CN102205142B - Water-soluble hemostatic material and preparation method thereof - Google Patents
Water-soluble hemostatic material and preparation method thereof Download PDFInfo
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 9
- -1 sodium carboxylate Chemical class 0.000 claims description 127
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- 238000000034 method Methods 0.000 claims description 31
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Abstract
Description
技术领域 technical field
本发明涉及一种止血材料及其制备方法。The invention relates to a hemostatic material and a preparation method thereof.
背景技术 Background technique
氧化再生纤维素(ORC)作为止血材料在医疗领域已被人们所熟知和广泛应用。氧化再生纤维素是以再生纤维素编织物为原料,采用适合的氧化体系(如二氧化氮类或TEMPO体系)对其进行选择性氧化,制得羧基含量介于3.56~5.33mmol/g之间的氧化再生纤维素织物,然后再经洗涤、干燥、封装和杀菌等过程制成临床医用氧化再生纤维素止血产品。Oxidized regenerated cellulose (ORC) has been well known and widely used as a hemostatic material in the medical field. Oxidized regenerated cellulose is made of regenerated cellulose braided fabric, and it is selectively oxidized with a suitable oxidation system (such as nitrogen dioxide or TEMPO system) to obtain a carboxyl content between 3.56 and 5.33mmol/g. The oxidized regenerated cellulose fabric is then washed, dried, packaged and sterilized to make clinical medical oxidized regenerated cellulose hemostatic products.
氧化再生纤维素可以激活创口处的血小板而加速止血。而且,随着血液中某些成分吸附到氧化再生纤维素表面,氧化再生纤维素会缓慢膨胀,进而压迫血管断端而止血,但是只适用于创口小,出血量低的情况,而且止血速度慢。Oxidized regenerated cellulose can activate platelets in the wound and accelerate hemostasis. Moreover, as certain components in the blood are adsorbed to the surface of the oxidized regenerated cellulose, the oxidized regenerated cellulose will slowly expand, and then compress the broken end of the blood vessel to stop the bleeding, but it is only suitable for small wounds, low bleeding volume, and the hemostasis speed is slow .
由于氧化再生纤维素为非水溶型止血材料,其pH值约为3.5,只能溶于pH值介于10~14范围内的碱性溶液中。所以,氧化再生纤维素在体内的生物可吸收性差,而且氧化再生纤维素的酸性较强,导致其对某些神经系统可能造成损伤,进而限制了氧化再生纤维素在脑部等敏感部位的应用。同时氧化再生纤维素止血材料的酸性也会引发一些酸敏感药物失效,如凝血酶等。Since oxidized regenerated cellulose is a water-insoluble hemostatic material, its pH value is about 3.5, and it can only be dissolved in alkaline solutions with a pH value in the range of 10-14. Therefore, the bioabsorbability of oxidized regenerated cellulose in the body is poor, and the acidity of oxidized regenerated cellulose is strong, which may cause damage to some nervous systems, thereby limiting the application of oxidized regenerated cellulose in sensitive parts such as the brain . At the same time, the acidity of the oxidized regenerated cellulose hemostatic material will also cause some acid-sensitive drugs to fail, such as thrombin.
氧化再生纤维素中酸性的羧基结构可以与血红蛋白中Fe3+结合起到一定的止血作用,但是在临床使用过程中由于氧化再生纤维素中的羧基会很快的被血液中的缓冲物质中和,所以这种止血效果短暂且不显著。The acidic carboxyl structure in oxidized regenerated cellulose can combine with Fe 3+ in hemoglobin to play a certain hemostatic effect, but in the process of clinical use, the carboxyl group in oxidized regenerated cellulose will be quickly neutralized by buffer substances in the blood , so this hemostatic effect is short-lived and insignificant.
氧化再生纤维素作为止血材料的改性研究一直在不断努力进行中。Doub等人公开了采用碳酸氢钠或乙酸钙的水溶液对氧化再生纤维素进行中和的方法,并且用凝血酶浸渍碳酸氢钠中和的氧化再生纤维素,然后对浸渍后的织物进行冻结处理并在此状态下干燥,制得了一种高效的氧化纤维素类外科手术止血材料。美国专利中Saferstein等人叙述了使用弱酸盐的醇水溶液,如乙酸钠,将氧化再生纤维素中和至pH值介于5~8之间,这种方法不但使氧化再生纤维素可以室温稳定储存,而且可以负载上类似凝血酶的酸敏感物质,进而提高氧化再生纤维素材料的止血性能。同时他们还发现,Doub等人采用碳酸氢钠中和的方法会导致氧化再生纤维素织物部分胶化、变形,并且致使最终中和的氧化再生纤维织物的拉伸强度太低而无法应用到实际的止血过程中。而Doub等人在专利中提到的乙酸钙中和的氧化再生纤维素虽然保证了织物的原有形态,但由于中和后材料钙含量过高,在使用过程中会对接触处的哺乳动物皮肤和其他体细胞产生刺激性,并在使用位置形成大的发白的肉芽肿块,妨碍材料的生物吸收。上述方法利用改性可以提高氧化再生纤维素的止血性能,但其生物可吸收性大幅降低。在另一份美国专利中Stilwell等人则采用中和的方法制备出了一种效果满意的钙改性的氧化再生纤维素止血材料,他们发现当氧化纤维素中的钙含量在0.4~5.0之间时,钙改性的氧化纤维素的止血性能优于未改性的氧化再生纤维素以及钠或钾改性的氧化再生纤维素,并且对材料的生物可吸收性影响不是太大。当采用钙和钠或钾混合改性时,所得的改性氧化再生纤维素具有较高的pH值来满足与酸敏感物质相容的条件,同时其中的含有的钙既可实现增强止血效果,又不至于导致生物组织刺激反应。Research on the modification of oxidized regenerated cellulose as a hemostatic material has been in continuous effort. Doub et al. disclose a method of neutralizing oxidized regenerated cellulose with an aqueous solution of sodium bicarbonate or calcium acetate, impregnating the neutralized oxidized regenerated cellulose with thrombin, and then freezing the impregnated fabric And drying in this state, a highly efficient oxidized cellulose surgical hemostatic material is prepared. In the U.S. patent, Saferstein et al. describe the use of an alcoholic aqueous solution of a weak acid salt, such as sodium acetate, to neutralize the oxidized regenerated cellulose to a pH value between 5 and 8. This method not only makes the oxidized regenerated cellulose stable at room temperature storage, and can be loaded with acid-sensitive substances like thrombin, thereby improving the hemostatic performance of oxidized regenerated cellulose materials. At the same time, they also found that the method of neutralization by Doub et al. with sodium bicarbonate would lead to partial gelation and deformation of the oxidized regenerated cellulose fabric, and the tensile strength of the final neutralized oxidized regenerated cellulose fabric would be too low to be applied in practice. in the process of hemostasis. Although the oxidized regenerated cellulose neutralized by calcium acetate mentioned in the patent by Doub et al. has guaranteed the original shape of the fabric, due to the high calcium content of the material after neutralization, it will be harmful to mammals at the contact point during use. Skin and other body cells are irritated and form large whitish granulation bumps at the site of application, preventing bioabsorption of the material. The above method can improve the hemostatic performance of oxidized regenerated cellulose by modification, but its bioabsorbability is greatly reduced. In another U.S. patent, Stilwell et al. prepared a calcium-modified oxidized regenerated cellulose hemostatic material with a neutralization method. They found that when the calcium content in oxidized cellulose was between 0.4 and 5.0 Over time, the hemostatic properties of calcium-modified oxidized cellulose were superior to those of unmodified oxidized regenerated cellulose and sodium or potassium-modified oxidized regenerated cellulose, and the effect on the bioabsorbability of the material was not too great. When calcium and sodium or potassium are mixed and modified, the obtained modified oxidized regenerated cellulose has a higher pH value to meet the conditions of compatibility with acid-sensitive substances, and the calcium contained therein can achieve enhanced hemostatic effect, It will not cause biological tissue irritation.
由于氧化再生纤维素可完全溶于pH值为10~14的碱性溶液,而且导致强度大大降低甚至不能保持氧化再生纤维素织物形状,所以,以往的专利和研究中都采用弱酸盐体系来中和改性氧化纤维素。虽然,上述研究对氧化再生纤维素止血材料的中和改性使氧化再生纤维素止血材料的酸性减弱,但是采用弱酸盐对氧化再生纤维素进行中和后的产品均属于非水溶型,聚合度降低幅度又很小,甚至不发生降解,因此仍然存在生物可吸收性差,无法提高其止血速度的缺陷。Since oxidized regenerated cellulose can be completely dissolved in an alkaline solution with a pH value of 10 to 14, and the strength is greatly reduced or even the shape of the oxidized regenerated cellulose fabric cannot be maintained. Therefore, weak acid salt systems have been used in previous patents and researches. Neutralizes modified oxidized cellulose. Although the neutralization and modification of the oxidized regenerated cellulose hemostatic material in the above research weakens the acidity of the oxidized regenerated cellulose hemostatic material, the products after neutralizing the oxidized regenerated cellulose with weak acid salts are all water-insoluble, polymeric The degree of reduction in the degree of reduction is very small, or even does not degrade, so there are still defects in the poor bioabsorbability and the inability to improve its hemostasis speed.
发明内容 Contents of the invention
本发明是为了解决现有氧化再生纤维素材料均为非水溶型,生物可吸收性差,止血速度慢的问题,并采用不同于现有氧化再生纤维素中和改性的角度制备了一种新的官能团浓度呈梯度分布的水溶型氧化再生纤维素止血材料。The present invention aims to solve the problems that the existing oxidized regenerated cellulose materials are non-water-soluble, have poor bioabsorbability and slow hemostasis speed, and prepare a new oxidized regenerated cellulose from the perspective of neutralization and modification different from the existing oxidized regenerated cellulose. A water-soluble oxidized regenerated cellulose hemostatic material with a gradient distribution of functional group concentrations.
水溶型止血材料由氧化再生纤维素羧酸钠织物与盐酸制成,水溶型止血材料中羧基官能团含量为0.10~5.21mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠的酸化度为3%~98%;其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.30~4.77mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠与盐酸中氢离子的摩尔比为(100∶1)~(1∶20)。The water-soluble hemostatic material is made of oxidized regenerated cellulose sodium carboxylate fabric and hydrochloric acid, the carboxyl functional group content in the water-soluble hemostatic material is 0.10-5.21mmol/g, and the acidification degree of sodium carboxylate in the oxidized regenerated cellulose sodium carboxylate fabric is 3%~98%; Among them, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.30~4.77mmol/g, the molar ratio of sodium carboxylate in the oxidized regenerated cellulose sodium carboxylate fabric to hydrogen ions in hydrochloric acid It is (100:1) ~ (1:20).
上述水溶型止血材料按以下步骤制备:The above-mentioned water-soluble hemostatic material is prepared according to the following steps:
将氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯上,再加入盐酸密闭酸化0.5~72h,酸化温度为10~30℃,然后用无水乙醇减压抽滤冲洗3~5次,再置于-10~-80℃环境中冷冻干燥24~120h,即得到水溶型止血材料;Wrap the oxidized regenerated cellulose sodium carboxylate fabric on the glass porous core of the acidification rotary reactor, then add hydrochloric acid for closed acidification for 0.5-72 hours, the acidification temperature is 10-30°C, and then rinse with absolute ethanol for 3-3~ 5 times, and then freeze-dried in an environment of -10 to -80°C for 24 to 120 hours to obtain a water-soluble hemostatic material;
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.30~4.77mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠与盐酸中氢离子的摩尔比为(100∶1)~(1∶20);酸化回转反应器的转速为100~400r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.30~4.77mmol/g, and the molar ratio of sodium carboxylate and hydrogen ion in the hydrochloric acid in the oxidized regenerated cellulose sodium carboxylate fabric is (100:1) ~(1:20); the rotating speed of the acidification rotary reactor is 100~400r/min, and the hydrochloric acid added to the acidification rotary reactor does not directly contact with the oxidized regenerated cellulose sodium carboxylate fabric when the acidification rotary reactor does not start .
本发明用盐酸对氧化再生纤维素羧酸钠织物进行可控酸化,将氧化再生纤维素羧酸钠织物中的羧酸钠结构部分转化为羧酸结构,由于采用的氧化再生纤维素羧酸钠织物结构中没有羧基的存在(氧化再生纤维素羧酸钠织物中羧基官能团含量为0),因此在酸化过程中酸化的羧酸官能团浓度呈现梯度分布,且仍能保持原有的形状;由于加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不与氧化再生纤维素羧酸钠织物接触,所以氧化再生纤维素羧酸钠织物不发生溶解,其强度符合临床止血要求。In the present invention, hydrochloric acid is used to controlly acidify the oxidized regenerated cellulose sodium carboxylate fabric, and the sodium carboxylate structure part in the oxidized regenerated cellulose sodium carboxylate fabric is converted into a carboxylic acid structure, because the oxidized regenerated cellulose sodium carboxylate used There is no carboxyl group in the fabric structure (the carboxyl functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 0), so the acidified carboxylic acid functional group concentration presents a gradient distribution during the acidification process, and the original shape can still be maintained; due to the addition of The hydrochloric acid in the acidification rotary reactor does not contact the oxidized regenerated cellulose sodium carboxylate fabric when the acidification rotary reactor is not started, so the oxidized regenerated cellulose sodium carboxylate fabric does not dissolve, and its strength meets the clinical hemostasis requirements.
本发明水溶型止血材料中除了被酸化形成的羧酸官能团外,还有部分的羧酸钠官能团存在,所以水溶型止血材料的酸性弱于氧化再生纤维素材料,可以降低、甚至消除造成人体神经系统损伤的可能性,进而扩大了止血材料的应用范围,并且水溶型止血材料的弱酸性使得本发明水溶型止血材料可与一些酸敏感止血材料或药物复合使用,有望进一步生产出更为快速的止血产品。In addition to the carboxylic acid functional groups formed by acidification, the water-soluble hemostatic material of the present invention also has some sodium carboxylate functional groups. Therefore, the acidity of the water-soluble hemostatic material is weaker than that of the oxidized regenerated cellulose material, which can reduce or even eliminate the occurrence of nerve damage in the human body. The possibility of system damage, thereby expanding the application range of hemostatic materials, and the weak acidity of the water-soluble hemostatic materials of the present invention can be used in combination with some acid-sensitive hemostatic materials or drugs, which is expected to further produce faster Hemostatic products.
本发明水溶型止血材料中的羧酸官能团浓度呈现梯度分布,羧酸钠官能团的含量由表及里逐渐升高,而羧酸官能团的含量由表及里逐渐降低。本发明水溶型止血材料所具有的官能团浓度梯度分布可在止血不同时期发不同的止血机制,更贴合创口的出血过程;本发明水溶型止血材料与血液接触初期,其所吸附的血液量较少,主要依靠表面分布的羧酸官能团与血红蛋白中Fe3+结合起止血作用,随着水溶型止血材料吸附血液量的增加,血液渗透至水溶型止血材料内部,水溶型止血材料中的羧酸钠官能团具备水溶性,在羧酸钠官能团的作用下水溶型止血材料迅速形成凝胶,填补创面空隙、压迫和堵塞血管末端而止血。本发明水溶型止血材料遇水或盐溶液后可以在短时间内迅速降解形成凝胶,因此,本发明水溶型止血材料的生物止血和物理止血的双重止血机制都在短时间内发挥作用,并大大缩短止血时间,提高止血效果。而且,本发明水溶型止血材料还可以激活创口处的血小板而加速止血。The concentration of carboxylic acid functional groups in the water-soluble hemostatic material of the present invention presents a gradient distribution, the content of sodium carboxylate functional groups gradually increases from the surface to the inside, and the content of carboxylic acid functional groups gradually decreases from the surface to the inside. The functional group concentration gradient distribution of the water-soluble hemostatic material of the present invention can produce different hemostatic mechanisms in different periods of hemostasis, which is more suitable for the bleeding process of the wound; the water-soluble hemostatic material of the present invention is in contact with blood at the initial stage, and the amount of blood absorbed by it is relatively small. The hemostatic effect mainly depends on the combination of carboxylic acid functional groups distributed on the surface and Fe 3+ in hemoglobin. With the increase of the amount of blood absorbed by the water-soluble hemostatic material, the blood penetrates into the water-soluble hemostatic material, and the carboxylic acid in the water-soluble hemostatic material The sodium functional group is water-soluble, and under the action of the sodium carboxylate functional group, the water-soluble hemostatic material quickly forms a gel, which fills the wound surface gap, oppresses and blocks the end of the blood vessel to stop bleeding. The water-soluble hemostatic material of the present invention can degrade rapidly to form a gel in a short time after encountering water or saline solution. Therefore, the dual hemostatic mechanisms of the water-soluble hemostatic material of the present invention, both biological hemostasis and physical hemostasis, play a role in a short time, and Greatly shorten the hemostatic time and improve the hemostatic effect. Moreover, the water-soluble hemostatic material of the present invention can also activate platelets at the wound to accelerate hemostasis.
由于本发明水溶型止血材料中的羧酸钠官能团具备水溶性,因此本发明水溶型止血材料具有比氧化再生纤维素更为优异的水溶性、降解性,可以在生物体内被更快的代谢吸收。Since the sodium carboxylate functional group in the water-soluble hemostatic material of the present invention has water solubility, the water-soluble hemostatic material of the present invention has better water solubility and degradability than oxidized regenerated cellulose, and can be absorbed by metabolism faster in the living body .
本发明水溶型止血材料的制备过程中不发生分解或降解,而且制备方法简单,反应条件易于操作和控制。本发明水溶型止血材料的制备过程中无水乙醇只作为冲洗用,用量少,可节省大量成本。The water-soluble hemostatic material of the invention does not decompose or degrade during the preparation process, and the preparation method is simple, and the reaction conditions are easy to operate and control. In the preparation process of the water-soluble hemostatic material of the present invention, the absolute ethanol is only used for washing, and the dosage is small, which can save a lot of cost.
附图说明 Description of drawings
图1是酸化回转反应器的结构示意图,旋转方向为图1中箭头方向。图2是酸化回转反应器的剖面图。图3是酸化回转反应器的横截面。图4是将氧化再生纤维素止血材料置于创面上方60s后的观察图。图5是将具体实施方式二十八制备的水溶型止血材料置于创面上方60s后的观察图。Fig. 1 is a structural schematic diagram of an acidification rotary reactor, and the rotation direction is the direction of the arrow in Fig. 1 . Figure 2 is a sectional view of an acidification rotary reactor. Figure 3 is a cross-section of an acidification rotary reactor. Fig. 4 is an observation diagram after placing the oxidized regenerated cellulose hemostatic material on the wound surface for 60 seconds. Fig. 5 is an observation diagram after placing the water-soluble hemostatic material prepared in Embodiment 28 above the wound for 60 seconds.
具体实施方式 Detailed ways
本发明技术方案不局限于以下所列举具体实施方式,还包括各具体实施方式间的任意组合。The technical solution of the present invention is not limited to the specific embodiments listed below, but also includes any combination of the specific embodiments.
具体实施方式一:本实施方式水溶型止血材料由氧化再生纤维素羧酸钠织物与盐酸制成,水溶型止血材料中羧基官能团含量为0.10~5.2lmmol/g,氧化再生纤维素羧酸钠织物中羧酸钠的酸化度为3%~98%;其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.30~4.77mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠与盐酸中氢离子的摩尔比为(100∶1)~(1∶20)。Specific Embodiment 1: In this embodiment, the water-soluble hemostatic material is made of oxidized regenerated cellulose sodium carboxylate fabric and hydrochloric acid. The carboxyl functional group content in the water-soluble hemostatic material is 0.10-5.2 mmol/g. The acidification degree of sodium carboxylate is 3% to 98%; wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.30 to 4.77mmol/g, and the sodium carboxylate in the oxidized regenerated cellulose sodium carboxylate fabric The molar ratio of hydrogen ion to hydrochloric acid is (100:1)~(1:20).
本实施方式中氧化再生纤维素羧酸钠织物中羧基官能团含量为0。In this embodiment, the carboxyl functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is zero.
氧化再生纤维素羧酸钠织物是利用氧化体系为2,2,6,6-四甲基哌啶氧化物自由基TEMPO-NaBr-NaClO与再生纤维素织物反应氧化制得,其中TEMPO(2,2,6,6-四甲基哌啶氧化物)的质量为再生纤维素织物质量的0.1%~8.0%,NaBr的质量为再生纤维素织物质量的5.0%~80.0%,NaClO溶液的有效氯含量为5%~16%、NaClO溶液体积为30~80ml,NaClO溶液采用分批加入方式,每次为5~10ml;氧化反应温度为0~15℃,氧化体系的pH值介于9.0~11.0,搅拌速度为200~400转/min。氧化再生纤维素羧酸钠织物制备方法具体实例:2g絮状粘胶纤维织物、TEMPO 100mg、NaBr 0.96g、NaClO溶液60ml,于8℃下发生反应,用0.4mol/L NaOH溶液保持反应液的pH在10.0左右,分4次加入NaClO溶液,消耗31ml NaOH时,终止反应,把反应液倾倒入过量的乙醇(300ml)中,析出物即为氧化再生纤维素羧酸钠织物。Oxidized regenerated cellulose sodium carboxylate fabric is made by oxidation system of 2,2,6,6-tetramethylpiperidine oxide free radical TEMPO-NaBr-NaClO and regenerated cellulose fabric, wherein TEMPO(2, The quality of 2,6,6-tetramethylpiperidine oxide) is 0.1%~8.0% of the quality of regenerated cellulose fabric, the quality of NaBr is 5.0%~80.0% of the quality of regenerated cellulose fabric, the available chlorine of NaClO solution The content is 5%-16%, the volume of NaClO solution is 30-80ml, and the NaClO solution is added in batches, 5-10ml each time; the oxidation reaction temperature is 0-15°C, and the pH value of the oxidation system is between 9.0-11.0 , the stirring speed is 200-400 rev/min. Specific examples of the preparation method of oxidized regenerated cellulose sodium carboxylate fabric: 2g floc viscose fabric, TEMPO 100mg, NaBr 0.96g, NaClO solution 60ml, react at 8°C, and keep the concentration of the reaction solution with 0.4mol/L NaOH solution When the pH is around 10.0, add NaClO solution in 4 times. When 31ml NaOH is consumed, the reaction is terminated, and the reaction solution is poured into excess ethanol (300ml), and the precipitate is oxidized regenerated cellulose sodium carboxylate fabric.
具体实施方式二:本实施方式与具体实施方式一的不同点是:盐酸的浓度为0.01~2.00mol/L。其它与实施方式一相同。Embodiment 2: The difference between this embodiment and
具体实施方式三:本实施方式与具体实施方式一的不同点是:盐酸的浓度为0.10~1.50mol/L。其它与实施方式一相同。Embodiment 3: The difference between this embodiment and
具体实施方式四:本实施方式与具体实施方式一至三之一的不同点是:水溶型止血材料中羧基官能团含量为0.17~2.25mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠的酸化度为5%~45%。其它与实施方式一至三之一相同。Embodiment 4: The difference between this embodiment and
具体实施方式五:本实施方式与具体实施方式一至五之一的不同点是:氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.40~4.14mmol/g。其它与实施方式一至四之一相同。Embodiment 5: The difference between this embodiment and
具体实施方式六:本实施方式与具体实施方式一至五之一的不同点是:氧化再生纤维素羧酸钠织物中羧酸钠与盐酸中氢离子的摩尔比为(4∶1)~(1∶10)。其它与实施方式一至四之一相同。Specific embodiment six: the difference between this embodiment and one of the specific embodiments one to five is: the mol ratio of sodium carboxylate and hydrogen ion in hydrochloric acid in the oxidized regenerated cellulose sodium carboxylate fabric is (4: 1)~(1 : 10). Others are the same as one of
具体实施方式七:本实施方式水溶型止血材料按以下步骤制备:Embodiment 7: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯上,再加入盐酸密闭酸化0.5~72h,酸化温度为10~30℃,然后用无水乙醇减压抽滤冲洗3~5次,再置于-10~-80℃环境中冷冻干燥24~120h,即得到水溶型止血材料;Wrap the oxidized regenerated cellulose sodium carboxylate fabric on the glass porous core of the acidification rotary reactor, then add hydrochloric acid for closed acidification for 0.5-72 hours, the acidification temperature is 10-30°C, and then rinse with absolute ethanol for 3-3~ 5 times, and then freeze-dried in an environment of -10 to -80°C for 24 to 120 hours to obtain a water-soluble hemostatic material;
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.30~4.77mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠与盐酸中氢离子的摩尔比为(100∶1)~(1∶20);酸化回转反应器的转速为100~400r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.30~4.77mmol/g, and the molar ratio of sodium carboxylate and hydrogen ion in the hydrochloric acid in the oxidized regenerated cellulose sodium carboxylate fabric is (100:1) ~(1:20); the rotating speed of the acidification rotary reactor is 100~400r/min, and the hydrochloric acid added to the acidification rotary reactor does not directly contact with the oxidized regenerated cellulose sodium carboxylate fabric when the acidification rotary reactor does not start .
氧化再生纤维素羧酸钠织物是利用氧化体系为2,2,6,6-四甲基哌啶氧化物自由基TEMPO-NaBr-NaClO与再生纤维素织物反应氧化制得,其中TEMPO(2,2,6,6-四甲基哌啶氧化物)的质量为再生纤维素织物质量的0.1%~8.0%,NaBr的质量为再生纤维素织物质量的5.0%~80.0%,NaClO溶液的有效氯含量为5%~16%、NaClO溶液体积为30~80ml,NaClO溶液采用分批加入方式,每次为5~10ml;氧化反应温度为0~15℃,氧化体系的pH值介于9.0~11.0,搅拌速度为200~400转/min。氧化再生纤维素羧酸钠织物制备方法具体实例:2g絮状粘胶纤维织物、TEMPO 100mg、NaBr 0.96g、NaClO溶液60ml,于8℃下发生反应,用0.4mol/L NaOH溶液保持反应液的pH在10.0左右,分4次加入NaClO溶液,消耗31ml NaOH时,终止反应,把反应液倾倒入过量的乙醇(300ml)中,析出物即为氧化再生纤维素羧酸钠织物。Oxidized regenerated cellulose sodium carboxylate fabric is made by oxidation system of 2,2,6,6-tetramethylpiperidine oxide free radical TEMPO-NaBr-NaClO and regenerated cellulose fabric, wherein TEMPO(2, The quality of 2,6,6-tetramethylpiperidine oxide) is 0.1%~8.0% of the quality of regenerated cellulose fabric, the quality of NaBr is 5.0%~80.0% of the quality of regenerated cellulose fabric, the available chlorine of NaClO solution The content is 5%-16%, the volume of NaClO solution is 30-80ml, and the NaClO solution is added in batches, 5-10ml each time; the oxidation reaction temperature is 0-15°C, and the pH value of the oxidation system is between 9.0-11.0 , the stirring speed is 200-400 rev/min. Specific examples of the preparation method of oxidized regenerated cellulose sodium carboxylate fabric: 2g floc viscose fabric, TEMPO 100mg, NaBr 0.96g, NaClO solution 60ml, react at 8°C, and keep the concentration of the reaction solution with 0.4mol/L NaOH solution When the pH is around 10.0, add NaClO solution in 4 times. When 31ml NaOH is consumed, the reaction is terminated, and the reaction solution is poured into excess ethanol (300ml), and the precipitate is oxidized regenerated cellulose sodium carboxylate fabric.
本实施方式水溶型止血材料中羧基官能团含量为0.10~5.21mmol/g,氧化再生纤维素羧酸钠织物中羧酸钠的酸化度为3%~98%。The content of carboxyl functional groups in the water-soluble hemostatic material of this embodiment is 0.10-5.21 mmol/g, and the acidification degree of sodium carboxylate in the oxidized regenerated cellulose sodium carboxylate fabric is 3%-98%.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
本实施方式酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。In the acidification process of this embodiment, the hydrochloric acid is brought to the top of the acidification rotary reactor by the raised
具体实施方式八:本实施方式与具体实施方式七的不同点是:盐酸的浓度为0.01~2.00mol/L。其它步骤及参数与实施方式七相同。Embodiment 8: The difference between this embodiment and Embodiment 7 is that the concentration of hydrochloric acid is 0.01-2.00 mol/L. Other steps and parameters are the same as those in Embodiment 7.
具体实施方式九:本实施方式与具体实施方式七的不同点是:盐酸的浓度为0.10~1.50mol/L。其它步骤及参数与实施方式七相同。Embodiment 9: The difference between this embodiment and Embodiment 7 is that the concentration of hydrochloric acid is 0.10-1.50 mol/L. Other steps and parameters are the same as those in Embodiment 7.
具体实施方式十:本实施方式与具体实施方式七至九之一的不同点是:氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.40~4.14mmol/g。其它步骤及参数与实施方式七至九之一相同。Embodiment 10: The difference between this embodiment and Embodiment 7 to Embodiment 9 is that the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.40-4.14 mmol/g. Other steps and parameters are the same as those in the seventh to ninth embodiments.
具体实施方式十一:本实施方式与具体实施方式七至十之一的不同点是:氧化再生纤维素羧酸钠织物中羧酸钠与盐酸中氢离子的摩尔比为(4∶1)~(1∶10)。其它步骤及参数与实施方式七至十之一相同。Embodiment eleven: the difference between this embodiment and embodiment seven to ten is: the mol ratio of sodium carboxylate and hydrogen ion in hydrochloric acid in the oxidized regenerated cellulose sodium carboxylate fabric is (4: 1)~ (1:10). Other steps and parameters are the same as Embodiments 7 to 11.
具体实施方式十二:本实施方式与具体实施方式七至十一之一的不同点是:酸化时间为8~48h,酸化温度为20~25℃。其它步骤及参数与实施方式七至十一之一相同。Embodiment 12: This embodiment differs from Embodiment 7 to Embodiment 11 in that: the acidification time is 8-48 hours, and the acidification temperature is 20-25°C. Other steps and parameters are the same as those in Embodiments 7 to 11.
本实施方式可以调节水溶型止血材料的酸化度,赋予本实施方式水溶型止血材料适合的强度和止血效果。This embodiment can adjust the acidification degree of the water-soluble hemostatic material, and endow the water-soluble hemostatic material with suitable strength and hemostatic effect.
具体实施方式十三:本实施方式与具体实施方式七至十二之一的不同点是:冷冻干燥温度为-20~-65℃、冷冻干燥时间为48~72h。其它步骤及参数与实施方式七至十二之一相同。Specific Embodiment Thirteen: The difference between this embodiment and Embodiments VII to Twelve is that the freeze-drying temperature is -20-65° C., and the freeze-drying time is 48-72 hours. Other steps and parameters are the same as those of Embodiments 7 to 12.
具体实施方式十四:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment Fourteen: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入55.77ml、浓度为0.01mol/L的盐酸,密闭酸化24h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥48h,即得到水溶型止血材料;Wrap 5.00g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.38mmol/g;酸化回转反应器的转速为100r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.38mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为0.11mmol/g,表明酸化度为3.10%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 0.11 mmol/g, indicating that the acidification degree is 3.10%.
本实施方式水溶型止血材料遇水或盐溶液后可以在10s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 10 seconds after encountering water or saline solution.
具体实施方式十五:本实施方式水溶型止血材料按以下步骤制备:Embodiment 15: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入135.20ml、浓度为0.01mol/L的盐酸,密闭酸化24h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥48h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.38mmol/g;酸化回转反应器的转速为150r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.38mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为0.27mmol/g,表明酸化度为7.93%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 0.27 mmol/g, indicating that the acidification degree is 7.93%.
本实施方式水溶型止血材料遇水或盐溶液后可以在10s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 10 seconds after encountering water or saline solution.
具体实施方式十六:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment Sixteen: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入1690.00ml、浓度为0.01mol/L的盐酸,密闭酸化24h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥48h,即得到水溶型止血材料;Wrap 5.00g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.38mmol/g;酸化回转反应器的转速为200r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.38mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.51mmol/g,表明酸化度为96.37%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.51 mmol/g, indicating that the acidification degree is 96.37%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
具体实施方式十七:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment Seventeen: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入11.83ml、浓度为0.50mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.38mmol/g;酸化回转反应器的转速为250r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.38mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为1.19mmol/g,表明酸化度为34.22%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 1.19 mmol/g, indicating that the acidification degree is 34.22%.
本实施方式水溶型止血材料遇水或盐溶液后可以在60s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 60 seconds after encountering water or saline solution.
具体实施方式十八:本实施方式水溶型止血材料按以下步骤制备:Embodiment 18: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入6.65ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为250r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为0.25mmol/g,表明酸化度为6.64%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 0.25 mmol/g, indicating that the acidification degree is 6.64%.
本实施方式水溶型止血材料遇水或盐溶液后可以在10s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 10 seconds after encountering water or saline solution.
具体实施方式十九:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment Nineteen: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入14.25ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为300r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为0.56mmol/g,表明酸化度为14.50%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 0.56 mmol/g, indicating that the acidification degree is 14.50%.
本实施方式水溶型止血材料遇水或盐溶液后可以在30s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 30 seconds after encountering water or saline solution.
具体实施方式二十:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment Twenty: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入28.5ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为350r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为1.12mmol/g,表明酸化度为28.87%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 1.12 mmol/g, indicating that the acidification degree is 28.87%.
本实施方式水溶型止血材料遇水或盐溶液后可以在60s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 60 seconds after encountering water or saline solution.
具体实施方式二十一:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment Twenty-one: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入38.00ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为400r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为1.47mmol/g,表明酸化度为37.52%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 1.47 mmol/g, indicating that the acidification degree is 37.52%.
本实施方式水溶型止血材料遇水或盐溶液后可以在60s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 60 seconds after encountering water or saline solution.
具体实施方式二十二:本实施方式水溶型止血材料按以下步骤制备:Specific embodiment twenty-two: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入61.75ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为200r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为2.49mmol/g,表明酸化度为62.17%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 2.49 mmol/g, indicating that the acidification degree is 62.17%.
本实施方式水溶型止血材料遇水或盐溶液后可以在60s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can quickly form a gel within 60 seconds after encountering water or saline solution.
具体实施方式二十三:本实施方式水溶型止血材料按以下步骤制备:Specific embodiment twenty-three: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入78.89ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为300r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.39mmol/g,表明酸化度为83.04%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.39 mmol/g, indicating that the acidification degree is 83.04%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
具体实施方式二十四:本实施方式水溶型止血材料按以下步骤制备:Specific Embodiment 24: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入95.00ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为200r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.98mmol/g,表明酸化度为96.33%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.98 mmol/g, indicating that the acidification degree is 96.33%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
具体实施方式二十五:本实施方式水溶型止血材料按以下步骤制备:Specific embodiment twenty-five: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入95.00ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为300r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.98mmol/g,表明酸化度为96.33%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.98 mmol/g, indicating that the acidification degree is 96.33%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
具体实施方式二十六:本实施方式水溶型止血材料按以下步骤制备:Specific embodiment twenty-six: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入190.00ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为200r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.99mmol/g,表明酸化度为96.58%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.99 mmol/g, indicating that the acidification degree is 96.58%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
具体实施方式二十七:本实施方式水溶型止血材料按以下步骤制备:Specific embodiment twenty-seven: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入190.00ml、浓度为0.20mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为120r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.99mmol/g,表明酸化度为96.58%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.99 mmol/g, indicating that the acidification degree is 96.58%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
具体实施方式二十八:本实施方式水溶型止血材料按以下步骤制备:Specific embodiment twenty-eight: In this embodiment, the water-soluble hemostatic material is prepared according to the following steps:
将5.00g氧化再生纤维素羧酸钠织物缠绕到酸化回转反应器的玻璃多孔芯1上,再加入95.00ml、浓度为2.00mol/L的盐酸,密闭酸化48h,酸化温度为25℃,然后用无水乙醇减压抽滤冲洗5次,再置于-50℃环境中冷冻干燥72h,即得到水溶型止血材料;Wrap 5.00 g of oxidized regenerated cellulose sodium carboxylate fabric on the glass
其中,氧化再生纤维素羧酸钠织物中羧酸钠官能团含量为3.80mmol/g;酸化回转反应器的转速为180r/min,且加入酸化回转反应器的盐酸在酸化回转反应器不启动的情况下不直接与氧化再生纤维素羧酸钠织物接触。Wherein, the sodium carboxylate functional group content in the oxidized regenerated cellulose sodium carboxylate fabric is 3.80mmol/g; Do not directly contact the oxidized regenerated cellulose sodium carboxylate fabric.
酸化回转反应器的结构示意图如图1所示,酸化回转反应器的剖面图如图2所示,酸化回转反应器的横截面如图3所示,玻璃多孔芯1位于酸化回转反应器的轴芯,旋转方向如图1所示。The schematic diagram of the structure of the acidification rotary reactor is shown in Figure 1, the cross section of the acidification rotary reactor is shown in Figure 2, the cross section of the acidification rotary reactor is shown in Figure 3, and the glass
酸化过程中盐酸由酸化回转反应器内部的凸起楞2带至酸化回转反应器内部顶端,再由重力落下与缠绕到酸化回转反应器的玻璃多孔芯1上的氧化再生纤维素羧酸钠织物接触。During the acidification process, the hydrochloric acid is carried from the raised
滴定本实施方式水溶型止血材料的羧基官能团含量为3.96mmol/g,表明酸化度为95.76%。Titration of the carboxyl functional group content of the water-soluble hemostatic material in this embodiment is 3.96 mmol/g, indicating that the acidification degree is 95.76%.
本实施方式水溶型止血材料遇水或盐溶液后可以在120s内迅速形成凝胶。In this embodiment, the water-soluble hemostatic material can rapidly form a gel within 120 seconds after encountering water or saline solution.
止血性能对比实验:Hemostatic performance comparison experiment:
选用体重3.0Kg新西兰白兔20只,随机分为4组每组5只;对应测试材料分别为:普通消毒纱布(空白对照组)、氧化再生纤维素(阳性对照组)、具体实施方式二十一制备的水溶型止血材料(羧基官能团含量为1.47mmol/g)和具体实施方式十四制备的水溶型止血材料(羧基官能团含量为0.11mmol/g)。将新西兰大白兔固定在解剖台上,耳缘静脉消毒后缓慢注射1ml 2.5%戊巴比妥钠溶液,待兔子麻醉后,逐层开腹,用无菌纱布吸干腹腔、腹壁上的组织液和血液,暴露肝脏。在肝叶上用手术刀作1.0cm×1.0cm×0.3cm的创面。在创面形成过程中渗血先用灭菌后的医用纱布吸收,然后将1.5cm×1.5cm上述止血材料敷压于创面,敷压时以灭菌医用纱布为辅助,观察止血效果,并用秒表计时,观察止血效果,待完全止血后记录止血时间;每种材料分别重复5次测试,分别记录完全止血时间,结果如表1。Select 20 New Zealand white rabbits with a body weight of 3.0Kg, and randomly divide them into 4 groups of 5 each; the corresponding test materials are respectively: common sterile gauze (blank control group), oxidized regenerated cellulose (positive control group), specific implementation methods 20 A prepared water-soluble hemostatic material (with a carboxyl functional group content of 1.47 mmol/g) and Embodiment 14 A prepared water-soluble hemostatic material (with a carboxyl functional group content of 0.11 mmol/g). New Zealand white rabbits were fixed on the dissection table, and 1ml of 2.5% pentobarbital sodium solution was slowly injected after disinfection of the ear veins. After the rabbits were anesthetized, the abdominal cavity was opened layer by layer, and the tissue fluid and blood, exposing the liver. A wound of 1.0 cm×1.0 cm×0.3 cm was made on the liver lobe with a scalpel. During the process of wound formation, oozing blood is first absorbed with sterilized medical gauze, and then the above-mentioned hemostatic material of 1.5cm×1.5cm is applied to the wound surface, and the sterilized medical gauze is used as an aid in compressing, and the hemostatic effect is observed and timed with a stopwatch , observe the hemostatic effect, and record the hemostatic time after complete hemostasis; repeat the test 5 times for each material, and record the complete hemostatic time respectively, the results are shown in Table 1.
表1Table 1
实验结果说明水溶型止血材料具有更快的止血速度。The experimental results show that the water-soluble hemostatic material has a faster hemostasis speed.
将氧化再生纤维素止血材料置于创面上方,60s后观察到氧化再生纤维素止血材料仍然位于创口上方,出血情况没有好转(如图4所示)。将本实施方式制备的水溶型止血材料置于创面上方,60s后观察到本实施方式制备的水溶型止血材料已经与新西兰白兔的肝相融合,变为透明凝胶状(如图5所示),并将创口封闭,达到止血效果。The oxidized regenerated cellulose hemostatic material was placed on the wound surface, and after 60 seconds, it was observed that the oxidized regenerated cellulose hemostatic material was still located on the wound surface, and the bleeding did not improve (as shown in Figure 4). The water-soluble hemostatic material prepared in this embodiment was placed on the wound surface, and after 60 seconds, it was observed that the water-soluble hemostatic material prepared in this embodiment had merged with the liver of New Zealand white rabbits and became a transparent gel (as shown in Figure 5 ), and seal the wound to achieve hemostasis.
生物降解性能对比实验:Biodegradation performance comparison experiment:
选用体重3.0Kg新西兰白兔18只,随机分为3组每组6只,对应测试材料分别为:氧化再生纤维素(对照组)、具体实施方式二十一制备的水溶型止血材料(羧基官能团含量为1.47mmol/g)和具体实施方式十四制备的水溶型止血材料(羧基官能团含量为0.11mmol/g)。将新西兰大白兔固定在解剖台上,耳缘静脉消毒后缓慢注射1ml 2.5%戊巴比妥钠溶液使兔子麻醉。分别在脊柱两侧切口,在肌肉中埋植测试材料,材料尺寸为2.0cm×0.5cm,然后缝合。分别在术后1天、3天、7天、10天、14天、21天取出埋植部位的肌肉组织及植入材料,并作病理切片观察,总结植入材料完全被生物体吸收的时间,实验结果见表2。18 New Zealand white rabbits with a body weight of 3.0Kg were selected, randomly divided into 3 groups of 6, and the corresponding test materials were respectively: oxidized regenerated cellulose (control group), water-soluble hemostatic material (carboxyl functional group) prepared in specific embodiment 21 content of 1.47mmol/g) and the water-soluble hemostatic material prepared in Embodiment 14 (carboxyl functional group content of 0.11mmol/g). New Zealand white rabbits were fixed on the dissecting table, and 1ml of 2.5% pentobarbital sodium solution was slowly injected to anesthetize the rabbits after disinfection of the ear veins. Incisions were made on both sides of the spine, and test materials were implanted in the muscles with a size of 2.0cm×0.5cm, and then sutured. Take out the muscle tissue and implanted material at the implanted
表2Table 2
实验结果说明水溶型止血材料生物可吸收性好。The experimental results show that the water-soluble hemostatic material has good bioabsorbability.
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CN114349872B (en) * | 2021-12-21 | 2023-06-27 | 赵建 | Preparation process of oxidized regenerated cellulose material |
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