KR20230145664A - Antifungal composition containing vanillin as effective component - Google Patents

Abstract

The present invention relates to an antifungal composition against pathogenic fungi containing vanillin as an active ingredient, and the vanillin of the present invention is used in the treatment of Trichophyton mentagrophyte , Malassezia pachydermatis , and Malassezia. It had excellent antifungal activity against Malassezia restricta and Malassezia globosa , and in particular, the antifungal effect of o -vanillin was more pronounced than that of p -vanillin, so vanillin, especially o -vanillin, contained The composition of the present invention can be usefully used as an antifungal agent against pathogenic fungi.

Description

Antifungal composition containing vanillin as effective component {Antifungal composition containing vanillin as effective component}

The present invention relates to an antifungal composition against pathogenic fungi containing vanillin as an active ingredient.

Fungi are a type of microorganism. It exists in nature in the form of mold or yeast. There are many types of fungi, but there are about 40 types that parasitize the human body and cause disease. Infections caused by fungi are called mycosis. Depending on the site of infection, there are two types of mycosis: superficial mycosis, which causes infection limited to the surface of the skin, such as the skin, hair, and nails, and deep-seated mycosis, which causes infection in the deep part of the skin or internal organs such as the lungs and brain. It can be shared. Among mycoses, there are cases where fungi residing in our body become pathogenic in patients with weakened immune function, and this is called opportunistic mycosis. Opportunistic mycoses are likely to appear in immunocompromised patients, such as patients who have undergone bone marrow transplant, organ transplant, major surgery, immunosuppressive therapy, cancer patients, acquired immune deficiency syndrome, elderly people, or premature infants.

Fungi that cause superficial infections include dermatophytes (causing ringworm on the feet, head, body, perineum, and nails), Malassezia (causing tinnitus), and Candida (causing candidiasis). Fungi that cause deep mycosis include Candida, Aspergillus, Cryptococcus, and Muco.

Antifungal drugs are drugs that treat fungal infections by inhibiting the proliferation and growth of fungi. In the case of superficial fungal infections where the infected area is limited to the skin, external antifungal agents are used, but in cases where the infected area is extensive or deep fungal infections, injections or oral antifungal agents are used.

However, the number of antifungal drugs available to date is much smaller than the number of antibiotics used for bacterial infections. Antifungal agents developed to date include polyene-based amphotericin B and azole-based fluconazole, itraconazole, voriconazole, and posaconazole for the treatment of systemic mycosis, but the emergence of azole-resistant bacteria has become a problem. Therefore, the development of new effective and safe antifungal agents is required.

Meanwhile, Korean Patent No. 0649121 discloses a complex antifungal agent containing pear extract essential oil and ketoconazole as active ingredients and a method of treating Trichophyton fungi using the complex antifungal agent, and Korean Patent No. 1951649 Although a method for producing an extract of Japanese knotweed with increased resveratrol content and an antifungal composition containing the same for fungi of the genus Malassezia are disclosed, the vanillin of the present invention, specifically, for pathogenic fungi containing o -vanillin as an active ingredient, is disclosed. There has been no disclosure regarding antifungal compositions.

The present invention was developed in response to the above needs, and provides an antifungal composition against pathogenic fungi containing vanillin, specifically o -vanillin, as an active ingredient, and wherein o -vanillin is more effective against pathogenic fungi than p -vanillin. The present invention was completed by confirming that the antifungal effect was significant.

In order to solve the above problems, the present invention provides an antifungal agent against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp. containing vanillin or an acceptable salt thereof as an active ingredient. A composition is provided.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of diseases caused by any one pathogenic fungal infection selected from seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, and ringworm, containing vanillin or an acceptable salt thereof as an active ingredient. to provide.

In addition, the present invention provides an antifungal cosmetic composition against one or more pathogenic fungi selected from Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient. .

In addition, the present invention provides an antifungal health functional food composition against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp. containing vanillin or an acceptable salt thereof as an active ingredient. to provide.

In addition, the present invention provides an antifungal adjuvant against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient.

In addition, the present invention provides a method of administering a pharmaceutically effective amount of vanillin to an individual other than a human, comprising: administering a pharmaceutically effective amount of vanillin to an individual other than a human; selecting from Trichophyton spp. and Malassezia spp. An antifungal method is provided for infection by one or more pathogenic fungi.

The present invention relates to an antifungal composition against pathogenic fungi containing vanillin as an active ingredient, and the vanillin of the present invention is used in the treatment of Trichophyton mentagrophyte , Malassezia pachydermatis , and Malassezia. It had excellent antifungal activity against Malassezia restricta and Malassezia globosa , and in particular, the antifungal effect of o -vanillin was more remarkable than that of p -vanillin.

In order to achieve the object of the present invention, the present invention provides a method for treating one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp. containing vanillin or an acceptable salt thereof as an active ingredient. A composition for antifungal use is provided.

The vanillin is preferably at least one selected from o -vanillin and p -vanillin, more preferably o -vanillin, but is not limited thereto.

The pathogenic fungi are preferably causative bacteria that cause seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, or ringworm, but are not limited thereto.

The fungus of the Trichophyton spp. is preferably Trichophyton mentagrophyte, but is not limited thereto.

The Malassezia spp. fungus is specifically selected from Malassezia pachydermatis , Malassezia restricta , and Malassezia globosa . It is desirable, but not limited thereto.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of diseases caused by any one pathogenic fungal infection selected from seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, and ringworm, containing vanillin or an acceptable salt thereof as an active ingredient. to provide.

The pharmaceutical composition according to the present invention can be formulated and used in the form of oral dosage forms such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods. You can.

The pharmaceutical composition according to the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent.

Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate. , cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. in the pharmaceutical composition. It is prepared by mixing. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, wethepsol, macrogol, Tween 61, cacao, laurin, glycerogelatin, etc. can be used.

The appropriate dosage of the pharmaceutical composition of the present invention may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. You can.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically on the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc.

In addition, the present invention provides an antifungal cosmetic composition against one or more pathogenic fungi selected from Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient. .

The pathogenic fungi cause seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, or ringworm, but are not limited thereto.

The cosmetic composition of the present invention contains ingredients commonly used in cosmetic compositions in addition to the vanillin, and includes conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers.

The cosmetic composition of the present invention can be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing products. , oil, powder foundation, emulsion foundation, wax foundation, spray, etc., but is not limited thereto. More specifically, it can be manufactured in the form of flexible lotion (skin), nourishing lotion (milk lotion), nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, shampoo, pack, spray or powder. You can.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacantha, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier ingredients. It can be.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient. In particular, when the formulation is a spray, chlorofluorohydrocarbon and propane may be used as carrier ingredients. /May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.

When the formulation of the present invention is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and microcrystals. Cellulose, aluminum metahydroxide, bentonite, agar or tragacantha can be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.

In addition, the present invention provides an antifungal health functional food composition against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp. containing vanillin or an acceptable salt thereof as an active ingredient. to provide.

The pathogenic fungi cause seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, or ringworm, but are not limited thereto.

The composition may be formulated with one or more types selected from granules, powders, tablets, coated tablets, capsules, solutions, syrups, juices, suspensions, emulsions and drops, but is not limited thereto.

When using the health functional food composition of the present invention as a food additive, the health functional food composition may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods. The amount of active ingredient can be appropriately used depending on the purpose of use (prevention or improvement). Generally, when manufacturing a food or beverage, the health functional food composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the total raw materials. However, in the case of long-term intake for health purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There are no particular restrictions on the types of health functional foods. Examples of foods to which the health functional food composition can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, and tea. There are drinks, alcoholic beverages, and vitamin complexes, and it includes all health foods in the conventional sense.

Additionally, the health functional food composition of the present invention can be manufactured into food, especially functional food. The functional food of the present invention includes ingredients commonly added during food production, and includes, for example, proteins, carbohydrates, fats, nutrients and seasonings. For example, when manufactured as a drink, natural carbohydrates or flavoring agents may be included as additional ingredients in addition to the active ingredient. The natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrins, cyclodextrins, etc.), or sugar alcohols (e.g., For example, xylitol, sorbitol, erythritol, etc.) is preferable. The flavoring agent may be a natural flavoring agent (e.g., thaumatin, stevia extract, etc.) or a synthetic flavoring agent (e.g., saccharin, aspartame, etc.).

In addition to the above health functional food composition, various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonic acid. It may further contain carbonating agents used in beverages. The ratio of the ingredients added is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.

In addition, the present invention provides an antifungal adjuvant against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient.

The pathogenic fungi cause seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, or ringworm, but are not limited thereto.

In addition, the present invention provides a method of administering a pharmaceutically effective amount of vanillin to an individual other than a human, comprising: administering a pharmaceutically effective amount of vanillin to an individual other than a human; selecting from Trichophyton spp. and Malassezia spp. An antifungal method is provided for infection by one or more pathogenic fungi.

The non-human entity may preferably be a mammal other than a human, but is not limited thereto.

The pathogenic fungi cause seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, or ringworm, but are not limited thereto.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for illustrating the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited thereto.

Example 1. Antifungal effect of vanillin

1) Trichophyton mentagrophyte ( Trichophyton mentagrophyte ) antifungal effect on

To measure the antifungal activity of o -vanillin and p -vanillin against athlete's foot fungi, Trichophyton mentagrophyte was cultured and treated with vanillin to determine the minimum inhibitory concentration (MIC, Minimum Inhibitory Concentration) was measured. MIC values were measured using the standard broth serial dilution method according to CLSI (Clinical and Laboratory Standard Institute) guidelines.

o -vanillin (CAS No. 148-53-8) and p -vanillin (CAS No. 121-33-5), products from Sigma-Aldrch, were dissolved in dimethyl sulfoxide (DMSO) and used in the test.

As a result, as shown in Table 1, vanillin had an excellent antifungal effect against Trichophyton mentagrophyte, and in particular, the antifungal effect of o -vanillin was more significant than that of p -vanillin.

compound MIC (㎍/mL) T. mentagrophyte o -vanillin 7.8125 p -vanillin 31.25

2) Malassezia genus ( Malassezia Antifungal effect against spp.)

To determine the antifungal activity of o -vanillin and p -vanillin against Malassezia spp., Malassezia pachydermatis , Malassezia restricta and Malassezia After culturing Malassezia globosa , the minimum inhibitory concentration (MIC) capable of inhibiting the growth of fungi was measured by treating it with vanillin. MIC values were measured using the standard broth serial dilution method according to CLSI (Clinical and Laboratory Standard Institute) guidelines.

As a result, as shown in Table 2, vanillin had excellent antifungal effects against Malassezia pachydermatis, Malassezia restricta , and Malassezia globosa , In particular, the antifungal effect of o -vanillin was more significant than that of p -vanillin.

compound MIC (㎍/mL) M. pachydermatis M. restricta M. globosa o -vanillin 7.8125 7.8125 7.8125 p -vanillin 15.625 15.625 15.625

Claims (11)

An antifungal composition against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient. The composition for antifungal use against pathogenic fungi according to claim 1, wherein the vanillin is o -vanillin. The antifungal composition for pathogenic fungi according to claim 1, wherein the pathogenic fungi are bacteria that cause seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, or ringworm. The composition for antifungal use according to claim 1, wherein the pathogenic fungus of the Trichophyton spp. is Trichophyton mentagrophyte. The method of claim 1, wherein the pathogenic fungi of the Malassezia spp. are Malassezia pachydermatis , Malassezia restricta , and Malassezia globosa . An antifungal composition against pathogenic fungi, characterized in that it is one or more selected from among. A pharmaceutical composition for the prevention or treatment of diseases caused by any one pathogenic fungal infection selected from seborrheic dermatitis, otitis externa, dandruff, atopic dermatitis, athlete's foot, and ringworm, containing vanillin or an acceptable salt thereof as an active ingredient. An antifungal cosmetic composition against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient. The method of claim 7, wherein the cosmetic composition is selected from solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing agents, oils, powder foundations, emulsion foundations, wax foundations and sprays. A cosmetic composition for antifungal use against pathogenic fungi, characterized in that it is a single formulation. A health functional food composition for antifungal use against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient. An antifungal adjuvant against one or more pathogenic fungi selected from the Trichophyton spp. and Malassezia spp., containing vanillin or an acceptable salt thereof as an active ingredient. An antifungal method for infection by pathogenic fungi in a subject other than a human, comprising: administering a pharmaceutically effective amount of vanillin to a subject other than a human.