WO2006064761A1

WO2006064761A1 - Adiponectin regultor and foods, drinks, food aditives and drugs containing the same

Info

Publication number: WO2006064761A1
Application number: PCT/JP2005/022769
Authority: WO
Inventors: Yoko Akazome; Tomomasa Kanda
Original assignee: Asahi Breweries, Ltd.
Priority date: 2004-12-17
Filing date: 2005-12-12
Publication date: 2006-06-22

Abstract

[PROBLEMS] To provide an adiponectin preparation having an effect of regulating adiponectin which is capable of regulating adiponectin, originates in a natural substance and, therefore, has a high safety. [MEANS FOR SOLVING PROBLEMS] An adiponectin regulator characterized by containing a hop bract extract or an apple extract.

Description

Specification

Adiponectin regulator, food and drink containing the same, food additive and pharmaceutical

[0001] The present invention relates to an adiponectin regulator obtained from a hop koji extract or an apple extract, a food or drink containing the same, a food additive, and a medicine.

Background art

[0002] There are an estimated 7 million diabetic and obese Japanese patients, and the number is still on the rise. General type II diabetes and obesity, which account for the majority of diabetes, are multifactorial diseases that are caused by a combination of multiple causative genes and overlapping environmental factors such as lifestyle habits. The biggest cause of increased diabetes and obesity is considered to be the increase in insulin resistance due to lifestyle habits such as the Westernization of diet, especially high-fat diet and decreased physical activity.

[0003] At present, arteriosclerotic diseases occupy a large position alongside cancer in Japanese statistics of death, and many of them suddenly develop on the job, resulting in a huge loss both socially and domestically. Therefore, the establishment of effective preventive and therapeutic measures is an essential issue (Non-patent Document 1).

[0004] Adiponectin was discovered as a secreted protein that is highly expressed specifically in adipocytes. In later studies, adhesion of monocytes to vascular endothelial cells and the proliferation of smooth muscle cells were suppressed. It became clear that it has an anti-arteriosclerotic action.

[0005] Regarding the relationship with diabetes mellitus, in animal models, in type II diabetic monkeys, adiponectin decreased with increasing insulin resistance, and correlated with the glucose uptake index (M value) in the glucose clamp. It has been shown that blood adiponectin increases (Non-patent Document 2). In addition, administration of physiological concentrations of adiponectin to type II diabetic mice (db / db mice, KKA ^y mice) improves insulin resistance, and adiponectin administration also improves insulin resistance in fat-deficient mice. It has been shown that reduced or deficient adiponectin expression is responsible for obesity insulin resistance, and thus obesity and type 2 diabetes. (Non-Patent Document 3).

[0006] Further, in patients with coronary artery disease and obesity, blood adiponectin concentration is higher than in healthy individuals. It is reported that the degree shows a low value.

[0007] Thus, adiponectin, a protein specific to adipose tissue, is known for its effects on vascular smooth muscle proliferation, migration inhibition, anti-arteriosclerosis, monocyte and macrophage activity, and anti-inflammatory. However, recent studies have also confirmed that it has the effects of suppressing liver fibrosis and promoting normal hepatocyte proliferation.

[0008] Therefore, there is an urgent need to establish a fundamental method for preventing and treating such lifestyle-related diseases.

Non-patent document 1: Guidelines for the treatment of arteriosclerotic diseases, Japan Atherosclerosis Society, 2002 Non-patent document 2: DIABETES Vol.50: 1126 · 1133 (2001)

Non-Patent Document 3: Nature Medecine Vol. 7: 941-946 (2001)

Disclosure of the invention

Problems to be solved by the invention

[0009] The spread of drug treatment is easily dependent on drugs, and there is a risk that the lifestyle will not be improved sufficiently. However, at the present time, those that are sufficiently satisfactory in that they are derived from natural products, have a wide range of functionalities for lifestyle-related diseases, and have extremely low potential for side effects are found. Therefore, an adiponectin preparation that satisfies these properties is desired.

[0010] The problem to be solved by the present invention is to provide an adiponectin modulator, food / beverage product, food additive or medicine that has an effect of regulating adiponectin and has an adiponectin regulatory action that is derived from natural substances and has high safety There is to do.

Means for solving the problem

[0011] As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a hop koji extract or an apple extract has an adiponectin-modulating action, thereby completing the present invention. It was.

That is, the gist of the present invention is as follows.

(1) An adiponectin regulator characterized by comprising a hop koji extract or an apple extract as an active ingredient.

(2) The hop koji extract is a hop koji-derived polyphenol (1) The adiponectin modulating agent described.

(3) The adiponectin regulating agent according to (1), wherein the apple extract is an apple-derived polyphenol.

(4) An adiponectin regulator characterized by containing, as an active ingredient, a substance that is a hop koji extract and does not permeate the membrane when treated with an ultrafiltration membrane having a molecular weight cut off of 1,000 or more.

(5) An adiponectin regulator that is a polyphenol-like substance contained in hop koji and does not permeate the membrane when treated with an ultrafiltration membrane having a molecular weight cut off of 1,000 or more.

(6) A food or drink containing the adiponectin regulator according to any one of (1) and (5).

(7) A food-added caroten containing the adiponectin regulator described in any one of (1) and (5).

(8) A medicine containing the adiponectin modulating agent according to any one of (1) and (5). The invention's effect

[0013] The adiponectin modulator comprising the hop koji extract or apple extract of the present invention as an active ingredient can regulate adiponectin with very few side effects.

[0014] In addition, foods and drinks, food additives, and medicines containing the above adiponectin regulator as an active ingredient can regulate adiponectin with very few side effects. BEST MODE FOR CARRYING OUT THE INVENTION

[0015] Decreased or deficient adiponectin expression has been found to be responsible for obesity insulin resistance and thus obesity and type II diabetes. Furthermore, it has been reported that patients with coronary artery disease and obese patients have lower blood levels of adiponectin than healthy individuals. Therefore, the adiponectin modulating agent in the present invention refers to those that normally adjust the blood concentration of adiponectin.

[0016] The hop koji-derived polyphenol in the present invention contains the derived polyphenol as an active ingredient in the hop koji extract. The adiponectin regulator in the present invention may be either a hop koji extract or a hop koji-derived polyphenol, but is preferably a hop koji-derived polyphenol. Highly purified polyphenols from hop lees When it is added to foods and drinks, it has high applicability in the form of being resistant to the occurrence of turbidity and turbidity, and also being able to suppress the influence of flavor on foods and drinks.

[0017] The hop koji extract containing the hop koji-derived polyphenol used in the present invention is obtained by removing the rubulin portion from the hop koji. Generally, the hop koji is crushed and then sieved. Hops are obtained by removing the Lublin part. However, in recent beer brewing, in order to save the trouble of sieving and removing hop cake, the hop fruit is directly formed into pellets without removing hop cake that is not useful for beer brewing. As such, it tends to be used for beer brewing. Accordingly, the raw material of the present invention is not particularly limited as long as it contains hop cake, and there is no problem even if hop fruit or hop pellet containing hop cake is used as a raw material.

[0018] The extraction method of the hop koji extract is not particularly limited, but, for example, hop koji or hop pellets containing hop koji or hop koji as a raw material is preferably 4 to 95 ° C, preferably Extract at 30-60 ° C with 0-50%, preferably 10-40% ethanol. The ratio of the raw material to the extraction solvent is 1:20 to 100 (weight ratio), preferably 1:30 to 90 (weight ratio), and is carried out with stirring for 20 to 60 minutes, preferably 30 to 50 minutes. Further clarification is performed by filtration through diatomaceous earth (trade name “Silica 300S”, manufactured by Chuo Silica Co., Ltd.) at 5 to 75 ° C., preferably 15 to 25 ° C. Since hop koji extract has a neutral fat metabolism control action, it is useful as a neutral fat reduction metabolism control agent.

[0019] The hop koji extract or hop koji-derived polyphenol has an adiponectin-modulating action and is therefore useful as an adiponectin-modulating agent.

[0020] Hop cocoon extract power To obtain hop cocoon-derived polyphenol, for example, hop cocoon extract is adsorbed with an adsorption resin that adsorbs a polyphenol-like substance, and hop cocoon-derived polyphenol-like is extracted from the hop cocoon extract. The material may be separated and purified. The adsorption treatment method is not particularly limited. For example, the hop koji extract may be adsorbed on the adsorption resin at 0 to 40 ° C, preferably 15 to 25 ° C.

[0021] The adsorbed resin is not particularly limited as long as it adsorbs a polyphenol-like substance. For example, hydrophilic bur polymer resin (“Toyopearl HW40” manufactured by Toso Co., Ltd.), styrene-di-vinylbenzene resin (Mitsubishi) "Separbeads SP-825" manufactured by Eigakusha), gel-type synthetic resin (Mitsubishi “Diaion HP-20” manufactured by Kagaku Co., Ltd.). The hop koji extract is passed through an adsorption column packed with these adsorbents to adsorb polyphenol-like substances. Subsequently, pure water is passed through to remove non-adsorbed substances (saccharides, organic acids, etc.) in the column, and then the polyphenol-like substance is eluted with 10 to 90%, preferably 30 to 80% ethanol. Good.

[0022] Of the hop koji extract or the hop koji-derived polyphenol-like substance, a substance that does not permeate the membrane when treated with an ultrafiltration membrane having a fractional molecular weight of 1,000 or more is preferable in terms of regulating adiponectin.

Next, a method using an ultrafiltration membrane will be described. The treatment liquid containing the hop koji extract or the hop koji-derived polyphenol-like substance obtained in the above extraction step or adsorption step has a molecular weight cutoff of 1,000 or more, preferably 10,000 to 50,000. Treat with filtration membrane. At that time, if necessary, the treatment liquid containing the hop koji-derived polyphenol-like substance can be concentrated under reduced pressure to lower the ethanol concentration. Depending on the concentration of the organic solvent in the extraction solvent and the ratio of the extraction solvent and hops or hops, the treatment is carried out until the amount of the remaining liquid is approximately iZio to iZioo, preferably 1Z20 to 1Z100 at the start of the treatment. . The pressure at that time is 9.8 kPa to 981 kPa, preferably 98 kPa to 686 kPa. It can be used in the liquid state as it is, but it can also be dried as described below. The obtained fractional force is also concentrated under reduced pressure at 25 to 100 ° C, preferably 35 to 90 ° C, and spray-dried or lyophilized with the concentrated solution as it is or with the addition of a powder auxiliary such as dextrin. Get the extracted powder product.

[0024] The method for obtaining a hop koji-derived polyphenol-like substance that does not pass through the membrane when treated with an ultrafiltration membrane having a molecular weight cut off of 1,000 or more is limited to the above method. After processing the extract derived from hops lees with an ultrafiltration membrane with a molecular weight cut off of 1,000 or more, the treatment liquid that does not permeate the ultrafiltration membrane may be adsorbed with a gel polymer. .

[0025] The apple-derived polyphenol in the present invention contains the derived polyphenol as an active ingredient in the apple extract. The adiponectin regulator in the present invention may be either an apple extract or an apple-derived polyphenol, but is preferably a lingo-derived polyphenol. Highly purified apple-derived polyphenols are used for food and drink When it is added to the product, it is difficult to generate odors and turbidity, and the influence of the flavor on the food and drink itself can be suppressed, so that the applicability on the cake is high.

[0026] An apple extract containing an apple-derived polyphenol used in the present invention is a fruit of a genus Rosaceae, for example, cultivars such as Fuji, Mutsu, Tsugaru, Starking Delicious, and original apples. Obtained by extraction by known extraction means.

[0027] As the fruit, both a mature fruit and an immature fruit can be used. However, since the fruit contains more polyphenol compounds and contains a large amount of various active ingredients having a wide range of physiological effects, Particularly preferred.

[0028] The apple-derived polyphenol contained in the apple extract of the present invention has a polyphenol fraction purified from an apple fruit, a juiced fruit juice of an immature fruit, or an extract, Purification of the polyphenol fraction is carried out by treating the juice and extract with an adsorbent, and the fraction adsorbed on the adsorbent (hereinafter referred to as the adsorbed fraction) contains polyphenol. The adsorbent is not particularly limited as long as it adsorbs polyphenol! / ヽ is, for example, a hydrophilic bur polymer resin (“Toyopearl HW40J” manufactured by Toso Co., Ltd.), styrene-dibul benzene resin ( Examples include “Separbeads SP-850” manufactured by Mitsubishi Chemical Corporation, and gel-type synthetic resins (“Diaion HP-20” manufactured by Mitsubishi Chemical Corporation).

[0029] The polyphenol fraction is purified by eluting the adsorbed fraction adsorbed on the adsorbent with an alcohol solvent such as hydrous ethanol. The polyphenol fraction can then be concentrated to obtain a liquid formulation, and further, a powder formulation can be obtained by subjecting the liquid formulation to spray drying or freeze drying.

[0030] As an extraction method of an apple extract used as a raw material for apple-derived polyphenol, for example, the washed raw material was obtained by crushing at pH 3.2 to 4.6, preferably pH 3.5 to 4.3. Add pectinase to fruit juice 5 ~ 75. C, preferably 30-60. 10 ~ at C: Clarify at LOOppm, preferably 20 ~ 30ppm, and after centrifugation, diatomaceous earth at 5 ~ 75 ° C, preferably 15 ~ 25 ° C (trade name "Silica 300S", Chuo Silica Manufacture) Further clarification is performed by filtration to obtain clarified juice. Alternatively, partitioning and filtering with an organic solvent such as hexane or black mouth form can be performed to obtain an apple extract as a clarified extract.

[0031] To obtain an apple-derived polyphenol from an apple extract, the clarified extract is then added to 0-40. . C, L << «15-25. C, pHl. 5 to 4.2, preferably pH 3.0 to 4.0, passed through an adsorption column (trade name “Separbeads SP-850”, manufactured by Mitsubishi Chemical Corporation) filled with the above adsorbent, and polyphenol To adsorb. Subsequently, pure water is passed through to remove non-adsorbed substances (saccharides, organic acids, etc.) in the column, and then the adsorbed fraction is eluted with 10 to 90%, preferably 30 to 80% ethanol. The obtained adsorption fraction can also be concentrated by distilling ethanol under reduced pressure at 25 to 100 ° C, preferably 35 to 90 ° C, and leaving the concentrated solution as it is as a liquid apple-derived polyphenol. Alternatively, powder auxiliary agents such as dextrin may be added and spray-dried or freeze-dried to obtain an apple-derived polyphenol extracted powder product.

[0032] The daily dose for adults to obtain the effect of regulating adiponectin by the adiponectin modulating agent of the present invention is 100 to 2500 mg as hop koji extract or hop koji polyphenol. Preferably it is 150-1500 mg, More preferably, it is 150-1000 mg, It is especially preferable that it is 150-750 mg.

[0033] When the adiponectin modulating agent of the present invention is used, in view of absorption of polyphenols, it is more preferable to take the amount of hop koji extract or hop koji-derived polyphenol per day in a smaller number of times. It is easy to express the action of polyphenols.

[0034] The adult daily dose for obtaining the effect of regulating adiponectin by the adiponectin modulator of the present invention is 10 0 as apple extract or apple polyphenol.

˜2500 mg, preferably 150-1500 mg, more preferably 150-1000 mg, especially 150-750 mg.

[0035] When the adiponectin modulating agent of the present invention is used, in view of the absorption of polyphenols, it is more effective to take the amount of apple extract per day or the amount of apple-derived polyphenol in a smaller number of times. The blood concentration is high and the action of polyphenols is likely to occur.

[0036] The adiponectin regulator of the present invention can be used by adding as a food additive to foods in general, including beverages, such as soups, beverages (juice, mineral water, coffee, tea, non-alcoholic beer, etc. ), Confectionery (gum, candy, chocolate, Suitable for snacks, jellies, etc.), potatoes (soba, udon, ramen, etc.), alcoholic beverages (beer, sparkling liquor, cocktail, chuhai, shochu, sake, whiskey, brandy, wine, etc.).

[0037] The pharmaceutical dosage form containing the adiponectin modulating agent of the present invention is not particularly limited, but for example, solid preparations such as tablets, powders, fine granules, granules, capsules, pills, liquids, suspensions Orally administered agents such as syrups and emulsions. This orally administered agent includes excipients, disintegrants, binders, lubricants, surfactants, alcohols, water, water-soluble polymers, sweeteners, corrigents that are commonly used in the art depending on the form. Further, it can be produced by a commonly used method by adding a sour agent, a pharmaceutical carrier and the like.

[0038] Examples

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

[0039] (Production Example 1) Preparation of hop blossom power with gel-type synthetic resin

20 g of hop blossom was pulverized in a mortar and extracted with 2 L of water at 90 ° C. for 40 minutes with stirring. After filtration, the mixture was allowed to cool, and the extract was passed through a column packed with 80 mL of hydrophilic bur polymer rosin (Toyopearl HW40 manufactured by Tosoh Corporation) over 2 hours (SV = 12.5), then 400 mL Washed with 5% ethanol aqueous solution. Further, 400 mL of an 80% ethanol aqueous solution was passed through the same column, and the same eluate was collected and freeze-dried to obtain 0.8 g of a light yellow powder having an odorless faint bitter taste. The yield from hop camellia was 4%.

[0040] (Production Example 2) Preparation from hop koji with gel-type synthetic resin

20 g of hop koji was extracted with 600 mL of a 50% aqueous ethanol solution at 80 ° C. for 40 minutes while stirring. After filtration, the solution was concentrated under reduced pressure until the volume reached 300 mL, and the concentrated solution was passed through a column packed with 80 mL of styrene-divinylbenzene resin (Separbeads SP-825, manufactured by Mitsubishi Chemical Co., Ltd.) over 1 hour. (SV = 3.75), then washed with 400 mL water. Further, 400 mL of an 80% ethanol aqueous solution was passed through the same column, and the same eluate was collected and freeze-dried to obtain 1.6 g of a light yellow powder having an odorless faint bitter taste. The yield from hop cake was 8%. When the extracted powder product was tested by high performance liquid chromatography, it was confirmed that it contained about 40% proanthocyanidin. [0041] (Production Example 3) Preparation of hop blossom force by ultrafiltration membrane

20 g of hop blossoms were pulverized in a mortar and extracted with 2 L of water at 95 ° C. for 40 minutes while stirring. After filtration, the mixture was allowed to cool, and the extract was treated with an ultrafiltration membrane having a molecular weight cut off of 50,000 (XM50 manufactured by Amicon Co., Ltd.) at 98 kPa at room temperature to 20 mL. The obtained remaining liquid was dried under reduced pressure to obtain 0.2 g of a pale yellow powder having an odorless faint bitterness. The yield from hop camellia was 1%.

[Production Example 4] Preparation from hop koji using ultrafiltration membrane

20 g of hop koji was extracted with 600 mL of a 50% aqueous ethanol solution at 80 ° C. for 40 minutes while stirring. After filtration, the extract was treated with an ultrafiltration membrane having a molecular weight cut-off of 10,000 (YM10 manufactured by Amicon Co., Ltd.) at 294 kPa at room temperature to 60 mL. The obtained remaining liquid was freeze-dried to obtain 0.8 g of a pale yellow powder having a faint bitter taste with no odor. The yield from hop cake was 4%.

[0043] (Production Example 5) Further purification of Hop Hopka preparation by gel-type synthetic resin)

0.8 g of the preparation from hop cake made of gel type synthetic resin obtained in Production Example 2 (preparation of hop cake made of gel type synthetic resin) was dissolved in 500 mL of 10% ethanol aqueous solution, and the molecular weight cut off was achieved. The sample was treated with an ultrafiltration membrane of 10,000 (Amicon YM 10) at 98 kPa at room temperature until it reached 20 mL. The obtained remaining liquid was freeze-dried to obtain 0.4 g of a pale yellow powder having a faint bitter taste with no odor.

[0044] (Comparative Example 1) Tablet

140 g of ratatoose and 17 g of corn starch were mixed, and this mixture was granulated with a paste prepared in advance from 70 g of corn starch. Magnesium stearate lg was added to the resulting granules and mixed well. The mixture was tableted with a tableting machine to produce 1000 tablets.

Example 1 Tablet

150 g of the hop koji polyphenol obtained in Production Example 1, 90 g of ratatoose and 17 g of corn starch were mixed, and the mixture was intensively mixed and granulated with a paste prepared from 70 g of corn starch. The resulting granules were mixed with magnesium stearate lg and mixed well, and the mixture was tableted with a tableting machine to produce 1000 tablets. [0046] (Test Example 1) Inhibition of fat accumulation by hops porphyrin (human)

Next, we investigated the effect of hops polyphenols on the accumulation of fat in clinical trials.

[Method]

1) Target

50 paid volunteers who volunteered to participate in this study, who were over 20 years old, who had a body mass index of 22 and BMI≤30 in a preliminary study conducted 4 weeks before the start of the study. Selected. However, those who are taking medicines and health foods that may affect lipid metabolism, those with a history of food allergies, and within 1 month of starting this study

Those who collected blood or blood exceeding 400 ml within 3 months (such as blood donation) and those judged by the investigator to be unsuitable for study participation were excluded from the subject. Based on the results of preliminary examinations (blood, physical examination) and CT examinations conducted before ingestion by doctors who did not participate directly in the trial, these 50 patients were given their age, weight, height, body mass index, blood pressure, They were divided into two groups so that backgrounds such as neutral fat, total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) waist / hip were aligned. In addition, this study was conducted in accordance with the purpose of the Declaration of Helsinki, with sufficient explanations of the research contents and methods, etc. to the subjects and with written consent.

[0047] 2) Test meal

This test meal was formulated with the hop-polyphenol-containing tablet (150 mg / 1 tablet) produced in Example 1 and the polyphenol produced in Comparative Example 1, and the control meal (Bracebo tablet) It was. Before conducting the study, the investigator confirmed that there was no distinction between the test beverage and the placebo tablet due to packages such as flavor and aroma.

[0048] 3) Intake method and schedule

The study was a parallel two-group comparative study employing a double-blind method with random assignment. The test period was set to a total of 20 weeks, including a pre-observation period of 4 weeks, an intake period of 12 weeks, and an observation period of 4 weeks after the end of intake. The subjects were divided into two groups and ingested the test tablets as follows.

[0049] Group A: Take 4 tablets each of test tablets (150 mg / 1 tablet) containing hops polyphenols before dinner (total 4 tablets / day), hops-polyphenol test tablet intake group

Group B: Placebo tablets (150 mg / 1 tablet) each 4 tablets before dinner (4 tablets / day in total), the following placebo tablet intake group The subjects except for taking test tablets daily Instructed them not to change their daily life such as eating, smoking and exercising.

[0050] 4) Blood test

All subjects had adiponectin, Na, Ca, Cl, K, GPT (ALT), LDH, total bilirubin, UIBC, Fe, y-GTP, total protein at the beginning of intake and 12 weeks after intake (end of intake) Quality, urea nitrogen, and blood cell components (white blood cells, red blood cells, hemoglobin, hematocrit, MCV, MCH, MCHC, platelet count) were measured. All tests were fasted for 12 hours or longer to avoid external effects such as food and exercise, and blood was collected in a sitting position after maintaining a resting state of 10 minutes or more after visiting the hospital.

[Result]

The results are shown in Table 1. Adiponectin was significantly decreased 12 weeks after ingestion in the placebo capsule group (p 0.001). Compared between groups, the placebo capsule intake group and the hop 苞 polyphenol test capsule intake group

A significant difference was observed at (p <0.05). In addition, no abnormalities were observed from various blood tests. During the intake period, no complaining complaints were found.

[0051] [Table 1] Item Test food group Start of intake 曰 Intake 1 2 weeks later Adiponectin hop 苞 polyphenol 6.67 ± 2.95 6.49

(〃 g / ml) Placebo 7.1 0 Sat 2.97 6.48 ± 2.46 *** Adiponectin Hops 苞 Polyphenol 0.00 ± 0.00 1 0.1 7 ± 0.81 # g / ml) Placebo 0.00 Sat 0.00 —0.84 ± 0.75 *** Comparison between groups: #p <0. 05 (Multiple comparison test with Bon ferr on i)

Comparison with ingestion start date: * p ku 0.001 (corresponding t test)

(Production Example 6)

300 kg of apple fruit from Aomori Prefecture was crushed and pressed to obtain 210 kg of fruit juice. The obtained fruit juice was clarified with 30 ppm of pectinase, centrifuged, and then clarified with a diatomaceous earth (silica 300S, manufactured by Chuo Silica Co.) to obtain a clarified fruit juice. The clarified juice was passed through an adsorption column (Separhees SP-850, manufactured by Mitsubishi Chemical Corporation) to adsorb polyphenols. Next, pure water After passing through the column and removing the non-adsorbed substance chamber (saccharides, organic acids, etc.) in the column, the column was eluted with 80% alcohol. About 2 kg of the extracted powder product was prepared by concentrating the alcohol from the obtained fraction force under reduced pressure. The extracted powder product was tested using reversed-phase high performance liquid chromatography.Chlorogenic acids (about 20%), phloretylene glycosides (about 5%), flavonols (about 15%), proanthocyanidins (about 50%) and other browning substances (about 10%). Furthermore, these procyanidins are composed of flavonols, which are flavonols, as a result of analysis using a matrix-assisted laser ionization one-flight time-of-flight mass spectrometer (MALDI-TOF / MS, manufactured by Applied Biosystems). It was confirmed to be an oligomer or polymer from dimer to 15-mer. (M.Ohnishi—kameyama et al. Mass spectrometry, 11, 31, ~ ό6, 1997)

[0053] (Comparative Example 2) Tablet

Example 2 Tablet

150 g of apple polyphenol obtained in Production Example 6, 90 g of ratatoose and 17 g of corn starch were mixed, and the mixture was mixed and granulated with a paste prepared from 70 g of corn starch. The resulting granules were mixed with magnesium stearate lg and mixed well, and the mixture was tableted with a tableting machine to produce 1000 tablets.

[Test Example 2] Inhibition of fat accumulation by apple polyphenol (human)

Next, the effect of apple polyfonol on fat accumulation was examined by clinical trials.

[Method]

1) Target

50 paid volunteers who volunteered to participate in this study, who were over 20 years old, who had a body mass index of 22 and BMI≤30 in a preliminary study conducted 4 weeks before the start of the study. Selected. However, those taking medicines and health foods that may affect lipid metabolism, those with a history of food allergies, within 1 month of starting this study 00

[0056] 2) Test meal

This test meal was prepared by mixing the tablet containing apple polyphenol produced in Example 2 (150 mg / l tablet) and the polyphenol produced in Comparative Example 2 into a control meal (placebo tablet). . In addition, before conducting the study, the investigator confirmed that there was no distinction between the test beverage and the placebo tablet due to the sensory features such as flavor and aroma.

[0057] 3) Ingestion method and schedule

The study was a parallel two-group comparative study using a double-blind method with random assignment. The test period was set to a total of 20 weeks: a pre-observation period of 4 weeks, an intake period of 12 weeks, and an observation period of 4 weeks after the end of intake. The subjects were divided into two groups and ingested the test tablets as follows.

[0058] Group A: Apple polyphenol-containing test tablets (150 mg / 1 tablet) 4 tablets each before dinner (total 4 tablets / day), hereinafter Apple Polyphenol test tablets intake group

[0059] 4) Blood test

All subjects had adiponectin, Na, Ca, Cl, K, GPT (ALT), LDH, total bilirubin, UIBC, Fe, y-GTP, total protein at the start of intake and 12 weeks after intake (end of intake) Quality, urea nitrogen, blood cell components (white blood cells, red blood cells, hemoglobin content, hematocrit, MCV, MCH, MCHC, platelet count) were measured. All tests were fasted for 12 hours or longer to avoid external effects such as food and exercise, and blood was collected in a sitting position after maintaining a resting state of 10 minutes or more after visiting the hospital.

[0060] (Result)

The results are shown in Table 2. Adiponectin was significantly decreased 12 weeks after ingestion in the placebo capsule group (p 0.001). In comparison between groups, placebo capsule intake group and apple polyphenol test capsule intake group

A significant difference was observed at (p <0.01). In addition, no abnormalities were observed from various blood tests. During the intake period, no complaining complaints were found.

[0061] [Table 2] Item Test food group Start of intake 曰 After 12 weeks of intake Adiponectin Apple polyph: Nord 6.01 Sat 2.35 6.05 Sat 2.70

g / ml) Placebo 7.10 ± 2.97 6.48 Sat 2.46 *** Adiponectin Apple Polyphenol 0.00 ± 0.00 0.04 Sat 0.87 ## (/ ml) Placebo 0.00 ± 0.00 -0.84 Shi 0.75 *** Comparison between groups: ## p <0 .01 (Multiple comparison test by Bonfer roni)

Comparison with ingestion start date: *** p <0.001 (corresponding t test) Industrial applicability

[0062] The adiponectin regulator comprising hop koji extract or apple extract as an active ingredient, and because adiponectin can be regulated with very little side effect, the present invention is useful.

[0063] In addition, the present invention is useful because foods and drinks, food additives and medicines containing the above-mentioned adiponectin regulator as an active ingredient can regulate adiponectin with very few side effects.

Claims

The scope of the claims

[1] An adiponectin regulator comprising hop koji extract or apple extract as an active ingredient.

[2] The adiponectin regulator according to [1], wherein the hop koji extract is a hop koji-derived polyphenol.

[3] The adiponectin regulator according to [1], wherein the apple extract is an apple-derived polyphenol.

[4] Adiponectin regulator that is a hop koji extract and does not permeate the membrane when treated with an ultrafiltration membrane with a molecular weight cut off of 1,000 or more.

[5] Adiponectin regulator that is a polyphenol-like substance contained in hop koji and does not permeate the membrane when treated with an ultrafiltration membrane with a molecular weight cut off of 1,000 or more

[6] A food or drink containing the adiponectin modulator according to claim 1, which is claim 1 or 5

[7] A food additive containing the adiponectin regulating agent according to claim 1, wherein the shift force is 1.

[8] A medicament comprising the adiponectin modulating agent according to [1], [5] and [1].