ° C temperature 20~60min; delay procedure is to cool the third step, to 0.3~1 (TC / min cooling rate continues to cool, the cooling when the temperature reaches _5 ° C, the temperature required to maintain a short back stage, the temperature is warm. -3~0 ° C, a hold time of 3-5min;. the fourth step is to continue the cooling process to 0.3~1 (TC / min cooling rate to continue to cool _40 ° C, and frozen at -40 ° C 30 . ~60min after complete freezing, the frozen material is obtained;

[0011] (4)将冷冻材料进行冻干:在负压为-80〜_20KPa的环境中冻干,冻干包含有四个步骤,第一步为快速升温阶段,温度由冷冻温度快速升温至0°C,升温时间为20-50min;第二步为延迟阶段,温度保持在0°C,延迟时间为400-600min ;第三步为继续快速升温阶段,温度由0°C快速升温至35〜40°C,升温时间为20-50min ;第四步为继续延迟阶段,温度保持在升温温度35〜40°C,延迟时间为20-50min ;冻干完成后,得到壳聚糖海绵; [0011] (4) The frozen material was lyophilized: in the negative pressure environment -80~_20KPa lyophilized, the lyophilized includes four steps, the first step for the rapid heat-up stage temperature is rapidly raised from the freezing temperature to 0 ° C, the heating time is 20-50min; the second step as a delay stage, the temperature was maintained at 0 ° C, the delay time is 400-600min; the third step to continue the rapid heating phase, a rapid heating temperature 0 ° C to 35 ~40 ° C, the heating time is 20-50min; the fourth step is to continue the delay stage, the temperature is maintained at raised temperature 35~40 ° C, the delay time is 20-50min; after lyophilization is completed, the obtained chitosan sponge;

[0012] (5)将壳聚糖海绵进行后处理:所述后处理包括三个步骤,第一步为壳聚糖海绵致密化处理阶段,采取热板压缩法,选用的温度为60-85 °C,加压压力为0.3-0.6MPa,所得壳聚糖海绵的厚度为0.6-10mm,密度为0.1〜0.5g/cm3 ;第二步为预处理阶段,采取烘烤,烘干温度为75-80°C,烘干时间为0.25-0.5h。 [0012] (5) chitosan sponge after treatment: The after-treatment comprises three steps, the first step is chitosan sponge densification stage compression method to take a hot plate, a temperature selected from 60 to 85 ° C, pressing pressure of 0.3-0.6MPa, thickness of the resulting chitosan sponge is 0.6-10mm, density 0.1~0.5g / cm3; the second step of the preprocessing stage, taking baking, drying at 75 -80 ° C, the drying time is 0.25-0.5h. 第三步为软化处理阶段,采用软化机器软化,所得壳聚糖海绵的Gurley硬度值为2000-10000。 The third step is the softening stage, using the machine to soften soften, resulting chitosan sponge Gurley stiffness value of 2000-10000.

[0013] 作为上述方案的优选,步骤(I)中,壳聚糖水溶液制备过程中需要对壳聚糖水溶液进行减压脱泡,脱泡压力为-8X 15〜-3X 15Pa,脱泡时间为5〜30min。 [0013] As the above-described preferred embodiment, step (I), the chitosan solution prepared in the process an aqueous solution of chitosan require vacuum degassing, defoaming pressure -8X 15~-3X 15Pa, defoaming time 5~30min. 步骤(I)中,制得的壳聚糖水溶液中酸性物质的浓度为为1.5%〜2.5%。 Step (I), the concentration of the acidic aqueous solution of chitosan material was prepared in 1.5% ~2.5%.

[0014] 步骤(2)中,模具表面设置有一层不黏涂层,不黏涂层选用特氟隆或者氟化乙烯、氟化丙烯。 [0014] Step (2), the mold surface is provided with a non-stick coating layer, non-stick coating of Teflon or fluorinated ethylene selection, fluorinated ethylene propylene. 步骤(2)中,在注模过程中,每个模具注入壳聚糖水溶液的质量为300〜455g。 Step (2), the injection molding process, each of the injection mold for the mass of the aqueous solution of chitosan 300~455g.

[0015] 本发明相比于现有技术具有的有益效果是:本发明方法采用壳聚糖水溶液为原料制备用于敷料的止血海绵,并且经过冷冻、冻干以及后处理等工序,使得生产出来的海绵不仅吸水能力强,即湿态稳定性好,而且也更加的安全可靠,止血效果也很明显,吸附能力强,适用范围更加广泛。 [0015] Compared to the prior art having the beneficial effects of the present invention: the method according to the present invention is employed as an aqueous solution of chitosan hemostatic sponge dressing for the preparation of starting materials, and after freezing, freeze-drying and post-treatment step, such that produced the sponge not only strong water absorption capacity, that is good wet stability, but also more secure, hemostatic effect is very clear, strong adsorption capacity, broader scope.

具体实施方式 detailed description

[0016] 下面结合实施例对本发明作进一步说明。 [0016] below with reference to embodiments of the present invention will be further described.

[0017] 在本实施例1中,首先制备壳聚糖水溶液:选取分子量为300千道尔的壳聚糖455g,壳聚糖的脱乙酰度为95%,壳聚糖水溶液的制备过程中加入水溶液中的酸性物质选取乙酸,制得的壳聚糖水溶液中乙酸的浓度为4%,壳聚糖的浓度为2.3%,壳聚糖水溶液制备过程中需要对壳聚糖水溶液进行减压脱泡,脱泡压力为-3 X 15Pa,脱泡时间为5min ; [0017] In the present embodiment 1, firstly an aqueous solution of chitosan prepared: Select one thousand molecular weight of 300 Seoul 455g chitosan, degree of deacetylation of chitosan is 95%, the preparation of an aqueous solution of chitosan was added selecting an aqueous solution of acetic acid in the concentration of the aqueous solution of chitosan prepared in 4% acetic acid, 2.3% concentration of chitosan, chitosan aqueous solution needs to vacuum degassing process for preparing chitosan solution defoaming pressure -3 X 15Pa, defoaming time of 5min;

[0018] 其次将所制备的壳聚糖水溶液注入模具中:用于壳聚糖水溶液注模的模具的长度为60〜70cm,宽度为9〜21cm,所述模具具有3个腔室,相邻的腔室用隔板隔开,腔室的高度为0.05〜0.2cm,宽度为2〜6cm。 [0018] Next an aqueous solution of chitosan is poured into a mold prepared: length of the mold for injection molding of an aqueous solution of chitosan 60~70cm, width 9~21cm, the mold having three chambers, adjacent chambers separated by a separator, the chamber height is 0.05~0.2cm, width 2~6cm. 模具表面设置有一层特氟隆不黏涂层; Mold surface is provided with a layer of Teflon non-stick coating;

[0019] 然后对模具中的壳聚糖水溶液进行冷冻:将模具置入冻干机冻干室,所述冷冻过程包含有四个步骤,第一步为温度平衡过程,温度平衡过程中温度优选为25°C,平衡时间优选为5h ;第二步为降温过程,以0.30C /min的降温速率降温至2°C,并保持2°C的温度60min ;第三步为降温延迟过程,以0.3°C /min的降温速率继续降温,当降温温度达到_5°C时,需要保持短暂的回温阶段,回温温度为_3°C,保持时间为5min ;第四步为继续降温过程,以0.30C /min的降温速率继续降温至_40°C,并在_40°C冷冻30min。 [0019] The chitosan solution was then frozen in a mold: the mold was placed into the lyophilization chamber lyophilizer, the freezing process comprises four steps, the first step of the process of temperature equilibration, the temperature during temperature equilibrium is preferably to 25 ° C, equilibration time is preferably 5H; the second step of the cooling process to 0.30C / min cooling rate cooling to 2 ° C, and maintaining the temperature by 2 ° C 60min; a third step of cooling the delay process to cooling rate 0.3 ° C / min to continue to cool, when the cooling temperature reaches _5 ° C, the temperature required to maintain a short back stage, the temperature is allowed to warm _3 ° C, the holding time is 5min; the fourth step is to continue the cooling process , at a cooling rate of 0.30C / min to continue to cool to _40 ° C, 30min and frozen at _40 ° C. 冷冻完成后,得到冷冻材料冷冻完成后,得到冷冻材料; After the completion of freezing, freeze to give the frozen material is completed, to give the frozen material;

[0020] 接着将冷冻材料进行冻干:在负压为_80KPa的环境中冻干,冻干包含有四个步骤,第一步为快速升温阶段,温度由冷冻温度快速升温至0°C,升温时间为50min ;第二步为延迟阶段,温度保持在(TC,延迟时间为600min ;第三步为继续快速升温阶段,温度由0°C快速升温至40°C,升温时间为50min ;第四步为继续延迟阶段,温度保持在升温温度40°C,延迟时间为50min。冻干完成后,得到壳聚糖海绵,升温过程可以使所得壳聚糖海绵柔韧性和吸水性更加良好,所述壳聚糖溶液冻干过程中所得的壳聚糖海绵无需后处理过程已经可以用于出血量较少的伤口敷料或用于抑菌敷料。 [0020] The frozen material is then lyophilized: in the negative pressure environment _80KPa lyophilized, the lyophilized includes four steps, the first step for the rapid heat-up stage temperature is rapidly raised from the freezing temperature to 0 ° C, the heating time was 50min; the second step as a delay stage, maintaining the temperature at (the TC, the delay time is 600min; the third step to continue the rapid heating phase, a rapid heating temperature 0 ° C to 40 ° C, the heating time is 50min; of to continue four-step delay stage, the temperature is maintained at a temperature raised 40 ° C, the delay time of 50min. after lyophilization is completed, the obtained chitosan sponge, the heating process can make the resulting chitosan sponge flexibility and water absorption is more favorable, the said chitosan solution during lyophilization resulting chitosan sponges have been no post processing may be used for smaller amount of bleeding wound dressing or bacteriostatic dressings.

[0021] 最后将壳聚糖海绵进行后处理:所述后处理包括三个步骤,第一步为壳聚糖海绵致密化处理阶段,采取热板压缩法,选用的温度为85 °C,加压压力为0.3MPa所得壳聚糖海绵的厚度为10mm,密度为0.1〜0.5g/m3 ;第二步为预处理阶段,采取烘烤,烘干温度为80°C,烘干时间为0.5h。 [0021] Finally, the chitosan sponge process: The process comprises the three steps, the first step is chitosan sponge densification treatment stage, taking a hot plate compression method selected temperature 85 ° C, add the resulting pressure was 0.3MPa pressure chitosan sponge with a thickness of 10mm, a density of 0.1~0.5g / m3; the second step of the preprocessing stage, taking baking, drying temperature 80 ° C, the drying time of 0.5h . 第三步为软化处理阶段,采用软化机器软化,所得壳聚糖海绵的格利硬度值为4000。 The third step is the softening stage, using the machine to soften softening Gurley stiffness value 4000 obtained chitosan sponge.

[0022] 对后处理过程所得的敷料进行装袋,包装袋具有防潮与阻菌功能,包装方法优选为热封塑。 [0022] The process of dressing obtained after bagging, packaging bag with a moisture-proof bacteria barrier function, heat-sealing process is preferably a plastic packaging. 装袋后对壳聚糖海绵灭菌,优选方法为伽玛射线,优选射线强度为为19kGy。 Chitosan sponge bag after sterilization, gamma radiation is a preferred method, the intensity of radiation is preferably of 19kGy.

[0023] 在本实施例2中,首先制备壳聚糖水溶液:选取分子量为150千道尔的壳聚糖455g,壳聚糖的脱乙酰度为85%,壳聚糖水溶液的制备过程中加入水溶液中的酸性物质选取乙酸,制得的壳聚糖水溶液中乙酸的浓度为0.8%,壳聚糖的浓度为0.1%,壳聚糖水溶液制备过程中需要对壳聚糖水溶液进行减压脱泡,脱泡压力为-8 X 15Pa,脱泡时间为5min ; [0023] Example 2 In the present embodiment, first prepared aqueous solution of chitosan: Select one thousand molecular weight of 150 Seoul 455g chitosan, chitosan deacetylation degree of 85%, the preparation of an aqueous solution of chitosan was added an aqueous solution of acetic acid in the selection, the resulting aqueous solution of chitosan acetate in a concentration of 0.8%, 0.1% concentration of chitosan, chitosan aqueous solution needs to vacuum degassing process for preparing chitosan solution defoaming pressure -8 X 15Pa, defoaming time of 5min;

[0024] 其次将所制备的壳聚糖水溶液注入模具中:用于壳聚糖水溶液注模的模具的长度为60〜70cm,宽度为9〜21cm,所述模具具有3个腔室,相邻的腔室用隔板隔开,腔室的高度为0.05〜0.2cm,宽度为2〜6cm。 [0024] Next an aqueous solution of chitosan is poured into a mold prepared: length of the mold for injection molding of an aqueous solution of chitosan 60~70cm, width 9~21cm, the mold having three chambers, adjacent chambers separated by a separator, the chamber height is 0.05~0.2cm, width 2~6cm. 模具表面设置有一层特氟隆不黏涂层; Mold surface is provided with a layer of Teflon non-stick coating;

[0025] 然后对模具中的壳聚糖水溶液进行冷冻:将模具置入冻干机冻干室,所述冷冻过程包含有三个步骤,第一步为温度平衡过程,温度平衡过程中温度优选为20°C,平衡时间优选为2h ;第二步为降温过程,以1.(TC /min的降温速率降温至10°C,并保持10°C的温度20min ;第三步为降温延迟过程,以1.(TC /min的降温速率继续降温,当降温温度达到_5°C时,需要保持短暂的回温阶段,回温温度为0°C,保持时间为3min ;第四步为继续降温过程,以1.(TC /min的降温速率继续降温至_40°C,并在_40°C冷冻50min,冷冻完成后,得到冷冻材料冷冻完成后,得到冷冻材料,冷冻完成后,得到冷冻材料; [0025] The chitosan solution was then frozen in a mold: the mold was placed into the lyophilization chamber lyophilizer, the freezing process comprises three steps, the first step of the process of temperature equilibration, the temperature during temperature equilibrium is preferably 20 ° C, equilibration time is preferably 2H; the second step of the cooling process, a cooling rate of 1. (TC / min cooling to 10 ° C, and maintaining the temperature of 10 ° C 20min; delay procedure is to cool the third step, to 1. (TC / min cooling rate continues to cool, the cooling when the temperature reaches _5 ° C, the temperature required to maintain a short back stage, the temperature was warmed to 0 ° C, a hold time of 3min; fourth step is to continue to cool process, at a cooling rate of 1. (TC / min to continue to cool to _40 ° C, and frozen at _40 ° C 50min, after completion of the freezing, the frozen material obtained after completion of freezing, frozen material obtained after the completion of freezing, freeze to give material;

[0026] 接着将冷冻材料进行冻干:在负压为_20KPa的环境中冻干,冻干包含有四个步骤,第一步为快速升温阶段,温度由冷冻温度快速升温至0°C,升温时间为20min ;第二步为延迟阶段,温度保持在(TC,延迟时间为400min ;第三步为继续快速升温阶段,温度由0°C快速升温至40°C,升温时间为20min ;第四步为继续延迟阶段,温度保持在升温温度40°C,延迟时间为20min。冻干完成后,得到壳聚糖海绵,升温过程可以使所得壳聚糖海绵柔韧性和吸水性更加良好,所述壳聚糖溶液冻干过程中所得的壳聚糖海绵无需后处理过程已经可以用于出血量较少的伤口敷料或用于抑菌敷料。 [0026] The frozen material is then lyophilized: in the negative pressure environment _20KPa lyophilized, the lyophilized includes four steps, the first step for the rapid heat-up stage temperature is rapidly raised from the freezing temperature to 0 ° C, the heating time was 20min; the second step as a delay stage, maintaining the temperature at (the TC, the delay time is 400min; the third step to continue the rapid heating phase, a rapid heating temperature 0 ° C to 40 ° C, the heating time is 20min; of to continue four-step delay stage, the temperature is maintained at a temperature raised 40 ° C, the delay time of 20min. after lyophilization is completed, the obtained chitosan sponge, the heating process can make the resulting chitosan sponge flexibility and water absorption is more favorable, the said chitosan solution during lyophilization resulting chitosan sponges have been no post processing may be used for smaller amount of bleeding wound dressing or bacteriostatic dressings.

[0027] 最后将壳聚糖海绵进行后处理:所述后处理包括三个步骤,第一步为壳聚糖海绵致密化处理阶段,采取热板压缩法,选用的温度为60°C,加压压力为0.6Mpa,所得壳聚糖海绵的厚度为0.6mm,密度为0.1〜0.5g/cm3 ;第二步为预处理阶段,采取烘烤,烘干温度为75°C,烘干时间为0.25h。 [0027] Finally, the chitosan sponge process: The process comprises the three steps, the first step is chitosan sponge densification treatment stage, taking a hot plate compression method selected temperature 60 ° C, add pressure pressure 0.6Mpa, the thickness of the resulting chitosan sponge is 0.6mm, a density of 0.1~0.5g / cm3; the second step of the preprocessing stage, taking baking, drying temperature 75 ° C, drying time 0.25h. 第三步为软化处理阶段,采用软化机器软化,所得壳聚糖海绵的格利硬度值为2000。 The third step is the softening stage, using the machine to soften soften, resulting chitosan sponge hardness value of 2000 Gurley.

[0028] 对后处理过程所得的敷料进行装袋,包装袋具有防潮与阻菌功能,包装方法优选为热封塑。 [0028] The process of dressing obtained after bagging, packaging bag with a moisture-proof bacteria barrier function, heat-sealing process is preferably a plastic packaging. 装袋后对壳聚糖海绵灭菌,优选方法为伽玛射线,优选射线强度为为15kGy。 Chitosan sponge bag after sterilization, gamma radiation is a preferred method, the intensity of radiation is preferably 15 kGy.

[0029] 在本实施例3中,首先制备壳聚糖水溶液:选取分子量为200千道尔的壳聚糖455g,壳聚糖的脱乙酰度为90%,壳聚糖水溶液的制备过程中加入水溶液中的酸性物质选取乙酸,制得的壳聚糖水溶液中乙酸的浓度为2%,壳聚糖的浓度为1%,壳聚糖水溶液制备过程中需要对壳聚糖水溶液进行减压脱泡,脱泡压力为-5 X 15Pa,脱泡时间为20min ; [0029] Example 3 In the present embodiment, the first aqueous solution of chitosan prepared: Select a molecular weight of 200 kilopascals Doyle 455g chitosan, chitosan deacetylation degree of 90%, the preparation of an aqueous solution of chitosan was added an aqueous solution of acetic acid in the selection, the resulting aqueous solution of chitosan in acetic acid concentration of 2%, 1% concentration of chitosan, chitosan aqueous solution needs to vacuum degassing process for preparing chitosan solution defoaming pressure of -5 X 15Pa, defoaming time is 20min;

[0030] 其次将所制备的壳聚糖水溶液注入模具中:用于壳聚糖水溶液注模的模具的长度为60〜70cm,宽度为9〜21cm,所述模具具有3个腔室,相邻的腔室用隔板隔开,腔室的高度为0.05〜0.2cm,宽度为2〜6cm。 [0030] Next an aqueous solution of chitosan is poured into a mold prepared: length of the mold for injection molding of an aqueous solution of chitosan 60~70cm, width 9~21cm, the mold having three chambers, adjacent chambers separated by a separator, the chamber height is 0.05~0.2cm, width 2~6cm. 模具表面设置有一层特氟隆不黏涂层; Mold surface is provided with a layer of Teflon non-stick coating;

[0031] 然后对模具中的壳聚糖水溶液进行冷冻:将模具置入冻干机冻干室,所述冷冻过程包含有三个步骤,第一步为温度平衡过程,温度平衡过程中温度优选为22°C,平衡时间优选为3h ;第二步为降温过程,以0.50C /min的降温速率降温至5°C,并保持5°C的温度40min ;第三步为降温延迟过程,以0.5°C /min的降温速率继续降温,当降温温度达到_5°C时,需要保持短暂的回温阶段,回温温度为_2°C,保持时间为4min ;第四步为继续降温过程,以0.50C /min的降温速率继续降温至_40°C,并在_40°C冷冻30min,冷冻完成后,得到冷冻材料; [0031] The chitosan solution was then frozen in a mold: the mold was placed into the lyophilization chamber lyophilizer, the freezing process comprises three steps, the first step of the process of temperature equilibration, the temperature during temperature equilibrium is preferably 22 ° C, equilibration time is preferably 3H; the second step of the cooling process, a cooling rate of 0.50C / min cooling to 5 ° C, and maintaining the temperature 5 ° C 40min; delay procedure is to cool the third step, 0.5 to ° C / min cooling rate continues to cool, the cooling when the temperature reaches _5 ° C, the temperature required to maintain a short back stage, the temperature is allowed to warm _2 ° C, the holding time is 4min; fourth step is to continue the cooling process, at a cooling rate of 0.50C / min to continue to cool to _40 ° C, and frozen at _40 ° C 30min, after completion of the freezing, the frozen material is obtained;

[0032] 接着将冷冻材料进行冻干:冻干过程中负压优选为_50KPa,冻干包含有四个步骤,第一步为快速升温阶段,温度由冷冻温度快速升温至0°C,升温时间为30min ;第二步为延迟阶段,温度保持在(TC,延迟时间为500min ;第三步为继续快速升温阶段,温度由0°C快速升温至40°C,升温时间为40min ;第四步为继续延迟阶段,温度保持在升温温度40°C,延迟时间为40min。冻干完成后,得到壳聚糖海绵,升温过程可以使所得壳聚糖海绵柔韧性和吸水性更加良好,所述壳聚糖溶液冻干过程中所得的壳聚糖海绵无需后处理过程已经可以用于出血量较少的伤口敷料或用于抑菌敷料。 [0032] The frozen material is then lyophilized: vacuum freeze-drying process is preferably _50KPa, lyophilized includes four steps, the first step for the rapid heat-up stage temperature is rapidly raised from the freezing temperature to 0 ° C, heated time was for 30 min; the second step as a delay stage, maintaining the temperature at (the TC, the delay time is 500 min; the third step to continue the rapid heating phase, a rapid heating temperature 0 ° C to 40 ° C, the heating time is 40min; fourth the step of delaying a phase, heating temperature was kept at a temperature of 40 ° C, the delay time of 40min. after lyophilization is completed, the obtained chitosan sponge, the heating process can make the resulting chitosan sponge more favorable flexibility and water absorption, the chitosan solution during lyophilization resulting chitosan sponges have been no post processing may be used for smaller amount of bleeding wound dressing or bacteriostatic dressings.

[0033] 最后将壳聚糖海绵进行后处理:所述后处理包括三个步骤,第一步为壳聚糖海绵致密化处理阶段,采取热板压缩法,选用的温度为80°C,加压压力为0.5Mpa,所得壳聚糖海绵的厚度为0.8mm,密度为0.1〜0.5g/cm3 ;第二步为预处理阶段,采取烘烤,烘干温度为78°C,烘干时间为0.4h。 [0033] Finally, the chitosan sponge process: The process comprises the three steps, the first step is chitosan sponge densification stage compression method to take a hot plate, the temperature chosen is 80 ° C, add pressure pressure 0.5Mpa, the thickness of the resulting chitosan sponge is 0.8mm, a density of 0.1~0.5g / cm3; the second step of the preprocessing stage, taking baking, drying temperature 78 ° C, drying time 0.4h. 第三步为软化处理阶段,采用软化机器软化,所得壳聚糖海绵的格利硬度值为3000。 The third step is the softening stage, using the machine to soften soften, resulting chitosan sponge hardness value of 3000 Gurley.

[0034] 对后处理过程所得的敷料进行装袋,包装袋具有防潮与阻菌功能,包装方法优选为热封塑。 [0034] The process of dressing obtained after bagging, packaging bag with a moisture-proof bacteria barrier function, heat-sealing process is preferably a plastic packaging. 装袋后对壳聚糖海绵灭菌,优选方法为伽玛射线,优选射线强度为为17kGy。 Chitosan sponge bag after sterilization, gamma radiation is a preferred method, the intensity of radiation is preferably of 17kGy.

Claims (4)

  1. 1.一种用于敷料的止血海绵的制备方法,其特征在于包括以下步骤: (1)制备壳聚糖水溶液:选取分子量为150〜300千道尔的壳聚糖,壳聚糖的脱乙酰度为75%〜97%,壳聚糖水溶液的制备过程中加入酸性物质,酸性物质选取谷氨酸、乳酸、盐酸、乙酸以及乙醇酸中的任意一种,制得的壳聚糖水溶液中酸性物质的浓度为0.8%〜4%,壳聚糖的浓度为0.1%〜2.7% ; (2)将所制备的壳聚糖水溶液注入模具中:用于壳聚糖水溶液注模的模具的长度为60〜70cm,宽度为9〜21cm,所述模具具有3个腔室,腔室的高度为0.05〜0.2cm,宽度为2〜6cm ;注模过程中,每个模具注入壳聚糖水溶液的质量为300〜455g ; (3)对模具中的壳聚糖水溶液进行冷冻:将模具置入冻干机冻干室,所述冷冻过程包含有四个步骤,第一步为温度平衡过程,温度平衡过程中温度为20-25°C,平衡时间为2-5h ;第二步为降温过程 1. A method of preparing for a hemostatic sponge dressing, comprising the steps of: (1) preparing an aqueous chitosan solution: selecting a molecular weight of one thousand 150~300 Seoul chitosan, deacetylated of 75% ~97% aqueous solution of chitosan prepared in the process of adding the acidic substance, the acidic substance is selected any one of glutamic acid, lactic acid, hydrochloric acid, acetic acid and glycolic acid was prepared an acidic aqueous solution of chitosan concentration of the substance is 0.8% ~ 4%, the chitosan concentration of 0.1% ~2.7%; (2) an aqueous solution of chitosan is poured into a mold prepared: length of the mold for injection molding of an aqueous solution of chitosan 60~70cm, width 9~21cm, the mold having three chambers, the chamber height is 0.05~0.2cm, width 2~6cm; injection molding process, each of the aqueous chitosan solution is injected into the mold mass is 300~455g; (3) an aqueous solution of chitosan freezing mold: the mold was placed into the lyophilization chamber lyophilizer, the freezing process comprises four steps, the first step of the process of temperature equilibration, the temperature equilibrium the process temperature is 20-25 ° C, equilibration time was 2 to 5h; the second step of the cooling process 以0.3〜1.(TC /min的降温速率降温至2〜10°C,并保持2〜10°C的温度20〜60min ;第三步为降温延迟过程,以0.3〜1.(TC /min的降温速率继续降温,当降温温度达到_5°C时,需要保持短暂的回温阶段,回温温度为-3〜0°C,保持时间为3-5min ;第四步为继续降温过程,以0.3〜1.(TC /min的降温速率继续降温至_40°C,并在-40°C冷冻30〜60min,冷冻完成后,得到冷冻材料; (4)将冷冻材料进行冻干:在负压为-80〜-20KPa的环境中冻干,冻干包含有四个步骤,第一步为快速升温阶段,温度由冷冻温度快速升温至0°C,升温时间为20-50min;第二步为延迟阶段,温度保持在0°C,延迟时间为400-600min ;第三步为继续快速升温阶段,温度由0°C快速升温至35〜40°C,升温时间为20-50min ;第四步为继续延迟阶段,温度保持在升温温度35〜40°C,延迟时间为20-50min ;冻干完成后,得到壳聚糖海绵; (5)将壳聚糖 . In 0.3~1 (TC / min cooling rate of 2~10 ° C to cooling, maintaining the temperature of 2~10 ° C 20~60min; a third step of cooling the delay process to 0.3~1 (TC / min. continue to cool the cooling rate, cooling when the temperature reaches _5 ° C, the temperature required to maintain a short back stage, the temperature is allowed to warm -3~0 ° C, the holding time is 3-5min; fourth step is to continue the cooling process, . in 0.3~1 (TC / min cooling rate continued to cool to _40 ° C, and frozen at -40 ° C 30~60min, after freezing is completed, to give frozen material; (4) the frozen material was lyophilized: in -80~-20KPa negative pressure environment in lyophilized, the lyophilized includes four steps, the first step for the rapid heat-up stage temperature is rapidly raised from the freezing temperature to 0 ° C, the heating time is 20-50min; second step delay stage, the temperature was maintained at 0 ° C, the delay time is 400-600min; the third step to continue the rapid heating phase, a rapid heating temperature 0 ° C to 35~40 ° C, the heating time is 20-50min; of to continue four-step delay stage, the temperature is maintained at raised temperature 35~40 ° C, the delay time is 20-50min; after lyophilization is completed, the obtained chitosan sponge; (5) chitosan 海绵进行后处理:所述后处理包括三个步骤,第一步为壳聚糖海绵致密化处理阶段,采取热板压缩法,选用的温度为60-85°C,加压压力为0.3-0.6MPa,所得壳聚糖海绵的厚度为0.6-10mm,密度为0.1〜0.5g/cm3 ;第二步为预处理阶段,采取烘烤,烘干温度为75-80°C,烘干时间为0.25-0.5h。第三步为软化处理阶段,采用软化机器软化,所得壳聚糖海绵的Gurley硬度值为2000-10000。 After processing the sponge: The post-treatment comprises three steps, the first step is chitosan sponge densification treatment stage, taking a hot plate compression method selected temperature 60-85 ° C, pressing pressure of 0.3 to 0.6 MPa, thickness of the resulting chitosan sponge is 0.6-10mm, density 0.1~0.5g / cm3; a second step of pre-processing stage, to take the baking, drying temperature is 75-80 ° C, drying time 0.25 -0.5h. the third step is the softening stage, using the machine to soften soften, resulting chitosan sponge Gurley stiffness value of 2000-10000.
  2. 2.根据权利要求1所述的制备方法,其特征在于:步骤(I)中,壳聚糖水溶液制备过程中需要对壳聚糖水溶液进行减压脱泡,脱泡压力为-8X105〜-3X 15Pa,脱泡时间为5〜30mino The production method according to claim 1, wherein: step (I), the chitosan solution prepared in the process an aqueous solution of chitosan require vacuum degassing, defoaming pressure -8X105~-3X 15Pa, defoaming time 5~30mino
  3. 3.根据权利要求1所述的制备方法,其特征在于:步骤⑴中,制得的壳聚糖水溶液中酸性物质的浓度为1.5% -2.5%。 3. The production method according to claim 1, wherein: the step ⑴, the concentration of the aqueous solution of chitosan prepared in the acidic substance is from 1.5% to 2.5%.
  4. 4.根据权利要求1所述的制备方法,其特征在于:步骤(2)中,模具表面设置有一层不黏涂层,不黏涂层选用特氟隆或者氟化乙烯、氟化丙烯。 The production method according to claim 1, wherein: step (2), the mold surface is provided with a non-stick coating layer, non-stick coating of Teflon or fluorinated ethylene selection, fluorinated ethylene propylene.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103520765B (en) * 2013-11-06 2015-04-01 中国科学院长春应用化学研究所 Method for preparing wound hemostasis dressing
CN103611180B (en) * 2013-11-21 2015-02-18 无锡中科光远生物材料有限公司 Preparation method of self-adhesion hemostasis anti-adhesion corpus fibrosum
CN103613781B (en) * 2013-11-22 2015-11-18 哈尔滨工业大学 A method for preparing a superhydrophobic oil-absorbing sponge particles based on three-dimensional network load Chitosan
CA2940012A1 (en) * 2014-02-20 2015-08-27 Ortho Regenerative Technologies Inc. Lyophilized polymer scaffold compositions, processes for preparation and use in anabolic wound repair
CN104497348A (en) * 2014-12-31 2015-04-08 武汉奥绿新生物科技有限公司 Softening technology and equipment for polysaccharides lyophilized sponge dressing
CN107261187B (en) * 2017-05-22 2018-05-08 广东泓志生物科技有限公司 A micro vacuum powered liquid absorbent material and method for creating protection

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001057121A1 (en) * 2000-02-03 2001-08-09 Menicon Co., Ltd. Spongy molding comprising water-soluble polymeric material and method of controlling pores thereof
US20070082023A1 (en) * 2002-06-14 2007-04-12 Hemcon Medical Technologies, Inc. Supple tissue dressing assemblies, systems, and methods formed from hydrophilic polymer sponge structures such as chitosan
US7371403B2 (en) * 2002-06-14 2008-05-13 Providence Health System-Oregon Wound dressing and method for controlling severe, life-threatening bleeding
US20050137512A1 (en) * 2003-12-23 2005-06-23 Campbell Todd D. Wound dressing and method for controlling severe, life-threatening bleeding
CN101066469B (en) * 2007-05-09 2010-05-19 上海理工大学 Preparation process of porous collagen sponge
CN101927027A (en) * 2010-04-16 2010-12-29 哈尔滨工业大学 Chitosan/carboxymethyl chitosan rapid hemostatic sponge and preparation method thereof
CN102049061A (en) * 2010-12-08 2011-05-11 苏州同科生物材料有限公司 Method for preparing chitosan collagen sponge burn dressing

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