KR101626473B1 - Composition for external application to the skin containing cyclohexane dicarboxylic acid derivatives - Google Patents

Abstract

The present invention relates to an external preparation for skin comprising a cyclohexane dicarboxylic acid derivative as a skin absorption enhancer of an active ingredient in an external composition for skin containing an active ingredient.

The composition for external application for skin of the present invention is applicable to a cosmetic composition or a pharmaceutical composition for promoting skin absorption of a skin-effective ingredient which has no problems such as skin irritation and skin damage and has a low affinity with horny layer or hardly absorbs skin.

Absorption enhancement, cyclohexanedicarboxylic acid derivatives, cosmetic composition, pharmaceutical composition

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for external application for skin containing a cyclohexane dicarboxylic acid derivative,

The present invention relates to a composition for external application for skin.

The skin consists largely of three parts, the stratum corneum, the epidermis, and the dermis, and the stratum corneum is present at the outermost part of the skin. Skin is the primary barrier of the human body and has functions to protect the internal organs of the body from changes in temperature and humidity, and from external stimuli such as ultraviolet rays and pollutants. The barrier function of such skin is mainly caused by the physical properties of the stratum corneum It depends on the chemical nature. The stratum corneum consists of keratinocytes composed mainly of a protein called keratin and a lipid layer filling between the cells. In the skin absorption of substances, it is very difficult to absorb through the keratinocytes, and the pathway through the lipid layer between keratinocytes is common (Patent Document 10-2003-0062492).

Particularly, since the stratum corneum is composed of keratinocytes comprising keratin protein as a main component and a lipid layer constituting between keratinocytes, the liposoluble active ingredient is smoothly absorbed into the skin, but active ingredients having high water solubility and molecular weight are difficult to penetrate through the skin. Therefore, the active ingredient contained in the external preparation for skin such as cosmetics, which is mostly water-soluble, is not easily absorbed into the skin. Accordingly, there has been known a method of using a non-polar solvent, a surfactant, a fatty acid or the like as a skin absorption promoter to solve such a problem [Chen LH, Chien YW, "Enhancement of skin penetration" , 60; Rhein LD, Robbins CR, Fernee K, Cantore R. "Surfactant structure effects on swellings of isolated human stratum corneum, J. Soc Cosmet Chem 1986; 37: 125; Cooper ER, Merritt EW, alcohols on the penetration of acyclovir across human skin in vitro J. Pharm Sci 1985; 74: 688].

The absorption enhancer is used to weaken the barrier function of the stratum corneum for the permeation of substances. The substance enhances the diffusion of the active ingredient into the stratum corneum by penetration and interaction of the stratum corneum component. It can be divided into substances that increase the distribution of the substance. Absorption accelerators should be pharmacologically inactive, not acting as a receptor in the skin, low in toxicity, irritation, allergenicity, penetration effect, persistence and proper control, Skin barrier function should be completely restored, and there should be no loss of moisture, electrolytes, endogenous substances, etc. within the skin.

Examples of the substance having such action include fatty acids such as lower alcohols, oleic acid, fatty acid esters such as isoprofil myristate, monoterpenes such as menthol, urea, salicylic acid, alphahydroxy acid, pyroiodecane and the like. Surfactants generally do not promote transdermal absorption, but they often interact with lipids in the skin barrier to promote transdermal absorption. However, up to now, these transdermal absorption accelerators have promoted a certain extent of permeation of the active ingredient through the skin, but have a problem in that they are absorbed into the skin together with the active ingredient due to their small molecular weight, resulting in severe irritation. Other alkane diols having about 4 to 8 carbon atoms, which have some amphipathic groups, are known to promote transdermal absorption. However, when the number of carbon atoms is short, the solubility of the water soluble active ingredient is increased due to the increase in hydrophilicity. However, Although the ground penetration is improved, there is a problem of irritation to the skin, so there is a limitation in using a large amount.

In addition, special techniques applied to effectively deliver efficacious ingredients into the skin or to exert their effects effectively include a patch type directly attached to the skin, a topical application type using a micro needle, an external application type using an emulsion, a liposome, or a microcapsule technique, In case of patch type widely used in the field of cosmetics, there is a disadvantage that it is necessary to use other medium and to shield it for a long time, and stabilizing the efficacy component by using liposome or nanocapsule, There are disadvantages such as the application of a separate high-pressure emulsifier or a limited emulsifier to make the formulation and the difficulty of adjusting the feeling depending on the encapsulation and the capsule.

In addition, a method of imparting sonophoresis or fine iontophoresis to skin to absorb the skin of a water-soluble substance is 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], it is difficult to apply this method to skin external preparations such as cosmetics in reality due to the necessity of expensive equipment. On the other hand, in addition to the above-mentioned methods, there are known patents on a method for enhancing skin absorption of an active ingredient by changing or weakening the skin barrier function using an enzyme. For example, US Pat. Nos. 5,534,260 and 5,296,222 disclose methods of enhancing skin absorption of drugs by adding proteolytic enzymes. However, this method is merely a method of adding a protease, so that the proteolytic enzyme is denatured or the activity is lost over time due to the influence of ingredient materials contained in the preparation. As a result, since it does not exhibit the effect of enhancing transdermal absorption by enzymes, it is not suitable for application to external preparations for skin, which contain various components in addition to active ingredients (Japanese Patent Laid-Open No. 2001-0104881).

In order to solve the above problems, the inventors of the present invention have found that, among the methods capable of enhancing skin absorption of active ingredients contained in external preparations for skin such as cosmetics, medicines and the like, And applicability of active ingredients. As a result, it has been found that the use of a cyclohexanedicarboxylic acid derivative having both hydrophilic and lipophilic properties and safety and formulation stability as a skin absorption promoter The degree of skin absorption of the active ingredient is enhanced, and the present invention is completed.

Accordingly, it is an object of one embodiment of the present invention to provide a composition for external application for skin which is capable of promoting skin absorption of an active ingredient contained in the composition.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention and claims.

According to one embodiment of the present invention, the present invention provides an external preparation for skin comprising a cyclohexanedicarboxylic acid derivative as a skin absorption enhancer of an active ingredient in an external preparation for skin containing an active ingredient.

In addition, one embodiment of the present invention provides a cosmetic composition comprising the composition.

In addition, one embodiment of the present invention provides a pharmaceutical composition comprising the composition.

Hereinafter, the present invention will be described in more detail.

The composition according to one embodiment of the present invention is free from problems such as skin irritation and skin damage, and has a cosmetic composition and a pharmaceutical composition for promoting skin absorption of a skin-effective ingredient having a low affinity with the horny layer or having a high molecular weight, Lt; / RTI >

An embodiment of the present invention provides an external preparation for skin comprising a cyclohexane dicarboxylic acid derivative as a skin absorption enhancer of an active ingredient in a composition for external application for skin containing an active ingredient.

In one embodiment of the present invention, it is particularly preferable that the water-soluble, oil-soluble, and amphipathic ones are applicable, but water-soluble. The cyclohexanedicarboxylic acid derivative is represented by the following formula (1).

The above formula is bis-ethoxydiglycol cyclohexane 1, 4-dicarboxylate.

The ester emulsion having the polyoxyethylene alkyl ether, especially the diethylene glycol ethyl ester residue, in the 1,4-cyclohexane dicarboxylic acid has both hydrophilic and lipophilic properties, And at the same time, it has a specific gravity higher than 1, which improves the stability of the formulation represented by emulsification system, improves the moisturizing property, affects skin, and has low irritation and skin irritation. In the case of an amphipathic compound having both a hydrophilic property and a lipophilic property, the compound itself can easily penetrate the skin, and at the same time, has affinity with a water-soluble or oil-soluble effect ingredient. Lt; / RTI >

In addition, the non-cyclic dicarboxylic acid having a carbon number of 8 or more tends to be usable, and when used for a cosmetic or dermatological external preparation, the feeling of use is deteriorated, and in the case of a non-cyclic dicarboxylic acid having less than 8 carbon atoms, hydrolysis is easy. And it causes problems such as skin irritation and the like. In addition, when an aromatic compound dicarboxylic acid is used, there may be a safety problem such as an endocrine disrupting action. As the selected dicarboxylic acid, a commercially available 1,4-cyclohexanedicarboxylic acid having a saturated cyclic structure Mixtures of trans-isomers and cis-isomers are commercially available, but either can be used.

The alkyl ether of the residue is preferably a C ₂ -C ₁₁ carbon atom. In the case of a hydrocarbon group having 13 or more carbon atoms, defects such as a decrease in the hydrophilicity of the emulsion and a feeling of heaviness may occur. In addition, methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, octyl and ethylhexyl groups are also preferable, but methyl group and ethyl group are preferable in view of reactivity, performance and economy.

In one embodiment of the present invention, the cyclohexanedicarboxylic acid derivative is contained in an amount of 0.01 to 10.0% by weight, preferably 0.1 to 5.0% by weight based on the total weight of the composition. When it is used in an amount less than 0.01% by weight, it is difficult to expect an appropriate absorption enhancing effect, and when it is used in an amount exceeding 10.0% by weight, the safety of the product may be adversely affected

In one embodiment of the present invention, the active ingredient is an efficacious ingredient conventionally used in cosmetic compositions in which skin absorption by the skin absorption enhancer of the present invention can be increased. The kind of the effective ingredient is not particularly limited, and any of water-soluble, oil-soluble, and ampholytic can be applied, but water-soluble ones are particularly preferable. For example, there can be mentioned, for example, L-ascorbic acid, L-ascorbyl phosphate, L-ascorbyl glucoside, vitamin B group, kojic acid, kojic acid, coinaminopropyl phosphate, hydroquinone, arbutin, glycerin, Polyols such as propylene glycol, propylene glycol, 1, 3-propanediol and dipropylene glycol, and polyols such as sorbitol, xylitol, erythritol, mannitol, maltose, trehalose, lactose, betaine, proline, But are not limited to, arginine, lysine, serine, glycine, alanine, tyrosine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, retinol, retinol acetate, retinol palmitate, retinoic acid, thiamine, nicotinamide, tocopherols, pantothenic acid, , Caffeine, cholesterol, uric acid and water-soluble natural extracts.

Soluble derivatives of L-ascorbic acid such as L-ascorbic acid, L-ascorbyl phosphate, L-ascorbyl glucoside and the like, vitamin B group, kojic acid, kojic acid, aminoaminopropyl phosphate, Is a whitening active ingredient and is a polyol such as glycerin, 1,3-butylene glycol, propylene glycol, 1,3-propanediol and dipropylene glycol, sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, Amino acids such as glucose, mannitol, glucose, mannitol, glucose, mannitol, glucose, mannitol, , Vitamins and derivatives thereof are moisturizing ingredients. In addition, retinol, retinol acetate, retinol palmitate, retinoic acid, etc. are wrinkle preventing and improving components. Thiamine, nicotinamide, tocopherol, pantothenic acid, biotin, oleanolic acid, adenosine, caffeine, cholesterol and uricolic acid are other effective ingredients.

One embodiment of the present invention is a cosmetic composition comprising a cyclohexane dicarboxylic acid derivative. The cosmetic composition may be a skin whitening composition containing the above-mentioned effective ingredients, a composition for preventing and improving wrinkles, and may be a composition for skin moisturizing.

The cosmetic composition is not particularly limited in its formulation, but may be used in the form of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant- Oils, powder foundations, emulsion foundations, wax foundations and sprays. More specifically, the present invention relates to a cosmetic composition for cosmetics such as softening lotion, nutritional lotion, lotion, cream, pack, gel, patch, O / W type, O / W type, lipstick, makeup base or foundation A cosmetic composition for hair such as a cleaning agent such as a color cosmetics, a shampoo, a rinse, a body cleanser, a toothpaste or an oral cleanser, a hair conditioner such as a hair tonic, a gel or a mousse, a hair conditioner or a hair dye. In one embodiment of the present invention, when the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, Benzyl benzoate, propylene glycol, 1, 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In one embodiment of the present invention, when the formulation of the present invention is a suspension, a carrier diluent such as water, a liquid diluent such as ethanol or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan A suspending agent such as an ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

In one embodiment of the present invention, when the formulations of the present invention are pastes, creams or gels, the carrier component is selected from the group consisting of animal oils, vegetable oils, waxes, paraffins, starches, tracans, cellulose derivatives, polyethylene glycols, silicones, bentonites, Talc or zinc oxide may be used.

In one embodiment of the present invention, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as the carrier component when the formulation of the present invention is a powder or a spray, In addition, propellants such as chlorofluorohydrocarbons, propane / butane or dimethyl ether may be included.

In one embodiment of the present invention, when the formulation of the present invention is an interface-active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, Fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester.

In one embodiment of the present invention, the cosmetic composition may further comprise an enhancer. The thickening agent included in the cosmetic composition of the present invention may be selected from the group consisting of methylcellulose, carboxymethylcellulose, carboxymethylhydroxyguanine, hydroxymethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, polyquaternium, cetearyl alcohol, Carrageenan, and the like. Among them, at least one of carboxymethyl cellulose, carboxyvinyl polymer, and polyquaternium can be used, and most preferably, it can be a carboxyvinyl polymer.

In one embodiment of the present invention, the cosmetic composition may contain various bases and additives as appropriate, and the kind and amount of these components can be easily selected by the inventors. The composition may contain an additive that is acceptable according to need, and may further include components such as preservatives, pigments, and additives customary in the art.

The preservative may specifically be phenoxyethanol or 1,2-hexanediol, and the perfume may be an artificial perfume or the like.

In one embodiment of the present invention, the cosmetic composition may comprise a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymeric polysaccharides, sphingolipids and seaweed extracts. Examples of the compounding ingredients that may be added include organic solvents such as a preservative component, a moisturizer, an emollient, a surfactant, an organic and inorganic pigment, an organic powder, an ultraviolet absorbent, a preservative, a bactericide, an antioxidant, a plant extract, a pH adjuster, A blood circulation accelerator, a cold agent, an antiperspirant agent, and purified water.

In addition, one embodiment of the present invention is a pharmaceutical composition comprising a cyclohexane dicarboxylic acid derivative. The pharmaceutical composition may be formulated into a parenteral dosage form in solid, semi-solid or liquid form by adding an inorganic or organic carrier to be used as an active ingredient.

Examples of the material for parenteral administration include drops, ointments, lotions, gels, creams, patches, sprays, suspensions, and emulsions.

 In order to formulate the active ingredient of the present invention, it can be easily formulated according to the conventional method. Surfactants, excipients, coloring agents, spices, preservatives, stabilizers, buffering agents, suspending agents and other adjuvants can be suitably used.

The pharmaceutical composition according to the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously and the like.

In addition, the dosage of the active ingredient will depend on the age, sex, body weight of the subject to be treated, the particular disease or condition to be treated, the severity of the disease or condition, the route of administration and the judgment of the prescriber. Dosage determinations based on these factors are within the level of those skilled in the art. Typical dosages are from 0.001 mg / kg / day to 2000 mg / kg / day, more specifically from 0.5 mg / kg / day to 1500 mg / kg / day.

Hereinafter, the constitution, action and effect of the present invention will be described in more detail with reference to examples and the like, but the present invention is not limited to these examples.

 [Test Example 1] Measurement of skin absorption of kojic acid

The skin absorption of kojic acid was measured by using a Franz permeation cell for guinea pig skin. Before the experiment, the skin of the abdomen of the guinea pig was taken and cut into an area of 1 cm 2 per square. Then, it was placed in a transparent cell having a diameter of 0.9 cm and fixed with a clamp. 0.5 ml of the cosmetic material of Example 1 and Comparative Example 1 to be measured was applied to one side of the skin, and the other side was brought into contact with a solvent mixed with purified water and glycerin in a weight ratio of 1: 1. During the experiment, the temperature was maintained at 32 ℃, which is the actual skin temperature. After the start of the experiment, a portion of the solvent was collected at regular time intervals, and the amount of kojic acid absorbed into the skin was measured using HPLC. The results are shown in Table 2.

The composition of Example 1 and Comparative Example 1 division Raw material name Example 1 Comparative Example 1 Oil component Diisostearyl malate 2.0 2.0 Cetearyl alcohol 0.2 0.2 Cetyl alcohol 0.7 0.7 Phage-75 stearate 0.5 0.5 Ceteth-20 0.3 0.3 Steareth-20 0.2 0.2 Octyldodecyl myristate 3.0 3.0 Chin type glyceryl stearate 0.5 0.5 Hydrogenated lecithin / C12-16 alcohol / palmitic acid liquid seed 0.5 0.5 antiseptic 0.3 0.3 Mango seed oil 2.0 2.0 Meadow Foam Seed Oil 1.0 1.0 Pentaerythrityl tetraisostearate 3.0 3.0 Salicylic acid 0.3 0.3 Dimethicone 3.0 3.0 Awards
ingredient Purified water To 100 To 100 Butylene glycol 5.0 5.0 Disodium iodide 0.02 0.02 Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 - Tiei 0.15 0.15 antiseptic 0.2 0.2 Xanthan gum 0.2 0.2 Inutetrauric carbamate 0.5 0.5 Café Chocolate 0.15 0.15 Polyacrylate-13 * polyisobutene * polysorbate 20 0.2 0.2 Kojic acid 0.5 0.5

[Manufacturing Method of Example 1 and Comparative Example 1]

1) The water component (except kojic acid) was heated (70 to 75 ° C) and uniformly dissolved and mixed.

2) The oil components were heated (70 ~ 75 ℃) and mixed uniformly.

3) The emulsion was prepared by adding the above-mentioned 2) to the above 1) under the condition of maintaining the temperature at 70 to 75 캜 under stirring, and the emulsion was cooled to 28 to 30 캜.

4) While stirring, kojic acid is dissolved in purified water and butylene glycol and mixed uniformly.

Skin absorption of kojic acid per application concentration (占 퐂 / cm2 / wt%) time Example 1 Comparative Example 1 0 0 0 4 5.58 1.45 8 12.93 3.58 24 35.11 9.18

Considering that the duration of make-up is generally between 4 hours and 8 hours, the skin absorption of kojic acid from Table 2 is at least 3 to 4 times higher than when the cyclohexanedicarboxylic acid derivative is added to the composition Or more.

[Test Example 2] Skin absorption measurement of ascorbyl glucoside

The amount of ascorbyl glucoside absorbed into the skin was measured in the same manner as in Test Example 1, except that the water-in-oil type cosmetic compositions of Example 2 and Comparative Example 2 were used, and the results are shown in Table 4.

The compositions of Example 2 and Comparative Example 2 division Raw material name Example 2 Comparative Example 2 Oil component Phage-7 Dimethicone 3.0 3.0 Decamethylcyclopentasiloxane 0.2 0.2 Dimethicone 0.7 0.7 Sorbitan isostearate 0.5 0.5 2-octyldodecanol 0.3 0.3 Steareth-20 0.2 0.2 Awards
ingredient Purified water To 100 To 100 Butylene glycol 5.0 5.0 Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 - Disodium iodide 0.02 0.02 Sodium chloride 0.15 0.15 antiseptic 0.2 0.2 Ascorbyl glucoside 2.0 2.0 Citric acid 0.5 0.5 Sodium citrate 0.15 0.15

[Manufacturing Method of Example 2 and Comparative Example 2]

1) Water components (except ascorbyl glucoside) were uniformly dissolved and mixed at room temperature.

2) The oil components were uniformly mixed at room temperature.

3) The above 1) is slowly added to the above 2) at room temperature under stirring to make an emulsion.

4) Ascorbyl glucoside is dissolved in purified water under stirring and mixed homogeneously

Skin absorption (/ / cm2 / wt%) of ascorbyl glucoside per application concentration time Example 2 Comparative Example 2 0 0 0 4 3.75 1.01 8 7.01 1.30 24 19.58 4.69

Considering that the duration of make-up is generally between 4 hours and 8 hours, the skin absorption of ascorbyl glucoside from Table 4 indicates that the addition of the cyclohexanedicarboxylic acid derivative to the composition is at least 5 ~ 6 times higher than that of the control group.

[Test Example 3] Measurement of skin absorption of arbutin

The amount of arbutin absorbed into the skin was measured in the same manner as in Test Example 1, and the results are shown in Table 6.

The compositions of Example 3 and Comparative Example 3 division Raw material name Example 3 Comparative Example 3 Oil component Stearic acid 0.7 0.7 Cetearyl alcohol 0.7 0.7 Hydrogenated oil 0.5 0.5 Chin type glyceryl stearate 0.5 0.5 Sorbitan stearate 0.3 0.3 Polysorbate 60 1.2 1.2 Hydrogenated polydecene 3.0 3.0 Cetyl octanoate 2.0 2.0 Decamethylcyclopentasiloxane 4.0 4.0 Dimethicone 1.0 1.0 Awards
ingredient Purified water To 100 To 100 Butylene glycol 5.0 5.0 glycerin 1.0 1.0 Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 - Disodium iodide 0.02 0.02 Tiei 0.15 0.15 antiseptic 0.2 0.2 Xanthan gum 0.2 0.2 Carbomer 0.15 0.15 Arbutin 2.0 2.0

[Manufacturing method of Example 3 and Comparative Example 3]

1) The water component (except arbutin) was heated (70 to 75 ° C) and uniformly dissolved and mixed.

2) The oil components were heated (70 ~ 75 ℃) and mixed uniformly.

3) The emulsion was prepared by adding the above-mentioned 2) to the above 1) under the condition of maintaining the temperature at 70 to 75 캜 under stirring, and the emulsion was cooled to 28 to 30 캜.

4) Arbutin is dissolved in purified water and butylene glycol under stirring, and mixed homogeneously.

Skin absorption of arbutin (占 퐂 / cm2 / wt%) per application concentration time Example 3 Comparative Example 3 0 0 0 4 18.32 3.21 8 37.02 6.32 24 109.47 18.33

Considering that the duration of make-up is generally between 4 hours and 8 hours, the skin absorption of arbutin from Table 6 is at least 5 to 6 times higher than when the cyclohexanedicarboxylic acid derivative is added to the composition Or more.

[Test Example 4] Measurement of skin absorption of vitamin A (retinoic acid)

The amount of vitamin A absorbed into the skin was measured in the same manner as in Test Example 1, and the results are shown in Table 8.

Example 4 and Comparative Example 4 division Raw material name Example 4 Comparative Example 4 Oil component Stearic acid 0.7 0.7 Cetearyl alcohol 0.7 0.7 Hydrogenated oil 0.5 0.5 Chin type glyceryl stearate 0.5 0.5 Sorbitan stearate 0.3 0.3 Polysorbate 60 1.2 1.2 Hydrogenated polydecene 3.0 3.0 Cetyl octanoate 2.0 2.0 Decamethylcyclopentasiloxane 4.0 4.0 Dimethicone 1.0 1.0 Awards
ingredient Purified water To 100 To 100 Butylene glycol 5.0 5.0 Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 - glycerin 1.0 1.0 Disodium iodide 0.02 0.02 Tiei 0.15 0.15 antiseptic 0.2 0.2 Xanthan gum 0.2 0.2 Carbomer 0.15 0.15 Retinoic acid 5.0 5.0

[Manufacturing method of Example 4 and Comparative example 4]

1) Water components (except for retinoic acid) were heated (70 to 75 ° C) and uniformly dissolved and mixed.

2) The oil components were heated (70 ~ 75 ℃) and mixed uniformly.

3) The emulsion was prepared by adding the above-mentioned 2) to the above 1) under the condition of maintaining the temperature at 70 to 75 캜 under stirring, and the emulsion was cooled to 28 to 30 캜.

4) While stirring, retinoic acid is dissolved in purified water and butylene glycol and mixed homogeneously.

Skin absorption (占 퐂 / cm2 / wt%) of vitamin A (retinoic acid) time Example 4 Comparative Example 4 0 0 0 4 10.35 5.31 8 20.57 10.23 24 41.32 15.57

Considering that the duration of make-up is generally between 4 hours and 8 hours, the skin absorption of retinoic acid from Table 8 is at least 2 to 3 times higher than when the cyclohexanedicarboxylic acid derivative is added to the composition Or more.

[Test Example 5] Measurement of skin absorption of caffeine

The amount of caffeine absorbed into the skin was measured in the same manner as in Test Example 1, and the results are shown in Table 10.

The compositions of Example 5 and Comparative Example 5 division Raw material name Example 5 Comparative Example 5 Awards
ingredient Purified water To 100 To 100 Propylene glycol 5.0 5.0 Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 - glycerin 1.0 1.0 Disodium iodide 0.02 0.02 Sodium salicylate 0.2 0.2 Sodium citrate 0.15 0.15 Tiei 0.3 0.3 antiseptic 0.2 0.2 Xanthan gum 0.2 0.2 Carbomer 0.3 0.3 Caffeine 2.0 2.0

[Production method of Example 5 and Comparative Example 5]

1) Components except carbomer were uniformly dissolved and mixed at room temperature in purified water.

2) Thickening agent is added at room temperature under agitation to make a clear viscous essence.

Skin absorption of caffeine per application concentration (占 퐂 / cm2 / wt%) time Example 5 Comparative Example 6 0 0 0 4 50.35 15.95 8 125.57 30.23 24 210.32 57.84

Considering that the duration of make-up is generally between 4 hours and 8 hours, the skin absorption of caffeine from Table 10 is at least 2 to 3 times higher than when the cyclohexanedicarboxylic acid derivative is added to the composition Or more.

Formulation examples of the cosmetic composition and the pharmaceutical composition according to the present invention will be described below. However, the present invention can be applied to various formulations other than the following examples.

[Formulation Example 1] Flexible lotion (skin lotion)

Flexible lotion was prepared by a conventional method according to the composition shown in Table 11 below.

ingredient Content (% by weight) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 glycerin 3.5 Oleyl alcohol 1.5 ethanol 5.5 Polysorbate 80 3.2 Carboxyl vinyl polymer 1.0 Butylene glycol 2.0 Propylene glycol 2.0 Preservative, fragrance Suitable amount Purified water Balance system 100

[Formulation Example 2] Nutritional lotion (Milk lotion)

Nutrition lotion was prepared according to a conventional method according to the composition shown in Table 12 below.

ingredient content
(weight%) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Wax 4.0 Polysorbate 60 1.5 Caprylic / capriciculiglyceride 5.0 Squalane 5.0 Sorbitacecequioleate 1.5 Cetearyl alcohol 1.0 Triethanolamine 0.2 Preservative, fragrance Suitable amount Purified water Balance system 100

[Formulation Example 3] Nourishing cream

Nutritive creams were prepared according to the compositions shown in Table 13 below in a conventional manner.

ingredient content
(weight%) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 glycerin 3.5 Butylene glycol 3.0 Liquid paraffin 7.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / capriciculiglyceride 3.0 Squalane 5.0 Cetearyl glucoside 1.5 Sorbitan stearate 0.4 Polysorbate 60 1.2 Triethanolamine 0.1 Preservative, fragrance Suitable amount Purified water Balance system 100

[Formulation Example 4] Massage cream

The nutritional creams were prepared according to the compositions shown in Table 14 below in a conventional manner.

ingredient Content (% by weight) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 glycerin 8.0 Butylene glycol 3.0 Liquid paraffin 45.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / capric triglyceride 3.0 Wax 4.0 Cetearyl glucoside 1.5 Sesquioleic acid sorbitan 0.9 paraffin 1.5 Preservative, coloring, fragrance Suitable amount Purified water Balance system 100

[Formulation Example 5] Pack

Nutrition creams were prepared according to the compositions shown in Table 15 below in a conventional manner.

ingredient Content (% by weight) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 glycerin 4.0 Polyvinyl alcohol 15.0 Hyaluronic acid extract 5.0 Beta Glucan 7.0 Allantoin 0.1 Nonyl phenyl ether 0.4 Polysorbate 60 1.2 Ethanol preservative Suitable amount Preservative, fragrance Suitable amount Purified water Balance system 100

[Formulation Example 6] Ointment in external preparation for skin

Ointments were prepared in a conventional manner according to the composition shown in Table 16 below.

ingredient Content (% by weight) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 Beta-1,3-glucan 10.0 Wax 10.0 Polysorbate 5.0 Piggy 60 hardened castor oil 2.0 Sorbitan sesquioleate 0.5 vaseline 5.0 Liquid paraffin 10.0 Squalane 5.0 Sheer butter 3.0 Caprylic / capric triglyceride 5.0 glycerin 10.0 Propylene glycol 10.2 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount Purified water Balance system 100

[Formulation Example 7] Preparation of drug (patch) for topical administration

Pharmaceutical preparations (patches) for topical administration were prepared in a conventional manner according to the composition shown in Table 17 below.

ingredient Content (% by weight) Bisethoxydiglycol cyclohexanedicarboxylate < RTI ID = 0.0 > 2.0 Beta-1,3-glucan 3.0 Diethylamine 0.7 Sodium sulphate 0.1 Polyoxyethylene lauryl ether (E.O. = 9) 1.0 Polyhydroxyethylene cetyl stearyl ether (Cetomacrogol 1000) 1.0 Viscous paraffin oil 2.5 Caprylic acid ester / capric acid ester (Cetiol LC) 2.5 Polyethylene glycol 400 3.0 Polyacrylic acid (Carbopol 934P) 1.0 Purified water Balance system 100

Those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (9)

As a skin absorption enhancer for promoting skin absorption of an active ingredient, Wherein the active ingredient is selected from the group consisting of L-ascorbyl glucoside, kojic acid, arbutin, retinoic acid and caffeine, 1. A skin absorption enhancer for an active ingredient, comprising a cyclohexanedicarboxylic acid derivative represented by the following formula (1). [Chemical Formula 1]

A cosmetic composition comprising the skin absorption enhancer of the active ingredient of claim 1. 3. The method of claim 2, Wherein the cyclohexanedicarboxylic acid derivative is contained in an amount of 0.01 to 10.0% by weight based on the total weight of the composition. The method of claim 3, Wherein the cyclohexanedicarboxylic acid derivative is contained in an amount of 0.1 to 5.0% by weight based on the total weight of the composition. delete 3. The method of claim 2, The cosmetic composition according to claim 1, wherein the cosmetic composition is a skin whitening composition containing an active ingredient selected from the group consisting of L-ascorbyl glucoside, kojic acid and arbutin. 3. The method of claim 2, Wherein the cosmetic composition contains retinoic acid as an active ingredient and is a composition for preventing and improving wrinkles. delete delete