KR102644808B1 - Composition for preventing, ameliorating or treating metabolic disease comprising leaf extract of new pepper cultivar as effective component - Google Patents

Abstract

The new red pepper leaf extract of the present invention reduces body weight, organ weight, blood neutral lipid, total cholesterol, AST (aspartate aminotransferase), and ALT (alanine aminotransferase) content in diabetic disease animal models, and increases HDL (high density lipoprotein) cholesterol content. Since it has an excellent effect, it can be usefully used as a composition for preventing, improving, or treating metabolic diseases caused by diabetes containing it as an active ingredient.

Description

Composition for preventing, ameliorating or treating metabolic disease comprising leaf extract of new pepper cultivar as effective component}

The present invention relates to a composition for preventing, improving or treating metabolic diseases containing extract of new varieties of red pepper leaves as an active ingredient.

If the blood sugar level remains high and is not treated, various complications due to diabetes may occur. Complications caused by diabetes can be broadly divided into acute complications and chronic complications. Acute complications of diabetes refer to a condition in which blood sugar levels rise sharply or drop excessively due to lack of blood sugar control, while chronic complications occur when diabetes is not managed over a long period of time, such as hyperlipidemia, hypercholesterolemia, obesity, liver disease, arteriosclerosis, and cardiovascular disease. Alternatively, there may be metabolic disease (metabolic syndrome) including high blood pressure, eye disease, kidney disease, or neurological disease.

If hyperglycemia continues for a long period of time, lipid deposition occurs inside the blood vessels, and when these symptoms become severe, arteriosclerosis occurs, which impedes the passage of blood and hardens the blood vessels. If a blood vessel with advanced arteriosclerosis is near the heart, angina pectoris or myocardial infarction may occur; if it is near the brain, a stroke may appear; and if it is near the legs, intermittent claudication, etc. may appear. The risk of developing cardiovascular disease in diabetic patients is approximately 2 to 4 times higher than in non-diabetic patients, and it is known that cardiovascular disease is the majority cause of death in diabetic patients.

Therefore, thorough blood sugar management in diabetic patients is very important to prevent complications. To maintain blood sugar within the normal range, you must maintain a regular lifestyle by combining diet, exercise, and drug therapy, and maintain appropriate weight, blood pressure, and blood cholesterol levels. In addition, regular examinations should be performed to determine the occurrence and progression of complications. In the case of type 2 diabetes, it is known that more than 5 to 10% of patients already have complications at the time of diagnosis, so it is recommended to undergo a complication test from the time of diagnosis and check for complications once a year thereafter.

Meanwhile, pepper ( Capsicum annuum ) is a plant belonging to the Solanaceae family and is one of the vegetable crops widely cultivated around the world. Recently, in Korea, the area under cultivation of peppers has been decreasing, and many processed pepper products are being imported from China due to various factors increasing unit prices. Therefore, in order to continuously maintain and develop the Korean pepper industry and create new demand, the development of functional pepper varieties and products is necessary. It is a necessary time. It has been reported that the fruits and leaves of peppers contain a large amount of bioactive substances that have effects such as improving memory, controlling blood pressure, and lowering blood sugar. In addition, red pepper leaves are known to be nutritious foods containing about 45 types of nutrients. The main nutrients are beta-carotene, which is 4 times that of carrots, calcium that is 13 times that of milk, potassium that is 5 times that of peanuts, and vitamin B2 that is 14 times that of spinach. It contains 12 times more essential amino acids than broccoli.

Meanwhile, Korean Patent No. 1344564 discloses ‘A composition for preventing and treating obesity or hyperlipidemia containing pepper and flower extracts, which are the main ingredients of Mara sauce, as active ingredients,’ and Korean Patent No. 1516582 discloses ‘Carnitine palmitoyl. An anti-obesity composition derived from green pepper that can improve the decomposition of fat in adipocytes by promoting the activity of transferase-1 has been disclosed, but the present invention is a 'composition for metabolic diseases containing a new variety of red pepper leaf extract as an active ingredient. There is no description of ‘composition for prevention, improvement or treatment’.

The present invention was developed in response to the above-mentioned needs. As a result of administering a new variety of red pepper leaf extract to an animal model of diabetes, the present inventors found that body weight, organ weight, blood neutral lipid, total cholesterol, AST (aspartate aminotransferase), and ALT (alanine) were The present invention was completed by confirming that the content of aminotransferase) decreased and the content of HDL (high density lipoprotein) cholesterol increased.

In order to solve the above problems, the present invention provides a health functional food composition for preventing or improving metabolic diseases containing a new variety (accession number BP1882979) red pepper leaf extract as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for preventing or treating metabolic diseases containing a new variety (accession number BP1882979) red pepper leaf extract as an active ingredient.

The new red pepper leaf extract of the present invention reduces body weight, organ weight, blood neutral lipid, total cholesterol, AST (aspartate aminotransferase), and ALT (alanine aminotransferase) content in diabetic disease animal models, and increases HDL (high density lipoprotein) cholesterol content. Since it has an excellent effect, it can be usefully used as a composition for preventing, improving, or treating metabolic diseases caused by diabetes containing it as an active ingredient.

Figure 1 shows the results of confirming the weight reduction effect of the new variety of red pepper leaf extract on the liver (A) and epididymis (B). Acarbose is a carbohydrate absorption delay agent and was used as a positive control. *** means that the weight of the liver or epididymis of the control group increased statistically significantly compared to the normal group, p<0.001, and ## means that the weight of the epididymis of the group administered new variety red pepper leaf extract compared to the control group was statistically significant. It means that it decreased significantly, p<0.01.
Figure 2 shows the results of confirming the effect of a new variety of red pepper leaf extract on reducing blood triglyceride (A) and total cholesterol (B) content. Acarbose is a carbohydrate absorption delay agent and was used as a positive control. *** means that the neutral fat or total cholesterol content of the control group increased statistically significantly compared to the normal group, p<0.001, and #, ##, ### indicate that the new variety of red pepper leaf extract group or It means that the neutral fat or total cholesterol content of the acarbose administration group decreased statistically significantly, # is p<0.05, ## is p<0.01, and ### is p<0.001.
Figure 3 shows the results of confirming the effect of the new variety of red pepper leaf extract on increasing the HDL cholesterol content in the blood. Acarbose is a carbohydrate absorption delay agent and was used as a positive control. *** means that the HDL cholesterol content of the control group decreased statistically significantly compared to the normal group, p < 0.001, and #, ## indicate that the HDL cholesterol content of the new variety red pepper leaf extract group or the acarbose group compared to the control group was significantly decreased. It means a statistically significant increase, # means p<0.05, ## means p<0.01.
Figure 4 shows the results of confirming the effect of a new variety of red pepper leaf extract on reducing blood AST (A) and ALT (B) contents. Acarbose is a carbohydrate absorption delay agent and was used as a positive control. *** means that the blood AST or ALT content of the control group increased statistically significantly compared to the normal group, p<0.001, and ### means the blood AST or ALT content of the new variety red pepper leaf extract group or the acarbose group compared to the control group. This means that the ALT content decreased statistically significantly, p<0.001.

In order to achieve the object of the present invention, the present invention provides a health functional food composition for preventing or improving metabolic diseases containing a new variety (accession number BP1882979) red pepper leaf extract as an active ingredient.

The new variety of pepper was developed by the present inventors using a polyploid breeding method, and is a leaf-only pepper with excellent hypoglycemic effect and does not bear fruit, and was named 'Salicho'. Salicho pepper was deposited with the Korea Research Institute of Bioscience and Biotechnology on June 19, 2020 (Deposit number: BP1882979).

The red pepper leaf extract can be prepared by a method comprising the following steps, but is not limited to this:

(1) Extracting by adding an extraction solvent to dried red pepper leaves;

(2) centrifuging the extract of step (1); and

(3) Preparing an extract by drying the centrifuged extract of step (2).

In step (1), the extraction solvent is preferably selected from water, lower alcohols of C ₁ to C ₄ , or mixtures thereof, and more preferably ethanol, but is not limited thereto. In the above manufacturing method, the extraction method can be any conventional method known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. The extraction solvent is preferably added at 1 to 20 times the weight of the red pepper leaves for extraction, more preferably at 5 to 15 times, and even more preferably at 8 times. The extraction temperature is preferably 40 to 70°C, and most preferably 55°C, but is not limited thereto. In addition, the extraction time is preferably 5 to 25 hours, more preferably 10 to 20 hours, and most preferably 15 hours, but is not limited thereto. In step (3), the drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying, or freeze drying, and vacuum drying is most preferable, but is not limited thereto.

In the composition of the present invention, the metabolic disease is preferably any one selected from the group consisting of hyperlipidemia caused by diabetes, hypercholesterolemia, obesity, fatty liver, arteriosclerosis, and cardiovascular disease, but is not limited thereto.

The new variety of red pepper leaf extract is characterized by reducing blood neutral lipid, total cholesterol, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) content, and increasing HDL (high density lipoprotein) cholesterol content.

The health functional food composition is preferably manufactured in a dosage form selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto. The health functional food composition of the present invention can be prepared by adding the new variety of red pepper leaf extract as is or mixing it with other foods or food ingredients, and can be prepared appropriately according to conventional methods. Examples of foods to which the red pepper leaf extract can be added include caramel, meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, and tea. , it may be in any form selected from drinks, alcoholic beverages, and vitamin complexes, and includes all health functional foods in the conventional sense. That is, there are no particular restrictions on the type of food. The health functional food composition includes various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, and protective colloidal thickeners. , pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Additionally, it may contain pulp for the production of natural fruit juice 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 flavoring agents or natural carbohydrates as additional ingredients, and the natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, dextrins, and cyclosaccharides. These are polysaccharides such as dextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The ratio of the natural carbohydrate is not very important, but is preferably 0.01 to 0.04 g, more preferably 0.02 to 0.03 g, per 100 g of the composition of the present invention, but is not limited thereto. As sweeteners, natural sweeteners such as thaumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used.

In addition, the present invention provides a pharmaceutical composition for preventing or treating metabolic diseases containing a new variety (accession number BP1882979) red pepper leaf extract as an active ingredient.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent in addition to the above active ingredients.

The pharmaceutical dosage form of the composition according to the present invention can be used alone or in combination with other pharmaceutically active compounds, as well as in appropriate combinations. The pharmaceutical composition according to the present invention can be formulated and used in the form of oral dosage forms such as capsules, powders, granules, tablets, suspensions, emulsions, syrups and aerosols, external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. You can. Carriers, excipients, and diluents that may be included in the pharmaceutical composition containing the red pepper leaf extract as an active ingredient include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, and gelatin. , calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. can be mentioned. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations are prepared by adding at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. to the red pepper leaf extract. It is prepared by mixing. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, Withepsol, Macrogol, Tween 61, cacao, laurin, glycerogelatin, etc. can be used.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the patient's condition and weight, degree of disease, drug form, administration route and period, but can be appropriately selected by a person skilled in the art.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for illustrating the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited thereto.

Preparation Example 1. Preparation of extract

The new variety of pepper leaves used in the present invention is a new variety (accession number BP1882979) that the present inventors bred using polyploid breeding.

For 250 mg of dried new pepper leaves, 2 ml of 70% (v/v) ethanol was added, extracted at 55°C for 15 hours, and then concentrated in a vacuum centrifugal concentrator. The concentrated pellet was dissolved in 500 ㎕ of sodium phosphate buffer (pH 6.9) and filtered through a syringe filter to obtain a red pepper leaf extract.

animal testing

The experimental animals used were C57BL/KsJ-db/db mice, a type 2 diabetes disease model, purchased from SLC Inc. (Japan) and raised at 22±2°C, 40-60% humidity, and 12-hour light/dark cycle. did. As the normal group, C57BL/KsJ Hetero(m+/db) mice, a normal mouse model, were used. After adapting to the environment for 7 days, type 2 diabetes model mice were randomly assigned to 4 groups of 5 each (diabetic control group, group administered 150 mg/kg of new variety red pepper leaf extract, group administered 300 mg/kg of new variety red pepper leaf extract, and acarbose 50 mg/kg). Animal experiments were conducted by dividing the subjects into two groups (administration group). The new variety of red pepper leaf extract or acarbose was administered orally using a sonde, once a day at the same time.

Example 1. Body weight and dietary efficiency analysis

Body weight was measured once a week at the same time during the total 8-week animal experiment period. Diet was provided once a week, and the weight of the remaining feed was measured after 24 hours, and the amount of food was calculated as the difference between the weight at the time of feeding and the weight of the remaining feed after consumption. Dietary efficiency was calculated by dividing the weight gain over 8 weeks by the total amount of food consumed over 8 weeks.

As a result, it was confirmed that the body weight and dietary efficiency of the diabetic control group increased compared to the normal group, while the body weight and dietary efficiency of the new variety red pepper leaf extract administered group decreased compared to the diabetic control group (Table 1).

Weight and dietary efficiency analysis group Weight (g) weight gain
(g/8 weeks) Dietary Efficiency Initial weight (g) Final weight (g) Jeongsang-gun 21.33 25.78 4.45 1.26±0.85 Diabetic control group 32.08 45.76 13.68 2.71±0.55 New variety of red pepper leaf extract
150㎎/㎏ administration group 31.96 43.95 11.99 2.64±0.49 New variety of red pepper leaf extract
300㎎/㎏ administration group 32.08 42.05 9.97 2.43±0.95 Acarbose administration group 32.08 42.05 9.97 2.90±0.39

Example 2. Organ weight measurements

After a total of 8 weeks of animal testing, the mice were sacrificed, the liver and epididymis were removed, and the weight of each organ was measured.

As a result, it was confirmed that the weight of the liver and epididymis of the diabetic control group increased compared to the normal group, while the weight of the liver and epididymis of the new variety red pepper leaf extract administered group decreased compared to the diabetic control group (Figure 1).

Example 3. Serum analysis

After a total of 8 weeks of animal testing, blood was collected from the abdominal vena cava. Blood triglyceride, total cholesterol, and HDL (high density lipoprotein) cholesterol content were measured using serum obtained by centrifuging the collected blood.

As a result, it was confirmed that the blood triglyceride and total cholesterol contents of the diabetic control group increased compared to the normal group, while the blood triglyceride and total cholesterol contents of the new variety red pepper leaf extract administered group decreased compared to the diabetic control group (Figure 2). In addition, the HDL cholesterol content of the diabetic control group decreased compared to the normal group, while the HDL cholesterol content of the new variety red pepper leaf extract administered group was confirmed to increase compared to the diabetic control group (Figure 3).

Example 4. Analysis of liver function improvement

After a total of 8 weeks of animal testing, blood was collected from the abdominal vena cava. The AST (aspartate aminotransferase) and ALT (alanine aminotransferase) contents in the blood were measured using serum obtained by centrifuging the collected blood.

As a result, it was confirmed that the blood AST and ALT contents of the diabetic control group increased compared to the normal group, while the blood AST and ALT contents of the new variety red pepper leaf extract-administered group decreased compared to the diabetic control group (Figure 4).

Claims (7)

A health functional food composition for preventing or improving one or more metabolic diseases selected from diabetes-induced hyperlipidemia, hypercholesterolemia, obesity, fatty liver, arteriosclerosis, and cardiovascular disease, containing ethanol extract of a new variety of red pepper leaves with accession number BP1882979 as an active ingredient. delete delete delete The method of claim 1, wherein the composition is prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup, and beverage for treating diabetes-induced hyperlipidemia, hypercholesterolemia, obesity, A health functional food composition for preventing or improving one or more metabolic diseases selected from fatty liver disease, arteriosclerosis, and cardiovascular disease. A pharmaceutical composition for the prevention or treatment of one or more metabolic diseases selected from diabetes-induced hyperlipidemia, hypercholesterolemia, obesity, fatty liver, arteriosclerosis, and cardiovascular disease, containing ethanol extract of a new variety of red pepper leaves with accession number BP1882979 as an active ingredient. The method of claim 6, wherein the composition is prepared in any one formulation selected from capsules, powders, granules, tablets, suspensions, emulsions, syrups, and aerosols for hyperlipidemia, hypercholesterolemia, and obesity caused by diabetes. A pharmaceutical composition for preventing or treating one or more metabolic diseases selected from fatty liver disease, arteriosclerosis, and cardiovascular disease.