JP2005179213A - Liver trouble inhibiting composition and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To supply health foods, drugs, pet foods or feeds which have safe and higher effective liver trouble inhibiting effects to be promised by combining food materials known to be safely edible from experiences. <P>SOLUTION: The composition comprises a combination of glutathione with turmeric (Curcuma longa). This composition can develop synergism higher than that predicted from their respective effects in the effect of inhibiting the liver trouble. It is confirmed that synergism higher than the sum of effects attained when they are used separately can be expected concerning the effect of inhibiting and ameliorating the liver trouble by combining glutachione heretofore used as a medicine for liver trouble amelioration, etc., and known to be safely edible from experience because of its presence in health foods such as yeast extract and in raw food materials such as liver with a turmeric (Curcuma longa) extract reported to have various desirable physiological actions including liver function enhancement and known to be safely edible from experience in e.g., curry. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a composition that can be applied to foods, pharmaceuticals, pet foods, feeds, and the like that have a safe and effective liver injury-suppressing effect, and a method for producing the same.

  Glutathione is a peptide composed of three amino acids, cysteine, glutamic acid, and glycine. It exists in all cells in the body and plays various important functions such as active oxygen scavenging, detoxification, and amino acid metabolism. In addition to internal medicine areas such as liver function improvement and detoxification, it has been widely used as a pharmaceutical, such as gynecological areas such as pregnancy intoxication and pregnancy prevention, ophthalmic areas such as corneal damage and cataracts, dermatology areas such as eczema and post-inflammation pigmentation. In addition, health foods containing glutathione have been used as yeast extracts and the like.

Turmeric (Curucuma Longa), on the other hand, is a perennial herb belonging to the ginger family that grows in tropical and subtropical regions, and is known as turmeric, which is the main component of curry spices. Other genus of turmeric include gejutsu (Curucuma zedoaria) and turmeric (Curcuma aromatica). The main component in the extract obtained by extracting dried turmeric rhizomes with ethanol or the like is curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5. -Dione), but demethoxycurcumin and bisdemethoxycurcumin are well known as related substances (curcuminoids). In addition to these, there are essential oil components mainly composed of sesquiterpenes such as turmerone. In addition to food, turmeric is a medicinal product because it has hemostatic, stomachic, antibacterial and anti-inflammatory effects in traditional therapies such as coloring for clothing, Chinese herbal medicine, Ayurveda in India, and Jamu in Indonesia. It's being used. The physiological effects of turmeric and its main component, curcumin, include antioxidant, bile secretion (bile), liver and pancreatic function, carcinogenesis, lipid metabolism, whitening, and hypoglycemic. In addition, the prevention and improvement action of visceral fat obesity (Patent Document 1), the suppression of blood pressure increase (Patent Document 2), the kidney damage improvement action (Non-Patent Document 1) and the like are known. Moreover, although the liver hydrolyzate which contains the hydrolyzate of an organ and the turmeric as a plant-derived liver function activation component is already known (patent document 3), these turmeric extract or curcumin, and glutathione are also known. Although both have a common purpose of improving liver function, there is no known research report that combining them can exert a synergistic effect on liver damage.
JP 2003-128539 A WO02 / 47699 JP2002-80388 Molecular and Cellular Biochemistry, 166, 169-175, 1997

  So far, turmeric and other foods that are considered good for liver damage have been used, but their effects have not been fully demonstrated. Therefore, an object of the present invention is to enable the supply of health foods, pharmaceuticals or feeds for the suppression and improvement of liver damage, which can be expected to be safe and more effective than ever, by combining food ingredients with sufficient eating experience. is there.

  Until now, it has been used for improving liver function and other medicines, as well as in health foods such as yeast extract and raw foods such as liver. Various favorable physiological effects have been reported, including the combination of both turmeric extracts with sufficient dietary experience in curry and the like, so that an amount that does not exert its effect on liver damage suppression and amelioration alone can be reduced. It was confirmed that a clear synergistic effect was obtained by the combined use, and the present invention was completed.

  That is, the present invention relates to a composition containing glutathione and turmeric.

  According to the present invention, glutathione, which is used as a medicine but is also contained in health foods and natural foods, has sufficient food experience, and turmeric, a food material that has been confirmed to have useful physiological effects. Provided are a composition that can be applied to foods, pharmaceuticals, pet foods, feeds, and the like that are safe and have an excellent liver injury-suppressing function when combined, and a method for producing the same.

  The composition of the present invention is a composition containing glutathione and turmeric, and has a safe and excellent liver injury-suppressing effect.

  In the present invention, “suppressing liver damage” and “liver damage suppressing action” are used to suppress values used as indicators of liver damage in humans and animals, such as blood GPT (glutamic pyruvic transaminase) concentration. It means to do.

  The glutathione used in the present invention is not particularly limited in its origin, and may be obtained by a synthesis method, biosynthesized by an enzymatic reaction, or derived from an animal liver or a microorganism. The microorganism is not particularly limited as long as the amount of glutathione is high, but yeast can be preferably used. The yeast used in the present invention is not particularly limited, and Saccharomyces, Torlas pora, Candida, Kluyveromyces, Pichia, Debariomyces, Rhodorula, Tolropsis, Schizosaccharomyces, Phaffia and the like can be used. The genus Saccharomyces, which is particularly used for beer, liquor, bread, etc. and has abundant food experience, can be used more preferably, and commercially available yeasts (for example, brewer's yeast and baker's yeast) can also be used, but contain glutathione at a high concentration (dried (5% or more per cell)) is most preferable.

  Bacteria obtained by culturing yeast itself, or those that break down cell walls and membranes by heat, enzymes, acids, alkalis, other chemicals, or physical treatment to make glutathione in cells easier to use In addition, after performing one or more of these treatments, the cell wall and other insoluble fractions are removed by centrifugation or filtration, and the obtained water-soluble fraction itself containing glutathione is further purified. Or a yeast extract obtained by concentrating them into a paste or drying them into powder or granules. The same yeast as described above can be used.

  The form of turmeric used in the present invention is not particularly limited, and it may be a powder obtained by pulverizing rhizome so as to be used for curry, but in terms of absorbability and storage stability, it is a fine powder dried. preferable. Moreover, the extract obtained by extracting with a water or an organic solvent from rhizome or its ground material and powder may be sufficient. The organic solvent used here is preferably one that is permitted for use in the production and processing of pharmaceuticals, foods, food additives, etc., and examples thereof include acetone, ethanol, glycerin, propanol, propylene glycol, hexane, and methanol. In addition, fats and oils such as edible oil may be used. In addition, at least two of these solvents may be mixed and used, or these water-containing solvents may be used. In the case of extraction with water or a solvent, for example, turmeric powder, pulverized or original form is immersed in 1 to 20 times the amount of the above solvent, and -20 ° C to 100 ° C, preferably 1 to 80 ° C, more preferably Is stirred at 20-60 ° C. for 0.1 hour to 1 month, preferably 0.5 hour to 7 days. Extracts obtained by extraction, and those obtained by removing the extraction solvent from them are referred to as turmeric extracts. Moreover, as long as it does not contain impurities inappropriate for pharmaceuticals and foods, it can be used in the present invention as a crude extract or semi-purified extract. Considering economic efficiency, safe use in foods and feeds, and subsequent operations, it is most preferable to use ethanol as an extraction solvent and filter the extract and concentrate.

  The weight mixing ratio of glutathione and turmeric extract in the composition of the present invention is preferably 0.01 to 100 for turmeric extract with respect to glutathione 100, and particularly preferred range is 0.1 to 10 for turmeric extract with respect to glutathione 100. It is only necessary to weigh and mix them so that they have the above ratios. When the turmeric is powder or crushed material, the turmeric is preferably 0.1 to 1000 with respect to glutathione 100, and 1 to 100 is particularly preferable. Glutathione is also present in the body, and even if it is ingested in large quantities, there is little risk of adversely affecting safety and taste, but if you ingest too much turmeric it is easy to affect the taste, so the range of this mixing ratio is preferable.

  Glutathione and turmeric prepared in this way are mixed together and may be in the form of powder, tablets and capsules, and emulsions and solutions, or each may be taken continuously without mixing, It can be mixed with various foods and ingested in a food form, or can be mixed with animal or fish feed. There is no particular limitation on the mixing method. For example, glutathione and turmeric may be mixed and adjusted so as to have the above weight ratio. When glutathione and turmeric powder are mixed, the powder may be mixed as it is. , Each may be dissolved in a solvent to be dissolved and mixed. Glutathione is water-soluble and can be used by dissolving in water, physiological saline, other water-soluble solvents, etc., but water or physiological saline is preferred because it is easy to handle. As the solvent for dissolving turmeric, the same solvents as those used for extraction of turmeric can be used. When producing the composition of the present invention, an emulsifier such as sucrose fatty acid ester, lecithin, glycerin fatty acid ester, polyglycerin ester, sorbitan fatty acid ester, or propylene glycol may be added as necessary. Two or more of these may be used. When these emulsifiers are used, the optimum amount may be appropriately used depending on the type of the emulsifier. For example, it is preferably contained in an amount of 0.1 parts by weight or more and 1000 parts by weight or less, preferably 1 part by weight or more, 100 More preferably, it is contained in parts by weight or less. The order of adding the emulsifier is not particularly limited, and after adding the emulsifier to the solution containing glutathione, turmeric may be added, or after adding the emulsifier to the solution containing turmeric, glutathione may be added. . If necessary, an excipient, a disintegrant, a lubricant, a binder, a coating agent, a colorant, an anti-aggregation agent, an absorption accelerator, a solubilizing agent, and a stabilizer may be added.

  The composition containing glutathione and turmeric obtained in the present invention has an action of suppressing liver damage when used in combination, and has a higher effect on suppressing liver damage than when each of them is used alone. The administration method of the composition in the present invention is not particularly limited, and a composition containing glutathione and turmeric may be administered orally, or may be administered as an injection or an infusion. The same effect can be obtained even if the composition containing glutathione and the composition containing turmeric are sequentially and sequentially administered.

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

(Example 1)
A glass bottle (for plum wine) was charged with 2 kg of turmeric powder (purchased from Kanekasan Spice), poured with 10 L of ethanol, covered with aluminum foil, and allowed to stand for 1 week in a dark place at room temperature for extraction. Two layers of filter paper (ADVANTEC No. 2 15 cm diameter) were overlaid on the extract, filtered under reduced pressure twice, and concentrated under reduced pressure (using a 40 ° C. water bath) with a rotary evaporator. Further, this partially concentrated liquid was transferred to an eggplant flask and concentrated to dryness with a vacuum pump to obtain 237.9 g of a turmeric extract.

(Example 2)
The synergistic effect of glutathione and turmeric extract on hepatotoxicity protective effect was examined using acetaminophen (AAP) oral hepatic injury model mice. Glutathione was prepared by dissolving a sample purchased from Wako Pure Chemicals in physiological saline at a concentration of 100 mg / 5 ml. As the turmeric extract, the extract of Example 1 was once dissolved (suspended) in corn oil at 10 mg / 5 ml, diluted with corn oil, and adjusted to a concentration of 1 mg / 5 ml. AAP was dissolved in distilled water at 400 mg / 20 ml. For the experiment, ICR male mice were purchased from Nippon Charles River Co., Ltd. at 5 weeks of age and tested at 7 weeks of age. Fasted from the evening of the day before the test, the experiment was conducted in the four administration groups shown in Table 1.

  A solution of glutathione and turmeric extract was orally administered at 5 ml per 1 kg body weight, and a control was orally administered 5 ml of physiological saline and 5 ml of corn oil per 1 kg body weight. Thirty minutes later, 20 ml of AAP solution per 1 kg body weight was orally administered, and blood was collected from the abdominal vena cava 5 hours later. The centrifuged plasma was stored refrigerated, and the following day, GPT (glutenic pyrotic transaminase) was measured using transaminase CII-Test Wako of Wako Pure Chemical Industries. The results are shown in Table 2.

  The upper limit of the physiological GPT value in ICR mice is set to 100 IU (biological characteristics data of experimental animals, Soft Science, 1989). Individuals showing a value of 100 IU or more are “disorders”, and individuals less than 100 IU are “ Statistical test (Dunnet type) was performed by scoring as “normal”. In all three groups of the control group, glutathione administration group, and turmeric administration group, all 10 mice were impaired mice with a plasma GPT value of 100 IU or more, whereas the glutathione + turmeric administration group had 7 impaired mice. The mice showed normal values with GPT values of 100 IU or less. This is a statistically significant difference (comparison of Dunnet's population means), and it can be said that glutathione and turmeric showed a synergistic effect on liver damage.

(Example 3)
20 strains of 15 Sakaguchi flasks (500 ml capacity) containing 50 ml of YPD medium (1% yeast extract, 2% polypeptone, 2% glucose) of FERM P-19072 (which belongs to the patent deposit strain Saccharomyces cerevisiae), which is a yeast strain that produces glutathione. A 5L jar fermenter was added to the 5L jar fermenter and 1.7L of medium containing 2.4g of urea, 2.4g of urea and 2.4g of phosphoric acid was added to the sterilized flask. While adding the seed of this amount and adding 270 g of molasses (sugar equivalent) in a fed-batch system, the temperature is 31 to 35 ° C., the lower pH limit is 5.0 (controlled with aqueous water), the air flow is 2 L / min, and the stirring is 14 at 600 rpm Incubate for hours. The culture broth was centrifuged to collect the cells and washed 3 times with 1 L of distilled water. The obtained bacterial cell was 132 g in dry weight (5 hours at 105 ° C.), and the glutathione content was 6.6% per dry cell. (The glutathione content was measured by the alloxan method. Here, the alloxan method is 0.4 ml of 0.5 M phosphate buffer (pH 7.5) and an aqueous sample solution containing glutathione (40% ethanol for yeast cells). 40 μl of the extracted solution) and 1.2 ml of an M / 30 alloxan aqueous solution were added and stirred. The mixture was allowed to react at 30 ° C. for 6 minutes, and then 1 ml of 1N NaOH was added and stirred to terminate the reaction. The background is measured by adding 1.2 ml of water in place of the alloxan aqueous solution.The glutathione standard solution is 200 μg of 0 to 1 g / ml of glutathione standard in 40% ethanol. The absorbance at 305 nm was measured by using about 6 dilutions per ml / ml. Shows an example using the alloxan method, but if there is no problem in accuracy and operability, other methods such as an enzymatic method, an iodometric titration method, a liquid chromatography method, etc. can be used.) In addition, a total amount of 1500 ml of suspension was formed and heat-treated at 90 ° C. for 30 minutes. After cooling to room temperature, 1/3 amount (500 ml) was centrifuged to remove the cells, 1.3 g of dextrin was added to the supernatant, and a dry powder was obtained with a spray dryer. The glutathione content in the dry powder was 16%. Glutathione content is obtained by mixing 64 parts by weight of this powder, 1 part by weight of the turmeric extract obtained in Example 1, 22 parts by weight of lactose, 10 parts by weight of crystalline cellulose, and 3 parts by weight of sucrose fatty acid ester. Tablets containing yeast and turmeric extract were obtained.

Example 4
500 g of the heat-treated cell suspension obtained in Example 3 was mixed with 1 g of sucrose fatty acid ester, 30 mg of turmeric extract obtained in Example 1 and 3 ml of ethanol, and a freeze dryer (Tokyo Science Machinery FD-). Lyophilized in 1). The obtained dried cells were milled to obtain a uniform powder. Thus, a dry powder containing glutathione, yeast cells, and turmeric extract was obtained.

(Example 5)
Centrifugation of 500 ml of the heat-treated cell suspension obtained in Example 3 and lyophilized supernatant obtained by removing the cells, 39.5 parts by weight, Turmeric extract obtained in Example 1 0.5 parts by weight, 55 parts by weight of sesame oil and 5 parts by weight of glycerin fatty acid ester were added to a gelatin capsule to prepare a capsule for health food or medicine containing glutathione and turmeric extract. .

Claims (7)

  A composition containing glutathione and turmeric.   The composition according to claim 1, wherein the glutathione is yeast or yeast extract.   The composition according to claim 1 or 2, wherein the turmeric is a turmeric extract.   The composition according to claim 3, comprising 0.01 parts by weight or more and 100 parts by weight or less of a turmeric extract with respect to 100 parts by weight of glutathione.   The liver injury inhibitory composition of Claims 1-4.   The manufacturing method of the composition in any one of Claims 1-5.   The method to suppress a liver disorder | damage | failure using the composition in any one of Claims 1-6.