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WO2006006273A1 - Activateur de cellules dendritiques - Google Patents

Activateur de cellules dendritiques Download PDF

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Publication number
WO2006006273A1
WO2006006273A1 PCT/JP2005/004068 JP2005004068W WO2006006273A1 WO 2006006273 A1 WO2006006273 A1 WO 2006006273A1 JP 2005004068 W JP2005004068 W JP 2005004068W WO 2006006273 A1 WO2006006273 A1 WO 2006006273A1
Authority
WO
WIPO (PCT)
Prior art keywords
rod
cells
cell activator
shaped
pharmaceutical composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2005/004068
Other languages
English (en)
Japanese (ja)
Other versions
WO2006006273A8 (fr
Inventor
Yasunori Matsui
Hiroshi Yukawa
Makoto Tamesada
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kobayashi Pharmaceutical Co Ltd
Original Assignee
Kobayashi Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kobayashi Pharmaceutical Co Ltd filed Critical Kobayashi Pharmaceutical Co Ltd
Publication of WO2006006273A1 publication Critical patent/WO2006006273A1/fr
Publication of WO2006006273A8 publication Critical patent/WO2006006273A8/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis

Definitions

  • the present application relates to a rod-shaped cell activator comprising a shiitake mycelium extract or a fraction thereof, particularly a rod-shaped cell maturation promoter. Furthermore, the present invention relates to a composition for oral intake, a pharmaceutical composition, a food composition and the like containing the rod-shaped cell activator.
  • Spider cells are a type of immune cell having a morphological feature of having dendritic processes, and are distributed in various tissues (for example, skin and mucous membranes) to serve as immune surveillance cells.
  • rod cells are cells that have the function of transporting antigen that has entered the body to lymphoid tissues and stimulating T cells to induce an immune response, and play a central role in the immune response together with lymphocytes.
  • rod cells present in the peripheral tissue are called immature rod cells because of their low T cell activity.
  • rod cells present in lymphatic organs are called mature rod cells because they have a strong ability to activate T cells.
  • cell adhesion and costimulatory molecules eg, CD40, CD54, CD58, CD80 and CD86
  • cytokines in addition to MHC (major histocompatibility complex) molecules This is due to changes in production capacity such as chemokines.
  • Non-patent Document 1 Cell Engineering, No. 19, No. 9, 2000, No. 1). 1311-1317).
  • TNF a produced by LPS (lipopolysaccharide), DNA, double-stranded RNA, or tissue cell force derived from induction of inflammatory response from infected bacteria or viruses.
  • TNF a tumor necrosis factor a
  • IL-1 interleukin 1
  • CD40L CD40 ligand
  • non-Patent Document 3 Bioth e mpy, 15 Certificates, No. 3, 2001, 385- 388 pp; non-Patent Document 4: Cancer Immunology and Immunotherapy, 52nd, 2003, 207-214).
  • Patent Document 1 International Patent Publication 01Z048 154 pamphlet.
  • Patent Document 2 Japanese Patent Application Laid-Open No. 2004-210768.
  • shiitake mushrooms which are representative edible mushrooms in Japan and China, have been ingested as a food for many years in Japan, and have been cultivated artificially for 300 years. It is considered to be excellent in safety when administered orally, especially when administered orally for a long period of time.
  • Patent Document 3 Japanese Patent Laid-Open No. 62-270532
  • Patent Document 4 Japanese Patent Laid-Open No. 2-237934
  • Patent Document 5 JP-A-2-134325
  • Patent Document 6 JP-A-12-12538, etc.
  • Non-patent Document 3 Biothempy, No. 15, No. 3, 2001, pp. 385-388. Therefore, there has been no report on shiitake extract that has any effect on rod cells.
  • Non-Patent Document 5 Nikkei Science, February 2003, pp. 84-91; Non-Patent Document 6: Contemporary Medicine, August 2003, pp. 86-92).
  • Non-Patent Document 6 Contemporary Medicine, August 2003, pp. 86-912.
  • a safe and efficient rod-shaped cell activation agent is required.
  • Patent Document 1 International Patent Publication 01Z048154 Pamphlet
  • Patent Document 2 JP 2004-210768 A
  • Patent Document 3 Japanese Patent Laid-Open No. 62-270532
  • Patent Document 4 Japanese Patent Laid-Open No. 2-237934
  • Patent Document 5 JP-A-2-134325
  • Patent Document 6 Japanese Patent Laid-Open No. 2003-012538
  • Non-Patent Document 1 Cell Engineering, 19th, 9th, 2000, 1311-1317
  • Non-Patent Document 2 Banchereau J et al., Nature, No. 392, 1998, pp. 245-252
  • Non-Patent Document 3 Biotherapy, No. 15, No. 3, 2001, pp. 385-388
  • Non-patent document 4 Cancer Immunology and Immunotherapy, 52nd article, 2003
  • Non-Patent Document 5 Nikkei Science, February 2003, pp. 84-91
  • Non-Patent Document 6 Contemporary Medicine, August 2003, pp. 86-92
  • An object of the present invention is to provide an extract derived from shiitake mycelium having a rod-like cell activation action, and a rod-like cell activator, immunostimulant, composition for oral consumption, and pharmaceutical composition containing the extract. Products, food compositions, foods and beverages.
  • a rod-like cell active agent containing shiitake mycelium extract is provided.
  • activation of rod cells means that some function of the rod cells is enhanced, or the amount of molecules such as proteins expressed in the rod cells is amplified.
  • the intent of the term includes, for example, promoting maturation of rod cells, enhancing antigen uptake ability, enhancing antigen presentation ability, and enhancing ⁇ lymphocyte stimulation ability.
  • the adhesion molecule Z Increased expression of stimulatory molecules (eg, CD40, CD54, CD58, CD80, CD86), enhanced production capacity of site force-in (eg, interleukin-12, interferon gamma and interleukin-1), MHC For example, increase in the expression level of the molecule.
  • stimulatory molecules eg, CD40, CD54, CD58, CD80, CD86
  • site force-in eg, interleukin-12, interferon gamma and interleukin-1
  • MHC For example, increase in the expression level of the molecule.
  • a pharmaceutical composition comprising the above rod-shaped cell activator.
  • the pharmaceutical composition is not particularly limited, and can be used, for example, for immunostimulation, treatment or prevention of cancer or malignant tumor, or treatment or prevention of infectious diseases.
  • the cancer and malignant tumor are not particularly limited, but for example, digestive organ cancer such as colon cancer and stomach cancer, myeloma, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, uterine cancer, lung cancer, oral cavity Examples include cancer and brain tumors.
  • infectious diseases include viral infections such as chronic hepatitis due to hepatitis C and hepatitis C virus, HIV, influenza, and the like.
  • the mycelium of shiitake mushroom in the present invention is not particularly limited, and, for example, a mycelium in a state before the edible fruit body can be used.
  • the mycelium may be produced by culturing or collected from nature.
  • a mycelium obtained by culturing shiitake mushrooms in a solid medium can be used.
  • the shiitake mycelium extract used in the present invention can be prepared by a method known in the art, but an extract obtained by hot water extraction after pulverization of the mycelium can be used.
  • an extract obtained by crushing and decomposing a solid medium containing mycelium in the presence of water and an enzyme can be used.
  • a solvent used for the preparation of the extract for example, water, ethanol, methanol, butanol, isopropanol, etc.
  • water preferably water
  • Extraction should be performed with ultrasonic waves at a lower temperature (for example, 25-50 ° C, preferably 30-45 ° C) than the force that can be performed under heating of the solvent (for example, about 85-105 ° C). You can also do this.
  • the shiitake mycelium extract is not limited, for example, an extract obtained by the following method can be used. That is, inoculate shiitake mushrooms on a solid medium based on bagasse (sugar cane scum) and defatted rice bran, and then grow the mycelium to obtain a solid medium containing mycelium that has a weight of 30%. %, And water and cellulase, protease, or darcosidase power are selected in the solid medium. At least 70% by weight of bagasse fiber by adding one or more of the enzymes to be added while maintaining the solid medium at a temperature of 30-55 ° C, and crushing and grinding the solid medium in the presence of the enzyme.
  • bagasse bagasse
  • the enzymes to be added while maintaining the solid medium at a temperature of 30-55 ° C, and crushing and grinding the solid medium in the presence of the enzyme.
  • the extract may be used as a shiitake mycelium extract, but it is convenient to store it as a powder by concentrating, lyophilizing, and using it in various forms at the time of use.
  • the powder obtained by freeze-drying is a brown powder, is hygroscopic and has a unique taste and smell.
  • the extract of the mycelium of shiitake mushroom thus obtained contains 15-50% carbohydrate, preferably 20-40% (w / w) by carbohydrate analysis by the phenol sulfate method, and 10-10 protein by lowry protein analysis. — 40%, preferably 13-30% (wZw), Folin—standard with gallic acid Contains 15% polyphenols, preferably 2.5-3.5% (wZw) by Denis method . Shiitake mycelium extract is not limited to this, including about 0.1% lipid, about 0.4% fiber, and about 20% ash.
  • the shiitake mycelium extract in the present invention may be a fraction obtained from the ability of shiitake mycelium extract.
  • the fraction is obtained by a fractionation method usually used in the technical field to which the present invention belongs, and examples of the fractionation method include fractionation by extraction using an arbitrary solvent, gel filtration column chromatography, ion This includes fractionation using an exchange column and silica gel column chromatography.
  • the fractionation method may be one type or a combination of multiple means.
  • the solvent used in the fractionation method is not particularly limited, and for example, water, methanol, ethanol, n-propanol, isopropanol, acetic acid, acetone, and a mixture thereof can be used.
  • the fraction can be used as a soluble fraction by concentrating, sticking, or solid, obtained by concentration and Z or lyophilization, if necessary.
  • the term "spider cell activator” generally refers to spider cells. By acting, it means a drug that has the effect of enhancing the function of rod cells or amplifying the amount of substance expressed on or in rod cells, For example, effects such as promoting maturation of rod-shaped cells and increasing the ability to produce cytodynamic force (eg, interleukin-12) can be obtained.
  • cytodynamic force eg, interleukin-12
  • the rod-shaped cell activator of the present invention can be used as an active ingredient of a pharmaceutical composition.
  • the pharmaceutical composition can be used in various dosage forms such as tablets, capsules, powders, granules, pills, solutions, emulsions, suspensions, solutions, spirits, syrups for oral administration.
  • parenteral preparations such as subcutaneous injections, intravenous injections, intramuscular injections and intraperitoneal injections. However, it is not limited to these. These preparations can be produced by known methods usually used in the preparation process.
  • the pharmaceutical composition may contain various commonly used ingredients, such as one or more pharmaceutically acceptable excipients, disintegrants, diluents, lubricants, dressings, and the like. Flavoring agents, coloring agents, sweetening agents, flavoring agents, suspending agents, wetting agents, emulsifying agents, dispersing agents, adjuvants, preservatives, buffering agents, binders, stabilizers, coating agents and the like can be included. Further, the pharmaceutical composition of the present invention may be a sustained or sustained release dosage form.
  • the dosage of the pharmaceutical composition of the present invention can be appropriately selected depending on the administration route, the patient's body shape, age, physical condition, degree of disease, elapsed time after onset, etc.
  • the pharmaceutical composition of the present invention The article can include a therapeutically effective amount and a Z or prophylactically effective amount of a rod cell activator.
  • Shiitake mycelium extract was originally used as a food and has little concern for hyperplasia! / It is a relatively safe substance, so it can be administered at high concentrations as needed. is there.
  • shiitake mycelium extract may be used at a dose of generally 100-5000 mgZ day Z adult, preferably 300-3000 mgZ day Z adult.
  • the pharmaceutical composition may be administered in a single dose or multiple doses such as other rod-like cell activity agents, immunostimulants, anticancer agents, antitumor agents, anti-infective agents, etc. It can be used in combination with drugs.
  • a method of inducing mature rod cells by treating immature rod cells with the above rod-shaped cell activator.
  • the mature rod-shaped cells are not particularly limited.
  • monocyte cells are cytosylated (for example, condylar sphere Z macrophage colony stimulating factor (hereinafter also referred to as “GM CFS”) and interleukin 4 (hereinafter referred to as “ It is also referred to as “IL 4”))).
  • GM CFS condylar sphere Z macrophage colony stimulating factor
  • IL 4 interleukin 4
  • the monocyte cell is not particularly limited.
  • a blood monocyte cell can be used, and a human blood monocyte cell is preferable.
  • the change of immature rod cells into mature rod cells can be confirmed by methods known to those skilled in the art in the art. For example, costimulatory factors common to rod cells (for example, CD40, CD80, CD86) and an increase in the expression level of a protein specific to mature rod cells (eg, CD83) can be determined. The expression levels of these proteins can be observed by, for example, a flowmetry method.
  • costimulatory factors common to rod cells for example, CD40, CD80, CD86
  • an increase in the expression level of a protein specific to mature rod cells eg, CD83
  • the expression levels of these proteins can be observed by, for example, a flowmetry method.
  • the rod-shaped cell activator of the present invention used when activating rod-shaped cells in vitro is, as shown in the table, in an amount of 10-1000 ⁇ gm, preferably 100-500 ⁇ gZmL per day. It can be added to the culture medium. Further, for example, the activity of rod-shaped cells can be induced by culturing for a period of 1 to 15 days, preferably 2 to 3 days.
  • the method of the present invention may further include a step of mixing the rod-shaped cells and the antigenic substance in order to cause the obtained mature rod-shaped cells to present a specific antigen.
  • the antigenic substance is not particularly limited, but tumor-derived peptides or virus-derived peptides can be used, and for example, CEA-derived peptides, MAGE-derived peptides and the like can be used.
  • Mixing of the rod-shaped cells and the antigenic substance may be performed before or after the activation of the rod-shaped cells or simultaneously with the activation of the rod-shaped cells, but is preferably performed simultaneously with the activation of the rod-shaped cells.
  • a mature rod cell obtained by treating an immature rod cell with a rod cell activator, and a pharmaceutical composition comprising the mature rod cell Is provided.
  • the pharmaceutical composition is not particularly limited, but can be used for preventing or treating cancer, malignant tumors or infectious diseases.
  • digestive organ cancer such as colon cancer and gastric cancer, bone marrow Cancer, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, eclampsia, lung cancer, oral cancer, brain tumor and other cancers or malignant tumors
  • an auxiliary activator for use in immunotherapy comprising the above-described rod-shaped cell activator.
  • the auxiliary activator is a substance (adjuvant) that is administered into the living body together with the rod cells in order to induce the activation of the rod cells during immunotherapy, and is included as one component of the pharmaceutical composition. It may be.
  • the diseases targeted by immunotherapy are not particularly limited.
  • auxiliary active agent of the present invention may contain various commonly used ingredients, and the dosage thereof depends on the route of administration, the patient's body shape, age, physical condition, degree of disease, elapsed time after onset, etc. Can be selected as appropriate.
  • the auxiliary activator of the present invention can be carried out in the same embodiment as the above-described pharmaceutical composition of the present invention.
  • a food composition comprising the above rod-shaped cell activator.
  • the food composition of the present invention includes a liquid beverage such as a functional beverage.
  • the food composition can be used as a quasi-drug, a component such as food or drink, or a food additive.
  • the food composition in the present specification can be used as a functional food as it is, and can also be used as a food and drink, a pharmaceutical product, a quasi-drug, a component of food and drink, a food additive, and the like.
  • the use enables daily and continuous ingestion of food, beverage, food composition or composition for oral intake having a rod-like cell activation effect and an immunostimulatory effect, and an effective rod-cell activation effect. It is possible to improve the constitution by immunostimulation effect, treat diseases such as cancer, malignant tumors and infectious diseases and prevent their onset.
  • Examples of food compositions, foods or beverages containing the rod-like cell activator or immunostimulatory agent of the present invention include functional foods and health foods having rod-like cell activation effects or immunostimulatory effects. , General foods (juice, confectionery, processed foods, etc.), nutritional supplements (nutrient drinks, etc.).
  • the food or beverage in this specification is not limited, but includes inorganic components such as iron and calcium, various vitamins, dietary fibers such as oligosaccharides and chitosan, proteins such as soybean extract, It can contain lipids such as tin, sugars such as sucrose and lactose, and plant extracts such as shiitake mushrooms.
  • the rod-shaped cell activator of the present invention has an action of promoting maturation of immature rod cells and an immunostimulatory action resulting from the action. Therefore, the present invention provides an effective means for treating and / or preventing cancer, malignant tumors and infectious diseases caused by immunostimulation.
  • the present invention provides a method for inducing mature rod cells by treating immature rod cells. Since the shiitake mycelium extract also has an antioxidant effect, the method of the present invention can efficiently activate rod-shaped cells in an environment with little oxidative stress.
  • FIG. 1 An example of test results comparing the ability of shiitake mycelium extract and PSK to activate rod-shaped cells.
  • FIG. 2 is an example of the results of microscopic observation of rod-shaped cells activated by shiitake mycelium extract and PSK supplementation.
  • RPMI1640 medium containing 10% FBS
  • the cell suspension was prepared so as to be / ml.
  • 500 L of the prepared cell suspension was dispensed into a 24-well plate, and further added to each of GM-CSF (Peprotech) and IL-4 (Peprotech) at 40 ng / ml.
  • the cells were cultured at 37 ° C and 5% CO for 3 days. After 3 days, add 300 ⁇ L of culture supernatant to the cells.
  • RPMI 1640 medium (sigma, containing 10% FBS) 300 / z L.
  • GM-CSF Peprotech
  • IL-4 Peprotech
  • Induction of immature rod cells is a protein-specific antibody that expresses the expression of CD14 protein, a monocyte marker on the cell surface, and the expression of costimulatory factors, CD40, CD80, and CD86.
  • Anti-CD14 antibody FITC labeling, anti-CD40 antibody FITC labeling, anti-CD80 antibody PE labeling, and anti-CD86 antibody PC5 labeling were measured with a flow cytometer (Beckman Coulter Epics XL) for confirmation.
  • shiitake mycelium extract and PSK were added to a final concentration of 200 ⁇ g / ml, and cultured for 2 days at 37 ° C, 5% CO. . Also, the control
  • the cells were cultured for 2 days at 37 ° C and 5% CO without adding anything. 2 days later, culture under each condition
  • the rod-shaped cell activator of the present invention has a higher T cell interaction activity than the conventionally known rod-shaped cell activator.

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Abstract

L'invention concerne un procédé d'activation sans danger et efficace de cellules dendritiques et un activateur de cellules dendritiques capable d'être utile pour le procédé. L'activateur de cellules dendritiques de l'invention comprend un extrait de mycéliums de shiitake. En outre, l'invention concerne une composition pharmaceutique, une composition d'aliment, un aliment, une boisson, etc. comprenant l'activateur de cellules dendritiques. Encore en plus, l'invention concerne un procédé d'induction de cellules dendritiques matures, comprenant de traiter des cellules dendritiques immatures avec l'activateur de cellules dendritiques. Toujours encore en plus, l'invention concerne des cellules dendritiques matures obtenues par le procédé ci-dessus et une composition pharmaceutique comprenant les cellules dendritiques matures.
PCT/JP2005/004068 2004-09-30 2005-03-09 Activateur de cellules dendritiques Ceased WO2006006273A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004-288511 2004-09-30
JP2004288511A JP2006104068A (ja) 2004-09-30 2004-09-30 樹状細胞活性化剤

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WO2006006273A1 true WO2006006273A1 (fr) 2006-01-19
WO2006006273A8 WO2006006273A8 (fr) 2006-03-02

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008228676A (ja) * 2007-03-22 2008-10-02 Ichimasa Kamaboko Co Ltd キノコから効率的にβグルカンを抽出する方法

Citations (2)

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Publication number Priority date Publication date Assignee Title
JP2001106637A (ja) * 1999-10-04 2001-04-17 Amino Up Chemical Co Ltd サイトカイン産生能評価方法、サイトカイン産生能回復剤組成物、その製造方法及び用途
WO2002062813A1 (fr) * 2001-02-08 2002-08-15 Amino Up Chemical Co., Ltd. Nouveau produit presentant une activite physiologique, preparation et utilisation de ce produit

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001106637A (ja) * 1999-10-04 2001-04-17 Amino Up Chemical Co Ltd サイトカイン産生能評価方法、サイトカイン産生能回復剤組成物、その製造方法及び用途
WO2002062813A1 (fr) * 2001-02-08 2002-08-15 Amino Up Chemical Co., Ltd. Nouveau produit presentant une activite physiologique, preparation et utilisation de ce produit

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
KODAMA N. ET AL: "Stimulation of the natural immune system in normal mice by polysaccharide from maitake mushroom.", MYCOSCIENCE., vol. 44, no. 3, 2003, pages 257 - 261, XP002996085 *
LUIGINA ROMANI: "Immunity to Fungal Infections.", NATURE REVIEWS IMMUNOLOGY., vol. 4, no. 1, 2004, pages 11 - 23, XP002996083 *
NAKANE K.ET AL: "Agaricus-dake Chushutsueki no in vitro deno Men'eki Fukatsu Kassei NK Kassei, Kijo Saibo Yudo ni Oyobosu Koka.", BIOTHERAPY., vol. 15, no. 3, 2001, pages 383, XP002998863 *
PARK SOON-KEW ET AL: "Acid polysaccharide isolated from phellinus linteus induce phenotypic and functional maturation of murine dendritic cells.", BIOCHEM BIOPHYS RES COMMUN., vol. 312, no. 12, 2003, pages 449 - 458, XP004473292 *
YAMASAKI H. ET AL: "Jikkenteki Mouse Haiten'i Model (B16F10) o Mochiita Lentinus edodes mycelia no Koshuyo Koka ni Kansuru Kento. (Experimental study on the antitumor effect of...metastasis model [B16F10])", BIOTHERAPY., vol. 17, no. 5, 2003, pages 467 - 472, XP002998862 *

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JP2006104068A (ja) 2006-04-20

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