WO2016208910A1 - Composition contenant l'osmotine protéine ou l'osmotine peptide en tant que principe actif pour la prévention ou le traitement des troubles de la fonction hépatique et de la fonction rénale - Google Patents

Composition contenant l'osmotine protéine ou l'osmotine peptide en tant que principe actif pour la prévention ou le traitement des troubles de la fonction hépatique et de la fonction rénale Download PDF

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Publication number
WO2016208910A1
WO2016208910A1 PCT/KR2016/006426 KR2016006426W WO2016208910A1 WO 2016208910 A1 WO2016208910 A1 WO 2016208910A1 KR 2016006426 W KR2016006426 W KR 2016006426W WO 2016208910 A1 WO2016208910 A1 WO 2016208910A1
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osmotin
liver
prevention
protein
peptide
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PCT/KR2016/006426
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English (en)
Korean (ko)
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김명옥
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경상대학교산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids

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  • the present invention relates to a composition for preventing or treating hepatic and renal dysfunction. More specifically, the present invention relates to a composition for the prevention or treatment of liver and renal function disorders containing an osmotin protein or an osmotin peptide as an active ingredient. The present invention relates to a composition that exerts an excellent prophylactic and therapeutic effect even on organ dysfunction.
  • kidneys have the function of excreting urine from drugs or toxins that are toxic substances introduced into the living body and wastes introduced into the blood by filtration and secretion apparatus in the tubules.
  • Osmotin derived from plants is involved in fatty acid oxidation regulation, glucose production, phosphorylation (AMP kinase) and signal transduction pathways.
  • Osmotin 24 kDa
  • Osmotin is a stable protein included in the PR-5 family homologous to the sugar-testing protein thaumatin and is known to induce intracellular signal transduction in yeast.
  • Osmotin is resistant to heat, acidity and enzymes and can circulate through the body without being degraded by digestion.
  • Osmotin is known to be homologous to adiponectin present in animals, and it has been found that adiponectin may have some anti-inflammatory, anti-diabetic, and anti-atherogenic ability.
  • osmotin is known for its effects mainly related to obesity and diabetes, and is known as a composition for preventing and treating neurological diseases containing osmotin in Korean Patent No. 1308232, but osmotin protein and osmotin peptide have liver function. And as a composition for preventing or treating renal dysfunction.
  • the present invention is derived from the above requirements, the present invention relates to a composition for the prevention, improvement or treatment of liver and renal function disorders containing osmotin protein or osmotin peptide as an active ingredient, Osmotin peptides reduce the levels of AST, ALT, BUN and creatine and activate hepatic metabolism in the blood of obese model rats.
  • the present invention was completed by confirming that the expression levels of the activated receptor alpha and PGC1- ⁇ (Peroxisome proliferator-activated receptor- ⁇ coactivator 1- ⁇ ) proteins were reduced in obese model mice and increased by treatment with osmotin protein. .
  • the present invention provides a health functional food composition for the prevention or improvement of liver function and renal function disorders containing osmotin protein or osmotin peptide as an active ingredient.
  • the present invention also provides a pharmaceutical composition for the prevention or treatment of liver and renal function disorders containing an osmotin protein or an osmotin peptide as an active ingredient.
  • the present invention relates to a composition for the prevention, improvement or treatment of liver and kidney disorders containing osmotin protein or osmotin peptide as an active ingredient. It is effective in preventing, ameliorating or treating an organ disorder.
  • 1 is a graph confirming the concentration changes of serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) after treating osmotin protein in OB / OB mice.
  • Figure 2 is a graph confirming the change in the concentration of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum after treatment with the osmotin protein in DB / DB mice.
  • AST aspartate aminotransferase
  • ALT alanine aminotransferase
  • AST aspartate aminotransferase
  • ALT alanine aminotransferase
  • Figure 4 is a high-calorie diet mice overweight for two months after a high-calorie diet was overweight, and then injected with intraperitoneal injection of osmotin protein for 10 days, the blood was collected by blood total cholesterol (A), neutral It shows the results of measuring the content of lipid (B), high density lipoprotein cholesterol (C) and low density lipoprotein cholesterol (D).
  • the control group is a group not administered osmotin peptide
  • the experimental group is a group administered osmotin peptide.
  • FIG. 5 is a graph showing the change in the concentration of BUN in the serum of OB / OB mice and DB / DB mice according to the treatment of the osmotin protein.
  • Figure 6 is a graph showing the change in the concentration of creatine in the serum of OB / OB mice and DB / DB mice according to the treatment of osmotin protein.
  • Figure 7 shows the result of confirming the expression level of pAMPK (A), PPAR ⁇ (B) and PGCl- ⁇ (C) in liver tissue by administering osmotin protein in OB / OB mice.
  • OB / OB is a positive control obesity model rat
  • OB / OB + OS is the experimental group administered 150 ⁇ l osmotin protein intraperitoneal Administration (IP) of OB / OB mice to be.
  • IP intraperitoneal Administration
  • FIG. 8 shows the result of confirming the expression level of pAMPK (A), PPAR ⁇ (B) and PGCl- ⁇ (C) in liver tissue by administering osmotin protein in DB / DB mice.
  • C is the normal control group as a negative control
  • DB / DB is a positive control obesity model rat
  • DB / DB + OS was administered to 150 ⁇ l osmotin protein intraperitoneal Administration (IP) of OB / OB mice to be.
  • IP intraperitoneal Administration
  • the present invention relates to a nutraceutical composition for the prevention or improvement of liver and renal function disorders containing osmotin protein or osmotin peptide as an active ingredient.
  • the osmotin protein is derived from a plant, and is composed of about 150 to 250 amino acids, depending on the individual, and the composition of the amino acids differs depending on the type of plant.
  • the osmotin protein is contained in mature fruits of plants, for example, fruits such as grapes, tobacco ( Nicotiana) tabacum ), orange ( Citrus sinensis ), Chinese equivalent ( Rosa roxburghii ), potato ( Solanum) tuberosum ), Piper colubrinum , Castor ( Ricinus) communis ), Arabidopsis thaliana , etc., but is not limited to the type of osmotin protein used in the present invention by the above examples. That is, the osmotin protein of the present invention is not limited in its origin, and the osmotin protein derived from various plants as described above may be used, and may be artificially synthesized and used according to known genetic engineering methods.
  • the osmotin peptide is (a) an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1, or (b) one or more amino acid residues are substituted, deleted or inserted into the amino acid sequence of SEQ ID NO. It can be prevented or improved and is preferably, but not limited to, an osmotin peptide derived from (a).
  • the osmotin protein or osmotin peptide is preferably contained in an amount of 0.1 to 100% by weight based on the weight of the composition, but is not limited thereto.
  • the osmotin protein or osmotin peptide is characterized by reducing the blood content of AST or ALT, and reducing the blood content of BUN or creatine.
  • AST and ALT are generally considered to have normal liver function when in the range of 30-40 U / l.
  • AST and ALT are enzymes used to produce oxaloacetic acid and pyruvic acid from aspartic acid and alanine and finally make sugar.
  • AST is present in the liver, myocardium, rhabdomyo, kidney, brain, pancreas, lung, leukocyte, and erythrocyte.
  • ALT is most present in the liver.
  • ALT is more specific for 'liver damage' than AST.
  • the causes of elevated liver or kidney function are: 1) chronic viral hepatitis, including chronic hepatitis B or chronic hepatitis C, 2) alcoholic liver disease, 3) weakly borne liver damage, 4) fatty liver and nonalcoholic fatty hepatitis (non-alcoholic steatohepatitis; NASH), 5) autoimmune hepatitis, 6) hemochromatosis, 7) Wilson's disease, 8) obesity, and the like.
  • Urea is a metabolite of protein.Ammonia produced by deaminoation is highly toxic, so it is converted from the liver to urea and then transported to the kidneys for release. Creatine is a non-enzymatic dehydration reaction mainly from muscle creatine. It is produced by and released through the kidneys, and because it is not reabsorbed, it is used as an indicator of abnormality in kidney function.
  • the health functional food composition of the present invention is preferably one of the formulations selected from beverages, pills, tablets, capsules, powders, but is not limited thereto. It may be prepared together with other foods or food ingredients, and may be appropriately prepared according to conventional methods.
  • foods to which the nutraceutical composition of the present invention may be added include caramel, meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups , Beverages, tea, drink, alcoholic beverages and vitamin complexes may be any one of the forms selected, and includes all of the health food in the conventional sense. That is, the kind of food is not particularly limited.
  • These foods include a variety of nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (such as cheese and chocolate), pectic acid and salts thereof, alkonic acid and salts thereof, organic acids, protective colloidal thickeners, pH It may contain a regulator, stabilizer, preservative, glycerin, alcohol, carbonation agent used in the carbonated beverage. It may also contain pulp for the production of natural fruit juices and vegetable drinks. The above components can be used independently or in combination.
  • the health functional food composition of the present invention may contain various flavors or natural carbohydrates, etc.
  • the natural carbohydrate is glucose, monosaccharides such as fructose, disaccharides such as maltose, sucrose, and dextrin, Polysaccharides such as cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • sweetening agent natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used.
  • the present invention also relates to a pharmaceutical composition for the prevention or treatment of liver and renal function disorders containing an osmotin protein or an osmotin peptide as an active ingredient.
  • the osmotin peptide is (a) an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1, or (b) one or more amino acid residues are substituted, deleted or inserted into the amino acid sequence of SEQ ID NO. It may be prevented or treated, and is preferably, but not limited to, an osmotin peptide derived from (a).
  • the liver function and renal function disorders are characterized by, but are not limited to, caused by obesity, the osmotin protein or osmotin peptide is preferably contained 0.1 to 100% by weight based on the weight of the composition, but is not limited thereto.
  • the osmotin protein or osmotin peptide decreases the content of AST or ALT in the blood and decreases the content of blood urea (BUN) or creatine in the blood.
  • the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent.
  • Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are conventionally used in the preparation, saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, lactose, dex Straw, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, syrups, methyl cellulose, methylhydroxybenzoate, propyl Hydroxybenzoate, talc, magnesium stearate and mineral oil, and the like.
  • the pharmaceutical composition of the present invention may further include antioxidants, buffers, bacteriostatic agents, diluents, surfactants, binders, lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents or preservatives, etc., in addition to the above components.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally, and preferably applied by oral administration.
  • Suitable dosages of the pharmaceutical compositions of the present invention may be prescribed in various ways depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be.
  • liver dysfunction means acute or chronic liver disease, which is abnormal in part or all of the liver function, alcoholic or non-alcoholic fatty liver, type A B or C acute hepatitis, chronic hepatitis, cirrhosis , Liver fibrosis and cirrhosis, toxic liver disease, etc., but is not limited thereto.
  • renal dysfunction refers to acute or chronic kidney disease, which is abnormal in part or all of renal function.
  • glomeruli such as acute pyelonephritis caused by drugs and chronic pyelonephritis, and acute pyelonephritis caused by bacterial and viral infections. It means, but not limited to, dysfunction in the kidneys, tubules, lupus and the like.
  • Osmotin protein (DOI: 10.2210 / pdb1pcv / pdb) used in the present invention was derived from tobacco ( Nicotiana t abacum ) seeds, and the osmotin peptide is the 157th to 165th amino acid sequence of the osmotin protein.
  • a high-calorie diet was used for two months, and overweight rats, leptin-deficient animal models, OB / OB mice and leptin receptor-deficient animal models, DB / DB mice, were used.
  • the experimental group was subjected to a high-calorie diet for 2 months, using 5 model rats, 5 OB / OB mice and 5 DB / DB mice made overweight, and injected with 5 ⁇ g / g of osmotin peptide.
  • the control group was injected with saline instead of osmotin peptide.
  • the control group and the experimental group measured the daily feed amount in the same manner, so that the daily basic diet was not exceeded.
  • the dietary limit was based on the creation of a high-fat dietary animal model and provided 13 g of feed based on the measurement of the average weekly diet (12.8 g of average feed decrease per week per cage). Except for feed, the other elements provided the same environment as the general experimental animals. There was no restriction on rehydration, and the day and night were maintained every 12 hours.
  • the dose of the control group was 150 ⁇ l of saline (intraperitoneal Administration; I.P.) and the control group was administered intraperitoneal administration (I.P.) of 150 ⁇ l of osmotin protein.
  • the duration of drug administration was 4 times for 2 weeks for OB / OB mice and 6 times for 3 weeks for DB / DB mice.
  • test items were liver function test.
  • the serum levels of AST and ALT were measured, and renal function test was performed for BUN and creatine test.
  • Blood collection method The blood was collected by heart puncture with a 5cc syringe with a 23gage needle.
  • Proteins extracted from the tissues of the model mice were separated using 10% SDS-PAGE and transferred to nitrocellulose membrane.
  • the protein-transported membrane was blocked with 3% skim milk containing Tris-buffer saline / Tween 20 solution and washed three times with TBS buffer.
  • pAMPK antibody (Santa Cruz Biotechnology), PPAR- ⁇ antibody (Santa Cruz Biotechnology) and PGC1- ⁇ antibody (Santa Cruz Biotechnology) were applied for antigen antibody reaction.
  • Horseradish perosidase-conjugated secondary antibody was treated to show an immunoreactive band, and then detected by WEST-ZOL plus Western Blot Detection System (iNtRON Biotechnology).
  • the serum content of the aminotransferases AST (aspartate aminotransferase) and ALT (alanine aminotransferase) was decreased by treatment with osmotin protein in OB / OB and DB / DB mice. It was confirmed.
  • osmotin peptide was added in an amount of 150 ⁇ l, once every two days, for a total of 10 Intraperitoneal injection was administered five times during the day, and blood was collected to measure total cholesterol (A), triglyceride (B), high density lipoprotein cholesterol (C) and low density lipoprotein cholesterol (D). The content of triglyceride and low density lipoprotein cholesterol was reduced, and the content of high density lipoprotein cholesterol was improved.

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Abstract

La présente invention concerne une composition contenant l'osmotine protéine ou l'osmotine peptide en tant que principe actif pour la prévention, l'amélioration ou le traitement des troubles de la fonction hépatique et de la fonction rénale. Le sang d'un modèle de souris obèses chez qui l'osmotine peptide a été administrée présente une baisse des valeurs numériques de l'ASAT, l'ALAT, BUN et de la créatine, et une hausse des taux d'expression des protéines pAMPK, PPAR-α et PGC1-α, ce qui permet d'activer le métabolisme hépatique.
PCT/KR2016/006426 2015-06-23 2016-06-17 Composition contenant l'osmotine protéine ou l'osmotine peptide en tant que principe actif pour la prévention ou le traitement des troubles de la fonction hépatique et de la fonction rénale WO2016208910A1 (fr)

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KR10-2015-0088960 2015-06-23
KR1020150088960A KR101735057B1 (ko) 2015-06-23 2015-06-23 오스모틴 단백질 또는 오스모틴 펩타이드를 유효성분으로 함유하는 간기능 및 신장기능 장애의 예방 또는 치료용 조성물

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KR20170074209A (ko) * 2015-12-21 2017-06-29 경상대학교산학협력단 오스모틴 또는 이의 활성화된 펩타이드를 함유하는 우울증 예방, 개선 또는치료용 약학적 조성물
WO2018182085A1 (fr) * 2017-03-28 2018-10-04 경상대학교산학협력단 Composition anti-inflammatoire ou immunopotentialisatrice contenant une protéine osmotine en tant que principe actif
CN111690666A (zh) * 2020-07-30 2020-09-22 江苏食品药品职业技术学院 一种重组thaumatin II结构基因、表达载体、生产甜蛋白的方法及应用

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KR20220129802A (ko) 2021-03-17 2022-09-26 고봉기 신장기능 개선용 한방 추출액 및 한방 환

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170074209A (ko) * 2015-12-21 2017-06-29 경상대학교산학협력단 오스모틴 또는 이의 활성화된 펩타이드를 함유하는 우울증 예방, 개선 또는치료용 약학적 조성물
KR101997017B1 (ko) 2015-12-21 2019-10-01 경상대학교산학협력단 오스모틴 또는 이의 활성화된 펩타이드를 함유하는 우울증 예방, 개선 또는치료용 약학적 조성물
WO2018182085A1 (fr) * 2017-03-28 2018-10-04 경상대학교산학협력단 Composition anti-inflammatoire ou immunopotentialisatrice contenant une protéine osmotine en tant que principe actif
CN111690666A (zh) * 2020-07-30 2020-09-22 江苏食品药品职业技术学院 一种重组thaumatin II结构基因、表达载体、生产甜蛋白的方法及应用
CN111690666B (zh) * 2020-07-30 2023-05-05 江苏食品药品职业技术学院 一种重组thaumatin II结构基因、表达载体、生产甜蛋白的方法及应用

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