JPH0584289A - Wound coating material - Google Patents

Abstract

PURPOSE:To provide the coating material which adheres tightly to a wound surface and can accelerate the regeneration of the skin when applied to the wound and peels easily without sticking to the wound surface when the coating material is heated or cooled particularly at the time of removal. CONSTITUTION:This wound coating material is constituted by coating the one surface of a porous polyolefin film or porous hologenated polyolefin film with a temp. sensitive high polymer having the lower limit critical solution temp. to water within a 0 to 35 deg.C range.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is applied to a skin defect due to a wound, a burn, etc., and is applied to the skin defect site, does not adhere to the wound surface in contact with the skin defect site, and easily peels off with healing. To possible wound dressings.

[0002]

2. Description of the Related Art As a wound healing method for a wound such as a traumatic skin wound or a bark and a wound associated with a disease,
Broadly classified, so-called dry dressing that keeps the wound in a dry state and forms crust to heal, and creates a moderately moist environment to rapidly migrate epidermal cells.
Known as t dressing, the former has less retention of exudate and is less susceptible to infection, and the latter has faster wound healing, less dry necrosis on the wound surface, and also has a protective effect on the wound surface. It has been known.

Conventionally, gauze and absorbent cotton have been used, but since the exudate is quickly absorbed, the wound surface becomes dehydrated and becomes dry, resulting in crusting. At this time, the gauze adheres to the wound surface and is difficult to separate, which causes pain to the patient when peeled off, which is accompanied by bleeding and the like. If exudate comes out to the surface through gauze, bacteria may enter the wound.

As an alternative to this, a dressing (Airstri) combining a hygroscopic pad, a sponge-like pad made of a non-adhesive film, and a waterproof adhesive plaster is used.
p ^R , Smith & Nephew Limite
d) or an adhesive dressing (Op-Site) comprising a polyurethane film having high water vapor permeability and an adhesive layer.
^R , Smith & New Limited Limited;
Bioplusive ^R , Johnson & Jo
hson; Tegaderm ^R 3M) and the like are commercially available. In addition, those that use biopolymers such as collagen, chitin, fibrin, etc. in the part of the dressing that comes into contact with the wound site, or by dispersing the moisturizing component in a rubber-based material to ensure adhesion, non-adhesion, high water content etc. The biocompatible hydrogel-forming support layer (for example, carboxymethylcellulose, alginate, etc.) in which at least a part of the site of the present invention, which has been previously proposed by the present inventors, is coated with a water-repellent substance. System, hyaluronate system, poly (meth) acrylate system), and a wound dressing material comprising a water permeation control layer formed on the side of the support layer opposite to the site in contact with the wound site (Japanese Patent Laid-Open Publication No. Sho. No. 62-183760)
Etc., and has achieved some results.

On the other hand, as a dry dressing, there is a porous polymer film. In this case, however, the dressing adheres to the wound surface and causes bleeding when peeled off. Therefore, recently, a non-adhesive porous film ( Melo
lin ^R , Smith & Nephew Limite
Dressings using d) are commercially available.

[0006]

Although the above-mentioned conventional covering materials also have some effects, the material used for forming the biocompatible base material layer of the portion in contact with the wound is It is easy to decompose and fall off, and there is a problem in the physical properties when used as a wound dressing material, and the decomposed and detached material may be recognized as a foreign matter, which may delay the healing of the wound.

Therefore, the present invention has good adhesion to the wound surface, does not easily decompose and detach even when contacted with a wound, and does not cause bleeding when peeling as the wound surface heals. It is an object of the present invention to provide a wound dressing which can be easily peeled off with.

[0008]

The above object is achieved by a wound dressing having the following constitution.

(1) Wound covering prepared by coating one surface of a porous polyolefin membrane or a porous halogenated polyolefin membrane with a temperature-sensitive polymer having a lower critical solution temperature in water in the range of 0 to 35 ° C. Material.

(2) Porosity 50% or less, average pore diameter 0.0
It is composed of a porous polyolefin membrane or a porous halogenated polyolefin membrane having a thickness of 1 to 1.0 μm, and has a lower critical dissolution temperature in water of 0 to 3 on its surface and pore inner surface.
A wound dressing material coated with a temperature-sensitive polymer in the range of 5 ° C.

(3) A wound dressing containing the physiologically active substance in the wound dressing according to item 1.

In the present invention, the upper limit critical dissolution temperature in water means a temperature at which the water is dissolved at a temperature higher than that temperature, but is not dissolved at a temperature below that temperature, and the water is divided into two layers. Further, the lower critical solution temperature for water is not dissolved in water at a temperature higher than that temperature, and does not dissolve in water even if it comes into contact with water to be divided into two layers, but below that temperature, the temperature at which it is dissolved in water Say. When a wound dressing is coated with a polymer having the above properties, the surface of the dressing becomes water-soluble by heating or cooling the dressing above or below the upper or lower critical solution temperature during removal. Therefore, the covering material can be easily peeled off, and the wound surface is not hurt or suffered. Furthermore, the balance between hydrophilicity and hydrophobicity of the surface of the base material can be easily controlled, and the release of the contained physiologically active substance from the base material can be controlled.

If a polymer having a lower limit temperature lower than 0 ° C. is used, the skin may be frostbite when the coating material is removed. Therefore, a polymer having a lower critical solution temperature in the above range is preferable.

The sensitive polymer or its copolymer used for coating in the present invention can be obtained by polymerizing or copolymerizing the following monomers. Examples of the monomer that can be used include (meth) acrylamide compounds such as acrylamide and methacrylamide, N-acryl-substituted (meth) acrylamide derivatives such as N-isopropyl (meth) acrylamide, diethylacrylamide, and N-ethoxyethyl (meth) acrylamide. , N, N-dimethyl (meth)
Examples thereof include, but are not limited to, N, N-dialkyl-substituted (meth) acrylamide derivatives such as acrylamide and N, N-ethylmethylacrylamide, vinyl ether derivatives such as methyl vinyl ether, and water-soluble cellulose ethers such as methyl cellulose.

As the one having a lower critical solution temperature of 0 to 35 ° C., N-isopropylacrylamide or diethylacrylamide homopolymer or copolymer is particularly preferably used.

The membrane used in the present invention is a porous polyolefin membrane or a porous halogenated polyolefin membrane. Considering general-purpose and low cost, polyethylene, polypropylene, polyvinylidene fluoride, polyvinylidene chloride, chlorinated polyethylene, etc. Is preferred. The obtained coating material has a porosity of 50% or less and an average pore diameter of 0.01 to 1.0.
μm, water vapor transmission rate 500-5000g / m ² · 24h
Those in the range of are preferable. The porosity is measured by measuring the film thickness and dry weight of the porous film, immersing the film in methanol, substituting the methanol in water for removal, and wiping the surface water to measure the wet weight of the film. Calculate the dry porosity from the film thickness, dry weight, and specific gravity of the raw materials. Further, the wet porosity is calculated from the dry weight and the wet weight. The porosity used in the present invention is dry porosity.

The physiologically active substance used in the present invention is not particularly limited as long as it can directly or indirectly promote the growth of skin cells and fibroblasts, which are skin cells. Insulin, hydrocortisone, epithelium Cell growth factor (E
GF), fibroblast growth factor (FGF), urogastrone and the like, and epidermal cell growth factor (EGF) and urogastrone are preferably used.

Epidermal growth factor (EGF) is a factor that promotes growth of epithelial cells separated from mouse submandibular gland, and mouse EGF (mEGF) is a peptide consisting of 53 amino acids. It has actions such as promoting cell proliferation and differentiation of epithelial tissues such as skin, tongue and esophagus.

Urogastron is a human epidermal growth factor isolated from human urine, and is the mouse EG described above.
F differs from F by 16 out of 53 amino acids. Urogastron has a cell proliferation action as well as a gastric juice secretion inhibitory action, and is expected to be used as a therapeutic drug for wounds.

In addition, hormones such as insulin and hydrocortisone are expected to have various effects on cells, particularly cell growth effects. Among them, hydrocortisone is now regarded as an essential drug for suppressing inflammation in wound healing.

The wound dressing of the present invention is manufactured, for example, as follows. First, a predetermined amount of liquid paraffin and a crystal nucleating agent are added to polypropylene powder, melt-kneaded and pelletized. The pellets are melted at 150 to 200 ° C., extruded by an extruder with a T-die, introduced into a cooling and immobilizing liquid to be cooled and immobilized to form a film, and liquid paraffin in the film is extracted. And heat-treated for about 2 minutes to obtain a polypropylene porous membrane.

On the other hand, poly-N-isopropylacrylamide is known to have a lower critical solution temperature at about 32 ° C. in an aqueous solution. For example, when the polypropylene porous film is coated with poly-N-isopropylacrylamide, the occupied volume of poly-N-isopropylacrylamide becomes small at a lower critical solution temperature of 32 ° C. or higher, and water molecules in the polymer are removed. Since they are adjacent to each other, the surface of the base material is hydrophobic, and conversely, the occupied volume of poly-N-isopropylacrylamide is large at 32 ° C. or lower, so that the volume fraction occupied by water molecules in the polymer is increased. The surface becomes hydrophilic.

Further, it can be obtained by the following method. It is obtained by plasma-initiated surface graft polymerization of N-isopropylacrylamide dissolved in isopropyl alcohol on a polypropylene porous membrane. It can be obtained by impregnating a powder of a physiologically active substance or an aqueous solution of a physiologically active substance with the coating material kept in a humid environment of 32 ° C. or lower and air-drying.

[0024]

EXAMPLES The present invention will be described more specifically below with reference to examples and experimental examples.

Example 1 (1) Synthesis of poly-N-isopropylacrylamide N-isopropylacrylamide (Tokyo Kasei Co., Ltd.) was dissolved in toluene and reprecipitated and purified with petroleum ether. 20 g of purified N-isopropylacrylamide was dissolved in 30 ml of a benzene solution, and 0.08 g of azobisisobutyronitrile as an initiator was added. Reaction temperature 60 under nitrogen stream
Polymerization was carried out by stirring at a reaction temperature of 24 hours for 24 hours. This polymer was dissolved in THF and reprecipitated with ethyl ether. The above reprecipitation purification operation was repeated twice. Furthermore, 16 g of the target product could be obtained by vacuum drying at room temperature for 72 hours.

(2) Preparation of Porous Membrane 400 parts by weight of liquid paraffin (average molecular weight 32) per 100 parts by weight of a polypropylene mixture having a melt flow index of 30 and 0.3 (mixing weight ratio 100: 40).
4) and 0.3 parts by weight of 1,3 as crystal nucleating agent
2,4-bis (p-ethylbenzylidene) sorbitol was melt-kneaded by a twin-screw extruder and pelletized. The pellets were heated to 150 to 200 by using the above twin-screw extruder.
It is melted at ℃, extruded into air from a T-die with a slit of 0.6 mm, and made into a film shape. This film-like material is introduced into a cooling immobilization solution by a guide roller placed directly under the T-die, cooled and fixed, and then wound up. .. The wound film-like material is cut into a certain size and fixed in both longitudinal and lateral directions,
10 in trichloro-1,2,2-trifluoroethane
The liquid paraffin in the film-like material is extracted by immersing it 4 times in total. Then, heat treatment was performed in air at 135 ° C. for 2 minutes to obtain a polypropylene porous film having a pore size of 0.6 μm and a film thickness of 100 μm.

(3) Preparation of Wound Dressing Material The polypropylene porous membrane prepared in Example 2 was coated with the ethanol solution of 2% poly-N-isopropylacrylamide synthesized in (1) above, and then in a clean bench. Obtained by air-drying.

Example 2 Preparation of Wound Dressing The polypropylene porous membrane prepared in Example 1 (2) was irradiated with argon plasma for 1 minute and immersed in a 5% N-isopropylacrylamide isopropyl alcohol solution. It was obtained by carrying out graft polymerization for 30 minutes.

Example 3 Preparation of Wound Dressing The wound dressing obtained in Example 2 above was dipped in a phosphate buffer containing epidermal growth factor and treated at 20 ° C. for 2 hours. Further, the temperature of the solution was raised to 37 ° C., taken out, and air-dried in a clean bench.

Example 4 Preparation of Porous Membrane 300 parts by weight of liquid paraffin (average molecular weight 324) and 0.3 parts by weight of crystals per 100 parts by weight of a random copolymer of propylene and ethylene (Mitsui Toatsu Chemicals, Inc.). 1,3,2,4-bis (p-ethylbenzylidene) sorbitol as a nucleating agent was melt-kneaded by a twin-screw extruder and pelletized. The pellets were melted at 150 to 200 ° C. using the above-mentioned twin-screw extruder and slit 0.6
A film is extruded in the air from a T-die of mm, and the film-like material is introduced into a cooling and immobilizing solution by a guide roller placed immediately below the T-die, cooled and immobilized, and then wound. This wound film-like material is cut into a certain size, fixed in both the vertical and horizontal directions, and 1,1,2-trichloro-1,2,2,
Dip in 2-trifluoroethane for a total of 4 times for 10 minutes,
Liquid paraffin in the film was extracted to obtain a polyolefin porous membrane having a porosity of 45% and a pore diameter of 0.07 μm.

Example 5 Preparation of Wound Dressing Material The polyolefin porous membrane prepared in Example 4 was coated with the ethanol solution of 2% poly-N-isopropylacrylamide synthesized in Example 1 (1) above, and then clean. Obtained by air-drying on the bench.

Example 6 Preparation of Wound Dressing Material The polyolefin porous membrane prepared in Example 5 was irradiated with argon plasma for 1 minute, immersed in a 5% N-isopropylacrylamide isopropyl alcohol solution, and grafted for 30 minutes. It was obtained by polymerization.

Example 7 Preparation of Wound Dressing The wound dressing obtained in Example 6 above was immersed in a phosphate buffer containing epidermal growth factor and treated at 20 ° C. for 2 hours. Further, the temperature of the solution was raised to 37 ° C., taken out, and air-dried in a clean bench.

Example (animal experiment) Transplantation of rat skin defect wound with wound dressing The dressing obtained above was transplanted to the back skin of a rat and tested. Wistar-KY rat (200-400
(g) was shaved under Nembutal anesthesia, 12/1000 (inch) of skin was peeled with a dermatome on the rat dorsal skin that had been disinfected with isodine to create a defect wound, which was bleeding stopped, dried, and a sample containing saline was added. Was affixed, and the four corners were fixed with Aron Alpha. On top of that, 4 sheets of Solfuren (made by Terumo) were stacked, and then stretched with elastic bandages such as Elasticon to be wrapped in a body and pressed and fixed.

To replace the wound dressing on the first day after transplantation, if the wound dressing was previously cooled with a frozen substance such as a refrigerant before peeling, it could be easily peeled off without damaging the wound surface.

[0036]

EFFECT OF THE INVENTION The wound dressing of the present invention has an upper critical solution temperature in water in the range of 40 to 50 ° C. or a lower critical solution temperature in the range of 0 to 35 ° C. on the surface in contact with the wound. Since a certain temperature-sensitive polymer is coated, when the coating material is applied to the wound surface, the polymer is held in a solid state and protects the wound surface, while the coating material is kept in the above range when peeling. By heating or cooling to the above temperature, the above polymer dissolves in water and the coating material can be easily removed.

Front page continued (72) Inventor Makoto Onishi, 1500 Inoguchi, Nakai-cho, Ashigagami-gun, Kanagawa Terumo Corporation (72) Inventor Kenichi Shimura 1500, Inoguchi, Nakai-cho, Ashigagami-gun, Kanagawa Terumo Corporation

Claims (3)

[Claims] 1. A wound dressing material comprising one surface of a porous polyolefin membrane or a porous halogenated polyolefin membrane coated with a temperature-sensitive polymer having a lower critical solution temperature in the range of 0 to 35 ° C. in water. .. 2. A porosity of 50% or less and an average pore diameter of 0.01 to.
It is composed of a porous polyolefin membrane or a porous halogenated polyolefin membrane having a thickness of 1.0 μm, and has a lower critical dissolution temperature in water of 0 to 35 ° C. on its surface and pore inner surface.
A wound dressing material coated with a temperature-sensitive polymer in the range of. 3. A wound dressing containing the wound dressing of claim 1 containing a physiologically active substance.