KR20100070109A - A composition for comprising trimethylphytospingosine derivatives of psoriasis preventing and treatment - Google Patents

Abstract

PURPOSE: A composition for preventing and treating psoriasis containing a trimethylphytospingosine derivative is provided to suppress immune response and inflammatory cytokine. CONSTITUTION: A composition for preventing and treating psoriasis contains phytospingosine derivatives as active ingredient. The phytospingosine is trimethylphytospingosine(TMP) of chemical formula 1, cyclic trimethylphytospingosine (cyclic TMP) of chemical formula 2, acidic trimethylphytospingosine of chemical formula 3, galactosyl diethylphytospingosine of chemical formula 4.

Description

A composition for comprising trimethylphytospingosine derivatives of psoriasis preventing and treatment}

The present invention relates to a composition for preventing and treating psoriasis containing a trimethyl phytosphingosine derivative having an inflammation inhibitory and selective Th1 immunomodulatory function, and more particularly, trimethyl phytosping as a trimethyl phytosphingosine derivative. High frequency (TMP), Anti-inflammatory and immunomodulatory functions by containing an active ingredient selected from cyclic trimethyl phytosphingosine (cyclic TMP), acidic trimethyl phytosphingosine (acidic TMP) and galactosyl dimethyl phytosphingosine (galctosyl DEP) derivatives It relates to a composition for preventing and treating psoriasis, characterized in that it has a.

In general, inflammatory skin diseases are caused by interactions with keratinocytes, or keratinocytes, in which various immune cells penetrate the skin and make up the majority of skin cells. These keratinocytes secrete various cytokines involved in immune function and are involved in the proliferation of these immune cells, and are also supplied with various factors involved in the proliferation of keratinocytes from the immune cells. In this respect, the skin is not only a protective film that protects our body, but also an immune system.

In particular, Psoriasis is one of the skin diseases related to inflammation and immune dysfunction, and keratinocytes show abnormal growth of keratinocytes, various inflammatory cells, especially T cells, and infiltrated T cells. This is a disease of abnormal growth.

The exact cause of psoriasis is unknown, but until now it is considered an autoimmune disease. That is, it is due to overproliferation of the lesion area of T cells and the formation of blood vessels in the vicinity thereof. The treatment of psoriasis using UV and psoralen to prevent cell invasion and immunosuppressive agents such as cyclosporine are used to treat psoriasis, suggesting that T cells are an important cause of psoriasis. In addition, angiogenesis has been shown to be closely related to psoriasis, and inhibition of angiogenesis is a factor that weakens psoriasis.

On the other hand, the main targets used to treat psoriasis until now are T cell activation inhibition, migration inhibition, selective destruction of T cells, T cell differentiation control technology to differentiate from Th1 to Th2, T cell stimulation cyto It is known to treat psoriasis to prevent psoriasis exacerbation by inhibiting the production of caine and inhibiting the mobilization of neutrophils.

Therefore, in the present invention, while the research and development of substances that inhibit the T cell activity, inhibit the secretion of inflammatory cytokines, and inhibit the T cell migration and angiogenesis, which cause the psoriasis as described above, trimethylphytospinning As it was confirmed that the hypersin (trimethylphytosphingosine) derivatives have an effect of significantly inhibiting the function of psoriasis, the composition for preventing and treating psoriasis was completed.

In the present invention, by using a trimethyl phytosphingosine (TMP) derivative which inhibits T cell activity, inflammatory cytokine secretion, T cell migration and angiogenesis, which are the cause of psoriasis, as an active ingredient, it is important for psoriasis. It is an object of the present invention to provide a composition for the prevention and treatment of psoriasis containing trimethylphytosphingosine derivatives, characterized in that it has an inhibitory and immunomodulatory function in response.

According to a feature of the present invention for achieving the above object the present invention

From the group consisting of trimethylphytosphingosine (TMP), cyclic trimethylphytosphingosine (cyclic TMP), acidic trimethylphytosphingosine (acidic TMP), and galactosyl diethylphytosphingosine (galctosyl DEP). As a composition for preventing and treating psoriasis containing a trimethyl phytosphingosine (TMP) derivative, characterized in that one or more selected and contained as an active ingredient,

The composition inhibits the proliferation of keratinocytes. It may further comprise a carrier of liposomes or nanoemulsions to inhibit immunosuppression, inflammation and angiogenesis,

The composition is selected from one or more of saline solution, Ringer's solution, dextrose solution, maltodextrin solution, glycerol, ethanol as a carrier, ointment, cream, emulsion gel, spray, lotion, liposome, nanoemulsion form It can be formulated as.

In addition, it can be used as a means for solving the problem that can be used, including 0.01 to 10.0 parts by weight of trimethyl phytosphingosine (TMP) derivative based on 100 parts by weight of such a composition for preventing and treating psoriasis.

As described above, a composition for preventing and treating psoriasis containing an inhibitory agent according to the present invention and a trimethylphytosphingosine derivative having a selective Th1 immunomodulatory function is characterized by T cell activity, secretion of inflammatory cytokines, and T cell migration. Trimethyl phytosphingosine (TMP), cyclic trimethyl phytosphingosine (cyclic TMP), acidic trimethyl phytosphingosine (acidic TMP), galactosyl dimethyl phytosphingosine derivative containing an active ingredient that inhibits Containing phytosphingosine derivatives with immunomodulatory function selected from galctosyl DEP, it can be used for the prevention and treatment of psoriasis, as well as inhibiting the immune response important for psoriasis and inhibiting inflammatory cytokines and cellular mobility. There is an advantage to being there.

The present invention is the following trimethyl phytosphingosine (TMP) of Formula 1, cyclic trimethyl phytosphingosine (cyclic TMP) of Formula 2, acidic trimethyl phytosphingosine of Formula 3 (acidic TMP), Formula 4 It relates to a composition for preventing and treating psoriasis containing a trimethyl phytosphingosine derivative containing one or more selected from the group consisting of galactosyl diethyl phytosphingosine derivatives (galctosyl DEP) as an active ingredient. . And it can be used as an iodine salt or a hydrochloride salt as an anion in formulas (1) and (2), the group represented by acid in formula (3) may be present in the form of anions or protons combined.

                 (Formula 1)

                   (Formula 2)

                   (Formula 3)

                   (Formula 4)

The present invention may also include pharmaceutical carriers such as liposomes and nanoemulsions containing substances that inhibit the proliferation of keratinocytes in compositions for preventing and treating psoriasis containing trimethylphytosphingosine derivatives.

In addition to the above-described active ingredients, the present invention may further selectively mix one or more of saline, Ringer's solution, dextrose solution, maltodextrin solution, glycerol and ethanol as a pharmaceutically acceptable carrier for administration of the composition. Can be used.

Also, if necessary, antioxidants such as pycnogenol, asataxanthin, bark bark extract, plant extracts such as willow bark extract, poloxamer / tween 20, poloxamer / limonene, poloxamer A surfactant such as Poloxamer / transcutol may be selected and additionally formulated.

The present invention configured as described above is preferably administered topically, and can be formulated in the form of ointments, creams, emulsion gels, sprays, lotions or suspensions for the treatment of skin and mucous membranes or in the form of liposomes, nanoemulsions.

And it is preferable that trimethylphytosphingosine (TMP) derivatives contain 0.01-10.0 weight part with respect to 100 weight part of compositions of this invention comprised as mentioned above, More preferably, it contains 0.1-5.0 weight part suitably Do.

Hereinafter, the configuration of the present invention will be described in detail through the following examples, but the present invention is not necessarily limited only by the following examples.

Example 1 Measurement of T Cell Cytotoxic Activity of Trimethylphytosphingosine (TMP) Derivatives

1. Culture and Measurement

Activation of T cells is a very important factor for psoriasis and can be used as a good psoriasis treatment if it can inhibit T cell activity. Therefore, the trimethylphytosphingosine (TMP) derivative is toxic to T cells and is measured by MTT (3- [4,5-dimethylthiazole-2-yl] -2,5-diphenyltetrazolium bromide) method. It was. First, the blood cancer cell line (Jurkat-T) was cultured in Dulbecco's modified eagle medium (DMEM) medium, and the cell number was adjusted to 2x10 ⁵ cell / ml, and then the blood cancer cell line (Jurkat-T) was 37 ° C, 5 After culturing for 24 hours in% CO ₂ culture conditions, the solution containing the TMP derivative was diluted appropriately and added to hematological cancer cells (Jurkat), followed by incubation for 24 to 48 hours, and then the supernatant was removed, and 0.5 mg / ml of MTT was added. In medium and incubated for 2 hours. After removing the supernatant, the resulting formazan was dissolved in dimethyl sulfoxide (DMSO), and then absorbance at 570 nm was measured for cytotoxicity.

2. Measurement result

As a result of measuring cytotoxicity using absorbance at 570 nm according to the method of 1 above, TMP derivatives were found to affect the activity of blood cancer cell line (Jurkat T), galactosyl DEP, acidic ) TMP, cyclic The growth of T cells was suppressed in the order of TMP, and the results showing cell viability according to the concentration of TMP derivatives are shown in [Table 1].

Comparison of survival rate of blood cancer cell line (Jurkat T) Unit:% division Dosing concentration (ug / ml) 0.28 0.57 1.14 2.27 4.55 TMP 58 56 57 58 71 Acidic-TMP 38 41 33 30 33 Galacto-dep 33 20 15 11 12 Cyclic-TMP 56 48 41 38 32

Example 2 Anti-inflammatory Effect of Trimethylphytosphingosine (TMP) Derivatives (TNF-a Inhibitory Effect)

1. Culture and Measurement

Skin diseases such as psoriasis and atopic dermatitis are diseases of high inflammatory response, so it is necessary to suppress the inflammatory response to act as a good psoriasis treatment. Therefore, in order to confirm the anti-inflammatory response of the TMP derivative, a tumor necrosis factor (TNF) -a secretion inhibition experiment was performed.

The cell line used in the experiment was a HaCaT cell line, a human keratinocyte cell line, and LPS (lipopolysaccaride) was used as a TNF-a inducer. TNF-a was induced by treatment with 2ug / ml LPS when the concentration of cells was about 2x10 ⁶ cells / ml, and treated with 1ug / ml of TMP derivatives together for 1 day, followed by incubation with supernatant. Was measured by Enzyme-Linked ImmunoSorbent Assay (ELISA).

2. Measurement result

According to the method of 1, the amount of TNF-a was measured by enzyme antibody binding method (ELISA), and TMP and cyclic TMP showed strong TNF-a inhibitory effect, whereas galactosyl TMP was normal. Acidic TMP had minimal effect. And the result is as [Fig. 1].

Example 3 Measurement of Th1 (IL-2) Secretion Inhibitory Activity of Trimethylphytosphingosine (TMP) Derivatives

1. Culture and Measurement

IL-2 is a Th1 cytokine involved in T cell activation. Since inhibition of IL-2 secretion may act as an important factor in the treatment of psoriasis, the inhibition of IL-2 secretion against TMP derivatives was measured using HaCaT cell line.

The blood cancer cell line (Jurkat T) was cultured in a culture condition containing RPMI 1640/10% fetal bovine serum / penicillin / strepmycin to a concentration of 1x10 ⁶ / ml, followed by PHA (Phytohemaglutinin) and PMA (phorbol 12- After activating with myristate 13-acetate, it was treated with cyclosporin A (CsA) with TMP derivative and positive control group for 24 hours, and then the amount of IL-2 resident in the culture acid solution was measured. Measured using 2 kits.

2. Measurement result

When PMA / PHA was used as an activator of immunostimulators, IL-2 production was induced by 550% compared to the control group. In the case of cyclosporin A (CsA), 2 production amount (nearly 100% inhibitory effect) was shown, and IL-2 production was completely inhibited at very low concentration regardless of concentration. On the other hand, TMP showed a slight difference according to derivatives, and TMP showed an inhibitory effect as the concentration increased. At a concentration of 5.68 ug / ml, the inhibitory effect was similar to that of the positive control CsA. Is showing. The measurement results are shown in [Table 2] and [FIG. 2].

Inhibitory Effect of Trimethylphytosphingosine (TMP) Derivatives on IL-2 Production division IL-2 (pg / ml) 5.68μg / ml 2.84μg / ml 1.42 μg / ml 0.71 μg / ml No treatment group 122.5 122.5 122.5 122.5 Activation group 673.3 673.3 673.3 673.3 CsA 107.3 117.9 127.1 127.9 TMP 125.4 150.5 208.6 306.2 Cyclic-TMP 152.5 231.7 286.5 505.5 Acidic-TMP 140.1 240.6 256.8 490.2 Galacto-dep 142.5 250.7 278.9 480.6

Example 4 Measurement of Inhibition of NF-aT Activity in Blood Cancer Cell Line (Jurkat-T)

1. Culture and Measurement

It was confirmed that trimethylphytosphingosine (TMP) derivatives inhibit IL-2 production. To investigate the mechanism of inhibition of IL-2 production, it was determined whether the inhibition of NF-aT activity was carried out using a blood cancer cell line (Jurkat-T). Measured.

First, blood cancer cells are left in serum-free medium for 30 minutes at a concentration of 2x10 ⁶ / ml. At this time, the cell density was about 70% confluency. The NF-aT gene and lipofectamine reagent are mixed at a ratio of 1: 3 to transform blood cancer cells (Jurkat), and then reacted for 4 hours to allow the NF-aT gene to enter Jurkat cells. In addition, the blood cancer cell line (Jurkat-T), which was cultured for 20 hours after completion of transfetion by treatment with 20% fetal bovine serum, was transferred to a 24-well plate, followed by a blood cancer cell line (Jurkat). -T) to 2x10 ⁵ / well, TMP derivative and the positive control cyclosporin A (CsA) pre-culture for 3 hours, then treated with CD3 to activate the blood cancer cell line (Jurkat-T), and cultured for 24 hours Then, the cells were collected and thawed, and then, NF-aT activity was measured by luciferase reaction.

2. Measurement result

Treatment with CD3 in the blood cancer cell line (Jurkat-T) activates NF-aT to express luciferase genesis, resulting in a 11.7-fold increase in luciferase expression, but when treated with cyclosporin A (CsA) As a result, the amount of luciferase expression is reduced. Unlike cyclosporin A (CsA), TMP derivatives were observed to have little effect on NF-aT activity even at high concentrations. Thus, TMP derivatives have been shown to inhibit IL-2 secretion by a different pathway than cyclosporin A (CsA). In addition, TMP derivatives are believed to inhibit IL-2 production by inhibiting NF-kB (Nuclear factor-kappaB) activity. And NF-aT activity results are shown in [Table 3].

Determination of NF-aT Activity of Trimethylphytosphingosine (TMP) Derivatives division Concentration (μg / ml) Expression Increased width (times) No treatment group 0 220.5 1.0 CD3 treatment group 5 2581.0 11.7
CsA
One 212.0 1.0 0.1 991.5 4.5 0.05 1286.0 5.8
TMP
10 1588.0 7.2 2 1945.0 8.8 0.4 2007.0 9.1

Example 5 Inhibition of Th1 / Th2 Cytokine Secretion of Trimethylphytosphingosine (TMP) Derivatives Using Mouse Spleen Cells

1. Culture and Measurement

In the case of psoriasis, the disease is caused by the activity of Th1 cells, the inhibition of Th1 cytokine secretion is an important factor in the treatment of the disease. The inhibitory effect of IL-2 was already measured in the blood cancer cell line (Jurkat-T), but mouse spleen cells were used to confirm the inhibitory effect of the representative gamma interferon (IFN-gamma) of Th1 cytokine. In addition, IL-4, a Th2 cytokine, was measured to determine whether TMP derivatives selectively inhibit Th1.

First, the cerebrospinal bone of the rat (Balb / c Mouse) is disinfected with alcohol, the abdomen is incised, the spleen is aseptically collected, and penicillin / streptomycin-added antibiotics are added to the RPMI (Rosewell Park Memorial Institue) medium. The spleen was ground completely and 2 ml of RPMI medium per spleen was used. And 1x10 to 0.84% ammonium chloride solution at a grinding spleen solution to treatment by destroying the red blood cells was added, and then the medium for 10 seconds a single spleen cell stops the red blood cell hemolysis reaction and centrifuged to collect a settled cells ⁹ / ml of splenocytes were obtained and then cell fractions were cultured for one day and used in the experiment.

In addition, mouse splenocytes were activated by treatment with PMA (phorbol 12-myristate 13-acetate) / PHA (phytohemaglutinin) and treatment with concanavalin A (Con A) to activate T cells. In addition, TMP derivatives were treated to determine the effect of inhibiting the production of gamma interferon (INF-gamma) and IL-4 using a biosource kit.

2. Measurement result

PMA has a function of stimulating both T cells and B cells, and PHA is measured as an adjuvant for maximizing PMA stimulation. As a result, PMA / PHA treated mouse spleen cells and gamma interferon (IFN-gamma) and Results that promote IL-4 production have been shown.

Results show that gamma interferon (IFN-gamma) produces 0.21 pg / ml of IFN-gamma at 5.68 μg / ml, while PMA / PHA treated groups produce up to 267.40 pg / ml and TMP. Processing produced 29.20 pg / ml. In 2.84 μg / ml, the untreated group secreted 0.21 pg / ml of gamma interferon (IFN-gamma), but the PMA / PHA treated group induced production of up to 267.40 pg / ml, and TMP treated 75.19 pg / ml. This production indicates that the production of gamma interferon (IFN-gamma) is significantly suppressed.

In case of IL-4, the untreated group produced 1.35 pg / ml at 5.68 μg / ml, but the production increased to 13.51 pg / ml in the PMA / PHA treated group, and 9.05 pg / ml when treated with TMP. At 2.84 μg / ml, the untreated group produced 1.35 pg / ml, but the PMA / PHA treated group increased 13.51 pg / ml, and TMP treatment resulted in 10.68 pg / ml, which was slightly inhibited.

Taken together, TMP significantly inhibits Th1 cytokine but weakly inhibits Th2 cytokine, suggesting that selective inhibition is possible, and it can be effectively used to treat psoriasis induced by Th1. It was evaluated and the results are shown in [Table 4].

Similar results were obtained in mouse splenocytes treated with Concanavalin A (Con A), which activates only T cells. In the case of IFN-gamma, the untreated group produced 5.71 pg / ml at 5.68 μg / ml, but increased to 114.00 pg / ml with PMA / PHA and 31.73 pg / ml with TMP. At 2.84 μg / ml, the untreated group produced 5.71 pg / ml, but increased to 114.00 pg / ml with PMA / PHA, and 56.06 pg / ml with TMP. The production is shown to be significantly suppressed.

In the case of IL-4, 2.39 pg / ml of the non-treated group was produced at 5.68 μg / ml, but increased to 55.14 pg / ml of the PMA / PHA treatment and 48.38 pg / ml of the TMP treatment. At 2.84 μg / ml, the untreated group produced 2.39 pg / ml, but increased to 55.14 pg / ml in the PMA / PHA treated group, and 55.00 pg / ml was produced when treated with TMP, indicating little inhibition. The results are shown in [Table 5].

Inhibitory Effects of Th1 / Th2 Cytokine Secretion on PMA / PHA-activated Mouse Spleen Cells division IFN-gamma (pg / ml) IL-4 (pg / ml) 5.68μg / ml 2.84μg / ml 5.68μg / ml 2.84μg / ml No treatment group 0.21 0.21 1.35 1.35 PMA / PHA 267.40 267.40 13.51 13.51 TMP 29.20 75.19 9.05 10.68 cyclic-TMP 27.69 95.96 8.38 12.16 Acidic-TMP 25.77 63.37 7.84 10.14 Galacto-tmp 20.29 55.00 7.30 10.00

Inhibitory Effects of Th1 / Th2 Cytokine Secretion on Mouse Splenocytes Activated by Concanavalin A (CoA) division IFN-gamma (pg / ml) IL-4 (pg / ml) 5.68μg / ml 2.84μg / ml 5.68μg / ml 2.84μg / ml No treatment group 5.71 5.71 2.39 2.39 PMA + PHA 114.00 114.00 55.14 55.14 TMP 31.73 56.06 48.38 55.00 cyclic-TMP 32.79 53.94 45.14 47.70 Acidic-TMP 41.25 53.94 45.14 47.70 Galacto-tmp 39.13 50.77 42.34 84.86

Example 6 Measurement of Cell Mobility of Trimethylphytosphingosine (TMP) Derivative

1. Culture and Measurement

As psoriasis develops, blood vessels grow into psoriasis to nourish the overgrown keratinocyte cells. In order for the guff tube to grow, vascular endothelial cells move, and a substance that suppresses it may be a good psoriasis treatment. To this end, human umbilical vein endotherial cells (HUVECs) were used to inhibit cell migration of TMP derivatives.

First, human umbilical vascular endothelial cells (HUVEC) and TMP derivatives were added and cultured until the cells were full, followed by cultivation. Human umbilical vascular endothelial cells (HUVEC) were observed to move between the created empty spaces, and cell mobility was measured. As a measure of the degree of migration, a method of measuring the number of cells penetrated into the empty spaces was used.

2. Measurement result

In the untreated group, as seen in FIG. 3, human umbilical vascular endothelial cells (HUVRC) can be observed to move over time, and it was confirmed that cell migration was inhibited by treatment with TMP. Similar to TMP, cyclic TMP, galactosyl DEP and acidic TMP were also inhibited.

Example 7 Preparation of Trimethylphytosphingosine (TMP) -Containing Nanoparticles

This example was prepared with liposomes and nanoemulsions for solubilization because TMP and its derivatives are insoluble in water.

 1. Trimethylphytosphingosine (TMP) -containing liposomes

end. Method for preparing liposomes

In order to prepare TMP-containing liposomes, TMP and lecithin are completely dissolved in ethanol, and then strongly chemically reacted (stirring), and distilled water is slowly added to make liposomes. Ultrasonic treatment or extruder is performed to reduce particle size. Particle size was adjusted. In addition, 0.5% of poloxamer / tween 20 skin permeation accelerators were used to promote skin permeation of liposome particles. Prepared by addition.

I. Preparation of Liposomes

Liposomes were prepared according to the above A. by the composition ratios of Experimental Examples 1 to 4 in Table 6 below.

                                                     Unit: parts by weight  Ingredient Experimental Example 1 Experimental Example 2 Experimental Example 3 Experimental Example 4 TMP 0.5 1.0 1.0 0.5 lecithin 3 3 3 3 ethanol 10 10 10 10 menthol 0.1 0.1 0.1 0.1 Poloxamer 0.5 0.5 0.5 0.5 Tween 20 0.5 0.5 0.5 0.5 Peel Extract 0 0 3 3 Willow Bark Extract 0 0 5 5 Distilled water 85.4 84.9 76.9 77.4 sum 100.0 100.0 100.0 100.0

2. Trimethylphytosphingosine (TMP) Containing Nanoemulsion

end. Manufacturing method of nanoemulsion

Lecithin and TMP are dissolved in ethanol and then PEG-8 caprylic / capric glycerides (LAS) and isopropyl myristate (IMP) are added to the ethanol solution. And distilled water dissolved in menthol was added to the ethanol solution and stirred for 30 minutes to 1 hour to prepare a nanoemulsion. In addition, in order to promote skin penetration of the nanoemulsion particles, 1 to 2 parts by weight of a skin permeation accelerator of Poloxamer / tween 20 is added. Prepared by addition.

I. Preparation of Nanoemulsions

The nanoemulsion was prepared according to the above A. by the composition ratio of Experimental Examples 5 to 8 in Table 7 below.

                                                       Unit: parts by weight Ingredient Experimental Example 5 Experimental Example 6 Experimental Example 7 Experimental Example 8 TMP 0.5 1.0 1.0 0.5 lecithin 2 2 2 2 LAS 15 15 15 15 IPM 3 3 3 3 ethanol 15 15
15 15 Bark Extract 0 0 3 3 Willow Bark Extract 0 0 5 5 menthol 0.1 0.1 0.1 0.1 Poloxamer One 2 2 One Tween20 One 2 2 One Distilled water 62.4 59.9 51.9 54.4 sum 100.0 100.0 100.0 100

3. Evaluation method

Liposomes prepared by the methods 1 and 2 (Experimental Examples 1 to 4) and nanoemulsions (Experimental Examples 5 to 8) were applied twice a day to the lesion site for each of four male and female adult patients, and observed for one week. It was.

4. Evaluation result

After applying twice a day to the lesion site according to the method of 3, and observed for a week, it was evaluated that the lesion site of the patient who applied liposomes and nanoemulsions improved very much. Therefore, TMP and its derivatives were evaluated to be able to selectively inhibit Th1 immune response, which is important for psoriasis treatment, to inhibit inflammatory cytokines such as TNF-a and to be an important substance for psoriasis treatment that inhibits cell mobility. .

As described above, the present invention has been proved to be excellent in its efficacy through the above embodiments, but the present invention is not necessarily limited only by the above configuration, and various substitutions may be made without departing from the technical spirit of the present invention. , Modifications and variations are possible.

1 is a graph showing the effect of the TNF-a induction of trimethyl phytosphingosine (TMP) derivative using HaCaT cell line as a human keratinocyte cell line according to the present invention.

Figure 2 is a graph showing the effect of inhibiting IL-2 production of trimethyl phytosphingosine (TMP) derivative using the HaCaT cell line according to the present invention.

Figure 3 is a diagram showing the cell migration capacity of the trimethyl phytosphingosine (TMP) derivative using the human umbilical cord vascular endothelial cells (HUVEC) according to the present invention.

Claims (9)

From the group consisting of trimethylphytosphingosine (TMP), cyclic trimethylphytosphingosine (cyclic TMP), acidic trimethylphytosphingosine (acidic TMP), and galactosyl diethylphytosphingosine (galctosyl DEP). A composition for preventing and treating psoriasis containing a phytosphingosine derivative, characterized in that it contains one or more selected as an active ingredient. The method of claim 1, The trimethyl phytosphingosine (TMP) is a composition for preventing and treating psoriasis containing a phytosphingosine derivative, characterized in that represented by the following formula (1).

                 (Formula 1) The method of claim 1, The ring trimethylphytosphingosine (cyclic TMP) is a composition for preventing and treating psoriasis containing a phytosphingosine derivative, characterized in that represented by the following formula (2).

                    (Formula 2) The method of claim 1, The acidic trimethylphytosphingosine (acidic TMP) is a composition for preventing and treating psoriasis containing a phytosphingosine derivative, characterized in that represented by the following formula (3).

                      (Formula 3) The method of claim 1, The galactosyl diethyl phytosphingosine (galctosyl DEP) is a composition for preventing and treating psoriasis containing a phytosphingosine derivative, characterized in that represented by the following formula (4).

                        (Formula 4) The method according to any one of claims 1 to 5, The composition is a composition for preventing and treating skin diseases and psoriasis, characterized in that it comprises a carrier of liposomes or nanoemulsion. The method according to any one of claims 1 to 5, The trimethylphytosphingosine derivative is a composition for preventing and treating skin diseases and psoriasis, characterized in that it comprises 0.01 to 10.0 parts by weight based on 100 parts by weight. The method according to any one of claims 1 to 5, The composition is selected from one or more of saline, Ringer's solution, dextrose solution, maltodextrin solution, glycerol, ethanol as a carrier, characterized in that the composition for preventing and treating skin diseases and psoriasis. The method according to any one of claims 1 to 5, The composition is an ointment, cream, emulsion gel, spray, lotion, liposome, a composition for preventing and treating skin diseases and psoriasis, characterized in that it can be formulated in the form of nanoemulsion.

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