Composition for exfoliating cuticles or improving skin condition

Abstract

This invention addresses the problem of reduced stability of proteolytic enzymes in the composition and the resulting reduced exfoliation effect by including a series of proteolytic enzyme exfoliating materials together with sugar alcohols and / or serine, and can provide a safe and stable composition with improved exfoliation and skin condition improvement effects.

Description

Technical Field

[0001] This invention relates to cosmetic compositions that provide excellent exfoliation and skin texture improvement effects by enhancing the stability of the active ingredient used for exfoliation. Background Technology

[0002] With increasing focus on beauty, the demand for and attention to exfoliation (pilling), or peeling, in skin management is gradually increasing. Exfoliation comes in various forms and methods, ranging from specialized treatments like surgical exfoliation at dermatology clinics or skin management parlors to home care using cosmetics and household products. However, compared to surgical exfoliation, home care using cosmetics often provides a less noticeable exfoliating experience.

[0003] Materials used for exfoliation mainly include chemical exfoliants such as AHA (alpha hydroxylacid) compounds like lactic acid and glycolic acid, BHA (beta hydroxy acid) compounds like salicylic acid, and PHA (polyhydroxyl acid) compounds like gluconolactone; protein-degrading enzymes such as papain, bromelain, and proteolytic enzymes; and physical exfoliants such as scrub ingredients. Chemical exfoliants are certified effective enough for routine use in dermatological procedures and are widely used; however, due to irritation and safety concerns, it is difficult to apply concentrations at levels that provide a noticeable effect to home care products.

[0004] Proteolytic enzymes mainly include plant-derived enzymes such as papain and bromelain, as well as proteolytic enzymes produced by culturing Bacillus sp. microorganisms, such as subtilisin. From the perspective of enzyme characteristics, a single molecule can act multiple times to break down proteins, thus exhibiting excellent exfoliation efficacy even at low concentrations. Furthermore, compared to chemical exfoliating materials, their larger molecular size prevents absorption or penetration into the skin, resulting in relatively less irritation. However, considering the characteristics of protein-based materials, their efficacy decreases during product application due to factors such as reduced activity over time and in response to environmental conditions, making commercialization difficult.

[0005] Therefore, against this background, the inventors developed a cosmetic composition that improves the stability of a series of protein-degrading exfoliating materials with exfoliating effects in cosmetic compositions and enhances the exfoliating effect, thus completing the present invention. Summary of the Invention

[0006] The problem to be solved

[0007] As described above, the results of research conducted to address the problem of reduced stability of proteolytic enzyme-based exfoliating materials in compositions and the resulting reduction in exfoliation effectiveness have confirmed that when serine and sugar alcohol are simultaneously included in a cosmetic composition containing proteolytic enzyme-based exfoliating materials as active ingredients, the stability of the active ingredients in the composition is improved, thereby increasing the duration of exfoliation ability and enhancing exfoliation efficacy, as well as improving skin texture, pore size, and wrinkles. This completes the present invention.

[0008] Therefore, the object of the present invention is to provide a cosmetic composition that enhances the stability of the active ingredient and the maintenance of its exfoliating activity, thereby causing less irritation and providing excellent exfoliating, skin texture improvement, pore reduction, and wrinkle reduction effects.

[0009] Solution to the problem

[0010] To achieve the above objectives, the present invention provides a composition comprising a protein-degrading enzyme and sugar alcohols and / or serine. Specifically, the composition may comprise a protein-degrading enzyme, sugar alcohols, and serine.

[0011] The compositions of the present invention simultaneously contain proteolytic enzymes and sugar alcohols, thereby improving the stability of the proteolytic enzymes and their ability to maintain exfoliation, thus providing enhanced or improved exfoliation effects. Additionally, the simultaneous presence of proteolytic enzymes and serine provides an enhanced exfoliation effect through this combination. In this respect, the present invention provides a composition for exfoliating the stratum corneum. The above compositions can be used as cosmetic compositions, pharmaceutical compositions, topical formulations, quasi-pharmaceutical compositions, or food compositions, depending on their intended use.

[0012] In this specification, "exfoliation" refers to the shedding or removal of keratinocytes accumulated in the stratum corneum of the skin. This is intended to include not only removal by applying physical force, but also removal from the stratum corneum of the skin by simple composition treatment without applying additional force.

[0013] The compositions of the present invention contain a keratolytic component with protease as an active ingredient.

[0014] In this specification, "protease" refers to an enzyme that hydrolyzes the peptide bonds of proteins, also known as a protein hydrolase. Any protease that has the function of exfoliating the skin is included in this invention without limitation.

[0015] As a specific example, the aforementioned protease may include papain, bromelain, keratinase, and subtilisin, and one or more selected from the group consisting of the above-mentioned components may be included as active ingredients in the cosmetic composition. Furthermore, commercially available substances containing one of the aforementioned protease components are also included in the protease of the present invention. For example, X-pressin (BASF), a component containing papain, and Wonderzyme, a component containing both papain and bromelain, are included in the present invention as proteases or individual enzyme substances. As components of the aforementioned keratinase, keratinase H or keratinase S may be included in the present invention.

[0016] According to one aspect of the invention, the composition of the invention preferably contains a proteolytic enzyme as an active ingredient. As the active ingredient, the proteolytic enzyme may be present in an amount of 0.0001% to 1.0% by weight relative to the total weight of the composition, preferably from 0.0001% to 0.5% by weight. When the content of the proteolytic enzyme is less than 0.0001% by weight, the effect of exfoliating or improving skin condition cannot be obtained; when it exceeds 1.0% by weight, the increase in effect due to the increased content is not significant.

[0017] In one embodiment of the present invention, the results of an experiment on the skin exfoliation effect of keratinase (LCS biotechnology), a protease, confirmed that the exfoliation efficacy increased with the increase of the concentration of keratinase (a protease) (Example 1).

[0018] The compositions of the present invention also contain a keratolytic agent with serine as an active ingredient.

[0019] In this specification, "serine" refers to an amino acid and is used to mean that it includes all isomers such as (S)-serine and L-serine.

[0020] As an amino acid, serine reaches saturation in exfoliation efficacy when contained in cosmetic compositions at a concentration exceeding 3.0% by weight, limiting its potential for enhanced effectiveness. However, when serine is incorporated in combination with proteolytic enzymes and sugar alcohols in the cosmetic compositions of the present invention, enhanced exfoliation capacity can be achieved compared to using only a single ingredient, thus overcoming the aforementioned limitations.

[0021] According to one aspect of the invention, the composition of the invention may contain serine at a concentration of 0.1% by weight or more, preferably from 0.1% by weight to 3.0% by weight, relative to the total weight of the composition. When the serine content is less than 0.1% by weight, its effect is not significant, and when it exceeds 3.0% by weight, the increase in effect due to the increase in composition content is not significant.

[0022] In this specification, "sugar alcohol" refers to an alcohol having two or more hydroxyl groups (-OH) formed by hydrogenation reduction of the aldehyde or ketone group in the carbonyl group of a monosaccharide, or a compound belonging to the same series. In the composition of the present invention, sugar alcohol plays a role in stabilizing the proteolytic enzyme, thereby increasing the enzyme's proteolytic activity and enhancing the duration of its degradative ability. This solves the problem of reduced proteolytic enzyme activity in exfoliating products, which leads to decreased product quality and effectiveness. Therefore, in a composition containing both proteolytic enzyme and sugar alcohol, the exfoliating ability of the proteolytic enzyme can be maintained for a long time, and a superior exfoliating effect can be obtained compared to a sample of the same concentration containing only proteolytic enzyme.

[0023] As a specific example, the aforementioned sugar alcohols are intended to include glycerol, erythritol, sorbitol, threitol, arabitol, xylitol, mannitol, sorbitol, ethyl glycol, propylene glycol, dipropylene glycol (DPG), and butanediol (e.g., 1,3-butanediol, 1,3-Butylene Glycol: 1,3-BG), as well as all isomers of the aforementioned components. Specifically, it may be a mixture of one or more sugar alcohols selected from the group consisting of sugar alcohol components.

[0024] When the protein-degrading enzyme and a single sugar alcohol are included, as a preferred example, the sugar alcohol may be glycerol, sorbitol, erythritol, dipropylene glycol or butylene glycol.

[0025] Furthermore, the aforementioned sugar alcohols may be contained in the form of a mixture of two or more components selected from the group consisting of glycerol, sorbitol, dipropylene glycol, butylene glycol, and erythritol. As a preferred example, the aforementioned sugar alcohol mixture may contain glycerol, sorbitol, dipropylene glycol, butylene glycol, and erythritol.

[0026] According to one aspect of the present invention, the cosmetic composition of the present invention may contain sugar alcohols from 0.001% to 30.0% by weight relative to the total weight of the composition. When the content of sugar alcohols is less than the above-mentioned 0.001% by weight, the effect of improving the stability of the active ingredient proteolytic enzymes is not significant, and when the content exceeds 30.0% by weight, the increase in effect due to the increased content is not significant.

[0027] Even when the above-mentioned sugar alcohols are included as a mixture of sugar alcohols, they can be mixed and included in the composition within the range of a maximum content of no more than 30% by weight of the mixture of sugar alcohols. As an example, when included in the composition as a mixture of sugar alcohols, it can be included such that the content of the entire sugar alcohol mixture relative to the entire composition is no more than 30% by weight relative to the entire composition, within the range of 0.001 to 20 w / w% of glycerol, 0.001 to 20 w / w% of sorbitol, 0.001 to 20 w / w% of DPG, 0.001 to 20 w / w% of 1,3-butanediol and 0.001 to 10 w / w% of erythritol.

[0028] In one specific example of the invention, the exfoliation effect was confirmed by mixing the proteolytic enzyme with a sugar alcohol including glycerol, sorbitol, dipropylene glycol, 1,3-butanediol and erythritol. It was confirmed that although the sugar alcohol does not have exfoliation activity, the exfoliation effect was significantly enhanced compared with the case of treating the proteolytic enzyme alone, and the proteolytic activity was maintained for a long time (Examples 2 and 3).

[0029] It is understood that the above-mentioned components can be used by purchasing commercially available compounds, and commercially available forms are also included in this invention.

[0030] Furthermore, the compositions of the present invention can improve skin condition through exfoliation. In this regard, the present invention provides a composition for improving skin condition.

[0031] In this specification, "improving skin condition" is intended to include not only improving the appearance of the skin, thereby making the skin texture smoother or alleviating the unevenness of the skin, or improving the skin tone to present a healthy complexion, but also restoring and improving imbalances in the skin's internal cells, etc. The compositions of the present invention can improve skin condition by effectively and stably exfoliating the keratin generated on the skin surface.

[0032] The aforementioned improvements in skin condition specifically include effects such as improving skin texture, improving skin tone, improving skin pores, improving skin wrinkles, alleviating skin unevenness, or improving skin tone. In this regard, the compositions of the present invention provide compositions comprising proteolytic enzymes, sugar alcohols, and serine for improving skin texture, compositions for improving skin tone, compositions for improving, shrinking, or reducing pores, or compositions for improving skin wrinkles.

[0033] In this instruction manual, "improving skin texture" refers to relieving or removing skin bumps and depressions through peeling, resulting in a smooth and healthy skin surface.

[0034] In this instruction manual, "improving skin tone" means brightening the skin by removing dull areas of the skin through exfoliation.

[0035] In this instruction manual, "improving pores" or "shrinking or reducing pores" means that the size (diameter, volume) of pores existing in the skin becomes smaller or the number of pores decreases.

[0036] In this instruction manual, "improving wrinkles" means preventing, inhibiting or preventing the formation of wrinkles on the skin, or alleviating wrinkles that have already formed.

[0037] In this specification, "composition" is intended to include cosmetic compositions, pharmaceutical compositions, topical compositions, quasi-pharmaceutical compositions, and food compositions. The categories of these compositions may be changed depending on their intended use, the content of the active ingredient, etc.

[0038] In one respect, the above-mentioned composition can be a cosmetic composition. In this respect, the present invention provides a cosmetic composition for exfoliation or for improving skin condition, comprising a proteolytic enzyme, a sugar alcohol, and serine.

[0039] In this specification, "cosmetic composition" refers to a composition made for the purpose of preparing cosmetics, and can be broadly interpreted to include topical compositions for external use.

[0040] The cosmetic compositions according to the present invention can also be prepared in any dosage form commonly prepared in this field. For example, the cosmetic compositions described above can be in the form of lotions such as softening lotions or nourishing lotions, spray lotions, emulsions such as facial lotions and body lotions, creams such as nourishing creams, moisturizing creams, and eye creams, sticks, serums, cosmetic ointments, sprays, gels, masks, sunscreens, makeup bases, liquid or spray foundations, powders, makeup removers such as cleansing lotions and cleansing oils, cleansing foams, soaps, shower gels, and other detergents, but are not limited thereto.

[0041] The cosmetic composition of the present invention can be used according to conventional methods, and the number of times it is used can be varied according to the user's skin condition or preference.

[0042] The cosmetic compositions of the present invention may also contain all kinds of ingredients that can be used in conventional cosmetics, such as moisturizers, UV blockers, neutralizers, thickeners, fragrances, preservatives, antioxidants, or pigments.

[0043] The ingredients described above in the cosmetic composition according to the present invention are preferably included in the cosmetic composition of the present invention within the range not exceeding the maximum usage amount specified in the laws or regulations concerning cosmetic safety of various countries.

[0044] In another aspect, the above-mentioned composition can be a pharmaceutical composition. In this respect, the present invention provides a pharmaceutical composition comprising a proteolytic enzyme, a sugar alcohol, and serine.

[0045] In this specification, "pharmaceutical composition" refers to a composition intended for the preparation of pharmaceutical products, specifically a composition intended for the diagnosis, treatment, mitigation, management, or prevention of diseases in animals, including humans. In a broader sense, it can be interpreted as including quasi-pharmaceutical compositions that are not available for purchase with a physician's permission but are distinct from cosmetics or general topical agents, and are intended for use for the aforementioned purposes.

[0046] The compositions of the present invention can provide a stable composition for exfoliating keratinocytes with excellent exfoliating effect. Therefore, the present invention can be a pharmaceutical composition comprising a proteolytic enzyme, a sugar alcohol and serine for the prevention or treatment of keratosis.

[0047] In this instruction manual, "keratosis" refers to a condition in which excessive keratin is produced on the skin surface due to genetic or environmental factors, specifically including keratosis pilaris or keratosis of the hands and feet.

[0048] In this specification, "improvement" means any action that, by administering the composition of the present invention, results in a better or more favorable change in the target symptoms compared to the symptoms before administration.

[0049] In this specification, "prevention" means all actions taken to prevent or delay the occurrence or appearance of a target symptom or disease by delivering the composition of the present invention.

[0050] In this specification, "treatment" means all actions that improve or eliminate target symptoms or diseases by delivering the composition of the present invention.

[0051] The proteolytic enzymes, sugar alcohols, and serine contained in the compositions of the present invention may be included in pharmaceutically effective amounts (effective quantities). The term "effective quantity" refers to the amount that, by exfoliating the keratinized skin, demonstrates an effect capable of preventing or treating keratosis or palmoplantar keratosis.

[0052] If the above-described composition can exhibit a keratolytic effect at a therapeutic level, it may be included in various weight percentages. When each active ingredient is included below the lower limit, it may not exert its keratolytic preventive or therapeutic effect, and when it is included above the upper limit, the physical properties, color, or characteristic fragrance of the active ingredient itself may affect the product.

[0053] The compositions of the present invention are delivered in a pharmaceutically effective amount. A pharmaceutically effective amount is defined as an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment without causing side effects. The effective dosage level can be determined based on factors including the patient's health status, the type and severity of the disease, the activity of the drug, the sensitivity to the drug, the method of delivery, the time of delivery, the route of delivery and the excretion rate, the duration of treatment, the drugs being formulated or used concurrently, and other factors well-known in the medical field.

[0054] In another aspect, the present invention provides a method for preventing or treating keratosis, comprising the steps of dispensing or applying a pharmaceutical composition comprising a proteolytic enzyme and a sugar alcohol to an object or object skin for which keratosis needs to be prevented or treated, and the steps of inhibiting or reducing the occurrence of keratosis in the object or object skin.

[0055] The above-described composition can be administered to mammals such as mice, rats, livestock, and humans via various routes, including non-oral and oral administration, and all possible routes of administration are foreseeable, such as via mucosal, skin, oral, rectal or intravenous, intramuscular, subcutaneous, intradural, or intracerebral (intracerebroventricular) injection. Skin administration includes external treatment of the composition with the skin.

[0056] The pharmaceutical compositions of the present invention may contain the above-described compositions as active ingredients alone, and may also contain pharmaceutically permissible carriers, excipients, diluents or by-products, depending on the dosage form, method of use and purpose of use.

[0057] More specifically, in addition to the above-mentioned active ingredients, it may also contain nutrients, vitamins, electrolytes, flavoring agents, coloring agents, fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, and carbonating agents used in carbonated beverages.

[0058] The term "pharmaceutically acceptable" as used above refers to something that is physiologically acceptable and, when administered to animals, preferably humans, generally does not cause gastrointestinal disturbances, dizziness, or other allergic reactions or similar reactions. The pharmaceutically effective dosage may be adjusted appropriately based on the disease and its severity, the patient's age, weight, health status, sex, route of administration, or duration of treatment.

[0059] Examples of pharmaceutically permissible carriers, excipients, or diluents include, but are not limited to, one or more of the following groups: lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylparaben, propylparaben, talc, magnesium stearate and mineral oil, propylparaben, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, and physiological saline. Conventional carriers, excipients, or diluents may also be used.

[0060] The above ingredients can be added independently or in combination to the above active ingredients.

[0061] The dosage form of the above-described pharmaceutical compositions can be changed depending on the method of use, and can be formulated using methods well known in the art to which this invention pertains to provide a rapid, sustained, or delayed release of the active ingredient upon administration to mammals. Examples of the above-described dosage forms include those selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, oral liquids, emulsions, syrups, aqueous solutions, non-aqueous solvents, suspensions, and oils.

[0062] For the above dosage forms, excipients may also be included, such as conventional fillers, extenders, binders, disintegrants, surfactants, anti-aggregators, lubricants, wetting agents, fragrances, emulsifiers, preservatives, sweeteners, flavorings, or preservatives.

[0063] Generally, solid dosage forms for oral administration include tablets, pills, soft or hard capsules, pills, powders, and granules. These preparations can be formulated by mixing with one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used.

[0064] In addition, liquid formulations for oral administration include suspensions, oral liquids, emulsions, and syrups. Besides water or liquid paraffin, which are commonly used as simple diluents, they may also include a variety of excipients, such as humectants, sweeteners, flavorings, and preservatives.

[0065] Examples that may be mentioned for use in skin delivery include carriers and / or excipients suitable for generating dusting powders, emulsions, suspensions, oils, sprays, ointments, greasy ointments, creams, gels, foams, or solutions, and suitable for transdermal drug delivery systems (TTS). The topical pharmaceutical formulations of the present invention can be semi-solid dosage forms, particularly ointments (solution ointments, suspension ointments), creams, gels, or ointments. The emulsions primarily use fatty alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol; fatty acids such as palmitic acid or stearic acid; liquid or solid paraffin or ceresin; liquid or solid waxes such as isopropyl myristate; natural fats or partially synthetic fats such as coconut fatty acid triglycerides; hardened oils such as hydrogenated peanut oil or castor oil; or fatty acid fractions of glycerol such as glyceryl monostearate or glyceryl distearate. Suitable emulsifiers include surfactants, such as nonionic surfactants, fatty acid esters of polyols or their ethylene oxide adducts, such as polyglycerol fatty acid esters or polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, such as sorbitan oleate or sorbitan isostearate, isostearates, sterols or polyoxyethylene fatty alcohol ethers or fatty acid esters; and anionic surfactants, such as alkali metal salts of fatty alcohol sulfonates, such as sodium lauryl sulfate, sodium cetyl sulfate or sodium stearyl sulfate, which are typically used in the presence of the aforementioned fatty alcohols, such as cetyl alcohol or stearyl alcohol. In particular, anti-frost drying agents, such as polyols like glycerol, sorbitol, propylene glycol or polyethylene glycol, can be added to the aqueous phase, or preservatives, fragrances, etc., can be added to the aqueous phase.

[0066] The pharmaceutical formulation of the present invention may be an anhydrous ointment suitable for topical use, containing paraffin, especially low-viscosity paraffin, which is liquid at body temperature, or may contain the aforementioned natural or partially synthetic fats such as coconut fatty acid triglycerides, hardened oils such as hydrogenated peanut oil or castor oil, fatty acid fractions of glycerol such as glyceryl monostearate and distearate, organosilicon such as polymethylsiloxane, such as hexamethyldisiloxane or octamethyltrisiloxane, and may contain fatty alcohols associated with water-based creams and increasing water absorption capacity, as well as sterols, wool wax, other emulsifiers and / or other additives.

[0067] In this invention, when the above-mentioned pharmaceutical composition is formulated into a pharmaceutical product, reference can be made to the disclosure in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, and the above-mentioned literature is included as part of this specification.

[0068] The above-mentioned pharmaceutical composition may be a quasi-pharmaceutical composition.

[0069] In this instruction manual, "quasi-medicinal product" refers to an article that exhibits effects of treatment, relief, management, or prevention of disease, but has a milder effect on the human body than a pharmaceutical product. This excludes articles intended for pharmaceutical use under the Pharmaceutical Affairs Law, and includes articles classified according to other standards prescribed by the Ministry of Health and Welfare. Specifically, it can be a topical skin preparation or a personal hygiene product, but is not limited to these.

[0070] When the compositions of the present invention are added to quasi-medicinal compositions for the purpose of preventing, improving, or treating skin peeling or improving skin condition, the compositions can be added directly or used together with other quasi-medicinal ingredients, and can be used appropriately according to conventional methods. The amount of active ingredients mixed can be appropriately determined according to the purpose of use.

[0071] The aforementioned topical skin agents are not particularly limited thereto, but may be prepared as ointments, lotions, sprays, patches, creams, powders, suspensions, gels, or gels for use. The aforementioned personal hygiene products are not particularly limited thereto, but may specifically include soaps, cosmetics, wet wipes, toilet paper, shampoos, moisturizing creams, face creams, toothpaste, lipsticks, perfumes, makeup, foundation, blush, mascara, eyeshadow, sunscreen, hair care products, air freshener gels, or cleansing gels. Other examples of the topical pharmaceutical compositions of the present invention include disinfectant cleaners, shower foams, wet wipes, detergent soaps, hand sanitizers, masks, or ointments.

[0072] Unless otherwise stated, the values ​​described in this specification shall be interpreted as including equal ranges.

[0073] Invention Effects

[0074] The compositions according to the invention can provide a safe and stable composition with improved exfoliation and skin condition by mitigating the reduced stability of proteolytic enzymes in the composition and the resulting reduced exfoliation effect. Attached Figure Description

[0075] Figure 1This demonstrates that when the protein-degrading enzyme of the present invention is used alone, the keratolytic effect is superior to that of the chemical exfoliating material gluconolactone (PHA).

[0076] Figure 2 The present invention demonstrates a mixed composition of proteolytic enzymes, sugar alcohols, and serine, which exhibits superior keratolytic performance compared to chemical exfoliating materials such as pharmacolactone (PHA), sugar alcohols alone, serine alone, proteolytic enzymes alone, mixtures of sugar alcohols and serine, mixtures of proteolytic enzymes and sugar alcohols, and mixtures of proteolytic enzymes and serine.

[0077] Figure 3 The sugar alcohols and serine of the present invention demonstrate that they prolong the duration of the exfoliating ability of the protein-degrading enzymes.

[0078] Figure 4 This invention demonstrates the effect of a composition comprising a proteolytic enzyme, a sugar alcohol, and serine on improving skin texture and pores.

[0079] Figure 5 The dosage form containing the composition of the present invention, comprising a proteolytic enzyme, a sugar alcohol, and serine, demonstrates the effect of improving pores and wrinkles. Detailed Implementation

[0080] The advantages and features of the present invention, as well as the methods for achieving them, will become clear by referring to the experimental and preparation examples described in detail below. However, the present invention is not limited to the experimental and preparation examples disclosed below, but will be implemented in various different forms, and is provided merely to complete the disclosure of the invention and to fully inform those skilled in the art of the scope of the invention.

[0081] [Example]

[0082] Example 1. Exfoliation effect of protein-degrading enzymes

[0083] Moisture was removed by pressing the pigskin (Medi Kenitics, 2.5cm x 2.5cm x 1000um) with a paper towel, and then holes were punched using a 6mm punch sterilized with ethanol. The pigskin slices were placed epidermally upwards in 96-well plates, and each experimental group was completely immersed in 125ul of the prescribed concentration of raw material, then stored at 37°C for 20 hours (50% humidity). Afterwards, the number of keratinocytes shed into the solution was counted using a cell counting chip, and the exfoliation efficacy was measured.

[0084] Water was used as the control group, gluconolactone was used as the PHA, and keratinase (LCS Biotechnology) was used as the proteolytic enzyme.

[0085] The treatment group of proteolytic enzymes was tested using a composition containing 0.005 w / w%, 0.0075 w / w%, 0.01 w / w%, 0.05 w / w%, 0.1 w / w%, or 1 w / w% of the proteolytic enzyme keratinase, 2 w / w% of hexanediol, and the balance being purified water.

[0086] In the PHA 10w / w% composition, the degree of exfoliation was confirmed under two conditions: pH 4, where gluconolactone has the highest exfoliating efficacy, and pH 6, a condition commonly used in leave-on cosmetic formulations. In this experiment, the amount of exfoliation caused by purified water was set as 0, and the amount of exfoliation caused by proteolytic enzymes was calculated by converting the amount of exfoliation in the PHA 10w / w% (pH 4) experimental group to 100.

[0087] The result, such as Figure 1 As shown, the exfoliating efficacy of 0.005 w / w% proteolytic enzyme (51.1%) was confirmed to be higher than that of PHA 10 w / w% (pH 6) commonly used in cosmetics (30.9%). It was confirmed that the exfoliating efficacy increased with increasing proteolytic enzyme concentration, and that at concentrations above 0.05 w / w%, efficacy saturated, thus no further increase in exfoliating effect was observed.

[0088] Example 2. Confirmation of the exfoliating effect of the composition containing proteolytic enzymes, sugar alcohols and serine. The exfoliating effect was confirmed by the same method as in Example 1 above.

[0089] The control group was treated with only purified water, while the PHA treatment group utilized a 10 w / w gluconolactone solution (pH 4) and a 10 w / w gluconolactone solution (pH 6). Figure 2 In the mixture, PHA pH 4 and PHA pH 6 were used. Sugar alcohols were utilized in a mixture, specifically comprising 5 w / w glycerol, 5 w / w sorbitol, 5 w / w DPG, 5 w / w 1,3-BG, and 2 w / w erythritol relative to the whole composition. Serine was utilized using a 0.5 w / w 0.5 w / w L-serine amino acid solution (pH 6).

[0090] The proteolytic enzyme used was keratinase (LCS biotechnology), and the proteolytic enzyme was contained in the experiment at a concentration of 0.01 w / w%. Figure 2 In this context, protease is involved.

[0091] When containing all of the protease, serine, and sugar alcohols (a mixture of sugar alcohols), a composition containing 0.01 w / w keratinase, 0.5 w / w serine, 5 w / w glycerol, 5 w / w sorbitol, 5 w / w DPG, 5 w / w 1,3-BG, 2 w / w erythritol, 0.02 w / w hexanediol, and the balance 77.47 w / w purified water was used.

[0092] Using the same method as in Example 1, the exfoliation effect was confirmed in each treatment group, particularly when proteolytic enzymes, serine, and sugar alcohols were combined, the effect of proteolytic enzymes on the exfoliation efficacy was confirmed.

[0093] The result, such as Figure 2 As shown, the sugar alcohol mixture did not exhibit exfoliating efficacy (2.3%), while serine alone demonstrated approximately 37% exfoliating ability. In the experimental group of mixtures of serine and sugar alcohol, no improvement in exfoliating ability was observed.

[0094] Surprisingly, it was confirmed that the exfoliating ability of the protease was significantly increased when treated with a combination of serine (0.5 w / w%) and proteolytic enzyme (0.01 w / w%), and when the protease was treated with sugar alcohol (176%). Furthermore, the exfoliating ability was significantly enhanced when all components of the protease, serine, and sugar alcohol were combined (223.1%). Therefore, it can be seen that the combination of protease with serine and / or sugar alcohol has a synergistic effect in exfoliation.

[0095] In addition, under the same conditions described above, the concentrations of serine and proteolytic enzymes were varied to confirm the exfoliation effect. Treatment with 0.5 w / w% serine and 0.005 w / w% keratinase alone, or with a combination of serine and keratinase, confirmed the exfoliation ability. Treatment with 0.5 w / w% serine and 0.005 w / w% keratinase alone showed exfoliation effects of 23% and 53%, respectively. However, using both components simultaneously increased the exfoliation effect to 86%, demonstrating the synergistic effect of combining the two components.

[0096] Example 3. Maintenance of the protein-degrading activity of proteolytic enzymes by sugar alcohols and serine.

[0097] To measure the activity of proteolytic enzymes, a clear zone assay was performed. A 6 mm paper disc was placed on a culture medium containing 1 w / w agarose and 0.5 w / w skim milk powder, and 40 μL of a solution containing proteolytic enzymes was dispensed onto the disc. After the solution dried completely, the disc was inverted and stored in a constant temperature and humidity environment (37°C, 50% humidity) for 24 hours. The proteolytic activity was then measured by measuring the diameter of the clear zone. The maintenance of proteolytic activity was measured by comparing the proteolytic activity after two weeks of storage under harsh conditions (50°C) with the proteolytic activity (diameter, mm) on day 0. If the activity was maintained by more than 25% compared to day 0, it was considered to retain activity.

[0098] The study determined whether sugar alcohols, which enhance exfoliation efficacy, could also enhance activity maintenance. Here, papain (0.5 w / w%) was used as the proteolytic enzyme. If papain was stored in aqueous solution at 50°C for 2 weeks, the proteolytic activity decreased to 0% based on day 0. In the above papain (0.5 w / w%), based on the total concentration of the composition, glycerol 5 w / w%, glycerol 20 w / w%, sorbitol 5 w / w%, sorbitol 20 w / w%, xylitol 20 w / w%, erythritol 2 w / w%, 1,3-butanediol (1,3-BG) 5 w / w%, or DPG 5 w / w% were mixed, and it was confirmed whether activity was maintained after storage at 50°C for 2 weeks.

[0099] In addition, the composition contains 22 w / w% of a sugar alcohol mixture relative to the whole composition. Specifically, the papain activity was also maintained under conditions containing 5 w / w% glycerol, 5 w / w% sorbitol, 5 w / w% DPG, 5 w / w% 1,3-BG and 2 w / w% erythritol relative to the whole composition, with the addition of 0.5 w / w% serine.

[0100] As a control group, poloxamer 1 w / w% or the antioxidant troxerutin 3 w / w were used to confirm whether papain maintained its activity under the same conditions.

[0101] This confirms that sugar alcohols and serine not only enhance the exfoliation effect, but also help maintain the activity of protein-degrading enzymes (Table 1).

[0102] [Table 1]

[0103]

[0104] Example 4. Maintenance of the enhanced exfoliation effect of sugar alcohols and serine on proteolytic enzymes

[0105] The exfoliating efficacy was tested in the same manner as in Example 1. The control group was purified water, pH 4 was 10 w / w gluconolactone at pH 4, and pH 6 was 10 w / w gluconolactone at pH 6. Sugar alcohols were contained as a mixture, specifically, relative to the whole composition, comprising 5 w / w glycerol, 5 w / w sorbitol, 5 w / w DPG, 5 w / w 1,3-BG, and 2 w / w erythritol. Serine was utilized using L-serine amino acid at 0.5 w / w, pH 6. The proteolytic enzyme used was keratinase (LCS Biotechnology), and the concentration of the proteolytic enzyme was tested at 0.01 w / w relative to the whole.

[0106] It was confirmed that storing the proteolytic enzyme at 50°C for 2 weeks reduced the exfoliation effect by more than 70% compared to the initial value, resulting in a residual activity of approximately 28% (130.3% -> 36.2%) compared to week 0. When a mixture of serine and sugar alcohol was added to the proteolytic enzyme and stored at 50°C for 2 weeks, the residual activity remained at approximately 71% compared to week 0, indicating that the reduction in exfoliation efficacy was mitigated to within 30%. This demonstrates that the mixture of serine and sugar alcohol not only enhances the exfoliation effect of the proteolytic enzyme but also maintains this enhanced exfoliation effect for a longer period. Figure 3 ).

[0107] Example 5. Confirmation of the immediate effect of a mixture of proteolytic enzymes, sugar alcohols, and serine on improving skin texture and pores.

[0108] After applying the dosage forms listed in Table 2 twice daily (morning and evening), the skin texture and pore size on the chin area were measured to determine if there was any improvement (n=1). Measurements were taken using Antera. (Miravex Limited) For skin texture, the volume and height of bumps and depressions with a diameter of 0.1-1 mm that protrude above the average skin surface were measured. For pores, the volume of pores with a diameter of less than 0.5 mm and the number of pores per unit area were measured.

[0109] [Table 2]

[0110] Bio-Sodium Hyaluronate 0.01 KELTROL F 0.06 purified water 47.205 Keratinase H 1 Sorbitol 5 1,3-BG 5 DPG 5 ELOGLYN R98F BULK 5 Propylene glycol (Zemea Select Propanediol) 5 HEPES 4 Trehalose 2 Coemdiol 2 NaCl (liquid detergent, hanju salt) 1.5 Genencare OSTMA BA (Amino Acid Moisturizer) 1 D-Panthenol 98% USP 1 EDTA 3NA 0.025 Allantoin 0.1 Serine 1 Arlamol HD (PUROLAN IHD) 8 Macadamia nut oil 4 PMX-0345 (DC 345) 1 Nutmeg L1 1 Carrot oil 0.1 total 100

[0111] like Figure 4 As shown, when using the composition in Table 2, after two uses, the volume and number of bumps and pores were reduced, and the volume and height of skin bumps were alleviated, thus visually confirming the effect of improving skin texture and pores.

[0112] Example 6. Confirmation of the effect of a formulation containing a mixture of proteolytic enzymes, sugar alcohols, and serine on improving pores and wrinkles.

[0113] After applying the dosage forms listed in Table 3 twice daily for 4 weeks, improvements in wrinkles and pores were measured (n=7). Measurements were performed using a Janus skin diagnostic instrument (PIE Co., Ltd.), covering the entire face.

[0114] [Table 3] Dosage Forms for Human Trial Evaluation of Wrinkle and Pore Improvement

[0115] Sodium hyaluronate 0.500 EDTA 3NA (5%) 0.400 CARBOPOL 981 0.200 PEMULEN TR2 0.050 D-Panthenol 98% USP 1.000 1,3-BG 5.000 Sorbitol 5.000 Pentavitin 2.000 Allantoin 0.100 serine enzyme 0.500 DPG-FG 5.000 Coemdiol 1.500 ELOGLYN R98F Glycerin BULK 5.000 DC SH 200 / 6Cs(SF1000NFX006) 4.000 SF1202 1.000 Croduret 60-so-(SG) 0.400 Tris Amino Ultra PC (10%) 2.250 Keratinase H 5.000 100.000

[0116] like Figure 5 As shown, it was confirmed that when the compositions in Table 3 were applied to the skin, the number of pores was reduced and the depth of wrinkles was reduced.

Claims

1. A composition for exfoliating keratinocytes, comprising a proteolytic enzyme, a sugar alcohol, and L-serine. in, The aforementioned protein-degrading enzyme is keratinase. The aforementioned sugar alcohols are a mixture of glycerol, sorbitol, dipropylene glycol, 1,3-butanediol, and erythritol. The content of the above mixture relative to the total weight of the composition is from 0.001 wt% to 30.0 wt%, and the above mixture contains 0.001 to 20 w / w% of glycerol, 0.001 to 20 w / w% of sorbitol, 0.001 to 20 w / w% of dipropylene glycol, 0.001 to 20 w / w% of 1,3-butanediol and 0.001 to 10 w / w% of erythritol. The protein-degrading enzyme comprises from 0.005% to 0.0075% by weight relative to the total weight of the composition. The L-serine mentioned above comprises 0.1% to 3.0% by weight relative to the total weight of the composition.

2. A pharmaceutical composition for the prevention or treatment of keratosis, comprising a proteolytic enzyme, a sugar alcohol, and L-serine. in, The aforementioned protein-degrading enzyme is keratinase. The aforementioned sugar alcohols are a mixture of glycerol, sorbitol, dipropylene glycol, 1,3-butanediol, and erythritol. The content of the above mixture relative to the total weight of the composition is from 0.001 wt% to 30.0 wt%, and the above mixture contains 0.001 to 20 w / w% of glycerol, 0.001 to 20 w / w% of sorbitol, 0.001 to 20 w / w% of dipropylene glycol, 0.001 to 20 w / w% of 1,3-butanediol and 0.001 to 10 w / w% of erythritol. The protein-degrading enzyme comprises from 0.005% to 0.0075% by weight relative to the total weight of the composition. The L-serine mentioned above comprises 0.1% to 3.0% by weight relative to the total weight of the composition.

3. The use of pharmaceutical compositions comprising proteolytic enzymes, sugar alcohols, and L-serine in the preparation of medicaments for the prevention or treatment of keratosis. in, The aforementioned protein-degrading enzyme is keratinase. The aforementioned sugar alcohols are a mixture of glycerol, sorbitol, dipropylene glycol, 1,3-butanediol, and erythritol. The content of the above mixture relative to the total weight of the composition is from 0.001 wt% to 30.0 wt%, and the above mixture contains 0.001 to 20 w / w% of glycerol, 0.001 to 20 w / w% of sorbitol, 0.001 to 20 w / w% of dipropylene glycol, 0.001 to 20 w / w% of 1,3-butanediol and 0.001 to 10 w / w% of erythritol. The protein-degrading enzyme comprises from 0.005% to 0.0075% by weight relative to the total weight of the composition. The L-serine mentioned above comprises 0.1% to 3.0% by weight relative to the total weight of the composition.

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