KR101193606B1 - Cosmetic Composition for Enhancing Skin Penetration Containing pH Responsive Nano Particles and Biomimetic Surfactant - Google Patents

Abstract

The present invention relates to a cosmetic composition having improved skin permeability containing pH-sensitive nanoparticles and bio-like surfactants, and more particularly, to skin permeability containing pH-sensitive nanoparticles and bio-like surfactants with active skin active ingredients. This improved cosmetic composition and method for producing the same.
The cosmetic composition with improved skin permeability according to the present invention has a skin active ingredient supported on pH-sensitive nanoparticles, so that the skin active ingredient is stably maintained from the external environment, and the skin has a high transmittance when the skin active ingredient is released from the skin. Penetrate into the stomach can maximize the efficacy of the active ingredient.

Description

Cosmetic composition with improved skin permeability containing pH sensitive nanoparticles and bio-like surfactants {Cosmetic Composition for Enhancing Skin Penetration Containing pH Responsive Nano Particles and Biomimetic Surfactant}

The present invention relates to a cosmetic composition having improved skin permeability containing pH-sensitive nanoparticles and bio-like surfactants, and more particularly, to skin permeability containing pH-sensitive nanoparticles and bio-like surfactants with active skin active ingredients. This improved cosmetic composition and method for producing the same.

Surfactants first industrialized alkylnaphthalinsulfonic acid at BASF, Germany in 1817, and later became the spotlight. Interfacial activity refers to a compound having an atomic group of hydrophobic groups and hydrophilic groups in one molecule, and dissolved in water or oil to significantly reduce the interfacial energy of the aqueous solution. However, the importance of environmentally friendly biosurfactants is increasing these days. Biosurfactants include glycolipids, phospholipids, fatty acids, lipopeptides and lipoproteins, lipopolysaccharides, sugar esters, and lipids. There are many kinds according to their structure, and they are applied to various fields according to their various characteristics.

Phospholipids, as examples of biosurfactants, are a type of lipid that contains phosphorus as a major component of the biofilm along with glycolipids, cholesterol, and proteins. Phospholipids have a structure similar to fats, but unlike fats in which three fatty acids bind to glycerol, two phospholipids and one phosphate group are combined. Phosphoric acid groups are combined with other organic substances, and the type of phospholipid varies depending on the type of organic substance bound.

Phospholipids, unlike fats, are polar, where the fatty acids are hydrophobic, easily mixed with non-polar substances, and hydrophilic, where the phosphate groups are easily mixed with water molecules or other polar molecules.

Due to the nature of these phospholipids, they are widely used as biomimetic surfactants in the pharmaceutical and cosmetic industries.

As a material widely used as a functional cosmetic material, a number of materials such as arbutin, adenosine, niacinamide, and alpha-bisabolol are being developed. However, these materials, despite their excellent efficacy as a cosmetic material, are limited in their ability to exert their effects on the skin due to insufficient skin absorption. Therefore, various techniques have been developed to increase the skin permeability of these functional cosmetic materials. A representative example is a technology for stabilizing functional cosmetic materials using nanofluidizers, phospholipids, etc. to nano size. Such nanotechnology has significantly increased the skin penetration efficiency of functional cosmetic materials, but causes a problem that the skin penetration efficiency is reduced by various variables such as surfactant, oil, thickener in the cosmetic formulation.

On the other hand, the inventors have developed a pH-sensitive nanoparticles to prevent the degradation of stability due to the external environment in a low pH environment and to be absorbed into the skin as the functional cosmetic material is released as the surrounding pH rises when applied to the skin ( Republic of Korea Patent No. 0925188).

However, in the case of the cosmetic composition containing the pH-sensitive nanoparticles, although the skin active ingredient is released on the skin surface according to the change of pH, there was a disadvantage in that the released skin active ingredient is not efficiently absorbed into the skin.

Therefore, it is essential to develop a cosmetic formulation for improving skin absorption using these functional cosmetic materials as a cosmetic raw material.

Thus, the present inventors have made efforts to develop a cosmetic composition with improved skin absorption rate, as a result of mounting a skin-active active ingredient on pH-sensitive nanoparticles, when mixing a bio-like surfactant having excellent skin affinity, pH-sensitive nano It was confirmed that the skin absorption of the active ingredient supported on the particles is improved, thereby completing the present invention.

SUMMARY OF THE INVENTION An object of the present invention is to provide a cosmetic composition having improved skin permeability, which contains JH sensitive nanoparticles and a bio-like surfactant.

It is another object of the present invention to provide a method for producing a cosmetic composition having improved skin transmittance containing ｐH sensitive nanoparticles and a bio-like surfactant.

In order to achieve the above object, the present invention provides a pH comprising (meth) acrylic acid or (meth) acrylate compound loaded with a skin active ingredient selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol A cosmetic composition is provided comprising sensitive nanoparticles and a biosimilar surfactant selected from the group consisting of phospholipids, glycolipids, fatty acids, lipopeptides, lipoproteins, lipopolysaccharides, sugar esters, and lipids.

The present invention also relates to pH-sensitive nanoparticles and phospholipids comprising (meth) acrylic acid or (meth) acrylate compounds loaded with a skin active ingredient selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol. It provides a method for producing a cosmetic composition containing a bio-like surfactant selected from the group consisting of, glycolipids, fatty acids, lipopeptides, lipoproteins, lipopolysaccharides, sugar esters and lipids.

The cosmetic composition with improved skin permeability according to the present invention has a skin active ingredient supported on pH-sensitive nanoparticles, so that the skin active ingredient is stably maintained from the external environment, and the skin has a high transmittance when the skin active ingredient is released from the skin. Penetrate into the stomach can maximize the efficacy of the active ingredient.

In one aspect, the present invention, pH-sensitive nanoparticles comprising a (meth) acrylic acid or a (meth) acrylate compound loaded with a skin active ingredient selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol And a biosimilar surfactant selected from the group consisting of phospholipids, glycolipids, fatty acids, lipopeptides, lipoproteins, lipopolysaccharides, sugar esters, and lipids.

In the present invention, the pH-sensitive nanoparticles may be selected from the group consisting of (meth) acrylic acid and (meth) acrylate-based compounds, the bio-like surfactants are glycolipids (phospholipids), phospholipids (phospholipids) ), Fatty acids, lipopeptides (lipopeptides) and lipoproteins (lipoproteins), lipopolysaccharides (lipopolysaccharides), sugar esters (sugar esters) and lipids (lipids).

In the present invention, the skin active ingredient may be selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol, and further comprising an acid solution or a base solution for pH adjustment. It can be characterized.

In addition, the pH-sensitive nanoparticles may be a copolymerized hydrogel (P (MAA-co-MA) hydrogel) of (meth) acrylic acid (MAA) and (meth) acrylate (MA) compound.

The pH sensitive nanoparticles used in the present invention have a property of shrinking at pH 5 or below and swelling at pH 5 or above. This is related to a phenomenon in which the pH sensitive nanoparticles exhibit a sharp difference in equilibrium mass swelling ratio around about pH 5 by (meth) acrylic acid contained in the pH sensitive nanoparticles. About pH 4.66 corresponds to pKa of (meth) acrylic acid.At pH above pKa of (meth) acrylic acid, carboxyl groups of (meth) acrylic acid are ionized to have a negative charge, and pH-sensitive nanoparticles are ionized in a pH environment of about pH 5 or higher. Due to the electrostatic repulsion between negatively charged groups. By using the characteristics of the hydrogel, various functional cosmetic raw materials mounted on the pH sensitive nanoparticles are released in the skin environment of pH 5 or higher.

Here, the equilibrium mass swelling ratio q is an index used to evaluate pH sensitivity and swelling behavior of the pH sensitive nanoparticles. The mass swelling ratio is represented by Equation 1 below.

Where q is the equilibrium mass swelling ratio, Wd is the mass (g) of the pH sensitive nanoparticles dried before swelling, and Ws is swelled by dipping the pH sensitive nanoparticles in a buffer solution between pH 2.0 and 8.0 for 24 hours, After removing the surface moisture of the swollen pH-sensitive nanoparticles, the swollen mass (g) is shown.

The pH sensitive nanoparticles used in the present invention include a (meth) acrylic acid and a (meth) acrylate-based compound, and the (meth) acrylic acid and the (meth) acrylate-based compound are prepared by photopolymerization.

 (Meth) acrylic acid is used to impart pH sensitivity to pH sensitive nanoparticles. Since the (meth) acrylic acid has a carboxyl group which can be ionized according to the surrounding pH, (meth) acrylic acid exists as (meth) acrylic acid before pH 4.66, which is pKa of (meth) acrylic acid, but at higher pH (meth) It is present as an acrylic acid anion.

In the present invention, acrylic acid (acrylic acid. AA) may be used instead of (meth) acrylic acid.

A (meth) acrylate type compound is used to adjust the pH sensitivity of (meth) acrylic acid. The (meth) acrylate compound can adjust the pH sensitivity of the pH sensitive nanoparticles by changing the composition ratio with (meth) acrylic acid or by using a (meth) acrylate compound having various molecular weights.

As the (meth) acrylate compound has a higher molecular weight, the equilibrium mass swelling ratio at pH 5 or more is reduced. This is because the electrostatic repulsion of anions formed by ionizing the carboxyl group of (meth) acrylic acid above pH 5 is hampered by the polymerized (meth) acrylate compound. As the molecular weight of the (meth) acrylate-based compound increases, the chain length of the (meth) acrylate to be grafted becomes longer, thereby preventing more electrostatic repulsion between the ionized carboxyl groups.

Although the kind of said (meth) acrylate type is not specifically limited, Methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) Acrylate, t-butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, n-octyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, 2-hydrate Oxyethyl (meth) acrylate, poly (ethylene glycol) (meth) acrylate, methoxy polyyl (ethylene glycol) (meth) acrylate, glycidyl (meth) acrylate, dimethyl aminoethyl (meth) acrylate, One kind or a mixture of diethyl aminoethyl (meth) acrylate, glycol di (meth) acrylate, allyl (meth) acrylate or n-alkyl (meth) acrylate can be used.

In this invention, it is preferable to use poly (ethylene glycol) (meth) acrylate (PEGMA). Poly (ethylene glycol) (meth) acrylate is used as a safe biocompatible material and can adjust the pH sensitivity of nanoparticles by changing the composition of poly (ethylene glycol).

The (meth) acrylate (MA) -based compound forms (meth) acrylic acid (MAA) and copolymerized hydrogel (P (MAA-co-MA) fine particles).

In the preparation of pH-sensitive nanoparticles, it is preferable that (meth) acrylic acid is added in an amount of 20 to 80% by weight, and 60% by weight based on the total amount of (meth) acrylic acid and (meth) acrylate compound as a monomer. More preferred. Since the equilibrium mass swelling ratio of the pH sensitive nanoparticles produced when the (meth) acrylic acid is 60% by weight is the highest, even when the added amount of the (meth) acrylic acid is used in an amount exceeding 80% by weight, no better effect can be expected. In addition, when the (meth) acrylic acid monomer is less than 20% by weight, the carboxyl group to be ionized is reduced, so that the equilibrium mass swelling ratio of the pH-sensitive nanoparticles is reduced, resulting in a decrease in the release of the functional cosmetic material.

The pH sensitive nanoparticles of the present invention may further comprise a crosslinking agent. The crosslinking agent is not particularly limited as long as it is a crosslinking agent commonly used in the art, but may be selected from poly (ethylene glycol) di (meth) acrylate, poly (ethylene glycol) diacrylate, butanediol di (meth) acrylate, and butanediol diacrylate. One kind or a mixture of two or more kinds may be used, and it is preferable to use poly (ethylene glycol) di (meth) acrylate. The crosslinking agent is preferably used in an amount of 1 to 5% by weight based on the total amount of the (meth) acrylic acid and the (meth) acrylate compound as monomers (that is, the (meth) acrylic acid and the (meth) acrylate compound on a weight basis. Sum: crosslinking agent = 100: 1 to 5). When the amount of the crosslinking agent is more than 5% by weight, the degree of crosslinking of the pH-sensitive nanoparticles increases, making it difficult to swell. When the amount of the crosslinking agent is less than 1% by weight, the physical properties of the pH-sensitive nanoparticles are weak.

The present invention relates to a pH sensitive nanoparticle delivery system for cosmetics in which a functional cosmetic material is mounted on a pH sensitive nanoparticle. Since the pH sensitive nanoparticles shrink or swell according to the change of pH, the functional cosmetic material may be mounted inside the pH sensitive nanoparticles. In an environment of pH 5 or above, the pH-sensitive nanoparticles swell, and thus functional cosmetic materials are mounted.

Here, the functional cosmetic material is not particularly limited, but may be an effective whitening effective material such as arbutin, nisinamide, adenosine, EGCG, peptides and the like. In particular, the present invention is preferably an anti-aging functional cosmetic material that is effective in preventing skin aging and improving wrinkles such as adenosine, EGCG, and peptides. The functional cosmetic material varies depending on the pKa, molecular weight and degree of hydrophilicity of the functional material to be mounted on the pH-sensitive nanoparticles. In the aqueous solution containing a functional cosmetic material using ultrapure water as a solvent, the pH-sensitive nanoparticles have a negative charge due to ionization of carboxyl groups. do. As a result, negatively charged pH-sensitive nanoparticles and electrostatic repulsive forces reduce the loading efficiency of functional cosmetic materials. On the contrary, when the pKa of the functional cosmetic material is higher than the pH of the ultrapure water, the mounting efficiency increases.

Here, ultrapure water refers to water in which a very small amount of ions are removed using an ion exchange resin, and the pH of the ultrapure water is 6.5. When the pH sensitive nanoparticles for cosmetics equipped with the functional cosmetic material are in contact with the skin, the functional cosmetic material is eluted to the outside of the pH sensitive nanoparticles. Usually the pH of the skin is between 5.5 and 6.0. Since the skin has a buffer function, when the cosmetic composition containing pH-sensitive nanoparticles having a pH of 3.0 to 4.5, especially pH-sensitive nanoparticles, comes into contact with the skin, the pH-sensitive nanoparticles are changed to a pH of 5.5-6.0 of the skin. . When the pH is changed to 5.5 to 6.0, the (meth) acrylic acid of the pH sensitive nanoparticles becomes an anion and swells by the electrostatic repulsive force between the anions. Therefore, the functional cosmetic material is eluted to the outside.

The method for producing the pH-sensitive nanoparticles used in the present invention is not particularly limited as long as it is prepared by photopolymerizing the (meth) acrylic acid, the (meth) acrylate-based compound and the crosslinking agent. Mixing step of preparing a monomer mixture by mixing (meth) acrylic acid, (meth) acrylate-based compound, crosslinking agent and photoinitiator as an example of a method for producing a pH-sensitive nanoparticles; A polymerization step of dispersing the monomer mixture in a dispersion solvent and then photopolymerizing to polymerize the pH-sensitive nanoparticles; And washing and drying the polymerized pH sensitive nanoparticles.

Photoinitiators are used to initiate the production of copolymerized hydrogels of (meth) acrylic acid and (meth) acrylate-based compounds, ie pH sensitive nanoparticles. The kind of the initiator is not particularly limited, but 1-hydroxy cyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis (2,6-dimethoxybenzoyl) -2, 4,4-trimethylpentyl phosphine oxide (DMBAPO), bis (2,4,6-trimethylbenzoyl) -phenyl phosphine oxide, 2,4,6-trimethylbenzyldiphenyl phosphine oxide or 2,4,6- One kind or a mixture of two or more kinds of trimethylbenzoyl diphenylphosphine oxide may be used, and it is preferable to use 1-hydroxy cyclohexyl phenyl ketone.

The photoinitiator is preferably added in an amount of 0.1 to 1.5% by weight based on the total amount of the monomer (meth) acrylic acid and the (meth) acrylate compound (that is, the (meth) acrylic acid and the (meth) acrylate compound on a weight basis. Sum: photoinitiator = 100: 0.1 to 1.5). If the initiator is less than 0.1% by weight, the reaction of producing pH-sensitive nanoparticles is not easy, and the polymerization time is also long. If the initiator is more than 1.5% by weight, the reaction proceeds too quickly to control the size of the particles.

In the polymerization step, a monomer mixture composed of (meth) acrylic acid, a (meth) acrylate compound, a crosslinking agent, and a photoinitiator is dispersed in a dispersion solvent and then photopolymerized.

It is preferable that the said dispersion solvent is oil-like, In this invention, it is more preferable to use a silicone oil. It is preferable to use the said dispersion solvent 10 to 50 times with respect to the total amount of the (meth) acrylic acid and the (meth) acrylate type compound which are monomers.

The dispersion solvent may further include a dispersion stabilizer. The dispersion stabilizer is used to solve the agglomeration of particles appearing in the preparation of pH-sensitive nanoparticles and to improve the dispersibility of the particles. The dispersion stabilizer is not particularly limited as long as it is harmless to the human body, but is not limited to (polyethylene glycol methyl ether) dimethylsilane, sorbitan monolaurate, polyoxyethylene methyl polysiloxane, polyethylene glycol trimethylonyl ether, 2- [methoxy (polyethyleneoxy) propyl ] A kind or a mixture of heptamethyltrisiloxane or bis (polyethylene glycol methyl ether) dimethylsilane can be used.

The dispersion stabilizer is preferably added in an amount of 0.5 to 3.0% by weight based on the total amount of the (meth) acrylic acid and the (meth) acrylate-based compounds which are monomers (that is, (meth) acrylic acid and (meth) acrylate-based on a weight basis. Sum of compounds: dispersion stabilizer = 100: 0.5 to 3.0.). When the content of the dispersion stabilizer is less than 0.5% by weight, the dispersibility of the particles to be prepared is lowered, and when the content of the dispersion stabilizer is more than 3.0% by weight, the viscosity increases.

Injecting nitrogen may be further performed before dispersing the monomer mixture in an organic solvent. Nitrogen is injected to remove oxygen contained in the dispersion solvent containing the monomer mixture. The photopolymerization reaction is a radical reaction, when oxygen is present in the reaction, the oxygen consumes radicals and inhibits polymerization, thereby injecting nitrogen into the dispersion solvent. The nitrogen is injected for about 2 minutes.

It is preferable to use an ultrasonic homogenizer or a homomixer to disperse the monomer mixture in the dispersing solvent, and more preferably to use a homomixer. The homomixer is used to stir at about 10,000 rpm for about 2 minutes to disperse the monomer mixture in the dispersion solvent.

The monomer mixture dispersed in the dispersion solvent is photopolymerized to produce pH sensitive nanoparticles. It is preferable that the said photopolymerization uses UV irradiation. UV irradiation for 200 to 400 seconds to photopolymerize the pH sensitive nanoparticles.

The polymerized pH sensitive nanoparticles are washed and separated from the dispersion solvent. Here, it is preferable to use ultrapure water for washing, and it is washed repeatedly. The wash is washed using centrifugation.

The washed pH-sensitive nanoparticles are dried, and preferably dried using a lyophilizer. The pH sensitive nanoparticles produced by the step of preparing the pH sensitive nanoparticles may be random copolymers or block copolymers, and have a uniform spherical shape of about 1000 nanometers (nm) or less.

As another example of a method for producing pH-sensitive nanoparticles, (meth) acrylic acid, (meth) acrylate compound, and a crosslinking agent are introduced into a cell of a supercritical fluid device, the cell is sealed, and CO ₂ is injected into the cell. Making; When the injected materials are dissolved, there is a method including photopolymerization while injecting an initiator.

The method uses supercritical CO ₂ to prepare pH-sensitive nanoparticles using a supercritical fluid without using a dispersing solvent, thereby dissolving a (meth) acrylic acid, a (meth) acrylate compound and a crosslinking agent. There is no need to use, and after the synthesis of pH-sensitive nanoparticles, the washing process can be omitted.

CO ₂ is injected into a closed cell into which (meth) acrylic acid, a (meth) acrylate-based compound and a crosslinking agent are added, and makes the CO ₂ into a supercritical state. The temperature of the supercritical fluid apparatus is adjusted to about 50 ° C. and the pressure to about 5000 psi to make the CO ₂ supercritical. When the CO ₂ is in a supercritical state, the (meth) acrylic acid, the (meth) acrylate compound, and the crosslinking agent, which were liquid, are dissolved in CO ₂ . Injecting the initiator into the cell is made through a separate valve. The polymerization of the (meth) acrylic acid, the (meth) acrylate-based compound and the crosslinking agent uses a photopolymerization method, and photopolymerization by irradiation with UV. Stirring during the photopolymerization reaction increases the efficiency of the reaction.

When the photopolymerization reaction is completed, water is introduced into the cell to collect the mixed particles, and the final temperature-sensitive nanoparticles are obtained by adjusting the temperature and pressure in the cell to room temperature and atmospheric pressure.

The method of mounting the functional cosmetic material on the pH-sensitive nanoparticles of the present invention is achieved by submerging the pH-sensitive nanoparticles in an aqueous solution containing a skin active ingredient (functional cosmetic material).

After the pH sensitive nanoparticles are immersed in an aqueous solution containing the skin active ingredient using ultrapure water as a solvent, after a predetermined time, the pH sensitive nanoparticles are removed from the solution containing the skin active ingredient and surfaced with distilled water in a filtration device. After washing, lyophilization is completed.

Here, the content of the functional cosmetic material contained in the aqueous solution of the skin active ingredient is preferably 0.01 to 2.5 mg / ml. If the content of the skin active ingredient is less than 0.01 mg / ml, it is not easy to mount the skin active ingredient in the pH-sensitive nanoparticles, and if it exceeds 2.5 mg / ml, since the maximum loading efficiency has already been obtained, You cannot expect an improvement.

The pH-sensitive nanoparticles are preferably added in an amount that can be submerged in an aqueous solution containing a skin active ingredient. The reaction of the pH-sensitive nanoparticles and the skin active ingredient is preferably carried out for 2 to 24 hours. If the reaction time is less than 2 hours, the maximum payload efficiency cannot be obtained, and if it exceeds 24 hours, since the maximum payload efficiency has already been obtained, further improvement in payload efficiency cannot be expected.

The pH sensitive nanoparticles on which the skin active ingredient is mounted are used as a constituent raw material of the cosmetic composition. The skin active ingredient reacts with organic and inorganic substances (moisture, fatty acids, polyols, surfactants, plant extracts, enzymes, proteins and various metal ions, etc.) which are other constituents of the cosmetic composition, and the effect is reduced. Mounting the functional cosmetic material on the pH-sensitive nanoparticles prevents the skin active ingredient from contacting other components of the cosmetic to stabilize the functional cosmetic material.

The cosmetic composition is not particularly limited in its formulation, for example, it can be selected and used as a formulation of astringent makeup, softening makeup, nutrient makeup, massage cream, essence, pack, lotion, cream and the like.

At this time, the pH of the cosmetic composition is preferably 4 to 4.5. The pH-sensitive nanoparticles do not have an electrostatic repulsion because the (meth) acrylic acid, which was an anion when pH-sensitive nanoparticles were mounted on the pH-sensitive nanoparticles (pH 6.5), became a (meth) acrylic acid at pH 4 to 4.5, the pH of the cosmetic composition. Contracts and release of the loaded skin active ingredient is blocked.

When the pH of cosmetics exceeds 4.5, the pKa of (meth) acrylic acid in the pH sensitive nanoparticles is about 4.66, so the (meth) acrylic acid is ionized at the pH and the pH sensitive nanoparticles are expanded due to the electrostatic repulsive force, resulting in skin active ingredient. There is a problem that elutes. If the skin active ingredient is eluted, the functional cosmetic material reacts with other components of the cosmetic to reduce or lose the effect of the functional cosmetic material.

The cosmetic composition with improved skin permeability according to the present invention contains pH-sensitive nanoparticles loaded with functional cosmetic raw materials (skin active ingredients) and bio-like surfactants for enhancing skin permeation efficiency, thereby making functional cosmetic materials stable. After release to the skin, it can be permeated to the skin with high efficiency.

In another aspect, the present invention, pH-sensitive nanoparticles comprising a (meth) acrylic acid or a (meth) acrylate compound loaded with a skin active ingredient selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol And it relates to a method for producing a cosmetic composition containing a bio-like surfactant selected from the group consisting of phospholipids, glycolipids, fatty acids, lipopeptides, lipoproteins, lipopolysaccharides, sugar esters and lipids.

In one aspect of the invention, skin cosmetic formulations are prepared using phospholipids as bio-like surfactants.

In another embodiment of the present invention, the skin permeation efficiency of the functional cosmetic raw material was confirmed through the skin permeation behavior experiment on the cosmetic formulation prepared by the above method. Functional cosmetic raw materials include arbutin, adenosine, niacinamide, alpha-bisabolol, etc., but in the present invention, adenosine, which is a wrinkle-improving functional raw material, was used, and the skin permeation behavior test was made of pH-sensitive nanoparticles prepared by the above method. As a result of depositing the same amount of adenosine on the particles and using the skin permeation device (diffusion cell), which is an in vitro experiment, on the skin permeation behavior of adenosine released at pH 6 for pH-sensitive nanoparticles carrying adenosine, the cosmetic according to the present invention Formulation method was confirmed to improve the skin permeation efficiency of adenosine supported on pH sensitive nanoparticles.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Example 1 Preparation of pH Sensitive Nanoparticles Loaded with Adenosine

To synthesize pH-sensitive nanoparticles, MAA and PEGMA as monomers, PEGDMA as crosslinkers, Irgacure ^® 184 as an initiator, silicon oil as a dispersion medium, and various kinds of dispersion stabilizers were used for good dispersion of the particles.

As a monomer, MAA and PEGMA were mixed at a ratio of 0.6: 1 mol, 1.0 mol% of crosslinking agent PEGDMA was used as the total monomer, and Irgacure ^® 184 as an initiator was used at 2 wt% based on the total monomer. The addition ratio of dispersion stabilizer was added in various ratios according to the kind of dispersion stabilizer. The monomer mixture consisting of the monomer, the crosslinking agent, the initiator and the dispersion stabilizer was placed in 50 ml of silicone oil as a dispersion medium to inject nitrogen to remove oxygen from the solution, and then stirred at 10000 rpm for 2 minutes using a homogenizer to prepare the monomer mixture. Evenly distributed in daily life. After the dispersion was completed, the particles synthesized by UV irradiation for 300 seconds were separated from the silicone oil by repeated washing using centrifugation several times using ultrapure water. The washed particles were completely dried using a lyophilizer and used in the next experiment.

The loading of adenosine was completed by adding 0.05 g of dried hydrogel particles to an aqueous solution of 2 mg / ml of active substance, and after a certain time, the particles were removed from the aqueous solution, surface-washed with distilled water in a reduced pressure filtering device, and lyophilized.

Example 2: Preparation and Stability Measurement of Cosmetic Formulation Using HPC

Phospholipids were used as analogous surfactants. Phospholipids were used as lecithin, which eliminated unsaturated components through hydrogenation, using LIPOID S 100-3 N (LIPOID) containing 95% or more of phosphatidylcholine, and was named as hydrogenated phosphatidyl choline (HPC). The HPC is a material that is used in cosmetics as a stable raw material with good oxidation safety compared to lecithin containing unsaturated fatty acid and does not cause discoloration and odor.

The HPC-containing formulation was designed to pH 4.0 using citric acid to maintain pH-sensitive nanoparticles loaded with adenosine in the formulation, and to compare the degree of skin permeation. And HPC content-specific formulations were prepared in the compositions shown in Table 1 using a homomixer.

Comparative formulation and composition of formulation by HPC content ingredient Comparative formulation Formulation One 2 3 4 5 CETEARYL ALCOHOL 1.80 1.80 1.80 1.80 1.80 1.80 GLYCERYL STEARATE 1.20 1.20 1.20 1.20 1.20 1.20 STEARIC ACID 0.70 0.70 0.70 0.70 0.70 0.70 MANGIFERA INDICA SEED BUTTER 0.80 0.80 0.80 0.80 0.80 0.80 GLYCERYL STEARATE, PEG-100 STEARATE 1.00 1.00 1.00 1.00 1.00 1.00 SORBITAN STEARATE 0.40 0.40 0.40 0.40 0.40 0.40 LIPOID S 100-3 0.00 0.10 0.50 1.00 3.00 5.00 METHYL PARABEN 0.20 0.20 0.20 0.20 0.20 0.20 PROPYL PARABEN 0.10 0.10 0.10 0.10 0.10 0.10 POLYSORBATE 60 1.20 1.20 1.20 1.20 1.20 1.20 POLYDECENE 2.00 2.00 2.00 2.00 2.00 2.00 CETYL ETHYLHEXANOATE 3.00 3.00 3.00 3.00 3.00 3.00 LIMNANTHES ALBA SEED OIL 2.00 2.00 2.00 2.00 2.00 2.00 OCTYLDODECYL MYRISTATE 2.00 2.00 2.00 2.00 2.00 2.00 CAPRYLIC / CAPRIC TRIGLYCERIDE 2.00 2.00 2.00 2.00 2.00 2.00 TOCOPHERYL ACETATE 0.10 0.10 0.10 0.10 0.10 0.10 DIMETHICONE 0.50 0.50 0.50 0.50 0.50 0.50 CYCLOMETHICONE 2.00 2.00 2.00 2.00 2.00 2.00 nanoparticles 0.40 0.40 0.40 0.40 0.40 0.40 DISODIUM EDTA 0.02 0.02 0.02 0.02 0.02 0.02 UREA 2.00 2.00 2.00 2.00 2.00 2.00 CITRIC ACID 0.05 0.05 0.05 0.05 0.05 0.05 PEG / PPG-17 / 6 COPOLYMER 5.00 5.00 5.00 5.00 5.00 5.00 GLYCERIN 5.00 5.00 5.00 5.00 5.00 5.00 BUTYLENE GLYCOL 5.00 5.00 5.00 5.00 5.00 5.00 SODIUM HYALURONATE 5.00 5.00 5.00 5.00 5.00 5.00 PRUNUS AMYGDALUS DULCIS SEED EXTRACT 0.10 0.10 0.10 0.10 0.10 0.10 HYDROLYZED WHEAT PROTEIN 0.10 0.10 0.10 0.10 0.10 0.10 PHENOXYETHANOL 0.30 0.30 0.30 0.30 0.30 0.30 FRAGRANCE (MARINE 2) 0.20 0.20 0.20 0.20 0.20 0.20 POLYACRYLATE-13, POLYISOBUTENE, POLYSORBATE 20 0.80 0.80 0.80 0.80 0.80 0.80 Purified water to
100 to
100 to
100 to
100 to
100 to
100

Each formulation prepared in the composition of Table 1 was put into each 4 ℃, 30 ℃, 37 ℃, 45 ℃ incubator, and confirmed the stability of discoloration, deodorization, separation for one month.

Formulation Stability of Comparative Formulation and HPC Content term 45 ° C 37 ℃ 30 ℃ cold storage
Comparative formulation 1 day stability stability stability stability 7 days stability stability stability stability 14 days stability stability stability stability 28 days stability stability stability stability
Example 1 1 day stability stability stability stability 7 days stability stability stability stability 14 days stability stability stability stability 28 days stability stability stability stability
Example 2 1 day stability stability stability stability 7 days stability stability stability stability 14 days stability stability stability stability 28 days stability stability stability stability
Example 3 1 day stability stability stability stability 7 days stability stability stability stability 14 days stability stability stability stability 28 days stability stability stability stability
Example 4 1 day stability stability stability stability 7 days stability stability stability stability 14 days stability stability stability stability 28 days stability stability stability stability
Example 5 1 day stability stability stability stability 7 days Instability stability stability stability 14 days Instability stability stability stability 28 days Instability stability stability stability

As a result, as shown in Table 2, the comparative formulation is a general lotion formulation, showing the stability of various properties with respect to temperature for one month. In addition, in Example 5, the formulation was unstable, such as the separation of the formulation due to some aggregation due to excessive surfactant capacity, while in Examples 1, 2, 3, and 4, it showed stability at each temperature for one month. Therefore, in the present invention, Example 4 was selected as a formulation containing a bio-like surfactant.

Example 3: Skin Permeability Measurement of Cosmetic Formulation Using HPC

Example 4 prepared by the method of Example 1 improves the skin permeation of adenosine supported on pH-sensitive nanoparticles by confirming the result of skin permeation experiments of adenosine as a result of skin permeation increase of about 30% or more compared to adenosine aqueous solution. Although adenosine-supported pH sensitive nanoparticles were applied to the bio-like formulation, the amount of adenosine permeated during skin penetration was about 7.5%, which is lower than that of 13.2% of the adenosine solution itself. This releases the supported adenosine only when it is swollen by the surrounding moisture, but the embodiment prepared by the method of Example 1 is a cream-type formulation, and it is determined that the amount of water required for swelling is small and the formulation is changed as shown in Table 3.

Composition of formulations by water content and thickener content ingredient Experimental Example One 2 3 4 5 6 CETEARYL ALCOHOL 1.80 1.62 1.26 0.90 0.90 0.90 GLYCERYL STEARATE 1.20 1.08 0.84 0.60 0.60 0.60 STEARIC ACID 0.70 0.63 0.49 0.35 0.35 0.35 MANGIFERA INDICA SEED BUTTER 0.80 0.72 0.56 0.40 0.40 0.40 GLYCERYL STEARATE, PEG-100 STEARATE 1.00 1.00 1.00 1.00 1.00 1.00 SORBITAN STEARATE 0.40 0.40 0.40 0.40 0.40 0.40 LIPOID S 100-3 3.00 3.00 3.00 3.00 3.00 3.00 METHYL PARABEN 0.20 0.20 0.20 0.20 0.20 0.20 PROPYL PARABEN 0.10 0.10 0.10 0.10 0.10 0.10 POLYSORBATE 60 1.20 1.20 1.20 1.20 1.20 1.20 POLYDECENE 2.00 1.80 1.40 1.00 1.00 1.00 CETYL ETHYLHEXANOATE 3.00 2.70 2.10 1.50 1.50 1.50 LIMNANTHES ALBA SEED OIL 2.00 1.80 1.40 1.00 1.00 1.00 OCTYLDODECYL MYRISTATE 2.00 1.80 1.40 1.00 1.00 1.00 CAPRYLIC / CAPRIC TRIGLYCERIDE 2.00 1.80 1.40 1.00 1.00 1.00 TOCOPHERYL ACETATE 0.10 0.10 0.10 0.10 0.10 0.10 DIMETHICONE 0.50 0.45 0.35 0.25 0.25 0.25 CYCLOMETHICONE 2.00 1.80 1.40 1.00 1.00 1.00 Purified water 52.03 55.83 63.43 71.03 71.23 71.43 nanoparticles 0.40 0.40 0.40 0.40 0.40 0.40 DISODIUM EDTA 0.02 0.02 0.02 0.02 0.02 0.02 UREA 2.00 2.00 2.00 2.00 2.00 2.00 CITRIC ACID 0.05 0.05 0.05 0.05 0.05 0.05 PEG / PPG-17 / 6 COPOLYMER 5.00 4.50 3.50 2.50 2.50 2.50 GLYCERIN 5.00 4.50 3.50 2.50 2.50 2.50 BUTYLENE GLYCOL 5.00 4.50 3.50 2.50 2.50 2.50 SODIUM HYALURONATE 5.00 4.50 3.50 2.50 2.50 2.50 PRUNUS AMYGDALUS DULCIS SEED EXTRACT 0.10 0.10 0.10 0.10 0.10 0.10 HYDROLYZED WHEAT PROTEIN 0.10 0.10 0.10 0.10 0.10 0.10 PHENOXYETHANOL 0.30 0.30 0.30 0.30 0.30 0.30 FRAGRANCE (MARINE 2) 0.20 0.20 0.20 0.20 0.20 0.20 POLYACRYLATE -13, POLYISOBUTENE, POLYSORBATE 20 0.80 0.80 0.80 0.80 0.60 0.40

As shown in Table 3, Experimental Examples 2, 3 and 4 increase the amount of purified water by reducing the amount of oil, fatty acids, and polyols to 90%, 70%, and 50% of the components of the formulation, and Experimental Examples 5 and 6 increase. The amount of Jane POLYACRYLATE-13, POLYISOBUTENE, and POLYSORBATE 20 was gradually reduced, resulting in a change from creamy formulations to skin-permeable formulations with lotion-type low viscosity formulations.

The formulations were prepared using a homomixer and calibrated to pH 4.0 with 10% citric acid at the end of the preparation, followed by addition of pH sensitive nanoparticles carrying adenosine, followed by pH sensitive nanoparticles carrying the same amount of adenosine The skin permeation behavior of adenosine released at pH 6 for the particles was confirmed using a diffusion cell, an in vitro experiment.

The identification of skin permeation behavior is described in the OECD guideline for the testing of chemicals. It was carried out according to TG 428. Specifically, a diffusion cell (diffusion cell drive, FCDV-15, Labfine) having a size of 0.785 cm ² was used, and the skin permeation sample was prepared in human epidermis (10 mg / cm ² with respect to 0.04% adenosine aqueous solution and Examples 1 to 6). After application to human epidermis) was maintained for 32 ℃, 500rpm, 24 hours, and the aqueous solution (receptor fluid) PBS (pH 7.4) was used.

Human epidermis is 3 ㅧ 3cm in size, which is well preserved in stratum basale, stratum spinosum, stratum granulosum and stratum corneum in Hans biomed, which operates skin tissue bank. Human epidermis was purchased and used.

After agitation at 32 ° C., 500 rpm for 24 hours, an aqueous solution (receptor fluid) was quantified through the epidermis by using HPLC (Zorbax Eclipse XDB-C18 2ea, 1200 series, Agilent). Skin permeability was calculated by the following equation.

As a result, when a 0.04% aqueous solution of adenosine, an active ingredient, was applied to the human epidermis in an amount of 10 mg / cm ² , about 13% of adenosine penetrated the skin (Table 4).

Skin Permeability of Adenosine Supported on pH-Sensitive Nanoparticles Prepared Using Bio-Similar Surfactants Test sample Skin permeation ratio (%) One 0.04% Adenosine 13.20 (± 1.12) 2 Experimental Example 1  7.50 (± 0.51) 3 Experimental Example 2 22.50 (± 1.03) 4 Experimental Example 3 22.50 (± 1.24) 5 Experimental Example 4 27.50 (± 0.98) 6 Experimental Example 5 75.00 (± 1.11) 7 Experimental Example 6 80.20 (± 0.56)

Experimental Examples 3, 4 and 5 showed no significant difference with 0.04% adenosine aqueous solution, whereas Experimental Examples 5 and 6 showed average 75% skin permeability. This resulted in an increase in skin permeability of about 50% or more relative to an aqueous 0.04% adenosine solution, thereby improving skin permeation of the active ingredient supported on the pH-sensitive nanoparticles.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (10)

PH-sensitive nanoparticles and phospholipids, glycolipids, fatty acids, including (meth) acrylic acid or (meth) acrylate compounds with a skin active ingredient selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol A cosmetic composition containing a bio-like surfactant selected from the group consisting of lipopeptides, lipoproteins, lipopolysaccharides, sugar esters, and lipids.
The compound according to claim 1, wherein the (meth) acrylate compound is methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acryl Late, t-butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, n-octyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, 2-hydroxy Ethyl (meth) acrylate, poly (ethylene glycol) (meth) acrylate, methoxy polyyl (ethylene glycol) (meth) acrylate, glycidyl (meth) acrylate, dimethyl aminoethyl (meth) acrylate, di Cosmetics, characterized in that one or more compounds selected from the group consisting of ethyl aminoethyl (meth) acrylate, glycol di (meth) acrylate, allyl (meth) acrylate or n-alkyl (meth) acrylate Cosmetic composition.
delete delete The cosmetic composition with improved skin permeability according to claim 1, further comprising an acid solution or a base solution for pH adjustment.
PH-sensitive nanoparticles and phospholipids, glycolipids, fatty acids, including (meth) acrylic acid or (meth) acrylate compounds with a skin active ingredient selected from the group consisting of arbutin, adenosine, niacinamide and alpha-bisabotol A method for producing a cosmetic composition containing a bio-like surfactant selected from the group consisting of lipopeptides, lipoproteins, lipopolysaccharides, sugar esters, and lipids.
The compound according to claim 6, wherein the (meth) acrylate compound is methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acryl Late, t-butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, n-octyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, 2-hydroxy Ethyl (meth) acrylate, poly (ethylene glycol) (meth) acrylate, methoxy polyyl (ethylene glycol) (meth) acrylate, glycidyl (meth) acrylate, dimethyl aminoethyl (meth) acrylate, di Cosmetics, characterized in that one or more compounds selected from the group consisting of ethyl aminoethyl (meth) acrylate, glycol di (meth) acrylate, allyl (meth) acrylate or n-alkyl (meth) acrylate Method for producing a food composition.
delete delete The method for preparing a cosmetic composition having improved skin permeability according to claim 6, wherein an acid solution or a base solution is further added to adjust pH.