JP2013199447A - Liver function protection or improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe liver function protection having high effect or an improving agent, food and drink containing the agent, and a perfume composition.SOLUTION: A liver function protection or an improving agent contains a shoot of a Mentha plant or a Lamiaceae plant, such as Melissa officinalis and Rosmarinus officinalis, an extract of the shoot or a fraction of the extract as an effective component. There are also provided food and drink adding the chemical agent, and a perfume composition comprising the chemical agent and perfume.

Description

  The present invention relates to an agent for protecting or improving liver function, a food and drink containing the same, and a fragrance composition, and a method for protecting or improving liver function of mammals other than humans, specifically liver function originating from Labiatae plants. It is related with the protection or improvement agent, etc.

  The liver is an important organ that synthesizes, decomposes, stores, and releases the three major nutrients such as carbohydrates, proteins, and lipids into the blood. In addition to these metabolic functions, the liver has the effect of detoxifying poisons such as alcohol, drugs, and ammonia. Liver disease can be acutely or chronically affected by viruses, alcohol, drugs, or autoimmune diseases. Reactive oxygen species produced in the liver are said to be the main cause of hepatocellular injury and liver fibrosis.

  The main source of reactive oxygen species is mitochondria. When the hepatocyte environment changes due to viruses, alcohol, drugs, etc., mitochondrial respiratory activity is enhanced, and a large amount of reactive oxygen species that cannot be erased by antioxidant enzymes and antioxidants are generated. Reactive oxygen species induce peroxidation of lipids, which are constituents of hepatocyte membranes, and destroy biological membrane functions. In addition, the DNA of the cell nucleus is oxidatively modified to cause dysfunction and lead to cell death. This series of processes is hepatocyte damage caused by oxidative stress.

  For the improvement of liver dysfunction, antiviral agents such as interferon and liver protective agents as coping therapy are known (Chineko Tanaka et al., “NEW Pharmacology Rev. 4th Edition”, pages 462-463, 2002. Year, Nankodo). However, since drug treatment is generally based on long-term treatment, it is necessary to pay sufficient attention to prevent side effects.

  Therefore, it is desirable from the viewpoint of safety to find an ingredient having an effect on a substance having food experience. And from the recent increase in health consciousness, various physiological activities have been studied in order to effectively utilize the functions of food.

  As foods and drinks that are effective in protecting or improving liver function, liver function activator (patent document 1) containing each extract of ginseng, maria thistle and turmeric, and liver containing black cohosh extract as active ingredients Liver using a protective agent composition (Patent Document 2), a liver function enhancer containing an extract derived from sweet potato as an active ingredient (Patent Document 3), a liver function normalizing agent containing Agaricus (Patent Document 4), and a liver using a swordfish extract A composition for preventing and treating liver disease (Patent Document 6) containing a functionally improved food (Patent Document 5) and a ginseng polysaccharide has been proposed.

  However, physical properties such as flavor, solubility, and stability of the liver function protecting or improving agent are different from each other. Depending on the product, a plurality of liver function protecting or improving agents may be used in combination. As the public's awareness of health and longevity rises, there are various types of products and usage patterns due to differences in age, sex, eating habits, life time, etc., providing liver function protection or improvement agents according to each purpose Is required.

Antiviral agents such as interferon and lamivudine are applied for the treatment of type B and C viral hepatitis, and steroids are applied for the treatment of autoimmune hepatitis. If the disease-specific treatment is not possible or is not effective due to complications, age and physical strength, or in combination with the disease-specific treatment, hepatic palliative treatment is performed to suppress the progression to cirrhosis and carcinogenesis. Therapy has been applied.
Liver asylum therapy is specifically prescribed glycyrrhizin (trade name “Strong Neominophagen C”), ursodeoxycholic acid (trade name “Urso”) and Koshisaikoto (Chinese medicine). It is a treatment method that suppresses the destruction of hepatocytes due to inflammation and lowers ALT (GPT) and AST (GOT).
However, these liver function improving drugs need to be taken continuously for a long time until ALT and AST become normal values, and the side effects associated therewith are problematic.

Therefore, in order to expand the range of drug selection in the treatment of hepatitis, provision of a new liver function protecting or improving agent is desired.
In addition to viral hepatitis, liver disease includes alcoholic liver disease and drug-induced liver injury. In recent years, people are increasingly interested in preventing liver disease and improving liver function. Accordingly, there is a strong demand for provision of new food and drink for liver function protection or improvement that can be easily obtained as a food form other than pharmaceuticals and can be safely and easily ingested over a long period of time.

JP-A-11-189539 JP 2007-55929 A JP 2001-302533 A JP 2004-91449 A JP 2005-261408 A Special table 2011-516543 gazette

  The present invention has been confirmed to be safe from dietary experience for a long time, has excellent liver function protection or ameliorating agent that is excellent in inhibiting damage to hepatocytes and improving the peroxidation state, and foods and drinks, fragrance compositions containing the same, and humans It is an object of the present invention to provide a method for protecting or improving the liver function of mammals excluding.

The inventors of the present invention have made extensive studies to solve the above problems.
As a result, it has been found that Lamiaceae plants, especially Mentha genus plants, lemon balm (Melissa officinalis) and rosemary (Rosmarinus officinalis) have an excellent liver function protecting or improving effect. It came to complete.

That is, the present invention is as follows.
(A) Lamiaceae plant body part, plant body part extract or a fraction of the extract containing as an active ingredient a liver function protecting or improving agent, Lamiaceae plant And at least one plant selected from the group consisting of Mentha plant, Lemon balm (Melissa officinalis) and Rosemary (Rosmarinus officinalis).
(B) The above extract is extracted with a solvent using water or an aqueous ethanol solution (concentration of 10 to 90%) in an amount of 0.5 to 50 parts by mass with respect to 1 part by mass of the dried body above the plant. It is characterized by being made.
(C) A liver function protecting or improving food or drink characterized by the addition of the above liver function protecting or improving agent, or a flavor composition comprising a natural or synthetic flavor added to the liver function protecting or improving agent.
(D) A method for protecting or improving the liver function of a mammal, further comprising administering an agent for protecting or improving liver function to a mammal (excluding humans).

The liver function protecting or improving agent comprising the above-ground part of the Labiatae plant of the present invention, an extract of the above-ground part of the plant body or a fraction of an extract of the above-ground part of the plant body as an active ingredient is thiobarbituric acid reactive Substance (TBARS) amount, aspartate aminotransferase (AST) activity, alanine aminotransferase (ALT) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, glutathione-S-transferase (GST) activity Therefore, it is excellent in suppressing injury of hepatocytes and improving the peroxidation state.
Furthermore, Lamiaceae plants (particularly mint genus plants, lemon balm and rosemary), which are raw materials for the liver function protecting or improving agent of the present invention, are herbs that have been used for a long time, and are used daily as a material that can be consumed with peace of mind. It can be taken continuously for a long time.
Therefore, even if it is administered to industrial animals such as cattle and pigs other than humans, there is no need to worry about the effects on human health (such as persistence) when humans eventually consume them as livestock and fishery products (food).

  In addition, although the raw material of the liver function protecting or improving agent of the present invention is a Labiatae plant having a unique strong flavor (Muscleus plant, lemon balm and rosemary), its extract or extraction of the above-ground part of the plant body As for the fractions of products, such a unique flavor is weak, so there is no risk of damaging the original flavor even when combined with food and drink or other flavors.

It is the graph which measured the amount of thiobarbituric acid reaction substance (TBARS) after administering a peppermint, lemon balm, and a rosemary extract (manufacture examples 1-3) to a rat. It is the graph which measured the aspartate aminotransferase (AST) activity after administering a peppermint, lemon balm, and a rosemary extract (manufacture examples 1-3) to a rat. It is the graph which measured the alanine aminotransferase (ALT) activity after administering a peppermint, lemon balm, and a rosemary extract (manufacture examples 1-3) to a rat. It is the graph which measured lactate dehydrogenase (LDH) activity after administering a peppermint, lemon balm, and a rosemary extract (manufacture examples 1-3) to a rat. It is the graph which measured superoxide dismutase (SOD) activity after administering a peppermint, lemon balm, and a rosemary extract (manufacture examples 1-3) to a rat. It is the graph which measured glutathione-S-transferase (GST) activity after administering a peppermint, lemon balm, and a rosemary extract (manufacture examples 1-3) to a rat.

[1] Liver function protecting or improving agent (1) Raw material plant The active ingredient of the liver function protecting or improving agent of the present invention is a Lamiaceae plant, especially Mentha, Mentha officinalis, Rose Herbs such as Marie (Rosmarinus officinalis) are preferred.
Examples of the mint plant include peppermint (Mentha x piperita), mint (Mentha arvensis L. var. Piperascens), horse mint (Mentha longifolia), penny royal mint (Mentha pulegium) and spearmint (Mentha spicata). In particular, peppermint is preferable from the viewpoint of versatility.

The above-ground part of these plants, that is, the leaf part, stem part and flower part exposed on the ground other than the root part of the herb, are used, but the leaf part is preferable in terms of flavor.
The liver function protecting or improving agent of the present invention contains, as an active ingredient, at least a part of the above-ground part of the plant body, an extract of the above-ground part of the plant body or a fraction of the extract.

All of the above plants have been used as flavored vegetables, spices and herbal teas as herbs containing medicinal ingredients since ancient times, and have been confirmed to be sufficiently safe.
Mentha genus plants such as peppermint contain a large amount of menthol, and are known to have antispasmodic, antiemetic and gustatory effects. In addition, lemon balm contains citral and citronellal, and is known to have sedation, antidepressant, hypnosis, antispasmodic, gustatory and antibacterial effects. Rosemary contains cineol and rosmarinic acid, and is known to have digestive promotion, wind drive, antispasmodic, analgesic, antibacterial and blood circulation promoting effects.
However, peppermint plants such as peppermint, lemon balm and rosemary plants, plant extracts or fractions of these extracts are excellent in inhibiting damage to hepatocytes and improving peroxidation, resulting in liver function It is not known to bring about a protective action or an improvement effect, and such an action effect was unexpected.

  The active ingredient of the liver function protecting or improving agent of the present invention is a Lamiaceae plant, especially peppermint plants such as peppermint, mint, horsemint, penny royal mint, spearmint, the terrestrial part of lemon balm and rosemary, that is, leaves of the plant body Part, stem part and flower part may be used as they are, and a dried product obtained by drying these or a powder obtained by pulverizing after drying can also be used.

(2) Extract The active ingredient of the liver function protecting or improving agent of the present invention is a solvent extraction, pressing, enzymatic degradation, supercritical extraction, concentration, dilution, solid-liquid separation, and purification of the above-ground plant parts of the raw material plant. It may be an extract or a powder obtained by combining known techniques such as these alone or in combination.
At this time, solvent extraction is mentioned as a preferable method. Examples of the solvent used include water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, ethyl acetate, ether, hexane, n-butanol, isobutanol, sec. -Butanol etc. and these mixed solvents are mentioned, Among these, water, ethanol, and ethanol aqueous solution (ethanol concentration is 10-90%) are especially preferable.

  The amount of the solvent to be used is not particularly limited, but is usually 0.5 to 50 parts by weight, preferably 1.0 to 30 parts by weight, and particularly preferably 5.0 to 1 part by weight of the dried plant. Used at 20 parts by mass. When the amount of the solvent is less than 0.5 parts by mass relative to 1 part by mass of the dried plant material, extraction may not be sufficient depending on the type of the solvent, while when the amount of the solvent exceeds 50 parts by mass, it is economical. May not be advantageous.

As an extraction method, it can be obtained as it is or by immersing the pulverized product in a suitable extraction solvent, a method of stirring under heating (range from room temperature to the boiling point of the solvent), or the like. The extraction operation is preferably performed at a temperature of 15 to 100 ° C. with water or a 20 to 70% aqueous ethanol solution.
For example, a method of obtaining an extract by stirring a plant pulverized product in 50% ethanol at room temperature for 10 to 60 minutes, or extracting a plant pulverized product by stirring in water at 100 ° C. under reflux for 30 to 60 minutes The method of obtaining a thing etc. are mentioned.

  The extract obtained by the above extraction operation may remove aroma components contained therein. Methods for removing aroma components from the extract include solvent extraction (eg, US Pat. No. 3,950,266), supercritical carbon dioxide (eg, JP-A-3-9985), and synthetic adsorption resin. A method to be used (for example, JP-A No. 2003-105337) can be used alone or in appropriate combination.

(3) Extracted fraction The active ingredient of the liver function protecting or improving agent of the present invention may be a fraction obtained by fractionating an extract obtained from the above-ground part of the plant of the raw material plant.
The fractionation method includes a method using liquid-liquid extraction and a method using a synthetic adsorbent, and fractionation using a synthetic adsorbent is particularly preferable.
Solvents used for fractionation are water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, ethyl acetate, ether, hexane, n-butanol, isobutanol, sec -Butanol etc. and these mixed solvents are mentioned, Among these, water, ethanol, and ethanol aqueous solution (ethanol concentration is 10-90%) are especially preferable.

The synthetic adsorbent used for the fractionation is generally an insoluble three-dimensional crosslinked structure polymer that is substantially free of functional groups such as ion exchange groups. As a synthetic adsorbent satisfying such conditions, the matrix is a styrene-based styrene-divinylbenzene copolymer, for example, “Separ beads SP70 (trade name)” manufactured by Mitsubishi Chemical Corporation (pore distribution: pore volume 1.6 ml). / G, specific surface area 870 m ² / g, maximum frequency radius 71 mm) and “Diaion HP20 (trade name)” (pore distribution: pore volume 1.3 ml / g, specific surface area 590 m ² / g, maximum frequency radius Can be used, but is not limited thereto.

  In addition, as a fractionation method using a synthetic adsorbent, either a batch method or a column method can be adopted, but the column method is preferable from the viewpoint of workability. As a method of fractionating by a column method, for example, by passing water or an alcohol aqueous solution containing an extract 10 to 1000 times the adsorbent through a column filled with the synthetic adsorbent as described above, An active ingredient can be obtained.

(4) Additional components In the liver function protecting or improving agent of the present invention, in addition to the active ingredients, other components usually used for food and drink are added, and the liver function protecting or improving agent is used as an aspect of the composition. Can be offered at.
Examples of optional components used additionally include sweeteners, coloring agents, preservatives, thickening stabilizers, antioxidants, bittering agents, acidulants, emulsifiers, reinforcing agents, manufacturing agents, excipients, and disintegrating agents. , Binders, lubricants, coating agents, plasticizers, fragrances, and the like, and these can be added and used as various preparations and dosage forms.

(5) Intake The intake of the liver function protecting or improving agent of the present invention is appropriately selected and determined according to age, body weight, symptoms, degree of disease, form of medicine or food / drink, etc., for example, extraction, drying The powder is about 1 mg to 10 g per day, preferably 10 mg to 1 g, and may be taken in several divided doses per day.
The daily dose of the active ingredient of the present invention is usually preferably in the range of 0.1 to 100 mg / kg body weight for humans.

[2] Method for protecting or improving liver function of mammals other than humans The liver function protecting or improving agent of the present invention can be applied to mammals other than humans to protect and improve their liver functions. Such mammals are pet animals and livestock animals, such as dogs, cats, cows, horses, pigs, sheep, goats and the like.
The dosage in that case is generally 0.1 to 100 mg / kg body weight per day according to humans, but the actual dosage varies depending on the mammalian species and individual species-specific biological effects.

[3] Fragrance composition for protecting or improving liver function In the present invention, examples of the fragrance that can be used together with the active ingredient include the following natural and synthetic fragrances.
Ethyl acetoacetate, acetophenone, anisaldehyde, α-amylcinnamaldehyde, methyl anthranilate, ionone, isoeugenol, isoamyl isovalerate, ethyl isovalerate, allyl isothiocyanate, 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate Benzyl isothiocyanate, 3-methylthiopropyl isothiocyanate, isothiocyanates, indole and its derivatives, γ-undecalactone, esters, ethyl vanillin, ethers, eugenol, octanol, octanal, ethyl octoate, isoamyl formate, formic acid Geranyl, citronellyl formate, cinnamic acid, ethyl cinnamate, methyl cinnamate, ketones, geraniol, isoamyl acetate, ethyl acetate, geranyl acetate, cyclohexyl acetate Citronellyl acetate,

Cinnamyl acetate, terpinyl acetate, phenethyl acetate, butyl acetate, benzyl acetate, l-menthyl acetate, linalyl acetate, methyl salicylate, allyl cyclohexylpropionate, citral, citronellal, citronellol, 1,8-cineol, fatty acids, aliphatic higher alcohols , Aliphatic higher aldehydes, aliphatic higher hydrocarbons, cinnamyl alcohol, cinnamaldehyde, thioethers, thiols, decanal, decanol, ethyl decanoate, terpineol, limonene, pinene, myrcene, tapinolen, terpene hydrocarbon Γ-nonalactone, vanillin, paramethylacetophenone, hydroxycitronellal, hydroxycitronellal dimethyl acetal, piperonal, isoamyl phenylacetate, phenylacetate Butyl, ethyl phenyl acetate, phenol ethers, phenols, furfural and derivatives thereof,

Propionic acid, isoamyl propionate, ethyl propionate, benzyl propionate, hexanoic acid, allyl hexanoate, ethyl hexanoate, ethyl heptanoate, l-perilaldehyde, benzyl alcohol, benzaldehyde, aromatic alcohols, aromatic aldehydes, Synthetic or naturally derived fragrances such as d-borneol, maltol, methyl N-methylanthranilate, methyl β-naphthyl ketone, dl-menthol, butyric acid, isoamyl butyrate, ethyl butyrate, cyclohexyl butyrate, butyl butyrate, lactones and linalool Citrus essential oils such as orange, lemon, lime, grapefruit, fruit-based essential oils such as apple, banana, grape, melon, peach, pineapple, strawberry or recovered flavor, milk, cream , Butter, cheese, milk-based extraction flavoring such as yogurt, green tea, oolong tea, black tea, coffee, cocoa, such as luxury goods system recovery flavors,

Asanomi, Asafetida, Ajowan, Anise, Angelica, Fennel, Turmeric, Oregano, Allspice, Orange Nopeel, Pepper, Cassia, Camomile, Mustard, Cardamom, Curry Leaf, Daylily, Caraway, Gardenia, Cumin, Watercress, Clove, Keshino Flea , Caper, pepper, sesame, coriander, sassafras, saffron, savory, salvia, salamander, cinnamon, shallot, juniper berry, ginger, star anise, horseradish, celery, sorrel, thyme, onion, tamarind, tarragon, chives, dill , Capsicum, nutmeg, sagebrush, nigera, carrot, garlic, basil, parsley, vanilla, paprika, hyssop, fenegreek, horseradish, marjoram Zingiber mioga, lavender, linden, lemon grass, lemon balm, rose, rosemary, laurel,

Spice extract obtained from horseradish etc., Iceland moss, Acaciasio, akebi, Asa, Asafetida, Asian Tam, Ajowan, Azuki, Asparagus sine Alice, Applemint, Artichoke, Anise, Avocado, Achacha, Achachazul, Amigasayuri, Amiris, Almond , Aritasaw, Arcanna, Artemisia, Arnica, Alfalfa, Aloe, Angostura, Angola Weed, Apricot, Apricot, Angelica, Amber, Ambergris, Ambret, Squid, Epimedium, Rabbit, East, Squid, Strawberry, Fig, Ginkgo, Wildflower Ylang Ylang, Iwaogi, Imperatoria, Inmortel, Wintergreen, Watercress, Uguigi, Turmeric, Usbasaishin, Woodruff, Two, plum, oolong tea, sesame, Flammulina velutipes, shrimp, sicklepod, Erigeron, Elder,

Eletrocock, Elecanpen, Elemi, Engosaku, Enju, Endive, European Thistle, Ouren, Psyllium, Okazeri, Krill, Oak, Oak Moss, Okera, Osmanthus, Opoponax, Ominaeshi, Omodaka, Dutch Sennici, Origanum, Oris, Olivian, Olive, All Spice, orange, orange flower, chi, cainous, cacao, oysters, cassai, cashew nuts, cascara, cascarilla, castrium, katsura, bonito, cassie, cassava fistula, catechu, crab, carnation, valerian, camomil, kayapte, mustard, crow cucumber, Crow Bishaku, Guarana, Karamus, Galanga, Currant, Carissa, Karin, Cardamom, Galvanam, Curry, Kawamidori, Kanzo , Gambia, cabbage, kiwi fruit over, Kikaigaratake, bellflower, chrysanthemum, fungus, catalpa,

Ghigishi, Kidachi aloe, Kina, Yellowfin, Hosta, Gymnema sylvestre, Catnip, Caraway, Carop, Cucumber, Kiraya, Kinzuhiki, Guava, Guayak, Cucumber, Kusasugi Kazura, Kubokeki, Kudzu, Kusunoki, Shibutsu Gummy, Cumin, Ground Ivy, Clara, Clarisage, Cranberry, Chestnut, Walnut, Cream, Grain of Paradise, Cretadi Tanny, Grapefruit, Clover, Clove, Chromoji, Chlorella, Mulberry, Washer, Caper, Ghetto, Cade, Quebraco, Germanic Dar, Kentur, Kemponashi, Gennoshouko, Kouji, Kodatake, Kocha, Kouhone, Coca, Koganebana, Kokuto, Kokului, Coconut, Shuyu, pepper, Costas, cost Marie, Kopaipa, coffee, fist, burdock, sesame seeds, cola,

Coriander, Coltsfoot, Golden Rod, Colombo, Consai, Cons Lango, Comfrey, Cypress, Fish, Sakura, Cherry, Pomegranate, Salmon Cass, Sasa, Sasakusa, Search, Sassafras, Saffron, Sapodilla, Cactus, Salamander, Salsaparilla, Salsify, Sarnophia , Hawthorn, sanshuyu, salamander, santa herb, sandalack, sandalwood, sandal red, shiitake, gene, cedar, citrus, citronella, sinus, civet, simarouba, shimeji, peonies, jasmine, janohige, jaborangi, charlotte, shukusha, Juniper berry, ginger, ginger, ginger, ginger rush, ginger, white mushroom, ginseng, cinnamon, vinegar, watermelon, syrup , Cedar, star anise, star fruit, Suchirakkusu, soft-shelled turtle, Phallus Impudicus, Zudorabettsu,

Snake root, spikenard, spruce, purslane, slow berry, savory, buffalo, sage, zedary, senega, geranium, celery, senkyu, centauria, sengen, st jones wort, senna, sauce, diou, soybean, thyme, bamboo shoot, octopus , Tade, Davana, Egg, Egg, Onion, Tamarind, Damiana, Tamogitake, Tarragon, Taranoki, Tansy, Tangerine, Dandelion, Cherimola, Cherry Laurel, Cherry Wild, Chigaya, Chicory, Cheese, Chichitake, Chives, Chervil, Champaca, Chubeca , Datura, Cirata, Tsukushi, Tsukumono, Ivy, Camellia, Tsuyukusa, Tsuruganeninjin, Tsurugukudami, Diatang, Tissl, Ditany, De Le, dates, Tendaiuyaku, Tenma, pepper, angelica, the dough food thingy protein situ,

Dorsett butterfly, honey, corn, dodami, eucommia, doggrass, tomato, dragon blood, durian, truffle, trout balsam, tonka, naginata, pear, naster sham, nuts, natto, jujube, nutmeg, nadesico, namako, narake, niuri , Nusangkin Baiyoueki, carrot, garlic, rat potato, nettle, white mulberry, knotgrass, violet, pineapple, hibiscus, malt, chickweed, basil, lotus, lotus cup, perth cup, parsley, butter, butter oil, buttermilk, birch, Honey, patchouli, buck bean, hakkoshu, hakkounyu, hakkoumieki, passion fruit, bamboo shoots, buffalo berry, pearl barley, hanasuge, banana, bani , Hanesakkuru, papaya, Burbury, engagement, purple nutsedge, rugosa rose, littoralis, witch hazel, rose, palmarosa, Pandana, Annona, cause, water chestnut, pistachio, hyssop, Hickory, peanuts, cypress, Hiba, Pipushishiwa, Polygala, hyacinth,

Oyster mushroom, loquat, betel nut, feijoa, phenegrek, fennel, fujibakama, fujimodoki, fusuma, fuselyu, petit grain, butchu, grapes, grape salmon casserole, beech, beech, beech haritake, black caraway, blackberry, plum, brionia, prickly ash Primrose, Prunella, Blueberry, Breadfruit, Hay, Bay, Hazelnut, Vetiver, Bethel, Safflower, Penny Royal, Snake, Pepino, Peptone, Bergamot, Bergamot Mint, Peruvian Sam, Verbena, Veronica, Benzoin, Boadrose, Hoahound, Hou, Bamboo Bamboo, Housho, Bofu, Whey, Honoki, Horseradish, Button, Hop, Poppy, Poplar, Popo, Jojoba, Hoya, Rudo, Bologna, maitake, mug Walt, marshmallows over, marjoram, mastic, Masoi,

Mata Tabi, Machiko, Matsu, Matsuouji, Mushroom, Matsutake, Matsubusa, Matsuhodo, Matecha, Beans, Marigold, Marbadio, Quince, Mullin, Mallow, Mango, Mangosteen, Citrus, Mishimashiko, Miso, Mitsumatsu, Mizuwa, Mito Myoga, Milk, Milte, Milfoil, Myrrh, Milobaran, Muicha, Musk, Murasaki, Mesquite, Meadouseat, Mehajiki, Maple, Melissa, Melilot, Melon, Mousengoke, Moniria Baiyo Eki, Mominoki, Peach, Morohaya, Yakuchi, Eucalyptus, Eucalyptus , Yukinoshita, yuzu, yucca, lily, yosai, yorogusa, lions foot, lychee, life everlasting flower, lime, lilac, lakanka, lakanshaw, razu Lee, Latania, Radish, Labdanum, Lavender, Langwald, Langmoth, Rambutan, Liqueur, Leak, Lyzea, Linaroe, Longan, Ryofungsou, Ryukcha, Apple, Linden, Gentian, Lou, Borage, Reseda, Lemon, Lemongrass, Forsythia Natural fragrances obtained from, for example, lotus, lotus, rosemary, lobe, laurel, longosa, wasabi, cottonweed, wormwood, wormseed, bracken, bracken, etc. are exemplified and used as appropriate.

  The amount of the fragrance is not particularly limited, but is generally 0.0001 to 50% by mass, preferably 0.001 to 30% by mass in the composition containing the liver function protecting or improving agent of the present invention. The most preferable amount is 0.01 to 10% by mass. The use form of the liver function protecting or improving agent of the present invention can be used as it is or in a diluted state, an emulsified state, and various powdered preparations.

[3] Food and drink for liver function protection or improvement To produce a food or drink containing the liver function protection or improvement agent according to the present invention, the active ingredient produced by the above method or a preparation containing the same can be used. Using a conventional means, it is possible to use a edible state, for example, granules, granules, tablets, capsules, soft capsules, pastes and the like.
This food and drink may be used for food as it is, and used by adding it to various foods (for example, ham, sausage, kamaboko, chikuwa, bread, butter, powdered milk, confectionery, etc.) or water, alcoholic beverages, fruit juice, milk It may be used by adding to beverages such as soft drinks.

  The addition amount of the liver function protecting or improving agent is not particularly limited, but is generally 0.001 to 90% by mass, preferably 0.00% in the food or drink containing the liver function protecting or improving agent of the present invention. It mix | blends so that it may become the addition amount of 01-70 mass%, Most preferably, 0.1-50 mass%. The use form of the liver function protecting or improving agent of the present invention can be used as it is or in a diluted state, an emulsified state, and various powdered preparations.

  EXAMPLES Hereinafter, although an Example etc. are given and this invention is further demonstrated, this invention is not limited to these.

[Production Example 1] Peppermint extract 3 kg of 50% ethanol aqueous solution was added to 150 g of dried peppermint leaves and stirred at room temperature for 10 minutes. The extract obtained by filtering off the residue was adsorbed on a column packed with the synthetic adsorbent SP70 and eluted with 30% ethanol. The eluate was concentrated under reduced pressure and freeze-dried to obtain 41 g of a powder product.

[Production Example 2] Lemon balm extract To 160 g of the dried lemon balm leaf, 3.2 kg of 50% ethanol aqueous solution was added and stirred at room temperature for 10 minutes. The extract obtained by filtering off the residue was adsorbed on a column packed with the synthetic adsorbent SP70 and eluted with 30% ethanol. The eluate was concentrated under reduced pressure and freeze-dried to obtain 38 g of a powder product.

[Production Example 3] Rosemary extract 4 kg of a 50% aqueous ethanol solution was added to 200 g of a dried product of rosemary leaves and stirred at room temperature for 10 minutes. The extract obtained by filtering off the residue was adsorbed on a column packed with the synthetic adsorbent SP70 and eluted with 30% ethanol. The eluate was concentrated under reduced pressure and freeze-dried to obtain 32 g of a powder product.

[Production Example 4] Peppermint extract 2 kg of distilled water was added to 100 g of dried peppermint leaf, and the mixture was refluxed for 30 minutes with stirring. The extract obtained by filtering off the residue was concentrated under reduced pressure and freeze-dried to obtain 20 g of a powder product.

[Production Example 5] Lemon balm extract 2.4 kg of distilled water was added to 120 g of dried lemon balm leaves, and the mixture was refluxed for 30 minutes with stirring. The extract obtained by filtering off the residue was concentrated under reduced pressure and freeze-dried to obtain 23 g of a powder product.

[Production Example 6] Rosemary extract 1.6 kg of distilled water was added to 80 g of dried rosemary leaves, and the mixture was refluxed for 30 minutes with stirring. The extract obtained by filtering off the residue was concentrated under reduced pressure and lyophilized to obtain 9 g of a powder product.

[Test Example 1] Action on carbon tetrachloride acute liver injury model animals 1000 mg / kg of each of the peppermint extract, lemon balm extract, or rosemary extract obtained in Production Examples 1 to 3 was administered to an SD male. Rats (6 weeks old, 7 animals; Nippon SLC Co., Ltd., Shizuoka) were orally administered intragastrically once a day for 5 days, and carbon tetrachloride (CCl ₄ ) as a liver damage load was 5 days. It was administered intraperitoneally 6 hours before administration of each eye extract.

A group was set in which each extract was orally administered to the stomach in the same manner as described above and carbon tetrachloride was not administered intraperitoneally.
As a negative control group, a group in which the same volume of distilled water was orally administered in the stomach instead of each extract and carbon tetrachloride was not administered intraperitoneally was set.
As a positive control group, a group was prepared in which the same volume of distilled water was orally administered in the stomach instead of various extracts, and carbon tetrachloride was intraperitoneally administered to cause liver damage.

  For the following items (a), (e), and (f), the liver was collected 20 hours after the administration of carbon tetrachloride, and the homogenate solution and cytoplasm fraction were prepared and used for measurement. The group not administered with carbon tetrachloride was similarly adjusted and used for measurement. On the other hand, for the following items (b) to (d), blood was collected 20 hours after the administration of carbon tetrachloride, and the obtained blood was centrifuged and plasma was separated and used for measurement. The group not administered with carbon tetrachloride was treated in the same manner and used for measurement.

(A) Measurement of the amount of thiobarbituric acid reactive substance (TBARS) Malondialdehyde produced by thiobarbituric acid and peroxidized lipid (highly reactive and naturally occurring in vivo, an indicator of oxidative stress The condensation product (thiobarbituric acid reactive substance) produced by the thiobarbituric acid reaction, which is a condensation reaction with the above, etc. exhibits a red color (λmax 530 nm) and emits fluorescence (λex 532 nm, λex 553 nm). Therefore, the thiobarbituric acid reaction is used as an indirect method for measuring lipid peroxides. Lipid peroxidation is related to aging, lung disease, liver disease, blood coagulation system and the like in the living body. The amount of lipid peroxide obtained by the thiobarbituric acid reaction is called the thiobarbituric acid value and is usually expressed as the absorbance per unit weight of the sample at 530 nm or the malondialdehyde content (mol / ml). In short, it is an index of the peroxidation state of living tissue.

Measurement of the amount of TBARS 0.5 ml of 1% phosphoric acid and 0.67% 2-thiobarbituric acid 1 were added to each test tube to which 0.5 ml of a homogenate solution (for sample) or 0.5 ml of physiological saline (for blind test) was added. After adding 0.0 ml and stirring rapidly, the lid of the test tube was closed and heated at 95 ° C. for 45 minutes. After the reaction, immediately cool to room temperature, add 4 ml of butanol, close the lid and shake vigorously for about 20 seconds. After centrifugation (2650 × g, 10 minutes), the butanol layer was removed, and the absorbance at 535 nm and 520 nm was measured for blind subjects, and the difference (A535-520) was determined. A calibration curve was prepared with 10 nmol / ml 1,1,3,3-Tetraethoxypropane.

(B) Aspartate aminotransferase (AST) activity AST is an enzyme conventionally referred to as GOT (glutamate-oxaloacetate transaminase), and is present in high concentrations in hepatocytes, myocardium, and skeletal muscle. Also distributed. Although it is sometimes called a liver function test, it is actually one of the enzymes that deviate into the blood due to cell damage (necrosis, degeneration). By measuring the enzyme activity value in blood, it is used as a test for determining the presence or absence of cell damage.
AST is a substance that rapidly increases in the blood in the case of hepatitis or serious injury.

(C) Alanine aminotransferase (ALT) activity ALT is an enzyme conventionally called GPT (glutamate-pyruvate transaminase). ALT exists in many organs, but its biodistribution, unlike AST, is overwhelmingly abundant in hepatocytes, so it breaks down into the blood mainly due to hepatocellular injury (deviation enzyme). ), Enzyme activity increases. For this reason, it is sometimes called a liver function test, but it is a test that estimates the presence or absence of liver cell damage, not the liver function.

(D) Lactate dehydrogenase (LDH) activity LDH (lactate dehydrogenase: lactate dehydrogenase) is an enzyme located in the final stage of glycolysis, and is an enzyme that converts pyruvate into lactic acid. Like AST and ALT, it is a kind of deviating enzyme. LDH is widely distributed in all tissues such as liver, red blood cells, muscles, malignant tumors and the like. Therefore, in clinical examination, this increase in enzyme activity indicates that there is an abnormality in any tissue, and is used as a screening test. There are various diseases in which LDH rises, such as hepatitis such as hepatitis, red blood cells broken by hemolysis, myocardial infarction with broken heart muscle, cancer, etc. Especially, blood with AST and ALT Liver damage is suspected when the medium concentration increases.

Measurement of AST, ALT, and LDH activities The blood was allowed to stand at room temperature for 30 minutes, and then centrifuged (1500 × g, 15 minutes) to separate the upper serum fraction. AST, ALT, and LDH activities in this serum were analyzed using a dry chemical chemistry analyzer (SporChem TM EZ SP-4403, ARKRAY, Kyoto) using Spotchem TMII liver function-2 (ARKRAY, Kyoto). It was measured by.

(E) Superoxide Dismutase (SOD) Activity SOD is an enzyme that catalyzes a reaction in which a superoxide anion and a hydrogen ion react to generate triplet oxygen and hydrogen peroxide. That is,
An enzyme that catalyzes the reaction of 2O ₂ ⁻ + 2H ⁺ → H ₂ O ₂ + O ₂ , has the effect of reducing the superoxide anion concentration in the cell to 1 / 100,000, and has the function of preventing lipid peroxidation . Many in liver, kidney, erythrocytes, etc., present in the cytoplasm.

Measurement of SOD activity 960 μl of 0.1 mM xanthine, 0.025 mM Nitro Blue Tetrazolium, 50 mM NaHCO ₃ -Na ₂ CO ₃ buffer (pH 10.2) containing 0.1 mM Na-EDTA was added to a 2 ml spectrophotometer cell. It was kept warm at 25 ° C. The absorbance at 560 nm at this time was taken as the initial value. 20 μl of xanthine oxidase solution and 20 μl of cytoplasm fraction were added simultaneously, and after stirring, the absorbance at 560 nm was measured every minute for 5 minutes.

(F) Glutathione-S-transferase (GST) activity GST is an enzyme that catalyzes the conjugation reaction between glutathione (GSH) and many electrophilic compounds. GST is a major enzyme involved in liver detoxification metabolism and accounts for about 10% of soluble protein in rat liver. Many molecular species exist and are classified into classes α, μ, π, θ, and the like. Some of these have activities such as peroxidase and steroid isomerase, and also play a role as binding proteins of organic ionic compounds such as bilirubin, cholic acid, lipids, and carcinogens, and are multifunctional enzymes. There are also molecular species that catalyze the reaction of leukotriene B4 and GSH to produce leukotrienes C, D, E, and the like. Furthermore, π-class GST-7-7 that is specifically expressed in precancerous liver and the like is also known. In glutathione conjugates, the glutathione moiety is metabolized and excreted in the urine as mercapturic acid.

Measurement of Glutatione-S-transferase (GST) activity 1.48 ml of 0.1 M K ₂ HPO ₄ -KH ₂ PO ₄ buffer (pH 7.4) and 60 μl of 30 mM GSH solution were added to a 2 ml spectrophotometer cell. The temperature was kept at 37 ° C., and the absorbance at 340 nm at this time was taken as the initial value. After adding 60 μl of 30 mM dinitrochlorobenzene and 300 μl of a cytosolic fraction containing diluted GST and stirring, the absorbance at 340 nm of S-2,4-dinitrophenylglutathione produced by the reaction was measured every minute for 5 minutes.

Data of TBARS amount, AST activity, ALT activity, LDH activity, SOD activity, and GST activity were determined to be significant when p <0.05 after testing by Duncan's test.
The results are shown in Table 1 and FIGS.

As shown in Table 1 and FIGS. 1 to 6, the peppermint extract administration group had significant TBARS amount, AST activity, ALT activity, LDH activity, SOD activity, and GST activity compared to the positive control group.
In addition, the lemon balm extract administration group had a significant amount of TBARS, SOD activity, and GST activity compared to the positive control group.
Furthermore, the rosemary extract administration group had significant TBARS amount, AST activity, ALT activity, LDH activity, and SOD activity compared to the positive control group.
Therefore, it was confirmed that peppermint, lemon balm and rosemary have an effect of protecting or improving liver function.

[Example 1] (mixed tea beverage)
To 500 ml of hot water at 90 ° C, add 1 g of green tea leaves, 8 g of hatomugi, 1 g of barley, 0.2 g of brown rice, 0.2 g of puer tea, 0.1 g of dokudami tea, 0.1 g of habucha and 0.1 g of chicory. For 8 minutes.
After extraction, solid-liquid separation was performed, and 0.1 g of vitamin C and water were added to make 10000 ml. After adjusting the pH to 5.5 with sodium bicarbonate, the peppermint extract of Production Example 1 was adjusted to 0.1%. Addition to obtain a mixed tea beverage.
As a result of tasting and sensory evaluation, it was found that the flavor of the peppermint extract was weak and did not affect the flavor of the tea beverage.

[Example 2] (Soft drink)
Valencia orange juice 30 ml, lemon juice 3 ml, fructose 1.5 g, citric acid 0.5 g, vitamin C 100 mg, 100 mg of the lemon balm extract fraction of Production Example 2 was added, and water was added to make 100 ml. Gas was sealed and a soft drink was obtained.
As a result of tasting and sensory evaluation, it was found that the flavor of lemon balm extract is weak and does not affect the flavor of soft drinks.

[Example 3] (chewing gum)
100 g of sugar, 0.5 g of fragrance, and 30 g of 1% aqueous solution of rosemary extract of Production Example 3 were added to 50 g of gum base, kneaded using a kneader, and completed after molding.
As a result of chewing on trial and sensory evaluation, it was found that the flavor of the rosemary extract was weak and did not affect the flavor of the tune gum.

[Example 4] (Biscuits)
100 g of strong powder, 100 g of shortening, 40 g of white sucrose, 30 g of weak flour, 20 g of water, 10 g of peppermint extract of Production Example 1, 4 g of whole milk powder milk, and 0.6 g of baking soda were mixed, molded and baked to obtain biscuits.
When the sample was tasted and sensory evaluation was performed, it was found that the flavor of the peppermint extract was weak and did not affect the flavor of the biscuits.

[Example 5] (Candy)
After mixing 280 g of starch syrup, 360 g of granulated sugar and 120 g of the fraction of the peppermint extract of Production Example 1, the mixture was heated to 155 ° C. Then, it cooled to 120 degreeC, citric acid 12g, the fragrance | flavor 1.2g, and glycerol 50g were added, and it completed after shaping | molding and cooling.
As a result of tasting and sensory evaluation, it was found that the flavor of the peppermint extract was weak and did not affect the flavor of the candy.

[Example 6] (Granule)
5.0 g of lactose and 5.0 g of corn starch were added to 5.0 g of the lemon balm extract of Production Example 2 and kneaded, granulated, dried and sized.
When the granule was put in the mouth and sensory evaluation was performed, the flavor of the lemon balm extract was weak, and the flavor unique to lemon balm was not felt.

[Example 7] (Capsule)
After thoroughly mixing 5.0 g of the peppermint extract fraction of Production Example 1, 5.0 g of corn starch, 5.0 g of lactose, and 1.0 g of crystalline cellulose, the capsules were filled into 40 capsules.
When the capsule was put in the mouth and sensory evaluation was performed, the flavor of the peppermint extract was weak, and the flavor unique to peppermint was not felt.

[Example 8] (Tablet)
After mixing 2.0 g of corn starch, 50 g of lactose, 0.2 g of calcium stearate, and 1.8 g of talc with 50 g of the rosemary extract of Production Example 3, the mixture was tableted with a tableting machine to give a tablet having a weight of 0.52 g. 200 tablets were manufactured.
When the tablet was put in the mouth and sensory evaluation was performed, the flavor of the rosemary extract was weak, and the flavor unique to rosemary was not felt.

  According to the present invention, a liver function protecting or improving agent can be provided. Since this drug can suppress hepatocyte injury and improve the peroxidation state, taking this drug can be expected to provide an effect of protecting or improving liver function.

Claims (6)

  A liver function protecting or improving agent comprising, as an active ingredient, an above-ground part of a Lamiaceae plant, an extract of the above-ground part of a plant, or a fraction of the extract.   The liver function protecting or improving agent according to claim 1, wherein the Labiatae plant is at least one plant selected from the group consisting of Mentha plant, Lemon balm (Melissa officinalis) and Rosemary (Rosmarinus officinalis). .   The extract is a solvent-extracted product using water or an aqueous ethanol solution (concentration of 10 to 90%) in an amount of 0.5 to 50 parts by mass with respect to 1 part by mass of the dried product on the ground part of the plant body. The liver function protecting or improving agent according to 1 or 2.   A liver function protecting or improving food or drink comprising the liver function protecting or improving agent according to any one of claims 1 to 3 added to the food or drink.   A fragrance composition for protecting or improving liver function, wherein a natural or synthetic fragrance is added to the liver function protecting or improving agent according to any one of claims 1 to 3.   A method for protecting or improving the liver function of a mammal, which comprises administering the liver function protecting or improving agent according to any one of claims 1 to 3 to a mammal (excluding humans).

Images