JPS5910225B2 - Wound dressing sheet material - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a wound dressing sheet material and a method for producing the same, and more specifically, the present invention relates to a wound dressing sheet material and a method for producing the same, and more specifically, it is made by incorporating a therapeutic agent such as a drug or an enzyme into an anisotropic film made of a saponified ethylene-vinyl acetate copolymer. The present invention relates to a wound dressing sheet material and a method for manufacturing the same.

Conventionally, antibiotics have been used as wound dressing sheets that are applied to wounds, burns, and other wounds to prevent bacterial infection, absorb body fluid exudate from the wound, dry the wound surface, and promote scab formation. A nylon gauze coated with ointment containing a substance or other drug is used.

However, such wound dressing sheet materials not only do not sufficiently prevent bacterial infection of the wound even in a short period of time, but as the wound dries, the proteinaceous exudate binds to the gauze in a glue-like manner. The patient will be forced to suffer needlessly during the replacement.

For this purpose, a wound dressing sheet material made by irradiating an aqueous solution of polyvinyl alcohol yahori vinylpyrrolidone with radiation to form a gel, and impregnating this gel with drugs and enzymes (Japanese Patent Publication No. 7493/1983), and a material made of vinylpyrrolidone monomer. A wound dressing sheet material has also been proposed in which a drug or enzyme is mixed in an aqueous solution, and then this mixed solution is irradiated with radiation to form a gel, and at the same time, the above-mentioned drugs, etc. are included in the gel (Japanese Patent Publication No. 1973- 7 4 9 No. 4), in the former, a large amount of drugs, etc. leaches out at the initial stage of use, and a long-term therapeutic effect can be expected; in the latter, drugs, etc. easily change in quality or are lost during the radiation irradiation stage. There are drawbacks that can be used.

In order to solve the various problems mentioned above, the present inventors aimed to
As a result of intensive research on wound dressing sheet materials that can be applied to wounds such as burns to effectively prevent bacterial infection over a long period of time and promote healing, we have discovered that saponified ethylene-vinyl acetate copolymer (hereinafter referred to as saponified ethylene-vinyl acetate copolymer) , called EVA-based copolymer.

) is dissolved in a water-miscible organic solvent or a mixed solvent of this and water, and a therapeutic agent such as a drug or enzyme is dissolved or dispersed in this polymer solution, and then a thin layer is formed on an appropriate substrate. Next, this thin layer of the stock solution for molding is brought into contact with a coagulating liquid mainly consisting of water, and the organic solvent in the thin layer is replaced with water to solidify the polymer, thus forming a dense surface layer with micropores. The therapeutic agent is encapsulated in a polymeric anisotropic membrane that is integrally continuous with a relatively coarse porous inner layer, and the therapeutic agent is gradually released from the anisotropic membrane depending on the type of therapeutic agent. As if
By forming micropores in the surface layer of the anisotropic membrane, the therapeutic agent can be delivered to the wound over a long period of time, thus well preventing bacterial infection, and by the water absorbency of the porous inner layer of the anisotropic membrane. The present invention was completed based on the discovery that a wound surface can be properly dried, thereby producing a remarkable healing effect.

That is, the wound dressing sheet material of the present invention contains 60 vinyl acetate units.
The ethylene-vinyl acetate copolymer consists of a polymer in which 80 mol% or more of the vinyl acetate units of the ethylene-vinyl acetate copolymer is saponified, and has a dense surface layer with micropores and a relatively coarse porous interior. A therapeutic agent such as a drug or an enzyme is contained in the polymer anisotropic membrane formed continuously with the membrane surface layer so that the therapeutic agent is gradually released from the membrane. According to the present invention, the above-mentioned polymer is dissolved in a water-miscible organic solvent or a mixed solvent of the same and water;
A therapeutic agent such as a drug or enzyme is dissolved or dispersed in this polymer solution, and the resulting molding stock solution is formed into a thin layer on a suitable base material. The organic solvent in the thin layer is replaced with water by contact with a coagulation liquid, and the polymer is solidified, so that a dense surface layer with micropores and a relatively coarse porous inner layer are integrated and continuous. This can be obtained by incorporating the therapeutic agent into an anisotropic membrane and forming micropores in the membrane surface layer so that the therapeutic agent is gradually released from the membrane.

The EVA copolymer preferably used in the present invention has ethylene units of 3 to 40% by weight, preferably 5 to 30% by weight.
and 60 to 97% by weight of vinyl acetate units, preferably << is 70
80 mol% or more of the vinyl acetate units of the ethylene-vinyl acetate copolymer consisting of ~95% by weight are saponified.

In addition, in the present invention, a terpolymer in which a part of the ethylene unit is substituted with an ethylenically unsaturated acid such as acrylic acid or maleic anhydride can also be used, and the term "EVA copolymer" It contains such a tertiary copolymer.

In such an EVA-based copolymer, when the ethylene unit content is less than 3% by weight, the resulting EVA-based copolymer has poor stability against water, and various problems may occur when forming an anisotropic film, which will be explained later. On the other hand, 40% by weight
If the EVA copolymer exceeds the
It becomes difficult to uniformly disperse therapeutic agents such as enzymes into the polymer.

In addition, when the degree of saponification is less than 80 mol% of the vinyl acetate unit, the hydrophilicity of the EVA copolymer is insufficient, and therefore the water absorbency of the obtained sheet material is low, resulting in noticeable dryness of the wound surface. It becomes ineffective and reduces the healing effect.

Solvents for dissolving such EVA-based copolymers include polar organic solvents that are miscible with water, specifically aprotic organic solvents such as dimethyl sulfoxide and dimethyl formamide, and phenols such as phenol and cresol. alcohols such as ethylene chlorohydrin, ethylene glycol, propylene glycol, cellosolve, glycerin, methanol, ethanol, propanol, butanol, and alicyclic ethers such as dioxane and tetrahydrofuran; A mixed solvent of these and water is used.

In particular, it is desirable to use glopanol, glycol, cyclic ether, etc. in combination with water to increase the solubility of the EVA polymer as an aqueous organic solvent.

Dimethyl sulfoxide and dimethyl formamide alone dissolve EVA copolymers well, but they may also contain water, alcohol, glycol, ether, etc. Furthermore, like acetone, they dissolve EVA copolymers well. It may contain a small amount of a solvent that does not dissolve.

In the present invention, dimethyl sulfoxide, its aqueous solvent, n-propanol/water mixed solvent, etc. are particularly preferably used.

The concentration of the EVA copolymer in the EVA copolymer solution is adjusted to 3 to 40% by weight, preferably 10 to 25% by weight.

As will be explained later, the EVA copolymer solution is made into a thin layer by uniformly dispersing or dissolving the therapeutic agent therein, and then immersing it in a coagulation solution mainly consisting of water to form an anisotropic layer. However, if the EVA copolymer concentration in the EVA copolymer solution is less than 3% by weight, it becomes difficult to form a dense layer on the surface and it does not have sufficient mechanical strength. Moreover, even if a dense layer can be formed, the pore diameter of the micropores is too large, making it impossible to effectively control the elution of the therapeutic agent contained in the membrane.

On the other hand, when it is greater than 40% by weight, the layer densae becomes thicker and the micropore diameter becomes significantly smaller, making it difficult for the therapeutic agent in the membrane to permeate through the layer densate and elute, making it difficult to prevent bacterial infection on the wound surface. Anti-inflammatory effect cannot be fully expressed.

When preparing an EVA-based copolymer solution, heating may be performed if necessary to promote dissolution of the EVA-based copolymer, but
When adding therapeutic agents such as drugs and enzymes to the polymer solution,
The temperature of the polymer solution should be adjusted within a range that does not alter or deactivate these therapeutic agents.

In particular, enzymes are prone to deactivation, so usually
The temperature when adding the enzyme to the polymer solution is preferably 0 to 50°C, preferably θ to 35°C.

Temperatures lower than 0° C. are not preferred because the viscosity of the polymer solution is generally high and it is difficult to uniformly dissolve or disperse the therapeutic agent in the solution.

Therapeutic agents such as drugs and enzymes may be added alone to the EVA-based copolymer solution, but preferably they are dissolved or dispersed in water, a buffer solution, etc. in advance, and then added to the polymer solution so as to be uniformly added. dissolve or disperse;

The amount of therapeutic agent added depends on the type, but usually EVA
0.001 to 30 parts by weight per 100 parts by weight of the copolymer,
The amount is preferably 0.01 to 20 parts by weight, but is not necessarily limited thereto.

The EVA copolymer solution to which the therapeutic agent was added in this manner (hereinafter referred to as a stock solution for molding).

) is formed in a thin layer on a suitable substrate by a method such as casting or coating, or is formed in a thin layer on a substrate by immersing the substrate in a stock solution for molding.

In the present invention, preferably, the porous sheet base material is immersed in the molding stock solution, or the molding stock solution is applied to both surfaces of the sheet base material, so that the molding stock solution is applied to both surfaces of the sheet base material. After forming a thin layer of water and then, if necessary, evaporating a portion of the solvent from this thin layer, a coagulating liquid consisting primarily of water (including water alone) is formed.

), the organic solvent contained in the thin layer is replaced with water, thereby coagulating the polymer and forming a film, forming a thin dense layer with micropores on the surface, and forming an internal layer integrally with this dense layer. A relatively coarse porous layer is formed, and the therapeutic agent is mainly encapsulated within this porous layer.

Suitable porous substrates include, for example, woven fabrics, nonwoven fabrics, paper, etc. made of natural fibers or synthetic fibers.

The coating thickness of the stock solution for molding onto these porous substrates is not particularly limited, but is usually about 30 to 500 microns.

Further, according to the present invention, after forming a thin layer of the stock solution by casting or coating the stock solution for molding onto a non-permeable substrate having a smooth surface such as glass, synthetic resin, stainless steel, etc. The substrate is immersed in a coagulation solution to form an anisotropic film having a dense layer only on the outside, that is, the surface opposite to the surface where the thin layer is in contact with the substrate, and the back surface of such an anisotropic film is Wound dressing sheet material that allows the therapeutic agent to be released only from the dense layer on the surface by bonding the porous layers of each other or by bonding a synthetic resin film that does not allow the therapeutic agent or water to pass through to the back side. can be obtained.

The coagulating liquid may be water alone, but preferably water contains phosphate,
Buffers such as borates and tris(oxymethyl)aminomethane, and inorganic salts such as sulfate and ammonium sulfate are dissolved in advance.

In particular, when the therapeutic agent contains an enzyme, this is to prevent the activity from decreasing.

The coagulation temperature of the thin layer of the stock solution for molding is not particularly limited as long as the therapeutic agent is not altered or deactivated, but if the therapeutic agent is an enzyme in particular, a temperature of 35°C or higher may cause the polymer to coagulate during the coagulation process. There is a strong tendency for the enzyme to be inactivated, while if the coagulation temperature is too high, the pores in the dense layer of the anisotropic membrane that is formed will become too large and the therapeutic agent will easily elute from the membrane, so 0 to 35°C, preferably θ to 20°C.

In the present invention, the pore size of the micropores in the stratum compactum is adjusted so that the therapeutic agent encapsulated in the membrane is gradually released over a long period of time.

As mentioned above, this micropore diameter can be controlled by the coagulation temperature, but it can also be controlled by the polymer concentration in the stock solution for molding. It can also be controlled by evaporating a portion of the organic solvent from the forming solution thin film after forming it on the substrate and before contacting it with the coagulating solution, for a period of several seconds to several hours, if necessary with heating or with air blowing. can.

Therefore, depending on the drug, enzyme, etc. used, the above-mentioned methods may be combined as appropriate so that these therapeutic agents contained within the anisotropic membrane are gradually released from the dense layer on the surface of the membrane. The pores are designed, typically with an average pore size of about 0.00
The thickness ranges from 1 μ to several tens of μ, and the thickness of the dense layer is usually about 0.05 to 0.5 μ.

On the other hand, the porous layer generally has relatively coarse pores with an average pore diameter of about 0.01 to several hundred microns, and in some cases may have cavities in which the polymer is missing.

In the present invention, the drugs include, for example, sulfamine drugs such as sulfamine, acetosulfamine, disulfamine, sulfaicazal, sulfathiazole, and homosulfamine, penicillin, streftomycin, chloramphenicol, tetracycline, aureomycin, and plastocycline. Cydin, kanamycin, cephalocedin, erythromycin, fradiomycin, trichomycin, mitomycin, micamicin, bactamycin,
S/L/ =r-qAntibiotics such as isin, resorcinol,
Traumatic agents such as carbolic acid and ribanol are used, and
As the enzyme, for example, animal proteases such as trypsin, α-chymotrypsin, and plasmin, bacterial proteases such as streptokinase, streptodornase, and nagase, vegetable proteases such as papain and bromelain, lysozyme, and lytic enzymes are used. However, in addition to these, any anti-inflammatory enzymes commonly used for wounds can be used.

As described above, according to the present invention, a thin film of a stock solution for molding is simply brought into contact with a coagulation bath mainly consisting of water, without using a crosslinking agent or radiation, to coagulate the polymer and form it into a film, and at the same time to treat the polymer. By incorporating the therapeutic agents into the membrane, it is possible to prevent the drugs and enzymes from deteriorating or deactivating during the coagulation process.Furthermore, since these therapeutic agents are released in a sustained manner, they can be easily applied to the wound surface. , the therapeutic agent can be administered to the wound over a long period of time without the risk of overdosing, and
Because the polymer anisotropic membrane has a porous inner layer, it is highly water-absorbent, and therefore effectively prevents bacterial infection in the wound over a long period of time, and also absorbs exudate from the wound and dries the wound properly. This makes it extremely effective in healing.

Furthermore, when the therapeutic agent contains protease, its enzymatic action prevents the scab from strongly bonding to the wound dressing sheet material in a glue-like manner, so that unnecessary pain may be caused to the patient when replacing the sheet material. do not have.

The present invention will be explained below with reference to Examples, but the present invention is not limited in any way by these Examples.

Example 1 Ethylene-vinyl acetate copolymer (ethylene unit content 1
3% by weight) of 98 mol% saponified product 20S' was dissolved under heating in a mixed solvent consisting of 35y of water and 50g of n-gropanol.

Separately, lysozyme 300rII9 was dissolved in 15 fIK of water at room temperature, added to the above polymer solution cooled to a temperature of 25° C., mixed, the enzyme dispersed, and defoamed to prepare a stock solution for molding.

Next, a polyester nonwoven fabric with a thickness of 0.1 mm was immersed in this molding solution, and then passed between rolls to reduce the overall thickness to 0.
．． It was adjusted to 3 mm and left in the air for 30 seconds to evaporate n-propanol and some of the water from the stock solution thin layer.

Next, this was immersed in water at a temperature of 0° C. for about 1 hour to replace n-glopanol in the thin layer of the stock solution with water, and the EVA polymer was integrally coagulated and formed into a film on the nonwoven fabric.

This anisotropic membrane integrated with the base material was lightly washed with water and used as a wound dressing sheet material.

Example 2 99% of EVA copolymer (ethylene content 25% by weight).
40ft of 8 mol% saponified product was added to dimethyl sulfoxide 14
The mixture was heated and dissolved in a mixed solvent consisting of 20 g of water, 20 g of water, and 40 g of acetone, and cooled to a temperature of 30°C.

This polymer solution was added with a lytic enzyme (YL-5 manufactured by Amano Pharmaceutical Co., Ltd.).
) was added, mixed, uniformly dispersed, and defoamed.

Next, the stock solution for molding obtained in this way was applied to both sides of the polyester nonwoven fabric to a thickness of 80 μm, and immediately heated to 10°C.
The polymer was placed in water and immersed for 1 hour to coagulate and form a film.

The membrane integrated with the nonwoven fabric base material was lightly washed with water to prepare a wound dressing sheet material.

Example 3 25 g of the same EVA copolymer as in Example 1 was dissolved in dimethyl sulfoxide 1001 while heating.

After cooling this polymer solution to 30° C., Mikamycin A50×, Bactamycin 507'IIIi and Penicillin G300× were added thereto, dissolved, and defoamed.

Next, the thus obtained molding stock solution was applied to a thickness of 80 μm on both sides of the polyester nonwoven fabric, and then immediately immersed in water at 0° C. for 30 minutes to coagulate the polymer and form a film.

The membrane integrated with the nonwoven fabric base material was washed lightly with water and used as a wound dressing sheet material.

Example 4 The same EVA copolymer 25S' as in Example 1 was heated and dissolved in a mixed solvent consisting of 50 tons of water and 50 f of n-propanol.

The polymer solution was cooled to 30°C, and 50 μg of bacterial protease, 50 μg of actinobacterial protease, 50 μg of Mikamycin A, and 0250 μg of penicillin were added.
After uniformly dissolving and dispersing, the solution was defoamed to prepare a stock solution for molding.

Next, a polyester nonwoven fabric with a thickness of 0.1 mW was immersed in this molding solution, and then passed between rolls to reduce the overall thickness to 0.
．． The film was adjusted to 3 m'llL, left in the air for 30 seconds, and then immersed in water at a temperature of 0° C. for 30 minutes to obtain a membrane integrated with the base material.

After lightly washing with water, this was freeze-dried to obtain a wound dressing sheet material.

Claims (1)

[Scope of Claims] 1. 80 mol% of vinyl acetate units in an ethylene-vinyl acetate copolymer consisting of 60 to 97% by weight of vinyl acetate units.
A drug is contained in an anisotropic polymer membrane consisting of a polymer in which the above has been saponified, and a dense surface layer with micropores and a relatively coarse porous inner layer are integrally and continuously formed. A wound care sheet material containing a therapeutic agent such as an enzyme, and having micropores formed in the membrane surface layer so that the therapeutic agent is gradually released from the membrane. 2. The wound dressing sheet material according to claim 1, wherein an anisotropic film is formed on both sides of the sheet-like porous base material so that the surface layer is located on the outside. 3 80 mol% of vinyl acetate units in an ethylene-vinyl acetate copolymer consisting of 60 to 97% by weight of vinyl acetate units
The above saponified polymer is dissolved in a water-miscible organic solvent or a mixed solvent of this and water, and therapeutic agents such as drugs and enzymes are dissolved or dispersed in this polymer solution, and the thus obtained molding material is The stock solution is formed into a thin layer on a suitable base material, and then this thin layer is brought into contact with a coagulating liquid mainly consisting of water to replace the organic solvent in the thin layer with water and coagulate the polymer. The therapeutic agent is encapsulated in an anisotropic membrane in which a dense surface layer with micropores and a relatively rough porous inner layer are integrally continuous, and the therapeutic agent is gradually released from the membrane. A method for producing a wound dressing sheet material, which comprises forming micropores in a membrane surface layer. 4. After applying a molding solution to both sides of the porous sheet base material to form a thin layer of the molding solution, the thin layer is immersed together with the base material in a coagulation solution, so that the surface layer is on both sides of the base material with the surface layer facing outward. 4. The method of manufacturing a wound dressing sheet material according to claim 3, wherein the anisotropic film is formed in such a manner that the anisotropic film is located in the same position as the anisotropic film.