CN112807475B

CN112807475B - High-air-permeability degradable drug-loaded skin wound dressing and preparation method thereof

Info

Publication number: CN112807475B
Application number: CN202110025707.8A
Authority: CN
Inventors: 陈娜
Original assignee: Xiangya Biomedicine Huzhou Co ltd
Current assignee: Xiangya Biomedicine Huzhou Co ltd
Priority date: 2021-01-08
Filing date: 2021-01-08
Publication date: 2022-11-04
Anticipated expiration: 2041-01-08
Also published as: CN114732936A; CN114732936B; CN112807475A

Abstract

The invention discloses a degradable drug-loaded skin wound dressing with high air permeability and a preparation method thereof. The invention comprises a dressing inner layer, a dressing outer layer and a repair adhesive layer; the repair adhesive layer is positioned between the dressing inner layer and the auxiliary material outer layer; the inner layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the inner layer, and the outer layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the outer layer. The material used in the invention is safe and nontoxic, has high biodegradation rate, does not cause pollution to the environment, and can effectively relieve the environmental pollution caused by medical waste. The preparation method disclosed by the invention is simple in preparation process, mild in reaction conditions, high in safety, very suitable for industrial production, and high in economic value and environmental protection value.

Description

High-air-permeability degradable drug-loaded skin wound dressing and preparation method thereof

Technical Field

The invention relates to the technical field of wound dressings, in particular to a degradable drug-loaded skin wound dressing with high air permeability and a preparation method thereof.

Background

The skin is the largest organ of the human body, can maintain the internal environment stability of the human body, prevent the invasion of microorganisms, protect the safety of important tissues such as blood vessels, nerves and the like in the human body and has important significance for the normal running of human physiological activities. However, human skin is inevitably damaged in daily life and labor, and after a certain period of time of repair, the wound can heal automatically, but the wound healing process is complex and slow, and the problems of inflammation, gangrene and the like are easily caused when the repair is not good. The main problems to be solved in China clinically are to reduce wound exudate, prevent bacterial infection of wounds, maintain stable wound microenvironment and accelerate the wound healing rate.

When a human body has a wound, covering the wound by using the wound dressing is one of effective methods for sterilizing and stopping bleeding of the wound, reducing the infection probability of the wound and improving the healing speed of the wound. At present, the most commonly used wound dressings such as gauze, cotton towel and the like can absorb wound exudates to a certain extent and prevent wound infection, but have the problems of poor antibacterial performance, insufficient hemostatic capacity, easy adhesion of the dressing to the wound, high replacement difficulty and the like, so that the pain of a patient is easily aggravated, secondary wound injury is caused, the wound healing time is prolonged, and the requirements of the patient are difficult to meet; however, some synthetic fiber dressings have the problems of poor air permeability, poor capability of absorbing seepage, easy breeding of bacteria and the like, so that the development of the synthetic fiber dressings is limited.

The electrostatic spinning fiber has higher length-diameter ratio and larger specific surface area, high surface porosity and good air permeability, and is very suitable for being used for manufacturing wound dressings; when people use the nano-fiber to prepare the wound dressing, in order to improve the wound repair efficiency, a medicament or a medicament-carrying microsphere for promoting wound healing is often added into the nano-fiber; the method of directly mixing the medicament and the spinning solution not only can easily reduce the medicinal effect of the medicament, but also can influence the mechanical property of the nano-fiber; the nanofiber prepared by directly mixing the drug-loaded microspheres with the spinning solution has the problems of low mechanical strength, easy breakage, insufficient air permeability and the like of the nanofiber caused by poor compatibility between the drug-loaded microspheres and the nanofiber. Thousands of tons of wound dressings are consumed in China every year, the waste wound dressings are generally buried or stacked in the open air after being used, and great pressure and waste of land resources are caused to the environment regardless of the burying or the stacking in the open air.

Therefore, a wound dressing with good mechanical properties, high air permeability, good antibacterial property, good hemostatic and repairing effects, high degradation rate and no environmental pollution and a preparation method thereof are needed to solve the problems in the background.

Disclosure of Invention

The invention aims to provide a degradable drug-loaded skin wound dressing with high air permeability and a preparation method thereof, and aims to solve the problems in the background art.

A degradable drug-loaded skin wound dressing with high air permeability comprises a dressing inner layer, a dressing outer layer and a repair adhesive layer; the repair glue layer is positioned between the dressing inner layer and the auxiliary material outer layer; the inner layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the inner layer, and the outer layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the outer layer.

Further, the repair glue layer comprises the following raw material components: 80-100 parts of porous drug-loaded microspheres, 30-60 parts of dialdehyde pectin, 30-60 parts of pullulan, 40-50 parts of o-aminobenzyl chloride, 15-35 parts of dopamine and 35-45 parts of hydroxyl cucurbituril; the thickness of the repair glue layer is 1-50 μm.

Further, the inner layer spinning solution comprises the following raw material components: 10-30 parts of polyvinylidene fluoride, 60-100 parts of gelatin, 50-90 parts of zein and 20-40 parts of 4-vinyl benzyl chloride.

Further, the outer layer spinning solution comprises the following raw material components: 80-100 parts of polycaprolactone, 80-100 parts of polyethylene glycol and 30-50 parts of sodium alginate by weight.

Further, the porous drug-loaded microsphere comprises the following raw material components: 20-30 parts of polyethyleneimine, 50-80 parts of hemostatic and 10-20 parts of medicament carrier.

Further, the medicament carrier is one or more of porous hydroxyapatite, porous starch, porous ceramic and hydrogel microspheres.

Further, the hemostatic agent is one or more of glycine, aminomethylbenzoic acid, hemagglutinase, and caffeic acid phenethyl ester.

A preparation method of a degradable drug-loaded skin wound dressing with high air permeability comprises the following steps:

s1, preparing a dressing outer layer:

A. putting polycaprolactone and polyvinyl alcohol into N, N-dimethylformamide, stirring and dissolving, adding a sodium alginate solution, and stirring to obtain a spinning solution of the outer layer of the dressing;

B. preparing the spinning solution on the outer layer of the dressing into outer-layer nano fibers by an electrostatic spinning technology, and collecting by a roller to obtain the outer layer of the dressing;

s2, preparing a repairing adhesive:

A. adding the polyethyleneimine solution into the hemostatic agent, and uniformly stirring to obtain a solution A;

B. heating the solution A, placing the medicament carrier in the solution A under a low pressure condition for ultrasonic dispersion, and taking out to obtain porous medicament-carrying microspheres;

C. uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating to melt, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring, adjusting pH value, adding hydroxy cucurbituril, and stirring to obtain a repair gum;

s3, synthesizing an inner layer spinning solution:

A. placing polyvinylidene fluoride in N, N-dimethylformamide, stirring and dissolving to obtain spinning solution A;

B. putting gelatin, zein and 4-vinyl benzyl chloride into ethanol, stirring and dissolving to obtain a spinning solution B;

C. adding the spinning solution A into the spinning solution B and stirring to obtain an inner-layer spinning solution;

s4, synthesizing the wound dressing:

A. coating the repair glue on the supporting layer to obtain a repair glue layer;

B. placing the repair glue layer on an electrostatic spinning receiving plate to serve as a supporting layer for receiving the inner-layer nano fibers;

C. preparing the inner layer spinning solution into inner layer nano fibers by an electrostatic spinning technology, collecting the inner layer nano fibers on the supporting layer, standing, taking out and drying to obtain the wound dressing.

The method specifically comprises the following steps:

s1, preparing an outer dressing layer:

A. dissolving polycaprolactone and polyvinyl alcohol in N, N-dimethylformamide under stirring, adding sodium alginate solution, and reacting under stirring for 30-50min to obtain spinning solution of the outer layer of the dressing;

s2, preparing a repairing adhesive:

B. heating the solution A, placing the medicament carrier in the solution A under a low pressure condition, ultrasonically dispersing for 1-2h, and taking out to obtain porous medicament-carrying microspheres; the proper heating can improve the molecular motion speed of the solution A, further improve the loading efficiency of the solution A on the medicament carrier and reduce the loading time. The low pressure environment is effective to increase the loading rate of solution a on the pharmaceutical carrier.

C. Uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating to melt at 30-40 ℃, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring to react for 30-50min, adjusting the pH value to 8-10, adding hydroxyl cucurbituril, and stirring to react for 10-20min at 100-200r/min to obtain a repair gum;

s3, synthesizing an inner layer spinning solution:

C. adding the spinning solution A into the spinning solution B under the heating condition of 80-100 ℃, and stirring and reacting for 1-2 hours to obtain an inner-layer spinning solution; this heating temperature is favorable for the polymerization of 4-vinylbenzyl chloride in the spinning dope B.

S4, synthesizing the wound dressing:

C. preparing the inner layer spinning solution into inner layer nano fibers by an electrostatic spinning technology, collecting the inner layer nano fibers on a supporting layer, standing for 30-50min at the temperature of 80-100 ℃, taking out, and drying for 3-5h at room temperature to obtain the wound dressing. Under the temperature condition, o-aminobenzyl chloride firstly reacts with hydroxyl and carboxyl on the outer layer of the dressing to be further modified on the outer layer of the dressing, the o-aminobenzyl chloride further reacts with tertiary amine on the porous medicine carrying microspheres to generate quaternary ammonium salt, and the quaternary ammonium salt further attracts hydroxyl cucurbituril to coat the quaternary ammonium salt, so that the temperature is favorable for smooth reaction and quickens the reaction rate; on the other hand, the wound dressing can be sterilized, and the quality of the wound dressing is improved.

Further, the electrostatic spinning process parameters are as follows: the spinning voltage is 12-32kV, the receiving distance is 12-22cm, and the spinning speed is 0.03-6ml/h.

Further, the heating temperature of the solution A in the step B of the step S2 is 30-40 ℃, and the low-pressure condition is 0.01-0.03MPa.

Further, the pH value of the repair glue in the step B of the step S2 is 8-10; the hydroxyl cucurbituril can maintain self stability under the environment, and effective coating of the porous drug-loaded microspheres is realized; the pH value of the body fluid and blood of a human body is about 6.8-7.8, when the repair glue absorbs the body fluid and blood secreted from a human wound, the pH value of the environment in the repair glue is reduced, the hydroxyl cucurbituril is gradually cracked and separated from the porous drug-carrying microspheres, the solution A in the porous drug-carrying microspheres is gradually dissociated, and the solution A permeates to the surface of the wound through pores on the nano fibers to perform the functions of hemostasis and sterilization.

The main materials of the dressing outer layer are polycaprolactone and polyvinyl alcohol, the polycaprolactone and the polyvinyl alcohol have good hydrophilic property and mechanical property, and the dressing outer layer can effectively adsorb interstitial fluid and blood secreted from a wound, keep the wound dry and comfortable and reduce bacterial growth, has excellent biodegradability and can effectively reduce the problem of environmental pollution caused by medical waste. According to the invention, sodium alginate is particularly added in the outer layer of the dressing, and the later stage of negative charge of the sodium alginate can generate charge interaction with the positively charged quaternary ammonium salt on the surface of the porous drug-loaded microsphere, so that the adhesive force between the supporting layer and the repairing adhesive layer is increased; the sodium alginate has certain moisture retention capacity, and can prevent the problem of dry and adhesive wounds caused by excessive evaporation of skin moisture; sodium alginate can also provide more active groups such as hydroxyl, carboxyl and the like for the supporting layer, and provide reaction sites for modification of o-aminobenzyl chloride; the sodium alginate has a strong bactericidal effect on cationic bacteria, the quaternary ammonium salt in the repair gel has a certain bactericidal effect on anionic bacteria, and the sodium alginate can act with the repair gel in a synergistic manner, so that the bacteriostatic range of the wound dressing is further expanded, and the bactericidal and bacteriostatic capacity of the wound dressing is enhanced; sodium alginate also can secrete free calcium ions under the action of body fluid to promote wound cell healing.

Because the outer layer of the dressing contains a large amount of hydroxyl and carboxyl, the dressing can react with amino in the o-aminobenzyl chloride, and then the o-aminobenzyl chloride is modified on the outer layer of the dressing; the dressing inner layer contains a large amount of poly (4-vinylbenzyl chloride), the poly (4-vinylbenzyl chloride) and the o-aminobenzyl chloride respectively react with tertiary amine on the porous drug-carrying microspheres, so that quaternary ammonium salt is generated on the porous drug-carrying microspheres, and the inner layer and the outer layer of the dressing are compounded; the quaternary ammonium salt generated on the porous drug-loaded microsphere can compound the inner layer and the outer layer of the dressing, and on the other hand, the bacteriostatic effect of the quaternary ammonium salt can not only hinder the propagation of bacteria on the wound dressing, but also protect the deterioration of the drug in the porous drug-loaded microsphere. Because the negative charge characteristic of the carbonyl oxygen atom is greater than the positive charge characteristic of the carbon atom, the carbonyl group is wholly in the negative charge characteristic, the hydroxyl group at the waist part of the hydroxyl cucurbituril ring and the carbonyl group at the end port in the repairing glue can generate charge interaction with the quaternary ammonium salt, so that the hydroxyl cucurbituril ring is coated on the surface of the porous drug-loaded microsphere, the coating of the hydroxyl cucurbituril ring can effectively prevent the hemostatic agent in the porous drug-loaded microsphere from being exposed in the air, the hemostatic agent is prevented from generating polyethyleneimine in the air, the polyethyleneimine is a water-soluble polymer and has certain viscosity, the viscosity of the hemostatic agent can be improved to a certain extent by mixing the hemostatic agent with the hemostatic agent, and the stability of the hemostatic agent in the porous drug-loaded microsphere is enhanced; the load of the polyethyleneimine on the medicament carrier introduces a large amount of amino, primary amine and tertiary amine into the medicament carrier, the amino is favorable for the cross-linking reaction with dialdehyde pectin and pullulan in the later period, the stability of the repair gum is improved, and the introduction of the tertiary amine is favorable for the reaction of generating quaternary ammonium salt in the porous medicament-carrying microspheres in the later period. The problems of deterioration, oxidation, evaporation and the like, and effectively prolongs the storage time of the wound dressing.

The polyethyleneimine is a water-soluble polymer and has certain viscosity, and the viscosity of the hemostatic can be improved to a certain extent by mixing the polyethyleneimine with the hemostatic, so that the stability of the hemostatic in the porous drug-loaded microspheres is enhanced; the load of the polyethyleneimine on the medicament carrier introduces a large amount of amino, primary amine and tertiary amine into the medicament carrier, the amino is favorable for the cross-linking reaction with dialdehyde pectin and pullulan in the later period, the stability of the repair gum is improved, and the introduction of the tertiary amine is favorable for the reaction of generating quaternary ammonium salt in the porous medicament-carrying microspheres in the later period.

Aldehyde groups in dialdehyde pectin and pullulan which are specially added in the invention can generate Schiff base reaction with amino groups on the porous drug-loaded microspheres to generate crosslinking, so that the viscosity of the repair adhesive is increased, the bonding property is improved, and the stability of the repair adhesive is improved; the dialdehyde pectin and the pullulan also have certain water absorption and moisture retention functions, can effectively adsorb body fluid tissue fluid secreted from a wound, keep the wound dry, reduce bacterial growth, simultaneously avoid the excessive drying of the wound caused by skin moisture evaporation, and maintain the wound healing in a stable environment. The dopamine in the invention can cooperate with dialdehyde pectin and pramipexole polysaccharide, further improve the viscosity of the repair glue, improve the binding force between the inner layer and the outer layer of the dressing, prevent the insufficient binding force of the interface of the wound dressing, easily cause the delamination phenomenon and strengthen the mechanical property of the wound dressing.

The main components of the inner layer of the wound dressing prepared by the invention are gelatin, zein and polyvinylidene fluoride; the gelatin and the zein are reproducible natural high-molecular proteins, have good oxidation resistance, film forming property and biodegradability, are good in compatibility with human cells, have small irritation to skin, can obviously reduce irritation and discomfort brought to the skin surface by the traditional dressing, have good hydrophobicity, and can prevent blood and tissue fluid secreted by a wound from being adhered to the same dressing when being used as an inner layer of the wound dressing, so that the wound and the wound dressing are adhered together, the replacement difficulty of the wound dressing is increased, and the problem of secondary injury of the wound is avoided. However, the mechanical property of the prepared nanofiber is poor due to the fact that gelatin and zein are directly spun, the nanofiber is very easy to break under the condition of external force, and the application of the nanofiber in the field of wound dressings is limited. After the gelatin and the zein are dissolved, a certain amount of polyvinylidene fluoride solution is added into the gelatin and the zein; the polyvinylidene fluoride has excellent wear resistance, chemical resistance and piezoelectric property, and can respond to a micro electric field near a wound under the action of pressure, so that the proliferation and differentiation of cells are promoted, and the wound healing rate is accelerated; because the compatibility among the gelatin, the zein and the polyvinylidene fluoride is insufficient, 4-vinylbenzyl chloride is added into the mixed spinning solution of the gelatin, the zein and the polyvinylidene fluoride, the 4-vinylbenzyl chloride is polymerized in a high-temperature environment to generate poly (4-vinylbenzyl chloride), a poly (4-vinylbenzyl chloride) molecular chain is entangled with gelatin, zein and a polyvinylidene fluoride molecular chain, a stable polymer network structure is formed, and the compatibility among the gelatin, the zein and the polyvinylidene fluoride is effectively enhanced. The inner layer nanofiber prepared by the method disclosed by the invention is good in compatibility with human epidermis, small in irritation and excellent in hydrophobicity, cannot be bonded with a wound, and the difficulty in replacing a wound dressing is reduced; the surface of the inner layer nanofiber prepared by the invention has abundant pore structures and high air permeability, can effectively inhibit the breeding of anaerobic bacteria at wounds and keep the wounds dry and comfortable; the prepared wound dressing can release electric signals under the condition of slight force application, stimulate cell proliferation and regeneration and accelerate the wound healing rate.

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

according to the invention, the o-aminobenzyl chloride and the poly (4-vinyl benzyl chloride) react with the porous drug-loaded microspheres to generate the quaternary ammonium salt, so that on one hand, the cohesiveness between the inner layer and the outer layer of the dressing is enhanced, the layering phenomenon of the wound dressing is reduced, the mechanical property of the wound dressing is improved, on the other hand, the antibacterial property of the wound dressing is enhanced, and the risk of bacterial infection of the wound is reduced.

According to the invention, hydroxyl and carbonyl on the hydroxyl cucurbituril and quaternary ammonium salt on the porous drug-loaded microsphere are utilized to generate charge interaction, so that the cucurbituril is coated on the surface of the porous drug-loaded microsphere, the coating of the porous drug-loaded microsphere can reduce the contact of the hemostatic with the external environment, reduce the problems of evaporation, deterioration and the like of the hemostatic, and prolong the storage time of the wound dressing.

Compared with the conventional spinning method of directly mixing the medicine or the medicine-carrying microspheres into the spinning solution, the method has the advantages of less influence on the mechanical property and the air permeability of the nanofiber, higher medicine utilization rate, difficult layering of the prepared wound dressing, strong bacteriostasis, small irritation to the skin, high air permeability, good moisture retention, longer storage period, obvious effect of accelerating the wound healing speed and high practicability.

The material used in the invention is safe and nontoxic, has high biodegradation rate, does not cause pollution to the environment, and can effectively relieve the environmental pollution caused by medical waste. The preparation method disclosed by the invention is simple in preparation process, mild in reaction conditions, high in safety, very suitable for industrial production, and high in economic value and environmental protection value.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.

Example 1

A degradable drug-loaded skin wound dressing with high air permeability comprises an inner dressing layer, an outer dressing layer and a repair adhesive layer; the repair adhesive layer is positioned between the dressing inner layer and the auxiliary material outer layer; the inner layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the inner layer, and the outer layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the outer layer.

The repair glue layer comprises the following raw material components: the drug-loaded porous microsphere comprises, by weight, 80 parts of porous drug-loaded microspheres, 30 parts of dialdehyde pectin, 30 parts of pullulan, 40 parts of o-aminobenzyl chloride, 15 parts of dopamine and 35 parts of hydroxyl cucurbituril; the thickness of the repair glue layer is 1 mu m.

The inner layer spinning solution comprises the following raw material components: the adhesive comprises, by weight, 10 parts of polyvinylidene fluoride, 600 parts of gelatin, 50 parts of zein and 20 parts of 4-vinyl benzyl chloride.

The outer layer spinning solution comprises the following raw material components: 80 parts of polycaprolactone, 80 parts of polyethylene glycol and 30 parts of sodium alginate.

The porous drug-loaded microsphere comprises the following raw material components: 20 parts of polyethyleneimine, 50 parts of hemostatic and 10 parts of medicament carrier.

S1, preparing an outer dressing layer:

A. putting polycaprolactone and polyvinyl alcohol into N, N-dimethylformamide, stirring for dissolving, adding sodium alginate solution, and stirring for reacting for 30min to obtain spinning solution of the outer layer of the dressing;

s2, preparing a repairing adhesive:

B. heating the solution A to 30 ℃, placing the medicament carrier in the solution A under the condition of 0.01MPa low pressure for ultrasonic dispersion for 1h, and taking out to obtain porous medicament-carrying microspheres;

C. uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating to melt at 30 ℃, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring to react for 30min, adjusting the pH value to 8, adding hydroxyl cucurbituril, and stirring at 100r/min to react for 10min to obtain a repair glue;

s3, synthesizing an inner layer spinning solution:

C. adding the spinning solution A into the spinning solution B under the heating condition of 80 ℃, and stirring for reacting for 1h to obtain inner-layer spinning solution;

s4, synthesizing the wound dressing:

C. preparing the inner spinning solution into inner nano-fibers by an electrostatic spinning technology, collecting the inner nano-fibers on a supporting layer, standing for 30min at the temperature of 80 ℃, taking out, and drying for 3h at room temperature to obtain the wound dressing.

The electrostatic spinning process parameters are as follows: the spinning voltage was 12kV, the take-up distance was 12cm, and the spinning rate was 0.03ml/h.

Example 2

A degradable drug-loaded skin wound dressing with high air permeability comprises a dressing inner layer, a dressing outer layer and a repair adhesive layer; the repair adhesive layer is positioned between the dressing inner layer and the auxiliary material outer layer; the inner layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the inner layer, and the outer layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the outer layer.

The repair glue layer comprises the following raw material components: the drug-carrying porous microsphere comprises, by weight, 90 parts of porous drug-carrying microspheres, 45 parts of dialdehyde pectin, 45 parts of pullulan, 45 parts of o-aminobenzyl chloride, 25 parts of dopamine and 40 parts of hydroxyl cucurbituril; the thickness of the repair glue layer is 25 mu m.

The inner layer spinning solution comprises the following raw material components: the anti-aging coating comprises, by weight, 20 parts of polyvinylidene fluoride, 80 parts of gelatin, 70 parts of zein and 30 parts of 4-vinylbenzyl chloride.

The outer layer spinning solution comprises the following raw material components: 90 parts of polycaprolactone, 90 parts of polyethylene glycol and 40 parts of sodium alginate by weight.

The porous drug-loaded microsphere comprises the following raw material components: 25 parts of polyethyleneimine, 75 parts of hemostatic and 15 parts of medicament carrier.

S1, preparing an outer dressing layer:

A. putting polycaprolactone and polyvinyl alcohol into N, N-dimethylformamide, stirring for dissolving, adding sodium alginate solution, and stirring for reacting for 40min to obtain spinning solution of the outer layer of the dressing;

s2, preparing a repairing adhesive:

B. heating the solution A to 35 ℃, placing the medicament carrier in the solution A under the condition of low pressure of 0.02MPa for ultrasonic dispersion for 1.5h, and taking out to obtain porous medicament-carrying microspheres;

C. uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating to melt at 35 ℃, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring to react for 40min, adjusting the pH value to 9, adding hydroxyl cucurbituril, and stirring at 150r/min to react for 15min to obtain a repair gel;

s3, synthesizing an inner layer spinning solution:

C. adding the spinning solution A into the spinning solution B under the heating condition of 90 ℃, and stirring and reacting for 1.5 hours to obtain inner-layer spinning solution;

s4, synthesizing the wound dressing:

C. preparing the inner layer spinning solution into inner layer nano fibers by an electrostatic spinning technology, collecting the inner layer nano fibers on the supporting layer, standing for 40min at the temperature of 90 ℃, taking out the inner layer spinning solution, and drying for 4h at room temperature to obtain the wound dressing.

The electrostatic spinning process parameters are as follows: the spinning voltage was 22kV, the take-up distance was 18cm and the spinning speed was 3ml/h.

Example 3

The repair glue layer comprises the following raw material components: the drug-loaded porous microsphere comprises, by weight, 100 parts of porous drug-loaded microspheres, 60 parts of dialdehyde pectin, 60 parts of pullulan, 50 parts of o-aminobenzyl chloride, 35 parts of dopamine and 45 parts of hydroxyl cucurbituril; the thickness of the repair glue layer is 50 μm.

The inner layer spinning solution comprises the following raw material components: the anti-aging coating comprises, by weight, 30 parts of polyvinylidene fluoride, 100 parts of gelatin, 90 parts of zein and 40 parts of 4-vinyl benzyl chloride.

The outer layer spinning solution comprises the following raw material components: 100 parts of polycaprolactone, 100 parts of polyethylene glycol and 50 parts of sodium alginate in parts by weight.

The porous drug-loaded microsphere comprises the following raw material components: 30 parts of polyethyleneimine, 80 parts of hemostatic and 20 parts of medicament carrier.

S1, preparing an outer dressing layer:

A. putting polycaprolactone and polyvinyl alcohol into N, N-dimethylformamide, stirring for dissolving, adding sodium alginate solution, and stirring for reacting for 50min to obtain spinning solution of the outer layer of the dressing;

s2, preparing a repairing adhesive:

B. heating the solution A to 40 ℃, placing the medicament carrier in the solution A under the condition of 0.03MPa low pressure for ultrasonic dispersion for 2 hours, and taking out to obtain porous medicament-carrying microspheres;

C. uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating to melt at 40 ℃, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring to react for 50min, adjusting the pH value to 10, adding hydroxyl cucurbituril, and stirring at 200r/min to react for 20min to obtain a repair gel;

s3, synthesizing an inner layer spinning solution:

C. adding the spinning solution A into the spinning solution B under the heating condition of 100 ℃, and stirring for reacting for 2 hours to obtain an inner-layer spinning solution;

s4, synthesizing the wound dressing:

C. preparing the inner spinning solution into inner nano-fibers by an electrostatic spinning technology, collecting the inner nano-fibers on a supporting layer, standing for 50min at the temperature of 100 ℃, taking out the inner nano-fibers, and drying for 5h at room temperature to obtain the wound dressing.

The electrostatic spinning process parameters are as follows: the spinning voltage was 32kV, the take-up distance was 22cm and the spinning rate was 6ml/h.

And (3) testing: the wound dressings obtained in examples 1 to 7 and comparative example were each cut into wound dressing samples of 2cm × 3cm in size to perform the following experiments:

in vitro coagulation test: and (3) establishing an acute bleeding emergency animal model by using the bandage placed for 1 day, and performing abdominal anesthesia on the experimental rabbits by using anesthetic. The blood vessels were fully exposed, cut with a scalpel, allowed to bleed freely for 10s, and then subjected to hemostatic intervention using the bandages prepared in the examples and comparative examples, and the clotting time was recorded, with the results shown in the table below.

And (3) aging test: after the bandages obtained in each example and comparative example were normally stored for 12 months, the in vitro coagulation test described above was continued and the coagulation time was recorded.

And (3) testing the antibacterial rate: the bacteriostasis rate of the candida albicans is tested according to the GB/T20944.3-2008 standard.

Water vapor transmission test (g/m 2/24 h): reference is made to YY/T0471.2-2004 contact wound dressing test method part 2: and (4) testing the breathable film dressing water vapor transmission rate according to the standard.

And (3) testing mechanical properties: and (4) testing the breaking strength and the breaking elongation by adopting a universal strength tester. Clamping distance: 50mm, 5mm in width and 100mm/min in drawing speed.

And (3) testing the degradation rate: the inventive and comparative wound dressing samples were weighed and embedded in soil, and after 60 days samples were taken and mass loss recorded. The formula of the degradation rate is as follows: d = (m) ₀ -m _t )/m ₀ X 100%: wherein m is ₀ The original mass of the wound dressing sample prior to degradation; m is _t The remaining mass of the wound dressing sample after 60 days of degradation.

Primary skin irritation test: selecting 6 tested guinea pigs, selecting 1 unhairing region with the area of 3cm multiplied by 3cm on each side of the vertebral column of the tested guinea pigs 24h before the experiment, unhairing the left side and the right side by using a hair remover, observing that the skin in the unhairing region is not damaged after one day, and performing a skin irritation experiment; the dressing samples prepared in each example and comparative example were applied to the test site, respectively, and after 24 hours of application, the patch was removed, the area of application was cleaned with warm water and blotted dry, and the skin was observed for erythema and edema 48 hours after removal of the patch.

As can be seen from the data in the table, the wound dressing samples prepared in the examples 1-3 have the bacteriostatic rate of more than 95 percent and have excellent bacteriostatic and antibacterial capabilities; the in vitro blood coagulation time is in the range of 209-230s, and compared with the common synthetic fiber wound dressing, the hemostatic efficiency is higher; after 12 months of storage, the hemostatic effect is not obviously changed, which shows that the wound dressing prepared by the invention can maintain the stability of the medicine in the dressing and prolong the storage time of the wound dressing; the mechanical strength is good and the fracture is not easy to occur; the water vapor transmission rate is 400g/m < 2 >/24 h, and the air permeability is higher; the degradation rate in soil is more than 85%, the biological degradation agent has excellent biodegradability and good environmental protection and safety performance, and no erythema or red swelling phenomenon appears on the skin surface of a tested guinea pig in a skin irritation test, so that the biological degradation agent has high safety and small irritation.

Example 4

Compared with the embodiment 3, the difference is that no o-aminobenzyl chloride is added, the amount of quaternary ammonium salt generated by the reaction of the poly (4-vinylbenzyl chloride) in the inner layer of the dressing and the porous drug-carrying microspheres is insufficient, the bacteriostatic effect of the wound dressing is reduced, meanwhile, as the drug-carrying microspheres are not completely coated by the cucurbituril, the problems of evaporation, deterioration, loss and the like of the hemostatic agent in the air environment are caused, the mechanical property of the prepared wound dressing is reduced, the hemostatic effect is insufficient compared with the embodiment 3, after 12 months of placement, the hemostatic effect of the wound dressing is obviously reduced, and the storage property of the wound dressing is poor.

Example 5

The difference from the example 3 is that the mechanical property of the inner layer of the dressing is reduced due to the absence of 4-vinylbenzyl chloride, and the generation quantity of quaternary ammonium salt is limited, the medicine carrying microspheres are difficult to completely coat by cucurbituril, and the bacteriostatic property, the mechanical property and the hemostatic effect of the wound dressing are reduced.

Example 6

The difference from the embodiment 3 is that the solution A is not loaded by using a medicament carrier, but is directly added into the repair glue, because the porosity of the inner layer and the outer layer of the dressing is high, the solution A is directly exposed in the natural environment to accelerate the oxidative deterioration of the solution A and influence the hemostatic effect, and the direct addition of the solution A also directly influences the viscosity of the repair glue, so that the mechanical property of the wound dressing is influenced.

Example 7

The difference from the embodiment 3 lies in that the porous drug-loaded microspheres are directly mixed into the inner layer spinning solution for electrostatic spinning, the addition of the porous drug-loaded microspheres obviously reduces the proportion of the inner layer spinning solution in the inner layer nano fibers, the prepared inner layer nano fibers have serious insufficient mechanical properties, the water vapor transmission rate is obviously reduced, and the influence on the overall performance of the wound dressing is large.

Comparative example: compared with the common synthetic fiber wound dressing in example 3, the common synthetic fiber wound dressing has the defects of poor biodegradation rate and easy generation of medical waste pollution.

From the above data and experiments, we can conclude that:

Compared with the conventional spinning method of directly mixing the medicine or the medicine-carrying microspheres into the spinning solution, the method has the advantages that the influence on the mechanical property and the air permeability of the nano-fibers is smaller, the medicine utilization rate is higher, the prepared wound dressing is not easy to delaminate, the bacteriostasis is strong, the irritation to the skin is small, the air permeability is high, the moisture retention is good, the storage period is longer, the effect of obviously accelerating the wound healing speed is achieved, and the practicability is very high.

Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described above, or equivalents may be substituted for elements thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The utility model provides a high gas permeability degradable medicine-carrying skin wound dressing which characterized in that: comprises a dressing inner layer, a dressing outer layer and a repairing glue layer; the repair glue layer is positioned between the dressing inner layer and the dressing outer layer; the inner layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the inner layer, and the outer layer of the dressing is obtained by carrying out electrostatic spinning on the spinning solution of the outer layer;

the repair glue layer comprises the following raw material components: 80-100 parts of porous drug-loaded microspheres, 30-60 parts of dialdehyde pectin, 30-60 parts of pullulan, 40-50 parts of o-aminobenzyl chloride, 15-35 parts of dopamine and 35-45 parts of hydroxyl cucurbituril;

the inner layer spinning solution comprises the following raw material components: 10-30 parts of polyvinylidene fluoride, 60-100 parts of gelatin, 50-90 parts of zein and 20-40 parts of 4-vinyl benzyl chloride.

2. The high gas permeability degradable drug-loaded skin wound dressing of claim 1, wherein: the outer layer spinning solution comprises the following raw material components: 80-100 parts of polycaprolactone, 80-100 parts of polyethylene glycol and 30-50 parts of sodium alginate by weight.

3. The high gas permeability degradable drug-loaded skin wound dressing of claim 2, wherein: the porous drug-loaded microsphere comprises the following raw material components: 20-30 parts of polyethyleneimine, 50-80 parts of hemostatic and 10-20 parts of medicament carrier.

4. A preparation method of a degradable drug-loaded skin wound dressing with high air permeability is characterized by comprising the following steps: s1, preparing an outer dressing layer: A. putting polycaprolactone and polyvinyl alcohol into N, N-dimethylformamide, stirring and dissolving, adding a sodium alginate solution, and stirring to obtain a spinning solution of the outer layer of the dressing; B. preparing the spinning solution on the outer layer of the dressing into outer-layer nano fibers by an electrostatic spinning technology, and collecting by a roller to obtain the outer layer of the dressing; s2, preparing a repairing adhesive: A. adding the polyethyleneimine solution into the hemostatic agent, and uniformly stirring to obtain a solution A; B. heating the solution A, placing the medicament carrier in the solution A under a low pressure condition for ultrasonic dispersion, and taking out to obtain porous medicament-carrying microspheres; C. uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating to melt, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring, adjusting pH value, adding hydroxy cucurbituril, and stirring to obtain a repair gum; s3, synthesizing an inner layer spinning solution: A. placing polyvinylidene fluoride in N, N-dimethylformamide, stirring and dissolving to obtain spinning solution A; B. putting gelatin, zein and 4-vinyl benzyl chloride into ethanol, stirring and dissolving to obtain a spinning solution B; C. adding the spinning solution A into the spinning solution B and stirring to obtain inner-layer spinning solution; s4, synthesizing the wound dressing: A. coating the repair glue on the supporting layer to obtain a repair glue layer; B. placing the repair glue layer on an electrostatic spinning receiving plate to serve as a supporting layer for receiving the inner-layer nano fibers; C. preparing the inner layer spinning solution into inner layer nano fibers by an electrostatic spinning technology, collecting the inner layer nano fibers on the supporting layer, standing, taking out and drying to obtain the wound dressing.

5. The preparation method of the high-breathability degradable drug-loaded skin wound dressing according to claim 4, wherein the drug-loaded skin wound dressing comprises the following steps: the method specifically comprises the following steps: s1, preparing an outer dressing layer: A. dissolving polycaprolactone and polyvinyl alcohol in N, N-dimethylformamide under stirring, adding sodium alginate solution, and reacting under stirring for 30-50min to obtain spinning solution of the outer layer of the dressing; B. preparing the spinning solution on the outer layer of the dressing into outer-layer nano fibers by an electrostatic spinning technology, and collecting by a roller to obtain the outer layer of the dressing; s2, preparing a repairing adhesive: A. adding the polyethyleneimine solution into the hemostatic agent, and uniformly stirring to obtain a solution A; B. heating the solution A, placing the medicament carrier in the solution A under a low pressure condition, ultrasonically dispersing for 1-2h, and taking out to obtain porous medicament-carrying microspheres; C. uniformly mixing dialdehyde pectin and pullulan, adding deionized water, heating and melting at 30-40 ℃, sequentially adding porous drug-loaded microspheres, o-aminobenzyl chloride and dopamine, stirring and reacting for 30-50min, adjusting the pH value to 8-10, adding hydroxyl cucurbituril, stirring and reacting for 10-20min at the speed of 100-200r/min, and obtaining a repair gum; s3, synthesizing an inner layer spinning solution: A. placing polyvinylidene fluoride in N, N-dimethylformamide, stirring and dissolving to obtain spinning solution A; B. putting gelatin, zein and 4-vinyl benzyl chloride into ethanol, stirring and dissolving to obtain a spinning solution B; C. adding the spinning solution A into the spinning solution B under the heating condition of 80-100 ℃, and stirring and reacting for 1-2 hours to obtain an inner-layer spinning solution; s4, synthesizing the wound dressing: A. coating the repair glue on the supporting layer to obtain a repair glue layer; B. placing the repair glue layer on an electrostatic spinning receiving plate to serve as a supporting layer for receiving the inner-layer nano fibers; C. preparing the inner layer spinning solution into inner layer nano fibers by an electrostatic spinning technology, collecting the inner layer nano fibers on a supporting layer, standing for 30-50min at the temperature of 80-100 ℃, taking out, and drying for 3-5h at room temperature to obtain the wound dressing.

6. The preparation method of the high-breathability degradable drug-loaded skin wound dressing according to claim 5, wherein: the electrostatic spinning process parameters are as follows: the spinning voltage is 12-32kV, the receiving distance is 12-22cm, and the spinning speed is 0.03-6mL/h.

7. The preparation method of the high-breathability degradable drug-loaded skin wound dressing according to claim 6, wherein the drug-loaded skin wound dressing comprises the following steps: the heating temperature of the solution A in the step B of the step S2 is 30-40 ℃, and the low-pressure condition is 0.01-0.03MPa.

8. The preparation method of the high-breathability degradable drug-loaded skin wound dressing according to claim 7, wherein: and the pH value of the repair glue in the step B of the step S2 is 8-10.