KR20080063186A - Transdermal composition for removing cellulite, cataplasma comprising the same and method for preparing thereof - Google Patents

Abstract

A transdermal composition for removing cellulite and a cataplasma comprising the same are provided to show excellent lipolysis and cellulite removing effect by improving in vivo permeability of lipolysis materials, enhance the hydration effect of skin, minimize skin irritation and exhibit excellent water holding capacity, elasticity and stability. A transdermal composition for removing cellulite comprises: 0.1-10.0 parts by weight of caffeine; 0.01-10.0 parts by weight of at least one biologically active material selected from the group consisting of an extract of green tea, an extract of ivy, an extract of seaweed, an extract of ginkgo biloba l. leaves, and an extract of fruit acid; 1.0-30.0 parts by weight of at least one adhesive polymer selected from the group consisting of polyacrylate, polyvinylalcohol, gelatin, methylcellulose, hydroxymethylcellulose, sodium methyl cellulose, methoxyethylene anhydrous maleic acid copolymer and polyol pre-polymer; and 0.001-20.0 parts by weight of at least one skin absorption promoting agent selected from the group consisting of methyl pyrrolidone, propylene glycol, isopropyl myristic acid, polysorbate, sorbitan fatty acid ester, poloxamer, dimethylsulfoxide, dodecanol, hexane ethoxylate, alcohol, eucalyptol, limonene oxide, laurocapram, peppermint oil, alpha-limonene, oleic acid, lauric acid, phenyl-4-butoxymethyl-2-methoxy-vinyl butyl ether, 1-dodecylazacycloheptane-2-one and lanoline. A method for preparing the transdermal composition for removing cellulite comprises the steps of: (a) after mixing the adhesive polymer with water, agitating it at a temperature of 50-70 deg.C to prepare a mixture solution; (b) after mixing the caffeine, biologically active material and skin absorption promoting agent, agitating it to prepare a mixture solution; and (c) mixing the mixture solution obtained from the step(a) with the mixture solution obtained from the step(b) with agitation to obtain an adhesive composition. A cataplasma comprises an impermeable protective layer, an adhesive matrix layer and a release layer, wherein the adhesive matrix layer includes the transdermal composition for removing cellulite.

Description

Transdermal composition for cellulite removal, poultice comprising the same and method for manufacturing the same {TRANSDERMAL COMPOSITION FOR REMOVING CELLULITE, CATAPLASMA COMPRISING THE SAME AND METHOD FOR PREPARING THEREOF}

The present invention relates to a transdermal composition for cellulite removal, a poultice comprising the same and a method for producing the same. More specifically, the present invention improves the body permeability of the lipolytic material, has excellent lipolysis and cellulite removal effect, enhances the hydration effect of the skin, removes or minimizes skin irritation, and a transdermal composition for cellulite removal; It relates to a poultice containing the same.

With the recent rise in social interest in health, there are various efforts to reduce body fat for health or cosmetic reasons. Interest in caffeine as a substance effective in reducing body fat has recently increased.

Caffeine is a substance found in coffee, tea, green tea, cocoa, and soft drinks. Medically, caffeine excites central nervous system excitation, cardiac excitation, coronary and peripheral blood vessel expansion, cerebrovascular export, skeletal muscle excitement, gastric acid secretion, and diuresis It is used for therapeutic purposes such as neonatal apnea, arousal maintenance, and central excitement.

Caffeine (1,3,7-trimethylxanthine) belongs to methylxanthine alkaloids such as theophylline or theobromine. Caffeine increases intracellular cAMP and blocks adenosine receptors, either directly or indirectly by increasing intracellular calcium ions or by inhibiting cyclic nucleotide phosphodiesterase. T _max is 15 to 45 minutes, T _1/2 is from 3 to 7.5 times, 4.9 time based on the adult.

As such, caffeine increases the secretion of catecholamines from the adrenal medulla, activates adenylate cyclase, and inhibits cAMP degrading enzyme phosphodiesterase (PDE). It is known to increase. That is, caffeine increases the concentration of cAMP that activates lipoprotein lipase (LPL), which promotes oxidation from body fat to free fatty acids (FFAs). Attempts have been made to use it for body fat reduction by topical application.

However, when oral administration of caffeine has symptoms such as progression, nausea, insomnia, irritability and systemic side effects, and side effects such as withdrawal symptoms when used for a long time. In addition, when applied by subcutaneous injection, there is a problem that it is difficult to topically apply a certain drug concentration due to the inconvenience of use.

Therefore, there is a need for transdermal administration of caffeine, which can eliminate side effects of concern in the conventional administration method while optimally utilizing the body fat reduction effect of caffeine.

Cataplasma, one of the modes of transdermal administration that may be considered in that respect, belongs to the patch together with the plaster, and is generally an essential oil component after admixing powdered pharmaceuticals with glycerin, water or other suitable liquid substances. Or it is an oil-in-water type (O / W) external preparation manufactured by adding and mixing a fragrance and evenly. The poultice agent has a sustained release property of the active ingredient, and since it uses a water-soluble solvent, there is no side effect such as skin irritation. On the other hand, there is a large amount of solids applied per area, difficult drug delivery is difficult, thickening and inconvenience to use.

In addition, in the case of using a generally used transdermal molding formulation, when the apical part of the initial affected area is softened by body temperature or sweat, or a part of the solid may stick to the skin and remain, it may change over time and become gypsum-like and completely. There may be problems such as not peeling.

In consideration of these problems, it is possible to improve the percutaneous absorption of caffeine to optimally reduce the body fat, while maintaining excellent water retention, flexibility, adhesion and adhesion, and changes in the ambient environment and time-dependent changes such as temperature and humidity. There is a need for development of transdermal absorbent preparations with high stability.

The present inventors earnestly researched to solve these problems, and as a result, the body fat decomposition effect of caffeine is contained by using a transdermal composition containing caffeine as a lipolytic drug and including a skin absorption accelerator to increase its absorption. The present invention was completed by discovering that it can be optimally exhibited.

It is an object of the present invention to provide a transdermal composition for cellulite removal comprising a caffeine, a biologically active substance, an adhesive polymer, and a skin absorption accelerator and a method for producing the same.

In addition, the present invention is to provide a poultice containing the transdermal composition, excellent body fat decomposition effect, minimized skin irritation and improved its properties.

The objects of the present invention are not limited to the above-mentioned objects, and other objects and advantages of the present invention which are not mentioned above can be understood by the following description, and will be more clearly understood by the embodiments of the present invention. Also, it will be readily appreciated that the objects and advantages of the present invention may be realized by the means and combinations thereof indicated in the claims.

The present invention is iii) caffeine 0.1 ~ 10.0 parts by weight; Ii) 0.01-10.0 parts by weight of at least one biologically active substance selected from the group consisting of green tea extract, ivy extract, sea horse extract, ginkgo biloba extract and fruit acid extract; Viii) 1.0-30.0 wt. Of at least one adhesive polymer selected from the group consisting of polyacrylate, polyvinyl alcohol, gelatin, methyl cellulose, hydroxymethyl cellulose, sodium methyl cellulose, methoxyethylene maleic anhydride copolymer and polyol prepolymer part; And iii) methylpyrrolidone, propylene glycol, isopropyl myristic acid, polysorbate, sorbitan fatty acid ester, poloxamer, dimethyl sulfoxide, dodecanol, hexane ethoxylate, alcohols, eucapitol, limonene oxide, lau Locapram, peppermint oil, alphalimonene, oleic acid, lauric acid, phenol-4-butoxymethyl-2-methoxy-vinylbutylether, 1-dodecylazacycloheptan-2-one and lanolin It provides a transdermal composition for cellulite removal comprising 0.001 to 20.0 parts by weight of at least one skin absorption promoter.

The present invention comprises the steps of: i) mixing 1.0 to 30.0 parts by weight of the tacky polymer with water, followed by stirring at a temperature of 50 to 70 ° C. to form a mixed solution; Ii) mixing 0.1-10.0 parts by weight of caffeine, 0.01-10.0 parts by weight of a biologically active substance and 0.001-20.0 parts by weight of a skin absorption accelerator, followed by stirring to form a mixed solution; Iii) mixing the mixed solution of step iii) and the mixed solution of step ii) to obtain a tacky composition, thereby providing a method for preparing the transdermal composition for cellulite removal.

The present invention also provides a poultice agent comprising an impermeable protective layer, an adhesive matrix layer, and a desorption layer, wherein the adhesive matrix layer contains the transdermal composition for cellulite removal.

According to the present invention, it improves the skin permeability of caffeine used as a lipolytic material to optimize the lipolytic effect and have an excellent cellulite removal effect, side effects while avoiding the deactivation or metabolism of the effective drug in the liver and gastrointestinal tract It can provide a transdermal composition for cellulite removal can be minimized.

In addition, according to the present invention, the drug can be continuously delivered at a constant speed, and the drug can be absorbed and infiltrated only at the target site, and the hydration effect of the skin is increased and the irritation of the skin is also eliminated or minimized. It is possible to provide a transdermal composition for easy cellulite removal.

In addition, the poultice containing the transdermal composition of the present invention is excellent in water retention, flexibility and adhesion to the skin, it can give a sense of adhesion according to the movement of the affected area, high temperature according to the ambient environment, such as temperature and humidity, changes over time It is possible to exhibit improved properties with stability.

The above objects, features, and advantages will become more apparent from the detailed description given hereinafter with reference to the accompanying drawings, and accordingly, those skilled in the art to which the present invention pertains may share the technical idea of the present invention. It will be easy to implement. In addition, in describing the present invention, when it is determined that the detailed description of the known technology related to the present invention may unnecessarily obscure the gist of the present invention, the detailed description thereof will be omitted. Hereinafter, the present invention will be described in detail.

The transdermal composition for cellulite removal of the present invention includes a caffeine, a biologically active substance, an adhesive polymer, and a skin absorption accelerator, and is used for a poultice, characterized in that it can exhibit improved properties. That is, in the present invention, by transdermal application of caffeine in the form of a poultice, it is possible to avoid the first-pass effect in which the drug is decomposed or metabolized and inactivated in the liver and gastrointestinal tract. Accordingly, side effects that may occur when applied by oral administration or subcutaneous injection can be eliminated, and the lipolytic effect of caffeine can be concentrated on the target site and is effective for removing cellulite.

In the present invention, caffeine, a lipolytic drug, is included in the transdermal composition, exhibits sustained release properties, and its skin permeability is improved, thereby intensively increasing the lipolytic effect. Caffeine is preferably included 0.1 to 10.0 parts by weight, when the caffeine content is less than 0.1 parts by weight it is difficult to show a lipolysis effect, when it exceeds 10.0 parts by weight can not show any further effect by increasing the content, rather caffeine There is a risk of side effects.

In addition, the transdermal composition according to the present invention contains 0.01 to 10.0 parts by weight of at least one biologically active substance selected from the group consisting of green tea extract, ivy extract, sea horse extract, ginkgo biloba extract and fruit acid extract. These biologically active substances can not only promote the lipolytic effect, but also facilitate the metabolism.

The catechins contained in the green tea extract have the effect of releasing triglycerides and wastes in the body and may provide additional lipolytic effects. In addition, green tea extract contains vitamin A, vitamin C, and tocopherol to help skin cell health, and is also effective in inhibiting skin aging.

Ivy extract has recently been used as a raw material for cosmetics, etc. It may have a skin protective effect, and sea horse extract may contain uric acid, thereby activating lipase, a lipolytic enzyme, to provide additional lipolytic effect, calcium and It contains a large amount of minerals and has a useful effect. In addition, ginkgo biloba extract may exhibit a variety of activities, such as blood circulation, improving blood circulation, improving liver function and protecting liver cells.

Examples of fruit acid extracts include extracts such as bilberry (vaccinium myrtillus), sugarcane (Saccharum officinarum), lemon (Citrus limonum), orange (Citrus Aurantium Dulcis), and silver leaf (Acer saccharinum). It can give an effect.

Such biologically active drugs are included in the transdermal composition at 0.01 to 10.0 parts by weight, and may be used alone or as a mixture of two or more thereof. When two or more kinds of mixtures are used, for example, 0.1 to 20.0 parts by weight of green tea extract, 0.1 to 10.0 parts by weight of ivy extract, and 0.1 to 20.0 parts by weight of seaweed extract, based on the total content of the biologically active drug contained in the transdermal composition. , A mixture containing 0.1-20.0 parts by weight of ginkgo leaf extract and 0.01-10.0 parts by weight of fruit acid extract may be used.

The transdermal composition according to the present invention is at least one adhesive selected from the group consisting of polyacrylate, polyvinyl alcohol, gelatin, methyl cellulose, hydroxymethyl cellulose, sodium methyl cellulose, methoxyethylene maleic anhydride copolymer and polyol prepolymer. It contains 1.0-30.0 weight part of polymers. When the adhesive polymer content is out of the above range, water retention and flexibility are lowered, skin adhesion is inferior, and there is a concern that stability due to changes in the surrounding environment and over time may be reduced.

The adhesive polymer may be used alone or in a mixture of two or more thereof. When used as a mixture, for example, 1 to 30 parts by weight of polyacrylate, 1 to 30 parts by weight of polyvinyl alcohol, 1 to 20.0 parts by weight of gelatin, methyl cellulose based on the total content of the adhesive polymer included in the transdermal composition Using a mixture comprising 0.1-20.0 parts by weight of a cellulose pressure-sensitive adhesive selected from the group consisting of hydroxymethyl cellulose and sodium methyl cellulose, 0.1-30 parts by weight of methoxyethylene maleic anhydride copolymer and 0.1-20.0 parts by weight of a polyol prepolymer. To form a poultice.

The transdermal composition according to the present invention is characterized in that it contains a skin absorption enhancer to improve skin permeability of the lipolytic drug caffeine and the biologically active substance. Skin absorption promoters that can be used in the present invention are methylpyrrolidone, propylene glycol, isopropyl myristic acid, polysorbate, sorbitan fatty acid ester, poloxamer, dimethyl sulfoxide, dodecanol, hexane ethoxylate, alcohol , Eucapitol, limonene oxide, laurocapram, peppermint oil, alpharimonene, oleic acid, lauric acid, phenol-4-butoxymethyl-2-methoxy-vinylbutyl ether, 1-dodecylazacycloheptan-2 And at least one substance selected from the group consisting of -one and lanolin. In the present invention, the skin absorption promoter is preferably included in 0.001 ~ 20.0 parts by weight, and if it is less than the above range can not obtain an effective skin absorption promoting effect, if it exceeds the above range further effect by increasing the content Can not get

These skin absorption promoters may be used alone or in a mixture of two or more thereof. When using the mixture, for example, methylpyrrolidone, propylene glycol, isopropyl myristic acid, polysorbate, sorbitan fatty acid ester, poloxamer, dimethyl based on the total content of the skin absorption promoter included in the transdermal composition. Sulfoxide, dodecanol, hexaneethoxylate, alcohol, eucapitol, limonene oxide, laurocapram, peppermint oil, alpharimonene, oleic acid, lauric acid, phenol-4-butoxymethyl-2-methoxy-vinylbutyl Mixtures comprising 0.0001 to 20.0 parts by weight of at least one substance selected from the group consisting of ether and 1-dodecylazacycloheptan-2-one and 0.1 to 10.0 parts by weight of lanolin may be used.

As described above, the transdermal composition according to the present invention includes caffeine, a biologically active substance, a tacky polymer and a skin absorption accelerator, and water in a residual amount, preferably purified water.

In addition, the transdermal composition according to the present invention, if necessary, further comprises one or more additives selected from the group consisting of moisturizers, gel formers, curing agents, excipients, preservatives, thickeners and pH adjusters contained in conventional dermal compositions for poultices. May be included.

The transdermal composition according to the present invention includes the steps of i) mixing 1.0 to 30.0 parts by weight of the tacky polymer with water, followed by stirring at a temperature of 50 to 70 ° C. to form a mixed solution; Ii) mixing 0.1-10.0 parts by weight of caffeine, 0.01-10.0 parts by weight of a biologically active substance and 0.001-20.0 parts by weight of a skin absorption accelerator, followed by stirring to form a mixed solution; V) mixing the mixed solution of step iii) and the mixed solution of step ii) with stirring to obtain an adhesive composition.

Water mixed with the adhesive polymer in the step iii) is about 70 to 90 parts by weight of the total content of the water contained in the transdermal composition, the remaining amount of water is preferably added during the preparation of the mixture of step ii).

The transdermal composition according to the present invention prepared by the above method may be formed into a poultice agent according to a generally known method. Although not particularly limited, the poultice agent can be prepared by uniformly applying the transdermal composition according to the present invention as an adhesive matrix layer to an appropriate thickness and forming an impermeable protective layer and a desorption layer.

The poultice agent according to the present invention can increase the skin permeability of caffeine and biologically active substances included as an active drug, thereby intensively exerting effective effects such as lipolysis, showing excellent effects on cellulite removal, and minimizing side effects and skin irritation. As well as high stability.

Hereinafter, the present invention will be described in detail with reference to Examples.

However, the following examples are merely to illustrate the present invention, the contents of the present invention is not limited to the following examples.

Example  One: Transdermal  Composition Preparation (1)

According to the ratio (parts by weight) of Table 1, gelatin and polyvinyl alcohol were mixed in purified water having 80 parts by weight of the total content, and then dissolved by stirring at a temperature of about 50 to 70 ° C to form a mixed solution (1). The other components were mixed with the remaining 20 parts by weight of purified water, followed by stirring to form a mixed liquid (2), followed by mixing while mixing the mixed liquid (1) and (2), thereby increasing the transdermal composition with increased adhesive strength over time. Got it. In the transdermal composition, EDTA, a gel forming agent, Grycinal, a curing agent, and glycerin, a moisturizing agent, were included as additional additives.

Furtherance Ratio (part by weight) gelatin 3.00 Polyvinyl Alcohol (PVA) 3.80 EDTA 0.15 Purified water 40.0 Sodium Polyacrylate Salt (PAS) 5.50 Grycinal 0.10 glycerin 40.0 Carbamol (cellulose) 1.00 Methoxyethylene Maleic Anhydride Copolymer 0.45 Ginkgo Leaf Extract 0.80 Lauric acid 0.20 Green tea extract 2.00 Orange (citrus aurantium) extract 1.50 Caffeine 1.50

Example  2: Transdermal  Composition Preparation (2)

A transdermal composition was prepared in the same manner as in Example 1 except that 1.5 parts by weight of methylpyrrolidone was used as a skin absorption accelerator, and the content of sodium polyacrylate salt was 4.00 parts by weight.

Furtherance Ratio (part by weight) gelatin 3.00 Polyvinyl Alcohol (PVA) 3.80 EDTA 0.15 Purified water 40.0 Sodium Polyacrylate Salt (PAS) 4.00 Grycinal 0.10 glycerin 40.0 Carbamol (cellulose) 1.00 Methoxyethylene Maleic Anhydride Copolymer 0.45 Ginkgo Leaf Extract 0.80 Lauric acid 0.20 Methylpyrrolidone 1.50 Green tea extract 2.00 Orange (citrus aurantium) extract 1.50 Caffeine 1.50

Example  3: Transdermal  Composition Preparation (3)

A transdermal composition was prepared in the same manner as in Example 1 except for including the same amount of floxamer as the skin absorption promoter instead of lauric acid.

Furtherance Ratio (part by weight) gelatin 3.00 Polyvinyl Alcohol (PVA) 3.80 EDTA 0.15 Purified water 40.0 Sodium Polyacrylate Salt (PAS) 5.50 Grycinal 0.10 glycerin 40.0 Carbamol (cellulose) 1.00 Methoxyethylene Maleic Anhydride Copolymer 0.45 Ginkgo Leaf Extract 0.80 Poloxamer 0.20 Green tea extract 2.00 Orange (citrus aurantium) extract 1.50 Caffeine 1.50

Example  4: Transdermal  Composition Preparation (4)

A transdermal composition was prepared in the same manner as in Example 1 except for including oleic acid in the same amount instead of lauric acid as a skin absorption promoter.

Furtherance Ratio (part by weight) gelatin 3.00 Polyvinyl Alcohol (PVA) 3.80 EDTA 0.15 Purified water 40.0 Sodium Polyacrylate Salt (PAS) 5.50 Grycinal 0.10 glycerin 40.0 Carbamol (cellulose) 1.00 Methoxyethylene Maleic Anhydride Copolymer 0.45 Ginkgo Leaf Extract 0.80 Oleic acid 0.20 Green tea extract 2.00 Orange (citrus aurantium) extract 1.50 Caffeine 1.50

Example  5: Transdermal  Composition Preparation (5)

A transdermal composition was prepared in the same manner as in Example 1 except for including limonene oxide in the same amount instead of lauric acid as a skin absorption promoter.

Furtherance Ratio (part by weight) gelatin 3.00 Polyvinyl Alcohol (PVA) 3.80 EDTA 0.15 Purified water 40.0 Sodium Polyacrylate Salt (PAS) 5.50 Grycinal 0.10 glycerin 40.0 Carbamol (cellulose) 1.00 Methoxyethylene Maleic Anhydride Copolymer 0.45 Ginkgo Leaf Extract 0.80 Limonene oxide 0.20 Green tea extract 2.00 Orange (citrus aurantium) extract 1.50 Caffeine 1.50

Example  6 to 10: Poultice  Manufacture (1) to (5)

The transdermal composition prepared in Examples 1 to 5 was transferred to a coating machine and coated to a thickness of 5 to 6 mm or less, but the coating area was adjusted to 10 × 7 cm ² (width × length), and the coating amount was adjusted to about 7-9 g to form a poultice agent. Prepared.

Experimental Example  1: adhesion test

1 hour after the preparation and the poultice prepared in Examples 6 to 10 aged for 1, 2, 3 days, was tested by the Quick-Stick (PSTC test) to determine the degree of adhesion . In the above method, the poultice agent was attached to the vertical steel sheet and then pulled at an angle of 180 degrees, and expressed in g per inch of the width of the deposit, and the poultice agents of Examples 6 to 10 showed results of 5-7 g or more. This was different depending on the purpose of use, but the result was no problem with the adhesive force as a poultice agent, and no residue remained on the steel sheet after the experiment.

Experimental Example  2: drug permeation experiment

(1) experimental conditions and reagents

Permeation testing was performed in a modified Franz cell (11 mL, pyrex), and pH meter (pH meter) was used by Cyberscan pH 1000. Cellulose membrane was made from Sigma Chemical, 0.45 µm PVDF membrane filter was used as product of WOONG KI Science.

Potassium phosphate monobasic for the manufacture of the receptor phase and sodium hydroxide and trifuoroacetic acid for the mobile phase production were obtained from aceto, Yakuri Pure Chemicals. Nitrile and deionized water are JT Baker product was used.

Animals used in the experiment were male hairless mice, 6 to 8 weeks old, adapted to the laboratory environment. Animal breeding conditions were maintained at a temperature of 20-25 ° C., a humidity of 60 ± 5 parts by weight, and a contrast shift time of 12 hours. Except during the experiment, water and food were sufficiently supplied and fasted 24 hours before the experiment.

(2) drug release experiment

The amount of caffeine released from the poultice agent prepared in Example 2 was obtained using a Modified Franz diffusion cell. 4 cm 2 of the poultice agent of Example 2 was attached onto a cellulose membrane (dialysis tubing, Sigma), and a pH 5.8 phosphate buffer prepared by warming to 37 ° C. before the experiment was used on a receptor. The volume of the cell was kept constant at 11 mL, the temperature during the experiment at 37 ± 0.5 ° C., and the stirring speed at 600 rpm. As the experiment proceeds, the sample is accurately collected by using a micropipette at the receptor side at intervals of 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8 hours, and then filtered with a 0.45 μm PVDF membrane filter. One sample was used as a sample and analyzed by HPLC. After each collection, the same amount of phosphate buffer solution was added to the receptor side.

(3) HPLC analysis conditions

The quantitative analysis instrument was composed of Shiseido Co. Shiseido Nanospace SI-2 3001 Pump, Shiseido Nanospace SI-2 3002 Detector, Shiseido Nanospace SI-2 3004 Column oven, and was used by Donam Instrument Inc. (Korea) for ds CHROM ^{2000 ( PI)} . As analytical conditions, the column was Xterra C ₁₈ (5 μm, Size 3.9 × 150 mm, Waters), the mobile phase was acetonitrile: 0.05 parts by weight trifluoroacetic acid (13: 87), the flow rate was 500 μL / min, UV The detector was analyzed at 254 nm, temperature 35 ° C. and injection volume 20 μl.

(4) Data analysis

Skin permeability of caffeine from the poultice was calculated using the modified Fick's equation.

J = steady-state flux (µg / cm 2 / hr)

dc / dt = concentration of drug passing through the skin per unit time at equilibrium

V = volume of receptor compartment (cm 3)

A = area of skin in which drug permeation occurs (cm 2)

That is, the amount of caffeine (Q) passing through the skin per unit area over time (t) was plotted and the skin penetration rate was calculated using the slope of the straight portion of the plot, and the The amount was calculated using the equation below.

Q: the amount of drug penetrating the skin at time t

D: diffusion coefficient (cm 2 / sec)

K: Distribution coefficient of drug in skin

A: effective surface area of the skin

h: thickness of the skin

C _d: the donor _(donor phase) the drug concentration

T _{L :} lag-time (hr)

In addition, in order to obtain the permeability coefficient, the amount of skin permeation drug at a specific time was first differentiated over time.

If the state of the receptor phase sink is maintained,

From this, the transmission coefficient was obtained using the above equation.

(5) results

The amount of caffeine that penetrated the hairless mouse skin from the poultices prepared in Examples 6 to 10 is shown in Table 6 below according to the skin absorption promoter content (n = 3, ± S.E.M.).

time 0 15 30 45 60 120 180 240 300 360 420 480     Amount (μg) Example 6 0 0.40 ± 0.42 1.20 ± 0.21 2.86 ± 0.01 3.78 ± 1.92 11.01 ± 1.71 20.48 ± 1.56 29.01 ± 1.37 39.25 ± 1.01 48.32 ± 1.86 58.22 ± 2.22 60.05 ± 2.62 Example 7 0 0.38 ± 0.85 1.42 ± 1.69 3.01 ± 1.24 3.95 ± 1.37 14.11 ± 1.65 20.18 ± 2.22 31.73 ± 1.92 40.25 ± 2.44 50.61 ± 1.89 60.67 ± 1.47 61.25 ± 2.12 Example 8 0 0.25 ± 0.26 0.82 ± 1.57 2.01 ± 1.78 2.82 ± 1.11 9.18 ± 1.01 17.42 ± 0.48 29.1 ± 3.32 35.67 ± 1.14 42.33 ± 1.59 50.25 ± 1.36 56.75 ± 2.45 Example 9 0 0.38 ± 2.04 1.58 ± 1.53 3.10 ± 0.86 3.92 ± 1.54 10.08 ± 1.29 20.28 ± 3.02 30.63 ± 1.67 41.85 ± 1.91 48.25 ± 1.35 53.46 ± 1.73 62.02 ± 2.13 Example 10 0 0.16 ± 1.31 1.28 ± 1.93 2.82 ± 2.25 3.02 ± 1.32 7.57 ± 1.35 16.72 ± 1.36 25.76 ± 3.45 37.13 ± 1.62 44.01 ± 2.11 48.52 ± 1.21 55.78 ± 1.87

As can be seen from the above-described examples and experimental examples, the transdermal composition and the poultice agent according to the present invention contain a specific part by weight of components, thereby improving skin permeability of caffeine and a biologically active substance, thereby intensively exerting efficacy on a target site. Can be. In addition, the skin adhesion, adhesiveness and stability is excellently improved, can exhibit excellent properties in water retention and flexibility.

The present invention described above is limited by the above-described embodiments as various substitutions, modifications, and changes are possible to those skilled in the art without departing from the spirit of the present invention. It is not.

Claims (7)

Iii) 0.1-10.0 parts by weight of caffeine; Ii) 0.01-10.0 parts by weight of at least one biologically active substance selected from the group consisting of green tea extract, ivy extract, sea horse extract, ginkgo biloba extract and fruit acid extract; Viii) 1.0-30.0 wt. Of at least one adhesive polymer selected from the group consisting of polyacrylate, polyvinyl alcohol, gelatin, methyl cellulose, hydroxymethyl cellulose, sodium methyl cellulose, methoxyethylene maleic anhydride copolymer and polyol prepolymer part; And Iii) methylpyrrolidone, propylene glycol, isopropylmyristin acid, polysorbate, sorbitan fatty acid ester, poloxamer, dimethyl sulfoxide, dodecanol, hexane ethoxylate, alcohol, eucapitol, limonene oxide, lauro Capram, peppermint oil, alphalimonene, oleic acid, lauric acid, phenol-4-butoxymethyl-2-methoxy-vinylbutylether, 1-dodecylazacycloheptan-2-one and lanolin At least one skin absorption promoter containing 0.001 to 20.0 parts by weight Transdermal composition for cellulite removal. The method of claim 1, The biologically active drug is based on the total content of the biologically active substance green tea extract 0.1 ~ 20.0 parts by weight, ivy extract 0.1 ~ 10.0 parts by weight, seaweed extract 0.1 ~ 20.0 parts by weight, ginkgo leaf extract 0.1 ~ 20.0 parts by weight and fruit acid extract 0.01 ~ It is a mixture comprising 10.0 parts by weight Transdermal composition for cellulite removal. The method of claim 1, The adhesive polymer is a group consisting of 1 to 30 parts by weight of polyacrylate, 1 to 30 parts by weight of polyvinyl alcohol, 1 to 20.0 parts by weight of gelatin, methyl cellulose, hydroxymethyl cellulose and sodium methyl cellulose based on the total content of the adhesive polymer. It is a mixture comprising a cellulose pressure sensitive adhesive selected from 0.1 to 20.0 parts by weight, 0.1 to 30 parts by weight of methoxyethylene maleic anhydride copolymer and 0.1 to 20.0 parts by weight of a polyol prepolymer. Transdermal composition for cellulite removal. The method of claim 1, The skin absorption accelerator is methylpyrrolidone, propylene glycol, isopropylmyristin acid, polysorbate, spans, poloxamer, dimethyl sulfoxide, dodecanol, hexane ethoxylate, alcohol based on the total content of skin absorption accelerator. , Eucapitol, limonene oxide, laurocapram, peppermint oil, alpharimonene, oleic acid, lauric acid, phenol-4-butoxymethyl-2-methoxy-vinylbutylether and 1-dodecylazacycloheptan-2- It is a mixture comprising 0.0001 to 20.0 parts by weight of the at least one substance selected from the group consisting of and 0.1 to 10.0 parts by weight of lanolin Transdermal composition for cellulite removal. The method of claim 1, Further comprising at least one additive selected from the group consisting of moisturizers, gel formers, curing agents, excipients, preservatives, thickeners and pH adjusters Transdermal composition for cellulite removal. V) mixing 1.0 to 30.0 parts by weight of the tacky polymer with water, followed by stirring at a temperature of 50 to 70 ° C. to form a mixed solution; Ii) mixing 0.1-10.0 parts by weight of caffeine, 0.01-10.0 parts by weight of a biologically active substance and 0.001-20.0 parts by weight of a skin absorption accelerator, followed by stirring to form a mixed solution; Iii) mixing the mixed liquid of step iii) and the mixed liquid of step ii) with stirring to obtain a tacky composition. A method for preparing a transdermal composition for removing cellulite according to any one of claims 1 to 5. A poultice comprising an impermeable protective layer, an adhesive matrix layer and a desorption layer, wherein the adhesive matrix layer contains a transdermal composition for removing cellulite according to any one of claims 1 to 5.