JPH10216215A - Wound coating material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a polyinyl alcohol (PVA) sheet wound coating material which is a wound coating material of a wet dressing type for treating the skin damaged by a burn, wound, etc., and which prevents shrinkage and deformation at the time of drying and has excellent wet holdability, transparency, antimicrobial property, etc. SOLUTION: This wound coating material of the wet dressing type is a wound coating material formed by applying a tacky adhesive to a PVA sheet contg. chitosan and coating the surface of the tacky adhesive layer with a transparent sheet having the water vapor transmission rate lower than the water vapor transmission rate of the PA sheet and, therefore, the wound coating material is free from the shrinkage and deformation at the time of drying, has the excellent wet holdability and is provided with the excellent antimicrobial property by adding a silver antimicrobial agent to PVA. The wound coating material having the excellent transparency and high practicable use value is obtd. by adding glycerol, propylene glycol or sugar alcohol, etc., to the material.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound dressing for treating skin damaged by burns, wounds and the like, and more particularly to a polyvinyl alcohol wound dressing excellent in moisture retention and dimensional stability.

[0002]

BACKGROUND OF THE INVENTION Numerous wound dressings have been developed and sold. For example, as those made of synthetic materials, there are a sheet made of nylon fiber or polyester fiber, a polyurethane porous sheet, a crosslinked polyvinyl alcohol sheet, a silicone film, a polyamino acid film, and the like.
Examples of the body-derived compound include collagen nonwoven fabric, frozen pig skin, fibrin membrane, chitin / chitosan membrane, and the like. However, each of these wound dressings has its own problems. For example, wound dressings made of synthetic materials
In general, there is a problem that affinity with a living body is low and a foreign body reaction is strong. In addition, wound dressing materials such as collagen and frozen pig skin of biological compounds are not suitable as long-term dressing materials because of their strong immunological rejection with the living body and rapid decomposition and absorption by the living body. There is a problem.

[0003] Such wound dressings are broadly classified into two types. That is, a dry dressing type for the purpose of performing healing by forming a crust while keeping the wound surface in a dry state, allowing the skin cells to migrate promptly in a moderately moist state without forming a crust There is a wet dressing type intended for healing. In general, it is known that the latter is advantageous because healing is rapid, skin cell death due to drying of the wound surface is small, excessive cell growth on the wound surface is suppressed, and traces are hardly left. Examples of the wound dressing belonging to the latter include the aforementioned porous polyurethane sheet, crosslinked polyvinyl alcohol sheet, and silicone film.

[0004] However, a disadvantage of such a wet dressing type is that since the covering sheet is in a wet state by storing exudates from the body inside, it is very easy to cause various bacterial infections. For this reason, measures such as adding antibiotics to the coating sheet to impart antibacterial properties have been taken, but the antibacterial properties are maintained for a long time until the antibiotics elute early and the wound surface is healed. It is difficult to maintain, and there is a problem that even if an antibiotic is present in the coating sheet, resistant bacteria will reproduce. On the other hand, there has been a strong demand for a wound dressing material having transparency so that the healing state of the wound part can be directly observed from above the sheet during treatment.

[0005] In the present situation as described above, the present inventors,
As a wound dressing belonging to the wet dressing type, 1) excellent sheet transparency, 2) hardly cause drug resistance of various germs, and sustained antibacterial effect during the healing period, 3) wound surface It has a protective effect and can maintain an appropriate moist state. 4) It has flexibility so that it can adhere to a complex wound site or a moving wound surface.
5) a wound dressing material having conditions such as good biocompatibility and 6) water vapor permeability and oxygen permeability, having a visible light transmittance at 380 nm to 780 nm of 5% or more; A method for producing a wound dressing comprising a polyvinyl alcohol sheet containing a system antibacterial agent was completed, and an application was filed earlier (Japanese Patent Application No. 7-125701).

However, as a result of further study on the wound dressing, if the wound exudate such as plasma does not come out much, or if the exudate does not come out of the wound at a relatively early stage, the wound dressing will be used. Due to the high water vapor permeability, the wound is healed, and the membrane dries and shrinks and peels off before the epithelialization is successfully completed, keeping the wound surface necessary for good epithelialization in a moist state. It became clear that there was none. Further, it was also found that the sustainability of the antibacterial action of the silver-based antibacterial agent was reduced with drying. Such a problem,
It is likely to occur in wounds with relatively shallow wounds and little exudate, or in periods of low humidity.

Therefore, this wound dressing may be difficult to use depending on the condition of the wound, etc., although it has excellent properties as a wound dressing containing an antibacterial agent, and its use and application are restricted. I was

[0008]

Accordingly, in the present invention, there is provided a wound dressing material comprising polyvinyl alcohol as a main material, which has a low water vapor permeability, maintains a good wet state for epithelialization, and hardly shrinks and peels off. The purpose is to:

[0009]

That is, the present invention comprises applying a pressure-sensitive adhesive to a polyvinyl alcohol sheet containing chitosan, and covering the pressure-sensitive adhesive layer with a transparent sheet having a lower water vapor permeability than the polyvinyl alcohol sheet. The present invention relates to a wound dressing.

[0010]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS First, the method for producing a wound dressing of the present invention will be described in detail as follows. That is, the wound dressing of the present invention comprises a mixture of an aqueous solution of polyvinyl alcohol (hereinafter, referred to as PVA) and an aqueous solution of chitosan crosslinked by freeze-drying to form a sheet, forming an adhesive layer on the sheet, and further forming an adhesive layer on the sheet. Is coated with a transparent sheet having a lower water vapor permeability than the PVA sheet. The base materials used for producing such a wound dressing are PVA and chitosan as described above.

The reason why chitosan is used in the present invention is to improve the bonding between the PVA sheet and the adhesive. That is, when chitosan is not used, PVA
This is because the sheet and the adhesive hardly join.

As a method of crosslinking a PVA aqueous solution,
In the following, a method for crosslinking by mainly freeze-drying a PVA aqueous solution will be described. The crosslinking by the freeze-drying method is characterized in that a sheet having a high moisture content is obtained. Instead of the freeze-drying method, a method of using a chemical such as chemical crosslinking or a method of performing crosslinking by irradiation with radiation may be used to obtain a wound dressing material having excellent characteristics of the present invention.

The PVA used in the present invention preferably has a degree of polymerization of 500 or more and a degree of suspension of 98 mol% or more. This is undesirable because the strength of the resulting wound dressing is reduced. The concentration of the PVA aqueous solution is desirably in the range of 5 to 20% by weight from the relationship between strength and transparency of the wound dressing of the present invention obtained after freeze-drying, and is preferably 5% by weight.
Below, the strength of the covering material is reduced, and at 20% by weight or more, the strength of the covering material is increased, but the transparency of the sheet is remarkably reduced, which is not preferable as a wound covering material.

As the chitosan used in the present invention, it is desirable to use a chitosan having a degree of deacetylation of 80% or more in view of the bonding property between the PVA and the adhesive. , The bonding property deteriorates, which is not desirable. The concentration of the aqueous chitosan solution to be used is desirably 10% by weight or less.
If the content is 0% by weight or more, the flexibility of the covering material is deteriorated and the transparency of the sheet is remarkably reduced. In the present invention, the aqueous PVA solution and the aqueous chitosan solution are then mixed. The mixing ratio of the two is such that the amount of chitosan is 0.1 to 50% by weight based on the total amount of PVA and chitosan. If the amount of chitosan is more than 50%, the flexibility of the film is lowered and the transparency is extremely lowered, which is not desirable. If the amount is less than 0.1% by weight, sufficient adhesion between the PVA sheet and the pressure-sensitive adhesive cannot be obtained.

As an example of the method for producing the wound dressing of the present invention, first, PVA is dissolved by heating with water, and a silver-based antibacterial agent is desirably added and dispersed therein. Apart from the PVA aqueous solution containing the silver-based antibacterial agent, a chitosan aqueous solution previously dissolved in 1% acetic acid is mixed with the PVA aqueous solution containing the silver-based antibacterial agent, and the mixture is poured into a molding frame and freeze-dried to obtain PVA. Form the sheet. The freezing temperature in this case is desirably in the range of −50 ° C. to −5 ° C.,
Below 50 ° C., the crosslinked PVA sheet obtained after freeze-drying becomes brittle in a wet state. On the other hand, if the temperature is higher than -5 ° C, the freeze-drying time is required for a long time, which is not industrial.
About the thickness of a PVA sheet, the range of 0.1-2 mm is suitable. When the thickness of the sheet is 0.1 mm or less, the sheet strength is low, and when the thickness is 2 mm or more, the transparency of the sheet deteriorates. Drying is performed according to a usual freeze-drying method, and is 10 ⁻² to 10 ⁻³ m.
Drying may be performed under a vacuum condition of about mHg.

The adhesive may be applied by dropping an appropriate amount of the adhesive described below onto the freeze-dried chitosan-containing PVA sheet, and applying the adhesive to the upper surface of the chitosan-containing PVA sheet using, for example, a rod coater. Then, on the pressure-sensitive adhesive layer, the PV
A transparent sheet having a lower water vapor permeability than the A sheet is coated according to a conventional method. The thickness of the transparent sheet is 1
A thickness of １００100 μm is desirable. The wound dressing material of the present invention comprising a chitosan-containing PVA sheet containing a silver-based antibacterial agent obtained in this manner is usually used in a wet state with a water content of about 30% by weight. Wetting is performed with water or physiological saline. More specifically, when a polyethylene sheet having a thickness of, for example, 10 μm is used as the transparent sheet, the water vapor permeability of the wound dressing of the present invention (when one side is contacted with ion-exchanged water, at a temperature of 30 ° C. and a humidity of 50%) The amount of water evaporating from the coating material)
It is about 20 (g / m ² / day). In the case of a single PVA sheet, the water vapor permeability is 3000 to 7000.
(G / m ² / day), the water vapor permeability is largely suppressed according to the present invention. In addition, thickness 10
When a μm polyurethane sheet is used, the water vapor permeability is about 100 to 250 (g / m ² / day).
That is, the water vapor permeability can be arbitrarily adjusted by selecting the transparent sheet.

As the pressure-sensitive adhesive used in the present invention, an acrylic pressure-sensitive adhesive is particularly recommended. Acrylic acid polymer, acrylic acid ester copolymer, acrylic acid- (meth) acrylic acid ester copolymer, acrylic acid-acetic acid Vinyl copolymer,
An acrylate-vinyl acetate copolymer, an acrylate-vinyl alkyl ether copolymer, an acrylate-vinyl alkyl ether copolymer, and the like are included.

The transparent sheet having a lower water vapor permeability than the PVA sheet to be coated on the pressure-sensitive adhesive layer used in the present invention has oxygen permeability, has very little elution in a liquid, and has elasticity and flexibility. It is desirable to have a superior quality. Desirable transparent sheets include polyethylene, polypropylene, polyisobutylene, polybutadiene, polyisoprene, polychloroprene, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, acrylic resin, polycarbonate, polyvinyl acetate, polyester resin, polyurethane resin, and polyamide resin. , Fluororesin, polystyrene, polyether, nitrocellulose and the like.

For the wound dressing of the present invention, it is particularly recommended to use a silver-based antibacterial agent. When the wound dressing of the present invention uses a silver-based antibacterial agent because it is used in a wet state,
The sustained release of silver ions over an extended period of time protects the wound from germs for an extended period of time. Examples of the silver-based antibacterial agent to be contained in the PVA sheet include zeolite, silica gel, a silver-based antibacterial agent in which silver is supported on a simple substance such as calcium phosphate,
Alternatively, there are silver sulfadiazine and an organic silver-based antibacterial agent in which silver is supported on organic polymer particles. In the present invention, there is no particular limitation on the type of silver-based antibacterial agent.
The proportion of the silver-based antibacterial agent varies depending on the silver content, the desired antibacterial property of the wound dressing material, and the like, and cannot be unconditionally determined. It is. If the amount is 0.1% by weight or less, the antibacterial property of the wound dressing of the present invention is not sufficient, and it is difficult to suppress infection by various bacteria.
The transparency of the wound dressing decreases, which is not preferable.

In the present invention, glycerin and propylene glycol (hereinafter abbreviated as PG) are added to a PVA aqueous solution before freezing in order to further increase the transparency of such a PVA sheet or to improve the dispersibility of an antibacterial agent. , Ethylene glycol, diethylene glycol, triethylene glycol, dipropylene glycol, diglycerin,
2,3-butanediol, polyoxyethylene butyl ether, sugar alcohol, polyethylene glycol (hereinafter abbreviated as PEG), triethyl citrate, triacetin, polyethylene glycol distearate, butyl phthalyl butyl glycol, dioctyl phthalate, dioctyl adipate, Polyoxyethylene hydrogenated castor oil, castor oil, phytosterols and the like can be added.

The types of sugar alcohols that can be used here include sorbitol, mannitol, zulcit, idit, erythritol, arabit, adnit, xylit, tarit, and the like. PEG is (-O-CH _2-
The number of units of CH _2- ) is preferably in the range of 3 to 22, and the molecular weight is preferably about 1,000 or less. The amount of these additives is determined according to the purpose.

[0022]

EXAMPLES Examples of the present invention will be further described below, but the present invention is not limited to only these examples. In this example, all percentages are by weight unless otherwise specified.

(Examples 1 to 6) 20 g of propylene glycol was placed in a 200 ml heat-resistant screw-neck bottle. P in it
VA (product name "PVA UF-20" manufactured by Unitika Ltd.)
0 "degree of polymerization 2000, degree of suspension 99.5 mol%) 10
g and 70 g of ion-exchanged water to make the total amount 100 g, followed by stirring. This was put in an autoclave at 110 ° C for 20 minutes.
Heat for 10 minutes to make a 10% PVA aqueous solution A. Then 20
Chitosan (Kyowa Technos Co., Ltd.) in a 0 ml beaker
5 g of brand name “Flownac C”) and acetic acid 2
g, and add 93 g of ion-exchanged water to make a total amount of 100 g.
Then, a uniform 5% chitosan aqueous solution B is prepared by stirring.
100 g of the aqueous solution A and 100 g of the aqueous solution B are mixed and stirred to obtain 200 g of a chitosan-containing aqueous PVA solution C.

An appropriate amount of this aqueous solution C was placed in a container fixed with a spacer having a thickness of 1 mm and sandwiched between two glass plates, and placed in a freezer at -10 ° C. for freezing. PVA
After the aqueous solution was frozen, one of the above glasses was removed, and then the glass was put into a freeze dryer and freeze-dried to obtain a chitosan-containing PVA sheet. Next, this was immersed in a 1N NaOH aqueous solution for 20 minutes to remove acetic acid, and neutralized again with 1N H ₂ SO ₄ . Next, place P on a glass plate that has been Teflon-treated.
The VA sheet was spread, fixed around with a clip, and then stretched and dried. The solid content concentration is 10% on the obtained dried sheet.
Is coated thinly with a rod coater and dried at room temperature. A 10 μm thick polyethylene sheet having a water vapor transmission rate of 5 g / m ² / day was laminated on the upper surface of the obtained PVA sheet (water vapor transmission rate of 5000 g / m ² / day) to obtain a chitosan-containing PVA wound dressing. (Example 1)

The amount of chitosan is 1% (Example 2), 10% (Example 3), 30% based on the total amount of PVA and chitosan.
(Example 4) A wound dressing was prepared in the same manner as in Example 1 except that the amount was changed to 50% (Example 5).

When the wound dressings of Examples 1 to 5 were wetted with ion-exchanged water, the moisture content of the wound dressings was 39% (Example 1), 40% (Example 2), and 38% ( Example 3), 41% (Example 4) and 41% (Example 5). In addition, the adhesion of the chitosan-containing PVA sheets of Examples 1 to 5 in a wet state was examined. In all of Examples 1 to 5, PVA sheets were left in a wet state for 2 weeks.
And the transparent sheet maintained good adhesion.

In addition, 2c was added to Wistar hairless rats.
As a result of surgically creating a wound of m × 2 cm × 200 μm depth and observing the healing state of the wound using the wound dressing,
The wound dressing of Example 1 maintained a good wet state, and after about 5 days, a favorable epithelialization was confirmed visually.

Next, in Example 1, except that a silver-based antibacterial agent (silver sulfadiazine) was added to the PVA aqueous solution and silver was contained in the PVA sheet (the Ag content in the sheet was 5%). A wound dressing was produced in exactly the same manner as in Example 1. A wound of 2 cm × 2 cm × 200 μm in depth is surgically made on Wistar hairless rats, and the antibacterial agent-containing PV
As a result of observing the healing state of the wound using the wound dressing A, the wet state was good and the epithelialization was confirmed visually after about 2 days (Example 6).

Comparative Example 1 A polyethylene-coated PVA wound dressing was prepared in the same manner as in Example 1 except that no aqueous chitosan solution was used. This was made wet with ion-exchanged water, and the adhesion of the polyethylene sheet and the PVA sheet in the wet state was examined.
When left for a while, the adhesive strength was reduced, and the sheet was separated.

(Comparative Example 2) The procedure of Example 1 was repeated except that the polyethylene sheet was not laminated.
A chitosan-containing PVA sheet of cm × 5 cm was prepared. After the sheet was sufficiently wetted with physiological saline and the area was measured, the sheet was placed on a glass plate and left at room temperature for 3 days, and the area was measured.
Had tripled.

(Examples 7 to 9) Instead of the polyethylene sheet used in Example 1, a polyvinylidene chloride sheet (Example 7), a polyvinyl acetate sheet (Example 8), and a nitrocellulose sheet (Example 9) were used. Used to obtain wound dressings with different water vapor permeability. Each of these wound dressings had a water vapor permeability of 11 g / m ² / day (Example 7),
144g / m ² / day (Example 8), 744g / m ² /
day (Example 9), and wound dressings having different water vapor permeability depending on the selected material were obtained. When the wound dressing was immersed in physiological saline for 2 weeks, the PVA sheet and the transparent sheet were well bonded.

[0032]

The present invention is directed to a wet dressing type wound dressing material, which comprises applying a pressure-sensitive adhesive to a PVA sheet containing chitosan, and forming a transparent sheet having a lower water vapor permeability than the PVA sheet on the pressure-sensitive adhesive layer. 1) The sheet is excellent in transparency, and 2) When a silver-based antibacterial agent is used, drug resistance of various bacteria is hardly generated, and the effect can be continuously exhibited during the healing period. ) Keeps the wound surface in an appropriate wet state; 4) has flexibility to be able to adhere to complex wound sites and moving wound surfaces; 5) has good biocompatibility; and 6) maintains the wound surface condition. It has good water vapor permeability.

Further, since the wound dressing of the present invention has excellent transparency, it is not necessary to peel off the wound dressing every time and observe the healing state, so that the healing agent can be replaced without damaging the new dermis. It is very beneficial because it can be reduced. The wound dressing material of the present invention having such excellent effects can be used not only for treating burns and skin damaged by wounds, but also for widespread hypertension, pressure sores, suture wounds, suppository wounds, etc. It is.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yukimasa Sawada 4-3-4 Kisaki, Hirosaki City, Aomori Prefecture (72) Inventor Tadashi Okubo 1-1, Gakuencho, Hirosaki City, Aomori Prefecture (72) Inventor Kenji Uno Tokyo 2-40-2 Hongo, Bunkyo-ku, Tokyo Seed Co., Ltd. (72) Inventor Hironobu Fukusaki 1-16-4 Ninomiya, Tsukuba, Ibaraki Prefecture (72) Inventor Naofumi Terada 25-10 Inari-mae, Tsukuba City, Ibaraki Prefecture Address (72) Inventor Fumiko Izutsu 2-2-20 Umezono, Tsukuba City, Ibaraki Prefecture (72) Inventor Maki Shiina 3467-3 Ino, Toride City, Ibaraki Prefecture

Claims (3)

[Claims] 1. A wound dressing comprising applying a pressure-sensitive adhesive to a chitosan-containing polyvinyl alcohol sheet, and coating the pressure-sensitive adhesive layer with a transparent sheet having a lower water vapor permeability than the polyvinyl alcohol sheet. 2. The wound dressing according to claim 1, wherein the amount of chitosan in the chitosan-containing polyvinyl alcohol sheet is in the range of 0.1 to 50% by weight based on the total amount of polyvinyl alcohol and chitosan. 3. The wound dressing according to claim 1, wherein the adhesive is an acrylic adhesive.