Topical composition

Abstract

[Problem] To provide a dressing material for moist wound healing, which has a novel function to promote wound healing. [Solution] Provided is a topical composition which comprises (A) nitrocellulose and (B) at least one alcohol selected from the group consisting of monohydric alcohols each having 1 to 4 carbon atoms and benzyl alcohol. The topical composition is used for moist wound healing in which a film formed by applying the topical composition to a wound surface is used as a dressing material.

Description

External composition

[0001] The present invention relates to a topical composition for moist wound healing.

[0002] Moist wound healing is a method of healing wounds by maintaining a moist wound surface. Wound healing by moist wound healing is achieved by retaining body fluids containing components that promote cell growth or regeneration at the wound site, thereby activating the animal's natural healing ability.

[0003] In other words, since the factors that hinder moist wound healing are "dryness" and "disinfection," the basic principles in wound treatment are "not to let the wound surface dry out" and "not to disinfect the wound surface" (Non-Patent Document 1).

[0004] In particular, the idea that wound surfaces should not be disinfected is based on the fact that disinfectants are indiscriminate cytotoxic agents that harm not only bacteria but also vital cells necessary for wound defense and repair, and this is now common knowledge in moist wound healing. The guidelines for the treatment of pressure ulcers published by the US Agency for Health Care Policy and Research (AHCPR) in 1994 also state that disinfectants should not be used even if there is infection (Non-Patent Document 2), and the Japanese Dermatological Association guidelines also warn that disinfectants can delay wound healing due to their tissue-damaging properties (Non-Patent Document 3).

[0005] Among the disinfectants for skin applications, representative examples of alcohol-based disinfectants include ethanol, isopropanol, benzyl alcohol, etc. It is also known that the toxicity of isopropanol is about twice as high as that of ethanol (Non-Patent Document 4).

[0006] In moist wound healing, dressing materials that can protect or close the wound surface and keep it moist, i.e., waterproof materials, are used. Specifically, polyurethane films or hydrocolloids are used as dressing materials (Non-Patent Document 3).

[0007] Liquid bandages are known as hygienic materials for protecting damaged skin, such as cracks, chapped skin, hangnails, and cuts. Liquid bandages are topical compositions in which the film-forming component nitrocellulose is dissolved in an alcohol-based solvent (e.g., isopropanol, ethanol, etc.) and an ester-based solvent (e.g., ethyl acetate, butyl acetate, etc.). The nitrocellulose material is also available as pyroxylin, a mixture of approximately 70% by weight of nitrocellulose and approximately 30% by weight of isopropanol. Such liquid bandages are commercially available, and instructions for use include that they should not be used on large or deep wounds, eczema, or bleeding areas (Non-Patent Document 5).

[0008] Yoshiro Ando, ​​Review: Future Wound Treatment - Approaches to Moist Wound Healing -, Communications Medicine, Vol. 67, No. 3, pp. 185-196 (2015). Shigeru Ichioka, Pros and Cons of Modern Wound Treatment, Wounds 4 (1): 1-2, 2013. Yuji Inoue et al., Guidelines for Wounds, Pressure Ulcers, and Burns - 1: General Wound Guidelines, Journal of the Japanese Dermatological Association, 127(8), 1659-1687, 2017. Garrison RF: Acute poisoning from the use of isopropyl alcohol in tepid sponging. JAMA 152: 317-318, 1953. Sakamcare a Liquid Bandage, Category 3 OTC Drug, Package Insert.

[0009] The function required for dressings used in moist wound healing is waterproofing. Hydrocolloids not only have waterproofing properties in the outer layer, but also have water absorption and gelling properties in the inner layer, but in either case, the function of dressings used in moist wound healing is moisture control. On the other hand, if there were a dressing that had a new function to promote wound healing in addition to the function of moisture control, it would be possible to supplement the wound healing effect due to the wound's self-healing ability and expect even greater wound healing effects.

[0010] Therefore, an object of the present disclosure is to provide a dressing material for moist wound healing that has a new function of promoting wound healing.

[0011] The inventors came up with the idea of ​​using liquid adhesive bandages, which have not previously been used in moist wound healing, as a moist wound healing dressing. Liquid adhesive bandages are generally not recommended for use on large or deep wounds that require moist wound healing. Furthermore, liquid adhesive bandages require an alcohol-based solvent (e.g., isopropanol, ethanol, etc.) to dissolve the film-forming component, nitrocellulose. Given that these alcohol-based solvents are also disinfectants, their use in moist wound healing is naturally contraindicated. However, when these liquid adhesive bandages were used in moist wound healing, they were found to heal wounds at an unexpectedly rapid rate. It was discovered that this rapid wound healing was promoted by the shrinkage of the application surface due to solvent evaporation during the formation of the nitrocellulose film, which causes the film to expand and contract, compressing and fixing the wound surface. This resulted in excellent wound healing effects, even when the disinfectant component contained in the liquid adhesive bandage was inevitably applied when the liquid adhesive bandage was applied to the wound. The present invention was completed through further investigation based on this finding.

[0012] That is, the present disclosure provides the following aspects of the invention. Item 1. A topical composition for moist wound healing, comprising (A) nitrocellulose and (B) at least one alcohol selected from the group consisting of monohydric alcohols having 1 to 4 carbon atoms and benzyl alcohol, and used for moist wound healing, wherein the composition is applied to a wound surface to form a film as a dressing. Item 2. The topical composition according to Item 1, wherein component (B) comprises isopropyl alcohol. Item 3. The topical composition according to Item 1 or 2, wherein the content of component (B) is 30 to 60 wt %. Item 4. The topical composition according to any one of Items 1 to 3, wherein the area of ​​the wound surface is 0.012% or more of the body surface area. Item 5. The topical composition according to any one of Items 1 to 4, wherein the wound is an erosion. Item 6. The topical composition according to any one of Items 1 to 4, wherein the wound is an ulcer. Item 7. The topical composition according to any one of Items 1 to 6, wherein the film is used as a compressive fixative for the wound surface. Item 8. Item 9. The topical composition according to any one of Items 1 to 7, which is used to proliferate keratinocytes in wound tissue. Item 10. The topical composition according to any one of Items 1 to 9, which is used to reduce inflammation in wound tissue. Item 11. The topical composition according to any one of Items 1 to 10, which is used to reduce neutrophil infiltration in wound tissue. Item 12. The topical composition according to any one of Items 1 to 11, which is used to increase macrophage influx in wound tissue. Item 13. The topical composition according to any one of Items 1 to 12, which is used to increase M2 macrophages in wound tissue.

[0013] According to the present disclosure, a moist wound healing dressing material having the function of promoting wound healing is provided.

[0014] 1 shows the healing rate of a wound treated with the topical composition of the present invention. 2 shows a microscopic image of an H&E-stained tissue section of a wound treated with the topical composition of the present invention after wound surface closure. 3 shows graphs showing the length a of hyperplastic epidermis, the distance b of the subcutaneous gap, and SEI in tissue of a wound treated with the topical composition of the present invention after wound surface closure. 4 shows a microscopic image of a Picro Mallory Trichrome-stained section of a wound treated with the topical composition of the present invention after wound surface closure. 5 shows a graph showing collagen signal intensity in tissue of a wound treated with the topical composition of the present invention after wound surface closure. 6 shows the results of immunohistochemical staining with Ki67 (a cell proliferation marker) in the early healing phase (inflammatory phase) of a wound treated with the topical composition of the present invention. 7 shows the results of quantification of Ki67-positive keratinocytes in the early healing phase (inflammatory phase) of a wound treated with the topical composition of the present invention. 8 shows the results of immunohistochemical staining of CD31 in the early healing phase (inflammatory phase) of a wound treated with the topical composition of the present invention.

[0033] Figure 1 shows the results of quantification of CD31-positive areas in the early healing stage (inflammatory phase) of wounds treated with the topical composition of the present invention.

[0034] Figure 2 shows the results of immunohistochemical staining of TNF-α in the early healing stage (inflammatory phase) of wounds treated with the topical composition of the present invention.

[0035] Figure 3 shows the results of quantification of TNF-α expression in the early healing stage (inflammatory phase) of wounds treated with the topical composition of the present invention.

[0036] Figure 4 shows the results of immunohistochemical staining of Ly6G in the early healing stage (inflammatory phase) of wounds treated with the topical composition of the present invention.

[0037] Figure 5 shows the results of immunohistochemical staining of Ly6G in the final healing stage of wounds treated with the topical composition of the present invention.

[0038] Figure 6 shows the results of immunohistochemical staining of F4 / 80 in the early healing stage (inflammatory phase) of wounds treated with the topical composition of the present invention.

[0033] Figure 1 shows the results of quantification of F4 / 80-positive cells in the early healing stage (inflammatory phase) of a wound treated with the topical composition of the present invention.

[0034] Figure 2 shows the results of immunohistochemical staining of F4 / 80 in the final healing stage of a wound treated with the topical composition of the present invention.

[0035] Figure 3 shows the results of quantification of F4 / 80-positive cells in the final healing stage of a wound treated with the topical composition of the present invention.

[0033] Figure 1 shows the results of immunohistochemical staining of tissue repair-related M2 macrophages (CD206 as a marker) in the early healing (inflammatory phase) of a wound treated with the topical composition of the present invention.

[0034] Figure 2 shows the results of quantification of CD206-positive cells in the early healing (inflammatory phase) of a wound treated with the topical composition of the present invention.

[0035] Figure 3 shows the results of immunohistochemical staining of CD206 in the final healing phase of a wound treated with the topical composition of the present invention.

[0036] Figure 4 shows the results of quantification of CD206-positive cells in the final healing phase of a wound treated with the topical composition of the present invention.

[0037] Figure 5 shows the healing rate of a wound treated with the topical composition of the present invention (Example 1). For comparison, the topical composition of Example 1 was applied to a smooth surface, rather than to the wound surface, and allowed to dry to form a film, which was used as a dressing to cover the wound surface and perform moist wound healing (Comparative Example 1), and the results of treatment with a film-forming liquid adhesive bandage using polyurethane (Comparative Example 2) are shown.

[0038] Figure 5 shows the results of an antibacterial test on a cell surface applied with the topical composition of the present invention (Example 1). 1 shows the results of an antibacterial test on a cell surface coated with a film-forming liquid adhesive bandage using polyurethane, and a control cell surface.

[0015] The topical composition of the present disclosure comprises (A) nitrocellulose (hereinafter also referred to as "ingredient (A)") and (B) a specific alcohol (hereinafter also referred to as "ingredient (B)"), and is characterized by being used in moist wound healing, with the film formed by application to the wound surface serving as a dressing. The topical composition of the present disclosure is described in detail below. In this specification, a numerical range indicated by two numbers and "to" includes the two numbers as the lower and upper limits. For example, the expression "2 to 15% by weight" means 2% by weight or more and 15% by weight or less.

[0016] (A) Nitrocellulose The topical composition of the present disclosure contains nitrocellulose as component (A). Nitrocellulose is a component that forms a coating when the topical composition of the present disclosure is applied to a wound surface of the skin.

[0017] The nitrocellulose used in the present disclosure is not particularly limited in terms of its molecular weight, nitrogen content, etc., as long as it is capable of forming a film on the wound surface of the skin, and any nitrocellulose that can be used as a film-forming component in general liquid bandages can be used.

[0018] Pyroxylin can also be used to blend component (A). Pyroxylin is nitrocellulose wetted with a solvent, and specifically, a mixture of about 70% by weight of nitrocellulose and about 30% by weight of isopropanol can be used. In the present disclosure, commercially available pyroxylin can also be used to blend component (A). Specific examples of commercially available pyroxylin include the pyroxylin sold by T.N.C. Industrial Co. , Ltd. RS 1 / 32 sec, RS1 / 16 sec, RS 1 / 8 sec, RS 1 / 8 L sec, RS 1 / 8 H sec, RS 1 / 4 sec, RS 1 / 4 H sec, RS 1 / 2 sec, RS 1 sec, RS 5~6 sec, RS 10-15 sec, RS 15-20 sec, RS 30-40 sec, RS 60-80 sec, RS 120 sec, RS 150 sec, RS 300 sec, RS 500 sec, RS 800 sec, RS 1200 sec, RS 2000 sec; RS 1 / 16, RS 1 / 8, RS 1 / 4, RS 1 / 2, RS 1, RS 2, RS 5, RS 7, RS 20, RS 60, RS 120, RS 500, RS 1000, RS 2000, etc. manufactured by KCNC Corporation. These may be used alone or in combination of two or more. In the present disclosure, when pyroxylin is used to blend component (A), the isopropanol contained in the pyroxylin constitutes at least a part of component (B).

[0019] In the topical composition of the present disclosure, the content of component (A) is not particularly limited as long as it is capable of forming a film on the wound surface of the skin, but examples include 0.5 to 14 wt% based on the total amount of the composition. From the viewpoint of improving the sealability of the wound surface, the content of component (A) is preferably 3.5 to 14 wt%, more preferably 5.6 to 14 wt%, even more preferably 6.5 to 14 wt%, even more preferably 7 to 14 wt%, and even more preferably 7.5 to 14 wt%. Furthermore, from the viewpoint of promoting wound healing by compressive fixation of the wound associated with film formation, the content of component (A) is preferably 3.5 to 11.2 wt%, more preferably 3.5 to 10 wt%, even more preferably 3.5 to 9 wt%, and even more preferably 3.5 to 8.7 wt%.

[0020] (B) Specific Alcohols The topical composition of the present disclosure contains, as component (B), at least one alcohol selected from the group consisting of monohydric alcohols having 1 to 4 carbon atoms and benzyl alcohol.

[0021] Specific examples of monohydric alcohols having 1 to 4 carbon atoms include methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, and tert-butanol. Among these, preferred are monohydric alcohols having 2 to 4 carbon atoms and benzyl alcohol, more preferred are ethanol, isopropanol, n-butanol, and benzyl alcohol, and more preferred are isopropanol and benzyl alcohol.

[0022] In the present disclosure, component (B) may be one of monohydric alcohols having 1 to 4 carbon atoms and benzyl alcohol, or two or more of them may be used in combination. In the present disclosure, component (B) preferably contains at least isopropanol.

[0023] In the topical composition of the present disclosure, the content of component (B) is not particularly limited, but may be, for example, 30 to 60 wt %, preferably 35 to 56 wt %, more preferably 40 to 53 wt %, and even more preferably 45 to 50 wt %.

[0024] When component (B) contains isopropanol, the isopropanol content is, for example, 15 to 54 wt %, preferably 30 to 50.5 wt %, more preferably 38 to 48 wt %, and even more preferably 42 to 46 wt %.

[0025] When the component (B) contains isopropanol, the content ratio of isopropanol per 100 parts by weight of the component (B) is, for example, 55 to 100 parts by weight, preferably 75 to 100 parts by weight, more preferably 80 to 100 parts by weight, and even more preferably 85 to 95 parts by weight.

[0026] The content ratio of the (A) component to the (B) component is not particularly limited, but the content of the (B) component per 1 part by weight of the (A) component is, for example, 2 to 70 parts by weight, preferably 2 to 10 parts by weight or 2 to 8 parts by weight, more preferably 3 to 7 parts by weight, even more preferably 4 to 6.5 parts by weight, and even more preferably 5 to 6 parts by weight.

[0027] (C) Specific Esters In addition to the above components, the topical composition of the present disclosure may further contain, as component (C), an ester of a monocarboxylic acid having 2 to 4 carbon atoms and a monohydric alcohol having 1 to 5 carbon atoms. The term "ester of a monocarboxylic acid having 2 to 4 carbon atoms and a monohydric alcohol having 1 to 5 carbon atoms" refers to a compound in which one molecule of a monocarboxylic acid having 2 to 4 carbon atoms is ester-bonded to one molecule of a monohydric alcohol having 1 to 5 carbon atoms.

[0028] Examples of monocarboxylic acids having 2 to 4 carbon atoms include acetic acid, lactic acid, propionic acid, butyric acid, etc. Among these monocarboxylic acids, preferred are monocarboxylic acids having 2 or 3 carbon atoms, more preferred are acetic acid and lactic acid, and even more preferred is acetic acid.

[0029] Examples of monohydric alcohols having 1 to 5 carbon atoms include methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, tert-butanol, benzyl alcohol, 1-pentanol, 3-methyl-1-butanol, 2-methyl-1-butanol, 2,2 dimethyl-1-propanol, 2-pentanol, 3-methyl-2-butanol, 3-pentanol, and 2-methyl-2-butanol. Among these alcohols, preferred are methanol, ethanol, n-propanol, isopropanol, n-butanol, 1-pentanol, and benzyl alcohol, and more preferred are ethanol, n-propanol, isopropanol, n-butanol, and 1-pentanol.

[0030] Specific examples of the component (C) include methyl acetate, ethyl acetate, propyl acetate (n-propyl acetate), isopropyl acetate, butyl acetate (n-butyl acetate), sec-butyl acetate, isobutyl acetate, pentyl acetate (1-pentyl acetate), ethyl lactate, butyl lactate, isoamyl acetate (3-methylbutyl acetate), ethyl butyrate, and ethyl propionate, of which ethyl acetate, butyl acetate, and ethyl lactate are preferred, and ethyl acetate and butyl acetate are more preferred.

[0031] In the topical composition of the present disclosure, as component (C), one of the above esters may be used alone, or two or more may be used in combination. When two or more esters are combined, two or more esters with different boiling points can be combined to adjust the film formation rate. Preferably, an ester with a boiling point of less than 100°C (e.g., ethyl acetate) can be combined with an ester with a boiling point of 100°C or higher (e.g., butyl acetate).

[0032] When the topical composition of the present disclosure contains component (C), the content of component (C) is not particularly limited, but may be, for example, 20 to 46 wt %, preferably 28 to 42 wt %, and more preferably 32 to 38 wt %.

[0033] (D) Plasticizer In addition to the above components, the topical composition of the present disclosure may further comprise a plasticizer as component (D), which can impart flexibility and / or stretchability to the coating formed on the wound surface of the skin.

[0034] The plasticizer used in the topical composition of the present disclosure is not particularly limited as long as it is pharmaceutically acceptable, and examples include vegetable oils, esters of mono-, di-, or tricarboxylic acids having 5 to 22 carbon atoms and monohydric alcohols having 1 to 9 carbon atoms, terpenoids, polyhydric alcohols, glycerin fatty acid esters, mineral oils, polyethers, polyesters, etc. Specific examples of the vegetable oils include castor oil, cottonseed oil, soybean oil, sesame oil, almond oil, fennel oil, corn oil, olive oil, orange oil, chamomile oil, cinnamon oil, wheat germ oil, safflower oil, perilla oil, citronella oil, ginger oil, spearmint oil, rice oil, clove oil, camellia oil, turpentine, spruce oil, rapeseed oil, peppermint oil, cedar oil, sunflower oil, bergamot oil, palm oil, eucalyptus oil, peanut oil, lavender oil, egg yolk oil, lemon oil, rose oil, turmeric oil, and Roman chamomile oil. Specific examples of the esters include isopropyl palmitate, isopropyl myristate, isopropyl stearate, ethyl linoleate, isopropyl linoleate, dimethyl phthalate, diethyl phthalate, dipropyl phthalate, dibutyl phthalate, dioctyl phthalate, diisobutyl adipate, diisopropyl adipate, diisononyl adipate, dioctyl adipate, diethyl sebacate, diisopropyl sebacate, dibutyl sebacate, triethyl citrate, tributyl citrate, and acetyltributyl citrate. Specific examples of the terpenoids include camphor, menthol, borneol, cineole, anethole, limonene, eugenol, geraniol, and peppermint oil. Specific examples of the polyhydric alcohols include propylene glycol, glycerin, and sorbitol. Specific examples of the glycerin fatty acid esters include glyceryl monostearate, glycerin monooleate, glycerin monomyristate, decaglyceryl laurate, and medium-chain fatty acid triglycerides.Specific examples of the mineral oils include silicone oil, liquid paraffin, and petrolatum.Specific examples of the polyethers include polyethylene glycol.Specific examples of the polyesters include polyester adipate.

[0035] In the topical composition of the present disclosure, the component (D) may be one of the above-mentioned plasticizers, or two or more of them may be used in combination. Among the above-mentioned plasticizers, preferred are vegetable oils, esters of mono-, di-, or tricarboxylic acids having 5 to 22 carbon atoms with monohydric alcohols having 1 to 9 carbon atoms, and terpenoids; more preferred are castor oil, isopropyl palmitate, isopropyl myristate, and camphor.

[0036] When the topical composition of the present disclosure contains component (D), the content of component (D) is not particularly limited, but may be, for example, 1 to 30 wt % based on the total amount of the preparation. Furthermore, from the viewpoint of achieving a good balance between the coating stretchability required for compressing and fixing the wound and the coating flexibility required for the coating to follow the movement of the skin, the content is preferably 3 to 20 wt %, more preferably 5 to 15 wt %, even more preferably 6 to 10 wt %, and even more preferably 7 to 9 wt %.

[0037] When an ester of a mono-, di-, or tricarboxylic acid having 5 to 22 carbon atoms and a monohydric alcohol having 1 to 9 carbon atoms is used as component (D), the content of the ester is, for example, 0.5 to 20 wt%, preferably 1 to 15 wt%, more preferably 2 to 9 wt%, even more preferably 3 to 7 wt%, and even more preferably 4 to 6 wt%. When a vegetable oil is used as component (D), the content of the vegetable oil is, for example, 0.1 to 7 wt%, preferably 0.3 to 5 wt%, more preferably 1 to 3 wt%, and even more preferably 1.5 to 2.5 wt%. When a terpenoid is used as component (D), the content of the terpenoid is, for example, 0.05 to 3.5 wt%, preferably 0.15 to 2.5 wt%, more preferably 0.5 to 1.5 wt%, and even more preferably 0.7 to 1.3 wt%.

[0038] Other Components The topical composition of the present disclosure may or may not further contain other solvents such as water, acetone, ethyl methyl ketone, diethyl ether, etc., as needed, to the extent that the effects of the present disclosure are not impaired.

[0039] Furthermore, the topical composition of the present disclosure may or may not contain other medicinal ingredients, such as angiogenic agents, anti-inflammatory agents, local anesthetics, analgesics, antihistamines, bactericides, antifungals, vitamins, moisturizers, whitening agents, tissue repair agents, skin protectants, keratin softeners, local irritants, antipruritics, astringents, UV protection agents, silicone gels, herbal extracts, amino acids, and minerals, as needed, to the extent that the effects of the present disclosure are not impaired. Among these medicinal ingredients, vitamins are preferred, and vitamin E is more preferred, specifically, tocopherol, tocotrienol, and tocopherol organic acid esters (e.g., tocopherol acetate). The topical composition of the present disclosure preferably contains only vitamin E as the other medicinal ingredient, more preferably only tocopherol organic acid esters, and even more preferably only tocopherol acetate.

[0040] Furthermore, the topical composition of the present disclosure may or may not contain additives such as thickeners, buffers, chelating agents, antioxidants, stabilizers, emulsifiers, preservatives, fragrances, refreshing agents, colorants, dispersants, fluidizing agents, thickening agents, adsorbents, moisturizers, humectants, moisture-proofing agents, and antistatic agents, as needed, to the extent that the effects of the present disclosure are not impaired.

[0041] Preparation Method The topical composition of the present disclosure can be prepared by mixing the desired amounts of the above-mentioned component (A) and component (B), as well as the component (C), component (D), other solvents, other medicinal ingredients, and / or additives, etc., which are blended as necessary.

[0042] Viscosity The viscosity of the topical composition of the present disclosure is not particularly limited, but examples thereof include a viscosity of 500 to 500,000 mPa·s at 20°C. From the viewpoint of imparting desirable compressive fixation ability to the film formed on the wound surface, the viscosity is preferably 1,000 to 100,000 mPa·s, more preferably 1,500 to 10,000 mPa·s, even more preferably 1,800 to 6,000 mPa·s, and even more preferably 2,000 to 4,500 mPa·s. Viscosity is measured as follows: First, 52 g of the solution is placed in a vial (NEG screw vial SV-50A, Sansho Co., Ltd.), sealed, and immersed in a water bath at 20°C for 30 minutes. Subsequently, a B-type viscometer, TVB-10 type viscometer (BL type, Toki Sangyo Co., Ltd.) with rotor No. 3 is operated at 12 rpm, and the value after 10 minutes is read.

[0043]

[0003] The topical composition of the present disclosure is liquid, but when applied to a wound, component (B) volatilizes, forming a film of component (A). The film of component (A) is water-resistant and forms in close contact with the wound surface, allowing it to heal the wound through moist wound healing without forming a skin. When applied to a wound, component (B), which is also a disinfectant, inevitably comes into contact with the wound surface, necessitating disinfection, which is contraindicated in moist wound healing. However, when a film is formed by component (A), the applied surface shrinks due to the evaporation of the solvent from component (B), etc., and the film expands and contracts, compressing and fixing the wound surface, thereby promoting wound healing. Therefore, even when component (B) is inevitably present when applied to a wound, excellent wound healing effects are achieved.

[0044] The topical composition of the present disclosure can be applied to skin wounds that are subject to moist wound healing. The wound is preferably a wound with a large area and / or a deep defect, and more preferably a wound with a large area and a deep defect.

[0045] For wounds with large wound areas, the wound surface area may be 0.012% or more of the body surface area. The topical composition of the present disclosure promotes wound healing by compressing and fixing the wound surface as the application area shrinks due to the solvent evaporation of component (B) and other components during the formation of a film by (A). Therefore, the larger the wound surface, the more easily the effect of compression and fixation can be enjoyed. From this perspective, the wound surface area is preferably 0.015% or more of the body surface area, more preferably 0.018% or more, 0.02% or more, or 0.025% or more, even more preferably 0.03% or more, 0.035% or more, or 0.04% or more, and even more preferably 0.045% or more, or 0.05% or more. The upper limit of each of these wound surface area ranges is not particularly limited, and examples thereof include 0.2% or less of the body surface area, preferably 0.1% or less, more preferably 0.08% or less, and even more preferably 0.06% or less.

[0046] A specific wound surface area is, for example, 2 cm when applied to a human. 2 More than 2.5 cm, preferably 2 More than 3 cm, preferably 2 More preferably, 3.5 cm 2 More than 3.8 cm 2 Above, 4.5cm 2 or more, or 5 cm 2 More preferably, 6 cm 2 Above, 6.5cm 2 More than 7cm 2 Above, 7.5cm 2 More than 8cm 2 or more, or 8.5 cm 2 The upper limit of the area of ​​each of these wound surfaces is not particularly limited, but for example, 25 cm 2 Less than 15 cm, preferably 2 Less than 10 cm, more preferably 2 Less than 9 cm, more preferably 2 The following are included:

[0047] Specific examples of deep defects include wounds with abrasion defects down to the basal layer (more specifically, erosion) and wounds with a defect beyond the dermis (more specifically, skin ulcers).

[0048] The cause of erosion is not particularly limited, but examples include erosion caused by skin damage due to infection, pressure, irritation, or temperature, preferably erosion caused by skin damage due to pressure, irritation, or temperature, and more preferably erosion caused by skin damage due to pressure or irritation.

[0049] The cause of skin ulcers is not particularly limited, but examples include skin ulcers caused by skin damage due to infection, pressure, irritation, or temperature, preferably skin ulcers caused by skin damage due to pressure, irritation, or temperature, and more preferably skin ulcers caused by skin damage due to pressure or irritation.

[0050] As described above, the topical composition of the present disclosure promotes wound healing by expanding and contracting the coating as the application surface shrinks due to solvent evaporation of component (B) etc., during the formation of a coating by component (A), thereby compressing and fixing the wound surface. Therefore, the topical composition of the present disclosure also uses the coating of component (A) formed on the wound surface as a compressive fixative for the wound surface.

[0051] Furthermore, the topical composition of the present disclosure forms a water-resistant coating of component (A) on the wound surface with high adhesion, and this coating compresses and fixes the wound surface, thereby enabling keratinocyte proliferation and reduction of inflammation in wound tissue during the early stage of wound healing, i.e., the inflammatory stage. These effects are thought to contribute to the promotion of wound healing. Therefore, the topical composition of the present disclosure can be used to promote keratinocyte proliferation in wound tissue and to reduce inflammation in wound tissue.

[0052] Furthermore, the topical composition of the present disclosure can increase the amount of collagen in wound tissue after the inflammatory phase. This effect allows collagen fibers to assume a randomly organized basketweave orientation during wound tissue reorganization, which is thought to contribute to the suppression of scar hypertrophy (the suppression of the development of hypertrophic scars). Therefore, the topical composition of the present disclosure can also be used to increase the amount of collagen in wound tissue.

[0053] The topical composition of the present disclosure is usually applied to both the wound surface and the surrounding normal skin. Preferably, the application area is 1.2 times or more, 1.6 times or more, or 2 times or more, preferably 2.5 times or more, 3 times or more, or 3.5 times or more, more preferably 4 times or more, 4.5 times or more, or 5 times or more, and even more preferably 5.5 times or more, or 6 times or more of the area of ​​the wound surface. The upper limit of each of these application areas is not particularly limited, and examples thereof include 60 times or less, 50 times or less, 40 times or less, 30 times or less, 20 times or less, 10 times or less, or 8 times or less of the area of ​​the wound surface.

[0054] The method for applying the topical composition of the present disclosure to the skin is not particularly limited, and examples thereof include application with fingers, direct application using the opening of a tube container, and application using a tool such as a spatula or a brush (preferably a brush).To increase convenience for users, the topical composition of the present disclosure is desirably provided in a container equipped with a tool such as a spatula or a brush (preferably a brush).

[0055] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0056] Test Example 1 [1] Preparation of topical composition The components shown in the table below were mixed to prepare a topical composition.

[0057] It was confirmed that the topical composition of Example 1 has a viscosity of 2000 to 4500 mPa·s at 20°C, and has the property that, assuming an applied area of ​​100%, the coating area formed by evaporation of the solvent decreases (shrinks) to 34%.

[0058] [2] Wound Healing Test [2-1] Test Method [2-1-1] Grouping Mice (8 weeks old) were divided into two groups: a control (untreated) group and a group treated with the topical composition of Example 1 (10 mice per group). Elizabethan collars (E-collars) were used to prevent the mice from licking or scratching the affected area. The mice used in the test were trained to wear the E-collars for 5 days before the test.

[0059] [2-1-2] Wound Creation Mice were anesthetized using isoflurane (3-5%) inhalation, and the loss of pedal reflex and respiratory rate were monitored. Under anesthesia, the back hair of the mouse was shaved and disinfected with 70% ethanol. The mouse was then placed in a lateral position and the skin was folded over. A punch (4 mm diameter) was slowly driven into the folded skin to excise the entire thickness of the skin, creating a wound. The development of an ulcer-equivalent wound (4 mm diameter, 0.054% of the body surface area) was confirmed by excising the entire thickness of the skin and confirming the exposure of the subcutaneous muscle at the wound surface.

[0060] [2-1-3] Treatment Using a clean small brush, the topical composition of Example 1 was applied to a 10 mm diameter circular area (6.25 times the area of ​​the wound surface) centered on the 4 mm diameter wound surface, including the surrounding normal skin. The topical composition formed a film upon evaporation of the solvent, and the formed transparent, water-resistant film occlusively covered the wound surface. Until the wound was completely healed, the film was removed using ethyl acetate, and the topical composition of Example 1 was applied and coated to a 10 mm diameter circular area centered on the wound surface, including the surrounding normal skin, as described above, every four days. Meanwhile, the wounds in the control group were left open during the wound healing process.

[0061] [2-1-4] Observation of the appearance of the wound surface and evaluation of the wound healing rate During the wound healing process, the appearance of the wound surface was observed, and the size of the wound surface was measured using software. The relative value (%) of the wound surface size at each observation point was calculated, with the size of the wound surface immediately after wound initiation being set at 100%. The results are shown in Figure 1. During this procedure, mice were briefly anesthetized using isoflurane (3%) inhalation.

[0062] [2-1-5] Histological Evaluation of Skin at the End of Treatment. Mice were euthanized on the day when wound closure was confirmed. Tissue from the wound site was collected using standard protocols, fixed in 4% paraformaldehyde, dehydrated in ethanol and xylene, and embedded in paraffin. Paraffin-embedded tissue was sectioned to a thickness of 4 μm. Tissue sections from the wound healing site were stained with hematoxylin and eosin (H&E) and observed under a microscope. Scar size, including the length of the hyperplastic epidermis and the intersubcutaneous gap, was histologically analyzed. Furthermore, the scar elevation index (SEI) was calculated according to a published method (Molecular Medicine Reports. 16 (2017) 4643-4649, Exp Cell Res. 418 (2022) 113263).

[0063] Tissue sections from the wound healing site were stained with Picro Mallory Trichrome and observed under a microscope to confirm the orientation of collagen fibers. Furthermore, the intensity of the collagen signal (blue staining) was measured, normalized by the total measurement area, and calculated as a multiple of the control group.

[0064] [2-1-6] Histological and Immunological Evaluation of Skin at Early Stage of Treatment. Mice were euthanized on day 4 of the study, and tissue sections (4 μm) were prepared from the wound site as described in section 2-1-5 above. These tissue sections were then subjected to immunohistochemical staining. Citrate buffer (pH 6) was primarily used for heat-induced antigen retrieval, while Tris-EDTA buffer (pH 9) was used for CD31 staining. After blocking, the tissues were incubated with primary antibodies overnight at 4°C. Primary antibodies, including anti-Ki67 polyclonal antibody (ab15580, Abcam) and anti-tumor necrosis factor α (TNF-α) polyclonal antibody (ab9739, Abcam), were used at a 1:200 dilution, while anti-CD31 monoclonal antibody (77699, Cell Signaling Technology) was used at a 1:100 dilution. After washing, the tissues were incubated with secondary antibodies at room temperature for 1 hour. Horseradish oxidase (HRP)-conjugated goat anti-rat IgG (ab97057, Abcam) or HRP-conjugated goat anti-rabbit IgG (7074, Cell Signaling Technology) was used at a 1:200 dilution, and signals were detected using ImpactDAB substrate (SK-4105, Vector Lab).

[0065] Immunostained tissue images showed that the levels of TNF-α and endothelial cells (CD31 + The density of Ki67 was quantified from the signal intensity per measurement area and calculated as a multiplication factor of the control value. For quantification of other parameters, signal particles in an area of ​​30 square microns (Ki67) were counted, and the number / percentage of signal-positive cells per measurement area was calculated.

[0066] [2-1-7] Immunological Evaluation of Skin at the Initial and End of Treatment The tissue sections from the wound surface on the day of closure, as used in section 2-1-5 above, and the tissue sections from the fourth day of the study, as used in section 2-1-6 above, were used. Citrate buffer (pH 6) was primarily used for heat-induced antigen retrieval. After blocking, the tissues were incubated with primary antibodies overnight at 4°C. Primary antibodies, including anti-Ly6G monoclonal antibody (551459, BD Biosciences), anti-F4 / 80 monoclonal antibody (70076, Cell Signaling Technology), and anti-CD206 monoclonal antibody (24595, Cell Signaling Technology), were used at a 1:200 dilution, while anti-CD31 monoclonal antibody (77699, Cell Signaling Technology) was used at a 1:100 dilution. After washing, the tissues were incubated with secondary antibodies at room temperature for 1 hour. Horseradish oxidase (HRP)-conjugated goat anti-rat IgG (ab97057, Abcam) or HRP-conjugated goat anti-rabbit IgG (7074, Cell Signaling Technology) was used at a 1:200 dilution, and signals were detected using ImpactDAB substrate (SK-4105, Vector Lab).

[0067] From the images of the immunostained tissues, signal particles were counted in an area of ​​45 square microns (Ly6G, F4 / 80, and CD206), and the number / percentage of signal-positive cells per measured area was derived.

[0068] [2-2] Results [2-2-1] Appearance of the Wound Surface In the control group, the formation of wound eschar was observed from day 1 after the injury. On the other hand, no wound eschar formation was observed in the treatment group. In other words, it was confirmed that the wound surface remained moist in the treatment group.

[0069] [2-2-2] Wound healing rate in the early stage of treatment As shown in Figure 1, the treatment group showed a significant promotion effect on wound healing. Specifically, a rapid healing effect was observed, with the wound area falling below 60% on day 1 and falling to about 40% on day 4. It was unexpected that such rapid wound healing was possible despite the fact that the topical composition of Example 1 contains isopropyl alcohol, which delays wound healing. Furthermore, this wound healing rate exceeded the rate expected from conventional moist wound healing (see Test Example 2 [1]).

[0070] As described above, the topical composition of Example 1 applied to the treatment group has the property that, assuming an application area of ​​100%, the coating area formed by solvent evaporation decreases (shrinks) to 34%. In other words, the topical composition of Example 1 has a unique property not found in conventional moist wound healing dressings: it can compress and fix the wound surface by applying it to the wound surface and shrinking during film formation while adhering to the wound surface. The significant wound healing promotion effect observed in Figure 1 is thought to be due not only to the effects of conventional moist wound healing, but also to the compressive fixation effect of the liquid topical composition on the wound surface, which is achieved by film formation on the wound surface. Furthermore, despite the fact that the topical composition of Example 1 contains isopropyl alcohol, which inherently contributes to prolonged wound healing, the significant wound healing promotion effect observed in Figure 1 is thought to be due to the significant contribution of the compressive fixation effect.

[0071] From the above, it was shown that the topical composition of Example 1 acts as an occlusive dressing that compresses and fixes the wound surface by forming a film on the wound surface, thereby causing the wound to contract early and promoting wound closure.

[0072] [2-2-3] Histological Analysis of Skin at the End of Treatment Figure 2A shows a microscopic image of an H&E-stained tissue section after wound closure. In Figure 2A, the length of the upper bar marked "a" in each photograph represents the length of the hyperplastic epidermis, and the length of the lower bar marked "b" represents the distance of the subcutaneous gap. The scale bar at the bottom right indicates 500 μm. Figure 2B is a graph showing the length of the hyperplastic epidermis (a), the distance of the subcutaneous gap (b), and SEI for the control group (n = 10) and the treatment group (n = 10). Bars represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (*p < 0.05, **p < 0.01).

[0073] As shown in Figure 2A, stained scar tissue histologically demonstrated complete wound closure. As shown in Figure 2B, the size of the upper scar (length of the hyperplastic epidermis a) was similar in the control and treatment groups, but the depth of the scar (distance of the subcutaneous gap b) was significantly smaller in the treatment group than in the control group. Furthermore, the scar elevation index (SEI) was significantly reduced in the treatment group compared to the control group, confirming a significant suppression of hypertrophic scar formation.

[0074] Figure 2C shows a micrograph of a Picro Mallory Trichrome-stained section after wound closure. The scale bar in the lower right corner of Figure 2C indicates 200 μm. Figure 2D is a graph showing the fold change in collagen signal intensity (control group = 1) for the control group and the treatment group (n = 10). Bars represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (*p<0.05, **p<0.01).

[0075] As shown in Figure 2C, control scars showed parallel orientation of collagen fibers, whereas treated scars showed a randomly organized basketweave orientation of collagen fibers, indicating better reorganization. Furthermore, as shown in Figure 2D, treated scars showed a significant 33% increase in collagen content compared to control scars.

[0076] [2-2-4] Histological Analysis of Skin in the Early Stage of Treatment Figure 3A shows the results of immunohistochemical staining for Ki67 (a cell proliferation marker) in wounds on day 4 after injury. The scale bar in Figure 3A is 50 pm. Figure 3B also shows the quantification results (n = 6) of Ki67-positive keratinocytes in wounds on day 4 after injury. Bar graphs represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (*p < 0.05, **p < 0.01).

[0077] As shown in Figure 3A, the treatment group had more Ki67 (cell proliferation marker) keratinocytes than the control group. As shown in Figure 3B, the treatment group had significantly more Ki67 (cell proliferation marker) keratinocytes than the control group. From the above, it is believed that the topical composition of Example 1 contributed to promoting wound healing through keratinocyte proliferation, at least in the early stages of wound healing.

[0078] [2-2-5] Immunological Analysis of Skin at Early Stage of Treatment Figure 4A shows the results of immunohistochemical staining for CD31 in wounds on day 4 after injury. In Figure 4A, the scale bar represents 100 μm. Figure 4B shows the quantification results (n=6) of CD31-positive areas in wounds on day 4 after injury. Figure 4C shows the results of immunohistochemical staining for TNF-α in wounds on day 4 after injury. In Figure 4C, the scale bar represents 50 μm. Figure 4D shows the quantification results (n=6) of TNF-α expression in wounds on day 4 after injury. Bar graphs represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (**p<0.01).

[0079] As shown in Figures 4A and 4B, the CD31-positive area in the treatment group only tended to increase compared to the control group, but as shown in Figures 4C and 4D, a significant decrease (50% decrease) in TNF-α expression was observed in the treatment group compared to the control group. In other words, it was found that the topical composition of Example 1 reduced inflammation in the wound during the inflammatory phase by forming a film on the wound surface.

[0080] [2-2-6] Immunological Analysis of Skin at Early and End of Treatment Figure 5A shows the results of immunohistochemical staining of Ly6G in the wound on day 4 after injury (early treatment), and Figure 5B shows the quantification of Ly6G-positive signals (n = 6). Figure 5C shows the results of immunohistochemical staining of Ly6G in the wound site on the day of wound closure (end of treatment), and Figure 5C shows the quantification of Ly6G-positive cells (n = 10). In Figures 5A and 5C, the scale bars indicate 50 pm. Bar graphs in Figures 5B and 5D represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (**p < 0.01).

[0081] At the early stage of treatment, Ly6G-positive cells were mainly present in the eschar in the control group, as shown in Figure 5A, whereas in the treatment group, only a small amount was distributed in the granulation tissue due to the absence of eschar formation. Quantitative analysis of neutrophil infiltration at the early stage of treatment showed a significant decrease (80% decrease) in the treatment group compared to the control group, as shown in Figure 5B. Meanwhile, at the end of treatment, no significant difference was observed between the control and treatment groups, as shown in Figures 5C and 5D. In other words, the topical composition of Example 1 was found to form a film on the wound surface, thereby reducing neutrophil infiltration at the wound surface at the early stage of treatment (inflammatory phase).

[0082] Figure 6A shows the results of immunohistochemical staining for F4 / 80 in the wound on day 4 after injury (early treatment), and Figure 6B shows the quantification of F4 / 80-positive cells (n = 6). Figure 6C shows the results of immunohistochemical staining for F4 / 80 in the wound site on the day of wound closure (end of treatment), and Figure 6C shows the quantification of F4 / 80-positive cells (n = 10). The scale bars in Figures 6A and 6C represent 50 pm. Bar graphs in Figures 6B and 6D represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (**p < 0.01).

[0083] At the early stage of treatment, the treatment group showed a significant increase in macrophage influx (50% increase) compared to the control group, as shown in Figures 6A and 6B. However, at the end of treatment, there was no significant difference in macrophage numbers between the control and treatment groups, as shown in Figures 6C and 6D.

[0084] Immunohistochemical staining results for tissue repair-related M2 macrophages (CD206 as a marker) in wounds on day 4 after injury (early treatment period) are shown in Figure 7A, and quantification results for CD206-positive cells (n = 6) are shown in Figure 7B. Furthermore, immunohistochemical staining results for CD206 in the wound site on the day of wound closure (end of treatment period) are shown in Figure 7C, and quantification results for CD206-positive cells (n = 10) are shown in Figure 7C. The scale bars in Figures 7A and 7C represent 50 pm. Bar graphs in Figures 7B and 7D represent the mean ± SEM. Data were analyzed by one-way analysis of variance with Tukey's multiple comparison test (*p < 0.05).

[0085] As shown in Figures 7A and 7B, there was no significant difference in M2 macrophages (CD206 as a marker) between the control and treatment groups at the early stage of treatment. However, at the end of treatment, there was a significant increase (50% increase) in M2 macrophages in the treatment group compared to the control group.

[0086] From the above, it is considered that the topical composition of Example 1 formed a coating on the wound surface, thereby attenuating inflammation and neutrophil infiltration while increasing wound macrophages during the inflammatory phase of the wound healing process, and promoting an increase in tissue repair-related M2 macrophages toward the end of the treatment period, thereby accelerating wound healing.

[0087] [Test Example 2] [1] Wound Healing Test Three groups (Example 1 group, Comparative Example 1 group, and Comparative Example 2 group) were selected using the same method as in "2-1-1 Grouping" in "2 Wound Healing Test" in Test Example 1. The Example 1 group was treated with the topical composition of Example 1 used in Test Example 1, and the tests were repeated up to "2-1-4 Observation of the Appearance of the Wound Surface and Evaluation of the Wound Healing Rate." The Comparative Example 1 group was treated with a film formed by applying the topical composition of Example 1 to a smooth surface, not the wound surface, and drying the film. The wound surface was covered with the film and subjected to moist wound healing. The Comparative Example 2 group was treated with the same procedure as the Example 1 group, except that a film-forming liquid bandage using polyurethane was used instead of the nitrocellulose of the topical composition of Example 1.

[0088]

[0089] For Example 1 group, Comparative Example 1 group, and Comparative Example 2 group, the relative values ​​(%) of the wound surface size at each observation time were calculated, assuming that the size of the wound surface immediately after wound initiation was 100%. The results are shown in Figure 8.

[0090] As shown in Figure 8, the Example 1 group showed a rapid healing effect.Compared with the Comparative Example 1 group, the effect of the Example 1 group is considered to be not only the effect of normal moist wound healing, but also the compressive fixation effect of the wound surface by forming a film with the liquid topical composition on the wound surface.Furthermore, compared with the Comparative Example 2 group, the effect of the Example 1 group is considered to be a unique effect due to the selection of nitrocellulose as the film-forming component of the film-forming liquid adhesive bandage.

[0091] [2] Water Resistance Test The water resistance of the coatings formed by the topical compositions of Example 1 and Comparative Example 2 was tested. Specifically, the topical composition of Example 1 or Comparative Example 2 was applied to a liquid penetration indicator seal that changes color from white to red when wet to form a coating, and the seal was then submerged in water for 10 minutes.

[0092] After 24 hours, the color of the indicator seal for Example 1 remained white, confirming excellent water resistance. On the other hand, the color of the indicator seal for Comparative Example 2 had turned red, confirming poor water resistance. In other words, the rapid healing effect of Example 1 group confirmed in Figure 8 is thought to be due to the excellent moist environment provided by the excellent water resistance of the coating.

[0093] [3] Antibacterial Test The antibacterial properties of the films formed by the topical compositions of Example 1 and Comparative Example 2 were tested.

[0094] [3-1] Expansion culture of bacteria Staphylococcus aureus was expanded using Nutrient Broth (BD234000) and stored frozen.

[0095] [3-2] Measurement of bacterial concentration The number of colonies in the stored bacterial solution was counted using the pour plate method on mannitol salt medium. As a result, the concentration of the bacterial solution was 8.5 x 10 8 CFU / mL.

[0096] [3-3] Staining of bacterial suspension 1. Immediately before use, the stored bacterial suspension (8.5 × 10 8 CFU / mL) and 1.5 mL of PBS were added to 4 mL of the medium. 8 The bacterial count was adjusted to CFU / mL. 2. 82.5 μL of CFDA was added to 5.5 mL of the prepared bacterial solution, and the solution was left to stand at room temperature for 15 minutes in the dark. 3. The solution was centrifuged at 500 × g for 5 minutes. 4. The supernatant was removed, and 5 mL of PBS was added and washed twice. 5. The solution was resuspended in 5.5 mL of PBS and used as a bacterial suspension.

[0097] [3-4] Antibacterial Effect Test 1. Cell growth medium was added to each well of a 12-well plate, and a TC insert was placed in the well. 2. 1 x 10 5 500 μL of a normal epidermal keratinocyte suspension adjusted to 100 cells / mL was seeded inside the TC insert. 3. The cells were cultured in the TC insert until they became confluent. 4. 500 μL of 4% paraformaldehyde phosphate buffer was added to the culture medium, and the culture was left to stand at room temperature for 30 minutes to fix the cells. 5. The cells were washed with PBS to remove the paraformaldehyde phosphate buffer. 6. The topical composition of Example 1 or BETADINE (R) 300 μL of a liquid adhesive bandage (similar to Comparative Example 2, in which the film-forming component is polyurethane) was applied to the cell surface. 300 μL of PBS was added to the control (n=3 for each). 7. After visually confirming that the specimen had solidified, 500 μL of a bacterial suspension in which live bacteria had been previously stained with CFDA was added to the inside of the TC insert and allowed to stand at room temperature for 30 minutes. 8. The bacterial suspension was removed, and the inside of the TC insert was washed with PBS. 9. The specimen was peeled off with tweezers. 10. The cells (bright field) and live bacteria (fluorescence) were observed and photographed under a fluorescence microscope, and a composite photograph of the cells and bacteria was created. A similar composite photograph was also created for a control in which the same procedure was performed except that no coating film was formed.

[0098] [3-5] Results The results of the application of the topical composition of Example 1 are shown in FIG. 9A. (R)The results for the coating film are shown in Figure 9B, and the control in Figure 9C. Fluorescent bright spots indicating live bacteria were observed in Figures 9B and 9C, but no such bright spots were observed in Figure 9A. In other words, the rapid healing effect observed in Figure 8 for Example 1 group is thought to be due to the provision of a highly antibacterial moist environment due to the excellent antibacterial properties of the coating film.

[0099] Formulation Examples Topical compositions with the formulations shown in Table 3 were produced in the same manner as in Example 1. All of the obtained topical compositions formed a film on the wound surface, thereby achieving the effect of promoting wound healing, the effect of increasing keratinocyte proliferation and inflammation reduction during the inflammatory phase, and the effect of increasing collagen amount after the inflammatory phase.

[0100]

Claims

1. A topical composition for use in moist wound healing, which contains (A) nitrocellulose and (B) at least one alcohol selected from the group consisting of monohydric alcohols having 1 to 4 carbon atoms and benzyl alcohol, and which is applied to a wound surface to form a film that serves as a dressing.

2. The topical composition according to claim 1, wherein component (B) comprises isopropyl alcohol.

3. The topical composition according to claim 1, wherein the content of component (B) is 30 to 60% by weight.

4. The topical composition according to claim 1, wherein the area of ​​the wound surface is 0.012% or more of the body surface area.

5. The topical composition according to claim 1, wherein the wound is an erosion.

6. The topical composition of claim 1, wherein the wound is an ulcer.

7. The topical composition according to claim 1, wherein the coating is used as a compressive fixative for the wound surface.

8. The topical composition according to claim 1, which is used to proliferate keratinocytes in wound tissue.

9. The topical composition according to claim 1, used to reduce inflammation in wound tissue.

10. The topical composition according to claim 1, which is used to increase collagen content in wound tissue.

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