阅读说明：本技术 一种医用创面修复用复合敷料及其制备方法 (Medical composite dressing for wound repair and preparation method thereof ) 是由 张佩华 孙玮 郭虹 高原 付少举 于 2020-04-16 设计创作，主要内容包括：本发明公开了一种医用创面修复用复合敷料,包括与创面接触的内层、中间层、外层三层,其特征在于,所述的内层为壳聚糖/聚乙烯醇/氧化海藻酸钠共混的纳米纤维抗菌层；所述的中间层为海藻酸钠/聚乙烯醇/羧甲基纤维素钠纳米纤维膜通过剪碎冻干等处理制备的气凝胶吸湿层；所述的外层为无纺布透气层,所述内层、中间层、外层经过医用胶复合而成。本发明的复合敷料,利用静电纺丝技术提高了敷料的机械性能,同时根据静电纺丝工艺制备的纳米纤维膜及后处理得到的纳米纤维膜气凝胶具备了高孔隙率和大表面积,能够保证高吸湿保湿性能的同时兼具优异的透气性,减少渗出液扩散,保持皮肤清洁,可在各种伤口的恢复治疗中广泛得到应用。(The invention discloses a medical composite dressing for wound repair, which comprises an inner layer, a middle layer and an outer layer which are in contact with a wound, and is characterized in that the inner layer is a nano-fiber antibacterial layer blended by chitosan/polyvinyl alcohol/oxidized sodium alginate; the middle layer is an aerogel moisture absorption layer prepared by shearing, crushing, freeze-drying and the like on a sodium alginate/polyvinyl alcohol/sodium carboxymethylcellulose nanofiber membrane; the outer layer is a non-woven fabric breathable layer, and the inner layer, the middle layer and the outer layer are formed by compounding medical adhesive. The composite dressing disclosed by the invention improves the mechanical property of the dressing by utilizing an electrostatic spinning technology, and the nanofiber membrane prepared according to the electrostatic spinning technology and the nanofiber membrane aerogel obtained by post-treatment have high porosity and large surface area, can ensure high moisture absorption and retention performance, simultaneously have excellent air permeability, reduce exudate diffusion, keep the skin clean, and can be widely applied to recovery treatment of various wounds.)

1. A medical composite dressing for wound surface repair comprises an inner layer, a middle layer and an outer layer which are in contact with a wound surface, and is characterized in that the inner layer is a nanofiber antibacterial layer blended by chitosan/polyvinyl alcohol/oxidized sodium alginate; the middle layer is an aerogel moisture absorption layer prepared by shearing, crushing, freeze-drying and the like on a sodium alginate/polyvinyl alcohol/sodium carboxymethylcellulose nanofiber membrane; the outer layer is a non-woven fabric breathable layer, and the inner layer, the middle layer and the outer layer are formed by compounding medical adhesive.

2. A medical composite dressing for wound repair as claimed in claim 1, wherein the diameter of the blended fiber of the nanofiber antibacterial layer is 100-300nm, and the thickness of the fiber layer is 0.1-0.3 mm.

3. A medical composite dressing for wound healing according to claim 1, wherein the aerogel moisture absorption layer in the middle layer has a thickness of 1 to 3mm and a porosity of 95 to 99%.

4. A medical composite dressing for wound healing as claimed in claim 1, wherein the grammage of the air-permeable layer of the outer non-woven fabric is 60g/m²And the thickness is 1 mm.

5. A method of manufacturing a medical wound healing composite dressing according to any of claims 1 to 4, comprising the steps of:

step 1, preparing an inner layer:

mixing chitosan and polyvinyl alcohol according to the mass percentage of 10-30:70-90, dissolving in 20-40% of acetic acid aqueous solution to obtain 10% spinning solution, heating in water bath at 90 ℃, stirring for 4-6 hours until the solution is dissolved, standing and cooling for 2 hours, adding 5-30% of oxidized sodium alginate into the spinning solution, and stirring at normal temperature until the solution is completely dispersed;

under the conditions of normal temperature and humidity of less than 50%, performing electrostatic spinning on the spinning solution, controlling the receiving distance to be 16-18cm, the flow rate of the spinning solution to be 0.3-0.7mL/h, the voltage to be 16-20KV and the needle head to be 20G, and collecting a chitosan/polyvinyl alcohol/sodium alginate oxide blended fiber membrane on a receiving board to obtain an inner layer nanofiber antibacterial layer;

step 2, preparing an intermediate layer:

sodium alginate, sodium carboxymethylcellulose and polyvinyl alcohol are mixed according to the mass percentage of 10-30: 1-12: 58-89, dissolving in water solution to obtain spinning solution with the concentration of 10%, heating in water bath at 90 ℃ and stirring for 4-6 hours until the spinning solution is completely dissolved, standing and cooling for 2 hours for later use;

under the conditions of normal temperature and humidity less than 50%, carrying out electrostatic spinning on the spinning solution, controlling the receiving distance to be 16-18cm, the flow rate of the spinning solution to be 0.3-0.7mL/h, the voltage to be 16-20KV and the needle head to be 21G, and collecting the sodium alginate/polyvinyl alcohol/sodium carboxymethylcellulose blended fiber membrane on a receiving board;

selecting 1-5% calcium chloride solution to perform crosslinking treatment on the fiber membrane for 24h, rinsing with anhydrous ethanol for 4 times, drying with filter paper in a vacuum oven at 50 deg.C for 30min, and packaging with a sealed bag;

shearing the crosslinked fiber membrane, and adding the fiber membrane into a tert-butyl alcohol aqueous solution with the volume ratio of 20% to obtain a fiber dispersion solution with the mass volume ratio of 0.5%; homogenizing the fiber dispersion liquid for 10-20min, stirring at room temperature for 2-4h, pouring into a culture dish, controlling the thickness of the fiber dispersion liquid to be 1-3mm, pre-freezing in a refrigerator for 12h, and drying in a freeze dryer for 24h to obtain the middle-layer aerogel moisture absorption layer.

Step 3, preparing a three-layer composite structure:

and (3) overlapping the outer non-woven fabric breathable layer, the middle aerogel moisture absorption layer and the inner nanofiber antibacterial layer together through a medical adhesive layer from bottom to top, and cutting the layers into the same shape and size to obtain the medical composite dressing for wound repair.

6. The method for preparing a medical composite dressing for wound repair as claimed in claim 5, wherein the preparation of sodium alginate oxide in step 1 specifically comprises: dissolving sodium alginate in absolute ethyl alcohol to obtain a sodium alginate ethanol solution, dissolving sodium periodate in deionized water to obtain a sodium periodate aqueous solution, mixing the two solutions, placing the two solutions on a magnetic stirrer in a dark place, stirring for 6 hours for oxidation reaction, adding glycol with the same mole as the sodium periodate after the reaction is finished, stopping the reaction for 30 minutes, dialyzing for 3 days, changing water for 1 time every 6 hours, and finally freeze-drying dialysate to obtain oxidized sodium alginate containing aldehyde groups; wherein the concentration of sodium alginate in the sodium alginate ethanol solution is 0.1g/mL, and the concentration of sodium periodate in the sodium periodate aqueous solution is 0.04 g/mL.

Technical Field

The invention relates to a preparation method of a medical composite dressing for wound repair, belonging to the field of medical materials.

Background

The formation of wounds is mainly due to damage to the skin, mucosal surfaces or the breakdown of the integrity of the organ tissue. The healing process is complex, the wound is slowly improved, medical dressing needs to be covered on the surface of the wound and is replaced periodically, the healing of the wound surface is accelerated, and the infection of bacteria and dust is prevented. Traditional medical dressings such as absorbent cotton yarn provide moisture absorption and skin protection to a certain extent. However, after moisture absorption, the dressing is easy to harden, adhere to damaged tissues and increase friction on the wound surface, and meanwhile, secondary damage is easy to cause on the skin when the dressing is replaced, and the antibacterial ability is poor. In the process of wound healing, the dressing with the specific tool can accelerate wound healing and meet the requirement of comfort. Therefore, the medical dressing with different structures and more comprehensive functions has multiple functions of accelerating wound healing, strongly resisting bacteria, stopping bleeding, reducing scars, absorbing moisture and the like.

The dressing prepared by the electrostatic spinning technology has high porosity and specific surface area, is similar to an extracellular matrix structure, is beneficial to the adhesion and growth of cells, has good air permeability and is beneficial to the respiration of the cells; the pore size is small, partial bacteria can be prevented from entering, wound infection is prevented, wound healing is promoted, and the medical dressing is suitable for medical dressings. The aerogel is a three-dimensional porous nano material, has large surface area and high porosity, has low density, excellent air permeability and good mechanical property, determines that the aerogel has good moisture absorption and air permeability and can provide excellent performance for wound healing.

Chitosan and polyvinyl alcohol are widely used in the biomedical field, but both are hydrophilic materials, and when the chitosan and polyvinyl alcohol are contacted with wound exudate, fibers are easy to dissolve, the wet strength is low, crosslinking treatment is required for further improving the water resistance of the fibers, but common crosslinking agents such as glutaraldehyde have a toxicity problem.

The medical dressing for wound healing has the advantages of good biocompatibility, antibiosis, moisture absorption, moisture retention, air permeability, prevention of bacterial breeding, absorption of wound exudate, provision of a microenvironment suitable for wound healing for the wound, promotion of wound healing, excellent skin feel and mechanical properties, and improvement of use experience of patients.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: the prior medical dressing has the problems that the dressing with a multilayer structure prepared by electrostatic spinning is less, the mechanical property of the prior medical dressing is poor, the use of non-medicinal cross-linking agents (such as glutaraldehyde and the like) is not beneficial to wound healing, the function is single and the like.

In order to solve the problems, the technical scheme of the invention is to provide a medical composite dressing for wound repair, which comprises an inner layer, a middle layer and an outer layer which are in contact with a wound, and is characterized in that the inner layer is a nano-fiber antibacterial layer blended by chitosan/polyvinyl alcohol/oxidized sodium alginate; the middle layer is an aerogel moisture absorption layer prepared by shearing, crushing, freeze-drying and the like on a sodium alginate/polyvinyl alcohol/sodium carboxymethylcellulose nanofiber membrane; the outer layer is a non-woven fabric breathable layer, and the inner layer, the middle layer and the outer layer are formed by compounding medical adhesive.

Preferably, the diameter of the blended fiber of the nanofiber antibacterial layer is 100-300nm, and the thickness of the fiber layer is 0.1-0.3 mm.

Preferably, the thickness of the aerogel moisture absorption layer in the middle layer is 1-3mm, and the porosity is 95-99%.

Preferably, the gram weight of the outer layer non-woven fabric breathable layer is 60g/m²And the thickness is 1 mm.

The invention also provides a preparation method of the medical composite dressing for wound repair, which is characterized by comprising the following steps:

step 1, preparing an inner layer:

mixing chitosan and polyvinyl alcohol according to the mass percentage of 10-30:70-90, dissolving in 20-40% of acetic acid aqueous solution to obtain 10% spinning solution, heating in water bath at 90 ℃, stirring for 4-6 hours until the solution is dissolved, standing and cooling for 2 hours, adding 5-30% of oxidized sodium alginate into the spinning solution, and stirring at normal temperature until the solution is completely dispersed;

under the conditions of normal temperature and humidity of less than 50%, performing electrostatic spinning on the spinning solution, controlling the receiving distance to be 16-18cm, the flow rate of the spinning solution to be 0.3-0.7mL/h, the voltage to be 16-20KV and the needle head to be 20G, and collecting a chitosan/polyvinyl alcohol/sodium alginate oxide blended fiber membrane on a receiving board to obtain an inner layer nanofiber antibacterial layer;

step 2, preparing an intermediate layer:

sodium alginate, sodium carboxymethylcellulose and polyvinyl alcohol are mixed according to the mass percentage of 10-30: 1-12: 58-89, dissolving in water solution to obtain spinning solution with the concentration of 10%, heating in water bath at 90 ℃ and stirring for 4-6 hours until the spinning solution is completely dissolved, standing and cooling for 2 hours for later use;

under the conditions of normal temperature and humidity less than 50%, carrying out electrostatic spinning on the spinning solution, controlling the receiving distance to be 16-18cm, the flow rate of the spinning solution to be 0.3-0.7mL/h, the voltage to be 16-20KV and the needle head to be 21G, and collecting the sodium alginate/polyvinyl alcohol/sodium carboxymethylcellulose blended fiber membrane on a receiving board;

selecting 1-5% calcium chloride solution to perform crosslinking treatment on the fiber membrane for 24h, rinsing with anhydrous ethanol for 4 times, drying with filter paper in a vacuum oven at 50 deg.C for 30min, and packaging with a sealed bag;

shearing the crosslinked fiber membrane, and adding the fiber membrane into a tert-butyl alcohol aqueous solution with the volume ratio of 20% to obtain a fiber dispersion solution with the mass volume ratio of 0.5%; homogenizing the fiber dispersion liquid for 10-20min, stirring at room temperature for 2-4h, pouring into a culture dish, controlling the thickness of the fiber dispersion liquid to be 1-3mm, pre-freezing in a refrigerator for 12h, and drying in a freeze dryer for 24h to obtain the middle-layer aerogel moisture absorption layer.

Step 3, preparing a three-layer composite structure:

and (3) overlapping the outer non-woven fabric breathable layer, the middle aerogel moisture absorption layer and the inner nanofiber antibacterial layer together through a medical adhesive layer from bottom to top, and cutting the layers into the same shape and size to obtain the medical composite dressing for wound repair.

Preferably, the preparation of oxidized sodium alginate in the step 1 specifically comprises: dissolving sodium alginate in absolute ethyl alcohol to obtain a sodium alginate ethanol solution, dissolving sodium periodate in deionized water to obtain a sodium periodate aqueous solution, mixing the two solutions, placing the two solutions on a magnetic stirrer in a dark place, stirring for 6 hours for oxidation reaction, adding glycol with the same mole as the sodium periodate after the reaction is finished, stopping the reaction for 30 minutes, dialyzing for 3 days, changing water for 1 time every 6 hours, and finally freeze-drying dialysate to obtain oxidized sodium alginate containing aldehyde groups; wherein the concentration of sodium alginate in the sodium alginate ethanol solution is 0.1g/mL, and the concentration of sodium periodate in the sodium periodate aqueous solution is 0.04 g/mL.

Compared with the prior art, the invention has the following excellent effects:

(1) the inner layer nanofiber antibacterial layer has the advantages that: the chitosan has good biocompatibility as a biological material with broad-spectrum antibacterial property, and has the performances of antibiosis, antiphlogosis, hemostasis and the like. The polyvinyl alcohol can provide excellent mechanical property and biocompatibility, and can be compounded with natural biological materials. The oxidized sodium alginate serving as a cross-linking agent can improve the water resistance of the fiber membrane, and the cross-linked fiber membrane can form hydrogel after being contacted with wound exudate, so that the skin feeling is improved, the diffusion area of the exudate is reduced, the peripheral healthy skin is prevented from being soaked, and meanwhile, the moisture retention performance of the dressing can be improved by the three-dimensional reticular gel structure, so that the wound healing is accelerated, tissues are not adhered, the pain is reduced, and the treatment course is shortened.

(2) The middle layer aerogel hygroscopic layer has the advantages that: the sodium alginate and the sodium carboxymethyl cellulose have high moisture absorption effects, can absorb exudates, and meanwhile, the aerogel layer prepared by shearing, crushing and freeze-drying the fiber membrane through electrostatic spinning has the dual characteristics of an electrospun membrane and aerogel, has high porosity and large surface area, can further absorb a large amount of wound exudates, and has good air permeability, so that the surface of a wound is relatively clean and tidy, the moist environment of the wound is kept, and the wound healing is accelerated.

(3) The oxidized sodium alginate as the cross-linking agent has the advantages that: sodium alginate can provide a moist repair environment for wounds, can be used for wounds with serious effusion, and promotes wound healing. According to the invention, sodium periodate is used for oxidizing sodium alginate, so that a large amount of aldehyde groups are generated on the structure of the sodium alginate to generate oxidized sodium alginate, the oxidized sodium alginate is used as a cross-linking agent to be mixed with chitosan/polyvinyl alcohol spinning solution, the conditions that fibers are easy to dissolve and the wet strength is low when chitosan and polyvinyl alcohol are used as hydrophilic materials and are contacted with wound exudate are avoided, the water resistance of the fibers is further improved, the toxicity problem caused by using an additional cross-linking agent is avoided, the cross-linking post-treatment is carried out after a fiber film is obtained, and the operation process is simplified.

(4) The composite structure dressing can protect wounds, can be directly attached to human skin, is excellent in skin feel, has high moisture absorption and moisture retention performance, reduces diffusion of exudates, keeps the skin clean, has good antibacterial and biocompatibility, effectively prevents wound infection, promotes the wounds to heal quickly, and can be widely applied to recovery treatment of various wounds.

Drawings

FIG. 1 is a schematic view of a composite dressing of the present invention; wherein: 1-inner layer, 2-middle layer, 3-outer layer.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.

The oxidized sodium alginate used in the embodiments of the invention is prepared by the following method: dissolving 5g of sodium alginate in 50ml of absolute ethanol to obtain a sodium alginate ethanol solution, dissolving 2g of sodium periodate in 50ml of deionized water to obtain a sodium periodate aqueous solution, mixing the two solutions, placing the two solutions on a magnetic stirrer in a dark place for stirring for 6 hours, adding ethylene glycol with the same mole as the sodium periodate after the oxidation reaction is finished, stopping the reaction for 30 minutes, dialyzing for 3 days, changing water for 1 time every 6 hours, and finally freeze-drying the dialyzate to obtain the oxidized sodium alginate containing aldehyde groups.