KR20150043027A - Composition for improving dry skin or skin barrierfunction comprising rutin - Google Patents

Abstract

The present invention relates to a composition for improving skin dryness or skin barrier function, and more particularly to a PPAR alpha activator, a cosmetic composition and a pharmaceutical composition containing rutin as an active ingredient.
The present invention also relates to a method for preventing, ameliorating or treating skin dryness or skin barrier dysfunction using the composition.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for improving skin dryness or skin barrier function,

The present invention relates to a composition for improving skin dryness or skin barrier function, and more particularly to a PPAR alpha activator, a cosmetic composition and a pharmaceutical composition containing rutin or a salt thereof as an active ingredient.

The present invention also relates to a method for preventing, ameliorating or treating skin dryness or skin barrier dysfunction using the composition.

Human skin consists of dermis and epidermis. The dermis consists mainly of fibroblasts that synthesize collagen and other proteins and produce small amounts of lipids.

In contrast, the epidermis contains keratinocytes, which mainly produce lipids and collagen does not substantially synthesize keratinocytes. The epidermis, located at the outermost part of the skin, performs a protective function to protect against various external physical, chemical and mechanical stimuli and to prevent excessive divergence of body water through the skin. This protective function is possible by normally forming and maintaining the stratum corneum composed of keratinocytes.

This keratinocyte is a cell formed by the basal cell which continuously grows in the stratum basale after passing through the stratum corneum and undergoes a morphological and functional change step by step, Forming cells are disappeared from the skin and new epidermal cells from the epidermal layer are repeatedly replaced by epidermis differentiation or keratinization.

In this keratinization process, keratinocytes produce intracellular lipids such as Natural Moisturizing Factor (NMF) and ceramide, cholesterol and fatty acid, which acts as a barrier for the outer layer of the stratum corneum, (Non-Patent Document 1).

Skin dryness, which is considered to be one of the major diseases of modern society, is one of the symptoms caused by skin barrier function abnormality. Recently, environmental pollution, increase in dry environment such as apartments and high rise building, increase in social stress, Bathing culture, skin aging, etc., and the cases where the symptoms are serious and require treatment are also increasing steadily.

Atopic dermatitis, which is present in 10% of children in recent years, is also known to be a cause of dry skin syndrome, and more fundamentally, abnormal skin barrier function. In order to treat such atopic dermatitis, studies have been carried out in order to supply water from the outside or minimize water loss from the body by focusing on proper moisture retention in the skin in the past. Actually, ceramide or derivatives thereof have been developed and are widely used in the pharmaceutical or cosmetic field.

However, the use of such a moisturizing agent is not only a fundamental treatment but a temporary symptom relief, and thus has not shown sufficient effect for treatment of dry skin and skin barrier function including atopic dermatitis. Therefore, it is urgent to develop a substance that can restore the damaged skin barrier fundamentally.

Recently, it has been known that PPAR alpha (peroxisome proliferator activated receptor-alpha) present in keratinocyte cells is activated by binding to its ligand, thereby promoting the differentiation of keratinocytes and reconstructing damaged skin barrier. In the case of applying Clofibrate (non-patent document 2) or WY 14643 (non-patent document 3) which is an agonist of known PPAR alpha to skin having a damaged skin barrier, differentiation of keratinocytes is accelerated And recovery of the skin barrier is promoted.

Accordingly, the present inventors have conducted studies to overcome the problem of the dry hair syndrome or skin barrier function abnormality including atopic dermatitis, which are heretofore unrecognized as a fundamental treatment method, It has been found for the first time that a rutin derived from a natural product having an activating function of PPAR alpha has an effect of restoring the skin barrier function fundamentally by promoting the differentiation of keratinocytes, Or a therapeutic composition.

 Irwin M. Freedberg et al., Fitzpatrick's dermatology in general medicine, Vol I, 6th ed.  Feingold et al., J. Invest. Dermatol., 110, pp 368-375, 1998.  Feingold et al., J. Invest. Dermatol., 115, pp 353-360, 2000.

The present invention provides a composition containing rutin or a salt thereof as an active ingredient, and is intended to prevent, ameliorate or treat dry skin disorder or skin barrier dysfunction, particularly atopic dermatitis, using the composition.

Specifically, one object of the present invention is to provide a Peroxisome Proliferator Activated Receptor (PPAR) alpha activator containing rutin or a salt thereof as an active ingredient.

Another object of the present invention is to provide a cosmetic composition for improving dryness of skin or skin barrier function abnormality which contains a rutin or a cosmetically acceptable salt thereof as an active ingredient.

It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating dry skin or a skin barrier function comprising rutin or a pharmaceutically acceptable salt thereof as an active ingredient.

It is still another object of the present invention to provide a method for preventing, ameliorating or treating skin dryness or skin barrier dysfunction by using the cosmetic composition or the pharmaceutical composition.

In one aspect of the present invention, there is provided a PPAR alpha (Peroxisome Proliferator Activated Receptor-alpha) activator containing Rutin or a salt thereof as an active ingredient.

Rutin in its natural state is extracted from the flower bud of Sophora japonica , a plant of Leguminosae, or Fagopyrum esculentum , a plant of Polygonaceae, and is a pale yellow needles . These routines are known to potentiate capillary blood vessels and to prevent cardiovascular diseases such as arteriosclerosis, hypertension and cerebral hemorrhage, and to treat diabetes and obesity.

The routine of the present invention may preferably be a routine having the structure of the following formula (1).

[Chemical Formula 1]

The present inventors have developed a substance having an excellent PPAR alpha activation function to activate the PPAR alpha expressed in the keratinocyte to promote the differentiation of the keratinocyte to rapidly recover the damage of the skin barrier and to solve the problem of skin dryness The inventors of the present invention firstly found that the rutin exhibits a very excellent PPAR alpha activation function and completed the present invention. Until now, there has been no report on the PPAR alpha activation function and skin barrier recovery ability of the routine.

As a result of the studies of the present inventors, it has been found that the rutin not only exhibits excellent PPAR alpha activation function but also effectively promotes the differentiation of keratinocyte cells, and when the routine is directly applied to the skin, the skin barrier recovery rate is remarkably increased .

In one specific example of the present invention, mouse-derived myoblasts, C2C12 cells, were cultured in a medium containing a routine, and the activity of PPAR alpha was significantly increased (Example 1).

In addition, it was confirmed that the routine of the present invention has an effect of promoting expression of filaggrin, a keratin-binding protein located in epidermal cells of mammals.

In a specific example of the present invention, HaCaT cells as a keratinocyte cell line from humans were cultured in a medium containing a routine, and it was confirmed that expression of filaggrin at the cell level was promoted (Example 2).

In the present invention, the routine may include a routine hydrate, a lutein derivative and the like within a range having the same effect, and may include a solvent or a stereoisomer thereof. The routine may be chemically synthesized or separated from natural materials, and purchased from domestic and overseas chemical companies. In the case where the routine of the present invention is separated from a natural substance, it may be a concept including both an extract of a natural product or a fraction thereof, as long as the routine is included.

The routine of the present invention may be used in the form of a pharmaceutical or cosmetically acceptable salt thereof.

As such salts, acid addition salts formed by pharmaceutical or cosmetically acceptable free acids are useful. Acid addition salts can be prepared in a conventional manner, for example, by dissolving the compound in an excess amount of an aqueous acid solution and precipitating the salt with a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. It is also possible to heat an equimolar amount of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water, and then evaporate the mixture to dryness, or the precipitated salt may be subjected to suction filtration.

As the free acid, an inorganic acid or an organic acid can be used. The inorganic acid may be, for example, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. These may be used alone or in admixture of two or more. Non-limiting examples of the organic acid include methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, The present invention also relates to the use of a compound of formula (I) as an acid, citric acid, lactic acid, glycollic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillyric acid, hydroiodic acid and the like. These may be used alone or in combination of two or more.

In addition, the routine may use a base to make a pharmaceutically or cosmetically acceptable metal salt. The alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble compound salt, and evaporating and drying the filtrate. As the metal salt, it is preferable to produce sodium, potassium or calcium salt in particular, but it is not limited thereto. The corresponding silver salt can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

The pharmaceutically or cosmetically acceptable salts of the above routines may include all salts of acidic or basic groups that may be present in the compounds of the above routines, unless otherwise indicated. For example, the pharmaceutically or cosmetically acceptable salts may include sodium, calcium, and potassium salts of hydroxy groups, and other pharmacologically or cosmetically acceptable salts of amino groups include hardro-bromide, sulfate (Salicylate) salts such as hydrogen sulfates, phosphates, hydrogen phosphates, dihydrogen phosphates, acetates, succinates, citrates, tartrates, lactates, mandelates, methanesulfonates (mesylates) and p- And can be prepared through a method for producing a salt known in the art.

As used herein, the term "PPAR alpha activator" refers to a substance that activates PPAR alpha (Peroxisome Proliferator Activated Receptor-alpha) present in keratinocytes.

The routine of the present invention was found to be excellent in the function of activating PPAR alpha.

The PPAR alpha activator of the present invention contains rutin or a salt thereof as an active ingredient. The effective amount of the rutin or its salt is not particularly limited and may be included in the amount of 0.00001 to 99.9% by weight based on the total weight of the PPAR alpha activator, or may be included in the total amount.

The PPAR alpha activator of the present invention may contain, in addition to the above-mentioned rutin or a salt thereof, an excipient, carrier and other additives, and may be manufactured by a pharmaceutical composition or a cosmetic composition containing them.

According to another aspect of the present invention, there is provided a cosmetic composition for improving skin dryness or skin barrier function abnormality comprising the above-mentioned routine or a cosmetically acceptable salt thereof as an active ingredient.

In the present invention, the rutin or a cosmetically acceptable salt thereof is the same as that described above in connection with the PPAR alpha activator of the present invention.

As used herein, the term "dry skin syndrome" refers to all the symptoms caused by dryness of the skin due to lack of moisture in the skin.

The term "skin barrier function" used in the present invention refers to a skin barrier function, in particular, as a barrier layer to the outside, such as preventing the outflow of moisture to the outside of the skin, The term "skin barrier function abnormality" as used in the present invention means any condition in which the skin barrier function is deteriorated or damaged as well as the possibility that the skin barrier function is degraded or damaged or needs to be prevented.

The symptom of the dry skin of the present invention is not particularly limited as long as it is a symptom caused by drying of the skin due to lack of moisture of the skin.

The skin barrier function abnormality of the present invention is not particularly limited as far as the symptom is caused by the deterioration or damage of the skin barrier function.

Non-limiting examples of the above-mentioned skin dryness or skin barrier function of the present invention include atopic dermatitis, dry eczema, psoriasis, pigmented scleroderma, and the like.

It has been found that the composition of the present invention has an excellent effect for improving the symptoms of atopic dermatitis in particular.

According to a specific embodiment of the present invention, 20 persons aged between the ages of 10 and 50 who were diagnosed with atopic dermatitis were divided into 2 groups (each 10 persons), and only one of them As a result of observing the improvement effect after applying the composition for four weeks to a site showing atopic symptoms, it was confirmed that the composition exhibited superior effect of improving the dermatitis in comparison with the other groups not applied with the composition of the present invention (Example 3 ).

The cosmetic composition of the present invention is excellent in the effect of improving the skin barrier function or preventing, ameliorating or treating the skin dryness or skin barrier function abnormality by the action of the above-mentioned rutin or its cosmetically acceptable salt, which is an effective ingredient, It is safe without applying any harmful effects to human body.

In the cosmetic composition of the present invention, the rutin or the cosmetically acceptable salt thereof may be contained in an amount of preferably 0.0001% by weight to 10% by weight, based on the total weight of the cosmetic composition, 0.0005% by weight to 10% by weight. Within this content range, the advantage of using the rutin or its cosmetically acceptable salt in an appropriate amount is economical, and the effect of the PPAR alpha activity of the rutin or its salt is sufficiently exhibited to achieve the object of the present invention have.

The cosmetic composition according to the present invention can be used as a cosmetic composition for oral use such as a solution, an ointment for external use, a cream, a foam, a nutritional lotion, a flexible lotion, a pack, a soft drink, a latex, a makeup base, an essence, But may be formulated into a formulation selected from the group consisting of emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays, It is not.

The cosmetic composition of the present invention may preferably be manufactured with a semi-solid preparation such as an external ointment, lotion and the like, but is not limited thereto.

The cosmetic composition of the present invention may further comprise at least one cosmetically acceptable carrier to be incorporated in a cosmetic composition for general skin. Examples of the cosmetic composition include ordinary ingredients such as oil, water, a surfactant, a moisturizer, a lower alcohol, , A chelating agent, a coloring agent, a preservative, a perfume, and the like may be appropriately compounded, but the present invention is not limited thereto.

The cosmetically acceptable carrier to be contained in the cosmetic composition of the present invention varies depending on the formulations.

When the formulations of the present invention are ointments, pastes, creams or gels, the carrier component may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc, zinc oxide May be used, but is not limited thereto. These may be used alone or in combination of two or more.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder and the like may be used as a carrier component. In particular, But are not limited to, propellants such as rocaborn, propane / butane or dimethyl ether. These may be used alone or in combination of two or more.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent may be 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 and the like can be used, and particularly fatty acid esters of cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or sorbitan May be used, but is not limited thereto. These may be used alone or in combination of two or more.

When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, but are not limited thereto. These may be used alone or in combination of two or more.

When the formulation of the present invention is a soap, use is made of an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolizate, isethionate, a lanolin derivative, an aliphatic alcohol, a vegetable oil, glycerol, But is not limited thereto. These may be used alone or in combination of two or more.

According to still another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating dry skin disorder or skin barrier function comprising the above-mentioned rutin or a pharmaceutically acceptable salt thereof as an active ingredient.

The above routine or its pharmaceutically acceptable salts, skin dryness, and skin barrier function abnormalities of the present invention are the same as those described above in connection with the PPAR alpha activator and cosmetic composition of the present invention.

As used herein, the term "prophylactic " means any act that inhibits or delays skin dryness or skin barrier function abnormality by administering the composition of the present invention to an individual.

The term "treatment ", as used herein, refers to any act which, by administering the composition of the present invention to an individual, alleviates or alleviates the symptoms of dry skin or skin barrier dysfunction.

The pharmaceutical composition of the present invention is excellent in the effect of improving the skin barrier function or preventing, improving or treating the skin dryness or skin barrier function due to the action of the above-mentioned rutin or its pharmaceutically acceptable salt, And thus it is safe without causing side effects even when applied to human body.

In the pharmaceutical composition of the present invention, the rutin or a pharmaceutically acceptable salt thereof may be contained preferably in an amount of 0.0001% by weight to 10% by weight based on the total weight of the pharmaceutical composition, By weight may be contained in an amount of 0.0005% by weight to 10% by weight. Within the above range, the advantage of using the rutin or a pharmaceutically acceptable salt thereof in an appropriate amount is economical, and the PPAR alpha activity effect of the rutin or a salt thereof is sufficiently exhibited to achieve the object of the present invention have.

The pharmaceutical composition of the present invention may further comprise, in addition to the above-mentioned rutin or a pharmaceutically acceptable salt thereof as an active ingredient, suitable carriers, excipients and diluents conventionally used in the production of pharmaceutical compositions have.

The pharmaceutical composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols or the like, oral preparations or sterilized injection solutions according to a conventional method Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, But are not limited to, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. These may be used alone or in combination of two or more.

When the pharmaceutical composition of the present invention is formulated, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, and surfactants that are usually used.

Solid formulations for oral administration may include tablets, pills, powders, granules, capsules and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose, lactose or gelatin. Can be mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have.

Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, external preparations, and the like. Examples of the non-aqueous solution and suspension include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.

The pharmaceutical composition of the present invention can be preferably, but not limited to, a semi-solid preparation such as an external ointment, lotion and the like.

The pharmaceutically effective amount and the effective dose of the pharmaceutical composition of the present invention may be varied depending on the formulation method, administration method, administration time and / or route of administration of the pharmaceutical composition. The type and severity of the response, the type of subject being treated, the age, body weight, general health status, severity or severity of the disease, sex, diet, excretion, drugs used simultaneously or simultaneously with the subject, , And the like, and those skilled in the art will readily determine and prescribe dosages that are effective for the desired treatment.

Administration of the pharmaceutical composition of the present invention can be administered once a day, or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The route of administration and the mode of administration of the pharmaceutical composition of the present invention may be independent of each other and are not particularly limited in the method and may be arbitrarily administered and administered as long as the pharmaceutical composition can reach the desired site It is possible to follow the method. The pharmaceutical composition may be administered orally or parenterally, and preferably parenterally.

The parenteral administration may be, for example, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration or subcutaneous administration, and a method of applying, spraying or inhalation the composition to a diseased site may also be used But are not limited to.

The pharmaceutical composition of the present invention may be administered by a topical application method, more preferably by percutaneous administration during parenteral administration, more preferably by applying the pharmaceutical composition to the skin of an individual.

According to another aspect of the present invention, there is provided a method of treating skin dryness or skin barrier disorder comprising administering a cosmetic composition for improving skin dryness or skin barrier abnormality containing the above-mentioned routine or a cosmetically acceptable salt thereof as an active ingredient, Lt; / RTI >

In the method for improving the skin dryness or skin barrier function abnormality of the present invention, the cosmetic composition is the same as that described above in connection with the cosmetic composition of the present invention.

The term "individual" as used herein refers to all animals, including mammals including rats, livestock, humans, and the like.

The term "application, " as used herein, refers to contacting the composition of the present invention to the skin of a subject by any suitable method, thereby aiming to absorb the composition into the skin.

The amount (dose) of application of the cosmetic composition of the present invention to the skin of an individual is replaced with the content of the dose described above in connection with the pharmaceutical composition of the present invention.

In the improvement method of the present invention, the cosmetic composition preferably functions to improve the skin dryness or skin barrier function abnormality by promoting differentiation of dermal keratinocytes by activating PPAR-alpha.

According to another aspect of the present invention, there is provided a method for preventing or treating dry skin or skin barrier function, which comprises administering a pharmaceutical composition containing the above-mentioned rutin or a pharmaceutically acceptable salt thereof as an active ingredient to a subject, ≪ / RTI >

In the method for preventing or treating dry skin disorder or skin barrier function of the present invention, the pharmaceutical composition is the same as that described above in connection with the pharmaceutical composition of the present invention.

In the above-mentioned prevention or treatment method of the present invention, said subject is the same as described above.

In the above-mentioned preventive or therapeutic method of the present invention, the dose, administration route and administration mode of the pharmaceutical composition are the same as those described above in connection with the pharmaceutical composition of the present invention.

In the above-mentioned preventive or therapeutic method of the present invention, the pharmaceutical composition may be administered by an oral or parenteral administration method without particular limitation, but more preferably, the composition may be administered in a manner such that the composition is applied to the skin of an individual .

In the above-mentioned preventive or therapeutic method of the present invention, the pharmaceutical composition preferably acts to prevent or treat skin dryness or skin barrier function by promoting differentiation of dermal keratinocytes by activating PPAR-alpha.

The composition containing the routine of the present invention can prevent, ameliorate, or treat dry skin disorder or skin barrier function abnormality, and further exhibit an effect of preventing, ameliorating or treating atopic dermatitis.

More specifically, the composition containing the above-mentioned routine of the present invention shows an effect of activating PPAR alpha in dermal keratinocytes, thereby promoting the differentiation of dermal keratinocytes, Can be used to treat diseases.

In addition, the composition containing the above-mentioned routine of the present invention exhibits an effect of promoting the expression of filla green.

Hereinafter, the present invention will be described in more detail by way of examples. It should be understood, however, that these examples are for illustrative purposes only and are not to be construed as limiting the scope of the invention.

Example  1: Routine of PPAR  Verification of Alpha Activation Promotion Effect

In order to confirm the PPAR alpha activation promoting effect of the routine, the following experiment was performed using a routine of high purity extracted form (purchased from Sichuan Hongjie Import & Export Co., Ltd., Sichuan, China) Respectively.

C2C12 cells (ATCC CRL-1772), a mouse myoblast cell line, were subcultured in DMEM (Dulbecco's Modified Eagle's Medium) medium containing 10% fetal bovine serum. 1) Encoding Ser ₁₆₇ to Tyr ₄₆₈ in the SV40 promoter of the pZEO vector (Invitrogen) in the yeast transcription factor GAL4-DBD (DNA Binding Domain) and human PPAR alpha LBD (Ligand Binding Domain) 2) a vector inserted into a multiple restriction enzyme recognition site of a pGL3 vector (Promega) expressing a luciferase, and 3) a vector containing a DNA fragment (gene bank information, NM 005036) A vector expressing b-galactodisase as a transfection internal control was used.

The cultured cells were plated on a 24-well plate at a concentration of 4 × 10 ⁴ and cultured for 12 hours. The three types of plasmid genes were transiently transfected using lipopectamine . After 8 hours, the routines were treated and incubated for 12 hours, washed with 1 x PBS and lysed with 1 x reporter lysis buffer, and luciferase assay kit (Promega) and b-gal The activity of luciferase was measured using a lactocidase assay kit (Promega). That is, the PPAR alpha activity was measured as " luciferase activity / b-galactose activity ".

Wy-14,643 (Calbiochem), the most potent ligand of PPAR alpha, was used as a positive control in this experiment, and DMSO 0.05% was used as a negative control.

According to the experimental method, the activity of PPAR alpha was measured according to the concentration by treating the rutin with C2C12 cells. The results are shown in Table 1 below. The values of PPAR alpha activity in Table 1 below refer to percentages relative to negative control (0.05% DMSO).

sample PPAR alpha activity (%) DMSO 0.05% 100 Wy-14,643 0.5 [mu] M 280 Wy-14,643 1 [mu] M 935 Routine 0.005% 580 Routine 0.05% 690 Routine 0.5% 980

As shown in the results of the above Table 1, it can be confirmed that the routine of the present invention exhibits a very strong PPAR alpha activity when compared with the positive control which is a purified compound.

Example  2: of the routine Pillar Green  Verification of Expression Promotion Effect

The following experiment was carried out in order to confirm the effect of promoting the expression of pine green in the rutin.

Routine was added to the human keratinocyte HaCaT cell culture medium to measure the expression promoting effect of pilgar green at the cell level. The above routines were added to the culture medium of HaCaT cells at 5 μg / ml and 10 μg / ml, respectively, and cultured for 1 day. The RNAs of the cells were separated to synthesize cDNA, and then the cells were stained with Taqman dye Real-time PCR was performed to measure the expression level of pilar green. The concentration of RNA in this experiment was normalized to S16 ribosomal RNA.

The experimental results are shown in Table 2 below. In Table 2, the numerical value of the increase in filla green means a multiple of the control group (untreated group).

sample Concentration (/ / ml) Increase in pillar green (times) Control group (untreated group) - 1.0 Routine 5 314.7 Routine 10 289.3

* Number of repetitions = 3

As shown in the results of Table 2 above, it was confirmed that the routine of the present invention promotes the expression of filaggrin in human keratinocyte HaCaT cells.

Manufacturing example  1 and Comparative Example  1: Routine of  Manufacture of ointment for external skin containing

Skin ointment containing rutin (Preparation Example 1) and ointment containing no rutin (Comparative Example 1) were prepared with the composition shown in Table 3 below.

Composition Production Example 1 (% by weight) Comparative Example 1 (% by weight) Routine 0.5 - Diethyl sebacate 8 8 Nonsense 5 5 Polyoxyethylene oleyl ether
Phosphate 6 6 Sodium benzoate Suitable amount Suitable amount

Manufacturing example  2 and Comparative Example  2: Routine of  Manufacture of cream containing

A cream containing rutin (Preparation Example 2) and a cream without the routine (Comparative Example 2) were prepared with the composition shown in Table 4 below.

Composition Production Example 2 (% by weight) Comparative Example 2 (% by weight) Routine 0.2 - Stearic acid 15.0 15.0 Cetanol 1.0 1.0 Potassium hydroxide 0.7 0.7 glycerin 5.0 5.0 Propylene glycol 3.0 3.0 antiseptic Suitable amount Suitable amount incense Suitable amount Suitable amount Purified water to 100 to 100

Manufacturing example  3 and Comparative Example  3: Routine of  Manufacture of Containing Lotion

(Preparation Example 3) containing rutin and a lotion-free lotion (Comparative Example 3) were prepared in the composition shown in Table 5 below.

Composition Production Example 3 (% by weight) Comparative Example 3 (% by weight) Routine 0.1 - ethanol 10.0 10.0 Polylauric acid
Polyoxyethylene
Sorbitan 1.0 1.0 Paraoxybenzoic acid methyl 0.2 0.2 glycerin 5.0 5.0 1,3-butylene glycol 6.0 6.0 incense Suitable amount Suitable amount Pigment Suitable amount Suitable amount

Manufacturing example  4 and Comparative Example  4: Routine of  Manufacture of nutritional lotion containing

A nutritional lotion (Preparation Example 4) containing rutin and a nutritive lotion containing no rutin (Comparative Example 4) were prepared in the composition shown in Table 6 below.

Composition Production Example 4 (% by weight) Comparative Example 4 (% by weight) Routine 0.05 - Vaseline 2.0 2.0 Sesquioleic acid sorbitan 0.8 0.8 Polyoxyethylene oleylethyl 1.2 1.2 Paraoxybenzoic acid methyl Suitable amount Suitable amount Propylene glycol 5.0 5.0 ethanol 3.2 3.2 Carboxyvinyl polymer 18.0 18.0 Potassium hydroxide 0.1 0.1 Pigment Suitable amount Suitable amount incense Suitable amount Suitable amount

Manufacturing example  5 and Comparative Example  5: Routine of  Manufacture of packs containing

(Preparation Example 5) and a pack containing no rutin (Comparative Example 5) were prepared with the composition shown in Table 7 below.

Composition Production Example 5 (% by weight) Comparative Example 5 (% by weight) Routine 0.05 - glycerin 5.0 5.0 Propylene glycol 4.0 4.0 Polyvinyl alcohol 15.0 15.0 ethanol 8.0 8.0 Polyoxyethylene oleyl ether 1.0 1.0 Paraoxybenzoic acid methyl 0.2 0.2 Pigment Suitable amount Suitable amount incense Suitable amount Suitable amount

Manufacturing example  6 and Comparative Example  6: Routine of  Manufacture of essences containing

Essences containing rutin (Preparation Example 6) and essences containing no rutin (Comparative Example 6) were prepared with the composition shown in Table 8 below.

Composition Production Example 6 (% by weight) Comparative Example 6 (% by weight) Routine 0.2 - Propylene glycol 10.0 10.0 glycerin 10.0 10.0 Sodium hyaluronate
Aqueous solution (1%) 5.0 5.0 ethanol 5.0 5.0 Polyoxyethylene hardened castor oil 1.0 1.0 Paraoxybenzoic acid methyl 0.1 0.1 incense Suitable amount Suitable amount Purified water to 100 to 100

Example  3: Routine of  Verification of the improvement effect of atopic dermatitis on ointment containing external skin

In order to measure the effect of improving the symptoms of atopic dermatitis of the rutin, 20 persons between the ages of 10 and 50 who were diagnosed with atopic symptoms such as severe dryness, dirtiness, itching and the like were divided into two groups of 10 persons each, Each group was provided with the ointment for external use of the skin of Comparative Example 1 or Preparation Example 1, and applied to a site showing atopic symptoms for 4 weeks.

The improvement effect of atopic dermatitis was evaluated by self - questionnaire after 4 weeks. The self-questionnaire was judged to have four degrees of improvement in terms of 'very good', 'good', 'normal', and 'insufficient' compared to before using the ointment for external use of Comparative Example 1 or Production Example 1 .

The results of the determination are shown in Table 9 below.

Application group Number of respondents (persons) Very good Good usually Inadequate Comparative Example 1 One 3 4 2 Production Example 1 2 5 3 0

As shown in the results of Table 9, it was confirmed that the ointment for external use containing the routine of the present invention (Preparation Example 1) showed an excellent improvement effect on the overall atopic dermatitis symptom as compared with Comparative Example 1 .

It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. More variations are possible within a range that does not. Accordingly, the present invention may be embodied in other ways than those specifically described and illustrated herein, and it may be understood by those skilled in the art.

Claims (17)

A PPAR alpha activator containing Rutin or a salt thereof as an active ingredient.
2. The PPAR alpha activator according to claim 1, wherein said routine is represented by the following formula (1).
[Chemical Formula 1]

A cosmetic composition for improving skin dryness or skin barrier function comprising Rutin or a cosmetically acceptable salt thereof as an active ingredient.
4. The cosmetic composition according to claim 3, wherein the routine is represented by the following formula (1).
[Chemical Formula 1]

The cosmetic composition according to claim 3, wherein the skin dryness or skin barrier function abnormality is atopic dermatitis.
4. The cosmetic composition according to claim 3, wherein the composition comprises 0.0001% to 10% by weight of the rutin or a cosmetically acceptable salt thereof, based on the total composition weight.
The composition according to claim 3, wherein the composition is at least one selected from the group consisting of a solution, an external ointment, a cream, a foam, a nutritional lotion, a flexible lotion, a pack, a flexible water, a latex, a makeup base, an essence, Wherein the composition is selected from the group consisting of suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays.
The cosmetic composition according to claim 3, further comprising a cosmetically acceptable carrier.
9. A method for improving the skin dryness or skin barrier function abnormality by applying the cosmetic composition according to any one of claims 3 to 8 to the skin of an individual.
10. The method of claim 9, wherein the improvement in skin dryness or skin barrier function is achieved by activating the cosmetic composition with PPAR-alpha.
A pharmaceutical composition for the prevention or treatment of dry skin disorder or skin barrier function comprising rutin or a pharmaceutically acceptable salt thereof as an active ingredient.
12. The pharmaceutical composition according to claim 11, wherein the routine is represented by the following formula (1).
[Chemical Formula 1]

12. The pharmaceutical composition according to claim 11, wherein the dry skin disorder or skin barrier function abnormality is atopic dermatitis.
12. The pharmaceutical composition of claim 11, wherein the composition comprises from 0.0001% to 10% by weight of the rutin, or a pharmaceutically acceptable salt thereof, based on the total weight of the composition.
A method for preventing or treating dry skin disorder or skin barrier function, which comprises administering the pharmaceutical composition according to any one of claims 11 to 14 to a subject other than human.
16. The method of claim 15, wherein said administration is applied to the skin of a subject.
16. The method of claim 15, wherein the prevention or treatment of the dry skin disorder or skin barrier function is achieved by activating the PPAR-alpha.