KR100970922B1 - Patch compositions being capable of phase transition at body temperature and improving skin elasticity, moisturization and drug penetration - Google Patents

Abstract

The present invention is a patch formulation composition of a new type to form a gel patch by the phase change from the liquid state to the gel (Gel) at the skin temperature, in particular to prevent the evaporation of the water contained in the phase change to the gel state to moisturize It is excellent in effect, it gives skin elasticity while maintaining gel structure, and at the same time, it is easy to deliver drug by pressure through patch formation, and it is easy to apply on the skin and relatively large amount of moisturizing ingredient and physiology It is easy to encapsulate the active material into small nano-sized particles with almost solubilization levels. After application to the skin, the polymer micelle structure changes to network due to skin temperature. It forms a patch of gel, and this patch of gel prevents evaporation of water, so it has excellent moisturizing effect and gives skin elasticity while maintaining gel structure. And, at the same time it consists in that facilitates the delivery of drugs at a pressure through a patch form.

Sol-Gel, Phase Transition, Patch, Polymeric Surfactant, Moisturizing, Elasticity Enhancement

Description

Patch compositions being capable of phase transition at body temperature and improving skin elasticity, moisturization and drug penetration}

The present invention relates to a patch composition for promoting skin elasticity, moisturizing and drug penetration that can be phase-transformed at body temperature, and a method of manufacturing the same, and in particular, to prevent evaporation of water contained in the phase-change in a gel state, and excellent in moisturizing effect. The present invention relates to a patch composition capable of imparting skin elasticity and maintaining the drug at the same time and facilitating delivery of the drug under pressure through patch formation.

Humans have been doing their best to protect themselves from aging, disasters and diseases, and to solve many problems, long since the establishment of the abstract system of culture, especially as women get older. Suffering from the various symptoms of aging (dryness, loss of elasticity, wrinkle formation, skin swelling, etc.) that are gradually felt, many efforts have been made to delay and improve it. In particular, as the standard of living improved, those in their twenties, thirties, and forties were breaking away from their main consumers, and older women in their fifties and sixties, who had become more adolescents and had given up, expressed their passion for their skin and beauty. In addition, even younger teenagers are actively interested in them, and the interest and demand for skin care cosmetics, which are mainly functional cosmetics, have exploded and have become a big part of the world. Accordingly, in recent years, consumers are increasingly interested in products having unique characteristics with multi-functions that visually differentiate and provide various effects at the same time. Products with unusual characteristics, such as similar to the actual eating products are gaining popularity, and products that simultaneously give the effect of skin and lotion to one product are receiving a good response in the cosmetics market.

However, it is possible to give the product a specificity that distinguishes it from other products, but in fact, by linking it with the efficacy of cosmetics, specific products that give consumers confidence with visual effects as well as fast and recognizable skin improvement effects It is virtually absent.

On the other hand, briefly introducing the technology of the conventional medicine field as follows.

In the case of injection or oral administration commonly used to administer the drug, the drug spreads throughout the system, so that the amount actually administered to the diseased area is only a very small amount, the bioavailability is low, and the therapeutic effect is insignificant. In order to solve this problem, the drug is encapsulated in a high biocompatibility polymer material and formulated into a form that can be administered locally using a syringe, and when injected into the skin from an easy-to-administer liquid formulation, it is solidified by the temperature in the skin. We have studied and commercialized grafts with topical graft sustained-release drug release effect to release slowly and continuously in affected area. Looking at these conventional techniques, biodegradable polymers include, for example, polypeptides, polyaminoacids, polysaccharides, polysaccharides, polyglycolic acids, and polylactic acids. Most of them have characteristics of low critical solution temperature (LCST), which phase change into liquid phase below a certain temperature and gel phase above a certain temperature by using the strength in aqueous solution of hydrophilic and lipophilic groups in polymer. May appear.

However, since the above-described conventional techniques have not been studied as external preparations for application on the skin, most of the low-critical solution temperature is controlled to be above 35 ° C. Although it is from 38 ℃, the outermost skin of the human body, although there is a difference depending on the ambient temperature, there is a problem that is difficult to use because it is a low temperature of 27 to 32 ℃. In addition, the conventional techniques are to be refrigerated and the therapeutic drug itself, there was a problem to apply to the cosmetics that may be left at room temperature or high temperature.

The present invention has been made to solve the problems of the prior art as described above, the technique to be applied in the present invention is to be applied to a cosmetic applying a film-type drug delivery technology that is actively studied in the pharmaceutical field on the skin In particular, in order to apply to cosmetics that have virtually no special temperature storage conditions, it is possible to control the low-critical solution temperature according to the various effects to obtain as a cosmetic for each composition by adjusting the suitable polymer type surfactant and their composition ratio In addition, it was also intended to solve a new technical problem that can also control the properties of changing from a liquid phase to a gel phase, and conversely restored to a liquid phase from a gel phase. In addition, in order to maximize the effect obtained when applying cosmetics to the skin, it is possible to maximize the time that the gel is formed and maintained in the air, and the patch composition to promote skin elasticity, moisturizing and drug penetration that can be phase-transformed at body temperature, and a method of manufacturing the same. The purpose is to provide.

Accordingly, the present invention, as a result of the efforts to solve the above problems, as a gel phase (gel) phase changes from the liquid state at the skin temperature to form a gel patch (Gel patch) of a new type, in particular gel state It is characterized in that it is excellent in moisturizing effect by preventing evaporation of the water contained in the phase change while maintaining the gel structure, and at the same time, facilitates drug delivery by pressure through patch formation.

Patch composition to promote skin elasticity, moisturizing and drug penetration capable of phase transition at body temperature according to the present invention, 40.0 to 75.0 parts by weight of water, 2.0 to 10.0 parts by weight of water-soluble moisturizer, 5.0 to 30.0 parts by weight of polymer surfactant, powder form 0.1 to 5.0 parts by weight of a moisturizing agent, 0.01 to 3.0 parts by weight of the powdered bioactive material and 0.01 to 10.0 parts by weight of the bioactive material is characterized in that it is made.

The water-soluble moisturizing agent may be selected from the group consisting of glycerin, diglycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, di-panthenol, 1,2-pentanediol or a mixture of two or more thereof. .

The polymeric surfactant is represented by the following Chemical Formula 1, wherein the ratio (a / b) of the hydrophilic group (a) and the lipophilic group (b) may be within 1.0 to 2.5.

The polymeric surfactant is poloxamer 124 (a = 11, b = 21), poloxamer 188 (a = 70, b = 30), poloxamer 217 (a = 52, b = 35), poloxamer 237 (a = 62, b = 39), poloxamer 238 (a = 97, b = 39), poloxamer 338 (a = 128, b = 54), poloxamer 407 (a = 98, b = 67) or two of them It may be selected from the group consisting of a combination of two or more mixtures.

Powder moisturizers in the group consisting of amino acids such as glycine, glutamic acid, arginine, lysine and sugars such as galactose-glucose-protose, fucose, pentaerythritol, sucrose, mannitol, sorbitol, or mixtures of two or more thereof Can be selected.

Powdered bioactive substance is vitamin C and its derivatives, arbutin, adenosine, niacinamide, N-acetylglucosamine, allantoin, madecasoside, copper peptide ( Copper peptide), ectoin, or a mixture of two or more thereof.

In the above bioactive substances are cactus, aloe, grapefruit bark, machi, chamomile, plant extracts including hollyhock extract, matrixyl (Matrixyl, palmitoyl pentapeptide-3), iris (Eyeliss, France SEDERMA company), agireline ( Peptides such as Argireline, LIPOTEC, USA, Haroxyl (SEDERMA, France), Legu-AGE (REGU-AGE, PENTAPHARM, Switzerland), Extensin (PROVITAL, Spain) and collagen, EGF, fullerene Fulleren or a mixture of two or more thereof.

The patch composition may further include an additive mixture in which 0.01 to 0.5 parts by weight of preservative and 0.01 to 0.5 parts by weight of ethanol are dissolved in 1.0 to 15.0 parts by weight of ethanol.

In addition, the method of producing a patch composition that promotes skin elasticity, moisturizing and drug penetration capable of phase transition at body temperature of the present invention, in the preparation of a patch composition that changes from a liquid to a gel phase by the body temperature on the skin, (1) water 40.0 To 75.0 parts by weight and 2.0 to 10.0 parts by weight of a water-soluble moisturizer are cooled to 15 ° C. to 0 ° C., and 5.0 to 30.0 parts by weight of the polymeric surfactant is added thereto, followed by dissolving a polymer surfactant dissolving part to obtain a first mixture. ; (2) dissolving powder part to obtain a second mixture by dissolving 0.1 to 5.0 parts by weight of a moisturizer in powder form and 0.01 to 3.0 parts by weight of powdered bioactive substance in the first mixture obtained in step (1); And (3) adding 0.01 to 10.0 parts by weight of the bioactive material to the second mixture obtained in step (2) and homogenizing the bioactive material homogenizing step to obtain a patch composition.

An additive mixing step of further mixing the additive mixture dissolved in 0.01 to 0.5 parts by weight and 0.01 to 0.5 parts by weight of preservatives in 1.0 to 15.0 parts by weight of ethanol between the step (2) and step (3); .

Therefore, according to the present invention, it is excellent to moisturize by preventing evaporation of the water contained in the phase change to a gel state, to impart skin elasticity while maintaining the gel structure, and at the same time to facilitate the delivery of drugs by pressure through patch formation. There is an effect of providing a possible patch composition and a method of manufacturing the same.

In particular, the skin elasticity and moisturizing sol-gel patch composition obtained in accordance with the present invention is easy to apply evenly on the skin by maintaining a liquid state at room temperature and low temperature, and almost dissolves a relatively large amount of moisturizing ingredients and bioactive substances ( It is easy to encapsulate into small nano size that is transparent at the level of solubilization, and after application to the skin, the micelle structure of the polymer is changed into a network by the skin temperature to form a patch on the gel. The patch on the top prevents the evaporation of water, so it has an excellent moisturizing effect, imparts skin elasticity while maintaining the gel structure, and at the same time, facilitates skin penetration of bioactive substances having sustained release by forming a shielding film through patch formation and osmotic pressure through the patch. There is a characteristic. Therefore, in the case of using the present invention, the specific form that is transformed from the liquid phase into the gel phase by the body temperature above the skin, as well as the moisturizing effect and physical elasticity promoting effect, as well as physiologically active substances over a relatively long time to exert the desired skin improvement effect It is possible to make a sol-gel patch product having a liquid form.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

Unless otherwise defined in the technical and scientific terms used herein, the present invention has the meanings that are commonly understood by those skilled in the art. Repeated descriptions of the same technical constitution and operation as those of the conventional art will be omitted.

Patch composition to promote skin elasticity, moisturizing and drug penetration capable of phase transition at body temperature according to the present invention, 40.0 to 75.0 parts by weight of water, 2.0 to 10.0 parts by weight of water-soluble moisturizer, 5.0 to 30.0 parts by weight of polymer surfactant, powder form 0.1 to 5.0 parts by weight of a moisturizing agent, 0.01 to 3.0 parts by weight of a powdered bioactive material and 0.01 to 10.0 parts by weight of a bioactive material, characterized in that made.

The water-soluble moisturizer is used for the purpose of helping to dissolve the polymer-based surfactants described later, to impart a moisturizing effect to the skin, glycerin, diglycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, di- Although selected from the group consisting of panthenol, 1,2-pentanediol or a mixture of two or more thereof, it may be used according to the desired feeling, but if it is less than the above-mentioned content, there may be a problem that the moisturizing effect is insignificant, and vice versa. If the content is more than one, there may be a problem in that the solubility of the polymer surfactant is excessively increased to hinder gel formation.

In the polymer type surfactant, the patch composition according to the present invention is a main component that changes from a liquid phase to a gel phase by the temperature on the skin of the user, and the polymer type surfactant is a copolymer having a plurality of intramolecular hydrophilic groups and hydrophilic groups. In case the temperature is low, the hydrophilicity of ethylene oxide and propylene oxide, which is repeated in the middle of the chain and the hydroxy group of the sock end, becomes stronger, maintaining a completely dissolved liquid state. When the temperature rises above the low-critical solution temperature, the hydrogen bonding force between the hydrophilic groups and the water is weakened, so that the relatively lipophilic propylene oxides themselves form chain aggregates to form a kind of network structure. It serves to make a gel having, as shown in the following formula (1), Depending on the number (a) and the number of lipophilic groups (b), the hydrophilic group (a) has 10 to 130, and the lipophilic group (b) has a hydrophilic group (a) in a commonly commercially available poloxamer having 20 to 80 Poloxamer 124 (a = 11, b = 21), poloxamer 188 (a = 70, b = 30) and poloxamer 217 (a / b) of 1.0 to 2.5 a = 52, b = 35), Poloxamer 237 (a = 62, b = 39), Poloxamer 238 (a = 97, b = 39), Poloxamer 338 (a = 128, b = 54), Poloxamer 407 (a = 98, b = 67) or a group selected from a combination of two or more thereof may be used. If the ratio (a / b) of the hydrophilic group and the lipophilic group is less than 1.0, the strength of the lipophilic group is relatively large and there may be a problem in solubility in water. On the contrary, if the ratio of the hydrophilic group and the lipophilic group (a / b) exceeds 2.5, There may be a problem that the strength of the lipophilic organ is too small so that the gel formation through the sol-gel transition is insufficient at the temperature on the skin.

[Formula 1]

In addition, when the polymeric surfactant is less than the above-mentioned amount, there may be a problem that the phenomenon of changing to a gel phase due to the temperature on the skin is not enough, on the contrary, when more than the above-mentioned content, it is difficult to dissolve properly, Even if it is dissolved, it may have a problem that the gel becomes too low at room temperature because it has a low critical solution temperature.

Water as the main solvent for dissolving the polymer emulsifier may have a problem that the polymer emulsifier is not completely dissolved when it is lower than the above-mentioned content, on the contrary, when the water content is higher than the above-mentioned content, the concentration of the polymer emulsifier is Low gel formation through sol-gel transition at a temperature above the skin is not easy, even if the gel may have a problem that the effect is not enough.

The powdery moisturizer acts as an internal moisturizer that penetrates into the skin and supplies moisture after gel formation, and amino acids such as glycine, glutamic acid, arginine, and lysine, and galactose-glucose-fructose, fucose, and pentaerythritol. , Selected from the group consisting of saccharides such as sucrose, mannitol, sorbitol, or a mixture of two or more thereof, can be used according to a desired feeling, and if it is lower than the content, there may be a problem that the substantial moisturizing effect is insufficient. On the contrary, if the content is higher than the content, there may be a problem of lowering the solubility of the polymeric surfactant due to the interaction between the powdery moisturizer and water.

Powdered bioactive substances are those having powdery properties among bioactive substances that give substantial improvement in addition to moisturizing to the skin, vitamin C and its derivatives, arbutin, adenosine, niacinamide, N-acetyl N-Acetylglucosamine, Allantoin, Madecasoside, Copper peptide, Ectoin, or a mixture of two or more thereof may be used. If less, there may be a problem that the substantial skin improvement effect is not sufficient, on the contrary, if the content is higher than the content, there may be a problem of lowering the solubility of the polymeric surfactant due to the interaction between the powdered bioactive substance and water. Can be.

The physiologically active substances are mainly liquid-type substances such as cactus, aloe, grapefruit peel, machi, chamomile, plant extracts including hollyhock extract, matrixyl (Matrixyl, palmitoyl pentapeptide-3), iris (Eyeliss, France SEDERMA Peptides such as agireline (Argireline, LIPOTEC, U.S.A.), Haroksil (Haloxyl, SEDERMA, France), Legu-AGE (REGU-AGE, Switzerland PENTAPHARM), Extensin (Extensin, Spain PROVITAL) And collagen, EGF, Fulleren (Fulleren) or may be selected from the group consisting of two or more of them, if less than the content may have a problem that the substantial skin improvement effect is insufficient, on the contrary higher than the content In this case, there may be a problem of lowering the solubility of the polymeric surfactant due to the interaction of the bioactive material and water. .

The ethanol in the additive mixture is used as a solvent to homogenize the preservative and the fragrance which is almost insoluble in water, and when less than the content, there may be a problem that it is difficult to uniformly mix the preservative and the fragrance, on the contrary, the content In more cases, as with the water-soluble moisturizer may be a problem that interferes with the gel formation. Ethanol constituting the additive mixture may further include a preservative or flavor widely used in cosmetics in the field of industry. The preservative mainly serves to prevent the decay of the cosmetics stored and used at room temperature, the fragrance is to give a direction to the user to improve the satisfaction of use and to satisfy the sense of smell of the user or those around them. The preservatives or flavors will be understood by those skilled in the art to the extent that it can be easily purchased and used commercially supplied by leading manufacturers at home and abroad.

In addition, the method of producing a patch composition that promotes skin elasticity, moisturizing and drug penetration capable of phase transition at body temperature of the present invention, in the preparation of a patch composition that changes from a liquid to a gel phase by the body temperature on the skin, (1) water 40.0 To 75.0 parts by weight and 2.0 to 10.0 parts by weight of a water-soluble moisturizer are cooled to 15 ° C. to 0 ° C., and 5.0 to 30.0 parts by weight of the polymeric surfactant is added thereto and dissolved to prepare a polymer surfactant dissolving part for obtaining a first mixture. ; (2) dissolving powder part to obtain a second mixture by dissolving 0.1 to 5.0 parts by weight of a moisturizer in powder form and 0.01 to 3.0 parts by weight of powdered bioactive substance in the first mixture obtained in step (1); And (3) adding 0.01 to 10.0 parts by weight of the bioactive material to the second mixture obtained in step (2) and homogenizing the bioactive material homogenizing step to obtain a patch composition.

The components used in the steps (1) to (3) and their contents can be understood with reference to the above description.

The temperature of water, which is the main solvent in the preparation step of dissolving the polymer surfactant in step (1), has a great effect on the solubility through the hydrogen bonding between the hydrophilic groups and the water of the polymer surfactant. In the actual production process, there may be a problem that some of the water is frozen and the process is not smooth, and if the temperature is higher than the above-mentioned temperature, the hydrogen bond between the hydrophilic groups and the water of the polymer surfactant is relatively loose and the dissolution is not smooth. There may be.

Dissolution of step (1) and homogenization of step (3) can be understood to be easily performed by those skilled in the art without excessively repetitive or trial and error experiments.

An additive mixing step of further mixing the additive mixture dissolved in 0.01 to 0.5 parts by weight and 0.01 to 0.5 parts by weight of preservatives in 1.0 to 15.0 parts by weight of ethanol between the step (2) and step (3); .

Hereinafter, preferred embodiments and comparative examples of the present invention will be described.

The following examples are intended to illustrate the invention and should not be understood as limiting the scope of the invention.

Reference Example  One

Before the embodiments are described in detail, first, one of the polymeric surfactants was selected to evaluate the solubility according to the amount of water used and the solubility according to the temperature. The preparation method is as follows.

First, water was maintained at each temperature according to the composition shown in Table 1 below, and the polymer surfactant was added thereto, stirred, and homogenized, and then the solubility of the polymer surfactant was checked.

ingredient Composition 1 Composition 2 Composition 3 Composition 4 Composition 5 Composition 6 Composition 7 Composition 8 water 35 50 65 80 65 65 65 65 Poloxamer
407 25 25 25 25 20 20 20 20 Temperature (℃) 5 5 5 5 2 12 18 27 Solubility × ○ ○ ◎ ◎ ○ △ × unit ; gram
◎: very soluble ○: soluble
(Triangle | delta): Only part melt | dissolves ×: It does not melt | dissolve

When dissolving the poloxamer 407 in Table 1, the solubility of the poloxamer 407 was very high as the amount of water used increases, on the contrary, the temperature is closer to 0 ℃ in the same composition, the higher the solubility, the higher than 15 ℃ It was confirmed that the solubility rapidly decreased. From the test results of Table 1, it was confirmed that the low temperature and the appropriate amount of water used as close as possible for ease in the dissolution process of the polymeric surfactant, which is actually the most important manufacturing process.

Example  1 to 4 and Comparative example  1 to 7

Table 2 below provides a preferable example of the number and ratio of the hydrophilic group and the lipophilic group in making a patch-type cosmetics sol-gel transition from the liquid phase to the gel phase by the temperature on the skin.

To the composition as shown in Table 2 was prepared a cosmetic comprising a patch composition that is transformed into a gel phase from the liquid by the body temperature above the skin according to the present invention, the production method is as follows.

After adding purified water and glycerin to a water melting tank capable of temperature control and stirring to the content shown in Table 2 in a separate dissolution tank and cooling to 5 ° C., slowly adding and dissolving a polymeric surfactant with a propeller mixer 500 RPM and dissolving the polymer interface. The active agent dissolution portion was prepared. Powdered moisturizer and powdered bioactive material were added and dissolved in a propeller mixer 500 RPM. Ethanol was added to a separate dissolution tank to dissolve the preservatives and fragrances, added to the water-dissolving tank, and homogenized with a propeller mixer 500 RPM. The physiologically active substance in the liquid was added to it and dissolved in a propeller mixer 500RPM to obtain a liquid patch cosmetic that is transformed into a gel form from the liquid by the body temperature on the skin.

The liquid patch cosmetics, which were transformed from liquid to gel by body temperature on the skin, were all transparent when observed with the naked eye. The viscosity was varied depending on the composition, and the low-critical solution temperature from liquid to gel was different. .

division Ingredient (% by weight) Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7


Polymer
Interface
Active agent
Melting part Purified water 78.87 67.87 60.87 67.87 81.87 50.87 56.87 73.87 67.87 61.87 53.87 glycerin 4.0 4.0 4.0 4.0 4.0 4.0 15.0 4.0 4.0 4.0 4.0 Poloxamer338 4.0 10.0 15.0 - 2.5 20.0 10.0 - - 10.0 10.0 Poloxamer 407 - - - 10.0 - - - - - - - Poloxamer333 - - - - - - - 8.0 - - - Poloxamer288 - - - - - - - - 10.0 - - Poloxamer188 - - - 8.0 - - - - - - - Poloxamer217 3.0 8.0 10.0 - 1.5 15.0 8.0 - - 8.0 8.0 Poloxamer108 - - - - - - - 4.0 - - - Poloxamer185 - - - - - - - - 8.0 - - Powder Award Glycine 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 8.0 2.0 Arbutin 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
additive ethanol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 18.0 Methylparaben
(antiseptic) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 incense 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 Bioactive substances Haroksil 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0

Properties Viscosity (cps)
25 ℃ 2,000 3,400 6,000 2,600 300 130,000 1,200 200 1,000 2,400 1,000 Solubility ◎ ○ ○ ○ ◎ △ ◎ △ ◎ △, precipitation ◎ Low threshold
Solution temperature (℃) 32.5 29.0 28.0 30.5 68.5 15.2 40.7 Not measurable 43.5 Not measurable 47.6 ◎: very soluble, ○: soluble, △: partially dissolved, ×: not soluble
1) Poloxamer 338 (a = 128, b = 54, a / b = 2.37): Poloxamer 338, BASF, Germany
2) Poloxamer 407 (a = 98, b = 67, a / b = 1.46): Poloxamer 407, BASF, Germany
3) Poloxamer 333 (a = 20, b = 54, a / b = 0.37): Poloxamer 333, BASF, Germany
4) Poloxamer 288 (a = 122, b = 47, a / b = 2.59): Poloxamer 288, BASF, Germany
5) Poloxamer 188 (a = 70, b = 30, a / b = 2.33): Poloxamer 188, BASF, Germany
6) Poloxamer 217 (a = 52, b = 35, a / b = 1.48): Poloxamer 217, BASF, Germany
7) Poloxamer 108 (a = 16, b = 48, a / b = 0.33): Poloxamer 108, BASF, Germany
8) Poloxamer 185 (a = 19, b = 30, a / b = 0.63): Poloxamer 185, BASF, Germany
9) Glycine: Aminocoat, Japan, Ajinomoto
10) Arbutin: Arbutin, UK, KAGEN
11) Ethanol: Ethanol, Korea, Korea Alcohol
12) Haroksil: Haloxyl, France, Sederma

From the analysis results of Table 2, the following facts could be confirmed.

In Examples 1 to 4, as shown in the mechanism shown in FIG. 1 and the photograph of FIG. 2 (Example 2 of Table 2), the sol from the liquid phase to the gel phase at a temperature of about 27 to 33 ° C. Gel patch formation through gel phase transition was easy, and it was confirmed that dissolution and homogenization were easy even in the manufacturing process.

In addition, as shown in Table 2, it can be seen that the low-critical solution temperature decreases as the content of the polymer surfactant poloxamer increases, so that the temperature of transition to the gel state varies with the type and content of poloxamer. It was confirmed that the adjustment is possible.

In addition, the gel formed strength of the gel patch was shown in the order of Comparative Example 2> Example 3> Example 2> Example 4> Example 1 as opposed to the low critical solution temperature.

However, when the amount of the polymeric surfactant less than the above-mentioned content was used as in Comparative Example 1, it was not possible to use the gel at 68.5 ° C., which is much higher than the skin temperature. On the contrary, as in Comparative Example 2, the polymeric surfactant was used. If the content is more than the above-mentioned content is very poor solubility is a problem, and there is a problem that the low critical solution temperature is too low than the skin temperature is not applicable to the skin. In addition, when a water-soluble moisturizer having a hydroxyl group (-OH) is used more than the above-mentioned content as in Comparative Example 3, the solubility of the polymeric surfactant becomes easier, but it becomes gel by the temperature on the skin. But it was formed at a higher than 40 ℃ higher than that, it was impossible to apply to actual cosmetics. Polymeric surfactants having a ratio (a / b) of the hydrophilic group (a) and the lipophilic group (b) of the macromolecular surfactant, which are the most important factors for the gel formation at the temperature on the skin, are lower than those mentioned above as in Comparative Example 4 In the case of using the gel, there was a big problem in the solubility due to the strong lipophilic strength did not form a gel, on the contrary, in the case of using a polymeric surfactant having a ratio (a / b) higher than the above mentioned value as in Comparative Example 5 The gel was not formed by the temperature on the skin as in 3, but was formed at a temperature higher than 40 ° C. When the powdered moisturizer is used more than the above-mentioned content as in Comparative Example 6, there is a problem that the moisturizer is precipitated and does not form gel, and when ethanol is used more than the above-mentioned content as in Comparative Example 7 As in the case of Comparative Example 3, the solubility was excellent, but the gel was formed at a temperature higher than the skin temperature, and it was confirmed that there was a problem in the actual product.

Example  5 to 15

Table 3 below presents a preferred example of the stabilization of the above-mentioned bioactive material in the preparation of a patch-type cosmetics sol-gel transition from the liquid phase to the gel phase by the temperature on the skin.

division Ingredient (% by weight) Example 5 Example 6 Example 7 Example 8 Example 9 Example 10 Example 11 Example 12 Example 13 Example 14 Example 15 Polymer
Interface
Active agent
Melting part Purified water 67.87 69.83 67.87 69.57 69.67 66.87 66.87 59.87 66.87 59.87 66.87 glycerin 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 Poloxamer338 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 Poloxamer217 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0

Powder Award Glycine 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 AA2G 2.0 - - - - 2.0 2.0 2.0 2.0 2.0 2.0 Adenosine - 0.04 - - - - - - - - - Niacinamide - - 2.0 - - - - - - - - Madecassoside - - - 0.3 - - - - - - - Copper Peptides - - - - 0.2 - - - - - -
additive ethanol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 Methyl paraben 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Spices 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03

Physiology
activation
matter Cactus Extract 2.0 2.0 2.0 2.0 2.0 - - - - - - Matrix room - - - - - 3.0 - - - - - Iris - - - - - - 3.0 - - - - Agireline - - - - - - - 10.0 - - - Collagen - - - - - - - - 3.0 - - E.G.F (100 ppm) - - - - - - - - - 10.0 - Fullerene - - - - - - - - - - 3.0

Properties Viscosity (cps)
25 ℃ 3,600 2,600 2,800 3,000 3,000 3,400 3,100 3,300 3,700 2,500 2,700 Solubility ◎ ◎ ◎ ◎ ◎ ◎ ◎ ○ ◎ ○ ◎ Low threshold
Solution temperature (℃) 31.0 28.0 29.0 31.5 29.5 30.2 31.1 28.5 30.5 28.5 29.5 ◎: very soluble, ○: soluble, △: partially dissolved, ×: not soluble
1) AA2G: Ascorbic acid-2-glucoside (Ascorbic acc-2-glucoside), Hayasibara, Japan
2) Adenosine: Adenosine, China, World best company
3) Niacinamide: Niacinamide, Germany, Roche
4) Madecassoside: Madecassoside, France, MMP
5) Copper peptide: Copper-peptide, Dermalab, Korea
6) Cactus Extract: Sunbio tech
7) Matrix yarn: Matrixyl (Palmitoylpentapeptide-3), France, Sederma
8) Iris: Eyeliss, France, Sederma
9) Agireline: Agireline (Acetylhexapeptide-8), United States, Lipotec
10) Collagen: Collagen, Australia, Colltec
11) EGF (100ppm): Epidermal GROWTH Factor, Horus, Japan
12) Fullerene: Fullerene, Japan, Vitamin C60 bioresearch lab

Examples 5 to 15 were prepared by the same process as in Examples 1 to 4 and Comparative Examples 1 to 7 of Table 2 above. In Examples 5 to 15, although there was a slight difference in the temperature of the low critical solution as shown in the mechanism shown in FIG. 1 and the photograph shown in FIG. 2 (Example 2 of Table 2), the temperature on the skin It was easy to form a gel patch through the sol-gel phase transition from the liquid phase to the gel phase at 27 to 33 ℃, it was confirmed that the dissolution and uniformity in the manufacturing process.

Experimental Example  One

Experiment to confirm the degree of gel retention

In order to examine the characteristics as a practical cosmetics, firstly, cosmetics such as the cosmetics obtained from Example 2 of Table 2 and a commercially available essence as a gel cosmetic made from a conventional polymer shown in Table 4 were subjected to a temperature of 29 to 30 ° C. While maintaining for 8 hours while maintaining the gel phase in the air while maintaining, the results are shown in FIG. As shown in FIG. 3, the gel-like cosmetics (control group) made of a conventional polymer shown in the left (A) picture were markedly reduced in volume, and the cosmetics obtained from Example 2 shown in the right (B) picture had a surface Except for the fact that almost no volume was reduced, it was confirmed that the high hydration (Hydration) effect.

division Ingredient (% by weight) Control Award Purified water 77.71 glycerin 4.0 Glycine 2.0 Arbutin 2.0 Polymer Department Carbomer (2%) 8.0 Neutralizer Triethanolamine 0.16 additive ethanol 4.0 Methyl paraben 0.1 Spices 0.03 Bioactive substances Haroksil 2.0 Properties Viscosity 3,000 pH 6.26 1) Carbomer: CARBOPOL 941, Germany, BF Goodrich
2) Triethanolamine: Triethanolamine, Korea, Taedong Chemical

Experimental Example  2

Moisturizing effect confirmation experiment

As a practical cosmetic product, how the formation of an elastic gel patch at the temperature above the skin forms a powerful hydration membrane on the skin, which has a positive effect on the moisturizing sustainability (CORNEOMETER; CK electronics, Germany) 9 hours, and the result is shown in FIG. 4 in comparison with the gel cosmetics (control) made of the conventional polymers mentioned in Table 4. As shown in FIG. 4, the cosmetics of the control group also appeared to have some moisturizing effect up to about 1 hour 30 minutes, but after 2 hours or more, the moisture retention was rapidly decreased, and almost 9 hours later, the phenomena were almost similar to before application. . On the other hand, the cosmetics according to the present invention obtained from Example 2 showed an excellent effect of increasing the moisturizing power by about 40% even after 9 hours, compared with the control, about 38% compared to the control group, the gel patch at the skin temperature of the present invention Due to the action of forming the skin was found to be greatly improved.

Experimental Example  3

Experiment on Skin Elasticity

Skin elasticity before and after applying cosmetics using the cosmetics obtained from the compositions of Examples 2 and Comparative Example 3 was measured using a cutometa (Cutometer, Model name MPA 580, CK Electronic, Germany) Is shown in FIG. 5. The skin elasticity is expressed by the device pulling the skin and then releasing it. When the value is repeated, the closer the value is to '1', the better the skin elasticity is, and the closer to the '0', the skin elasticity is expressed as bad. As shown in FIG. 5, the elasticity values before use were 0.82, respectively, and when the cosmetics obtained from Example 2 were used for 8 hours, about 15% rose to 0.93 immediately after use, and almost increased to 0.825 for Comparative Example 3. As it can be confirmed that, as mentioned above, it was found that the skin elasticity improved effect when making cosmetics with a composition capable of forming a gel patch at a temperature above the skin.

Experimental Example  4

Percutaneous Absorption Experiment

In addition, the amount of percutaneous absorption was checked to see how the above-mentioned physiologically active substance penetrates arbutin, a commonly used physiologically active substance depending on the presence of patch formation on the skin. This transdermal absorption test was carried out in the dissolution tester (Dissolution tester, ERWEKA DT800 Dissolution Tester, Germany) in the same amount of the sample prepared in Example 2 and Comparative Example 3 0.2g of the actual human skin (65 years old male back, Hans Biomed ) Was placed in an Enhancer cell (ERWEKA, Germany), and 500 ml of buffer solution (buffer solution containing 0.02 g citric acid and 0.4 g sodium citrate) was filled with sodium chloride, and the temperature was the amount of elution of the real periodic arbutin for 360 minutes and adjusted to 37 ℃ similar to the body temperature of a person was observed by using a high performance liquid chromatography (HPLC, Japan, Shimadzu (Shimadzu), LC-10VP) . As a result, after about 8 hours, the eluted amount of arbutin was measured for accurate comparison and plotted as a percentage (%) of the eluted amount compared to the initial dose.

The time that the drug delivery can occur efficiently during the time of applying this patch-type cosmetics is 8 hours, and then the percent (%) curve of the initial dose is a gel patch formed at the temperature on the skin after application. In the case of Example 2 and Comparative Example 3 which is not, the arbutin release behavior and permeation effect were very different as shown in FIG. 6. In the case of Example 2 was released while showing a constant sustained release (Time-release) over 8 hours, after 8 hours the arbutin permeation effect was also very good as 92.3%. In the case of Comparative Example 3 was released arbutin over 8 hours, but after 4 hours compared to the initial release of arbutin was reduced, and after 8 hours the arbutin permeation effect was also 52.7%, which showed a significantly lower result than in Example 2 . It is possible to form a patch on the gel when applied to the skin, it is possible to release the drug slowly for a desired time due to the excellent gel properties, and also the concentration of the drug promoted by the pressure generated during the formation of the patch phase (Diffusion Although it can be efficiently released by the), if the gel patch phase is not formed it can be confirmed that the smooth skin delivery of the drug is not achieved because the above mentioned two effects are not obtained than when the gel patch phase is possible.

The present invention was found to be very excellent in the specific properties that change from the liquid phase to the gel phase at the temperature on the skin, excellent moisturizing sustaining effect due to the formation of the gel patch, instantaneous skin elasticity effect and effective skin transfer of physiologically active substances.

According to the present invention, it is excellent in the moisturizing effect by preventing evaporation of the water contained in the phase change to the gel state, to impart skin elasticity while maintaining the gel structure, and at the same time to facilitate the delivery of drugs by pressure through the patch formation Possible patch compositions and methods for their preparation may be utilized in the field of industry.

In particular, according to the present invention is a new type of patch to form a gel patch by the phase change from the liquid state to the gel (Gel) at the skin temperature, the liquid formulation is easy to apply on the skin, relatively It is easy to encapsulate a large amount of moisturizing ingredients and bioactive substances into small nano-sized with almost solubilization level. After application to the skin, the micelle structure of the polymer is converted into the network by the skin temperature. It changes and forms a patch on the gel, and the patch on the gel prevents or suppresses the evaporation of water, thereby providing an excellent moisturizing effect, giving skin elasticity while maintaining the gel structure, and at the same time, delivering the drug under pressure through patch formation. There is a great effect to facilitate, moreover, the present invention, as well as the moisturizing and physical elasticity effect obtained in the formulation itself, Possible combinations of physiologically active substance for a variety of skin lesions, and can obtain the excellent effect completely different from the conventional cosmetics.

Although the present invention has been described in detail only with respect to the described embodiments, it will be apparent to those skilled in the art that various modifications and variations are possible within the technical scope of the present invention, and such modifications and modifications are within the scope of the appended claims.

1 is a view showing the mechanism of the Sol-Gel (Sol-Gel) behavior in which the patch composition according to the present invention is transferred from the liquid state to the gel state.

Figure 2 is a photograph showing the appearance at or below the skin temperature for the sol-gel patch composition made of the composition ratio of Example 2 of the present invention.

FIG. 3 is a photograph showing the degree of gel retention of a sol-gel patch composition made of the composition ratio of Example 2 of the present invention and a gel made of a conventional polymer.

Figure 4 is a view showing the result of measuring the skin moisturizing power of the sol-gel patch composition made of the composition ratio of Example 2 of the present invention and a gel made of a conventional polymer.

5 is a view showing the results of measuring the skin elasticity after applying the sol-gel patch composition made of the composition ratio of Example 2 of the present invention and the cosmetic product made of the composition ratio of Comparative Example 3 to the skin for 4 hours.

6 is a view showing the results of measuring the drug delivery effect of the sol-gel patch composition made of the composition ratio of Example 2 of the present invention and the cosmetics made of the composition ratio of Comparative Example 3.

Claims (10)

40.0 to 80.0% by weight of water, 2.0 to 10.0% by weight of water-soluble moisturizer, 5.0 to 30.0% by weight of polymeric surfactant, 0.1 to 5.0% by weight of powdered moisturizer, 0.01 to 3.0% by weight of bioactive substance, 0.01 to 3.0% by weight of bioactive substance 10.0% by weight and ethanol 3.0 to 5.0% by weight, The polymeric surfactant is represented by the following Chemical Formula 1, wherein the ratio (a / b) of the hydrophilic group (a) and the lipophilic group (b) is within 1.0 to 2.5, and poloxamer 217 (a = 52, b = 35) And a mixture of poloxamer 338 (a = 128, b = 54) or poloxamer 188 (a = 70, b = 30) and poloxamer 407 (a = 98, b = 67), A patch composition for promoting skin elasticity, moisturizing and drug penetration that can be phase-transformed at body temperature, characterized in that phase transition from sol to gel is performed at a temperature of 27 to 33 ° C. on the skin. [Formula 1]

The method of claim 1, The water-soluble moisturizing agent is selected from the group consisting of glycerin, diglycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, di-panthenol, 1,2-pentanediol or mixtures of two or more thereof A patch composition that promotes skin elasticity, moisturizing, and drug penetration that can be phase-transferred. delete delete The method of claim 1, Wherein the powdered moisturizer is selected from the group consisting of glycine, glutamic acid, arginine, lysine, galactose-glucose-protose, fucose, pentaerythritol, sucrose, mannitol, sorbitol, or a mixture of two or more thereof. A patch composition that promotes skin elasticity, moisturizing, and drug penetration that can be phase-transferred. The method of claim 1, Powdered bioactive substance in the vitamin C, arbutin, adenosine, niacinamide (Niacinamide), N-acetylglucosamine (N-Acetylglucosamine), allantoin (Allantoin), Madecasoside (Madecassoside), copper peptide (Copper peptide), Ectoin (Ectoin) or a patch composition that promotes skin elasticity, moisturizing and drug penetration capable of phase transition at body temperature, characterized in that selected from the group consisting of two or more thereof. delete The method of claim 1, Skin resilience, moisturizing and drug penetration at body temperature, characterized in that the patch composition further comprises 0.01 to 0.5% by weight and fragrance 0.01 to 0.5% by weight dissolved in 3.0 to 5.0% by weight of ethanol Promotes patch composition. delete delete

Images