KR20160053820A - Food composition and pharmaceutical composition for improving and preventing diabetes mellitus with a new variety of red pepper (KCTC18413P) - Google Patents

Abstract

The present invention relates to a food composition for improving diabetes mellitus comprising, as an active ingredient, a new variety of red pepper called Capsicumannuum/Hana 4176 (Accession No. KCTC18413P) or an extract thereof, and to a pharmaceutical composition for preventing or treating diabetes mellitus. According to the present invention, the new variety of red pepper called Capsicumannuum/Hana 4176 (Accession No. KCTC18413P) or the extract thereof: increases insulin reactivity in an insulin tolerance test (ITT); increases phosphorylation of Akt protein which is a biomarker of insulin signal transduction; and shows an excellent effect of improving, preventing, or treating diabetes mellitus.

Description

[0001] The present invention relates to a food composition for improving diabetes and a pharmaceutical composition for preventing or treating diabetes, which contains a novel variety of pepper (accession number KCTC18413P) or an extract thereof, and a pharmaceutical composition for preventing or treating diabetes mellitus

The present invention relates to a 'diabetic food composition for improving diabetes' and a 'pharmaceutical composition for the prevention or treatment of diabetes', which contains as an active ingredient a new variety of capsicum ' Capsicum annuum / Hana 4176' (accession number KCTC18413P) will be.

Diabetes mellitus, as well as itself, can lead to various complications leading to death, and the danger is emphasized. The prevalence of diabetes mellitus is high throughout the world. In Korea, the prevalence of diabetes and complications is above the OECD average. As a result, social costs are gradually increasing, which is attracting attention as a task to be solved.

There are two main types of diabetes: first, the pancreatic beta cell function is destroyed, insulin secretion is not done properly and the blood sugar is not controlled. The first type is called insulin secretion, but insulin sensitivity is low. Insulin Type 2 diabetes mellitus does not control blood sugar properly because the signal is not properly transmitted.

Type 1 diabetes mellitus is mostly congenital, and insulin secretion is poor, so it can be managed with simple treatment of insulin.

On the other hand, type 2 diabetes occurs mainly as acquired factors, and it is known that type 2 diabetes occurs mainly due to insulin resistance. In normal people, digestion and absorption after food intake increases glucose in the blood, which facilitates insulin secretion. Cells in each tissue that are supposed to take glucose normally recognize insulin, absorbing sugar, and producing energy or producing glycogen By using sugar according to the purpose, blood sugar is lowered. However, in the case of a person with insulin resistance, the cells in each tissue are less sensitive to insulin, failing to recognize secreted insulin normally, and maintaining proper glucose absorption and utilization, resulting in a high blood glucose level. If insulin does not play a role in insulin resistance, glucose can not be absorbed as an energy source in each tissue, or glucose can not be decomposed into glucose, Eventually leading to type 2 diabetes.

In addition, in the case of type 2 diabetes, insulin is present at a high concentration in the blood, but the insulin sensitivity is low, so that the blood glucose control is not smooth and the insulin is continuously secreted in the pancreatic beta cells. As a result, when type 2 diabetes progresses, the function of the beta cells gradually decreases. Finally, the beta cells are destroyed and the insulin secretion disorder observed in the type 1 diabetes mellitus is accompanied, which makes the treatment very difficult. Therefore, it is very important to maintain and manage insulin sensitivity to prevent type 2 diabetes early on.

There are many factors known to date for insulin resistance such as genetic factors, obesity, stress, abnormal mitochondrial function, and decreased physical activity. However, the precise cause is unclear yet, and exercise and diet management is recommended as an improvement method.

Managing diabetes more effectively involves additional medication in addition to basic exercise and diet management. Currently, type 1 diabetes therapy can be treated simply by administering insulin itself or by stimulating insulin secretion by stimulating beta cells of the pancreas. However, as a type 2 diabetes therapeutic agent, However, there are a variety of adverse drug reactions that are reported to limit the use of drugs. Currently, only Metformin is prescribed to most patients, and Thiazolidinedione and DPP-IV are only limited if necessary. However, all of these cases are caused by few side effects. New drugs and health functional foods with other effective mechanisms are required. Therefore, pharmaceutical companies are interested in the development of diabetes medicines that can control blood sugar, and food companies are also focusing on the development of functional foods that can improve blood sugar control.

Korean Patent No. 10-0626336 entitled "Pharmaceutical Composition and Health Functional Food Containing Chilli Extracts as Active Ingredients" (invention title) includes extracts of Capsicum annuum and a pharmaceutical composition for preventing or treating diabetic complications Compositions and functional foods. In Korean Patent Publication No. 10-2011-0014421 (entitled "Natural Spice for Controlling Blood Glucose in Diabetic Patients"), powders of natural foods having blood glucose controlling effect, including red pepper powder and red pepper seed powder, Discloses natural spices for controlling blood sugar levels in diabetic patients, which can be utilized in food preparation of dietary foods of patients (including obese persons).

The present invention provides a food composition for improving diabetes and a pharmaceutical composition for the prevention or treatment of diabetes by newly discovering a variety of red peppers having the effect of improving or preventing or treating type 2 diabetes through improvement of insulin sensitivity and enhancing insulin responsiveness The purpose.

In order to achieve the above object, the present invention provides a method for improving diabetes mellitus, which comprises, as an effective ingredient, a new variety of red pepper ' Capsicum annuum / Hana 4176' (accession number KCTC18413P) To provide a food composition. The new variety of pepper of the present invention ' Capsicum annuum / Hana 4176' (deposit number KCTC18413P) or an extract thereof exhibits a remarkably superior diabetic improvement effect than conventional saccharified red pepper and endless red pepper. In addition, it has an effect of increasing insulin responsiveness and increasing the degree of phosphorylation of Akt protein, which is an insulin signaling biomarker.

In the food composition for improving diabetes mellitus according to the present invention, the above-mentioned new varieties ' Capsicum annuum / Hana 4176' (accession number KCTC18413P) or an extract thereof is preferably contained in an amount of 0.0001 to 99 wt% It should be included.

In the food composition for improving diabetes mellitus of the present invention, it is preferable that the above-mentioned extract of the new variety of red pepper ' Capsicum annuum / Hana 4176' (accession number KCTC18413P) is preferably 10 μM to 1 mM in concentration.

In the diabetic improvement food composition of the present invention, the above-mentioned extract of the new variety " Capsicum annuum / Hana 4176" (accession number KCTC18413P) is prepared according to a conventional method known in the art, For example, water, anhydrous or lower alcohols having 1-4 carbon atoms, propylene glycol, butylene glycol, glycerin, acetone, ethyl acetate, chloroform, butyl acetate, diethyl For example, a solvent extraction method using an extraction solvent selected from the group consisting of ether, dichloromethane, hexane, and mixtures thereof, supercritical extraction, and ultrasonic extraction.

The food composition for improving diabetes mellitus of the present invention may be, for example, meat, cereal, caffeinated beverage, ordinary beverage, chocolate, bread, snack, confectionery, pizza, jelly, noodle, gum, ice cream, alcoholic beverage, And a health supplementary food.

Meanwhile, the second aspect of the present invention provides a pharmaceutical composition for preventing or treating diabetes, which contains, as an active ingredient, a new variety of red pepper ' Capsicum annuum / Hana 4176' (Accession No. KCTC18413P) or an extract thereof.

In the pharmaceutical composition for preventing or treating diabetes according to the present invention, the above-mentioned new variety ' Capsicum annuum / Hana 4176' (accession number KCTC18413P) or its extract is preferably contained in an amount of 0.0001 to 99 wt% % Should be included.

In the pharmaceutical composition for preventing or treating diabetes according to the present invention, it is preferable that the extract of Capsicum annuum / Hana 4176 (accession number KCTC18413P) of the new variety, red pepper, is preferably 10 μM to 1 mM in concentration.

In the pharmaceutical composition for the prevention or treatment of diabetes according to the present invention, the 'Capsicum annuum one 4176 (accession number KCTC18413P)' extract may be prepared according to a conventional method known in the art, that is, For example, water, anhydrous or lower alcohols having 1-4 carbon atoms, propylene glycol, butylene glycol, glycerin, acetone, ethyl acetate, chloroform, butyl acetate, diethyl ether, A solvent extraction method using an extraction solvent selected from the group consisting of dichloromethane, hexane and a mixture thereof, a supercritical extraction method and an ultrasonic extraction method.

The pharmaceutical composition for the prevention and treatment of diabetes according to the present invention may further comprise, in addition to the active ingredient, a pharmaceutically acceptable carrier, diluent or excipient. Examples of usable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and one or more selected from among them may be used. In case of a pharmaceutical composition for the prevention and treatment of diabetes, it may further include at least one selected from a filler, an anti-coagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent or an antiseptic agent.

Meanwhile, the pharmaceutical composition for the prevention and treatment of diabetes according to the present invention may be in a preferable form depending on the method of use, and it is known in the art to be able to provide rapid, sustained or delayed release of the active ingredient, It is recommended to adopt the method of formulation. Examples of specific formulations include, but are not limited to, PLASTERS, GRANULES, LOTIONS, LINIMENTS, LEMONADES, AROMATIC WATERS, POWDERS, SYRUPS, OPHTHALMIC OINTMENTS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXTRACTS, ELIXIRS, OINTMENTS, FLUIDEXTRACTS, EMULSIONS, ), Suspensions, DECOCTIONS, INFUSIONS, OPHTHALMIC SOLUTIONS, TABLETS, SUPPOSITORIES, INJECTIONS, SPIRITS, CATAPLSMA, ), Capsules, CREAMS, TROCHES, TINCTURES, PASTES, PILLS, soft or hard gelatin capsules.

On the other hand, the dosage of the pharmaceutical composition for the prevention and treatment of diabetes according to the present invention is preferably determined in consideration of the administration method, the age, sex, weight, and severity of the disease. For example, the pharmaceutical composition for the prevention and treatment of diabetes according to the present invention may be administered once or more per day at a dose of 0.00001 to 100 mg / kg (body weight) based on the active ingredient. However, the dosage is only an example and may be changed by a doctor's prescription depending on the condition of the recipient.

The new variety of pepper ' Capsicum annuum / Hana 4176' (Accession No. KCTC18413P) or its extract of the present invention increases insulin responsiveness and increases the degree of phosphorylation of the Akt protein which is an insulin signaling biomarker, Preventive or therapeutic effect.

FIG. 1 is a graph showing the results of a comparison between the groups of 'general diet group', 'high fat diet group', 'high fat diet group and saccharified red pepper group', 'high fat diet and infant fat red pepper fed group'≪ / RTI > No. KCTC18413P).
FIG. 2 is a graph showing the results of a comparison between the 'general diet group', 'high fat diet group', 'high fat diet group and saccharified red pepper fed group', 'high fat diet and infant fat red pepper fed group' (KCTC18413P) was tested in insulin tolerance test by insulin according to body weight.
FIG. 3 shows the result of Western blot analysis of phosphorylation of Akt protein, which is an important factor in insulin signal transduction.

Hereinafter, the structure and function of the present invention will be described in more detail with reference to the following examples. However, the scope of the present invention is not limited to the following examples, but includes modifications of equivalent technical ideas.

[ Experimental Example  1: New variety pepper (Accession number KCTC18413P ) On mouse body weight]

In this experiment, to investigate the effect of a new variety of pepper (Accession No. KCTC18413P) on the body weight of mice, a mouse mouse obtained by crossing C57BL / 6J mouse purchased from a central laboratory animal was used.

Animal experiments were carried out under the permission of Seoul National University Animal Experimental Ethics Committee (IACUC). Feeds were prepared by mixing 60% by weight of high-fat diet provided by harlan with 0.83% by weight of new varieties of pepper (KCTC18413P) . Body weight was measured once a week and expressed as the mean value of five measurements. At this time, the comparative samples were 'high fat diet group', 'high fat diet and low fat diet', 'high fat diet and low fat red pepper diet'.

As a result of the experiment, it was confirmed that 'the group which received the new variety of pepper (KCTC18413P) of the present invention and the high fat diet group' were compared with the control group 'high fat diet group,' 'high fat diet group, Mice were less weight than those fed the infantile red pepper (Fig. 1). FIG. 1 is a graph showing the results of a comparison between the groups of 'general diet group', 'high fat diet group', 'high fat diet group and saccharified red pepper group', 'high fat diet and infant fat red pepper fed group' ≪ / RTI > No. KCTC18413P).

[ Experimental Example  2: New variety pepper (Accession number KCTC1 8413P) to improve insulin sensitivity and measure insulin responsiveness improvement effect]

In this Experimental Example, the insulin resistance test (ITT) was performed when the weight of the mouse used for body weight measurement was significantly different from that of the seventh week in Experimental Example 1.

The mice were fasted for 5 to 6 hours, and insulin (Sigma-Aldrich) was diluted in phosphate buffered saline (PBS), and 0.75 units / kg of insulin was intraperitoneally administered. Blood was collected from mouse tail vein at 0, 15, 30, 60, 90, and 120 minutes after administration, and blood glucose was measured by measuring with an AccuCheck blood glucose meter by Roche Diagnostics Inc. At this time, the comparative samples were 'high fat diet group', 'high fat diet and low fat diet', 'high fat diet and low fat red pepper diet'.

As a result of the experiment, the group of 'the new variety of pepper (the accession number KCTC18413P) and the group which received the high fat diet together' were compared with the high fat diet group, the high fat diet group and the saccharified red pepper fed group, (Fig. 2), which is similar to that of the normal diet group. FIG. 2 is a graph showing the results of a comparison between the 'general diet group', 'high fat diet group', 'high fat diet group and saccharified red pepper fed group', 'high fat diet and infant fat red pepper fed group' (KCTC18413P) was tested in insulin tolerance test by insulin according to body weight.

[ Experimental Example  3: New variety pepper (Accession number KCTC1 8413P) to improve insulin signaling]

In Experimental Example 2, tissue samples were collected at the time of mouse sacrifice in Experimental Example 2, placed in liquid nitrogen, stored in a deep freezer at a temperature of 80 ° C, and gastrocnemius muscle (GAS) To insulin response to insulin.

It is a place where it is mainly analyzed when you see reactivity to insulin in mouse muscle. At the time of mouse sacrifice, insulin was intraperitoneally injected 18 minutes later, the spleen was collected and stored at -80 ° C. To compare the degree of protein phosphorylation in tissues, 10 mM Sodium fluoride, a phosphate phosphatase inhibitor, NaF) and 1 mM phenylmethylsulfonylfluoride (PMSF) which is a protease inhibitor.

To remove the protein from the muscle tissue, take a small amount of tissue from the muscle, place it in an eppendorf tube, add 500 μl of RIPA buffer (Cell signaling, Beverly, MA), cut into small pieces with sterilized scissors, For 3 minutes using a homogenizer.

Then, it was centrifuged at 14000 rpm for 10 minutes, and the process of taking only the supernatant was repeated to obtain proteins excluding fat and other debris.

The protein thus obtained was quantified by the lowry method using a protein quantification kit (Bio-Rad Corp., Richmond, Calif., USA), and about 80 μg of protein from each protein extract was subjected to western blotting Western blot) to confirm Akt phosphorylation. The cells were separated by electrophoresis in 10% SDS-PAGE and reacted using a phosphorylated Akt antibody (Cell Signaling, Beverly, MA). The cells were detected in an ECL kit (Amersham, Life Science, Denver, USA) Respectively.

As a result of the experiment, it was confirmed that the degree of increase of phosphorylation of Akt protein according to insulin administration was higher than that of high protein phosphorylation in the high-fat group, in the group fed with the new variety pepper (KCTC18413P) It was confirmed that the new variety pepper (accession number KCTC18413P) improved insulin sensitivity and improved insulin responsiveness (Fig. 3). FIG. 3 shows the result of Western blot analysis of phosphorylation of Akt protein, which is an important factor in insulin signal transduction.

[ Example 1: diabetes  Preparation of Food Composition for Improvement]

In this Example, a food composition for diabetic improvement was prepared as follows.

(1) Manufacturing of wire

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and then the mixture was prepared into powder having a particle size of 60 mesh by a pulverizer. Black beans, black sesame seeds and perilla seeds were each steamed and dried by known methods, and then power distribution and pulverization were carried out to prepare powder having a particle size of 60 mesh. Thereafter, 3 wt% of powder of a new variety of red pepper (KCTC18413P), 30 wt% of brown rice, 15 wt% of yulmu, 20 wt% of barley, 9 wt% of glutinous rice, 7 wt% of perilla, 8 wt% 0.5% by weight of manure, and 0.5% by weight of sulfur.

(2) Production of chewing gum

Chewing gum was prepared in a conventional manner by mixing 20% by weight of a gum base, 76.9% by weight of sugar, 1% by weight of a flavor, 2% by weight of water and 0.1% by weight of an extract of a new variety of pepper (KCTC18413P).

(3) Candy manufacturing

Candy was prepared by mixing 60% by weight of sugar, 39.8% by weight of starch syrup, 0.1% by weight of fragrance and 0.1% by weight of an extract of a new variety of red pepper (KCTC18413P).

(4) Manufacturing of biscuits

By weight of starch, 0.77% by weight of glucose, 0.78% by weight of glucose, 11.78% by weight of palm shortening, 1.54% by weight of ammonia, 0.17% by weight of sodium bicarbonate, 0.16% by weight of sodium bisulfite 1.45 wt% of rice flour, 0.0001 wt% of vitamin B, 0.0001 wt% of vitamin B, 0.04 wt% of milk fractions, 20.6998 wt% of water, 1.16 wt% of whole milk powder, 0.29 wt% 0.29% by weight of spray salt and 7.27% by weight of spray oil and 1% by weight of powder of a new variety of red pepper (KCTC18413P) were mixed in a usual manner to prepare a biscuit.

(5) health drink manufacturing

0.0001% by weight of honey, 0.0002% by weight of chitosanic acid amide, 0.0004% by weight of nicotinic acid amide, 0.0001% by weight of sodium riboflavin hydrochloride, 0.0001% by weight of pyridoxine hydrochloride, 0.001% by weight of inositol, 0.002% by weight of orthoacids, , And 1% by weight of the 1-mM concentration of the new variety of pepper (Accession No. KCTC18413P) obtained by extracting the juice was blended to prepare a health drink by a conventional method.

(6) Production of sausages

1% by weight of powder of 65.18% by weight of pork, 25% by weight of chicken meat, 3.5% by weight of starch, 1.7% by weight of soybean protein, 1.62% by weight of salt, 0.5% by weight of glucose and 1.5% by weight of glycerin and a red pepper (KCTC18413P) And sausages were prepared in a conventional manner.

(7) Health supplement manufacturing

A mixture of 55% by weight of spirulina, 10% by weight of guar gum enzyme hydrolyzate, 0.01% by weight of vitamin B hydrochloride, 0.01% by weight of vitamin B6 hydrochloride, 0.23% by weight of DL-methionine, 0.7% by weight of magnesium stearate, And 10% by weight of an extract of a new variety of pepper (Accession No. KCTC18413P) were blended to prepare a refillable health supplement food.

[ Example  2: Preparation of pharmaceutical composition for prevention or treatment of diabetes]

In this Example, a pharmaceutical composition for the prevention or treatment of diabetes was prepared as follows.

(1) Manufacture of powders

A mixture of 2 g of the extract of New Variety Red Pepper (Accession No. KCTC18413P) and 1 g of lactose was mixed and filled in airtight bags to prepare powders.

(2) Preparation of tablets

100 mg of the extract of the new variety, KCTC18413P (accession number KCTC18413P), 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate were mixed and tableted by a conventional tabletting method.

(3) Manufacture of capsules

100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate were mixed with a new variety of pepper (accession number KCTC18413P) extract, and the mixture was filled in gelatin capsules to prepare capsules.

(4) Injection preparation

An injection was prepared by dissolving 100 mg of the extract of New Variety Red Pepper (Accession No. KCTC18413P) in distilled water in an appropriate amount, adjusting the pH to about 7.5, and filling and sterilizing the ampule of 2 mg capacity.

Korea Biotechnology Research Institute KCTC18413P 20151019

Claims (4)

A diabetic food composition for improving diabetes characterized by containing as an active ingredient a new variety of capsicum " Capsicum annuum / Hana 4176" (accession number KCTC18413P) or an extract thereof.
The method according to claim 1,
The above-mentioned extract of the new variety, ' Capsicum annuum / Hana 4176' (Deposit No. KCTC18413P)
Wherein the concentration is 10 μM to 1 mM.
A pharmaceutical composition for the prevention or treatment of diabetes characterized by containing as an active ingredient a new variety of capsicum " Capsicum annuum / Hana 4176" (accession number KCTC18413P) or an extract thereof.
5. The method of claim 4,
The above-mentioned extract of the new variety, ' Capsicum annuum / Hana 4176' (Deposit No. KCTC18413P)
Wherein the concentration is 10 [mu] M to 1 mM.

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