KR102584548B1 - Antifungal composition comprising 6-pentyl-α-pyrone as an active ingredient - Google Patents

Abstract

The present invention relates to an antifungal composition containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient, and the 6-pentyl-α-pyrone of the present invention It has excellent antifungal activity against Candida spp., Cryptococcus spp., Malassezia spp., and Trichophyton spp., so it can be useful as an antifungal composition. .

Description

Antifungal composition comprising 6-pentyl-α-pyrone as an active ingredient}

The present invention relates to an antifungal composition containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient.

Fungus refers to a group of microorganisms including mold, yeast, and mushrooms. Most of them cannot synthesize nutrients on their own and live as parasites on other organisms. In humans, most infections occur on the skin, such as the scalp, hair, face, arms, legs, fingernails or toenails, where dead and peeling cells are distributed, but infections can also occur on the intestinal mucosa or vaginal mucosa, and can also spread to internal organs, resulting in systemic infection. It also wakes up. Meanwhile, fungal infections occur due to immune deficiency, old age, use of immunosuppressants or steroids, nutritional deficiencies, poor hygiene, and contact with infected patients.

Antifungal agents are substances used to prevent or treat symptoms caused by fungal infections by inhibiting the growth or reproduction of fungi.

Meanwhile, cryptococcosis is caused by infection with Cryptococcus neoformans, and in patients with weakened immunity, such as AIDS patients, it infects all parts of the body, including the skin, and especially the meninges. It causes meningitis, brain abscess, and brain tumor. Candidasis is a fungal disease caused by Candida albicans and was first isolated from a patient with thrush. It causes vaginitis in women and diaper rash in infants.

In addition, it has recently become known that the bacteria that cause dandruff are fungi, that is, yeast. In particular, the yeast of the genus Malassezia sp., which exists as a normal flora on skin such as the scalp, is the main cause, and stress and climate are the main causes. It has been reported that when Malassezia fungi overproliferate due to environmental factors such as changes, sweat, and food, dandruff symptoms such as scaling and itching appear, and when overgrowth is severe, seborrheic dermatitis occurs. In addition, when dandruff occurs a lot, the scalp is rubbed excessively due to itchiness, which can cause wounds or, in some cases, inflammation, and can also cause hair loss. In the case of compositions aimed at treating, preventing or improving dandruff and itching, it is an essential requirement to contain ingredients that can inhibit the growth of Malassezia sp., the main cause of dandruff. Currently commercially available compositions mainly include antifungal agents such as ketoconazole, zinc pyrithion, itraconazole, or piroctone olamine. Additionally, tar, sulfur, and salicylic acid have been used to relieve itching and scaling, and selenium sulfide has been used to suppress hyperproliferation of epidermal cells. However, while the antifungal agents that have been used for the treatment of dandruff are effective in treating dandruff, most of them are artificially synthesized substances, raising questions about their safety in the human body. However, a problem has been raised that ketoconazole, the active ingredient in dandruff treatments such as Nizoral sold domestically, may cause adverse effects on the endocrine system when used for a long period of time.

The area where ringworm occurs and the characteristics of the lesion are determined by the type of dermatophyte infected. Additionally, the anatomical characteristics of the area where symptoms occur are involved in the onset of symptoms. In cases of infection from animals, Trichopyton mentagrophytes is the most common causative agent. It mainly occurs in exposed areas such as the scalp (tinea capitis), face (tinea facial), chest and limbs (tinea corporis), and causes relatively severe itching. In case of infection from another person, Trichophyton rubrum is the most common causative bacteria, and lesions usually start on the feet (tinea pedis) and spread to other areas such as hands (tinea pedis), groin (tinea pedis), and fingernails and toenails (tinea nails). The symptoms are not severe and tend to progress to chronic disease. Depending on the area where it occurs, it is classified into tinea capitis, tinea corporis, jock itch, tinea pedis, tinea facial, tinea palms, tinea pedis, and tinea nails. Clinical characteristics differ depending on the characteristics of the skin, hair, fingernails, and toenails of the relevant area, the thickness of the stratum corneum depending on the anatomical location of the skin, and the physiological characteristics, and this results in differences in treatment methods and periods.

Current commercially available antifungal agents have the disadvantages of toxicity, narrow activity range, and strong fungistatic rather than fungicidal characteristics. Some of these also exhibit drug-drug interactions, which makes treatment very complex. In accordance with the recent trend in which fungal infections occur frequently in immunosuppressed patients and this patient population is steadily increasing, the demand for new antifungal agents with broad activity and excellent pharmacological properties is increasing.

Republic of Korea Patent No. 10-1302678

Accordingly, the present inventors found that 6-pentyl-α-pyrone is used to treat Candida albicans , a pathogenic fungus that causes thrush and vaginitis in the human body, Cryptococcus neoformans, which causes meningitis and pneumonia, dandruff, and seborrheic dermatitis. , Malassezia restricta, Malassezia globosa, Malassezia sympodialis, Malassezia furfur, dog otitis externa, It exhibits a strong antifungal effect against Malassezia pachydermatis , which causes atopic dermatitis , and Trichophyton rubrum and Trichophyton mentagrophytes, which cause athlete's foot and psoriasis. Upon confirmation, the present invention was completed.

Therefore, the purpose of the present invention is to provide an antifungal composition containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of pathogenic fungal infectious diseases containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient. It is done.

Another object of the present invention is to provide a cosmetic composition for preventing or improving pathogenic fungal infectious skin diseases containing 6-pentyl-α-pyrone or a cosmetically acceptable salt thereof as an active ingredient. It is done.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

Accordingly, the present invention provides an antifungal composition containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for preventing or treating pathogenic fungal infectious diseases containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient. .

In addition, the present invention provides a cosmetic composition for preventing or improving pathogenic fungal infectious skin diseases comprising 6-pentyl-α-pyrone or a cosmetically acceptable salt thereof as an active ingredient. .

In one embodiment of the present invention, the 6-pentyl-α-pyrone may be represented by the following formula (1), but is not limited thereto.

[Formula 1]

In another embodiment of the present invention, the antifungal composition is composed of Candida spp. , Cryptococcus spp. , Malassezia spp. , and Trichophyton sp . It may have antifungal activity against one or more fungi selected from the group, but is not limited thereto.

In another embodiment of the present invention, the infectious disease is composed of Candida spp. , Cryptococcus spp. , Malassezia spp. , and Trichophyton spp. The disease may be caused by one or more fungi selected from the group, but is not limited thereto.

In another embodiment of the present invention, the infectious disease may be one or more selected from the group consisting of candidiasis, cryptococcosis, seborrheic dermatitis, dandruff, atopic dermatitis, otitis externa, athlete's foot, and ringworm, but is not limited thereto.

In another embodiment of the present invention, the candidiasis may be one or more selected from the group consisting of thrush, esophageal candidiasis, vaginal candidiasis, Candida fungemia, Candida endophthalmitis, Candida peritonitis, Candida osteoarthritis, Candida spondylitis, and hepatosplenic candidiasis. It is not limited to this.

In another embodiment of the present invention, the pathogenic fungal infectious skin disease may be caused by Malassezia spp. or Trichophyton spp. , but is not limited thereto.

In another embodiment of the present invention, the pathogenic fungal infectious skin disease may be one or more selected from the group consisting of seborrheic dermatitis, dandruff, atopic dermatitis, athlete's foot, and ringworm, but is not limited thereto.

In another embodiment of the present invention, the cosmetic composition may be selected from the group consisting of shampoo, rinse, hair tonic, hair treatment, foot cream, detergent, skin care, and soap, but is not limited thereto.

Additionally, the present invention provides an antifungal method comprising administering an effective amount of 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof to a subject.

Additionally, the present invention provides an antifungal use of 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof.

Additionally, the present invention provides the use of 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof for preparing an antifungal agent.

In addition, the present invention provides a method for preventing or treating pathogenic fungal infectious diseases comprising administering to an individual an effective amount of 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof. do.

Additionally, the present invention provides the use of 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof for the prevention or treatment of pathogenic fungal infectious diseases.

In addition, the present invention provides the use of 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof for manufacturing a drug for pathogenic fungal infectious diseases.

6-pentyl-α-pyrone of the present invention has antifungal activity against Candida spp., Cryptococcus spp., Malassezia spp., and Trichophyton spp. It is excellent and can be usefully used as an antifungal composition.

Figure 1 shows the structural formula and ¹ H-NMR data for 6-pentyl-α-pyrone isolated and purified from Trichoderma gamsii .

Therefore, the present invention provides an antifungal composition containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for preventing or treating pathogenic fungal infectious diseases containing 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient. .

In addition, the present invention provides a cosmetic composition for preventing or improving pathogenic fungal infectious skin diseases comprising 6-pentyl-α-pyrone or a cosmetically acceptable salt thereof as an active ingredient. .

Hereinafter, the present invention will be described in detail.

In the present invention, 6-pentyl-α-pyrone may also be called 6-Amyl-α-pyrone, 6-pentyl-2-pyrone, or 6PP, and may be referred to as 6-pentylpyran-2. It can have an IUPAC name of -one.

In the present invention, the 6-pentyl-α-pyrone may be represented by the following formula (1), but is not limited thereto.

[Formula 1]

In the present invention, the 6-pentyl-α-pyrone may be isolated from Trichoderma gamsii or its culture, but is not limited thereto.

In the present invention, the antifungal composition is one or more selected from the group consisting of Candida spp. , Cryptococcus spp. , Malassezia spp. , and Trichophyton spp. It may have antifungal activity against fungi, but is not limited thereto.

In the present invention, the 6-pentyl-α-pyrone may have an antifungal effect, but is not limited thereto.

The 6-pentyl-α-pyrone may have a non-aromatic double bond and one or more asymmetric centers. Accordingly, they may occur as racemates and racemic mixtures, single enantiomers, individual diastereomers, diastereomeric mixtures, and cis- or trans-isomers. All these isomeric forms are considered.

6-pentyl-α-pyrone according to the present invention can be isolated from nature or prepared by chemical synthesis of compounds known in the art.

Additionally, the compound of the present invention can be isolated and purified from Trichoderma gamsii or its culture.

In the present invention, the infectious disease is one or more selected from the group consisting of Candida spp. , Cryptococcus spp. , Malassezia spp. , and Trichophyton spp. It may be a disease caused by fungi, but is not limited to this.

In the present invention, the infectious disease may be one or more selected from the group consisting of candidiasis, cryptococcosis, seborrheic dermatitis, dandruff, atopic dermatitis, otitis externa, athlete's foot, and ringworm, but is not limited thereto.

In the present invention, the candidiasis may be one or more selected from the group consisting of thrush, esophageal candidiasis, vaginal candidiasis, Candida fungemia, Candida endophthalmitis, Candida peritonitis, Candida osteoarthritis, Candida spondylitis, and hepatosplenic candidiasis, but is not limited thereto. .

In the present invention, cryptococcosis is caused by infection with Cryptococcus neoformans and infects all parts of the human body, including the skin, in patients with weakened immunity such as AIDS patients, and especially infects the meninges. It causes meningitis, brain abscess, and brain tumor.

In the present invention, the pathogenic fungal infectious skin disease may be caused by Malassezia spp. or Trichophyton spp. , but is not limited thereto.

In the present invention, the pathogenic fungal infectious skin disease may be one or more selected from the group consisting of seborrheic dermatitis, dandruff, atopic dermatitis, athlete's foot, and ringworm, but is not limited thereto.

In the present invention, the Candida genus fungus may be Candida albicans , but is not limited thereto.

In the present invention, the Cryptococcus genus mold may be Cryptococcus neoformans , but is not limited thereto.

In the present invention, the Malassezia genus fungi include Malassezia restricta , Malassezia globosa , Malassezia sympodialis , and Malassezia pachydermatis ( It may be one or more selected from the group consisting of Malassezia pachydermatis ) and Malassezia furfur , but is not limited thereto.

In the present invention, the fungus of the Trichophyton genus may be Trichophyton rubrum or Trichophyton mentagrophytes , but is not limited thereto.

In the present invention, the composition may be a pharmaceutical composition, food composition, or cosmetic composition, but is not limited thereto.

The present invention may also include a pharmaceutically acceptable salt of 6-pentyl-α-pyrone as an active ingredient. As used herein, the term “pharmaceutically acceptable salt” includes salts derived from pharmaceutically acceptable inorganic acids, organic acids, or bases.

Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid. , benzoic acid, malonic acid, gluconic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, etc. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excessive amount of aqueous acid and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone, or acetonitrile. It can also be prepared by heating equimolar amounts of the compound and an acid or alcohol in water and then evaporating the mixture to dryness, or suction filtering the precipitated salt.

Salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. The alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving the compound in an excessive amount of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, it is particularly pharmaceutically suitable to produce sodium, potassium or calcium salts as metal salts, and the corresponding silver salts can be obtained by reacting an alkali metal or alkaline earth metal salt with an appropriate silver salt (eg, silver nitrate).

The content of 6-pentyl-α-pyrone in the composition of the present invention can be appropriately adjusted depending on the symptoms of the disease, the degree of progression of the symptoms, the patient's condition, etc., for example, 0.0001 to 99.9% by weight, or 0.001%, based on the total weight of the composition. It may be from 50% by weight, but is not limited thereto. The content ratio is a value based on the dry amount with the solvent removed.

The pharmaceutical composition according to the present invention may further include appropriate carriers, excipients, and diluents commonly used in the preparation of pharmaceutical compositions. The excipient may be, for example, one or more selected from the group consisting of diluents, binders, disintegrants, lubricants, adsorbents, humectants, film-coating materials, and controlled-release additives.

The pharmaceutical composition according to the present invention can be prepared as powder, granules, sustained-release granules, enteric-coated granules, solutions, eye drops, ellipsis, emulsions, suspensions, spirits, troches, perfumes, and limonadese according to conventional methods. , tablets, sustained-release tablets, enteric-coated tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric-coated capsules, pills, tinctures, soft extracts, dry extracts, liquid extracts, injections, capsules, perfusate, It can be formulated and used in the form of external preparations such as warning agents, lotions, pasta preparations, sprays, inhalants, patches, sterilized injection solutions, or aerosols, and the external preparations include creams, gels, patches, sprays, ointments, and warning agents. , it may have a dosage form such as lotion, liniment, pasta, or cataplasma.

Carriers, excipients, and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, and calcium. These include 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.

Additives to tablets, powders, granules, capsules, pills, and troches according to the present invention include corn starch, potato starch, wheat starch, lactose, white sugar, glucose, fructose, di-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, and phosphoric acid. Calcium monohydrogen, calcium sulfate, sodium chloride, sodium bicarbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropylmethyl. Excipients such as cellulose, (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, and Primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose acetate phthalate, carboxymethyl cellulose, calcium carboxymethyl cellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethyl cellulose, sodium methyl cellulose, methyl cellulose, microcrystalline cellulose, dextrin. , hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, refined shellac, starch, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, etc. binders can be used, Hydroxypropyl methyl cellulose, corn starch, agar powder, methyl cellulose, bentonite, hydroxypropyl starch, sodium carboxymethyl cellulose, sodium alginate, calcium carboxymethyl cellulose, calcium citrate, sodium lauryl sulfate, silicic acid anhydride, 1-hydroxy Propylcellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, Disintegrants such as amylopectin, pectin, sodium polyphosphate, ethyl cellulose, white sugar, magnesium aluminum silicate, di-sorbitol solution, light anhydrous silicic acid; Calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodium, kaolin, petrolatum, sodium stearate, cocoa fat, sodium salicylate, magnesium salicylate, polyethylene glycol 4000, 6000, liquid paraffin, hydrogenated soybean oil (Lubri) wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, Macrogol, synthetic aluminum silicate, silicic anhydride, higher fatty acids, higher alcohol, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, sodium chloride, Lubricants such as sodium acetate, sodium oleate, dl-leucine, and light anhydrous silicic acid may be used.

Additives for the liquid according to the present invention include water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, sucrose monostearate, polyoxyethylene sorbitol fatty acid esters (twin esters), polyoxyethylene monoalkyl ethers, lanolin ethers, Lanolin esters, acetic acid, hydrochloric acid, aqueous ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethyl cellulose, sodium carboxymethyl cellulose, etc. can be used.

A solution of white sugar, other sugars, or sweeteners, etc. may be used in the syrup according to the present invention, and if necessary, flavoring agents, colorants, preservatives, stabilizers, suspending agents, emulsifiers, thickening agents, etc. may be used.

Purified water can be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. can be used as needed.

The suspension according to the present invention may include acacia, tragacantha, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose, HPMC 1828, HPMC 2906, and HPMC 2910. Surfactants, preservatives, stabilizers, colorants, and fragrances may be used as needed.

Injections according to the present invention include distilled water for injection, 0.9% sodium chloride injection, IV solution, dextrose injection, dextrose + sodium chloride injection, PEG, lactated IV solution, ethanol, propylene glycol, non-volatile oil - sesame oil. , solvents such as cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristic acid, and benzene benzoate; Solubilizers such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, Tween, nicotinic acid amide, hexamine, and dimethylacetamide; Weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and buffering agents such as gums; Isotonic agents such as sodium chloride; Stabilizers such as sodium bisulfite (NaHSO ₃ ) carbon dioxide gas, sodium metabisulfite (Na ₂ S ₂ O ₃ ), sodium sulfite (Na ₂ SO ₃ ), nitrogen gas (N ₂ ), and ethylenediaminetetraacetic acid; Sulfurizing agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetate, and acetone sodium bisulfite; Analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; It may contain suspending agents such as CM sodium, sodium alginate, Tween 80, and aluminum monostearate.

Suppositories according to the present invention include cacao oil, lanolin, witepsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cacao butter + Cholesterol, lecithin, Lanet wax, glycerol monostearate, Tween or Span, Imhausen, monolene (propylene glycol monostearate), glycerin, Adeps solidus, Buytyrum Tego -G), Cebes Pharma 16, Hexalide Base 95, Cotomar, Hydrocote SP, S-70-XXA, S-70-XX75(S-70-XX95), Hydro Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Massaupol, Masupol-15, Neosupostal-N, Paramound-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), suppositories type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecobi (W, R, S, M, Fs), Tegestor triglyceride base (TG-95, MA, 57) and The same mechanism can be used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include the extract with at least one excipient, such as starch, calcium carbonate, and sucrose. ) or prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium styrate talc are also used.

Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. 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. there is. 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.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, drug activity, and It can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the medical field.

The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art to which the present invention pertains.

The pharmaceutical composition of the present invention can be administered to an individual through various routes. All modes of administration are contemplated, including oral administration, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, paraspinal space (intrathecal) injection, sublingual administration, buccal administration, intrarectal injection, vaginal injection. It can be administered by internal insertion, ocular administration, ear administration, nasal administration, inhalation, spraying through the mouth or nose, dermal administration, transdermal administration, etc.

The pharmaceutical composition of the present invention is determined depending on the type of drug as the active ingredient along with various related factors such as the disease to be treated, the route of administration, the patient's age, gender, weight, and severity of the disease.

In the present invention, “individual” refers to a subject in need of treatment for a disease, and more specifically, human or non-human primates, mice, rats, dogs, cats, horses, cows, etc. It may be a mammal, but is not limited thereto.

In the present invention, “administration” means providing a given composition of the present invention to an individual by any appropriate method.

In the present invention, “prevention” refers to any action that suppresses or delays the onset of the desired disease, and “treatment” refers to the improvement or improvement of the desired disease and its associated metabolic abnormalities by administration of the pharmaceutical composition according to the present invention. It refers to all actions that are beneficially changed, and “improvement” refers to all actions that reduce parameters related to the target disease, such as the degree of symptoms, by administering the composition according to the present invention.

Additionally, the composition of the present invention may be provided in the form of a quasi-drug composition.

In addition to the above ingredients, the quasi-drug composition of the present invention may further include pharmaceutically acceptable carriers, excipients, or diluents as needed. The pharmaceutically acceptable carriers, excipients, or diluents are not limited as long as they do not affect the effect of the present invention, and include, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, flavoring agents, and preservatives. It may include etc.

Representative examples of carriers, excipients or diluents acceptable for the quasi-drug composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, maltitol, starch, gelatin, glycerin, gum acacia, alginate, calcium phosphate, calcium. Carbonate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil. , injectable esters, Wethepsol, Macrogol, Tween 61, Kakaoji, Lauridge, etc.

The quasi-drug composition of the present invention may include, but is not limited to, disinfectant cleaner, shower foam, ointment, wet tissue, coating agent, etc., and the formulation method, dosage, usage method, and components of the quasi-drug are commonly known in the technical field. It can be appropriately selected from the techniques.

Additionally, the composition of the present invention may be provided in the form of a food composition.

When using 6-pentyl-α-pyrone of the present invention as a food additive, 6-pentyl-α-pyrone can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when producing food or beverages, 6-pentyl-α-pyrone of the present invention may be added in an amount of 15% by weight or less, or 10% by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, 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 special restrictions on the types of foods above. Examples of foods to which the above substances can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, These include alcoholic beverages and vitamin complexes, and include all health functional foods in the conventional sense.

The health drink composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used. The proportion of natural carbohydrates is generally about 0.01-0.20 g, or about 0.04-0.10 g per 100 mL of the composition of the present invention.

In addition to the above, the composition of the present invention contains 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, It may contain carbonating agents used in carbonated drinks. In addition, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01-0.20 parts by weight per 100 parts by weight of the composition of the present invention.

Additionally, the composition of the present invention may be provided in the form of a cosmetic composition.

6-pentyl-α-pyrone of the present invention can be used as a cosmetic additive to manufacture cosmetic compositions for keeping hands or feet clean. Examples include soap (solid soap, liquid soap, foam soap, body soap, hand soap, etc.), cleansing foam, shampoo (hair shampoo, dry shampoo, etc.). Among these, soap is preferable and can be used in formulations such as liquid soap and body soap.

The formulation of the cosmetic composition according to the present invention includes skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, mist, moisture cream, hand cream, hand lotion, foundation, It may be in the form of essence, nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, cleansing oil, cleansing balm, body lotion, or body cleanser.

The cosmetic composition of the present invention may further include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, and sphingolipids.

Water-soluble vitamins may be any that can be mixed into cosmetics, but examples include vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, and vitamin H. and their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbic acid-2-phosphate, magnesium ascorbic acid-2-phosphate, etc.) are also water-soluble vitamins that can be used in the present invention. Included. Water-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial cultures, enzymatic methods, or chemical synthesis.

Oil-soluble vitamins may be any that can be mixed into cosmetics, but examples include vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), etc. , their derivatives (ascorbic palmitate, ascorbic stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinic acid, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl ether, etc.) are also included in the oil-soluble vitamins used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial cultures, enzymatic or chemical synthesis.

Any polymer peptide that can be blended into cosmetics may be used, and examples include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. High molecular weight peptides can be purified and obtained by conventional methods such as purification from microbial culture media, enzymatic methods, or chemical synthesis, or they can usually be purified and used from natural products such as dermis of pigs or cows or silk fiber of silkworms.

The high molecular weight polysaccharide may be anything that can be blended into cosmetics, but examples include hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate, or its salts (sodium salt, etc.). For example, chondroitin sulfate or its salt can usually be purified and used from mammals or fish.

The sphingolipid may be any one that can be blended into cosmetics, and examples include ceramide, phytosphingosine, and sphingolipid. Sphingolipids can usually be purified by conventional methods from mammals, fish, shellfish, yeast, or plants, or obtained by chemical synthesis.

In addition to the above-mentioned essential ingredients, the cosmetic composition of the present invention may contain other ingredients usually blended in cosmetics as needed.

Other ingredients that may be added include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohol, colorants, fragrances, Examples include blood circulation promoters, cooling agents, antiperspirants, and purified water.

Examples of oil and fat components include ester-based fats and oils, hydrocarbon-based fats and oils, silicone-based fats and oils, fluorine-based fats and oils, animal fats and oils, and vegetable fats and oils.

Ester oils include glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, and stearic acid. Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine. Diisopropyl acid, isoalkyl neopentanoate, tri(caprylic, capric acid)glyceryl, trimethylolpropane tri2-ethylhexanoate, trimethylolpropane triisostearate, pentaelislitol tetra2-ethylhexanoate , cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinooleate, isostear laurate. Reyl, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetoester 2-ethylhexanoate Aryl, 2-ethylhexanoate stearyl, hexyl isostearate, ethylene glycol dioctanate, ethylene glycol dioleate, propylene glycol dicapric acid, di(capryl, capric acid) propylene glycol, propylene glycol dicaprylate, dicapric acid Neopentyl glycol prinate, neopentyl glycol dioctanate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate. , octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerol oleic acid ester, polyglycerol isostearic acid ester, Triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate, dimalate Isostearyl, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, Cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytsteryl isostearate, phytsteryl oleate, 12-stealoyl hydroxystearate isocetyl, 12-stealoyl hydride. Ester systems such as stearyl hydroxystearate and isostearyl 12-stealoylhydroxystearate can be mentioned.

Hydrocarbon-based fats and oils include squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybudene, microcrystalline wax, and petroleum jelly.

Silicone oils include polymethyl silicone, methylphenyl silicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane/methylcetyloxysiloxane copolymer, dimethylsiloxane/methylstealoxysiloxane copolymer, and alkyl. Modified silicone oil, amino-modified silicone oil, etc. can be mentioned.

Examples of fluorine-based fats and oils include perfluoropolyether.

Animal or plant oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, birdflower oil, soybean oil, corn oil, rapeseed oil, apricot oil, palm kernel oil, palm oil, castor oil, sunflower oil, and grape seed oil. , cottonseed oil, palm oil, cucumber nut oil, wheat germ oil, rice germ oil, shea butter, walnut colostrum oil, marker damia nut oil, meadow oil, egg yolk oil, beef tallow, horse oil, mink oil, orange rape oil, jojoba oil. , animal or plant oils such as candelier wax, carnaba wax, liquid lanolin, and hydrogenated castor oil.

Moisturizers include water-soluble low-molecular-weight moisturizers, oil-soluble molecular moisturizers, water-soluble polymers, and fat-soluble polymers.

Water-soluble low-molecular-weight moisturizers include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (degree of polymerization n = 2 or more), and polypropylene. Examples include glycol (degree of polymerization n = 2 or more), polyglycerin B (degree of polymerization n = 2 or more), lactic acid, lactate, etc.

Examples of fat-soluble low-molecular-weight moisturizers include cholesterol and cholesterol esters.

Water-soluble polymers include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water-soluble chitin, chitosan, and dextrin. You can.

Examples of oil-soluble polymers include polyvinylpyrrolidone/eicosene copolymer, polyvinylpyrrolidone/hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and polymer silicone.

Examples of emollients include long-chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.

Examples of surfactants include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.

Nonionic surfactants include self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE. Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POEㆍPOP (polyoxyethyleneㆍpolyoxypropylene) copolymer, POEㆍPOP alkyl ether, polyether modified silicone, lauric acid Examples include alkanolamide, alkylamine oxide, and hydrogenated soybean phospholipid.

Anionic surfactants include fatty acid soap, alpha-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkyl amide sulfate, alkyl phosphate, POE alkyl phosphate, and alkyl amide phosphate. , alkyloyl alkyl taurine salt, N-acylamino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, sodium alkyl sulfoacetate, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate ester, etc. .

Cationic surfactants include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, and cationic surfactant. Benzalkonium, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, quaternary ammonium salt of lanolin derivative, etc. are mentioned.

Amphoteric surfactants include carboxy beta type, amide beta type, sulfo beta type, hydroxy sulfo beta type, amide sulfo beta type, phosphobeta type, aminocarboxylate type, imidazoline derivative type, and amide amine type. Amphoteric surfactants, etc. can be mentioned.

Organic and inorganic pigments include silicic acid, anhydrous silicic acid, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, and aluminum oxide. Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine and complexes thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluorine resin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene/styrene copolymer, Examples include organic pigments such as silk powder, cellulose, CI pigment yellow, and CI pigment orange, and complex pigments of these inorganic pigments and organic pigments.

Examples of organic powder include metal soap such as calcium stearate; Alkyl phosphate metal salts such as sodium zinc cetilate, zinc laurylate, and calcium laurylate; Acyl amino acid polyvalent metal salts such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroyl glycine calcium; Amidesulfonic acid polyvalent metal salts such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylizine, N-alpha-paritoylolnithine, N-alpha-lauroylarginine, N-alpha-hydrogenated beef tallow fatty acid acylarginine, etc. -Acyl basic amino acid; N-acyl polypeptides such as N-lauroylglycylglycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; Examples include polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene/styrene copolymer, and ethylene tetrafluoride.

UV absorbers include para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, and benzyl cinnamate. , paramethoxycinnamic acid-2-ethoxyethyl, paramethoxycinnamic acid octyl, diparamethoxycinnamic acid mono-2-ethylhexane glyceryl, paramethoxycinnamic acid isopropyl, diisopropylㆍdiisopropylcinnamic acid ester mixture, uro Kaninic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone disulfonate sodium, dihydroxybenzophenone , tetrahydroxybenzophenone, 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1 , 3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, etc.

Disinfectants include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincphyllithione, benzalkonium chloride, and photosensitive. Sub-No. 301, mononitroguaiacol sodium, undecirenic acid, etc. can be mentioned.

Antioxidants include butylhydroxyanisole, propyl gallate, and elisorbic acid.

Examples of pH adjusters include citric acid, sodium citrate, malic acid, sodium malate, fumal acid, sodium fumalate, succinic acid, sodium succinate, sodium hydroxide, and sodium monohydrogen phosphate.

Examples of alcohol include higher alcohols such as cetyl alcohol.

In addition, the ingredients that can be added are not limited to this, and any of the above ingredients can be mixed within the range that does not impair the purpose and effect of the present invention, but in an amount of 0.01-5% by weight or 0.01-3% based on the total weight. Can be formulated in % weight percentages.

When the formulation of the present invention is a lotion, paste, cream or gel, the carrier ingredients include animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. It can be used.

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, solvating 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 microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar, or tracant may 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, linoline derivative, or ethoxylated glycerol fatty acid ester can be used.

In addition, in the present specification, the composition may be one or more formulations selected from the group consisting of shampoo, rinse, hair tonic, hair nourishing lotion, hair essence, hair serum scalp treatment, hair treatment, hair conditioner, hair shampoo, and hair lotion. may be possible, but is not limited thereto.

The composition according to the present invention may further contain appropriate ingredients depending on the formulation, which will be described in detail as follows.

In the present specification, it further contains one or more selected from the group consisting of surfactants, preservatives, viscosity adjusters, pH adjusters, fragrances, dyes, hair conditioning agents, and water.

In this specification, the surfactant is at least one selected from anionic surfactants, amphoteric surfactants, and nonionic surfactants.

In this specification, the anionic surfactant may be alkyl sulfate or alkyl ether sulfate, and specific examples thereof include sodium lauryl sulfate, ammonium lauryl sulfate, triethanolamine lauryl sulfate, polyoxyethylene sodium lauryl sulfate, and polyoxyethylene la. Examples include ammonium sulfate.

In the present specification, the amphoteric surfactant may be alkyl betaine or alkyl amidopropyl betaine, and specific examples thereof include cocodimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, and lauryldimethyl alpha-carboxyethyl betaine. Phosphorus, cetyldimethyl carboxymethyl betaine, cocamidopropyl betaine, etc. can be mentioned.

In the present specification, the nonionic surfactant may be alkanol amide or amine oxide, and specific examples thereof include lauryl diethyl amine oxide, palm oil alkyldimethyl amine oxide, lauric acid diethanolamide, palm oil fatty acid diethanolamide, Coconut oil fatty acid monoethanolamide, etc. can be mentioned.

In the present specification, the preservative is at least one selected from the group consisting of methyl para-oxybenzoate, propyl para-oxybenzoate, sodium benzoate, methylchloroisothiazolinone, methylisothiazolinone, and sodium benzoate.

In the present specification, the viscosity modifier is one or more of cocamide ME (CME), cocamide DEA (CDE), and sodium chloride.

In this specification, the pH adjuster is one or more of sodium phosphate, disodium phosphate, citric acid, and sodium citrate.

As used herein, the hair conditioning agent is dimethicone base, cationic polymer, or a combination thereof.

In the present specification, the hair conditioning agent may further include any one or more of a tertiary amidoamine, a quaternary ammonium compound, a high melting point compound, and a silicone compound.

Specific examples of the tertiary amidoamine include cocaamidopropyl dimethylamine, stearamidopropyl dimethylamine, beheniramidopropyl dimethylamine, oleamidopropyl dimethylamine, isostearamidopropyl dimethylamine, etc. You can.

Specific examples of the quaternary ammonium compounds include alkyl (14 to 22 carbon atoms) trimethyl ammonium chloride, dialkyl (14 to 22 carbon atoms) dimethyl ammonium chloride, hydrogenated tallow alkyl trimethyl ammonium chloride, and tallow alkyl dimethyl ammonium chloride. there is.

Specific examples of the high melting point compounds include fatty alcohols, fatty acids, fatty alcohol derivatives, and hydrocarbons, and more specifically, cetyl alcohol, stearyl alcohol, and cetostearyl alcohol.

Specific examples of the silicone compound include polyalkylsiloxane-based, polyarylsiloxane-based, polyalkylarylsiloxane-based, and polyethersiloxane copolymers.

In addition, 6-pentyl-α-pyrone can be used in a variety of ways, such as antifungal building materials, pesticides, and household product additives, and can be mixed with known antifungal agents used in the field. For example, pesticide-related antifungal agents are listed in, for example, the Pesticide Dictionary (Pesticide Manual, 12th ed., British Crop Protection Council, 2000).

Below, preferred embodiments are presented to aid understanding of the present invention. However, the following examples are provided only to make the present invention easier to understand, and the content of the present invention is not limited by the following examples.

Experimental Example 1: Native strains Trichoderma gamsii Separation of 6-Pentyl-α-pyrone from

Trichoderma gamsii was cultured on 5 kg of potato dextrose agar medium at 25°C in the dark for 7 days and extracted with 10 L of methanol. The crude extract was fractionated using silica gel column chromatography by increasing and decreasing the ratio of hexane and ethyl acetate by 20%. The antifungal activity of each extract was measured, and the fractions that showed activity were refractionated using Sephadex LH-20, ODS-A, and prep-HPLC. Among the refractionated substances, the structure of a single substance that showed antibacterial activity was confirmed through ¹ H-NMR.

As shown in Figure 1, the identified antifungal substance was 6-pentyl-α-pyrone.

Experimental Example 2: Evaluation of antifungal activity of 6-pentyl-α-pyrone

A total of 9 types of human pathogenic fungi ( Candida albicans , Cryptococcus neoformans, Malassezia restricta, Malassezia globosa, Malassezia About Malassezia sympodialis , Malassezia pachydermatis , Malassezia furfur , Trichophyton rubrum , Trichophyton mentagrophytes ) The antifungal activity of 6-pentyl-α-pyrone was confirmed. MIC values were measured using the standard broth serial dilution method according to CLSI (Clinical and Laboratory Standard Institute) guidelines. Fluconazole and Ketoconazole were used as positive controls.

As shown in Table 1, 6-pentyl-α-pyrone was 31.25-62.50 μg/mL against Candida albicans, 15.62 μg/mL against Cryptococcus neoformans, and 7.81-15.62 against Malassezia restricta. μg/mL for Malassezia globosa 62.50 μg/mL for Malassezia sympodialis 31.25-62.50 μg/mL for Malassezia pachydermatis 31.25-62.50 μg/mL for Malassezia puffer The minimum inhibitory concentration (MIC) value was 31.25 μg/mL for Trichophyton rubrum and 62.50 μg/mL for Trichophyton mentagrophytes at 125.00 μg/mL.

These results are comparable to the antifungal drugs Fluconazole and Ketocoanzole, which are already widely used clinically.

Control MIC
(Unit: μg/mL) MIC
(Unit: μg/mL) Candida albicans SC5314 FLZ ^* - 0.5 31.25 - 62.50 Cryptococcus neoformans H99 FLZ-4 15.62 Malassezia restricta KCTC27527 KTZ ^** - 0.0625 7.81 - 15.62 Malassezia globosa CBS7966 KTZ - 0.125 62.50 Malassezia sympodialis CBS7222 KTZ - 0.0625 31.25 - 62.50 Malassezia pachydermatis CBS1879 KTZ - 0.125 31.25 - 62.50 Malassezia furfur CBS1878 KTZ - 0.25 125.00 Trichophyton rubrum KCTC6375 ITZ - 0.25 31.25 Trichophyton mentagrophytes 636 ITZ - 0.5 62.50 *FLZ: Fluconazole
**KTZ: Keoconazole

From the above results, it is expected that 6-pentyl-α-pyrone can be used as an antifungal composition because it has a significant antifungal effect against bacteria of the genus Candida, Cryptococcus, Malassezia, and Trichophyton.

The description of the present invention described above is for illustrative purposes, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

Claims (11)

In the antifungal composition,
The composition contains 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient,
The fungus is characterized in that it is at least one selected from the group consisting of Malassezia spp. and Trichophyton spp., excluding Trichophyton mentagrophytes,
The Malassezia genus includes Malassezia restricta, Malassezia globosa, Malassezia sympodialis, Malassezia pachydermatis, or Mala. Characterized by being Malassezia furfur,
The Trichophyton genus excluding the Trichophyton Mentagrophytes is characterized as Trichophyton rubrum,
An antifungal composition specific to Trichophyton spp., excluding Malassezia spp. and Trichophyton mentagrophytes.
According to paragraph 1,
The 6-pentyl-α-pyrone is an antifungal composition characterized in that it is represented by the following formula (1).
[Formula 1]

delete In the pharmaceutical composition for preventing or treating pathogenic fungal infectious diseases,
The composition contains 6-pentyl-α-pyrone or a pharmaceutically acceptable salt thereof as an active ingredient,
The fungus is characterized in that it is at least one selected from the group consisting of Malassezia spp. and Trichophyton spp., excluding Trichophyton mentagrophytes,
The Malassezia genus includes Malassezia restricta, Malassezia globosa, Malassezia sympodialis, Malassezia pachydermatis, or Mala. Characterized by being Malassezia furfur,
The Trichophyton genus excluding the Trichophyton Mentagrophytes is characterized as Trichophyton rubrum,
A pharmaceutical composition, wherein the disease is at least one selected from the group consisting of seborrheic dermatitis, dandruff, atopic dermatitis, otitis externa, athlete's foot, and ringworm.
delete delete delete In the cosmetic composition for preventing or improving pathogenic fungal infectious skin diseases,
The composition contains 6-pentyl-α-pyrone or a cosmetically acceptable salt thereof as an active ingredient,
The fungus is characterized in that it is at least one selected from the group consisting of Malassezia spp. and Trichophyton spp., excluding Trichophyton mentagrophytes,
The Malassezia genus includes Malassezia restricta, Malassezia globosa, Malassezia sympodialis, Malassezia pachydermatis, or Mala. Characterized by being Malassezia furfur,
The Trichophyton genus excluding the Trichophyton Mentagrophytes is characterized as Trichophyton rubrum,
A cosmetic composition, wherein the disease is at least one selected from the group consisting of seborrheic dermatitis, dandruff, atopic dermatitis, athlete's foot, and ringworm.
delete delete According to clause 8,
The cosmetic composition is characterized in that it is selected from the group consisting of shampoo, rinse, hair tonic, hair treatment, foot cream, detergent, skin care, and soap.