KR102048977B1 - Composition for Anti-allergy Using Extracts of Ulmus davidiana and Perillae Folium - Google Patents

Abstract

The present invention discloses an anti-allergic composition using an extract of Ulmus davidiana bark and an extract of Perilla frutescens. A composition of the present invention can be usefully used in treating atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, or allergic keratitis.

Description

Composition for Anti-allergy Using Extracts of Root-derived Roots and Extracts of Pleurotus eryngii Extracts of Ulmus davidiana and Perillae Folium

The present invention relates to an anti-allergic composition using the extract of Root-derived Root and Pleurotus eryngii.

Allergy is a compound word formed by combining Greek 'allos' which means 'changing' and 'ergo' which means 'action'. As the etymology suggests, allergens, which are allergic to normal people, cause hypersensitivity reactions such as hives, itching, runny nose, and coughing in certain people due to innate or acquired immune function abnormalities. Typical allergens include pollen, drugs, vegetable fiber, bacteria, fungi, house dust mites, foods (egg albumin, milk proteins, peanuts), dyes, and chemicals. Recent allergens such as increased indoor living and new material chemicals Allergic diseases are on the rise worldwide due to increased substances, environmental pollution, reduced immune function due to stress, and changes in diet.

Allergic reactions are classified into five types, type I anaphylaxis type, type II lysis type, type III immunocomplex type, type IV cell mediating type and type V irritable hypersensitivity type, most of which belong to type I. Allergic reactions have the same meaning as Type I (Roitt I, Brostoff J, Male D. Immunology 6th eds. USA. Mosby. 2001: 323-383).

Representative allergic diseases include atopic dermatitis, bronchial asthma, allergic rhinitis, allergic keratitis, and skin urticaria. Mast cells are known as important effector cells (Wills-Karp M., et al., Science, 282: 2258-61, 1998; Grunig G., et al., Science, 282: 2261-2263, 1998). Mast cells are widely distributed in organs of the whole body such as skin, respiratory tract, lymphatic vessels, gastrointestinal mucosa, blood vessels, and brain (Ishizaka t., Et al. J. Immunol. 119: 1589, 1997).

Allergic reactions are induced through activation of intracellular signaling pathways when allergens bind to IgE, which is bound to the IgE high affinity receptor (FcεRI) on the surface of mast cells. Specifically, when allergen invades the living body, T-helper cells and B cells are sequentially activated to generate IgE. Allergens invading the living body are recognized by the antigen presenting cells, which differentiate T0 (T helper cell type 0) into Th2 cells by presenting allergens. These differentiated Th2 cells secrete cytokines such as IL-4, IL-5 and IL-13, which promote the development of acidic white blood cells in the bone marrow to induce acidic white blood cells into inflamed tissues, as well as B cells. Acts to induce the production of IgE and IgG1.

The generated IgE binds to the high-affinity IgE receptor (FcRIα) of the mast cell membrane and aggregates when the allergens such as mites and pollen bind to form a crosslink. By crosslinking and aggregation of the receptor (FcRIα), mast cells are activated to increase calcium ion (Ca ⁺⁺ ) concentration in the cytoplasm. The increase in calcium ion concentration acts on various kinds of intracellular regulatory factors such as cholesterol and cytoskeleton of the cell membrane to move the granules to the cell membrane and at the same time degranulates through phobia of granules, fusion of granules and fusion of granules and cell membranes. Causes Degranulation releases preformed mediators that are pre-stored in mast cells such as histamine and releases newly synthesized prostaglandin and leukotriene. Chemotransmitters liberated by degranulation include NCF, which acts as a chemotactic factor for inflammatory cells such as eosinophils or neutrophils, in addition to histamine, serotonin, and leukotriene, which have the effects of vasodilation, vascular permeability, and contraction or secretion of bronchial smooth muscle. , ECF, PAF, etc., causing allergic reactions (Ennis M, et al., Br J Pharmacol 70: 329-334, 1980; Metcalfe DD, et al., Crit Rev Immunol 3: 23-74, 1981; Miyajima I, et al., J Clin Invest 99: 901-914, 1997; Church MK, et al., J Allergy Clin Immunol 99: 155-160, 1997; Jones DA, et al., J Biol Chem 268: 9049- 9054, 1993).

Cyclooxygenase (COX) and lipoxygenase (LO) are known to catalyze part of the process of producing allergic symptoms of prostaglandins and leukotrienes from arachidonic acid (Sekiya K). , et al., Biochem Biophys Acta 713: 68-72, 1982)

Therefore, substances that inhibit the activation of mast cells, inhibit histamine release, or inhibit the synthesis of prostaglandins and leukotrienes can be effective therapeutic drugs for allergies.

As anti-allergic drugs, antihistamines (alkylamines, desloratadine, etc.), mast cell stabilizers (cromoglycate, etc.), leukotriene blockers (montelukast, etc.), and anti-IgE antibodies (Omalizumab) are used. However, these drugs are often temporary and often have severe side effects. Therefore, it can be said that the development of a new substance with less side effects and lasting effects while preventing and improving allergic diseases is still required. In particular, natural extracts can have excellent advantages in terms of side effects.

The present invention discloses the anti-allergic activity of the extracts of the roots of the root and the extract of the oleander.

An object of the present invention to provide an anti-allergic composition using the extract of the roots and extracts of the lobules.

Other and specific objects of the present invention will be presented below.

The present invention has been completed by confirming that the root extract and root leaf extract exhibits inhibitory activity of degranulation of mouse-derived mast cell line RBL-2H3, as confirmed in the following examples.

The anti-allergic composition of the present invention is characterized in that it comprises the extract of roots and extracts of the lobules as an active ingredient.

In the present specification, the "derived bark extract" refers to the bark of the bark of the root of the extract, namely, elm ( Ulmus davidiana var. Japonica Nakai), water, lower alcohols having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.), methylene chloride, ethylene, Using acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol or a mixed solvent thereof An extract obtained by leaching, extract obtained by using a supercritical extraction solvent such as carbon dioxide, pentane, or a fraction obtained by fractionating the extract.The extraction method is cold extraction, reflux, Arbitrary methods, such as heating, ultrasonic radiation, supercritical extraction, can be applied. In the case of the fractionated extract, the fraction obtained by suspending the extract in a specific solvent and mixing and standing with a solvent having a different polarity, the crude extract is adsorbed on a column filled with silica gel and the like, and then a hydrophobic solvent, a hydrophilic solvent, or a mixed solvent thereof is added. It is meant to include fractions obtained by mobile phase. In addition, the meaning of the extract includes a concentrated liquid extract or solid extract in which the extraction solvent is removed in a manner such as freeze drying, vacuum drying, hot air drying, spray drying, and the like. Preferably it refers to an extract obtained by using water, ethanol or a mixed solvent thereof as the extraction solvent, more preferably an extract obtained by using a mixed solvent of water and ethanol as the extraction solvent.

In addition, in the present specification, the "leaflet extract" may be defined as the root extract of the extract except for Perilla frutescens .

In addition, in the present invention, the active ingredient alone refers to a component that can exhibit the desired activity, or itself can exhibit the activity with a carrier without activity.

In addition, in the present invention, the anti-allergic is meant to include improvement (reduction of symptoms), treatment, and prevention (inhibition or delay of development) of allergic diseases as defined below.

In addition, in the present invention, the allergic disease means a pathological symptom caused by an allergic reaction mediated by activation of mast cells such as degranulation of mast cells, and such allergic diseases include atopic dermatitis, asthma, Allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, allergic keratitis, and the like.

The anti-allergic composition of the present invention may include the active ingredient in any amount (effective amount) as long as it can exhibit the improvement activity of the allergic disease intended to be treated according to the use, formulation, formulation purpose, etc. It will be determined within the range of 0.001% to 15% by weight based on the total weight of the composition. Here, the term "effective amount" refers to the intended medical and pharmacological effects, such as the improvement effect of allergic disease, when the composition of the present invention is administered to a mammal, preferably a human, for the period of administration according to the suggestion of a medical professional. The amount of the active ingredient included in the composition of the present invention can be mentioned. Such effective amounts can be determined experimentally within the range of ordinary skill in the art.

In addition to the active ingredient, the anti-allergic composition of the present invention may further include any compound or natural extract, which has already been tested for safety and is known to have anti-allergic activity, in order to increase and enhance anti-allergic activity.

Specifically, such compounds or extracts include Enterococcus faecalis heat-treated dried powders, guava leaf extracts, etc., which are individually recognized as functional 'relieving hypersensitivity reactions' according to the Act on Health Functional Foods, wormwood extracts, leaflet extracts, picaopreto Complex such as powder, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol), and L. sakei Probio 65, which has been individually recognized for its 'improved skin condition' function, contains oil-containing gamma linolenic acid, vegetable origin Lactic acid bacteria ( L.plantarum CJLP133), probiotic ATP and the like.

One or more such compounds or natural extracts may be included in the anti-allergic composition of the present invention together with the active ingredients.

The anti-allergic composition of this invention can be grasped | ascertained as a food composition in a specific aspect. When the composition of the present invention is identified as a food composition, its use may be understood as suppressing allergic skin hypersensitivity.

The food composition of the present invention may be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, ionic beverages, processed oils such as milk, yogurt, gums, rice cakes, sweets, bread, sweets, noodles, and the like. Foodstuffs, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, and the like can be prepared as functional food preparations.

In addition, the food composition of the present invention can distinguish any product as long as it conforms to the enforcement regulations at the time of manufacture and distribution in the legal and functional divisions. For example, confectionery, soybeans, teas, beverages according to each food type, or health functional foods in accordance with the Act on Health Functional Foods, or in the Food Code of the Korean Food Sanitation Act , Special purpose foods, and the like.

The food composition of the present invention may include food additives in addition to the active ingredient. Food additives can generally be understood as substances which are added to the food, mixed or infiltrated in the manufacture, processing or preservation of the food, which must be ensured because of its daily and long-term intake with the food. The Food Additives Code of Korea ("Food Sanitation Act" in Korea) governs the manufacture and distribution of foods, and food additives with guaranteed safety are limited in terms of ingredients or functions. In the Korean Food Additives Code (KFDA Notification and Standards of Food Additives), food additives are classified into chemical synthetics, natural additives, and mixed preparations in terms of ingredients. These food additives are sweeteners, flavors in terms of function. Agent, preservative, emulsifier, acidulant, thickener and the like.

Sweeteners are used to impart a suitable sweetness to foods, either natural or synthetic, which can be used in the compositions of the present invention. Preferably, a natural sweetener is used. Examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.

Flavoring agents can be used to enhance the taste or aroma, both natural and synthetic. It is the case of using a natural thing preferably. In addition to flavors, the use of natural ones can be combined with nutritional purposes. The natural flavor may be obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or may be obtained from green tea leaves, round leaves, jujube leaves, cinnamon, chrysanthemum leaves, jasmine and the like. In addition, ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo and the like can be used. Natural flavors can be liquid concentrates or solid extracts. In some cases, synthetic flavoring agents may be used, and synthetic flavoring agents may include esters, alcohols, aldehydes, terpenes, and the like.

Sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. may be used as a preservative, and as an emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin etc. can be mentioned, As acidic acid, acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, etc. can be used. The acidulant may be added so that the food composition is at an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to the purpose of enhancing the taste.

As the thickener, suspending implementers, sedimenting agents, gel formers, swelling agents and the like can be used.

In addition to the food additives described above, the food composition of the present invention may include a bioactive substance or minerals known in the art for the purpose of supplementing and reinforcing the functionality and nutritional properties and ensuring the stability as a food additive.

Examples of such physiologically active substances include catechins, vitamin B1, vitamin C, vitamin E, vitamin B12 and the like, tocopherol, dibenzoylthiamine, and the like contained in green tea. Examples of the minerals include calcium preparations such as calcium citrate and magnesium stearate. Magnesium preparations such as iron, iron preparations such as iron citrate, chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc and the like.

In the food composition of the present invention, the food additive as described above may be included in an amount that can achieve the purpose of addition according to the product type.

Regarding other food additives that may be included in the food composition of the present invention, reference may be made to each country's food or food additives.

The composition of the present invention may be regarded as a pharmaceutical composition in another specific embodiment.

The pharmaceutical compositions of the present invention may be prepared in oral or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. The route of administration here can be any suitable route, including the topical route, the oral route, the intravenous route, the intramuscular route, and direct absorption through mucosal tissue, and may be used in combination of two or more routes. An example of a combination of two or more routes is where a drug of two or more formulations according to the route of administration is combined, for example when one drug is administered first by the intravenous route and the other by the local route.

Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or formulation, and specific reference may be made to the pharmacopoeia of each country, including "Korea Pharmacopoeia."

When the pharmaceutical composition of the present invention is prepared in an oral dosage form, powders, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, wafers according to methods known in the art with suitable carriers It may be prepared in a formulation such as. Examples of suitable carriers include lactose, glucose, sucrose, dextrose, sorbitol, sugars such as mannitol, xylitol, starch such as corn starch, potato starch, wheat starch, cellulose, methyl cellulose, ethyl cellulose, sodium carboxymethyl cellulose, Celluloses such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, and Cerrol etc. are mentioned. If formulated, appropriate binders, lubricants, disintegrants, colorants, diluents and the like may be included as needed. Suitable binders include starch, magnesium aluminum silicate, starch ferrite, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweeteners, sodium alginate, polyethylene glycol, waxes, and the like. Sodium, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, magnesium salts thereof, calcium salts, polydetylene glycol and the like, and the disintegrating agents include starch, methyl cellulose And agar, bentonite, xanthan gum, starch, alginic acid or its sodium salt and the like. Moreover, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine etc. are mentioned as a diluent.

When the pharmaceutical compositions of the present invention are prepared in parenteral formulations, they may be formulated in the form of injections, transdermal administrations, nasal inhalants and suppositories with suitable carriers according to methods known in the art. When formulated as an injection, a suitable carrier may be an aqueous isotonic solution or suspension. Specifically, an isotonic solution such as phosphate buffered saline (PBS) containing triethanol amine, sterile water for injection, or 5% dextrose may be used. . When formulated as a transdermal administration, it may be formulated in the form of an ointment, cream, lotion, gel, external solution, pasta, linen, aerosol, and the like. Nasal inhalants can be formulated in the form of aerosol sprays using suitable propellants, such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. witepsol), tween 61, polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearate, sorbitan fatty acid esters and the like.

Specific formulations of pharmaceutical compositions are known in the art and can be found, for example, in Remington's Pharmaceutical Sciences (19th ed., 1995). The document is considered part of this specification.

Preferred dosages of the pharmaceutical compositions of the present invention range from 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g, depending on the condition, body weight, sex, age, severity of the patient and route of administration. It can range from / kg. Administration can be done once a day or divided into several times. Such dosage should not be construed as limiting the scope of the invention in any aspect.

The composition of this invention can be grasped | ascertained as a cosmetic composition in another specific aspect. When the composition of the present invention is grasped as a cosmetic composition, the use thereof may be understood as a use for suppressing allergic skin problems, allergic skin irritation, and the like.

Even when the composition of the present invention is identified as a cosmetic composition, the cosmetic composition can be classified into any product according to its purpose and law, and specifically, a functional cosmetic having a use such as skin trouble improvement, atopic dermatitis improvement, and non-functionality. General cosmetics, and the like. The product form can also be in any product form, specifically solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, waxes You can find product types such as foundation and spray. In a specific product form, it may be a softening lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder formulation.

The cosmetic composition of the present invention may include, in addition to the active ingredient, components conventionally used in the cosmetic composition, for example, conventional adjuvants such as stabilizers, solubilizers, surfactants, vitamins, pigments and pharmaceuticals, and carriers.

When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as the carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan and the like can be used.

When the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and microcrystals are used as carrier components. Castle cellulose, aluminum metahydroxy, bentonite, agar and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The cosmetic composition of the present invention can be prepared according to the manufacturing method of the cosmetic composition commonly carried out in the art, except that the active ingredient exhibiting an antiallergic activity.

As described above, according to the present invention can provide a composition for anti-allergic using the extract of the roots and extracts of cotyledon, such an anti-allergic composition can be commercialized as food, drugs or cosmetics.

1 and 2 show the results of degranulation inhibitory activity in mast cell line RBL-2H3 (rat basophilic leukemia).

Hereinafter, the present invention will be described with reference to Examples. However, the scope of the present invention is not limited to these examples.

<Example 1> Anti-allergic activity experiment of the extract of Rhizome lanceolum and Pleurotus eryngii extract

1. Preparation of Sample

Both the root extract and the leaf extract were extracted using 80% ethanol.

10 times weight of 80% ethanol was added to each dry powder, followed by extraction at room temperature for 24 hours, followed by filtration to remove the extraction residue. The filtrate was concentrated under reduced pressure and lyophilized to prepare a powder to be used in the experiment.

2. Experimental method-β-hexosaminidase assay

The secretion of β-hexosaminidase was measured to investigate the inhibitory effect on degranulation, an allergic marker. The rat basophilic leukemia cell line (RBL-2H3) was used by the Korea Cell Line Bank (Seoul, Korea). Cell cultures were incubated at 37 ° C. and 5% CO ₂ in DMEM (Gibco BRL, USA) cultures containing 10% FBS (Gibco BRL, USA), 1% penicillin and streptomycin (Gibco BRL, USA).

Cultured RBL-2H3 cells were dispensed into 24-well plates at 2 × 10 ⁵ cells / well, sensitized with 500 ng / ml of anti-DNP-IgE, and incubated at 37 ° C. and 5% CO ₂ for 24 hours. Cells were washed with siraganian buffer (119 mM NaCl, 5 mM KCl, 04 mM MgCl 2, 25 mM PIPES, 40 mM NaOH, pH 7.2) and 5.6 mM glucose, 1 mM CaCl ₂ , 0.1% bovine serum albumin (BSA) Siraganian buffer was added and incubated at 37 ° C. for 20 minutes. After the sample was treated and incubated for 10 minutes, 20 μl of DNP-HSA at a concentration of 10 μg / ml was added thereto and reacted at 37 ° C. for 10 minutes. Thereafter, the reaction mixture was terminated by standing in an ice bath for 10 minutes, and 20 µl of the supernatant was added to a substrate solution (4- p- Nitrophenyl- N- acetyl-bD-glucosaminide 1 mM, sodium citrate 0.05 M, pH 4.5). Μl was added and reacted at 37 ° C. for 1 hour. Next, 100 µl of the reaction stopping solution (0.1 M Na ₂ CO ₃ / NaHCO ₃ , pH 10.0) was added to stop the reaction, and the absorbance was measured at 405 nm using a microplate reader (Molecular Devices, USA). The results were calculated as a degranulation inhibitory effect as a percentage compared to the sample untreated group.

3. Experimental Results

The results were calculated as a degranulation inhibitory effect as a percentage compared to the sample untreated group.

As shown in Figure 1, at 5 mg / ml treatment concentrations of the root extract, root leaf extract and all mixtures showed degranulation inhibitory activity, the mixture of root root extract and leaf extract was 8: 2 to 6: 4 weight ratio mixture ( The extracts of the roots of the roots were 8 and 2 weight ratios, and the degranulation inhibitory activity was excellent (A: roots of bark extracts alone, B: roots of bark roots and extracts of botanical leaves = 8: 2, C: roots of bark and bark extracts of 6: 4, D : Root skin extract and leaflet extract = 5: 5, E: Root leaf extract and leaflet extract = 4: 6, F: Root leaf extract and leaflet extract = 2: 8, G: Root leaf extract alone).

Figure 2 shows the degranulation inhibitory activity according to the treatment concentration of the most active 6: 4 weight ratio mixture (C). It can be seen that the degranulation inhibitory activity increases in proportion to the treatment concentration.

Claims (6)

It includes a mixture of the root extract and the leaf extract as active ingredients,
The mixture is characterized in that the extract of the roots and extracts of the cotyledon leaves is a mixture of weight ratio of 8: 2 to weight ratio of 6: 4
Anti-allergic composition.
The method of claim 1,
The extract is a composition characterized in that the water, ethanol or a mixed solvent extract thereof.
The method of claim 1,
The anti-allergic means improving, treating, suppressing or delaying the onset of such an allergic disease,
The allergic diseases include atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis ), And allergic keratitis.
The method according to any one of claims 1 to 3,
The composition is a composition, characterized in that the food composition.
The method according to any one of claims 1 to 3,
Wherein said composition is a pharmaceutical composition.
The method according to any one of claims 1 to 3,
The composition is a composition, characterized in that the cosmetic composition.

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