JP2008044872A - Health food containing isolariciresinol, blood cholesterol-reducing agent and body fat-reducing agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a health food which is high in safety, can easily be taken, and exhibits a blood cholesterol-reducing action and a body fat-reducing action, to provide a blood cholesterol-reducing agent, and to provide a body fat-reducing agent. <P>SOLUTION: The health food comprises isolariciresinol, and a blood cholesterol-reducing agent and a body fat-reducing agent are provided. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to health foods, isolariciresinol-containing health foods, blood cholesterol lowering agents, and body fat lowering agents.

  Cholesterol is an essential lipid in vivo as a raw material for biological membranes, steroidal hormones, vitamin D and the like. However, when the blood cholesterol level is high due to causes such as excessive intake of cholesterol, metabolic failure, or poor excretion, specifically, when the blood cholesterol level is 220 mg / dl or higher, hypercholesterolemia is assumed. Furthermore, the disease may lead to arteriosclerosis, cerebral infarction, ischemic heart disease. In recent years, the number of people with high blood cholesterol levels has been increasing due to changes in dietary habits. In contrast, statins and other lipid-lowering drugs can lower cholesterol to some extent, and are said to reduce the risk of complications. Plant sterols and stanols are also known as food ingredients having a cholesterol lowering action by suppressing reabsorption of cholesterol, and are sold as health foods.

  On the other hand, it has become widely known in recent years that body fat, particularly visceral fat, is also a causative factor of arteriosclerosis together with hypercholesterolemia, and has been said to be the cause of metabolic syndrome.

  Isolariciresinol is a kind of lignan, and it is known that flux seeds exist as glycosides in which two glucoses are bound. Conventionally, lignan is famous for its sesame sesamin, which has a strong antioxidant activity and is known to have a function of suppressing arteriosclerosis. In addition, it has been used for antimitotic activity and fungicidal activity to prevent or treat breast cancer, prostate cancer, and colon cancer, as well as to reduce hot flashes and prevent osteoporosis, and has also been reported to have an antiviral effect. Plant lignans are also used in foods as antioxidants.

  On the other hand, blood cholesterol lowering action is known for isolariciresinol glycosides derived from flux seeds (Non-patent Document 1). However, although the flux has a dietary experience only with the seed oil, the seed coat of the flux containing a large amount of isolariciresinol glycoside is considered to have a poor dietary experience and a safety problem.

Atherosclerosis 179 (2005) 269-275

  An object of the present invention is to provide a health food exhibiting a blood cholesterol lowering action and a body fat lowering action that are safer and easier to take, and a blood cholesterol lowering agent and a body fat lowering agent.

  It has been found that isolariciresinol, one of the components of fermented tea, has a blood cholesterol lowering action and a body fat reducing action, and the present invention has been completed.

  That is, this invention relates to the health food containing isolariciresinol as an active ingredient.

  In the health food, the dosage form is preferably selected from the group consisting of tablets, capsules, dry powder solids, beverages and powdered tea.

  It is preferable that the content of isolariciresinol in one intake of the health food is 0.01 mg to 10 mg.

  The present invention also relates to a blood cholesterol lowering agent containing isolariciresinol.

  In the blood cholesterol lowering agent, the content of isolariciresinol in one dose is preferably 0.01 mg to 10 mg.

  The present invention further relates to a body fat reducing agent containing isolariciresinol.

  In the body fat lowering agent, the content of isolariciresinol in one dose is preferably 0.01 mg to 10 mg.

  The health food, blood cholesterol lowering agent and body fat lowering agent of the present invention can safely lower blood cholesterol and reduce body fat.

  Isolariciresinol is a compound having the following structure, and can be obtained by treating fermented tea obtained by fermenting tea leaves with straw. Moreover, the glycoside extracted from the flux can be obtained by treating it with β-glucosidase to release it and purify it, and it can also be produced by a chemical synthesis method.

  In the present invention, isolariciresinol was isolated from fermented tea obtained by fermenting tea leaves with straw as described above, and glycosides extracted from the flux were treated with β-glucosidase and released / purified. Can be used, or can be used as an extract obtained by concentrating a hot water extract of fermented tea or a dried extract powder.

  The safety of isolariciresinol has been confirmed by conducting long-term administration tests on animals and humans in the examples below and showing no abnormalities.

  The health food of the present invention, and the blood cholesterol-lowering agent and body fat-lowering agent can be produced by containing isolariciresinol in an excipient. It can also be produced by adding to other foods.

  Excipients include lactose, glucose, mannitol, dextrin, cyclodextrin, starch, sucrose, magnesium aluminate metasilicate, synthetic aluminum silicate, sodium carboxymethylcellulose, hydroxypropyl starch, carboxymethylcellulose calcium, ion exchange resin, methylcellulose , Gelatin, gum arabic, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, light anhydrous silicic acid, magnesium stearate, talc, tragacanth, bentonite, bee gum, titanium oxide, sorbitan fatty acid ester, sodium lauryl sulfate, glycerin, Fatty acid glycerin ester, refined lanolin, glycero gelatin, polysorbate, macrogo Le, vegetable oils, waxes, liquid paraffin, white petrolatum, fluorocarbons, nonionic surfactants, propylene glycol, and the like.

  The form of the health food and blood cholesterol lowering agent and body fat lowering agent of the present invention are not particularly limited, but tablets, powders, powders, extracts, liquids, granules, syrups, suspensions Suppositories, ointments, creams, gels, patches, inhalants, injections, etc. From the viewpoint of stability and ease of oral intake, tablets, capsules, dry powder solids, beverages and Powdered tea is preferred.

  Specific examples of foods for which isolariciresinol is added to other foods include the following, but are not limited thereto.

(1) Agricultural and hydro-acid processed products Harusame, Koshian, Konnyaku, Bread, Noodles (instant noodles, pasta, raw noodles, dried noodles), rice cakes, cereal foods, processed soy products (tofu, soy milk, natto, frozen tofu), hydrolyzed products [ Kneaded product, (crab flavor) salmon, (fish meat) ham, (fish sausage), (fish meat) winner, sprinkle, tea paste, egg-containing food (soup, salmon, etc.), canned (oil sardine, yakitori), retort Food (curry, stew, spaghetti)

(2) Dairy milk, processed milk, lactic acid bacteria beverages, butter, cheese, condensed milk, powdered milk

(3) Confectionery cake, mousse, (powder) dessert, ice cream, candy, chocolate, gummy, candy, cookie, wafer, jelly

(4) Seasoning miso, soy sauce, umami (flavor) seasoning, (powder) natural seasoning, sauce, dressing, grilled meat sauce, mirin, curry, stew, spices, spices, yogurt

(5) Beverage soft drinks (carbonated drinks, fruit drinks, sports drinks, nutrition drinks), beverages (coffee, cocoa, wort)

(6) Nutritional supplements (I) Saponin-containing foods (Ginseng root-containing foods, Ezokogi-containing foods)
Sugar-containing foods [oligosaccharides (fructo-oligosaccharide-containing foods, isomaltoligosaccharide-containing foods, galactooligosaccharide-containing foods), polysaccharides (shiitake-containing foods, mucopolysaccharide-containing foods, protein-containing foods, chondroitin sulfate-containing foods, mannentake) Containing food), food containing chitin and chitosan]
(B) Mineral-containing foods (calcium-containing foods, alfalfa-containing foods, prunes extract-containing foods, β-carotene-containing foods)
(C) Oils and fats-containing foods Vitamin E-containing fats and oils [wheat (wheat, pigeon) germ oil, soybean germ oil, rice germ oil] Eicosapentanoic acid-containing foods, soybean lecithin-containing foods, γ-linolenic acid-containing foods (Evening primrose oil, Borage oil), docosahexaenoic acid-containing foods (d) protein-containing foods, soy protein-containing foods, casein-containing foods, whey protein-containing foods, koji processed foods (e) taurine oyster processed foods, shijimi processed foods

(7) Other processed foods, foods for abnormal amino acid metabolism, liquid food (disease food)
The content of isolariciresinol in a single intake of the health food of the present invention can be appropriately selected depending on the dosage form, age, weight, and symptoms, but is preferably 0.01 mg to 10 mg, More preferably, it is 0.03 mg to 3 mg. If it is 0.01 mg or less, there is a possibility that a sufficient effect cannot be obtained.

  The content of isolariciresinol in the blood cholesterol lowering agent and body fat lowering agent of the present invention in a single dose can be appropriately selected depending on the dosage form, age, body weight and symptoms, but in the case of oral administration , 0.01 mg to 10 mg is preferable, and 0.03 mg to 3 mg is more preferable. If it is 0.01 mg or less, sufficient effects may not be obtained.

  Ingestion of the health food and administration of the blood cholesterol lowering agent and the body fat lowering agent in the present invention may be either before or after a meal, and may be taken or administered multiple times or once, but three times a day. It is preferably taken or administered before every meal.

  The route of administration for blood cholesterol lowering agents and body fat lowering agents is not particularly limited, but includes oral administration, intragastric administration, enteral administration, etc. Administration is preferred.

  Next, the present invention will be described with reference to examples, but the present invention is not limited to these examples.

  In the examples, “parts” and “%” are based on weight unless otherwise specified.

Example 1 (Production of tea leaf extract)
Chinese large leaf tea leaves and tea stems were cut into an average size of 0.8 cm using a grinder. Next, 100 parts of crushed tea leaves and 37 parts of tea stalks were placed in a direct-fired kettle and roasted at 90 ° C. for 250 minutes. After allowing to cool to room temperature, water is sprayed using a spray bottle to reduce the water content to 32%, then placed in the fermentation room, and 0.1% of Aspergillus mold is added to the total amount of tea leaves and tea stems. The mixture was sufficiently mixed and the temperature in the system was raised to 40 ° C. in 50 hours, and then the fermentation was continued at that temperature for 80 hours.

  198 g of the fermented tea leaves obtained above were put into an extraction tank, 1000 mL of water was added, and the mixture was extracted at 120 ° C. for 1 hour to obtain 1150 mL of an extract. After centrifuging the extract, foreign matters were removed by a filter press, concentrated, and lyophilized to obtain 60 g of fermented tea extract A.

  150 g of the obtained fermented tea extract A was liquid-liquid extracted with water / ethyl acetate, and the ethyl acetate layer B was recovered. The obtained extract B13.5g was made to adsorb | suck to Diaion HP20 (made by Mitsubishi Chemical Corporation), and it eluted with 75% methanol, and obtained elution fraction C3g. Of the eluted fraction C, 2.4 g was further adsorbed onto a silica gel column (Wakogel C-300, manufactured by Wako Pure Chemical Industries, Ltd.) and eluted with a chloroform solution containing 10% methanol to obtain an eluted fraction D. Further, 330 mg of this eluted fraction D was adsorbed on a reverse phase column (Cosmosil 75C18, manufactured by Nacalai Tesque) and eluted with 30% acetonitrile to obtain 5 mg of isolariciresinol.

Example 2 (Single administration of fermented tea extract A to mice)
Forty ddy female 9-week-old mice (SRC) having an average body weight of 30.7 g were divided into 4 groups of 10 control groups and administration groups 1 to 3, respectively, and cholesterol (162.5 mg / kg) alone, cholesterol (162 0.5 mg / kg) and fermented tea extract A prepared in Example 1, 0.075 g / kg, 0.15 g / kg and 0.3 g / kg were dissolved in 0.5 mL of water and orally administered. Blood samples were collected before administration and at 0, 4 and 6 hours after administration, cholesterol levels were measured, and the difference from the values before administration was calculated.

  The results are shown in FIG. In mice loaded with cholesterol, blood cholesterol concentration increased after administration, and a peak of cholesterol was observed 4 hours after administration. In the group to which fermented tea extract A was added, the increase was suppressed in a dose-dependent manner. In the 0.3 g / kg administration group, the increase in cholesterol level was significantly suppressed. From this, the cholesterol absorption suppression effect of the fermented tea extract A became clear.

  In addition, FIG. 2 shows the area under increased cholesterol (Δcholesterol AUC) of each group based on FIG. Fermented tea extract A suppressed cholesterol absorption in a dose-dependent manner and was significantly suppressed at 0.3 g / kg. From these results, it was clarified that the fermented tea extract A has an effect of suppressing blood cholesterol elevation.

Example 3 (Long-term administration of fermented tea extract A to rats)
An AIN97G diet with soybean oil added was prepared, 0.5% cholesterol was added thereto, and the fermented tea extract A produced in Example 1 was added at 0.01, 0.03, 0.1 and 0.3. An extract mixed diet was prepared with the addition of%. Table 1 shows the composition of the AIN97G diet to which soybean oil was added.

  Twenty-five male SD strain 4-week-old rats were preliminarily raised on a soybean oil-added AIN97G diet for 1 week, and then divided into 5 groups of 5 control groups and 4 to 7 administration groups. The control group 2 and the administration groups 4 to 7 were each bred for 3 weeks on the cholesterol-added AIN97G diet and the extract mixed diet (0.01, 0.03, 0.1, and 0.3%) at the respective concentrations. . The day before the end of the test period, the food was removed and the following morning was sacrificed and blood and various organs were removed.

  During the administration period, food intake and body weight were measured. After the test period, heart, liver, spleen and kidney organ weights and adipose tissue (kidney, testis) were measured. In addition, blood tests were performed on total cholesterol, HDL cholesterol, LDL cholesterol, neutral fat, α-tocophenol, GOT, and GPT.

  The results are shown in Table 2 and Figures 3, 4, 5, 6 and 7. In Table 2, all the test results are shown as an average value ± standard error (SE). For statistical processing of test results such as blood tests, Kruskal-Wallis test was performed to avoid interaction, and the significance level was set to 0.5% or less. As a result, it was found that weight gain was suppressed in a dose-dependent manner and was significantly suppressed in administration group 7. From this, it became clear that administration of fermented tea extract A has an effect of suppressing body weight gain and reducing body fat. In addition, fermented tea extract A described in Example 1 is considered to have no safety problem because it did not significantly affect the weight of various organs, GOT value, GPT value, and α-tocophenol value in blood. It was. Further, FIG. 3 shows the amount of fat around the kidney (A) and the amount of fat around the testicles (B) at the end of the test. Kruskal-Wallis test was performed as in Table 2. *: P <0.5. By breeding with fermented tea extract A-added diet, it became clear that any fat weight decreased in a dose-dependent manner and had a body fat reducing action. Furthermore, the amount of fat around the kidney, which is considered to be more equivalent to human visceral fat, was significantly decreased in the administration group 7, and it was clarified that there was a body fat reducing action. Further, FIG. 4 shows the total cholesterol value, and FIG. 5 shows the LDL cholesterol value. Total cholesterol and LDL cholesterol decreased in a dose-dependent manner, and were significantly decreased in administration groups 6 and 7. Thus, the effect of improving hypercholesterolemia was revealed. On the other hand, FIG. 6 shows the HDL cholesterol value, and FIG. 7 shows the neutral fat value. It was found that HDL cholesterol level and triglyceride level had little effect.

Example 4 (Production Example 1)
Tablet To 66.7 kg of fermented tea extract A described in Example 1, 15 kg of maltitol, 6.4 kg of crystalline cellulose, 5 kg of sucrose fatty acid ester, 5 kg of tricalcium phosphate and 2 kg of dextrin were added and mixed with a mixer. This was put into a tableting machine to produce 250 mg / grain tablets.
The resulting tablets were used in the following examples.

Example 5 (single administration to human)
Sixty fermented tea processed tablets produced in Example 4 (10 g in terms of fermented tea extract A) were administered once to 8 people with borderline hypercholesterolemia including healthy subjects, and normal blood and urine tests Was done.

  The results are shown in Table 3. No abnormalities were observed in blood tests, urinalysis, subjective symptoms, and objective symptoms, confirming high safety.

Example 6 (long-term administration to humans)
Eight persons with borderline hypercholesterolemia, 2 processed tablets of fermented tea produced in Example 4 each time, 333 mg / meal, 3 times a day in terms of fermented tea extract A, about 1000 mg / day in total Ingested for months.

  The results are shown in Table 4. A clear total cholesterol lowering action and LDL (bad) cholesterol lowering action were observed.

  No abnormalities were observed in blood tests, subjective symptoms, and objective symptoms, and it was confirmed that there were no side effects and safety was high.

Example 7 (Production Example 2)
To 43.3 kg of the fermented tea extract A described in Example 1, 49.4 kg of trehalose and 20 kg of oolong tea extract powder were added and granulated by a granulator. The obtained granules were divided into 1 g portions to produce sachets. If one bag is taken with each meal, a predetermined effect can be obtained.

Cholesterol levels when 10 mg of ddy female 9-week-old mice with an average body weight of 30.7 g were orally administered by dissolving the fermented tea extract A described in Example 1 together with cholesterol in 0.5 mL of water. It is a graph which shows a time-dependent change of a difference. It is a graph which shows (DELTA) cholesterol AUC of each group to 6 hours after administration based on FIG. It is a graph which shows the effect with respect to the renal peripheral fat amount and testicular peripheral fat amount at the time of administering the fermented tea extract A manufactured in Example 1 in the rat for 3 weeks. *: P <0.05. It is a graph which shows the effect with respect to total cholesterol at the time of administering the fermented tea extract A manufactured in Example 1 in the rat for 3 weeks. *: P <0.05. **: <0.01. It is a graph which shows the effect with respect to LDL cholesterol at the time of administering the fermented tea extract A manufactured in Example 1 in the rat for 3 weeks. *: P <0.05. **: <0.01. It is a graph which shows the effect with respect to HDH cholesterol at the time of administering the fermented tea extract A manufactured in Example 1 in the rat for 3 weeks. It is a graph which shows the effect with respect to neutral fat at the time of administering the fermented tea extract A manufactured in Example 1 in the rat for 3 weeks.

Claims (7)

A health food containing isolariciresinol as an active ingredient. The health food according to claim 1, wherein the dosage form is selected from the group consisting of tablets, capsules, dry powder solids, beverages and powdered tea. The health food according to claim 1 or 2, wherein the content of isolariciresinol in a single intake is 0.01 mg to 10 mg. A blood cholesterol-lowering agent containing isolariciresinol. The blood cholesterol-lowering agent according to claim 4, wherein the content of isolariciresinol in a single dose is 0.01 mg to 10 mg. A body fat lowering agent containing isolariciresinol. The body fat lowering agent according to claim 6, wherein the content of isolariciresinol in a single dose is 0.01 mg to 10 mg.

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