JPH05123354A - Wound covering material - Google Patents

Abstract

PURPOSE:To provide a wound covering material, which presents good flexibility, tight attachment, water permeability, and excellent quick effect for prevention of infection, and can favorably serve for remedy of wound by including anti-bacterial substance and/or disinfection agent in pores of a porous film made from polyurethane resin. CONSTITUTION:A wound covering material is manufacturable by either a wet or dry process belonging to the method for manufacturing a porous film consisting of polyurethane series resin. According to the wet process, dimethylholm amide solution of polyurethane series resin is applied to a base and solidified under the water, wherein the porous film is impregnated with aqueous solution of anti-bacterial substance and/or disinfection agent. According to the dry process, water-in-oil type emulsion of polyurethane-based resin is applied to the base and dried, wherein anti-bacterial substance and/or disinfection agent is in advance dissolved in water when emulsion is to be formed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound dressing material, and more particularly to a wound dressing material having excellent flexibility, adhesion, moisture permeability and antibacterial property.

[0002]

2. Description of the Related Art Conventionally, wound dressing materials using freeze-dried pig skin, polyurethane film, silicone resin / collagen / nylon knitted composite membrane, chitin nonwoven fabric, etc. have been used for treating wounds such as burns and trauma. Are known.

[0003]

In the treatment of wounds, the covering material is flexible and adheres well to the affected area.
In the early stage of treatment, it is important to drain the exudate of the affected area appropriately without storing it and prevent infection by bacteria. In response to these requirements, the conventional wound dressing is
Although satisfying certain aspects, it cannot be said to be sufficient for various requirements such as flexibility, adhesiveness, water permeability and antibacterial property. The present invention has been made in view of the above circumstances, and its purpose is to have flexibility and adhesiveness, can be applied to various wound sites, prevent the storage of exudate, and prevent infection from bacteria. The present invention is to provide a wound dressing having a fast-acting effect.

[0004]

Means for Solving the Problems As a result of various studies to achieve the above-mentioned object, the present inventors have found that a porous film made of a polyurethane resin has a specific structure,
The present invention has been completed based on the finding that the above object can be easily achieved. That is, the gist of the present invention is a wound dressing characterized in that a porous film made of a polyurethane resin contains an antibacterial agent and / or a bactericidal agent inside the pores. Exist in.

The present invention will be described in detail below. The wound dressing of the present invention can be manufactured by a wet method or a dry method according to a method for manufacturing a porous film made of a polyurethane resin. The wet method is a method in which a dimethylformamide solution of a polyurethane-based resin is applied onto a substrate and coagulated in water. In the wound dressing of the present invention, a porous membrane is impregnated with an aqueous solution of an antibacterial agent and / or a bactericide. It is obtained by The dry method is a water-in-oil type (W
/ O type) emulsion is applied onto a substrate and dried, and the wound dressing of the present invention is prepared by preliminarily dissolving an antibacterial agent and / or a bactericidal agent in water when forming the emulsion. can get.

In the present invention, the uniformity of the internal pores of the porous membrane and the water permeability are good, the porous membrane can be peeled off from the substrate and used alone as described later, and the production is easy. In particular, the dry method is preferable because it is easy to take a predetermined amount of the antibacterial agent and the like into the pores.

The water-in-oil emulsion of a polyurethane resin is prepared by dissolving or dispersing the polyurethane resin in an organic solvent having an appropriate mutual solubility with water, and adding an emulsifier and water thereto with stirring. Obtained by When the above emulsion is applied on a base material and dried, most of the organic solvent evaporates, and then water and the residual solvent evaporate, thereby solidifying the urethane resin,
A uniform and dense porous film having communicating pores is formed. The maximum diameter of the pores of such a porous membrane is usually 20 μm or less. By previously dissolving and adding the antibacterial agent and / or bactericidal agent in water, the antibacterial agent and the like can be contained in the inner wall surface of the pores of the porous membrane after the water is evaporated.

The organic solvent having an appropriate mutual solubility with water is not particularly limited, and examples thereof include methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, ethyl acetate, butyl acetate and the like. If the mutual solubility in water is adjusted by mixing with another solvent, a solvent having a low mutual solubility in water such as toluene or xylene, or alcohols, cellosolves, acetone,
It is also possible to use a solvent having a high mutual solubility in water, such as tetrahydrofuran, dioxane, or dimethylformamide. Since a solvent having a high boiling point takes a long time in a post-process, for example, when such a solvent is mixed and used, it is preferable to use the amount thereof as small as possible.

Polyurethane resin is a usual urethane raw material, that is, organic diisocyanate, polyether type, polyester type polyol, low molecular diol,
It is obtained by the reaction of a chain extender such as diamine. The reaction is
It is carried out in a solvent having no active hydrogen among the above solvents. The polyurethane resin is preferably obtained as a dispersion liquid containing polyurethane fine particles insoluble in a solvent so that the emulsion stability and the desired porosity can be easily obtained during film formation. Such a polyurethane fine particle is mainly composed of a hard segment in which an organic diisocyanate and a chain extender are reacted, and its particle diameter is usually 5 μm or less.

As the emulsifier, any emulsifier having a water-in-oil emulsifying property may be used, but a hydrophilic group such as polyoxyethylene group which has good emulsion stability is suitable. A polyurethane-based emulsifier having a ratio is particularly preferable. Such an emulsifier is synthesized in the same solvent as described above.

In the present invention, as the antibacterial agent and bactericidal agent, all water-soluble antibacterial agents and bactericidal agents used for medical purposes can be used. For example, any of water-soluble sulfa drugs, penicillins, cephem / oxacephems, macrolides, chloramphenicol, tetracyclines, lincomycins, aminoglycosides, polypeptides, etc. can be used. Is. And, although these can be selected according to the target wound, as an example of particularly preferable ones,
Sulfisomidine sodium, piperacillin sodium, cefsulodin sodium, fradiomycin sulfate,
Examples include gentamicin sulfate and polymyxin B sulfate. The antibacterial agent and the bactericidal agent can be used alone or in combination of two or more depending on the application.

The substrate is not particularly limited, and examples thereof include woven fabric, non-woven fabric, knitted fabric, film, paper, release paper, plastic plate, glass plate and metal plate.

In the film formation by the dry method described above, a porous film having desired physical properties can be obtained by appropriately selecting the solid content concentration, viscosity, coating amount or impregnation amount of the emulsion. Then, as in the case of a normal urethane film, additives such as a cross-linking agent, a deterioration inhibitor, and a filler can be blended in the preparation of the emulsion, if necessary.

The porous film obtained as described above can be used by peeling it off from the base material, but in the case of a flexible or stretchable base material such as a woven fabric, a non-woven fabric or a knitted fabric, the composite membrane is directly used. You may use as. When used alone, the thickness of the porous membrane is 20 in terms of strength, flexibility, moisture permeability, etc.
-80 μm is preferable. If it is thinner than the above range, a problem may occur in strength, and if it is thicker than the above range, problems may occur in flexibility and water permeability. When used as a composite film, it is appropriately selected in consideration of the thickness of the base material. Further, when it is necessary to further accelerate the discharge of the exudate from the wound site, it is preferable to provide the porous membrane with through holes of an appropriate size at regular intervals.

According to the wound dressing of the present invention, when used on an affected area, it is possible to prevent the invasion of bacteria from the outside and at the same time to immediately release the antibacterial agent or the like to the affected area to suppress the growth of bacteria. ..

[0016]

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to the following examples unless it exceeds the gist thereof. In the following examples, "part" means "part by weight" and "%" means "% by weight".

Production Example 1 (Production of Polyurethane Dispersion Liquid (1)) 175 parts of polytetramethylene ether glycol having an average molecular weight of 1000, 75 parts of polybutylene adipate having an average molecular weight of 1000, diphenylmethane diisocyanate (hereinafter abbreviated as “MDI”) 73 0.5 parts, ethylene glycol 4.65 parts, methyl ethyl ketone (hereinafter, "ME
K)) and 0.016 parts of dibutyltin dioctoate (hereinafter abbreviated as “DBTDO”) are charged into a reactor and reacted at 60 ° C. for about 9 hours to obtain a solid content concentration of 30.
% Polyurethane solution was obtained. Then, 27.3 parts of ethylene glycol, 13.3 parts of MDI and 328 parts of MEK were added to the above solution and reacted at 60 ° C. for about 12 hours, then cooled to 30 ° C. with continuous stirring and having a particle size of 2 μm or less. A milky white polyurethane dispersion (1) containing fine particles and having a solid content concentration of 30% was obtained.

Production Example 2 (Production of Polyurethane Emulsifier Solution (1)) Polypropylene glycol 100 having an average molecular weight of 2000
0 parts and 88.8 parts of isophorone diisocyanate were charged into a reactor and, after uniformly mixing, 0.22 part of DBTDO was added and reacted at 80 ° C. for about 5 hours under a nitrogen stream to obtain a polyurethane solution. Then, 17.0 parts of methacryloyloxyethyl isocyanate was added to the above solution,
By reacting at 80 ° C. for about 8 hours, a polyurethane having unsaturated double bonds at the ends was obtained. In a separate reactor, 94 parts of the above-mentioned unsaturated double bond-containing polyurethane, average molecular weight 440
56 parts of polyethylene glycol monomethacrylate and 350 parts of MEK were charged and uniformly dissolved, then 3 parts of azobisisobutyronitrile was added, and the mixture was mixed under a nitrogen stream to give 7
The reaction was carried out at 0 ° C. for about 8 hours to obtain a hydrophilically modified polyurethane emulsifier solution (1) having a solid content concentration of 30%.

Production Example 3 (Production of Polyurethane Dispersion (2)) Polycaprolactone diol 20 having an average molecular weight of 2000
0 part, MDI 26.8 part, ethylene glycol 1.86
Parts, MEK 534 parts and DBTDO 0.023 parts were charged into a reactor and reacted at 60 ° C. for about 8 hours to obtain a solid content concentration of 3
A 0% polyurethane solution was obtained. Next, 19.0 parts of ethylene glycol, 79.0 parts of MDI and 228 parts of MEK were added to the above solution, and the mixture was reacted at 60 ° C. for about 16 hours, then cooled to 30 ° C. while stirring, and having a particle size of 3 μm or less. A milky white polyurethane dispersion (2) containing fine particles and having a solid content concentration of 30% was obtained.

Production Example 4 (Production of Polyurethane Emulsifier Solution (2)) Polypropylene glycol 400 having an average molecular weight of 2000
Parts, MDI 75 parts and DBTDO 0.175 parts were charged in a reactor and reacted at 70 ° C. for about 5 hours, and then MEK8
75 parts of it was added and dissolved, 400 parts of polyethylene glycol having an average molecular weight of 2000 was further added, and the mixture was reacted at 60 ° C. for about 6 hours to obtain a polyurethane emulsifier solution (2) having a solid content concentration of 50%.

Production Example 5 (Production of Comparative Polyurethane Solution) 200 parts of polytetramethylene ether glycol having an average molecular weight of 2000 and 65.5 parts of dicyclohexylmethane diisocyanate were charged in a reactor, and the mixture was charged under a nitrogen stream at 1
After reacting at 00 ° C. for about 9 hours, 1168 parts of dimethylformamide was added and dissolved, and 26.5 parts of isophoronediamine was further added and reacted at about 30 ° C. for about 4 hours to prepare a polyurethane solution having a solid content of 20%. Obtained.

Example 1 100 parts of the polyurethane dispersion (1) obtained in Preparation Example 1, 10 parts of the polyurethane emulsifier solution (1) obtained in Preparation Example 2, M
20 parts of EK and 20 parts of toluene are mixed, and while stirring vigorously with a homomixer, gentamicin sulfate 0.03 is added.
An aqueous solution prepared by dissolving 3 parts in 50 parts of water was gradually added, and then 4 parts of Coronate L (crosslinking agent manufactured by Nippon Polyurethane) was added to ME.
A water-in-oil emulsion was prepared by dissolving in K5 part and adding. The obtained emulsion had a solid content concentration of 17% and a viscosity of 8000 cp / 25 ° C. Apply the above emulsion onto release paper to a thickness of 300 μm.
Dry at 0 ° C for 3 minutes, then 120 ° C for 3 minutes to a thickness of 5
A porous membrane wound dressing having a white and uniform appearance of 0 μm was obtained.

An agar medium prepared by dissolving 5 g of meat extract, 10 g of peptone, 5 g of sodium chloride, 5 g of yeast powder and 15 g of agar powder in 1 liter of distilled water was sterilized by an autoclave and then cooled to 45 ° C. to obtain Pseudewora.
S. aeruginosa (IFO12045) suspension was added to adjust the inoculation density of the bacteria to 5.1 × 10 ⁵ cells / cm ^2, and 1 plate was placed on 4 petri dishes with an inner diameter of 90 mm.
5 ml each was dispensed and solidified to prepare four assay petri dishes.

The above-mentioned wound dressing was sterilized and covered on the agar medium of each assay petri dish described above, and placed in a refrigerator at 4 ° C. so that the bacteria would not grow, and the antimicrobial agent was released from the wound dressing. In order to check the speed, the leaving time of each assay petri dish was changed to 0, 4, 8, and 24 hours. Then, after culturing at 37 ° C. for 48 hours, the wound dressing is peeled off, and the agar medium thereunder is cut out with a cork borer having an inner diameter of 10 mm, 1
It was put in 0 ml of sterilized water and stirred, and the number of bacteria was measured. Further, with respect to the assay petri dish that had been left to stand for 0 hour, the assay petri dish was also sampled from the agar medium of the uncoated portion of the wound dressing, and the number of bacteria was measured in the same manner as above. The results of measuring the number of bacteria are shown in Table 1.

As is clear from Table 1, the number of bacteria grew on the order of 10 ¹⁰ cells / cm ^{2 in} the uncovered part of the wound dressing, whereas it did not depend on the standing time before culturing in the covered part. No fungus was detected. From the above results, it was confirmed that the wound dressing of the present invention has a rapid release of the antibacterial agent and has a rapid effect on the prevention of bacterial growth.

Example 2 100 parts of the polyurethane dispersion (2) obtained in Production Example 3, 5 parts of the polyurethane emulsifier solution (2) obtained in Production Example 4, ME
Mix 20 parts of K and 20 parts of toluene, and, while stirring vigorously with a homomixer, polymyxin sulfate B0.033
Aqueous solution of 50 parts of water is gradually added, followed by 3 parts of Coronate EH (crosslinking agent made by Nippon Polyurethane) and M
A water-in-oil emulsion was prepared by adding a mixed solution of 3 parts of EK. The obtained emulsion had a solid content concentration of 18% and a viscosity of 5000 cp / 25 ° C.

From the above emulsion, a white wound dressing material having a uniform appearance with a thickness of 50 μm was obtained in the same manner as in Example 1. The above wound dressing was tested for antibacterial properties using an agar medium in the same manner as in Example 1, and the results are shown in Table 1. As is clear from Table 1,
No bacteria were detected in the wound dressing regardless of the standing time before culturing.

Comparative Example 1 (using a non-porous polyurethane film) To 100 parts of the polyurethane solution obtained in Production Example 5, 0.02 parts of gentamicin sulfate and 40 parts of toluene were added and mixed uniformly to obtain a thickness of 300 μm. It was applied on a release paper and dried at 100 ° C. for 1 hour to obtain a non-porous wound dressing having a thickness of 30 μm. The above wound dressing was tested for antibacterial properties using an agar medium in the same manner as in Example 1, and the results are shown in Table 1. As is clear from Table 1, bacteria were detected at 0, 4, and 8 hours where the standing time before culturing was short. This is believed to be due to insufficient release of gentamicin sulfate due to the non-porous wound dressing.

[0029]

TABLE 1 Antimicrobial Test Results in agar fold locations (37 ° C., the viable cell number after 48 hours of culture (number / cm ²⁾ ──────────────────── ────────────────Leaving time until culture (Hr) Example 1 Example 2 Comparative Example 1 (4 ° C.) Uncoated part Covered part Covered part Covered part ──── ──────────────────────────────── 0 5.5 × 10 ¹⁰ 0 0 5.1 × 10 ⁸ 4 −0 0 9.8 × 10 ⁵ 8-0 0 1.5 × 10 ² 24-0 0 0 ───────────────────────────────────── (Note) Inoculation density of bacteria at the start of culture: 5.1 × 10 ⁵ cells / cm ²

[0030]

EFFECTS OF THE INVENTION The wound dressing of the present invention has good flexibility, adhesiveness, and water permeability, and because of the rapid release of the antibacterial agent contained therein, it has excellent quick-acting effect against infection.
Therefore, it can be suitably used for treating wounds.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Takashi Mikawa 1000, Kamoshida-cho, Midori-ku, Yokohama-shi, Kanagawa Sanryo Kasei Co., Ltd.

Claims (2)

[Claims] 1. A wound dressing material comprising a porous film made of a polyurethane resin containing an antibacterial agent and / or a bactericidal agent inside the pores. 2. The porous membrane is formed from a water-in-oil emulsion of a polyurethane resin, and an antibacterial agent and / or a bactericidal agent is dissolved in the aqueous phase at the time of emulsion formation and contained inside the bubbles. The wound dressing according to claim 1, wherein