HK40072301A - Cosmetic composition comprising eutectic mixture - Google Patents
Cosmetic composition comprising eutectic mixture Download PDFInfo
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- HK40072301A HK40072301A HK62022060997.3A HK62022060997A HK40072301A HK 40072301 A HK40072301 A HK 40072301A HK 62022060997 A HK62022060997 A HK 62022060997A HK 40072301 A HK40072301 A HK 40072301A
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Description
Technical Field
The present invention relates to cosmetic compositions comprising a co-crystal mixture comprising an alpha-hydroxy acid, an amino acid and purified water; and a cosmetic composition comprising a eutectic mixture containing the 1 st amino acid and the 2 nd amino acid, more specifically, to a cosmetic composition comprising: comprising purified water, a eutectic mixture of an amino acid and an alpha-hydroxy acid or a eutectic mixture of a1 st amino acid and a 2 nd amino acid, has excellent skin permeability and keratolytic effect and low-temperature stability even under a pH condition with little skin irritation, and can maintain the keratolytic effect even under severe conditions.
Background
Alpha-hydroxy acid (hereinafter referred to as AHA) is a commonly used ingredient for softening or removing excessively keratinized skin layers, and has skin improvement effects of promoting turnover rate of keratin (turnover), collagen synthesis, enhancing skin moisturization, relieving fine wrinkles, and treating and preventing acne, etc. (volume 10, No. 2, 2015, 161-169, korea health maintenance association). Most AHAs have excellent skin penetration and skin improvement effects under low pH conditions, but cannot be used at high levels because of severe skin irritation such as itching, and heat-drying sensation and various inflammatory irritation such as erythema and edema caused by low pH. In addition, AHA is ionized when dissolved in water, resulting in slow absorption by the skin. In particular, when AHA is formulated into cosmetics, the pH of the formulation decreases, which leads to a decrease in the safety of the formulation, and causes a negative effect of irritation on the skin. To supplement this, if the pH of the dosage form is raised with a neutralizing agent, the problem of a decrease in the effectiveness of AHA results.
In addition to The above AHA, amino acids which have a keratolytic effect on dry skin have been widely used in cosmetics for skin application (Tatsuya Ozawa et al, The role of human in skin mobility retention. skin Research 27, 276-. But by [ S.E.Wolverton, α -hydroxy acids, In Comprehensive Dermatologic Drug Therapy, 3rdedition，Elsevier，570(2012)]It has been found that the AHA and the amino acid described above cause a significant decrease in skin permeability at a weakly acidic or neutral pH, and cause an uncomfortable feeling of skin irritation particularly for a person having sensitive skin at a strongly acidic pH.
On the other hand, the eutectic (eutectic) phenomenon is a phenomenon in which the melting point decreases as two or more substances are mixed, and each component contained in the mixture shows a solid state at normal temperature, but when the mixture is prepared, the component does not crystallize due to van der waals interaction or hydrogen bonding between the components, and becomes an anhydrous solution existing as a liquid at room temperature. On the other hand, when AHA is selected as one component contained in the mixture, a liquid state in which water is removed can be obtained. In the anhydrous state, AHA is not ionized and thus does not exhibit acid (acid) characteristics, so that not only can AHA be used with weak stimulation, but also it is very advantageous for skin penetration since AHA is uncharged.
However, such a eutectic mixture has a problem that it cannot be stably present in a cosmetic. In the case where a protic solvent (hydrogen bond) that may have a hydrogen bond is added to a composition containing a eutectic mixture, the solvent interacts with each constituent component of the eutectic mixture (hydrogen bond) to inhibit the bonding between the constituents of the eutectic mixture, and thus it is difficult to maintain the characteristics of the eutectic mixture. In addition, although a cosmetic containing a eutectic mixture is suitable as an anhydrous preparation, most of the eutectic mixtures have a higher specific gravity than water, and therefore, when the eutectic mixture is mixed with oil, the eutectic mixture precipitates, which causes a problem that the eutectic mixture is difficult to uniformly disperse in low-viscosity oil. Conventionally, in order to solve this problem, hydrophilic powder has been added to the composition, but a eutectic mixture having hydrophilicity adsorbs and agglomerates on the surface of the hydrophilic powder, and uniform dispersion is difficult.
Therefore, under such a background, the present inventors studied and developed a cosmetic composition in which a eutectic mixture comprises purified water, AHA and amino acid or 2 amino acids and which improves the irritation problem caused by a lower pH and the formulation stability, thereby completing the present invention.
Disclosure of Invention
Technical subject
The present inventors have studied in order to develop a cosmetic composition that improves the problem of AHA irritation at a low pH and the problem of low skin permeation effect when AHA or an amino acid is applied to skin pH, and as a result, have confirmed that purified water, AHA, and an amino acid are added to a cosmetic composition in the form of a eutectic mixture; 2 kinds of amino acids; or purified water and 2 kinds of amino acids, whereby the skin permeability of AHA or amino acids can be improved without skin irritation at a pH ranging from weak acidity to neutrality, the amino acids are not precipitated even at low temperatures and are kept stable and uniform, and the exfoliating effect can be maintained under severe conditions (e.g., high temperature, high pressure, etc.), thereby completing the present invention.
Accordingly, an object of the present invention is to provide a cosmetic composition comprising: comprises purified water, AHA and amino acids in the form of eutectic mixture in cosmetic composition; 2 kinds of amino acids; or purified water and 2 kinds of amino acids, whereby excellent exfoliating effect is achieved even under weakly acidic to neutral conditions, irritation is small, low-temperature safety is excellent, and exfoliating effect is maintained even under severe conditions.
Means for solving the technical problem
As means for solving the above problems, the cosmetic composition of the present invention provides a cosmetic composition containing purified water, an amino acid, and an α -hydroxy acid (AHA) or a eutectic mixture of 1 st amino acid and 2 nd amino acid.
In one embodiment, the cosmetic composition of the present invention comprises a eutectic mixture containing purified water, amino acids, and alpha-hydroxy acids (hereinafter AHA).
In the present invention, the above-mentioned α -hydroxy acid (AHA) and amino acid are contained in a eutectic mixture and are used for achieving skin improvement effects such as promotion of exfoliation of the skin, improvement of pores, improvement of fine lines, improvement of acne, or improvement of the skin color of the face, respectively.
In the present invention, the α -hydroxy acids are a general term for compounds in which an alcohol group (alcohol group) or a hydroxyl group (hydroxyl group) is added to a carbon at the α -position of a carboxylic acid, and reduce the ion binding energy of keratinocytes, thereby removing excessive keratoses, promoting the formation of new cells, shortening the cycle of keratinization process that is prolonged by aging of the skin, promoting the activity of skin cells, and improving the skin. AHA promotes the production of collagen and elastin by fibroblasts (fibroblasts), makes the skin elastic and tender, promotes the production of mucopolysaccharides (mucopolysaccharides), which are important extracellular matrix components of the dermis, and enhances skin moisture retention. AHA helps to remove the links between corneas in the stratum corneum by the action of acid, achieving the effect of melting and softening the corneas. The AHA may be one or more selected from the group consisting of lactic acid (lactic acid) contained in putrefying milk, tomato juice, or the like, citric acid (citric acid) contained in oranges, or the like, malic acid (malic acid) contained in apples, or the like, tartaric acid (tartaric acid) contained in wine, or the like, glycolic acid (glycolic acid) contained in sugar cane, or the like, and mandelic acid (mandelic acid), but is not limited thereto.
In one embodiment, the AHA may be lactic acid (lactic acid) or malic acid (malic acid). The lactic acid rapidly penetrates the skin due to its low molecular weight in AHA, thereby rapidly exhibiting the effect of targeted AHA, while malic acid (malic acid) retains a plurality of carboxyl groups (carboxyl groups) to induce stronger binding when preparing a eutectic mixture, and has a molecular structure similar to amino acids, particularly serine (serine), thereby facilitating the preparation of a structurally stable eutectic mixture in dimer or multimer form.
In an embodiment of the present invention, in the case where the AHA is contained in the eutectic mixture, the AHA may be contained in an amount of 1 to 50 parts by weight, for example, 5 to 40 parts by weight, 10 to 30 parts by weight, 15 to 20 parts by weight, 3 to 25 parts by weight, 5 to 20 parts by weight, or 6 to 18 parts by weight, based on 100 parts by weight of the eutectic mixture. When the AHA contained in the eutectic mixture is less than 1 part by weight, the intended effect cannot be achieved, and when the AHA contained in the eutectic mixture exceeds 50 parts by weight, a skin-irritating feeling is produced.
As described above, in the case where the AHA is contained in the eutectic mixture, the eutectic mixture can be prepared by mixing the AHA with an amino acid which is a component that can be bound by dipole-dipole attraction between polar molecules, dipole-induced dipole attraction, hydrogen bonding, or van der waals interaction. In this case, the AHA functions as a Hydrogen Bond Donor (HBD) and the amino acid functions as a Hydrogen Bond Acceptor (HBA). For example, the amino acids may include alanine (alanine), cysteine (cysteine), aspartic acid (aspartic acid), glutamic acid (glutamic acid), phenylalanine (phenylalanine), glycine (glycine), histidine (histidine), isoleucine (isoleucin), lysine (lysine), leucine (leucine), methionine (methionine), asparagine (aspartic acid), pyrrolysine (pyrroline), proline (proline), glutamine (glutamine), arginine (arginine), serine (serine), threonine (threonine), selenocysteine (selenocysteine), valine (valine), tryptophan (tryptophan), or tyrosine (tyrosine).
In the present invention, the total content of the amino acids in the eutectic mixture may be 1 to 75 parts by weight, 5 to 70 parts by weight, 10 to 60 parts by weight, 15 to 50 parts by weight, 20 to 47 parts by weight, 10 to 70 parts by weight, 20 to 65 parts by weight, 30 to 60 parts by weight, 35 to 55 parts by weight, 40 to 50 parts by weight, 42 to 47 parts by weight, based on all 100 parts by weight of the eutectic mixture, but is not limited thereto. When the amount of the amino acid contained in the eutectic mixture is less than 1 part by weight, the intended effect cannot be obtained, and when the amount of the amino acid contained in the eutectic mixture exceeds 75 parts by weight, the skin is irritated and the composition is not dissolved and precipitates. In one embodiment, the amino acid comprised in the eutectic mixture is serine, proline, threonine, arginine or cysteine.
In the present invention, the eutectic mixture may be prepared from AHA and an amino acid, and preferably, purified water, AHA and an amino acid.
In the present invention, the AHA and the amino acid are contained in the eutectic mixture in a weight ratio of 1:0.1 to 1:10, for example, in a weight ratio of 1:0.3 to 1:5, in a weight ratio of 1:0.5 to 1:3, in a weight ratio of 1:0.7 to 1:2, in a weight ratio of 1:3 to 1:10, and in a weight ratio of 1:5 to 1: 8.
In general, AHAs within the eutectic mixture are ionized in the presence of purified water, leading to the problem of increased skin irritation. In contrast, in the case of a conventional eutectic mixture, an additional step of removing the solvent (purified water) by evaporation, cooling, or freeze drying is required. However, in the eutectic mixture of the present invention, the binding between AHA and amino acid molecules, which is achieved by dipole-dipole attraction, dipole-induced dipole attraction, hydrogen bonding, or van der waals interaction, is not ionized even in the presence of purified water, and is relatively safe without being adversely affected by increased skin irritation.
In this regard, the eutectic mixture of the present invention comprises purified water. The eutectic mixture of the present invention includes purified water, thereby having a low melting point of 0 ℃ or less by purified water and stably maintaining the amino acids in the composition. In addition, pure water is contained in the eutectic mixture, so that AHA and amino acid are exposed to excessive moisture and gradually dissociated, thereby exhibiting a skin improvement effect by promoting exfoliation of keratin. Therefore, the eutectic mixture of the present invention does not precipitate amino acids even under various environmental changes, and remains in a liquid state uniformly and stably.
In the present invention, the purified water is contained in an amount of 25 to 80 parts by weight relative to 100 parts by weight of the total eutectic mixture. When the content of the purified water contained in the eutectic mixture is less than 25 parts by weight, the melting point of the eutectic mixture cannot be lowered, and thus the amino acid cannot be stably present, and when the content of the purified water contained in the eutectic mixture exceeds 80 parts by weight, the stability of hydrogen bonds is lowered, the skin permeability of AHA and the amino acid is lowered, and the content of the amino acid is lowered, whereby the intended effect is hardly exhibited. For example, in the eutectic mixture of the present invention, purified water may be included by 30 to 75 parts by weight, 35 to 70 parts by weight, 40 to 65 parts by weight, 50 to 55 parts by weight, based on the total weight of the eutectic mixture, but is not limited thereto.
In other embodiments, the cosmetic compositions of the present invention comprise a eutectic mixture comprising the 1 st amino acid and the 2 nd amino acid.
In the present invention, the 1 st amino acid and the 2 nd amino acid may be one or more selected from the group consisting of alanine (alanine), cysteine (cysteine), aspartic acid (aspartic acid), glutamic acid (glutamic acid), phenylalanine (phenylalanine), glycine (glycine), histidine (histidine), isoleucine (isoluteine), lysine (lysine), leucine (leucine), methionine (methionine), asparagine (aspartic acid), pyrrolysine (pyrolysine), proline (proline), glutamine (glutamine), arginine (arginine), serine (serine), threonine (threonine), selenocysteine (selenocysteine), valine (valine), tryptophan (tryptophan), and tyrosine (tyrosine). For example, the 1 st amino acid and the 2 nd amino acid may be 2 kinds selected from the group consisting of serine, arginine, and glutamic acid.
In the above-described embodiments, the total content of amino acids in the eutectic mixture may be 1 to 75 parts by weight, 5 to 70 parts by weight, 10 to 60 parts by weight, 15 to 50 parts by weight, 20 to 47 parts by weight, 10 to 70 parts by weight, 20 to 65 parts by weight, 30 to 60 parts by weight, 35 to 55 parts by weight, 40 to 50 parts by weight, 42 to 47 parts by weight, based on all 100 parts by weight of the eutectic mixture, but is not limited thereto. When the amount of the amino acid contained in the eutectic mixture is less than 1 part by weight, the intended effect cannot be obtained, and when the amount of the amino acid contained in the eutectic mixture exceeds 75 parts by weight, the skin is irritated, and the composition is not dissolved and precipitates. At this time, the 1 st amino acid may be contained in an amount of 1 to 50 parts by weight, and the 2 nd amino acid may be contained in an amount of 75 parts by weight excluding the 1 st amino acid, based on 100 parts by weight of the total eutectic mixture. For example, the above-mentioned 2 nd amino acid may be contained in an amount of 1 to 25 parts by weight. In the present invention, the 1 st amino acid may be contained in an amount of 1 to 50 parts by weight, preferably 5 to 40 parts by weight, 10 to 35 parts by weight, 15 to 30 parts by weight.
In addition, the eutectic mixture of the present invention may further comprise purified water. The purified water may be included in an amount of 25 to 80 parts by weight, based on 100 parts by weight of the total eutectic mixture. The contents described above can be directly applied to the purified water contained in the eutectic mixture.
In the present invention, the eutectic mixture may be prepared from the 1 st amino acid and the 2 nd amino acid, and preferably, the eutectic mixture is prepared from purified water, the 1 st amino acid and the 2 nd amino acid.
As described above, in the case of including purified water, the eutectic mixture of the 1 st amino acid and the 2 nd amino acid, 25 to 80 parts by weight of purified water, 1 to 50 parts by weight of the 1 st amino acid, and 1 to 25 parts by weight of the 2 nd amino acid are included, based on 100 parts by weight of the eutectic mixture as a whole.
In the following examples, it was confirmed that a eutectic mixture of 2 amino acids has skin-improving effects such as reduction in the number of pores, improvement of wrinkles, promotion of skin regeneration, increase in the total amount of collagen, and enhancement of skin elasticity, and the skin-improving effects as described above are maintained even after storage under severe conditions such as high temperatures. In addition, even when the eutectic mixture of only 2 kinds of amino acids and purified water is contained without AHA, excellent skin permeability, keratolytic effect, low-temperature safety, and the like are exhibited under weakly acidic or neutral acidic conditions.
In the present invention, the "eutectic mixture" means a mixture of two or more solid or liquid substances, and two components having high melting points are mixed, and form a polymer by dipole-dipole attraction between polar molecules, dipole-induced dipole attraction, hydrogen bonding between molecules, or van der waals interaction. The polymer formed as described above has a melting point lower than that of the component having the lowest melting point among the components, and exhibits a liquid state at room temperature, in order to inhibit the ability of each component to crystallize, i.e., to return to a solid state. In the present invention, the eutectic mixture contains purified water so that the lowest melting point is formed below zero, thereby maintaining a stable composition form in various environments.
In the eutectic mixture, the eutectic mixture may be formed by bonding of compounds having polarity. The compound having polarity may be a polar molecule (polar molecule) or a charged molecule (charged molecule). In addition, a difference in polarity (polarity) is required between the above-mentioned compounds having polarity, and the same compounds cannot constitute a eutectic mixture. More specifically, the components constituting the eutectic mixture have a difference in pKa or pI value of, for example, 1.0 or more, 2.0 or more, 3.0 or more, 4.0 or more, 5.0 or more, 6.0 or more, or 7.0 or more. In this case, when the components constituting the eutectic mixture are components having a plurality of pKa values, the pKa1 value is selected as a reference.
More specifically, the compound having polarity may be selected among AHA or Amino Acids (AA). More specifically, when one of the components constituting the eutectic mixture is AHA, an amino acid having a pI higher than the pKa1 value of AHA can be selected as the other compound. For example, the difference between the pKa1 value and the pI value between the AHA and the amino acid that make up the eutectic mixture may be 1.0 or more, 2.0 or more, 3.0 or more, 4.0 or more, 5.0 or more, 6.0 or more, or 7.0 or more. More specifically, when one of the components constituting the eutectic mixture is an amino acid, an amino acid having a pI higher or lower than that of the amino acid can be selected as the other compound. For example, the difference between the pI values of two amino acids constituting the eutectic mixture may be 1.0 or more, 2.0 or more, 3.0 or more, 4.0 or more, 5.0 or more, 6.0 or more, or 7.0 or more.
More specifically, the compound having polarity may be selected from polar AA, positively charged AA (+ charged AA), and negatively charged AA (-charged AA). For example, a eutectic mixture may be formed with any of the polar amino acids and any of the positively charged amino acids. For example, a eutectic mixture may be formed with any of the polar amino acids and any of the negatively charged amino acids. For example, a eutectic mixture may be formed with any of the positively charged amino acids and any of the negatively charged amino acids. The polar amino acid represents any one of threonine, tyrosine, glutamine, serine, and asparagine. The positively charged amino acid represents any of histidine, lysine and arginine. The negatively charged amino acid represents any of aspartic acid and glutamic acid.
The ratio of the substances required in the eutectic mixture is determined by the charge of the molecules constituting the components of the eutectic mixture, the type and number of functional groups of the molecules, and the polarity of the molecules or functional groups. In addition, the ratio between the substances required in the eutectic mixture is determined according to the size or similarity of the molecules. For example, arginine and glutamic acid, arginine and aspartic acid, lysine and glutamic acid, lysine and aspartic acid, arginine and asparagine, and arginine and glutamine form a eutectic mixture at a molar ratio of 1: 1. For example, arginine and serine, arginine and threonine, arginine and tyrosine, arginine and asparagine, and arginine and glutamine form a eutectic mixture at a molar ratio of 1: 2.
In the present invention, the eutectic mixture may be used as a term having the same meaning as "eutectic solvent (eutectic solvent)", "eutectic", or "eutectic mixture aqueous solution".
In general, in the case of a eutectic mixture, the eutectic mixture is broken under severe conditions such as high temperature, and the effect of the eutectic mixture is reduced. As is apparent from comparison of the exfoliating effect of the cosmetic composition (a) containing the eutectic mixture of the present invention and the cosmetic composition (B) after a certain period of time of a at high temperature, a is higher than B by 5%, preferably, by 10%, more preferably, by 12%, and most preferably, by 15% or more. Further, as is apparent from comparison of the skin permeability of the cosmetic composition (a) containing the eutectic mixture of the present invention and the cosmetic composition (B) after a certain period of time under high temperature conditions, a is 5% higher, preferably 10% higher, more preferably 12% higher, and most preferably 15% higher than B. In this case, the cosmetic composition which has been stored at a high temperature for a predetermined period of time is stored at 50 ℃ for 6 weeks or at 60 ℃ for 5 weeks or more.
The eutectic mixture of the present invention is adjusted to a value of pH3.5 to pH10 in order to improve discomfort such as skin irritation when applied to the skin. The eutectic mixture of the present invention is structurally prepared in a region where both the amine group of the amino acid and the carboxyl group of AHA have charges, and thus the above-mentioned region may be ph3.5 or more. For example, the eutectic mixture is adjusted to have acidity ranging from weak acidity to neutral such as pH4 to pH9, pH5 to pH8, and pH6 to pH 7.
The eutectic mixture of the present invention comprises purified water, AHA and amino acid or 2 kinds of amino acids, so that the solubility is reduced at low temperature due to the melting point depression characteristic of the eutectic mixture, and the low temperature safety of the composition can be enhanced. In general, the skin permeability of AHA and/or amino acid decreases rapidly with increasing pH, and thus conventional cosmetics maintain a low pH. However, the co-crystal mixture of the present invention reduces skin irritation that occurs in mildly acidic to neutral acidity while maintaining the high skin permeability of AHA and/or amino acids at lower pH.
The eutectic mixture of the present invention can be prepared by selecting any method generally used by those skilled in the art and then adding water to the method, and an exemplary method for preparing the eutectic mixture is as follows:
i) a method of heating a component having the lowest melting point among the components constituting the eutectic mixture to a temperature at which the component melts to form a liquid, and completely dissolving the remaining components in the molten liquid,
ii) a method of dissolving completely in a solvent in which one or more of the respective ingredients constituting the eutectic mixture are dissolved, and dissolving at a high temperature of 50 ℃ or higher to achieve homogenization.
In this case, in the method of ii), the solvent is evaporated as necessary.
In one embodiment, the eutectic mixture of the invention is prepared by the process of ii).
As a specific example of ii), a sample is prepared in a reaction tank and a homogeneous disperser (homo-disper) which require heating. The material of the reaction vessel is not limited, and for example, a glass beaker or an SUS reaction vessel can be used. To prepare the co-crystal mixture, serine and arginine were prepared in a molar ratio of 2:1 in the case of amino acid-amino acid, and serine and malic acid were prepared in a molar ratio of 2:1 in the case of amino acid-AHA. The purified water may be used in an amount of 25 to 99 parts by weight, based on the total weight of the prepared amino acid-amino acid or amino acid-AHA. Preferably, the purified water is prepared in such a manner that the content of the purified water is 50 parts by weight in the same amount as the total weight of the amino acid-amino acid or amino acid-AHA, i.e., relative to the total weight. The speed of the homogenizing disperser is suitably 600 to 4000rpm, but may be higher or lower. For example, the speed of the homogenizing disperser may be 600 to 3000rpm, 600 to 2000rpm, 600 to 1500rpm, 800 to 1200rpm, 900 to 1100 rpm. The heating may be performed under a temperature condition of 45 to 70 ℃, for example, the heating may be performed at 45 to 65 ℃, 45 to 60 ℃, 45 to 55 ℃. The reaction time is preferably at least 15 minutes, and when homogeneity is confirmed, heating is stopped and natural cooling is performed.
As a method for grasping the homogeneity of the eutectic mixture obtained as described above, there is a method including:
i) a method of confirming whether or not a precipitate is absent and a transparent mixture is formed when a eutectic mixture, which is a super-molten solution dissolved at a solubility of each component or higher, is placed in front of a black background and irradiated with light for confirmation, and
ii) a single melting point is formed at a lower temperature than the melting points of the individual components when forming the eutectic mixture, so that the melting point of the individual components is determined by means of DSC (Differential scanning calorimetry: differential scanning calorimetry) machine to confirm the melting point.
When AHA and/or amino acid are completely dissolved, the obtained mixture is transparent and homogeneous, and can maintain a liquid state and transparency even after the cooling process. The eutectic mixture thus prepared as described above does not cause phase separation at very low temperatures, for example, at temperatures below 0c, and exists uniformly, thereby maintaining a transparent liquid phase. In addition, even if the solidification and dissolution processes are repeated, the eutectic mixture is not broken and the bonding is maintained.
In the cosmetic composition of the present invention, the above eutectic mixture may be contained in an amount of 0.01 to 50 parts by weight, for example, 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 30 parts by weight, 10 to 40 parts by weight, 15 to 35 parts by weight, 20 to 30 parts by weight, relative to the total weight of the cosmetic composition, but not limited thereto. The content of the above-mentioned eutectic mixture may be appropriately adjusted according to the formulation of the cosmetic composition.
In the following examples it was confirmed that even a high content of the above eutectic mixture in the cosmetic material showed low skin irritation and high skin permeability.
As described above, the cosmetic composition containing the eutectic mixture of the present invention can realize excellent skin-improving effects such as a keratolytic effect, a pore number-reducing effect, an elasticity-enhancing and wrinkle-improving effect, and a skin regeneration-promoting effect.
The cosmetic composition of the present invention may additionally contain an oily component. The oily component is contained within the composition and is present in the outer phase of the eutectic mixture, thereby facilitating stable presence of the eutectic mixture within the composition.
The oily component may be one or more of oil and wax. As the oil and wax, any oil or wax generally used as an ingredient of cosmetics in the art can be used. For example, as the oil, silicone oil, ester oil, triglyceride oil, hydrocarbon oil, or vegetable oil can be used, and one or more of these components can be blended and used as necessary.
For example, as the silicon-based oil, a silicon-based fluid oil, a silicon-based crosslinked polymer dispersed in an oil, or the like can be used. For example, as the silicone-based fluid oil, cyclopentasiloxane, cyclohexasiloxane, cycloheptasiloxane, cyclomethicone, methylphenylmethane, cyclotetrasiloxane, cyclotrisiloxane, dimethicone, octanediylmethane, octyltrimethicone, octylmethicone, cetostearyl methicone, hexadecylmethicone, hexylmethicone, lauryl methicone, myristone, phenylmethylsilicone, stearyl methicone, stearyl dimethicone, trifluoropropylmethicone, hexadecyldimethicone, diphenylsiloxyphenyltrimethicone, dimethylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, methyltrimethicone, phenyltrimethicone, or the like can be used. The silicone oil component may be used alone or in combination of two or more oils. As the silicone-based crosspolymer, a dimethicone/vinyl dimethicone crosspolymer, a polydimethylsiloxane PEG-10/15 crosspolymer or a PEG-12 dimethicone/PPG-20 crosspolymer may be used, but not limited thereto.
As the ester oil, ascorbyl palmitate, ascorbic acid, ascorbyl stearate, diisostearyl malate, benzyl benzoate, benzolaurate, butanediol dicaprylate/dichloroammonium, butanediol diisopelargonate, butanediol glycyrrhizate, butanediol stearate, butyl isostearate, cetearyl isononanoate, cetearyl pelargonate, cetyl octanoate, cetyl hexanoate, hexadecyl isononanoate, ethylhexanol octanoate/caprate, ethyl hexyl isononanoate, ethylhexyl isostearate, ethylhexyl laurate, hexyl laurate, dodecyl isostearate, isopropyl isostearate, isononanoate isostearate, isostearic acid isostearate, hexadecyl ethylhexanoate, neopentyl glycol didecanoate, neopentyl glycol diethylhexanoate, neopentyl glycol diisopelargonate, Neopentyl glycol diisostearate, pentaerythritol stearate, pentaerythritol tetraethylhexanoate, dipentaerythritol hexa-stearate, polyglycerol-2 diisostearate, polyglycerol-2 isostearate, polyglycerol-2 tetraisostearate, polyglycerol-2 triisostearate, polyglycerol-3 diisostearate, polyglycerol-3 isostearate, polyglycerol-4 diisostearate, polyglycerol-4 isostearate, polyglycerol-6 diisostearate, or triethylhexanoic acid.
As the triglyceride oil, C8-C12 acid triglyceride, C12-C18 acid triglyceride, caprylic/capric/lauric triglyceride, C10-C40 isoalkyl acid triglyceride, C10-C18 triglyceride, glyceryl triacetyl stearate, soyabean glyceride, methyl behenate, tricaprin, triethylhexanoic acid, triheptanoic acid, triisostearin, tripalmitin or tristearin can be used.
As the hydrocarbon oil, liquid paraffin (liquid paraffin, mineral oil), paraffin, vaseline, microcrystalline wax, squalene, or the like can be used.
As the vegetable oil, avocado oil, wheat germ oil, rose hip oil, shea butter, almond oil, olive oil, hawaii nut oil, argan nut oil, meadowfoam seed oil, sunflower seed oil, castor oil, camellia oil, corn oil, safflower oil, soybean oil, canola oil, macadamia nut oil, jojoba oil, palm kernel oil, or coconut oil can be used.
As the wax, any of hydrocarbon waxes, vegetable waxes, silicone waxes, and the like generally used in cosmetics can be used. For example, candelilla wax, carnauba wax, rice wax, pearl wax, lanolin, Ozokerite (Ozokerite), Ceresin wax (Ceresin wax), paraffin wax, microcrystalline wax, C30-C45 alkyldimethylsilylpropylsilsesquioxane, ethylene/propylene polymer, or polyethylene wax, but is not limited thereto.
The content of the oily component is not particularly limited, and may include the remaining content in the composition other than the eutectic mixture described above.
The cosmetic composition of the present invention may additionally contain all kinds of components usable in general cosmetics, for example, moisturizers such as glycerin, butylene glycol, propylene glycol, hexylene glycol, methyl glucose-20, diglycerin, and ethylhexyl glycerin; sunscreen creams such as ethylhexyl methoxycinnamate, ethylhexyl salicylate, ethylhexyl triazinone, octocrylene, bis-ethylhexyloxyphenol methoxyphenyl triazine; a pH adjuster such as triethanolamine; thickeners such as carbomer, xanthan gum, acrylic acid ester/C10-30 alkyl acrylate crosspolymer, and hyaluronic acid; preservatives such as phenoxyethanol, methyl benzoate and propyl paraben; antioxidants such as BHT, ethyl ascorbate ether, and ascorbic acid; skin conditioning agents such as beta-glucan; surfactants such as cetearyl glucoside and sorbitol stearate; the perfume or the coloring matter is not limited to the above components.
The above-mentioned components contained in the cosmetic composition of the present invention are each preferably contained in the cosmetic composition of the present invention within a range not exceeding the maximum usage amount specified in "cosmetic safety and technical specifications" specified by the government of china.
The cosmetic composition of the present invention can be prepared in any dosage form conventionally prepared in the art. For example, the cosmetic composition may include, but is not limited to, lotions such as elastic lotions and nutrient lotions, lotions such as spray-type lotions, moisturizing lotions, body lotions, creams such as nutrient creams, moisturizing creams, eye creams, ointments, sprays, gels, masks, sunscreens, foundations, foundation creams such as liquid-type or spray-type foundation creams, powders, face washes, color cosmetics removers such as face foams, toilet soaps, and body washes.
In one embodiment, the cosmetic composition is in the form of balm oil (palm), water-in-oil (W/O), oil-in-water (O/W), solubilized, or oily.
In the present invention, the "solubilized type" refers to a type in which a small amount of oil component is transparently dissolved in water, and is a type in which the diameter of oil droplets (drops) is smaller than the wavelength of visible light, and scattering or reflection does not occur, and linearity of light is not hindered, thereby indicating a transparent phase. The cosmetic composition having the solubilizing agent type may be transparent toner, hair growth perfume, or hair care liquid, but is not limited to these types.
The cosmetic composition of the present invention can be used according to a general method of use, and the number of times of use can be changed according to the skin condition or preference of the user.
In addition, the present invention provides a method for preparing the cosmetic composition.
In one embodiment, the cosmetic composition comprises: mixing purified water, amino acid and alpha-hydroxy acid to prepare a eutectic mixture; and
a step of preparing a cosmetic composition comprising the above eutectic mixture.
In the above preparation method, the above contents can be directly applied to purified water, amino acids and α -hydroxy acids, eutectic mixture and cosmetic composition.
In addition, the step of preparing the above eutectic mixture is performed under the homogenization conditions of 600 to 4000rpm and 45 to 70 ℃. According to the present invention, the components constituting the eutectic mixture are uniformly mixed under such homogenization conditions to achieve the skin improvement effect, low irritation to the skin, and excellent formulation safety of such eutectic mixture.
In other embodiments, the cosmetic composition comprises: a step of mixing the 1 st amino acid and the 2 nd amino acid to prepare a eutectic mixture; and
a step of preparing a cosmetic composition comprising the above eutectic mixture.
In addition, the step of preparing the eutectic mixture includes a step of adding purified water.
In the above preparation method, the above contents can be directly applied to the 1 st amino acid, the 2 nd amino acid, purified water, the eutectic mixture and the cosmetic composition.
In addition, the step of preparing the above eutectic mixture is performed under the homogenization conditions of 600 to 4000rpm and 45 to 70 ℃. According to the present invention, the components constituting the eutectic mixture are uniformly mixed under such homogenization conditions as described above, thereby achieving the skin-improving effect, low irritation to the skin, and excellent formulation safety of such eutectic mixture.
Advantages and features of the present invention, and methods of achieving the advantages, will be clearly understood by reference to the examples and preparations described later. However, the present invention is not limited to the experimental examples and the preparation examples disclosed below, and may be embodied in various forms different from each other.
Effects of the invention
The cosmetic composition of the present invention comprises an alpha-hydroxy acid (AHA), an amino acid, and purified water or 2 kinds of amino acids in the form of a eutectic mixture, and thus improves the skin permeability of the AHA and/or the amino acids at a pH of weak acidity or neutral without skin irritation, thereby achieving an excellent exfoliating effect, pore number reducing effect, skin elasticity enhancing effect, and skin regeneration promoting effect, and stably and uniformly maintaining the same without precipitation of the amino acids at low temperatures.
Drawings
Fig. 1 shows the results of confirming the lowest melting point according to the formation of the eutectic mixture at-20 ℃, (a) shows the results of an aqueous serine solution containing a high content of serine (comparative example 1), (B) shows the results of a mixture of serine and malic acid (comparative example 2), (C) shows the results of the eutectic mixture of the present invention (example 1), (D) shows the results of an aqueous serine solution containing a low content of serine (comparative example 3), and (E) shows the results of the aqueous eutectic mixture of the present invention (example 2).
Fig. 2 is a result of confirming the degree of skin permeation with respect to the absence or formation of the eutectic mixture according to the present invention.
A of fig. 3 represents a change in viscosity according to a molar ratio of serine to arginine, and B represents a change in conductivity (conductivity) according to a molar ratio of serine to arginine.
In FIG. 4a, A represents the result of NMR analysis of serine (Ser), and B represents the result of NMR analysis of arginine (Arg).
In FIG. 4b, C represents the result of NMR analysis of the eutectic mixture of serine and arginine, D represents the result of NMR analysis when citric acid is added to the eutectic mixture of serine and arginine, and E represents the result of NMR analysis after 1 month of storage under severe conditions (40 ℃ C.) after citric acid is added to the eutectic mixture of serine and arginine.
In FIG. 5, A represents the result of IR spectrum analysis of serine (Ser), B represents the result of IR spectrum analysis of arginine (Arg), and C represents the result of IR spectrum analysis of a eutectic mixture of serine and arginine.
Fig. 6 shows the results of confirmation of the effect of reducing the number of pores in each age group of 20-40 years of age participants by using the essence (emulsion) containing the serine-arginine eutectic mixture.
Fig. 7 shows sensory evaluation (evaluation of experience) results of the pore number reduction effect of participants aged 20 to 40 years achieved by using essence (emulsion) containing a serine-arginine eutectic mixture.
Fig. 8 is a dermal density test result of participants aged 20 to 40 years by using essence (emulsion) containing a serine-arginine eutectic mixture.
Fig. 9 shows sensory evaluation (evaluation of experience) results of dermal density increase (increase in skin elasticity) of participants aged 20 to 40 years by using essence (emulsion) containing a serine-arginine eutectic mixture.
Fig. 10 shows the results of applying an arginine-glutamic acid eutectic mixture to HaCaT cells, which are human-derived keratinocyte cell lines, and confirming the skin regeneration promoting effect.
Detailed Description
The present invention will be described in detail below with reference to examples. However, the following examples merely illustrate the present invention, and the contents of the present invention are not limited to the following examples.
Examples 1 and 2 preparation of aqueous eutectic mixture solutions comprising AHA and amino acid
An aqueous eutectic mixture solution was prepared by the following method.
Regarding the eutectic mixture of example 1, 18 parts by weight of malic acid (DL-malic acid, FUSO, Japan: DL-malic acid, hibiscus japonica) having a melting point of about 130 ℃ was prepared based on 100 parts by weight of the eutectic mixture, and the malic acid was heated until reaching the melting point to prepare a liquid state. To the above liquid malic acid, 20 parts by weight of serine (L-serine, EVONIK, Germany: L-serine, Woodford Germany) was added, followed by maintaining the temperature and stirring at 1,300rpm for 30 minutes to completely dissolve it. The completely dissolved liquid was neutralized with NaOH to pH 6.5. Thereafter, the eutectic mixture was naturally cooled at room temperature, water was added by Karl Fischer titration until the water content in the entire eutectic mixture became 53 parts by weight, and then stirring was performed, thereby finally setting the serine content to 20 parts by weight and the malic acid content to 18 parts by weight.
The eutectic mixture of example 2 was prepared by adding 25 parts by weight of the eutectic mixture of example 1, which was previously prepared, to purified water, based on 100 parts by weight of the entire eutectic mixture. In this case, serine and malic acid were contained in amounts of 5 parts by weight and 4.5 parts by weight, respectively, in the aqueous solution.
TABLE 1
| Ingredients (parts by weight) | Example 1 | Example 2 |
| Purified water | 53 | 88.25 |
| Malic acid | 18 | 4.5 |
| Serine | 20 | 5 |
| NaOH | 9 | 2.25 |
| Sum of | 100 | 100 |
Comparative example 1 preparation of an aqueous serine solution containing a high content of serine
An aqueous Serine solution was prepared by mixing purified water in such a manner as to contain 20 parts by weight of Serine (L-Serine, EVONIK, Germany) based on 100 parts by weight of the total aqueous solution.
Comparative example 2 preparation of an aqueous solution of serine and malic acid containing high content of serine and malic acid
Serine and malic acid were mixed in purified water and adjusted with NaOH to pH 6.5. The finally prepared mixture aqueous solution contained 20 parts by weight of Serine (L-Serine, EVONIK, Germany), 18 parts by weight of Malic acid (DL-Malic acid, FUSO, Japan) based on 100 parts by weight of the whole mixture.
Comparative example 3 preparation of aqueous serine solution containing Low serine content
An aqueous Serine solution was prepared by mixing purified water in such a manner as to contain 5 parts by weight of Serine (L-Serine, EVONIK, Germany) based on 100 parts by weight of the total aqueous solution.
Comparative example 4 preparation of an aqueous solution of serine and malic acid containing Low amounts of serine and malic acid
Serine and malic acid were mixed in purified water and adjusted with NaOH to pH 6.5. The final aqueous mixture solution was prepared by mixing 5 parts by weight of Serine (L-Serine, EVONIK, Germany) and 4.5 parts by weight of Malic acid (DL-maleic acid, FUSO, Japan) to purified water based on 100 parts by weight of the total mixture.
Comparative example 5 preparation of aqueous malic acid solution
An aqueous Malic acid solution was prepared by mixing purified water so as to contain 4.5 parts by weight of Malic acid (DL-maleic acid, FUSO, Japan) based on 100 parts by weight of the total aqueous solution.
Examples 3 and 4 preparation of aqueous eutectic mixture solutions containing 2 amino acids
An aqueous eutectic mixture solution composed of 2 kinds of amino acids was prepared by the following method.
The eutectic mixture of example 3 was prepared by the following method: based on 100 parts by weight of the eutectic mixture, 21 parts by weight of arginine (L-arginine, DAESANG, Republic of Korea: L-arginine, elephant, Korea) having a melting point of about 220 ℃ was prepared, and 26 parts by weight of serine (L-serine, EVONIK, Germany) was added thereto, followed by 10 parts by weight of purified water, and stirred at 1,300rpm for 30 minutes while maintaining a temperature of 90 ℃ to completely dissolve it. The eutectic mixture of example 4 was prepared by the following method: to the eutectic mixture of example 3 was added 6 parts by weight of aqueous Citric acid (Citric acid, CIBA SPECIALITY CHEMICALS, Switzerland: Citric acid, Ciba specialty Chemicals, Inc., Switzerland) for pH adjustment, and the mixture was stirred at 1,300rpm for 30 minutes while maintaining a temperature of 90 ℃ to completely dissolve it. Thereafter, the eutectic mixture of examples 3 and 4 was naturally cooled at room temperature, water was added to the eutectic mixture by Karl Fischer (Karl Fischer) titration until the water content in the entire eutectic mixture became 50 to 55 parts by weight, and then the mixture was stirred. The pH of examples 3 and 4 above show values of 8.7 and 6.5, respectively.
TABLE 2
| Ingredients (parts by weight) | Example 3 | Example 4 |
| Purified water | 53 | 52 |
| Arginine | 21 | 15 |
| Serine | 26 | 27 |
| Aqueous citric acid | 0 | 6 |
| Sum of | 100 | 100 |
Experimental example 1 confirmation of melting Point, Low temperature stability and stability of eutectic mixture aqueous solution
1) Melting Point identification
The properties of the aqueous eutectic mixture solution prepared in example 1, the aqueous serine solution of comparative example 1, and the aqueous serine and malic acid solution of comparative example 2 were compared with each other in terms of melting point depression. In the above experiment, the solutions of example 1 and comparative examples 1 and 2 were allowed to stand at-20 ℃ to confirm the change of phase, thereby detecting the melting point. The results are shown in FIG. 1. In fig. 1, A, B and C represent comparative example 1, comparative example 2, and example 1, respectively, in this order.
As can be seen from fig. 1, in the case of the eutectic mixture of serine, malic acid and purified water as in example 1, the melting point was below-20 ℃ and the eutectic mixture was maintained in a liquid state at-20 ℃. The aqueous eutectic mixture solutions prepared in examples 3 and 4 also caused a decrease in melting point through the formation of the eutectic mixture, thereby having a melting point of about-20 ℃ or less lower than that of water having a melting point of 0 ℃.
2) Confirmation of Low temperature safety
In order to confirm the low-temperature safety of the aqueous solution to which the eutectic mixture was added, the process of freezing and storing the aqueous solutions of comparative example 3 and example 2 at a low temperature (-20 ℃) to completely solidify the aqueous solutions, and then dissolving the aqueous solutions at room temperature (25 ℃) was repeated 7 times, whereby the safety was visually confirmed. The results are shown in FIG. 1, where D in FIG. 1 shows the results of the aqueous solution of comparative example 3, and E shows the results of the aqueous solution of example 2.
From fig. 1D and E, it was confirmed that in the case of the serine aqueous solution of comparative example 3, serine was precipitated by the decrease in solubility at low temperature, and the precipitated serine was precipitated after the dissolution, and no precipitation occurred in the aqueous solution containing the eutectic mixture as in example 2. It was found that safety was maintained at a low temperature of-20 ℃ in an aqueous solution containing a eutectic mixture.
In addition, it was confirmed that the aqueous eutectic mixture solutions prepared in examples 3 and 4 did not precipitate or remelted by gentle stirring after standing at normal temperature. It is understood from this that, in examples 3 and 4 including the eutectic mixture containing 2 kinds of amino acids, safety was maintained at a low temperature such as-20 ℃.
3) Confirmation of stability
In order to confirm the stability of the eutectic mixture aqueous solution, the serine aqueous solution of comparative example 1 and the eutectic mixture aqueous solutions of examples 1,3 and 4, which have the same serine content as that of example 1, were charged into a 50ml test tube and left to stand at room temperature (25 ℃) and-20 ℃ for 12 hours for 4 weeks. The stability of the solution was confirmed by whether or not the solution precipitated in the sample, and the results are shown in table 3 below.
TABLE 3
As shown in Table 3, it was confirmed that the sample was not precipitated in the aqueous solution of the eutectic mixture of examples 1,3 and 4 of the present invention and the aqueous solution phase was maintained, although the mixture was repeatedly allowed to stand at room temperature and-20 ℃. On the contrary, the results of precipitating the sample at-20 ℃ were shown in the case of comparative example 1, which is an aqueous serine solution having the same concentration as in example 1.
Experimental example 2 keratolytic Effect of eutectic mixture aqueous solution
In order to confirm the keratolytic effect of the eutectic mixture aqueous solution of serine of example 2, which varied depending on the concentration, the aqueous solution was applied to the back skin of the pig. Specifically, a 6mm diameter sample was taken on a 1mm thick pig dorsal skin using a biopsy (biopsy) instrument. This was placed in a 96-well plate, washed 1 time with Phosphate Buffered Saline (PBS), and then 100. mu.l of the aqueous eutectic mixture of example 2 above was added. At this time, in order to compare the exfoliating effect, 100. mu.l of the serine-malic acid mixture of comparative example 4 was added to the back skin of swine by the same method. The pig back skin samples treated with each aqueous solution were stored at 37 ℃ and 50% humidity for 16 hours, and the amount of the removed cutin was measured by a cell counter, whereby the cutin peeling effect was confirmed. In this case, purified water was added as a negative control group, 10% gluconolactone (PHA, polyhydroxy acid) at pH4, which is one component of the exfoliating components, was added as a 1-time positive control group, and 10% gluconolactone at pH6 was added as a 2-time positive control group. In the case of the positive control group 2 times, the exfoliation effect was evaluated on the basis of the condition that the effect was 15 to 20% with respect to the positive control group 1 time. Here, the 1-time positive control group was used as a reference for comparing values between actual experimental examples, and the relative exfoliation (%) was calculated from [ (result value of sample)/(value of 1-time positive control group) × 100 ]. The results are shown in Table 4.
TABLE 4
As shown in table 4 above, the results of example 2 using the aqueous eutectic mixture solution of the present invention showed a higher exfoliating effect than the aqueous serine solution. Further, as compared with gluconolactone (PHA) at 10%, which is a keratolytic ingredient at pH4 (1-time positive control group), it was confirmed that the aqueous solution of example 2 of the present invention had a higher pH, but exhibited a keratolytic effect at a level similar to (pH 6.5). That is, the aqueous solution of example 2 of the present invention can exhibit a similar level or more excellent exfoliating effect to a conventional exfoliating composition having a low pH even under a weakly acidic or neutral pH condition with little irritation. In addition, the keratin exfoliation efficacy was enhanced in the aqueous eutectic mixture solution of the present invention compared to the malic acid solution and the serine-malic acid simple mixed solution, and thus it was confirmed that the eutectic mixture including purified water had more excellent keratin exfoliation efficacy.
Experimental example 3 confirmation of skin permeability of eutectic mixture aqueous solution under weakly acidic conditions
The skin permeability of the aqueous solution of the eutectic mixture under weakly acidic conditions (pH6.5) was confirmed. 10 μ g of each of the aqueous solutions of comparative examples 1 and 2 and example 1 was prepared and applied to a uniform area of pig skin. A tissue wetted with Phosphate Buffered Saline (PBS) was placed on the 6-well plate, and the tissue was stored at 37 ℃ and 50% humidity for 12 hours with the skin of a pig placed thereon. Thereafter, the sample which did not penetrate into the skin was removed with a cotton swab and a cutin tape, and the weight of the skin of the pig was measured. The pig skin was broken up with a homogenizer, and 1ml of water was added to dissolve the amino acid and eutectic mixture in the sample sufficiently, followed by 10-minute circle center separation at 12,000 rpm. After the center separation, 0.5ml of the supernatant was separated, and the concentration of the sample (serine) that permeated through the skin was quantified by liquid chromatography of a standard sample used in the present experiment, and then divided by the weight of the pig skin, whereby the mass of the sample (serine) per g tissue was compared with the mass of serine initially charged to determine the transmittance. The results of the above skin permeability are shown graphically in fig. 2.
From fig. 2, it was confirmed that the results of example 2 (co-crystal of fig. 2) using the aqueous eutectic mixture solution of the present invention showed higher pig skin transmittance than the results of the aqueous serine solution (L-serine of fig. 2) under ph 6.5. In addition, it was confirmed from FIG. 2 and the references that example 2 exhibited superior skin permeation efficacy compared to that of salicylic acid (reference 2), which is one of lactic acid (lactic acid; reference 1) and beta-hydroxy acid (beta-hydroxy acid, hereinafter referred to as BHA), which are one of AHA. Furthermore, the eutectic mixture of the present invention comprising purified water shows higher skin penetration of pigs compared to the simple mixture of serine-malic acid (serine-malic acid of fig. 2). That is, it is found that the high skin permeability of the eutectic mixture of the present invention can achieve the excellent exfoliating effect as confirmed in experimental example 2.
[ reference documents ]
1.SE Wolverton，α-Hydroxy acids.In Comprehensive Dermatologic Drug Therapy，3rdet.，Elsevier，2012，570.
2.S.E.Wolverton，α-hydroxy acids，In Comprehensive Dermatologic Drug Therapy，3rdedition，Elsevier，570(2012)
Examples 5 to 7 preparation of aqueous solutions of eutectic mixtures
Aqueous solutions of the eutectic mixtures of examples 5 to 7 were prepared with the compositions and contents as shown in table 5 below. First, Malic acid (DL-Malic acid, FUSO, Japan) having a melting point of 130 ℃ was prepared and heated until reaching the melting point to prepare a liquid state. Proline (L-Proline, Sigma Aldrich, USA: L-Proline, Sigma Aldrich, USA) and Threonine (L-Threonine, Sigma Aldrich, USA: L-Threonine, Sigma Aldrich, USA) and cysteine (L-cysteine, Sigma Aldrich, USA) were added to the prepared liquid malic acid, respectively, and stirred at 1,300rpm for 30 minutes while maintaining the temperature to completely dissolve it. When the solution was completely dissolved, the solution was neutralized to ph6.5 with NaOH, then naturally cooled at room temperature, and the water content in the entire eutectic mixture was measured by Karl Fischer titration, and whether the eutectic mixture was formed or not and whether the sample was precipitated after 4 weeks of storage was confirmed. The results are shown in Table 6 below. In this case, the aqueous solution of the eutectic mixture to which proline was added was described as example 5, the aqueous solution of the eutectic mixture to which threonine was added was described as example 6, and the aqueous solution of the eutectic mixture to which cysteine was added was described as example 7.
TABLE 5
TABLE 6
Preparation example 1 preparation of cosmetic composition in form of balsam (palm)
Cosmetic compositions in the form of balm oils containing the above aqueous eutectic mixture were prepared with the compositions of table 7 below. Specifically, the water phase portion (purified water, 1, 2-hexanediol, composition of example 1) among the following components was uniformly dissolved at room temperature, the oil phase portion except the water phase portion was uniformly dissolved at 90 ℃ in all the components, and then the water phase portions were mixed and cooled to solidify at room temperature to prepare a cosmetic composition of a balm oil type.
TABLE 7
EXAMPLE 8 AND COMPARATIVE EXAMPLES 6 AND 7 preparation of serine cosmetic composition in oil-in-Water (Oilin Water) dosage form
Cosmetic compositions in the form of oil-in-water (O/W) formulations containing a eutectic mixture or an aqueous solution of serine were prepared with the compositions of Table 8 below. Specifically, the water phase part of the following ingredients was uniformly dissolved at room temperature, and the oil phase part was uniformly dissolved at 90 ℃. Then, an oil phase was mixed with the dissolved water phase and cooled, thereby preparing an oil-in-water type cosmetic composition.
TABLE 8
| Ingredients (parts by weight) | Example 8 | Comparative example 6 | Comparative example 7 |
| Purified water | 47.3 | 67.1 | 72.1 |
| 1, 2-hexanediol | 2 | 2 | 2 |
| Glycerol | 10 | 10 | 10 |
| Butanediol | 2 | 2 | 2 |
| Cyclopentasiloxane | 7 | 7.2 | 7.2 |
| Dimethicone | 4.5 | 4.5 | 4.5 |
| Polysorbate 60 | 1.5 | 1.5 | 1.5 |
| Carbomer | 0.35 | 0.35 | 0.35 |
| Tromethamine | 0.35 | 0.35 | 0.35 |
| Example 1 (serine content in weight parts in parentheses) | 25(5) | - | - |
| Serine | - | 5 | - |
| Sum of | 100 | 100 | 100 |
Experimental example 4 confirmation of skin permeation Effect
The skin permeation effect was confirmed by the following method using the oil-in-water type cosmetic compositions, i.e., example 8, comparative example 6, and comparative example 7.
10 μ g of each of example 8 and comparative examples 6 and 7 was prepared and applied to a uniform area of pig skin. A tissue wetted with a salt-buffered saline (PBS) was placed on the 6-well plate, and the plate was stored for 12 hours at 37 ℃ and 50% humidity with the skin of a pig placed on the tissue. Thereafter, the sample that did not penetrate the skin was removed with a cotton swab and a cutin tape, and the weight of the pig skin was measured. The pig skin was broken up by a homogenizer, 1ml of water was added to dissolve the amino acid and eutectic mixture in the sample sufficiently, and then the center of the circle was separated at 12,000rpm for 10 minutes. After the center separation, 0.5ml of the supernatant was separated, the concentration of the sample (serine) that permeated into the skin was quantified by liquid chromatography of a standard sample used in the present experiment, and the mass of the sample (serine) per g of tissue was divided by the weight of the pig skin and compared with the mass of serine initially charged to determine the transmittance. The results are shown in Table 9.
TABLE 9
From the above table 9, it was confirmed that in the case of example 8, the skin permeability was improved by about 77% as compared with comparative example 6 containing the same amount of serine.
Preparation example 2 preparation of Water in Oil (Water in Oil) type cosmetic composition
A water-in-oil (W/O) formulation of cosmetic compositions comprising an aqueous eutectic mixture was prepared with the compositions of Table 10 below. Specifically, the water phase part of the following ingredients was uniformly dissolved at room temperature, and the oil phase part was uniformly dissolved at 90 ℃. Then, the water phase was mixed with the dissolved oil phase and cooled to prepare a water-in-oil type cosmetic composition.
Watch 10
| Ingredients (parts by weight) | Preparation example 2 |
| Purified water | 45.4 |
| Example 1 (aqueous solution of serine-malic acid-aqueous eutectic mixture) | 15 |
| Sodium chloride | 1 |
| 1, 2-hexanediol | 0.7 |
| Glycerol | 17 |
| Dipropylene glycol | 5 |
| Dimethicone | 9.5 |
| Diphenylsiloxy phenyl trimethicone oil | 1 |
| PEG-10 dimethicone | 0.2 |
| Dimethicone, dimethicone/PEG-10/15 crosspolymer | 5.2 |
| Sum of | 100 |
Example 9 and comparative example 8 preparation of cosmetic composition in Oil-in-Water (Oil in Water) dosage form
Cosmetic compositions in the form of oil-in-water (O/W) formulations containing aqueous solutions of the eutectic mixtures were prepared with the compositions of Table 11 below. Specifically, the water phase and the oil phase of the following ingredients were uniformly dissolved at room temperature, and the oil phase was mixed with the dissolved water phase to prepare an oil-in-water type cosmetic composition.
TABLE 11
| Ingredients (parts by weight) | Example 9 | Comparative example 8 |
| Purified water | 58.3 | 73.3 |
| Example 1 (aqueous solution of serine-malic acid-water eutectic mixture) | 15 | - |
| 1, 2-hexanediol | 1 | 1 |
| Glycerol | 10 | 10 |
| Butanediol | 2 | 2 |
| Cyclopentasiloxane | 7 | 7 |
| Dimethicone | 4.5 | 4.5 |
| Polysorbate 60 | 1.5 | 1.5 |
| acrylate/C10-30 alkyl acrylate crosspolymer | 0.35 | 0.35 |
| Tromethamine | 0.35 | 0.35 |
| Sum of | 100 | 100 |
Example 10 and comparative example 9 preparation of solubilized cosmetic composition
Cosmetic compositions in the solubilized form comprising an aqueous solution of the eutectic mixture were prepared with the compositions of table 12 below. Specifically, the water phase and a small amount of the oil phase in the following ingredients were uniformly dissolved at room temperature, and then a small amount of the oil phase was mixed with the dissolved water phase to prepare a solubilized cosmetic composition.
TABLE 12
| Ingredients (parts by weight) | Example 10 | Comparative example 9 |
| Purified water | 79.7 | 87.7 |
| Example 3 (aqueous solution of serine-arginine eutectic mixture) | 8 | - |
| Modified alcohol | 2 | 2 |
| Glycerol | 4 | 4 |
| Butanediol | 2 | 2 |
| 1, 2-hexanediol | 2 | 2 |
| PEG-40 hydrogenated Castor oil | 0.6 | 0.6 |
| Carbomer | 0.8 | 0.8 |
| Tromethamine | 0.8 | 0.8 |
| Perfume | 0.1 | 0.1 |
| Sum of | 100 | 100 |
Example 11 and comparative example 10 preparation of oil-type cosmetic composition
An oil-type cosmetic composition containing an aqueous solution of the eutectic mixture was prepared with the composition of table 13 below. Specifically, a small amount of each of the aqueous phase part and the oil phase part of the following ingredients was uniformly dissolved at room temperature, and then the dissolved small amount of the aqueous phase part was mixed with the oil phase part to prepare an oil-type cosmetic composition.
Watch 13
| Ingredients (parts by weight) | Example 11 | Comparative example 10 |
| Example 3 (aqueous solution of serine-arginine eutectic mixture) | 0.5 | - |
| Mineral oil | 8 | 8 |
| Olive oil | 10 | 10 |
| Hexanoic acid cetyl ester | 76.6 | 76.6 |
| PEG-30 sorbitan tetraoleate | 4.9 | 4.9 |
| Purified water | - | 0.5 |
| Sum of | 100 | 100 |
Experimental example 5 confirmation of skin improving Effect
The cosmetic compositions of example 9 and comparative example 8 prepared as described above were applied to the skin for 9 weeks to evaluate the skin-improving effect (skin color, skin texture, number of pores, and number of black heads). The face of the subject was divided into half by a virtual line passing through the nose, and the cosmetic composition of example 9 was applied to the right side skin and the cosmetic composition of comparative example 8 was applied to the left side skin of the subject, respectively. Thereafter, the skin improvement effects on the right and left sides were compared with each other by looking at a mirror at week 3 and week 9, and sensory evaluation was performed using a 5 point standard. The results are shown in Table 14. In table 14 below, the scores of annoyance to each respective item at week 0 are shown using the 5-score criterion. In order to exclude external factors such as seasons, personal physical states, moods, and the like, which differ according to time, changes in satisfaction of each week were not evaluated, and the efficacy of the eutectic mixture was evaluated only by comparing the states of the right and left sides at each time point.
[ evaluation criteria for skin-improving Effect ]
< week 0 >
5 points out that the skin condition of the item was very excellent and completely free from trouble
4 points that the skin condition of the item is relatively good and hardly causes troubles
3 points that the item is in a normal skin state and has slight trouble
2 points that the skin condition of the item is not good and has trouble
Score 1. the skin condition of the item is very poor and has great trouble
< week 3 and week 9 >
5 points of excellent skin improving effect on the left side and the right side
4 points of excellent skin improving effect on the left side and the right side
3 points that it was difficult to experience the skin improvement effects of the right and left sides
2 points of excellent skin improving effect on the right and left sides
1 point the skin-improving effect was very excellent in the right side and the left side
TABLE 14
At week 3 and week 9, on average at 3 points, the higher the score value, indicating that the consumer had a significant skin improvement experience on the right after application of the eutectic mixture. On the other hand, it can be confirmed from table 14 that the cosmetic of the present invention applied for 9 weeks can provide a skin improvement effect, and particularly, skin troubles such as blackheads, the number of pores, black pores, and the like, which make it difficult to obtain an experience effect with respect to consumers, are dramatically improved.
Experimental example 6 confirmation of enhancement of experience Effect of Wash-off type
The cosmetic compositions of examples 10 and 11 and comparative examples 9 and 10 prepared as described above were applied to the skin and then scrubbed with warm water, thereby evaluating the experience improvement effect achieved by short-term application in the wash-off type. The receiving test was conducted on the first day using the product selected at random in example 10 or comparative example 9 and on the second day using the other product not selected on the first day in example 10 or comparative example 9, whereby the change in the experience effect before the product was applied and after the product was wiped off with warm water was blindly measured on the first day and the second day of the experiment, respectively, and then subjected to sensory evaluation on a scale of 5. In this evaluation, the test performer, i.e., the inventor, knows which product the subject selected, and the subject performed blind tests until the questionnaire survey was concluded. Also in example 11 or comparative example 10, evaluation was performed in the same manner as described above. Through the above experiment, it was confirmed whether the consumer experienced short-term efficacy depending on the presence or absence of the eutectic mixture in two different dosage forms, i.e., the solubilized dosage form (example 10 and comparative example 9) and the oil dosage form (example 11 and comparative example 9). The results are shown in tables 15 and 16, respectively.
[ evaluation criteria for skin-improving Effect ]
Skin improvement experience Excellent
General skin improvement experience
Skin free improvement of experience
Watch 15
| Consumer experience item | Example 10 | Comparative example 9 |
| The whole pore state becomes good | ○ | × |
| Significant blackhead reduction when viewing a mirror | △ | × |
| Reduction in the number of pores evident when looking into the mirror | △ | × |
| Reduction of the number of blackhead-like pores | △ | × |
| Reduced rough skin feel when touched with a hand | ○ | △ |
| The smoothness of the skin is improved | ○ | × |
| The evenness of skin color is improved | ○ | △ |
TABLE 16
| Consumer experience item | Example 11 | Comparative example 10 |
| The whole pore state becomes good | △ | × |
| Significant blackhead reduction when viewing a mirror | △ | × |
| Reduction in the number of pores evident when looking into the mirror | △ | × |
| Reduction of the number of blackhead-like pores | △ | × |
| Reduced rough skin feel when touched with a hand | △ | △ |
| The smoothness of the skin is improved | ○ | × |
| The evenness of skin color is improved | △ | △ |
As shown in tables 15 and 16, it was confirmed by sensory evaluation that the cosmetic compositions of the present invention exhibited an enhanced skin-improving effect as a whole after use.
Example 12 preparation of a eutectic mixture comprising serine and arginine
As components constituting the eutectic mixture, serine: arginine were prepared in a molar ratio of 2:1, and purified water was prepared in an amount equal to the total weight. That is, the purified water is in an amount of 50 wt% with respect to the total weight. The speed of the homogenizing disperser was 1000rpm and the temperature was heated to 50 ℃. After the reaction for 20 minutes, when homogeneity was confirmed, heating was stopped and natural cooling was performed.
Experimental example 7 confirmation of characteristics of eutectic mixture containing serine and arginine
1) Confirmation of physical Properties of eutectic mixture
In preparing the eutectic mixture of example 12, the characteristics and long-term safety of the composition according to the molar ratio of serine to arginine were compared. Specific molar ratios and characteristics and long-term safety are shown in table 17 below.
TABLE 17
From Table 17, it was confirmed that serine and arginine were stably mixed at a molar ratio of 2:1, and that no precipitation occurred even after 2 months of storage. From this, it is understood that a eutectic mixture is formed when serine and arginine are contained at a molar ratio of 2: 1.
2) Confirmation of the viscosity and conductivity of the eutectic mixture
Viscosity and conductivity of the composition of serine and arginine varied according to the molar ratio as shown in table 17 above were confirmed and are shown in fig. 3.
First, referring to fig. 3 a in which the viscosity was confirmed, the viscosity was highest at a molar ratio of 2:1 in forming the eutectic mixture. This is because the eutectic mixture is dissolved at a solubility higher than the solubility of the eutectic mixture, and the eutectic mixture becomes an over-dissolved state, which increases the viscosity. In addition, referring to the conductivity result (B), it was confirmed that the eutectic mixture was formed and the conductivity was decreased when serine and arginine had a molar ratio of 2:1 due to stabilization of the surface charge (i.e., increase in lipid affinity).
3) NMR analysis
To analyze the NMR of the eutectic mixture, NMR analyses of serine and arginine were performed, respectively (a and B of fig. 4 a). Fig. 4a and 4b show the NMR analysis result of the eutectic mixture of serine and arginine (C in fig. 4 b), the NMR analysis result of the eutectic mixture of serine and arginine (D in fig. 4 b) obtained by adding citric acid (citric acid) as a pH adjuster having a strong surface charge that affects the binding in the dosage form and that imparts weak acidity to the cosmetic dosage form, and the NMR analysis result (E in fig. 4 b) obtained after 1 month of storage under severe conditions (40 ℃) by adding citric acid to the eutectic mixture.
As a result, a single peak (single peak) was formed as a serine-arginine eutectic mixture and separated (split) into 2 peaks as observed in the NMR analysis result of arginine (B of fig. 4 a). That is, separation (split) of a hydrogen peak of a main chain (main chain) nearest to guanidine of arginine by intermolecular bonding is observed in the serine-arginine eutectic mixture, and this can be interpreted as the fact that intermolecular bonding is achieved by inhibiting rotational movement of the main chain. In addition, NMR analysis was performed by adding citric acid to the serine-arginine eutectic mixture (D in fig. 4 b), and the result showed the same analysis result even when the serine-arginine eutectic mixture was broken by the addition of citric acid and the peak of the serine-arginine eutectic mixture was observed similarly, and the mixture was stored under severe conditions (40 ℃) for 1 month (E in fig. 4 b). It was thus demonstrated that the serine-arginine eutectic mixture of the invention is stable under harsh conditions.
4) IR spectral analysis
The IR spectra of serine and arginine (a and B in fig. 5) and the serine-arginine eutectic mixture were analyzed (fig. 5). As a result, a special red shift was observed in the IR spectrum as a eutectic mixture of serine and arginine was formed. This indicates that the guanidine and serine carboxyl groups of arginine are red-shifted (red-shift), which occurs by the intramolecular loosening of the binding (i.e., increase in the binding length) through the binding between the molecules. Therefore, the bonding between the molecules of the eutectic mixture was confirmed by the above-described structural analysis results, and structural stability was confirmed.
Experimental example 8 confirmation of skin improving Effect
1) Confirmation of the Effect of reducing the number of pores
The skin was applied with the essence (emulsion) containing the eutectic mixture of serine and arginine prepared in example 12 above to 60 subjects aged 20 to 40 years, and the number of pores was measured over 6 cycles to confirm the effect of reducing the number of pores. In this case, the effect of reducing the number of pores is the number of pores recognized by the machine, and if the machine does not recognize a pore due to a decrease in the size, color, or saliency of a single pore, it is determined that the number of pores has decreased. Using AnteraCS skin analyzing camera (Miravex), was evaluated by the same evaluator by examining the same site of the left and right faces after achieving the same skin condition by 20 minutes of adaptation to the skin of the subject under a constant temperature and humidity environment. That is, the pore number reducing effect indicates an enlarged pore improving effect. The results are shown in fig. 6 and table 18 below for each age group.
Watch 18
**:p<0.01，***:p<0.001
As is clear from table 18 and fig. 6, the effect of reducing the number of pores was continuously exhibited on the skin to which the essence (emulsion) containing the eutectic mixture of serine and arginine was applied among the test participants of all ages.
2) Sensory evaluation of reduction in pore count
In addition, sensory evaluation was performed on the reduction in the number of pores achieved by using the essence containing the eutectic mixture of serine and arginine of example 12 described above. The results are shown in FIG. 7 below.
As with the results of 1), it was confirmed that more participants achieved an excellent pore number reducing effect in the essence-treated group containing a eutectic mixture of serine and arginine.
3) Confirmation of elasticity-improving Effect-confirmation of dermis Density
The same method as in 1), the dermal density improvement effect was confirmed for 20-40 year-old participants according to age group, and is shown in fig. 8.
As shown in fig. 8, the dermis density was high in the experimental group coated with the essence containing the eutectic mixture of serine and arginine in all ages. That is, it is understood that the elasticity improving effect is achieved by increasing the dermal density with the use of the serine-arginine eutectic mixture.
4) Sensory evaluation with respect to elasticity improvement
In addition, sensory evaluation was performed on the case where the dermal density was increased with the use of the essence containing the eutectic mixture of serine and arginine of example 12 described above. The results are shown in FIG. 9.
As with the results of 3), the number of participants who achieved an excellent dermal density increasing effect in the experimental group using the essence containing the eutectic mixture of serine and arginine increased.
Comparative example 11 preparation of a simple mixture of serine and arginine
To 100 parts by weight of the mixture, 5 parts by weight of serine and 4.1 parts by weight of arginine were added to 90.5 parts by weight of purified water and were simply mixed using a homogenizing disperser until no precipitate was present. The simple mixing means room-temperature mixing without a separate heating step.
EXAMPLE 9 keratolytic Effect of the eutectic mixture
In order to confirm the keratolytic effect of the eutectic mixture of serine and arginine of example 12 and the simple mixture of serine and arginine of comparative example 11, the eutectic mixture and the simple mixture were applied to the back skin of swine. The specific experimental method was the same as in experimental example 2. The results are shown in Table 19 below.
Watch 19
From the above table 19, it was confirmed that the serine-arginine eutectic mixture of the present invention exhibited a higher exfoliating effect than the simple mixture of serine and arginine. As compared with the 1-time positive control group, the eutectic mixture of the present invention had a higher pH (pH9.1) than experimental example 2, but exhibited a keratolytic effect at a level similar to PHA. In addition, the test group in which the pH was adjusted to 6.0 using citric acid also showed a similar level of exfoliating effect to the eutectic mixture before adjustment.
Experimental example 10 confirmation of skin permeability
The skin permeability of the eutectic mixture prepared in example 12 was confirmed. The specific experimental method was the same as in experimental example 3. The results of example 12 are shown in table 20.
Watch 20
When the pH of the eutectic mixture of the present invention was adjusted to 6.0 by adding citric acid thereto, the eutectic mixture of example 12 of the present invention showed excellent skin permeability even under the condition of pH9.1 without adjusting the pH. In contrast, a single mixture of serine and arginine showed significantly lower skin permeability than example 12, and even with a pH adjusted to 6.0, showed lower results than the co-crystal mixture of the present invention.
Example 13 preparation of a Co-Crystal mixture comprising arginine and glutamic acid
As components constituting the eutectic mixture, arginine to glutamic acid were prepared at a molar ratio of 1:1, and purified water was prepared in an amount equal to the total weight. That is, the content of purified water is 50 wt% with respect to the total weight. The speed of the homogenizing disperser was 1000rpm and the temperature was kept at 50 ℃ with heating. After the reaction for 20 minutes, heating was stopped when homogeneity was confirmed, and natural cooling was performed, and a eutectic mixture was prepared by the same method as in example 12 described above.
Experimental example 11 confirmation of characteristics of eutectic mixture containing arginine and glutamic acid
The formation of a eutectic mixture of arginine and glutamic acid was evaluated overall. Solubility of glutamic acid and a simple arginine/glutamic acid mixture and an arginine-glutamic acid eutectic mixture in water was confirmed, and the solubility of glutamic acid and arginine-glutamic acid eutectic mixture in water was shown in table 21 below as to whether or not the mixture was soluble by 1% or more.
TABLE 21
| Solute dissolved in water (solvent) | Whether or not it can be dissolved by more than 1% |
| Glutamic acid | X (solubility)<0.5％) |
| Arginine/glutamic acid simple mixture | X (solubility)<0.5％) |
| Arginine-glutamic acid eutectic mixture | O (solubility about 15.2%) |
As a result, as shown in table 21, in the case of glutamic acid and a simple arginine/glutamic acid mixture, the solubility in water was very low, less than 0.5%, and it was difficult to dissolve 0.5% or more in a real dosage form such as an oil or a water phase. On the contrary, in the case of the arginine-glutamic acid eutectic mixture, the solubility to water is 15.2%, the water solution phase may be present, and additional dissolution may be achieved by eutectic bonding.
Experimental example 12 confirmation of skin regeneration promoting Effect
HaT cells, a keratinocyte (Keratinocyte) cell line, derived from humans, were cultured at 37 ℃ under 5% CO2 using DMEM medium (ADDEXBIO TECHNOLOGIES, san Diego, CA, USA) supplemented with 10% fetal bovine serum (total bovine serum, Gibco, Waltham, MA, USA: fetal bovine serum, Gibco, Waltherm, Mass., USA), 100mg/ml penicillin, and 100mg/ml streptomycin. Cultured cells were seeded (seeding) in a manner that 2.0 × 105 cells were present in each well, and then cultured for 24 hours, and then the cells were washed once with PBS and scraped out with a 200 μ l small pipette (pipetip), thereby preparing a vertical line-shaped scratch in the middle. To remove the dropped cell debris (cell debris), washing was performed 2 times with PBS, and the medium was replaced with PBS-free DMEM containing each experimental substance. In order to always take the same portion at the time of taking a photograph, minute labeling was performed in the middle of the well, and the photograph was taken of the cells in the labeled portion at the same time as the start of the experiment (0 hour). Likewise, photographs were taken of cells after 2, 4 and 24 hours. The area of the scratch formed on a single layer of cells was examined for photographs after 0 hour and 24 hours using an image analysis program (ImageJ), and then a region including the area of the scratch was shown by a Wound healing percentage (percent) according to the following general formula 1. The results are shown in table 22 and fig. 10 below. In this case, the concentration of the Arg/Glu (10:1) pure mixture is based on the concentration of arginine.
[ general formula 1]
TABLE 22
| Wound recovery after 24 hours (%) | |
| FBS 0% (negative control group) | 48.6 |
| FBS 10% (Positive control group) | 72.7 |
| Arg-Glu eutectic mixture 1ppm | 88.9 |
| Arg-Glu eutectic mixture 10ppm | 92.2 |
| Arg10ppm | 73.5 |
| Glu1ppm | 70.1 |
| Simple mixture of Arg/Glu (10:1) 10ppm | 80.6 |
As shown in table 22 and fig. 10, when the arginine-glutamic acid eutectic mixture (Arg-Glu eutectic mixture) and a simple mixture of arginine alone, glutamic acid alone, and two amino acids were compared with each other using FBS-free DMEM medium as the negative control group and 10% FBS-DMEM corresponding to the optimal growth conditions for the cell lines as the positive control group, the treatment group treated with 1ppm of the Arg-Glu eutectic mixture was more excellent in the wound recovery rate than the treatment group treated with FBS 10% (positive control group). Further, the wound recovery rate of the Arg-Glu eutectic mixture (10 ppm based on the concentration of arginine) was 92.2%, and it was confirmed on a microscope image that most of the empty space due to scratching was covered with cells. The effect of 10ppm Arg-Glu eutectic mixture was superior to that of the group treated with arginine 10 ppm/glutamic acid 1ppm (the maximum concentration of glutamic acid that can be produced was 1ppm) and the group treated with arginine 1ppm, which are simple mixtures of two amino acids, and thus it was found that Arg-Glu eutectic mixture was more effective in promoting cell regeneration and contributing to skin regeneration than when they were used alone or when they were mixed alone.
Experimental example 13 Effect of increasing the Total amount of collagen
In order to confirm the effect of increasing the total amount of collagen in the eutectic mixture of example 13, the arginine-glutamic acid eutectic mixture was applied to human fibroblasts, and then the total amount of collagen produced in the human fibroblasts was measured. Specifically, the increase in total collagen at the cellular level was confirmed by adding arginine-glutamic acid eutectic mixture (Arg-Glu eutectic mixture), arginine (Arg), glutamic acid (Glu), and arginine-glutamic acid simple mixture (Arg/Glu simple mixture) to the culture medium of human fibroblasts. The total amount of collagen was quantified using a PICP EIA KIT (Procollagen Type I C-Peptide Enzyme ImmunoAssay KIT: Type I Procollagen C-peptidase ImmunoAssay KIT). Before the experiment, cytotoxicity was evaluated by varying the concentration of the Arg-Glu eutectic mixture (μ g/ml) and the increase in the total amount of collagen was evaluated by selecting a concentration without cytotoxicity (100 μ g/ml) for human-derived fibroblasts.
Specifically, each sample was added to a medium for human fibroblasts and cultured for 1 day, and then the culture solution was taken out and the increase in the total amount of collagen at each concentration was measured at 450nm using a PICP EIA kit and a spectrophotometer. For comparison of effects, the degree of increase in the total amount of collagen was confirmed in the same manner for a medium containing fibroblasts (negative control group) which had not been added at all and for samples (positive control group) to which TGF-. beta. fmf had been added at a final concentration of 10 mg/ml. The total amount of collagen was measured by UV absorbance, and the increase rate of the total amount of collagen was calculated as a ratio to the total amount of collagen in the control group, and the results are shown in table 23 below. In this case, the concentrations of the Arg-Glu eutectic mixture and the Arg/Glu (1:10) simple mixture were based on the concentration of arginine.
TABLE 23
| Test material | Average absorbance | Collagen increase rate (%) |
| Control group (without addition) | 2.036 | - |
| TGF-β10ng/ml | 2.335 | 14.7 |
| Arg-Glu eutectic mixture 10ppm | 2.728 | 34.0 |
| Arg10ppm | 2.429 | 19.3 |
| Glu10ppm | 2.240 | 10.0 |
| Arg/Glu (1:10) pure mixture 10ppm | 2.531 | 24.3 |
Collagen production increasing effect (repetition number ═ 3)
As shown in Table 23, the Arg-Glu eutectic mixture promotes collagen synthesis depending on the concentration, and has the effect of increasing the total amount of collagen, and at a concentration of 1ppm or more, the collagen increase rate is superior to that of the Arg/Glu (1:10) simple mixture at the same concentration. The Arg-Glu eutectic mixture also has an excellent collagen increase rate compared to Arg and Glu, which are single amino acids.
Experimental example 14 confirmation of skin elasticity-enhancing Effect
In order to confirm the elasticity-enhancing effect of the eutectic mixture of example 13 on the skin of an actual human, experiments were conducted to prepare a and B into a cream formulation with the composition of table 24 below. For this experiment, an arginine-glutamic acid eutectic mixture (Arg-Glu eutectic mixture) was used. Specifically, 20 women of 25 to 45 years old were coated on the face 2 times a day in the morning and evening, and the skin elasticity improvement effect was examined using a skin elasticity detector (Cutometer SEM 575, C + K electronics co., Germany). The results are shown in Table 25 below. The result value represents the skin viscoelasticity (viscoelasticity) of the skin elasticity detector.
Watch 24
| Composition (I) | A | B |
| Arg-Glu eutectic mixture | 1 | 0 |
| Purified water | Residual amount | Residual amount |
| Glycerol | 8.0 | 8.0 |
| Butanediol | 4.0 | 4.0 |
| Hyaluronic acid extract | 5.0 | 5.0 |
| Beta-glucan | 7.0 | 7.0 |
| Carbomer | 0.15 | 0.15 |
| Caprylic/capric triglyceride | 8.0 | 8.0 |
| Squalane | 5.0 | 5.0 |
| SpermacetiStearyl glucoside | 1.5 | 1.5 |
| Sorbitol stearate | 0.4 | 0.4 |
| Cetostearyl alcohol | 2.0 | 2.0 |
| Preservative | Proper amount of | Proper amount of |
| Pigment | Proper amount of | Proper amount of |
| Triethanolamine | 0.15 | 0.15 |
| Sum of | 100 | 100 |
TABLE 25
| Skin elasticity change rate after 8 weeks (%) | |
| A | 29 |
| B | 12 |
As shown in table 25, skin elasticity was enhanced in the group of experiments using the arginine-glutamic acid eutectic mixture. From this, it is understood that the arginine-glutamic acid eutectic mixture has an excellent skin elasticity-enhancing effect.
Experimental example 15 confirmation of separation conditions of eutectic mixture
In general, when a eutectic mixture is formed in a specific solvent, the eutectic mixture is in a state of being over-dissolved to a solubility of each component species or more. In the present invention, when the solvent is water to form the hypermolten solution of the eutectic mixture, the bonding of the eutectic mixture is confirmed by the presence or absence of the irreversible precipitation under the following conditions, for example:
i) storing at 50 deg.C for more than 6 weeks, or more than 8 weeks, or more than 10 weeks, or more than 12 weeks;
ii) storing the mixture at 60 ℃ for 4 weeks or more, or 5 weeks or more, or 6 weeks or more, or 8 weeks or more; and/or
iii) storing at 80 deg.C for more than 10 days, or more than 15 days, or more than 20 days, or more than 30 days.
That is, the bonding between the eutectic substances in the eutectic mixture is broken by the generation or non-generation of the irreversible precipitates under the above conditions i) to iii), and it is confirmed that the breaking is occurred. In addition, whether the eutectic mixture is dissociated or not is confirmed using a substance that breaks the bond between eutectic substances, for example, a substance such as EDTA, a protic solvent (protic solvent), urea (urea) or guanidine HCl at a high concentration.
In this case, the reversible precipitation means a precipitation that is recovered to a transparent (homogeneous) solution state by a simple mixing (exchange) about 10 to 20 times after observing a precipitate of the eutectic mixture, and the precipitation is confirmed to temporarily occur in the case of standing at a low temperature (-20 ℃) instead of the dissociation conditions of the above i) to iii), but is homogenized by the simple mixing. Irreversible precipitation is precipitation which is not homogenized when subjected to the above-described process
Further, the cosmetic preparation (essence) containing the eutectic mixture of example 12 left to stand under the separation condition of the eutectic mixture was visually observed for properties (table 27) and examined by dsc (differential scanning measurement) to confirm the melting point change (table 28) and the exfoliating effect (table 29), thereby confirming whether the eutectic mixture was dissociated or not. In this case, the essence containing the eutectic mixture is prepared by adding the eutectic mixture to the essences prepared with the compositions shown in table 26 below, and the exfoliating effect was confirmed in the same manner as described in experimental example 2. At this time, the melting point was detected by a power-compensated Differential Scanning Calorimeter (Perkin Elmer Diamond DSC) (Differential Scanning Calorimeter; Perkin Elmer, Waltham, MA, USA). The melting point was expressed by the heat flow of the sample in the DSC, and the accuracy was 0.01 ℃. Melting point detection was performed in a pure nitrogen environment, and in order to maintain the nitrogen environment, the temperature of the chamber was increased by 10 ℃ per minute by feeding into the detection chamber at a rate of 20 cc/min. The mass of the test sample was confirmed by subtracting the weight of the pan (pan) containing the sample in the DSC from the weight of the entire sample. The pan was left to stand inside the DSC and heated to a temperature of-50 ℃ to 90 ℃ to detect the heat flow. After that, the results were confirmed by a data analysis program connected to the DSC.
Watch 26
| Composition (I) | Content (parts by weight) |
| Isohexadecane | 5.0 |
| Glycerol | 3.6 |
| Purified water | 83.94 |
| 1, 2-hexanediol | 1.0 |
| Propylene glycol | 6.0 |
| Xanthan gum | 0.1 |
| acrylate/C10-30 alkyl acrylate crosspolymer | 0.2 |
| Perfume | 0.06 |
| Tromethamine | 0.1 |
| Total up to | 100 |
Watch 27
| Separation conditions | Traits |
| Separating at 50 deg.C for 6 weeks | Irreversible precipitation (separation of eutectic mixture) |
| Separating at 60 deg.C for 5 weeks | Irreversible precipitation (separation of eutectic mixture) |
As shown in table 27, when the eutectic mixture was allowed to stand at a temperature of 50 ℃ for 6 weeks or more or at a temperature of 60 ℃ for 5 weeks or more, irreversible precipitation occurred, and thus it was confirmed that the eutectic mixture was dissociated. When the eutectic mixture is dissociated, the melting point is not expected to be lowered and the skin permeation efficacy improving effect cannot be expected, and therefore, the characteristics when the eutectic mixture is formed or dissociated are confirmed by the following tables 28 and 29.
Watch 28
As a result, it was confirmed that the melting point of the cosmetic including the simple mixture in which the eutectic mixture was not formed was 0 ℃ which is the melting point of water, and the melting point of the cosmetic including the eutectic mixture was-3.83 ℃ due to the melting point depression phenomenon. In the case of the cosmetics containing the eutectic mixture stored under the dissociation conditions (6 weeks at 50 ℃) in table 27, the observed melting point was 0 ℃, at which time the eutectic mixture was dissociated into a form of a simple mixture.
Watch 29
In the case where the eutectic mixture identified in table 28 is dissociated to form a simple mixture, it is identified from table 29 whether the level of the exfoliating effect is similar to that of the simple mixture. When the exfoliating effect of the essence comprising the eutectic mixture was 100 and compared relatively, the essence comprising the simple mixture or the dissociation of the eutectic mixture all achieved similar levels of effect. At this time, the essence containing the eutectic mixture of [ example 12] showed a keratolytic effect higher by about 20% or more than the essence (including the dissociation product of the eutectic mixture) after the essence containing the eutectic mixture of [ example 12] was stored at 50 ℃ for 6 weeks (severe conditions).
As shown in tables 28 and 29, it was confirmed that the extract containing the eutectic mixture and the extract containing the dissociation product of the eutectic mixture have a melting point and a keratolytic effect similar to those of the extract containing the simple mixture by comparing the melting point and the keratolytic effect. That is, it was confirmed that whether the eutectic mixture was dissociated or not was confirmed by the above results.
Claims (29)
1. A cosmetic composition comprising a eutectic mixture (eutectoid) containing purified water, amino acids and alpha-hydroxy acids (AHA).
2. The cosmetic composition according to claim 1, wherein,
the α -hydroxy acid is one or more selected from the group consisting of lactic acid (lactic acid), citric acid (citric acid), malic acid (malic acid), tartaric acid (tartaric acid), mandelic acid (mandelic acid), and glycolic acid (glycolic acid).
3. The cosmetic material composition according to claim 1,
the amino acid is one or more selected from the group consisting of serine (serine), proline (proline), threonine (threonine), cysteine (cysteine), glycine (glycine), alanine (alanine), valine (valine), leucine (leucin), isoleucine (isoluteine), aspartic acid (aspartic acid), glutamic acid (glutamate), glutamine (glutamine), arginine (arginine), lysine (lysine), tyrosine (tyrosine), methionine (methionine), phenylalanine (phenylalanine), histidine (histidine) and tryptophan (tryptophane).
4. The cosmetic material composition according to claim 1,
the above-mentioned alpha-hydroxy acid is contained in an amount of 1 to 50 parts by weight relative to 100 parts by weight of the total eutectic mixture.
5. The cosmetic composition according to claim 1, wherein,
the above amino acid is contained in a total amount of 1 to 75 parts by weight with respect to 100 parts by weight of the whole eutectic mixture.
6. The cosmetic composition according to claim 1, wherein,
the purified water is contained in an amount of 25 to 80 parts by weight relative to 100 parts by weight of the total eutectic mixture.
7. The cosmetic composition according to claim 1, wherein,
the eutectic mixture is contained in an amount of 0.01 to 50 parts by weight relative to 100 parts by weight of the total composition.
8. The cosmetic composition according to claim 1, wherein,
the purified water, amino acids, and alpha-hydroxy acids (AHAs) are contained within the eutectic mixture by association via dipole-dipole attraction between polar molecules, dipole-induced dipole attraction, hydrogen bonding between molecules, or van der waals interactions.
9. The cosmetic composition according to claim 1, wherein,
the alpha-hydroxy acid and the amino acid are contained in the above eutectic mixture in a weight ratio of 1:0.1 to 1: 10.
10. The cosmetic composition according to claim 1, wherein,
the cosmetic composition has a pH of 3.5 to 10.
11. The cosmetic composition according to claim 1, wherein,
the cosmetic composition is used for improving skin by promoting exfoliation of keratin.
12. The cosmetic composition according to claim 1, wherein,
the cosmetic composition is in the form of balm oil (palm), water-in-oil (W/O), oil-in-water (W/O), solubilized, or oily.
13. A method for preparing a cosmetic composition comprising the steps of:
mixing purified water, amino acid and alpha-hydroxy acid (AHA) to prepare eutectic mixture; and
the above eutectic mixture was added to prepare a cosmetic composition.
14. The method for preparing a cosmetic composition according to claim 13,
the step of preparing the eutectic mixture is performed under homogenization conditions of 600 to 4000rpm and 45 to 70 ℃.
15. A cosmetic composition includes a eutectic mixture (eutectoid mixture) containing a1 st amino acid and a 2 nd amino acid.
16. The cosmetic composition according to claim 15,
the 1 st amino acid and the 2 nd amino acid are at least one selected from the group consisting of serine (serine), proline (proline), threonine (threonine), cysteine (cysteine), glycine (glycine), alanine (alanine), valine (valine), leucine (leucine), isoleucine (isoleucine), aspartic acid (aspartic acid), glutamic acid (glutamate), glutamine (glutamine), arginine (arginine), lysine (lysine), tyrosine (tyrosine), methionine (methionine), phenylalanine (phenylalanine), histidine (histidine) and tryptophan (tryptophane).
17. The cosmetic composition according to claim 15,
the 1 st amino acid and the 2 nd amino acid are contained in a total amount of 1 to 75 parts by weight relative to 100 parts by weight of the total eutectic mixture.
18. The cosmetic composition according to claim 15,
the eutectic mixture further comprises purified water.
19. The cosmetic composition according to claim 18,
the purified water is contained in an amount of 25 to 80 parts by weight with respect to 100 parts by weight of the whole eutectic mixture.
20. The cosmetic composition according to claim 15,
the eutectic mixture is contained in an amount of 0.01 to 50 parts by weight relative to 100 parts by weight of the total composition.
21. The cosmetic composition according to claim 15,
the cosmetic composition has a pH of 3.5 to 10.
22. The cosmetic composition according to claim 15,
the cosmetic composition improves pores by reducing the number of pores.
23. The cosmetic composition according to claim 15,
the cosmetic composition is used for increasing elasticity.
24. The cosmetic composition according to claim 15,
the cosmetic composition is used for skin regeneration.
25. The cosmetic composition according to claim 15,
the cosmetic composition is used for improving wrinkle.
26. The cosmetic composition according to claim 15,
the cosmetic composition is used for improving cutin peeling.
27. A method for preparing a cosmetic composition comprising the steps of:
mixing the 1 st amino acid and the 2 nd amino acid to prepare a eutectic mixture (eutectic mixture); and
the above eutectic mixture was added to prepare a cosmetic composition.
28. The method for preparing a cosmetic composition according to claim 27, wherein,
the step of preparing the eutectic mixture is performed under homogenization conditions of 600 to 4000rpm and 45 to 70 ℃.
29. The method for preparing a cosmetic composition according to claim 27, wherein,
the step of preparing the eutectic mixture includes the step of adding purified water.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2019-0102243 | 2019-08-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK40072301A true HK40072301A (en) | 2022-11-25 |
| HK40072301B HK40072301B (en) | 2024-05-31 |
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