KR100348826B1 - A Method for Manufacturing a Cosmetic Composition of o/w Type with Improved Skin-Absorption of an Aqueous Nutritional Supplement - Google Patents

Abstract

The present invention relates to a method for producing an oil-in-water cosmetic composition with improved skin absorption of the water-soluble active ingredient, the method according to the present invention comprises a dissolving step of dissolving the water-soluble active ingredient in a solvent consisting of a mixture of water and ethanol; Capturing the water-soluble active ingredient in the porous microbeads by physically contacting the porous microbeads having a pore volume of 0.1 to 50 μg / g to the solution in which the water-soluble active ingredient is dissolved; A drying step of separating only the porous microbeads in which the active ingredient is collected through filtration after the collecting step and then removing excess solvent adsorbed in the pores together with the water-soluble active ingredient through a process of vacuum drying, freeze drying or washing; And an addition step of adding the porous microbeads, which have been subjected to the drying step, to the active ingredient-collected porous microbeads to the aqueous phase of the oil-in-water cosmetic composition.

The present invention does not destroy the structure of the stratum corneum in the mechanism of skin absorption enhancement, so that there is almost no problem such as skin irritation, and even at low concentration, a water-soluble active ingredient having low affinity with the stratum corneum is effectively applied to the skin through hydrophobic porous microbeads. Can be absorbed.

Description

A method for manufacturing a cosmetic composition of o / w type with improved skin-absorption of an aqueous nutritional supplement}

The present invention is a method for enhancing skin absorption by trapping a water-soluble active ingredient, such as L-ascolic acid in the pores of a hydrophobic porous microbead, and a cosmetic or dermatological external preparation comprising a water-soluble active ingredient prepared by such a method as an active ingredient. It relates to a composition.

More specifically, the present invention relates to a method for encapsulating a water-soluble active ingredient in pores of a hydrophobic porous microbead, dissolving the water-soluble active ingredient in a solvent composed of a mixture of water and ethanol, and physically dissolving the porous microbead and the water-soluble active ingredient solution. It relates to a method comprising the step of contacting.

The skin is composed of three parts, stratum corneum, epidermis and dermis, and the stratum corneum is present at the outermost skin. In skin absorption of substances, the first barrier is the stratum corneum, and the stratum corneum is composed of keratin cells mainly composed of keratin proteins and lipid layers constituting the keratinocytes. In the skin absorption of the substance it is very difficult to absorb the substance through the keratinocytes, and the pathway through the lipid layer between the keratinocytes is known to be common. Therefore, while skin absorption of fat-soluble substances such as tocopherol or retinoid is relatively smooth, water-soluble substances that are difficult to distribute to lipid layers are generally known to have very low absorption.

Another route in the skin absorption of the substance is through the pores open to the outside, such as sweat glands and pores, the proportion of pores or sweat glands of the total skin area is very small, generally contributes greatly to the skin absorption of the substance It is not known.

On the other hand, water-soluble active ingredients that can be applied to the skin and exhibit a certain effect include L-ascorbic acid and its water-soluble derivatives, vitamin B group, kojic acid, kojiccapic acid, kozylaminopropyl phosphate, arbutin and water-soluble natural extracts. .

In particular, L-ascorbic acid (vitamin C) is a kind of water-soluble vitamins, essential ingredients for human life or one of the essential vitamins that are not synthesized in the body to be consumed from the outside. In addition, L-ascorbic acid has been known to have various physiological effects on the skin such as whitening, wrinkle improvement, skin elasticity, and removal of harmful oxygen from the past, and has been used as an active ingredient in cosmetic or topical dermatological preparations. However, L-ascorbic acid is a representative water-soluble vitamin that has a solubility in water of about 30% by weight at room temperature, and despite its potentially various skin effects, it has been difficult to be effectively used as a cosmetic or dermatological agent until now. .

As such, the water-soluble active ingredients such as L-ascorbic acid are hydrophilic components having high polarity and high solubility in water, and thus have low skin affinity and thus do not penetrate into the skin during skin application, or only a very small portion thereof.

On the other hand, in order to realize the skin collagen synthetizing or tyrosinase specific to the L- ascorbic acid, the improvement of wrinkles through melanin synthesis intermediate reduction, whitening effect, etc., absorption to the base or dermis layer of the epidermis should be made. It is known that skin absorption occurs to some extent when a high concentration of L-ascorbic acid is applied or applied to the skin for a long time, but in this case, significant skin irritation is expected due to a decrease in skin pH caused by L-ascorbic acid. Therefore, there is a high demand for skin absorption enhancement technology that enables effective skin absorption even at low concentrations.

Methods for imparting sonophoresis or microiontophoresis to the skin to enhance the skin absorption of L-ascorbic acid are known [Sloan JB, Slotani K. Iontophoresis in dermatology: a review, J. Am. Acad.Dermatol. 1986, 4: 671; Langer R. Ultrasound-mediated transdermal protein delivery Science 1995; 269: 850], such methods are difficult to apply to cosmetic or dermatological external preparations due to the need for expensive equipment. There is also known a method of adding an organic solvent, a surfactant, or a lower fatty acid which has a skin absorption promoting effect to a composition containing L-ascolic acid [Chen LH, Chien YW, Enhancement of skin penetration In Novel cosmetic delivery systems 1999, 60; Rhein LD, Robbins CR, Fernee K, Cantore R. Surfactant structure effects on swelling of isolated human stratum corneum, J. Soc Cosmet Chem 1986; 37: 125; Cooper ER, Merritt EW, Smith RL. Effect of fatty acids and alcohols on the penetration of acyclovir across human skin in vitro J. Pharm Sci 1985; 74: 688], the types and contents of organic solvents applicable to cosmetics and external preparations are regulated, and most organic solvents, surfactants, and lower fatty acids, which have a percutaneous absorption promoting effect, destroy the structure of the stratum corneum. There is a problem in that it often causes skin irritation. In addition, cosmetic compositions using patch preparations, liposomes, or cyclodextrins containing high concentrations of L-ascorbic acid have been developed and sold on the market, but the absorption of L-ascorbic acid in these formulations has been objectively demonstrated. It is difficult to judge the efficacy of these formulations.

On the other hand, there is a known technique for sustained release by capturing the active ingredient in the porous microbeads, but this method reduces the release rate from the microbeads of fat-soluble substances such as retinol to reduce irritation and increase the contact time with the skin (US Pat. No. 5,145,675), which is characterized by facilitating the formulation of materials that are difficult to formulate as external preparations or by stabilizing an unstable fat-soluble component from an external base (US Pat. No. 5,703,041).

The above known techniques mainly target fat-soluble active ingredients which are relatively easy to absorb skin, and isolate them from the external environment by controlling the release rate of fat-soluble active ingredients from the microbeads, or by adsorption or collection. It is intended to be used only, and microbeads have not been used to enhance skin absorption of water-soluble components that are difficult to absorb skin, such as L-ascorbic acid. In addition, in the case of capturing the fat-soluble component into the pores of the hydrophobic microbeads, no special technique is required, but in the case of the water-soluble active ingredient, the collection rate of the active ingredient may vary greatly depending on which solvent is selected.

Therefore, the present invention is a water-soluble active ingredient, such as L- ascorbic acid is low in the affinity with the stratum corneum layer, the skin is not absorbed or only part of the skin is absorbed to the active effect of the active ingredient as an active ingredient of cosmetic or dermatological composition for dermatology In order to solve the difficult to implement as, the water-soluble active ingredient by encapsulating in the pores of the hydrophobic porous microbeads to improve the degree of skin absorption.

In order to solve the above problems, a method for preparing an oil-in-water cosmetic composition with improved skin absorption of the water-soluble active ingredient according to the present invention includes a dissolving step of dissolving the water-soluble active ingredient in a solvent composed of a mixture of water and ethanol; Capturing the water-soluble active ingredient in the porous microbeads by physically contacting the porous microbeads having a pore volume of 0.1 to 50 μg / g to the solution in which the water-soluble active ingredient is dissolved; A drying step of separating only the porous microbeads in which the active ingredient is collected through filtration after the collecting step and then removing excess solvent adsorbed in the pores together with the water-soluble active ingredient through a process of vacuum drying, freeze drying or washing; And an addition step of adding the porous microbeads, which have been subjected to the drying step, to the active ingredient-collected porous microbeads, to the aqueous phase, which is an external agent of the oil-in-water cosmetic composition. The content of ethanol in the water is characterized in that 5 to 95% by weight.

According to the present invention, a method for capturing an active ingredient in a pore of a hydrophobic porous microbead by dissolving the water-soluble active ingredient in a solvent composed of a mixture of water and ethanol and physically dissolving the porous microbead and the water-soluble active ingredient solution The first step is to adsorb the active ingredient in the pores of the porous microbeads by contact, and to separate only the porous microbeads through filtration, and then adsorbed in the pores with the active ingredient through a process such as vacuum drying, lyophilization or washing The method may further include a second step of removing excess solvent. Furthermore, when the active ingredient collected in the porous microbead is added to the cosmetic or dermatological external preparation composition as an active ingredient, the void of the porous microbead pores is an oil which is incompatible with the water-soluble active ingredient to prevent excessive leakage of the water-soluble active ingredient. An additional third step of filling the space may optionally be added.

The method of collecting the water-soluble active ingredient in the pores of the hydrophobic porous microbeads is as follows.

Porous microbeads that can be used in the present invention are those produced while the following high molecular polymers or copolymers form voids through three-dimensional crosslinking. Such polymers or copolymers include silica, alumina, cellulose and derivatives thereof, polyamides (nylon-11, nylon-12, nylon-6, nylon-6,6), polyimide, polyethylene, polypropylene, polystyrene, polyester , Divinylbenzene, vinyl stearic acid, 4-vinylpyridine, ethylene glycol dimethacrylic acid, methyl methacrylic acid, methacrylic acid, allyl methacrylic acid and the like, but is not limited thereto. All the above polymers or copolymers can be easily purchased on the market, and porous microbeads formed through three-dimensional crosslinking can also be easily purchased on the market, and those skilled in the art can chemically synthesize them. Can be. In addition, a technique for preparing porous microbeads using the above polymer or copolymer is known (US Pat. No. 5,145,675).

The diameter of the porous microbeads used in the present invention is preferably 5 to 100 μm, and in particular, 10 to 50 μm, in order to be uniformly distributed on the surface of the skin without the unpleasant feeling peculiar to the powder when added to the cosmetic composition and applied to the skin. Is preferred. The pore volume in the porous microbeads is preferably 0.1 to 50 dl / g, and if the pore volume is too low, the adsorption amount of the active substance will be lowered. If the pore volume is too large, the mechanical strength of the microbeads will be lowered. g is preferred.

Adsorption into the porous microbead pores is generally accomplished by physical contact between the porous microbeads and a solution of the active ingredient. In order to facilitate the adsorption, a method such as stirring, warming or adding a surfactant to the porous microbead dispersion may be employed. Conventional capture methods have been previously reported (William Klein and Alfred DiSapio, 1989, HAPPI magazine, 26: 7; U.S. Patent 5,145,675), but the adsorption rate per unit weight of porous microbeads depends on the properties of the active ingredient and the choice of solvent. This can change.

Solvents that can be used for the adsorption of the active ingredient may be water, methanol, ethanol, glycerin, acetone, butylene glycol, propylene glycol, or the like alone or in a mixture of two or more thereof. In the case of water-soluble active ingredients having very high solubility in water and low solubility in other solvents, such as L-ascorbic acid, the higher the water content in the mixed solvent, the higher the solubility in the solvent, and thus the collection rate into the microbeads. Is higher. However, since the microbeads used are hydrophobic, when the water content is too high, the microbeads may not be uniformly dispersed in the solvent, and thus the collection rate may be deteriorated. Therefore, it is necessary to appropriately adjust the content of water in the mixed solvent. Solvents such as acetone and methanol are toxic to the human body and must be completely removed after adsorption. Solvents such as glycerin, butylene glycol and propylene glycol have problems such as difficulty in filtration due to viscosity increase and skin irritation. Therefore, it is preferable to use a mixture of water and ethanol for collecting the water-soluble active ingredient. The content of ethanol in the mixture is 5 to 95% by weight. In the case of using a solvent in which water and ethanol are mixed in a weight ratio of 70:30, when using porous microbeads composed of methacrylic acid-based polymer, an adsorption rate of about 50 to 90% by weight can be obtained.

The collected porous microbeads are subjected to atmospheric pressure, under vacuum or lyophilization to remove excess solvent present in the voids. However, this may be omitted in cases where the extra solvent present in the void does not have a human health problem or does not affect the properties of the final composition containing the microbeads.

On the other hand, when the water-soluble active ingredient-containing porous microbead prepared according to the present invention is added to the cosmetic and dermatological external preparations, the skin absorption is different depending on whether the position is added in the water-in-oil composition in general. In the case of porous microbeads containing L-ascorbic acid, it is best to add it to the external water phase for water-in-oil cosmetics. On the other hand, when the water-soluble active ingredient-containing porous microbead prepared according to the present invention is added to the cosmetic and dermatological external preparations, the skin absorption is different depending on whether the position is added in the general oil-in-water composition. In the case of porous microbeads containing L-ascorbic acid, it is best to add it to the external water phase for water-in-oil cosmetics.

The method of adding the porous microbeads containing the water-soluble active ingredient to the outer phase of the oil-in-water composition is as described in the following examples.

As described above, when the water-soluble active ingredient such as L-ascolic acid is collected in the hydrophobic porous microbead and added to the cosmetic and dermatological external preparation composition, enhancement of skin absorption can be predicted through the following formula.

Skin absorption of drugs generally occurs through passive diffusion mechanism, and the formula describing this is as follows.

J =-D × dC / dX

J: Mass transfer flux of the drug

D: diffusion coefficient of drug

C: concentration of the drug

X: Movement distance of drug

Equation 1 can be modified as follows in skin absorption.

J = K × DSC / h × dC

K: Partition coefficient between the drug base and the stratum corneum

D: diffusion coefficient of drug in the stratum corneum

h: thickness of the stratum corneum

Based on Equation 2, methods for enhancing skin absorption can be broadly classified into a method of enhancing the distribution of the drug to the stratum corneum, enhancement of the diffusion coefficient of the drug by modifying the stratum corneum structure, removal of the stratum corneum, and an increase in the application concentration. Of these methods, the structural modification of the stratum corneum or the removal of the stratum corneum is generally associated with skin irritation. If the drug itself causes skin irritation, there is a risk of skin irritation even if the application concentration is increased. Therefore, the most effective method of enhancing skin absorption is to enhance the partition coefficient between the drug and the stratum corneum. In particular, in the case of water-soluble substances such as L-ascorbic acid, one of the main causes of low skin absorption is known as the low distribution of the stratum corneum of the drug, so the method of enhancing the distribution coefficient of the active ingredient in the stratum corneum is to promote skin absorption. It can be very effective. In the present invention, by trapping a water-soluble substance such as L- ascorbic acid in the hydrophobic porous microbead having a high degree of distribution to the stratum corneum, it is a method of increasing the distribution of the stratum corneum of the active substance and ultimately enhancing the skin absorption of the active substance. . Therefore, it is expected that the skin absorption enhancing effect of the present invention is not limited to L-ascorbic acid, but can be effectively applied to other water-soluble active ingredients having high polarity and which are difficult to distribute to the stratum corneum.

Other water-soluble active ingredients applicable to the present invention include water-soluble derivatives of L-ascorbic acid, such as L-ascorbyl phosphate and L-ascorbyl glucoside, vitamin B group, kojic acid, kojal capic acid, and kojalaminopropyl phosphate. , Arbutin and the like, and water soluble natural extracts extracted from natural products such as green tea and grape seeds with polar solvents such as water or ethanol are also applicable. Examples of water-soluble natural extracts include oligoproanthocyanidins extracted from water or ethanol alone or in mixtures from grape seeds.

Hereinafter will be described in detail the configuration and effect of the present invention through the examples, the present invention is not limited to these examples.

Example 1 Preparation of Porous Microbeads Containing L-Ascorbic Acid

In a solvent in which water and ethanol were mixed at a weight ratio of 70:30, the L-ascorbic acid powder was dissolved to 20% by weight to prepare 500 ml of L-ascorbic acid solution. To the L-ascorbic acid solution, 10 g of porous microbeads consisting of three-dimensional crosslinking of allylmethacrylic acid polymer was added and then dispersed completely with stirring at a speed of 150 rpm. The resulting dispersion was filtered to separate the porous microbeads, and the porous microbeads obtained therefrom were lyophilized for 2 days. The L-ascorbic acid content after freeze-drying was 35% by weight.

<Example 2: Preparation of oil-in-water cosmetic composition containing the porous microbeads collected L- ascorbic acid contained in the outer phase>

A cosmetic composition was prepared as follows.

Oil type cosmetic composition ingredient weight% One Stearic acid 1.0 2 Cetostearyl alcohol 0.7 3 Microcrystalline Lead 0.2 4 Glycerin Monostearate 0.5 5 Liquid paraffin 5.0 6 Sorbate monostearate 0.3 7 Squalane 3.5 8 Purified water To 100 9 Concentrated glycerin 6.5 10 Hyruronic Extract 0.5 11 Sepigel 350 0.7 12 incense Quantity 13 antiseptic Quantity

The preparation method of the oil-in-water cosmetic composition is as follows.

1) Heat A (components 1-7) and B (components 8-10) to 75 ° C, respectively.

2) Add A little by little and emulsify at 7000 rpm speed. Immediately after adding the entire amount of A, component 12 and component 13 were added, followed by emulsification for 2 minutes.

3) The component 11 is added and then emulsified and stirred for 2 minutes.

4) Degas the composition by stirring at 2500 rpm for 1 minute.

5) The beaker containing the composition is immersed in ice water and cooled to 28-30 ° C.

6) The prepared composition is stabilized by standing at room temperature for 24 hours.

To the oil-in-water cosmetic composition prepared as described above was added to the microbead prepared in Example 1 to 2.5% by weight, and stirred at 150 rpm to homogenize.

<Example 3: Preparation of oil-in-water cosmetic composition containing the porous microbeads collected L- ascorbic acid in the inner phase>

It is the same as Example 2 except that the porous microbeads containing L-ascorbic acid are first added to 5% by weight of A, followed by stirring at a speed of 150 rpm.

Comparative Example 1

To the composition of Example 2, instead of the L- ascorbic acid-containing microbeads of Example 1 to add 1% by weight of the powder of L- ascorbic acid was homogenized by stirring at a speed of 150 rpm.

Comparative Example 2

To the composition of Example 2, instead of the L- ascorbic acid-containing microbeads of Example 1 to add 10% by weight of L- ascorbic acid powder, it was homogenized by stirring at 150 rpm.

Comparative Example 3

Ethoxydiglycol was added to the composition of Example 2 in an amount of 25% by weight instead of the L-ascorbic acid-containing microbead of Example 1, followed by homogenization by stirring at 150 rpm. Ethoxydiglycol is a substance that promotes skin absorption by modifying the structure of the stratum corneum.

Experiment 1: Skin Permeation Measurement of L-Ascorbic Acid

Skin permeation of L-ascorbic acid was measured using Franz permeable cells in guinea pig skin. Immediately before the experiment, the abdominal skin of the guinea pig was taken and cut into an area of 1 cm 2, which was then placed in a transmission cell having a diameter of 0.9 cm and fixed with a clamp. 0.5 ml of L-ascorbic acid solution or composition (Examples 2 and 3, Comparative Examples 1 to 3) to be measured is applied to one side of the skin, and the other side is a solvent in which purified water and glycerin are mixed in a 1: 1 weight ratio (C ) In contact with Experimental temperature was maintained at 32 ℃, the actual skin temperature. After the start of the experiment, a portion of the C was taken at regular intervals and the amount of L-ascorbic acid that penetrated the skin was measured using HPLC. The results are shown in Table 2.

Skin permeation of L-ascorbic acid per application concentration (wt%) (mg / cm2 / wt%) time Comparative Example 1 Comparative Example 2 Comparative Example 3 Example 2 Example 3 0 0 0 0 0 0 4 0 1.42 1.65 96.15 6.95 8 0 3.09 8.90 185.98 13.83 24 0 15.11 62.47 308.13 31.27

Given that the duration of makeup in general is between 4 hours and 8 hours, from Table 2, the degree of skin absorption of L-ascorbic acid, when collected in hydrophobic porous microbeads, is added to the outer layer of the oil-in-water composition, L -Ascorbic acid can be seen to increase at least 60 times more than when added directly to the composition.

When the percutaneous absorption enhancer (Comparative Example 3) was added, the percutaneous absorption was observed from 8 hours after application.However, after 24 hours after application, the skin of the guinea pig was removed from the Franz transmission cell and visually observed. Swelling was observed, and collagen mucus leaked out of the dermis. From this, skin damage can be predicted when the percutaneous absorption accelerator is added as a base.

Comparing the results of Example 2 and Example 3, when the porous microbeads containing L-ascorbic acid were added to the water-in-oil type composition, it was found that adding to the external wound was more effective in terms of skin absorption than adding to the internal wound. Able to know.

In the case of Example 2 and Example 3, the skin of Guinea Pig, which was 24 hours after application, was taken out of the Franz transmission cell and visually observed, and no difference was found in appearance compared to normal skin. From this, it can be predicted that porous microbeads containing L-ascorbic acid do not cause special skin damage. In addition, the composition of Example 2 and Example 3 on the back of the live hairless mouse was applied to the same site 300 ml once a day for 30 days. Skin irritation such as swelling and erythema was visually observed every day, but no symptoms were observed.

According to the present invention, water and ethanol are used as a solvent to collect a water-soluble active ingredient such as L-ascorbic acid into a porous microbead having hydrophobicity, and then added to a cosmetic or dermatological external preparation composition, thereby to obtain a water-soluble like L-ascoholic acid. Skin absorption was enhanced by enhancing the affinity between the active ingredient and the stratum corneum.

The present invention does not destroy the structure of the stratum corneum in the mechanism of skin absorption enhancement, so that there is almost no problem such as skin irritation, and even at low concentration, a water-soluble active ingredient having low affinity with the stratum corneum is effectively applied to the skin through hydrophobic porous microbeads. Can be absorbed.

Claims (6)

In the method for producing an oil-in-water cosmetic composition with improved skin absorption of the water-soluble active ingredient, A dissolving step of dissolving the water-soluble active ingredient in a solvent composed of a mixture of water and ethanol; Capturing the water-soluble active ingredient in the porous microbeads by physically contacting the porous microbeads having a pore volume of 0.1 to 50 μg / g to the solution in which the water-soluble active ingredient is dissolved; A drying step of separating only the porous microbeads in which the active ingredient is collected through filtration after the collecting step, and then removing excess solvent adsorbed in the pores together with the water-soluble active ingredient through a process of vacuum drying, freeze drying or washing ; And The oil-in-water cosmetic composition of the improved water absorption of the water-soluble active ingredient, characterized in that it comprises the addition step of adding the porous microbeads, the active ingredient collected through the drying step, to the aqueous phase of the water-in-oil cosmetic composition Manufacturing method. The method of claim 1, wherein the content of ethanol to water is 5 to 95% by weight. delete delete delete delete