JP2003116907A - External use lesion protective material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external use lesion protective material which is capable of efficiently inactivating an objective hazardous material by a photocatalyst reaction without exerting a serious damage occurring in the photocatalyst reaction to the tissue and cells of a lesion. SOLUTION: The external use lesion protective material (20) is provided with a sheet (21) which is worn at the lesion and a photocatalyst (26) held in a light receivable state at this sheet, and this sheet is provided with a porous layer (25) having gaps of sizes to accept the exudate from the lesion and the foreign matter mingled in the exudate. More preferably, one or >=2 kinds of captive materials (28) having selective bondability to one or >=2 kinds of the materials which can be inactivated by the photocatalyst reaction are arranged in a position proximate to the photocatalyst.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an externally-affected part protective material directed to an affected part outside the body, and more particularly to an externally-affected part protective material containing a photocatalyst and a manufacturing technique thereof.

[0002]

2. Description of the Related Art A lesion such as a tumor or the like on the outside of the body (typically, the body surface), or a burn surface or a wound surface (hereinafter, these are collectively referred to as "affected area") is protected and affected. Recovery of
Various artificial skins and plasters are used as a protective material to be attached to the affected area in order to promote healing. Further, there has been proposed a diseased part protecting material having not only a function of physically covering and protecting the affected part, but also a function of simultaneously sterilizing and disinfecting the affected part (that is, preventing the occurrence of infection and inflammation). For example, Japanese Patent No. 2645098 and Japanese Patent Laid-Open No. 10-711.
Japanese Patent Publication No. 99 discloses artificial skin containing antibacterial agents such as silver sulfadiazine and gentamicin.
Generally, when an antibacterial drug is used, if the applied amount is too small, the generation of drug resistant bacteria is promoted, which is not preferable. On the other hand, if the applied amount is too large, not only harmful substances such as bacteria to be eliminated but also tissues and cells in the affected area are likely to be damaged to some extent. Therefore, in order to realize a condition in which the cells / tissues of the affected area are not seriously damaged and have a sufficient infection preventive effect and the occurrence of resistant bacteria is prevented in advance, the content of the antibacterial drug in the affected area protective material and It is necessary to pay attention to its existence form. For example, Suzuki is a protector for an affected area in which an antibacterial drug (antibiotic: gentamicin) is bound to a base material (polyvinyl alcohol hydrogel), and the antibacterial drug is released to the affected area only when a bacterial infection occurs. Drug delivery system)
We have proposed a protective material for the affected area with (J. Biomed. Mate
r. Res., Vol. 42, pp. 112-116 (1998)). D like this
According to the affected part protective material provided with DS, the antibacterial drug is not released to the affected part when the problematic bacteria and viruses are not infected to the affected part, and the tissues and cells of the affected part are damaged by the antibacterial drug. Can be deterred.
However, even if such DDS is adopted, the same problem may occur when the amount of antibacterial drug released during bacterial infection is too large or too small.

On the other hand, in place of an antibacterial drug having the above-mentioned problems (appearance of resistant bacteria and damage to affected tissues), there is no risk of drug-resistant bacteria being generated and damage to tissues and cells in affected regions. It is considered to include a photocatalyst, which is hard to give, as a treatment agent in the affected part protective material. For example, JP-A-9-322935 and JP-A-2000-136129.
Japanese Unexamined Patent Publication No. 2000-237230 discloses a plaster-type affected part protecting material in which a photocatalyst such as titanium dioxide is held on a sheet-shaped substrate. By attaching such a photocatalyst-containing affected part protective material to the affected part and irradiating the photocatalyst with light (typically, ultraviolet rays),
It is possible to generate various active oxygen and free radicals such as hydroxy radicals around the photocatalyst and cause a redox reaction accompanying it (hereinafter, the reaction via the photocatalyst is collectively referred to as "photocatalytic reaction"). Then, due to the photocatalytic reaction, bacteria and viruses present in the affected area and harmful foreign substances produced by them (toxins, enzymes, nucleic acids, etc.)
Can be inactivated.

[0004]

However, the conventional photocatalyst-containing affected material protection material as described in each of the above publications is obtained by simply holding a powdery photocatalyst on a base material such as a nonwoven fabric. Nothing more. Therefore, when the photocatalyst contained in the affected part protection material is irradiated with light, harmful substances such as microorganisms and virus particles that are inactivated by the photocatalytic reaction (including sterilization, decomposition and detoxification; the same applies below) , Those that are present on the photocatalyst or in the vicinity of the photocatalyst. Therefore, in order to more efficiently inactivate a harmful substance with respect to light irradiation for a certain period of time and intensity, a large amount of photocatalyst must be contained in a state in which light can be transmitted.
However, there is a physical limit to the amount of photocatalyst that can be held on the sheet-shaped base material that constitutes the affected part protective material. Further, if a large excess of photocatalyst is present in the affected area, the amount of active oxygen and free radicals generated per unit time may be excessive, and there is a concern that the active substances may adversely affect the affected tissue or cells.

Therefore, the present invention was created to solve the above-mentioned problems relating to a material for protecting an affected area for external use containing a photocatalyst, and its object is to prevent serious damage to tissues and cells of the affected area. It is an object of the present invention to provide an externally-affected part protective material capable of highly efficiently and / or selectively inactivating a predetermined harmful substance existing in the affected part based on a photocatalytic reaction.

[0006]

Means for Solving the Problems The present invention provides an externally-affected-part protection material for protecting an affected part generated outside the body. One of the external affected part protective materials is provided with a sheet to be attached to the affected part, and a photocatalyst held in the sheet in a light-receivable state. The sheet is provided with a porous layer having voids sized to receive exudate from the affected area and foreign substances mixed in the exudate. The photocatalyst is disposed on the surface side of the porous layer that does not face the affected area (that is, the outer surface that does not face the affected area when attached to the affected area. The same applies below) and / or inside the voids of the porous layer. ing.

In the external-use diseased part protective material having such a structure, the photocatalyst and the surface of the affected part are isolated by the interposition of the porous layer (including mesh-like one having a relatively large void size). This can prevent the photocatalyst from directly contacting the affected tissue. On the other hand, exudate existing in the affected area and harmful substances (harmful microorganisms, viruses, etc.) mixed therein can enter the voids of the porous layer. Therefore, when the external use affected part protective material of the present configuration is attached to the affected part and the photocatalyst is irradiated with light, the affected part tissue is prevented from being damaged by the photocatalytic reaction, and selectively and / or efficiently the harmful substance Can be inactivated by a photocatalytic reaction (hereinafter, treatment of harmful substances based on such photocatalytic reaction is abbreviated as “phototreatment”).

Further, another one of the externally-affected part protective materials provided by the present invention is a sheet to be attached to an affected part, a photocatalyst held in a light-receivable state on the sheet, and inactivated by a photocatalytic reaction. It is provided with one or two or more trapping substances having a selective binding ability to one or two or more substances that can be used. The trapping substance is arranged close to the photocatalyst.

In the external-affected part protective material of the present invention having such a constitution, a predetermined one or two kinds to be inactivated by the selective binding ability of the trapping substance, that is, the function of selectively binding a specific substance or a group of substances. The above substances (typically harmful microorganisms, viruses or high molecular compounds such as polypeptides and nucleic acids originating from them) can be selectively collected around the photocatalyst. Therefore, when the externally-affected part protective material of this configuration is attached to the affected part and the photocatalyst is irradiated with light, the target harmful substance can be selectively and efficiently inactivated by the photocatalytic reaction. Further, according to the external use affected part protective material, as a result of capturing a predetermined harmful substance to be subjected to light treatment by the trapping substance, the exudate present on the affected part surface and its surface region (blood exuding from affected part tissue, It is also possible to remove the harmful substances from body fluid such as lymph and its contents. The same shall apply hereinafter.). Such elimination ability is advantageous when the harmful substance is a substance that can be an allergen.

A preferred material for protecting the affected area for external use having the above-mentioned constitution is characterized in that the capture substance is bound to the photocatalyst. With the external-use diseased part protection material having such a configuration, the substance to be photoprocessed can be collected around the photocatalyst with high efficiency. Further, another preferable externally-affected-part protecting material having the above-mentioned configuration is that the sheet is provided with a porous layer having a void having a size for receiving exudate from the affected part and foreign substances mixed in the exudate, and the photocatalyst is , The surface side of the porous layer that does not face the affected area and / or the inside of the void of the porous layer. In the external use affected part protective material, since it is possible to prevent direct contact between the photocatalyst and the affected tissue due to the interposition of the porous layer, it is possible to prevent the affected tissue from being damaged by the photocatalytic reaction, and It is possible to achieve a high level of compatibility with the selective phototreatment of harmful substances.

Particularly preferred as the external-use diseased part protective material of the present invention having each of the above-mentioned constitutions is that the above-mentioned sheet is provided with a water permeation control layer for controlling the evaporation of water from the surface of the affected part, and the photocatalyst has the water permeation rate. The adjustment layer is arranged on the surface side facing the affected area (that is, the inner surface side facing the affected area when attached to the affected area. The same applies hereinafter). In the external-use diseased part protective material having such a structure, the evaporation of water from the surface of the affected part is caused by the interposition of the water permeation control layer (which has a high water-retaining ability and can limit the amount of water evaporated from the outer surface side of this layer). Moderately controlled. This prevents dryness of the affected area (typically the disappearance of exudate present on the surface of the affected area),
By the photocatalytic reaction, various active oxygen and free radicals can be efficiently generated from the water around the photocatalyst. Therefore, the optical processing can be effectively performed.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Preferred embodiments of the present invention will be described below.

The externally-affected part protective material of the present invention is a therapeutic material which can be widely applied to a wound surface caused by scratches, burns or the like, or a lesion such as athlete's foot. Therefore, as long as the selective phototreatment of the harmful substance can be performed by the photocatalytic reaction, the overall size and shape can be appropriately determined according to the intended use.

The photocatalyst contained in the external-affected part protective material of the present invention is a high photocatalytically active substance that efficiently produces active oxygen and / or free radicals from the water present in the surroundings when irradiated with light. The substance itself is preferably one that is less likely to adversely affect the affected tissue and cells, for example, one that is non-toxic and mild to skin tissue. Examples of such substances include inorganic substances such as titanium dioxide and zinc oxide. Suitable photocatalytically active substances (metal oxides) include titanium dioxide (titania), zinc oxide, iron oxide, tungsten oxide, bismuth oxide, nickel oxide and the like. In particular, titanium dioxide and zinc oxide, which have high photocatalytic activity and are also used in cosmetics and pharmaceuticals, are suitable.

The photocatalyst to be contained in the external-affected part protective material of the present invention is a highly purified product of these metal oxides having photocatalytic activity (preferably, a substance consisting essentially of the oxide except for unavoidable impurities). ), Or may contain other substances to the extent that the photocatalytic activity of these metal oxides is not excessively reduced. For example, metal oxides such as zirconium oxide, aluminum oxide, and magnesium oxide are added to titanium dioxide (titania) and zinc oxide (preferably about 0 to 5 wt% of the total material to be added as a photocatalyst to the external affected part protection material). ) May be used. By adding such a metal oxide, the amount of active oxygen and free radicals generated during light irradiation can be adjusted so as not to be excessive. Alternatively, it may be a composite of a metal oxide having photocatalytic activity as described above and other inorganic substances.
For example, a composite of an inorganic substance such as silica, apatite, or zeolite and a metal oxide having a photocatalytic activity such as titanium dioxide (for example, refer to JP-A Nos. 11-138017 and 9-276706). Can be used as the photocatalyst according to the present invention. Preferable examples of such a composite include metal oxide particles having photocatalytic activity such as titania coated on a porous ceramic film which is inactive as a photocatalyst (see Japanese Patent Laid-Open No. 9-276706). The coated metal oxide particles can protect the sheet (for example, a polyurethane resin sheet) described later from decomposition / deterioration due to a photocatalytic reaction, although it is not particularly limited because it depends on the material. Therefore, an externally-affected part protective material containing such a photocatalyst (composite of the above-mentioned inorganic substance and a metal oxide having photocatalytic activity) is suitable for a purpose of being attached to the affected part for a relatively long time.

A typical example of the shape of the photocatalyst used for constructing the external-use lesion-protecting material of the present invention is powder. In particular, a fine powder having an average particle size of 10 μm or less (more preferably 1 μm or less) is preferable. According to such a fine powder photocatalyst,
It can be held evenly on the surface of the sheet described below. Alternatively, a photocatalyst formed in a sheet shape may be used instead of the photocatalyst in powder (fine particles) form. For example, an externally-affected part protective material having a photocatalyst layer formed by applying a paste containing a photocatalyst such as titanium dioxide to the surface of a sheet made of the material described below is also preferable as an embodiment of the present invention.

Next, the trapping substance that can be contained in the externally-affected part protective material of the present invention will be described. The capture substance according to the present invention is a substance whose main purpose is to selectively collect harmful substances to be photoprocessed on or near the surface of a substance having a photocatalytic activity (typically, a metal oxide such as titanium dioxide). Is.
Examples of the capture substance suitable for such purpose include an antibody (immunoglobulin such as IgG) having a high binding specificity for a specific antigen. For example, by adopting as a capture substance a polyclonal antibody or a derivative thereof contained in antiserum that recognizes bacterial structures (cell wall, capsule, etc.) and products (proteins such as toxins and enzymes) as antigens, It does not selectively capture substances derived from the affected tissue (neutrophils, macrophages, etc.), and specifically binds to the foreign substances (bacteria itself and bacteria-derived substances) that are the targets of phototreatment, and at or near the photocatalyst surface. It is possible to collect the target substance relating to the above in the vicinity of the photocatalyst. When an antibody is used as the capture substance, there is no particular limitation on the type and number, and what kind and what type is used are determined according to the application. For example, as a target for optical processing, MRS
When a specific bacterium or virus such as A or HIV is assumed, a monoclonal antibody or the like having a high binding specificity only to the specific bacterium or virus can be used. On the other hand, when the purpose is to prevent general infection of the wound surface, use a globulin fraction of antiserum capable of binding a wide range of Gram-positive bacteria, Gram-negative bacteria, etc., a polyclonal antibody, etc. Is preferred.
For example, the antibody group in the antiserum produced and collected by immunizing a rabbit or the like with several kinds of pathogenic microorganisms or virus particles as an antigen may be used without particular separation. Also,
The capture substance that can be used for the external-use diseased part protecting material of the present invention is not limited to an antibody. A target cell tissue (receptor) of a virus (HIV or the like) invading specific cells or tissue or an analog thereof may be used as a capture substance as long as it does not seriously adversely affect the affected tissue or the physiological condition of the patient. Alternatively, it may be an enzyme or the like that utilizes substrate specificity.

Therefore, in the present invention, these trapping substances are arranged in the vicinity of the photocatalytic substance (typically the above-mentioned metal oxide). Suitably, it is bound to the surface of the photocatalytic substance itself.
The binding means is not particularly limited, and a general method for binding a protein such as an antibody molecule to the surface of an inorganic substance such as metal or ceramic, which is often used in the field of immunochemistry, can be adopted. Typically, FIG.
As shown schematically in FIG. 1, a photocatalyst 1 (typically a metal oxide such as titanium dioxide) and a capture substance 3 (eg, an antibody or a fragment thereof) are connected via a suitable linker (binder) 2.
It is good to connect and indirectly. For example, using a suitable silane coupling agent having an amino group such as p-aminophenyltrimethoxysilane, 3-aminopropyltrimethoxysilane and N-2-aminoethyl-3-aminopropyltrimethoxysilane, the photocatalyst 1 The surface of is silanized and an amino group is introduced, and a linker 2 such as glutaraldehyde is bonded to the amino group. Next, a capture substance (protein) 3 such as an antibody molecule may be bound to the terminal functional group (aldehyde group or the like) of the linker 2.

Next, the sheet constituting the externally-affected part protective material will be described. The sheet employed in the externally-affected part protective material of the present invention has a function of covering and protecting the site when it is addressed to the affected part, and a function of holding the photocatalyst in a state where light treatment can be performed in the affected part, The material is not particularly limited as long as it can transmit light (typically, ultraviolet rays) from the outside. However, since it is in direct contact with the affected area, it is desirable that it be harmless or hypoallergenic to the human body. The material forming the sheet and the structure thereof differ depending on the use of the externally-affected part protective material of the present invention. For example, when the externally-affected part protective material of the present invention is used for the purpose of protecting the affected part for a relatively short period of time similarly to the conventional adhesive plaster, the material of the sheet may be a natural fiber such as cotton or hemp. . Further, polyester, polyamide (nylon), and acrylic synthetic fibers may be used. Typically, a woven fabric, a non-woven fabric, or a knitted fabric prepared from these natural fibers or synthetic fibers is used to form a mesh-like sheet having voids of a size that accepts exudate from an affected area and foreign substances mixed in the exudate. Can be configured. Such a mesh-like portion corresponds to the porous layer in the externally-affected part protective material of the present invention. A non-woven fabric made of synthetic fibers is particularly preferable as a material for forming the mesh sheet. There is no particular limitation on the means for holding the photocatalytic substance (typically, a metal oxide such as titanium dioxide) on such a nonwoven fabric. For example, a photocatalyst (typically a metal oxide powder such as titanium dioxide or zinc oxide) can be attached to the surface of the non-woven fabric by a method such as coating, dipping, spraying or sputtering. Then 100-
The photocatalyst can be fixed on the surface of the nonwoven fabric by heating the nonwoven fabric to about 500 ° C.

In such a plaster-type patch for externally affected area protection, an outer sheet for attaching the externally applied affected area protection material to the affected area can be provided on the outer surface side of the sheet holding the photocatalyst (see FIG. 2 described later). Typically, such an outer sheet is formed from a synthetic resin film such as polyolefin. Then, at least a part of the side of the outer sheet facing the affected area can be coated with an adhesive material for attaching / fixing the external affected area protecting material to the affected area.

Further, in the adhesive plaster-type external use affected part protective material, a water permeation control layer is laminated on one surface of the mesh sheet (sheet base material forming the porous layer) (that is, the outer surface which does not face the affected part in use). Those obtained are preferred. Such a water permeation control layer has a relatively high water retention capacity (water retention capacity) and can appropriately control the evaporation of water from the affected area, for example, water at room temperature, atmospheric pressure and relative humidity of 60%. Permeability is generally 0.1-2.0 mg / hr · c
m ² is preferable, and the water permeability under such conditions is the same as that of the skin of a healthy person 0.9 to 1.7 mg /
Those of hr · cm ² are particularly preferable. The material of the water permeation control layer that can realize such water permeability is
Silicone, polyurethane, polyacrylate ester, polymethacrylate ester, porous polytetrafluoroethylene (PTFE), polyvinyl alcohol,
Examples thereof include polyacrylamide and polysaccharides (eg, chitin, chitosan, cellulose, agarose or their derivatives). A water permeation control layer having a high light transmittance and capable of easily forming a thin film water permeation control layer made of silicone or a polysaccharide having high biocompatibility is particularly preferable.

On the other hand, when the externally-affected part protective material of the present invention is used for a relatively long period of time to protect an affected part where skin tissue is extensively lost due to burns or the like (that is, when it is used as artificial skin), the above-mentioned water content is used. A sheet including a permeation control layer and a matrix layer formed on the affected area attachment side of the water permeation control layer is preferable. The matrix layer can generally be formed from fibrillar collagen and / or denatured collagen. A matrix substantially composed of such collagen or modified collagen (gelatin),
It forms a porous layer with pores that accept fibroblasts involved in the regeneration of dermal-like connective tissue. Therefore, such a matrix layer corresponds to the porous layer in the externally-affected part protective material of the present invention.

Next, with reference to the drawings, some preferred forms of the externally-affected part protective material of the present invention and a manufacturing method thereof will be illustrated. FIG. 2 shows one form of the external affected part protective material 10 which is preferable for protecting small-scale wounds and light burns. The sheet 11 of the externally-affected part protective material 10 of this form includes a light-transmittable outer sheet (typically made of polyolefin) 12 for attaching the main protective material 10 to the affected part S, and the affected part S of the outer sheet 12. It is composed of a moisture permeation control layer 14 formed of a silicone resin or the like fixed to one surface. Around the water permeation control layer of the outer sheet 12, an adhesive material (not shown) for attaching and fixing the protective material 10 to the affected area S is applied.
Further, the outer sheet 12 is provided with a large number of holes and slits (not shown) for ensuring good air permeability and light transmission when it is attached to the affected area S (not shown). On the other hand, as shown in FIG. 2, on the surface of the moisture permeation control layer 14 facing the affected area S, the photocatalyst 1 in the form of powder that is combined with the trapping substance 18 is attached.
6 is carried.

The externally-affected part protective material 10 having such a form is
Typically, it can be manufactured as follows. That is, a silicone film forming solution (eg, 50% Silastic silicone adhesive type A (Dow Cornin
hexane solution) (product of company g). On the other hand, PTF
The surface of a synthetic resin mesh sheet (not shown) having high heat resistance such as E (not shown) and the inside of voids are filled with the photocatalyst powder 16. Then, the mesh sheet is placed on the surface of the portion coated with the silicone film forming solution. Then
The coating film on which the mesh sheet is placed is dried under appropriate temperature conditions (preferably 50 to 80 ° C.). After that, the mesh sheet is removed and further dried for a predetermined time (for example, at 100 to 120 ° C. for 1 to 2 hours). This makes it possible to form the external-use diseased part protection material 10 in which the water permeation adjusting layer 14 is formed on one surface of the outer sheet 12 and the photocatalyst 16 is held on the side of the water permeation adjusting layer 14 facing the affected part. Then, by performing a capture substance binding treatment via the linker as described above (see Examples described later), the capture substance (antibody molecule etc.) 1 is formed on the surface of the photocatalyst 16 and the surface of the water permeation control layer 14 facing the affected area.
8 can be combined.

Externally-affected-part protection material 1 having a form as shown in FIG.
According to 0, it is possible to protect the affected area S while maintaining an appropriate amount of water on the surface of the affected area S. Then, under the condition that an appropriate amount of water is retained, external natural light or light having a predetermined wavelength (for example, 400 nm when the photocatalyst is titanium dioxide is used).
When the external affected part protection material 10 is irradiated with a certain degree of ultraviolet light),
Due to the presence of the photocatalyst 16, various active oxygen and free radicals are generated, and harmful substances (not shown) collected (held) on the surface of the photocatalyst 16 or in the vicinity thereof by the trapping substance 18 are selectively and efficiently lighted. Can be processed.

Next, another preferred embodiment of the external-use diseased part protecting material of the present invention will be described with reference to FIG. The sheet 21 of the external-affected part protective material 20 in this form has a light-transmittable outer sheet 22 similar to that shown in FIG. 2 and a moisture permeation adjusting layer 24 fixed to the surface of the outer sheet 22. Further, a mesh layer (porous layer) 25, which is preferably made of a nonwoven fabric made of polyolefin such as polyethylene or nylon, is provided on the surface of the moisture permeation control layer 24 facing the affected area. As shown in FIG. 3, in the external-use diseased part protection material 20, the powdery photocatalyst 26 combined with the trapping substance 28 is arranged outside the mesh layer 25 (on the side not facing the diseased part) and / or in the void thereof. And
It is not substantially exposed on the side of the mesh layer 25 facing the affected area.

The externally-affected part protective material 20 having such a form is
Typically, it can be manufactured as follows. That is, the water permeation control layer 24 is formed on one surface of the outer sheet 22 and the photocatalyst 26 is held on the side of the water permeation control layer 24 facing the affected area by the same method as the external affected part protection material 10 shown in FIG. 2 described above. An externally-affected part protective material thus obtained is obtained (see FIG. 2). Next, a mesh pad (corresponding to the mesh layer 25) made of a nonwoven fabric made of polyolefin is fixed to the surface of the moisture permeation control layer 24 facing the affected area using a chemical means such as an adhesive or a physical means such as heat treatment. . As a result, the mesh layer (porous layer) 25 is laminated on the affected surface side of the water permeation control layer 24,
The external diseased part protection material 20 in which the photocatalyst 26 is held inside the voids of the porous layer can be prepared. Then, by performing a capture substance binding treatment via the linker as described above, the surface of the photocatalyst 26 and the water permeation control layer 2
The capture substance 28 can be bound to the affected surface of No. 4 above.

Externally-affected-part protection material 2 having a form as shown in FIG.
According to 0, it is possible to perform the same light treatment as the above-described external-use diseased part protection material 10 shown in FIG. 2, and it is possible to prevent the photocatalyst 26 from directly contacting the surface of the affected part.
Therefore, it is possible to prevent damage to the affected tissue due to active oxygen or free radicals generated by the photocatalytic reaction. On the other hand, harmful substances (bacteria, viruses, etc.) mixed in the exudate on the surface of the affected area may enter the voids of the mesh layer 25 together with the exudate, so that the trapping substance 2
8 and collected (held) around the photocatalyst 26. As a result, the external affected part protection material 20 of the present embodiment
Then, the harmful substance to be treated can be selectively and efficiently phototreated by the photocatalytic reaction.

Next, with reference to FIG. 4, another preferred embodiment of the externally-affected part protective material of the present invention will be described. The external-affected-part protection material 30 in this form is a type that functions as so-called artificial skin, and is suitable for the purpose of protecting the affected part in which skin tissue such as severe burns is lost in a relatively wide range and preventing infection. The protective material 30. A sheet 31 of this type of external-use diseased part protective material (artificial skin) 30 is composed of a water permeation control layer 34 corresponding to the epidermis and a matrix layer 33 having pores into which fibroblasts enter.
As shown in FIG. 4, in the external-use diseased part protection material 30, the powdery photocatalyst 36 combined with the trapping substance 38 is arranged on the side of the moisture permeation adjusting layer 34 facing the diseased part, and the matrix layer 33 faces the affected part. It is not exposed on the face side.

The externally-affected part protective material (artificial skin) 30 having such a form can be typically manufactured as follows. That is, the external-affected-part protection material 10 of FIG. 2 described above.
The photocatalyst 36 is held on the surface of a sheet material (typically, a sheet made of silicone or polysaccharide) capable of controlling water permeation in the same manner as in the above. Then, by performing the capture substance binding treatment via the linker as described above, the capture substance 38 is bound to the surface of the photocatalyst 36 and the surface of the water permeation control layer 34 facing the affected area, while the porous material mainly composed of collagen is used. Prepare the matrix. That is, an acidic collagen solution (a solution of fibrous atelocollagen is preferable from the viewpoint of suppressing the expression of antigenicity and easiness of forming a crosslinked structure), and homogenizes this solution sufficiently.
Then, the homogenized solution is freeze-dried to obtain a porous collagen sponge. Then, collagen, which is a component of the sponge, is crosslinked. The cross-linking method is not particularly limited, and conventionally known cross-linking agents and cross-linking methods can be used. For example, as a chemical cross-linking agent, an aldehyde-based cross-linking agent such as glutaraldehyde, a carbodiimide-based cross-linking agent such as carbodiimide, or an isocyanate-based cross-linking agent such as hexamethylene diisocyanate is used to dip the sponge in a solution containing the sponge for a predetermined time. It can be crosslinked. Alternatively, heat dehydration crosslinking treatment (for example, heat treatment of the collagen sponge at about 110 ° C. under vacuum condition) may be performed. Then, the cross-linked collagen sponge 33 and the water permeation adjusting sheet material 34 thus obtained are attached to each other with an adhesive or the like having a high biocompatibility, whereby the external diseased part protective material (artificial skin) 30 shown in the figure can be obtained.

External form affected material protective material (artificial skin) in this form
According to 30, it is possible to perform the same light treatment as that of the external diseased part protection materials 10 and 20 shown in FIGS. 2 and 3 described above, and it is possible to prevent the photocatalyst 36 from directly contacting the surface of the affected part. Therefore, it is possible to prevent damage to the affected tissue due to active oxygen or free radicals generated by the photocatalytic reaction. On the other hand, harmful substances (bacteria, viruses, etc.) mixed in the exudate on the affected surface
Can enter the voids of the matrix layer 33 together with the exudate, so that they are captured by the capture substance 38 and collected (held) around the photocatalyst 36. As a result, in the externally-affected part protective material 30 of the present embodiment, the harmful substance to be treated can be selectively and efficiently phototreated by the photocatalytic reaction. Then, new skin tissue can be formed on the surface of the affected area at an early stage by the fibroblasts or the like that have entered the matrix layer.

The preferred embodiments of the externally-affected part protective material of the present invention have been described above with reference to the drawings. However, the externally-affected part protective material in the form schematically shown in each drawing is used for practicing the present invention. However, it is not intended to limit the externally-affected part protective material of the present invention to these forms. For example, a light-emitting substance capable of emitting light having a wavelength (ultraviolet ray) capable of causing a photocatalytic reaction to at least one of the above-mentioned sheet, that is, at least one of the outer sheet, the moisture permeation control layer, the mesh layer and the matrix layer. May be provided. For example, a fine powder of a spontaneous or phosphorescent luminescent ceramic (e.g., strontium carbonate containing strontium carbonate, europium, dysprosium, etc.) capable of radiating ultraviolet rays of a suitable wavelength, in a state in which radiant ultraviolet rays can reach the photocatalyst It is dispersed on a part of the above-mentioned sheet (for example, the surface of the outer sheet or the inside of the moisture permeation control layer). As a result, a photocatalytic reaction can be caused even when there is no light irradiation from the outside.

The sheet constituting the externally-affected part protective material of the present invention includes the above-mentioned outer sheet, water permeation control layer,
It may have a portion (layer position) other than the mesh layer and the matrix layer. For example, it may be provided with an antireflection film (layer) that can transmit light from the outside but prevents light reflected by a part of the affected part or a part of the external affected part protection material from diverging from the affected part protection material. .

[0034]

EXAMPLES The present invention will be described in more detail with reference to the examples described below, but the present invention is not intended to be limited to those shown in the examples.

<Example 1: Preparation of external protective material for affected area (1)
> A sheet provided with a silicone membrane as a moisture permeation control layer, titanium dioxide as a photocatalyst, and an externally-affected part protective material provided with immunoglobulin as a capture substance were prepared as follows. That is, finely powdered titanium dioxide (“ST-1”, a product of Ishihara Techno Co., Ltd.) was applied to a PTFE mesh sheet (opening 50 μm), and was uniformly filled between the meshes. On the other hand, 50% Silastic silicone adhesive type A (Dow Cornin
Hexane solution (product of Company g) was applied using a precision coating tool to form a 50 μm thick silicone film (uncured state). Then, before the silicone was cured, the mesh sheet filled with the titanium dioxide was placed on the silicone film and dried in an oven at 60 ° C. for 1 hour. After that, remove the mesh sheet, and
The temperature was raised to 0 ° C., and heat treatment was performed at that temperature for 2 hours.
Then, it cooled to room temperature. After cooling, excess titanium dioxide was washed with physiological saline. By the above processing, PTF
An E sheet was used as an outer sheet, and a sheet having a silicone film (corresponding to a moisture permeation control layer) formed on one surface thereof was prepared, and titanium dioxide could be retained on the surface of the silicone film.

Next, a globulin fraction (a high IgG content fraction) obtained by purifying an antiserum of a rabbit immunized with a crushed product of Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) in advance Min) was used to bind the antibody to the titanium dioxide particles retained on the silicone membrane.
That is, a hydroxyl group was introduced into titanium dioxide by immersing a silicone film holding titanium dioxide in dilute nitric acid and then washing. Then, the surface of the titanium dioxide particles was silanized and amino groups were introduced by immersing the silicone film holding titanium dioxide in a toluene solution containing 3-aminopropyltriethoxysilane. Next, the silicone film was immersed in an aqueous solution containing glutaraldehyde, and glutaraldehyde (linker according to this example) was bonded to the amino group on the silanized titanium dioxide surface. This introduced a terminal aldehyde functional group on the titanium dioxide surface via a linker.
Then, the silicone film was washed with an aqueous sodium chloride solution to remove excess glutaraldehyde. Next, the silicone membrane was immersed in a phosphate buffer containing the above globulin fraction to bind an immunoglobulin (IgG or the like) to the above aldehyde functional group. By this series of operations, the external-affected-site protective material according to the present example in which titanium dioxide (photocatalyst) and immunoglobulin (capturing substance) are held on the surface of the silicone film (water permeation control layer) that faces the affected area was prepared. .

<Example 2: Preparation of external protective material for affected area (2)
> A sheet provided with an agarose gel as a water permeation control layer, titanium dioxide as a photocatalyst, and an externally-affected part protective material provided with immunoglobulin as a capture substance were prepared as follows. That is, agarose powder was added to boiling water to prepare an agarose solution having a concentration of 10%. This solution was applied onto a PTFE sheet so as to have a thickness of 50 μm. Then, finely powdered titanium dioxide (“ST-1” above) was thinly dispersed on the agarose coating film. Then, it aged at room temperature (about 20 degreeC) for 12 hours, and made the titanium dioxide adhere and hold | maintain on the agarose gel surface. By the above-mentioned treatment, a PTFE sheet is used as an outer sheet, and a sheet having a gelated agarose membrane (corresponding to a water permeation control layer) formed on one side thereof is prepared, and titanium dioxide is retained on the surface of the membranous agarose gel. We were able to. Then, the same treatment as in Example 1 was carried out to bind immunoglobulin to the surface of titanium dioxide via glutaraldehyde. Through this series of operations, an external-use diseased part protective material according to the present example was prepared in which titanium dioxide (photocatalyst) and immunoglobulin (capturing substance) were held on the side of the membranous agarose gel (water permeation control layer) facing the affected part. .

<Example 3: Preparation of external protective material for affected area (3)
A sheet for protecting the affected area for external use comprising a sheet having a moisture permeation control layer made of a silicone membrane and a porous layer made of an amorphous silica fiber membrane, titanium dioxide as a photocatalyst, and immunoglobulin as a trapping substance It was produced in this way. That is, 100 g of high-purity amorphous silica fiber (product of Shuller), which is excellent in flexibility, biocompatibility and light transmittance.
Was dispersed in 10 L of dilute hydrochloric acid (pH 1-2). 3 g of boron nitride (manufactured by Denki Kagaku Kogyo Co., Ltd.) was added to this dispersion, and the pH of the dispersion was adjusted to 5 to 7 with ammonia. Next, the dispersion was tested using a commercially available paper making machine to form a fiber membrane having a thickness of about 40 μm. The obtained film was baked at about 1350 ° C. to prepare an inorganic fiber film. Next, a portion other than one surface portion (the surface side facing the affected area) of the obtained inorganic fiber membrane was immersed in a slurry containing finely powdered titanium dioxide (“ST-K01” manufactured by Ishihara Techno Co., Ltd.). . Then, heat drying treatment was performed at 80 ° C. for 1 hour. Then, it heat-processed at 500 degreeC for 1 hour, and obtained the inorganic fiber membrane carrying the powdery titanium dioxide.

On the other hand, the same processing as in the first embodiment is carried out, and PT
A silicone film was formed on one side of the FE sheet. Therefore,
The titanium dioxide-retaining inorganic fiber membrane obtained above was placed on the silicone membrane before the silicone was cured, and dried in an oven at 60 ° C. for 1 hour or more. Then, the temperature was further raised to 110 ° C., and heat treatment was continued for 2 hours at that temperature. Then, it cooled to room temperature. By the above processing, the PTFE sheet is used as an outer sheet,
It is possible to prepare a sheet in which a silicone membrane (corresponding to a moisture permeation control layer) and an inorganic fiber membrane (corresponding to a porous layer) are laminated and formed on one surface of the sheet, and to retain titanium dioxide in the voids of the inorganic fiber membrane. did it. Then, the same treatment as in Example 1 was carried out to bind immunoglobulin to the surface of titanium dioxide via glutaraldehyde. Through this series of operations, titanium dioxide (photocatalyst) and immunoglobulin (capturing substance) were retained on the side of the silicone membrane (water permeation control layer) facing the affected area, that is, inside the voids of the inorganic fiber membrane (porous layer). An externally-affected part protective material according to this example was produced.

<Example 4: Preparation of external affected part protective material (4)
A sheet for protecting an affected area for external use comprising a sheet having a moisture permeation adjusting layer made of a silicone membrane and a porous layer made of an organic fiber membrane, titanium dioxide as a photocatalyst, and immunoglobulin as a trapping substance is prepared as follows. It was made. In other words, an organic fiber film made of nylon mesh, which has excellent biocompatibility and light transmittance, is coated with a silicon-based coating agent (Nippon Soda Co., Ltd. product: product name "Vistrater LNSC-".
200A ") was spray coated. Then 90 ℃
Then, the coating was cured for 30 minutes to form a thin silicon intermediate layer on the nylon fiber membrane. Next, a titanium dioxide coating agent (manufactured by Nippon Soda Co., Ltd .: trade name "Vistrater LNSC-200C") was spray-coated on the silicon intermediate layer. Then, heat treatment was performed at 120 ° C. for 30 minutes to obtain an organic fiber (nylon mesh) film supporting titanium dioxide.

On the other hand, the same processing as in the first embodiment is carried out, and PT
A silicone film was formed on one side of the FE sheet. Therefore,
Before the silicone was cured, the titanium dioxide-carrying organic fiber membrane obtained above was placed on the silicone membrane. At this time, the titanium dioxide holding surface of the organic fiber membrane and the PT
The FE sheet was placed so as to face the silicone film. Then, this sheet is placed in an oven at 60 ° C / 1
The drying process was performed for more than an hour. Then, the temperature was further raised to 110 ° C., and heat treatment was continued for 2 hours at that temperature. Then, it cooled to room temperature. By the above processing, P
A sheet in which a TFE sheet is used as an outer sheet and a silicone membrane (corresponding to a moisture permeation control layer) and an organic fiber membrane (corresponding to a porous layer) are laminated and formed on one surface thereof is prepared, and the organic fiber membrane (porous layer) is prepared. It was possible to retain titanium dioxide on the side not facing the affected area. Then, the same treatment as in Example 1 was carried out to bind immunoglobulin to the surface of titanium dioxide via glutaraldehyde. Through this series of operations, titanium dioxide (photocatalyst) and immunoglobulin (capturing substance) are applied to the surface side of the silicone membrane (water permeation control layer) that faces the affected area and not to the affected area of the organic fiber membrane (porous layer). ) Was held, and an externally-affected part protective material according to this example was produced.

<Example 5: Antibacterial test (1)> The following antibacterial test was performed using the externally-affected-site protective material obtained in Examples 1 to 4 described above. That is, a Brain Heart Infusion (BHI) agar medium sterilized in an autoclave was sterilized with a diameter of 100 mm (dishes).
The medium in the plate was solidified by dispensing into a plate and leaving it at room temperature for 1 hour. Then, separately, a part of each colony of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus that had been cultured on BHI agar medium for a few days was collected and added separately to sterilized physiological saline. A bacterial solution for inoculation was prepared for each of the above three types of bacteria by serially diluting with saline. Next, each inoculum solution was dropped onto a plate containing BHI agar medium so that the number of inoculum of each bacterium was 10 ⁴ per plate, and the whole surface of the medium was applied using a conradi stick.

Next, fragments having a size of 50 mm × 50 mm were prepared from the externally-affected part protective material obtained in each of the above-mentioned examples and placed on the surface of the medium of the plate coated with the above-mentioned bacterial solution. Then, while irradiating pseudo sunlight with a solar simulator, it was cultured at 37 ° C. for 18 hours. As a result, in the bacterial liquid coating plate on which the external affected part protective material as a comparative control was not placed, the growth of bacteria was observed on the entire surface of the agar medium, but the above fragments of each external applied affected part protective material were placed. In each of the plates, a blocking circle having a shape corresponding to the external-affected-site protective material fragment was formed. This is because Example 1
It is shown that the external protective material for an affected area obtained in 4 can effectively photo-process (inactivate) harmful substances such as bacteria and their products (toxins) by photocatalytic reaction.

<Example 6: Antibacterial test (2)> 100 mm
On the bottom surface of the sterilized plate (dishes), the externally-affected part protective material, the size of which was adjusted to the same shape, was placed. E. coli, Pseudomonas aeruginosa, and Staphylococcus aureus used in Example 5 were adjusted to have a concentration of 10 ⁴ cells / ml. 1 for each bacterial preparation
Each 100 μm was dropped onto the external-use diseased part protective material, and the entire surface of the protective material was applied using a conradi stick. Next, the external affected part protective material was irradiated with simulated sunlight for 1 hour using a solar simulator. Then, a mixture of Brain Heart Infusion (BHI) liquid medium and soft agar was dispensed onto the external protective material for affected area to a thickness of 1 mm, and the mixture was incubated at 37 ° C. for 24 hours. . As a result, colonies of each of the above-mentioned bacteria were confirmed in the soft agar in the case of performing the same treatment as above without irradiating pseudo sunlight as a comparative control. On the other hand, in the case of the present example irradiated with pseudo sunlight, colonies of any of the above-mentioned bacteria were not confirmed in the soft agar.

[0045]

As is apparent from the above embodiments,
According to the externally-affected part protective material provided by the present invention, the target substance to be inactivated is selectively and / or efficiently phototreated without seriously damaging the tissues and cells of the affected part due to the photocatalytic reaction. can do.

[Brief description of drawings]

FIG. 1 is an explanatory diagram schematically showing a binding state between a photocatalyst and a capture substance via a linker.

FIG. 2 is an explanatory view showing a schematic cross-sectional configuration of the external-use diseased part protection material of the present invention according to one embodiment.

FIG. 3 is an explanatory diagram showing a schematic cross-sectional configuration of the external-use diseased part protection material of the present invention according to one embodiment.

FIG. 4 is an explanatory diagram showing a schematic cross-sectional configuration of the external-use diseased part protection material of the present invention according to one embodiment.

[Explanation of symbols]

1,16,26,36 Photocatalyst 2 linker 3,18,28,38 Capture substances 10, 20, 30 External protective material for affected area 11,21,31 sheets 14, 24, 34 Water permeation control layer 25 mesh layer (porous layer) 33 Matrix layer

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Takeshi Kobayashi             4-29 Shimomachi, Chikusa-ku, Nagoya-shi, Aichi             No. 1 (72) Inventor Masashige Shinkai             6 Maehata, Takayokosuka Town, Tokai City, Aichi Prefecture (72) Inventor Shinji Kato             Noritake Shincho 3-chome 1-36, Nishi-ku, Nagoya-shi, Aichi             Noritake Co., Ltd. Limited             Within (72) Inventor Hirokazu Watanabe             Noritake Shincho 3-chome 1-36, Nishi-ku, Nagoya-shi, Aichi             Noritake Co., Ltd. Limited             Within (72) Inventor Kurutoku Hisanori             Noritake Shincho 3-chome 1-36, Nishi-ku, Nagoya-shi, Aichi             Noritake Co., Ltd. Limited             Within (72) Inventor Yoichi Kondo             Noritake Shincho 3-chome 1-36, Nishi-ku, Nagoya-shi, Aichi             Noritake Co., Ltd. Limited             Within (72) Inventor Misao Iwata             Noritake Shincho 3-chome 1-36, Nishi-ku, Nagoya-shi, Aichi             Noritake Co., Ltd. Limited             Within F-term (reference) 4G069 AA03 AA08 BA04B BA48A                       CD10 DA06 EA01Y FA03                       FB23

Claims (5)

[Claims] 1. An externally-affected part protective material for protecting an affected part outside the body, comprising a sheet to be attached to the affected part and a photocatalyst held in the sheet so as to be capable of receiving light. Is provided with a porous layer having voids of a size that accepts exudate from the affected area and foreign substances mixed in the exudate, and the photocatalyst is a surface side of the porous layer that does not face the affected area and / or the porous layer. Externally-affected part protective material disposed inside the void. 2. An externally-affected part protective material for protecting an affected part outside the body, which can be inactivated by a photocatalytic reaction with a sheet to be attached to the affected part, a photocatalyst held in the sheet in a receivable state. One or more trapping substances having a selective binding ability to one or two or more substances are provided, and the trapping substances are arranged in proximity to the photocatalyst,
External affected area protection material. 3. The external-use diseased part protection material according to claim 2, wherein the capture substance is bound to the photocatalyst. 4. The sheet is provided with a porous layer having voids sized to receive exudate from the affected area and foreign substances mixed in the exudate, and the photocatalyst does not face the affected area of the porous layer. The surface side and / or the inside of the void of the porous layer are arranged.
Or the externally-affected part protective material according to item 3. 5. The sheet is provided with a moisture permeation adjusting layer that controls evaporation of water from the surface of the affected area, and the photocatalyst is disposed on the surface side of the moisture permeation adjusting layer facing the affected area. The externally-affected part protective material according to any one of claims 1 to 4.