COMPOSITION FOR PREVENTING OR TREATING PRURITUS

Abstract

The present disclosure relates to a composition for preventing, improving or treating pruritus by using a naturally derived ingredient. The composition of the present disclosure may be used to improve or treat pruritus caused by various causes safely and effectively without the risk of side effects.

Claims

1. A method of preventing or treating pruritus, comprising: providing a pharmaceutical composition to an individual in need thereof, wherein the pharmaceutical composition comprises a compound of Chemical Formula 1 as an active ingredient: ##STR00006## wherein R is H or OH.

2. The method according to claim 1, wherein the pruritus is selected from a group consisting of paroxysmal pruritus, winter itch, pruritus ani, pruritus vulvae, pruritus scroti, aquagenic pruritus, scalp pruritus, nasal pruritus, neck itch, oral pruritus and ocular pruritus.

3. The method according to claim 1, wherein the pruritus is pruritus accompanied by an internal disease selected from a group consisting of cholestatic pruritus, chronic renal failure, malignant tumor, iron-deficiency anemia, polycythemia vera, hyperparathyroidism, hypoparathyroidism, diabetes and acquired immune deficiency syndrome.

4. The method according to claim 1, wherein the pruritus is pruritus accompanied by a psychocutaneous disorder selected from a group consisting of lichen simplex chronicus, prurigo, trichotillomania, neurotic excoriation, cutaneous behavior disorder and delusional parasitosis.

5. The method according to claim 1, wherein the composition is in a form selected from a group consisting of a formulation for external application to the skin, an aerosol, a spray, an eye drop, an oral medication and an injection.

6. The method according to claim 1, wherein the composition is formulated in the form selected from the group consisting of a solution in an oily or aqueous medium, a suspension, an emulsion, an extract, a powder, a granule, a tablet, and a capsule.

7. The method according to claim 1, wherein the pharmaceutical composition is administered orally.

8. The method according to claim 1, wherein the pharmaceutical composition is administered parenterally from a group selected from the group consisting of nasally, ocularly, intravenously, subcutaneously, intramuscularly, intraperitoneally, and transdermally.

9. The method according to claim 1, wherein the pharmaceutical composition is administered as a daily dosage in the amount of 0.001-100 mg/kg.

10. The method according to claim 1, wherein R is OH.

11. The method according to claim 1, wherein R is H.

12. A method for preventing or improving pruritus, comprising: providing a food composition comprising a compound of Chemical Formula 1 as an active ingredient to be ingested by an individual in need thereof: ##STR00007## wherein R is H or OH.

13. The method according to claim 12, wherein the food composition further comprises a at least one ingredient selected from the group consisting of a protein, a carbohydrate, a fat, a nutrients, a seasoning agent, and a flavoring agent.

14. The method according to claim 12, wherein the food composition is a drink.

15. A method for preventing or improving pruritus, comprising: providing a cosmetic composition comprising a compound of Chemical Formula 1 as an active ingredient; and applying the cosmetic composition to the skin of an individual in need thereof: ##STR00008## wherein R is H or OH.

16. The method of claim 15, wherein the cosmetic composition is in the form of a tonic, a shampoo, a rinse, a hair conditioner, a hair spray, a powder, a gel, a cream, an essence, a lotion, a sol-gel, an emulsion, an oil, a wax, a spray or a mist.

17. The method of claim 15, wherein the cosmetic composition further comprises an ingredient selected from the group consisting of an antioxidant, a stabilizer, a solubilizer, a vitamin, a pigment, a flavor, and a carrier.

18. The method of claim 15, wherein the cosmetic composition is incorporated into a mask that is worn by the individual.

19. The method according to claim 15, wherein R is OH.

20. The method according to claim 15, wherein R is H.

Description

DESCRIPTION OF DRAWINGS

[0079] FIG. 1 compares the pruritus-alleviating effect of genistein, daidzein, glycitein and equol at concentrations of 1 μM and 10 μM after inducing pruritus by treating with histamine (p<0.01 versus histamine-treated group).

[0080] FIG. 2 compares the pruritus-alleviating effect of genistein, daidzein, glycitein and equol at concentrations of 1 μM and 10 M after inducing pruritus by treating with chloroquine (p<0.01 versus chloroquine-treated group).

[0081] FIG. 3 compares the pruritus-alleviating effect of genistein, daidzein, glycitein and equol at concentrations of 1 μM and 10 M after inducing pruritus by treating with DNCB (p<0.01 versus DNCB-treated group).

[0082] FIG. 4 compares the pruritus-alleviating effect of genistein, daidzein, glycitein and equol at concentrations of 1 μM and 10 M after inducing pruritus by treating with SLIGRL (p<0.05 versus SLIGRL-treated group).

[0083] FIG. 5 compares the pruritus-alleviating effect of genistein, daidzein, glycitein and equol at concentrations of 1 μM and 10 M after inducing pruritus by treating with TSLP (p<0.05 versus TSLP-treated group).

BEST MODE

[0084] Hereinafter, the present disclosure will be described in detail through examples. However, the following examples are for illustrative purposes only and it will be apparent to those of ordinary skill in the art that the scope of the present disclosure is not limited by the examples.

EXAMPLES

<Example 1> Test Animals

[0085] Six-week-old, specific-pathogen-free male BALB/c mice were purchased from Orient Bio Korea Inc. (Gapyeong, Gyeonggi-do, Korea) and housed in a laminar flow cabinet. They were provided with standard solid chows ad libitum. At the onset of the test, the mice were 7-8 weeks old. All animal care and use were performed in accordance with the protocol of the Institutional Animal Care and Use Committee of the Chonbuk National University Medical School.

<Example 2> Preparation of Reagents

[0086] Isoflavone-based compounds genistein, daidzein, glycitein and equol were purchased from Sigma. They were dissolved in DMSO and diluted with distilled water. Care was taken such that the content of DMSO did not exceed 0.1%. Histamine, chloroquine and DNCB were also purchased from Sigma.

<Example 3> Induction of Pruritus

[0087] 1. Histamine- and Chloroquine-Induced Pruritus

[0088] Pruritus was induced by subcutaneously injecting histamine and chloroquine to the mice. Specifically, 0.1 mL of 2 mg/mL histamine and 4 mg/mL chloroquine were injected respectively.

[0089] 2. DNCB (2,4-Dinitrochlorobenzene)-Induced Pruritus

[0090] Pruritus was induced with DNCB. Specifically, after removing hair from the right ear of the mouse, 20 μL of 1% DNCB dissolved in a mixture of olive oil and ethanol (1:4) was applied for sensitization. 10 μL of 0.5% DNCB was applied on the same ear 7 days later (Exp. Dermatol., 2002, 11:285-291).

[0091] *1073. SLIGRL (H-Ser-Leu-Ile-Gly-Arg-Leu-NH.sub.2)-Induced Pruritus

[0092] Pruritus was induced with SLIGRL. Specifically, 20 μg of SLIGRL was dissolved in 0.1 mL of physiological saline and injected subcutaneously to induce pruritus.

[0093] 4. TSLP (Thymic Stromal Lymphopoietin)-Induced Pruritus

[0094] Pruritus was induced with TSLP. 0.67 μg of TSLP was dissolved in 0.1 mL of physiological saline and injected subcutaneously to induce pruritus.

<Example 4> Measurement of Pruritus

[0095] Pruritus was evaluated using MicroAct (Neuroscience, Inc., Tokyo, Japan) according to the method established by the company. The mouse was anesthetized and a magnet piece was inserted into the foot skin of the left hind leg. The mouse was put in a chamber surrounded by a coil and the number of scratching actions was recorded by a computer based on the electrical field generated by the scratching. The experimental conditions of the MicroAct were set as follows. Threshold p-p limit, 0.125 V; threshold minimum duration, 0.2 s; maximum amplitude range, 0.5 V; minimum amplitude range, 0.05 V; maximum frequency, 20 Hz; minimum frequency, 5 Hz. Recording was made only for 3 or more consecutive scratching actions.

<Example 5> Statistical Analysis

[0096] All the experiments were performed for at least 3 times and 2-3 mice were used per each group. Statistical data were represented by means and standard deviations. Statistical comparison was conducted by one-way ANOVA and the Fisher test. Significant difference between the groups was determined by the unpaired Student's t-test. The significant level of the p-value was less than 0.05.

<Example 6> Effect of Inhibiting Pruritus

[0097] 1. Effect of Inhibiting Histamine-Induced Pruritus

[0098] In order to measure the effect of inhibiting histamine-induced pruritus of genistein, daidzein, glycitein and equol, 100 μg of histamine was dissolved in 0.1 mL of physiological saline and injected subcutaneously to induce pruritus. After injecting each of genistein, daidzein, glycitein and equol at 1 μM and 10 μM together with the histamine, the number of scratching actions was counted for 1 hour. Genistein and daidzein significantly inhibited histamine-induced pruritus at concentrations of 1 μM and 10 μM (p<0.01) (FIG. 1). However, glycitein and equol did not inhibit histamine-induced pruritus at the concentrations (FIG. 1).

[0099] 2. Effect of Inhibiting Chloroquine-Induced Pruritus

[0100] In order to measure the effect of inhibiting chloroquine-induced pruritus of genistein, daidzein, glycitein and equol, 200 μg of chloroquine was dissolved in 0.1 mL of physiological saline and injected subcutaneously to induce pruritus. After injecting each of genistein, daidzein, glycitein and equol at 1 μM and 10 μM together with the chloroquine, the number of scratching actions was counted for 1 hour. Genistein and daidzein significantly inhibited chloroquine-induced pruritus at concentrations of 1 μM and 10 μM (p<0.01) (FIG. 2). However, glycitein and equol did not inhibit chloroquine-induced pruritus at the concentrations (FIG. 2).

[0101] 3. Effect of Inhibiting DNCB-Induced Pruritus

[0102] In order to measure the effect of inhibiting DNCB-induced pruritus of genistein, daidzein, glycitein and equol, 20 μL of a 1% DNCB solution was applied on the right ear of the mouse for 7 days for sensitization. 10 μL of 0.5% DNCB was applied on the same ear 7 days later, 1 μM or 10 μM genistein, daidzein, glycitein or equol and 1% DNCB dissolved in physiological saline was applied on the right ear (physiological saline was applied for a negative control group) and the number of scratching actions was counted for 1 hour. Genistein and daidzein significantly inhibited DNCB-induced pruritus at concentrations of 1 μM and 10 μM (p<0.01) (FIG. 3). However, glycitein and equol did not inhibit DNCB-induced pruritus at the concentrations (FIG. 3).

[0103] 4. Effect of Inhibiting SLIGRL-Induced Pruritus

[0104] In order to measure the effect of inhibiting pruritus induced by SLIGRL, which is an agonist for the protease activated receptor 2, of genistein, daidzein, glycitein and equol, 20 μg of SLIGRL was dissolved in 0.1 mL of physiological saline and injected subcutaneously to induce pruritus. After injecting each of genistein, daidzein, glycitein and equol at 1 μM and 10 μM together with the SLIGRL, the number of scratching actions was counted for 1 hour. Genistein and daidzein significantly inhibited SLIGRL-induced pruritus at concentrations of 1 μM and 10 μM (p<0.05) (FIG. 4). However, glycitein and equol did not inhibit SLIGRL-induced pruritus at the concentrations (FIG. 4).

[0105] 5. Effect of Inhibiting TSLP-Induced Pruritus

[0106] In order to measure the effect of inhibiting thymic stromal lymphopoietin (TSLP)-induced pruritus of genistein, daidzein, glycitein and equol, 0.67 μg of TSLP solution dissolved in 0.1 mL of physiological saline and injected subcutaneously to induce pruritus. After injecting each of genistein, daidzein, glycitein and equol at 1 μM and 10 μM together with the TSLP, the number of scratching actions was counted for 1 hour. Genistein and daidzein significantly inhibited TSLP-induced pruritus at concentrations of 1 μM and 10 μM (p<0.05) (FIG. 5). However, glycitein and equol did not inhibit TSLP-induced pruritus at the concentrations (FIG. 5).

[0107] While the present disclosure has been described with respect to the specific embodiments, it will be apparent to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the disclosure as defined in the following claims and their equivalents.