CN111632187B

Movatterモバイル変換

Info

Publication number: CN111632187B
Application number: CN202010537296.6A
Authority: CN
Inventors: 郑芸芳; 杨鹏云; 周旺; 王在贵; 张欣欣
Original assignee: Anhui Agricultural University AHAU
Current assignee: Beijing Taike Siman Technology Development Co ltd
Priority date: 2020-06-12
Filing date: 2020-06-12
Publication date: 2021-05-18
Anticipated expiration: 2040-06-12
Also published as: CN111632187A

Abstract

Translated fromChinese

本发明公开了一种生物可降解医用敷料，以靠近创面一侧为内层，由内至外依次包括隔离层、抗菌促愈合层、诱导修复层和背衬层，隔离层和背衬层的尺寸大于抗菌促愈合层和诱导修复层；抗菌促愈合层包括以下重量份的原料：聚羟基丁酸戊酸共聚酯、I型胶原蛋白、羟丙基纤维素、生物活性玻璃、硝酸银溶液、可可籽脂、丙三醇1‑3份、醋酸、溶剂；诱导修复层包括以下重量份的原料：卡波姆、羟丙基四氢吡喃三醇、三肽‑1铜、超氧化物歧化酶、白藜芦醇、润湿剂。本发明的敷料抗菌促愈合层和诱导修复层协同作用，将创面愈合和瘢痕修复相结合，其中抗菌促愈层采用生物可降解高分子材料，具有较低的免疫原性，有利于创面愈合。

The invention discloses a biodegradable medical dressing, which takes the side close to the wound surface as an inner layer, and includes an isolation layer, an antibacterial healing-promoting layer, an inducing repair layer and a backing layer in sequence from the inside to the outside. The size is larger than that of the antibacterial healing-promoting layer and the inducing repair layer; the antibacterial healing-promoting layer includes the following raw materials by weight: polyhydroxybutyric acid valeric acid copolyester, type I collagen, hydroxypropyl cellulose, bioactive glass, silver nitrate solution , cocoa seed butter, 1-3 parts of glycerol, acetic acid, solvent; the induced repair layer includes the following raw materials by weight: carbomer, hydroxypropyl tetrahydropyrantriol, tripeptide-1 copper, superoxide Dismutase, resveratrol, humectant. The antibacterial and healing-promoting layer and the inducing repairing layer of the dressing of the present invention cooperate to combine wound healing and scar repair.

Description

Biodegradable medical dressing and preparation method thereof

Technical Field

The invention relates to a medical dressing, in particular to a biodegradable medical dressing and a preparation method thereof.

Background

The healing of the skin wound is a complex dynamic process, mainly involving three overlapping stages of inflammation, proliferation and remodeling, and the medical dressing plays an important role in the healing process of the wound. The traditional gauze dressing is mainly prepared by deeply processing cotton and hemp raw materials, has simple manufacturing process and low price, but the traditional gauze dressing can not maintain the humid environment required by wound healing, is easy to adhere wound tissues and causes secondary mechanical injury during dressing change. In addition, the traditional dressing has no antibacterial property, the wound surface is easy to be infected by bacteria, bad smell is generated, wound complications are caused, and the wound healing is not facilitated. With the progress of modern science and technology, new medical dressings are continuously appeared, and new clinical efficacy is also continuously improved.

The biodegradable material is a biological material which has special performance and can be degraded without generating adverse effect on human tissues in medicine. With the development of tissue engineering technology, biodegradable materials are rapidly developed. The biodegradable material comprises the following components: (1) natural degradable high molecular material: mainly comprises collagen, gelatin, chitose, alginic acid, polyamino acid, etc. The material has the advantages that degradation products are easy to absorb and do not generate inflammatory reaction, but the weakness of poor mechanical property exists, and natural materials have certain difference in molecular weight, physical property and the like of the same material due to different sources, so that unstable influence is caused on the release performance of the medicine. (2) Synthesized degradable high molecular material: is the main research object of the biological material for the tissue engineering at present, wherein the main research object is polylactide series materials; the material has adjustable degradation speed and strength, is easy to mold and construct a high-porosity three-dimensional bracket, and has the defects that the concentrated release of degradation products of the material is easy to generate inflammatory reaction, so that the acidity of a contact environment is overhigh, the affinity of the material to cells is weak, the adhesiveness to the cells is poor, the healing of a wound surface is not facilitated when the material is contacted with the wound surface, and the healed wound surface is easy to generate scars to influence the attractiveness.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide a biodegradable medical dressing which has the characteristics of promoting the rapid healing of wounds and being not easy to generate scars.

The second purpose of the invention is to provide a preparation method of the biodegradable medical dressing.

One of the purposes of the invention is realized by adopting the following technical scheme:

a biodegradable medical dressing takes one side close to a wound surface as an inner layer, and sequentially comprises an isolation layer, an antibacterial healing promoting layer, an induced repair layer and a backing layer from inside to outside, wherein the sizes of the isolation layer and the backing layer are larger than those of the antibacterial healing promoting layer and the induced repair layer;

the antibacterial healing promoting layer comprises the following raw materials in parts by weight: 55-65 parts of polyhydroxybutyrate-hydroxyvalerate, 5-10 parts of type I collagen, 1-3 parts of hydroxypropyl cellulose, 0.1-1 part of bioactive glass, 0.5-1 part of silver nitrate solution, 0.05-0.1 part of cocoa seed fat, 1-3 parts of glycerol, 0.1-0.3 part of acetic acid and 60-70 parts of solvent;

the induced repair layer comprises the following raw materials in parts by weight: 10-15 parts of carbomer, 0.1-1 part of hydroxypropyl tetrahydropyrane triol, 0.1-0.5 part of tripeptide-1 copper, 0.1-0.5 part of superoxide dismutase, 0.1-0.3 part of resveratrol and 5-10 parts of wetting agent.

Further, the carbomer is carbomer 974P.

Further, the solvent is purified water.

Further, the wetting agent is an aqueous solution of sodium chloride, calcium chloride or aluminum chloride.

Further, the back lining layer is a medical polyurethane film, and the isolation layer is release paper.

The second purpose of the invention is realized by adopting the following technical scheme:

the preparation method of the biodegradable medical dressing comprises the following steps:

(1) taking part of solvent, adding bioactive glass, glycosaminoglycan and silver nitrate solution, fully stirring and dissolving, adding cocoa seed butter, and uniformly mixing to obtain a component A;

(2) adding polyhydroxybutyrate-hydroxyvalerate, type I collagen, hydroxypropyl cellulose and acetic acid into the residual solvent, heating to 70-75 ℃, stirring until the mixture is dissolved, adding glycerol, and continuously stirring until the mixture is uniformly mixed to obtain a component B;

(3) mixing the component A and the component B, uniformly stirring at 55-60 ℃, putting into a mould, and freeze-drying to obtain a composite membrane, namely the antibacterial healing promoting layer;

(4) adding a wetting agent into hydroxypropyl tetrahydropyrane triol, tripeptide-1 copper, superoxide dismutase and resveratrol, uniformly mixing, adding carbomer, and fully swelling to obtain a gel matrix component C;

(5) and (3) compounding the composite film and the isolating layer in the step (3), uniformly coating the gel matrix component C on the composite film to form an induced repair layer, covering a back lining layer on the induced repair layer, and performing irradiation sterilization to obtain the product.

Further, the coating thickness of the induction repairing layer in the step (5) is 0.5-1 mm.

Further, the temperature of the freeze drying in the step (3) is-20 to-10 ℃.

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

1. according to the biodegradable medical dressing provided by the invention, the antibacterial healing promoting layer adopts polyhydroxybutyrate-valerate and type I collagen as a membrane scaffold, and the hydroxypropyl cellulose is added as a water-soluble pore-forming agent, so that the affinity and adhesion of the membrane material to cells are improved; on the other hand, under the action of the seepage, a plurality of micropores are formed on the surface of the membrane, so that the permeability of the membrane is improved, the absorption capacity of the seepage is increased, and the active substances in the induced repair layer are facilitated to contact with the wound surface through diffusion.

2. The bioactive glass is combined with a film bracket formed by the bioactive glass, the polyhydroxybutyrate-valerate and type I collagen, the acidity of the contacted wound surface can be increased under the action of seepage by the film material, the skin pricking feeling caused by the transient overhigh pH of the wound caused by the bioactive glass can be relieved, and the bioactive glass is beneficial to keeping the stability of the polyhydroxybutyrate-valerate.

3. The antibacterial healing promoting layer of the biodegradable dressing is also added with silver ions, the silver ions have a sterilization effect and reduce wound inflammation, and the silver ions and bioactive glass jointly act on a wound to promote the healing of the wound.

4. The biodegradable dressing disclosed by the invention is prepared by compounding glycosaminoglycan and cocoa seed fat, so that the lubrication degree of a wound surface is improved, and the wound is prevented from being adhered when the dressing is taken down and being damaged.

5. The biodegradable dressing also comprises an induction repairing layer, which helps the healed wound to be further repaired and avoids scars. Particularly, carbomer 974P is used as a matrix, the carbomer has good permeability, hydroxypropyl tetrahydropyrane triol, tripeptide-1 copper, superoxide dismutase and resveratrol are added for compounding, the hydroxypropyl tetrahydropyrane triol can promote the generation of hyaluronic acid of the skin of a wound, and meanwhile, the tripeptide-1 copper induces cells to generate more elastic substances such as collagen and the like, so that the construction of an internal network of the skin cells is promoted, and the tripeptide-1 copper and the hydroxypropyl tetrahydropyrane triol have synergistic effect to help the skin of the wound to recover elasticity and avoid the generation of scars. Superoxide dismutase and resveratrol can repair damaged cells, further inhibit scar generation, and copper in tripeptide-1 copper can promote superoxide dismutase to better play a role in resisting oxidation and scavenging free radicals.

6. The biodegradable dressing antibacterial healing promoting layer and the induced repairing layer have synergistic effect, wound healing and scar repairing are combined, the antibacterial healing promoting layer is made of biodegradable high polymer materials, has low immunogenicity, and cannot cause an organism to generate additional inflammatory reaction, the antibacterial healing promoting layer is a membrane support made of degradable high polymer, can be used as a carrier of active substances to act on the wound, and the active substances of the induced repairing layer pass through the antibacterial healing promoting layer and then contact the wound along with healing of the wound, so that wound healing is facilitated, and scar generation is avoided.

Drawings

FIG. 1 is a schematic structural diagram of a biodegradable medical dressing according to the present invention;

in the figure: 1. an isolation layer; 2. an antibacterial healing promoting layer; 3. an induction repair layer; 4. a backing layer.

Detailed Description

The present invention will be further described with reference to the accompanying drawings and the detailed description, and it should be noted that any combination of the embodiments or technical features described below can be used to form a new embodiment without conflict.

Example 1

A biodegradable medical dressing takes one side close to a wound surface as an inner layer, and sequentially comprises an isolation layer 1, an antibacterial healing promoting layer 2, an inducedrepair layer 3 and a backing layer 4 from inside to outside, wherein the sizes of the isolation layer 1 and the backing layer 4 are larger than those of the antibacterial healing promoting layer 2 and the inducedrepair layer 3, as shown in figure 1;

the antibacterial healing promoting layer is composed of the following raw materials in parts by weight: 60 parts of polyhydroxy butyric acid and valeric acid copolyester, 8 parts of type I collagen, 2 parts of hydroxypropyl cellulose, 0.5 part of bioactive glass, 0.8 part of silver nitrate solution, 0.08 part of cocoa seed fat, 2 parts of glycerol, 0.2 part of acetic acid and 65 parts of purified water;

the induced repair layer is composed of the following raw materials in parts by weight: carbomer 974P 12 parts, hydroxypropyl tetrahydropyrane triol 0.3 part, tripeptide-1 copper 0.3 part, superoxide dismutase 0.2 part, resveratrol 0.1 part and sodium chloride aqueous solution 8 parts.

(1) taking one fifth of purified water, adding bioactive glass, glycosaminoglycan and silver nitrate solution, fully dissolving, adding cocoa seed butter, and mixing uniformly to obtain a component A;

(2) adding polyhydroxybutyrate-hydroxyvalerate, type I collagen, hydroxypropyl cellulose and acetic acid into the residual solvent, heating to 775 ℃, stirring until the mixture is dissolved, adding glycerol, and continuously stirring until the mixture is uniformly mixed to obtain a component B;

(3) mixing the component A and the component B, uniformly stirring at 60 ℃, putting into a mould, and freeze-drying at the temperature of minus 20 ℃ to obtain a composite film, namely the antibacterial healing promoting layer;

(4) adding hydroxypropyl tetrahydropyrane triol, tripeptide-1 copper, superoxide dismutase and resveratrol into a wetting agent, uniformly mixing, adding carbomer 974P, and fully swelling to obtain a gel matrix component C;

(5) and (3) compounding the composite film and the isolating layer in the step (3), uniformly coating the gel matrix component C on the composite film to form an induced repair layer, wherein the coating thickness is 0.5mm, covering a back lining layer on the induced repair layer, and performing irradiation sterilization to obtain the product.

Example 2

the antibacterial healing promoting layer is composed of the following raw materials in parts by weight: 55 parts of polyhydroxy butyric acid and valeric acid copolyester, 5 parts of type I collagen, 1 part of hydroxypropyl cellulose, 0.1 part of bioactive glass, 0.5 part of silver nitrate solution, 0.05 part of cocoa seed fat, 1 part of glycerol, 0.1 part of acetic acid and 60 parts of purified water;

the induced repair layer is composed of the following raw materials in parts by weight: carbomer 974P 1 part, hydroxypropyl tetrahydropyrane triol 0.1 part, tripeptide-1 copper 0.1 part, superoxide dismutase 0.1 part, resveratrol 0.1 part and calcium chloride aqueous solution 5 parts.

(2) adding polyhydroxybutyrate-hydroxyvalerate, type I collagen, hydroxypropyl cellulose and acetic acid into the residual solvent, heating to 73 ℃, stirring until the polyhydroxybutyrate-hydroxyvalerate is dissolved, adding glycerol, and continuously stirring until the components are uniformly mixed to obtain a component B;

(3) mixing the component A and the component B, uniformly stirring at 58 ℃, putting into a mould, and freeze-drying at-10 ℃ to obtain a composite film, namely the antibacterial healing promoting layer;

(5) and (3) compounding the composite film and the isolating layer in the step (3), uniformly coating the gel matrix component C on the composite film to form an induced repair layer, wherein the coating thickness is 0.8mm, covering a back lining layer on the induced repair layer, and performing irradiation sterilization to obtain the product.

Example 3

the antibacterial healing promoting layer is composed of the following raw materials in parts by weight: 65 parts of polyhydroxybutyrate-hydroxyvalerate, 10 parts of type I collagen, 3 parts of hydroxypropyl cellulose, 1 part of bioactive glass, 1 part of silver nitrate solution, 0.1 part of cocoa seed fat, 3 parts of glycerol, 0.3 part of acetic acid and 70 parts of purified water;

the induced repair layer is composed of the following raw materials in parts by weight: 15 parts of carbomer 974P, 1 part of hydroxypropyl tetrahydropyrane triol, 0.5 part of tripeptide-1 copper, 0.5 part of superoxide dismutase, 0.3 part of resveratrol and 10 parts of wetting agent.

(1) taking part of solvent, adding bioactive glass, glycosaminoglycan and silver nitrate solution, fully dissolving, adding cocoa seed butter, and mixing uniformly to obtain a component A;

(2) adding polyhydroxybutyrate-hydroxyvalerate, type I collagen, hydroxypropyl cellulose and acetic acid into the residual solvent, heating to 75 ℃, stirring until the polyhydroxybutyrate-hydroxyvalerate is dissolved, adding glycerol, and continuously stirring until the components are uniformly mixed to obtain a component B;

(5) and (3) compounding the composite film and the isolating layer in the step (3), uniformly coating the gel matrix component C on the composite film to form an induced repair layer, wherein the coating thickness is 1mm, covering a back lining layer on the induced repair layer, and performing irradiation sterilization to obtain the product.

Comparative example 1

Comparative example 1 provides a biodegradable medical dressing, which is different from example 1 in that: hydroxypropyl cellulose was omitted and the procedure was as in example 1.

Comparative example 2

Comparative example 2 provides a biodegradable medical dressing, which is different from example 1 in that: the bioactive glass was omitted and the procedure was as in example 1.

Comparative example 3

Comparative example 3 provides a biodegradable medical dressing, which is different from example 1 in that: the tripeptide-1 copper was omitted and the amount of hydroxypropyl tetrahydropyrane triol used was adjusted to 0.6 part, the rest being the same as in example 1.

Comparative example 4

Comparative example 4 provides a biodegradable medical dressing, which is different from example 1 in that: hydroxypropyl tetrahydropyrane triol was omitted, and the amount of the tripeptide-1 copper was adjusted to 0.6 part, and the rest was the same as in example 1.

Comparative example 5

Comparative example 5 provides a biodegradable medical dressing, which is different from example 1 in that: the superoxide dismutase was omitted and the amount of resveratrol was adjusted to 0.3 parts, the remainder being the same as in example 1.

Comparative example 6

Comparative example 6 provides a biodegradable medical dressing, which is different from example 1 in that: resveratrol was omitted, and the amount of superoxide dismutase was adjusted to 0.3 part, and the rest was the same as in example 1.

Experimental example 1

The liquid absorption amount and the liquid absorption rate of the biodegradable medical dressings prepared in example 1 and comparative examples 1 to 2 were measured, respectively, according to the following procedure: a sample to be detected is taken and cut into a size of 2cm multiplied by 5cm, after the separation layer is removed, an equal amount of aqueous solution of sodium chloride and calcium chloride dihydrate is dripped on the surface, and the liquid absorption capacity of each dressing group at 37 ℃ for 24h is measured according to the method in YY/T0471.1-2004, and the result is shown in Table 1.

TABLE 1

Sample (I)	Example 1	Comparative example 1	Comparative example 2
				Liquid absorption amount (g)	2.5	1.5	1.7

As can be seen from Table 1, the dressing of example 1 has the largest liquid absorption amount, which is higher than that of comparative example 1 and comparative example 2, and illustrates that the permeability of the composite membrane formed by the high molecular polymer is improved and the absorption amount of the seepage is effectively increased by adding hydroxypropyl cellulose and bioactive glass in the membrane material of the high molecular polymer of the antibacterial healing promoting layer.

Experimental example 2

Establishing a mouse wound model: 8 male healthy mice of 5-6 weeks old were taken, were subjected to intraperitoneal injection of 350mg/kg chloral hydrate for anesthesia, and after dorsal skin unhairing and sterilization, wounds were made with a corneal trephine having a diameter of 8mm, the dressings of example 1 and comparative examples 1 to 6 were applied to the wounds, one of the mice was used as a control group, and the wound healing time of each mouse was counted using a common commercially available gauze, and the skin condition of the healed wound was observed, with the results shown in table 2.

TABLE 2

As can be seen from Table 2, the control mice using common commercial gauze had slower wound healing and severe scarring. The wound healing time was minimal with the dressing of example 1 and no significant scarring of the skin surface after healing, essentially returning to normal skin color. In comparative examples 1 to 2, the healing time reaches 6 to 7 days, and scars are formed on the surface of the skin after healing, which shows that after hydroxypropyl cellulose is omitted, on one hand, the permeability of the antibacterial healing promoting layer is reduced, and the components such as hydroxypropyl tetrahydropyrane triol, tripeptide-1 copper and the like in the induced repair layer are influenced to act on the wound surface, so that scars are generated; on the other hand, the affinity and the adhesiveness of the antibacterial healing promoting layer to cells are reduced, and the wound healing is influenced. After the bioactive glass is omitted, the acidity of the surface of the wound can be improved by the polymer film material in the antibacterial healing promoting layer, and the stability of the polymer film can be influenced after the bioactive glass is omitted, so that the wound healing is not facilitated.

In comparative examples 3 to 6, the composition of the induced repair layer was adjusted, and although the healing time of the wound surface was shortened as compared with comparative examples 1 to 2, the skin scar after healing was evident. For example, after the hydroxypropyl tetrahydropyrane triol is omitted, even if the dosage of the tripeptide-1 copper is adjusted, obvious scars are generated on the surface of the skin, and the synergistic effect of the peptide-1 copper and the hydroxypropyl tetrahydropyrane triol can induce cells to generate more elastic substances such as collagen, hyaluronic acid and the like, promote the construction of an internal network of the skin cells, help the skin of a wound recover elasticity and avoid the generation of the scars. The superoxide dismutase and the resveratrol can help to repair damaged cells and promote the cells to recover normal functions as soon as possible, and the copper in the tripeptide-1 copper can also promote the superoxide dismutase to better play a role in resisting oxidation and removing free radicals, so that scars at healed wounds are further avoided.

The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.

Claims

1. A biodegradable medical dressing is characterized in that one side close to a wound surface is taken as an inner layer and sequentially comprises an isolation layer, an antibacterial healing promoting layer, an induced repair layer and a backing layer from inside to outside, wherein the sizes of the isolation layer and the backing layer are larger than those of the antibacterial healing promoting layer and the induced repair layer;

2. The biodegradable medical dressing according to claim 1, wherein the carbomer is carbomer 974P.

3. The biodegradable medical dressing according to claim 1, wherein the solvent is purified water.

4. The biodegradable medical dressing according to claim 1, wherein the wetting agent is an aqueous solution of sodium chloride, calcium chloride or aluminum chloride.

5. The biodegradable medical dressing of claim 1, wherein the backing layer is a medical polyurethane film and the barrier layer is a release paper.

6. The method of making a biodegradable medical dressing of claim 1, comprising the steps of:

7. The method of preparing a biodegradable medical dressing according to claim 6, wherein the inducing repair layer is coated to a thickness of 0.5 to 1mm in the step (5).

8. The method for preparing a biodegradable medical dressing according to claim 6, wherein the temperature of the freeze-drying in the step (3) is-20 to-10 ℃.