JP2018197220A - Composition for improving metabolic syndrome - Google Patents

Abstract

The present invention provides a composition for improving metabolic syndrome, a composition for improving abnormal lipid metabolism, a composition for improving hyperlipidemia, a composition for improving blood cholesterol, a composition for improving blood glucose level, and the like. A composition for improving metabolic syndrome comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients. [Selection] Figure 3

Description

  The present invention relates to a composition for improving metabolic syndrome.

Major diseases derived from lifestyle include hypertension, hyperlipidemia, arteriosclerosis and the like. These diseases are thought to be one of the main causes of obesity in which fat accumulated in the viscera. Obesity due to the accumulation of fat in the internal organs is mainly caused by lifestyle habits such as an increase in fat intake from meals and a decrease in physical activity. In particular, due to a significant increase in fat intake due to the recent intake of high-fat foods, the frequency of developing obesity due to visceral fat accumulation has increased.
The state in which various pathologies are caused by visceral fat accumulation is called metabolic syndrome, and is one of lifestyle-related diseases that has been attracting attention in recent years. Since metabolic syndrome is based on impaired glucose tolerance and insulin resistance, it is said that special attention is required as a risk factor for adult disease.

In recent years, it has been clarified that the frequency of developing obesity due to visceral fat accumulation has increased, and in periodic health examinations such as at work and school, metabolic syndrome is diagnosed according to the following criteria.
Japan Society of Obesity (2005 criteria)
(1) Abdominal circumference Male 85 cm, Female 90 cm or more Two or more of the following (2) to (4) (2) Neutral fat 150 mg / dL or more and / or HDL cholesterol less than 40 mg / dL (3) Blood pressure systole 130 mmHg or more and / or diastole 85 mmHg or more (4) Fasting blood glucose level 110 mg / dL or more

  Metabolic syndrome may not be a disease state, but as a result of its progression, hyperinsulinemia, hyperlipidemia, lipid metabolism abnormalities, fatty liver, and adult diseases such as arteriosclerosis, myocardial infarction, cerebral infarction, etc. Therefore, it is desired to develop an effective and safe medicine / treatment method for improving metabolic syndrome.

  As described above, since metabolic syndrome is derived from lifestyle habits, it can be improved by improving diet and carrying out appropriate exercise even during lifestyle habits. However, sustaining diet and exercise varies among individuals, and in recent years supplements and health foods for improving metabolic syndrome have been developed.

Patent Document 1 describes that a composition containing bergamotin derived from grapefruit fruit is used as an improving agent for metabolic syndrome.
Patent Document 2 discloses a composition for preventing and improving metabolic syndrome, a composition for preventing and improving blood HDL cholesterol level lowering, and antihyperinsulinemia, which contain three branched chain amino acids of isoleucine, leucine and valine as active ingredients. , Antilipidemia, antihyperlipidemia, anti-fatty liver and anti-arteriosclerotic compositions are disclosed.
Patent Document 3 includes a soy sapogenol B derived from soybean as an active ingredient for suppressing blood sugar level elevation, suppressing blood pressure elevation, improving lipid metabolism, lowering cholesterol, improving metabolic syndrome, suppressing feeding, and preventing obesity A composition is disclosed.
Patent Document 4 proposes a composition for preventing and improving metabolic syndrome, which comprises γ-carboxylated osteocalcin contained in a pork bone extract as an active ingredient.
On the other hand, the present inventors show that a composition containing black ginger extract, ginger extract, baboon extract, Gymnema sylvestre extract, mulberry leaf extract, green tea extract, chitosan, kidney bean extract increases body temperature and promotes energy metabolism. A patent application has already been filed for a composite tablet containing the same (see Patent Document 5).

International Publication No. 2006/077975 International Publication No. 2007/069744 JP, 2006-193941, A JP 2017-039652 A JP 2006-011295 A

The present inventors have been researching food compositions having an effect of improving metabolic syndrome. In the course of this research, it was discovered that a composition containing black ginger extract, gymnema sylvestre extract, mulberry leaf extract, green tea extract, chitosan and kidney bean extract further improves the metabolic syndrome.
That is, the subject of the present invention is a composition for improving metabolic syndrome, a composition for improving abnormal lipid metabolism, a composition for improving hyperlipidemia, a composition for improving blood cholesterol level, a composition for improving blood glucose level, and the like. Is to provide.

The present invention has the following configuration.
(1) A composition for improving metabolic syndrome comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.
(2) A composition for improving abnormal lipid metabolism, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.
(3) A composition for improving hyperlipidemia, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.
(4) A composition for improving blood cholesterol, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.
(5) A composition for improving blood glucose level, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.
(6) As an effective amount per time,
Black ginger extract 100-300mg,
Gymnema sylvestre extract 30-300 mg,
Mulberry leaf extract 100-300mg,
Green tea extract 100-300mg,
Chitosan 50-150mg,
The composition in any one of (1)-(5) containing 1-30 mg of kidney bean extract.

  The present invention provides a new composition for improving metabolic syndrome, a composition for improving lipid metabolism abnormality, a composition for improving hyperlipidemia, a composition for improving blood cholesterol, and a composition for improving blood glucose level.

2 is a graph showing changes in body weight, BMI, and body fat percentage before and after administration of the composition of the present invention and placebo in human clinical trials. It is a graph which shows the variation | change_quantity of abdominal girth, hip girth, abdominal girth (waist) / hip ratio before and after administration of this invention composition and a placebo in a human clinical trial. It is a graph which shows the variation | change_quantity of the abdominal total fat area, the abdominal visceral fat area, and the abdominal subcutaneous fat area before and behind administration of this invention composition and a placebo in a human clinical trial. 2 is a graph showing changes in neutral fat, total cholesterol, LDL cholesterol, and HDL cholesterol before and after administration of the composition of the present invention and placebo in human clinical trials. It is a graph which shows the variation | change_quantity of the blood pressure (systole and diastole) before and after administration of this invention composition and a placebo in a human clinical trial. It is a graph which shows the variation | change_quantity of blood glucose and HbAlc before and after administration of this invention composition and a placebo in a human clinical trial.

The present invention relates to a composition for improving metabolic syndrome, a composition for improving lipid metabolism abnormality, hyperlipidemia, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, Gymnema sylvestre extract, kidney bean extract as active ingredients It is invention which concerns on the composition for improvement, and the composition for blood cholesterol level improvement.
The components of the composition of the present invention will be described.

Black ginger (black ginger) is a plant belonging to the genus Banturcum in the family Ginger, and its scientific name is Kaempferia parviflora. It is distributed in Southeast Asia such as Thailand and is easily available from this region. It is called Krachaidum in the country of origin, and it has been used as a healthy food for many years. In vitro, cyclic AMP phosphodiesterase (hereinafter cAMP-PDE) inhibitory action has been confirmed for 3,5,7,3 ', 4'-pentamethoxyflavone, a kind of polymethoxyflavone contained in black ginger, It has been suggested that increasing the intracellular cAMP concentration activates hormone-sensitive lipase and suppresses fat accumulation due to the promotion of heat production and fatty acidization. As the black ginger extract, an extract extracted using water, a hydrophilic organic solvent, or a mixed solvent thereof is commercially available from Maruzen Pharmaceutical Co., Ltd. and may be used.
The black ginger extract is blended in an amount of 50 to 1000 mg, preferably 100 to 300 mg, particularly preferably 150 mg as a blending amount of the composition of the present invention.

Mulberry leaves are leaves of plants belonging to the genus Mulaceae and have long been used as tea in addition to feeding on silkworms. Typical plants that are called mulberry include M. bombycis, M. laevigata, and M. tiliaefolia. In the present invention, commercially available mulberry leaf extract can be used, and is sold by Nippon Shinyaku Co., Ltd., Toyoda Flavor Co., Ltd. and the like. The mulberry leaf extract is preferably a hot water extract or a hydrous ethanol extract. For example, raw or dried leaves of mulberry leaves are chopped and extracted in hot water for 15 minutes or longer, then concentrated and dried to form powder. In the present invention, as the mulberry leaf extract, not only the powdery product but also a concentrated liquid obtained without drying, a liquid extract obtained without concentration, and the like can be used.
The mulberry leaf extract is blended in an amount of 50 to 1000 mg, preferably 100 to 300 mg, particularly preferably 200 mg as a blending amount of the composition of the present invention.

Green tea extract refers to an extract extracted from camellia plants and tea buds. In general, green tea, which is extracted from water or alcohol and dried, is commercially available. The green tea extract is preferably a water extract. In the present invention, a commercially available green tea extract can be used.
The green tea extract is blended in an amount of 50 to 1000 mg, preferably 100 to 300 mg, particularly preferably 200 mg as a blending amount of the composition of the present invention.

Chitosan is a kind of polysaccharide and is poly-β1 → 4-glucosamine. It is a linear polysaccharide, a 1,4-polymer of glucosamine, and is a polymer with a molecular weight ranging from thousands to hundreds of thousands.
Examples of chitosan used in the present invention include those obtained from cell walls such as crab, shrimp crust, insect crust, squid, mushrooms and filamentous fungi. Preferably, those obtained from crab and shrimp crusts. Chitosan is composed of glucosamine and acetylglucosamine and dissolves in acidic water. The average molecular weight is usually 10,000 or more, but preferably has an average molecular weight of 100,000 or more and a rotational viscosity of 20 mPa · s or more. More preferably, the average molecular weight is 800,000 or more and the rotational viscosity is 100 mPa · s or more. Further, the particle size of chitosan is not particularly limited, but is preferably 30 mesh pass or less, more preferably 80 mesh pass or less. Chitosan is commercially available as a raw material for diet foods and can be used.
Chitosan is blended in an amount of 10 to 500 mg, preferably 50 to 150 mg, particularly preferably 100 mg as a blending amount of the composition of the present invention.

Gymnema is a Gymnema sylvestre that belongs to the genus Musca, native to India, Southeast Asia, China, and other countries. The main component of the extract of Gymnema (Gymnema Sylvestre Extract) is gymnemaic acid, and it is known that the water or alcoholic extract of its leaves has a sweetness-inhibiting effect and an intestinal sugar absorption-inhibiting effect. Gymnema sylvestre extract has an astringent bitter taste, suppresses the sense of sugar and other sweet substances, and loses the taste of other foods and drinks since it does not feel sweet for a while after it is ingested.
Gymnema sylvestre extract is commercially available from Dainippon Meiji Sugar Co., Ltd., and can be used in the present invention.
Gymnema sylvestre extract is blended in an amount of 10 to 5000 mg, preferably 30 to 300 mg, particularly preferably 40 mg as a blending amount of the composition of the present invention.

White kidney bean seeds contain an ingredient that inhibits the activity of α-amylase, a digestive enzyme, and prevents starch from being decomposed into dextrin and glucose. It is commercially available. The kidney bean extract has been confirmed to work as a starch blocker, and also has a function of slowing the absorption of glucose from the digestive tract into the blood, so it is also included in supplements for diabetes and obesity . The kidney bean extract is commercially available from Bioactives Japan Co., Ltd., and can be used in the present invention.
The kidney bean extract is blended in an amount of 0.1 to 100 mg, preferably 1 to 30 mg, particularly preferably 4.8 mg as a blending amount of the composition of the present invention.

The composition of the present invention can be taken as it is or dissolved in water, but is preferably formulated by adding various excipients. Examples of the preparation include granules, tablets, and capsules.
In the preparation, it can be used as long as the purpose of the composition of the present invention is not impaired. Specifically, hemicellulose, lignin, guar gum, konjac mannan, isagole, alginic acid, agar, carrageenan, chitin, carboxymethylcellulose, dietary fiber and thickeners other than vegetables such as calcium, iron, sodium, Minerals such as zinc, copper, potassium, phosphorus, magnesium, iodine, manganese, selenium; fat-soluble or water-soluble vitamins such as vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, niacin, folic acid, pantothenic acid , Glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, phospholipid, gum arabic, xanthan gum, tragacanth gum, locust bean gum, etc. Agents, preservatives / antioxidants, flavor adjusters and flavors, flavoring agents such as sodium chloride, sodium glutamate, glycine, succinic acid, sodium lactate, citric acid, sodium citrate, acetic acid, adipic acid, fumaric acid, apple Acids and other acidulants, maltitol, low-calorie sweeteners such as aspartame, and coloring agents.

Examples of the present invention and test examples are shown below to further explain the present invention.
1. Production of Supplement Tablets Containing Composition The supplement tablets of the present invention were produced.
Table 1 below shows the compounding composition when the composition of the present invention is administered as a supplement tablet. Table 1 shows the content per 4 supplements.
Each component was mixed, granulated, and tableted according to a conventional method at the composition ratio shown in Table 1 to obtain a supplement tablet.

2. Human clinical trials using supplement tablets Human clinical trials using supplement tablets (hereinafter “test food”) and placebo tablets (“placebo food”) having the composition shown in Table 1 were conducted.
(1) Target person In the screening test 1, a subject corresponding to the selection criteria was selected in screening test 1 by measuring body measurements, waist circumference, and hip circumference. Selected subjects were visited and screening test 2 was performed. In screening test 2, blood tests, urine tests, and interviews were conducted. Subject selection is as follows: 1. Women who are 40 to 65 years old Body mass index (BMI) is BMI23kg / ^{m 2} or more 30kg / ^{m 2} less persons, 3. 112 subjects whose abdominal circumference was 80 cm or more and did not meet the following exclusion criteria were selected. The subjects who excluded dropouts and became the final analysis subjects were 44 cases of the composition of the present invention (test food) and 46 placebos. All of the subjects were obese people with high visceral fat accumulation.
Exclusion criteria are as follows.
1) Those who are currently receiving pharmacotherapy or exercise therapy 2) Having diseases such as diabetes, liver disease, kidney disease, heart disease, diseases affecting the secretion of corticosteroids, and other metabolic diseases 3) Those who may have allergic symptoms to the test food 4) Those who are pregnant or who plan to become pregnant or breastfeeding during the test period 5) Influence on body fat and lipid metabolism 6) Those who regularly use dietary medicines (including OTC), quasi-drugs, and health foods 6) Those who are currently on a diet (weight loss) 7) Participate in other clinical trials within the past month 8) Person who is judged to be inappropriate for the examination by the person in charge of the examination

(2) Study design Study design: Randomized double-blind placebo-controlled parallel-group comparative study Study group: 2 groups, 44 compositions of the present invention (test food), 46 placebo Intake method / period: Test food 12 tablets / day (4 tablets x 3 times), taken for 12 weeks Test period: Screening, before ingestion, 4 weeks after ingestion, 8 weeks after ingestion, 12 weeks after ingestion

(3) Test method The person in charge of the test explained the test contents to the test candidates, obtained consent, and then conducted a screening test on the subjects.
In screening test 1, body measurements, waist circumference, and hip circumference measurements were performed, and subjects who met the selection criteria were selected. Selected subjects were visited and screening test 2 was performed. In screening test 2, blood tests, urine tests, and interviews were conducted. From the results of screening test 2, assignment was made after selecting eligible subjects.
Assignments were randomly assigned to test food groups or placebo groups using random numbers by personnel not involved in the study. The assigned subjects were sent to a pre-intake inspection and a pre-intake inspection was conducted. In the pre-intake examination, we conducted interviews, physical measurements, waist circumference, hip circumference measurements, blood pressure measurements, abdominal CT scans, exercise amount surveys (pedometers), and meal surveys. Food intake was started. The subjects were not instructed or instructed lifestyle habits such as dietary restrictions or exercise.
Four weeks after the start of the test food intake, as a test after 4 weeks, an interview, physical measurement, waist circumference, hip circumference measurement, blood pressure measurement, blood test, urinalysis, exercise amount survey (pedometer), meal survey were conducted. . After that, the intake of the test food is continued, and after 8 weeks and 12 weeks after the intake, the interview, physical measurement, waist circumference, hip circumference measurement, blood pressure measurement, blood test, urinalysis, abdominal CT scan, momentum survey (steps) Total) and conducted a meal survey. A diary was recorded during the test food intake period.
In the abdominal CT scan, the central part of the fourth lumbar vertebra was imaged in two slices using a SOMATOM Spirit model 10045692 (Siemens Healthcare GmbH). The total abdominal fat area, abdominal visceral fat area, and abdominal subcutaneous fat area were calculated from the photographed CT images using Somaris / 5.5 VB36A (syngo CT2010.C, Siemens Healthcare).

(4) Examination item / evaluation item Examination contents: Physical examination (height, weight, BMI, body fat percentage), abdominal CT, abdominal circumference, dietary survey, momentum survey Hematology examination: Red blood cell count (RBC), white blood cell count (WBC) , Hematocrit value (Ht), hemoglobin value (Hb), platelet count (PLT)
Blood biochemistry: total protein (TP), albumin (Alb), AST (GOT), ALT (GPT), γ-GT (γ-GTP), total bilirubin (T-Bil), lactate dehydrogenase (LDH) , Alkaline phosphatase (ALP), uric acid (UA), urea nitrogen (BUN), creatinine (Cre), neutral fat (TG), total cholesterol (TC), LDL cholesterol (direct method) (LDL-C), HDL cholesterol (HDL-C), Na, K, Cl, blood glucose level (Glc), HbA1c, insulin (IRI)
Urinalysis: Urine sugar, urine protein, urinary occult blood reaction

(5) Statistical analysis The measurement results are shown in Fig. 1 to Fig. 6 as an average value ± standard error, and Tables 2 to 7 are shown as an average value ± standard deviation. In comparison between test food groups, a paired t-test was performed for data following a normal distribution, and a Wilcoxon signed rank test was performed for data not following a normal distribution. For the time course within the test food group, Dunnett's multiple comparison test was performed after repeated measures analysis of variance for data following normal distribution, and Bonferroni correction was performed after Wilcoxon signed rank test for data not following normal distribution. Statistical processing software is SPSS Ver. 22 (Nippon IBM Corporation) was used. The significance level was set to 5% by two-sided test (#: P <0.05, ##: P <0.01).

(6) Results The evaluation items for metabolic syndrome will be described below separately for physical measurement, abdominal circumference, abdominal fat, and blood test.
1) Body weight, BMI, body fat percentage Measurement results of body weight, BMI, body fat percentage are shown in Table 2 below. In addition, changes in body weight, BMI, and body fat percentage from before administration are shown in FIG.

  In the composition (test food) administration group of the present invention, body weight, BMI, and body fat percentage all decreased. In terms of the rate of change (rate of change), the rate of change in body weight, BMI, and body fat rate significantly decreased compared to the rate of decrease in the placebo group.

2) Waist (abdominal circumference), hip circumference, waist / hip ratio The waist (abdominal circumference), hip circumference, and waist / hip ratio are shown in Table 3 below. Further, FIG. 2 shows changes in waist (abdominal circumference), hip circumference, and waist / hip ratio from before administration.

  In the composition (test food) administration group of the present invention, the waist (abdominal circumference), hip circumference, and waist / hip ratio all decreased. In terms of the rate of decrease (change rate), the amount of change in any of the waist (abdominal circumference), hip circumference, and waist / hip ratio values was significantly larger than the percentage of reduction after administration in the placebo group. Declined.

3) Abdominal total fat area, abdominal visceral fat area, abdominal subcutaneous fat area The abdominal total fat area, abdominal visceral fat area, and abdominal subcutaneous fat area based on CT examination are shown in Table 4 below. Moreover, the change of the abdominal total fat area, the abdominal visceral fat area, and the abdominal subcutaneous fat area from before administration is shown in FIG.

  In the composition (test food) administration group of the present invention, the abdominal total fat area, the abdominal visceral fat area, and the abdominal subcutaneous fat area all decreased. On the other hand, in the placebo group, the total abdominal fat area, abdominal visceral fat area, and abdominal subcutaneous fat area increased or remained unchanged. In addition, in terms of the rate of change (rate of change), the amount of change in any value with respect to the placebo was significantly and greatly reduced.

4) Lipid metabolism The measurement results of neutral fat (triglyceride: TG), total cholesterol (TC), HDL cholesterol, and LDL cholesterol (LDL), which are indicators of lipid metabolism, are shown in Table 5 below. FIG. 4 shows the amount of change in TG, TC, HDL, and LDL from before administration.

  In the composition of the present invention (test food), neutral fat (triglyceride: TG), total cholesterol (TC), and LDL cholesterol were reduced, and lipid metabolism was improved. On the other hand, in the placebo group, neutral fat (triglyceride: TG), total cholesterol (TC), and LDL cholesterol were higher than before administration.

5) Blood pressure Measurement results of systolic blood pressure and diastolic blood pressure are shown in Table 6 below. FIG. 5 shows changes in systolic blood pressure and diastolic blood pressure from before administration.

  As shown in Table 6 and FIG. 5 above, the composition of the present invention (test food) improved the hypertension of the subject and significantly lowered the blood pressure.

6) Sugar metabolism The measurement results of blood glucose, HbAlc, and insulin are shown in Table 7 below. In addition, the amount of change in blood glucose from before administration is shown in FIG.

In the placebo-administered group, blood glucose level and HbAlc increased with time. On the other hand, the blood sugar, HbAlc, and insulin showed a stable or decreasing tendency in the group administered with the present composition (test food).
(7) Discussion As described above, from the results of this test, all of body weight, abdominal circumference, LDL cholesterol, triglyceride, blood sugar, and blood pressure, which are indicators of metabolic syndrome, were reduced by ingestion of the composition of the present invention (test food). From this, it can be determined that the composition of the present invention has an improving effect on the metabolic syndrome.
In addition, the composition of the present invention was found to be useful for improving obesity derived from lifestyle habits, improving neutral fat, improving cholesterol, and improving hyperglycemia.

Claims (6)

  A composition for improving metabolic syndrome, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.   A composition for improving abnormal lipid metabolism, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.   A composition for improving hyperlipidemia, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.   A composition for improving blood cholesterol, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients.   A composition for improving blood glucose level, comprising black ginger extract, mulberry leaf extract, green tea extract, chitosan, gymnema sylvestre extract and kidney bean extract as active ingredients. As an effective amount per time,
Black ginger extract 100-300mg,
Gymnema sylvestre extract 30-300 mg,
Mulberry leaf extract 100-300mg,
Green tea extract 100-300mg,
Chitosan 50-150mg,
The composition in any one of Claims 1-5 containing 1-30 mg of kidney bean extracts.

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