Cosmetic composition comprising complex of mandelic acid and carnitine

Abstract

The present invention relates to a complex comprising mandelic acid and carnitine, and a cosmetic composition comprising same. The cosmetic composition of the present invention comprises a deep eutectic solvent complex, thereby having high skin permeability and exfoliation effects under pH conditions that cause low skin irritation, and excellent low-temperature stability.

Description

Cosmetic composition containing a mandelic acid and carnitine complex

[0001] The present invention relates to a complex comprising mandelic acid and carnitine, and a cosmetic composition comprising the same. The cosmetic composition of the present invention has high skin permeability and exfoliation effects even under pH conditions that cause minimal skin irritation, and exhibits excellent low-temperature stability.

[0002]

[0003] Alpha-hydroxy acids (AHAs) are one of the ingredients commonly used to soften or remove hyperkeratinized skin layers, exhibiting skin-improving effects such as promoting keratin turnover, collagen synthesis, enhancing skin hydration, reducing fine lines, and treating and preventing acne (Non-patent Literature 1). Most AHAs exhibit excellent skin permeability and skin-improving effects under low pH conditions; however, due to the low pH, it is difficult to use high concentrations because they cause severe skin irritations such as itching, stinging, and burning, as well as various inflammatory irritations such as erythema and edema. Additionally, AHAs have the disadvantage of slowing down skin absorption when dissolved in water due to ionization. In particular, when AHAs are formulated into cosmetics, the pH of the formulation is lowered, which reduces formulation stability and can have negative effects such as skin irritation. If the pH of the formulation is raised using a neutralizing agent to compensate for this, there is a problem in that the effectiveness of the AHA is reduced.

[0004] Therefore, there is a need for a low-irritation yet highly effective exfoliating material that mitigates the trade-off between irritation and exfoliation efficacy.

[0005]

[0006] [Prior Art Dispute]

[0007] [Non-patent literature]

[0008] 1. Journal of the Korean Wellness Society, Vol. 10, No. 2, 2015, 161-169

[0009]

[0010] The present invention aims to provide a cosmetic composition that includes a complex comprising mandelic acid and carnitine, which has high skin permeability even under weakly acidic to neutral conditions, excellent exfoliation effect, low irritation, and excellent low-temperature stability.

[0011]

[0012] The present invention provides a cosmetic composition comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0013]

[0014] In addition, the present invention comprises the step of heating a mixture containing mandelic acid and carnitine at 60 to 85°C for at least 10 minutes, and stopping the heating when it becomes a liquid phase in which no precipitates are present;

[0015] A method for preparing a cosmetic composition is provided, comprising the step of preparing a cosmetic composition comprising a liquid complex obtained in the above step.

[0016]

[0017] In addition, the present invention provides a quasi-drug composition comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0018]

[0019] In addition, the present invention provides a pharmaceutical composition for treating dry skin diseases comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0020]

[0021] The cosmetic composition according to the present invention includes mandelic acid and carnitine in the form of a complex, thereby improving the skin permeability of mandelic acid and / or carnitine without skin irritation at a weakly acidic to neutral pH, and thus can provide various skin improvement effects such as improvement of skin texture, improvement of skin pores, improvement of exfoliation, or improvement of the skin barrier. In addition, the composition can be maintained stably and uniformly without precipitation of carnitine even at low temperatures.

[0022]

[0023] Figure 1 shows the results of DSC analysis of a DES complex containing mandelic acid and carnitine.

[0024] Figure 2 shows the FT-IR analysis results of a DES complex containing mandelic acid and carnitine.

[0025]

[0026] The present invention relates to a cosmetic composition comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0027]

[0028] The cosmetic composition of the present invention will be described in more detail below.

[0029] When a part is said to "include" a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but rather allows for the inclusion of additional components.

[0030] The complex of the present invention comprises mandelic acid and carnitine. Specifically, the complex of the present invention is composed of mandelic acid and carnitine, and such a complex may be a deep eutectic solvent (DES) complex of mandelic acid and carnitine.

[0031] In this invention, the term deep eutectic solvent (DES) complex is used to distinguish it from a general eutectic mixture.

[0032] A "eutectic mixture" refers to a complex formed by two or more components with high melting points through polar intermolecular dipole-dipole attraction, dipole-induced dipole attraction, intermolecular hydrogen bonding, or van der Waals interactions. In a eutectic mixture, the ability of each component to crystallize—that is, its ability to return to a solid state—is weakened, resulting in a melting point lower than that of the component with the lowest melting point, thereby allowing it to exhibit a liquid state at room temperature.

[0033] In this regard, the deep eutectic solvent complex (DES) of the present invention refers to a special solvent having an actual melting point lower than the ideal eutectic point, composed of a eutectic mixture of Lewis acid / base or Brønsted acid / base combinations. The DES forms a complex that exists stably in a liquid state at room temperature, with the melting point lowered by a much larger margin than the melting points of the individual components due to strong interactions between a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA).

[0034] In the present invention, when mandelic acid is used as the alpha-hydroxy acid acting as the hydrogen bond donor (HBD) and carnitine is used as the hydrogen bond acceptor (HBA), the two components form a DES complex under specific manufacturing conditions and can exist stably within the cosmetic composition.

[0035] In this invention, mandelic acid strengthens the skin barrier by promoting the exfoliation of the skin, thereby providing various skin improvement effects such as pore improvement, fine wrinkle improvement, acne improvement, or facial skin tone improvement.

[0036] In one embodiment, when the complex is composed of mandelic acid and carnitine, mandelic acid may be included in an amount of 15 to 83 weight% relative to the total weight of the complex, specifically 15 to 59 weight%, 15 to 66 weight%, 15 to 74 weight%, 15 to 80 weight%, 19 to 59 weight%, 19 to 66 weight%, 19 to 74 weight%, 19 to 80 weight%, 19 to 83 weight%, 23 to 59 weight%, 23 to 66 weight%, 23 to 74 weight%, 23 to 80 weight%, 23 to 83 weight%, 32 to 59 weight%, 32 to 66 weight%, 32 to 74 weight%, 32 to 80 weight%, 32 to 83 weight%, 38 to 59 weight%, It may be included in an amount of 38 to 66 weight%, 38 to 74 weight%, 38 to 80 weight%, or 38 to 83 weight%. If the content of mandelic acid is less than 15 weight%, the desired effect cannot be achieved, and if it exceeds 83 weight%, a problem of skin irritation may occur.

[0037] In the present invention, carnitine, like mandelic acid, has various skin improvement effects such as improving pores, fine wrinkles, acne, or facial skin tone.

[0038] In one embodiment, when the complex is composed of mandelic acid and carnitine, the carnitine may be included in an amount of 17 to 86 weight% relative to the total weight of the complex, specifically 17 to 62 weight%, 17 to 68 weight%, 17 to 77 weight%, 17 to 81 weight%, 20 to 62 weight%, 20 to 68 weight%, 20 to 77 weight%, 20 to 81 weight%, 20 to 85 weight%, 26 to 62 weight%, 26 to 68 weight%, 26 to 77 weight%, 26 to 81 weight%, 26 to 85 weight%, 34 to 62 weight%, 34 to 68 weight%, 34 to 77 weight%, 34 to 81 weight%, 34 to 85 weight%, 41 to 62 weight%, It may be included in an amount of 41 to 68 weight%, 41 to 77 weight%, 41 to 81 weight%, or 41 to 86 weight%. If the carnitine content is less than 17 weight%, the desired effect cannot be achieved, and if it exceeds 86 weight%, it may cause skin irritation and precipitation problems as it does not dissolve in the composition.

[0039] In one embodiment, the molar ratio of mandelic acid and carnitine may be 5:1 to 1:5. Specifically, the upper limit of the ratio may be 1:5 or less, 1:4.5 or less, 1:4 or less, 1:3.5 or less, 1:3 or less, 1:2.5 or less, 1:2 or less, or 1:1.5 or less, and the lower limit may be 5:1 or more, 4.5:1 or more, 4.0:1 or more, 3.5:1 or more, 3:1 or more, 2.5:1 or more, 2:1 or more, or 1.5:1 or more. Specifically, the molar ratio may be 4:1 to 1:4, 3:1 to 1:3, 2:1 to 1:2, or 1:0.5 to 1:1.5.

[0040] In the present invention, the deep eutectic solvent complex may not contain water. In the present invention, carnitine mandelian acid can form a DES complex through strong hydrogen bonding without containing water. Such a complex can be used as a solvent. When used as a solvent, it has the advantage of being utilized to improve the stability of materials susceptible to hydrolysis.

[0041] Generally, when alpha-hydroxy acids are ionized, they cause skin irritation; however, if alpha-hydroxy acids form a eutectic mixture with amino acids and water, the ionization of the alpha-hydroxy acids can be controlled while exhibiting other useful effects. In the present invention, carnitine mandelian acid forms a eutectic mixture without containing water, and skin irritation is minimal.

[0042] In one embodiment, mandelic acid and carnitine can form a deep eutectic solvent complex through hydrogen bonding. In this case, the mandelic acid acts as a hydrogen bond donor (HBD), and the carnitine acts as a hydrogen bond acceptor (HBA).

[0043] In one embodiment, the complex comprising mandelic acid and carnitine may be in a liquid form that is non-flowing at room temperature. In this case, room temperature means 20 to 25°C.

[0044] The complex comprising mandelic acid and carnitine of the present invention is included in a cosmetic composition. Such deep eutectic solvent complexes may be included in an amount of 0.01 to 50 parts by weight, 0.05 to 40 parts by weight, 0.1 to 30 parts by weight, 0.5 to 25 parts by weight, 0.1 to 50 parts by weight, 1 to 35 parts by weight, 5 to 30 parts by weight, 0.5 to 40 parts by weight, 1 to 30 parts by weight, 5 to 28 parts by weight, 8 to 25 parts by weight, 1 to 50 parts by weight, 5 to 40 parts by weight, 10 to 35 parts by weight, 15 to 25 parts by weight, 18 to 25 parts by weight, 15 to 20 parts by weight, 10 to 20 parts by weight, 10 to 30 parts by weight, 10 to 40 parts by weight, 15 to 35 parts by weight, and 20 to 30 parts by weight relative to the total weight of the cosmetic composition. The content of the above deep eutectic solvent complex can be adjusted to suit the formulation of the cosmetic composition.

[0045] A cosmetic composition comprising a complex containing mandelic acid and carnitine according to the present invention, in order to improve discomfort such as skin irritation when applied to the skin, has a pH of 4 to 7.5, pH 4.5 to 7.5, pH 5 to 7.5, pH 5.5 to 7.5, pH 6.0 to 7.5, pH 6.5 to 7.5, pH 7.0 to 7.5, pH 4 to 7, pH 4.5 to 7, pH 5 to 7, pH 5.5 to 7, pH 6.0 to 7, pH 6.5 to 7, pH 4 to 6.5, pH 4.5 to 6.5, pH 5 to 6.5, pH 5.5 to 6.5, pH 6.0 to 6.5, pH 4 to 6, pH 4.5 to 6, pH 5 to 6, pH 5.5 to 6, pH 4 to It may also be adjusted to have a weakly acidic to neutral acidity, such as 5.5, pH 4.5 to 5.5, or pH 5 to 5.5.

[0046] A cosmetic composition comprising a deep eutectic solvent complex according to the present invention can improve the skin permeability of mandelic acid and / or carnitine without skin irritation at a weakly acidic to neutral pH, thereby providing effects such as improving skin texture, improving skin pores, improving exfoliation, or improving the skin barrier. The cosmetic composition according to the present invention may additionally include an oil phase component. The oil phase component is included in the composition and exists on the surface of the deep eutectic solvent complex, thereby helping the deep eutectic solvent complex to exist stably within the composition.

[0047] In one embodiment, the oil phase component may be one or more of an oil or a wax. Any oil or wax commonly used as an ingredient in cosmetics in the industry may be used. For example, the oil may be a silicone-based oil, an ester-based oil, a triglyceride-based oil, a hydrocarbon-based oil, or a vegetable oil, and one or more of these components may be combined as needed.

[0048] For example, silicone-based oils may include silicone-based fluid oils or silicone-based crosspolymers dispersed in oil. For example, silicone-based fluid oils may include cyclopentasiloxane, cyclohexasiloxane, cycloheptasiloxane, cyclomethicone, cyclophenylmethicone, cyclotetrasiloxane, cyclotrisiloxane, dimethicone, capryldimethicone, caprylyltrimethicone, caprylylmethicone, cetearylmethicone, hexadecylmethicone, hexylmethicone, laurylmethicone, myristylmethicone, phenylmethicone, stearylmethicone, stearyldimethicone, trifluoropropylmethicone, cetyldimethicone, diphenylsiloxyphenyltrimethicone, dimethylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, methyltrimethicone, or phenyltrimethicone. The above silicone-based oil components may be used alone or in combination with two or more types of oils. As silicone-based crosspolymers, dimethicone crosspolymers, dimethicone / vinyl dimethicone crosspolymers, dimethicone PEG-10 / 15 crosspolymers, or PEG-12 dimethicone / PPG-20 crosspolymers may be used, but are not limited thereto.

[0049] Ester oils include ascorbyl palmitate, ascorbillinoleate, ascorbyl stearate, diisostearyl malate, benzyl benzoate, benzyl laurate, butylene glycol dicaprylate / dicaprate, butylene glycol diisononanoate, butylene glycol urate, butylene glycol stearate, butyl isostearate, cetearyl isononanoate, cetearyl nonanoate, cetyl caprylate, cetyl ethylhexanoate, cetyl isononanoate, ethylhexyl caprylate / caprate, ethylhexyl isononanoate, ethylhexyl isostearate, ethylhexyl laurate, hexyl laurate, octyldodecyl isostearate, isopropyl isostearate, isostearyl isononanoate, Isostearyl isostearate, isocetyl ethylhexanoate, neopentyl glycol dicaprate, neopentyl glycol diethylhexanoate, neopentyl glycol diisononanoate, neopentyl glycol diisostearate, pentaerythrityl stearate, pentaerythrityl tetraethylhexanoate, dipentaerythrityl hexaacid ester, polyglyceryl-2 diisostearate, polyglyceryl-2 sesquiisostearate, polyglyceryl-2 isostearate, polyglyceryl-2 tetraisostearate, polyglyceryl-2 triisostearate, polyglyceryl-3 diisostearate, polyglyceryl-3 isostearate, polyglyceryl-4 diisostearate, polyglyceryl-4 isostearate, Polyglyceryl-6 diisostearate, polyglyceryl-6 sesquiisostearate, or triethylhexanoin, etc., may be used.

[0050] As triglyceride-based oils, C8-C12 acid triglyceride, C12-C18 acid triglyceride, caprylic / capric / triglyceride, caprylic / capric / lauric triglyceride, C10-C40 isoalkyl acid triglyceride, C10-C18 triglyceride, glyceryl triacetyl hydrostearate, soybean glyceride, tribehenin, tricaprin, triethylhexanoin, triheptanoin, triisostearin, tripalmitin, or tristearin may be used.

[0051] Hydrocarbon oils that can be used include liquid paraffin (liquid paraffin, mineral oil), paraffin, petroleum jelly, microcrystalline wax, or squalene.

[0052] Vegetable oils that may be used include avocado oil, wheat germ oil, rosehip oil, shea butter, almond oil, olive oil, macadamia oil, argan oil, meadowfoam oil, sunflower oil, castor oil, camellia oil, corn oil, safflower oil, soybean oil, rapeseed oil, macadamia nut oil, jojoba oil, palm oil, palm kernel oil, or coconut oil.

[0053] As for the wax, any wax commonly used in cosmetics, such as hydrocarbon waxes, vegetable waxes, or silicone waxes, may be used. For example, it may include, but is not limited to, candelilla wax, carnauba wax, rice wax, beeswax, lanolin, ozokerite, ceresin wax, paraffin wax, microcrystalline wax, C30-C45 alkyldimethylsilylpolypropylsilsesquioxane, ethylene / propylene copolymer, or polyethylene wax.

[0054] In one embodiment, the oil phase component is not particularly limited in content and may be included in the composition in the remaining amount excluding the deep eutectic solvent complex described above.

[0055] The cosmetic composition of the present invention comprises all types of ingredients usable in conventional cosmetics, for example, moisturizers such as glycerin, butylene glycol, propylene glycol, hexanediol, methylgluceth-20, diglycerin, and ethylhexylglycerin; sunscreens such as ethylhexyl methoxycinnamate, ethylhexyl salicylate, ethylhexyl triazone, octocrylene, and bis-ethylhexyloxyphenol methoxyphenyl triazine; pH adjusters such as triethanolamine; thickeners such as carbomer, xanthan gum, acrylate / C10-30 alkyl acrylate crosspolymer, and hyaluronic acid; preservatives such as phenoxyethanol, methylparaben, and propyl paraben; antioxidants such as BHT, ethyl ascorbyl ether, and ascorbic acid; and skin conditioning agents such as beta-glucan. Surfactants such as cetearyl glucoside and sorbitan stearate; may additionally include fragrances or colorants, but are not limited to the ingredients.

[0056] Each of the above-mentioned ingredients included in the cosmetic composition according to the present invention may preferably be included in the cosmetic composition of the present invention within a range that does not exceed the maximum usage amount prescribed in the "Cosmetic Safety and Technical Standards" established by the Chinese government.

[0057] The cosmetic composition according to the present invention may be prepared in any formulation conventionally manufactured in the art. For example, the cosmetic composition may have a formulation such as a lotion, such as a softening lotion or a nourishing lotion; a spray-type lotion; a fluid, such as a facial lotion or a body lotion; a cream, such as a nourishing cream, a moisturizing cream, or an eye cream; a stick; an essence; a cosmetic ointment; a spray; a gel; a pack; a sunscreen; a makeup base; a foundation, such as a liquid or spray type; a powder; a makeup remover, such as a cleansing lotion or a cleansing oil; a cleansing foam; a soap; a body wash; but is not limited thereto.

[0058] In one embodiment, the formulation of the cosmetic composition may be a balm, water-in-oil (W / O), oil-in-water (O / W), solubilized formulation, or oil formulation.

[0059] In the present invention, the "solubilized formulation" refers to a formulation in which a small amount of oil component is transparently dissolved in water, and is a formulation in which the diameter of the oil drop is smaller than the wavelength of visible light, so as not to hinder the rectilinear propagation of light without scattering or reflection, thereby exhibiting a transparent appearance. A cosmetic composition having the above-mentioned solubilized formulation may be a transparent skin toner, hair tonic, or hair liquid, but is not limited thereto.

[0060] The cosmetic composition of the present invention can be used according to a conventional method of use, and the frequency of use may be varied depending on the user's skin condition or preference.

[0061]

[0062] In addition, the present invention relates to a cosmetic composition for skin improvement comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0063] The complex of the present invention is composed of mandelic acid and carnitine, and the complex may be a deep eutectic solvent (DES) complex of mandelic acid and carnitine.

[0064] In the present invention, mandelic acid, carnitine, complex, deep eutectic solvent complex, and cosmetic composition may be applied as described above.

[0065] In the present invention, skin improvement may be improvement of skin texture, improvement of skin pores, improvement of exfoliation, or improvement of the skin barrier.

[0066]

[0067] In addition, the present invention relates to a method for manufacturing the aforementioned cosmetic composition.

[0068] A cosmetic composition according to the present invention comprises: (S1) a step of heating a mixture containing mandelic acid and carnitine at 60 to 85°C for at least 10 minutes, and stopping the heating when it becomes a liquid phase in which no precipitates are present; and

[0069] (S2) A cosmetic composition comprising the liquid complex obtained in the above step can be prepared through the step of preparing a cosmetic composition.

[0070] The complex of the present invention is composed of mandelic acid and carnitine, and the complex may be a deep eutectic solvent (DES) complex of mandelic acid and carnitine.

[0071] In the present invention, mandelic acid, carnitine, complex, deep eutectic solvent complex, and cosmetic composition may be applied as described above.

[0072] In one embodiment, the mixture in step (S1) may consist of mandelic acid and carnitine. Alternatively, the mixture may not contain water.

[0073] In one embodiment, in step (S1), heating may be performed for 10 minutes or more, 15 minutes or more, 20 minutes or more, or 30 minutes or more, and may be performed for 120 minutes or less, 100 minutes or less, 90 minutes or less, or 60 minutes or less.

[0074] In one embodiment, heating in step (S1) may be performed under stirring. At this time, stirring may be performed at 100 rpm or more, 150 rpm or more, 200 rpm or more, or 250 rpm or more, and may be performed at 800 rpm or less, 700 rpm or less, 600 rpm or less, or 500 rpm or less. If the stirring speed is too fast, it may actually hinder the formation of the composite.

[0075] In one embodiment, after performing step (S1), an additional step of cooling to room temperature may be performed. The cooling may be natural cooling.

[0076] In one embodiment, the liquid complex prepared in step (S1) may be a deep eutectic complex of mandelic acid and carnitine.

[0077]

[0078] In addition, the present invention relates to a quasi-drug composition comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0079] The complex of the present invention is composed of mandelic acid and carnitine, and the complex may be a deep eutectic solvent (DES) complex of mandelic acid and carnitine.

[0080] In the present invention, the mandelic acid, carnitine, complex, and deep eutectic solvent complex can be applied as described above.

[0081] In the present invention, the quasi-drug composition may be applied for skin improvement. In one embodiment, skin improvement may be improvement of skin texture, improvement of skin pores, improvement of exfoliation, or improvement of the skin barrier.

[0082] In the present invention, "quasi-drug" refers to articles used for the purpose of diagnosing, treating, improving, alleviating, managing, or preventing diseases in humans or animals, and which have a milder effect than pharmaceuticals. For example, according to the Pharmaceutical Affairs Act, quasi-drugs are defined as products excluding those used for pharmaceutical purposes, and may be products used for the treatment or prevention of diseases in humans or animals, or products that have a mild effect on the human body or do not act directly on it. For example, they may be selected from the group consisting of disinfectants, detergents, kitchen detergents, cleaning detergents, wet wipes, detergents, soaps, hand washes, hair detergents, hair softeners, and ointments, but are not limited thereto.

[0083]

[0084] In addition, the present invention relates to a pharmaceutical composition for treating dry skin diseases comprising a complex containing mandelic acid and carnitine as an active ingredient.

[0085] The complex of the present invention is composed of mandelic acid and carnitine, and the complex may be a deep eutectic solvent (DES) complex of mandelic acid and carnitine.

[0086] In the present invention, the mandelic acid, carnitine, complex, and deep eutectic solvent complex can be applied as described above.

[0087] In the present invention, dry skin disease may be keratosis, xerosis, or atopic dermatitis.

[0088] In this invention, “treatment” refers to any act of alleviating, reducing, stopping, or reversing desired symptoms by administering the composition of this invention.

[0089] The above “pharmaceutical composition” refers to a composition used for the purpose of diagnosing, treating, alleviating, managing, or preventing diseases in animals, including humans.

[0090] The composition of the present invention may be administered in a pharmaceutically effective amount. The pharmaceutically effective amount refers to an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and that does not cause side effects. The effective dose level may be determined based on factors including the patient's health status, type and severity of the disease, drug activity, sensitivity to the drug, method of administration, time of administration, route of administration and elimination rate, duration of treatment, drugs used in combination or concurrently, and other factors well known in the medical field. Specifically, it may be 0.1 mg / kg to 100,000 mg / kg per day, more specifically 1 mg / kg to 10,000 mg / kg. The pharmaceutical composition of the present invention may be administered once a day or divided into several doses. Therefore, the above dosage does not limit the scope of the present invention in any way.

[0091] The above composition may be administered to mammals such as rats, mice, livestock, and humans via various routes, such as parenteral or oral, and all modes of administration are expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater, or intracerebroventricular injection.

[0092] The pharmaceutical composition of the present invention may further include pharmaceutically acceptable carriers, excipients, diluents, and / or auxiliary components depending on its formulation, method of use, and purpose of use.

[0093]

[0094] In addition, the present invention relates to the use of a composition comprising a complex containing mandelic acid and carnitine for the preparation of a cosmetic composition for skin improvement.

[0095] In addition, the present invention relates to the use of a composition comprising a complex containing mandelic acid and carnitine for the preparation of a quasi-drug composition for skin improvement.

[0096] In addition, the present invention relates to the use of a composition comprising a complex of mandelic acid and carnitine for the preparation of a pharmaceutical composition for treating dry skin diseases.

[0097]

[0098] In addition, the present invention relates to a skin improvement method comprising the step of applying a cosmetic composition containing an effective amount of mandelic acid and a complex containing carnitine to the skin of a subject in need thereof.

[0099] In addition, the present invention relates to a skin improvement method comprising the step of applying a quasi-drug composition containing an effective amount of mandelic acid and carnitine to the skin of a subject who requires it.

[0100] In addition, the present invention relates to a method for treating dry skin diseases comprising the step of applying a pharmaceutical composition containing an effective amount of mandelic acid and a complex containing carnitine to the skin of a subject in need thereof.

[0101]

[0102] The present invention will be described in detail below through examples. The following examples are merely illustrative of the present invention and do not limit the scope of the present invention to the following examples. These examples are provided to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims.

[0103]

[0104] Examples

[0105] Preparation Example 1. Preparation of Mandelic Acid-Carnitine DES Complex

[0106] Mandelic acid (melting point: 119-121°C) and carnitine (melting point: 197-212°C) were placed in a beaker in a molar ratio of 1:1 and heated to 65°C. Then, the mixture was stirred at 500 rpm for 30 minutes, after which the presence of precipitates or deposits was checked; if present, the mixture was stirred for an additional 10 minutes. Subsequently, it was allowed to cool naturally until it reached room temperature.

[0107] The manufactured composite had very high viscosity and was a liquid that did not flow at room temperature.

[0108]

[0109] Comparative Manufacturing Example 1. Preparation of a mixture of mandelic acid and carnitine

[0110] A mixture was prepared by adding 30.4g of mandelic acid and 32.2g of carnitine to 1L of water and dissolving them.

[0111]

[0112] Experimental Example 1. Structural analysis of the mandelic acid-carnitine DES complex

[0113] DSC analysis was performed on Preparation Example 1. Specifically, the 30 to 150°C range was analyzed using a PerkinElmer DSC 4000 under conditions of a rise of 50°C per minute, and the results are shown in Figure 1.

[0114] If mandelic acid and carnitine are simply mixed without forming a complex, a peak of mandelic acid appears in the analysis range. However, as shown in Figure 1, no peak of mandelic acid appeared when Preparation Example 1 was analyzed. Through this, it can be confirmed that the complex of Preparation Example 1 is in a deep eutectic solvent state without containing water.

[0115]

[0116] FT-IR analysis was performed on each of Preparation Example 1, Comparative Preparation Example 1, mandelic acid, and carnitine. Specifically, Preparation Example 1, Comparative Preparation Example 1, and mandelic acid were each diluted or dissolved in water to a concentration of 1 wt% mandelic acid, and carnitine was dissolved in water to a concentration of 1.06 wt%. Subsequently, FT-IR was performed on each solution, and the results are shown in Figure 2.

[0117] As shown in Fig. 2, it can be confirmed that peaks generated by each substance are present in mandelic acid alone, carnitine alone, and the mixture of mandelic acid and carnitine. On the other hand, a peak at 3000–3500 cm⁻¹, which was not found in the complex prepared in Preparation Example 1, appears. -1 Confirmed in (-OH stretching), 2900 cm -1 (OH stretching of carboxylic acid) and 1475 cm -1 A peak shift can be observed in (NH stretching of the amino group).

[0118] This shows that while there was no interaction between mandelic acid and carnitine in the simple mixture, an interaction occurred between the two components in the complex, confirming that a deep eutectic solvent different from the simple mixture was prepared.

[0119]

[0120] Experimental Example 2. Confirmation of exfoliating effect of mandelic acid-carnitine DES complex

[0121] The exfoliation efficiency of the mandelic acid-carnitine complex and mandelic acid was compared using pig skin. First, a 2.5 x 2.5 cm pig skin (Micropig Franz Cell Membrane, Apures, Korea) was punched into a 6 mm diameter disc, washed with PBS buffer, and placed in a 96-well plate. Subsequently, samples were prepared by diluting or dissolving mandelic acid or the complex of Preparation Example 1 in distilled water to the concentrations shown in Table 1. In this case, the concentration of the sample containing the complex of Preparation Example 1 was determined based on the weight percentage of mandelic acid in the complex relative to the total weight of distilled water. The pH of each sample was adjusted using KOH and HCl.

[0122] Next, 100 μL of each sample was treated with 0.1% Triton X-100 on pig skin and incubated for 24 hours at a temperature of 37°C and a relative humidity of 50%. Then, the number of keratinocytes released from the pig skin was counted using a hemocytometer on 10 μL of the supernatant from each sample. Samples treated with 10% gluconolactone (diluted with distilled water, pH 4.0) were set as a positive control, and the relative keratinization efficiency of each sample was calculated with the results of the positive control set to 100%, and the results are shown in Table 1.

[0123]

[0124] Exfoliation Efficiency (%) Sample 1 Mandelic acid 0.1% (pH 4.5) 5.1 Sample 2 Mandelic acid, Carnitine complex 0.1% (pH 4.5) 11.8 Sample 3 Mandelic acid 1% (pH 4.5) 14.9 Sample 4 Mandelic acid, Carnitine complex 1% (pH 4.5) 61.5 Sample 5 Mandelic acid 2% (pH 4.5) 25.2 Sample 6 Mandelic acid, Carnitine complex 2% (pH 4.5) 73.1 Sample 7 Mandelic acid 3% (pH 4.5) 37.4 Sample 8 Mandelic acid, Carnitine complex 3% (pH 4.5) 93.0

[0125]

[0126] As shown in Table 1, in the case of mandelic acid, an exfoliating material (samples 1, 3, 5, and 7), it can be confirmed that at pH 4.5, the exfoliating effect is not sufficient even when the concentration is increased.

[0127] On the other hand, in the case of the mandelic acid-carnitine complex of the present invention (samples 2, 4, 6, 8), it shows a much higher exfoliating effect than mandelic acid at the same concentration, and at the 3% level, it shows an exfoliating effect similar to that of a positive control at a much higher concentration, confirming that it can be used as an effective exfoliating material.

[0128]

[0129] Experimental Example 3. Evaluation of Skin Permeability

[0130] The skin penetration amount of the mandelic acid-carnitine complex of Preparation Example 1 was compared with the mixture of Comparative Preparation Example 1 using a Franz Cell.

[0131] Specifically, skin permeability was evaluated using Labfine’s FCDV-15 and APURES’ Micropig Franz Cell Membrane (FCM), a transdermal diffusion testing membrane capable of predicting skin permeability.

[0132] First, a Micropig FCM was positioned between the Donor chamber and the Receptor chamber, and 3 ml of PBS solution was added to the Receptor chamber. Subsequently, samples were prepared by diluting or dissolving mandelic acid, the mixture of Comparative Example 1, and the complex of Example 1 in distilled water to concentrations as shown in Table 2. 100 μl of each sample was applied onto the respective Micropig FCM. Afterward, the samples were rolled 10 times with a polyethylene stick for 30 seconds, and then placed in a constant temperature and humidity chamber at 37.5°C and 50% relative humidity for 24 hours to allow permeation. Subsequently, the content of mandelic acid permeated toward the Receptor chamber was quantified.

[0133] HPLC (Agilent 1260 series) was used for the quantitative analysis of mandelic acid. An Agilent Poroshell C18 column (4.6 x 50 mm, 2.7 µm) was used, and the mobile phase was varied between A:B (95:5, 1 min) and (50:50, 5 min), with the flow rate set to 1.2 ml / min. Detection was performed at 210 nm, and quantification was determined by comparison with a standard reagent. The relative value (percentage) compared to 2 wt% of mandelic acid applied to the skin was expressed as the skin permeability and is shown in Table 2.

[0134] reagent:

[0135] Mobile phase A: 0.1% Phosphoric acid (H3PO4)

[0136] Mobile phase B: Acetonitrile

[0137]

[0138] Skin permeability (%) Mandelic acid 4%1.125Mandelic acid 4%, Carnitine 4.24%1.350Mandelic acid, Carnitine Complex 4%19.94

[0139]

[0140] As shown in Table 2, it can be confirmed that the skin permeability of mandelic acid is significantly higher when the complex according to the present invention is used compared to when mandelic acid is used alone or when mandelic acid is mixed with carnitine.

[0141]

[0142] Experimental Example 4. Confirmation of skin improvement effect of mandelic acid-carnitine DES complex 1

[0143] Thirty-three female volunteers aged 20 to 68 were instructed to use a cosmetic composition containing the complex according to the present invention (composition of Table 3) twice a day, in the morning and evening, after washing their face for two weeks. During this period, the use of other functional cosmetics was restricted, and in particular, products related to exfoliation were prohibited. In addition, treatments that could affect skin improvement, such as masks or massages, were also restricted.

[0144] Skin analysis was conducted in the same location after first washing the face and then stabilizing the skin for 30 minutes under conditions where temperature, humidity, light, and airflow were controlled. The analysis was performed once on the day before the applicant began using the cosmetic composition, and once more after using the cosmetic composition for two weeks. Blackheads, whiteheads, and the proportion of dead skin cells were analyzed using a video microscope (KONG PC Camera, Bomtech, Korea) and image analysis software (ImagePro 10, Media Cybernetics, USA). In addition, the pore-affected area was analyzed using an ANTERA 3D system (Miravex, Ireland). The results before using the cosmetic composition and after two weeks of use are shown in Table 4 below.

[0145]

[0146] Ingredient Content (Weight%) Purified Water to 100 Complex of Preparation Example 1 (1%) 2.06 Hydroxyethylpiperazine Ethanesulfonic Acid 1.00 Trisodium EDTA 0.02 KOH (20%) 0.41 Glycerin 10.00 1,2-Hexanediol 1.50 Polysorbate 600.50

[0147]

[0148] Period Blackheads Whiteheads Pore affected area Proportion of dead skin cells 0 weeks 1.8 10.9 41.47 9.39 2 weeks 1.38 *** 0.6 *** 31.47 *** 1.26 ***

[0149] (***p < 0.001).

[0150]

[0151] As shown in Table 4, it was confirmed that when a cosmetic product containing the complex according to the present invention was used for 2 weeks, the proportion of blackheads, whiteheads, areas affected by pores, and dead skin cells were all improved.

[0152]

[0153] Experimental Example 5. Confirmation of skin improvement effect of mandelic acid-carnitine DES complex 2

[0154] Thirty-one female volunteers aged 28 to 65 were instructed to use a cosmetic composition containing the complex according to the present invention (composition of Table 5) twice a day, in the morning and evening, after washing their face for one week. During this period, the use of other functional cosmetics was restricted, and in particular, products related to exfoliation were prohibited. In addition, treatments that could affect skin improvement, such as masks or massages, were also restricted.

[0155] Skin analysis was conducted in the same location after first washing the face and then stabilizing the skin for 30 minutes under conditions where temperature, humidity, light, and airflow were controlled. The analysis was first conducted once on the day before the applicant started using the cosmetic composition, and once more after using the cosmetic composition for one week.

[0156] The analysis was performed by measuring four items related to pores (volume, maximum depth, density, count) and one item related to skin texture (texture small) using the ANTERA 3D system (Miravex, Ireland). The results before using the cosmetic composition and after using it for one week are shown in Table 6 below.

[0157]

[0158] Ingredient Content (Weight%) Purified Water to 100 Complex of Preparation Example 1 (0.1%) 0.21 Hydroxyethylpiperazine Ethanesulfonic Acid 1.00 Trisodium EDTA 0.02 KOH (20%) 0.04 Glycerin 10.00 1,2-Hexanediol 1.50 Polysorbate 600.50

[0159]

[0160] Period VolumeMaximum depthDensityCountTexture small0week0.520.03131.14230.166.21week0.42**0.027*27.68**205.06**5.79***

[0161] (*p < 0.05, **p < 0.01, **p < 0.001).

[0162]

[0163] As shown in Table 6, it was confirmed that when a cosmetic composition containing the complex according to the present invention was used for one week, various pore-related factors were all improved and skin texture was also improved.

Claims

1. A cosmetic composition comprising a complex containing mandelic acid and carnitine as an active ingredient.

2. In Paragraph 1, The complex is a cosmetic composition that is a complex composed of mandelic acid and carnitine.

3. In Paragraph 2, The complex is a cosmetic composition that is a deep eutectic solvent (DES) complex of mandelic acid and carnitine.

4. In Paragraph 2, A cosmetic composition containing mandelic acid in an amount of 15 to 83 weight percent relative to the total weight of the complex.

5. In Paragraph 2, A cosmetic composition containing carnitine in an amount of 17 to 86 weight percent relative to the total weight of the complex.

6. In Paragraph 1 or 2, A cosmetic composition in which the molar ratio of mandelic acid and carnitine is 5:1 to 1:

5.

7. In Paragraph 1, The cosmetic composition is a cosmetic composition having a pH of 4 to 8.

8. A cosmetic composition for skin improvement comprising a complex containing mandelic acid and carnitine as an active ingredient.

9. In Paragraph 8, A cosmetic composition for skin improvement in which skin improvement is improvement of skin texture, improvement of skin pores, improvement of exfoliation, or improvement of the skin barrier.

10. A step of heating a mixture containing mandelic acid and carnitine at 60 to 85°C for at least 10 minutes, and stopping the heating when it becomes a liquid phase in which no precipitates are present; and A method for preparing a cosmetic composition comprising the step of preparing a cosmetic composition comprising a liquid complex obtained in the above step.

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