WO2016208908A1 - Composition containing osmotin peptide as active ingredient for prevention, improvement or treatment of diabetes - Google Patents

Composition containing osmotin peptide as active ingredient for prevention, improvement or treatment of diabetes Download PDF

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WO2016208908A1
WO2016208908A1 PCT/KR2016/006404 KR2016006404W WO2016208908A1 WO 2016208908 A1 WO2016208908 A1 WO 2016208908A1 KR 2016006404 W KR2016006404 W KR 2016006404W WO 2016208908 A1 WO2016208908 A1 WO 2016208908A1
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diabetes
osmotin peptide
osmotin
preventing
composition
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PCT/KR2016/006404
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French (fr)
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, improving or treating diabetes containing osmotin peptide as an active ingredient, and more particularly to preventing, improving or treating diabetes containing osmotin peptide consisting of 9 amino acids as an active ingredient. It relates to a composition for.
  • Diabetes is a type of metabolic disease such as insufficient insulin secretion or normal functioning. It is characterized by high blood sugar, which increases the concentration of glucose in the blood.It causes various symptoms and signs and releases glucose from urine. . Diabetes is divided into type 1 and type 2, type 1 diabetes, previously called 'diabetes mellitus', is a disease caused by not producing any insulin at all. Type 2 diabetes, which is relatively low in insulin, is characterized by insulin resistance, in which the ability of insulin to lower blood sugar is reduced and cells do not effectively burn glucose. This type 2 diabetes seems to be caused by environmental factors such as high calorie, high fat, high protein diet, lack of exercise, stress due to westernization of diet, diabetes can also occur due to specific gene defects, It can also be caused by surgery, infections, or drugs.
  • hyperglycemia At low hyperglycemia, most patients do not feel symptoms or ambiguous, making it difficult to think of diabetes. If your blood sugar goes up a lot, you will be thirsty to drink a lot of water, and your urine volume will go to the toilet often. You will also lose weight. Maintaining hyperglycemia for a long period of time causes a number of complications in the body. Representative complications include retinopathy, renal dysfunction, neuropathy (fever, pain), and an increased risk of cardiovascular disease.
  • Diagnosis of diabetes is called diabetes when blood sugar is measured at 126 mg / dL or more after fasting for 8 hours or more, or 200 mg / dL or more after 2 hours of oral glucose tolerance test. Diabetes mellitus is also diagnosed when drinking too much water, increasing urine, losing weight, and measuring blood sugar above 200 mg / dL, and fasting blood glucose tests should be done after fasting for at least 8 hours.
  • the oral glucose load test takes 2 hours after taking 75 g of glucose solution to measure glucose and takes the glucose solution while fasting. In the case of type 1 diabetes, insulin treatment is necessary. Type 2 diabetes is based on lifestyle correction and may require additional drug administration.
  • Insulin secretagogues include sulfonylurea and meglitinide. Sulfone urea drugs are often prescribed and have no major side effects, except that they can cause hypoglycemic conditions.
  • Amaryl component: glimepiride
  • dimamirong component name: glyclazide
  • daionyl Ingredient name: Glibenclamide
  • Meglitinide a type of insulin secretagogue, is a very fast-acting drug that is taken before meals. Old mitiglinide).
  • Insulin sensitivity improvers are characterized by almost no hypoglycemia when taken alone, metformin, a biguanide-based drug, and avandia (thiazolidinedione), constituent of rosiglitazone, and actose Ingredient Name: pioglitazone).
  • Other drugs include glucoby (component name: acarbose) and basin (component name: voglibose) that delay carbohydrate absorption in the small intestine.
  • new drugs include GLP-1 (glucagon-like), a hormone that lowers blood sugar.
  • GLP-1 agonists developed using the action of peptide-1 (glucagon-like peptide-1), and exenatide and liraglutide.
  • DPP-4 inhibitor that inhibits the action of DPP-4 (dipeptidyl peptidase-4; dipeptidyl peptidase-4), an enzyme that rapidly inactivates GLP-1, is a newly developed drug.
  • DPP-4 dipeptidyl peptidase-4; dipeptidyl peptidase-4
  • an enzyme that rapidly inactivates GLP-1 is a newly developed drug.
  • Sitagliptin gabs (ingredient name: vildagliptin), saxagliptin, and the like.
  • Osmotin derived from plants is involved in fatty acid oxidation regulation, glucose production, phosphorylation (AMP kinase) and signal transduction pathways.
  • Osmotin (24kDa) 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 as an adiponectin and homologue present in animals, and it has been found that adiponectin may have some anti-inflammatory, anti-diabetic and anti-atherogenic ability, and in the case of osmotin, Korea Patent Registration 1308232 is known as a composition for preventing and treating neurological diseases containing osmotin, and Japanese Patent Laid-Open Publication No. 2009-256264 discloses a cosmetic composition containing osmotin, which has an effect related to obesity or diabetes. Molecular Cell, 2005; 17: 171-180).
  • compositions for preventing, improving or treating diabetes are known as a composition for preventing, improving or treating diabetes.
  • the present invention is derived from the above requirements, the present invention relates to a composition for the prevention, improvement or treatment of diabetes mellitus containing osmotin peptide as an active ingredient, the blood glucose content by administration of the osmotin peptide By confirming the decreasing effect, the present invention has been completed.
  • the present invention provides a dietary supplement for the prevention or improvement of diabetes, characterized in that it contains an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
  • the present invention also provides a pharmaceutical composition for preventing or treating diabetes, characterized in that it contains an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
  • the present invention relates to a composition for the prevention, improvement or treatment of diabetes mellitus containing osmotin peptide as an active ingredient, and after inducing obesity by a high-calorie diet for 2 months, administering the osmotin peptide which is the active ingredient of the present invention It was confirmed that the blood glucose content of one group was significantly lower than the blood glucose content of the non-administered group.
  • Figure 1 is a high-calorie diet ingested for two months, and intraperitoneally injected with an osmotin peptide in the overweight model rats for 10 days, the blood glucose content was measured as a control group was not administered osmotin peptide, experimental group Is the group to which osmotin peptide was administered.
  • Figure 2 shows that after intraperitoneal injection of osmotin peptide into OB / OB mice for 10 days, the blood glucose content was measured, and the control group was not administered osmotin peptide, and the experimental group was administered osmotin peptide. .
  • FIG. 3 is a group in which the osmotin peptide was intraperitoneally injected into DB / DB mice for 10 days, and then the blood glucose content was measured, and the control group was not administered with the osmotin peptide, and the experimental group was administered with the osmotin peptide. .
  • Figure 4 shows that after intraperitoneal injection of osmotin peptide into OB / OB mice for 10 days, the blood glycated hemoglobin (HbA1c) content was measured, and the control group was not administered osmotin peptide, and the experimental group received osmotin peptide. Administered group.
  • HbA1c blood glycated hemoglobin
  • FIG. 5 shows the results of measuring the glycated hemoglobin (HbA1c) content in the DB / DB mice after intraperitoneal injection of osmotin peptide for 10 days.
  • HbA1c glycated hemoglobin
  • the present invention (a) is an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1, or (b) one or more amino acid residues in the amino acid sequence of SEQ ID NO: 1 is substituted, deleted or inserted, can prevent or improve diabetes, It relates to a health functional food composition for the prevention or improvement of diabetes containing the osmotin peptide derived from (a) as an active ingredient.
  • the osmotin peptide may reduce the content of glucose and glycated hemoglobin (HbA1c) in the blood, and the osmotin, a source of the osmotin peptide, is derived from plants and is about 150 to 250 amino acids depending on the individual. As a protein composed, the composition of amino acids differs depending on the type of plant.
  • HbA1c glucose and glycated hemoglobin
  • the osmotin protein is contained in the ripened fruits of plants, for example, fruit such as grapes, cultivated tobacco ( Nicotiana tabacum ), orange ( Citrus sinensis ), Chinese ginkgo ( Rosa roxburghii ), potato ( Solanum) tuberosum ), Piper colubrinum , Castor ( Ricinus communis ), Arabidopsis thaliana ) and the like, but the type of osmotin protein used in the present invention is not limited 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 preferably included in an amount of 0.1 to 100% by weight based on the weight of the composition, but is not limited thereto.
  • the composition may be any one selected from beverages, pills, tablets, capsules, and powders. Although it is preferable that the formulation is not limited thereto, the nutraceutical composition of the present invention may be added as it is or prepared with other food or food ingredients, and may be appropriately prepared according to a conventional method.
  • Examples of 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 (a) is an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1, or (b) one or more amino acid residues in the amino acid sequence of SEQ ID NO: 1 is substituted, deleted or inserted, can prevent or treat diabetes It relates to a pharmaceutical composition for the prevention or treatment of diabetes mellitus containing the osmotin peptide derived from (a) as an active ingredient.
  • the osmotin peptide is preferably included in 0.1 to 100% by weight based on the weight of the composition, but is not limited thereto.
  • a carrier, excipient or diluent may be further included.
  • 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.
  • Osmotin peptide used in the present invention is the amino acid sequence of -CTQGPCGPT-, which is the 157th to 165th amino acid sequence of the osmotin protein (DOI: 10.2210 / pdb1pcv / pdb) derived from tobacco ( Nicotiana t abacum ) seeds The resulting peptide was synthesized and used.
  • 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.
  • control group osmotin peptide non-administered group
  • experimental group osmotin peptide-administered group
  • 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 drug was controlled by intraperitoneal administration (I.P.) with 150 ⁇ l of saline, and experimental group was administered with intraperitoneal administration (I.P.) with 150 ⁇ l of osmotin peptide.
  • 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.
  • osmotin peptide In order to confirm the change in the blood glucose content according to the administration of osmotin peptide, 5 ⁇ g / g osmotin peptide was administered to overweight model rats, OB / OB mice, and DB / DB mice that were subjected to a high-calorie diet for 2 months. Was administered by intraperitoneal injection for 10 days in an amount of 150 ⁇ l, and blood was collected. The amount of glucose contained in the collected blood was measured at the Seoul Central Medical Research Institute.
  • HbA1c blood glycated hemoglobin
  • the osmotin peptide is effective in preventing or treating diabetes Confirmed that there is.

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Abstract

The present invention relates to a composition containing osmotin peptide as an active ingredient for the prevention, improvement or treatment of diabetes. Specifically, the present invention provides a composition containing osmotin peptide as an active ingredient for the prevention, improvement or treatment of diabetes by having confirmed that blood glucose content markedly decreased in a model mouse which had obesity induced therein, and then was treated with osmotin peptide.

Description

오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방, 개선 또는 치료용 조성물Composition for the prevention, improvement or treatment of diabetes mellitus containing osmotin peptide as an active ingredient
본 발명은 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방, 개선 또는 치료용 조성물에 관한 것으로, 더욱 상세하게는 9개의 아미노산으로 이루어진 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, improving or treating diabetes containing osmotin peptide as an active ingredient, and more particularly to preventing, improving or treating diabetes containing osmotin peptide consisting of 9 amino acids as an active ingredient. It relates to a composition for.
당뇨병은 인슐린의 분비량이 부족하거나 정상적인 기능이 이루어지지 않는 등의 대사 질환의 일종으로, 혈중 포도당의 농도가 높아지는 고혈당을 특징으로 하며, 고혈당으로 인하여 여러 증상 및 징후를 일으키고 소변에서 포도당을 배출하게된다. 당뇨병은 제1형과 제2형으로 구분되는데, 제1형 당뇨병은 이전에 '소아당뇨병'이라고 불렸었으며, 인슐린을 전혀 생산하지 못하는 것이 원인이 되어 발생하는 질환이다. 인슐린이 상대적으로 부족한 제2형 당뇨병은 혈당을 낮추는 인슐린의 기능이 떨어져 세포가 포도당을 효과적으로 연소하지 못하는 인슐린 저항성(insulin resistance)을 특징으로 한다. 이와 같은 제2형 당뇨는 식생활의 서구화에 따른 고열량, 고지방, 고단백의 식단, 운동 부족, 스트레스 등 환경적인 요인이 크게 작용하는 것으로 보이지만, 이외에 특정 유전자의 결함에 의해서도 당뇨병이 발생할 수 있으며, 췌장의 수술, 감염, 약제에 의해서도 발병할 수 있다. Diabetes is a type of metabolic disease such as insufficient insulin secretion or normal functioning. It is characterized by high blood sugar, which increases the concentration of glucose in the blood.It causes various symptoms and signs and releases glucose from urine. . Diabetes is divided into type 1 and type 2, type 1 diabetes, previously called 'diabetes mellitus', is a disease caused by not producing any insulin at all. Type 2 diabetes, which is relatively low in insulin, is characterized by insulin resistance, in which the ability of insulin to lower blood sugar is reduced and cells do not effectively burn glucose. This type 2 diabetes seems to be caused by environmental factors such as high calorie, high fat, high protein diet, lack of exercise, stress due to westernization of diet, diabetes can also occur due to specific gene defects, It can also be caused by surgery, infections, or drugs.
낮은 고혈당에서는 대부분의 환자들이 증상을 느끼지 못하거나 모호해서 당뇨병이라고 생각하기 어렵다. 혈당이 많이 올라가면 갈증이 나서 물을 많이 마시게 되고, 소변량이 늘어 화장실을 자주 가게 된다. 또한 체중이 빠지게 된다. 오랜 기간 고혈당 상태가 유지되면 신체에서 여러 합병증이 발생하는데, 대표적인 합병으로는 망막병증, 신기능장애, 신경병증(저림, 통증)이 있고, 심혈관계 질환의 위험이 높아지게 된다.At low hyperglycemia, most patients do not feel symptoms or ambiguous, making it difficult to think of diabetes. If your blood sugar goes up a lot, you will be thirsty to drink a lot of water, and your urine volume will go to the toilet often. You will also lose weight. Maintaining hyperglycemia for a long period of time causes a number of complications in the body. Representative complications include retinopathy, renal dysfunction, neuropathy (fever, pain), and an increased risk of cardiovascular disease.
당뇨병의 진단은 증상이 없는 경우 8시간 이상 금식 후에 측정한 혈당이 126mg/dL 이상이거나, 경구 당부하 검사 2시간 후 혈당이 200mg/dL 이상인 경우를 당뇨병이라 한다. 물을 많이 마시거나 소변이 많아지고 체중이 감소하는 동시에 식사와 무관하게 측정한 혈당이 200mg/dL 이상일 때도 당뇨병으로 진단하며, 공복 혈당검사는 적어도 8시간 동안 금식한 후 행해져야 한다. 경구 당부하 검사는 75g의 포도당 용액을 마신 후 2시간 후에 채혈하여 포도당을 측정하며, 금식 상태에서 포도당 용액을 복용하게 된다. 제1형 당뇨병의 경우에는 인슐린 치료가 필요하다. 제2형 당뇨병의 경우에는 생활 습관 교정을 기본으로 하며 추가로 약물 투여가 필요할 수 있다. Diagnosis of diabetes is called diabetes when blood sugar is measured at 126 mg / dL or more after fasting for 8 hours or more, or 200 mg / dL or more after 2 hours of oral glucose tolerance test. Diabetes mellitus is also diagnosed when drinking too much water, increasing urine, losing weight, and measuring blood sugar above 200 mg / dL, and fasting blood glucose tests should be done after fasting for at least 8 hours. The oral glucose load test takes 2 hours after taking 75 g of glucose solution to measure glucose and takes the glucose solution while fasting. In the case of type 1 diabetes, insulin treatment is necessary. Type 2 diabetes is based on lifestyle correction and may require additional drug administration.
먹는 약의 경우 하루 1~3회 복용하며 약의 작용 시간에 따라 먹는 시간이라든지 부작용 등이 조금씩 다르다. 먹는 혈당강하제는 크게 인슐린 분비 촉진제와 인슐린 감수성 개선제로 나뉜다. 인슐린 분비 촉진제는 설폰요소제(sulfonylurea)와 메글리티나이드(meglitinide)계가 있다. 설폰요소제는 흔히 처방되는 약으로, 저혈당 상태를 유발할 수 있다는 것을 제외하고는 큰 부작용이 없는 편이며, 아마릴(성분: 글리메프라이드 glimepiride), 디아미크롱(성분명: 글리클라자이드 gliclazide), 다오닐(성분명: 글리벤클라마이드 glibenclamide) 등이 이에 속한다. 인슐린 분비 촉진제의 일종인 메글리티나이드계는 약효가 매우 빠른 제제로 식전에 복용하며, 노보넘(성분명: 레파글리나이드 repaglinide), 파스틱(성분명: 나테글리나이드 nateglinide), 글루패스트(성분명: 미티글리나이드 mitiglinide) 등이 있다. 인슐린 감수성 개선제는 단독으로 복용 시 저혈당이 거의 없는 것이 특징이며, 바이구아나이드(biguanide) 계열 약물인 메트포르민(metformin)과, 치아졸리딘다이온(thiazolidinedione) 계열의 아반디아(성분명: 로지글리타존 rosiglitazone), 액토스(성분명: 피오글리타존 pioglitazone) 등이 있다. 그 외에 소장에서 탄수화물 흡수를 지연시키는 글루코바이(성분명: 아카보즈 acarbose), 베이슨(성분명: 보글리보스 voglibose) 등이 있고, 최근 신약으로는 혈당을 낮추는 역할을 하는 호르몬인 GLP-1(glucagon-like peptide-1; 글루카곤 유사 펩타이드-1)의 작용을 이용하여 개발된 GLP-1 작용제(agonist)가 있으며, 익스에나티드(exenatide)와 리라글루티드(liraglutide)가 여기에 해당된다. 또한 GLP-1을 신속하게 불활성화시키는 효소인 DPP-4(dipeptidyl peptidase-4; 디펩티딜 펩티데이즈-4)의 작용을 억제하는 DPP-4 억제제(inhibitor)도 최근 개발된 신약이며, 자누비아(성분명: 시타글립틴 sitagliptin), 가브스(성분명: 빌다글립틴 vildagliptin), 삭사글립틴(saxagliptin) 등이 있다. 하지만 이들 각각이 가지고 있는 부작용, 독성 또는 낮은 치료효과로 인해 증진되거나 지속적인 치료효과 및 인체 내에 부작용이 없는 천연물 유래의 당뇨병 치료제는 시급한 실정이다.In the case of medicine to take once or three times a day, depending on the time of action of the drug or side effects slightly different. Eating hypoglycemics are largely divided into insulin secretagogues and insulin sensitivity improvers. Insulin secretagogues include sulfonylurea and meglitinide. Sulfone urea drugs are often prescribed and have no major side effects, except that they can cause hypoglycemic conditions. Amaryl (component: glimepiride), dimamirong (component name: glyclazide), daionyl ( Ingredient name: Glibenclamide). Meglitinide, a type of insulin secretagogue, is a very fast-acting drug that is taken before meals. Old mitiglinide). Insulin sensitivity improvers are characterized by almost no hypoglycemia when taken alone, metformin, a biguanide-based drug, and avandia (thiazolidinedione), constituent of rosiglitazone, and actose Ingredient Name: pioglitazone). Other drugs include glucoby (component name: acarbose) and basin (component name: voglibose) that delay carbohydrate absorption in the small intestine. Recently, new drugs include GLP-1 (glucagon-like), a hormone that lowers blood sugar. There are GLP-1 agonists developed using the action of peptide-1 (glucagon-like peptide-1), and exenatide and liraglutide. In addition, a DPP-4 inhibitor (hibitor) that inhibits the action of DPP-4 (dipeptidyl peptidase-4; dipeptidyl peptidase-4), an enzyme that rapidly inactivates GLP-1, is a newly developed drug. Sitagliptin), gabs (ingredient name: vildagliptin), saxagliptin, and the like. However, due to the side effects, toxicity, or low therapeutic effects of each of them, there is an urgent need for a diabetes-derived therapeutic agent derived from natural products which has no enhanced or continuous therapeutic effects and no side effects in the human body.
한편, 식물에서 유래된 오스모틴은 지방산 산화 조절, 글루코오스 수득, 인산화(AMP 키나아제) 및 신호 변환 경로에 관여한다. 오스모틴(24kDa)은 당분-측정 단백질 타우마틴(sweet-testing protein thaumatin)과 상동성을 가지는 PR-5 패밀리에 포함되는 안정한 단백질이고, 효모에서 세포 내 신호 전달을 유도하는 것으로 알려져 있다. 오스모틴은 열, 산성 및 효소에 저항성을 가지므로 소화에 의해 분해되지 않고 신체를 순환할 수 있다. 이러한 오스모틴은 동물에 존재하는 아디포넥틴과 상동체로 알려져 있는데, 아디포넥틴의 경우 일부 항-염증, 항-당뇨, 항-죽상경화 능력을 가질 가능성이 있다고 밝혀진 바 있고, 오스모틴의 경우, 한국등록특허 제1308232호에 오스모틴을 함유하는 신경질환의 예방 및 치료용 조성물로 알려져 있으며, 일본공개특허 제2009-256264호에 오스모틴을 함유하는 화장품 조성물이 알려져 있고, 비만이나 당뇨병과 관련된 효과가 있다는 것(Molecular Cell, 2005; 17: 171-180)이 알려져 있다. Osmotin derived from plants, on the other hand, is involved in fatty acid oxidation regulation, glucose production, phosphorylation (AMP kinase) and signal transduction pathways. Osmotin (24kDa) 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 as an adiponectin and homologue present in animals, and it has been found that adiponectin may have some anti-inflammatory, anti-diabetic and anti-atherogenic ability, and in the case of osmotin, Korea Patent Registration 1308232 is known as a composition for preventing and treating neurological diseases containing osmotin, and Japanese Patent Laid-Open Publication No. 2009-256264 discloses a cosmetic composition containing osmotin, which has an effect related to obesity or diabetes. Molecular Cell, 2005; 17: 171-180).
하지만, 오스모틴 단백질 서열 중에서 선택된 일부의 서열로 이루어진 특정 펩타이드가 당뇨의 예방, 개선 또는 치료용 조성물로 알려진 바는 없다. However, no specific peptide consisting of a part of the sequences selected from the osmotin protein sequences is known as a composition for preventing, improving or treating diabetes.
본 발명은 상기와 같은 요구에 의해 도출된 것으로서, 본 발명은 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방, 개선 또는 치료용 조성물에 관한 것으로, 혈중 글루코오스의 함량이 오스모틴 펩타이드의 투여에 의해 감소하는 효과를 확인함으로써, 본 발명을 완성하였다.The present invention is derived from the above requirements, the present invention relates to a composition for the prevention, improvement or treatment of diabetes mellitus containing osmotin peptide as an active ingredient, the blood glucose content by administration of the osmotin peptide By confirming the decreasing effect, the present invention has been completed.
상기 목적을 달성하기 위하여, 본 발명은 서열번호 1의 아미노산 서열로 이루어진 오스모틴 펩타이드를 유효성분으로 함유하는 것을 특징으로 하는 당뇨의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In order to achieve the above object, the present invention provides a dietary supplement for the prevention or improvement of diabetes, characterized in that it contains an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
또한, 본 발명은 서열번호 1의 아미노산 서열로 이루어진 오스모틴 펩타이드를 유효성분으로 함유하는 것을 특징으로 하는 당뇨의 예방 또는 치료용 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition for preventing or treating diabetes, characterized in that it contains an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
본 발명은 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방, 개선 또는 치료용 조성물에 관한 것으로, 2개월 동안 고칼로리 식이요법으로 비만을 유도한 후, 본 발명의 유효성분인 오스모틴 펩타이드를 투여한 군의 혈중 글루코오스 함량이 비투여군의 혈중 글루코오스의 함량보다 현저하게 낮아진 효과가 있다는 것을 확인하였다.The present invention relates to a composition for the prevention, improvement or treatment of diabetes mellitus containing osmotin peptide as an active ingredient, and after inducing obesity by a high-calorie diet for 2 months, administering the osmotin peptide which is the active ingredient of the present invention It was confirmed that the blood glucose content of one group was significantly lower than the blood glucose content of the non-administered group.
도 1은 2개월 동안 고칼로리 식이 섭취하여 과체중 상태의 모델쥐에 오스모틴 펩타이드를 10일간 복강 내 주사한 후, 혈중 글루코오스 함유량을 측정한 결과로 대조군은 오스모틴 펩타이드를 투여하지 않은 군이고, 실험군은 오스모틴 펩타이드를 투여한 군이다. Figure 1 is a high-calorie diet ingested for two months, and intraperitoneally injected with an osmotin peptide in the overweight model rats for 10 days, the blood glucose content was measured as a control group was not administered osmotin peptide, experimental group Is the group to which osmotin peptide was administered.
도 2는 OB/OB 마우스에 오스모틴 펩타이드를 10일간 복강 내 주사한 후, 혈중 글루코오스 함유량을 측정한 결과로 대조군은 오스모틴 펩타이드를 투여하지 않은 군이고, 실험군은 오스모틴 펩타이드를 투여한 군이다.Figure 2 shows that after intraperitoneal injection of osmotin peptide into OB / OB mice for 10 days, the blood glucose content was measured, and the control group was not administered osmotin peptide, and the experimental group was administered osmotin peptide. .
도 3은 DB/DB 마우스에 오스모틴 펩타이드를 10일간 복강 내 주사한 후, 혈중 글루코오스 함유량을 측정한 결과로 대조군은 오스모틴 펩타이드를 투여하지 않은 군이고, 실험군은 오스모틴 펩타이드를 투여한 군이다.FIG. 3 is a group in which the osmotin peptide was intraperitoneally injected into DB / DB mice for 10 days, and then the blood glucose content was measured, and the control group was not administered with the osmotin peptide, and the experimental group was administered with the osmotin peptide. .
도 4는 OB/OB 마우스에 오스모틴 펩타이드를 10일간 복강 내 주사한 후, 혈중 당화혈색소(HbA1c) 함유량을 측정한 결과로 대조군은 오스모틴 펩타이드를 투여하지 않은 군이고, 실험군은 오스모틴 펩타이드를 투여한 군이다.Figure 4 shows that after intraperitoneal injection of osmotin peptide into OB / OB mice for 10 days, the blood glycated hemoglobin (HbA1c) content was measured, and the control group was not administered osmotin peptide, and the experimental group received osmotin peptide. Administered group.
도 5는 DB/DB 마우스에 오스모틴 펩타이드를 10일간 복강 내 주사한 후, 혈중 당화혈색소(HbA1c) 함유량을 측정한 결과로 대조군은 오스모틴 펩타이드를 투여하지 않은 군이고, 실험군은 오스모틴 펩타이드를 투여한 군이다.FIG. 5 shows the results of measuring the glycated hemoglobin (HbA1c) content in the DB / DB mice after intraperitoneal injection of osmotin peptide for 10 days. As a result, the control group was not administered osmotin peptide, and the experimental group received osmotin peptide. Administered group.
본 발명은 (a) 서열번호 1의 아미노산 서열로 이루어진 오스모틴 펩타이드이거나, (b) 서열번호 1의 아미노산 서열 내에 하나 이상의 아미노산 잔기가 치환, 결실 또는 삽입되고, 당뇨를 예방 또는 개선할 수 있으며, (a)로부터 유도된 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방 또는 개선용 건강기능식품 조성물에 관한 것이다.The present invention (a) is an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1, or (b) one or more amino acid residues in the amino acid sequence of SEQ ID NO: 1 is substituted, deleted or inserted, can prevent or improve diabetes, It relates to a health functional food composition for the prevention or improvement of diabetes containing the osmotin peptide derived from (a) as an active ingredient.
상기 오스모틴 펩타이드는 혈중 글루코오스 및 당화혈색소(HbA1c)의 함량을 감소시킬 수 있으며, 상기 오스모틴 펩타이드의 소스(source)인 오스모틴은 식물에서 유래된 것으로, 개체에 따라 약 150 내지 250개의 아미노산으로 이루어진 단백질로서, 식물의 종류에 따라 아미노산의 구성은 상이하다. 상기 오스모틴 단백질은 식물체의 숙성한 과일에 함유되어 있는 것으로, 예를 들면, 포도 등의 과일, 재배 담배(Nicotiana tabacum), 오렌지(Citrus sinensis), 중국 해당화(Rosa roxburghii), 감자(Solanum tuberosum), 후추과(Piper colubrinum), 피마자(Ricinus communis), 애기장대(Arabidopsis thaliana) 등에 존재하는 것으로 알려져 있으나, 상기 예에 의해 본 발명에서 사용되는 오스모틴 단백질의 종류가 제한되는 것은 아니다. 즉, 본 발명의 오스모틴 단백질은 그 기원에 제한이 없으며, 상기와 같은 다양한 식물체로부터 유래된 오스모틴 단백질이 사용될 수 있고, 공지된 유전공학적 방법에 따라 인위적으로 합성되어 사용될 수도 있다.The osmotin peptide may reduce the content of glucose and glycated hemoglobin (HbA1c) in the blood, and the osmotin, a source of the osmotin peptide, is derived from plants and is about 150 to 250 amino acids depending on the individual. As a protein composed, the composition of amino acids differs depending on the type of plant. The osmotin protein is contained in the ripened fruits of plants, for example, fruit such as grapes, cultivated tobacco ( Nicotiana tabacum ), orange ( Citrus sinensis ), Chinese ginkgo ( Rosa roxburghii ), potato ( Solanum) tuberosum ), Piper colubrinum , Castor ( Ricinus communis ), Arabidopsis thaliana ) and the like, but the type of osmotin protein used in the present invention is not limited 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.
상기 오스모틴 펩타이드는 조성물의 중량에 대하여 0.1 내지 100 중량%로 포함되는 것이 바람직하지만 이에 한정하지 않으며, 상기 조성물은 음료, 환, 정제(tablet), 캡슐제(capsule), 산제 중에서 선택된 어느 하나의 제형인 것이 바람직하지만 이에 한정하지 않으며, 본 발명의 건강기능식품 조성물은 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 제조될 수 있고, 통상적인 방법에 따라 적절하게 제조될 수 있다. 본 발명의 건강기능식품 조성물을 첨가할 수 있는 식품의 예로는 카라멜, 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올음료 및 비타민 복합제 중에서 선택된 어느 하나의 형태일 수 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다. 즉, 상기 식품의 종류에는 특별한 제한은 없다. The osmotin peptide is preferably included in an amount of 0.1 to 100% by weight based on the weight of the composition, but is not limited thereto. The composition may be any one selected from beverages, pills, tablets, capsules, and powders. Although it is preferable that the formulation is not limited thereto, the nutraceutical composition of the present invention may be added as it is or prepared with other food or food ingredients, and may be appropriately prepared according to a conventional method. Examples of 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.
상기 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 및 천연 풍미제, 착색제 및 증진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알킨산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 또한, 천연 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 상기의 성분은 독립적으로 또는 조합하여 사용할 수 있다. 또한, 본 발명의 건강기능식품 조성물은 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있으며, 상기 천연 탄수화물은 포도당, 과당과 같은 단당류, 말토스, 슈크로스와 같은 이당류, 및 덱스트린, 사이클로덱스트린과 같은 다당류, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이 있다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 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. In addition, the health functional food composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, 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. As the 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.
또한, 본 발명은 (a) 서열번호 1의 아미노산 서열로 이루어진 오스모틴 펩타이드이거나, (b) 서열번호 1의 아미노산 서열 내에 하나 이상의 아미노산 잔기가 치환, 결실 또는 삽입되고, 당뇨를 예방 또는 치료할 수 있으며, (a)로부터 유도된 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방 또는 치료용 약학 조성물에 관한 것이다. 상기 오스모틴 펩타이드는 조성물의 중량에 대하여 0.1 내지 100 중량%로 포함되는 것이 바람직하지만 이에 한정하지 않는다. In addition, the present invention (a) is an osmotin peptide consisting of the amino acid sequence of SEQ ID NO: 1, or (b) one or more amino acid residues in the amino acid sequence of SEQ ID NO: 1 is substituted, deleted or inserted, can prevent or treat diabetes It relates to a pharmaceutical composition for the prevention or treatment of diabetes mellitus containing the osmotin peptide derived from (a) as an active ingredient. The osmotin peptide is preferably included in 0.1 to 100% by weight based on the weight of the composition, but is not limited thereto.
상기 약학 조성물에서 유효성분인 오스모틴 펩타이드 이외에 추가로 담체, 부형제 또는 희석제를 포함할 수 있다. 본 발명의 약학 조성물에 포함되는 약학적으로 허용되는 담체는 제제 시에 통상적으로 이용되는 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤, 에탄올, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. In addition to the osmotin peptide which is an active ingredient in the pharmaceutical composition, a carrier, excipient or diluent may be further included. 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.
본 발명의 약학 조성물은 상기 성분들 이외에 항산화제, 완충액, 정균제, 희석제, 계면활성제, 결합제, 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제 또는 보존제 등을 추가로 포함할 수 있다. 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.
본 발명의 약학 조성물은 경구 또는 비경구 투여할 수 있으며, 바람직하게는 경구 투여 방식으로 적용된다. 본 발명의 약학 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다.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.
이하, 실시예를 이용하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로 본 발명의 범위가 이들에 의해 제한되지 않는다는 것은 당해 기술분야에서 통상의 지식을 가진 자에게 있어 자명한 것이다. Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for explaining the present invention in more detail, it is obvious to those skilled in the art that the scope of the present invention is not limited by them.
[시료][sample]
본 발명에 사용된 오스모틴 펩타이드는 담배(Nicotiana t abacum) 종자로부터 유래한 오스모틴 단백질(DOI:10.2210/pdb1pcv/pdb)의 아미노산 서열 중에서 157번째 부터 165번째의 서열인 -CTQGPCGPT-의 아미노산 서열로 이루어진 펩타이드를 합성하여 사용하였다. Osmotin peptide used in the present invention is the amino acid sequence of -CTQGPCGPT-, which is the 157th to 165th amino acid sequence of the osmotin protein (DOI: 10.2210 / pdb1pcv / pdb) derived from tobacco ( Nicotiana t abacum ) seeds The resulting peptide was synthesized and used.
[실험모델]Experimental Model
고칼로리 식이를 2달간 실시하여 과체중으로 만든 모델쥐, 렙틴(leptin) 결함이 있는 동물모델인 OB/OB 마우스와 렙틴 수용체(leptin receptor)에 결함이 있는 동물모델인 DB/DB 마우스를 사용하였다.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.
실험군은 고칼로리 식이를 2개월 동안 실시하여 과체중으로 만든 모델쥐 5마리, OB/OB 마우스 5마리와 DB/DB 마우스 5마리를 사용하였으며, 5㎍/g의 오스모틴 펩타이드를 주사하여 실험하였다. 대조군은 오스모틴 펩타이드 대신에 염수(Saline)를 주사하였다.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 μg / g of osmotin peptide. The control group was injected with saline instead of osmotin peptide.
[환경설정][Preferences]
대조군(오스모틴 펩타이드 비투여군)과 실험군(오스모틴 펩타이드 투여군)은 동일하게 일일 사료량을 측정하여 일일 기본 식이량이 초과하지 않도록 제공하였다.The control group (osmotin peptide non-administered group) and the experimental group (osmotin peptide-administered group) were equally measured to provide a daily basic diet so as not to exceed.
식이 제한 기준은 고지방 식이 동물모델을 만드는 기준으로 일주일 간의 평균 식이량(케이지당 일주일 간 감소하는 평균 사료량 12.8g)의 측정결과를 기준으로 13g의 사료를 제공하였다. 사료를 제외한 나머지 요소는 일반적인 실험동물과 동일한 환경을 제공하였다. 수분보충에는 제한을 하지 않았고, 12시간 주기로 낮과 밤을 유지하도록 하였다.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.
약물의 투여량은 대조군은 150㎕의 염수(Saline)를 복강 내 (intraperitoneal Administration; I.P.) 투여하였고, 실험군은 150㎕의 오스모틴 펩타이드를 복강 내 (intraperitoneal Administration; I.P.) 투여하였다.The dose of the drug was controlled by intraperitoneal administration (I.P.) with 150 μl of saline, and experimental group was administered with intraperitoneal administration (I.P.) with 150 μl of osmotin peptide.
약물의 투여기간은 OB/OB 마우스의 경우, 2주간 총 4회 투여하였고, DB/DB 마우스는 3주간 총 6회 투여하였다.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.
실시예 1. 혈중 글루코오스 함량의 분석Example 1 Analysis of Blood Glucose Content
오스모틴 펩타이드의 투여에 따른 혈중 글루코오스 함량의 변화 여부를 확인하기 위하여, 고칼로리 식이를 2달간 실시하여 과체중으로 만든 모델쥐, OB/OB 마우스 및 DB/DB 마우스에 5㎍/g의 오스모틴 펩타이드를 150㎕의 양으로 10일간 복강 내 주사로 투여한 후, 채혈하였다. 서울 중앙의학연구소에서 상기 채혈한 혈액에 함유된 글루코오스의 함량을 측정하였다. In order to confirm the change in the blood glucose content according to the administration of osmotin peptide, 5 µg / g osmotin peptide was administered to overweight model rats, OB / OB mice, and DB / DB mice that were subjected to a high-calorie diet for 2 months. Was administered by intraperitoneal injection for 10 days in an amount of 150 μl, and blood was collected. The amount of glucose contained in the collected blood was measured at the Seoul Central Medical Research Institute.
도 1 내지 3에 개시한 바와 같이, 고칼로리 식이를 통한 과체중의 모델쥐 뿐만 아니라 비만쥐인 OB/OB 마우스 및 DB/DB 마우스 모두에서 오스모틴 펩타이드를 투여하지 않은 대조군 대비, 오스모틴 펩타이드 투여군의 혈중 글루코오스 함량이 현저하게 감소하는 것을 확인함으로써, 오스모틴 펩타이드가 당뇨의 예방 또는 치료에 효과가 있다는 것을 알 수 있었다.As shown in Figures 1 to 3, as compared to the control group not administered osmotin peptides in both overweight model mice as well as obese mice OB / OB and DB / DB mice through a high-calorie diet, By confirming that the blood glucose content was significantly reduced, it was found that the osmotin peptide was effective in preventing or treating diabetes.
실시예 2. 혈중 당화혈색소(HbA1c) 함량의 분석Example 2. Analysis of glycated hemoglobin (HbA1c) content in blood
오스모틴 펩타이드의 투여에 따른 혈중 당화혈색소(HbA1c) 함량의 변화 여부를 확인하기 위하여, OB/OB 마우스 및 DB/DB 마우스에 5㎍/g의 오스모틴 펩타이드를 150㎕의 양으로 10일간 복강 내 주사로 투여한 후, 채혈하였다. 서울 중앙의학연구소에서 상기 채혈한 혈액에 함유된 글루코오스의 함량을 측정하였다. 서울 중앙의학연구소에서 상기 채혈한 혈액에 함유된 당화혈색소(HbA1c) 함량을 측정하였다. In order to determine whether the blood glycated hemoglobin (HbA1c) content was changed according to the administration of osmotin peptide, 5 μg / g of osmotin peptide was intraperitoneally in OB / OB mice and DB / DB mice for 10 days. After administration by injection, blood was collected. The amount of glucose contained in the collected blood was measured at the Seoul Central Medical Research Institute. The glycated hemoglobin (HbA1c) content in the collected blood was measured at the Seoul Central Medical Research Institute.
도 4 및 5에 개시한 바와 같이, 오스모틴 펩타이드를 투여하지 않은 대조군 대비, 오스모틴 투여군의 혈중 당화혈색소(HbA1c) 함량이 현저하게 줄어든 것을 확인함으로써, 오스모틴 펩타이드가 당뇨의 예방 또는 치료에 효과가 있다는 것을 확인하였다. As shown in Figures 4 and 5, by confirming that the blood glycosylated hemoglobin (HbA1c) content of the osmotin-administered group is significantly reduced compared to the control group not administered the osmotin peptide, the osmotin peptide is effective in preventing or treating diabetes Confirmed that there is.

Claims (8)

  1. (a) 서열번호 1의 아미노산 서열로 이루어진 오스모틴 펩타이드이거나, (b) 서열번호 1의 아미노산 서열 내에 하나 이상의 아미노산 잔기가 치환, 결실 또는 삽입되고, 당뇨를 예방 또는 개선할 수 있으며, (a)로부터 유도된 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방 또는 개선용 건강기능식품 조성물.(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: 1, preventing or ameliorating diabetes, and (a) Health functional food composition for preventing or improving diabetes containing osmotin peptide derived from.
  2. 제1항에 있어서, 상기 오스모틴 펩타이드는 혈중 글루코오스 및 당화혈색소(HbA1c)의 함량을 감소시키는 것을 특징으로 하는 당뇨의 예방 또는 개선용 건강기능식품 조성물.[Claim 2] The health functional food composition for preventing or improving diabetes of claim 1, wherein the osmotin peptide reduces the content of glucose and glycated hemoglobin (HbA1c) in the blood.
  3. 제1항에 있어서, 상기 오스모틴 펩타이드는 조성물의 중량에 대하여 0.1 내지 100 중량%로 포함되는 것을 특징으로 하는 당뇨의 예방 또는 개선용 건강기능식품 조성물.According to claim 1, wherein the osmotin peptide is a health functional food composition for preventing or improving diabetes, characterized in that it comprises 0.1 to 100% by weight based on the weight of the composition.
  4. 제1항에 있어서, 상기 조성물은 음료, 환, 정제(tablet), 캡슐제(capsule), 산제 중에서 선택된 어느 하나의 제형인 것을 특징으로 하는 당뇨의 예방 또는 개선용 건강기능식품 조성물.According to claim 1, wherein the composition is a beverage, pills, tablets (tablet), capsules (capsule), a dietary supplement composition for preventing or improving diabetes, characterized in that any one selected from powders.
  5. (a) 서열번호 1의 아미노산 서열로 이루어진 오스모틴 펩타이드이거나, (b) 서열번호 1의 아미노산 서열 내에 하나 이상의 아미노산 잔기가 치환, 결실 또는 삽입되고, 당뇨를 예방 또는 치료할 수 있으며, (a)로부터 유도된 오스모틴 펩타이드를 유효성분으로 함유하는 당뇨의 예방 또는 치료용 약학 조성물.(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: 1 to prevent or treat diabetes, and from (a) A pharmaceutical composition for preventing or treating diabetes, including the induced osmotin peptide as an active ingredient.
  6. 제5항에 있어서, 상기 오스모틴 펩타이드는 혈중 글루코오스의 함량을 감소시키는 것을 특징으로 하는 당뇨의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating diabetes of claim 5, wherein the osmotin peptide reduces the content of glucose in the blood.
  7. 제5항에 있어서, 상기 오스모틴 펩타이드는 조성물의 중량에 대하여 0.1 내지 100 중량%로 포함되는 것을 특징으로 하는 당뇨의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating diabetes of claim 5, wherein the osmotin peptide is included in an amount of 0.1 to 100 wt% based on the weight of the composition.
  8. 제5항에 있어서, 상기 유효성분 이외에 추가로 담체, 부형제 또는 희석제를 포함하는 것을 특징으로 하는 당뇨의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating diabetes of claim 5, further comprising a carrier, an excipient, or a diluent in addition to the active ingredient.
PCT/KR2016/006404 2015-06-23 2016-06-16 Composition containing osmotin peptide as active ingredient for prevention, improvement or treatment of diabetes WO2016208908A1 (en)

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Citations (2)

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KR20150064423A (en) * 2013-12-03 2015-06-11 경상대학교산학협력단 Composition for improving cognitive ability comprising osmotin

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KR101308232B1 (en) * 2010-01-19 2013-11-06 경상대학교산학협력단 Composition for preventing and treating neurological disorder comprising osmotin
KR20150064423A (en) * 2013-12-03 2015-06-11 경상대학교산학협력단 Composition for improving cognitive ability comprising osmotin

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