WO2019240336A1 - Composition pour prévenir ou traiter la dermatite atopique, contenant un extrait de phaseolus vulgaris var humilis alef - Google Patents

Composition pour prévenir ou traiter la dermatite atopique, contenant un extrait de phaseolus vulgaris var humilis alef Download PDF

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WO2019240336A1
WO2019240336A1 PCT/KR2018/013100 KR2018013100W WO2019240336A1 WO 2019240336 A1 WO2019240336 A1 WO 2019240336A1 KR 2018013100 W KR2018013100 W KR 2018013100W WO 2019240336 A1 WO2019240336 A1 WO 2019240336A1
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extract
kidney
atopic dermatitis
kidney beans
present
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PCT/KR2018/013100
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Korean (ko)
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박찬경
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박찬경
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating atopic dermatitis, or a functional food for improving atopic dermatitis, comprising a kidney bean extract as an active ingredient.
  • Atopic dermatitis is a common chronic inflammatory skin disease that often progresses to food allergies, asthma or rhinitis.
  • Atopic dermatitis is characterized by repeated itching at regular intervals, which is characterized by repetitive relief and improvement as the characteristic skin lesions such as semi papules, eczematous lesions, thyroiditis and glandular erosions constantly change.
  • Atopic dermatitis is a chronic or recurrent eczema dermatitis characterized by pruritus, which forms blisters in the epidermis in the acute phase and is accompanied by thickening of the skin and skin in the chronic phase.
  • Atopic dermatitis is a disease that often occurs in children and can seriously affect the health and quality of life of patients.
  • the main immunological changes in atopic dermatitis are an increase in IgE and imbalance of T helper type 1 (Th1) cells and T helper type 2 (Th2) cells.
  • Th1 cells decrease in activity, thereby reducing cytokine-induced cytokines (IL) -2 and interferon (IFN) - ⁇ , which are induced by Th2 cells.
  • the cytokines IL-4, IL-5, IL-6 and IL-10 are increased.
  • Inflammation and damage of skin tissue also results in overexpression of IL-3, Il-4, Il-5, IL-10, and granulocyte-macrophage colony stimulating factor (GM-CSF), Inflammatory cytokines, IL-8, also increase.
  • GM-CSF granulocyte-macrophage colony stimulating factor
  • Topical corticosteroids have been used as a standard treatment for acute atopic dermatitis, but it has been reported to cause adverse effects on skin genes (Lubach D. et al., Dermatologica, 1989, 179, 67-72). It is necessary to develop a safe anti-inflammatory factor even without using steroids for a long time.
  • tacrolimus a topical immunosuppressive agent
  • tacrolimus a topical immunosuppressive agent
  • Tacrolimus effectively penetrates the skin as it has a relatively small molecular size and is therefore used in the form of topical ointment (Akhavan A. et al., Semin Cutan Med Surg., 2008, 27, 151-155).
  • Tacrolimus does not cause collagen synthesis or sclerosis, which is a side effect of corticosteroids, and can be used safely on thin and very fragile areas such as the face or neck.
  • research has been reported that the long-term use of tacrolimus halved the effect and may cause side effects, the development of a new drug for the treatment of atopic dermatitis is required.
  • kidney beans are a year-round plant of the dicotyledon rose Rosaceae legumes have been used for the improvement of various folk remedies in addition to edible.
  • Republic of Korea Patent No. 10-0574848 has described that the cosmetic composition containing the kidney bean extract as an active ingredient has a skin improvement effect by acting as a female hormone.
  • kidney bean extract is effective in the prevention and treatment of atopic dermatitis and completed the present invention.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising a kidney bean extract as an active ingredient.
  • the kidney bean extract preferably comprises root extracts of kidney beans ( Phaseol vulgaris var. Humilis ALEF) and stem extracts of vine beans ( Phase kidney vulgaris L.).
  • the extract is dried and powdered roots of kidney beans and stems of vine kidney beans, water, methanol, ethanol, acetone, ethyl acetate, 1,3-butylene as an extraction solvent for the powdered kidney beans Extracted using glycol, hexane, diethyl ether, n-propanol, iso-propanol, n-butanol or mixtures thereof Can be.
  • the extract is preferably extracted after roasting kidney beans at 150 to 200 °C for 5 to 10 minutes.
  • the roots of the kidney beans and the stems of the vine beans may be blended in a mass ratio of 1: 1.5 to 1:10 or 10: 1 to 1.5: 1.
  • the present invention also provides a functional food for improvement of atopic dermatitis comprising a kidney bean extract as an active ingredient.
  • the kidney bean extract preferably comprises root extracts of kidney beans ( Phaseol vulgaris var. Humilis ALEF) and stem extracts of vine kidney beans ( Phase kidney vulgaris L.).
  • the present invention can effectively inhibit and treat atopic dermatitis by providing a novel pharmaceutical composition or functional food comprising kidney bean extract as an active ingredient.
  • a novel pharmaceutical composition or functional food comprising kidney bean extract as an active ingredient.
  • by combining the roots of kidney beans with the stems of vine kidney beans can provide a novel therapeutic and functional foods that are non-toxic and excellent in treating atopic dermatitis.
  • 1 is a graph showing the weight change of the rat according to the administration of kidney bean extract alone according to an embodiment of the present invention.
  • Figure 2 is a graph showing the weight change of the rat according to repeated administration of kidney bean extract according to an embodiment of the present invention.
  • Figure 3a is an image taken after the hair removal of the back of the mouse.
  • Figure 3b is an image inducing contact dermatitis by applying the DNCB solution to the back of the mouse.
  • Figure 3c is an image of a rat ingested 30mg / kg kidney beans extract according to an embodiment of the present invention.
  • Figure 3d is an image of a rat ingested 150mg / kg kidney beans extract according to an embodiment of the present invention.
  • Figure 4 is a graph of itching behavior of day 4 of the extract administration of the present invention.
  • Figure 5 is an image extracted the spleen of the mouse according to an embodiment of the present invention.
  • Figure 6 shows the result of measuring the weight of the spleen of the mouse according to an embodiment of the present invention.
  • Figure 7 is a graph showing the IgG concentration of the rat serum according to an embodiment of the present invention.
  • FIG. 8 is a graph showing the concentration of interferon-gamma in the rat serum according to an embodiment of the present invention.
  • FIG. 9 is a graph showing the concentration of IL-4 in the rat serum according to an embodiment of the present invention.
  • the present invention relates to a pharmaceutical composition for the prophylaxis or treatment of atopic dermatitis comprising a kidney bean extract as an active ingredient.
  • Kidney beans Phaseolus vulgaris var. Humilis are perennial plants of the dicotyledonous rosacea legumes, vine kidney beans (Pyundudu, yongdu, and green beans; Phaseolus vulgaris L.) and red kidney beans (safflower, polycarpeia, kidney beans, peanuts; and the like, Phaseolus multiflorus WILLD), kidney beans (Phaseolus vulgaris var. humilis ALEF) , white kidney beans (Phaseolus multiflorus WILLD for. albus BAIKEY ), seeds of the kidney beans are used in folk medicine tongyu, boils, diuretic alone, edema, etc. .
  • the leaves, stems, and roots of kidney beans have different material compositions and different mechanisms of action, which are combined to appear as one representative.
  • the leaves, stems, roots of the beans appear to be a big difference between the components, depending on how the combination, taste, shape, function, etc. are expressed in various ways.
  • the color difference that is the result of natural enrichment shows a difference in symptomatic treatment.
  • the roots of the black kidney beans ( Phase vulgaris var. Humilis ALEF) and the stems of the white vine bean ( Phase vulgaris L.) have a very good effect in the treatment of atopic dermatitis as a very ideal combination.
  • color is an important target for the orientation of matter, with white kidney beans attacking the outside of the atopy and black kidney beans approaching the inside.
  • the roots of the kidney beans and the stems of the vine kidney beans are antagonistic to each other, the root portion also acts as a control material for toxicity at the same time, as a whole it was confirmed that the therapeutic efficacy for atopic dermatitis is further enhanced.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising the root extract of Phaseolus vulgaris var. Humilis ALEF and the stem extract of Phaseolus vulgaris L. as an active ingredient.
  • the extract may be prepared by a method generally used in the art.
  • the roots of the kidney beans and the stems of the vine beans are dried and powdered, and water, lower alcohols (methanol, ethanol), a mixture of water and lower alcohols, acetone, ethyl as extracting solvents for the powdered kidney beans.
  • Acetate, 1,3-butylene glycol, hexane, hexane, diethyl ether, n-propanol, iso-propanol, and n-butanol Extracts can be prepared using
  • the extract is most preferably extracted for 3 hours to 24 hours using water as the extraction solvent.
  • the extract may be used after preparing the extracts for the roots of the kidney beans and the stems of the vine kidney beans, respectively, and may be used by extracting the roots of the kidney beans and the stems of the vine kidney beans with a solvent.
  • Roots of the kidney beans and stems of the vine kidney beans can be further enhanced drug efficacy when roasting.
  • the roasting may be divided into a suitable size (for example, 2 cm or less) in a dry state, and then roasted at 150 to 200 ° C. for 5 to 10 minutes.
  • the roots of the kidney beans and the stems of the vine kidney beans may be blended in a mass ratio of 1: 1.5 to 1:10 or 10: 1 to 1.5: 1, and more preferably in a mass ratio of 1: 1.5 to 1: 5.
  • the roots of the kidney beans and the stems of the vine kidney beans have the weakest efficacy at a mass ratio of 1: 1, the most effective at a mass ratio of 1: 2 or 2: 1, and then gradually decrease in efficacy as the ratio increases. Indicates.
  • IgE IgE, IL in serum known to affect the atopic dermatitis, as well as to mitigate skin inflammation in rats expressing atopic dermatitis, the composition containing the root extract of kidney beans and stem extracts of vine kidney beans It was confirmed that there is a significant effect on the concentration of -4, IL-5, IL-6 and IL-10.
  • the pharmaceutical composition according to the invention may comprise a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier is conventionally used in the preparation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like.
  • the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like.
  • a lubricant e.g., talc, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, kaolin, a kaolin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mannitol, mann
  • compositions of the present invention may be oral or parenteral, and parenteral administration includes intravenous infusion, subcutaneous infusion, intramuscular injection, intraperitoneal injection, transdermal administration and the like.
  • composition according to the invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level refers to the type, severity, and activity of the patient's disease. , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of the drug, and other factors well known in the medical arts.
  • the composition according to the present invention may be administered as a separate therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.
  • the effective amount of the composition according to the present invention may vary depending on the age, sex and weight of the patient, and generally 0.001 to 150 mg, preferably 0.01 to 100 mg per 1 kg of body weight is administered daily or every other day or 1 to 1 day. It can be divided into three doses. However, the dosage may be increased or decreased depending on the route of administration, sex, weight, age, etc., and the above dosage does not limit the scope of the present invention in any way.
  • compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporating into a multi-dose container.
  • the formulation may be in the form of a solution, suspension or emulsion in an oil or an aqueous medium, or may be in the form of extracts, powders, granules, tablets or capsules, and may further include a dispersant or stabilizer.
  • kidney bean extract itself, but also pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof.
  • the present invention also relates to a functional food for improving atopic dermatitis containing kidney beans extract as an active ingredient.
  • the functional food is not particularly limited, and may be, for example, beverages, gums, teas, vitamin complexes, health supplements, and more specifically, dairy products, confectionery, seasonings, beverages and drinks, snacks, candy, jelly. , Ice cream and frozen desserts, breakfast cereals, nutrition bars, snack bars chocolate products, processed foods, grain products and pastas, soups, sauces and dressings, confectionery products, oils and fats products, dairy drinks and milk drinks, Tea, soy milk and soy dairy-like products, frozen foods, cooked foods and substitutes, meat products, cheese, yogurt, bread and buns, cakes, cookies and crackers.
  • the functional food may be prepared in the form of capsules, tablets, powders, liquid suspensions, pills and granules containing kidney beans extract.
  • the functional food in addition to the kidney bean extract may further include ingredients that are commonly added at the time of food production as an active ingredient.
  • Functional foods of the present invention include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and salts thereof , Organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonation agent used in carbonated drinks, and the like, and may contain fruit juice or pulp for preparing vegetable drinks.
  • the extract was repeatedly extracted three times for 3 hours using 6L of distilled water at 100 ° C using an extractor and filtered.
  • the obtained extract was concentrated at 60 ° C. or lower using a rotary evaporator, and then dried with a lyophilizer to obtain powder of kidney bean root and vine kidney bean stem.
  • mice Five-week-old male ICR mice were supplied by Coatech Co., Ltd., and then used for experiments at six-week-old males (23-25 g) after one week of laboratory purification. Animals were housed in mouse cages five times, and allowed to freely consume solid feed and drinking water for experimental animals. The laboratory environment was maintained at a temperature of 23 ⁇ 2 ° C., humidity of 50-60% and a 12 hour light and dark cycle.
  • the extract powder prepared in Preparation Example was orally administered to 500, 1,000 and 5,000 mg / kg at a proper dose (10 ml / kg) in physiological saline and observed for 14 days. Animals were observed daily for 14 days to record mortality, general symptom weight change, and autopsy was performed on day 15 post-mortem to analyze the histopathological findings only in tissues with gross anatomical lesions.
  • the extract powder was dissolved in physiological saline at an appropriate dose (10 ml / kg), and male mice were orally administered once a day for 28 days at 100, 500, 1,000 and 5,000 mg / kg, and fasted at 29 days after fasting.
  • FIG. 1 is a graph showing the weight change of the mice according to single administration
  • Figure 2 is a graph showing the weight change of the mice according to repeated administration. Both graphs show weight gain graphs similar to controls.
  • animals exhibiting abnormal behavior compared to the control group such as skin, hair, respiration, exercise status, and diarrhea, which are common symptoms due to test substance administration, during the 14-day observation period after the single administration and the 28-day observation period after repeated oral administration. Was not observed and no animals died in the test group.
  • Observations of thymus, lung, heart, spleen, liver, kidney and testicles showed no specific findings in the administration group compared to the control group and showed a decrease in spleen weight in the 5,000 mg / kg administration group, but no significant change. .
  • the experimental animals were male 4-week old 18-22g BALB / c mice, and were fed to feed solid foods and water freely during the experimental period.
  • DNCB 2,4-dinitrochlorobenzene
  • the extract powder prepared in Preparation Example was dissolved in 0.9% saline solution, and orally administered twice daily for 7 days at 30 mg / kg and 150 mg / kg, respectively, and 0.9% saline was added to the control group per day 2 Oral administration 7 times a day.
  • Figure 3c and 3d is an image of the skin appearance of the mice ingested at 30mg / kg and 150mg / kg of the extract of the present invention, respectively.
  • mice ingested with 30 mg / kg of the extract of the present invention were visually identified as having reduced inflammation of the skin.
  • the inflammation of the skin was not relieved to the naked eye in the case of the mice ingested 150 mg / kg of the extract of the present invention in Figure 3d.
  • the DNCB-administered group showed a significant increase in the itch behavior compared to the normal group, but the DNCB + extract (30 mg / kg) and the (150 mg / kg) -administered group showed a significant decrease in the itch. It became.
  • the rats were opened and spleens were extracted to measure their respective weights.
  • the appearance and weight measurement results of the spleen are shown in FIGS. 5 and 6, respectively.
  • mice were anesthetized, the abdomen was opened, and blood was collected from the abdominal aorta using a syringe. Blood was centrifuged (3,000 rpm, 4 ° C., 15 minutes) in a heparinized tube to separate serum.
  • the concentration of IgE in serum was measured using enzyme-linked immunosorbent assay (ELISA). Dispense 100 ⁇ L of serum into each well of the 96 well plate, react for 30 minutes at room temperature, and wash three times. Dispense 100 ⁇ l of enzyme-antibody into each well, react for 30 minutes at room temperature, wash with three wash buffers, and then TMB. After 10 minutes of 100ul of solution was added to each well, the absorbance was measured at 450 nm using an ELISA reader containing 100ul of stop solution. The results are shown in FIG.
  • ELISA enzyme-linked immunosorbent assay
  • the concentrations of interferon-gamma and IL-4 were measured using an ELISA kit (BD Biosciences, CA, USA) as follows. 50 ul of serum was dispensed into each well, and 50 ul of biotin-conjugated antibody (Pharmingen, CA, USA) was added and mixed. The mixture was reacted at 37 ° C. for 2 hours and washed four times using a washing buffer. 100 ⁇ L of streptavidin-HRP working solution was added thereto, followed by reaction at room temperature for 30 minutes, and then washed four times using washing buffer. After 100 ul of stabilized chromogen was added and left in the dark for 30 minutes, 100 ul of stop solution was treated and absorbance was measured at 450 nm with ELISA reader. The results are shown in FIGS. 8 and 9.
  • serum IGE showed a significant decrease in both extract-treated groups of the present invention compared to the control group, and inhibition rates were 18.83% and 26.28% for the 30 mg / kg and 150 mg / kg administration groups, respectively.

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Abstract

La présente invention concerne une composition pharmaceutique et un aliment fonctionnel pour prévenir ou traiter la dermatite atopique, contenant tous les deux un extrait de Phaseolus vulgaris var. humilis ALEF en tant que principe actif. La présente invention concerne une nouvelle composition pharmaceutique et un aliment fonctionnel contenant un extrait de Phaseolus vulgaris var. humilis ALEF en tant que principe actif, permettant ainsi d'inhiber et de traiter efficacement la dermatite atopique.
PCT/KR2018/013100 2018-06-11 2018-10-31 Composition pour prévenir ou traiter la dermatite atopique, contenant un extrait de phaseolus vulgaris var humilis alef WO2019240336A1 (fr)

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KR1020180067001A KR101891822B1 (ko) 2018-06-11 2018-06-11 강낭콩 추출물을 함유하는 아토피 피부염의 예방 또는 치료용 조성물

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KR101891822B1 (ko) * 2018-06-11 2018-08-27 박찬경 강낭콩 추출물을 함유하는 아토피 피부염의 예방 또는 치료용 조성물

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KR101891822B1 (ko) * 2018-06-11 2018-08-27 박찬경 강낭콩 추출물을 함유하는 아토피 피부염의 예방 또는 치료용 조성물

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KR100574848B1 (ko) * 1999-10-21 2006-04-27 주식회사 코리아나화장품 강낭콩 추출물을 함유하는 화장료 조성물
KR20140040721A (ko) * 2011-04-21 2014-04-03 마리 케이 인코포레이티드 식물 추출물을 포함하는 국소 스킨 케어 제형
KR101502687B1 (ko) * 2013-07-11 2015-03-16 주식회사 바이오에프디엔씨 두류 태좌 세포 배양 추출물을 함유한 항노화, 항염, 항산화 화장료 조성물
KR101821712B1 (ko) * 2013-08-22 2018-01-24 주식회사 아데나 삼칠근 추출물, 비누풀잎 추출물, 검정콩 잎 추출물, 녹두 잎 추출물 및 호랑이콩 잎 추출물을 포함하는 Ｔｈ2-매개 면역 질환 개선, 예방 또는 치료용 조성물
KR101891822B1 (ko) * 2018-06-11 2018-08-27 박찬경 강낭콩 추출물을 함유하는 아토피 피부염의 예방 또는 치료용 조성물

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