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

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

Composition for the prevention, improvement or treatment of diabetes mellitus containing osmotin peptide as an active ingredient

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.

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.

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.

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).

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.

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.

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.

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.

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.

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. 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. 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.

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.

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.

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.

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.

[sample]

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.

Experimental Model

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 μg / g of osmotin peptide. The control group was injected with saline instead of osmotin peptide.

[Preferences]

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.

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 μl of saline, and experimental group was administered with intraperitoneal administration (I.P.) with 150 μl 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.

Example 1 Analysis of Blood Glucose Content

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.

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.

Example 2. Analysis of glycated hemoglobin (HbA1c) content in blood

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.

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) 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. [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. 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. 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) 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. The pharmaceutical composition for preventing or treating diabetes of claim 5, wherein the osmotin peptide reduces the content of glucose in the blood.
7. 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. 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.

Images