JPH0584288A - Wound coating material - Google Patents

Abstract

PURPOSE:To provide the wound coating material which has good adhesion to a wound surface, does not easily break down and peel in spite of contact with the wound part and can easily be peeled without bleeding at the time of peeling by coating a base material with a temp. sensitive high polymer having the lower limit critical solution temp. to water within a 0 to 35 deg.C range. CONSTITUTION:The base material is coated with the temp. sensitive high polymer having the lower limit critical solution temp. to water within the 0 to 35 deg.C range. A physiologically active material is incorporated into the coating agent. N-isopropylacrylamide is adequately used as the sensitive high polymer having 0 to 35 deg.C lower limit critical solution temp. A polyester mesh is coated with an ethanol soln. of the poly-N-isopropylacrylamide obtd. by repeating the process of dissolving, refining, etc., and is air dried within a clean bench, by which the wound coating material is obtd. The high polymer is held in a solid state to protect the wound surface when the coating material is applied to the wound surface. On the other hand, the easy removal of the coating material is possible.

Description

Detailed Description of the Invention

[0001]

INDUSTRIAL APPLICABILITY The present invention is applied to a skin defect site caused by a wound, a burn, etc., does not adhere to the wound surface in contact with the skin defect site, and can be easily peeled off with healing. Wound dressing.

[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, and 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, or disperse moisturizing ingredients in rubber-based materials to ensure adhesion, non-adhesion, high water content etc. The biocompatible hydrogel-forming support layer (for example, carboxymethyl cellulose, alginate, etc.) in which at least a part of the intended part and the part of the present inventors previously proposed to contact the wound is coated with a water repellent material. 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) The lower critical solution temperature in water is 0 to
A wound dressing material obtained by coating a substrate with a temperature-sensitive polymer in the range of 35 ° C.

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

In the present invention, the upper limit critical dissolution temperature in water means that when the temperature is higher than that temperature, it dissolves in water,
At a temperature below that temperature, it does not dissolve in water, and water is a temperature at which it 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 coating material can be easily peeled off, and the wound surface is not hurt or suffered. Further, 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 polymer may have a frostbite on the skin due to cooling when removing the coating material, and therefore a polymer having a lower critical solution temperature in the above-mentioned range is desirable.

The sensitive polymer or copolymer thereof 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., homo- or copolymer of N-isopropyl acrylamide or diethyl acrylamide is particularly preferably used.

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 epidermal cells and fibroblasts which are skin cells, and 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 the growth of epithelial cells isolated from the 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 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. As the base material of the wound dressing material, conventionally known materials can be used without particular limitation. For example, a non-woven fabric, a woven fabric, a knitted fabric, or a polymer having a mesh shape, a film shape, a porous shape or a sponge shape is used.

The wound dressing of the present invention is manufactured, for example, as follows. First, poly-N-isopropylacrylamide is known to have a lower critical solution temperature at about 32 ° C. in an aqueous solution.

For example, polyester mesh material may be poly-
When N-isopropylacrylamide is coated, the occupied volume of poly-N-isopropylacrylamide becomes small at the lower critical dissolution temperature of 32 ° C. or higher, and it separates from water molecules in the polymer, so that the substrate surface exhibits hydrophobicity, On the contrary, at 32 ° C. or less, the occupied volume of poly-N-isopropylacrylamide becomes large and the volume fraction of water molecules in the polymer increases, so that the surface of the base material 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 onto a polyester mesh. 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 at 32 ° C. or lower and air-drying.

[0022]

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 the purified N-isopropylacrylamide was dissolved in 30 ml of a benzene solution, and 0.08 g of the initiator azobisisobutyronitrile 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 tetrahydrofuran and reprecipitated with ethyl ether. The above reprecipitation purification operation was repeated twice. Furthermore, by vacuum drying at room temperature for 72 hours, 16 g of the target product is obtained.
I was able to get

(2) Preparation of Wound Dressing Material A polyester mesh was coated with the ethanol solution of 2% poly-N-isopropylacrylamide synthesized in the above (1) and then air-dried in a clean bench to obtain the wound dressing material.

Example 2 Preparation of Wound Dressing A polyester mesh was irradiated with argon plasma for 1 minute, dipped in a solution of 5% N-isopropylacrylamide in isopropyl alcohol, and graft-polymerized 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.

Experimental Examples Animal Experiments Transplantation of rat skin defect wounds with wound dressing The dressings (Examples 1 and 2) obtained above were transplanted to the dorsal skin of rats for testing. Wistar-KY rats (200-400 g) were depilated under Nembutal anesthesia,
Dermatome on rat dorsal skin disinfected with isodine 12
/ 1000 (inch) of skin was peeled off to make a defect wound, and after hemostasis and drying, specimens containing saline were affixed, and four corners were fixed with Aron Alpha. in addition,
Four sheets of Soflen (made by Terumo) were stacked, and then stretched with elastic bandage such as Elasticon to make a body roll and press and fix. To replace the wound dressing on the first day of 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.

[0028]

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.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masato Onishi 1500 Inoguchi, Nakai-cho, Ashigaragami-gun, Kanagawa Terumo Corporation (72) Inventor Kenichi Shimura 1500 Inoguchi, Nakai-cho, Ashigarakami-gun, Kanagawa Terumo Corporation

Claims (2)

[Claims] 1. The lower critical solution temperature for water is 0 to 35.
A wound dressing material obtained by coating a substrate with a temperature-sensitive polymer in the range of ° C. 2. A wound dressing material comprising the wound dressing material of claim 1 containing a physiologically active substance.