KR101572721B1 - Composition for improving dry skin or skin barrierfunction comprising hyoscine - 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 hiosin 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 The present invention relates to a composition for improving skin dryness or skin barrier function comprising hiosin as an active ingredient. BACKGROUND OF THE INVENTION 1. Field of the Invention [0001]

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 hiosin 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 hyaloxin derived from a natural product having an activating function of PPAR alpha has an effect of restoring skin barrier function fundamentally by promoting differentiation of keratinocyte, Thereby completing a composition for improvement or treatment.

 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 hiosin or a salt thereof as an active ingredient, and is intended to prevent, ameliorate or treat dry skin 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 chiosin or a salt thereof as an active ingredient.

Another object of the present invention is to provide a cosmetic composition for improving dry skin or skin barrier function abnormality comprising hiosin 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 skin barrier function comprising hiosin 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 Hyoscine or a salt thereof as an active ingredient.

The natural state of Hyoscine is the seed or leaf of the Solanaceae plant, Hyoscyamus niger , or Datura stramonium seed, atropa belladonna ) and the like. This hiosin has the function to block the parasympathetic nerve, and is used as analgesic agent or antispasmodic agent as a parasympathetic nerve blocker and is used as a main component of the parasitic drug.

The above-mentioned hiosin of the present invention may preferably be a hosin 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 present inventors have found that hiosin exhibits an excellent PPAR alpha activation function, and completed the present invention. To date, there has been no report on the PPAR alpha activation function and skin barrier recovery ability of hiosin.

As a result of the studies conducted by the present inventors, it has been found that hiosin not only exhibits excellent PPAR alpha activation but also effectively promotes differentiation of keratinocytes. When the hiosin is directly applied to the skin, .

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

In addition, it has been confirmed that the present hiosin exhibits an effect of increasing ceramide formation by increasing the activity of Sphingomyelinase, an enzyme involved in ceramide formation.

In a specific example of the present invention, human cultured HaCaT cells, which are human keratinocyte lines, were cultured in a medium containing hiosin, and the activity of sphingomyelinase was significantly increased (Example 2).

In the present invention, the hiosin may include a hosinhydrate, a hiocin derivative or the like within a range having the same effect, and may include a solvate or a stereoisomer thereof. The hiosin may be chemically synthesized, separated from natural materials, or purchased from domestic and overseas chemical companies. When the hiosin of the present invention is isolated from a natural substance, it may be a concept including all of the extracts of natural products or fractions thereof, as long as the hiosin is contained.

The hyosin 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 hyosin can be used to make a pharmaceutically or cosmetically acceptable metal salt using a base. 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-mentioned hiosins may, unless otherwise indicated, include all salts of acidic or basic groups which may be present in the compounds of the above-mentioned hyosin. 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 inventive hirosine was found to be excellent in the function of activating PPAR alpha.

The PPAR alpha activator of the present invention contains hiosin or a salt thereof as an active ingredient. The effective amount of the hiosin or a salt thereof 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 hiosin or a salt thereof, an excipient, carrier, and other additives, and may be manufactured with 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 dry skin or skin barrier function abnormality comprising the above-mentioned hiosin or a cosmetically acceptable salt thereof as an active ingredient.

In the present invention, the above-mentioned hiosin 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, improving or treating the skin dryness or skin barrier function due to the action of the above-mentioned hiosin or its cosmetically acceptable salt, And thus it is safe without causing side effects even when applied to human body.

In the cosmetic composition of the present invention, the hiosin or a 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, May be contained in an amount of 0.0005 wt% to 10 wt%. Within the above-mentioned content range, the use of the above-mentioned hiosin or its cosmetically acceptable salt in an appropriate amount is economical, and the PPAR alpha activity effect of the above-mentioned hiosin or its salt is sufficiently exhibited to be more suitable for achieving the object of the present invention There is an advantage.

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 flexible water, 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 or skin barrier function, comprising the above-mentioned hiosin or a pharmaceutically acceptable salt thereof as an active ingredient.

The above-mentioned hiosin or pharmaceutically acceptable salt thereof, skin dryness, and skin barrier function abnormality 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, ameliorating or treating the skin dryness or skin barrier function abnormality by the action of the above-mentioned hiosin or its pharmaceutically acceptable salt, It is safe because it is not toxic and does not cause side effects when applied to human body.

In the pharmaceutical composition of the present invention, the hiosin or a pharmaceutically acceptable salt thereof may be contained in an amount of preferably 0.0001 wt% to 10 wt% based on the total weight of the pharmaceutical composition, Preferably from 0.0005% by weight to 10% by weight. Within the above-mentioned content range, the use of the above-mentioned hiosin or a pharmaceutically acceptable salt thereof in an appropriate amount is economical, and the PPAR alpha activity effect of the above-mentioned hiosin or its salt is sufficiently exhibited to be more suitable for achieving the object of the present invention There is an advantage.

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

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 comprising the above-mentioned hiosin or a cosmetically acceptable salt thereof as an active ingredient, The present invention provides a method for improving the above.

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.

According to another aspect of the present invention, there is provided a method for preventing or preventing dry skin disorder or skin barrier function, which comprises administering a pharmaceutical composition containing the above-mentioned hiosin or a pharmaceutically acceptable salt thereof as an active ingredient, Provide a treatment method.

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 .

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

More specifically, the composition containing the hiosin of the present invention shows an effect of activating PPAR alpha in dermal keratinocytes, thereby promoting the differentiation of keratinocyte cells, thereby providing various effects resulting from incomplete differentiation of epidermis Can be used to treat skin diseases.

In addition, the composition containing the above-described hiosin of the present invention has an effect of increasing ceramide formation by increasing the activity of sphingomyelinase, an enzyme involved in ceramide formation.

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  One: Hiyosin PPAR  Verification of Alpha Activation Promotion Effect

In order to confirm the promoting effect of PPAR alpha activation of hioshin, hioxine (hereinafter referred to as Hiosin source) extracted from high purity, purchased from Sichuan Hongjie Import & Export CO., LTD., China, Experiments were performed.

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 cells were treated with hiosin and incubated for 12 hours. Then, the cells were washed with 1 x PBS, lysed with 1 x reporter lysis buffer, and luciferase assay kit (Promega) and b- The activity of luciferase was measured using a galactosidase 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 above experimental method, the activity of PPARalpha was measured according to the concentration by treating hiosin 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 0.005% 575 0.05% 690 0.5% 960

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

Example  2: Hiyosin Ceramide  Verification of formation activation effect

The following experiment was carried out in order to confirm the effect of activation of ceramide formation of hiocin.

Hiosin was added to human keratinocyte HaCaT cell culture medium to measure the activity of sphingomyelinase, an enzyme involved in ceramide formation, which is a component of lipid. The hosin was added to the culture medium of HaCaT cells at a concentration of 20 μg / ml and cultured for 1 day. The cells were harvested and the activity of the enzyme was measured using a sphingomyelinase assay kit (Cayman).

The experimental results are shown in Table 2 below. In Table 2 below, the level of sphingomyelinase activity refers to the percentage of the control group (untreated group).

sample Sphingomyelinase activity (%) Control group (hiosin treated group) 100 Hiyosin 130.4

As shown in the results of the above Table 2, it was confirmed that the hirosine of the present invention activates sphingomyelinase of human keratinocyte HaCaT cells to increase ceramide formation.

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

(Ophthalmic ointment containing ointment (Preparation Example 1) and ointment-free skin ointment (Comparative Example 1) were prepared in the composition shown in Table 3 below.

Composition Production Example 1 (% by weight) Comparative Example 1 (% by weight) Hiyosin 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: Hiyosin  Manufacture of cream containing

(Example 2) containing hyssin and a cream containing no hiosin (Comparative Example 2) were prepared with the composition shown in Table 4 below.

Composition Production Example 2 (% by weight) Comparative Example 2 (% by weight) Hiyosin 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: Hiyosin  Manufacture of Containing Lotion

(Production Example 3) containing hysosine and a soft lotion containing no hyssin (Comparative Example 3) were prepared in the composition shown in Table 5 below.

Composition Production Example 3 (% by weight) Comparative Example 3 (% by weight) Hiyosin 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: Hiyosin  Manufacture of nutritional lotion containing

In the composition shown in the following Table 6, a nutritional lotion containing hiosin (Preparation Example 4) and a non-hyposine-containing nutrition lotion (Comparative Example 4) were prepared.

Composition Production Example 4 (% by weight) Comparative Example 4 (% by weight) Hiyosin 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: Hiyosin  Manufacture of packs containing

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

Composition Production Example 5 (% by weight) Comparative Example 5 (% by weight) Hiyosin 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: Hiyosin  Manufacture of essences containing

(Example 6) containing the hyssin and the essence without the hyssin (Comparative Example 6) were prepared in the composition shown in Table 8 below.

Composition Production Example 6 (% by weight) Comparative Example 6 (% by weight) Hiyosin 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: Hiyosin  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 hioshin, 20 persons between the ages of 10 and 50 who were diagnosed with atopic symptoms such as severe dryness, dirtiness and itching were divided into two groups of 10 persons each, Each of the above-mentioned groups was provided with the ointment for external use of the skin of Comparative Example 1 or Production Example 1, and was applied to a region 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 2 4 3 Production Example 1 3 3 4 0

As shown in the results of the above Table 9, it was found that when the oily external ointment containing the above-mentioned hiosin of the present invention was used (Production Example 1), the improvement effect of the overall atopic dermatitis symptoms .

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 will be understood by those skilled in the art.

Claims (15)

delete delete A cosmetic composition for the treatment of dry skin or atopic dermatitis comprising hyoscine or a cosmetically acceptable salt thereof as an active ingredient.
The cosmetic composition according to claim 3, wherein the hiosin is represented by the following formula (1).
[Chemical Formula 1]

delete 4. The cosmetic composition of claim 3, wherein the composition comprises from 0.0001% to 10% by weight, based on the weight of the total composition, of hiosin or a cosmetically acceptable salt thereof.
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.
A method for improving skin dryness or atopic dermatitis by applying the cosmetic composition of any one of claims 3, 4, and 6 to 8 to the skin of a subject other than human.
A pharmaceutical composition for the prevention or treatment of dry skin or atopic dermatitis comprising hyoscine or a pharmaceutically acceptable salt thereof as an active ingredient.
11. The pharmaceutical composition according to claim 10, wherein the hiosin is represented by the following formula (1).
[Chemical Formula 1]

delete 11. The pharmaceutical composition of claim 10, wherein the composition comprises from 0.0001% to 10% by weight, based on the total weight of the composition, of hiosin or a pharmaceutically acceptable salt thereof.
A method for preventing or treating dry skin or atopic dermatitis comprising administering the pharmaceutical composition according to any one of claims 10, 11, and 13 to a subject other than human.
15. The method according to claim 14, wherein said administration is applied to the skin of an individual.