KR102157247B1 - A composition for improving, preventing and treating of pruritus comprising Porphyra yezoensis extract - Google Patents

Abstract

The present invention relates to itching using a laver extract as an active ingredient, and more particularly, the laver extract of the present invention inhibits the expression of a genetic material or protein (MDC, TARC, ET-1, PAR-2) related to itching. It can be used for therapeutic purposes.

Description

A composition for improving, preventing and treating of pruritus comprising Porphyra yezoensis extract}

The present invention relates to itching using a laver extract as an active ingredient, and more particularly, the laver extract of the present invention inhibits the expression of a genetic material or protein (MDC, TARC, ET-1, PAR-2) related to itching. It can be used for therapeutic purposes.

Modern people are exposed to various environmental factors such as changes in dietary habits and pollution, skin dryness, house dust mites, animal hair and secretions due to rapid urbanization, so the number of patients visiting hospitals with various diseases accompanied by itching is increasing. . Itching (pruritus) is defined as an unpleasant sensation that causes the desire to scratch or rub the skin (Andersen HH et al., Human surrogate models of histaminergic and non-histaminergic itch, Acta Dermato-Venereologica. 95 (7): 771 -7.(2015)), although it is a common symptom in skin and systemic diseases, its characteristics are not sufficiently known.

Itching can be triggered or increased by a number of stimuli, including physical, mechanical, and chemical factors. In addition, inflammatory mediators cause itching in many inflammatory skin diseases. However, not all forms of itching are associated with the mediator, and itching caused by mechanical or electrical stimulation, and dry skin may appear unrelated to the mediator.

Itching has been revealed to date: histamine, serotonin, prostaglandin E, tachykinin, cytokines, protease, opioid peptides, platelet activator platelet-activating factor).

Histamine is synthesized by the skin's mast cells, stored in mast cell granules, and secreted in response to various stimuli. Both H1 and H2 receptors are present in the skin, but histamine causes itching through the H1 receptor. Histamine is involved in a number of inflammatory skin diseases, including UV-induced dermatitis.

Serotonin is present in platelets and activates dermal mast cells to release histamine or act on 5-HT3 receptors in the central nervous system, causing itching.

Prostaglandin E by itself does not cause itching, but it has the property of increasing itching caused by other mediators. Prostaglandin E is elevated in skin diseases associated with itching, such as eczema and UV-induced inflammation.

P substance (Substance P) is a tachykinin-based neuropeptide, synthesized in the dorsal root ganglion of C nerve fibers, and is present by moving to the anhydrous sensory nerve fibers as granules, and as a neurotransmitter. Works. P substance is a powerful vasodilator and causes redness and itching. P substance is released by trypsinase of mast cells, and by releasing histamine of dermal mast cells either directly or through NK-1 receptor, it causes itching.

Cytokines are low molecular weight proteins produced in all eukaryotic cells and act as cell surface receptors, including interleukin (IL), chemokine, and interferone. IL-1 and IL-8 do not cause itching, but when human recombinant IL-2 is injected into cancer patients for therapeutic purposes, skin redness and severe itching with eosinophilia are caused.

One of the proteases, kallikrein, causes itching when injected into the skin. Proteases other than kallikrein, chymotrypsin, trypsin, papain, etc., also cause itching.

Opioid peptides act on the central or peripheral nervous system and cause itching. There are three opioid peptides, μ, δ, and κ, and most pharmacological actions are inhibited by naloxone, so it can be seen that they act through μreceptors. Morphine induces itching in most patients when injected into the spinal cord, and itching and redness when injected into the dermis regardless of the release of prostaglandin or histamine.

Platelet activating factor is a potent inflammatory inducer secreted from a wide range of inflammatory cells, and platelet activating factor has been reported to cause itching directly in animal experiments, but in humans, it induces the secretion of histamine by mast cells and indirectly causes itching.

Categorizing itching according to the cause is as follows: 1) paroxysmal itching, 2) sinus itching, anal itching, vulvar itching, scrotal itching, water-borne itching, skin itching including scalp itching, 3) bile itching, chronic renal failure , Malignant tumors, iron deficiency anemia, polycythemia vera, hyperthyroidism and hypothyroidism, itching accompanying medical diseases including diabetes, acquired immunodeficiency syndrome, 4) chronic lichen planus, itching rash, hair growth wall, nerve scratches, Mental skin disorders such as behavioral disorders, parasitic delusions, etc.Itching of the skin, 5) Itching of the nose and itching of the neck, itching of the eyeballs with eye diseases such as conjunctivitis, and the oral cavity with dental diseases My itching and so on.

As the treatment for itching, external steroids, antihistamines, calcineurin inhibitors, antibiotics, and ultraviolet therapy have been mainly used.However, in the case of long-term use, as steroids are absorbed through the skin layer to the blood vessels, adverse reactions such as skin atrophy and capillary vasodilation Has occurred, and there is a limitation due to various side effects such as the risk of inducing adrenal suppression, so there is an urgent need to develop a new therapeutic agent that has relatively few side effects and can prevent, alleviate and treat itching.

Therefore, it is necessary to develop a new therapeutic agent for the prevention and treatment of itching with no side effects and excellent therapeutic effect.

The matters described as the above-described background art are only for enhancing understanding of the background of the present invention, and should not be taken as acknowledging that they correspond to the prior art already known to those of ordinary skill in the art.

Patent Document 1. Korean Patent Application Publication No. 1999-0083931

The present inventors have made diligent efforts to discover a novel drug with excellent stability that can inhibit the expression of inflammatory-related genetic materials and proteins, which are the cause of itching. As a result, the present invention was completed by confirming that the expression of MDC, TARC, ET-1, and PAR-2 genes or proteins in human-derived keratinocytes was suppressed using the laver extract.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating itching, containing a laver extract as an active ingredient.

Another object of the present invention is to provide a food composition for improving or preventing itching containing a laver extract as an active ingredient.

Other objects and advantages of the present invention will become more apparent by the following detailed description, claims and drawings.

According to an aspect of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of itching containing a laver extract as an active ingredient.

It is known that high concentrations of TSLP and MDC (macrophage-derived chemokine) are present in keratinocytes of patients suffering from itching. TSLP stimulates CD11c+ dendritic cells to increase thymus and activation-regulated chemokine (TAC) and MDC production. The concentration of these cytokines has been found to be closely related to the symptoms of itching, and it can be seen that TARC and MDC are reliable biomarkers that best reflect the severity of itching.

In addition, ET-1 protein is known to play a role in constricting blood vessels and raising blood pressure in body organs, but is an itching-related protein that is expressed independently of histamine-related itching (pruritus) in the skin. PAR-2 is a protein known as G-protein coupled receptor 11, and generally acts as a sensor for the activity of proteases produced in inflammatory reactions and obesity, but in skin tissues, itching caused when the skin protective barrier is damaged ( It is known as a protein that regulates itching. Therefore, ET-1 and PAR-2 are reliable biobarkers that can best reflect the itching caused by inflammation in the skin tissue.

Therefore, in the present invention, itching caused by thymic stromal lymphopoietin (TSLP), itching caused by macrophage-derived chemokine (MDC), itching caused by ET-1 (Endothelin-1), and PAR-2 (Protease-activated raceptor-2). It showed a significant therapeutic effect on itching caused by various causes such as itching caused by.

Therefore, the present inventors inhibit the expression of MDC, TARC, ET-1, PAR-2, which are biomarkers that show symptoms of itching, such as MDC, TARC, ET-1, and PAR-2, and use IFNγ and TNFα, which are inflammation inducing substances. Efforts were made to discover new substances that do not exhibit cytotoxicity in the treated cells, and as a result, the extract obtained by extracting the laver extract, especially the radiated laver ( Porphyra yezoensis ) with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, is atopy. It was confirmed that it effectively inhibits dermatitis.

Specifically, one aspect of the present invention relates to a pharmaceutical composition for the prevention or treatment of itching containing a laver extract as an active ingredient, and in the present invention, it is preferable that the laver is radiated.

The radiation patterned seaweed ( Pyropia yezoensis) is a seaweed of the red algae Kimparat family, the length is 5 to 20 cm, the butterfly is 2 to 8 cm, and the body is a leaf shape made of one layer of cells, and at the beginning of maturation It is characterized by asexual reproduction and later sexual reproduction. In Korea, young fronds appear in October and grow into mature individuals until early December, and may flourish from December to May of the following year.

In the present invention, the'extract' includes not only the crude extract obtained by treating the extraction raw material with the extraction solvent, but also the processed product of the crude extract. For example, the laver extract may be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze drying or spray drying.

In addition, the'extract' in the present invention also includes a fraction obtained by further fractionating the crude extract. That is, the laver extract includes not only those obtained using an extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, fractions obtained by passing through an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatography (made for separation according to size, charge, hydrophobicity or affinity), etc. It can be purified through.

In addition, the'laver extract' in the present invention is an extract of the laver, particularly radiated laver, using water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, and the extraction method does not need to be particularly limited. Preferably, the laver extract may be laver hot water extract or laver ethanol aqueous solution, for example, laver alcohol extract.

The laver extract may be used directly as an extract, but preferably, in order to contain an excess of the active substances present in laver, natural laver obtained from nature may be naturally dried or roasted, and an oxidizing agent for the laver , Add additives such as chitosan or pulverize and dry or perform a vinegar method, or mix seaweed with peracetic acid, treat seaweed with electron ionization energy, treat seaweed with microwave, or wash seaweed with mushroom strains, yeast, etc. Any method of fermentation with microorganisms can be used without limitation.

For example, in order to contain excessive amounts of active substances present in laver, before extraction, the laver is recovered and dried in the shade for at least 1 week, preferably at least 1 month, more preferably at least 3 months, and then crushed or as it is. Can be used.

When using water as a solvent, the seaweed extract can be extracted repeatedly once or twice or more for 0.5 to 50 hours, preferably 1 to 6 hours in water at 40 to 105°C, preferably 90 to 100°C. I can. Even if hot water is not used as a solvent, that is, the ingredients of laver may be extracted from a diluted solution obtained by diluting laver in cold water or room temperature water.

The extract by lower alcohol having 1 to 4 carbon atoms may be used. For example, extraction is performed with an aqueous alcohol solution such as ethanol, methanol, and isopropanol, preferably 20 to 80% by weight of an aqueous alcohol solution, and more preferably 80% by weight of an aqueous alcohol solution. In the case of using an alcohol extract, the concentrate or alcohol extract in which the alcohol content is lowered by vaporizing the alcohol in the alcohol extract is concentrated and dried, and then dissolved in water before use.

The solid content of the laver extract does not need to be particularly limited, but when there is no other concentration process after extraction, it is 1 to 15% by weight, and it may be used immediately, concentrated and used, or concentrated or dried and then diluted.

It was confirmed that the seaweed extract did not exhibit cytotoxicity in cells treated with IFNγ and TNFα, which are inflammation-inducing substances, as in the experiments to be described later, and it can be seen that it is very stable even when used on skin weakened by itching. Biomarkers related to itching (MDC, TARC, ET-1, PAR-2) such as TARC, MDC, ET-1, and PAR-2 in cells where itching is induced by an inflammatory response by IFN-γ and TNF-α against Since it was confirmed that the expression of 2) was inhibited and inhibited, the composition of the present invention has an excellent effect in preventing or treating itching, and more preferably, it is effective in preventing, treating or improving severe atopic dermatitis accompanied by itching. . The laver extract may use a liquid extract as such, or may be dried and powdered.

In the present specification, the term "including as an active ingredient" means including an amount sufficient to achieve the efficacy or activity of improving, treating or preventing itching of the seaweed extract of the present invention.

In the present invention, the term'prevention' may mean any action of suppressing, delaying, or alleviating itching by administering the composition according to the present invention to an individual. In the present invention, the term'treatment' may refer to any action in which the composition according to the present invention is administered to an individual suspected of itching to improve or benefit from itching symptoms.

In the present specification, the term "itch" or "pruritus" is not particularly limited, and paroxysmal itching, sinus itching, anal itching, vulvar itching, scrotal itching, water-borne itching, scalp itching, nose itching, throat itching, itching in the mouth and eyeball Itching; Itching associated with medical diseases such as bile itching, chronic renal failure, malignant tumors, iron deficiency anemia, true red blood cell hypercytosis, hyperthyroidism, hypothyroidism, diabetes and acquired immunodeficiency syndrome; And mental skin diseases such as chronic lichen planus, itchy rash, hair growth wall, nerve scratches, behavioral disorders that invade the skin, and parasitic delusions, and itching associated with atopic dermatitis.

Paroxysmal itching is itching that occurs as a seizure, and is seen in chronic lichen planus or dermatitis.

Winter itch occurs in more than 50% of the elderly over 70 years of age, and it should be differentiated from itching caused by pruritic skin diseases such as scabies and lichen planus or systemic diseases. In women, it can appear as a symptom of postmenopausal syndrome. Skin dryness due to a decrease in the moisture content of aged skin and a gradual decrease in sebum secretion is the main cause, and fine cracks and scales are mainly found in the upper limbs and tibia.

Anal itching is an unpleasant sensation of wanting to scratch the skin around the anus, and psychogenic factors are often involved. It can occur at any age, but it is more common after middle age. However, not all anal itching is caused by psychogenicity, and contamination and irritation around the anus can be the cause. Colon and anal diseases such as dentition, hemorrhoids, fistula, and chronic diarrhea, spicy foods, and drugs can cause further irritation. Several infectious diseases such as staphylococcus, streptococcus, fungi, candida, and herpes simplex virus can cause itching. Of these, Candida infection is the most common, and cracks appear during infection, and the epidermis appears to be swollen. Skin diseases such as psoriasis, seborrheic dermatitis, lichen planus, etc. can cause severe itching even in the anus area, and lesions can be observed in other areas. Neurodermatitis of the anus may show the same findings as chronic lichen planus in other areas by scratching the affected area until bleeding due to severe itching.

The most common cause of vulvar itching is a Candida infection. As other factors, contact dermatitis caused by trichomonas vaginitis, pads, contraceptives, vaginal washing fluid, and condoms may be the cause. After middle age, lichen planus is a common cause. Fox-Fordyce disease can also cause severe itching. However, temporary itching of the vulva may also be caused by friction, sweating, or congestion of the vulva during pregnancy.

Regarding itching of the scrotum, the adult scrotum is immune to fungal infections like the scalp of an adult, but it is a site where local chronic lichen planus occurs well.The cause is often caused by psychogenic factors, severe lichenification, and even intensive treatment. It may last for years.

Water-borne itching develops in a few minutes after exposure to water or after stopping exposure to water, with severe discomfort, such as a needle stick, and lasts for about an hour. Irrespective of the temperature of the water in contact, no special changes are observed in the skin. It can also be caused by changes in ambient temperature in some patients. About a third of patients have a family history and are usually chronic and do not respond well to treatment. Although it shows an increase in histamine concentration in the skin and blood, it is believed that histamine is not the only mediator when the symptoms are not relieved by antihistamines. Since it is similar to the symptoms that appear when there is an increase in true red blood cell count, it is necessary to differentiate it.

Scalp itching can appear as an independent symptom without a distinct lesion of the scalp, and it can be seen in middle-aged or elderly people, but the cause is not well known. Itching is very severe and appears seizure, which gets worse when tired or stressed. Differential diseases include herpes dermatitis, chronic lichen planus, seborrheic dermatitis, and psoriasis.

Patients with biliary cirrhosis are accompanied by severe systemic itching. Itching is associated with an increase in plasma bile acid concentration, and when a bile acid at a clinically itching-inducing concentration is applied directly to blistered skin lesions, severe itching can be induced.

Itching occurs in about 20-50% of patients with chronic kidney failure undergoing hemodialysis treatment. Itching is local or systemic, and in most cases the symptoms worsen during hemodialysis, but hemodialysis may cause temporary relief. It has been reported that there is no direct relationship between the levels of histamine, urea, and creatinine in the blood and the degree of itching. Some of the patients have dry skin, but most have normal skin, and the use of moisturizers does not relieve or reduce symptoms.

Regarding malignant tumors, if systemic itching occurs without any specific cause in middle or old age, extensive examination for malignant tumors is required. 15-25% of patients with Hodgkin (a typical disease that causes swelling of the lymph nodes) consistently develop itching, sometimes accompanied by burning pain and burning, but the cause is unknown. Systemic itching can also occur in leukemia.

Iron deficiency can also cause itching. There is a report that the itching was reduced as a result of oral administration of iron drugs to patients with PV and iron deficiency.

About 50% of patients with PH patients experience severe itching within minutes after contact with water, and these symptoms last about 15-60 minutes. It usually occurs after bathing and is called bath itch. There is no specific change in the skin and it occurs regardless of the temperature of the water. However, histamine was increased in serum and urine. Platelet aggregation is thought to be the cause of several itching mediators, including histamine.

In hyperthyroidism, severe systemic itching may occur. The increase in blood flow to the skin increases the skin surface temperature and lowers the itching threshold. In hypothyroidism, myxedema may cause the skin to become very dry, resulting in systemic itching. In addition, itching of the genital area due to mucosal candidiasis may occur in both diseases.

Some diabetic patients may develop itching of the anal genital area due to mucosal candidiasis. However, some patients may develop systemic itching.

One of the important symptoms of acquired immunodeficiency syndrome is itching. The causes of itching in patients with acquired immunodeficiency syndrome include scabies, ear syndrome, candidiasis, seborrheic dermatitis, and systemic diseases such as kidney failure and cholestasis. In addition, systemic papules or pigmented rashes that cause severe itching may occur.

Chronic simple lichen is a disease in which the skin becomes thick like leather by repeatedly rubbing or scratching the skin. Itching may occur on the normal skin, and secondary chronic lichen planus may occur. It usually occurs in the 30s and 50s, and it occurs more often in women than in men.

Itchy rash is a disease characterized by multiple nodules accompanied by severe itching and is not well treated and has a characteristic that persists for a long time. The cause is not well known and can be caused by anemia, liver disease, HIV disease, pregnancy, kidney failure, and mental stress.

The hair growth wall is a neurosis in which the hair is pulled out of an abnormal desire. Mental and social stress is the cause, and stress within the family, stress in school life, a sense of competition between siblings, moving, hospitalization of mothers, mother-daughter relationships, etc. can be problems. It occurs in almost all age groups, from children to adults.

Neurotic scratch is a disease in which skin lesions are caused by repetitive and obsessive pitting, digging, and scraping of one's own skin. The patient admits that the lesion has occurred as a result of his or her behavior, but cannot suppress the behavior. It can occur at any age, but it is common in middle-aged women and may be caused by psychological stress. It may occur in areas with skin lesions such as itching and insect cuts. Neurotic scratches have also been linked to depression, obsessive-compulsive disorder, and anxiety. These symptoms are more common in people who are obsessive, stubborn, controllable, and a perfectionist with fear of wrongdoing.

Artificial dermatitis is a dermatitis that is caused by artificially injuring one's skin to induce sympathy or avoid responsibility. Skin lesions are caused by mechanical methods, chemicals, or caustic agents. Other causes include nails, sharp tools, and hot metal. Patients injure their bodies to satisfy their psychological needs, more common in women and can appear in all age groups. The majority of patients have personality disorders that are infantile, dependent, and impulse-controlled.

Behavioral disorders that invade the skin are self-injury caused by obsessive and repetitive behaviors that are repeated over a long period of time and cause various physical damage. The lacerations inflicted on oneself are made for the purpose of suicide and are sometimes attempted to show off bravery during puberty.

Parasite delusion is a disease in which there is a firm obsession with parasites on the patient's own skin. It is a single symptom of health anxiety with only chronic body-related delusions as the main symptom without impairing personality or thinking ability. Patients are asked to bring small pieces of epidermal debris between small boxes, paper tissues, and tapes to be examined, and 2-3% of the patients are reported to have experienced a parasitic infection.

In addition, there may be itching of the nose associated with nose-related diseases such as rhinitis, itching of the eyeball associated with eye diseases such as conjunctivitis, and itching in the oral cavity caused by dental causes.

The type of itching to be prevented or treated by the present invention is not limited, and preferably, it may be severe itching with MDC, TARC, ET-1, PAR-2 as a biomarker due to severe atopic dermatitis.

The food composition may be formulated in the form of capsules, tablets, powders, granules, liquids, pills, flakes, pastes, syrups, gels, jelly or bars of the seaweed extract, or beverages, teas, spices It is manufactured in the form of general food by adding it to food ingredients such as gum, confectionery, etc., and when ingested, it means that it has a specific effect on health, but unlike general drugs, it occurs when taking a drug for a long time using food as a raw material. It has the advantage of not having any side effects, etc.

The food composition is very useful because it can be consumed on a daily basis. The amount of seaweed extract added in such a food composition varies depending on the type of target food and cannot be uniformly defined, but may be added within a range that does not impair the original taste of the food, and is usually 0.01 to 50 wt. %, preferably 0.1 to 20% by weight. In addition, in the case of foods in the form of capsules, tablets, powders, granules, liquids, pills, flakes, pastes, syrups, gels, jelly or bars, usually 0.1 to 100% by weight, preferably 0.5 to 80% by weight. Just add it within the range.

The food composition may include not only seaweed extract as an active ingredient, but also ingredients commonly added during food production, and includes, for example, proteins, carbohydrates, fats, nutrients, flavoring agents and flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.

As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made of drinks and beverages, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts, in addition to the seaweed extract of the present invention, may be further included.

The food composition of the present invention includes human food, beverage, animal feed, and feed additives.

Further, in the animal feed additive containing the laver extract obtained by the present invention as an active ingredient, the extract is composed of a polysaccharide, and prepared in a powder form to prepare an animal feed additive further included in the animal feed. have. At this time, the animal feed may be selected from the group consisting of powdered animal feed, calf substitute oil, or piglet biting feed, and the content of the powdered extract is within the range of 1-2 g (0.1% level) per 1 kg of feed. Is enough.

In addition, in the pharmaceutical composition for the treatment or prevention of itching using the seaweed extract as an active ingredient, the seaweed extract is, for example, 0.001 mg/kg or more, preferably 0.1 mg/kg or more, more preferably 10 mg/kg or more, Even more preferably 100 mg/kg or more, even more preferably 250 mg/kg or more, and most preferably 0.1 g/kg or more. Since the seaweed extract is a natural product and does not have side effects on the human body even if it is administered in an excessive amount, the upper limit of the quantity of the seaweed extract contained in the composition of the present invention can be selected and carried out by a person skilled in the art within an appropriate range.

The pharmaceutical composition may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant may be an excipient, a disintegrant, a sweetener, a binder, a coating agent, an expanding agent, a lubricant, a lubricant, or Flavoring agents and the like can be used. The pharmaceutical composition may be formulated for administration by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above.

The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, lacquercanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

Acceptable pharmaceutical carriers for compositions formulated as liquid solutions are sterilized and suitable for living organisms, such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and these One or more of the components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.

Further, it can be preferably formulated according to each disease or ingredient using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

The pharmaceutical composition may be administered orally or parenterally. In the case of parenteral administration, the pharmaceutical composition may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.

The appropriate dosage of the pharmaceutical composition varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, and is usually skilled. The physician who has been trained can easily determine and prescribe the effective dosage for the desired treatment or prophylaxis. According to a preferred embodiment, the daily dosage of the pharmaceutical composition is 0.001-10g/kg.

The pharmaceutical composition is prepared in a unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person having ordinary knowledge in the art, or It can be manufactured by enclosing it in a dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.

The pharmaceutical composition of the present invention includes human and animal medicines. Specifically, the laver extract can be used in the manufacture of various veterinary drugs. At this time, veterinary medicines can be used as veterinary medicines or adjuvants that can effectively treat and prevent atopic dermatitis disease in animals, as well as auxiliary treatments and feed additives that can enhance therapeutic efficacy.

For this purpose, the composition of the present invention is formulated as such or with a carrier commonly accepted in the pharmaceutical field and used for oral administration of conventional preparations, such as tablets, capsules, solutions, and suspensions. It can be formulated in a variety of formulations such as formulations, formulations for injection or suspensions, and feed additives. In addition, in order to prevent the drug from being decomposed by gastric acid during oral administration, an antacid may be used in combination, or a solid preparation for oral administration such as a tablet may be formulated as an enteric-coated formulation and administered.

The dosage of the polysaccharide fraction of the laver extract according to the present invention to the human body should be appropriately used depending on the absorption, inactivation rate and excretion rate of the active ingredient in the body of the animal, and the age, sex, and condition of the animal. A dose of 100-400 mg/day per kg should be administered.

In addition, another aspect of the present invention relates to a cosmetic composition for improving or preventing itching containing a laver extract as an active ingredient. Preferably it may be itching induced by the expression of MDC, TARC, ET-1, PAR-2, and more preferably MDC, TARC, ET-1, PAR-2 due to severe atopic dermatitis as a biomarker It can be severe itching.

The cosmetic composition for improving or preventing itching is an ointment for external use, cream, softening lotion, nutrient lotion, pack, essence, hair tonic, shampoo, conditioner, hair conditioner, hair treatment, gel, skin lotion, skin softener, skin toner , Astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, eye cream, moisture cream, hand cream, mask pack, foundation, nutrition essence, sunscreen, soap, cleansing foam, cleansing lotion, cleansing cream , It may have a formulation selected from the group consisting of a body lotion and a body cleanser, but is not limited thereto. The composition of each of these formulations may contain various bases and additives necessary and appropriate for the formulation of the formulation, and the types and amounts of these components can be easily selected by those skilled in the art.

When the formulation of the present invention is a paste, cream, or gel, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc acid may be used as a carrier component. I can.

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

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

When the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol as a carrier component, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like may be used.

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

The features and advantages of the present invention are summarized as follows:

(I) The present invention provides a pharmaceutical composition for preventing or treating itching, containing a laver extract as an active ingredient.

(Ii) In addition, the present invention provides a food composition for improving or preventing itching containing a laver extract as an active ingredient.

(Iii) The composition of the present invention suppresses itching induced by the expression of MDC, TARC, ET-1, PAR-2, and does not show cytotoxicity in weakened cells in which inflammation is induced, so using this function, MDC, It can be usefully utilized as a therapeutic agent for itching induced by the expression of TARC, ET-1, and PAR-2.

Figure 1a is a graph showing the results of measuring the cell viability of the inflammation-induced HaCaT cells according to the concentration of the laver extract, Figure 1a is a measurement of the cell viability when the laver extract is added to HaCaT cells in which no inflammation is induced will be.
Figure 1b shows the measurement of the cell viability when the ethanol extract of laver is added to the inflammation-induced HaCaT cells.
Figure 1c shows the measurement of cell viability when laver extract is added to inflammation-induced HaCaT cells.
Figure 2 is a graph showing the result of measuring the itching-related gene expression in inflammation-induced HaCaT cells according to the concentration of the laver ethanol extract, Fig. 2a is MDC when the laver ethanol extract is added to the HaCaT cells that induce inflammation with IFNγ It is shown by measuring the gene expression pattern.
Figure 2b shows the measurement of the MDC gene expression pattern when the ethanol extract of laver is added to HaCaT cells inducing inflammation with TNFα.
Figure 2c shows the measurement of the expression pattern of TARC gene when the ethanol extract of laver is added to HaCaT cells induced by IFNγ.
Figure 2d shows the measurement of the expression pattern of the TARC gene when the ethanol extract of laver is added to HaCaT cells inducing inflammation with TNFα.
Figure 3a shows the measurement of the MDC protein expression patterns when the ethanol extract of laver is added to HaCaT cells inducing inflammation with IFNγ.
Figure 3b shows the measurement of the MDC protein expression pattern when the ethanol extract of laver is added to HaCaT cells inducing inflammation with TNFα.
Figure 4a shows the measurement of the expression pattern of ET-1 gene when the ethanol extract of laver is added to HaCaT cells induced by IFNγ.
Figure 4b shows the measurement of the ET-1 gene expression pattern when the ethanol extract of laver is added to HaCaT cells inducing inflammation with TNFα.
Figure 5a shows the measurement of the expression pattern of PAR-2 gene when the ethanol extract of laver is added to HaCaT cells inducing inflammation with IFNγ.
Figure 5b shows the measurement of the expression pattern of the PAR-2 gene when the ethanol extract of laver is added to HaCaT cells induced by TNFα.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for describing the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

statistics

Figures 2 to 5 obtained in this experiment were statistically processed as follows. The data obtained through each experiment set the normalized expression rate to 1 in the untreated control group, and the data showing a significant difference after one-way ANOVA (α=0.05) was Tukey's honestly Significance difference [HSD]) was used post-test. ### P <0.001, control versus IFN-γ or TNF-α (10 ng / mL) alone. *P<0.05, **P<0.01, ***P<0.001 were considered statistically significant.

Example

<Example 1> Method for producing ethanol extract of laver

Radiation pattern Kim (Porphyra yezoensis) was used and dried with Kim domestic radiation patterns (Porphyra yezoensis), cold storage.

Into an Erlenmeyer flask, 10 g of the dried radiant laver and 100 ml of 80 wt% ethanol aqueous solution were added, immersed and extracted twice at 45°C for 24 hours, filtered, concentrated with a vacuum concentrator, and freeze-dried, and the first laver extract powder Got it.

After adding 40 ml of third distilled water to the completely concentrated laver extract powder, dissolving it for one day, removing the less dissolved part using a centrifuge, taking the supernatant, and then using an organic solvent (chloroform/methanol/distilled water). = 2:1:0.9, v/v) was added and mixed, and the supernatant was separated by a centrifuge. The separated supernatant was dried with a freeze dryer to obtain a final laver ethanol extract powder.

Thereafter, the laver ethanol extract powder was diluted with DMSO (dimethyl sulfoxide, Sigma, USA) to a final concentration of 200 mg/ml, and then a membrane filter paper (0.2 μm, Millipore, USA) passed through the sterile state was used in the experiment.

<Experimental Example 1: Analysis of cell viability according to the ethanol extract of laver-1>

Under conditions of 37° C. and 5% CO ₂ , human-derived keratinocytes, HaCaT cell lines, were respectively 1% penicillin-streptomycin and DMEM (Dulbecco's Modified Eagle's Medium) containing 10% fetal bovine serum. ) Cultured in medium (Gibco BRL, USA).

The HaCaT cell line cultured under the above conditions was dispensed into a 96-well plate or a 10 ml culture dish at 1×10 ⁵ cell/ml, cultured for 24 hours, and then the medium was removed and a new medium was added.

The control group did not contain the inflammation inducing factor, the laver ethanol extract, and only the medium was added, and the experimental group was the laver ethanol extract (1.56, 3.12, 6.25, 12.5, 25, 40, 50, obtained in Example 1) to each cell. 100, 125, 200, 250, 500, 1000, 1500, 2000 µg/ml) were added. The control group and the experimental group were cultured for 24 hours, and then cell viability was measured.

In order to compare the cell viability according to the concentration of the ethanol extract of laver, after recovering each of the cells prepared in Experimental Example 1, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium) solution (0.05 mg/ml concentration) was added, and a reduction reaction was induced while incubating in a cell incubator for 4 hours, and then the MTT solution was removed and DMSO was added to completely dissolve the formazan crystals. 200 µl of this was put into each well and measured by absorbance of 570 nm using a microplate reader.

Figure 1a is a graph showing the results of measuring the cell viability of the inflammation-induced HaCaT cells according to the concentration of the ethanol extract of laver, Figure 1a is a measurement of the cell viability when the ethanol extract of laver is added to the HaCaT cells that do not cause inflammation Is shown.

As shown in Figure 1a, when the ethanol extract of laver at a concentration of 1.56 to 1000 µg/ml was treated with the HaCaT cell line, no cytotoxicity was observed. However, in the case of treatment with 2000 ㎍ / ㎖ concentration of laver ethanol extract, the cell viability decreases by about 20%, so the effect of the laver ethanol extract on cell survival is weak, but to ensure higher stability, the concentration is less than 2000 ㎍ / ㎖ It is preferable to treat the ethanol extract of laver.

<Experimental Example 2: Analysis of cell viability according to the ethanol extract of laver-2>

Under conditions of 37° C. and 5% CO ₂ , human-derived keratinocytes, HaCaT cell lines, were respectively 1% penicillin-streptomycin and DMEM (Dulbecco's Modified Eagle's Medium) containing 10% fetal bovine serum. ) Cultured in medium (Gibco BRL, USA).

The HaCaT cell line cultured under the above conditions was dispensed into a 96-well plate or a 10 ml culture dish at 1×10 ⁵ cell/ml, cultured for 24 hours, and then the medium was removed and a new medium was added.

In the control group, only 10 ng/ml of IFN-γ, which is an inflammation-inducing substance, was added, and in the experimental group, IFN-γ (10 ng/ml) and the laver ethanol extract obtained in Example 1 (1.56, 3.12, 6.25) were added to each cell. , 12.5, 25, 40, 50, 100, 125, 200, 250, 500, 1000, 1500, 2000 µg/ml) was added. The control group and the experimental group were cultured for 24 hours, and then cell viability was measured.

In order to compare the cell viability according to the concentration of the ethanol extract of laver, after recovering each of the cells prepared from Experimental Example 2, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium) solution (0.05 mg/ml concentration) was added, and a reduction reaction was induced while incubating in a cell incubator for 4 hours, and then the MTT solution was removed and DMSO was added to completely dissolve the formazan crystals. 200 µl of this was put into each well and measured by absorbance of 570 nm using a microplate reader.

Figure 1b shows the measurement of the cell viability when the ethanol extract of laver is added to the inflammation-induced HaCaT cells. Accordingly, further, even in the cells in which inflammation is induced by treatment with the inflammation-inducing substance IFN-γ, laver ethanol of the present invention It was confirmed that the extract (1.56 to 1000 ㎍ / ㎖) was not observed cytotoxicity. Therefore, even if the inflamed cells are treated with the ethanol extract of laver, cytotoxicity does not occur, so it is very stable.

<Experimental Example 3: Analysis of cell viability according to the ethanol extract of laver-3>

Under conditions of 37° C. and 5% CO ₂ , human-derived keratinocytes, HaCaT cell lines, were respectively 1% penicillin-streptomycin and DMEM (Dulbecco's Modified Eagle's Medium) containing 10% fetal bovine serum. ) Cultured in medium (Gibco BRL, USA).

The HaCaT cell line cultured under the above conditions was dispensed into a 96-well plate or a 10 ml culture dish at 1×10 ⁵ cell/ml, cultured for 24 hours, and then the medium was removed and a new medium was added.

In the control group, only 10 ng/ml of TNF-α, which is an inflammation inducing substance, was added, and in the experimental group, TNF-α (10 ng/ml) and the laver ethanol extract obtained in Example 1 (1.56, 3.12, 6.25) were added to each cell. , 12.5, 25, 40, 50, 100, 125, 200, 250, 500, 1000, 1500, 2000 µg/ml) was added. The control group and the experimental group were cultured for 24 hours, and then cell viability was measured.

In order to compare the cell viability according to the concentration of the ethanol extract of laver, after recovering each of the cells prepared from Experimental Example 3, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium) solution (0.05 mg/ml concentration) was added, and a reduction reaction was induced while incubating in a cell incubator for 4 hours, and then the MTT solution was removed and DMSO was added to completely dissolve the formazan crystals. 200 µl of this was put into each well and measured by absorbance of 570 nm using a microplate reader.

Figure 1c shows the measurement of the cell survival rate when the laver ethanol extract is added to the inflammation-inducing HaCaT cells. Accordingly, furthermore, even in the cells in which inflammation is induced by treatment with the inflammation-inducing substance TNF-α, the laver ethanol of the present invention It was confirmed that the extract (1.56 to 1000 ㎍ / ㎖) was not observed cytotoxicity. Therefore, even if the inflamed cells are treated with the ethanol extract of laver, cytotoxicity does not occur, so it is very stable.

Taken together, it can be seen that the seaweed ethanol extract of the present invention is a very stable material that does not exhibit cytotoxicity to all of the HaCaT cells in which inflammation or did not occur.

<Experimental Example 4: Analysis of gene expression level related to itching>

The purpose of this study was to analyze the expression patterns of pruritus-related genes (MDC and TARC) in HaCaT cells in which inflammatory reactions were induced by addition of various concentrations (40, 200, 1000 ㎍/㎖) of laver ethanol extract (P. yezoenisis).

It was measured using RT-PCR for gene analysis. Specifically, the inflammation inducing substance IFN-γ or TNF-α was treated at 10 ng/ml, and at the same time, various concentrations (40, 200, 1000 ㎍/㎖) of laver ethanol extract (P. yezoenisis) were treated, and then, After incubation for 24 hours, RNA was isolated by treatment with Trizol reagent, and synthesized as complementary DNA using a cDNA synthesis kit (TOYOBO, Japan). The synthesized cDNA is mixed with the prepared MDC, TARC, ET-1 or PAR-2 Primer (BIONEER, Korea), and then 2 minutes at 60 ℃ using a SYBR Green PCR Master Mix (BIO-RAD, USA) reagent. , After heating at 95° C. for 10 minutes, reaction at 95° C. for 30 seconds, 60° C. for 30 seconds, and 72° C. for 30 seconds in a total of 40 cycles when the inflammation-causing factor and laver ethanol extract were added, The gene expression patterns of itching-related factors were analyzed.

2 is a graph showing the result of measuring the expression of itching-related genes in inflammation-induced HaCaT cells according to the concentration of the laver ethanol extract, and FIG. 2A is MDC when the laver ethanol extract is added to HaCaT cells that induce inflammation with IFNγ. The gene expression pattern was measured and shown, and FIG. 2B is a measurement of the MDC gene expression pattern when a laver ethanol extract was added to HaCaT cells inducing inflammation with TNFα, and FIG. 2C is a HaCaT cell that induced inflammation by IFNγ. It is shown by measuring the expression pattern of the TARC gene when the ethanol extract of laver is added, and Figure 2d shows the measurement of the expression pattern of the TARC gene when the ethanol extract of laver is added to HaCaT cells that induce inflammation with TNFα. 4a shows the measurement of the ET-1 gene expression pattern when the ethanol extract of laver is added to HaCaT cells that induce inflammation with IFNγ, and Fig. 2d is when the ethanol extract of laver is added to HaCaT cells that induce inflammation with TNFα. It is shown by measuring the expression pattern of PAR-2 gene of.

As shown in FIG. 2, in HaCaT cells that induce inflammation with IFNγ, the amount of gene expression of MDC and TARC related to atopic dermatitis was concentration-dependently, as the ethanol extract (40, 200, 1000 ㎍/㎖) was treated. It was confirmed that it was significantly reduced.

In addition, it was confirmed that the amount of TARC gene expression was significantly decreased in a concentration-dependent manner by treatment with ethanol extract (40, 200, 1000 ㎍/㎖) of laver in HaCaT cells induced by TNFα.

However, in HaCaT cells that induce inflammation with TNFα, the amount of MDC gene expression decreased the most when 40 ng/ml of laver ethanol extract was treated, and a significant degree of MDC gene when 200 ng/ml of laver ethanol extract was treated. The amount of expression was observed, but when treated with the ethanol extract of 1000 ng/ml, it was somewhat lower, but it can be seen that the amount of MDC gene expression was reduced compared to that in HaCaT cells treated with only TNFα.

As shown in Figures 4a and b, it can be seen that ET-1 is significantly increased when keratinized skin cells (HaCaT cells) are stimulated by treatment with IFN-γ or TNF-α.

On the other hand, when IFN-γ or TNF-α was treated to stimulate skin keratinized cells (HaCaT cells) and then 40, 200, 1000 ㎍/㎖ of laver ethanol extract was treated, the amount of protein produced by ET-1 was significantly reduced. Confirmed.

That is, the ethanol extract of laver of the present invention can significantly reduce the expression of ET-1, a genetic material related to itching (pruritus), which is independently expressed from histamine-related itching (pruritus) in skin keratinized cells that induce inflammation. Confirmed that there is.

As shown in FIGS. 5A and 5B, it can be seen that when IFN-γ or TNF-α is treated to stimulate skin keratinized cells (HaCaT cells), the skin protective barrier is damaged and the expression of PAR-2 protein is increased.

On the other hand, IFN-γ or TNF-α was treated to stimulate skin keratinized cells (HaCaT cells) and then treated with 40, 200, 1000 ㎍/㎖ of laver ethanol extract, the amount of PAR-2 protein produced was significantly increased. have.

That is, the ethanol extract of laver of the present invention induces a decrease in skin protective barrier-related factors (PAR-2) induced by an inflammatory reaction in the skin, resulting in an effect of improving skin itching.

<Test Example 5: Analysis of protein expression level related to itching>

The purpose of this study was to analyze the expression pattern of itching-related protein MDC in HaCaT cells in which inflammatory reactions were induced by addition of various concentrations (40, 200, 1000 ㎍/㎖) of laver ethanol extract ( P. yezoenisis ).

For quantification of the MDC protein, an ELISA test method was used, and specifically, an ELISA kit manufacturer (R&D systems, USA) was carried out according to the method.

Figure 3a shows the measurement of the MDC protein expression pattern when the ethanol extract of laver is added to HaCaT cells that induce inflammation with IFNγ, and Figure 3b shows the addition of the ethanol extract of laver to HaCaT cells that induce inflammation with TNFα. It is shown by measuring the expression pattern of MDC protein.

As shown in Figure 3a, b, if the HaCaT cells inducing inflammation by treatment with IFN-γ, 40, 200, 1000 ㎍ / ㎖ of the ethanol extract of laver, the amount of protein production of MDC is significantly reduced. Confirmed.

That is, in the ethanol extract of laver of the present invention, it was confirmed that MDC had a slight decrease in the amount of gene expression, but the amount of protein produced was significantly reduced. Accordingly, the composition according to the present invention suppresses the expression of MDC, TARC genes and proteins related to itching, and improves against itching by reducing the expression of ET-1, PAR-2 genes and proteins related to itchiness (pruritus) of the skin, It can be seen that it has a prophylactic or therapeutic effect.

As described above, specific parts of the present invention have been described in detail, and it is clear that these specific techniques are merely preferred embodiments, and the scope of the present invention is not limited thereto for those of ordinary skill in the art. Therefore, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims (19)

Contains seaweed extract as an active ingredient,
The seaweed extract is a pharmaceutical composition for the prevention or treatment of itching, characterized in that by water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. delete The composition of claim 1, wherein the mixed solvent is an aqueous solution of 20 to 80% by weight of methanol, ethanol, butanol or propanol. The composition of claim 1, wherein the mixed solvent is an aqueous ethanol solution of 20 to 80% by weight. The composition of claim 1, wherein the itching is induced by expression of MDC, TARC, ET-1, and PAR-2. The method of claim 1, wherein the itching is selected from the group consisting of paroxysmal itching, sinus itching, anal itching, vulvar itching, scrotal itching, water-borne itching, scalp itching, nose itching, throat itching, oral itching, and eyeball itching. Composition characterized by. The method of claim 1, wherein the itching is accompanied by an internal medical disease selected from the group consisting of bile itching, chronic renal failure, malignancies, iron deficiency anemia, polycythemia vera, hyperthyroidism, hypothyroidism, diabetes, and acquired immunodeficiency syndrome. Composition, characterized in that itching. The method of claim 1, wherein the itching is itching associated with a mental skin disease selected from the group consisting of chronic lichen planus, itching rash, hair growth wall, nerve scratches, behavioral disorders invading the skin, and parasitic delusions. Composition. Contains seaweed extract as an active ingredient,
The seaweed extract is a food composition for improving or preventing itching, characterized in that by water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. delete The composition of claim 9, wherein the mixed solvent is an aqueous solution of 20 to 80% by weight of methanol, ethanol, butanol or propanol. The composition of claim 9, wherein the mixed solvent is an aqueous ethanol solution of 20 to 80% by weight. The composition of claim 9, wherein the itching is induced by expression of MDC, TARC, ET-1, and PAR-2. The method of claim 9, wherein the itching is selected from the group consisting of paroxysmal itching, sinus itching, anal itching, vulvar itching, scrotal itching, water-borne itching, scalp itching, nose itching, neck itching, itching in the mouth, and itching in the eyes. Composition characterized by. The method of claim 9, wherein the itching is accompanied by an internal medical disease selected from the group consisting of biliary itching, chronic renal failure, malignancies, iron deficiency anemia, polycythemia vera, hyperthyroidism, hypothyroidism, diabetes, and acquired immunodeficiency syndrome. Composition, characterized in that itching. The method of claim 9, wherein the itching is itching associated with a mental skin disease selected from the group consisting of chronic lichen planus, itching rash, hair growth wall, nerve scratches, behavioral disorders invading the skin, and parasitic delusions. Composition. The composition according to claim 9, wherein the food composition is selected from the group consisting of capsules, tablets, powders, granules, liquids, pills, flakes, pastes, syrups, gels, jelly, and bars. Contains seaweed extract as an active ingredient,
The laver extract is a cosmetic composition for improving or preventing itching, characterized in that by water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The method of claim 18, wherein the formulation of the cosmetic composition is in the form of tonic, shampoo, conditioner, hair conditioner, hair spray, powder, gel, cream, essence, lotion, sol gel, emulsion, oil, wax, spray or mist. Composition.

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