WO2006025329A1

WO2006025329A1 - Antitumor agent

Info

Publication number: WO2006025329A1
Application number: PCT/JP2005/015664
Authority: WO
Inventors: Shigetoshi Mizutani; Yuka Hirota; Makiko Naka; Mayu Hashimoto; Takashi Kawai; Takeshi Sakai; Ikunoshin Kato
Original assignee: Takara Bio Inc.
Priority date: 2004-08-30
Filing date: 2005-08-29
Publication date: 2006-03-09
Also published as: JPWO2006025329A1

Abstract

It is intended to provide an antitumor agent characterized by containing, as the active ingredient, at least one member selected from the group consisting of Lyophyllum shimeji and processed products thereof. Because of originating in an edible mushroom, this antitumor agent is at low risk for side effects. Thus, this antitumor agent is useful in drugs, foods or feeds for treating or preventing tumor.

Description

Antitumor agent

Technical field

[0001] The present invention relates to an antitumor agent using hon-shimeji (Lyophyllum shimeji), and a medicine, food or feed containing the same.

Background art

[0002] It is widely known that various edible basidiomycetes such as shiitake, maitake and enokitake have antitumor properties, and various antitumor compositions have been prepared so far from these fruit bodies or mycelia. It has been. In addition, it has also been clarified that Bunashimeji, one of the edible basidiomycetes, has antitumor properties (for example, Patent Document 1). Furthermore, it has been clarified that bioactive substance EEM-S having a molecular weight of 6,000 to 60,000 obtained by heat treatment after suspending buna shimeji in water or a hydrophilic solvent has antitumor activity (for example, , Patent Document 2)

[0003] With regard to honshimeji (Lyophyllum shimeji), a mass production method using a stable strain has just been established (for example, Patent Document 3), and there is no report on its physiological activity.

[0004] Although the fruiting bodies of various edible basidiomycetes have been shown to have antitumor properties, few have been shown to be effective by oral ingestion. So far, antitumor effects have been reported by oral ingestion: extracts from maitake (for example, Non-patent Document 1), extracts from Shiitake (for example, Non-patent Document 2), enokitake Extract (for example, Non-Patent Document 3), an extract from Bunashimeji (for example, Patent Document 1) and an extract from Hatake-Shimeji (for example, Patent Document 4). However, the anti-tumor effect by oral ingestion is weak, and there is no one that has a stable effect.

Patent Document 1: Japanese Patent Laid-Open No. 5-306233

Patent Document 2: International Publication No. 01Z51070 Pamphlet

Patent Document 3: Japanese Patent Laid-Open No. 2000-103752

Patent Document 4: JP-A-11-302191 Non-patent literature l: Chem Pharm Bull, 36 (5), 1819-1827, 1988 Non-patent literature 2: Chem Pharm Bull, 35 (6), 2453-2458, 1987

Non-Patent Document 3: Jpn J Cancer Res (Gann), 76, 130-136, 1985

Disclosure of the invention

Problems to be solved by the invention

[0006] An object of the present invention is to provide an antitumor agent exhibiting an excellent effect orally, and a medicine, food or feed containing the same.

Means for solving the problem

[0007] As a result of intensive studies to solve the above problems, the present inventors have found that hon-shimeji mushroom and its processed product have antitumor activity, and have completed the present invention.

That is, when the present invention is outlined, the first invention of the present invention is characterized by containing, as an active ingredient, at least one selected from the group consisting of honshimeji (Lyophyllum shimeji) and processed products thereof. It relates to an antitumor agent. Examples of the processed hon-shimeji mushroom include dry powder, extract or extraction residue.

[0008] A second invention of the present invention relates to a pharmaceutical comprising the antitumor agent of the first invention of the present invention.

[0009] A third invention of the present invention relates to a food or feed for treating or preventing a tumor characterized by containing the antitumor agent of the first invention of the present invention.

[0010] A fourth invention of the present invention relates to a method for treating a tumor, comprising administering to a subject at least one selected from the group consisting of an effective amount of hon-shimeji mushroom and a processed product thereof.

[0011] A fifth invention of the present invention relates to at least one use selected from the group consisting of hon-shimeji mushroom and its treated product for the production of the antitumor agent of the first invention of the present invention.

The invention's effect

[0012] An orally effective antitumor agent characterized by containing at least one selected from the group of hon-shimeji mushroom and its processed product strength as an active ingredient is provided. Since the antitumor agent of the present invention is derived from edible mushrooms, it is less likely to cause side effects. Therefore, the antitumor agent is useful as a medicament, food or feed for treating or preventing tumors. BEST MODE FOR CARRYING OUT THE INVENTION

[0013] Hereinafter, preferred embodiments of the present invention will be described in detail. Honshimeji is occurring in nature! / In the fall, a lot of scallops occur in the Quercus serrata forest. For a long time, it has been said to be “scented squeeze taste shimeji” and is said to be a representative of the delicious taste. It is said to be widely distributed in East Asia including Japan. Honshimeji has been difficult to cultivate in the past, but recently it has been reported that artificial culturing has become possible (for example, JP 2000-106752, JP 2001-120059). This makes it possible to harvest mushrooms stably throughout the year regardless of the season. That is, honshimeji serving as a raw material for the active ingredient of the present invention can be easily obtained and used as a raw material for pharmaceuticals, foods or feeds.

[0014] In the present invention, the strain used as hon-shimeji (Lyophyllum shimeji) may be a natural or artificially grown product. July 13, 1999;) :: Lyophyllum shimeji LaOl-20 (FERM P-16841, deposit date: June 16, 1998) All of the above strains have been deposited with the National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center (1st, 1st, 1st, Tsukuba, Higashi, Ibaraki 305-8566, Japan).

In the present invention, hon-shimeji means those classified as Lyophyllum shimeji in terms of taxonomy. Traditionally, the power that has been circulated as “Yamabiko Honshimeji” or “Honjimeji” is a categorized as “Hypsizigus marmoreusj” (previously classified as Lyophyllu mulmarium). Yes (Mushroom Cultivation Index, January 1989, Nagano Prefecture, Nagano Agricultural Cooperative Federation, Nagano Prefectural Economics and Agricultural Cooperative Federation, Nagano Forestry Union Federation; Sankei Color Directory Japan Mushroom Showa 63 1 January 10th, published by Yamato Gorge Co., Ltd.), not used as a hon-shimeji of the present invention.Lyophyllum shimeji was first used for fungus bed artificial cultivation in Shiga Prefecture Forest Center in 1993 Successful reports have been reported (Mushroom Yearbook 2004, published on April 1, 2004, published by Special Information Company Mushroom Yearbook Co., Ltd.). With the exception of is analogy is "Bunashimeji" The Honshimeji is a mycorrhizal fungus (occurs in the roots of living straw trees (active parasites) and ingests nutrients), whereas Bunashimeji is a wood-rotting fungus (occurs in dead dead trees (dead parasites)). It is clear that these are different mushrooms.

[0015] As the hon-shimeji used in the present invention, fruit bodies or mycelia thereof can be used. The fruit bodies can be raw or dried fruit bodies dried by heating, sun drying, freeze drying, etc. The fruit body can be used as a stock or crushed. As the mycelium, live or dried mycelium obtained by culturing inoculum in a medium containing a carbon source and a nitrogen source can be used, and a dried one is easy to use.

[0016] In the present invention, the treated product is not particularly limited as long as it is obtained by subjecting hon-shimeji to artificial treatment. For example, a dry powder, an extract, an extraction residue, a heat-treated product, a pulverized product, a juice, Examples include crushed products, dried products, frozen products, enzyme-treated products, chemical-treated products, and processed products obtained by combining these treatment processes. Particularly preferably, dry powder, extract, and extraction residue are exemplified. There are no particular limitations on the form of the treated product as long as it can be used as the active ingredient of the present invention. In addition, as a raw material of these processed products, either a fruit body or a mycelium of Honshimeji can be used.

[0017] When a dry powder is used as the treated product of the present invention, the production method is not particularly limited. For example, the raw material of the treated product as described above is sun-dried, freeze-dried, dry heat dried, The dried product obtained by performing a known drying process such as air drying can be obtained by pulverizing with various pulverizing mixers such as a bead mill, a milling blender, and a homogenizer.

[0018] In the present invention, an extract refers to a thread and product obtained through a process of performing an extraction operation using an extraction solvent. Specific examples include a water extract, a hot water extract, an ethanol extract, an ethyl acetate extract, a methanol extract, an acetone extract, a hexane extract and the like. In the present invention, a hot water extract is used. An ethyl acetate extract is preferably used. Extraction can be performed as follows by a known extraction method. For example, after the raw material is pulverized or shredded, extraction can be performed batchwise or continuously using a solvent. In addition, as the raw material, the above-mentioned dry powder of hon-shimeji mushroom, and the following chemical-treated or enzyme-treated product of hon-shimeji mushroom can be used. The extraction solvent for obtaining the extract is not particularly limited. Water, hexane, chloroform, alcohols such as ethanol, methanol, isopropyl alcohol, ketones such as acetone and methyl ethyl ketone, and hydrophilic or lipophilic solvents such as methyl acetate and ethyl acetate. If desired, it can be used alone or as appropriate as a mixed solution. The amount of the extraction solvent may be determined as appropriate, but usually 0.1 to LOO times the amount of extraction solvent is preferably used relative to the weight of the raw material used in the extraction operation. The extraction temperature may be appropriately determined according to the purpose, but in the case of water extraction, it is usually preferably 4 to 130 ° C, more preferably 25 to 100 ° C. In this specification, water extraction at an extraction temperature of 50 ° C or higher is called hot water extraction, and an extract obtained by hot water extraction is called hot water extract. Further, when ethanol is contained in the solvent, the range of 4 to 60 ° C is preferable. The extraction time may be determined in consideration of the extraction efficiency. Usually, the raw material, the extraction solvent, and the extraction temperature are set to be preferably in the range of several seconds to several days, more preferably 5 minutes to 24 hours. Is preferred. The pressure at the time of extraction can be appropriately determined as desired without particular limitation. The extraction operation can be performed by selecting conditions as desired, for example, under normal pressure, under pressure, or under reduced pressure by suction filtration or the like. The extraction operation may be performed with stirring or standing, for example, and may be repeated several times as necessary. By the above operation, an extract of hon-shimeji mushroom used in the present invention (hereinafter sometimes referred to as the extract of the present invention) is obtained. If necessary, the extract can be treated by filtration, centrifugation, concentration, ultrafiltration, molecular sieving, etc. to prepare an extract in which the target component having antitumor activity is concentrated. The antitumor action of the extract or concentrated extract can be measured according to the method described in Example 2 described later. In the present invention, two or more extracts obtained by different extraction methods can be used in combination. The extract of the present invention thus obtained can be subjected to treatments such as vacuum concentration, sterilization, freeze drying, spray drying and the like to remove the extraction solvent and obtain a dried hon-shimeji extract. In the present invention, an extract obtained by extracting the extraction residue with a different solvent can also be used as the extract of the present invention. For example, as described in Example 4 described later, an ethyl acetate extract of a hot water extraction residue can be used.

In the present invention, the fraction obtained by fractionating the extract of the present invention by a known method and the fraction obtained by repeating the fractionation operation a plurality of times are also the extract of the present invention. Is included. Examples of the fractionation means include extraction, fractional precipitation, column chromatography, thin layer chromatography and the like. The active ingredient can also be isolated by further purifying the obtained fraction using the antitumor action as an index. Those components are also included in the active ingredients of the present invention.

[0020] In the present invention, the extraction residue means a residue obtained after extraction as described above, and these can also be used as an active ingredient of the present invention. For example, hon-shimeji hot water extraction residue obtained by the process as described in Example 1 is exemplified.

[0021] In addition, when a heat-treated product of hon-shimeji is used as the treated product of the present invention, the production method is not particularly limited. For example, a dry powder of hon-shimeji is suspended in water and 50-120. C, preferably 60 to 110 ° C, and more preferably 70 to 100 ° C. There are no particular limitations on the heating time, but examples include a range of several seconds to several days, more preferably 5 minutes to 24 hours.

[0022] Further, when hon-shimeji mushroom juice is used as the processed product of the present invention, the production method thereof can be carried out in the same manner as the known method of squeezing plants, and is not particularly limited. A method using a squeezing machine such as a clew type, a gear type, a cutter type or a juicer can be used. Further, as a pretreatment, the raw material can be shredded or ground and then squeezed with the above-mentioned juicer or cloth to obtain a juice.

[0023] In the present invention, the crushed material is a material obtained by crushing hon-shimeji mushroom used as a raw material for the active ingredient, and generally has a tissue piece larger than the pulverized material. For example, a crusher is used. Can be manufactured. The dried product can be obtained by drying a hon-shimeji mushroom used as a raw material of an active ingredient by sun-drying and performing a known drying treatment such as freeze drying, dry heat drying, hot air drying or the like. The frozen product is not particularly limited as long as it is obtained by a known freezing method. For example, a frozen product obtained by the method described in JP-A-6-284858 or JP-A-2000-69927 can be used. . The chemically treated product is not particularly limited, but is obtained by subjecting hon-shimeji to acid treatment, alkali treatment, oxidation treatment, reduction treatment, osmotic pressure treatment, etc., for example, hydrochloric acid, sulfuric acid, Honshimeji is soaked in an aqueous solution containing an inorganic or organic acid such as nitric acid, citrate, or acetic acid, or an inorganic base or organic base such as sodium hydroxide, potassium hydroxide, or ammonia, and heated as necessary. To manufacture by Can do. Chemically treated products include all those derived from hon-shimeji that have been subjected to chemical treatment as described above. The enzyme-treated product is, for example, an enzyme-treated product such as pectinase, cellulase, xylanase, amylase, mannanase, gnorecosidase, hemicenolase, chitinase, a-and-j8-darc mouth nidase, a-and-j8-dalcanase, etc. An enzyme reaction product (for example, a fermented product) obtained by the above-mentioned method can be produced, for example, by reacting hon-shimeji mushroom with the above enzyme in an appropriate buffer. Enzyme-treated products include all those derived from hon-shimeji that have been subjected to the enzyme treatment as described above.

[0024] The active ingredient of the present invention is not particularly toxic as described later. In addition, the possibility of side effects is low. Therefore, the antitumor activity can be expressed safely and appropriately. Therefore, the antitumor agent of the present invention comprising the active ingredient and the medicine, food or feed containing the same are effective for treating or preventing tumors.

[0025] In the present invention, the disease targeted by the antitumor agent is not particularly limited as long as it is a disease that requires an antitumor action for treatment, and examples thereof include all malignant tumors. Although the present invention is not particularly limited, examples of the disease include gastric cancer, colon cancer, esophageal cancer, skin cancer, uterine cancer, prostate cancer, bladder cancer and lung cancer. Furthermore, malignant tumors of hematopoietic organs such as leukemia can also be targeted for the antitumor agent of the present invention. The antitumor agent of the present invention exhibits remarkable antitumor activity against sarcoma cells, and thus occurs in tissues other than epithelium, such as muscle, vascular, cartilage, bone, hematopoietic tissue, nerves, etc. Tumors, so-called sarcomas, are also subject to the antitumor agent of the present invention.

[0026] The antitumor agent of the present invention is characterized in that it contains at least one selected from the group consisting of hon-shimeji mushroom and its processed product as an active ingredient. In the present specification, at least one selected from the group consisting of the above-mentioned hon-shimeji mushroom and its processing power may be referred to as an active ingredient of the present invention. The antitumor agent of the present invention may be the active ingredient itself or a composition containing the active ingredient. Examples of the antitumor agent of the present invention include those prepared by combining the active ingredient according to the present invention with a known carrier. Further, in the antitumor agent of the present invention, the active ingredient can be used for other components that can be used for the same purpose as the active ingredient, for example, known antitumor agents Can be blended or used together.

[0027] The production of the antitumor agent of the present invention is usually carried out by blending the active ingredient with a pharmaceutically acceptable liquid or solid carrier, and if desired, a solvent, a dispersant, an emulsifier, a buffer. Agents, stabilizers, excipients, binders, disintegrants, lubricants, etc., solids such as tablets, granules, powders, powders, capsules, etc., usually liquids, suspensions, emulsions, etc. Can be a liquid. It can also be made into a dry product that can be made liquid by adding a suitable carrier before use, or other external preparations.

[0028] The carrier can be selected depending on the dosage form and dosage form of the antitumor agent of the present invention. In the case of an oral preparation comprising a solid composition, it can be a tablet, pill, capsule, powder, fine granule, granule, etc., for example, starch, lactose, sucrose, mannitol, carboxy Methyl cellulose, corn starch, inorganic salts, etc. are used as carriers. In preparation of the oral preparation, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a corrigent, a coloring agent, a fragrance and the like can be further added. For example, in the case of tablets or pills, it may be coated with a sugar coating such as sucrose, gelatin or hydroxypropylcellulose, or a film of a gastric or enteric substance, if desired. In the case of an oral preparation comprising a liquid composition, it can be a pharmacologically acceptable emulsion, solution, suspension, syrup, etc. For example, purified water, ethanol, etc. are used as a carrier. Is done. Further, if desired, adjuvants such as wetting agents and suspending agents, sweetening agents, flavoring agents, preservatives and the like may be added.

[0029] On the other hand, when a parenteral preparation is used, distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil are used according to a conventional method, and the active ingredient of the present invention is used as a diluent. It can be prepared by dissolving or suspending in corn oil, propylene glycol, polyethylene glycol or the like, and adding a bactericidal agent, stabilizer, tonicity agent, soothing agent, etc., if necessary. In addition, a solid composition can be produced and used by dissolving in sterile water or a sterilized solvent for injection before use.

[0030] External preparations include solid, semi-solid or liquid preparations for transdermal administration or transmucosal (intraoral or intranasal) administration. Also included are suppositories and the like. For example, emulsions, emulsions such as mouth lotions, tinctures for external use, liquid preparations such as liquids for transmucosal administration, oily Ointments such as ointments and hydrophilic ointments, patches for transdermal administration or transmucosal administration such as films, tapes, and nops can be used.

[0031] Each of the above-mentioned various preparations can be appropriately produced by a conventional method using a known pharmaceutical carrier or the like. In addition, the content of the active ingredient in a potent formulation is not particularly limited as long as the active ingredient can be administered within the dosage range described below, taking into consideration its administration form, administration method and the like. Absent. The content of the active ingredient in the antitumor agent of the present invention is about 0.1 to about LOO% by weight.

[0032] The antitumor agent of the present invention is administered by an appropriate administration route according to the preparation form. The administration method is not particularly limited, and can be internal, external, and injection. An injection can be administered, for example, intravenously, intramuscularly, subcutaneously, or intradermally. For an external preparation, for example, a suppository should be administered by an appropriate administration method.

[0033] The dose as the antitumor agent of the present invention is appropriately set depending on the preparation form, administration method, purpose of use, and age, weight, and symptom of the patient to whom the antitumor agent is administered, and is not constant. In general, for example, the daily dose for an adult is 150 g to 1 kgZkg body weight, preferably 150 g to 500 gZkg body weight, more preferably 1.5 mg, in terms of the dry weight of hon-shimeji, an active ingredient contained in the preparation. ˜500 gZkg body weight, more preferably 1.5 mg to 200 gZkg body weight, even more preferably 15 mg to 150 gZkg body weight, even more preferably 15 mg˜: LOOg / kg body weight is desirable. Here, the dry weight conversion of the active ingredient hon-shimeji mushroom contained in the preparation means, for example, when the active ingredient is an extract, the amount of the extract contained in the preparation is the dry weight of the hon-shimeji mushroom used as a raw material. Says the value expressed. Since the dosage varies depending on various conditions, an amount smaller than the above dosage may be sufficient, or it may be necessary to exceed the range. Administration may be carried out once or divided into several times within a desired dosage range within one day. The administration period is also arbitrary. Further, the antitumor agent of the present invention can be administered orally as it is, or it can be added to any food and regularly ingested.

[0034] The production method, dosage form, active ingredient content, dose, administration route, administration method and the like of the medicament of the present invention are the same as those of the antitumor agent. Since the medicament of the present invention contains the antitumor agent, it can safely and appropriately exhibit antitumor activity. [0035] The term "containing" in the food or feed of the present invention means inclusion, addition and / or dilution. Here, “containing” means that the active ingredient used in the present invention is contained in food or feed, and “addition” means that the active ingredient used in the present invention is added to the raw material of food or feed. In other words, “dilution” means that when an ingredient for food or feed is added to the active ingredient used in the present invention, the aspect is changed.

[0036] The food production method of the present invention is not particularly limited! For example, formulation, cooking, power! ] And the like can be produced by the production method of ordinary foods, and the obtained food contains the active ingredient according to the present invention! I'm good!

[0037] The food of the present invention is not particularly limited. For example, processed food products (eg, processed flour products, starch cake products, premix processed products, rice cakes, macaroni products, bread products, Shrimp, buckwheat, rice bran, rice noodles, harsame, packaging rice cake, etc.), processed oils and fats (eg, plastic oil, sesame oil, salad oil, mayonnaise, dressing, etc.), processed soybeans (eg, tofu, miso, Natto, etc.), processed meat products (eg, ham, bacon, pressed ham, sausage, etc.), fishery products (eg, frozen groundnut, power boiled rice, chikuwa, hampen, deep-fried sweet potato, tsunami, streaks, fish ham, sausage, Bonito, processed egg products, canned fish, tsukudani, etc.), dairy products (eg, raw milk, cream, yogurt, butter, cheese, condensed milk, powdered milk, ice cream, etc.), vegetables' fruit calories (eg, pastes) , Ja Foods, pickles, fruit drinks, vegetable drinks, mixed drinks, etc.), confectionery (e.g. chocolate, biscuits, confectionery breads, cakes, cakes, rice confectionery, etc.), alcohols (e.g., sake, China) Liquor, wine, whiskey, shochu, vodka, brandy, gin, rum, beer, soft alcoholic beverages, fruit liquor, liqueur, etc., beverages (eg green tea, tea, oolong tea, coffee, soft drinks, lactic acid beverages) Etc.), seasonings (eg, soy sauce, sauce, vinegar, mirin, etc.), canned 'bottled' packaged foods (eg, beef rice, kettle rice, red rice, curry, other cooked foods, etc.), semi-dried Or concentrated food (eg, liver paste, other spreads, buckwheat noodle soup, concentrated soup, etc.), dried food (eg, instant coffee, instant curry, instant coffee, powdered juice, powdered soup, instant miso soup, Key Finished foods, cooked beverages, cooked soups, etc.), frozen foods (eg, sukiyaki, chawanmushi, eel cabbage, hamburg steak, sweet potato, dumplings, various sticks, fruit cocktails, etc.), solid foods, liquid foods (eg, soup Agricultural products such as spices, processed forest products, processed livestock products, marine products Products.

[0038] In the food of the present invention, if the active ingredient is contained alone or in plural, added and Z or diluted, and the content corresponds to a necessary amount for developing anti-tumor activity, The shape includes tablets, granules, capsules and the like that can be taken orally. Moreover, it can also be set as the health food which concentrated the active ingredient by adding glycerol etc. to the said active ingredient.

[0039] In addition, as an alcoholic beverage which is one embodiment of the food of the present invention, a product obtained by immersing the fruit body of Honshimeji used in the present invention in drinking alcohol is used as it is or in a known method for producing an alcoholic beverage. It can be used for drinking as an alcoholic beverage obtained in a similar manner.

[0040] Furthermore, processed products of hon-shimeji fruit bodies or mycelium used as an active ingredient in the present invention, for example, pulverized products and crushed products formed into tablets, granules, etc. according to known methods are also used. Included in the food product of the invention.

[0041] The content of the active ingredient in the food of the present invention is not particularly limited, and can be appropriately selected from the viewpoint of its sensory and activity expression, but in 100% by weight of the food, 0.01% by weight or more of the active ingredient. In addition, preferably 0.1 to 95% by weight, more preferably 1 to 90% by weight, and the food of the present invention is preferably a human (in terms of dry weight of hon-shimeji, an active ingredient contained therein) For example, adult) 150 / zg per day: LkgZkg body weight, more preferably 150 / ζ _{8 to} 500 ₈ kg body weight, more preferably 1.5 mg to 500 g Zkg body weight, even more preferably 1.5 mg to 2 OOgZkg The body weight, more preferably 15 mg to 150 gZkg body weight, and even more preferably 15 mg to: LOOgZkg body weight may be taken. Here, the dry weight conversion of the active ingredient hon-shimeji mushroom contained in food means, for example, when the active ingredient is an extract, the amount of extract contained in the food is expressed as the dry weight of hon-shimeji mushroom used as a raw material. Say the value. The amount of intake varies depending on various conditions, such as the type of extraction solvent and the amount of solvent used, so an amount smaller than the above intake amount may be sufficient, or it may be necessary to exceed the range. is there.

[0042] The food of the present invention is a food for treating or preventing tumors, and is particularly useful in maintaining the homeostasis of the living body by ingesting and eating the food of the present invention. In addition The food may be, for example, a health food (a food for specified health use) with a label indicating that it is used for manifestation of a desired effect due to antitumor activity.

[0043] Further, the present invention provides a biological feed comprising the active ingredient, and as another aspect, the active ingredient is administered to the living organism. It also provides a method of rearing. Moreover, as another aspect of the present invention, there is provided a biological breeding agent comprising the above-mentioned active ingredient. Here, “containing” means the above-mentioned inclusion, addition and / or dilution.

[0044] In these inventions, the living organisms are, for example, farm animals, pet animals, etc., and the farm animals include domestic animals such as horses, bushes, pigs, hidges, goats, ratadas, llamas, mice, rats, Examples include laboratory animals such as guinea pigs and rabbits, poultry such as tiger birds, ducks, turkeys and eagle birds, fish, crustaceans and shellfish, and examples of pet animals include dogs and cats. Examples of feed include feed for tumor treatment and Z or prevention. Examples of biological breeding agents include soaking agents, feed additives, and beverage additives.

[0045] According to these inventions, based on the antitumor action of the active ingredient used in the present invention in the living organisms exemplified above to which they are applied, Similar effects can be expected.

[0046] The active ingredient used in the feed of the present invention is usually the active ingredient in 100% by weight of the feed in terms of dry weight of hon-shimeji mushroom when the active ingredient is a dry powder of the fruit body of hon-shimeji mushroom. .01 wt% or more, preferably 0.1 to 95 wt%, more preferably 1 to 90 wt%, and the feed of the present invention is preferably converted into dry weight of hon-shimeji as an active ingredient contained therein. The target organism is 150 g to 1 kgZkg body weight per day, more preferably 150 / ζ _{8 to} 500 ₈ kg body weight, more preferably 1.5 mg to 500 g Zkg body weight, even more preferably 1.5 mg to 200 g Zkg body weight, Even more preferably, 15 mg to 150 gZkg body weight, even more preferably 15 mg to: LOOgZkg body weight may be administered. Here, when the active ingredient is an extract, for example, when the active ingredient is an extract, the amount of the extract contained in the feed is expressed in terms of the dry weight of the original hon-shimeji. Say the value. The dosage varies depending on various conditions, for example, the type of extraction solvent, the amount of solvent used, etc., so an amount smaller than the above dosage may be sufficient. Or beyond the scope.

[0047] The method for producing the feed of the present invention is not particularly limited, and if the formulation is similar to that of general feed, the prepared feed can contain the above-described antitumor agent of the present invention. Yo ... The biological breeding agent may be produced, used, etc. according to the case of the feed.

[0048] Treatment of tumors in livestock, laboratory animals, poultry, pet animals, etc. by administering a feed comprising the antitumor agent of the present invention or immersing the target organism in a liquid containing an antitumor agent or Prevention can be done. These aspects form one aspect of the method for raising organisms provided by the present invention.

[0049] The present invention also provides a method for treating a tumor, comprising administering to a subject at least one selected from the group consisting of an effective amount of hon-shimeji mushroom and its treatment ability.

[0050] In the present specification, the subject is preferably a human being who requires antitumor action, and may be a cultured animal, a pet animal or the like as described above.

[0051] In the present specification, the effective amount means that when at least one (active ingredient) selected from the group consisting of hon-shimeji mushroom and its processed product is administered to the subject, the active ingredient is administered. The amount of the component that exerts an anti-tumor effect compared to a subject that has not. The specific effective amount is appropriately set according to the administration form, administration method, purpose of use and age, weight, symptom, etc. of the subject, but is preferably constant, as in the above-mentioned medicine. The amount is 150 / zg to 1 kgZkg body weight per day for humans (eg adults), more preferably 150 / zg to 500 gZkg body weight.

[0052] In the tumor treatment method of the present invention, at least one selected from an effective amount of hon-shimeji mushroom and a group capable of treating the same may be administered to the subject as it is, or the medicament as described above. It may be administered as a food or feed. Also, there is no limitation on the administration method, and for example, it may be administered by oral administration, injection or the like, similar to the above-mentioned medicine.

[0053] According to the treatment method of the present invention, the disease targeted for the pharmaceutical, food or feed of the present invention can be treated. For example, the effect of suppressing cancer treatment, progression, and metastasis is exhibited. Get.

[0054] The active ingredient used in the present invention does not show toxicity even when an effective amount for the expression of its action is administered to the organism. For example, acetic acid extracted from Honshimeji hot water extraction residue Toxicity is not observed even when the ethyl extract fraction is orally administered to lgZ mice on day Z.

Example

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples. In the description of the examples, the term “tumor inhibitory activity” is used as a term synonymous with antitumor activity.

[0056] Example 1

Fresh hon-shimeji fruiting body (Hon-shimeji LaOl-27: cultivated in Takarano) 16. 7kg was dried by dry heat at 60 ° C for 2 days to obtain 1,377g of dried hon-shimeji. The dried hon-shimeji was pulverized with a Warinda blender to prepare 1,365 g of hon-shimeji dry powder. Next, 500 g of dried hon-shimeji powder was suspended in 10 L of water, extracted by heating at 95 ° C. for 3 hours, left to stand for 1 hour, and centrifuged to obtain 8.9 L of extract and an extraction residue. The extract was concentrated with an evaporator and then freeze-dried to prepare 243 g of Honshimeji hot water extract. The extraction residue was lyophilized as it was to prepare 245 g of Honshimeji hot water extraction residue.

[0057] Example 2

ICR mice (Japan SLC) purchased 5-week-old females and used them at 6-week-old. Sarcoma-180 (hereinafter S-180) tumor cells were transplanted into the abdominal cavity of ICR mice to make ascites, and transplanted to another mouse every 7 days. After passage, ascites was collected on the 7th day, centrifuged and washed with phosphate buffer, suspended in the same buffer, and after counting the number of cells, adjusted to 5 × 10 ⁷ ZmL. This 0.1 mL was transplanted subcutaneously into the right flank of ICR mice, and the size of the solid tumor 7 days later was measured. Mice were divided into groups so that the average tumor size was uniform in each group, with 10 mice per group. The dried hon-shimeji powder was prepared by mixing the powder prepared in Example 1 with a normal powdered feed CE-2 (CLEA Japan) at a mixing ratio of 10% and giving it to mice. In addition, the hot water extract and hot water extraction residue prepared in Example 1 were also lyophilized and powdered, and similarly mixed with powdered feed CE-2. The dose was converted to Honshimeji fruit body powder and used to be equivalent to the case where 10% by volume of powder sample CE-2 was mixed. The actual dose is about 15 gZkg Z days for mice administered with Honshimeji fruit body powder, and about 7.5 g / kg / day for mice administered with hot water extract and mice administered with hot water extraction residue. The control group received only CE-2. Tumor size is S— 1 Measurements were made 5 weeks after 80 transplants. In addition, the major and minor diameters of the tumor were measured, and the volume was calculated according to the following calculation formula for comparison.

Tumor volume (mm ³ ) = (major axis) X m V 2

Tumor suppressive activity was calculated according to the following formula.

Tumor suppressive activity (%) = (tumor volume in the control group, tumor volume in the hon-shimeji treated group) tumor volume in the Z control group X 100

[0058] [Table 1] Mouse tumor volume Visceral suppression ¾ ft

(Average soil standard error) (%)

C E-2 (control □ —control) 2 6 3 3 people 4 7 1

Honshimeji fruit body powder 1 G% 1 8 9 1 ± 4 2 8 2 8 .2 Hot water extract (equivalent to 10% fruit body powder) 7 3 9 ± 1 7 4 7 1 .9 Hot water extraction residue <child (Equivalent powder 10%) 1 1 3 1 Sat 2 2 7 5 7 .0

[0059] The results are shown in Table 1. When hon-shimeji fruiting body powder was administered in a diet containing 10%, an action to suppress the tumor was observed. In addition, when hot water extraction was performed, this inhibitory effect was observed not only in the hot water extract but also in the hot water extraction residue.

[0060] Example 3

250 g of dried hon-shimeji fruiting body powder prepared in the same manner as in Example 1 was suspended in 5 L of water, extracted by heating at 95 ° C for 3 hours, allowed to stand overnight, and then centrifuged (4200 rpm, 30 minutes, 25 ° C). 624 g of residue was obtained. Ethyl acetate was added thereto until the total amount became 5 L, and the mixture was stirred at room temperature for 3 hours. The extract was obtained by suction filtration using No. 2 filter paper (manufactured by Advantech). This was concentrated under reduced pressure while heating at 40 ° C. to dryness to obtain 9.4 g of an extract. Saratoko was dissolved in 100% ethanol and then dried to repeat twice to remove ethyl acetate.

[0061] Example 4

In the same manner as in Example 2, SCR-180 was transplanted and ICR mice (Japan SLC) 1 week later were mixed with the cetyl acetate extract prepared in Example 3 in powdered feed CE-2. The experiment was conducted with 10 animals per group. The dose was converted to hon-shimeji fruiting body powder, and it was used so as to be equivalent to the case where 10% by volume was mixed with powder sample CE-2. Actual throw The dose is approximately 628 mg / kg / day. The control group received only CE-2. Tumor size and tumor suppressive activity (%) were calculated in the same manner as in Example 2.

[0062] [Table 2]

Mouse tumor volume tumor suppressive activity

(Average soil standard error) (%)

C E-2 (Control) 3 5 9 1 ± 4 9 1

Honshimeji Hot Water Extraction Residue Ethyl Acetate Extraction Fraction 2 0 4 7 3 7 0 4 3. 0

(Approx. 6 2 8 mg / kg)

[0063] The results are shown in Table 2. In the hon-shimeji hot water extraction residue, the ethyl acetate extract fraction suppressed S-180 solid tumor growth compared to the control group. That is, the tumor suppressive activity transferred to the hot water extraction residue was transferred to the ethyl acetate extract fraction.

[0064] Example 5

Honshime cultured in PGY agar plate medium (composition: glucose 2.0%, peptone 0.2%, yeast extract 0.2%, KH PO 0.05%, MgSO · 7Η OO. 05%, Agarl. 5%)

2 4 4 2

Di-strain LaOl—27 strains in 200 ml of PGY liquid medium (composition: glucose 2.0%, peptone 0.2%, yeast extract 0.2%, KH PO 0.05%, MgSO 7Η OO. 05%) Entered 50

2 4 4 2

Four 0 ml Erlenmeyer flasks were inoculated and cultured with shaking at 25 ° C for 10 days under lOOrpm. Furthermore, inoculate the 200L jar mentor containing 120L of PGY liquid medium with the above liquid culture and shake culture under the lOOrpm culture condition at 25 ° C for 5 days. Obtained. Centrifugation (36500 g, 30 minutes, 4 ° C.) was performed on 36 L of the obtained mycelium culture solution to obtain mycelium in the precipitate fraction. Add 6 L of deionized water to the mycelium obtained, stir, and then centrifuge again (6500 g, 30 minutes, 4 ° C) to obtain about about Honshimeji mycelium from which the medium components have been removed from the precipitate fraction. 3. Obtained 4kg. The mycelium was lyophilized to obtain 215 g of a lyophilized hon-shimeji mycelium.

[0065] Example 6

The hon-shimeji mycelium obtained in Example 5 was dried at 60 ° C. for 6 days to obtain 160 g of mycelium powder. Suspended with 3.2 L of water and extracted at 95 ° C for 3 hours. 4200rp at 25 ° C Centrifugation was carried out for 30 minutes to separate the extract and the extraction residue. The hot water extract was concentrated under reduced pressure at 40 ° C. and then freeze-dried to obtain 100.lg of powder. As in Example 2, S-180 was transplanted and ICR mice (Japan SLC) were mixed with mycelium powder or hot water extract prepared here for powdered feed CE-2. Gave. The experiment was conducted with 10 animals per group. The dose was converted to hon-shimeji mycelium powder so that it was equivalent to the powder sample CE-2 mixed with 10% by volume. The actual dose is about 15 gZkgZ in mice administered with Honshimeji mycelium powder, and about 9 gZkgZ days in mice administered with Honshimeji mycelium hot water extract. The control group received only CE-2. Tumor size and tumor suppressive activity (%) were calculated in the same manner as in Example 2. The results are shown in Table 3.

[0066] [Table 3] Mouse Tumor volume Tumor suppressive activity

(Mean ± standard error) (%)

C E— 2 (Control) 2 9 9 4 ± 3 8 8

Honshimeji mycelium powder 1 0% 1 8 44 ± 3 0 2 3 8. 4 Honshimeji mycelium hot water extract 1 2 9 7 ± 2 5 9 5 6. 7

(ffi thread body powder equivalent to 10%)

[0067] When 10% Honshimeji mycelium powder was administered as a diet, tumor growth was suppressed. This activity was also observed in the hot water extract.

Industrial applicability

[0068] According to the present invention, there is provided an antitumor agent characterized by containing at least one selected from the group consisting of hon-shimeji mushroom and processed products thereof as an active ingredient. The antitumor agent is useful as a medicament, food or feed for treating or preventing tumors.

Claims

The scope of the claims

[1] An antitumor agent comprising at least one selected from the group consisting of Lyophyllum shimeji and its processing power as an active ingredient.

[2] The antitumor agent according to [1], wherein the treated product is a dry powder, an extract, or an extraction residue.

[3] A medicament comprising the antitumor agent according to claim 1 or 2.

[4] A food or feed for treating or preventing a tumor, comprising the antitumor agent according to claim 1 or 2.

[5] The subject is at least selected from the group consisting of an effective amount of hon-shimeji and its processing power.

A method of treating a tumor, comprising administering one.

[6] Use of at least one selected from the group consisting of hon-shimeji mushroom and its processed product for the production of the antitumor agent according to claim 1.