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WO2018066952A1 - Composition comprenant un extrait de rhizome de crassirhizomae utilisé comme principe actif pour prévenir, soulager ou traiter l'hyperuricémie ou des troubles métaboliques liés à l'hyperuricémie - Google Patents

Composition comprenant un extrait de rhizome de crassirhizomae utilisé comme principe actif pour prévenir, soulager ou traiter l'hyperuricémie ou des troubles métaboliques liés à l'hyperuricémie Download PDF

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Publication number
WO2018066952A1
WO2018066952A1 PCT/KR2017/011041 KR2017011041W WO2018066952A1 WO 2018066952 A1 WO2018066952 A1 WO 2018066952A1 KR 2017011041 W KR2017011041 W KR 2017011041W WO 2018066952 A1 WO2018066952 A1 WO 2018066952A1
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WIPO (PCT)
Prior art keywords
hyperuricemia
gout
extract
related metabolic
metabolic disorders
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Ceased
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PCT/KR2017/011041
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English (en)
Korean (ko)
Inventor
김동선
이영실
손은정
이윤미
김온순
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Korea Institute of Oriental Medicine KIOM
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Korea Institute of Oriental Medicine KIOM
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • 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
    • A61K36/11—Pteridophyta or Filicophyta (ferns)
    • A61K36/12—Filicopsida or Pteridopsida
    • 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
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts

Definitions

  • the present invention relates to a composition for the prevention, improvement or treatment of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient.
  • Hyperuricemia is defined by blood uric acid values above 6.8-7.0 mg / dL in men or above 6 mg / dL in women. Hyperuricemia and hyperuricemia-related metabolic disorders (eg gout) occur in 3 to 5 million people in the United States. In the United States, African Americans are twice as likely to have gout than whites. In addition, gout and hyperuricemia are prevalent in China, Japan, Polynesia, and sub-Saharan Africa, with approximately twice the incidence of gout between 1990 and 2010, and an increase of 14% in gout in Korea. That's the trend.
  • Metabolic disorders related to hyperuricemia include not only gout, but also uric acid crystals, deposition of urate crystals in joints, acute, monoarticular, painful attacks of inflammatory arthritis due to deposition of urate crystals in the renal region, urolithiasis, nephrolithiasis and gout Nephropathy is included. Long-term nephrolithiasis and gout nephropathy are known to increase the risk of kidney damage and kidney failure.
  • uric acid the product of the body's metabolism of purine, which is ingested through food
  • urate uric acid in the blood, body fluids, and joint fluids
  • Crystals are diseases that deposit in cartilage, tendons and surrounding tissues of joints. These phenomena cause inflammation of the joints, causing recurrent seizures with severe pain, and deformation and disability occur as the gout nodules (tophi) due to urate crystals are deposited.
  • nephroolithiaisis nephrolithiasis
  • kidney diseases and causes stones in the kidneys due to uric acid may appear.
  • gout occurs through stages of asymptomatic hyperuricemia, acute gouty arthritis, intermittent gout, chronic nodular gout, and the like.
  • Asymptomatic hyperuricemia in the early stage of serum uric acid concentration increased, but symptoms such as arthritis, gout nodule, uric acid kidney disease have not yet appeared.
  • Acute gouty arthritis is a stage in which gout seizures or kidney stones develop after hyperuricemia, which usually lasts for at least 20 years, and the most characteristic symptom is an acute attack of very painful arthritis. It is invasive and does not have systemic symptoms, but it gradually involves multiple joints and is accompanied by fever.
  • Intermittent gout refers to the period of no symptoms between gout attacks, most often experiencing a second seizure between six months and two years after the first one, depending on treatment, but with increasing frequency, Will be violated.
  • Chronic nodular gout looks similar to other types of arthritis at the time of chronic nodular gout over an intermittent period without gout. Gradual stiffness and constant pain develop in the joints of the affected area.
  • Gout is known to be a clear and successfully treated disease, but it is often accompanied by other diseases such as hypertension and chronic renal failure, so it is often necessary to carefully consider side effects of the drug and to change lifestyles as a non-pharmaceutical treatment.
  • the patient's effort is essential to improve prognosis in long-term treatment.
  • Gout and hyperuricemia have clinical features such as hypertension, hyperlipidemia, hyperglycemia, abdominal obesity, and are not included in the diagnostic criteria for metabolic syndrome, a complex condition that increases the risk of adult diseases such as atherosclerotic heart disease and type 2 diabetes. Metabolic syndrome is thought to be closely related. In Korea, 44% of gout patients reported metabolic syndrome.
  • Gout usually occurs in the form of acute monoarthritis but may involve minor or rarely polyarthritis.
  • Non-steroidal anti-inflammatory drugs NSAIDs
  • Colchicine has anti-inflammatory effects by inhibiting the activity and migration of white blood cells. Both steroids are effective drugs to treat gout attacks, and selective cyclooxygenase (COX-2) inhibitors are also known to have the same effect as conventional nonsteroidal anti-inflammatory drugs.
  • Allopurinol is an xanthine oxidase (XO) inhibitor that can be used effectively regardless of the cause of hyperuricemia, but the most serious side effect of allopurinol is hypersensitivity syndrome, which causes fever, erythema, Increased eosinophils, hepatitis, kidney failure, etc. are known to be at risk of death.
  • Febuxostat unlike xanthine oxidase inhibitors and allopurinol, is a nonpurine-based selective blocker that is metabolized mainly in the liver to form glucuronide. Most gouts are chronic, with prophylactic anti-inflammatory and uric acid-lowering medications, even if no symptoms.
  • Root stocks are 8 ⁇ 10mm in diameter, lump-shaped, stand at an angle, about 25cm long, and leaves are turned. Petioles are 10-25cm long, much shorter than petiole, with dense scales. Scale scales are basal, 10-25mm long, glossy, yellowish brown or blackish brown with pointed ends and long projections on the edges.
  • the leaf body is inverted basso and deeply split into two feathers.
  • Leaf fragments are 20-30 pairs, stripe-shaped, bar-shaped, without sack, pointed at the end, with curly hairy scales on both sides.
  • the leaf fragment in the middle of the leaf body is the largest, and the leaf fragment is smaller in size toward the bottom, and the running distance is wider.
  • the leaf fragments have long oval shape, dull ends and dull teeth on the edges, and the leaf veins from the central vein are usually divided into Y-shapes. Spore cysts run in two rows near the central vein of leaf fragments on upper part of leaf body. Eat young leaves.
  • the root stem is used as a medicinal herb, which eliminates parasites, has antipyretic and detoxifying effects, and also has a hemostatic effect. In both cases, the ingredients are extracted to make medicines such as cotton tablets. It is distributed in Korea, Japan, Sakhalin, Kuril Islands, and northeastern China.
  • Korean Patent No. 1486523 discloses a pharmaceutical composition or a health functional food composition for preventing or treating thrombosis containing an extract or a fraction thereof as an active ingredient, and Korea
  • Korean Patent Application Publication No. 2015-0073261 there is disclosed a pharmaceutical composition for preventing and treating degenerative brain diseases, which includes the extract of the spectral extract as an active ingredient, and a mixture of the sweet rice feed comprising the extract of the tract is disclosed in Korean Patent Publication No. 2016-0080654. It is.
  • compositions for the prevention, improvement or treatment of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract of the present invention as an active ingredient.
  • the present invention is derived by the above requirements, the present invention provides a composition for the prevention, improvement or treatment of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient, The present invention was completed by confirming that the spectral extract inhibits the activity of xanthine oxidase and reduces uric acid in serum of an animal model.
  • the present invention provides a health functional food for the prevention or improvement of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient.
  • the present invention also provides a pharmaceutical composition for the prevention or treatment of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient.
  • the present invention relates to a composition for the prevention, improvement or treatment of hyperuricemia or hyperuricemia-related metabolic disorders containing the extract as an active ingredient, and has an inhibitory effect on the activity of xanthine oxidase and can reduce the amount of uric acid in serum. It can be widely used in industries related to metabolic disorders related to hyperuricemia or hyperuricemia. In particular, it can be effectively used for the prevention, amelioration or treatment of gout or gouty arthritis.
  • the normal group means a normal animal model group
  • the 200 mg / kg spectral group refers to an animal model group in which 200 mg / kg spectral extract is administered to the normal animal model.
  • Figure 2 is a result of confirming the decrease in the amount of uric acid in the serum after administration of the spectral extract of the present invention to the hyperuricemia-induced SD-let animal model.
  • Normal group refers to a normal animal model group
  • hyperuricemia group refers to an animal model group induced hyperuricemia by administering 150 mg / kg of potassium oxonate (Potassium oxonate).
  • the present invention relates to a dietary supplement for the prevention or improvement of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient.
  • the hyperuricemia-related metabolic disorder is preferably one selected from acute or chronic gout, gout redness, gouty arthritis, gout nephrolithiasis and gout nephropathy, but is not limited thereto.
  • the gout redness refers to a symptom of reddening due to inflammation caused by gout.
  • the spectral extract is preferably extracted using C 1 ⁇ C 4 lower alcohol, water or a mixture thereof as a solvent, more preferably ethanol as a solvent, more preferably 70%
  • extraction is carried out using (v / v) ethanol as a solvent, it is not limited thereto.
  • Health functional foods for the prevention or improvement of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient may be prepared by any one selected from beverages, pills, tablets, capsules, powders, or other It may be prepared by adding to food or ingredients of food, and may be appropriately prepared according to conventional methods.
  • Examples of foods to which the spectral extract of the present invention may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, Tea, drink, alcoholic beverages and vitamin complexes can be any one of the forms selected, and includes all of the health food in the conventional sense.
  • the dietary supplement includes various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alkonic acid and salts thereof, organic acids, protective colloidal thickeners. , pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. Others may contain pulp for the production of natural fruit juices and vegetable drinks. These components can be used independently or in combination.
  • the health functional food of the present invention may contain various flavors or natural carbohydrates as additional ingredients.
  • the natural carbohydrates are sugars such as glucose, monosaccharides such as fructose, malsaccharides, disaccharides such as sucrose, and polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol, and erythritol.
  • natural sweeteners such as tautin and stevia extract, or synthetic sweeteners such as saccharin or aspartame may be used.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of hyperuricemia or hyperuricemia-related metabolic disorders containing the spectral extract as an active ingredient.
  • Metabolic disorders related to hyperuricemia in the pharmaceutical composition are preferably any one selected from acute or chronic gout, gout redness, gouty arthritis, gout nephrolithiasis and gout nephropathy.
  • the gout redness refers to a symptom of reddening due to inflammation caused by gout.
  • uric acid lowering agent In addition to the active ingredient, it may further include a uric acid lowering agent, and a preferable uric acid lowering agent is one or more selected from xanthine oxidase inhibitors, uric acid excretion agents, uric acid oxidases, urinary alkalizing agents, and fenofibrate, but is not limited thereto.
  • a pharmaceutically acceptable carrier in addition to the tract extract may further comprise a pharmaceutically acceptable carrier, excipient or diluent.
  • compositions of the present invention may be in various oral or parenteral formulations.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may comprise at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
  • excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
  • lubricants such as magnesium stearate, talc and the like are also used.
  • Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycero gelatin and the like can be used.
  • composition of the present invention may be administered orally or parenterally, and when parenteral administration, it is preferable to select a skin external or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection method.
  • 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 means 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 compositions of the present invention may be administered as individual therapeutic agents 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 achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.
  • the dosage of the composition of the present invention can be used in a variety of ranges depending on the weight, age, sex, health, diet, time of administration, administration method, excretion rate and severity of the patient.
  • Example 2 Spectrum of Ethanol Extracts Xanthine Oxidase ( Xanthine oxidase Confirmation of inhibitory activity
  • Xanthine oxidase inhibitory activity assay was performed by Sirpe and Della corte [Stirpe F, Della Corte E. 1969. The regulation of rat liver xanthine oxidase. J Biol Chem 244: 3855-3563.
  • 0.1 ml of 500 ⁇ g / ml ethanol extract prepared in Example 1 and 0.6 ml of 0.1 M potassium phosphate buffer (pH 7.5) were added 0.2 ml of a substrate solution containing 2 mM Xanthine. .
  • 0.1 ml of Xanthine oxidase (0.2 U / ml) was added thereto and reacted at 37 DEG C for 5 minutes, and then 1 ml of 1N HCl was added to stop the reaction, followed by uric acid produced in the reaction solution.
  • the absorbance was measured at 292 nm.
  • the inhibitory activity of Xanthine oxidase on ethanol extracts in the tube was expressed as a percentage (%). As a result, it was confirmed that the inhibitory activity of xanthine oxidase was observed by treatment of the ethanol extract in the tube (Table 1). .
  • a 200 mg / kg spectral extract and a positive control 50 mg / kg allopurinol were suspended in 0.01 M PBS (phosphate buffered saline) buffer solution containing 0.1% polyoxyethylene sorbitane monooleate, respectively.
  • PBS phosphate buffered saline
  • uric acid assay kit (ab65344, abcam, USA).
  • the result of measuring the amount of uric acid in the blood was found to be about 1.0 mg / dl due to the decrease of uric acid by administration of the extract of the duct, and the blood uric acid was reduced by about 50% compared to the normal group. It was.
  • Example 4 Analyzing the effect of reducing uric acid in blood in hyperuricemia-induced animal model
  • urine was used to select a model animal induced with hyperuricemia using an uric acid assay kit (ab65344, abcam, USA).
  • the solution was suspended orally for 3 days and fasted for 16 hours on the day before necropsy. Two hours after the last oral administration, after anesthesia with ethyl ether, blood was taken and the amount of uric acid was measured using a uric acid assay kit (ab65344, abcam, USA).
  • the amount of uric acid increased by the administration of potassium oxonate appeared to be about 3.2mg / dl
  • the extract of the spectral extract of the present invention 200mg / kg / day
  • the amount of uric acid in the serum was confirmed to decrease by about 40.66%.

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Abstract

La présente invention concerne une composition comprenant un extrait de rhizome de Crassirhizomae utilisé comme principe actif pour prévenir, soulager ou traiter l'hyperuricémie ou des troubles métaboliques liés à l'hyperuricémie. L'extrait de rhizome de Crassirhizomae de la présente invention a pour effets de réduire la teneur en acide urique sérique chez des modèles animaux ainsi que d'inhiber l'activité de la xanthine oxydase. L'extrait de rhizome de Crassirhizomae est sûr et une matière première pour celui-ci est relativement facile à fournir puisque l'extrait est un principe actif dérivé d'une matière naturelle, de sorte que l'extrait peut être largement utilisé dans les industries associées à l'hyperuricémie ou aux troubles métaboliques liés à l'hyperuricémie. En particulier, l'extrait peut être utilisé efficacement pour prévenir, soulager ou traiter la goutte ou l'arthrite goutteuse.
PCT/KR2017/011041 2016-10-04 2017-09-29 Composition comprenant un extrait de rhizome de crassirhizomae utilisé comme principe actif pour prévenir, soulager ou traiter l'hyperuricémie ou des troubles métaboliques liés à l'hyperuricémie Ceased WO2018066952A1 (fr)

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KR10-2016-0127732 2016-10-04
KR1020160127732A KR101881144B1 (ko) 2016-10-04 2016-10-04 관중 추출물을 유효성분으로 함유하는 고요산혈증 또는 고요산혈증 관련 대사 장애의 예방, 개선 또는 치료용 조성물

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KR102582805B1 (ko) 2021-02-26 2023-09-25 우석대학교 산학협력단 요산염으로 유발된 급성통풍개선용 조성물 및 이의 제조 방법

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KR101457117B1 (ko) * 2012-07-27 2014-11-04 한국 한의학 연구원 관중 추출물을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학적 조성물 및 건강기능식품
KR101590842B1 (ko) * 2014-05-23 2016-02-01 한국과학기술연구원 고요산혈증 또는 통풍에 유효한 섬쑥부쟁이 추출물, 이의 분획물 및 이로부터 분리된 활성화합물

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KR101457117B1 (ko) * 2012-07-27 2014-11-04 한국 한의학 연구원 관중 추출물을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학적 조성물 및 건강기능식품
KR101590842B1 (ko) * 2014-05-23 2016-02-01 한국과학기술연구원 고요산혈증 또는 통풍에 유효한 섬쑥부쟁이 추출물, 이의 분획물 및 이로부터 분리된 활성화합물

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YANG, YANYAN: "ERK1-and TBK1-targeted anti-inflammatory activity of an ethanol extract of Dryopteris crassirhizoma", JOURNAL OF ETHNOPHARMACOLOGY, vol. 145, no. 2, 2013, pages 499 - 508, XP055604736, DOI: 10.1016/j.jep.2012.11.019 *

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