MXPA06009302A - Remedy for external use for skin and mucosal injuries caused by viral infection - Google Patents

Abstract

A remedy for external use for treating skin and mucosal vesicle, sore or ulcer caused by viral infection which contains, as the active ingredient, acetylsalicylic acid or a pharmacologically acceptable salt thereof.

Description

MEDICATION FOR EXTERNAL USE FOR SKIN AND MUCOSA INJURIES CAUSED BY VIRAL INFECTION TECHNICAL FIELD The present invention relates to an excellent external preparation containing acetylsalicylic acid as an active ingredient, which has a therapeutic effect on symptoms of skin or mucosal lesions, such as vesicle, sore or ulcers caused by a viral infection such as varicella zoster virus, herpes simplex virus or enterovirus, together with an effect of inhibiting a pain and pruritus in these affected or injured parts, and methods for treating these symptoms in this way.

BACKGROUND OF THE INVENTION Although symptoms of skin or mucosal lesion caused by a viral infection such as varicella zoster virus, herpes simplex virus or enterovirus are often observed, specific therapeutic methods have not been established in these symptoms. Now, to prevent secondary infection, an antibiotic is administered, or disinfection is carried out in the parts affected by povidone iodide, etc. It is a current state that there is hardly any external preparation which improves a symptom of injury by viral infection such as a vesicle, sore or ulcer caused by a viral infection such as varicella zoster virus, herpes simplex virus or enterovirus, and simultaneously inhibits a pain and itching in these affected parts. Recently antiviral agents have been developed, but these agents are said to be just satisfied with improvements in the symptoms of injury by viral infection such as vesicles, sores or ulcers, especially in pain inhibition and pruritus in these affected parts. In addition, the effect of an external preparation containing a non-steroidal anti-inflammatory agent or a spheroid on the symptoms is not satisfactory, and thus, one is anxious about the side effects, such as sensation of local irritation and redness. By the way, acetylsalicylic acid (which can later be called aspirin), is mainly and widely used in the form of oral administration as an antipyretic analgesic for many years, due to its potent analgesic, antipyretic and antirheumatism activities, and is a medicine with high security and with some side effects. In recent years, the search in the application to external preparations of acetylsalicylic acid is advanced. Ointments for the treatment of neuralgia are reported respectively in Japanese Patent Publication A 3-72426, external preparations for skin lesion in Japanese Patent Publication A 9-235232, dermal administration system for anti-aging treatment. thrombus and for the prevention of cancer in Japanese Patent Publication (Toku Hyo Hei) 8-504198, external preparations for the treatment of allergic dermatitis in Japanese Patent Publication A 2001-187739, external preparations for anti-pruritus in the document WO 01/47525, etc. However, there are no reports on external preparations containing acetylsalicylic acid, which are used for the purpose of treating an injury by viral infection such as gall bladder, sores or ulcers, caused by a viral infection such as varicella zoster virus, virus of herpes simplex or enterovirus and inhibit a pain or pruritus in these affected parts.

BRIEF DESCRIPTION OF THE INVENTION The present invention is to solve the above problems, and its aim is to provide an excellent external preparation containing acetylsalicylic acid as an active ingredient, which has few side effects, has a therapeutic effect on a symptom of injury by viral infection such as vesicle, sore or ulcer caused by a viral infection such as varicella zoster virus, herpes simplex virus or enterovirus, along with an effect of inhibiting a pain or itching in these affected parts. The present inventors have studied extensively to solve the above problems and found that an excellent external preparation containing acetylsalicylic acid as an active ingredient has few side effects., has an excellent therapeutic effect in a symptom of injury by viral infection such as a vesicle, sore or ulcer caused by a viral infection such as varicella zoster virus, herpes simplex virus or enterovirus, together with a superior inhibitory effect in a pain or itching in these affected parts. Furthermore, even if the external preparation containing acetylsalicylic acid is applied to a pain and itching in the affected parts of the symptoms of injury by viral infection such as vesicle, sore or ulcer, caused by a viral infection such as varicella zoster virus , herpes simplex virus or enterovirus, there is no delay in the healing of the symptoms of injury due to viral infection, such as gall bladder, sore and ulcers. Furthermore, although this activity and effect depend on the concentration of acetylsalicylic acid in a preparation, the activity and effect almost do not change in excess of a certain fixed concentration of acetylsalicylic acid.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an excellent external preparation containing acetylsalicylic acid or a pharmacologically acceptable salt thereof as an active ingredient, which is used for the treatment of symptoms of injury by viral infection caused by a viral infection such as a virus of the varicella zoster, herpes simplex virus or enterovirus together with an effect of inhibiting a pain and pruritus in these affected parts. The present invention also relates to an excellent external preparation containing acetylsalicylic acid, or a pharmacologically acceptable salt thereof as an active ingredient, which is used for treatment of gallbladder, sore or ulcer of skin and mucosa caused by a viral infection together with an effect of inhibiting a pain or pruritus in these affected parts. The present invention also relates to an excellent external preparation containing acetylsalicylic acid, or a pharmacologically acceptable salt thereof as an active ingredient, which is used for treatment of pain and pruritus in the affected parts in symptoms of injury by viral infection caused by a viral infection. The present invention also relates to an excellent external preparation containing acetylsalicylic acid, or a pharmacologically acceptable salt thereof as an active ingredient, which is used for treatment of pain and pruritus in the gallbladder, ulcer or ulcer parts of the skin and mucosa caused by virus infection such as varicella zoster virus, herpes simplex virus or enterovirus. The present invention also relates to a method for the treatment of skin or mucosal injury caused by a viral infection by administering an effective amount of acetylsalicylic acid or a pharmacologically acceptable salt thereof to an affected part of a patient. The present invention relates to a method for the treatment of vesicles, sores or ulcers of the skin or mucosa caused by viral infections such as varicella zoster virus, herpes simplex virus or enterovirus, by administering an effective amount of an external preparation that contains acetylsalicylic acid or a pharmacologically acceptable salt thereof to an affected part of a patient. In addition, the present invention relates to a method for the treatment of pain and pruritus in skin and mucosal injury caused by a viral infection such as varicella zoster virus, herpes simplex virus or enterovirus, by administering an effective amount of a external preparation containing acetylsalicylic acid or a pharmacologically acceptable salt thereof to an affected part of a patient. The acetylsalicylic acid contained in the external preparations of the present invention is listed in the Japanese Pharmacopoeia. The content of acetylsalicylic acid contained in the external preparations, changes in accordance with the forms of the preparation, and is 0.05 to 80% by total weight to exhibit a sufficient effect, preferably 0.05 to 70% by weight, and more preferably 0.01 to 50. % Of weight. When the content of acetylsalicylic acid is more than 80% by weight, its physical property is almost not preserved, and when the content is less than 0.01% by weight, the activity of acetylsalicylic acid is not completely exhibited.

Acetylsalicylic acid and its pharmacologically acceptable salt can be used such as a salt formed with an amino acid, such as DL-lysine, or a mineral salt such as sodium salt, as the active ingredient contained in the external preparations of the present invention. Especially, if the external preparations of the present invention are in such a dosage form, it will not be limited as an active ingredient is administered directly to the local surface of the skin, and, for example, ointments, creams, gels, solutions may be used. (suspensions, emulsions, lotions, etc.), cataplasms, tapes, aerosols and powders for external use All can be used as they are an ingredient used for the usual external preparations, as an ingredient for the external preparations containing salicylic acid of the present invention. In the case of ointments, creams, gels, solutions, suspensions, emulsions and lotions, bases, such as white petrolatum, yellow petrolatum, lanolin, white beeswax, cetyl alcohol, stearyl alcohol, stearic acid, hydrogenated oil, hydrocarbon gel, polyethylene glycols, liquid paraffin and squalene; solvents and solubilizing agents, such as oleic acid, isopropyl myristate, diisopropyl adipate, isopropyl sebacate, glyceryl triisooctanoate, crotamiton, diethyl sebacate, hexyl laurate, a fatty acid, a fatty acid ester, an aliphatic alcohol, a vegetable oil and a alcohol; antioxidants, such as a tocopherol derivative, L-ascorbic acid, dibutylhydroxytoluene and butylated hydroxyanisole; antiseptics such as p-hydroxybenzoate; humectants, such as giicerin, propylene glycol and sodium hyaluronate; surface active agents, such as polyoxyethylene derivatives, glycerol ester of a fatty acid, sucrose ester of a fatty acid, sorbitan ester of a fatty acid, propylene glycol of a fatty acid and lecithin; thickeners, such as carboxy vinyl polymer, xanthan gum, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose; stabilizers; condoms; absorption enhancers and other suitable excipients, you can mix in these. In the case of poultices, tackifiers, such as polyacrylic acid and polyacrylic acid copolymer; crosslinking agents, such as aluminum sulfate, potassium aluminum sulfate, aluminum chloride, magnesium aluminometasilicate and dihydroxy aluminum acetate; thickening agents, such as sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, sodium alignate, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose and hydroxypropyl methylcellulose; polyhydric alcohols such as glycerin, propylene glycol and 1,3-butanediol; solvents and solubilizing agents such as oleic acid, isopropyl myristate, diisopropyl adipate, isopropyl sebacate, glyceryl trisooctanate, crotamiton, diethyl sebacate, hexyl laurate, a fatty acid, a fatty acid ester, an aliphatic alcohol, a vegetable oil and a alcohol; active surface agents such as a polyoxyethylene derivative; flavors such as 1 -mentol; antiseptics such as p-hydroxybenzoate; purified water; and other suitable excipients, can be mixed therein. In the case of tapes, adhesives, such as styrene-isoprene-styrene block copolymer and an acrylic resin; tackifiers, such as alicyclic saturated hydrocarbon resin, rosin resin and terpene resin; softeners, such as liquid rubber and liquid paraffin; antioxidants such as dibutylhydroxytoluene; polyhydric alcohols such as propylene glycol; solvents and solubilizing agents, such as oleic acid, isopropyl myristate, diisopropyl adipate, isopropyl sebacate, glyceryl triisooctanoate, crotamiton, diethyl sebacate, hexyl laurate, a fatty acid, a fatty acid ester, an aliphatic alcohol, a vegetable oil and a alcohol; surface active agents such as a polyoxyethylene derivative; Absorption enhancers and other suitable excipients can be mixed in these. However, aqueous tapes can be prepared by adding a polymer which may contain water such as sodium polyacrylate or polyvinyl alcohol and a small amount of purified water. In case of external powders, vehicles, such as potato starch, rice starch, corn starch, talc and zinc oxide and other suitable excipients, can be mixed in these. In the case of aerosols, excipients used in ointments, creams, gels, solutions, emulsions, suspensions, lotions, external powders, etc., ie bases such as white petrolatum, yellow petrolatum, lanolin, white beeswax, cetyl alcohol, stearyl alcohol, stearic acid, hydrogenated oil, hydrocarbon gel, polyethylene glycol, liquid paraffin and squalene; solvents and solubilizing agents, such as oleic acid, isopropyl myristate, diisopropyl adipate, diisopropyl sebacate, glyceryl trisooctanoate, crotamiton, diethyl sebacate, hexyl laurate, a fatty acid, a fatty acid ester, an aliphatic alcohol, a vegetable oil and an alcohol; antioxidants, such as a tocopherol derivative, L-ascorbic acid, dibutylhydroxytoluene, and butylated hydroxyanisole; antiseptics such as p-hydroxybenzoate; humectants, such as glycerin, propylene glycol and sodium hyaluronate; surface active agents, such as a polyoxyethylene derivative, glycerol ester of a fatty acid, sucrose ester of a fatty acid, sorbitan ester of a fatty acid, propylene glycol of a fatty acid and lecithin; stabilizers such as thickening agents, such as carboxy vinyl polymer, xanthan gum, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose and hydroxypropyl methylcellulose; vegetables, such as potato starch, rice starch, corn starch, talc and zinc oxide; propellants, such as liquefied petroleum gas, liquefied carbon dioxide, dimethyl ether, nitrogen, kerosene and carbon dioxide; pH regulators; Corrective agents, suspending agents, emulsifiers, perfumes, preservatives, and other suitable excipients, can be mixed in these. The external preparations of the present invention are manufactured using the conventional method for external preparations such as combining each component and, if necessary, a base.

They are used by applying them in usual methods directly to the affected region, or they are suspended in or submerged in cloth, etc., to be applied in the affected region. To prepare ointments using grease, fatty oil, lanolin, wax, resin, plastics, glycol, a higher alcohol, glycerin, water, an emulsifier, a suspending agent or other suitable excipient such as a raw material, or using these materials as a base , an active ingredient is added in this, and the mixture is homogeneously mixed to prepare ointments. The base is fused by heating to uniformly mix and if necessary, an additive, such as an absorption enhancer, an antioxidant, an antiseptic, an active surface agent or purified water, is added thereto, and in addition, fine powders of the active ingredient, are mixed with these to prepare ointments or creams. For example, to prepare oleaginous ointments, after fusing by heating a base, mixing and partially cooling, the active ingredients other than the base are liquefied or the fine powders made are mixed with part of the base, and the remaining base is added in this . The resulting mixture is kneaded together until all parts become homogeneous. For example, to prepare emulsifying ointments and water-soluble ointments, after a solid base is fused in a water bath, it is maintained at about 75 ° C and water, in which a water-soluble base dissolves, is heated to this temperature or it is added to this a slightly higher temperature. Then, the mixture is homogeneously mixed to prepare it. For example, to prepare cataplasms, the active agents are pre-mixed with an ointment base mainly containing a water-soluble polymer, which is rich in water retention, such as gelatin, carmellose sodium, methylcellulose, and sodium polyacrylate. , and the mixture is expanded on a support such as a nonwoven fabric, a surface of the base is covered with a plastic film, such as polyethylene or polypropylene, and is cut to a desired size to prepare poultices. To prepare tapes, for adhesives such as acrylic resin, or styrene-isoprene-styrene block copolymers, thickeners are added such as saturated alicyclic hydrocarbon resin, such as rosin resin and terpene resin, softeners such as liquid rubber and liquid paraffin , absorption enhancers, an antioxidant, etc., and the mixture is dissolved in an organic solvent, such as toluene. The mixture is combined or fused under heating and mixed, and powdered or liquefied active ingredients are added thereto. The mixture is expanded on a release paper, and when the tape is a soluble type, after expansion and drying, it is laminated with a flexible support, such as a polyurethane film, a polyethylene film, a chloride film of polyvinyl, a woven fabric, and a non-woven fabric, and is cut to a desired size to prepare the tapes.

To prepare lotions, an active ingredient, a solvent, an emulsifier, a suspending agent, etc., are added to an aqueous liquid, and the mixture becomes homogeneous. With regard to suspensions-lotions, after an active ingredient is pulverized and is easily moistened in water by glycerin or ethanol, a solution of a suspending agent or a lotion base is gradually added to it, and the mixture is homogeneously mixed to prepare suspensions-lotions. With respect to emulsions-lotions, an oil-soluble drug and an oily phase are placed in a container, and the aqueous phase is placed in the other container, and both containers are heated. In the case of preparation of an Ag / Ac emulsion, an oily phase is gradually added to an aqueous phase, and in the case of producing an Ac / Ag emulsion, an aqueous phase is gradually added to an oily phase on the contrary, and the mixture it continues mixing until the emulsion is completely homogenized and serves as a homogeneous liquid. To prepare external powders, an active ingredient, an additive and excipients such as potato starch, rice starch, corn starch, talc and zinc oxide, are uniformly dispersed. To prepare aerosols, solutions containing an active ingredient, ointments, creams, gels, suspensions, emulsions, solutions, lotions, external powders, etc., are prepared in accordance with the methods mentioned above and are filled in a well-closed container with gas liquefied or compressed gas.

As a skin wound accompanied with pain which is the objective treatment of the external preparations of the present invention, there are mentioned for example, pandemic herpes, such as herpetic eczema, neonatal pandemic herpes and herpes of the fetus; herpes areata, such as herpes de lip or face, herpetic stomatitis, genital herpes, herpetic whitlow and herpes of natural incubation; varicella or zoster virus, such as hand-foot-mouth disease, infectious enterovirus disease (except for hand-foot-mouth disease); syndromes of skin or mucosal lesions, such as vesicles due to herpes simplex virus infection, enterovirus, etc., sore or ulcer; local pain or itching in these affected parts. Subsequently, although by examples of illustration and test examples in external preparations of this invention containing acetylsalicylic acid, the present invention should not be limited to these examples.

EXAMPLES 1 TO 2 (Ointments) In accordance with the formulation shown in Table 1, acetylsalicylic acid was added to a mixture of a base and a solvent, and the mixture was kneaded well under agitation to prepare ointments.

TABLE 1 Formulation of ointment containing acetylsalicylic acid EXAMPLES 3 AND 4 (Creams) In accordance with the formulation shown in Table 2, after a solid base is fused in a water bath, acetylsalicylic acid was added to it which is dissolved or dispersed in a solvent. To this is added an aqueous base which is dissolved in water and heated. The mixture is combined until it becomes homogeneous to prepare the creams.

TABLE 2 EXAMPLE 5 (Poultices) In accordance with the formulation shown in Table 3, a tackifier and a thickening agent are dissolved in a hot polyhydric alcohol. Afterwards they are cooled, to this is added acetylsalicylic acid and other additives, and the mixture is combined homogeneously. A crosslinking agent is added thereto to prepare an adhesive gel base. The gel base is sprayed on a support such as non-woven fabric and cut into a desired size to prepare poultices.

TABLE 3 Formulation of poultice containing acetylsalicylic acid EXAMPLE 6 (Powders) In accordance with the formulation shown in Table 4, potato starch, zinc oxide and acetylsalicylic acid are mixed until the mixture becomes homogeneous to prepare powders.

TABLE 4 Formulation of powder containing acetylsalicylic acid COMPARATIVE EXAMPLES 1 TO 3 In accordance with the formulation shown in Table 5, vidarabine (arabinoside adenine: antiviral agent) is homogenously mixed in white petrolatum to prepare ointments, and povidone iodide is dissolved in purified water to prepare solutions.

TABLE 5 Comparative Example EXAMPLE OF PROOF The effect was evaluated by administering an external preparation of the present invention containing aspirin, to patients (volunteers) who have symptoms of injury by viral infection such as gall bladder, sore or ulcers caused by an infection of the varicella zoster virus, herpes virus simple or enterovirus infection accompanied with pain and pruritus in said affected parts. The improvement in the lesion was evaluated by viral infection, such as vesicle, sore or ulcer, and pain and pruritus following five standard stages: A: remarkably effective, B: effective, C: slightly effective, D: no change and E: worse . In case of slightly cash or more than slightly cash, the cases are judged to be effective and the effectiveness is calculated.

EXAMPLE OF TEST 1 Improvement of pain and pruritus associated with skin or mucosal lesion caused by an infection of varicella zoster virus, herpes simplex virus or enterovirus To the affected party in patients (total of 32 patients) who have a lesion due to a viral infection such as a vesicle, sore or ulcer caused by an infection of the varicella zoster virus, herpes simplex virus or enterovirus associated with pruritus and pain, an external preparation containing aspirin is administered and the improvement in itching and pain is calculated. In addition, as controls, an ointment containing an active ingredient is administered which is used for such symptoms (Comparative Example 1) and disinfections are used for the treatment of symptoms of mucosal injury (Comparative Examples 2 and 3) and also evaluates the improvement in them. The sample result in table 6.

TABLE 6 Improvement in pain and pruritus in the affected part of a lesion due to a viral infection such as a vesicle, sore or ulcer caused by infection of the varicella zoster virus, herpes simplex virus or enterovirus.

As shown in the result in Table 6, Examples 1, and 5 containing aspirin, compared to Comparative Example 1, more or equally inhibit pain and pruritus in the affected parts of a symptom of injury by viral infection such as vesicle, sore or ulcer caused by an infection of varicella zoster virus, herpes simplex virus or enterovirus. On the other hand, Comparative Examples 2 and 3 show almost no inhibition in pain and pruritus.

EXAMPLE OF TEST 2 Improvement in a symptom of 'injury by viral infection such as gall bladder, sore or ulcer caused by infection of varicella zoster virus, herpes simplex virus or enterovirus To the affected parts of patients (total of 35 patients) who have a symptom of injury from a viral infection such as a vesicle, sore or ulcer, caused by varicella zoster virus infection, herpes simplex virus or enterovirus, a preparation is given externally containing aspirin, and the improvement of a symptom of injury due to viral infection such as a vesicle, sore or ulcer caused by varicella zoster virus infection, herpes simplex virus or enterovirus is evaluated. In addition, as controls, an ointment containing an active ingredient is administered which is used to treat such symptoms (Comparative Example 1) and disinfections are used to treat the symptoms of mucosal injury (Comparative Examples 2 and 3) and the improvement in them is also evaluated.

The results are shown in Table 7.

TABLE 7 Improvement in patients who have a symptom of injury from a viral infection such as a vesicle, sore or ulcer caused by varicella zoster virus infection, herpes simplex virus or enterovirus As shown in the result in Table 7, Examples 2, 3 and 6 containing aspirin, compared to Comparative Example 1, showed more or equally the therapeutic effect in a symptom of injury by viral infection such as vesicle, sore or ulcer, caused by an infection of varicella zoster virus, herpes simplex virus or enterovirus. On the other hand, Comparative Examples 2 and 3 show almost no inferior effect of the skin on them.

INDUSTRIAL APPLICABILITY Applying the external preparation of the present invention, with some side effects and without delaying the healing of a symptom of injury by viral infection, it becomes possible the improvement in a symptom of injury by viral infection such as vesicle, sore or ulcer caused by viral infection of varicella zoster virus, herpes simplex virus or enterovirus and inhibition of pain and pruritus in these affected parts.

Claims (12)

NOVELTY OF THE INVENTION CLAIMS

1. An external preparation containing acetylsalicylic acid or a pharmacologically acceptable salt thereof as an active ingredient, for the treatment of skin or mucosal lesion caused by a viral infection, together with an effect of inhibiting a pain or pruritus in said part affected

2. An external preparation containing acetylsalicylic acid or a pharmacologically acceptable salt thereof as an active ingredient, for the treatment of gallbladder, sore or ulcer of skin and mucosa caused by a viral infection together with an effect of inhibiting a pain or itching in said affected part.

3. The external preparation according to claim 1 or 2, further characterized in that the viral infection is due to varicella zoster virus, herpes simplex virus or enterovirus.

4. An external preparation containing acetylsalicylic acid, or a pharmacologically acceptable salt thereof as an active ingredient, for the treatment of a pain or pruritus in a part affected in the skin or mucosal lesion caused by a viral infection.

5. A preparation containing acetylsalicylic acid, or a pharmacologically acceptable salt thereof as an active ingredient, for the treatment of pain or pruritus in a part of the gallbladder, sore or ulcer of the skin or mucosa caused by a viral infection .

6. The external preparation according to claim 4 or 5, further characterized in that the virus infection is due to varicella zoster virus, herpes simplex virus or enterovirus.

7. The external preparation according to any of claims 1 to 6, further characterized in that the concentration of acetylsalicylic acid or a pharmacologically acceptable salt thereof is 0.05 to 80% by weight.

8. The use of acetylsalicylic acid or a pharmacologically acceptable salt thereof for the preparation of an external preparation for the treatment of skin or mucosal lesion caused by a viral infection in a patient.

9. The use of acetylsalicylic acid or a pharmacologically acceptable salt thereof for the preparation of an external preparation for the treatment of gallbladder, sore or ulcer of the skin or mucosa caused by a viral infection in a patient.

10. The use claimed in claim 8 or 9, wherein the viral infection is due to varicella zoster virus, herpes simplex virus or enterovirus.

11. The use of acetylsalicylic acid or a pharmacologically acceptable salt thereof for the preparation of an external preparation for the treatment of pain and pruritus in the skin or mucosal lesion caused by a viral infection in a patient.

12. The use claimed in claim 11, wherein the viral infection is due to varicella zoster virus, herpes simplex virus or enterovirus.