阅读说明：本技术 一种皮肤创面覆盖膜及其制备方法 (Skin wound covering film and preparation method thereof ) 是由 赵鲁苹 鲁建国 张锐 于 2021-09-30 设计创作，主要内容包括：本发明提供了一种皮肤创面覆盖膜及其制备方法,所述皮肤创面覆盖膜为单层结构膜或者双层结构膜,所述单层结构膜通过胶原原料制成的基质浸入含有第一生长组分的溶液后交联制成,所述双层结构膜通过将胶原原料制成的基质与单层结构膜结合,浸入含有第二生长组分的溶液后交联制成。本发明的皮肤创面覆盖膜柔软舒适,贴合紧密,维持了胶原蛋白的活性,可修剪成任意形状,可降解,无需去除,配方全面,利于愈合。(The invention provides a skin wound covering film and a preparation method thereof, wherein the skin wound covering film is a single-layer structure film or a double-layer structure film, the single-layer structure film is prepared by immersing a substrate prepared from a collagen raw material into a solution containing a first growth component and then crosslinking, and the double-layer structure film is prepared by combining the substrate prepared from the collagen raw material with the single-layer structure film and immersing the substrate into a solution containing a second growth component and then crosslinking. The skin wound covering film disclosed by the invention is soft and comfortable, is tightly attached, maintains the activity of collagen, can be trimmed into any shape, is degradable, does not need to be removed, has a comprehensive formula, and is beneficial to healing.)

1. The skin wound covering film is characterized by being a single-layer structure film or a double-layer structure film, wherein the single-layer structure film is prepared by immersing a substrate prepared from a collagen raw material into a solution containing a first growth component and then crosslinking, and the double-layer structure film is prepared by combining the substrate prepared from the collagen raw material with the single-layer structure film and immersing the substrate into a solution containing a second growth component and then crosslinking.

2. The skin wound cover film of claim 1, wherein the collagen material comprises type I collagen, type ii collagen, type iii collagen, type v collagen or type xi collagen.

3. A wound cover film according to claim 1, wherein said first growth component comprises epidermal growth factor and 1.3-1.6 x 10⁶Da sodium hyaluronate.

4. A wound cover film according to claim 1, wherein said second growth component comprises sodium chondroitin sulfate and has a molecular weight of < 1.0 x 10⁴Da sodium hyaluronate.

5. A method for preparing the skin wound covering film according to any one of claims 1 to 4, wherein when the skin wound covering film is a single-layer structure film, the method comprises the following steps:

1) preparing a collagen solution, injecting the collagen solution into a mould with the liquid height of 0.2-0.5cm, and freeze-drying to obtain freeze-dried collagen A;

2) preparing a solution containing a first growth component, immersing the freeze-dried collagen A obtained in the step 1), and carrying out low-temperature air drying or freeze drying to obtain a dried collagen membrane A;

3) carrying out cross-linking reaction on the collagen membrane A obtained in the step 2), rinsing with purified water, and carrying out low-temperature air drying or freeze drying to obtain a skin wound surface covering film with a single-layer structure;

when the skin wound covering film is a double-layer structure film, the preparation method comprises the following steps:

a) preparing a collagen solution, flatly paving the single-layer structure membrane in a mould, injecting the collagen solution with the liquid height of 0.3-0.6cm, and freeze-drying to obtain freeze-dried collagen B;

b) preparing a solution containing a second growth component, immersing the freeze-dried collagen B obtained in the step a), and carrying out low-temperature air drying or freeze drying to obtain a dried collagen membrane B;

c) and c) carrying out crosslinking reaction on the collagen membrane B obtained in the step B), rinsing with purified water, and carrying out low-temperature air drying or freeze drying to obtain the skin wound covering film with the double-layer structure.

6. The method for preparing a skin wound cover film according to claim 5, wherein in step 1), the mass fraction of the collagen solution is 0.4-0.7%; in the step a), the mass fraction of the collagen solution is 0.4-0.7%.

7. A method for preparing skin wound cover film according to claim 5, wherein in step 2), the mass fraction of epidermal growth factor in the solution containing the first growth component is 0.1-0.2%, 1.3-1.6 x 10⁶The mass fraction of the sodium hyaluronate of Da is 0.5-1%; in the step b), the step (c),the solution containing the second growth component contains sodium chondroitin sulfate 0.1-0.5 wt% and molecular weight < 1.0 x 10⁴The mass fraction of the sodium hyaluronate of Da is 0.5-1%.

8. The method for preparing a skin wound covering film according to claim 5, wherein in the step 3) and the step c), the crosslinking reaction is performed for 1h-2h by using 0.02% by mass of glutaraldehyde or formaldehyde solution.

Technical Field

The invention belongs to the technical field of medical treatment, relates to a wound surface covering dressing, and particularly relates to a wound surface covering dressing which is beneficial to protecting and healing damaged skin; a skin wound covering film which is soft and comfortable to attach and a preparation method thereof.

Background

The skin is composed of epidermis, dermis and subcutaneous tissue, and has the function of protecting internal tissues from external damage; metabolism such as absorption, perspiration, sebum secretion, and waste excretion; the skin can regulate body temperature, and has effects of pain, touch, pressure, temperature and cold stimulation, and immunity. People inevitably suffer from various injuries in different weights in life, and particularly, the injuries caused by trauma, natural disasters and postoperative injuries after illness are difficult to avoid. When skin damage reaches a certain level, skin wound repair will end up with scarring due to a fibroproliferative response. Various body surface scars can damage the integrity of the original skin, damage the appearance and bring physical and psychological harm to patients.

After the skin is damaged, the wound needs to be protected and the healing needs to be promoted, and the existing skin wound covering is various dressings, such as gauze, vaseline oil gauze or biosynthetic covering and the like.

The main defects of the existing covering are as follows: 1) the adhesive tape is uncomfortable to fit and easy to stick or warp edges; 2) the required nutrients are not provided or the nutrients are provided singly.

Disclosure of Invention

The invention aims to provide a novel protective cover for damaged skin, which is beneficial to the protection and healing of damaged skin and aims to overcome the defects that the existing cover is uncomfortable to fit, is easy to stick or warp edges, and cannot provide required nutrients or provides single nutrients; the skin wound covering film is soft and comfortable to attach.

The invention also aims to provide a preparation method of the skin wound covering film.

In order to achieve the purpose, the invention adopts the following technical scheme:

the invention firstly provides a skin wound covering film which is a single-layer structure film or a double-layer structure film, wherein the single-layer structure film is prepared by immersing a substrate prepared from a collagen raw material into a solution containing a first growth component and then crosslinking, and the double-layer structure film is prepared by combining the substrate prepared from the collagen raw material with the single-layer structure film, immersing the substrate into a solution containing a second growth component and then crosslinking.

In the invention, the skin wound covering film is a single-layer structure film or a double-layer structure film, the single-layer structure film is suitable for the skin with damaged epidermis, and the double-layer structure film is suitable for the skin with damaged dermis and epidermis.

Collagen is one of the most important extracellular matrixes of human skin, and collagen in natural skin tissues forms a fiber network and has a supporting effect. The collagen with bioactivity can be extracted by the prior art, has a triple helix configuration, can be identified by cells, has chemotactic property on the cells, promotes the healing of cell proliferation wound surfaces, and has no toxicity after degradation.

Sodium hyaluronate is also one of the most important extracellular matrixes of human skin, and can promote the proliferation and differentiation of skin cells and clear oxygen radicals. The macromolecular hyaluronic acid can form a film, so that the skin can be smooth and moist, bacteria and dust can be blocked, the protective effect can be achieved, the invasion of external bacteria, dust and ultraviolet rays can be blocked, and the skin can be protected from being damaged; the small molecular hyaluronic acid can penetrate into dermis, and has effects of slightly dilating capillary, increasing blood circulation, improving metabolism, and promoting skin nutrition absorption. The existing extraction method is usually obtained in the form of salt due to the process limitation, and collagen and HA in the form of salt are oppositely charged, and polymer is easily formed in a liquid state to generate precipitation.

Chondroitin sulfate has protective effect on collagen fiber, and can promote growth of fibroblast in dermis, enhance permeability, improve blood circulation, accelerate metabolism, promote absorption of penetrating fluid and eliminate inflammation.

The epidermal growth factor not only has the functions of promoting the healing of skin and mucous membrane wounds, preventing and treating ulcer, diminishing inflammation, relieving pain and the like, but also can effectively promote and regulate the growth and proliferation of epidermal cells.

The double-layer structure of the invention achieves the functional comprehensiveness of the covering film by adding macromolecular sodium hyaluronate, epidermal growth factor, micromolecular sodium hyaluronate and chondroitin sulfate.

In a preferred embodiment of the present invention, the collagen material comprises type I collagen, type II collagen, type III collagen, type V collagen or type XI collagen.

As a preferred embodiment of the present invention, the first growth component comprises epidermal growth factor and 1.3-1.6 x 10⁶Da sodium hyaluronate.

As a preferred embodiment of the present inventionSaid second growth component comprising sodium chondroitin sulphate and having a molecular weight < 1.0 x 10⁴Da sodium hyaluronate.

The invention further provides a preparation method of the skin wound covering film, and when the skin wound covering film is a single-layer structure film, the preparation method comprises the following steps:

1) preparing a collagen solution, injecting the collagen solution into a mould with the liquid height of 0.2-0.5cm, and freeze-drying to obtain freeze-dried collagen A;

2) preparing a solution containing a first growth component, immersing the freeze-dried collagen A obtained in the step 1), and carrying out low-temperature air drying or freeze drying to obtain a dried collagen membrane A;

3) carrying out cross-linking reaction on the collagen membrane A obtained in the step 2), rinsing with purified water, and carrying out low-temperature air drying or freeze drying to obtain a skin wound surface covering film with a single-layer structure;

when the skin wound covering film is a double-layer structure film, the preparation method comprises the following steps:

a) preparing a collagen solution, flatly paving the single-layer structure membrane in a mould, injecting the collagen solution with the liquid height of 0.3-0.6cm, and freeze-drying to obtain freeze-dried collagen B;

b) preparing a solution containing a second growth component, immersing the freeze-dried collagen B obtained in the step a), and carrying out low-temperature air drying or freeze drying to obtain a dried collagen membrane B;

c) and c) carrying out crosslinking reaction on the collagen membrane B obtained in the step B), rinsing with purified water, and carrying out low-temperature air drying or freeze drying to obtain the skin wound covering film with the double-layer structure.

In the prior art, due to process limitations, precipitation occurs when sodium hyaluronate and type I collagen are normally compounded.

The preparation method of the invention overcomes the defect that normal compounding of sodium hyaluronate and I type collagen can generate precipitate, and the skin wound covering film prepared by the preparation method of the invention can guarantee the properties of the skin wound covering film, and the preparation method is simple and convenient.

As a preferable scheme of the invention, in the step 1), the mass fraction of the collagen solution is 0.4-0.7%; in the step a), the mass fraction of the collagen solution is 0.4-0.7%.

In a preferred embodiment of the present invention, in step 2), the epidermal growth factor in the solution containing the first growth component is present in an amount of 0.1 to 0.2% by mass, 1.3 to 1.6 x 10 by mass⁶The mass fraction of the sodium hyaluronate of Da is 0.5-1%; in step b), the solution containing the second growth component has a sodium chondroitin sulfate content of 0.1-0.5 wt% and a molecular weight of less than 1.0 x 10⁴The mass fraction of the sodium hyaluronate of Da is 0.5-1%.

In a preferable embodiment of the invention, in the step 3) and the step c), the crosslinking reaction is performed for 1h-2h by using 0.02% by mass of glutaraldehyde or formaldehyde solution.

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

1) the invention overcomes the defect that the normal compounding of the sodium hyaluronate and the type I collagen can generate precipitate;

2) the skin wound surface covering film is soft and comfortable, is tightly attached, maintains the activity of collagen, can be trimmed into any shape, is degradable, does not need to be removed, has a comprehensive formula, and is beneficial to healing;

3) the preparation method has simple steps and low cost.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The raw materials used in the present invention are all commercially available.

Example 1

The skin wound covering film provided by the embodiment is a single-layer structure film, is suitable for skin with damaged epidermis, and the preparation method comprises the following steps:

1) taking a collagen I raw material, preparing 0.4-0.7% of collagen solution at 4-8 ℃, injecting the collagen solution into a mould, wherein the liquid height is 0.2-0.5cm, and freeze-drying to obtain freeze-dried sponge;

2) preparing the composition containing 0.1% -0.2% of epidermal growth factor and 0.5% -1% of 1.3-1.6 x 10⁶Da, soaking the freeze-dried sponge in the step 1) into the solution, draining the solution after full imbibition, placing the solution in a mold, and air-drying the sponge at a low temperature or freeze-drying the imbibed sponge to obtain a dried collagen membrane;

3) crosslinking the membrane in the step 2) for 1-2 h by using 0.02% glutaraldehyde or formaldehyde solution, and rinsing by using purified water; and continuously air-drying or freeze-drying the membrane at low temperature to obtain the skin wound covering membrane with a single-layer structure.

Example 2

The skin wound covering film provided by the embodiment is a double-layer structure film, is suitable for skin with damaged dermis and epidermis, and the preparation method comprises the following steps:

a) taking a collagen type I raw material, and preparing a collagen solution with the concentration of 0.4-0.7% at the temperature of 4-8 ℃; spreading the single-layer structure membrane prepared in the embodiment 1 at the bottom of a mould, pouring a collagen solution with the liquid height of 0.3cm-0.6cm, and freeze-drying to obtain a freeze-dried composite sponge;

b) preparing the mixture containing 0.1-0.2% of sodium chondroitin sulfate and 0.5-1% of sodium chondroitin sulfate with molecular weight less than 1.0 x 10⁴Da in sodium hyaluronate; b, immersing the composite sponge prepared in the step a into the solution, draining the solution after full liquid absorption, placing the solution into a mould, and freeze-drying the solution to obtain a dry composite membrane;

c) and c, crosslinking the composite membrane prepared in the step b for 1 to 2 hours by using 0.02 percent glutaraldehyde or formaldehyde solution, rinsing, and freeze-drying to obtain the skin wound surface covering membrane with the double-layer structure.

The using method comprises the following steps: when the wound surface is shallow and does not hurt the dermis, the skin wound surface covering film prepared in the embodiment 1 can be used for isolating and protecting the damaged skin and promoting healing; when the wound surface is deep and damages the dermis, the skin wound surface covering film prepared in the embodiment 2 can be used for supporting, protecting and promoting healing of the damaged skin.

The method comprises the following steps: taking out the wound surface covering material, dripping purified water to soak, covering the wound surface, fixing by using suture or secondary dressing, and automatically degrading without taking out after covering, so that the wound surface is healed.

While the invention has been described with respect to a preferred embodiment, it will be understood by those skilled in the art that the foregoing and other changes, omissions and deviations in the form and detail thereof may be made without departing from the scope of this invention. Those skilled in the art can make various changes, modifications and equivalent arrangements, which are equivalent to the embodiments of the present invention, without departing from the spirit and scope of the present invention, and which may be made by utilizing the techniques disclosed above; meanwhile, any changes, modifications and variations of the above-described embodiments, which are equivalent to those of the technical spirit of the present invention, are within the scope of the technical solution of the present invention.