WO2003034962A1

WO2003034962A1 - External affected area protective material

Info

Publication number: WO2003034962A1
Application number: PCT/JP2002/010771
Authority: WO
Inventors: Takeshi Kobayashi; Masashige Shinkai; Shinji Kato; Hirokazu Watanabe; Hisanori Kurobe; Yoichi Kondo; Misao Iwata
Original assignee: Noritake Co.,Limited
Priority date: 2001-10-17
Filing date: 2002-10-17
Publication date: 2003-05-01
Also published as: JP2003116907A

Abstract

An external affected area protective material (20) capable of efficiently deactivating specified harmful substances allowed to be present in the affected area on the outside of a body by photocatalytic reaction, comprising a sheet (21) installed on the affected area and photocatalysts (26) held on the sheet in a light receivable state, the sheet further comprising a porous layer (25) having pores of such sizes that can receive exudate from the affected area and foreign matter mixed in the exudate, wherein one or more types of arresting substances (28) having a selective combining ability for one or more types of substances allowed to be deactivated by the photocatalytic reaction are desirably disposed in the porous layer at positions close to the photocatalysts.

Description

Specification

External protection for affected area Technical field

The present invention relates to an external affected part protecting material addressed to an affected part outside the body, and more particularly, to an external affected part protecting material containing a photocatalyst and its production. Background art

Protects lesions such as tumors formed on the outside of the body (typically the body surface), or burns and wounds (hereinafter collectively referred to as “affected areas”), and promotes recovery and healing of the affected areas Various artificial skins and adhesive plasters are attached to the affected area as protective materials for the skin. In addition, there has been proposed an affected part protective material which has a function of not only covering and physically protecting the affected part but also sterilizing and disinfecting the affected part (that is, preventing the occurrence of infection and inflammation).

For example, Japanese Patent No. 2645098 and Japanese Patent Application Laid-Open No. 10-71199 disclose artificial skin containing an antibacterial agent such as silver sulfadiazine and gentamicin. ing.

In general, when an antibacterial drug is used, if its application amount is too small, it is not preferable because it promotes the development of drug-resistant bacteria. On the other hand, if the applied amount is too large, it tends to damage not only harmful substances such as bacteria to be eliminated but also tissues and cells of the affected area. Therefore, antimicrobial drugs should be included in the material for protecting the affected area in order to achieve a condition in which cells and tissues in the affected area are not seriously damaged, have sufficient infection-preventing effects, and prevent the development of resistant bacteria. It is necessary to pay attention to the quantity and its form. For example, Suzuki et al. Is a protective material for an affected area in which an antibacterial drug (antibiotic: gentamicin) is bonded to a base material (polyvinyl alcohol hydrogel), and the antibacterial drug is released to the affected area only at the time of bacterial infection. A material for protecting an affected area with a DDS (Drug Delivery System) has been proposed (J. Biomed. Mater. Res., Vol. 42, pp. 112-116 (1998)). According to the affected part protective material provided with such a DDS, the antibacterial drug is not released to the affected part when the bacterium or virus in question does not infect the affected part, and the tissue or cells in the affected part are damaged by the antibacterial drug. Deterring them Can be. However, even with the adoption of such a DDS, the above-mentioned problems can similarly arise if the amount of antibacterial drug released during bacterial infection is too high or too low.

On the other hand, in place of antibacterial drugs that have the above-mentioned problems (emergence of resistant bacteria and damage to affected tissues), there is no risk of developing drug-resistant bacteria and it is difficult to damage tissues and cells in affected areas. It has been considered to include a photocatalyst as a treatment agent in the affected part protective material. For example, Japanese Patent Application Laid-Open Nos. Hei 9-132295, Japanese Patent Publication No. 2000-0-136129 and Japanese Patent Publication No. 2000-23072 A bandage-type affected part protection material in which a photocatalytic substance such as titanium dioxide is held on a sheet-like base material is disclosed. By attaching such a photocatalyst-containing protective material to the affected area and irradiating the photocatalyst with light (typically ultraviolet light), free radicals such as various active oxygens and hydroxy radicals are generated around the photocatalyst. It can generate redox reactions that accompany it. (Hereinafter, these reactions that occur in the presence of photocatalysts irradiated with light are collectively referred to as "photocatalytic reactions.") Then, by such a photocatalytic reaction, bacteria and viruses existing in the affected area and harmful foreign substances (toxins, enzymes, nucleic acids, etc.) produced by them can be inactivated.

However, the conventional photocatalyst-containing diseased part protection material described in each of the above-mentioned publications is merely a material in which a powdery photocatalyst substance is typically held on a substrate made of a nonwoven fabric or the like. Therefore, when the photocatalyst contained in the affected part protective material is irradiated with light, harmful effects such as microorganisms and virus particles that are inactivated by the photocatalytic reaction (including sterilization, decomposition and detoxification; the same applies hereinafter). Substances (biohazardous substances) are limited to those that are attached to or close to the photocatalyst. Therefore, the efficiency of deactivating harmful substances for a fixed time and constant intensity of light irradiation depends on the amount of photocatalyst. However, there is a physical limit to the amount of photocatalyst that can be held on the sheet-like substrate constituting the affected part protective material. Disclosure of the invention

An object of the present invention is to provide an externally-used affected part protective material (affected part protective device) capable of efficiently and / or selectively inactivating a predetermined biological harmful substance existing in an affected part based on a photocatalytic reaction. To provide. Another object of the present invention is to provide a method for selectively inactivating, by photocatalysis, a predetermined biological harmful substance that may be present in an affected area, by applying such an externally applied affected area protective material to the affected area. It is to provide. Another object of the present invention is to provide a method for preventing the occurrence or proliferation of a predetermined biological harmful substance in the affected area by applying such an externally applied affected area protective material to the affected area. That is.

One external-use affected-part protecting material (affected-part protective device) provided by the present invention is a sheet that is attached to an affected part outside the body and has a size that can receive exudate from the affected part and foreign substances mixed in the exudate. A sheet provided with a porous layer forming a void, a surface of the sheet not facing the affected part of the porous layer, and Z or the inside of the void in the porous layer (that is, the sheet was applied to the affected part normally. In this case, a photocatalyst held in a state capable of receiving light is provided inside the sheet which does not directly contact the affected part.

In the present specification, the `` sheet '' relating to the above-mentioned externally affected part protective material refers to a base material constituting the affected part protective material and having a substantially flat shape applicable to an affected part outside the body. It is not limited to a specific size surface area or thickness, except. “Affected area” refers to the area where tissue has been changed or damaged due to infection or disease by a pathogen.

The term "foreign matter" refers to a substance (for example, a microorganism or virus) introduced from outside the body or a substance (for example, a toxin, inflammatory substance, or pyrogen produced by a microorganism or virus) generated in the body (including the affected surface). A substance that does not fit into body tissues. The term "biologically harmful substances" refers to biologically dangerous organisms such as viral bacteria, or substances such as toxins produced by those organisms. In this specification, the term “photocatalyst” or “photocatalytic substance” refers to a compound that causes a photocatalytic reaction when irradiated with light, or a complex containing the compound. Transition metal oxides and other semiconductors, such as titanium dioxide, are typical examples encompassed by the photocatalysts defined herein.

In the externally affected affected part protective material provided by the present invention, the photocatalyst and the surface of the affected part are isolated by the interposition of the porous layer (including a mesh-like material having a relatively large void size). This allows direct contact between the photocatalyst and the affected tissue Can be prevented. On the other hand, exudate present in the affected area and microscopic foreign substances (typically harmful substances such as harmful microorganisms, viruses, and their production substances) that can be mixed therein can enter the pores of the porous layer. . For this reason, when the external-part affected part protective material of this configuration is attached to the affected part and the photocatalyst is irradiated with light, the harmful substance can be efficiently removed while avoiding damage to the affected part due to the photocatalytic reaction. It can be inactivated by the reaction (hereinafter, the treatment of harmful substances based on the photocatalytic reaction is abbreviated as “photocatalytic treatment”).

Further, another one of the external affected part protecting materials provided by the present invention is a sheet to be attached to the affected part, a photocatalyst held in a state capable of receiving light on the sheet, and one or a kind that can be inactivated by a photocatalytic reaction. It is characterized in that one or more capturing substances having selective binding ability to two or more substances are provided. Typically, the trapping substance is located close to the photocatalyst.

In the externally applied diseased part protective material having the above-mentioned trapping substance, a specific kind or a substance which is desired to be inactivated by a selective binding ability of the trapping substance, that is, a function of selectively binding (adsorbing) a specific substance or a group of substances. Two or more substances (typically, harmful microorganisms, viruses, or high molecular compounds such as polypeptides and nucleic acids derived from them) can be selectively collected around the photocatalyst. For this reason, by attaching the protective material to the affected area and irradiating the protective material with light having a wavelength that can excite the photocatalyst (for example, ultraviolet rays are preferable when the photocatalyst is titanium dioxide or the like), Can be selectively and efficiently inactivated by a photocatalytic reaction.

Further, according to the externally affected part protecting material of this configuration, as a result of capturing the predetermined harmful substance to be subjected to the photocatalytic treatment by the above-mentioned capturing substance, exudate existing on the surface of the affected part and its surface region (blood exuding from the affected part tissue) Harmful substances from the body fluids such as lymph fluid and the contents thereof. Such elimination ability is advantageous when the harmful substance is a substance that can be an allergen.

A preferred externally affected part protecting material having the above configuration is characterized in that the above-mentioned trapping substance is bound to the above-mentioned photocatalyst. In the externally affected part protection material having such a configuration, the substance to be subjected to the photocatalyst treatment can be efficiently collected around the photocatalyst. Particularly preferably, the scavenger is bound to the photocatalyst via a suitable linker. Further, another preferable example of the externally affected part protecting material having the above-mentioned structure is that the sheet is provided with a porous layer having voids sized to receive exudate from the affected part and foreign substances mixed in the exudate, and a photocatalyst is provided. Is characterized by being disposed on the surface of the porous layer that does not face the affected part and / or inside the void of the porous layer.

In the external affected part protecting material having such a configuration, the photocatalyst and the affected part tissue can be prevented from directly contacting each other due to the interposition of the porous layer. Therefore, it is possible to both prevent the affected tissue from being damaged by the photocatalytic reaction and selectively perform the photocatalytic treatment of a predetermined harmful substance. Such a porous layer can be produced, for example, from a synthetic fiber nonwoven fabric.

Further, a further preferable externally affected part protective material taught in the present specification is characterized in that the sheet is provided with a moisture permeation control layer for controlling water evaporation from the affected part surface. In the externally affected affected part protective material having such a configuration, the moisture permeation controlling layer (which is made of a material having a high water retention ability and capable of limiting the amount of moisture evaporating from the outer surface of the layer) is interposed. The evaporation of water from the soil is moderately controlled. This can prevent the affected area from drying out (typically exudate present on the surface of the affected area) and promote healing of the affected area. A moisture permeation controlling layer characterized by having a water permeability of 0.1 to 2.0 mg Zhr · cm ² at room temperature, atmospheric pressure and a relative humidity of 60% is particularly preferred.

One protective material that is preferable as an externally affected affected area protective material having such a moisture permeation controlling layer is a surface or the vicinity of the surface of the moisture permeation controlling layer facing the affected area when the photocatalyst is attached to the affected area ( That is, when the seat is attached to the diseased part, it refers to the surface on the side facing the diseased part or its vicinity.) Or a position closer to the diseased part than the surface. By arranging the photocatalyst at such a position, various active oxygens and free radicals can be efficiently generated from the water around the photocatalyst. Therefore, the photocatalytic treatment can be performed more effectively.

Another protective material which is particularly preferable as a protective material for an externally affected area having a moisture permeation controlling layer is further characterized by further comprising a matrix layer in which pores through which fibroblasts existing in the affected area can enter are formed. By providing such a matrix layer, healing of the affected part can be promoted. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is an explanatory view schematically showing a state of binding between a photocatalyst and a capturing substance via a linker.

FIG. 2 is a side view schematically showing an example of an external-use affected part protective material provided with a sheet (substrate) having a moisture permeation controlling layer.

FIG. 3 is a side view schematically showing an example of an externally applied diseased part protection material provided with a sheet (base material) having a moisture permeation control layer and a porous layer.

FIG. 4 is a side view schematically showing an example of an external-use affected-part protecting material provided with a sheet (substrate) having a matrix layer. BEST MODE FOR CARRYING OUT THE INVENTION

A preferred embodiment of the present invention will be described with reference to the drawings. It should be noted that technical matters other than those specifically mentioned in the present specification and necessary for implementing the present invention can be grasped as design matters of those skilled in the art based on the conventional technology. The present invention can be carried out based on the technical contents disclosed in the present specification, Z, and drawings and by appropriately referring to common general technical knowledge in the relevant field.

The material for protecting an externally applied diseased part of the present invention is a therapeutic material that can be widely applied to wound surfaces caused by abrasions, burns and the like, and lesions such as athlete's foot. Therefore, as long as the selective photocatalytic treatment 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-use affected-part protective material of the present invention includes a high photocatalytic activity capable of efficiently generating active oxygen, free radicals, and the like from the water present in the surroundings when irradiated with light (typically, ultraviolet light). It is preferable that the compound itself has no adverse effect on the affected tissue and cells, for example, a compound having no toxicity and low irritating property to skin tissue. Such substances include inorganic substances such as titanium dioxide and zinc oxide. Suitable photocatalytic materials include metal oxides such as titanium dioxide (titania), zinc oxide, iron oxide, tungsten oxide, bismuth oxide, nickel oxide, and the like. In particular, it has high photocatalytic activity and is used in cosmetics, pharmaceuticals, etc. Titanium oxide / zinc oxide is preferred.

The photocatalyst to be used may be a high-purity purified metal oxide having photocatalytic activity (preferably, a substance consisting essentially of the oxide except for unavoidable impurities), or It may contain other substances to such an extent that the photocatalytic activity 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, 5 wt% or less of the total amount of the material added to the external-use affected-part protective material as a photocatalyst. l to 5 wt%). By the addition of 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 another inorganic substance. For example, a composite of an inorganic substance such as silica, apatite, or zeolite and a metal oxide having photocatalytic activity such as titanium dioxide (for example, Japanese Patent Application Laid-Open Nos. Can be used as a photocatalyst according to the present invention. Preferred as such a composite is a metal oxide particle having photocatalytic activity such as titania coated on a porous ceramic film which is inactive as a photocatalyst (see Japanese Patent Application Laid-Open No. 91-276706). Is fisted. According to such coated metal oxide particles, although it is not particularly limited because it depends on the material, a sheet (for example, a sheet made of polyurethane resin) described later can be protected from decomposition and deterioration due to a photocatalytic reaction. . Therefore, the external affected part protecting material containing such a photocatalyst (composite of the above-mentioned inorganic substance and a metal oxide having photocatalytic activity) is suitable for use in which the material is allowed to adhere to the affected part for a relatively long time.

A typical example of the shape of the photocatalyst used for constructing the external affected part protecting material of the present invention is a powder. Particularly, a fine powder having an average particle diameter of 10 m or less (more preferably, 1 μπι or less) is preferable. Such a finely divided photocatalyst can be uniformly held on the surface of a sheet described later. Alternatively, a photocatalyst formed in the form of a sheet or a film may be used in place of the photocatalyst in the form of powder (fine particles). For example, an externally-applied diseased part protection material in which a photocatalyst layer is formed by applying a paste containing a photocatalyst such as titanium dioxide to the surface of a sheet of a material as described later is also preferable as an embodiment of the present invention. Next, the trapping substance that can be included in the externally-applied diseased part protection material of the present invention will be described. The main purpose of the trapping substance according to the present invention is to selectively collect harmful substances to be photocatalyzed on or near the surface of a substance having photocatalytic activity (typically, a metal oxide such as titanium dioxide). Substance. Examples of the capture substance suitable for such a purpose include an antibody (immunoglobulin such as IgG) having high binding specificity to a specific antigen or various fragments (Fab or the like) obtained by treating the antibody with an enzyme or the like. ). For example, polyclonal antibodies and their derivatives contained in antiserum that recognize bacterial structures (cell walls, capsules, etc.) and products (eg, proteins such as toxins and enzymes) as antigens can be used as capture substances. It does not greatly affect substances (neutrophils, macrophages, etc.) derived from diseased tissues, and specifically binds to foreign substances (bacteria itself or substances derived from bacteria, for example, toxin proteins) that are targets for photocatalytic treatment. Such target substances can be concentrated on the surface of the photocatalyst or in the vicinity thereof. When an antibody is used as the capture substance, there is no particular limitation on the type and kind of the antibody to be used, and what kind and how many kinds are used is determined according to the use. For example, if the target for photocatalytic treatment is specific bacteria and viruses such as MRSA (methicillin-resistant Staphylococcus aureus) and HIV (human immunodeficiency virus), the target is high only for those specific bacteria and viruses. Monoclonal antibodies having binding specificity can be used. On the other hand, for the purpose of general infection prevention until the wound surface is healed, globulin fraction of antiserum that can bind gram-positive bacteria, gram-negative bacteria, etc. widely, polyclonal antibody, etc. It is preferable to use as a capturing substance. By using various kinds of antibodies (or fragments thereof) with different antigens, the range of harmful substances targeted for photocatalytic treatment can be expanded. For example, several kinds of pathogenic microorganisms and virus particles can be used as antigens to immunize (sensitize) egrets, etc., and the antibody group in the antiserum produced and collected can be used without particular classification.

Further, the capture substance that can be used in the externally-applied disease-part protecting material of the present invention is not limited to an antibody. For example, a target cell tissue (receptor) of a virus (such as HIV) that invades a specific cell / tissue or an analog thereof may be used as the capture substance, as long as it does not significantly affect the affected tissue or the physiological condition of the patient. Alternatively, even if the enzyme uses substrate specificity, Good.

In the present invention, these trapping substances are arranged near the photocatalytic substance (typically, the above-mentioned metal oxide). Preferably, it is attached to the surface of the photocatalytic substance itself. There is no particular limitation on such binding means, and it is possible to adopt a general method of binding proteins such as antibody molecules to the surface of an inorganic substance such as metal or ceramic, which is often used in the field of immunochemistry and the like. it can.

Typically, as schematically shown in FIG. 1, a photocatalyst 1 (typically a metal oxide such as titanium dioxide) and a trapping substance 3 (eg, an antibody) are applied via a suitable linker (binder) 2. Or a fragment thereof). Various coupling agents can be used for this purpose. For example, using a suitable silane coupling agent having an amino group such as p-aminophenyltrimethoxysilane, 3-aminopropyltrimethoxysilane, N-2-aminoethyl-3-aminopropylbiltrimethoxysilane, the surface of the photocatalyst 1 is cleaned. At the same time as silanization, an amino group is introduced, and a linker 12 such as dartaldehyde is bonded to the amino group. Next, a capture substance (protein) 3 such as an antibody molecule may be bound to a terminal functional group (such as an aldehyde group) of the linker 1-2.

Next, the sheet constituting the externally affected part protection material will be described. The sheet used for the externally affected part protection material of the present invention includes a function of covering and protecting the affected part when it is addressed to the affected part, and a function of holding the photocatalyst in a state where the photocatalyst treatment can be performed on the affected part. The material is not particularly limited as long as it can transmit light (typically, ultraviolet light) from the outside. However, it is desirable to be harmless or less irritating to the human body because of direct contact with the affected area.

The material constituting the sheet and the configuration thereof differ depending on the use of the externally affected part protecting material of the present invention. For example, when the externally-applied affected-part protecting material of the present invention is used for protecting the affected part in a similar manner as a conventional bandage for a relatively short period of time, the material of the sheet may be a natural fiber such as cotton or hemp. . Further, synthetic fibers such as polyester-based, polyamide (nylon) -based, and atarinole-based synthetic fibers may be used. Typically, a woven, nonwoven or knitted fabric prepared from these natural or synthetic fibers has a mesh shape having voids of a size that can receive exudate from the affected area and foreign substances mixed in the exudate. Composed of sheets can do. Such a mesh-shaped portion corresponds to the porous layer in the external-use affected-part protective material of the present invention. A nonwoven fabric made of synthetic fibers is particularly preferable as a material constituting the mesh sheet. There is no particular limitation on means for holding a photocatalytic substance (typically, a metal oxide such as titanium dioxide) in such a nonwoven fabric. For example, a photocatalyst (typically, a metal oxide powder such as titanium dioxide and zinc oxide) can be attached to the surface of the nonwoven fabric by a method such as coating, dipping, spraying, or sputtering. Next, the photocatalyst can be fixed to the surface of the nonwoven fabric by heating the nonwoven fabric to about 100 to 500 ° C.

In such a bandage-type externally affected part protection material, an outer sheet for attaching the externally affected part protection material to the affected part 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. At least a part of the outer sheet facing the affected part can be coated with an adhesive for sticking and fixing the external-use affected part protecting material to the affected part.

In addition, the bandage-type externally affected part protecting material is a mesh sheet (sheet base material forming a porous layer) in which a moisture permeation controlling layer is laminated on one side (that is, an outer surface which does not face the affected part when used). Is preferred. As such a moisture permeation control layer, a layer having a relatively high water retention capacity (water retention capacity) and capable of appropriately controlling water evaporation from an affected part is preferable. The water permeability (water vapor permeability: defined by the amount of water vapor that passes through a sample such as a sheet having a unit area per unit time under predetermined temperature and humidity conditions) can be measured by various methods. . For example, Japanese Industrial Standards (JIS) K 7129 (1992) specifies the Α method (moisture sensor method) and the B method (infrared sensor method). Method A involves exposing one side of the sample to water vapor saturation and setting the other side to a predetermined relative humidity (eg, 60%). Then, a change in humidity caused by water vapor that has passed through the sample is detected by a humidity sensor that has been installed on a predetermined relative humidity side in advance, and the water vapor permeability is calculated based on the data. For example, the water permeability (water vapor permeability) of the sheet can be evaluated using the water vapor permeability tester (2) based on the above method A.

For example, at room temperature, atmospheric pressure and relative humidity of 60%, the water permeability is approximately 0.1. O 2 / O mg / hr · cm ² (for example, based on JISK71129), and the water permeability under such conditions is equivalent to that of healthy human skin 0.9 to 1.7 mg. / hr · cm ² is particularly preferred. Examples of the material of the moisture permeation control layer that can realize such moisture permeability include silicone, polyurethane, polyacrylate ester, polymethacrylate ester, porous polytetrafluoroethylene (PTFE), polybutyl alcohol, polyacrylamide, and the like. Polysaccharides (eg, chitin, chitosan, cellulose, agarose or derivatives thereof) and the like. Further, those having light transmittance are suitable. A water permeation control layer substantially composed of a silicone which can easily form a thin film-shaped water permeation control layer having high light transmittance and a polysaccharide having high biocompatibility is particularly preferable.

On the other hand, when the external-use affected-part protective material of the present invention is used for a relatively long-term protection of an affected part in which skin tissue is extensively damaged by a burn or the like (ie, when the external-use affected-part protective material is used as so-called artificial skin). Preferably, the sheet is provided with the above-mentioned moisture permeation control layer and a matrix layer formed on the diseased part attachment side of the water permeation control layer. The matrix layer can generally be formed from fibrous collagen and / or denatured collagen. Matrix substantially composed of such collagen or denatured collagen (gelatin) forms a porous layer having pores for receiving fibroblasts that contribute to the regeneration of dermis-like connective tissue. Therefore, such a matrix layer corresponds to the porous layer in the externally affected disease protecting material of the present invention.

Next, with reference to the drawings, some preferred embodiments of the external-use affected-part protecting material of the present invention and a method for producing the same will be exemplified. FIG. 2 shows one form of the externally applied affected part protective material 10 which is preferable for protecting small wounds and light burns. The sheet 11 of the externally applied affected part protection material 10 in this form is a light-transmittable filter sheet (typically made of polyolefin) 12 for attaching the present protection material 10 to the affected part S, and its outer sheet. 12 and a moisture permeation controlling layer 14 formed of a silicone resin or the like fixed to one surface. An adhesive (not shown) for applying and fixing the protective material 10 to the affected area S is applied around the moisture permeation control layer of the outer sheet 12. The outer sheet 12 is provided with a large number of holes and slits for securing good air permeability and light transmission when affixed to the affected area S (see FIG. Zu). On the other hand, as shown in FIG. 2, a powdery photocatalyst 16 combined with a trapping substance 18 is carried on the surface of the moisture permeation control layer 14 facing the affected area S.

The external affected part protecting material 10 of such a form can be typically manufactured as follows. That is, a silicone film forming solution (for example, a hexane solution of 50% Silastic silicone adhesive type A (a product of Dow Corning)) is applied to one side of the outer sheet 12 of a predetermined size on which the adhesive is applied. I do. On the other hand, the photocatalyst powder 16 is filled in the surface and inside the voids of a synthetic resin mesh sheet (not shown) having high heat resistance such as PTFE. Then, the mesh sheet is placed on the surface of the portion where the solution for forming a silicone film is applied. Next, the coating film is dried under an appropriate temperature condition (preferably 50 to 80 ° C.) with the mesh sheet placed thereon. After that, the mesh sheet is removed and dried for a predetermined time (for example, 100 to 120. C for 1 to 2 hours).

As a result, a moisture permeation control layer 14 is formed on one surface of the outer sheet 12, and a photocatalyst 16 is held on the side of the water permeation control layer 14 opposite to the affected part. Can be created. Next, by performing the binding substance binding treatment via a linker as described above (see the example described later), the binding substance (antibody) is trapped on the surface of the photocatalyst 16 or the surface of the moisture permeation control layer 14 facing the affected part. Molecule or a fragment thereof such as Fab, etc.) 18 can be bound.

According to the externally affected part protection material 10 in the state as shown in FIG. 2, the affected part S can be protected while maintaining the surface of the affected part S in an appropriate amount of water. Then, under the condition that an appropriate amount of water is held, natural light or light of a predetermined wavelength (for example, ultraviolet light having a wavelength of about 400 nm when the photocatalyst is titanium dioxide) is applied to the external affected part protecting material 10 from the outside. Then, various active oxygen and free radicals are generated by the presence of the photocatalyst 16, and harmful substances collected (retained) on or near the surface of the photocatalyst 16 by the trapping substance 18 (not shown) ) Can be selectively and efficiently treated with a photocatalyst.

Another preferred embodiment of the external affected part protecting material of the present invention will be described based on FIG. The sheet 21 of the externally affected part protection material 20 of this embodiment includes an outer sheet 22 that can transmit light similar to that shown in FIG. 2 and a moisture permeation control layer 24 fixed to the surface of the outer sheet 22. And Furthermore, the moisture permeation control layer 24 faces the affected area. On the surface side, a mesh layer (porous layer) 25 preferably made of a non-woven fabric made of polyolefin such as polyethylene or nylon is provided.

As shown in FIG. 3, in the external affected part protecting material 20, in the powdery photocatalyst 26 combined with the trapping substance 28, the powdery photocatalyst 26 is outside the mesh layer 25 (the side not facing the affected part) and / or The mesh layer 25 is not substantially exposed on the side facing the affected part of the mesh layer 25.

The external affected part protecting material 20 having such a form can be typically manufactured as follows'. That is, the water permeation control layer 24 is formed on one surface of the outer sheet 22 by the same method as that for the external affected part protection material 10 shown in FIG. Obtain a protective material for the externally affected area holding the photocatalyst 26 (see Fig. 2). Next, a mesh pad (equivalent to the mesh layer 25) made of a non-woven fabric made of polyolefin is provided on the surface of the moisture permeation controlling layer 24 facing the affected part by chemical means such as an adhesive or physical means such as heat treatment. And fix it. As a result, a mesh layer (porous layer) 25 is laminated on the surface of the moisture permeation controlling layer 24 facing the affected part, and the external affected part protecting material 20 comprising the photocatalyst 26 held inside the void of the porous layer. Can be created.

Next, by performing the binding substance binding treatment via the linker as described above, the binding substance 28 can be bound to the surface of the photocatalyst 26 or the affected area facing surface of the moisture permeation control layer 24. .

According to the external affected part protecting material 20 of the form shown in FIG. 3, the same photocatalytic treatment as that of the external affected part protecting material 10 shown in FIG. 2 described above can be performed, and the photocatalyst 26 is provided on the surface of the affected part. Direct contact can be prevented. Therefore, it is possible to prevent the affected tissue from being damaged by the active oxygen-free radical generated by the photocatalytic reaction. On the other hand, harmful substances (bacteria, viruses, etc.) mixed in the exudate on the surface of the affected part can enter into the voids of the mesh layer 25 together with the exudate, so that they are trapped by the trapping substance 28 and the photocatalyst 26 Collected around (held). Thus, in the external affected part protective material 20 of the present embodiment, harmful substances to be treated can be selectively and efficiently subjected to photocatalytic treatment by a photocatalytic reaction.

Next, another preferred embodiment of the external-use affected-part protecting material of the present invention will be described with reference to FIG. I will tell. The externally applied affected part protecting 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 where skin tissue such as a severe burn is lost in a relatively wide area and preventing infection. The external affected part protective material 30.

The sheet 31 of this type of externally affected part protective material (artificial skin) 30 is composed of a moisture permeation control layer 34 corresponding to the epidermis and a matrix layer 33 having pores into which fibroblasts and the like enter. ing.

As shown in FIG. 4, in the external affected part protecting material 30, the powdery photocatalyst 36 combined with the trapping substance 38 is disposed on the surface of the moisture permeation controlling layer 34 facing the affected part, and the matrix The layer 33 is not substantially exposed on the side facing the affected area.

The externally affected affected part protective material (artificial skin) 30 in such a form can be typically manufactured as follows. That is, the photocatalyst 36 is held on the surface of a sheet material (typically, a sheet made of silicone or polysaccharide) whose moisture permeation can be adjusted by the same method as that of the externally applied diseased part protection material 10 in FIG. 2 described above. . Next, the capturing substance binding treatment is performed via the linker as described above, so that the capturing substance 38 is bonded to the surface of the photocatalyst 36 or the affected area facing surface of the moisture permeation controlling layer 34.

Meanwhile, a porous matrix mainly composed of collagen is prepared. That is, an acidic collagen solution (preferably a fibrillated atelocollagen solution is preferred from the viewpoint of suppressing the expression of antigenicity and forming a crosslinked structure easily), and sufficiently homogenizing this solution. Next, a porous collagen sponge can be obtained by freeze-drying the homogenized solution. Then, the collagen which is a component of the sponge is crosslinked. The crosslinking method is not particularly limited, and a conventionally known crosslinking agent and crosslinking method can be used. For example, collagen sponge is added to a solution containing an aldehyde-based crosslinking agent such as glutaraldehyde, a carbodiimide-based crosslinking agent such as carpoimide, or an isocyanate-based crosslinking agent such as hexamethylene diisocyanate as a chemical crosslinking agent. The sponge can be cross-linked by immersing the sponge for a predetermined time. Alternatively, a thermal dehydration crosslinking treatment (for example, heating the collagen sponge to about 110 ° C. under a vacuum condition) may be performed.

Then, the obtained cross-linked collagen sponge 33 and the sheet material 34 for controlling moisture permeation are bonded together with an adhesive having high biocompatibility, so that the The affected part protective material (artificial skin) 30 can be obtained.

According to the externally affected part protecting material (artificial skin) 30 having such a form, the same photocatalytic treatment as the externally affected part protecting materials 10 and 20 shown in FIGS. 2 and 3 described above can be performed. The photocatalyst 36 can be prevented from directly touching the surface of the photocatalyst. Therefore, it is possible to prevent the affected tissue from being damaged by 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 part surface can enter into the space of the matrix layer 33 together with the exudate, and are trapped by the trapping substance 38 to form the photocatalyst 36. Collected around (held). Thus, the external-use affected-part protecting material 30 of the present embodiment can selectively and efficiently perform photocatalytic treatment of harmful substances to be treated by photocatalytic reaction. Then, a new skin tissue can be formed on the affected surface at an early stage by the fibroblasts and the like that have entered the matrix layer.

The preferred embodiment of the externally affected part protecting material of the present invention has been described above with reference to the drawings. The externally affected part protecting material in the form schematically shown in each drawing is used in implementing the present invention. This is merely an example, and is not intended to limit the externally-applied affected-part protective material of the present invention to those forms.

For example, light capable of emitting light having a wavelength (ultraviolet light) capable of causing a photocatalytic reaction is generated in at least one of the above-described sheet, that is, at least one of the outer sheet, the moisture permeation control layer, the mesh layer, and the matrix layer. It may be provided with a release substance. For example, fine powder of spontaneous or phosphorescent luminescent ceramics (e.g., strontium carbonate, eutrophium, dysprosium, etc., containing strontium carbonate, dysprosium, etc.) capable of emitting ultraviolet light of a suitable wavelength is used as a photocatalyst. It is dispersed in a part of the sheet (for example, on the surface of the outer sheet or inside the moisture permeation control layer) in a state where it can be reached. As a result, a photocatalytic reaction can occur even when there is no external light irradiation.

In addition, the sheet constituting the externally affected part protection material of the present invention may include a part (layer) other than the outer sheet, the moisture permeation control layer, the mesh layer, and the matrix layer described above. For example, an anti-reflective coating that allows external light to pass through but prevents light reflected from the affected part or part of the protective material for external use from escaping from the affected part protective material (Layer). The present invention will be described in more detail with reference to examples described below, but it is not intended to limit the present invention to those shown in the examples.

A sheet provided with a silicone film as a moisture permeation controlling layer, a titanium dioxide as a photocatalyst, and an externally-used affected part protective material provided with an immunoglobulin as a trapping substance were produced as follows.

That is, a fine powder of titanium dioxide (ST-1J, a product of Ishihara Techno Co., Ltd.) was applied to a PTFE mesh sheet (opening 50 m) and uniformly filled between the meshes. A hexane solution of 50% Silastic Silicone Adhesive Type A (Dow Corning) is applied on the surface of the PTFE sheet using a precision coating tool, and a 50-thick silicone film (uncured state) is applied. Before the silicone hardened, the mesh sheet filled with the titanium dioxide was placed on the silicone membrane and dried at 60 ° C for 1 hour in the open state. Processing was performed.

Thereafter, the mesh sheet was removed, the temperature was further raised to 110 ° 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 saline. Through the above process, a sheet was prepared in which a PTFE sheet was used as the outer sheet and a silicone film (corresponding to a moisture permeation control layer) was formed on one side, and titanium dioxide could be retained on the surface of the silicone film. . Next, a globulin fraction (IgG-rich fraction) obtained by purifying the rabbit's antiserum, which had been previously immunized with crushed cells of gram-negative bacteria (Escherichia coli) and gram-positive bacteria (Staphylococcus aureus). ) Was used to bind the antibody to the titanium dioxide particles held on the silicone membrane.

That is, a hydroxyl group was introduced into titanium dioxide by immersing the silicone film holding titanium dioxide in dilute nitric acid and then washing it. After that, the surface of the titanium dioxide particles is silanized by immersing the silicone film holding titanium dioxide in a toluene solution containing 3-aminobutyryltriethoxysilane. In both cases, an amino group was introduced. Next, the silicone film was immersed in an aqueous solution containing glutaraldehyde, and dartal aldehyde (the linker according to the present example) was bonded to the amino group on the surface of the silanized titanium dioxide. As a result, a terminal aldehyde functional group was introduced to the titanium dioxide surface via a linker. Thereafter, the silicone film was washed with an aqueous solution of sodium chloride to remove excess daltaldehyde.

Next, the silicone membrane was immersed in a phosphate buffer containing the glopurin fraction to bind immunoglobulin (such as IgG) to the aldehyde functional group. Through this series of operations, the external-use affected-part protecting material according to the present embodiment, in which titanium dioxide (photocatalyst) and immunoglobulin (capturing substance) are held on the surface of the silicone membrane (water permeation controlling layer) facing the affected part, is used. Produced.

A sheet provided with agarose gel as a moisture permeation control layer, a titanium dioxide dioxide as a photocatalyst, and an externally applied diseased part protective material provided with imnoglopurin as a capturing substance were produced as follows.

That is, agarose powder was added to boiling water to prepare a 10% concentration agarose solution. This solution was applied on a PTFE sheet to a thickness of 50 m. Next, finely divided titanium dioxide ("ST-1" above) was thinly sprayed on the agarose coating film. Thereafter, aging was performed at room temperature (about 20 ° C.) for 12 hours, and titanium dioxide was adhered to and retained on the agarose gel surface. Through the above process, the PTFE sheet is used as the outer sheet, and a sheet having a gelled agarose film (corresponding to a moisture permeation control layer) formed on one surface thereof is prepared, and titanium dioxide is retained on the surface of the film-like agarose gel. I was able to.

Next, the same treatment as in Example 1 was performed to bind imnoglobulin to the surface of the titanium dioxide via darthal aldehyde. Through this series of operations, the external-part affected part protecting material according to the present example, in which titanium dioxide (photocatalyst) and immunoglobulin (trapping substance) are held on the side of the affected part of the membrane-shaped agarose gel (water permeation controlling layer) facing the affected part, is produced. did. <Example 3: Preparation of protective material for external affected area (3)>

An externally-used affected part protective material comprising a sheet having a moisture permeation controlling layer composed of a silicone membrane and a porous layer composed of an amorphous silicon fiber membrane, titanium dioxide as a photocatalyst, and imnoglobulin as a trapping substance is as follows. It was produced as described above.

That is, 100 g of high-purity amorphous silica fiber (manufactured by Shuller) having excellent flexibility, biocompatibility, and light transmittance was dispersed in 10 L of dilute hydrochloric acid (ρΗ1-2). 3 g of boron nitride (a product of Denki Kagaku Kogyo KK) was added to the dispersion, and the pH of the dispersion was adjusted to 5 to 7 using ammonia. Next, the dispersion was subjected to a commercially available paper strainer to form a fiber membrane having a thickness of about 40 m. The obtained film was fired at about 135 ° C. to produce an inorganic fiber film.

Next, a slurry containing finely divided titanium dioxide (ST-K01

J) was immersed in a portion of the obtained inorganic fiber membrane except for one surface (the surface facing the affected part). Thereafter, a heat drying treatment was performed at 80 ° C. for 1 hour. Subsequently, heat treatment was performed at 500 ° C. for 1 hour to obtain an inorganic fiber membrane supporting powdered titanium dioxide.

On the other hand, the same processing as in Example 1 was performed to form a silicone film on one surface of the PTFE sheet. Thus, before the silicone was cured, the titanium dioxide-holding inorganic fiber membrane obtained above was placed on the silicone membrane, and dried in an oven at 60 ° C. for 1 hour or more. Thereafter, the temperature was further increased to 110 ° C., and the heat treatment was continued at that temperature for 2 hours. Then, it cooled to room temperature. By the above processing, a sheet in which a PTFE sheet is used as an outer sheet, and a silicone film (corresponding to a moisture permeation control layer) and an inorganic fiber film (corresponding to a porous layer) are laminated and formed on one surface thereof is prepared. Titanium dioxide could be retained in the voids of the fiber membrane.

Next, the same treatment as in Example 1 was performed to bind imnoglobulin to the surface of the titanium dioxide via darthal aldehyde. Through this series of operations, titanium dioxide (photocatalyst) and immunoglobulin (capture substance) are placed on the side of the silicone membrane (water permeation control layer) facing the affected part, that is, inside the voids of the inorganic fiber membrane (porous layer). The retained affected external part protection material according to the present example was produced. <Example 4: Preparation of protective material for external affected area (4)>

An externally applied diseased part protecting material comprising a sheet having a moisture permeation controlling layer composed of a silicone membrane and a porous layer composed of an organic fiber membrane, titanium dioxide as a photocatalyst, and immoglobulin as a trapping substance is as follows. Produced.

In other words, an organic fiber membrane consisting of a nylon mesh with excellent biocompatibility and light transmittance was spray-coated with a silicon-based coating agent (Nippon Soda Co., Ltd., product name: PISTRATER LNSC-200A). Next, a heat treatment was performed at 90 ° C. for 30 minutes, and the coating was cured to form a thin silicon intermediate layer on the Ni-nit fiber film.

Next, a titanium dioxide coating agent (product name: Vis Reiter-I L NSC-200C) was spray-coated on the silicon intermediate layer. Thereafter, a 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 treatment as in Example 1 was performed to form a silicone film on one surface of the PTFE sheet. Thus, before the silicone was cured, the obtained titanium dioxide-containing organic fiber membrane was placed on the silicone membrane. At this time, the substrate was placed so that the titanium dioxide holding surface of the organic fiber film and the silicone film on the PTFE sheet faced each other. The sheet was dried at 60 ° C for 1 hour or more while the sheet was open. Thereafter, the temperature was further raised to 110 ° C., and the heat treatment was continued at that temperature for 2 hours. Then, it cooled to room temperature. By the above processing, a PTFE sheet is formed into a single sheet, and a sheet in which a silicone film (corresponding to a moisture permeation control layer) and an organic fiber film (corresponding to a porous layer) are laminated and formed on one side is prepared. Titanium dioxide could be retained on the side of the organic fiber membrane (porous layer) not facing the affected part. Then, the same treatment as in Example 1 was performed to bind immoglobulin to the surface of titanium dioxide via darthal aldehyde. Through this series of operations, titanium dioxide (photocatalyst) and immunoglobulin (photocatalyst) are placed on the side of the silicone membrane (water permeation control layer) that faces the affected part and the side that does not face the affected part of the organic fiber membrane (porous layer). The externally affected part protecting material according to the present example, which retained the trapping substance), was produced. Example 5: Antibacterial test (1)>

The following antibacterial tests were performed using the externally affected part protective materials obtained in Examples 1 to 4 described above.

That is, a plain 'heart' infusion (BHI) agar medium sterilized in an autoclave is dispensed into a sterilized plate (dish) having a diameter of 10 mm and left at room temperature for 1 hour to remove the medium in the plate. Hardened. Then, a part of each colony of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, which had been separately cultured on BHI agar medium for several days, was collected and separately added to sterile physiological saline and sterilized. The inoculum was prepared for each of the above three types of bacteria by serially diluting them with physiological saline. Then, inoculation bacteria count of each bacteria was dropped each inoculation bacterial suspension each BHI agar medium containing plate at 1 per plate respectively 1 0 ^4, was applied to the entire surface of the medium have use a Conradi rod.

Next, fragments each having a size of 5 mm × 5 mm were prepared from the externally affected part protecting material obtained in each of the above Examples, and placed on the surface of the culture medium of the plate coated with the bacterial solution. Then, the cells were cultured at 37 ° C for 18 hours while simulating sunlight with a solar simulator.

As a result, in the bacterial solution-coated plate on which the external protective material for the affected area was not placed as a control, the growth of the bacteria was observed on the entire surface of the agar medium. In each of the plates, a blocking circle having a shape corresponding to the externally affected area protection material fragment was formed. This means that the external-use affected part protective materials obtained in Examples 1 to 4 can effectively light-treat (inactivate) harmful substances such as bacteria and their products (toxins, etc.) by photocatalytic reaction. It shows.

On the bottom surface of a 100-mm sterile plate (dish), an externally affected disease-protecting material whose size was adjusted to the same shape was placed. E. coli was used, the concentration aeruginosa及Pi Staphylococcus sphere bacteria were each adjusted to 1 0 ⁴ Roh m 1 in Example 5. Each of the bacterial preparations was dropped 100 μm at a time onto the protective material for the externally affected area, and applied to the entire surface of the protective material using a conical rod. Next, the solar cell simulator was used to irradiate the pseudo-sunlight to the external affected part protecting material for one hour. After that, a mixture of Brain 'Heart Infusion (BHI) liquid medium and soft agar was dispensed to a thickness of 1 mm on the external affected area protective material, and the mixture was poured at 37 ° C for 24 hours. Cultured for hours.

As a result, colonies of each of the above-mentioned bacteria were confirmed in the soft agar in the case where the same treatment was performed without simulating sunlight as a control. On the other hand, in the case of the present example irradiated with pseudo-sunlight, the coagulation of any of the above-mentioned bacteria was not confirmed in the soft agar.

As is evident from the above examples, according to the protective material for externally affected area disclosed in the present specification, the inactivated tissues and cells of the affected area can be inactivated without causing serious damage due to the photocatalytic reaction. The target substance can be selectively and efficiently or efficiently subjected to photocatalytic treatment. The specific examples of the present invention have been described above in detail, but these are only examples and do not limit the scope of the claims of the present invention. The technology described in the claims includes various modifications and alterations of the specific examples illustrated above.

Further, the technical elements described in the present specification or the drawings exhibit technical utility singly or in various combinations, and are not limited to the combinations described in the claims at the time of filing. Further, the technology exemplified in the present specification or the drawings achieves a plurality of objects at the same time, and has technical utility by achieving one of the objects.

Claims

The scope of the claims

1. a sheet to be attached to an affected area outside the body, the sheet provided with a porous layer forming a void having a size capable of receiving exudate from the affected area and foreign substances mixed in the exudate;

A photocatalyst held in a state in which light can be received in the surface of the sheet not facing the affected part of the porous layer and / or in the void of the porous layer;

An external-use affected-part protective material having:

2. A seat that is attached to the affected area outside the body,

A photocatalyst held in a state capable of receiving light on the sheet,

One or more capturing substances having a selective binding ability to one or more substances that can be inactivated by a photocatalytic reaction, the capturing substances being disposed in proximity to the photocatalyst;

An external-use affected-part protective material having:

3. The external affected part protecting material according to claim 2, wherein the trapping substance is bonded to the photocatalyst.

4. The external affected part protecting material according to claim 3, wherein the trapping substance is bonded to the photocatalyst via a linker.

5. 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,

3. The external affected part protecting material according to claim 2, wherein the photocatalyst is disposed on a surface of the porous layer that does not face the affected part and / or inside a void of the porous layer.

6. The external affected part protecting material according to claim 1, wherein the porous layer is formed of a nonwoven fabric of synthetic fibers.

7. The externally applied diseased part protection material according to any one of claims 1 to 5, wherein the sheet includes a moisture permeation control layer that controls evaporation of water from the affected part surface.

8. The moisture permeability of the moisture permeation controlling layer is 0.1 to 2.0 mg / hr-cm ² under the conditions of room temperature, atmospheric pressure, and 60% relative humidity. Protective material for externally affected areas described in.

9. The external affected part protecting material according to claim 7, wherein the moisture permeation controlling layer is substantially composed of light-transmitting silicone or polysaccharide.

10. The photocatalyst is mainly disposed on the surface of the moisture permeation control layer facing the diseased part when the sheet is mounted on the diseased part, in the vicinity thereof, or at a position closer to the diseased part than the surface. The external-use affected-part protecting material according to claim 7, which is provided.

11. The outline affected part protecting material according to claim 10, further comprising a light transmissible outer sheet, wherein the moisture permeation controlling layer is fixed to the outer sheet.

12. The externally affected part protecting material according to claim 7, further comprising a matrix layer in which pores capable of entering fibroblasts present in the affected part are formed.

13. The affected external part protection material according to claim 12, wherein the matrix layer is substantially composed of collagen or denatured collagen.