阅读说明：本技术 用于预防或治疗瘙痒的组合物 (Composition for preventing or treating pruritus ) 是由 韩明光 李何九 金昭正 严善永 赵白焕 朴正秀 于 2017-12-12 设计创作，主要内容包括：本公开涉及通过使用天然衍生的成分预防、改善或治疗瘙痒的组合物。本公开的组合物可用于安全有效地改善或治疗由各种原因引起的瘙痒,而没有副作用的风险。(The present disclosure relates to compositions for preventing, ameliorating, or treating pruritus through the use of naturally derived ingredients. The composition of the present disclosure can be used to safely and effectively improve or treat pruritus caused by various causes without risk of side effects.)

1. A pharmaceutical composition for preventing or treating pruritus, comprising a compound of chemical formula 1 as an active ingredient:

wherein R is H or OH.

2. The composition of claim 1, wherein the pruritus is selected from the group consisting of paroxysmal pruritus, winter pruritus, anal pruritus, vulval pruritus, scrotal pruritus, aqueous pruritus, scalp pruritus, nasal pruritus, neck pruritus, oral pruritus and ocular pruritus.

3. The composition of claim 1, wherein the pruritus is a pruritus associated with a medical condition selected from the group consisting of cholestatic pruritus, chronic renal failure, malignancy, iron-deficiency anemia, polycythemia vera, hyperparathyroidism, hypoparathyroidism, diabetes and acquired immunodeficiency syndrome.

4. The composition according to claim 1, wherein the pruritus is an accompanying pruritus of a psychocutaneous disorder selected from the group consisting of lichen simplex chronicus, prurigo, hirsutism, neurogenic pruritus, skin behavioral disorders and paranoid parasitic diseases.

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

6. A food composition for preventing or improving pruritus, comprising a compound of chemical formula 1 as an active ingredient:

wherein R is H or OH.

7. A cosmetic composition for preventing or improving itch, comprising a compound of chemical formula 1 as an active ingredient:

wherein R is H or OH.

8. The composition of claim 7, wherein the cosmetic composition is in the form of a skin lotion, shampoo, conditioner, pomade, hair spray, powder, gel, cream, serum, lotion, sol-gel, emulsion, oil, wax, spray, or mist.

9. A mask pack comprising the cosmetic composition of claim 7.

Technical Field

The present disclosure relates to a composition for preventing or treating pruritus, which contains natural ingredients.

Background

Pruritus (pruritus) is defined as the unpleasant sensation that one wants to scratch the skin (Andersen HH et al, Human surfate models of histaminergic and non-histaminergic itch, acta dermatoo-venereology.95 (7):7717. (2015)). Although it is a common symptom in skin diseases and systemic diseases, its characteristics are not well understood.

It is estimated that about 2.8 million people (4% of the world's population) suffer from pruritus. This exceeds 2% to 3% of the population with psoriasis (Vos, T et al, Yeast live with diagnosis (YLDs) for 1160 sequence of289diseases and peptides 19902010: a systematic analysis for the Global Burdenof Disease Study 2010, Lancet.380(9859):216396. (2012)).

Pruritus can be caused or exacerbated by a variety of stimuli, including physical, mechanical, and chemical factors. Inflammatory mediators also cause itching in various inflammatory skin diseases. However, not all types of itching are associated with mediators, and itching caused by mechanical or electrical stimulation and dry skin may occur without mediators.

According to the national health information portal (http:// health. mw. go. kr), histamine, serotonin, prostaglandin E, tachykinin, cytokines, proteases, opioid peptides, platelet activating factor, etc. are known as mediators that cause itching.

Histamine is synthesized by mast cells in the skin, stored in mast cell granules, and secreted in response to various stimuli. There are two types of histamine receptors in skin, H1 and H2. Binding of histamine to the H1 receptor results in pruritus. Histamine is associated with a number of inflammatory skin disorders, including UV-induced dermatitis.

Serotonin is present in platelets. It causes itching by activating dermal mast cells, thereby releasing histamine, or by acting on 5-HT3 receptors of the central nervous system.

Prostaglandin E does not cause itching by itself, but can exacerbate itching caused by other mediators. Prostaglandin E is increased in itch-associated skin conditions such as eczema and UV-induced inflammation.

Substance P is a member of the tachykinin neuropeptide family. It is synthesized in the dorsal root ganglia of nociceptor C fibers, transmitted to unmyelinated sensory nerve fibers and acts as a neurotransmitter. Substance P causes allergy and itching by acting as an effective vasodilator. Substance P is released by tryptase of mast cells and releases histamine from dermal mast cells directly or through NK-1 receptors to cause itching.

Cytokines are small proteins produced in all eukaryotic cells. They act as cell surface receptors including Interleukins (IL), chemokines, interferons, and the like. Although IL-1 and IL-8 do not induce itch, when human recombinant IL-2 is injected into cancer patients for treatment, it causes severe itch accompanied by skin allergy and eosinophilia.

Among proteases, kallikrein causes itching when injected into the skin. In addition to kallikrein, other proteases such as chymotrypsin, trypsin, papain, etc. also cause itching.

Opioid peptides cause itching by acting on the central or peripheral nervous system. Opioid peptides have three subtypes, μ, δ, and κ. However, its pharmacological action is exerted through the μ -receptor, since it is mainly inhibited by naloxone. When morphine is injected into the spinal cord, itching is caused in most patients, while when injected into the dermis, the release of prostaglandins or histamine is not considered, resulting in itching and allergy.

Platelet-activating factor is a potent inflammation-inducing substance secreted by a variety of inflammatory cells. Platelet activating factor is reported to directly cause itching in animal experiments. In humans, it indirectly causes itching by inducing histamine secretion from mast cells.

Itching can be classified according to different causes: 1) paroxysmal pruritus with paroxysmal attack; 2) skin pruritus including winter pruritus, anal pruritus, vulval pruritus, scrotal pruritus, pruritus due to water and scalp pruritus; 3) pruritus associated with medical conditions including cholestatic pruritus, chronic renal failure, malignancy, iron-deficiency anemia, polycythemia vera, hyperparathyroidism, hypoparathyroidism, diabetes and acquired immune deficiency syndrome; 4) itch accompanied with psychodermal diseases such as chronic simple lichen, prurigo, trichotillomania, nervous itch, skin behavioral disorders, paranoid parasitic diseases, etc.; and 5) nasal itching accompanying cold and the like, cervical itching, ocular itching accompanying eye diseases such as conjunctivitis and the like, oral itching accompanying dental diseases and the like.

There are a number of treatments currently available, including antihistamines, steroids, antibiotics, antivirals, antifungals, anesthetics, probiotics, immunosuppressants, light therapy such as UV, and the like. However, depending on the type of pruritus, the therapeutic effect is temporary or limited. The use of adrenocortical hormones or corticosteroids is limited to acute or severe cases due to side effects and long-term use is not desirable. Therefore, there is a need to develop safe and effective treatments for pruritus due to various causes.

The above description is merely for background to aid in understanding the present disclosure and should not be considered as being known to those of ordinary skill in the relevant art.

Disclosure of Invention

Technical problem

The inventors of the present disclosure have endeavored to find naturally derived substances that can be safely used for pruritus caused by various causes without risk of side effects. As a result, they have determined that some isoflavone-based compounds are very effective against pruritus caused by various causes and have completed the present disclosure.

The present disclosure relates to providing pharmaceutical compositions for preventing or treating pruritus.

The present disclosure also relates to providing a food composition for preventing or improving itch.

The present disclosure also relates to providing a cosmetic composition for preventing or improving itch.

Other features and aspects will be apparent from the following detailed description, the accompanying drawings, and the claims.

Technical scheme

In one aspect, the present disclosure provides a pharmaceutical composition for preventing or treating pruritus, which contains a compound of chemical formula 1 as an active ingredient:

wherein R is H or OH.

As a result of efforts to find a naturally derived substance that can safely treat pruritus due to various causes, the inventors of the present disclosure have determined that the compound of chemical formula 1 is very effective for pruritus due to various causes.

According to experiments conducted by the inventors of the present disclosure, the compounds of the present disclosure showed significant therapeutic effects on pruritus caused by various causes including histamine-induced pruritus, chloroquine-induced pruritus, DNCB (2, 4-dinitrochlorobenzene) -induced pruritus, SLIGRL (H-Ser-Leu-Il)e-Gly-Arg-Leu-NH₂) Induced pruritus, TSLP (thymic stromal lymphopoietin) -induced pruritus, and the like. Furthermore, the improvement and therapeutic effect on pruritus was observed only in genistein and daidzein, but not in all isoflavone-based compounds (genistein, daidzein, glycitein and equol) (example 6).

Genistein is one of the active ingredients of the present disclosure, and has a structure of chemical formula 2. Has excellent antioxidant effect (Han, Rui-Min et al, company of Flavonoids and Isolavonoids as antioxidants, Journal of Agricultural and Food chemistry.57(9):37805.(2009)), which is commonly used as a cosmetic additive. However, no knowledge is known about the effect of improving itching.

Daidzein, another active ingredient of the present disclosure, has the structure of chemical formula 3. It is known to activate PPARs (DangZ.C. et al, The Balance between Current Activation of ERs and PPARS Desters Daidzein-Induced Osteeogenesis and Adipogenesis, Journal of Bone and mineral research.19(5):853861.(2004)) and to reduce The risk of breast cancer when administered at high concentrations (deLemos, M.L., Effects of breast cancer genetic and Daidzein on Breastcancer growth, Annals of Pharmacology.35 (9): 11118-. However, no knowledge is known about the effect of daidzein on improvement of pruritus.

In the present disclosure, the term "pruritus" or "pruritus" is not particularly limited, but is interpreted to include paroxysmal pruritus, winter pruritus, anal pruritus, vulval pruritus, scrotal pruritus, aqueous pruritus, scalp pruritus, nasal pruritus, neck pruritus, oral pruritus, ocular pruritus, pruritus accompanied by medical diseases such as cholestatic pruritus, chronic renal failure, malignant tumor, iron-deficiency anemia, polycythemia vera, hyperparathyroidism, hypoparathyroidism, diabetes, and acquired immunodeficiency syndrome, etc., and pruritus accompanied by psychodermal diseases such as chronic lichen simplex, prurigo, trichotillomania, neuropathic pruritus, skin behavior disorder, paranoid parasitic disease, etc.

Paroxysmal pruritus is paroxysmal pruritus and is commonly seen in chronic simple lichen, dermatitis and the like.

Winter pruritus occurs in about 50% of people aged 70 or over 70 years, and should be distinguished from pruritus caused by pruritic skin diseases or systemic diseases such as scabies, lichen planus, etc. In the female population, it may appear as a symptom of postmenopausal syndrome. Decreased moisture content and gradual decrease in sebum secretion from aging skin are the major causes of dry skin, and fine cracks and scales are common in upper limbs and tibia.

Pruritus ani is an unpleasant irritation around the anus, resulting in a desire to scratch, often involving psychological factors. This may occur regardless of age, but is more common in the elderly population. However, not all pruritus is psychogenic and perianal contamination and irritation may be the cause. Colorectal disorders such as fissures, hemorrhoids, fistulas and chronic diarrhea, spicy food, medications, and the like may exacerbate irritation. Such pruritus may be caused by various infectious diseases such as staphylococci, streptococci, fungi, candida, herpes simplex virus, etc. Among them, candida infection is the most common cause, and cracks and swelling of the skin are observed. Perianal skin diseases such as psoriasis, seborrheic dermatitis, lichen planus, etc. may also cause severe itching, and lesions may also be found in other areas. Anal neurodermatitis, characterized by repeated rubbing until bleeding due to severe itching, may show symptoms similar to chronic simple lichen elsewhere.

The most common cause of vulvar pruritus is candida infection. Other causes include trichomonas vaginitis and contact dermatitis caused by pads, contraceptives, vaginal washes, condoms, and the like. Lichen sclerosus is a common cause in the elderly. Severe itching may also occur in apocrine prurigo of the sweat (Fox-force) disease. However, temporary vulvar pruritus may also be caused by rubbing during pregnancy, sweating or vulvar congestion.

With respect to scrotal pruritus, adult scrotum is immune to fungal infections, just like adult scalp, but is a frequent site of chronic simple lichen. It is mainly caused by psychological factors. Despite intensive therapy, lichenification still occurs severely, with symptoms usually lasting years.

Aqueous pruritus is characterized by severe, unpleasant, needle-prick-like pruritus that occurs within minutes, lasting about 1 hour after contact with water. It is independent of the temperature of the water and no significant change in the skin is observed. For some patients, this may be caused by changes in ambient temperature. Patients of about 1/3 have a family history. Symptoms are usually chronic and non-responsive to treatment. Although increased histamine levels are observed in skin and blood, histamine is not considered the only mediator because antihistamines do not alleviate symptoms. Because of the similarity of symptoms, it is necessary to distinguish from polycythemia vera.

Scalp itching may occur as an independent symptom without significant lesions on the scalp. It is found in middle-aged or elderly people, but the cause thereof is not clear. Itching is very severe and is a paroxysmal attack. Fatigue or stress further worsens the situation. It is to be distinguished from dermatitis herpetiformis, lichen simplex chronicus, seborrheic dermatitis, psoriasis, and the like.

Biliary cirrhosis is associated with severe systemic pruritus. Pruritus is associated with elevated plasma levels of bile acids. Severe itching may be induced by direct application of bile acids at concentrations that clinically result in blistering cutaneous lesions.

Itching occurs in about 20% to 50% of chronic renal failure patients receiving hemodialysis treatment. Itching occurs locally or systemically. In most cases, symptoms worsen during hemodialysis. However, the symptoms may be temporarily alleviated. There is no direct relationship reported between blood levels of histamine, urea and creatinine and the degree of itching. Some patients suffer from dry skin disease, but most patients have normal skin and the use of moisturizers does not alleviate or reduce the symptoms.

Regarding malignant tumors, if systemic pruritus occurs in middle-aged or elderly people without clear causes, extensive diagnosis of malignant tumors is required. Itching persists in 15% to 25% of patients with hodgkin's disease, a representative disease that causes enlargement of lymph nodes. It is often accompanied by burning pain and flushing, the cause of which is not clear. Systemic pruritus may also occur in leukemia.

Iron deficiency may also be a cause of itching. It has been reported that pruritus is reduced in patients with polycythemia vera and in patients with iron deficiency when iron supplement is orally administered.

About 50% of polycythemia vera patients develop severe itching within a few minutes after exposure to water, and symptoms last for about 15 to 60 minutes. Since it usually occurs after bathing, it is called bath itch. There was no significant change in the skin and symptoms appeared regardless of the water temperature. However, elevated histamine levels were found in serum and urine. Platelet aggregation is thought to result in the release of several mediators of itch, including histamine.

Severe systemic pruritus may occur with hyperparathyroidism. The increase in skin temperature caused by the increase in blood flow and the resulting decrease in the threshold for pruritus are the cause of systemic pruritus. Hypoparathyroidism-related and mucoedema-related systemic pruritus may be associated with severe dryness of the skin. In both diseases, itching may occur around the genitals due to mucocutaneous candidiasis.

In some diabetic patients, itching may occur around the anus and genitals due to mucocutaneous candidiasis. However, systemic pruritus may also occur in some patients.

One of the important symptoms of acquired immunodeficiency syndrome is pruritus. The reasons for pruritus of patients with acquired immunodeficiency syndrome include scabies, pediculosis, candidiasis, seborrheic dermatitis, renal failure, cholestasis, etc. Usually, systemic papules or pigmented rashes occur, causing typically severe itching.

Lichen simplex chronicus is a disease characterized by repeated rubbing or scratching of the skin, resulting in thickening and tough skin. Chronic lichen simplex may be secondary to normal skin due to repeated itching. It is more common between the ages of 30 and 50, with women being more common than men.

Prurigo is a disease characterized by multiple nodules and severe itching. It does not heal well and often lasts for a long time. The cause is not clear, but anemia, liver disease, AIDS, pregnancy, renal failure, mental stress, etc. may be the cause.

Epilation is an impulse control disorder characterized by abnormal impulses that result in plucking of hairs. Mental and social stress are the causes. Family or school stress, sibling competition, moving home, hospitalization of parents, maternal-maternal relationship, etc. may be the cause. It occurs in almost all age groups from children to adults.

Neuropathic pruritus is a disease characterized by impulses that repeatedly dig and detain one's own skin, often resulting in skin lesions. Patients acknowledge their behavior as the cause of the pathology, but are not resistant. It can occur at any age, but occurs more frequently in middle-aged women. It often occurs due to mental stress. It often occurs in areas of skin lesions such as itching, insect bites, and the like. Neuropathic pruritus is also associated with depression, obsessive compulsive disorder, and anxiety. This symptom occurs more frequently in people with obsessive, refractory, supervised and perfect sense tendencies and fear of failure.

An artificial dermatitis is a dermatitis caused by intentionally causing self skin damage in order to cause sympathy or evasion of responsibility. Skin damage is caused by mechanical or chemical means, corrosion, and the like. In addition, nails, sharp instruments, hot metals, and the like are also used. The patient harms himself in order to satisfy psychological needs. This occurs more often in women and may occur in all age groups. Most patients are naive and dependent, with impulse control disorders.

A skin behavior disorder is a long-term repetitive compulsive self-injuring behavior. Self-injurious behavior is often a suicide behavior, and in puberty, such attempts may be made to dazzle brave courage.

Paranoid parasitic disease is a delusional disorder in which patients mistakenly believe that they are infected with parasites. It is a chronic, single-symptom, suspicious condition that does not impair personality or mental ability. The patient provides skin, lint, tissue, tape, etc., and requires a parasite exam. It has been reported that 2% to 3% of patients have previously experienced parasitic infections.

Other possibilities include nasal itching with nasal disorders such as rhinitis, ocular itching with ocular disorders such as conjunctivitis and oral itching with dental disorders.

The active ingredient used in the composition of the present disclosure includes not only the compound of chemical formula 1 itself but also a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof.

The term "pharmaceutically acceptable salt" refers to a salt of the compound of chemical formula 1 that exerts a desired pharmacological effect, i.e., an activity of improving pruritus. The salts may be prepared by using inorganic acids (e.g., hydrochloride, hydrobromide and hydroiodide) or organic acids (e.g., acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, p-toluenesulfonate, bisulfate, sulfamate, sulfate, sulfamate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, bisgluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, 2-hydroxyethanesulfate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, toluenesulfonate and undecanoate).

The term "pharmaceutically acceptable hydrate" refers to a hydrate of the compound of chemical formula 1 that exerts a desired pharmacological effect. The term "pharmaceutically acceptable solvate" refers to a solvate of the compound of chemical formula 1 that exerts a desired pharmacological effect. Hydrates and solvates may also be prepared by using the above acids.

The term "pharmaceutically acceptable prodrug" refers to a derivative of the compound of chemical formula 1, which must be biotransformed to exhibit the pharmacological effect of the compound of chemical formula 1. Prodrugs are prepared to improve chemical stability, patient compliance, bioavailability or organ selectivity, to improve ease of preparation, to prolong duration of action or to reduce side effects. Prodrugs of the disclosure can be readily prepared from compounds of formula 1 according to methods commonly used in the art (e.g., Burger's Medicinal Chemistry and Drug Chemistry, 5 th edition, 1:172-178 and 949-982 (1995)).

The pharmaceutically acceptable carrier included in the pharmaceutical composition of the present disclosure may be a carrier commonly used in the art, and may include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, and the like, but is not limited thereto. In addition to these ingredients, the pharmaceutical compositions of the present disclosure may contain lubricating agents, wetting agents, sweeteners, flavors, emulsifiers, suspending agents, preservatives and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19 th edition, 1995).

The pharmaceutical compositions of the present disclosure may be administered orally or parenterally. Parenteral administration can be performed nasally, ocularly, intravenously, subcutaneously, intramuscularly, intraperitoneally, transdermally, and the like.

The appropriate administration dose of the pharmaceutical composition of the present disclosure may vary depending on factors such as formulation method, administration method, age, body weight and sex of a patient, pathological conditions, diet, administration time, administration route, excretion rate and reactivity. The ordinarily skilled physician can readily determine and prescribe an effective amount of the drug for the desired treatment or prevention. In specific exemplary embodiments of the present disclosure, the pharmaceutical composition of the present disclosure is administered at a daily dose of 0.001mg/kg to 100 mg/kg.

The pharmaceutical compositions of the present disclosure may be formulated into unit dosage forms or multi-dose containers using pharmaceutically acceptable carriers and/or excipients according to methods that can be readily implemented by those of ordinary skill in the art to which the present disclosure pertains. The preparation can be in the form of solution, suspension, emulsion, extract, powder, granule, tablet or capsule in oily or aqueous medium, and optionally contains dispersant or stabilizer.

The pharmaceutical composition of the present disclosure may also be prepared into preparations for external use on the skin, aerosols, sprays, eye drops, oral drugs, or injections.

In another aspect, the present disclosure provides a food composition for preventing or improving pruritus, which contains a compound of chemical formula 1 as an active ingredient:

wherein R is H or OH.

When the composition of the present disclosure is prepared into a food composition, it may include ingredients, such as protein, carbohydrate, fat, nutrient, flavoring agent, or aromatic, which are generally added during the preparation of food, in addition to the compound of chemical formula 1 as an active ingredient. Examples of carbohydrates are common sugars, e.g. monosaccharides such as glucose, fructose, etc., disaccharides such as maltose, sucrose, oligosaccharides, etc., polysaccharides such as dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As the aromatic agent, natural flavors (thaumatin, stevia extract (e.g., rebaudioside a, glycyrrhizin, etc.) or synthetic flavors (saccharin, aspartame, etc.) can be used.

For example, when the composition of the present disclosure is prepared as a drink, citric acid, fructose syrup, sucrose, glucose, acetic acid, malic acid, fruit juice, eucommia ulmoides extract, jujube extract, licorice extract, etc. may be contained in addition to the compound of chemical formula 1.

The composition of the present disclosure exerts a very superior effect in improving itching. In addition, the composition of the present disclosure is very safe to the human body because it uses isoflavone-based compounds having proven biosafety as active ingredients.

In another aspect, the present disclosure provides a cosmetic composition for preventing or improving pruritus, which contains a compound of chemical formula 1 as an active ingredient:

wherein R is H or OH.

When the composition of the present disclosure is prepared into a cosmetic composition, the composition of the present disclosure may further include ingredients generally used in cosmetic compositions, for example, commonly used adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and perfumes and carriers, in addition to the compound of chemical formula 1. Further, the composition of the present disclosure may further include a itch improving agent used heretofore within a range not adversely affecting the (itch improving) effect of the active ingredient, in addition to the compound of chemical formula 1.

As the carrier, purified water, monohydric alcohol (ethanol or propanol), polyhydric alcohol (glycerin, 1, 3-butylene glycol or propylene glycol), higher fatty acid (palmitic acid or linoleic acid), oil or fat (wheat germ oil, camellia oil, jojoba oil, olive oil, squalene, sunflower seed oil, macadamia nut oil, avocado oil, hydrogenated soybean lecithin or fatty acid glyceride), and the like can be used, but not limited thereto. Surfactants, biocides, antioxidants, UV absorbers, anti-inflammatory agents or cooling agents may also be added if desired.

The surfactant may be selected from the group consisting of polyoxyethylene, hydrogenated castor oil, polyoxyethylene oleyl ether, polyoxyethylene monooleate, polyoxyethylene glyceryl monostearate, sorbitan, sucrose fatty acid ester, hexaglycerol monolaurate, polyoxyethylene reduced lanolin, POE, glyceryl pyroglutamate, isostearic acid, diesters, N-acetylglutamine and isostearyl esters.

The sterilizing agent is selected from the group consisting of hinokitiol, triclosan, chlorhexidine gluconate, phenoxyethanol, resorcinol, isopropyl methylphenol, azulene, salicylic acid, and zinc pyrithione.

As the antioxidant, any of tert-butyl-4-hydroxyanisole, gallic acid, propyl gallate and isoascorbic acid can be used.

As the UV absorber, any of benzophenones such as dihydroxybenzophenone and the like, melanin, ethyl p-aminobenzoate, 2-ethylhexyl p-dimethylaminobenzoate, cinoxate, 2-ethylhexyl p-methoxycinnamate, 2- (2-hydroxy-5-methylphenyl) benzotriazole, urocanic acid and fine metal oxide particles can be used.

As the anti-inflammatory agent, dipotassium glycyrrhetinate or allantoin can be used. Further, as the coolant, capsicum tincture or 1-menthol can be used.

The composition can be prepared into any preparation in which the compound of chemical formula 1 can be mixed as an active ingredient. Examples of the cosmetic preparation for improving itch include, but are not limited to, skin lotions, shampoos, conditioners, rinses, gels, powders, gels, creams, essences, lotions, sol-gels, emulsions, oils, waxes, sprays, mists, and the like. In addition, it can be prepared into a mask containing the compound of chemical formula 1.

Advantageous effects

The features and advantages of the present disclosure may be summarized as follows:

(i) the present disclosure provides compositions for preventing, ameliorating, or treating pruritus through the use of naturally derived ingredients.

(ii) The composition of the present disclosure can be used to safely and effectively improve or treat pruritus caused by various causes without risk of side effects.

Drawings

FIG. 1 compares the itch-reducing effects of genistein, daidzein, glycitein and equol at concentrations of 1. mu.M and 10. mu.M after the induction of itch by treatment with histamine (p <0.01 compared to histamine-treated group).

FIG. 2 compares the itch-relieving effects of genistein, daidzein, glycitein and equol at concentrations of 1. mu.M and 10. mu.M after the induction of itch by treatment with chloroquine (p <0.01 compared to chloroquine-treated group).

FIG. 3 compares the itch relieving effects of genistein, daidzein, glycitein and equol at concentrations of 1. mu.M and 10. mu.M after the induction of itch by treatment with DNCB (p <0.01 compared to DNCB-treated group).

FIG. 4 compares the effect of reducing itching of genistein, daidzein, glycitein and equol at concentrations of 1. mu.M and 10. mu.M after induction of itching by treatment with SLIGRL (p <0.05 compared to SLIGRL treated group).

FIG. 5 compares the itch-reducing effects of genistein, daidzein, glycitein and equol at 1. mu.M and 10. mu.M concentrations after the induction of itch by treatment with TSLP (p <0.05 compared to TSLP-treated group).

Best mode for carrying out the invention

Hereinafter, the present disclosure will be described in detail by examples. However, the following examples are for illustrative purposes only, and it is 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 animal

Male BALB/c mice, 6 weeks old, free of specific pathogens were purchased from Orient Bio Korea Inc (gapeong, kyonggi tract, Korea) and housed in a laminar flow cabinet. Standard solid food was taken ad libitum. At the beginning of the test, mice were 7-8 weeks old. All animal care and Use was performed according to the protocols of the Institutional animal care and Use Committee of the korean national university Medical School (Chonbuk national Medical School).

<Example 2>Preparation of reagents

Isoflavone-based compounds genistein, daidzein, glycitein and equol were purchased from Sigma. They were dissolved in DMSO and diluted with distilled water. Note that the DMSO content is not more than 0.1%. Histamine, chloroquine and DNCB were also purchased from Sigma.

<Example 3>Induction of pruritus

1. Histamine-and chloroquine-induced pruritus

Pruritus was induced by subcutaneous injection of histamine and chloroquine into mice. Specifically, 0.1mL of 2mg/mL histamine and 4mg/mL chloroquine, respectively, was injected.

DNCB (2, 4-dinitrochlorobenzene) -induced pruritus

Pruritus was induced with DNCB. Specifically, 20 μ L of 1% DNCB dissolved in a mixture of olive oil and ethanol (1:4) was used for sensitization after hair removal from the right ear of the mouse. After 7 days, 10. mu.L of 0.5% DNCB (exp. Dermatol.,2002,11: 285-.

3.SLIGRL(H-Ser-Leu-Ile-Gly-Arg-Leu-NH₂) Induced pruritus

Pruritus was induced with SLIGRL. Specifically, 20 μ g of SLIGRL was dissolved in 0.1mL of physiological saline and injected subcutaneously to induce pruritus.

TSLP (thymic stromal lymphopoietin) induces pruritus

Pruritus was induced with TSLP. 0.67 μ g of TSLP was dissolved in 0.1mL of physiological saline and injected subcutaneously to induce pruritus.

<Example 4>Measurement of itch

Itch was evaluated using MicroAct (Neuroscience, inc., tokyo, japan) according to a method established by Neuroscience, inc. The mice were anesthetized and the magnetic sheet was inserted into the foot skin of the left hind leg. The mouse was placed in a chamber surrounded by a coil and the number of scratching actions was recorded by a computer based on the electric field generated by the scratching. The experimental conditions for MicroAct were set as follows. Threshold p-p limit, 0.125V; threshold minimum duration, 0.2 s; maximum amplitude range, 0.5V; minimum amplitude range, 0.05V; maximum frequency, 20 Hz; minimum frequency, 5 Hz. Only 3 or more consecutive scratching movements are recorded.

<Example 5>Statistical analysis

All experiments were performed at least 3 times, using 2 to 3 mice per group. Statistical data are expressed as mean and standard deviation. Statistical comparisons were made by one-way ANOVA and Fisher test. Significant differences between the two groups were determined by unpaired t-test. Significant levels of p-value were less than 0.05.

<Example 6>Effect of suppressing itching

1. Effect of suppressing histamine-induced itching

To measure the effect of genistein, daidzein, glycitein and equol in inhibiting histamine-induced itching, 100 μ g of histamine was dissolved in 0.1mL of physiological saline and injected subcutaneously to induce itching. After 1. mu.M and 10. mu.M of genistein, daidzein, glycitein and equol were injected together with histamine, respectively, the number of scratching movements was counted for 1 hour. Genistein and daidzein significantly inhibited histamine-induced pruritus at concentrations of 1 μ M and 10 μ M (p <0.01) (FIG. 1). However, glycitein and equol did not inhibit histamine-induced pruritus at this concentration (fig. 1).

2. Inhibiting effect of chloroquine-induced pruritus

To measure the effect of genistein, daidzein, glycitein and equol in inhibiting chloroquine-induced pruritus, 200 μ g of chloroquine was dissolved in 0.1mL of physiological saline and injected subcutaneously to induce pruritus. After 1. mu.M and 10. mu.M of genistein, daidzein, glycitein and equol were injected together with chloroquine, the number of scratching movements for 1 hour was counted. Genistein and daidzein significantly inhibited chloroquine-induced pruritus (p <0.01) at concentrations of 1 μ M and 10 μ M (fig. 2). However, glycitein and equol did not inhibit chloroquine-induced pruritus at this concentration (figure 2).

3. Effect of inhibiting DNCB-induced pruritus

To measure the effect of genistein, daidzein, glycitein and equol in inhibiting DNCB-induced pruritus, 20 μ L of a 1% DNCB solution was applied to the right ear of mice for 7 days for sensitization. After 7 days, 10. mu.L of 0.5% DNCB was applied to the same ear, 1% DNCB in physiological saline and 1. mu.M or 10. mu.M of genistein, daidzein, glycitein or equol were applied to the right ear (physiological saline was used for the negative control group), and the number of 1-hour scratches was counted. Genistein and daidzein significantly inhibited DNCB-induced pruritus (p <0.01) at concentrations of 1. mu.M and 10. mu.M (FIG. 3). However, glycitein and equol did not inhibit DNCB-induced pruritus at this concentration (fig. 3).

4. Inhibiting SLIGRL-induced pruritus

To measure the effect of genistein, daidzein, glycitein and equol in inhibiting SLIGRL, an agonist of protease activated receptor 2, induced pruritus, 20. mu.g of SLIGRL was dissolved in 0.1mL of physiological saline and injected subcutaneously. Together with SLIGRL, 1 μ M and 10 μ M of genistein, daidzein, glycitein and equol were injected, respectively, and the number of scratching movements was counted for 1 hour. Genistein and daidzein significantly inhibited SLIGRL-induced pruritus (p <0.05) at concentrations of 1 μ M and 10 μ M (fig. 4). However, glycitein and equol did not inhibit SLIGRL-induced pruritus at this concentration (fig. 4).

5. Effect of suppressing TSLP-induced pruritus

To measure the effect of genistein, daidzein, glycitein and equol in inhibiting Thymic Stromal Lymphopoietin (TSLP) -induced pruritus, 0.67 μ g of TSLP solution was dissolved in 0.1mL of physiological saline and injected subcutaneously to induce pruritus. With TSLP, the number of scratching movements was counted for 1 hour after injection of 1. mu.M and 10. mu.M of genistein, daidzein, glycitein and equol, respectively. Genistein and daidzein significantly inhibited TSLP-induced pruritus (p <0.05) at concentrations of 1. mu.M and 10. mu.M (FIG. 5). However, glycitein and equol did not inhibit TSLP-induced pruritus at this concentration (figure 5).

Although the present disclosure has been described in terms of 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.