KR20130005667A - A composition for the treatment of acne containing phthalimidoperoxycaproic acid - Google Patents

Abstract

PURPOSE: A pharmaceutical composition, a cosmetic composition, and an antibacterial composition containing phthalimido peroxy carproic acid are provided to ensure excellent antibacterial property and to be used an agent for preventing or treating acne. CONSTITUTION: A composition for preventing or treating acne contains phthalimido peroxy carproic acid as an active ingredient. The composition prevents Propionibacterium acnes, Streptococcus pyogenes, Staphyllococcus aureus, or a mutant strain of Staphyllococcus aureus. An antibacterial composition contains phthalimido peroxy carproic acid as an active ingredient. The antibacterial composition has an antibacterial function against Propionibacterium acnes, Streptococcus pyogenes, Staphyllococcus aureus, or a mutant strain of Staphyllococcus aureus.

Description

Pharmaceutical composition for the prevention or treatment of acne containing phthalimidoperoxy caproic acid {A COMPOSITION FOR THE TREATMENT OF ACNE CONTAINING PHTHALIMIDOPEROXYCAPROIC ACID}

The present invention relates to a pharmaceutical composition, cosmetic composition and antimicrobial composition for acne prevention or treatment containing phthalimidoperoxy caproic acid (Phthalimido Peroxy Caproic Acid) as an active ingredient.

Acne is a symbol of puberty, and statistics show that about 9 out of 10 men and women in puberty experience acne. Recently, as women's opportunities for social advancement and self-realization have increased, the number of people experiencing acne for the first time in their twenties or thirties has increased, and the interest in acne prevention and treatment is increasing.

Acne is an inflammatory disease of the hair follicle and sebaceous glands that show various skin lesions such as closed or open scrim, papules, cysts and nodules on the face, upper chest, back and upper limbs. The same thing comes out, and these rashes are called scalp, which is a characteristic of acne. (Kim, H.Y., Kor. J. Dermatol., 16: 417, 1978).

Acne occurs mainly in areas where there are more than three million sebaceous glands, including the face, neck, back, and chest, and can be divided into four stages depending on the symptoms. It can be called an early stage, and in the second stage papular acne stage, acne bacteria are multiplying and inflammatory reactions occur, resulting in red acne, which is called erythematous papules and may cause scars if not properly managed. Stage 3 purulent acne is a more severe red acne inflammatory response to the pus inside the pus, which is called pustules, at this stage may leave scars after treatment, so professional treatment is required. The final stage 4 nodular acne is a stage in which the pus ruptures inside the skin, causing more inflammation in the acne affected area, resulting in a nodule that is just a finger rash, requiring professional treatment and prolonged treatment. Can be.

The cause of acne has not yet been clearly identified, but it is estimated that various causes are involved. However, there are two main factors that are caused by the action of acne bacteria, which are caused by hyperactivity of the gonads, which are thought to be caused by hormones and genetic backgrounds, and by breeding in the fur branch, which break down sebum and produce free fatty acids.

In particular, sebum stagnated in the hair follicles block the hair follicles to block the circulation of air, so inside the hair follicles anaerobic bacteria that reside in the hair follicles can grow well. The cotton cloth thus produced creates a living environment for microorganisms such as propionibacterium acnes, staphylococcus epidermidis, and pytirosporum ovale. Kearney, JK et al., J. Gen. Microbiol., 130 (4): 797, 1984).

These are fat-compatible microorganisms, Staphylococcus epidermidis, which are aerobic and grow in the middle of hair follicles or hair follicles, and Propionibacterium acnes are anaerobic and grow inside hair follicles. Malassezia, the causative agent of Malassezia folliculitis, is also a mixture of acne, which is a local affinity fungus.

When acne bacteria proliferate in sebaceous glands due to genetic or environmental factors, triglycerides that make up sebum are converted into free fatty acids and act as irritants to skin It acts as a comonogenic substance to promote acne production. In addition, the immune response to acne bacteria is accompanied by inflammation.

Thus, acne treatment studies to date have included sebum secretion control using anti-male hormones, exfoliation of pores using retinoic acid, a salicylic acid or vitamin A derivative, and antibiotics such as erythromycin and clindamycin. Has been concentrated on increasing the bactericidal power for acne bacteria.

However, while these methods are somewhat effective in treating acne, the use of anti-hormonal agents has side effects due to inhibition of epidermal growth and other hormonal abuse, and in the case of salicylic acid preparations may cause skin redness, swelling or skin scleroderma, In the case of retinoic acid preparations, there is an effect through inhibition of hyperkeratosis, but side effects such as contact dermatitis, erythema, skin dryness and tearing may occur. It became.

In particular, erythromycin has been frequently used as an acne treatment because it showed excellent bacteriostatic effect by inhibiting bacterial protein synthesis through interaction of ribosomes with rRNA, but recently, resistance mediated through methylation of rRNA is almost 50% of the treated patients. Found in, the appearance of a new acne treatment was an urgent reality.

In order to alleviate such side effects, it has excellent antibacterial function, low MIC against mold, and generally low skin irritation with 3-iodo-2-propynylbutylcabamate. Invention is disclosed using benzophenanthridine alkaloids derived from the plant of Sanguinaria canadensis (Republic of Korea Patent Application No. 10-1998-0007651), but the eye irritation It is known to cause, has the disadvantage that the price is relatively expensive, yellowing may occur over time.

As mentioned above, various researches and efforts have been made to treat acne until now, and various compounds have been developed as acne treatments until now, but there were problems of side effects and did not have a desirable effect. There is an urgent need to develop safe and effective products.

Meanwhile, the inventors of the present invention have not known the effects of phthalimidoperoxycaproic acid on preventing and treating acne.

The phthalimidoperoxycaproic acid, which is a kind of peroxide, is widely used in various industries as a bleaching agent, but only a few companies have recently used it for removing keratin to improve wrinkles on cosmetics. Phthalimidoperoxy caproic acid according to the present invention has never been used to treat acne until now.

Accordingly, the present inventors have made intensive efforts to develop a composition for preventing or treating acne, while the phthalimidoperoxycaproic acid exhibits high antibacterial activity against propionibacterium acnes, which is an acne-causing bacterium, while having little toxicity. The present invention was confirmed to be useful for preventing or treating acne.

An object of the present invention is to provide a pharmaceutical composition for preventing or treating acne containing phthalimidoperoxy caproic acid as an active ingredient.

Another object of the present invention to provide a cosmetic composition for preventing or treating acne containing phthalimidoperoxy caproic acid as an active ingredient.

Still another object of the present invention is to provide an antimicrobial composition containing phthalimidoperoxycaproic acid as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating acne containing phthalimidoperoxy caproic acid as an active ingredient.

The present invention also provides a cosmetic composition for preventing or treating acne containing phthalimidoperoxy caproic acid as an active ingredient.

The present invention also provides an antimicrobial composition containing a phthalimidoperoxy caproic acid as an active ingredient.

As used herein, the term "active ingredient" means a component of a pharmaceutical composition that is applied to the skin condition to provide a prophylactic or therapeutic effect.

As used herein, the term “pharmaceutical composition” refers to a composition containing a pharmaceutically effective amount, which herein includes propionibacterium acnes containing phthalimidoperoxycaproic acid as an active ingredient. Pharmaceutical preparations for preventing or treating a skin condition caused by

As used herein, the term "skin condition" refers to a condition in which the site of infection of the skin is changed due to infection by propionibacterium acnes, which condition is considered a skin disease and is not considered a skin disease. Includes all of the states.

Thus, the term "acne" as used herein encompasses all skin conditions such as open blemishes, obstructive blemishes, red acne (erythematous papules), purulent acne, nodular acne and cystic acne and the like. More specifically, it includes all skin conditions caused by or partially caused by Propionibacterium acnes and closed and open scrims.

As used herein, the term “treatment” encompasses the cure of acne symptoms as well as the partial cure, improvement and alleviation of acne symptoms as a result of applying the pharmaceutical composition of the present invention to the acne site.

As used herein, the term "prevention" means the application of the pharmaceutical composition of the present invention to the body part to inhibit or block the infection or growth of Propionibacterium acnes so that acne symptoms do not occur beforehand.

The term "cosmetic composition" as used herein is a composition used in the human body to clean and beautify the human body to add charm and brighten the appearance, or to maintain or promote the health of the skin and hair (detergents and cosmetics ( cosmetics).

The term "antimicrobial composition" as used herein contains an effective amount of phthalimidoperoxycaproic acid having an antimicrobial activity as an active ingredient to kill or grow bacteria or fungi, including the acne causing bacterium Propionibacterium acnes. It means a substance that suppresses.

In the present invention, the compound phthalimidoperoxycaproic acid used as an active ingredient in the pharmaceutical composition is represented by the following general formula (1):

The compound phthalimidoperoxycaproic acid represented by Chemical Formula 1 may be prepared by chemical synthesis as described by Yun et al. As a kind of peroxy acid (Yun L. et al., AOCS press , Proceedings of the 4th World Conference on Detergents Strategies for the 21st Century: Synthesis and Application of Phthalimidoperoxycaproic Acid, Chapter 15; 238, 1999).

The phthalimidoperoxycaproic acid, which is a kind of peroxide, is widely used in various industries as a bleaching agent, but only a few companies have recently used it for removing keratin to improve wrinkles on cosmetics.

Phthalimidoperoxy caproic acid according to the present invention has never been used to treat acne until now.

In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating acne containing phthalimidoperoxycaproic acid as an active ingredient.

The acne is a skin disease selected from the group consisting of obstructive cotton cloth, open cotton cloth, red acne (erythema papule), purulent acne, nodular acne and cystic acne, in particular, by propionibacterium acnes known as acne causative bacteria It may be generated.

The acne may be a skin disease caused by acne bacteria susceptible to phthalimidoperoxy caproic acid, for example, Staphylococcus aureus.

The range of prophylactic or therapeutic doses for acne in the composition may vary with severity and dosage form, and the number of applications may also vary with age, weight and constitution of the patient. In general, the phthalimidoperoxycaproic acid used as an active ingredient in the pharmaceutical composition of the present invention, when the content is lower than 0.0001% by weight of the composition, there is no antimicrobial activity against propionibacterium acnes, 30% of the composition If higher than% is not preferred in terms of cost, it may be present in a concentration of 0.0001 to 30% by weight, preferably 0.001 to 20% by weight, more preferably 0.01 to 10% by weight of the total pharmaceutical composition.

Within this range the concentration is determined by the use to which the pharmaceutical composition is applied. In addition, certain formulations, such as concentrated formulations, which must be diluted before use, may contain higher concentrations.

The pharmaceutical composition may contain a thickener for imparting a viscosity to the formulation in the range of about 4,000 to about 9,000 cps at room temperature. When the thickener is added, the formulation can be maintained at various temperature ranges, a stable viscosity can be obtained, and at the same time, the usability can be improved, such as a feeling when used on the skin for external use is improved. ₃₀ include alkyl acrylates, acrylic acid and / or methacrylic copolymer carbopol 1342 of methacrylic _{acid-increasing} agent such a sucrose allyl ether and C _10. Other thickeners that may be used in addition include cellulose derivatives such as hydroxypropyl methylcellulose, hydroxyethylcellulose, carboxymethyl cellulose and the like. Small additions of salts (NaCl) also serve to control the viscosity of the final formulation. Usually the amount of salt added is about 0.25 to 0.6% by weight.

The pharmaceutical composition contains acid, base and buffer as necessary to maintain the pH at 3.0 to 9.0, preferably 4.5 to 8.0, more preferably 5.0 to 7.0. The nature and manner of use of such pH adjusting materials are well known in the art.

The formulation of the pharmaceutical composition is not particularly limited, but may be characterized in that it is for transdermal administration, and the composition for transdermal administration may include ointments, creams, pastes, lotions, liniments, pastes. External preparations, tinctures, skin gels, It may have a formulation selected from the group consisting of glycerogelatins, external acids, aerosols and plasters. These formulations are described in the literature, which is a prescription generally known in all pharmaceutical chemistry (Blaug et al., Remington's Pharmaceutical Science, 15th Edition, 1975).

A preferred embodiment of the formulation is an ointment. The ointment is petrolatum, white petrolatum, yellow ointment, hydrocarbon base such as mineral oil, hydrophilic petrolatum, absorbent base such as anhydrous lanolin, lanolin, cold cream, washable base such as hydrophilic ointment, polyethylene glycol Any water-soluble base such as an ointment can be prepared. Their selection and preparation take into account factors such as the release rate of the drug from the base, the expected increase in percutaneous absorption by the base, whether the skin is sealed by the base, the stability of the drug in the base, and the effect of the drug on the base. But belong to those of ordinary skill in the art.

A preferred embodiment of the formulation is a cream. The creams include W / O types, such as cold creams and emollient creams, and O / W types, such as shaving creams, varnishing creams, hand creams, and lining creams. More preferred creams are typically varnishing creams containing water and stearic acid. Usually patients or doctors prefer creams to ointments because o / w creams are easier to wash away than ointments.

A preferred embodiment of the formulation is a lotion. The lotions are prepared by methods such as suspending agents, emulsions, solutions and the like, which also belong to those of ordinary skill in the art to those skilled in the pharmaceutical formulation art. More preferred in the present invention is a white lotion and this formulation also belongs to conventional techniques for those skilled in the formulation arts.

Another preferred embodiment of the formulation is a wax. The friction agent may be prepared as either an oily agent or an ethanol agent. Preferred are oily waxes with low irritation to the skin. In the case of oil-based lubricants, there is a combination of nonvolatile oils such as almond oil, peanut oil, cottonseed oil, volatile oils such as wintergreen and turpentine, or nonvolatile oils.

In another aspect, the present invention relates to a cosmetic composition for preventing or treating acne containing phthalimidoperoxycaproic acid as an active ingredient.

In the present invention, the cosmetic composition is a lotion, cream, massage cream, nutrition cream, moisturizing cream, hand cream, lotion, moisturizing lotion, milk lotion, nutrition lotion, skin lotion, skin softener, skin toner, ice cream, pack , Foundation, essence, nutrition essence, skin gel, skin oil, skin toner, face lotion, converging water and deodorant.

The cosmetic composition may be for cleaning the skin, the cosmetic composition for cleaning the skin, cream, cleanser, foam, cleansing foam, peeling gel, body wash, scrub, soap, oil, emulsion, hair soap, hair rinse, body cleanser, shampoo It may have a formulation selected from the group consisting of, emulsion, solid detergent and liquid detergent.

Phthalimidoperoxycaproic acid is used as an active ingredient in the cosmetic composition, when the content is lower than 0.0001% by weight of the composition, there is no antimicrobial activity against propionibactrum acnes, and when the content is higher than 30% by weight of the composition Since it is not preferable from the side, it may be present in a concentration of 0.0001 to 30% by weight, preferably 0.001 to 20% by weight, more preferably 0.01 to 10% by weight of the total cosmetic composition. Within this range the concentration is determined by the use to which the cosmetic composition is applied.

In addition, certain formulations, such as concentrated formulations, which must be diluted before use, may contain higher concentrations.

Cosmetic compositions containing phthalimidoperoxycaproic acid as an active ingredient may include at least one adjuvant of surfactants, stabilizers, preservatives, wetting agents, anti-inflammatory agents, antioxidants, colorants, water and mixtures thereof. These adjuvants may be present in amounts of about 98.0 to 99.1 weight percent of the total composition.

Surfactants used in cosmetic compositions include both anionic, cationic and amphoteric and the amount of use is typically at least 30% by weight, preferably at least 70% by weight. Selecting and determining the type and amount of surfactant can be easily made by those skilled in the art.

Preferred stabilizers that can be used in the cosmetic composition include, but are not limited to, glycol stearate. When stabilizers are used, they are generally about 0.1 to 5 weight percent of the composition.

Preferred preservatives that can be used in cosmetic compositions include, but are not limited to, tetrasodium ethylenediamine tetraacetic acid (EDTA), 1- (3-chloroallyl) -3,5,7-traaza-1-adama Tan, paraben, methylparaben, mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, salicylic acid, benzoic acid, triclosan, phenoxyethanol , Benzyl alcohol, benzophenone-4, methylchloroisothiazolinone and methylisothiazolinone or mixtures thereof. If a preservative is used, its amount is typically about 0.01 to 6% by weight of the composition, the preferred amount is about 0.05 to 4% by weight, more preferably about 0.1 to 2% by weight.

Preferred wetting agents that can be used in cosmetic compositions include wheat protein (e.g., laudimonium hydroxypropyl hydrolyzed wheat protein), hair keratin amino acids, sodium peroxylincarbolic acid, panthenol, tocopherol (vitamin E) and dimethicone Or mixtures thereof. Sodium chloride may also be present, especially when hair keratin amino acids are included as wetting agents. Wetting agents are typically used from about 0.01 to 10% by weight, preferably from about 0.05 to 1.5% by weight, more preferably from about 0.01 to 1% by weight of the composition.

Preferred colorants which can be used in cosmetic compositions are FD & C Green No. 3, Ext. D & C Violet 2, FD & C Yellow 5 and FD & C Red 40, or mixtures thereof. Colorants, if used, are typically from about 0.001 to 0.1% by weight of the composition, preferably from about 0.005 to 0.05% by weight.

Preferred anti-inflammatory agents that may be used in cosmetic compositions include any pharmaceutically acceptable compound suitable for topical administration, preferably allantoin. Anti-inflammatory agents, when used, are used in an amount sufficient to inhibit or relieve inflammation and are typically from about 0.1 to 2% by weight, preferably from about 0.3 to 1.5% by weight, more preferably from about 0.1 to 1% by weight of the composition.

Antioxidants that can be used in cosmetic compositions can be used both enzymatic and non-enzymatic antioxidants. Examples of natural enzymatic antioxidants include peroxide dismutase (SOD), catalase and glutathione peroxidase. Suitable non-enzymatic antioxidants include vitamin E (e.g. tocopherol), vitamin C (ascorbic acid), carotenoids, echinacoside, caffeoyl derivatives, oligomeric proanthocyanidins, proantanol (e.g. grapes). Seed extract), silymarin (eg, milk thistle extract, silyboom marianium), Ginkgo biloba and green tea polyphenols or mixtures thereof. Carotenoids are potent antioxidants and examples include beta-carotene, canthaxanthin, zeaxanthin, lycopene, lutein, crocetin, and capxanthin. Preferred antioxidants are vitamin E, vitamin C or carotenoids. Antioxidants, if used, are used in an amount sufficient to inhibit or mitigate the effects of free-radicals on the skin. Typical amounts of antioxidants are from about 0.001 to 1% by weight of the composition, with a preferred amount of about 0.01 to 0.5% by weight.

Cosmetic compositions may contain other adjuvants commonly used in the art. Examples of such adjuvants include perfumes, dyes (including dyes that simultaneously dye or tint hair), solvents, opacifiers, pearlescent agents (eg esters of fatty acids and polyols, magnesium salts of fatty acids and zinc) Salts), copolymer-based dispersions, thickening agents (e.g. sodium chloride, potassium chloride, ammonium chloride and sodium sulfate), fatty acid alkylolamides, cellulose derivatives, natural gums, plant extracts, albumin derivatives (e.g. gelatin), collagen valences Degradation products, natural or synthetic polypeptides, egg yolk, lecithin, lanolin or lanolin derivatives, fats, oils, fatty alcohols, silicones, diorrents, antibacterial substances, anti-seborrheic substances, keratinants (e.g. sulfur, salicylic acid, benzoyl) Peroxides, selenium sulfides, PG, FA, enzymes) and keratant (eg tars, sulfur, salicylic acid, selenium sulfides, antibacterial agents, benzoyl peroxides, L'hexyl City of Aberdeen, iodine, triclosan, an antifungal agent and an enzyme), or a mixture thereof.

All of the above formulations according to the present invention can be formulated in the desired form to compositions comprising phthalimidoperoxycaproic acid using techniques common in the art. Various formulations containing phthalimidoperoxycaproic acid prepared according to the present invention can be used in a conventional manner, preferably applied to the acne area or massaged.

In still another aspect, the present invention relates to an antimicrobial composition containing a phthalimidoperoxy caproic acid as an active ingredient.

The phthalimidoperoxycaproic acid of the present invention is selected from the group consisting of mutant strains of Propionibacterium acnes (Propionibacterium acnes), Streptococcus pyogenes, Staphyllococcus aureus and Staphylococcus aureus. There is an excellent antimicrobial effect against the strain.

The strain strain of Staphylococcus aureus may be MRSA (Methilline Resistant Staphyllococcus aureus) which is a strain strain having methicillin resistance.

The strains of propionibacterium, Staphylococcus aureus, Staphylococcus aureus, and purulent Streptococcus are generally skin floras always present on the face, such as propionibacterium, Staphylococcus aureus, and Staphylococcus aureus strains. Since natural substances having antimicrobial activity are known to have antimicrobial activity against P. aureus (Kim Narae et al., Kor. J. Microbiol. Biotechnol., 37 (1): 80, 2009), the phthalimidoperoxycaproic of the present invention. The acid will also have antimicrobial activity against purulent streptococci.

Therefore, there is no side effect is phthalimido peroxy caproic yimido ikae said de of the present invention, the excellent antimicrobial effect can be usefully employed for the purpose of removing the causative agent of acne, which merchandise to the skin.

Phthalimidoperoxy caproic acid is used as an active ingredient in the antimicrobial composition of the present invention, if the content is lower than 0.0001% by weight of the composition, there is no antimicrobial activity, if higher than 30% by weight of the composition is not preferable in terms of cost The antimicrobial composition may be present in a concentration of 0.0001 to 30% by weight, preferably 0.001 to 20% by weight, more preferably 0.01 to 10% by weight. Within this range, the concentration is determined depending on the application to which the antimicrobial composition is applied. In addition, certain formulations, such as concentrated formulations, which must be diluted before use, may contain higher concentrations.

The antibacterial composition containing the phthalimidoperoxy caproic acid is used for the purpose of efficiently removing bacteria or fungi, but is not particularly limited in the formulation, the composition may be an external composition for the skin, specifically It can be prepared in a formulation selected from the group consisting of solutions, suspensions, sprays, patches, pads, creams, ointments, gels.

The solution may include conventional excipients in addition to the active compound, for example, water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene Glycol, dimethylformamide, oil, cottonseed oil, peanut oil, camellia oil, aloe vera, glycerin, natural corn seed oil, olive oil, castor oil, almond oil and sesame oil, glycerol, glycerol form alcohol, tetirahydrofurfuryl alcohol, polyethylene Solvents, solubilizers and emulsifiers comprising fatty acid esters of glycols and sorbitan or mixtures of these materials. It may also include those selected from the group consisting of methyl or propyl-p-hydroxybenzoate and sorbic acid or mixtures thereof as preservatives.

Suspending agents, in addition to the active compounds, include conventional excipients, for example liquid diluents (eg water, ethyl alcohol, propylene glycol and polyethylene glycol), suspending agents (eg ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, sorbent) Non-crystalline esters, cellulose derivatives and hydrogenated edible fats and oils), microcrystalline cellulose, aluminum metahydroxy, bentonite, agar, ethyl oleate and tragacanth or mixtures of these materials.

Ointments, creams and gels may be used in addition to the active compounds, as usual excipients, for example animal and vegetable fats, wax paraffins, starches, targacanths, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide or these substances It may contain one selected from the group consisting of a mixture of.

Hereinafter, the present invention will be described in more detail with reference to Examples. The following examples illustrate the toxicity testing of the compound phthalimidoperoxycaproic acid and the preparation of a formulation containing phthalimidoperoxycaproic acid as an active ingredient. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.

The composition according to the present invention has low toxicity and excellent antibacterial activity against acne bacteria, and thus has an effect of preventing or treating acne, and thus may be applicable to the production of medicines or cosmetics using the same.

The phthalimidoperoxycaproic acid of the present invention is selected from the group consisting of mutant strains of Propionibacterium acnes (Propionibacterium acnes), Streptococcus pyogenes, Staphyllococcus aureus and Staphylococcus aureus. There is an excellent antimicrobial effect against the strain.

Figure 1 shows the growth inhibitory effect on the propionibacterium acnes strain of phthalimidoperoxy caproic acid of the present invention.
Figure 2 shows the minimum inhibitory concentration for propionibacterium acnes strain of phthalimidoperoxycaproic acid of the present invention.
Figure 3 shows the growth inhibitory effect on Staphylococcus aureus of the phthalimidoperoxy caproic acid of the present invention.
Figure 4 shows the growth inhibitory effect against Staphylococcus aureus having antibiotic resistance of the phthalimidoperoxy caproic acid of the present invention.
Figure 5 shows the minimum inhibitory concentration for Staphylococcus aureus of the phthalimidoperoxy caproic acid of the present invention.
Figure 6 shows the minimum inhibitory concentration for Staphylococcus aureus with antibiotic resistance of the phthalimidoperoxycaproic acid of the present invention.

Example 1: Of phthalimidoperoxy caprol acid  Antimicrobial Activity Test

(One) Propionibacterium  Confirm antimicrobial effect on Acnes

The paper disc diffusion method was used for this experiment. GAM agar medium (NIssui, Tokyo, Japan) was dispensed on a 87 mm diameter plate and solidified horizontally. To observe the antimicrobial effect on propionibacterium acnes, propionibacte incubated in anaerobic gas generation pouch (GasPak EZ, Becton, Dickinson and Company, Sparks, USA) for 24 hours at 37 ° C using GAM liquid medium Leeum Acnes bacteria (KCTC 3314) were plated at 200 μl in a cfu / ml concentration on a plate medium. After removing the water from the plate medium on which the strain was smeared, 45 μl of an acetone solution containing 50 ppm of phthalimidoperoxycaproic acid was dispensed on a paper disk to completely evaporate acetone, and then the propionibacterium acnes bacteria were smeared. On top of the badge.

As a control, the phthalimidoperoxy caproic acid was not included and cultured anaerobicly at 37 ° C. for 24 hours to determine the formation of hypolipidemic acid. As a result, it was found to have an antipropionibacterium acnes effect (FIG. 1). .

(2) Propionibacterium  For Acnes Of phthalimidoperoxy caprol acid  Minimum inhibitory concentration measurement

Propionibacterium acnes (KCTC 3314) was inoculated in the GAM liquid medium and placed in an anaerobic gas generation pouch, which was incubated anaerobicly at 37 ° C. for 24 hours and used as a test bacterium. The medium was prepared so that the phthalimidoperoxy caproic acid concentration was 10, 30, 50, 80, and 100 ppm, respectively, and the medium without the phthalimidoperoxy caproic acid was added as a control. Inoculate each strain with a drop of cfu / mL in each medium and incubate at 37 ° C for static periods after placing it in an anaerobic gas generation pouch, and count the number of colonies to minimize the concentration that inhibited the growth of bacteria (Minimum Inhibiton Concentration: MIC).

As a result, as shown in Figure 2, it was confirmed that the minimum inhibitory concentration of propionibacterium acnes of phthalimidoperoxycaproic acid is 50 ppm.

(3) Staphylococcus aureus ( Staphyllococcus aureus ) And antibiotic-resistant Staphylococcus aureus ( Methicilline Resistant Staphyllococcus Aureus Antimicrobial effect on Confirm

The paper disc diffusion method was used for this experiment. Agar plates (Yeast extract 2 g / L, Peptone 1 g / L, agar 15 g / L) were dispensed on a 87 mm diameter plate and solidified horizontally. In order to observe the antibacterial effect of phthalimidoperoxycaproic acid against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33591, liquid medium (Yeast extract 2 g / L, Peptone 1 g / L) was used for 24 hours at 37 ° C. 200 microliters were plated on a plate medium at a concentration of cfu / ml of each microbe cultured during the shaking. After the strain of the plated medium was removed, 45 μl of an acetone solution containing 50 ppm of phthalimidoperoxycaproic acid was dispensed on a paper disk to completely evaporate acetone, and then the respective cells were placed on the plated medium. . As a control, it did not contain phthalimidoperoxy caproic acid was cultured under aerobic conditions at 37 ℃ for 24 hours, and then the presence of anti-staining staphylococcus and anti-MRSA effect was determined ( 3 and 4).

(4) against Staphylococcus aureus and Staphylococcus aureus with antibiotic resistance Phthalimi Determination of Minimum Inhibitory Concentration of Doperoxy Caproic Acid

Staphylococcus aureus ATCC 25923 and MRSA ATCC 33591, which were shaken at 37 ° C. for 24 hours using a liquid medium (Yeast extract 2 g / L, Peptone 1 g / L), were used as the test bacteria. The medium was prepared so that the phthalimidoperoxy caproic acid concentration was 10, 30, 50, 80, and 100 ppm, respectively, and the medium without the phthalimidoperoxy caproic acid was added as a control. Test strains were inoculated in each medium at a concentration of cfu / mL, and the colonies were counted after incubating at 37 ° C. for 24 hours to determine the concentration at which the growth of bacteria was inhibited as the minimum inhibitory concentration (MIC).

As shown in Figures 5 and 6, it was confirmed that the minimum inhibitory concentration of phthalimidoperoxycaproic acid against Staphylococcus aureus and MRSA was about 50 ppm.

Example 2: Of phthalimidoperoxy caprol acid Percutaneous Toxicity Test

Purified phthalimidoperoxycaproic acid isolated from the culture filtrate was tested for acute dermal toxicity in rats (magnetic, 4 week old) according to the Korea Food and Drug Administration. The test method was observed for 15 days after hair removal of rats uniformly applied at a concentration of 4000 mg / kg (body weight) to about 10% of the body surface area.

As a result, skin irritation such as skin erythema and skin formation was not seen. Therefore, phthalimidoperoxy caproic acid was judged to be a low toxicity antibacterial substance.

Example 3: Hydrophilic Ointment Formulation hydrophilic ointment Manufacturing

A hydrophilic ointment was prepared which was washed with water using the ingredients of the following formulation. Stearyl alcohol and white petrolatum were dissolved in a steam bath and warmed to about 75 ° C. Separately water was heated to 75 ° C. to which lauryl sulfate, propylene glycol, methylparaben and propylparaben were added. The aqueous phase and the active ingredient phthalimidoperoxycaproic acid were added and stirred until condensation gave an ointment.

ingredient weight%    Phthalimidoperoxy caproic acid 0.5    White Petrolatum 25    Stearyl alcohol 25    Propylene glycol 12    Sodium lauryl sulfate One    Methyl paraben 0.025    Purified water 100 adjustment amount

Example 4: Preparation of Cream Formulations

O / W creams were prepared using the ingredients of the following formulation. The oil phase and the aqueous phase were separately heated to 70 ° C. and then the oil phase was added slowly to the aqueous phase with stirring to give a crude emulsion. The emulsion was cooled to about 55 ° C. and homogenized. Cooling with shaking until the homogenate condensed gave a cream.

ingredient weight% (Oil phase)    Phthalimidoperoxy caproic acid 0.5    Stearyl alcohol 15    beeswax 8    Sorbitan monooleate 1.25 (Aqueous phase)    Sorbitol Solution, 70% USP 7.5    Polysorbate 80 3.75    Methyl paraben 0.025    Propylparaben 0.015    Purified water 100 adjustment amount

Example 5: Varnishing  Preparation of Cream Formulations

A varnishing cream was prepared using the ingredients of the following formulation. The oil phase and the aqueous phase were separately heated to about 65 ° C. The oily phase was added slowly with stirring to form a crude emulsion. The emulsion was cooled to about 50 ° C and homogenized. Cooling with shaking until the homogenate condensed gave a varnishing cream.

ingredient weight% (Oil phase)    Phthalimidoperoxy caproic acid 0.5    Stearic acid 13    Stearyl alcohol One    Cetyl alcohol One    Propylparaben 0.05 (Aqueous phase)    glycerin 10    Methyl paraben 0.1    Potassium hydroxide 0.9    Purified water 100 adjustment amount

Example 6: Preparation of Gel Formulations

A gel (lubricating jelly) was prepared using the ingredients of the following formulation. The solution was prepared by dispersing in 40 ml of hot water (80 ° C. to 90 ° C.) and placing in a refrigerator overnight to cool. Separately, Carbopol 934 was dispersed in 20 ml of water and a sufficient amount of 1% sodium hydroxide solution (approximately 12 ml required per 100 ml) was adjusted to pH 7.0 and purified water was added to make 40 ml. . In addition, methylparaben and phthalimidoperoxycaproic acid were dissolved in propylene glycol separately. The three solutions prepared above were mixed with care to avoid entering air to obtain a gel.

ingredient weight%    Phthalimidoperoxy caproic acid 0.5    Methocel 90 H.C. 4000 0.8    Carbopol 934 0.24    Propylene glycol 16.7    Sodium hydroxide pH 7 adjusted amount    Purified water 100 adjustment amount

Example 7: Skin irritation test

The skin irritation test was conducted by a paper published by Genji Imokawa et al. (Genji Imokawa and Yutaka Mishma, Nichihikaishi, 86 (8): 473, 1976), and closed using a Finn Chamber of Norgesplaster A / S Closed patch test was performed.

The formulations prepared in Examples 3 to 6 were absorbed by 10 μl in a paper disc fitted with a Finn Chamber and placed in a Finn Chamber for 48 hours on 10 adult male skin. After 48 hours the Finn Chamber was immediately removed, washed in running tap water and dried and after 2 hours the skin condition was determined according to the following criteria:

Criteria (stimulation intensity)

-: No change with the naked eye

O: light redness

+: Moderate redness

++: strong redness and edema

As a result, as shown in Table 5, the transdermal formulation of the present invention was shown to be not toxic at all by not irritating the skin.

Judgment result Example 3 - Example 4 - Example 5 - Example 6 -

Example 8 Acne Prevention Effect Test

Ten male patients in their 20s and 40s with red acne were selected and tested as follows. First, the face part was divided into two parts, one side using the cream of Example 4 containing phthalimidoperoxycaproic acid as the test group, and the other side corresponding to the control group containing no phthalimidoperoxycaproic acid as the control group. The creams were applied twice daily for 14 days and then visually assessed for acne counts at two-day intervals.

Evaluation criteria were used in the following four steps, the entire face was determined.

0: no further acne has occurred;

1: Less acne was seen compared to the control group;

2: when acne showed a degree similar to that of the control group; And

3: When more acne is seen than the control group.

The average of each rating was computed and shown in Table 6 below. To calculate the average rating of the acne in the test group and the control group was measured for 10 patients every two days intervals of 0 to 3 to determine the corresponding step was added to calculate the rating.

Judgment grade O 0 to 1.5 X 1.5 to 3.0

Here, "○" indicates that there is an acne prevention effect, and "X" indicates that there is no acne prevention effect.

As a result of the test, after applying the cream of Example 4 containing phthalimidoperoxy caproic acid, the number of acne was similar to the control group with a score of 2.1 until the second day in the test group, but it was 1.1 from the fourth day and acne than the control group. Less was observed. After that, no further acne occurred from day 8 to day 14, which was calculated as a rating of 0, indicating that there was an acne prevention effect, and in the control group, acne occurred more than the initial test, which was determined as a rating of 3.

Example 9 Acne Treatment Effect Test

Most people with severe acne have red acne and purulent acne. In these cases, the effective acne treatment will begin to go away as soon as 2-3 days after application.

The extent of recovery against acne inflammation of the cream preparation test group containing phthalimidoperoxy caproic acid and the corresponding cream formulation containing no phthalimidoperoxy caproic acid as a control group was examined.

Ten patients with acne with red acne and purulent acne were treated for 30 days. The cream prepared in Example 4 was rubbed into the acne area and visually checked the condition of the acne once every two days. The face part was divided into two, one side was a test group, and the other side was a control group. As a criterion for evaluating the therapeutic effect on acne inflammation, the following five steps were used, and the entire face was performed.

0: failure to identify inflammation of acne;

1: acne inflammation recovered by 80% compared to control;

2: acne inflammation recovered by 50% compared to control;

3: acne inflammation recovered by 30% compared to control; And

4: When acne inflammation has not recovered at all compared to the control.

The average of each rating was computed and shown in Table 7 below. The average method of calculating the ratings was to measure the acne inflammatory state of the test group and the control group for 10 patients at intervals of 2 days, and then set the corresponding step of 0 to 4 and calculate the rating.

Judgment grade O 0 to 1.5 X 1.5 to 4.0

Here, "○" indicates that there is an acne treatment effect, and "X" indicates that there is no acne treatment effect.

As a result of the test, the cream-treated test group of Example 4 containing phthalimidoperoxy caproic acid showed a rating of 3.0 from the 4th day, and began to show the effect on inflammation, and markedly marked with a score of 1.2 from the 14th day. From day 18, there was almost no inflammation with a rating of 0.1. In the control group, a rating of 3.5 was determined. Therefore, from day 18, the acne inflammation was completely cured in all patients in the test group.

The specific parts of the present invention have been described in detail above, and it is apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. something to do. Therefore, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (5)

Containing phthalimidoperoxy caproic acid as an active ingredient,
A composition for preventing or treating acne.
The method of claim 1,
The composition is characterized in that it exhibits a prophylactic or therapeutic activity against a strain selected from the group consisting of propionibacterium acnes, purulent Streptococcus, Staphylococcus aureus and Staphylococcus aureus,
A composition for preventing or treating acne.
3. The method according to claim 1 or 2,
50 ppm minimum inhibitory concentration for the mutant strains of Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus aureus of phthalimidoperoxycaproic acid,
A composition for preventing or treating acne.
Containing phthalimidoperoxy caproic acid as an active ingredient,
Antimicrobial composition.
5. The method of claim 4,
The antimicrobial composition is characterized in that it exhibits antimicrobial activity against a strain selected from the group consisting of propionibacterium acnes, purulent Streptococcus, Staphylococcus aureus and Staphylococcus aureus strains,
Antimicrobial composition.

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