HK40094271A - Cosmetic composition comprising carnitine-salicylate as active ingredient - Google Patents

Description

Cosmetic compositions containing carnitine salicylate as an active ingredient

Technical Field

This invention relates to cosmetic compositions containing carnitine salicylate (CA-SA) as an active ingredient.

Background Technology

Skin aging is a gradual and continuous physiological process caused by external environmental exposure (extrinsic aging) and genetic factors (intrinsic aging). In particular, among various tissues in the human body, skin tissue is frequently exposed to sunlight, leading to the death of epidermal stem cells or pigmentation due to the aging of melanocytes, and inducing the degradation of dermal components related to wrinkles, such as collagen and elastin. Furthermore, external stimuli such as sunlight induce inflammation by promoting cytokine secretion, causing not only discomfort such as erythema, stinging, and itching, but also contributing to skin aging. Various substances used to alleviate skin conditions and aging caused by these external stimuli have long been employed in cosmetics. For example, substances such as retinoids, hydroquinone, L-ascorbic acid, and alpha-hydroxy acids (AHAs) are known to have anti-aging effects, while D-panthenol and glycyrrhizic acid are known to have anti-inflammatory effects. It is understood that salicylates, specifically known as β-hydroxy acids (BHA), have been used in Egypt since 1550 BC as substances with anti-aging and anti-inflammatory effects. In particular, they have attracted considerable attention as cosmetic ingredients due to their bactericidal effects against Propionibacterium acnes. However, salicylates exhibit acidity in aqueous solutions below pH 3.0, which may induce irritation when repeatedly applied to the skin. Therefore, the Cosmetic Ingredient Review Expert Panel recommends the use of salicylates in their salicylate form at pH 3.5 or higher, and suggests a maximum concentration of 3.0% or less in cosmetics. However, it is also understood that when salicylates are used in their ionized form under weakly acidic conditions, there are limitations in skin permeability and efficacy, making it difficult to perceive high efficacy without skin irritation. In addition, salicylates have low solubility in weakly acidic water. Therefore, existing technologies have designed methods such as i) converting them into salt form, ii) derivatizing them, or iii) dissolving them in strongly acidic water and then neutralizing them with a weak acid. However, when applying the above three methods, there is a problem that the original bactericidal effect of salicylates cannot be fully utilized.

A topical skin agent containing carnitine and exhibiting acne-improving effects has been disclosed (Korean Patent Publication No. 10-2010-0095447). A method for incorporating salicylic acid into a hydroxyalkylated cyclodextrin to improve its solubility in water and thereby incorporating it into a cosmetic composition at a high concentration is also known (Korean Registered Patent No. 10-2307186). Furthermore, cosmetic compositions containing salicylic acid derivatives that inhibit tyrosinase activity and thereby exhibit skin-whitening effects are also known (Korean Patent Publication No. 10-2017-0076091).

However, the aforementioned existing technologies not only have complex processes, but also fail to maintain the inherent efficacy of each component in its original form in terms of purpose and effect.

[Existing Technical Documents]

1. Korean Patent Publication No. 10-2010-0095447

2. Korean Patent No. 10-2307186

3. Korean Patent Publication No. 10-2017-0076091

Summary of the Invention

Technical issues

Against the above background, the inventors have confirmed that carnitine salicylate (CA-SA) as the active ingredient, under weakly acidic conditions, through the ionic pairing of carnitine and salicylate, exhibits the effects of relieving acne and exfoliating keratin as a skin-improving material, and at the same time, as a skin-soothing material, it can relieve inflammation and erythema, thus completing the present invention.

Therefore, the object of the present invention relates to a cosmetic composition comprising carnitine salicylate (CA-SA) as an active ingredient.

Technical solution

As a means of solving the above-mentioned problems, the present invention provides a cosmetic composition containing carnitine salicylate (CA-SA) as an active ingredient.

To achieve the above objectives, a method is provided that can alleviate acne and exfoliate by improving the skin, while also relieving inflammation and erythema by soothing the skin, comprising treating the skin with a cosmetic composition containing carnitine salicylate (CA-SA) as an active ingredient.

To achieve the above objectives, a method is provided that can alleviate acne and exfoliate by improving the skin, while also relieving inflammation and erythema by soothing the skin, comprising the step of administering a cosmetic composition containing carnitine salicylate (CA-SA) as an active ingredient to a subject.

To achieve the above objectives, a composition containing carnitine salicylate (CA-SA) as an active ingredient is provided for use in the preparation of cosmetics that exhibit acne-relieving and exfoliating effects by improving the skin, while simultaneously relieving inflammation and erythema by soothing the skin.

The structure of the present invention will now be described in detail.

This invention relates to cosmetic compositions containing carnitine salicylate (CA-SA) as an active ingredient.

In this invention, the carnitine is 4-trimethylamino-3-hydroxybutyric acid, and L-carnitine, DL-carnitine, their hydrochlorides, and their derivatives can be used. L-carnitine is preferred.

Carnitine is reportedly a low-irritant amino acid exfoliant that exhibits higher efficacy than alpha-hydroxy acids (AHAs) under weakly acidic and neutral conditions. Furthermore, its ammonium group structure facilitates skin penetration and allows for easy absorption into the stratum corneum.

A topical skin agent containing carnitine and exhibiting acne-improving effects has been disclosed (Korean Patent Publication No. 10-2010-0095447). However, the aforementioned prior art merely uses carnitine as an additive to promote ceramide synthesis, with varying proportions, and it does not constitute a component exhibiting the main efficacy. Furthermore, regarding the acne-improving effects, only the results of acne bacteria experiments and functional evaluation experiments are described, while objective results based on standard test methods are not presented regarding the cytotoxicity, exfoliation, inflammation relief, and erythema relief effects of the topical skin agent.

In one specific example of the present invention, the preparation of carnitine salicylate (CA-SA) and the results of in vitro and in vivo efficacy tests showed that it had almost no cytotoxicity. Therefore, as a skin-improving material, it exhibited the effects of relieving acne and exfoliating keratin without irritating the skin, and at the same time, as a skin-soothing material, it could maximize the effects of relieving inflammation and erythema.

Salicylic acid, as commonly used, has low solubility in water, making it difficult to apply in high concentrations in cosmetics and limiting its application formulation. It may also induce skin irritation. Therefore, although its use in salicylate form is recommended, this also has the following limitations: skin penetration and efficacy are reduced when applied in a weakly acidic environment.

A method is known to incorporate salicylic acid into a cosmetic composition at a high concentration by encapsulating it with a hydroxyalkylated cyclodextrin to improve its solubility in water (Korean Patent Registration No. 10-2307186). Furthermore, cosmetic compositions containing salicylic acid derivatives are known to inhibit tyrosinase activity, thereby exhibiting a skin-whitening effect (Korean Patent Publication No. 10-2017-0076091). However, the aforementioned prior art describes cosmetic compositions containing salicylic acid as a derivative. Furthermore, regarding skin-improving effects, only tyrosinase inhibition results and functional evaluation experimental results are described; objective results based on standard test methods are not presented regarding the cytotoxicity, acne relief, exfoliation, inflammation relief, and erythema relief efficacy of the topical agent.

In one specific example of the present invention, the preparation of carnitine salicylate (CA-SA) and the results of in vitro and in vivo efficacy tests showed that it had almost no cytotoxicity. Therefore, as a skin-improving material, it exhibited the effects of relieving acne and exfoliating keratin without irritating the skin, and at the same time, as a skin-soothing material, it could maximize the effects of relieving inflammation and erythema.

In this invention, salicylic acid is used not in the form of a salt, but in the form of carnitine salicylate (CA-SA), which is ionically paired with carnitine, to prepare a eutectic mixture. The cosmetic composition of this invention contains carnitine salicylate (CA-SA), allowing it to be prepared under weakly acidic conditions and exhibiting improved effects compared to the original efficacy of each component. Specifically, compared to simple mixtures, the skin-improving effect can be improved by more than 120%, 140%, or 160%. Furthermore, the cosmetic composition of this invention contains carnitine salicylate (CA-SA), thereby improving the stability of the composition. Additionally, it exhibits almost no cytotoxicity, thus demonstrating efficacy in relieving acne and exfoliating without irritating the skin, and maximizing the effects of relieving inflammation and erythema as a skin-soothing material.

The aforementioned eutectic mixture refers to a mixture of two or more solid or liquid substances, specifically two components with high melting points, which combine to form a complex through polar intermolecular dipole-dipole attraction, dipole-induced dipole attraction, intermolecular hydrogen bonding, or van der Waals interactions. In other words, the bonding of a eutectic mixture refers to the intermolecular bonding formed while maintaining the inherent molecular structure, based on hydrogen bonding and dipole bonding caused by partial molecular charge (the formation of a eutectic mixture).

Furthermore, the aforementioned eutectic mixtures can be formed by the combination of polar compounds. These polar compounds can be polar molecules or charged molecules. Additionally, there must be a difference in polarity between the polar compounds, and identical compounds cannot form eutectic mixtures.

The required proportions of the substances in the aforementioned eutectic mixture can be determined based on the charge of the molecules constituting the mixture, the type and number of functional groups possessed by the molecules, and the polarity of the molecules or functional groups. Furthermore, the required proportions of the substances in the eutectic mixture can be determined based on the size or similarity of the molecules.

In this invention, the ratio of substances in the eutectic mixture of carnitine salicylate (CA-SA) is determined based on the charge and functional groups of carnitine and salicylate molecules, as well as the polarity of the molecules or functional groups. The carnitine salicylate (CA-SA) can be mixed in molar ratios of carnitine:salicylate = 1 to 6:2, for example 6:2, 5:2, 4:2, 3:2, 2:2, 1:2, 5.5:2, 4.5:2, 3.5:2, 2.5:2, or 1.5:2. Experimental Example 1-1 confirmed that carnitine salicylate (CA-SA) is stable within this molar ratio range.

Carnitine and salicylates can form eutectic mixtures by dipole bonding caused by partial charge of specific functional groups, and can form eutectic mixtures by their chemical structures at molar ratios within the range mentioned above.

When the molar ratio exceeds the above, the low-temperature stability of carnitine decreases, salicylates cannot form ion pairs with carnitine, and the remaining salicylate molecules exceed their solubility in water, thus they may precipitate at low temperatures.

In this invention, the carnitine salicylate (CA-SA) is preferably a transparent phase that does not precipitate when left to stand at low temperatures. More specifically, no precipitate may form even when left to stand at 0°C for 3, 4, 5, or 6 weeks or more.

In this invention, the cosmetic composition can be in the form of a general emulsifier or a soluble agent. For example, it can be in the form of lotions such as softening lotions or nourishing lotions, emulsions such as facial lotions and body lotions, creams such as nourishing creams, moisturizing creams, and eye creams, serums, cosmetic ointments, balms, sprays, gels, masks, sunscreens, makeup bases, liquid, solid, or spray foundations, powders, makeup removers such as cleansing creams, cleansing lotions, and cleansing oils, and cleansing agents such as cleansing foams, soaps, and shower gels.

In addition, the cosmetics described above may additionally contain adjuvants commonly used in the field of cosmetics, such as fatty substances, organic solvents, solubilizers, concentrates and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, metal ion blocking agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, liposomes, or any other ingredients commonly used in cosmetics.

For the aforementioned cosmetic formulations, wash-off cosmetics such as makeup removers and cleansers, where the active ingredients remain on the skin for a short period, may contain a higher concentration of the composition of the present invention. Conversely, for leave-on cosmetics such as lotions, emulsions, creams, and serums, where the active ingredients remain on the skin for a longer period, it is acceptable to contain a lower concentration of the composition of the present invention than that of wash-off cosmetics. However, not limited to this, in one specific example of the present invention, the composition of the present invention may contain, relative to the total weight of the composition, 0.01 to 20 parts by weight, for example, 0.01 to 20 parts by weight, 0.01 to 1.2 parts by weight, 0.01 to 1.8 parts by weight, 0.01 to 2.5 parts by weight, 0.01 to 4.7 parts by weight, 0.1 to 7.3 parts by weight, 0.01 to 10 parts by weight, 1.2 to 20 parts by weight, or 1.8 to 10 parts by weight of carnitine salicylate (CA-SA).

Compared to the whole composition, when the carnitine salicylate (CA-SA) of the present invention is contained in less than 0.01 parts by weight, it is not expected to have sufficient effects in relieving acne, promoting exfoliation, relieving inflammation and relieving erythema, while when it is contained in more than 20 parts by weight, undesirable reactions such as allergies or skin safety issues may occur. Therefore, this invention is intended to prevent such problems.

The above-mentioned ingredients included in the cosmetic composition of the present invention may each be included in the cosmetic composition of the present invention within the range not exceeding the maximum usage amount specified in the cosmetic safety regulations of various countries.

In addition, the present invention provides a method for preparing a cosmetic composition containing carnitine salicylate (CA-SA).

The following is a detailed description of the preparation method of the present invention.

The preparation method of the present invention may include: a step of preparing a mixture of carnitine and salicylic acid; a step of stirring the mixture of carnitine and salicylic acid at 50°C to 70°C to prepare carnitine salicylate (CA-SA); and a step of adding the carnitine salicylate (CA-SA) to prepare a cosmetic composition.

The steps for preparing the mixture of carnitine and salicylic acid described above may include adding purified water.

In the above steps for preparing carnitine salicylate (CA-SA), eutectic mixing cannot be fully carried out below 50°C, and is destroyed above 70°C, resulting in a reduction in the effectiveness of the eutectic mixture.

The steps for preparing carnitine salicylate (CA-SA) described above may include homogenizing the mixture using a homogenizer. This may include homogenization until the eutectic mixture becomes a colorless or light brown transparent phase. Further purification can then be omitted.

According to the present invention, under the above-mentioned homogenization conditions, the components constituting the eutectic mixture are uniformly mixed, thereby achieving the skin-improving effect, low skin irritation, and excellent dosage form stability of the eutectic mixture.

If carnitine salicylate (CA-SA) is completely dissolved, it will maintain its liquid state and transparency even after cooling. The eutectic mixture prepared as described above does not separate and exists homogeneously even at very low temperatures, such as below 0°C, thus maintaining a transparent liquid phase. Furthermore, the bonds of the eutectic mixture can be maintained without being broken even after repeated solidification and melting processes.

The above steps for preparing carnitine salicylate (CA-SA) are carried out at a pH of 3.0 to 7.0. Sufficient dissolution within this acidity range also helps maintain efficacy.

The above steps for preparing carnitine salicylate (CA-SA) can be performed by eutectic mixing in a molar ratio of carnitine:salicylate = 1 to 6:2, for example 6:2, 5:2, 4:2, 3:2, 2:2, 1:2, 5.5:2, 4.5:2, 3.5:2, 2.5:2, or 1.5:2.

In the steps of preparing the cosmetic composition described above, based on 100 parts by weight of the whole composition, 0.01 to 20 parts by weight, for example 0.01 to 20 parts by weight, 0.01 to 1.2 parts by weight, 0.01 to 1.8 parts by weight, 0.01 to 2.5 parts by weight, 0.01 to 4.7 parts by weight, 0.1 to 7.3 parts by weight, 0.01 to 10 parts by weight, 1.2 to 20 parts by weight, or 1.8 to 10 parts by weight of carnitine salicylate (CA-SA) may be added.

The preparation of the carnitine salicylate (CA-SA) of the present invention is not limited to the above-mentioned carnitine and salicylate forms.

Invention Effects

The cosmetic composition of the present invention contains carnitine salicylate (CA-SA) as an active ingredient, thereby exhibiting the effects of relieving acne and exfoliating as a skin-improving material under weakly acidic conditions through the ionic pairing of carnitine and salicylate. At the same time, it can relieve inflammation and erythema as a skin-soothing material, and further improve skin safety.

Attached Figure Description

Figure 1 shows the macroscopic and chemical analysis results of the carnitine salicylate (CA-SA) of the present invention. Figure 1a shows the results of confirming the macroscopic stability based on the molar ratio of carnitine salicylate (CA-SA), Figure 1b shows the 1H NMR spectrum of carnitine, Figure 1c shows the 1H NMR spectrum of salicylate, Figure 1d shows the 1H NMR spectrum of carnitine salicylate (CA-SA), and Figure 1e shows the IR spectra of carnitine, salicylate, and carnitine salicylate (CA-SA).

Figure 2 shows the results of in vitro confirmation of the cytotoxicity of carnitine, salicylates, and carnitine-salicylic acid (CA-SA).

Figure 3 shows the in vivo efficacy confirmation results of the carnitine salicylate (CA-SA) of the present invention. Figure 3a shows the results confirming the exfoliating efficacy of the cosmetic composition containing carnitine salicylate (CA-SA), and Figure 3b shows the results confirming the erythema relief efficacy of the cosmetic composition containing carnitine salicylate (CA-SA).

Detailed Implementation

This invention relates to cosmetic compositions containing carnitine salicylate (CA-SA) as an active ingredient.

In this invention, the carnitine is 4-trimethylamino-3-hydroxybutyric acid, and L-carnitine, DL-carnitine, their hydrochlorides, and their derivatives can be used. L-carnitine is preferred.

Carnitine is reportedly a low-irritant amino acid exfoliant that exhibits higher efficacy than alpha-hydroxy acids (AHAs) under weakly acidic and neutral conditions. Furthermore, its ammonium group structure facilitates skin penetration and allows for easy absorption into the stratum corneum.

A topical skin agent containing carnitine and exhibiting acne-improving effects has been disclosed (Korean Patent Publication No. 10-2010-0095447). However, the aforementioned prior art merely uses carnitine as an additive to promote ceramide synthesis, with varying proportions, and it does not constitute a component exhibiting the main efficacy. Furthermore, regarding the acne-improving effects, only the results of acne bacteria experiments and functional evaluation experiments are described, while objective results based on standard test methods are not presented regarding the cytotoxicity, exfoliation, inflammation relief, and erythema relief effects of the topical skin agent.

In one specific example of the present invention, the preparation of carnitine salicylate (CA-SA) and the results of in vitro and in vivo efficacy tests showed that it had almost no cytotoxicity. Therefore, as a skin-improving material, it exhibited the effects of relieving acne and exfoliating keratin without irritating the skin, and at the same time, as a skin-soothing material, it could maximize the effects of relieving inflammation and erythema.

Salicylic acid, as commonly used, has low solubility in water, making it difficult to apply in high concentrations in cosmetics and limiting its application formulation. It may also induce skin irritation. Therefore, although its use in salicylate form is recommended, this also has the following limitations: skin penetration and efficacy are reduced when applied in a weakly acidic environment.

A method is known to incorporate salicylic acid into a cosmetic composition at a high concentration by encapsulating it with a hydroxyalkylated cyclodextrin to improve its solubility in water (Korean Patent Registration No. 10-2307186). Furthermore, cosmetic compositions containing salicylic acid derivatives are known to inhibit tyrosinase activity, thereby exhibiting a skin-whitening effect (Korean Patent Publication No. 10-2017-0076091). However, the aforementioned prior art describes cosmetic compositions containing salicylic acid as a derivative. Furthermore, regarding skin-improving effects, only tyrosinase inhibition results and functional evaluation experimental results are described; objective results based on standard test methods are not presented regarding the cytotoxicity, acne relief, exfoliation, inflammation relief, and erythema relief efficacy of the topical agent.

In one specific example of the present invention, the preparation of carnitine salicylate (CA-SA) and the results of in vitro and in vivo efficacy tests showed that it had almost no cytotoxicity. Therefore, as a skin-improving material, it exhibited the effects of relieving acne and exfoliating keratin without irritating the skin, and at the same time, as a skin-soothing material, it could maximize the effects of relieving inflammation and erythema.

In this invention, salicylic acid is used not in the form of a salt, but in the form of carnitine salicylate (CA-SA), which is ionically paired with carnitine, to prepare a eutectic mixture. The cosmetic composition of this invention contains carnitine salicylate (CA-SA), allowing it to be prepared under weakly acidic conditions and exhibiting improved effects compared to the original efficacy of each component. Specifically, compared to simple mixtures, the skin-improving effect can be improved by more than 120%, 140%, or 160%. Furthermore, the cosmetic composition of this invention contains carnitine salicylate (CA-SA), thereby improving the stability of the composition. Additionally, it exhibits almost no cytotoxicity, thus demonstrating efficacy in relieving acne and exfoliating without irritating the skin, and maximizing the effects of relieving inflammation and erythema as a skin-soothing material.

The aforementioned eutectic mixture refers to a mixture of two or more solid or liquid substances, specifically two components with high melting points, which combine to form a complex through polar intermolecular dipole-dipole attraction, dipole-induced dipole attraction, intermolecular hydrogen bonding, or van der Waals interactions. In other words, the bonding of a eutectic mixture refers to the intermolecular bonding formed while maintaining the inherent molecular structure, based on hydrogen bonding and dipole bonding caused by partial molecular charge (the formation of a eutectic mixture).

Furthermore, the aforementioned eutectic mixtures can be formed by the combination of polar compounds. These polar compounds can be polar molecules or charged molecules. Additionally, there must be a difference in polarity between the polar compounds, and identical compounds cannot form eutectic mixtures.

The required proportions of the substances in the aforementioned eutectic mixture can be determined based on the charge of the molecules constituting the mixture, the type and number of functional groups possessed by the molecules, and the polarity of the molecules or functional groups. Furthermore, the required proportions of the substances in the eutectic mixture can be determined based on the size or similarity of the molecules.

In this invention, the ratio of substances in the eutectic mixture of carnitine salicylate (CA-SA) is determined based on the charge and functional groups of carnitine and salicylate molecules, as well as the polarity of the molecules or functional groups. The carnitine salicylate (CA-SA) can be mixed in molar ratios of carnitine:salicylate = 1 to 6:2, for example 6:2, 5:2, 4:2, 3:2, 2:2, 1:2, 5.5:2, 4.5:2, 3.5:2, 2.5:2, or 1.5:2. Experimental Example 1-1 confirmed that carnitine salicylate (CA-SA) is stable within this molar ratio range.

Carnitine and salicylates can form eutectic mixtures by dipole bonding caused by partial charge of specific functional groups, and can form eutectic mixtures by their chemical structures at molar ratios within the range mentioned above.

When the molar ratio exceeds the above, the low-temperature stability of carnitine decreases, salicylates cannot form ion pairs with carnitine, and the remaining salicylate molecules exceed their solubility in water, thus they may precipitate at low temperatures.

In this invention, the carnitine salicylate (CA-SA) is preferably a transparent phase that does not precipitate when left to stand at low temperatures. More specifically, no precipitate may form even when left to stand at 0°C for 3, 4, 5, or 6 weeks or more.

In this invention, the cosmetic composition can be in the form of a general emulsifier or a soluble agent. For example, it can be in the form of lotions such as softening lotions or nourishing lotions, emulsions such as facial lotions and body lotions, creams such as nourishing creams, moisturizing creams, and eye creams, serums, cosmetic ointments, balms, sprays, gels, masks, sunscreens, makeup bases, liquid, solid, or spray foundations, powders, makeup removers such as cleansing creams, cleansing lotions, and cleansing oils, and cleansing agents such as cleansing foams, soaps, and shower gels.

In addition, the cosmetics described above may additionally contain adjuvants commonly used in the field of cosmetics, such as fatty substances, organic solvents, solubilizers, concentrates and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, metal ion blocking agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, liposomes, or any other ingredients commonly used in cosmetics.

For the aforementioned cosmetic formulations, wash-off cosmetics such as makeup removers and cleansers, where the active ingredients remain on the skin for a short period, may contain a higher concentration of the composition of the present invention. Conversely, for leave-on cosmetics such as lotions, emulsions, creams, and serums, where the active ingredients remain on the skin for a longer period, it is acceptable to contain a lower concentration of the composition of the present invention than that of wash-off cosmetics. However, not limited to this, in one specific example of the present invention, the composition of the present invention may contain, relative to the total weight of the composition, 0.01 to 20 parts by weight, for example, 0.01 to 20 parts by weight, 0.01 to 1.2 parts by weight, 0.01 to 1.8 parts by weight, 0.01 to 2.5 parts by weight, 0.01 to 4.7 parts by weight, 0.1 to 7.3 parts by weight, 0.01 to 10 parts by weight, 1.2 to 20 parts by weight, or 1.8 to 10 parts by weight of carnitine salicylate (CA-SA).

Compared to the whole composition, when the carnitine salicylate (CA-SA) of the present invention is contained in less than 0.01 parts by weight, it is not expected to have sufficient effects in relieving acne, promoting exfoliation, relieving inflammation and relieving erythema, while when it is contained in more than 20 parts by weight, undesirable reactions such as allergies or skin safety issues may occur. Therefore, this invention is intended to prevent such problems.

The above-mentioned ingredients included in the cosmetic composition of the present invention may each be included in the cosmetic composition of the present invention within the range not exceeding the maximum usage amount specified in the cosmetic safety regulations of various countries.

In addition, the present invention provides a method for preparing a cosmetic composition containing carnitine salicylate (CA-SA).

In another aspect, a method is provided to alleviate acne and exfoliate by improving the skin, while also relieving inflammation and erythema by soothing the skin, including the step of treating the skin with a cosmetic composition containing carnitine salicylate (CA-SA) as an active ingredient.

In another aspect, a method is provided to alleviate acne and exfoliate by improving the skin, while also relieving inflammation and erythema by soothing the skin, comprising the step of administering a cosmetic composition containing carnitine salicylate (CA-SA) as an active ingredient to a subject.

In another aspect, the use of a composition containing carnitine salicylate (CA-SA) as an active ingredient in the preparation of a cosmetic that exhibits acne-relieving and exfoliating effects by improving the skin, while also relieving inflammation and erythema by soothing the skin.

The following is a detailed description of the preparation method of the present invention.

The preparation method of the present invention may include: a step of preparing a mixture of carnitine and salicylic acid; a step of stirring the mixture of carnitine and salicylic acid at 50°C to 70°C to prepare carnitine salicylate (CA-SA); and a step of adding the carnitine salicylate (CA-SA) to prepare a cosmetic composition.

The steps for preparing the mixture of carnitine and salicylic acid described above may include adding purified water.

In the above steps for preparing carnitine salicylate (CA-SA), eutectic mixing cannot be fully carried out below 50°C, and is destroyed above 70°C, resulting in a reduction in the effectiveness of the eutectic mixture.

The steps for preparing carnitine salicylate (CA-SA) described above may include homogenizing the mixture using a homogenizer. This may include homogenization until the eutectic mixture becomes a colorless or light brown transparent phase. Further purification can then be omitted.

According to the present invention, under the above-mentioned homogenization conditions, the components constituting the eutectic mixture are uniformly mixed, thereby achieving the skin-improving effect, low skin irritation, and excellent dosage form stability of the eutectic mixture.

If carnitine salicylate (CA-SA) is completely dissolved, it will maintain its liquid state and transparency even after cooling. The eutectic mixture prepared as described above does not separate and exists homogeneously even at very low temperatures, such as below 0°C, thus maintaining a transparent liquid phase. Furthermore, the bonds of the eutectic mixture can be maintained without being broken even after repeated solidification and melting processes.

The above steps for preparing carnitine salicylate (CA-SA) are carried out at a pH of 3.0 to 7.0. Sufficient dissolution within this acidity range also helps maintain efficacy.

The above steps for preparing carnitine salicylate (CA-SA) can be performed by eutectic mixing in a molar ratio of carnitine:salicylate = 1 to 6:2, for example 6:2, 5:2, 4:2, 3:2, 2:2, 1:2, 5.5:2, 4.5:2, 3.5:2, 2.5:2, or 1.5:2.

In the steps of preparing the cosmetic composition described above, based on 100 parts by weight of the whole composition, 0.01 to 20 parts by weight, for example 0.01 to 20 parts by weight, 0.01 to 1.2 parts by weight, 0.01 to 1.8 parts by weight, 0.01 to 2.5 parts by weight, 0.01 to 4.7 parts by weight, 0.1 to 7.3 parts by weight, 0.01 to 10 parts by weight, 1.2 to 20 parts by weight, or 1.8 to 10 parts by weight of carnitine salicylate (CA-SA) may be added.

The preparation of the carnitine salicylate (CA-SA) of the present invention is not limited to the above-mentioned carnitine and salicylate forms.

Implementation

The present invention will now be described in detail through embodiments. These embodiments are merely illustrative and the scope of the invention is not limited to them. These embodiments are provided to fully disclose the invention and to clearly inform those skilled in the art of its scope, and the invention is defined only by the scope of the claims.

Preparation Example 1. Preparation of Carnitine Salicylate (CA-SA)

Carnitine and salicylate were mixed at a molar ratio of 1 to 6:2, with a small amount of purified water added, and stirred at 50 to 70°C until homogeneous and clear. At this point, solutions exhibiting weak acidity were prepared in each preparation, based on a final salicylate content of 0.5% and a pH of 5.5. No further purification was performed thereafter. The stable eutectic mixture solution formed without precipitates was observed.

Experimental Example 1: Analysis of Carnitine Salicylate (CA-SA)

<Experimental Example 1-1> Evaluation of the solubility and stability of carnitine salicylate (CA-SA)

To confirm the stability of carnitine salicylate (CA-SA), the carnitine salicylate (CA-SA) prepared in the above preparation example was left to stand at 25°C and 0°C for 4 weeks, and the macroscopic changes in its properties were observed to evaluate its stability. After 4 weeks, the separation and precipitation of the phases were observed with the naked eye, and the results are shown in Table 1 and Figure 1a below.

[Table 1]

CA: Carnitine

SA: Salicylate

As shown in Table 1 and Figure 1a, the results of Examples 1 to 4 confirmed that carnitine salicylate (CA-SA) is stable when the molar ratio of carnitine to salicylate is 1 to 6:2. In Comparative Example 1, where the carnitine to salicylate ratio was 1:3, salicylate remained above its solubility in water, indicating that it precipitated at low temperature.

Based on the above results, carnitine salicylate (CA-SA) is stable at room temperature and low temperature, and therefore can be used in cosmetic compositions.

<Experimental Examples 1-2> 1H-NMR Analysis

To conduct comparative structural analysis of carnitine, salicylate, and carnitine salicylate (CA-SA), 1H-NMR spectra were measured at 500 MHz using an Avance III-500 NMR spectrometer (Bruker Instruments, USA) at 35 °C. For ^1H -NMR determination, samples were prepared using _D₂O . Measurements were performed with a 90° pulse width of 12.2 μs, a relaxation delay of 4 s, and 100 scans. Tetramethylsilane was used as a standard. The structure of carnitine salicylate (CA-SA) was analyzed using Example 2 of Experimental Example 1-1. The results are shown in Figures 1b, 1c, and 1d.

Figures 1b, 1c, and 1d show the components constituting carnitine salicylate (CA-SA) and its 1H-NMR spectrum. Before and after the formation of CA-SA, at the d-peak of carnitine's spin-spin splitting, it can be confirmed that the number of splitting peaks decreases after CA-SA formation. A corresponding change can also be confirmed in salicylate, and all peaks a, b, and c shift upwards. In particular, the upward shift is largest in peak a, suggesting that the functional group involved in the binding of CA-SA in salicylate is a carboxyl group. By inducing changes in the number of hydrogens around the d-hydrogen in carnitine and the intermolecular bonding of the carboxyl group in salicylate, it can be inferred that carnitine and salicylate form proton-sharing hydrogen bonds.

The above results confirm that carnitine and salicylate do indeed undergo ion pairing.

<Experimental Examples 1-3> FT-IR Analysis

The functional group binding sites of carnitine, salicylate, and carnitine salicylate (CA-SA) were analyzed by FT-IR spectroscopy. FT-IR spectra were measured at 2 ^cm⁻¹ intervals within the range of 3600 to 500 ^cm⁻¹ using a Vertex 70, Hyperion 2000 (FTIR spectrophotometer, Bruker Instruments) model. Subsequently, the spectra were deconvolved using Opus 5.5 software (Bruker Instruments). The structure of carnitine salicylate (CA-SA) was analyzed using Example 2 of Experimental Example 1-1. The results are shown in Figure 1e.

As shown in Figure 1e, firstly, in the IR spectrum of L-carnitine, enhancement of the IR peaks was observed due to vibrations caused by the -COOH and -OH groups. The main peaks were located at 1396-1385 (COOH), 1245 (CC), 1137-1195 (CCO,COH), 913 (C-COOH), and 625-634 (COH) ^cm⁻¹ . Additionally, a characteristic band was observed caused by the ammonium group. This group (CN ⁺ ( _CH₃ ) _₃ ) showed characteristic peaks at 970, 944, and 772 ^cm⁻¹ . For salicylates, characteristic vibrational peaks were observed at 3233 ^cm⁻¹ and 999-2831 ^cm⁻¹ caused by OH and CH, respectively, and peaks of C＝O (COO-) were observed at 1652-1670 ^cm⁻¹ and 1386 ^cm⁻¹ . In addition, a peak caused by C＝C (phenol group) was observed at 1558-1610 ^cm⁻¹ , and characteristic peaks were observed at 1324 OH (phenol group) ^cm⁻¹ , 1296 (COO₂ ^- (CO)) ^cm⁻¹ , and 1156-1248 C₂OH (phenol group) ^cm⁻¹ . When the changes in these peaks after the formation of carnitine salicylate (CA-SA) were confirmed, changes in spectral morphology caused by intermolecular bonding were observed at the 1137-1195 (CCO,COH) and 625-634 (COH) ^cm⁻¹ peaks of carnitine and the 1652-1670 C＝O (COO₂) ^cm⁻¹ peaks of salicylate. Therefore, it was determined that, consistent with the 1H-NMR analysis results, carnitine salicylate (CA-SA) forms hydrogen bonds in the form of shared protons between the OH and COO₂ groups of carnitine and salicylate.

The above results confirm that carnitine and salicylate do indeed undergo ion pairing.

Experiment Example 2: Evaluation of the in vitro keratolytic, cytotoxic, and anti-inflammatory effects of carnitine salicylate (CA-SA).

<Experimental Example 2-1> Confirms the in vitro keratolytic efficacy of carnitine salicylate (CA-SA).

To compare and confirm the exfoliative efficacy of carnitine (CA), salicylate (SA), a simple mixture of carnitine and salicylate (SA+CA, MIX), and carnitine-salicylate (SA-CA), the relative keratolytic efficacy was evaluated in vitro using porcine back skin (Apures, Korea) under weakly acidic conditions (pH 5.5) that did not induce skin irritation. The porcine back skin surface was washed with phosphate-buffered silane (PBS), then cut into appropriate sizes and prepared. Subsequently, the stratum corneum of the porcine skin was exposed, placed in 96-well plates, and 100 μl of each sample was spread. The 96-well plates were then incubated in a constant temperature and humidity chamber for 16 h. Afterward, the supernatant of each sample was thoroughly mixed with trypan blue solution in the 96-well plates, and the number of exfoliated keratinocytes was measured. The following method was used to validate the applicability of the relative keratolytic efficacy evaluation method used in this study. DL-gluconolactone at pH 4.0 and 6.0 was used as a positive control group. After treating pig skin samples using the above method, the number of exfoliated keratinocytes was counted, and the relative exfoliation efficacy was evaluated with the number of exfoliated keratinocytes in pH 4.0 (DL-gluconolactone) as 100%. All evaluations were performed at n=5 to ensure reliability through repeated results. The exfoliation efficacy was compared and evaluated using the mean and standard deviation of the number of exfoliated keratinocytes, and the results are shown in Table 2.

[Table 2]

Exfoliation rate (%) 10% gluconolactone, pH 4 100.0 10% gluconolactone, pH 6 32.0 CA 2% 55.2 SA 2% 19.2 SA-CA 2% 91.8 SA 1% + CA 1% 56.5

As shown in Table 2, when comparing relative efficacy using 10.0% gluconolactone at pH 4.0 as 100%, carnitine salicylate (CA-SA) exhibited a 91.8% exfoliating efficacy. On the other hand, equal amounts of salicylate showed 19.2%, carnitine showed 55.2%, and a simple mixture of carnitine and salicylate (CA+SA, MIX) showed 56.5% exfoliating efficacy. These results demonstrate that carnitine salicylate (CA-SA) possesses significant exfoliating effects even under low-irritation, weakly acidic conditions.

<Experimental Example 2-2> Confirmation of the in vitro cytotoxicity of carnitine salicylate (CA-SA)

The cytotoxicity of carnitine salicylate (CA-SA) was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Raw264.7 cell lines and fibroblasts obtained from human skin tissue were seeded into 24-well plates at concentrations of 1 to 2 x ^10⁵ cells/ml using DMEM medium supplemented with 10% FBS and cultured in a 5% _CO₂ incubator for 24 hours. The medium was then removed, and each sample was added to FBS-free medium and cultured for 24 hours. The medium was then removed again, and MTT solution was added at a concentration of 1 μg/ml. The reaction was incubated at 37°C for 3 hours. Unreacted MTT solution was removed, and 100 μl of DMSO was added to dissolve the resulting reaction mixture. The absorbance was then measured at 540 nm to confirm cytotoxicity.

The cytotoxicity of salicylates, carnitine, and carnitine salicylates (CA-SA) was evaluated by treating mouse macrophages (Raw 264.7) and human fibroblasts with the substance. Raw 264.7 cells, representative of NO inhibition efficacy in anti-inflammatory efficacy evaluation, were used to evaluate cytotoxicity. For fibroblasts, cytotoxicity was evaluated to confirm the potential toxicity induced by repeated application of the material to the skin in cosmetics. Carnitine salicylates (CA-SA) were evaluated using Example 2 of Experimental Example 1-1, based on the salicylic acid content in the eutectic mixture rather than the carnitine salicylates (CA-SA) content. The results are shown in Figure 2.

As shown in Figure 2, treatment of Raw 264.7 with salicylate resulted in 96.16% cell viability at 50 ppm and 79.74% at 100 ppm. For fibroblasts, 94.83% cell viability was confirmed at 50 ppm and 85.36% at 100 ppm. This is a result of the potential for cytotoxicity induced by salicylate treatment at cellular levels above 50 ppm. However, for carnitine and carnitine salicylate (CA-SA), cell viability above 95% was observed across the entire concentration range up to 100 ppm, with no cytotoxicity observed.

Based on the above results, since carnitine and salicylate undergo ion pairing, they do not exhibit the cytotoxicity originally present in each component. Therefore, they have a relatively small impact on cell activity and can be safely used in humans.

<Experimental Example 2-3> Confirmed the in vitro anti-inflammatory efficacy of carnitine salicylate (CA-SA).

A confirmatory assay for the anti-inflammatory effect of carnitine salicylate (CA-SA) was performed. Based on the results of Experiment 2-2 above, the anti-inflammatory effects induced by the NO inhibition efficacy of salicylate, carnitine, and carnitine salicylate (CA-SA) were evaluated at 10 ppm, where no cytotoxicity was observed in any of the materials. Treatment with 500 ng/ml of the inflammatory precipitant LPS (lipopolysaccharide) and 100 mM of the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) served as a positive control to confirm the NO inhibition rate.

To evaluate the efficacy of externally stimuli in relieving inflammation in vitro, the mouse macrophage cell line Raw264.7 (ATCC number: CRL-2788) was treated with lipopolysaccharide (LPS, Sigma-Aldrich, USA), and the experiment was performed using the GRIESS method to evaluate NO production inhibition. Raw264.7 cells pre-cultured in growth medium (DMEM with 10% FBS added, Welgene, USA) were added to 24-well tissue culture plates at a concentration of 1 to 2 x ^10⁵ cells/ml and cultured for one day in a 5% _CO₂ incubator. The medium was removed, and the cells were starved with serum-free medium for 12 hours. Then, the test substance was pretreated at 0.1 to 100 ppm for 30 minutes, followed by the addition of LPS at a concentration of 500 ng/ml and incubation for 18 hours. After culturing, the supernatant was transferred to a 96-well plate, GRIESS reagent was added, and the mixture was incubated at room temperature for 15 minutes. The absorbance at 540 nm was measured using an ELISA reader. Carnitine salicylate (CA-SA) was used in Example 2 of Experiment 1-1. The results are shown in Table 3.

[Table 3]

NO inhibition rate negative control group 0% L-MMMA (100mM) 62.2% SA 10ppm 16.4% CA 10ppm 0.0% SA-CA 10ppm 60.0% SA 10ppm + CA 10ppm 20.4%

As shown in Table 3, salicylate exhibited a NO inhibition efficacy of 16.4%, carnitine showed a NO inhibition efficacy of 0.0%, a simple mixture of carnitine and salicylate (SA+CA) showed a NO inhibition efficacy of 20.4%, and carnitine salicylate (CA-SA) showed a NO inhibition efficacy of 60.0%. These results confirm that the carnitine salicylate (CA-SA) of the present invention exhibits superior anti-inflammatory efficacy than the individual components themselves, through ion pairing. This is an advanced material that can even demonstrate skin-soothing effects that may be induced by the inherent exfoliating effects of the individual components.

<Experimental Example 2-4> Confirmed the in vitro antibacterial efficacy of carnitine salicylate (CA-SA) against Propionibacterium acnes.

The bactericidal efficacy of carnitine salicylate (CA-SA) against Propionibacterium acnes was confirmed using a time-killing assay. First, bacteria were inoculated into samples to a concentration of ^10⁶ CFU/mL. After inoculation, 1 mL samples were taken at 20 minutes, 1 hour, 3 hours, and 6 hours post-inoculation. These samples were diluted in D/E solution to remove preservative activity. The following samples were diluted to appropriate dilutions and spread onto mLNA medium. Each sample was incubated at 30°C for at least 48 hours, and the bacterial count was then confirmed. Sample preparation is shown in Table 4 below, and the results are shown in Table 5 below.

[Table 4]

Example 5 Comparative Example 2 Comparative Example 3 Comparative Example 4 composition CA-SA 0.5% SA 0.5% CA 0.5% SA 0.5% pH 5.5 5.5 6.0 2.7

SA: Salicylate; CA: Carnitine; CA-SA: Carnitine Salicylate

[Table 5]

Over time Example 5 Comparative Example 2 Comparative Example 3 Comparative Example 4 1h <100 <![CDATA[5.02x 10⁵]]> <![CDATA[4.96x 10⁵]]> <100 3h <100 <![CDATA[1.75x 10⁵]]> <![CDATA[4.96x 10⁵]]> <100 6h <100 <![CDATA[2.00x 10³]]> <![CDATA[3.44x 10⁵]]> <100 24h <100 <100 <![CDATA[2.04x 10⁵]]> <100

As the results above show, under weakly acidic conditions, Example 5 exhibited a significantly higher acne-killing rate compared to Comparative Examples 2 and 3, each containing a single component. Furthermore, despite being weakly acidic, it reached a level similar to Comparative Example 4, which had the lowest pH. Therefore, it is determined that the carnitine salicylate (CA-SA) of the present invention can adequately remove acne-causing bacteria even under weakly acidic conditions, thereby improving acne-prone skin without irritation.

Experiment Example 3: Evaluation of the in vivo keratolytic and erythema-inhibiting effects of carnitine salicylate (CA-SA)

<Experimental Example 3-1> Confirms the in vivo keratolytic efficacy of carnitine salicylate (CA-SA).

To evaluate the exfoliating efficacy of carnitine salicylate (CA-SA), a clinical trial was conducted on six randomly selected participants (aged 25–35 years). 5.0% DHA was applied to the forearms of the subjects and maintained for 24 hours to stain the keratin. The stained areas were evaluated using a colorimeter (CR-400, Konica Minolta, Japan), and four areas with the same staining level were selected. An aqueous solution of carnitine salicylate (CA-SA) (Example 6) and a substrate without a sample (Comparative Example 5) were applied twice daily, morning and evening, to the same area for 14 days. One area was left untreated for comparison. All areas were maintained under identical conditions, and no separate physical or chemical exfoliation was performed during the evaluation period. Exfoliating efficacy was evaluated by changes in the brightness of the stained areas using a colorimeter after 7 and 14 days. The exfoliating efficacy was evaluated as follows.

t: measurement time point, -1: time point before keratin staining, 0: time point after keratin staining. Statistical significance was analyzed using a paired t-test. The substrate used for evaluation was prepared from materials that might affect keratin exfoliation and was prepared to not affect the induction and relief of inflammation; the results are shown in Figure 3a.

[Table 6]

Ingredient name Example 6 Comparative Example 5 Deionized water Up to 100 Up to 100 Carnitine salicylate (SA-CA) 5.00 - 1,2-Hexanediol 2.00 2.00 glycerin 8.00 8.00 1,3-Butanediol 3.00 3.00 Cyclopentasiloxane 7.00 7.00 polydimethylsiloxane 4.50 4.50 Polysorbate 60 (Tween 60) 1.50 1.50 Acrylic ester/C10-30 alkyl acrylate crosspolymer 0.35 0.35 Tromethamine 0.35 0.35 total 100 100

As shown in Figure 3a, for the uncoated and substrate application groups (Comparative Example 5), improvement rates of 4.65% and 10.41% and 43.00% and 47.30% were observed on days 7 and 14, respectively. For the carnitine salicylate (CA-SA) application group (Example 6), improvement rates of 49.16% and 65.49% were observed. Furthermore, when carnitine salicylate (CA-SA) was applied, a 38.46% improvement in keratolytic effect was confirmed on day 14 compared to the substrate application group.

Based on the above results, it is determined that including the carnitine salicylate (CA-SA) of the present invention in the cosmetic composition can exhibit exfoliating effects when applied to the human body.

<3-2> Confirming the in vivo erythema-inhibiting effect of carnitine salicylate (CA-SA).

Erythema inhibition efficacy confirmation test was conducted using Example 6 of Experimental Example 3-1. To evaluate erythema inhibition efficacy, the erythema index was assessed in nine volunteers (aged 25–35 years) before erythema induction, after erythema induction, and 5 and 12 days after product use. A 1% SDS dilution was applied to the forearm for 24 hours to induce skin barrier damage and erythema. Then, a carnitine salicylate (SA-CA) aqueous solution (based on 0.5% salicylate, pH 5.5) and a substrate without the sample were applied twice daily, morning and evening, to the same site for 12 days. The erythema index was measured using a Mexameter (MX 18, Courage+Khazaka electronic GmbH, Germany) after 5 and 12 days. The erythema index recovery rate was evaluated as follows.

(t: product usage date, -1: time point before erythema induction, 0: time point immediately after erythema induction)

Statistical significance was analyzed using a paired t-test. The results are shown in Figure 3b.

As shown in Figure 3b, after 5 and 12 days, the untreated subjects showed recovery rates of 40.32% and 51.82%, respectively, while the subjects using the substrate formulation showed recovery rates of 46.76% and 59.86%, respectively. However, the subjects using carnitine salicylate (CA-SA) (Example 6) showed a recovery rate of 63.08% after 5 days and 74.03% after 12 days. Thus, it can be confirmed that compared with the subjects using the substrate formulation, the erythema recovery rate was improved by 34.90% after 5 days and by 23.67% after 12 days.

Based on the above results, the carnitine salicylate (CA-SA) of the present invention is included in the cosmetic composition, thereby exhibiting the effects of relieving inflammation and erythema when applied to the human body.

Experimental Example 4: Functional Evaluation of Cosmetic Compositions Containing Carnitine Salicylate (CA-SA)

A functional evaluation test was conducted using Example 6 of Experimental Example 3-1. To evaluate the perceived effects of applying a cosmetic composition containing carnitine salicylate (CA-SA) on keratinization and skin soothing, volunteers with sensitive skin who used cosmetics daily, experienced significant skin problems, and frequently suffered from skin irritation were evaluated. Volunteers used their usual cosmetics as well as, as the first step after cleansing, the cosmetic composition containing carnitine salicylate (CA-SA) of this invention. Evaluations were conducted using a 5-point scale (5 points: significant improvement, 4 points: perceived improvement, 3 points: no perceived change, 2 points: perceived worsening, 1 point: very worsening), and the results are shown in Table 7 below.

[Table 7]

Experimental Project average score Non-irritating and gentle to use 4.32 Remove skin redness 3.50 Soothes skin immediately after use 3.67 Remove roughness from the skin 3.61 Overall product preference 4.12

As the results above show, the cosmetic composition containing carnitine salicylate (CA-SA, Example 6) was evaluated to show improvements in skin irritation and redness, as well as skin texture, after periodic and repeated application. The skin texture became softer, seemingly due to continuous exfoliation. These results indicate that including carnitine salicylate (CA-SA) in a cosmetic composition not only allows for daily exfoliation with low irritation but also provides a perceived relief from inflammation caused by irritants.

[Industrial Applicability]

The cosmetic composition of the present invention contains carnitine salicylate (CA-SA) as an active ingredient, thereby exhibiting the effects of relieving acne and exfoliating as a skin-improving material under weakly acidic conditions through the ionic pairing of carnitine and salicylate. At the same time, it can relieve inflammation and erythema as a skin-soothing material, and further improve skin safety.