Absorbable hemostatic yarn and preparation process thereof

Abstract

The invention relates to the technical field of medical materials, and particularly discloses an absorbable hemostatic yarn and a preparation process thereof. The preparation technology of the absorbable hemostatic yarn comprises the steps that natural fibers are used as raw materials, a sodium periodate solution is used as an oxidation solution for oxidation to obtain prefabricated oxidized regenerated fibers, then the prefabricated oxidized regenerated fibers are modified through a glutathione activation solution to obtain modified oxidized regenerated fibers, and then alcohol cleaning, airing, loosening, weaving, cutting, inner wrapping, irradiation sterilization and outer wrapping are conducted to obtain the absorbable hemostatic yarn. The absorbable hemostatic yarn can be used for hemostasis in surgical operations, wound hands and the like, has excellent hemostatic performance, good mechanical property and biodegradability, and can be absorbed as soon as possible.

Description

Technical Field

[0001] The present application relates to the technical field of medical materials, and more specifically, to an absorbable hemostatic gauze and a preparation process thereof. Background Art

[0002] In surgical operations and trauma care, effective hemostatic materials are essential for controlling bleeding, reducing postoperative complications, and improving patient survival. As a new type of hemostatic material, absorbable hemostatic gauze has attracted widespread attention for its excellent biocompatibility, biodegradability, and non-toxicity.

[0003] When ligation or other conventional control methods are not applicable or ineffective during surgery, absorbable hemostatic gauze can be used as an auxiliary product to provide a mechanical framework for the mutual adhesion of platelets, allowing them to quickly form brown or black gel substances to seal bleeding points, control bleeding in capillaries, veins and arterioles, and thus achieve the effect of hemostasis. After completing the hemostatic task, absorbable hemostatic gauze can be gradually absorbed by the human body, significantly reducing the risks of long-term retention in the human body.

[0004] At present, absorbable hemostatic gauze is usually made from oxidized regenerated cellulose. Oxidized regenerated cellulose is a derivative of cellulose. It is obtained by first obtaining regenerated cellulose from natural fibers and then undergoing an oxidation process. The absorbable hemostatic gauze prepared in this way has good tissue compatibility, is biodegradable, can be completely absorbed by the body, and has almost no specific reaction to surrounding tissues. No toxic, allergic, or rejection reactions have occurred during the treatment process.

[0005] In view of the above-mentioned related technologies, the inventors found that the existing absorbable hemostatic gauze is usually highly acidic, which easily causes deformation of nerve fibers, limiting the application of absorbable hemostatic gauze in sensitive areas such as the brain. In addition, absorbable hemostatic gauze has problems such as excessive degradation speed and poor mechanical properties during use, which affects the sustainability of its hemostatic effect and seriously limits its application in the field of medical materials. Summary of the invention

[0006] In order to improve the mechanical properties of absorbable hemostatic yarn, improve the hemostatic effect of absorbable hemostatic yarn, and broaden the application scope of absorbable hemostatic yarn, the present application provides an absorbable hemostatic yarn and a preparation process thereof.

[0007] In a first aspect, the present application provides a preparation process of absorbable hemostatic gauze, which adopts the following technical solution: S1: Place the natural fiber in an oxidizing solution and soak it in dark at 35-45°C for 4-6 hours; S2: draining the oxidation liquid, placing the natural fiber soaked in the oxidation liquid in an ethylene glycol solution for soaking for 0.5-1h to obtain prefabricated oxidized regenerated fiber; S3: placing the prefabricated oxidized regenerated fiber in a glutathione active solution for immersion for 2.5-3.5 hours to obtain a modified oxidized regenerated fiber; S4: ultrasonically cleaning the modified oxidized regenerated fiber with an alcohol solution; S5: drying the cleaned modified oxidized regenerated fiber, and loosening it after natural drying for 6-8 hours to obtain oxidized regenerated fiber; S6: weaving and cutting the oxidized regenerated fiber to obtain a prefabricated absorbable hemostatic gauze; S7: The prefabricated absorbable hemostatic gauze is inner-wrapped, then sterilized by irradiation, and then outer-wrapped.

[0008] By adopting the above technical scheme, the prefabricated oxidized regenerated fiber is modified by an active solution of glutathione, and glutathione is loaded on the oxidized regenerated fiber while effectively controlling the carboxyl content in the oxidized regenerated fiber.

[0009] First, there is an activated ester intermediate in the glutathione activation solution, and this activated ester intermediate has a higher reaction selectivity to the carboxyl group in the oxidized regenerated cellulose after the natural fiber is oxidized under the reaction conditions of the present application. It can react with the carboxyl group formed by excessive oxidation to form a stable amide bond and reduce the reaction with the aldehyde group in the oxidized regenerated cellulose, thereby effectively reducing the carboxyl content in the oxidized regenerated fiber and reducing the interference with the functional groups in the regenerated cellulose that may be involved in the hemostatic performance, such as the aldehyde group, and maintaining the hemostatic performance of the absorbable hemostatic yarn.

[0010] Secondly, glutathione contains thiol (-SH), which can form disulfide bonds with carboxyl groups in oxidized regenerated cellulose to produce new cross-linking points, which can effectively improve the overall strength and toughness of the regenerated hemostatic yarn prepared from oxidized regenerated fibers. Due to the rotational freedom of the peptide bonds in glutathione, glutathione is flexible, which can improve the elasticity of the absorbable hemostatic yarn prepared from oxidized regenerated fibers, making the hemostatic yarn less likely to break when stretched, further improving the mechanical properties of the absorbable hemostatic yarn.

[0011] In addition, glutathione may stabilize platelets and coagulation factors through its antioxidant effect, enhancing the hemostatic effect of hemostatic gauze. As an important peptide in cells, glutathione can provide essential amino acids for wound healing, support cell growth and repair, and promote wound healing.

[0012] Optionally, the natural fiber is a natural plant fiber selected from any one of cotton fiber, flax fiber, wood pulp fiber and bamboo fiber.

[0013] Optionally, the oxidizing liquid is a 0.02-0.04 mol / L sodium periodate solution with a pH value of 5.7-6.3.

[0014] By adopting the above technical scheme, sodium periodate selectively oxidizes the secondary hydroxyl groups of oxidized cellulose in natural fibers, so that the secondary hydroxyl groups at the C2 and C3 positions of cellulose are oxidized, thereby introducing a dialdehyde structure into the cellulose chain.

[0015] Optionally, the method for preparing the glutathione activation solution comprises the following steps: Mixing glutathione with 2-(N-morpholino)ethane sulfonic acid buffer and adjusting the pH to 6-7 to form a glutathione buffer, wherein the concentration of glutathione is 1-1.6 mol / L; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide is added to glutathione buffer, stirred for reaction for 2-4 hours, and then N-hydroxysuccinimide is added, and the reaction is continued for 1.5-2.5 hours to obtain the product; the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to glutathione is 1:(3-4); the molar ratio of N-hydroxysuccinimide to glutathione is 1:(2-3).

[0016] By adopting the above technical scheme, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide is added to a buffer solution containing glutathione. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as an activator can activate the carboxyl group of glutathione and react with the carboxyl group of glutathione to form a highly reactive carboxyl activated intermediate.

[0017] N-hydroxysuccinimide reacts with the amino group of glutathione under the activation of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to form an NHS activated ester intermediate. This NHS activated ester intermediate has a higher reaction selectivity for the carboxyl group of oxidized regenerated fiber, and can preferentially react with the carboxyl group in oxidized regenerated cellulose to form a stable amide bond, reduce the reaction with the aldehyde group, and protect the functional groups involved in hemostasis in the regenerated cellulose.

[0018] Optionally, step S4 specifically includes the following steps: (1) adding the modified oxidized regenerated fiber to a 75% alcohol solution for ultrasonic cleaning for 15-25 minutes, and drying for 1-2 minutes; (2) adding the modified oxidized regenerated fiber dried in step (1) to an 80% alcohol solution for ultrasonic cleaning for 15-25 minutes, drying for 1-2 minutes, and repeating 1-3 times; (3) Add the modified oxidized regenerated fiber dried in step (2) into a 95% alcohol solution and perform ultrasonic cleaning for 15-25 minutes, and then dry for 1-2 minutes to obtain the fiber.

[0019] By adopting the above technical scheme, the oxidized regenerated fibers are cleaned with alcohol solutions of different concentration gradients. On the one hand, multiple cleanings with different concentrations of medium-concentration alcohol can effectively kill microorganisms and various impurities on the fiber surface without affecting the absorbable hemostatic gauze fiber structure.

[0020] On the other hand, the final cleaning with high concentration of alcohol can form a proper amount of microporous structure on the fiber surface and improve the roughness of the fiber surface. This makes the absorbable hemostatic gauze applicable to various non-planar hemostatic sites, increases the contact area between the absorbable hemostatic gauze and the hemostatic site, promotes blood coagulation and platelet adhesion, enhances the hemostatic effect of the absorbable hemostatic gauze, and facilitates the absorption of the absorbable hemostatic gauze.

[0021] Optionally, the prefabricated absorbable hemostatic gauze is pretreated as follows before inner packaging: Mixing Ganoderma lucidum polysaccharide and water at a solid-liquid ratio of 1:(15-20) to obtain a loading solution; The prefabricated absorbable hemostatic gauze is immersed in a loading liquid for 2-6 hours, then washed and filtered with deionized water for 4-6 times, and then vacuum-freeze-dried to obtain the hemostatic gauze.

[0022] By adopting the above technical solution, Ganoderma lucidum polysaccharide is loaded onto the absorbable hemostatic gauze. Ganoderma lucidum polysaccharide has an immunomodulatory effect, while glutathione promotes the growth and repair of immune cells. The synergistic effect of the two can effectively improve the wound's resistance to infection, reduce the risk of infection, and promote wound healing.

[0023] Optionally, the prefabricated absorbable hemostatic gauze is sterilized by irradiation after inner wrapping by using cobalt 60 gamma rays, and the irradiation dose is 20 kGy.

[0024] By adopting the above technical solution, the absorbable hemostatic gauze can be efficiently sterilized by using cobalt 610 gamma ray irradiation to ensure that the hemostatic gauze reaches a sterile state, while having little impact on the fiber structure and maintaining the hemostatic properties of the oxidative regenerated fiber.

[0025] In a second aspect, the present application provides an absorbable hemostatic gauze, which adopts the following technical solution: An absorbable hemostatic gauze is prepared by a preparation process of the absorbable hemostatic gauze of the present application.

[0026] In summary, this application has the following beneficial effects: 1. The present application modifies natural fibers by using glutathione activation solution. On the one hand, the activated ester in the glutathione activation solution is used to modify the oxidized regenerated fibers formed by oxidation of natural fibers, thereby effectively reducing the excess carboxyl groups formed during the oxidation process and protecting the groups with hemostatic properties in the oxidized regenerated fibers. On the other hand, the thiol (-SH) in glutathione can form disulfide bonds with the carboxyl groups in the oxidized regenerated cellulose to generate new cross-linking points, thereby improving the cross-linking network in the oxidized regenerated fibers, effectively improving the overall strength and toughness of the renewable hemostatic yarn, and improving the hemostatic properties of the absorbable hemostatic yarn.

[0027] 2. The present application modifies the surface of oxidative regenerated fibers and loads glutathione on it. The antioxidant property of the fiber stabilizes platelets and coagulation factors, while participating in the immune regulation and repair process of cells, providing essential amino acids for wound cells, supporting cell growth and repair, and significantly improving the hemostatic effect of the absorbable hemostatic gauze and promoting wound healing performance.

[0028] 3. The present application uses alcohol of different gradient concentrations to clean the oxidized regenerated fibers, which can form an appropriate amount of microporous structure on the fiber surface while sterilizing, thereby increasing the roughness of the fiber surface, thereby increasing the contact area between the absorbable hemostatic gauze and the hemostatic site, promoting blood coagulation and platelet adhesion, enhancing the hemostatic effect of the absorbable hemostatic gauze, and facilitating the absorption of the absorbable hemostatic gauze.

[0029] 4. The absorbable hemostatic gauze prepared by the preparation method of the present application has good degradability and a moderate degradation rate, and can meet the continuous hemostasis requirements. The carboxyl content of the oxidized regenerated cellulose in the absorbable hemostatic gauze is between 16.0-23%, and will not cause damage to the body's nerve fibers. It has broad prospects for application in the field of hemostasis of surgical wounds in sensitive areas such as the brain. DETAILED DESCRIPTION

[0030] The following examples further illustrate the present application in detail.

[0031] raw material Unless otherwise specified, the raw materials used in the examples and comparative examples of this application are all commercially available products, specifically: The natural fiber of the present application is a natural plant fiber, cotton fiber, which is derived from cotton, a plant of the genus Gossypium in the Malvaceae family, and has an average cellulose content of 92.5%; Glutathione, selected from Shanghai Yuanye Biotechnology Co., Ltd., reduced type S20186; 2-(N-Morpholino)ethanesulfonic acid, selected from Yingxin Laboratory, CAS: 4432-31-9, molecular formula: C6H 13 NO4S; 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, selected from Shanghai Yuanye Biotechnology Co., Ltd., S30053; N-hydroxysuccinimide, selected from Shanghai Yuanye Biotechnology Co., Ltd., S20179; Ganoderma lucidum polysaccharide, selected from Donghefu Biotechnology, Ganoderma lucidum polysaccharide 50%.

[0032] Preparation Example of Glutathione Activation Solution Preparation Example 1 Glutathione activation solution, and its preparation method, comprising the following steps: S1: Mix glutathione with 2-(N-morpholino)ethane sulfonic acid buffer, adjust the pH of the solution to 6, and form a glutathione buffer, wherein the concentration of glutathione is 1.3 mol / L; S2: Add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to glutathione buffer, stir and react at constant temperature for 3 hours at 25°C, then add N-hydroxysuccinimide and continue the reaction for 2 hours to obtain the product, wherein the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to glutathione is 1:3, and the molar ratio of N-hydroxysuccinimide to glutathione is 1:2.

[0033] Preparation Example 2 Glutathione activation solution, and its preparation method, comprising the following steps: S1: Mix glutathione and 2-(N-morpholino)ethane sulfonic acid buffer, adjust the pH of the solution to 6, and form a glutathione buffer, wherein the concentration of glutathione is 1 mol / L; S2: Add 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to glutathione buffer, stir and react at constant temperature for 2 hours at 25°C, then add N-hydroxysuccinimide and continue the reaction for 1.5 hours to obtain the product, wherein the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to glutathione is 1:4, and the molar ratio of N-hydroxysuccinimide to glutathione is 1:3.

[0034] Preparation Example 3 Glutathione activation solution, and its preparation method, comprising the following steps: S1: Mix glutathione and 2-(N-morpholino)ethane sulfonic acid buffer, adjust the solution pH to 7, and form a glutathione buffer, wherein the concentration of glutathione is 1.6 mol / L; S2: Add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to glutathione buffer, stir and react at constant temperature for 4 hours at 25°C, then add N-hydroxysuccinimide and continue the reaction for 2.5 hours to obtain the product, wherein the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to glutathione is 1:3, and the molar ratio of N-hydroxysuccinimide to glutathione is 1:2. Example

[0035] Example 1 An absorbable hemostatic gauze, and a preparation process thereof, comprising the following steps: S1: Use a cotton reaction tank, wrap the mesh cloth on a stainless steel barrel, then evenly wind the natural fiber on the stainless steel barrel, and then wrap the outer layer with mesh cloth, fix the upper and lower ends with a rolling belt, and then put on the stainless steel net barrel, and finally lock it with a top cover, put it into the reaction tank for sealing, and then use a diaphragm pump to add oxidation liquid to the reaction tank until the fiber is submerged, and soak it in the dark at 35°C for 6 hours. The oxidation liquid is 0.03 mol / L sodium periodate solution with a pH value of 6; S2: Open the drain valve to drain the oxidation liquid, add 20% ethylene glycol solution into the reaction tank until the fiber is submerged, soak for 1 hour, drain the ethylene glycol solution, dry it in air and take it out to obtain prefabricated oxidized regenerated fiber; S3: placing the prefabricated oxidized regenerated fiber in the glutathione active solution obtained in Preparation Example 1, and soaking it for 3 hours to obtain a modified oxidized regenerated fiber 1; S4: Ultrasonic cleaning of the modified oxidized regenerated fiber using alcohol solutions of different gradient concentrations: (1) adding the modified oxidized regenerated fiber to a 75% alcohol solution for ultrasonic cleaning for 15 minutes and centrifugation drying for 2 minutes; (2) adding the modified oxidized regenerated fiber dried in step (1) to an 80% alcohol solution for ultrasonic cleaning for 25 minutes, centrifugation drying for 2 minutes, and repeating once; (3) adding the modified oxidized regenerated fiber dried in step (2) to a 95% alcohol solution for ultrasonic cleaning for 25 minutes, and centrifugally drying for 2 minutes; S5: placing the cleaned modified oxidized regenerated fiber on a drying rack for natural drying for 8 hours, and then loosening it to obtain oxidized regenerated fiber; S6: Add the oxidized regenerated fiber into a braiding machine for braiding and cutting to obtain a prefabricated absorbable hemostatic yarn, wherein the unit mass of the prefabricated absorbable hemostatic yarn is 80 g / m 3 ; S7: The prefabricated absorbable hemostatic gauze is first wrapped with sulfuric acid paper and then placed in an aluminum foil bag and sealed for inner packaging. It is then sterilized by irradiation with cobalt 60γ rays with an irradiation dose of 20kGy. Finally, it is placed in a packaging box for outer packaging.

[0036] Example 2 An absorbable hemostatic gauze, and a preparation process thereof, comprising the following steps: S1: Use a cotton reaction tank, wrap the mesh cloth on a stainless steel barrel, then evenly wind the natural fiber on the stainless steel barrel, and then wrap the outer layer with mesh cloth, fix the upper and lower ends with a rolling belt, and then put on the stainless steel net barrel, and finally lock it with a top cover, put it into the reaction tank for sealing, and then use a diaphragm pump to add oxidation liquid to the reaction tank until the fiber is submerged, and soak it in the dark at 45°C for 4 hours. The oxidation liquid is 0.04 mol / L sodium periodate solution with a pH value of 6.3; S2: Open the drain valve to drain the oxidation liquid, add 20% ethylene glycol solution into the reaction tank until the fiber is submerged, soak for 0.5h, drain the ethylene glycol solution, dry it in air and take it out to obtain prefabricated oxidized regenerated fiber; S3: placing the prefabricated oxidized regenerated fiber in the glutathione active solution obtained in Preparation Example 1, and soaking it for 2.5 hours to obtain a modified oxidized regenerated fiber; S4: Ultrasonic cleaning of the modified oxidized regenerated fiber using alcohol solutions of different gradient concentrations: (1) adding the modified oxidized regenerated fiber to a 75% alcohol solution for ultrasonic cleaning for 25 minutes and centrifugation drying for 1 minute; (2) adding the modified oxidized regenerated fiber dried in step (1) to an 80% alcohol solution for ultrasonic cleaning for 15 minutes, centrifugation drying for 1 minute, and repeating twice; (3) adding the modified oxidized regenerated fiber dried in step (2) to a 95% alcohol solution for ultrasonic cleaning for 15 minutes, and centrifugally drying for 1 minute; S5: placing the cleaned modified oxidized regenerated fiber on a drying rack for natural drying for 6 hours, and then loosening it to obtain oxidized regenerated fiber; S6: Add the oxidized regenerated fiber into a braiding machine for braiding and cutting to obtain a prefabricated absorbable hemostatic yarn, wherein the unit mass of the prefabricated absorbable hemostatic yarn is 80 g / m 3 ; S7: The prefabricated absorbable hemostatic gauze is first wrapped with sulfuric acid paper and then placed in an aluminum foil bag and sealed for inner packaging. It is then sterilized by irradiation with cobalt 60γ rays with an irradiation dose of 20kGy. Finally, it is placed in a packaging box for outer packaging.

[0037] Example 3 An absorbable hemostatic gauze, and a preparation process thereof, comprising the following steps: S1: Use a cotton reaction tank, wrap the mesh cloth on a stainless steel barrel, then evenly wind the natural fiber on the stainless steel barrel, and then wrap the outer layer with mesh cloth, fix the upper and lower ends with a rolling belt, and then put on the stainless steel net barrel, and finally lock it with a top cover, put it into the reaction tank for sealing, and then use a diaphragm pump to add oxidation liquid to the reaction tank until the fiber is submerged, and soak it in the dark at 45°C for 6 hours. The oxidation liquid is 0.02 mol / L sodium periodate solution with a pH value of 5.7; S2: Open the drain valve to drain the oxidation liquid, add 20% ethylene glycol solution into the reaction tank until the fiber is submerged, soak for 1 hour, drain the ethylene glycol solution, dry it in air and take it out to obtain prefabricated oxidized regenerated fiber; S3: placing the prefabricated oxidized regenerated fiber in the glutathione active solution obtained in Preparation Example 1, and soaking it for 3.5 hours to obtain a modified oxidized regenerated fiber; S4: Ultrasonic cleaning of the modified oxidized regenerated fiber using alcohol solutions of different gradient concentrations: (1) adding the modified oxidized regenerated fiber to a 75% alcohol solution for ultrasonic cleaning for 20 minutes and centrifugation drying for 1 minute; (2) adding the modified oxidized regenerated fiber dried in step (1) to an 80% alcohol solution for ultrasonic cleaning for 20 minutes, centrifugation drying for 2 minutes, and repeating 3 times; (3) adding the modified oxidized regenerated fiber dried in step (2) to a 95% alcohol solution for ultrasonic cleaning for 20 minutes, and centrifugally drying for 2 minutes; S5: placing the cleaned modified oxidized regenerated fiber on a drying rack for natural drying for 7 hours, and then loosening it to obtain oxidized regenerated fiber; S6: Add the oxidized regenerated fiber into a braiding machine for braiding and cutting to obtain a prefabricated absorbable hemostatic yarn, wherein the unit mass of the prefabricated absorbable hemostatic yarn is 80 g / m 3 ; S7: The prefabricated absorbable hemostatic gauze is first wrapped with sulfuric acid paper and then placed in an aluminum foil bag and sealed for inner packaging. It is then sterilized by irradiation with cobalt 60γ rays with an irradiation dose of 20kGy. Finally, it is placed in a packaging box for outer packaging.

[0038] Example 4 An absorbable hemostatic gauze is different from Example 1 in that the glutathione active liquid used in step S3 is obtained from Preparation Example 2, and the other steps are the same as Example 1.

[0039] Example 5 An absorbable hemostatic gauze is different from Example 1 in that the glutathione active liquid used in step S3 is obtained from Preparation Example 3, and the other steps are the same as Example 1.

[0040] Example 6 An absorbable hemostatic gauze is different from Example 1 in that in step S4, the modified oxidized regenerated fiber is not ultrasonically cleaned using alcohol solutions of different gradients, and the other steps are the same as those in Example 1. The specific method is as follows: The modified oxidized regenerated fiber was added to a 75% alcohol solution for ultrasonic cleaning for 15 minutes, and centrifuged for 2 minutes, and the above operation was repeated 3 times.

[0041] Example 7 An absorbable hemostatic gauze is different from Example 1 in that in step S4, the modified oxidized regenerated fiber is not ultrasonically cleaned using alcohol solutions of different gradients, and the other steps are the same as those in Example 1. The specific method is as follows: The modified oxidized regenerated fiber was added to 80% alcohol solution for ultrasonic cleaning for 15 minutes, centrifuged and dried for 2 minutes, and the above operation was repeated 3 times; The unit mass of the obtained prefabricated absorbable hemostatic gauze is 80 g / m 3 .

[0042] Example 8 An absorbable hemostatic gauze is different from Example 1 in that in step S4, the modified oxidized regenerated fiber is not ultrasonically cleaned using alcohol solutions of different gradients, and the other steps are the same as those in Example 1. The specific method is as follows: The modified oxidized regenerated fiber was added to a 95% alcohol solution for ultrasonic cleaning for 15 minutes, centrifuged and dried for 2 minutes, and the above operation was repeated 3 times; The unit mass of the obtained prefabricated absorbable hemostatic gauze is 80 g / m 3 .

[0043] Example 9 An absorbable hemostatic gauze, which is different from Example 1 in that the prefabricated absorbable hemostatic gauze obtained in step S6 is subjected to the following pretreatment before the operation of step S7: (1) mixing Ganoderma lucidum polysaccharide and water at a solid-liquid ratio of 1:15 to obtain a loading solution; (2) The prefabricated absorbable hemostatic gauze was immersed in the loading liquid for 2 hours, then washed with deionized water, filtered 4 times, and vacuum-freeze-dried to obtain the pretreated absorbable hemostatic gauze. The other steps were the same as those in Example 1. The unit mass of the obtained prefabricated absorbable hemostatic gauze is 80 g / m 3 .

[0044] Example 10 An absorbable hemostatic gauze, which is different from Example 1 in that the prefabricated absorbable hemostatic gauze obtained in step S6 is subjected to the following pretreatment before the operation of step S7: (1) mixing Ganoderma lucidum polysaccharide and water at a solid-liquid ratio of 1:20 to obtain a loading solution; (2) The prefabricated absorbable hemostatic gauze was immersed in the loading liquid for 6 hours, then washed with deionized water, filtered 6 times, and vacuum-freeze-dried to obtain the pretreated absorbable hemostatic gauze. The other steps were the same as those in Example 1. The unit mass of the obtained prefabricated absorbable hemostatic gauze is 80 g / m 3 .

[0045] Comparative Example Comparative Example 1 An absorbable hemostatic gauze, which differs from Example 1 in that the modification treatment of the glutathione activation solution in step S3 is not performed, and the prefabricated oxidized regenerated fiber is directly cleaned with an alcohol solution. The other steps are the same as those in Example 1. The unit mass of the obtained prefabricated absorbable hemostatic gauze is 80 g / m 3 .

[0046] Performance testing The following relevant performance test was performed on an absorbable hemostatic gauze obtained in Examples 1-8 and Comparative Example 1. When conducting animal experiments, all animal experiments complied with the animal protection regulations and relevant laws and regulations to ensure that the animals received proper care and treatment during the experiment, and the animals were properly handled after the experiment.

[0047] 1. Carboxyl content detection: S1: Before the absorbable hemostatic gauze is wrapped, dry it at 90℃ for 2h, take 1g and place it in a 250mL conical flask, add 10mL of 0.5mol / L sodium hydroxide solution, rotary evaporate, add 100mL of water and 2 drops of phenolphthalein solution (the volume ratio of phenolphthalein to ethanol is 1:100), and immediately titrate with 0.1mol / L hydrochloric acid solution until the phenolphthalein solution is colorless. Perform blank correction, 1mL of 0.1mol / L hydrochloric acid solution is equivalent to 4.5mg of carboxyl (COOH); S2: Calculate the carboxyl content, based on X1, X1 = (V1-V2) cM / (1000×m)×100%; Wherein V1 is the volume of 0.1 mol / L hydrochloric acid standard titration solution consumed by the blank, in mL; V2 is the volume of 0.1 mol / L hydrochloric acid standard titration solution consumed by the sample, in mL; c is the exact concentration of 0.1 mol / L hydrochloric acid standard titration solution, in mol / L; m is the mass of the sample, in g; M is the molar mass of carboxyl group (45), in g / mol.

[0048] 2. Detection of average hemostasis time: S1: 33 healthy beagle dogs with similar growth conditions and body weight of 10-15 kg were selected as the test group to establish a canine cranial cerebral cortical vascular hemorrhage model for animal experiments. They were divided into 11 groups, with 3 dogs in each group; S2: After anesthesia, the animal was placed supine on the operating table. A scalpel was used to cut the scalp and fascia along the midline of the skull, and an electric knife was used to cut and separate the muscles of the skull. Then, a periosteal stripper was used to peel off the periosteum to expose the top skull. A high-speed drill was used to create a 3×2 cm bone window on the top skull. A dura mater defect was made on the exposed bone window avoiding the superior sagittal sinus to expose the cerebral cortex. Gauze was used to scratch the blood vessels of the cerebral cortex to create a bleeding model in the dog's cerebral cortex. S3: After the bleeding model is successfully prepared, the wound surface is allowed to bleed freely for 5 seconds, and then the absorbable hemostatic gauze prepared in Examples 1-10 and Comparative Example 1 of equal weight is accurately weighed and applied to the bleeding wound surface, and the same pressure is applied to press it to ensure that it is in close contact with the bleeding site; S4: After pressing for 60 seconds, cancel the pressing and observe the bleeding of the wound. If bleeding is observed, continue pressing and gently relax every 30 seconds to observe the bleeding. If there is no bleeding after removing the finger pressure, it is considered that the hemostasis is successful and the complete hemostasis time is recorded. The complete hemostasis time refers to the time from the use of absorbable hemostatic gauze to the cessation of bleeding from the wound. If the bleeding cannot be effectively stopped after continuous observation for 5 minutes, it is considered that the bleeding cannot be stopped. S5: Calculate the complete hemostasis time of three beagle dogs in each group, calculate the average value as the final result and record it in Table 1.

[0049] 3. Degradation speed detection: S1: 33 New Zealand rabbits with similar growth conditions and body weight of 2-2.5 kg were selected as the test group to establish a bleeding model for animal experiments. They were divided into 11 groups, with 3 rabbits in each group; S2: The New Zealand rabbit was disinfected with iodine near the thigh vein, and then a 10 mm wound was made with a scalpel; S3: Weigh the same mass of the absorbable hemostatic gauze obtained in Examples 1-10 and Comparative Example 1 respectively, the size of which can completely cover the wound surface, quickly insert it into the wound, clean the blood oozing from the wound with ordinary sterilized gauze, and then suture the wound; S4: The wound was observed and the stitches were removed on the 7th day after surgery. The remaining amount of each absorbable hemostatic gauze of three New Zealand rabbits in each group was measured and recorded, and the average value was calculated as the final result and recorded in Table 1.

[0050] 4. Viscosity work index: 1 g of the absorbable hemostatic gauze obtained in Examples 1-8 and Comparative Example 1 was taken as samples respectively, water was added until saturated with water to form a viscous gel of a coagulated water mixture, and the viscosity work index thereof was measured using a texture analyzer.

[0051] The test probe is: P36R (cylindrical probe), the test conditions are room temperature, the speed before the test is 0.7mm / s; the test speed is 1.5mm / s; the speed after the test is 18mm / s; the stress is 120g; the recovery distance is 6.0mm; the contact time is 16s; the trigger type is automatic-5g.

[0052] 5. Mechanical properties: Referring to the provisions and methods of GB / T 24218.3-2010, the tensile strength of the absorbable hemostatic gauze obtained in Examples 1-8 and Comparative Example 1 was tested. Each group of experiments was performed 3 times, and the average value was taken as the final result and the final result was recorded in Table 1.

[0053] Table 1 According to the performance test results in Table 1, it can be seen that the carboxyl content of the oxidized regenerated cellulose in the absorbable hemostatic yarn of the present application is between 16.0-23.0%, the viscosity function index is between 228-265g·sec, and the tensile strength is between 5.12-6.68MPa. When it is used as a medical hemostatic material for clinical surgical operations and trauma care, the average hemostasis time is less than 182s. It can be absorbed and degraded by the body with a moderate degradation rate, can meet the continuous hemostasis requirements, and can be used for wound hemostasis in sensitive parts such as the brain without causing damage to the body's nerve fibers.

[0054] According to the performance test results of Examples 1-10 and Comparative Example 1, it can be seen that the absorbable hemostatic gauze prepared by the preparation process of the present application significantly reduces the carboxyl content, improves the problems of excessive degradation rate and poor mechanical properties of the absorbable hemostatic gauze during use caused by the high carboxyl content, effectively improves the sustainability of the hemostatic effect of the absorbable hemostatic gauze, and improves the hemostatic effect of the absorbable hemostatic gauze and its performance in promoting wound recovery.

[0055] According to the performance test results of Examples 1-5 and Examples 6-8, it can be seen that cleaning the modified oxidized regenerated fibers with alcohol solutions of different gradients can form an appropriate amount of microporous structure on the fiber surface while effectively sterilizing and removing impurities, thereby increasing the roughness of the fiber surface, thereby increasing the contact area between the absorbable hemostatic gauze and the hemostatic site, promoting blood coagulation and platelet adhesion, and enhancing the hemostatic effect of the absorbable hemostatic gauze, while facilitating the absorption and degradation of the absorbable hemostatic gauze.

[0056] Then, using only high concentration of alcohol to wash the modified oxidized regenerated fiber multiple times will affect the fiber structure of the absorbable hemostatic yarn, destroy the structure of the oxidized regenerated fiber, and thus have an adverse effect on the performance of the absorbable hemostatic yarn. The fiber damage will also cause the mechanical properties of the absorbable hemostatic yarn to be damaged.

[0057] According to the performance test results of Examples 1-5 and Examples 9-10, it can be seen that loading Ganoderma lucidum polysaccharide onto absorbable hemostatic gauze shortens the average hemostasis time. This is because Ganoderma lucidum polysaccharide and glutathione work synergistically to improve the wound's anti-infection ability, promote the growth and repair of immune cells, and promote wound healing.

[0058] The loading of Ganoderma lucidum flavonoids can improve the wettability of the hemostatic gauze, making the fibers more uniform after absorbing water and swelling, which helps to improve the viscosity function index of the absorbable hemostatic gauze, further improve the hemostatic performance of the absorbable hemostatic gauze, and promote the degradation and absorption of the absorbable hemostatic gauze.

[0059] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A process for preparing absorbable hemostatic gauze, characterized in that: The following steps are involved: S1: Place the natural fiber in an oxidizing solution and soak it in dark at 35-45°C for 4-6 hours; S2: draining the oxidation liquid, placing the natural fiber soaked in the oxidation liquid in an ethylene glycol solution for soaking for 0.5-1h to obtain prefabricated oxidized regenerated fiber; S3: placing the prefabricated oxidized regenerated fiber in a glutathione active solution for immersion for 2.5-3.5 hours to obtain a modified oxidized regenerated fiber; S4: ultrasonically cleaning the modified oxidized regenerated fiber with an alcohol solution; S5: drying the cleaned modified oxidized regenerated fiber, and loosening it after natural drying for 6-8 hours to obtain oxidized regenerated fiber; S6: weaving and cutting the oxidized regenerated fiber to obtain a prefabricated absorbable hemostatic gauze; S7: The prefabricated absorbable hemostatic gauze is inner-wrapped, then sterilized by irradiation, and then outer-wrapped.

2. The preparation process of absorbable hemostatic gauze according to claim 1, characterized in that: The natural fiber is a natural plant fiber selected from any one of cotton fiber, flax fiber, wood pulp fiber and bamboo fiber.

3. The preparation process of absorbable hemostatic gauze according to claim 1, characterized in that: The oxidizing liquid is a 0.02-0.04 mol / L sodium periodate solution with a pH value of 5.7-6.

3.

4. The preparation process of absorbable hemostatic gauze according to claim 1, characterized in that: The preparation method of the glutathione activation solution comprises the following steps: Mixing glutathione with 2-(N-morpholino)ethane sulfonic acid buffer and adjusting the pH to 6-7 to form a glutathione buffer, wherein the concentration of glutathione is 1-1.6 mol / L; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide is added to glutathione buffer, stirred for reaction for 2-4 hours, and then N-hydroxysuccinimide is added, and the reaction is continued for 1.5-2.5 hours to obtain the product; the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to glutathione is 1:(3-4); the molar ratio of N-hydroxysuccinimide to glutathione is 1:(2-3).

5. The preparation process of absorbable hemostatic gauze according to claim 1, characterized in that: Step S4 specifically includes the following steps: (1) adding the modified oxidized regenerated fiber to a 75% alcohol solution for ultrasonic cleaning for 15-25 minutes, and drying for 1-2 minutes; (2) adding the modified oxidized regenerated fiber dried in step (1) to an 80% alcohol solution for ultrasonic cleaning for 15-25 minutes, drying for 1-2 minutes, and repeating 1-3 times; (3) Add the modified oxidized regenerated fiber dried in step (2) into a 95% alcohol solution and perform ultrasonic cleaning for 15-25 minutes, and then dry for 1-2 minutes to obtain the fiber.

6. The preparation process of absorbable hemostatic gauze according to claim 1, characterized in that: The prefabricated absorbable hemostatic gauze is pretreated as follows before inner packaging: Ganoderma lucidum polysaccharide and water are mixed at a solid-liquid ratio of 1:(15-20) to obtain a loading liquid; The prefabricated absorbable hemostatic gauze is immersed in a loading liquid for 2-6 hours, then washed and filtered with deionized water for 4-6 times, and then vacuum-freeze-dried to obtain the hemostatic gauze.

7. The process for preparing the absorbable hemostatic gauze according to claim 1, characterized in that: The prefabricated absorbable hemostatic gauze is sterilized by irradiation after inner packaging by using cobalt 60 gamma rays, and the irradiation dose is 20 kGy.

8. An absorbable hemostatic gauze, characterized in that: The absorbable hemostatic gauze is prepared by the preparation process of any one of claims 1 to 7.

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