JP5677763B2 - Pressure ulcer treatment external liquid and pressure ulcer treatment device - Google Patents

Description

  The present invention relates to a technique for an external pressure remedy for treating pressure ulcer and a pressure ulcer treatment apparatus for supplying bath water for pressure ulcer treatment including the same.

  Pressure sores are the continuous compression / extension / shear stress in the same posture on the human body or livestock / competent animals in the same posture by external force including the bed for the physiological skin and soft tissue around the bone-like protuberance. As a result of this, the blood microcirculation in the tissue becomes defective and tissue necrosis is caused. This refers to a tissue defect or skin ulcer caused thereby. Generally, it is also called bed slip.

  The origin of pressure ulcers is first caused by the external force applied to a specific part of the body to reduce or stop the blood flow of the soft tissue between the bone and the skin surface. And when this situation is maintained for a certain period of time, the tissue irreversibly falls into an ischemic disorder, and as a result, the location becomes a pressure ulcer. According to the theory, pressure ulcers occur when pressure over 32 mmHg is applied for 2 hours. In addition, the sites where pressure ulcers are likely to occur are usually the occipital region, scapula, elbow, greater trochanter, sacrum, coccyx, and heel, but the sites vary depending on individual differences and sleeping postures.

  At present, as reported by Berlowitz et al. As the mechanism of pressure ulcers, the mechanism is not limited to mere ischemia. The following four mechanisms are used: (1) ischemic disorder, (2) reperfusion (post-ischemic / blood It is considered to be effective that (flow resumption) disorder, (3) dysfunction of lymphatic system, and (4) morphological mechanical deformation of cells / tissues are involved in a complex manner. Among these four types, ischemic disorders are mainly caused by accumulation of lactic acid in the tissue due to anaerobic metabolism associated with ischemia and a decrease in tissue pH. On the other hand, reperfusion injury is accompanied by resumption of blood flow that occurs after ischemia, and produces a tissue disorder stronger than mere ischemia itself. This is regarded as important as one of the main factors that cause serious pressure ulcers, particularly when the posture is changed.

  As for the classification of pressure ulcers, pressure ulcers in the short term after onset are called “acute pressure ulcers”, and it is difficult to grasp because the range and depth of necrosis are unclear. The boundary with the surrounding healthy skin becomes clear and the necrotic range becomes clear. However, it is difficult to visually determine the depth of necrosis from the appearance, and it becomes clear after debridement. A pressure ulcer that has progressed further and necrotized deeper than the subcutaneous adipose tissue is called “chronic pressure ulcer”, and usually requires several months for healing and sometimes a year or more. For the chronic stage pressure ulcer, the healing process is determined according to the color tone on the surface of the wound for each subsequent progression sequence. (A) Black stage: state in which massive necrotic tissue is attached, (b) yellow stage: state in which exudative change with remaining necrotic tissue is observed, (c) red stage: state in which granulation is observed, (D) White phase: A state in which wound contraction and epithelialization are observed.

  At present, the following methods are mainly used for treating pressure ulcers. (I) Suppress inflammation and improve local blood circulation. For example, a non-steroidal anti-inflammatory topical agent or an ointment containing a heparin-like substance is applied to improve skin circulation, and when erosion occurs in the skin epidermis, a zinc white ointment or an azulene ointment is applied. (Ii) Leave the blisters without breaking as much as possible. Then, the skin ulcer is washed, the necrotic tissue is removed when necrotic tissue is present in the skin ulcer, and the skin ulcer is disinfected when infected. An external preparation that promotes granulation is applied. Furthermore, in order to protect the wound surface, silicon gauze, polyurethane film, pig skin, etc. are pasted. (Iii) If the damaged site is pocket-shaped, fill with gauze or make a skin incision. In addition, the wound is closed with a flap. (Iv) Excise the affected affected area.

  On the other hand, hydrotherapy is mainly known as a physical treatment for treating pressure ulcer. This is known as Hubbard bath therapy in which the whole body is physically stimulated by warm water or vortex prepared at an insensitive temperature, or vortex bath therapy that is locally applied. In such a hydrotherapy method, treatment is usually performed by directly contacting the wound surface with warm water or covering the wound surface with an occlusive dressing material. Such physical treatment for pressure ulcers is usually water whose dissolved hydrogen concentration does not reach 0.01 ppm below the detection limit, and its therapeutic effect is also a cleaning effect and blood circulation by cleaning the wound surface. The promotion effect is only expected.

  By the way, as a method for reforming water, a method for obtaining hydrogenated water by mixing hydrogen gas into raw material water has been known. The hydrogenated water thus obtained has a very low oxidation-reduction potential of −100 mV or less, although the pH is close to 9.0 or less, and its utilization method is as reducing water. It is attracting attention in various areas.

  In recent years, the influence of “reactive oxygen” has been suggested as a cause of diseases such as cancer. That is, active oxygen is frequently produced in cancer cells, and inhibition of a reactive oxygen scavenging enzyme called SOD (superoxide dismutase) is inhibited. Is known to be sensitive. Therefore, since the effect of removing the above-mentioned active oxygen due to its reducibility can be expected by ingesting hydrogenated water or the like, for example, as disclosed in Patent Document 1 or Patent Document 2 or the like, Techniques relating to cancer inhibitors and the like focusing on the pharmacological effects of these have been proposed.

  In addition, hydrogenation focusing on the very low redox potential of hydrogenated water, assuming that the skin does not adversely affect the biological reaction, that is, the redox potential and pH are the same or very similar to the biological reaction of the skin. New uses for water have also been proposed. For example, Patent Document 3 discloses a method for cleaning the skin of a mammal such as a dog using hydrogenated water.

  However, the conventional hydrogenated water can be used for various applications utilizing the antitumor effect such as cancer in addition to the effect of enhancing the biological activity of the living body by daily ingestion (administration). However, in the treatment of pressure ulcers as described above, there has been no report on the external effects of hydrogenated water by directly contacting the pressure ulcer part or immersing the pressure ulcer part. In particular, Patent Document 3 discloses hydrogenated water used for mammalian skin washing, but does not disclose an external effect in treating pressure ulcer based on the pharmacological effect of hydrogenated water.

Japanese Patent No. 3444849 JP 2007-254435 A JP 2007-228936 A

  Accordingly, the present invention relates to an external solution for pressure ulcer treatment and a pressure ulcer treatment device, which solves the above-mentioned conventional problems, and provides an external solution for pressure ulcer treatment and a pressure ulcer treatment device that provides a safe and safe healing effect without side effects on pressure ulcers. The purpose is to provide.

The problem to be solved by the present invention is as described above. Next, means for solving the problem will be described.
As a result of repeated investigations in view of the current situation that pressure ulcers are a serious problem for a large number of bedridden patients and severely ill patients who have entered an aging society, no effective treatment has been found. Finally, it was found that a liquid containing hydrogen gas in the base has an external effect effective for treating pressure ulcers, and the present invention has been completed.

That is, in claim 1, hydrogen gas in the water base and at least vitamin C, or provitamin C selected from ascorbic acid phosphate, ascorbic acid glucoside, ascorbyl palmitate, and ascorbic acid stearate And one or more selected from polyvinyl pyrrolidone, polyvinyl alcohol, sodium polyacrylate, gelatin, collagen-containing protein hydrolyzate, and vitamin A, and the dissolved hydrogen concentration is 1.0 ppm to 1. 4 ppm and the oxidation-reduction potential is -300 mV to -680 mV.

In Claim 2 , 1 type, or 2 or more types chosen from zinc, copper, calcium, iron, and the compound containing these are contained.

In claim 3 , carbon dioxide gas is contained in the water base.

In Claim 4, it contains a platinum colloid.

In claim 5 , a water base at a predetermined temperature is supplied at a high pressure to a preparation device in which a diffusion tube and a porous element having a predetermined pore diameter are provided in a double-tube structure tube. Hydrogen gas is supplied according to the supply amount of the water base so that the dissolved hydrogen concentration and the oxidation-reduction potential are obtained, and a mixed fluid in which the water base and hydrogen gas are mixed in the diffusion chamber is supplied to the porous element. It contains hydrogen gas in the form of fine bubbles obtained by passing through.

In Claim 6 , a dosage form is a coating agent.

  As an effect of the present invention, it is possible to bring about a safe and secure healing effect with no side effects on pressure ulcers.

The schematic diagram which showed the whole structure of the pressure ulcer treatment apparatus which concerns on one Example of this invention. Sectional drawing which shows the structure of the bath water preparation part. The schematic diagram which showed the whole structure of the pressure sore treatment apparatus of another Example.

  In the external preparation for pressure ulcer treatment of the present invention, tap water, distilled water, purified water, natural mineral water, and the like can be used as a water base. The water base of the present invention is preferably prepared so as to be a hot water of 35 to 43 ° C., and particularly preferably prepared to be a low temperature hot water of 35.5 to 36.6 ° C. which is referred to as a dead temperature.

  In the external preparation for pressure ulcer treatment of the present invention, hydrogen gas is contained in a state dissolved in a water base and in a state of bubbles. In particular, the external liquid for pressure ulcer treatment of the present invention preferably contains fine bubbles of hydrogen gas having a wide range of diameters, such as millibubbles, microbubbles, and micronanobubbles. By forming fine bubbles in this way, it is expected to be excellent in uniformity and dispersibility in the solution and to increase the biological activity of the pressure ulcer part. The nanobubble ratio of hydrogen gas (the ratio of gaseous hydrogen gas in the water base) is 20% or more, preferably 70% or more with a light scattering particle size measuring device manufactured by Beckman Coulter, Inc. It is good for.

  As a method for mixing hydrogen gas, a known method can be adopted. For example, in the case of electrolysis, hydrogen gas is generated by directly electrolyzing the water base by applying the water base to an electrolysis device, and the hydrogen gas is contained in the water base. In such a case, an ultra-smooth surface electrode terminal plate in which a titanium base material is platinum-plated as an electrode terminal is preferably used as an electrolysis device, particularly in order to increase the nanobubble ratio of hydrogen gas.

  In addition, in the case of the bubbling method, a water base is supplied at a high pressure to a preparation apparatus in which a double tube structure tube is provided with a diffusion chamber and a porous element having a predetermined pore diameter. Hydrogen gas is supplied according to the supply amount of the water base so as to obtain a dissolved hydrogen concentration and redox potential, and a mixed fluid in which the water base and hydrogen gas are mixed in the diffusion chamber passes through the porous element. Thus, hydrogen gas is contained in the water base (see FIG. 1 and FIG. 2 described later). In such a case, hydrogen gas is not mixed with the water base in the form of bubbles, but once a mixed fluid of the water base and hydrogen gas is formed, it is passed through the porous element to pass the hydrogen gas. Bubbles are included.

  Thus, hydrogen gas is contained in the water base, so that the dissolved hydrogen concentration is adjusted to 0.5 to 2.0 ppm and the oxidation-reduction potential is adjusted to -300 to -680 mV and maintained. Compared to the fact that the dissolved hydrogen concentration in the water base alone does not reach the detection limit of 0.01 ppm or less and the redox potential is +50 to +200 mV, in the external solution for treating pressure ulcers of the present invention, the dissolved hydrogen concentration is low. It is 0.5 to 2.0 ppm, which is about 50 times that, and the redox potential is adjusted and maintained at -300 to -680 mV, which is excellent in reducing power.

  In particular, the dissolved hydrogen concentration is preferably adjusted to 0.8 to 1.6 ppm, more preferably 1.0 to 1.4 ppm, and the oxidation-reduction potential is preferably adjusted to -350 mV to -600 mV. Furthermore, it is prepared so that the dissolved hydrogen concentration after 30 to 60 minutes after the preparation maintains at least 0.4 ppm or more. Further, the dissolved oxygen concentration is preferably adjusted to 5.0 ppm or less, more preferably 1.0 to 3.5 ppm.

  As described above, the external solution for treating pressure ulcers of the present invention contains hydrogenated water containing hydrogen gas in the water base as an active ingredient, and can be used for deep pressure ulcers or recurrent pressure ulcers regardless of the stage of pressure ulcers. It can be expected to be effective for treatment. In particular, the ischemic disorder reported as one of the pressure ulcer mechanisms is said to be caused mainly by the accumulation of lactic acid in the tissue due to the increase in anaerobic metabolism accompanying ischemia, resulting in a decrease in tissue pH. According to the external preparation for pressure ulcer treatment of the present invention, it is considered that it contributes to the neutralizing action of pH lowered by such an ischemic disorder. Moreover, in reperfusion injury, it is considered to be related to the scavenging effect of active oxygen such as superoxide anion radical that increases rapidly immediately after reperfusion after ischemia.

  In the liquid preparation for external treatment of pressure ulcer of the present invention, it is preferable that other active ingredients are contained in hydrogenated water containing hydrogen gas in the water base because complementary and synergistic effects can be expected. As such an additive component, in addition to hydrogen gas as an essential component, an antioxidant vitamin, a hydrogen gas stabilizer, a protein hydrolyzate, minerals, inorganic salts, carbon dioxide gas, platinum colloid, etc. are appropriately selected. It is preferably contained as an additive component.

  These additional components may be added in advance to hydrogenated water containing a water base or hydrogen gas, or may be added in a timely manner when using a liquid for external treatment of pressure ulcers. You can make a selection based on your gender.

  Specifically, the additive component contains at least vitamin C or provitamin C, and at least one selected from polyvinyl pyrrolidone, polyvinyl alcohol, sodium polyacrylate, gelatin, collagen-containing protein hydrolyzate, vitamin A or It can contain and use 2 or more types. Moreover, you may use including 1 type, or 2 or more types chosen from the compound containing zinc, copper, calcium, iron, and these.

  In the external preparation for pressure ulcer treatment of the present invention, vitamin C, vitamin E, and β-, which can be expected to promote the elimination of active oxygen produced by activation and proliferation of cell functions and protect cells involved in skin regeneration. Antioxidant vitamins such as carotene are contained, and vitamin C or provitamin C is particularly preferably contained. Vitamin C or provitamin C is brought into contact with the surface of the pressure ulcer site, penetrates into the skin and is supplied to cells in the skin, thereby causing pressure ulcer collagen formation, xenobiotic detoxification, induction of interferon production, antihistamine action In addition, various actions such as immune function enhancement, antiviral, antibacterial and the like are also expected.

  As vitamin C, a pharmacologically acceptable free acid of ascorbic acid or a salt thereof is preferably used. Examples of the salt of ascorbic acid include alkali metal salts (for example, sodium salts) and alkaline earth metal salts (for example, calcium salts, magnesium salts, etc.), and sodium ascorbate is preferably used.

  As provitamin C, a pharmacologically acceptable ester of ascorbic acid is preferably used as a derivative of vitamin C. For example, ascorbic acid phosphate (ascorbic acid-2-O-phosphate), ascorbic acid glucoside (Ascorbic acid-2-O-α-D-glucoside), ascorbic acid palmitic acid ester (ascorbic acid-6-O-palmitic acid ester), ascorbic acid stearic acid ester (ascorbic acid-6-O-stearic acid ester) Etc.

  The external preparation for pressure ulcer treatment of the present invention contains a hydrogen gas stabilizer such as a given thickener or water-soluble polymer in order to maintain the dissolved hydrogen concentration and redox potential for a long time. One or more selected from polyvinyl alcohol, sodium polyacrylate, and gelatin are preferably contained. In particular, sodium polyacrylate is preferably used as a highly water-absorbing polymer as hydrogen gas, a carbon dioxide gas described later, or an occlusion support.

  Examples of the hydrogen gas stabilizer include guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, methyl hydroxypropyl cellulose, chondroitin sulfate, dermatan sulfate. , Glycogen, heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, kerato sulfate, locust bean gum, succinoglucan, caronic acid, chitin, chitosan , Carboxymethyl chitin, agar, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone, cal Carboxyvinyl polymers, sodium polyacrylate, polyethylene glycol, bentonite and the like, can be used by arbitrarily selecting one or two or more of these.

  In the external preparation for pressure ulcer treatment of the present invention, a protein hydrolyzate, which is a decomposition product obtained by hydrolyzing a raw material containing a protein that is useful as a material for promoting pressure ulcer wound repair or as a promoting factor with an enzyme, acid, alkali, or the like In particular, a collagen-containing protein hydrolyzate is preferably contained.

  Examples of protein-containing raw materials include milk, silk, wheat, corn, rice, peas, oats, sunflowers, fish, seaweed, casein, collagen, elastin, keratin, soybeans, etc., particularly collagen, elastin Keratin is preferably used. Examples of the collagen source include mammalian skin, bone, avian cartilage and bone, fish cartilage and bone, skin, scales, and the like, and particularly, fish cartilage, bone, skin, and scales. Fish collagen made from these fishes is preferably used.

  The external solution for treating pressure ulcer of the present invention contains a given vitamin useful as a nutritional component having a therapeutic effect for pressure ulcer and as a wound repair promoting factor for pressure ulcer, and in particular, a vitamin that can be expected to have an effective wound healing effect. A is preferably contained.

  Examples of other vitamins include retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), lycopene (provitamin A), thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), pyridoxine (Vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, ubiquinones , Phytonadione (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, ferulic acid, γ-oryzanol Orotic acid, vitamin P such (rutin, eriocitrin, hesperidin), and the like vitamins U.

  The pressure ulcer treatment external preparation of the present invention contains inorganic salts that are useful as a factor for promoting pressure ulcer wound repair in cooperation with hydrogen gas and carbon dioxide, which will be described later, in particular, zinc, copper, calcium, iron, and these. 1 type or 2 types or more chosen from the compound to contain is contained preferably. In particular, zinc oxide, copper sulfate, calcium chloride, iron sulfate, and the like are preferably contained as compounds containing zinc, copper, calcium, and iron.

  Inorganic salts include sodium chloride-containing salts such as salt, common salt, rock salt, sea salt, natural salt, potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, ammonium chloride, sodium sulfate, aluminum sulfate, Aluminum sulfate / potassium sulfate (alum), aluminum sulfate / ammonium sulfate, barium sulfate, calcium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate, iron sulfate, copper sulfate, sodium phosphates such as 1Na, 2Na and 3Na phosphates, phosphoric acid Potassium, calcium phosphates, and magnesium phosphates can be mentioned.

  In the external preparation for pressure ulcer treatment of the present invention, carbon dioxide gas present in a state dissolved in a water base (hydrogenated water) and in the form of bubbles is preferably contained. As a method for mixing the carbon dioxide gas, a known method can be employed, and it is preferable that the carbon dioxide gas be contained in the water base by bubbling the carbon dioxide gas or by a carbon dioxide gas generator. In the case of the bubbling method, carbon dioxide gas is dissolved in the water base through a porous filter from a carbon dioxide gas cylinder. When a carbon dioxide generator is used, sodium hydrogen carbonate is mainly mixed with sodium sulfate, sodium carbonate, potassium chloride, sodium chloride, calcium chloride, etc., and these are made into tablets, granules, and powder. It is thrown into the agent.

  In the external preparation for pressure ulcer treatment of the present invention, a colloidal platinum group element which is an effective hydrogen storage factor or a compound containing the same is contained, and in particular, a platinum colloid is preferably contained among the platinum group elements. Among the elements belonging to Group VIII of the Periodic Table, the platinum group elements include six elements of ruthenium (Ru), rhodium (Rh), palladium (Pd), osmium (Os), iridium (Ir), and platinum (Pt). It is a generic name and is expected to act as a so-called reduction catalyst that exhibits activity in various reactions of dehydrogenation and oxidation in hydrogen gas dissolved in a water base by being colloidal.

  As the platinum colloid, platinum colloid comprising 4% of platinum with polyvinylpyrrolidone and carboxymethylcellulose as a support, and preferably having a particle diameter in the range of 1 to 10 μm is used. The amount added to the water base (hydrogenated water) is adjusted to 0.02 to 30 ppm, preferably 0.05 to 10 ppm, more preferably 0.1 to 6.0 ppm. It is prepared as follows.

  As a method for producing a platinum colloid, a known method can be adopted. (1) A method of reducing the surface of a hexachloroplatinic acid aqueous solution by applying an external flame of a Bunsen burner, or (2) Protection with a hexachloroplatinic acid aqueous solution. Add sodium ascorbate, gum arabic, or gelatin as a colloid and reduce with a reducing agent such as hydrazine. (3) Put pure water into the evaporating dish and cool it between two platinum wires immersed in it. It is manufactured by a method such as a Bledich method in which an arc is discharged.

  In addition to the above-mentioned active ingredients and additive ingredients, the liquid preparation for external treatment of pressure ulcers of the present invention usually contains a pharmaceutically acceptable carrier or general pharmaceutical additive, such as oil, surfactant, etc. , Moisturizer, thickener, water-soluble polymer, film agent, water-insoluble polymer, lower alcohol, polyhydric alcohol, saccharide, UV absorber, amino acids, anti-inflammatory agent, skin activator, blood circulation promoter Necessary drugs such as seborrheic agents, anti-inflammatory agents, organic acids, organic amines, sequestering agents, pH adjusters, antioxidants, antibacterial agents, antiseptics, astringents, refreshing agents, perfumes, pigments, water, etc. Accordingly, the present invention can be appropriately used within a range not impairing the effects of the present invention.

  The external preparation for pressure ulcer treatment of the present invention can be made into various dosage forms according to the formulation, and can be used as a transdermal preparation such as a liquid, a poultice, a bathing agent, a lotion, an aerosol. In particular, it is preferably used as bath water for treatment used in physical treatment as a treatment for pressure ulcers by directly contacting the pressure ulcer part or immersing the pressure ulcer part. For example, an external solution for treating pressure ulcers is filled into an appropriate container to make a product, and an appropriate amount of the liquid is dripped onto the pressure ulcer site at once, or the pressure ulcer site is immersed in a container or bathtub, gauze, absorbent cotton, etc. It is applied by applying with an applicator or the like. Moreover, it is also possible to make the product form applicable to the spray container by filling the spray container.

  Next, a pressure ulcer treatment apparatus that supplies the external liquid for pressure ulcer treatment of the present invention as bath water will be described with reference to FIGS. 1 to 3.

  The pressure ulcer treatment device 10 shown in FIG. 1 is generated by a hot water supply unit 1 that supplies hot water, a hydrogen gas generation unit 2 that generates hydrogen gas, and a hot water and hydrogen gas generation unit 2 that are supplied by the hot water supply unit 1. A predetermined additive is added to the bath water preparation unit 3 for preparing the bath water by the supplied hydrogen gas and the hot water supplied from the hot water supply unit 1 or the bath water prepared by the bath water preparation unit 3 An additive supply unit 4 to supply, a bath water discharge unit 5 for discharging bath water from the bath water preparation unit 3 via a supply line 7, and a bath water discharged from the bath water discharge unit 5 And a bath portion 6 in which the soaker is soaked, and is used for physical treatment in the treatment of pressure ulcers.

  The hot water supply unit 1 is configured as a hot water supply device (hot water boiler) that supplies hot water to the bath water preparation unit 3. Hot water prepared at 35 to 43 ° C., particularly preferably 35.5 to 36.6 ° C., is supplied to the bath water preparation unit 3 by the hot water supply unit 1. The hydrogen gas generation unit 2 is connected to the bath water preparation unit 3 and is configured as a hydrogen supply source that supplies hydrogen gas to the hot water supplied to the bath water preparation unit 3. Although the structure is not specifically limited, the well-known electrolytic cell which electrolyzes raw material water and generates hydrogen gas is comprised.

  The bath water preparation unit 3 mixes the hot water supplied by the hot water supply unit 1 with the hydrogen gas generated by the hydrogen gas generation unit 2 and dissolves the water for hydrogen (hydrogenated water) in which fine bubble hydrogen gas is dissolved. The composition can be prepared. The configuration of the bath water preparation unit 3 is not particularly limited, but the hydrogen gas generation unit 2 is integrally attached to the electrolysis method in which the hot water supplied from the bath water preparation unit 3 is directly electrolyzed, or separately. A bubbling method for forming a mixed fluid of hydrogen gas and hot water supplied from the hydrogen gas generation unit 2 can be employed.

  An example of the bath water preparation unit 3 will be described with reference to FIG. 2. The bath water preparation unit 3 employs an ejector structure for mixing hydrogen gas with hot water, and has a double tube-like structure 30. A supply supply path from the hot water supply section 1 and a supply supply path from the hydrogen gas generation section 2 are connected to the diffusion chamber 31, the diameter of which is reduced from both ends toward the center, and the diffusion chamber 31. The disposed porous element 32 and the like are provided.

  The diffusion chamber 31 is configured to have a reduced diameter structure (a diaphragm structure) from both ends toward the center. By supplying hot water and hydrogen gas to the tube body 30, a negative pressure is formed at the throttle portion of the diffusion chamber 31, thereby forming a mixed fluid of hot water and hydrogen gas. The porous element 32 is formed in a filter structure having a predetermined pore diameter and is filled in the diffusion chamber 31. The mixed fluid formed in the diffusion chamber 31 is injected through the porous element 32, whereby hydrogen gas bubbles having a diameter substantially the same as the diameter of the hole formed in the porous element 31 are formed.

  As described above, in the bath water preparation unit 3, hydrogen gas is mixed with hot water in the diffusion chamber 31 using the ejector effect, and a mixed fluid (bath water) in which hydrogen gas is dissolved in the hot water is formed. By passing the mixed fluid through the porous element 31, fine bubbles are contained in the mixed fluid. The bath water produced by the bath water preparation unit 3 includes bubbles of hydrogen gas having a wide range of diameters from millibubbles to microbubbles and micronanobubbles as fine bubbles, and is excellent in uniformity and dispersibility and has an effect of improving pressure ulcers. It is good for.

  In the bath water preparation unit 3 of this embodiment, bath water having a dissolved hydrogen concentration of 0.8 to 2.0 ppm and an oxidation-reduction potential of −300 to −680 mV is prepared. The dissolved hydrogen concentration and oxidation-reduction potential of the bath water should be easily adjusted to arbitrary values by adjusting the pressure and flow rate of hot water and hydrogen gas supplied to the bath water preparation unit 3. (See FIG. 3).

  The bath water discharge part 5 is a discharge part from which the bath water prepared from the bath water preparation part 3 via the supply line 7 is discharged. In the present embodiment, the bath water is stored in the bath soaking the pressure ulcer part. Switching to the part 6 and the shower part 8 from which the bath water is discharged in a shower form, the bath water is discharged. In this way, the bath water discharge part 5 switches to the bathtub part 6 or the shower part 8 to discharge the bath water, so that the patient bathes in the bath water in the bathtub part 6 soaking the pressure ulcer part, An optimal pressure ulcer treatment can be performed by bringing bath water directly into contact with the pressure ulcer part of the patient at the shower unit 8.

  The additive supply unit 4 supplies a predetermined additive to the hot water supplied by the hot water supply unit 1 or the bath water prepared by the bath water preparation unit 3, and in this embodiment, the preparation of bath water is performed. It is arrange | positioned in the middle part of the supply line 7 which connects the part 3 and the bath water discharge part 5, and is comprised so that a predetermined additive may be supplied to the bath water prepared in the bath water preparation part 3. .

  The “predetermined additive” is an additive component added to bath water in order to exert a significant pharmacological effect in treating pressure ulcers. Specifically, it has been described above that it is preferably selected as an additive component, particularly selected from antioxidant vitamins, hydrogen gas stabilizers, protein hydrolysates, minerals, inorganic salts, carbon dioxide gas, platinum colloid, and the like. It is as follows. The additive is added in a predetermined amount that exhibits a significant pharmacological effect in the bath water used for treatment.

  In addition, the arrangement configuration of the additive supply unit 4 is not limited to this, for example, a configuration in which a predetermined additive is contained in the hot water before being connected to the hot water supply unit 1 and supplied to the bath water preparation unit 3 Alternatively, it may be provided at one or a plurality of places such as the bath water discharge part 5, the bathtub part 6 or the shower part 8.

Next, a pressure ulcer treatment apparatus 100 according to another embodiment will be described below with reference to FIG.
The pressure ulcer treatment apparatus 100 shown in FIG. 3 includes a hot water supply unit 101 that supplies hot water, a hydrogen gas generation unit 102 that generates hydrogen gas, a bath water preparation unit 103 that prepares bath water, and a hot water supply unit 1. An additive supply unit 104 that supplies a predetermined additive to the bath water prepared by the hot water or bath water preparation unit 103 that is supplied, and a bath that discharges the bath water from the bath water preparation unit 103 via the supply line 107 A water discharge unit 105, a bath unit 106 that contains bath water discharged from the bath water discharge unit 5 and immerses the pressure ulcer part, and a hydrogen concentration measurement unit 110 that measures the dissolved hydrogen concentration of bath water in the bath unit 106, And a control unit 111 that adjusts the dissolved hydrogen concentration of the bath water produced by the bath water preparation unit 103 based on the dissolved hydrogen concentration measured by the hydrogen concentration measuring unit 110.

  In the pressure ulcer treatment device 100 shown in FIG. 3, the pressure ulcer treatment device 10 shown in FIG. 1 described above is based on the dissolved hydrogen concentration of the bath water in the bathtub portion 106 measured by the hydrogen concentration measurement unit 110. The difference is that the dissolved hydrogen concentration of the bath water supplied to the bathtub portion 106 can be adjusted. That is, since the hydrogen gas contained in the bath water contained in the bathtub portion 106 is in a gas state of fine bubbles, the dissolved hydrogen concentration of the bath water decreases with time and is contained in the bathtub portion 106. If the dissolved hydrogen concentration in the bath water is excessively reduced, the amount of hydrogen may be insufficient and may not be effective in treating pressure ulcers. Therefore, the pressure sore treatment apparatus 100 is configured such that the dissolved hydrogen concentration in the bath water in the bathtub portion 106 can be kept constant.

  The hydrogen concentration measuring unit 110 is provided in the bathtub unit 106, and the dissolved hydrogen concentration of the bath water in the bathtub unit 106 is continuously measured. The dissolved hydrogen concentration measured by the hydrogen concentration measurement unit 110 is sent to the control unit 111 and fed back to the preparation of bath water in the bath water preparation unit 103. In the control unit 111, based on the dissolved hydrogen concentration of the bath water measured by the hydrogen concentration measuring unit 110, when the concentration is different from the preset dissolved hydrogen concentration of the bath water, the predetermined dissolved hydrogen concentration is set. The pressure or flow rate of the hydrogen gas in the bath water preparation unit 103 is controlled.

  Thus, by controlling by the control part 111, it becomes possible in the pressure sore treatment apparatus 100 to maintain the dissolved hydrogen density | concentration of the bath water in the bathtub part 106 to a higher density | concentration. That is, when used for a patient with a high pressure ulcer disorder (decubitus stage), it is necessary to incorporate more hydrogen gas into the skin surface in order to remove excess active oxygen at the pressure ulcer site. Therefore, in such a case, the dissolved hydrogen concentration in the bath water in the bathtub portion 106 can be appropriately set to be maintained at a higher level.

  In the pressure ulcer treatment apparatus 100 shown in FIG. 3, the arrangement configuration of the additive supply unit 104 is not particularly limited, and a predetermined addition to the bath water prepared in the bath water preparation unit 103 arranged in the supply line 107. It may be configured to supply the agent, or may be provided in one or a plurality of places such as the bath water discharge part 105 or the bathtub part 106.

<Preparation of liquid for external treatment of pressure ulcer and comparative sample>
In the external preparation for pressure ulcer treatment of this example, using a known electrolysis method or hydrogenated water (bath water) supplied from the pressure ulcer treatment apparatus 1 described above, the temperature is 35.8 to 36.4 ° C., The dissolved hydrogen concentration was adjusted to 1.02 to 1.35 ppm, the dissolved oxygen concentration was 1.30 to 3.28 ppm, the oxidation-reduction potential was −349 to −583 mV, and the pH was 5.34 to 8.06. On the other hand, the comparative example sample was prepared so that it might become temperature 35.8-36.4 degreeC using normal tap water or distilled water as a water base. In the comparative sample, a sample having a dissolved hydrogen concentration of less than 0.01 ppm, a dissolved oxygen concentration of 6.07 to 9.16 ppm, a redox potential of +77 to +284 mV, and a pH of 6.19 to 7.44 was used.

  The additive component contained in the pressure ulcer treatment external preparation or the comparative example sample was added in advance to the water base or hydrogenated water containing hydrogen gas, and a predetermined amount was added. In addition to the bubbling method, carbon dioxide gas was contained using a mixed tablet (generator) in which sodium bicarbonate and sodium sulfate were blended at a ratio of 1:19.

<Pressure treatment effect test 1>
First, the center part (1.5 × 2.5 cm) of the back of a ddY mouse was shaved with a clipper so as not to be wounded, and then a rounded rectangular methacryl plate (1.0 mm) with rounded corners and polished smoothly. × 2.0 cm) was covered with double cotton gauze, and the shaved surface of the mouse's back was pressurized with 32 mmHg. In the pressurization period of 2 to 4 days, the skin on the back of the mouse sandwiched between the methacrylic plate and the spine is subjected to physical compression similar to bed slipping in a bedridden patient, etc. Damage to the basement membrane type IV collagen that laminated the epidermis and dermis resulted in skin symptoms comparable to the NPUAP (National Pressure Ulcer Advisory Panel) pressure ulcer stage I. And, at any point in 3 to 6 days when almost the entire shaved part showed the above-mentioned symptoms, pressurization was stopped for each mouse individual, and immediately after that, treatment treatment was performed on 8 animals per test section. I went there for 3 weeks.

  Treatment methods include soaking the pressure ulcer stage I symptom site in an external solution for pressure ulcer treatment or a comparative example sample (immersion treatment) every day for 10 minutes, and applying a pressure ulcer treatment external solution or comparative example sample to the pressure ulcer stage I symptom site. A treatment (drip treatment) of continuous dripping for 10 minutes every day and a treatment (sticking treatment) of applying a pressure ulcer treatment external solution or a sample for comparison with a pressure ulcer treatment external symptom to the site of pressure ulcer stage I symptom and replacing it every day (sticking treatment) were performed. In addition, the therapeutic effect was evaluated based on the change in the area reduction rate (%) of the pressure ulcer stage I symptom photographed with a digital camera and subjected to image processing for each treatment treatment.

  Table 1 shows test results (Comparative Examples 1 to 5) when a given treatment is performed using the comparative sample.

  Table 2 shows a given vitamin C or provitamin C as a liquid for external use for treating pressure ulcers in a water base containing hydrogen gas (Example 1) and a water base containing hydrogen gas. The test result at the time of performing immersion treatment using what was added (Examples 2-6) is shown.

  In Table 3, as a liquid medicine for external treatment of pressure ulcers, given hydrogen gas stabilizer, protein hydrolyzate, mineral containing water base containing hydrogen gas and vitamin C or provitamin C (ascorbic acid phosphate) The test result at the time of performing immersion treatment using the thing (Examples 7-14) which added the metal, inorganic salt, or platinum colloid is shown.

  In Table 4, given as liquids for external treatment of pressure ulcers, water bases containing hydrogen gas and carbon dioxide (Examples 15 and 16) and water bases containing hydrogen gas and carbon dioxide were given. The test result at the time of performing immersion treatment using what added the hydrogen gas stabilizer of this, protein hydrolyzate, minerals, or inorganic salt (Examples 17-22) is shown.

  In Table 5, as a liquid medicine for external treatment of pressure ulcer, a given vitamin C or provitamin C is added to a water base containing hydrogen gas (Example 23) and a water base containing hydrogen gas (Examples 24 to 28), and water base containing hydrogen gas and vitamin C or provitamin C (ascorbic acid) added with protein hydrolyzate (Example 29) The test result at the time of performing a dripping process is shown.

  In Table 6, as a liquid for external use for treating pressure ulcers, water given in hydrogen base and carbon dioxide (Example 30) and water base containing hydrogen gas and carbon dioxide were given hydrogen. The test result at the time of performing a dripping process using what added the gas stabilizer or platinum colloid (Examples 31 and 32) is shown.

  In Table 7, as a liquid medicine for external use for treating pressure ulcers, a water base containing hydrogen gas (Example 33), a water base containing hydrogen gas, given vitamin C or provitamin C, hydrogen Gas stabilizers, protein hydrolysates, minerals, inorganic salts, or platinum colloid added (Examples 34 to 38), and water base containing hydrogen gas and carbon dioxide gas (Example 39) The test result at the time of performing a sticking process using is shown.

  As described above, as shown in Tables 1 to 7, it has been recognized that the liquid preparation for external treatment of pressure ulcer containing hydrogen gas or the like in the water base of this example has an improvement effect on the pressure ulcer model artificially formed in the mouse. It was.

<Pressure treatment effect test 2>
First, human skin fibroblasts OUMS-36 are seeded in type I collagen gel in a Bronnov chamber for skin tissue culture, and Matrigel, which is a reconstituted basement membrane component, is layered thereon. Artificial skin was prepared by a 3D human skin tissue model formation method in which keratinocytes HaCaT cells were seeded and grown, and finally the stratum corneum was formed by airlifting. Kato S et al., J. of Photochem. & Photobiol.B: Biology., (2010), vol.98, P.99-105, and Kato S et al., Journal of Biomedical Nanotechnology, 10). .6, P.1-7 etc.).

Next, the artificial skin prepared by the above method was directly applied to a circular methacryl plate with rounded corners and polished smoothly, and pressurized with 32 mmHg. Three days after the pressurization, the skin tissue was cut out and embedded in an OCT compound, and a vertical thin piece having a thickness of 4 μm was prepared with a cryostat. This vertical slice was treated with a human type IV collagen-recognizing rabbit antibody, and after rinsing, treated with a rabbit immunoglobulin-recognized goat secondary antibody of FITC (fluorescein isothiocyanate) conjugate. Fluorescence is obtained by detecting fluorescence with a confocal scanning laser fluorescence microscope, and this processed product is image-processed. Based on the fluorescence intensity per unit area, the degree of construction of type IV collagen (floor.unit) is obtained. / Mm ² ) was calculated.

  After 3 days of pressurization, the degree of construction of type IV collagen decreased, but this was treated as an untreated test group, treated as various treatment groups and a comparative control group, and then treated for one week. Measured. In the treatment treatment group and the comparative control group in this example, this was performed using the pressure ulcer treatment external preparation and the comparative example sample prepared in the same manner as described above in <Preparation of pressure remedy treatment external preparation and comparative example sample>. The layer was overlaid on the stratum corneum, and the degree of type IV collagen construction was calculated using 6 pieces of artificial skin per test section, and its statistical significance was evaluated. In the confocal scanning laser fluorescence microscope, the fluorescence intensity was measured at an excitation wavelength of 508 nm and a fluorescence wavelength of 630 nm, with the gain, exposure time, and offset being unified.

  In Table 8, as a comparative sample, only a water base (Comparative Example 7), vitamin C or provitamin C given to the water base, hydrogen gas stabilizer, protein hydrolyzate, minerals, inorganic salts, carbonic acid The test result at the time of using what added gas or platinum colloid (Comparative Examples 8-15) is shown.

  In Table 9, as a liquid medicine for external treatment of pressure ulcers, a given vitamin C or provitamin C included in a water base containing hydrogenated water (Example 40) and a water base containing hydrogenated water The test result at the time of using what added the hydrogen gas stabilizer, protein hydrolyzate, minerals, inorganic salt, carbon dioxide gas, or platinum colloid (Examples 41-48) is shown.

  As shown in Table 8 and Table 9, the liquid preparation for external treatment of pressure ulcer containing hydrogen gas or the like in the water base of this example has a main component type IV collagen construction degree in the skin basement membrane directly linked to the prevention treatment of pressure ulcer. It was verified to improve.

<Pressure treatment effect test 3>
The pressure ulcer treatment external preparation prepared in the same manner as described above in <Preparation of pressure ulcer treatment external preparation and comparative sample> was used as bath water (temperature 35.8 to 36.4 ° C., dissolved hydrogen concentration 1.02-1). .35 ppm, dissolved oxygen concentration 1.30 to 3.28 ppm, redox potential −349 to −583 mV, pH 5.34 to 8.06), and pressure ulcer site by either bathing or showering for pressure ulcer patients The healing effect of the bath water against pressure ulcers was verified by bringing the bath water into contact therewith. Specifically, for pressure ulcer patients with different symptoms in the pressure ulcer stage and pressure ulcer site, a method of bathing the pressure ulcer part in bath water for 10 minutes once every day in a bath containing bath water (bath treatment method) ), Or bathing water once a day for 10 minutes in the shower and applying the physical treatment method of either contacting the bathing water to the pressure ulcer site (shower treatment method) Continued for 4 weeks. In the comparative test, the same physical therapy was performed using normal water. The therapeutic effect was evaluated at each stage of DTI pseudo and stages I to IV according to the NPUAP classification for each pressure ulcer site, and the stage improvement degree was evaluated by comprehensive judgment.

  Table 10 shows the treatment results of physical treatment (bath treatment and shower treatment) using normal water as bath water as a comparative test (subjects A to F).

  Table 11 shows the treatment results of physical treatment (bath treatment and shower treatment) using water water containing hydrogen gas as bath water (subjects GL).

  As shown in Tables 10 and 11, in the bath water of this example, the pressure ulcer improving effect was remarkably recognized, and it was shown that the pressure ulcer has a healing effect.

DESCRIPTION OF SYMBOLS 1 Hot water supply part 2 Hydrogen gas generation part 3 Bath water preparation part 4 Additive supply part 5 Bath water discharge part 6 Bath part 7 Supply line 10 Pressure ulcer treatment apparatus

Claims (6)

Hydrogen gas in the water base,
At least vitamin C, or provitamin C selected from ascorbic acid phosphate, ascorbyl glucoside, ascorbyl palmitate, and ascorbic acid stearate ;
One or more selected from polyvinylpyrrolidone, polyvinyl alcohol, sodium polyacrylate, gelatin, collagen-containing protein hydrolysate, and vitamin A;
And a dissolved hydrogen concentration of 1.0 ppm to 1.4 ppm and an oxidation-reduction potential of -300 mV to -680 mV.   The external solution for pressure ulcer treatment of Claim 1 containing 1 type, or 2 or more types chosen from the compound containing zinc, copper, calcium, iron, and these.   The liquid preparation for external treatment of pressure ulcer according to claim 1 or 2, wherein carbon dioxide gas is contained in the water base.   The external preparation for pressure ulcer treatment as described in any one of Claims 1 thru | or 3 containing a platinum colloid. In a preparation device provided with a diffusion chamber and a porous element having a predetermined pore diameter in a tube body of a double tube structure,
While supplying a water base at a predetermined temperature at a high pressure, hydrogen gas is supplied according to the supply amount of the water base so as to obtain a target dissolved hydrogen concentration and oxidation-reduction potential,
Obtained by passing a mixed fluid obtained by mixing a water base and hydrogen gas through the porous element in the diffusion chamber,
The liquid for external use for treatment of pressure ulcer according to any one of claims 1 to 4, comprising hydrogen gas in the form of fine bubbles.   The liquid preparation for external treatment of pressure ulcer according to any one of claims 1 to 5, wherein the dosage form is a coating agent.

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