KR20160060836A - Composition for protecting and treating dermatophytosis comprising chlorin e6 having an improved stability - Google Patents

Abstract

The present invention relates to a composition for preventing and treating dermatophytosis, comprising chlorin e6. More specifically, the composition for preventing and treating dermatophytosis using chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient has excellent antifungal activities with respect to dermatophytosis, and can be used as a composition for preventing and treating dermatophytosis, as medicine such as an agent for external application to the skin or the like, and as a cosmetic product.

Description

[0001] The present invention relates to a composition for preventing and treating dermatophytosis comprising chlorin e6,

The present invention relates to a composition for preventing and treating dermatophytosis comprising chlorin e6.

Ancient Egypt, India and Chinese civilizations used ancient light to treat diseases in a wide range of psoriasis, rickets, and vitiligo, among others. In 1900, Oscar Raab of Germany discovered a photodynamic reaction in which sandworms died when exposed to only light without color, or exposed to light alone, but exposed light and pigment together . In 1903, Herman Von Tappeiner and A. Jesionek applied eosin to skin cancer and exposed it to white light for the first time to perform a "photodynamic response" treatment. A photodiagnostic concept began with a combination of reagents and light that corresponded to photosensitizers and a study in 1904 that demonstrated the need for oxygen in the photosensitization reaction led to the development of oxygen-dependent photosensitization phenomena in 1907 This basic principle, photodynamic therapy (PDT), was created.

The three essential elements of photodynamic therapy are light, photosensitizer, and oxygen. Activating the photosensitizer by irradiating the appropriate wavelength with an appropriate amount of light activates the activated photosensitizer directly or generates reactive oxygen to act on the target cell.

In photodynamic therapy, the photosensitizer plays an important role in producing active oxygen that is activated by absorbing a specific wavelength of a light source irradiated for the destruction of cancer cells and capable of destroying cancer cells. The photosensitizer shows little cytotoxicity even at high concentrations if it is not exposed to light, but only when reactive oxygen species (oxygen, O2, oxygen radical, superoxide, and peroxide) are excited by light of specific intrinsic wavelength. And toxicity. Depending on the time of development, it can be divided into first generation, second generation and third generation light sensing agents. The first-generation photosensitizer is hematoporphyrin and its derivatives. The second-generation photosensitizer is ALA (5-Aminolevulinic acid), Chlorin, Purpurin, Benzoporphyrin, Phthalocyanine, Texaphyrin and derivatives. Third-generation photosensitizers are photosensitizers that modify the chemical structure or morphology and allow it to bind well to specific tissues such as cancer.

Photodynamic therapy (PDT), which is used for bacteria, fungi and viruses, is called PDI (Photodynamic Inactivation), which is emerging as a new way to treat bacterial, fungal and viral infections due to resistance to antibiotics. In practice, the use of such PDIs has been clinically tried to treat a variety of dangerous diseases. PDI functions based on the use of photosensitizers that bind to cell microbial surfaces through the accumulation of target cells. Various types of microorganisms show sensitivity to PDI without any resistance. The expression of fungal resistance has become a global problem in both clinical and environmental fields. PDI has no fungal resistance and has the potential for an antifungal therapy with a new mechanism.

Chlorine e6, derived from chlorophyll, is a safe substance used as a second-generation photosensitizer in photodynamic therapy. It is not toxic to normal cells but has a higher photochemical activity against malignant cells compared to other photosynthetic compounds used for tumor therapy. It accumulates in cells at high concentration and provides antitumor effect. When a specific light is irradiated to the tissue cell in which chlorin e6 is accumulated, the photosensitizer chlorin e6 is activated to generate active oxygen species such as singlet oxygen, thereby exhibiting a therapeutic effect. Chlorine e6 is shown in the following formula (1).

[Chemical Formula 1]

Chlorine e6 is a chlorophyll derivative isolated and purified from green algae chlorella and spirulina. It is a natural compound that has no toxicity in the human body because it is a natural compound and its effect on anti-inflammation, antioxidant, tissue regeneration etc. is reported in the presence of light source. .

The extraction and purification method of chlorin e6 is described in Patent Document 1. To briefly explain, extraction and filtration of spirulina, a kind of marine algae, is carried out using a polar solvent such as ethanol and then re-extracted with hexane. The solution is washed with purified water and ethanol in that order, followed by filtration to obtain a chlorophyll hexane solution. The obtained chlorophyll hexane solution is treated with hydrochloric acid to pH 2, neutralized to pH 7, and washed with ethanol to obtain a pheophytin hexane solution. The solvent of the pheophytin hexane solution is removed by volatilization, then dissolved in acetone, adjusted to pH 13 with sodium hydroxide, and subjected to a reflux reaction at 60 ° C. The solution was neutralized to pH 7 with hydrochloric acid, and then acetone was added to precipitate crystals. The precipitated crystals were filtered, washed again with acetone, and dried under reduced pressure at room temperature to give Chlorin e6 trisodium trisodium) powder.

Among fungi in nature, there are pathogenic fungi that cause diseases in humans. Efforts to develop antifungal agents to combat these pathogenic fungi have not been actively pursued compared to other antibiotics. One of the reasons is that common fungal infections are not associated with skin surface or mucosal membranes and deep-seated infection is rarely seen as a serious infectious disease. In addition, the need for improvement of the antifungal therapeutic agent was low because the invasion of fungal pathogens was difficult for the most normal people with normal immune function. However, with the increase in chemotherapy-based chemotherapy and organ transplants surgery, life-threatening systemic fungal infections have increased rapidly.

Like plants and animals, fungi are eukaryotic organisms with nuclei in the nuclear membrane. The various cytoplasmic structures and biosynthetic pathways are similar to those of mammalian cells, and photosynthesis does not take place and uses already generated energy, such as heterotrophic organisms. Of the more than 100,000 known fungi, more than 100 species are known to be directly related to human and animal disease.

Infection by fungi is called mycoses. Candidiasis and dermatophytosis, the most common fungi among the fungi, are normal fungi in the human body or fungi adapted to live in the human body. Mycosis can be divided into superficial mycosis, skin mycosis, subcutaneous mycosis, systemic mycosis, and opportunistic mycosis.

Dermatophyte is a generic term for fungus parasitic on skin, nails, hair, and whiskers of human and most animals. It is called skin fungus or dermatophyte in Korea. Dermatomycetes are causative agents of various symptoms such as ringworm, athlete's foot, and mechanical impulse. They are classified as anthropophilic, zoophilic, and soil-friendly depending on their habitat. Anthropophilic dermatophyte is limited to humans as a host, resulting in light and chronic inflammation. Zoophilic dermatophyte is found primarily in animals and produces a strong immune response in people who are in contact with animals. Geophilic dermatophyte is usually found in soil but sometimes infects humans and animals. They cause a strong and pronounced immune response, but the spread of the infection is limited and may be treated spontaneously, but the scar can remain. It is known that three species of fungi belonging to the genus Microsporum, Trichophyton and Epidermophyton belong to this species, and 42 species are included in three species worldwide.

Fungi are also called keratinophilic fungi because most of them enter into the horn, nail, and horny layer and grow inside. The constituent material of these parasitic sites is mainly keratin, and mold bacteria are also called keratin-decomposing fungi because they decompose keratin by the action of keratinase which they have and use it as a nutrient source.

Mycoplasma is a skin disease caused by parasitic on the stratum corneum of the epidermis, skin, nails, hair, and whiskers, and is sometimes referred to as skin surface fungal infection or skin fungus. It means all skin diseases caused by mold and can be divided into superficiality and deepness. There are tofu white line, facial and body line line, Wan player foot line, and white line. The foot-to-foot ring is infected through the horny when it comes out from the patient in many places such as public baths and swimming pools, and it is a cause of the hot and humid environment and mechanical friction with sweaty obesity. Treatment is based on topical application. In case of chronic dermatophytosis, where the area of infection of the nail and tinea ringweed is too broad, or where topical application has failed, antifungal drugs should be taken. Currently, compounds such as tolnaftate, miconazole, clotrimazole, and terbinafine, which are antifungal agents for the treatment of dermatophytosis, are made into 1% liquid and cream formulations and used as topical treatments.

Treatment of fungal infections requires long-term use of antifungal agents due to their nature. However, most of the antifungal agents currently on the market cause various side effects such as hepatotoxicity and renal toxicity. In addition, as fungi resistant to existing antifungal agents and novel pathogenic fungi are found, there is a growing need for the development of new antifungal agents that can treat infections caused by them but have few side effects.

Korean Patent No. 1180695

Accordingly, the present inventors have conducted studies to solve the above-mentioned problems. As a result, they have found that the use of a substance such as chlorin e6 can reduce adverse effects on the human body which may occur in the treatment of dermatophycemic disease, The present invention has been accomplished by developing a composition capable of preventing and treating dermatophyte even under daylight conditions in which a therapeutic laser light source is not used.

Accordingly, it is an object of the present invention to provide a composition for preventing and treating dermatosis, comprising chlorine e6 or a pharmaceutically acceptable salt thereof as an active ingredient.

As a means for solving the above problems, the present invention provides a composition for preventing and treating dermatosis, comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.

As another means for solving the above problems, the present invention provides an external preparation for skin for prevention and treatment of dermatophytosis, comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.

As another means for solving the above problems, the present invention provides cosmetics for preventing and improving dermatophytosis comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.

The chlorin e6 used in the present invention exhibits antimicrobial activity against dermatophytes in a sunlight condition which does not use a laser light source used in photodynamic therapy as a photosensitizer and has less side effects than general antifungal therapy, It is possible to minimize the side effects that may occur in the treatment by the therapeutic method, to obtain an excellent prevention and treatment effect of the dermatophyte, and to be manufactured in various formulations, thereby enabling commercialization according to the taste and convenience of the patient.

1 is a photograph showing the antifungal activity of chlorin e6 on T. mentagrophytes irradiated with 30,000 lux light for 30 minutes [a; Blank, b: chlorine e6 concentration of 600 占 퐂 / ml, c: chlorine e6 concentration of 800 占 퐂 / ml, d: chlorine e6 concentration of 1,000 占 퐂 / ml).
Fig. 2 is a photograph showing antifungal activities in the absence of light on dermatophytes (T. mentagrophytes) of chlorin e6 [a; Blank, b: chlorine e6 concentration of 600 占 퐂 / ml, c: chlorine e6 concentration of 800 占 퐂 / ml, d: chlorine e6 concentration of 1,000 占 퐂 / ml).
FIG. 3 is a photograph of the antifungal activity of chlorin e6 and fluconazole in T. mentagrophytes.
4 is a photograph showing antifungal activity against the preparations of Examples 1 to 6 and Comparative Examples 1 to 6 against T. mentagrophytes.

The present invention relates to a composition for preventing and treating dermatophytosis comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.

The chlorin e6 of the present invention may be prepared as a pharmaceutically acceptable salt according to methods conventional in the art.

The pharmaceutically acceptable salts include, unless otherwise indicated, salts of acidic or basic groups that may be present in chlorin e6. For example, pharmaceutically acceptable salts include the sodium, calcium, and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, (Salicylate) salts, which are known in the art and which are known in the art, such as, for example, ≪ / RTI >

The pharmaceutical dosage forms of chlorin e6 according to the present invention may also be used in the form of their pharmaceutically acceptable salts and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable set.

The present invention provides a composition for preventing and treating dermatophytosis comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient, which is a photosensitizer having the above-mentioned effect.

Specifically, in the present invention, chlorin e6 or a pharmaceutically acceptable salt thereof used for photodynamic therapy for dermatomyositis can be contained in an amount of 0.00001 to 1% by weight based on the total composition weight, preferably 0.0001 to 1% by weight, 0.5% by weight. If the active ingredient is contained in an amount less than 0.00001% by weight based on the total weight of the composition, the effect as a photosensitizing agent is low and the efficacy can be reduced. If the effective ingredient is contained in an amount exceeding 1% by weight, cytotoxicity due to side effects of photosensitizer .

In order to ensure the stability of chlorin e6, stabilizers such as trehalose may be further used. May be contained in an amount of 0.00001 to 1% by weight, preferably 0.0001 to 0.5% by weight, based on the total weight of the composition. If the stabilizer is contained in an amount less than 0.00001% by weight based on the total weight of the composition, the effect as a stabilizer is low and stability is not secured. If the stabilizer is contained in an amount exceeding 1% by weight, cytotoxicity due to side effects of the stabilizer have.

Such a composition may further comprise a pharmacologically acceptable excipient, wherein the pharmacologically acceptable excipient may be a forming agent, a diluent, a stabilizer, a surfactant, a thickening agent, a pH adjusting agent, and the like , And an external agent such as a liquid preparation, a gel, an ointment, a cream, a spray, etc. by mixing with an excipient.

The gel agent in the present invention can be defined as a gel-like (semi-circular) external preparation made of organic molecules having a large molecular weight permeating a liquid to be applied to the skin. The gels include aqueous gels and oily gels. Typically, cellulose derivatives such as hydroxypropylcellulose and the like are usable as polymeric materials used for preparing gels; Natural gums such as xanthan gum, alginate, gum arabic and the like; Other polymeric materials may be carbomers, povidone, and the like. The diluent may be polyethylene glycol, propylene glycol, glycerin, butylene glycol, and the like. Examples of the stabilizer include sodium edetate, ammonium glycyrrhizin, potassium dipotassium glycyrrhizate, and the like. . In addition, gradually increasing triethanolamine and the like can be used, and a pH adjusting agent (citric acid, sodium citrate, etc.) and fragrance can be additionally used.

In addition to the active ingredient, other ingredients may be used within a range that does not deteriorate the effects of the present invention if necessary. Examples of the present invention include 0.5 to 15% by weight of a polymer material; 80 to 97% by weight of a solvent; 0.5 to 10% by weight of a diluent; A gel containing 0.1 to 5% by weight of the thickening agent can be prepared.

In the present invention, the cream preparation containing the active ingredient is mixed with the secretions of the skin as a liquid type or a semi-solid type emulsion, which is a water-in-water type or an underwater type, containing medicines which can be easily applied to the skin. Stearyl alcohol, cetyl alcohol, glycerin monostearate, isopropyl palmitate, lanolin, cetyl esters waxes, minerals, white pigments and the like are used as the oil phase in order to form a water-in-oil type or an underwater type. A cationic surfactant, and a nonionic surfactant can be used. As the pH adjuster, phosphoric acid, sodium phosphate, citric acid and the like can be used. As the solvent, water, ethanol, polyethylene glycol, polypropylene Etc. may be used.

The ointment containing the active ingredient in the present invention is generally prepared by adding a topical ointment such as petroleum jelly, paraffin, plastic base, vegetable oil, lard, Water-soluble vaseline, purified lanolin, absorbent ointment, lanolin, cold cream, etc., water-soluble base oil such as polyethylene glycol ointment, and emulsifiable base oil such as hydrophilic ointment, vanishing cream, , Gel base, FAPG, and the like. The selected ointment base may be manufactured through a process such as association, melting, and dispersion.

In the present invention, when formulating a liquid dispersion containing an active ingredient or a fine dispersion of a liquid or a solid substance under a gas pressure in an operating condition, the surfactant, solvent, pH adjuster, stabilizer, Can be manufactured. The diluent may be polyethylene glycol, propylene glycol, glycerin, butylene glycol, etc. The surfactant may be an anionic surfactant, a cationic surfactant, a cationic surfactant, an anionic surfactant, A nonionic surfactant can be used. As the stabilizer, sodium edetate, ammonium glycyrrhizinate, potassium dipotassium glycyrrhizinate and the like can be used. As the pH regulator, citric acid, sodium citrate or the like can be used to prepare a liquid agent. Propane gas, butane gas, compressed air, nitrogen gas and the like can be used as a spraying material for spraying the gas.

As described above, the present invention can be applied by directly applying a formulation containing chlorin e6 and a stabilizer to a lesion site infected by dermatophytes, as described above, and can be used as a carrier suitable for transdermal administration, if necessary, (fatty acid) and the like can be further blended to prepare an external preparation for skin.

The prepared external skin preparation of the present invention may be administered in various ways other than the above-described formulations, for example, as a transdermal patch, lotions, powders, cataplasma or pastes .

The present invention also provides a cosmetic comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient for the purpose of prevention and improvement of dermatophytosis.

Reference may be had to the disclosure of International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association, Inc., Washington, 1995, for formulation into cosmetics. Which are incorporated herein by reference.

When the composition for preventing or alleviating dermatophytosis of the present invention is a cosmetic composition, the composition may include, but is not limited to, a lotion such as a facial lotion, a facial lotion, a body lotion, Makeup remover such as cream, essence, cosmetic lotion, spray, gel, pack, sunscreen, makeup base, liquid type, solid type or spray type such as cream, powder, cleansing cream, cleansing lotion, cleansing oil A foam, a foam, a soap, a body wash, and the like. In this case, the cosmetic composition may contain at least one selected from the group consisting of a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent, a lubricant, a stabilizer, an antioxidant, a water, a lower alcohol, a thickener, a chelating agent, Antioxidants, antifungal agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, flocculants, humectants, fragrances, fragrance carriers, preservatives, proteins, silicones, solubilizers, sugar derivatives, sunscreens, vitamins , Plant extracts, and waxes. The pharmaceutical composition of the present invention may contain one or more pharmacologically acceptable excipients.

In the case of cosmetics, the active ingredient may be used in an amount of 0.00001 to 1.0% by weight, preferably 0.0001 to 0.5% by weight, based on the dry weight of the entire cosmetic composition. The stabilizer may be used in an amount of 0.00001 to 1.0% by weight, preferably 0.0001 to 0.5% by weight, based on the dry weight of the whole cosmetic composition.

Advantages and features of the present invention and methods of achieving them will become apparent with reference to the embodiments described in detail below. However, it is to be understood that the present invention is not limited to the disclosed embodiments, but may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, To fully disclose the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.

Experimental Example  One: To skin mold  About Antifungal activity  Experiment

To determine the antifungal activity of dermatophytes of chlorin e6, T. mentagrophytes (KTCC 6077) was used as a dermatophytic strain and cultured for 2 weeks in a 28 ° C incubator using SDA (Sabouraud dextrose agar) medium. Lt; / RTI > Cultured T. mentagrophytes 50 μl of the bacterial solution and 50 μl of the chlorine e6 dilution were mixed, and the SDA medium was uniformly plated using a spreader. The concentration of chlorin e6 mixture was 600, 800, and 1,000 μg / ml, respectively. The irradiated medium was irradiated with a halogen lamp under a light intensity of 30,000 lux for 30 minutes and then cultured in a 28 ° C incubator for 2 weeks. In the control group, the mycelia and chlorine e6 were plated at the same concentration, followed by incubation for 2 weeks in a 28 ° C incubator without light irradiation.

As a result, the control group did not inhibit the proliferation of T. mentagrophytes, and the test bacteria inhibited the proliferation of 600, 800 and 1,000 μg / ml. As a result, it was found that the photosensitizer chlorin e6 inhibits the proliferation of dermatophytes in response to irradiation of light (FIG. 1).

Experimental Example  2: To skin mold  Comparison with antifungal agents in Korea

Chlorin e6 and fluconazole, an antifungal agent, were compared by modified broth broth dilution method.

100 μl of the T. mentagrophytes cultured in Experimental Example 1 was placed in a 96-well plate, and then a chlorine e6 dilution was added thereto to give final concentrations of 600, 800 and 1,000 μg / ml. Likewise, after the addition of the fluconazole diluted solution, the final concentrations were 600, 800, and 1,000 μg / ml. A 96-well plate was irradiated with 30,000 lux for 5 minutes using a halogen lamp, incubated for 6 hours in a 28 ° C incubator, and absorbance was measured at 492 nm to evaluate the inhibition of proliferation of dermatophytes.

In the case of chlorin e6, which was not irradiated with light, there was almost no proliferation inhibition, and when irradiated, it exhibited a very excellent proliferation inhibitory effect (Fig. 2). Fluconazole showed proliferation inhibition irrespective of light irradiation, but showed a level lower than the light-irradiated chlorin e6 (Fig. 3).

Example  One: Liquid  Produce

0.1 g of chlorin e6

0.1 g of trehalose

Concentrated glycerin 2.0 g

1.0 g of propylene glycol

0.7 g of hydroxyethylcellulose

Triethanolamine 1.2 g

Ethanol 30.0 g

Purified water 64.9 g

The raw material was placed in a preparation vessel and completely dissolved with stirring at 80 DEG C, cooled to 40 DEG C, adjusted to pH 7.0, and defoamed in vacuo to prepare 100 g of a liquid agent.

Comparative Example  One: Liquid  Produce

0.1 g of trehalose

Concentrated glycerin 2.0 g

1.0 g of propylene glycol

0.7 g of hydroxyethylcellulose

Triethanolamine 1.2 g

Ethanol 30.0 g

Purified water 65.0 g

The raw material was placed in a preparation vessel and completely dissolved with stirring at 80 DEG C, cooled to 40 DEG C, adjusted to pH 7.0, and defoamed in vacuo to prepare 100 g of a liquid agent.

Example  2: Gelatin  Produce

0.1 g of chlorin e6

0.1 g of trehalose

Potassium glycyrrhizinate 50.0 mg

3.0 g of butylene glycol

Povidone K30 1.0 g

Carbomer 0.3 g

0.4 g of triethanolamine

Purified water 95.05 g

The raw material was placed in a preparation container and completely dissolved with stirring at 80 DEG C, cooled to 40 DEG C, adjusted to pH 7.0, and vacuum degassed to prepare 100 g of a gel.

Comparative Example  2: Gelatin  Produce

0.1 g of trehalose

Potassium glycyrrhizinate 50.0 mg

3.0 g of butylene glycol

Povidone K30 1.0 g

Carbomer 0.3 g

0.4 g of triethanolamine

Purified water 95.15 g

The raw material was placed in a preparation container and completely dissolved with stirring at 80 DEG C, cooled to 40 DEG C, adjusted to pH 7.0, and vacuum degassed to prepare 100 g of a gel.

Example  3: Manufacture of cream agent

0.1 g of chlorin e6

0.1 g of trehalose

Stearic acid 5.0 g

5.0 g of cetanol

Hard liquid paraffin 6.4 g

Propylene glycol 16.0 g

Polysorbate 60 2.0 g

Citric acid 0.1 g

2.0 g of sorbitan monostearate

Purified water 63.3 g

The raw material was placed in a preparation vessel and completely dissolved with stirring at 80 DEG C, cooled to 40 DEG C, adjusted to pH 7.0, and defoamed under vacuum to prepare 100 g of a cream agent.

Comparative Example  3: Manufacture of cream agent

0.1 g of trehalose

Stearic acid 5.0 g

5.0 g of cetanol

Hard liquid paraffin 6.4 g

Propylene glycol 16.0 g

Polysorbate 60 2.0 g

Citric acid 0.1 g

2.0 g of sorbitan monostearate

Purified water 63.4 g

The raw material was placed in a preparation vessel and completely dissolved with stirring at 80 DEG C, cooled to 40 DEG C, adjusted to pH 7.0, and defoamed under vacuum to prepare 100 g of a cream agent.

Example  4: Manufacture of ointment

0.1 g of chlorin e6

0.1 g of trehalose

Polyethylene glycol 4000 25.0 g

Polyethylene glycol 400 64.0 g

Hard liquid paraffin 1.0 g

Polyoxyethylene hardened castor oil 1.0 g

0.5 g of zinc stearate

Purified water 8.3 g

The ingredients were placed in a preparation vessel and completely dissolved with stirring at 80 DEG C, and the pH was adjusted to 7.0 at 40 DEG C, followed by cooling and defoaming in vacuo to prepare 100 g of an ointment agent.

Comparative Example  4: Manufacture of ointment

0.1 g of trehalose

Polyethylene glycol 4000 25.0 g

Polyethylene glycol 400 64.0 g

Hard liquid paraffin 1.0 g

Polyoxyethylene hardened castor oil 1.0 g

0.5 g of zinc stearate

Purified water 8.4 g

The ingredients were placed in a preparation vessel and completely dissolved with stirring at 80 DEG C, and the pH was adjusted to 7.0 at 40 DEG C, followed by cooling and defoaming in vacuo to prepare 100 g of an ointment agent.

Example  5: Manufacture of spray agent

0.1 g of chlorin e6

0.1 g of trehalose

3.5 g of butylene glycol

Ethanol 3.0 g

0.5 g of glycerin

≪ tb > < tb > Pigment-60 Hydrogenate castor oil 0.3 g

Citric acid 20.0 mg

Sodium citrate 80.0 mg

Ammonium glycyrrhizine 10.0 mg

50.0 mg of potassium glycyrrhizin potassium

Purified water 92.34 g

The raw material was placed in a preparation vessel and completely dissolved with stirring at 80 ° C. The mixture was cooled to 40 ° C, the pH was adjusted to 7.0, and then defoamed in vacuo to prepare 100 g of a solution. The solution was filled in a pressure vessel, Filled and sealed to prepare an aerosol agent.

Comparative Example  5: Manufacture of spray agent

0.1 g of trehalose

3.5 g of butylene glycol

Ethanol 3.0 g

0.5 g of glycerin

≪ tb > < tb > Pigment-60 Hydrogenate castor oil 0.3 g

Citric acid 20.0 mg

Sodium citrate 80.0 mg

Ammonium glycyrrhizine 10.0 mg

50.0 mg of potassium glycyrrhizin potassium

Purified water 92.44 g

The raw material was placed in a preparation vessel and completely dissolved with stirring at 80 ° C. The mixture was cooled to 40 ° C, the pH was adjusted to 7.0, and then defoamed in vacuo to prepare 100 g of a solution. The solution was filled in a pressure vessel, Filled and sealed to prepare an aerosol agent.

Example  6: Preparation of essence

0.1 g of chlorin e6

0.1 g of trehalose

3.0 g of glycerin

Benzophenone-9 0.04 g

0.2 g of carboxyvinyl polymer

0.18 g of triethanolamine

0.6 g of oxydoteth-25

1.0 g of glyceryl monostearate

Preservative 0.01 g

Fragrance 0.01 g

Purified water 94.76 g

Essences were prepared in the same composition as above according to a conventional method for producing an essence.

Comparative Example  6: Preparation of essence

0.1 g of trehalose

3.0 g of glycerin

Benzophenone-9 0.04 g

0.2 g of carboxyvinyl polymer

0.18 g of triethanolamine

0.6 g of oxydoteth-25

1.0 g of glyceryl monostearate

Preservative 0.01 g

Fragrance 0.01 g

Purified water 94.86 g

Essences were prepared in the same composition as above according to a conventional method for producing an essence.

Experimental Example  3: Dermatophyte Antifungal activity  Experiment

Antifungal activity tests were carried out on dermatophytes of the preparations of Examples 1 to 6 and Comparative Examples 1 to 6.

The cultured T. mentagrophytes (KCTC6077) were cultured in SDA medium for 2 weeks at 28 ℃. The bacterial cultures were taken to prepare bacterial solutions. The bacterial solutions were diluted by adding the preparations of Examples 1 to 6 and Comparative Examples 1 to 6 to 50 쨉 l of the bacterial solution and diluted to a chlorine e6 concentration of 500 쨉 g / ml. The diluted solution containing the bacterial solution was placed in a 96-well plate, irradiated with a halogen lamp at 30,000 lux for 10 minutes, incubated in a 28 ° C incubator for 6 hours, and the absorbance was measured at 492 nm using a microplate reader. Respectively. Separately, dermatophytes were cultured and used as a control.

As a result of measuring the antifungal activity, Examples 1 to 6 showed that the proliferation of dermatophytes was inhibited by 60% or more compared to that of the control. In Comparative Examples 1 to 6, the inhibition of dermatophytes was hardly shown [Fig. 4] .

Claims (10)

A composition for preventing and treating dermatophytosis comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.
The method according to claim 1,
Wherein the chlorin e6 or a pharmaceutically acceptable salt thereof contains 0.00001 to 1% by weight based on the total weight of the composition.
The method according to claim 1,
A composition for the prevention and treatment of dermatophytosis, which further comprises a pharmacologically acceptable excipient in addition to the active ingredient.
A dermatological preparation for prevention and treatment of dermatophytosis comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.
5. The method of claim 4,
Wherein said chlorin e6 or a pharmaceutically acceptable salt thereof contains 0.00001 to 1% by weight based on the total weight of the composition.
5. The method of claim 4,
An external preparation for skin for preventing and treating dermatophytosis, which further comprises a pharmacologically acceptable excipient in addition to the active ingredient.
6. The method of claim 5,
An external preparation for preventing and treating dermatophyte which is an ointment, a liquid preparation, a cream, a gel or a spray.
A cosmetic for preventing and improving dermatophytosis comprising chlorin e6 or a pharmaceutically acceptable salt thereof as an active ingredient.
9. The method of claim 8,
Wherein the chlorin e6 or a pharmaceutically acceptable salt thereof contains 0.0001 to 1% by weight based on the total weight of the composition.
10. The method of claim 9,
Cosmetics for the prevention and improvement of dermatophytosis which is formulated into one selected from the group consisting of lotion, milky lotion, cream, essence, cosmetic lotion, spray, gel, pack, sunscreen, makeup base, foundation, powder, makeup remover and detergent .

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