KR101355830B1 - Pharmaceutical compositions and functional food for diabetes prevention comprising allyl isocyanate - Google Patents

Abstract

The present invention relates to pharmaceutical compositions and health functional foods for preventing or treating diabetes, comprising allyl isocyanate as an active ingredient. The pharmaceutical compositions and health functional foods of the present invention can reduce blood glucose and blood sugar in the body and improve insulin sensitivity, by comprising, as an active ingredient, allyl isocyanate derived from the mustard family plants.

Description

Pharmaceutical compositions and functional food For diabetes prevention comprising allyl isocyanate}

The present invention relates to a pharmaceutical composition and health functional food for preventing or treating diabetes containing allyl isocyanate as an active ingredient which can reduce glucose and blood glucose in the body and increase the sensitivity of insulin.

Diabetes is a disease in which glucose in the blood is excreted through urine and is one of the chronic degenerative diseases that is not fundamentally cured. In modern times, due to changes in diet and lack of exercise, a great change occurred in the body's own energy metabolism process, resulting in an increase in chronic degenerative diseases such as diabetes.

Diabetes prevalence is known to reach 5 to 10% in Korea and is showing a continuous increase. In the United States, diabetes has increased six-fold over the last 40 years, and this growth rate is projected to reach 26 million in 2050.

Diabetes is a metabolic syndrome characterized by hyperglycemia caused by a deficiency in insulin action, insulin secretion, or both. The causes of diabetes are various, such as insulin resistance due to autoimmune mechanism, and in most patients, insulin secretion disorder and insulin resistance are often present at the same time. This diabetes causes chronic hyperglycemia and causes disorders in lipid and protein metabolism as well as carbohydrate metabolism, leading to complications such as retina, kidney, nerve, and cardiovascular system.

In diabetes, oxidative stress is considered to be the cause of insulin resistance, type 1 and type 2 diabetes (Ceriello et al. Metabolism 2000; 49:27). Hyperglycemia causes oxidative stress in the body, leading to superoxide ions, glycosylation of proteins, and automatic oxidation of glucose (Brownlee. Nature 2001; 414: 813, Baynes.Clin Chem Lab Med 2003; 41: 813, Wollff et al. Biochem J 1987; 245: 243, Wolff Free Radic Biol Med 1991; 10: 339).

Type 2 diabetes and its complications should be treated naturally through the diet and lifestyle of daily life in the long term, so toxic drugs have limitations, and safe diabetes prevention and treatment without side effects that can be taken in the form of food in the long term Is urgently needed.

Accordingly, there is a need for a preventive and therapeutic agent for diabetes using a material that is not toxic.

An object of the present invention to provide a pharmaceutical composition for preventing or treating diabetes containing allyl isocyanate as an active ingredient capable of reducing glucose and blood glucose in the body and increasing the sensitivity of insulin.

In addition, another object of the present invention to provide a health functional food containing allyl isocyanate as an active ingredient.

The pharmaceutical composition for preventing or treating diabetes of the present invention for achieving the above object may contain allyl isocyanate as an active ingredient.

The allyl isocyanate may be derived from a mustard plant, and the mustard plant may be cabbage, cabbage, turnip, broccoli or mustard.

The allyl isocyanate may be obtained from leaves, fruits or seeds of the mustard plant.

The content of the allyl isocyanate may be 0.001 to 15% by weight based on the total pharmaceutical composition.

Health functional foods for preventing or improving diabetes of the present invention for achieving the above another object may contain allyl isocyanate as an active ingredient.

The health functional food may be for lowering blood sugar, and may be selected from the group consisting of capsules, tablets, powders, granules, liquids, pills, flakes, pastes, syrups, gels, jellies, and bars.

The pharmaceutical composition for preventing or treating diabetes containing allyl isocyanate of the present invention as an active ingredient is excellent in preventing and treating diabetes because it reduces glucose and blood glucose in the body and increases the sensitivity of insulin.

In addition, since the pharmaceutical composition for preventing or treating diabetes of the present invention is not toxic, it can be ingested in the form of food, which can prevent diabetes and diabetic complications through diet and lifestyle of daily life in the long term, and is useful as a diabetic treatment agent. It may be commercially available.

In addition, the health functional food of the present invention can prevent or improve diabetes.

FIG. 1 is a graph showing weekly fasting blood glucose levels for the AIN-76 experimental diet group and the AIN-76 experimental diet group and orally administered allyl isocyanate.
Figure 2 is a graph showing changes in blood glucose levels over time after treatment with the AIN-76 dietary group and the AIN-76 experimental diet and the group orally administered allyl isocyanate at the same time as the IP ITT method.
Figure 3 is a graph showing the cumulative concentration of blood sugar by treatment with the AIT-76 experimental diet group and the AIN-76 experimental diet and the group orally administered allyl isocyanate at the same time as the IP ITT method.
4 is a graph showing changes in blood glucose over time after glucose administration by treatment with the AIN-76 dietary group and the AIN-76 experimental diet with the group administered orally with allyl isocyanate at the same time as the IP GTT method.
FIG. 5 is a graph showing the cumulative concentration of blood glucose by treatment with the AIN-76 dietary group and the AIN-76 experimental diet with the group administered orally with allyl isocyanate by the IP GTT method.
Figure 6 is a graph showing the results of measurement of glycated hemoglobin in the group orally administered allyl isocyanate at the same time as the AIN-76 diet.
Figure 7 is a graph showing the survival rate of NIT-1 pancreatic cells treated with allyl isocyanate (AIC) and allyl isocyanocyanate (AITC).

The present invention relates to a pharmaceutical composition and health functional food for preventing or treating diabetes containing allyl isocyanate as an active ingredient which can reduce glucose and blood glucose in the body and increase the sensitivity of insulin.

Hereinafter, the present invention will be described in detail.

The pharmaceutical composition and health functional food for preventing or treating diabetes of the present invention include allyl isocyanate as an active ingredient, and the allyl isocyanate is derived from a mustard plant.

The mustard plant is one selected from the group consisting of cabbage, cabbage, turnip, broccoli and mustard, and allyl isocyanate is obtained from the leaves, berries or seeds of the plant. Specifically, allyl glucosinolate, a glucosinolate present in mustard plants, such as sinigrin, is present in the tissues when grinding leaves, fruits or seeds of mustard plants. Hydrolysed by Cioglucosidase to form allyl isocyanate.

The pharmaceutical composition for preventing or treating diabetes containing allyl isocyanate of the present invention as an active ingredient comprises allyl isocyanate at 0.001 to 15% by weight, preferably 0.01 to 12% by weight, based on the total weight of the pharmaceutical composition.

 The pharmaceutical composition for preventing or treating diabetes may be formulated in various oral or parenteral dosage forms.

Formulations for oral administration include, for example, tablets, pills, hard capsules, soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. These formulations may contain diluents (e.g., lactose, dextrose, water, etc.) in addition to the active ingredients. Cross, mannitol, sorbitol, cellulose and / or glycine), lubricants such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols. The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally starch, agar, alginic acid. Or disintegrant or boiling mixtures such as sodium salts thereof and / or absorbents, colorants, flavors and sweeteners. The formulations may be prepared by conventional mixing, granulating or coating methods.

Representative of parenteral formulations are also injectable preparations, which may include water, Ringer's solution, isotonic saline or suspensions as solvents for injectable preparations. Sterile fixed oils of the injectable preparations may be used as solvents or suspending media and any non-irritating fixed oil may be used for this purpose, including mono- and di-glycerides. In addition, the injectable preparation may use a fatty acid such as oleic acid.

The dosage of the pharmaceutical composition for preventing or treating diabetes containing allyl isocyanate of the present invention as an active ingredient depends on the age, sex, weight, and severity of the disease of the patient, but the pharmaceutical composition of the present invention is used per 1 kg of the patient's weight. 300 mg or less, preferably 100 to 200 mg is administered 1 to 4 times a day, but is not limited thereto.

The health functional food for preventing or improving diabetes containing allyl isocyanate of the present invention as an active ingredient can be used for lowering blood sugar, and contains 0.0001 to 10% by weight of allyl isocyanate based on the total weight of the health functional food.

The health functional food is made up of capsules, tablets, powders, granules, liquids, pills, tablets, pastes, syrups, gels, jelly and bars for the purpose of supplementing nutrients that may be lacking in daily meals or supplementing functional ingredients useful to the human body. It is selected from the group and one-time preparation is easily manufactured and operated.

In addition, the health functional food is glucose, citric acid, liquid oligosaccharides, corn syrup (corn syrup), soy lecithin, butter, vegetable cured, skim milk, sugar, margarine, salt, starch, flour, syrup, maltose, It may be prepared using commonly used ingredients such as sodium bicarbonate and sugar esters.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention. Such variations and modifications are intended to be within the scope of the appended claims.

Mouse preparation

Experimental animals were 5 weeks old male C57BLKS / J Iar- + Lepr ^db / + Lepr ^db 20 mice were purchased from Korea Research Institute of Bioscience and Biotechnology (Daejeon, Korea). One week before the start of the experiment, two groups of mice were reared for 4 weeks by randomized block design. The diet used in this experiment was the AIN-76 basic experimental diet, and all test substances were orally administered at the same time every day.

2 groups of mice

A: 10 AIN-76 dietary groups (comparative)

B: 10 allyl isocyanate (AIC) 25 mg / kg oral administration group at the same time as the AIN-76 experimental diet (Example)

Test Example  1. Blood glucose measurement

The diets of group A and B mice were removed before fasting and fasted for 4 hours, and then collected from the tail vein in a fasted state, and the fasting blood glucose level was measured using a blood glucose meter (G-doctor, Greencross, Korea). , 2, 3 and 4 weeks were measured, the average value is shown in FIG.

As shown in FIG. 1, the group B mice orally administered with allyl isocyanate were found to inhibit fasting blood glucose elevation as compared to the group A mice not administered with allyl isocyanate. Therefore, it can be seen that allyl isocyanate has a blood glucose raising inhibitory effect.

Test Example  2. IP ITT ( Abdominal cavity  Insulin resistance test)

The diets of group A and B mice were removed before fasting and fasted for 4 hours, and then collected from the tail vein in a fasted state, and glucose levels were measured using a blood glucose meter (G-doctor, Greencross, Korea). Insulin solution containing sterile insulin (using sterile water for injection, stored at 4 ° C.) was administered to the abdominal cavity of mice, and glucose levels were measured at 15, 30, 60, 90 and 120 minutes using a blood glucose meter. And 3.

As shown in Figures 2 and 3, it was confirmed that the group B mice orally administered allyl isocyanate effectively induces blood glucose reduction effect by insulin as compared to the group A mice not administered allyl isocyanate. In addition, the blood glucose concentration (area under curve, AUC) was also found to be lower than the group A mice to which allyl isocyanate was administered.

The results show that allyl isocyanate increases insulin sensitivity.

Description of insulin sensitivity is as follows.

Insulin plays an important role in the use of glucose in the blood as an energy source, supplying glucose to each cell through the insulin receptor on each cell membrane. However, when each cell's insulin receptors are less sensitive, the cells do not recognize the arrival of the glucose and cannot absorb it properly, so the remaining glucose floats the blood and raises the blood sugar.

In addition, if insulin resistance persists for a long time with low insulin sensitivity, our body's ability to make insulin hits the limit, which reduces insulin secretion. When this balance is broken, blood sugar rises due to insufficient insulin secretion. This leads to higher insulin resistance.

Test Example  3. IP GTT ( Abdominal cavity Glucose  Tolerance test)

The diets of group A and B mice were removed before fasting and fasted for 4 hours, and then collected from the tail vein in a fasted state, and glucose levels were measured using a blood glucose meter (G-doctor, Greencross, Korea). Glucose solution containing glucose (using sterile water for injection, stored at 4 ° C.) was administered to the abdominal cavity of mice, and glucose levels were measured at 15, 30, 60, and 120 minutes using a blood glucose meter. Indicated.

As shown in Figure 4 and 5, the group B mice orally administered with allyl isocyanate slightly lower glucose levels up to 30 minutes compared to the group A mice, it was confirmed that after that it is significantly lower. In addition, the blood glucose concentration (area under curve, AUC) was also found to be lower than the group A mice to which allyl isocyanate was administered.

The results show that allyl isocyanate increases insulin sensitivity.

Test Example  4. Glycosylated hemoglobin ( HbA1c ) Measure

After 4 weeks of experiment, group A and B mice were fasted for 12 hours prior to dissection, and blood was collected from the tail vein in an empty stomach, and 50 μl of whole blood was mixed in a tube containing a small amount of 500 mM EDTA, followed by in2it Analyzer (Bio-Rad) Using the glycated hemoglobin was measured, the average value is shown in FIG.

Glycated hemoglobin is a form of hemoglobin that is used to determine blood glucose (glucose) levels for long periods of time and is formed by exposure of hemoglobin to high blood glucose. The blood of our body has a life span of about 120 days of red blood cells, and hemoglobin in the red blood cells combine with glucose to form glycated hemoglobin. If the blood sugar is poorly controlled in diabetic patients, the glycated hemoglobin level is increased, and the glycated hemoglobin has a shorter lifespan, so the glycated hemoglobin level reflects the blood glucose level for about 3 months.

As shown in FIG. 6, the group B mice orally administered with allyl isocyanate were found to have lower glycated hemoglobin levels than the group A mice.

Through the above results, it can be seen that allyl isocyanate has a blood glucose control ability by reducing blood glucose.

Test Example  5. Toxicity test

Pancreatic cell lines of mice were treated with allyl isocyanate (AIC) and allyl isocyanate (AITC) for 48 hours, and then cell viability was measured.

As shown in Figure 7, allyl isocyanate (AIC) -treated pancreatic cells were similar to untreated pancreatic cells (control), but allyl isocyanate (AITC) -treated pancreatic cells survived 54.3%. As low as confirmed.

Hereinafter, the formulation examples of the composition containing the allyl isocyanate of the present invention will be described, but the present invention is not intended to limit the present invention but merely to explain in detail.

Formulation example  One. Sanje  Produce

Allyl Isocyanate 500 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2. Preparation of tablets

Allyl isocyanate 300 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3. Preparation of capsules

Allyl Isocyanate 200 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

Allyl Isocyanate 600 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO _{4 ,} 12H ₂ O 26 mg

It is prepared by the above-mentioned component content per ampoule according to the usual injection preparation method.

Formulation example  5. Liquid  Produce

4 g of allyl isocyanate

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added, the above ingredients are mixed, purified water is added, the whole is adjusted to 100 g by adding purified water, and then filled in a brown bottle and sterilized. To prepare a liquid solution.

Formulation example  6. Preparation of Granules

Allyl Isocyanate 1,000 mg

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 [mu] g vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is a composition which is relatively suitable for granules in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above components are mixed according to a conventional granulation method and then granulated. It can be prepared and used in the manufacture of health functional food composition according to a conventional method.

Formulation example  7. Manufacture of functional beverages

Allyl Isocyanate 1,000 mg

Citric acid 1,000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 L container, It is used in the production of the functional beverage composition of the invention.

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (8)

A pharmaceutical composition for preventing or treating diabetes, comprising allyl isocyanate as an active ingredient. The pharmaceutical composition for preventing or treating diabetes of claim 1, wherein the allyl isocyanate is derived from a mustard plant. The pharmaceutical composition for preventing or treating diabetes of claim 2, wherein the mustard plant is cabbage, cabbage, turnip, broccoli or mustard. According to claim 2, wherein the allyl isocyanate is a pharmaceutical composition for preventing or treating diabetes, characterized in that obtained from leaves, berries or seeds of the mustard plant. The pharmaceutical composition for preventing or treating diabetes of claim 1, wherein the content of allyl isocyanate is 0.001 to 15% by weight based on the total pharmaceutical composition. A health functional food for preventing or improving diabetes, which comprises allyl isocyanate as an active ingredient. 7. The dietary supplement for preventing or improving diabetes, wherein the dietary supplement is for lowering blood sugar. The health functional food according to claim 6, wherein the health functional food is selected from the group consisting of capsules, tablets, powders, granules, liquids, pills, flakes, pastes, syrups, gels, jellies and bars.

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