KR20150025286A - Cmposition for treating or preventing atopic dermatitis or skin wound comprising phytosphingosine-1-phosphate or its derivatives - Google Patents

Abstract

The present invention relates to a composition containing phytosphingosine-1-phosphate or derivatives thereof for treating or relieving atopic dermatitis. The composition of the present invention is prepared using a substitute for sphingosine, a precursor of ceramide, thereby being very effective in treating atopic dermatitis as well as economical.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a composition for treating or preventing atopic or skin wounds containing phytosphingosine-1-phosphate or a derivative thereof, a phytosphingosine-1-phosphate or its derivatives,

FIELD OF THE INVENTION The present invention relates to the treatment of skin diseases, and more particularly to the field of atopic treatment using phytosphingosine-1-phosphate or a derivative thereof.

Atopy is a skin disease caused by excessive skin reaction to various pollutants or bacteria such as Staphylococcus aureus. It is especially susceptible to dry skin or skin dryness, characterized by chronic, periodic onset and recurrence .

Atopic dermatitis is not a fatal disease, but it is a disease that lowers the quality of life by causing serious obstacles to the daily life of many patients, which is known as an incurable disease that mankind must solve with cancer, AIDS, and dementia. Especially, adolescents and children are becoming increasingly problematic in academic affairs such as anxiety and concentration, and are increasing in adults because of environmental and psychological stress. According to a US survey, 56 percent of respondents said they felt uncomfortable with their social life, and 80 percent had experienced sleep disorders.

85% of patients develop before 5 years of age, and 60% of them have adult atopic dermatitis. In general, 51% of the population is known to experience these diseases, but the problem is increasingly due to environmental factors. For example, in the United States, the incidence of patients has tripled since the 1970s. Korea has a high incidence rate of atopic patients in the world, but it seems to be closely related to apartment living environment.

Although atopy is presumed to be caused by a combination of genetic, environmental and immunological factors, the cause of it is still unclear, and its fundamental treatment has not been developed yet. Steroidal ointments and antihistamines are the main treatment modalities. Antibiotics are used for the treatment of skin infections accompanied by the progression of the lesions. In severe cases, ultraviolet irradiation or immunosuppressants may be used.

Steroid ointment is a good treatment for atopic dermatitis. However, when used for long term, steroid ointment may cause a decrease in skin irritation and disproportion, redness due to decrease of skin barrier recovery ability, skin hardening, allergy, contact dermatitis Resulting in side effects, and when the use is discontinued, atopic dermatitis recurred.

Korean Patent No. 0404072 relates to a composition for treating a wide spectrum of skin diseases, and relates to a composition for treating a broad spectrum skin disease, which is capable of curing or improving dermatitis, bacterial infectious skin diseases, etc. including sphingolipids and lysophosphatidic acid, ≪ / RTI >

Considering these problems, it is required to develop an economical atopic treatment or mitigation material which exhibits safer and superior effects against side effects.

The present invention provides a composition that can be effectively used for the treatment of atopic skin diseases using phytosphingosine-1-phosphate or a derivative thereof.

In one aspect, the present invention provides a pharmaceutical composition for the treatment of atopic or skin wounds, comprising phytosphingosine-1-phosphate or a derivative or a pharmaceutically acceptable salt thereof. Wherein said derivative comprises N-acetyl phytosphingosine-1-phosphate or cyclic phytosphingosine-1-phosphate, especially cyclic phytosphingosine-1-phosphate is O-cyclic Phytosphingosine-1-phosphate.

Phytosphingosine-1-phosphate or a derivative thereof is included in the composition according to the present invention in an amount of about 0.001 wt% to 1 wt%.

In one embodiment according to the present application, N-acetyl phytosphingosine-1-phosphate and cyclic phytosphingosine-1-phosphate are used in combination.

The compositions according to the present invention have formulations suitable for topical application to the skin and include, for example, creams, ointments, pastes, foams, gels, lotions, sprays, sticks or aerosols.

In another aspect, the compositions herein may be provided in cosmetics.

Compositions comprising one or more of the phytosphingosine-1-phosphate or derivatives thereof (N-acetyl phytosphingosine-1-phosphate, cyclic phytosphingosine-1-phosphate) It can be effectively used for the treatment of wounds such as atopic dermatitis and wound healing without side effects such as lowering of reaction and unbalance, reduction of skin barrier recovery ability, redness, skin hardening, allergy and contact dermatitis.

1 is a schematic diagram showing the metabolic process of sphingosine-1-phosphate.
FIG. 2 is a graph illustrating the wound healing ability of a composition according to one embodiment of the present invention after depriving the side of a C57 / BL6 mouse and inducing inflammation in the skin. In treatment 1, phytosphingosine-1- %, And treatment 2 was a subcutaneous injection of each composition containing 0.01% by weight of O-cyclic phytosphingosine-1-phosphate, each time subcutaneously injected 10 days later, compared with the control group It is a photograph.
FIG. 3 is a photograph showing a result of applying a nanoemulsion containing phytosphingosine-1-phosphate to the affected part of a patient with atopic dermatitis for 8 weeks, compared with that before application.
FIG. 4 is a graph showing changes in skin moisture and skin pH at lesions and non lesions of a patient while applying 8-week nanoemulsion to a lesion of a patient with atopic dermatitis.
FIG. 5 is a photograph of a patient with contact dermatitis (erythema) improved erythema by applying a nanoemulsion containing O-cyclic phytosphingosine-1-phosphate for 2 weeks and 3.5 weeks.

The present invention relates to a pharmaceutical composition for the prevention or treatment of atopic dermatitis or skin wounds comprising one or more phytosphingosine-1-phosphate or a derivative thereof, a pharmaceutically acceptable salt or solvate thereof.

Atopic dermatitis or atopic dermatitis is a chronic and recurrent inflammatory dermatosis that starts in early childhood or childhood. It refers to skin disease accompanied by pruritus (itching), dry skin, and characteristic eczema. In infancy, it begins with eczema on the unfolded side of the face and limbs, but it appears as a form of eczema on the part where the arm is bent and on the bending part behind the knee in growth, and in many cases it tends to improve naturally . In adults, lichenification appears, which causes thickening of the folded area, and eczema often occurs on the face compared to the pediatric period.

Skin wounds, as used herein, All diseases caused by abnormality of skin barrier, immune response, sebum secretion, abnormal proliferation of keratinocyte, microbial infection and external stimulation, which are deviated from the normal function of skin and are caused by atopy, contact dermatitis, acne, psoriasis, scarring, burn , And a pressure ulcer.

Sphingosine-1-phosphate is a signaling substance responsible for cell migration, cell proliferation (cell death suppression), neovascularization, wound healing, etc. and acts on the cell surface to cause various reactions. On the other hand, measurement of sphingosine-1-phosphate content showed a significant decrease in the content of sphingosine-1-phosphate in the atopic region and blood (J Invest Daermatol 131: 266-268, 2011). However, sphingosine-1-phosphate was very expensive at 421,000 won per 1 mg (Sigma price) and could not be used for the treatment of atopy.

In the present application, 2-amino-3,4-dihydroxyoctadecyl hydrogen phosphate is represented by the following formula (I).

(I)

The term "derivative " as used herein is a similar compound obtained by chemically modifying a portion of a compound. Usually refers to a compound in which a hydrogen atom or a specific atomic group in a compound is substituted by another atom or atomic group. N-acetyl-2-amino-3,4-dihydroxyoctadecyl hydrogen phosphate of formula (IIa) or a pharmaceutically acceptable salt thereof as a derivative of phytosphingosine-1-phosphate O-cyclic phytosphingosine-1-phosphate (5-amino-2-hydroxy-4- (1-

hydroxypentadecyl) -1,3,2-dioxaphosphinane 2-oxide).

≪ RTI ID = 0.0 &

≪ RTI ID =

Compounds according to the present invention can be prepared using conventional knowledge known in the art of organic chemistry and include, for example, (S. Li, WK Wilson, GJ Schroepfer, Chemical synthesis of D-ribo-phytosphingosine- potential modulator of cellular processes. J. Lipid Res. 40: 117-125, 1999), and the method for producing O-cyclic phytosphingosine-1-phosphate is described in Example 1.

Pharmaceutically acceptable salts, or solvates thereof, of the compounds of formula (I), (IIa) or (IIb) may be suitably prepared or selected using knowledge known to those skilled in the art.

Salts are those that are physiologically acceptable and do not cause an allergic reaction or similar reaction that is common in humans, and the salt is preferably an acid addition salt formed by free acid. The free acid may be an organic acid or an inorganic acid. The organic acids include, but are not limited to, citric, acetic, lactic, tartaric, maleic, fumaric, formic, propionic, oxalic, trifluroacetic, benzoic, gluconic, methosulfonic, glycolic, succinic, Glutaric acid and aspartic acid. In addition, the inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid, and phosphoric acid. In one embodiment according to the present disclosure, the pharmaceutically acceptable salt may be present as an acid addition salt wherein the compound of formula (I), (IIa) or (IIb) forms a salt with the free acid. In addition, the compound of formula (I), (IIa) or (IIb) according to the present invention may include not only pharmaceutically acceptable salts, but also all salts, hydrates and solvates which can be prepared by conventional methods.

The compound of formula (I), (IIa) or (IIb) may be stabilized by an anion mating with an ammonium cation in the compound, and the anion may be any anion capable of being paired with an ammonium cation, For example, iodide (I ^- ), sulfonate (SO ₃ ^{2 -} ), chloride (Cl ^- ) and the like.

As used herein, the term "treatment" means any action that improves or alleviates the symptoms of atopic dermatitis by administration or application of the composition. Those skilled in the art will be able to ascertain the precise criteria of atopic dermatitis or diseases for which the composition of the present invention is effective, and determine the degree of improvement, improvement and treatment It will be possible.

The term "prophylactic, " as used herein, refers to any act that, by administration of a composition according to the present application, inhibits or delays the onset of a disease for which the composition is effective. It will be apparent to those skilled in the art that compositions of the present invention that are effective in the treatment of atopy and skin wounds can prevent the early symptoms of a related disease, or such a disease when taken prior to appearance.

The composition of the present application contains phytosphingosine-1-phosphate or a derivative thereof alone or as a mixture thereof as an active ingredient, and exhibits the effect of alleviating and treating atopic dermatitis without using steroids or antihistamines. The content of phytosphingosine-1-phosphate or a derivative thereof contained in the composition of the present invention is not limited thereto, but may be about 0.001% by weight to 1% by weight, particularly about 0.005% by weight based on the total weight of the total composition .

The composition according to the present invention may be administered at a dose of from 0.0001 to 1000 mg / kg, preferably from 0.001 to 1000 mg / kg per day, of a compound of formula (I), (IIa) or have.

Upon topical administration, the compound of formula (I), (IIa) or (IIb) may be administered by applying once or twice a day to a site where treatment or prevention of atopic or skin wound is desired. When the active ingredient is 1% by weight, the daily dose is about 0.5-3 mg, which can be increased or decreased depending on the area of the application site. The dosage and the number of the compound of the formula (I), (IIa) or (IIb) may be suitably increased or decreased according to the patient's age, sex, disease progression, route of administration,

The composition according to the present invention may use phytosphingosine-1-phosphate or a derivative thereof in combination of two or more species. In one embodiment according to the present invention, phytosphingosine-1-phosphate and cyclic phytosphingosine-1-phosphate, in particular o-cyclic phytosphingosine-1-phosphate, are used in combination, Effect can be expected.

A composition comprising the present phytosphingosine-1-phosphate or a derivative thereof is formulated together with a pharmaceutically acceptable carrier, optionally an excipient or stabilizer.

Pharmaceutically acceptable carriers herein are physiologically compatible materials including, for example, any solvent, dispersion medium, coating antibacterial and antifungal agent, isotonic solution, absorption / resorption retarder, and the like. In one embodiment, a carrier is used which is particularly suited for injection and infusion. For example, pharmaceutically acceptable carriers may include sterile aqueous or isotonic buffered saline or dispersion and sterile powders for the preparation of sterile injectable solutions, and those skilled in the art will be able to select appropriate formulations depending on the type of active ingredient (s) included in the composition.

If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, it can be formulated into injection formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like by additionally adding diluents, dispersants, surfactants, binders and lubricants, Specific antibody or other ligand can be used in combination with the carrier. Can further be suitably formulated according to the respective disease or ingredient according to the appropriate method in the art or using the methods disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA have.

Compositions according to the present application, when prepared for application, may be prepared in solid and semi-solid forms, for example in the form of creams, ointments, pastes, foams, gels, lotions, sprays, sticks or aerosols.

The cream is an oil-in-water emulsion containing more than 50% water. The oil-containing substrates used herein are typically selected from the group consisting essentially of fatty alcohols such as lauryl, cetyl or stearyl alcohols, fatty acids such as palmit or stearic acid, liquid to solid waxes such as isopropyl myristate Or a wax and / or a hydrocarbon compound, for example paraffin oil. Suitable emulsifiers are mainly surfactants having hydrophilic properties, for example fatty acid esters of polyols with corresponding nonionic emulsifiers, for example ethylene oxide adducts, for example polyglycerol fatty acid esters or polyoxyethylene sorbitan fatty acids Ether (Tween brand); Polyoxyethylene fatty alcohol ethers or esters thereof or the corresponding ionic emulsifiers such as alkali metal salts of fatty alcohol sulfonates, sodium cetyl sulfate or sodium stearyl sulfate, which are usually cetyl alcohol or fatty alcohols such as stearyl alcohol .

Ointment is a water-in-oil emulsion containing not more than 70%, for example 20% to 50%, of water or an aqueous phase. The oil-containing phase contains mainly hydrocarbons such as paraffin oil and / or solid paraffin, which contain hydroxy compounds such as, for example, fatty alcohols such as cetyl alcohol or their esters, or wool waxes to enhance water absorption. Emulsifiers correspond to lipophilic substances such as sorbitan fatty acid esters. In addition, the ointment contains, for example, a moisturizing agent such as glycerol, propylene glycol, sorbitol and / or polyalcohol such as polyethylene glycol, as well as a preservative.

The paste is a cream and ointment containing a powdered ingredient that absorbs secretions, for example, a metal oxide such as titanium dioxide or zinc oxide, and also tallow and / or aluminum silicate which binds with moisture or absorbed secretions.

The foam is a liquid oil-in-water emulsion in the form of an aerosol. In the case of oil-containing phases, in particular hydrocarbon compounds such as paraffin oil, fatty alcohols such as cetyl alcohol, fatty acid esters such as isopropyl myristate, and / or waxes are used. Suitable emulsifiers are, in particular, emulsifiers which are mainly hydrophilic, such as polyoxyethylene sorbitan fatty acid esters, and also emulsifiers, for example, sorbitan fatty acid esters, which have predominantly lipophilic properties. Commercially available additives are typically further used, for example preservatives.

The gel may be in particular an active substance in which the gel formers are dispersed or swollen, in particular cellulose ethers such as methylcellulose, hydroxyethylcellulose, carboxymethylcellulose or vegetable hydrocolloids such as sodium alginate, tragacanth, Gum arabic and polyacrylate thickener systems. The gel further contains, for example, a polyalcohol such as propylene glycol or glycerol as a humectant, and a wetting agent such as a polyoxyethylene sorbitan fatty acid ester. The gel also contains commercially available preservatives such as benzyl alcohol, phenethyl alcohol, phenoxyethanol, and the like.

The pharmaceutical composition comprising the phytosphingosine-1-phosphate or a derivative thereof of the present invention not only provides an excellent therapeutic effect against atopic dermatitis but also can be safely used for long-term injection and application without toxicity and side effects caused by drugs . Accordingly, the composition of the present invention can be used as cosmetics and the like.

Accordingly, in view of the above, the present invention relates to a composition comprising the above-described phytosphingosine-1-phosphate or a derivative thereof of the present invention is provided as a cosmetic product such as a cream, an ampule, a skin, an essence, a shampoo, (Cream, essence, cleansing foam and cleansing water), color cosmetic composition (foundation, lipstick, mascara, makeup base), hair product composition (shampoo, , Rinse, hair conditioner, hair gel) and soap.

As used herein, the term "cosmetic product" refers to an article used in the human body to change or brighten the appearance of a human body or to maintain or improve the health of skin hair, and refers to a slight action on the human body. Is intended to include both shampoos, rinses, lotions, creams, oils, cleansing products, and functional cosmetics in the usual sense.

Functional cosmetics are physical cosmetics, biochemistry, and biotechnological techniques to control the body's defense rhythm, cosmetic composition and cosmetics to add value to the function of the cosmetics. Refers to a cosmetic product which is processed by designing the body control function to be sufficiently expressed in living body, and preferably refers to a cosmetic product for improving a skin disease symptom, for example, atopic dermatitis.

The above-mentioned functional cosmetics are not particularly limited to the components other than the phytosphingosine-1-phosphate or derivatives thereof of the present invention as essential components in the indicated ratios. In the case of ordinary cosmetics such as hair or body cleansing agents, Emulsifying agents, preservatives, flavoring agents and antioxidants, and in the case of body creams, vegetable oils, emulsifiers, thickeners, perfumes, water, antioxidants, and UV absorbers.

Hereinafter, embodiments are provided to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited to the following examples.

Example 1 O- Cyclic phytosphingosine -One- Phosphate  synthesis

A. Preparation of N-Boc-Phytosphingosine

Blood Phytophthora bosom . Korean Chem . N-Boc-phytosphingosine was prepared by reacting (Boc) ₂ O in t-butanol with a protecting group (Boc) in the amino group according to the method described in Soc ., 2003, 24, 267-268.

B. N- Boc - Phytosphingosine -O- Of cyclic phosphate  Produce

1.05 equivalent of POCl ₃ was slowly added dropwise to a pyridine solvent (1/3 of the total volume) cooled to about -30 to prepare a POCl ₃ / pyridine solution. The above-prepared N-Boc-phytosphingosine (1 equivalent) was dissolved in a pyridine solvent (2/3 of the total volume), cooled to -20, and the POCl ₃ / pyridine solution prepared above Respectively. After the reaction temperature rose to room temperature, the solvent pyridine was removed under reduced pressure, the pH was adjusted to 2 with 6N HCl and extracted with ethyl acetate. The ethyl acetate extract was dried over MgSO _4, and the solvent was concentrated under reduced pressure to obtain the desired substance N-Boc-phytosphingosine-O-cyclic phosphate quantitatively.

C. O- Cyclic phytosphingosine -One- Phosphate  Produce

The prepared N-Boc-phytosphingosine-O-cyclic phosphate was dissolved in CH ₂ Cl ₂ , and 1/3 of the volume of CH ₂ Cl ₂ solvent was added at room temperature, followed by stirring at room temperature for 1 hour . The solvent was removed under reduced pressure, and Conc-HCl solvent was added to the mixture to vigorously stir. The resulting white solid was filtered, washed with water, and then washed with acetone and dried to obtain the final product, O-cyclic phytosphingosine- -Phosphate in the form of the hydrochloride salt (total yield: 90%).

Further, the obtained hydrochloride was treated with the same equivalent amount of KOH ethanol solution to obtain O-cyclic phytosphingosine-1-phosphate from which hydrochloride had been removed.

Further, the obtained O-cyclic phytosphingosine-1-phosphate was treated with 3 equivalents of an aqueous NaOH solution to prepare an O-cyclic phytosphingosine-1-phosphate disodium salt. ¹ H NMR (300 MHz, CD ₃ OD: CD ₃ COOD = 1: 1) data of the finally obtained material is as follows.

^{1 H-NMR (300MHz, MeOH} -d4: AcOH-D4 / 1: 1) ppm, 0.83 (t, 3H), 1.23 (bs, 24H), 1.5 (m, 1H), 1.75 (m, 1H), 3.7 (bs, IH), 3.8 (dd, IH), 4.1 (bm, IH), 4.18 (bq, IH), 4.4 (bt, IH).

Example 2 Preparation of nanoemulsion containing phytosphingosine-1-phosphate or a derivative thereof

In this Example, a nanoemulsion containing phytosphingosine-1-phosphate, N-acetyl phytosphingosine-1-phosphate and O-cyclic phytosphingosine-1-phosphate, And its detailed manufacturing method is described in Korean Patent No. 1199580. [ Table 1 shows the composition.

Ingredients Composition 1
(Unit weight%) Composition 2
(Unit weight%) Composition 3
(Unit weight%) Phytosphingosine-1-phosphate 0.005 0 0 N-acetyl phytosphingosine-1-phosphate 0 0.005 0 0-cyclic phytosphingosine-1-phosphate 0 0 0.005 Phage-8 caprylic / capric glyceride 5 5 5 Herbal extract 20 20 20 glycerin 5 5 5 Centipede extract 6 6 6 Dimethysulfone 6 6 6 Peony root extract 5 5 5 Hexanediol 2.5 2.5 2.5 Bacillus / soybean fermented extract 3 3 3 Glycosyl trehalose 1.5 1.5 1.5 White chestnut mushroom extract 1.5 1.5 1.5 lecithin One One One Citric acid 0.2 0.2 0.2 Phytosphingosine 0.05 0.054 0.05 oil 0.5 0.5 0.5 Polysorbate 80 0.5 0.5 0.5 Poloxamer 407 0.5 0.5 0.5 Tocopherol acetate 0.5 0.5 0.5 Purified water 41.245 41.245 41.245 gun 100 100 100

Example 3 Phytosphingosine -One- Phosphate  Or a derivative thereof Emulsion  Wound healing effects of C57 / BL6 mice

Six-week-old C57 / BL6 male mice (purchased from Orient Bio, average weight 20 g) After adaptation in the breeding room, hair was cut off at the side of the mouse, the hair was completely removed by treating the depilator, and the experiment was conducted on the mouse without scratching.

After epilating mice were adapted for one day, 100% alcohol was subcutaneously injected into the control group. In treatment group 1, 0.1 mL of 100% alcohol containing 0.01% phytosphingosine-1-phosphate was subcutaneously injected once (once) in the same manner and in O-cyclic phytosphingosine- 1-phosphate was subcutaneously injected once at the same concentration (0.01%). After 10 days, inflammation and wound restoration were compared (Fig. 2).

As a result, when 100% alcohol was subcutaneously injected, 100% alcohol treatment group 1 containing phytosphingosine-1-phosphate and O-cyclic phytosphingosine-1-phosphate, which did not heal inflammation reaction and wound, 2, the inflammatory reaction disappeared, and the effect of wound healing could be seen. Phosphate did not show a significant difference in wound healing between phytosphingosine-1-phosphate and O-cyclic phytosphingosine-1-phosphate.

Example 4 Clinical treatment effect of emulsion containing phytosphingosine-1-phosphate or a derivative thereof

To evaluate the effect of the composition according to the present invention on atopic dermatitis, the following clinical tests were conducted on atopic dermatitis patients (10 male and female, including children and adolescents, average age 19 years). The nanoemulsion containing the phytosphingosine-1-phosphate prepared in Example 1 was applied to the affected part of the atopic patient twice a day for eight weeks, and then it was observed whether or not the lesion area of the atopic patient was improved (Fig. 3). The TEWL (Tewameter, Tewameter TM 300, Courage & Khazaka, Germany) and skin pH were compared between lesions and non lesions at 4 and 8 weeks (Fig. 4).

As a result, the skin moisture evaporation amount (TEWL) after the application of the nano emulsion containing the phytosphingosine-1-phosphate (Composition 1) was compared and as a result, the moisture evaporation amount and skin pH decreased Respectively.

In addition, patients with atopic dermatitis (49 years, male) (Erythema) of O-cyclic phytosphingosine-1-phosphate (Composition 3) was applied for 2 to 4 weeks under the same conditions as above, contact dermatitis (erythema) Respectively.

Example 5 Phytosphingosine -One- Phosphate  Or a derivative thereof Emulsion  Therapeutic effect of atopy on dogs

Compositions 1 to 3 of Example 1 were diluted 1: 1 with water and prepared by spraying. Nano emulsion was applied to the lesion against pet dogs (mean age 5 years, average weight 5 kg) with severe atopy for 3 to 5 years Respectively. The results are shown in Table 2. Six groups per group were used, and the numbers in Table 2 indicate the number of digits improved on each day. As a result, it was shown that the composition according to the present invention improved atopy in a very short time compared with the existing product (huililac).

 In the case of conventional products, it is effective to apply for about one month, whereas the nanoemulsion containing sphingosine-1-phosphate and its derivatives of the present invention showed rapid recovery of atopy.

The time required for recovery after treatment (day) 2 days 3 days 4 days 5 days Huamilac 0 0 0 One Composition 1 One 2 2 One Composition 2 0 One One 3 Composition 3 One 2 2 One

In Table 2, the number in parentheses is the number of raised digits.

While the present invention has been described in connection with what is presently considered to be the preferred embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, .

All technical terms used in the present invention are used in the sense that they are generally understood by those of ordinary skill in the relevant field of the present invention unless otherwise defined. The contents of all publications, which are incorporated herein by reference, are incorporated herein by reference.

Claims (8)

A pharmaceutical composition for preventing or treating atopic or skin injury, comprising phytosphingosine-1-phosphate or a derivative or a pharmacologically acceptable salt thereof.
The pharmaceutical composition according to claim 1, wherein the derivative is N-acetyl phytosphingosine-1-phosphate or cyclic phytosphingosine-1-phosphate, for the prevention or treatment of atopy or skin wounds.
The pharmaceutical composition according to claim 2, wherein the cyclic phytosphingosine-1-phosphate is O-cyclic phytosphingosine-1-phosphate, for the prevention or treatment of atopy or skin wounds.
The pharmaceutical composition according to claim 1, wherein the phytosphingosine-1-phosphate or a derivative thereof comprises about 0.001 wt% to 1 wt%.
The pharmaceutical composition according to claim 2, wherein the combination comprises N-acetyl phytosphingosine-1-phosphate and O-cyclic phytosphingosine-1-phosphate.
The pharmaceutical composition according to claim 1, wherein the composition has a formulation suitable for topical application to the skin.
The pharmaceutical composition according to claim 6, wherein the formulation is a cream, ointment, paste, foam, gel, lotion, spray, stick or aerosol, atopic or skin wound.
The pharmaceutical composition according to any one of claims 1 to 6, wherein the composition is provided as a cosmetic product for preventing or treating atopic or skin wounds.

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