JP2010215585A - Hepatopathy inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hepatopathy inhibitor with naturally occurring plant(s) as material(s), particularly, a protective inhibitor against alcoholic hepatopathy, besides, to provide a food/drink having protective inhibitory effects on hepatopathy, alcoholic one, in particular. <P>SOLUTION: The hepatopathy inhibitor is provided, whose active ingredient(s) is (are) processed product(s) of at least one plant selected from the group consisting of Melissa officinalis and orthosiphon aristatus. As active ingredients for the food/drink, the respective processed products of Melissa officinalis and orthosiphon aristatus are to be used in the weight ratio of (7:3) to (4:6). <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a liver disorder inhibitor containing a plant component. In particular, the present invention relates to a liver disorder inhibitor excellent in protective effect against alcoholic liver disorder. Moreover, this invention relates to the food-drinks which have a liver disorder inhibitory effect.

  Liver disorders are clinically divided into acute hepatitis, chronic hepatitis, fatty liver, cirrhosis and liver cancer, and are classified into viral hepatitis due to viral infection and alcoholic hepatitis due to heavy drinking of alcohol. Among viral hepatitis, some hepatitis A heals spontaneously, but hepatitis B and hepatitis C have become fulminant, and there are many cases related to life. It is also known that viral hepatitis and alcoholic hepatitis become chronic and cause fibrosis of the liver, leading to cirrhosis and liver cancer.

  Liver disorders have few subjective symptoms and are often not noticed with minor lesions. Therefore, a liver function test is usually performed to measure AST (GOT) or ALT (GPT) in blood for early detection of liver damage.

  For treatment of liver disorders, glycyrrhizin preparation, polyenephosphatidylcholine, malotilate, diisopropylamine dichloroacetate, thiopronin, protoporphyrin sodium, methylmethionine sulfonium chloride, interferon, ursodeoxycholic acid, Shosaikoto, liver hydrolyzate, glutathione, etc. Is used. However, these drugs have a low effect of promptly improving liver disease, often require a long time for treatment, and even if it is possible to improve liver disease to some extent quickly, AST (GOT) value, ALT (GPT) value, γ-GTP value is often the upper limit of normal values, and even if there is a therapeutic effect on liver disease, there are side effects It has been pointed out that there are some problems (see Patent Document 1).

  In folk remedies, extracts and decoctions of plants such as turmeric, Maria thistle, red perilla, Kawara mugwort, and hypericum are said to be good for reducing liver damage (Non-patent Document 1, Patent Document 2). (See 3 etc.). These dietary plant ingredients are highly safe and can be used to reduce and improve liver damage on a daily basis, making them ideal as liver damage inhibitors, liver function improvers, or liver protectants. Although it is considered to be a material, its effect is not sufficient.

  On the other hand, Melissa Sou (English name: Lemon balm, scientific name: Melissa officinalis, Japanese name: Kousuihakka, Azalea) is a kind of herb that has been widely used for flavoring foods and drinks and herbal teas. It has long been said to have pharmacological effects such as sedation and analgesia (Non-patent Document 2). In addition, cumixtin (Orthosiphon aristatus (Blume) Miq. Or Orthosiphon stamineus Benth.) (Also known as Nekonohige) has been known to have a diuretic effect (Non-patent Document 3), and recently, health tea aimed at promoting health. Has been drunk as. However, it has not been conventionally known that it has an action of decreasing the ALT (GPT) value released when hepatocytes are damaged, that is, an action of suppressing liver damage or an action of protecting hepatocytes.

JP 2006-199708 A JP-A-11-189539 WO2002 / 062365

"Explanation of supplement ingredients Supplements that are expected to improve liver function, Maria Thistle, Turmeric, Zinc" EB Supplement, December 2004, 6-9 SOULIMANI R et al., Planta Med, vol. 157 No. 2 105-109, 1991.04 ENLERT J et al., Planta Med, vol. 158 No. 3 237-238, 1992.

  An object of this invention is to provide the liver disorder inhibitor excellent in the liver disorder inhibitory action (liver protective action) which uses the plant with a dietary experience as a raw material. Furthermore, the present invention is a liver disorder inhibitor that can be continuously taken over a long period of time from the viewpoint of safety and price, and can effectively reduce and improve liver damage while taking it daily. The purpose is to provide. Moreover, an object of this invention is to provide the food-drinks which have a liver disorder inhibitory effect.

  The inventor has been diligently studying to solve the above-mentioned problems, and has an effect of reducing the ALT (GPT) value released when hepatocytes are damaged by the processed product of Melissas and cumixtin, that is, It was found that there is an action of protecting hepatocytes and suppressing liver damage, and further confirming that the action of suppressing liver damage is further enhanced by the combined use of Melissasou and cumixtin.

The present invention has been completed based on such findings, and includes the following aspects.
Item 1. The liver disorder inhibitor containing the processed material of the at least 1 sort (s) of plant selected from the group which consists of Melissas and cumixtin.
Item 2. Item 2. The liver disorder inhibitor according to Item 1, wherein the processed product is a processed product of Melissasou and cumixtin, and the mixing ratio of Melissasou and cumixtin is 7: 3 to 4: 6 (weight ratio).
Item 3. Item 3. The liver injury inhibitor according to Item 1 or 2, wherein the processed product is a solvent extract of the plant or a dried product thereof.
Item 4. Item 4. The liver injury inhibitor according to any one of Items 1 to 3, wherein the liver injury is caused by alcohol.
Item 5. A food / beverage product comprising a processed product of Melissa Sou and a processed product of Cumixtine, wherein the mixing ratio of the processed product of Melissa Sou and the processed product of Cumixtin is 7: 3 to 4: 6 (weight ratio).

  The hepatic disorder inhibitor of the present invention has an action of protecting hepatocytes and suppressing damage of hepatocytes caused by viruses, alcohols and the like. In particular, it is excellent in the protective action (inhibition action) of hepatocyte damage caused by alcohol, and is useful as an alcoholic liver disorder inhibitor.

  Since the liver disorder suppressant and food and drink of the present invention are formulated with Melissa Sou and / or cumixtin with herbicidal experience as herbal tea and health tea, they are highly safe, and thus are consumed daily. It can improve liver damage, especially alcoholic liver damage.

The result of having investigated the influence on the ALT value of the primary culture hepatocyte by alcohol is shown (refer Experimental example 2). The vertical axis shows the relative ratio of primary cultured rat hepatocytes when the ALT (GPT) value is 100% when no plant extract is present and no alcohol is treated.

  The liver injury-suppressing agent of the present invention is characterized by containing at least one plant processed product selected from Melissasou and cumixtin described later.

(1) Melissaso processed product Melissasou (English name: Lemon balm, scientific name: Melissa officinalis, Japanese name: Kousuihakka, pokeweed mint) has traditionally been used for flavoring and herbal teas of food and drink As can be seen from its widespread use, it is a Labiatae plant that has been eating for many years.

  The application site in the present invention is not particularly limited, and a site conventionally used as a herbal medicine, for example, whole grass, or a part thereof (branches, leaves, stems, flowers, fruits, flower ears, bark, seeds, roots and rhizomes). Etc.) can be widely used, but a flower part, a leaf part, or a part including these is preferable.

  These parts of Melissas are usually dried and then subjected to various processing treatments [pulverization treatment, extraction treatment, concentration treatment, drying treatment (spray drying treatment, freeze drying treatment) according to the form of the present invention and the target dosage form. The processed product of Melissasow, which is the object of the present invention, is also simply referred to as “Melissasaw processed product”).

  Examples of the processed melissa saw targeted by the present invention include, for example, a pulverized processed product (including both coarse powder and fine powder), an extract extracted with a solvent, a dried product thereof (dried extract), and a powder thereof. The powder dry extract extract made into can be mentioned. Preferably, it is an extract or a dried product thereof (dry extract or powder dry extract).

  In addition, the extract is a mixture of Melissa's extraction target as it is or if necessary, dried, shredded, crushed, pressed or boiled with cold water, hot water or an organic solvent, or a mixture of water and an organic solvent. It can be obtained by extraction with an extraction solvent such as a liquid. As an organic solvent used for this extraction, for example, methanol, ethanol, isopropanol, propylene glycol, 1,3-butylene glycol, acetone, ethyl acetate, chloroform, pentane, hexane, heptane, etc., alone or in combination of two or more kinds are used. Can be mentioned. Among the above extraction solvents, water, lower alcohols such as methanol, ethanol and isopropanol (more preferably ethanol), or a mixture of water and these lower alcohols can be mentioned.

  The method for preparing such an extract is not particularly limited, and can be performed according to a conventional method. As an example, 2 to 500 parts by weight, preferably 10 to 200 parts by weight of water is added to 1 part by weight of the dry pulverized product of the portion containing the flower part and leaf part of Melissas, and room temperature to about 100 ° C, preferably An example is a method in which extraction is performed for about 1 to 300 minutes, preferably about 30 to 180 minutes with stirring at about 50 to 100 ° C., and then the solid content is removed by filtration.

  The extract thus obtained is a liquid material in which the soluble components of Melissas are dissolved in the extraction solvent. As a method of drying this to obtain a dry extract, a method of removing the extraction solvent by distillation under reduced pressure or the like, a method of removing the extraction solvent by performing a drying treatment such as vacuum drying or freeze drying, dry spray or spray drying Processing.

  In addition, as the processed product of Melissas, for example, hot water extract powder of Melissas leaves is commercially available from Amla Pharmaceuticals Co., Ltd., and anyone can obtain it commercially (Melissasou dry extract: product number 85.646). ).

(2) Cumixtin processed product Cumixtin (also known as Nekonohige) is a low dendritic perennial plant (Orthosiphon aristatus (Blume) Miq. Or Orthosiphon stamineus Benth.), Which has traditionally reduced diuretic action and renal inflammation. However, recently, it has been attracting attention as a health tea.

  In the present invention, the application site is not particularly limited, and for example, whole grass or a part thereof (branches, leaves, stems, flowers, fruits, cones, bark, seeds, roots, rhizomes, etc.) can be widely used. Preferably a branch, leaf, stem, flower, fruit, cone, bark, seed, or part containing it.

  These parts of cumixtin are usually dried and then subjected to various processing treatments (pulverization treatment, granulation treatment, extraction treatment, concentration treatment, drying after drying, depending on the form and intended dosage form. The processed product (including spray-drying treatment and freeze-drying treatment) is prepared as a processed product (hereinafter, the processed product of cumixin targeted by the present invention is also simply referred to as “cumixtin processed product”).

  Examples of processed cumicustin targeted by the present invention include, for example, a pulverized processed product (including both coarse powder and fine powder), an extract extracted with a solvent such as an organic solvent, water, or a mixture thereof, and a dried product thereof. (Dry extract) and powder dry extract obtained by pulverizing it. Preferably, it is an extract or a dried product thereof (dry extract or powder dry extract). In addition, the preparation method of an extract can be performed according to the preparation method of the extract of Melissasou mentioned above.

  As an example, 2 to 700 parts by weight, preferably 50 to 300 parts by weight, with respect to 1 part by weight of a dry pulverized product of a part containing the above-ground part (branches, leaves, stems, flowers, fruits, cones, bark, seeds) of cumixtine. A method of removing solids by filtration after adding a part of water and performing extraction for about 1 to 300 minutes, preferably about 10 to 90 minutes with stirring at room temperature to about 100 ° C, preferably about 50 to 80 ° C. Can be mentioned.

  As the processed cumixtin, for example, the ethanol-extracted powder of cumixtin above-ground part is commercially available from Amra Pharmaceutical Co., Ltd., and anyone can obtain it commercially (Java tea dry extract: product number 85.901).

(3) Hepatic disorder inhibitor The hepatic disorder inhibitor of the present invention contains either one of the aforementioned processed melissaso or processed kumixtin, or a combination of both, and thus has excellent liver damage. It has a suppressive action (see experimental example). In particular, the hepatic disorder inhibitor of the present invention effectively acts on alcoholic liver disorder in which hepatocytes are damaged by the influence of alcohol.

  The processed product of Melissa Sou and the processed product of cumixtine can be used alone and added to the liver injury inhibitor of the present invention, respectively, but as shown in Experimental Example 3, the combination of both due to the strength of the liver injury inhibitory action It is preferable to use it as a product (mixture). In addition, the processed product of Melissa Sou and the processed product of Cumixtin may be prepared by once preparing the processed product of Melissa Sou and the processed product of Cumikustin, or may be prepared by mixing both. Can also be processed and processed at the same time.

  Due to the enhancement effect of liver damage inhibiting action, the mixing ratio (mixing ratio) of Melissas processed product and Cumixtin processed product is 7-6 parts by weight for Melissas processed product and 3-6 parts by weight for Cumixtin processed product ( Melissa Sow processed product: Cumixtin processed product = 7: 3 to 4: 6), preferably 7 to 5 parts by weight of Melissa Sow processed product, 3 to 5 parts by weight of processed Kumikustin (Melissa Saw processed product: Cumistin processed Product = 7: 3 to 5: 5), more preferably 6 parts by weight of the processed Melissaw product, and 4 parts by weight of the processed product of Comixtin (Melissaw processed product: processed Cumixtin = 6: 4).

  The hepatic disorder inhibitor of the present invention is not particularly limited as long as the hepatic disorder suppressing action (hepatocyte protecting action) can be effectively used. Oral compositions such as pharmaceuticals, particularly preferably oral pharmaceuticals and foods are preferred.

  Here, the foods targeted by the present invention include foods for specified health use (including conditional foods for specified health use) that have the effect of suppressing or improving liver damage. The food for specified health use is characterized in that it contains an effective amount of processed melissaso and processed cumixin that prevents or ameliorates liver damage, and is effective in the packaging package or advertisement of food (liver It is a food that can be described with respect to a disorder inhibiting action or liver disorder improving action, and is a preferred embodiment in the present invention in that it can be differentiated from other foods.

  When the liver injury-suppressing agent of the present invention is a food, when the food is ingested, an effective amount of the various plant processed products (Melissa sow processed product and cumixtin processed product) that exerts an effect of suppressing liver injury in vivo. It is necessary to include "generalized plant products"). Although not limited, for example, when the hepatopathy inhibitor of the present invention contains a processed product of Melissas, the amount of the processed products of Melissas contained per daily intake of the composition is 40 to 6000 mg, preferably 400 To 1800 mg (equivalent to dry matter). Moreover, when the liver disorder inhibitor of this invention contains a cumixtin processed material, as a quantity of the cumixtin processed material contained per daily intake of the said composition, it is 50-7500 mg, Preferably it is 500-2250 mg (dry matter equivalent amount) ). Furthermore, when the hepatopathy inhibitor of the present invention contains both a processed product of Melissasou and a processed product of Cumixtine, the total amount of processed Melissaw and processed product of Cumixtine contained per daily intake of the composition is 12 To 1800 mg, preferably 120 to 540 mg (equivalent to a dry product).

  The hepatic disorder inhibitor of the present invention may consist of the above-mentioned plant processed product itself, or is formulated with other ingredients such as a pharmaceutically or food hygienically acceptable carrier or additive. It may be. The type and blending amount of the carrier or additive can be appropriately selected and adjusted according to the dosage form, product form, or purpose of use of the drug or food, as long as the effects of the present invention are not impaired.

  As long as the effect of the present invention is not hindered, the liver disorder inhibitor of the present invention can further contain other plant processed products, functional components, or medicinal components in addition to the processed products. In addition, these components may be used alone or in combination with the processed plant product, or two or more types may be arbitrarily combined and used in combination with the processed product.

  As other processed plant products, like the processed Melissaw product and the processed kumixtin product used in the present invention, it can be mentioned that has an action of suppressing liver damage. For example, plant processed products such as turmeric, Maria thistle, red perilla, pearl millet, hypericum, walnut, carrot, licorice, saiko, ginger, broccoli, black cohosh, barley, ginkgo biloba, sesame, and achacha can be mentioned.

  Examples of the functional component include an antioxidant, a hypoglycemic agent, an anticholesterol agent, and an immunostimulant.

  Antioxidants include, but are not limited to, dry yeast, glutathione, lipoic acid, quercetin, catechin, coenzyme Q10, enzodinol, proanthocyanidins, anthocyanidins, anthocyanins, carotenes, lycopene, flavonoids, resaveratrol, isoflavones, Examples include zinc, ginkgo biloba, moon peach leaf, hibiscus, and melatonin. Among these, dry yeast is preferable because it contains a relatively large amount of glutathione known as an antioxidant and various minerals.

  Examples of antihyperglycemic agents include, but are not limited to, indigestible dextrin, guava leaf, wheat albumin, L-arabinose, bean extract, mulberry leaf, ginger, salacia, α-linolenic acid, macaque, barley, kidachi aloe, dandelion , Daidai, Korean thistle, garlic, pearl barley, banaba, bilberry, black cohosh, makomo, kotarahim, and tanaka.

  Examples of anticholesterol agents include, but are not limited to, soy protein, phospholipid-bound soy peptide, chitosan, plant sterol ester, plant sterol, plant stanol ester, resistant digestive dextrin, sodium alginate, psyllium seed coat, astaxanthin, inositol, coenzyme A, Calcium, Magnesium, Carnitine, Silk Protein, Taurine, Methionine, α-Linolenic Acid, Gua Gum, Chondroitin Sulfate, Achacharu, Alfalfa, Ginkgo, Psyllium, Barley, Oats, Olives, Gadju, Gymnema, Cat's Claw, Cuco, Chlorella Spirulina, hawthorn, soy saponin, chili, garlic, bilberry, safflower, yucca, ruffa, agaricus, red yeast rice.

  The immunostimulants include agaricus, lactoferrin, cordyceps, arginine, tryptophan, valine, leucine, chitin, chitosan, aloe, kidachi aloe, echinacea, ogi, cats claw, wolfberry, spirulina, pearl barley, safflower, maca, makomo, Rafuma can be mentioned.

  Examples of medicinal ingredients include vitamins, amino acids, peptides, proteins, minerals (such as iron, zinc, magnesium, and iodine), and fatty acids (such as EPA and DHA). Here, as vitamins, vitamins belonging to the vitamin A group (for example, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene and pharmacologically acceptable salts thereof (for example, retinol acetate, retinol palmitate, etc.) Etc.), vitamins belonging to the group B (eg thiamine, thiamine disulfide, discetiamine, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide , Pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid, tetrahydrofolate, dihydrofolate, nicotinic acid, nicotinamide Nicotinic alcohol, pantothenic acid, panthenol, biotin, choline, inositol, pangamic acid and their pharmacologically acceptable salts thereof (eg thiamine hydrochloride, thiamine nitrate, dicetiamine hydrochloride, fursultiamine hydrochloride, riboflavin butyrate) Flavin adenine dinucleotide sodium, pyridoxine hydrochloride, pyridoxal phosphate phosphate, pyridoxal phosphate calcium, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, calcium pantothenate, sodium pantothenate, etc.), vitamins belonging to the vitamin C group (ascorbic acid and its Derivatives, erythorbic acid and its derivatives and pharmacologically acceptable salts thereof (for example, sodium ascorbate, sodium erythorbate, etc.), vitamin Vitamins belonging to group D (for example, ergocalciferol, cholecalciferol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxosterol and their pharmacologically acceptable salts), vitamin E group Vitamins belonging to (for example, tocopherol and derivatives thereof, ubiquinone derivatives and pharmacologically acceptable salts thereof (such as tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol calcium succinate, etc.)), other vitamins (for example, Carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin (vitamin P), eriocitrin, hesperidin and their pharmacologically acceptable salts (such as carnitine chloride). .

  As amino acids, leucine, isoleucine, valine, methionine, threonine, alanine, phenylalanine, tryptophan, lysine, glycine, asparagine, aspartic acid, serine, glutamine, glutamic acid, proline, tyrosine, cysteine, histidine, ornithine, hydroxyproline, hydroxy Examples thereof include lysine, glycylglycine, aminoethylsulfonic acid (taurine), cystine or pharmacologically acceptable salts thereof (for example, potassium aspartate, magnesium aspartate, cysteine hydrochloride, etc.). Preferably, branched chain amino acids such as valine, leucine and isoleucine, glutathione, cysteine, glutamic acid, glycine, serine, tryptophan, tyrosine, phenylalanine, histidine, methionine, threonine, lysine, cystine, arginine, alanine, aspartic acid, proline, amino Ethyl sulfonic acid, collagen and calcium.

  When the hepatic disorder inhibitor of the present invention is prepared as a food, the above composition may be used as an oral composition as it is, and if necessary, tablets, pills, capsules (soft capsules, hard capsules) Various solid preparations such as capsules), powders (powder), and granules (including dry syrup), or liquid preparations such as liquids for internal use (including liquids, suspensions, and syrups) Can be in dosage form. From the stability of each component, it is preferably a solid preparation form (dosage form).

  Formulation can be performed by a normal formulation method employed in the field of medicine and food (particularly supplements). For example, a tablet can be prepared by adding and blending each component according to the formulation, crushing, granulating, drying, sizing and mixing, and tableting the resulting preparation mixture.

  Furthermore, additives for formulation, for example, excipients, lubricants, binders, disintegrating agents, fluidizing agents, dispersing agents, wetting agents, preservatives, thickeners, pH adjustments as necessary An agent, a coloring agent, a flavoring agent, a surfactant, a solubilizing agent, and the like can be blended, and a coating tablet can also be formed using a coating agent. It can also be used as a paste glue.

  The daily intake of the liver disorder inhibitor of the present invention can be appropriately set and adjusted according to the age, sex, body weight, and symptoms of liver disorder of the subject. For example, adults (weight 60 kg) In general, an amount of 10 to 10000 mg can be mentioned. In addition, in this daily intake, in the case of each processed product of Melissas, 0.1 to 5000 mg, preferably 1 to 1000 mg, and more preferably 5 to 500 mg (dry weight) in the case of Melissas processed product. In addition, in the case of a processed cumicustin product, it is desirable to adjust it to be 0.01 to 5000 mg, preferably 0.1 to 1000 mg, more preferably 0.5 to 500 mg (dry weight). In addition, this intake can also be ingested in 1 to several times a day.

  Liver disorders (liver dysfunction) include viral diseases such as acute hepatitis (hepatitis caused by hepatitis A virus, EB virus, cytomegalovirus, etc.) and chronic hepatitis (hepatitis caused by hepatitis B, C virus). Examples include liver dysfunction caused by hepatitis, fatty liver, alcoholic hepatitis, or cirrhosis. In addition to the above-mentioned liver dysfunction, the liver disorder targeted by the present invention is a liver such as AST (or GOT), ALT (or GPT) or γGTP (or γGT), preferably ALT (GPT), although the cause is not clear. This includes situations where abnormalities are found in the numerical values used as function indicators. Preferred is liver dysfunction caused by alcoholic hepatitis (alcoholic liver disorder).

  By the way, according to the “Guidelines on Judgment of Ningen Dock Results and Subsequent Guidance in 2002 (Partially Revised in Fiscal 2003)” (Guidelines for Subsequent Examination of Ningen Dock Results and Post-Guide Guidance) AST (GOT), ALT (GPT) or γGTP concentration (IU / L) in the medium can be determined according to the following criteria as a biochemical index.

  Among them, ALT (GPT) is an enzyme that is distributed specifically in the liver, and is released into the blood when liver cells are broken, and is therefore a suitable determination index that serves as a barometer of the degree of progression of liver damage. AST (GOT) is an enzyme that has the property of rising when systemic fatigue, waste, etc. increase. Generally, when liver damage occurs, AST (GOT) and ALT (GPT) increase. Therefore, if these values are 36 IU / L or more, there is a high possibility of liver damage. On the other hand, γGTP is an enzyme that is released a lot in the blood when hepatocytes are destroyed by alcohol or drugs that are toxic to the liver. In particular, γGTP reacts sensitively to alcohol, increases when the amount of alcohol consumed increases, and decreases immediately when the amount of alcohol consumed decreases, and can therefore be a biochemical indicator of liver damage caused by alcohol. Usually, the alcoholic liver disorder is diagnosed by AST, ALT and γGTP, alcohol liver cell membrane antibody, serum transferrin micromutation (GDT), GLDH / OCT, cytokine (TNF-α) and adhesion factor (ICAM-1). ), PIVKA-II, serum IgA and MCV (mean corpsular volume), in addition to biochemical indicators such as interviews including hearing history and physical findings, etc. ("alcoholic liver Disability ",-Clinical and research, Vol. 80, No. 2 (February 2003)).

(4) Food / beverage products containing Melissaw processed product and Cumixtin processed product The food / beverage product of the present invention contains the aforementioned Melissas processed product and Cumixtin processed product, and the mixing ratio of Melissasaw processed product and Cumixtin processed product is 7 : 3 to 4: 6 (weight ratio).

  The mixing ratio (combination ratio) of the Melissas processed product and the Cumixtine processed product is preferably 3 to 5 parts per 5 parts by weight for the Melissas processed product with respect to 7 to 5 parts by weight of the liver disorder inhibiting effect. Parts by weight (Melissa's processed product: Cumixtin processed product = 7: 3 to 5: 5), more preferably Melissa's processed product is 6 parts by weight, and Cumixtin processed product is 4 parts by weight (Melissa's processed product: Cumixtin processed product Things = 6: 4).

  The foods and drinks provided by the present invention include health foods (including functional foods) having a liver disorder suppressing action or liver disorder improving action in addition to general foods and drinks. Here, the health food means food with the purpose of health, health maintenance and promotion in a more positive sense than normal food.

  The food / beverage product of the present invention may be any one that contains an effective amount for exerting a liver injury-suppressing effect on the processed product of Melissasou and the processed product of Cumixtin having the above-mentioned mixing ratio. However, it may be prepared with a carrier or an additive that can be used as a food in addition to the processed product, or with other food materials.

  In the food and drink, Melissaw processed product and cumixtine processed product having the above mixing ratio, tablets, pills, capsules, granules, powders, powders, together with food-acceptable carriers and additives as necessary Supplements prepared in various pharmaceutical forms such as drugs or solutions (drinks) are included. In addition, the food and drink of the present invention can be obtained by adding the processed Melissaw product and the processed cumixtin product having the above-mentioned mixing ratio to a general food (in other words, the processed product of Melissasou and the processed product of Cumixin product having the above-mentioned mixing ratio). Foods and beverages (including health foods for the purpose of preventing or improving liver damage) prepared by using as one of the raw materials of food are included.

  Examples of such foods and beverages include milk drinks, lactic acid bacteria drinks, fruit juice soft drinks, soft drinks, carbonated drinks, fruit juice drinks, vegetable drinks, vegetable / fruit juice drinks, alcoholic drinks, powdered drinks, coffee drinks, tea drinks, green tea drinks, barley tea Beverages such as beverages; custard pudding, milk pudding, souffle pudding, puddings such as pudding with fruit juice, desserts such as jelly, bavaroa and yogurt; ice cream, ice milk, lacto ice, milk ice cream, ice cream with fruit juice and Frozen confectionery such as soft cream, ice candy, sherbet, ice confectionery; gums such as chewing gum and bubble gum (plate gum, sugar-coated granule gum); chocolate such as chocolate with flavor such as strawberry chocolate, blueberry chocolate and melon chocolate Kind; hard carrier Dee (including bonbon, butterball, marble, etc.), soft candy (including caramel, nougat, gummy candy, marshmallow, etc.), drop, toffee, etc .; baked confectionery such as hard biscuits, cookies, rice crackers, rice crackers (Above, confectionery); soups such as consomme soup and potage soup; jams such as strawberry jam, blueberry jam, marmalade, apple jam, apricot jam, presaber; fruit wine such as red wine; syrup pickled cherry, apricot, Fruits for processing apples, strawberries, peaches, etc .; processed meat products such as ham, sausage, grilled pork; fish products such as fish ham, fish sausage, fish surimi, salmon, bamboo rings, hampen, fried Satsuma, Date roll, whale bacon; Udon noodles, cold wheat, somen noodles, buckwheat noodles, buckwheat noodles, spaghetti It can be given other, various processed foods such as various delicatessen; tee, macaroni, rice vermicelli, noodles such as vermicelli and wonton. Beverages and confectionery are preferred.

  The amount of Melissas processed product and cumicustin processed product to be contained in the food and drink can be appropriately adjusted according to the intake of the food and drink. The intake of the food and drink varies depending on its type, the type of human liver disorder and the degree of symptoms, and other conditions, but for a person with a normal body weight of 60 kg per day The total amount of the product and the processed product of cumixtin is about 10 to 2000 mg / 60 kg, preferably 100 to 1200 mg / 60 kg.

  In addition, the intake of the food / beverage products of this invention does not necessarily need to be once a day, and can also be taken in 3-4 times a day.

  The food / beverage products of the present invention, as shown in the following experimental examples, are various liver disorders caused by Melissas processed products and cumixtin processed products, especially liver dysfunctions caused by alcoholic hepatitis (alcoholic hepatic disorders). Exerts an action of suppressing or improving Therefore, the food and drink of the present invention are exclusively used for the prevention (liver function reduction suppression) or improvement (liver function) for humans having such various liver disorders, particularly liver disorders caused by alcohol or those concerned. Improvement).

  Hereinafter, although an example of an experiment and an example are given and the present invention is explained, the present invention is not limited to these examples.

In the following experimental examples and examples, the following plant processed products were used as Melissas extract, Cumixtin extract, Maria thistle extract, and Red perilla extract.
(1) Melissas extract: Melissas dry extract (dry powder of hot water extract of Melissas leaves) (Part No. 85.646) from Amla Yakuhin Co., Ltd. is used.
(2) Cumixtin extract: Amla Pharmaceutical Co., Ltd.'s Java tea dry extract (dry powder of ethanol extract of cumixtin above ground) (Part No. 85.901) is used.
(3) Maria thistle extract: A dried maria thistle extract from Ask Chemical Co., Ltd. (a dried powder obtained by concentrating the fruit extracted from an ethanol extract after defatting the fruit of thistle thistle) (part number 012.088).
(4) Red perilla extract:
100 g of fresh red perilla leaves were added to 1000 mL of purified water and extracted with hot water for 60 minutes while heating to 93 ° C. The extracted solution was filtered to remove solids, and then dried with a spray dryer to obtain a powdered red perilla extract powder. The drying with a spray dryer was performed while dropping the above extract onto an atomizer with a rotation speed of 10,000 rpm and supplying hot air of 150 ° C. air.

Experimental Example 1 Inhibitory action on liver damage ALT (alanine aminotransferase) is an aminotransferase having pyridoxal phosphate as a coenzyme, also called GPT (glutamaic-pyruvic transaminae). ALT (GPT) is an enzyme that is localized only in hepatocytes and is originally in liver cells, but leaks into the blood when hepatocytes are destroyed. Alternatively, it is widely used as an index for measuring whether or not liver cells are broken by drugs or the like, that is, as a barometer for measuring the presence or absence (development state) of liver damage.

  Using primary cultured hepatocytes, the inhibitory effect on liver damage was examined for Melissas extract and cumixtin extract according to the following method using ALT (GPT) as an index.

(A) Experimental method
(1) From 6-week-old rats (齢) purchased from Japan SLC Co., Ltd., hepatocytes were isolated by perfusion method to obtain primary cultured hepatocytes. This was seeded in a 48-well plate (non-collagen coat) (Akita Sumitomo Bake Co., Ltd.) to be confluent (1 × 10 ⁵ cells / cm ² ), and WEI medium (1 nM insulin / dexamethasone, 10% FBS, 1 Incubate for 4 hours at 37 ° C. and 5% CO ₂ .
(2) After 4 hours, the WEI medium is removed and cultured in a test sample (final concentration 0-8 mg / mL) and WEII medium (10% FBS, 1% penicillin streptomycin) in which PBS (Con) is dissolved.
(3) The obtained culture is centrifuged at 1000 rpm at 4 ° C. for 3 minutes, and 200 μL of the supernatant of each well is collected in a 96-well plate.
(4) GPT (ALT) is measured with a GOT / GPT test Wako kit (manufactured by Wako Pure Chemical Industries, Ltd.) according to the following method. At the same time, the number of living cells (450 nm) is measured with a cell counting kit (manufactured by Dojindo Laboratories).

<ALT (GPT) measurement>
(a) GPT enzyme solution and coloring solution equipped in the kit are mixed 1: 1 (volume ratio) to obtain a GPT coloring solution.
(b) Add 100 μL of the prepared GPT coloring solution to a 96-well plate, and heat for 10 minutes with a 37 ° C. thermostat.
(c) Add 6 μL of 1/3 diluted supernatant to each well, and proceed the reaction while warming with a 37 ° C. thermostat for 25 minutes.
(d) Add 200 μL of the reaction stop solution provided in the kit, stir well, and then measure the absorbance at 550 nm.

(B) Experimental results Table 2 shows the results. The values in parentheses in Table 2 are relative to the ALT (GPT) value (100%) measured for hepatocytes (plant extract concentration: 0 mg / mL) cultured without blending plant extracts (Melissa soup and cumixtin extract). Indicates the ratio.

  From these results, it was found that Melissasou extract and Cumixtin extract have an action to reduce the ALT (GPT) value increased in cultured hepatocytes in a concentration-dependent manner. This means that the melissasou extract and cumixtin extract have a hepatocyte protective effect, that is, a liver injury inhibitory effect. There was no difference in the number of viable cells in the test section.

Experimental Example 2 Effect of alcohol on hepatocytes In order to examine the effect of alcohol on hepatocytes, rat primary cultured hepatocytes were cultured in WEI medium for 4 hours in the same manner as in Experimental Example 1, and then the WEI medium was removed. The cells were cultured in WEII medium (10% FBS, 1% penicillin streptomycin) in ethanol (final concentration: 3%) and PBS (Con) for 2 hours. Subsequently, the GPT (ALT) value was measured according to the methods (3) and (4) of the experimental method of Experimental Example 1.

  As a result, by culturing hepatocytes in the presence of ethanol (final concentration 3%), the ALT (GPT) value was higher than the ALT (GPT) value (100%) when cultured in the absence of ethanol. It was confirmed that it increased by 141% (see FIG. 1). As in Test Example 1, no difference was observed in the number of viable cells with and without ethanol.

Experimental Example 3 Inhibitory Effect on Alcoholic Liver Injury Using the hepatic model of alcoholic liver injury prepared in Experimental Example 2, the liver injury-inhibiting action of Melissa Sou extract and Cumixtin extract was examined. In these experiments, as test samples, Melissa Sou extract and Cumixtin extract prepared in Preparation Examples 1 and 2, mixtures thereof, and red perilla extract and Maria Thistle prepared in Reference Preparation Examples 1 and 2 were used. Extract was used.

(A) Experimental method
(1) Liver cells were isolated from 6-week-old rats (♂) purchased from Japan SLC Co., Ltd. by perfusion method to obtain primary cultured hepatocytes. This was seeded in a 48-well plate (non-collagen coated) (Akita Sumitomo Bake Co., Ltd.) to be confluent (1 × 10 ⁵ cells / cm ² ), and then in WEI medium at 37 ° C. under 5% CO ₂ condition. Incubate for 4 hours.
(2) After 4 hours, the WEI medium was removed, and the test samples [Melissa Sou extract (final concentration: 0 to 8 mg / mL), Cumixtin extract (final concentration: 0 to 8 mg / mL), Melissa Sou extract (M) and Mixture with cumixtin extract (K) (mixing weight ratio (M9: K1), (M8: K2), (M7: K3), (M6: K4), (M5: K5), (M4: K6), (M3: K7), (M2: K8), (M1: K9)) (final concentration: 0-8 mg / mL), red perilla extract (final concentration: 0-8 mg / mL), and Maria thistle extract (final concentration: 0-8 mg / mL)], and PBS (Con) in WEII medium dissolved for 2 hours.
(3) The obtained culture is centrifuged at 1000 rpm at 4 ° C. for 3 minutes, and 200 μL of the supernatant of each well is collected in a 96-well plate.
(4) According to the following method, the GPT (ALT) value is measured in the same manner as in Experimental Example 1 using a GOT / GPT test Wako kit (manufactured by Wako Pure Chemical Industries, Ltd.). At the same time, the number of living cells (450 nm) is measured with a cell counting kit (manufactured by Dojindo Laboratories).

(B) Experimental results The results are shown in Tables 3 and 4. Tables 3 and 4 show ALT (GPT) values measured on hepatocytes (plant extract concentration: 0 mg / mL) cultured in the presence of ethanol without blending the test sample (plant extract) (100%, see Experimental Example 2). The IC50 value (mg / mL) calculated about the relative ratio with respect to each plant extract is shown.

  From this result, it can be seen that Melissasou extract and Cumixtin extract alone and in combination of them both have an action to protect and inhibit hepatocyte damage caused by alcohol (alcohol-induced liver disorder inhibiting action). When using Melissa Sou extract and Cumixtin extract together, Melissa Sou extract and Cumixtin extract are 7: 3-4: 6 (weight ratio), preferably 7: 3-5: 5 (weight ratio), especially It has been confirmed that by combining preferably at a ratio of 6: 4 (weight ratio), a higher alcoholic liver injury inhibiting effect can be obtained than when used alone.

Example 1
Compositions (formulation examples 1 to 20) comprising the formulations described in Tables 5 and 6 were prepared as tablets according to a conventional method. Specifically, each component was blended according to the formulation, pulverized, granulated, dried, sized and mixed, and tableted according to a standard method to prepare a 250 mg tablet.

Example 2
Compositions (formulation examples 21 to 44) composed of the formulations described in Tables 7 and 8 were prepared as granules according to a conventional method. Specifically, each component was blended according to the formulation and mixed, granulated, dried and sized according to a conventional method to prepare 2 g granules.

Example 3
A powder composition (Prescription Examples 45 to 55) having the formulation described in Table 9 was prepared, and then dissolved in commercially available green tea to obtain a 200 g tea beverage.

Claims (5)

  The liver disorder inhibitor containing the processed material of the at least 1 sort (s) of plant selected from the group which consists of Melissas and cumixtin.   The liver according to claim 1, wherein the processed product is a processed product of Melissa Sou and Cumixtin, and a mixing ratio of the processed product of Melissa Sou and the processed product of Cumixtin is 7: 3 to 4: 6 (weight ratio). Disorder inhibitor.   The liver disorder inhibitor according to claim 1 or 2, wherein the processed product is a solvent extract of the plant or a dried product thereof.   The liver disorder inhibitor according to any one of claims 1 to 3, wherein the liver disorder is a liver disorder caused by alcohol.   A food / beverage product comprising a processed product of Melissa Sou and a processed product of Cumixtine, wherein the mixing ratio of the processed product of Melissa Sou and the processed product of Cumixtin is 7: 3 to 4: 6 (weight ratio).

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