WO2006006271A1 - Activateur de cellules dendritiques - Google Patents

Activateur de cellules dendritiques Download PDF

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Publication number
WO2006006271A1
WO2006006271A1 PCT/JP2005/004066 JP2005004066W WO2006006271A1 WO 2006006271 A1 WO2006006271 A1 WO 2006006271A1 JP 2005004066 W JP2005004066 W JP 2005004066W WO 2006006271 A1 WO2006006271 A1 WO 2006006271A1
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WO
WIPO (PCT)
Prior art keywords
rod
cells
shaped cell
cell activator
shaped
Prior art date
Application number
PCT/JP2005/004066
Other languages
English (en)
Japanese (ja)
Inventor
Yasunori Matsui
Hiroshi Yukawa
Makoto Tamesada
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 WO2006006271A1 publication Critical patent/WO2006006271A1/fr

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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 COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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 COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present application relates to a rod-shaped cell activator comprising a mesimacob extract, particularly a rod-shaped cell maturation promoting agent. 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.
  • the 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.
  • Such functional differences include increased expression of cell adhesion and costimulatory molecules (eg, CD40, CD54, CD58, CD80 and CD86) and cytokines in addition to MHC (major histocompatibility complex) molecules. This is due to changes in production capacity such as Nychemokines.
  • the rod-shaped cells also begin to move to the lymph nodes due to restructuring of the cytoskeleton into a structure with strong structural strength and high motility.
  • the rod-like cells promote the activity of T cells by producing chemokines (Non-patent Document 1: Cell Engineering, No. 19, No. 9, No. 2000) Pp. 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 It is known to be induced by (tumor necrosis factor a) and IL-1 (interleukin 1), as well as CD40 ligand (CD40L) expressed on active platelets, basophils, mast cells, etc.
  • 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 It is known to be induced by (tumor necrosis factor a) and IL-1 (interleukin 1), as well as CD40 ligand (CD40L) expressed on active platelets, basophils, mast cells, etc.
  • TNF a produced by LPS (lipopolysaccharide), DNA, double-stranded RNA, or tissue cell force derived from induction of
  • Non-Patent Document 4 Cancer Immunology and Immunotherapy, 52nd, 2003, 207-214 Page;). It has also been reported that the maturation of rod-shaped cells is promoted by the cell wall skeleton of certain gram-positive bacteria (Patent Document 1: International Patent Publication 01Z048154 pamphlet). Further, it has been reported that a specific low molecular weight compound obtained by chemical synthesis has a rod-like cell activating action (Patent Document 2: Japanese Patent Application Laid-Open No. 2004-210768).
  • Meshimakobu is a mushroom-like mushroom belonging to the genus Mushroom of Paramecidae that parasitizes the trunk of an old hardwood tree such as mulberry. It has long been used in China as a decoction herbal medicine called “Kuwa Huang”. Recent studies have reported various physiological activities of components contained in Meshimakobu (e.g., Non-Patent Document 7: Abstracts of the Annual Meeting of the Japan Society for Agricultural Chemistry, VOL 2004, 2004, 2004, p. 197; non Patent Document 8: Annual Meeting of the Agricultural Chemical Society of Japan, Vol. 2004, 2004, p. 281; Non-patent document 9: Biochem Biophys Res Commun, p. 309, No. 2, 2003, p. 399-pp. 407 Such). However, there has been no report on the effect of mesimacob 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).
  • a safe and efficient rod cell activation agent is required.
  • Patent Document 1 International Patent Publication 01Z048154 Pamphlet
  • Patent Document 2 JP 2004-210768 A
  • 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
  • Non-Patent Document 7 Abstracts of the Japanese Agricultural Chemistry Conference, VOL2004, 2004, p.197
  • Non-patent Literature 8 Abstracts of the Agricultural Chemical Society of Japan Conference, VOL2004, 2004, p.281 Biophys Res Commun, No. 309, No. 2, 2003, pp. 399-407
  • the present inventor conducted extensive research to solve the above problems, and found that mesimacob has a rod-like cell activating action to complete the present invention.
  • An object of the present invention is to provide rod-shaped cell activators, immunostimulants, compositions for oral consumption, pharmaceutical compositions, food compositions, foods and beverages containing mesimacob.
  • a rod-shaped cell activator containing mesimacob is provided.
  • activation of rod cells means that some function of rod cells is enhanced, or the amount of a molecule such as a protein expressed in rod cells is amplified.
  • the intended meaning of the term includes, for example, promotion of maturation of rod cells, enhancement of antigen uptake ability, enhancement of antigen presentation ability, and enhancement of ⁇ lymphocyte stimulation ability.
  • the phenomenon observed in the rod cells with the activation includes increased expression of adhesion molecule Z costimulatory molecules (eg, CD40, CD54, CD58, CD80, CD86, etc.), cyto force-in (eg, Interleukin 12, interferon gamma, and interleukin 1) and the like, and increased expression of MHC molecules.
  • adhesion molecule Z costimulatory molecules eg, CD40, CD54, CD58, CD80, CD86, etc.
  • cyto force-in eg, Interleukin 12, interferon gamma, and interleukin 1
  • 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.
  • digestive organ cancer such as colon cancer and gastric cancer, myeloma, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, uterine cancer, lung cancer, oral cavity
  • infectious diseases include viral infections, such as chronic hepatitis due to hepatitis B and hepatitis C viruses, HIV, influenza, and the like.
  • the Meshimakobu (Phellinus Linteus Aoshima) used in the present invention is a fruit body, a mycelium, or a mixture thereof.
  • the force that can be used as a powder is preferably used as an extract, and particularly preferably an extract of fruiting bodies is used.
  • Meshimakobu may be produced by culture or collected from nature. In the present invention, for example, a mycelium obtained by culturing Meshimakobu fungus in a solid medium can be used.
  • the mesimacob used in the present invention may be used as a powder or the like.
  • an extract of Meshimakobu obtained by a method known in the art may be used.
  • the solvent used for the preparation of the extract of Meshimakobu for example, water, ethanol, methanol, butanol, isopropanol, etc., preferably water can be used.
  • Extraction can be performed under heating of a solvent (for example, about 85 to 105 ° C), but irradiation with ultrasonic waves at a lower temperature (for example, 25 to 50 ° C, preferably 30 to 45 ° C). You can do it with
  • the extract when the extract of Messimacob is used, the extract may be a fraction obtained from the extract strength.
  • the fractionation method is a method commonly 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 exchange column. Fractionation using silica gel, silica gel column chromatography and the like.
  • the fractionation method may be one type of method or a combination of a plurality of means.
  • the solvent used in the fractionation method is not particularly limited. For example, water, methanol, ethanol, n-propanol, isopropanol, acetic acid, acetone, and mixtures thereof can be used.
  • the extract and fraction used in the present invention use, as necessary, a concentrate, a viscous substance or a solid obtained by concentration and Z or freeze-drying as a soluble fraction. Can do.
  • the term "spider cell activator” generally enhances the function of a spider cell by acting on the spider cell, or on a spider cell. Alternatively, it means a drug that has the effect of amplifying the amount of a substance expressed in a cell. 12, the production ability of interferon ⁇ or interleukin-1 etc.) can be increased.
  • 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 sputum or prophylactically effective amount of a rod-shaped cell activator.
  • Meshimakobu was originally used as a traditional Chinese medicine and is a relatively safe substance, so it can be administered at a high concentration as needed.
  • mesimacob can generally be used at a dose of 100-5000 mgZ ⁇ adults, preferably ⁇ 300-lOOOOmgZ ⁇ adults.
  • Administration of the pharmaceutical composition may be a single dose or multiple doses. However, it can also be used in combination with other agents such as other rod-like cell activators, immunostimulants, anticancer agents, antitumor agents, and anti-infective agents.
  • immature immature rod cells are not particularly limited.
  • monocyte cells are cytosylated (for example, condylar granule Z macrophage colony stimulating factor (hereinafter also referred to as “GM-CFS”) and interleukins. 4 (hereinafter also referred to as “IL 4”)).
  • GM-CFS condylar granule Z macrophage colony stimulating factor
  • IL 4 interleukins. 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 for activating rod-shaped cells is, for example, a culture solution in an amount of 10 to 1000 ⁇ gm, preferably 100 to 500 ⁇ g / mL per tube. It can be added to the inside.
  • 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 comprise 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 cancer, malignant tumor Or can be used to prevent or treat infectious diseases, such as digestive organ cancers such as colon cancer and stomach cancer, myeloma, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, eclampsia cancer, lung cancer Can be applied to cancer or malignant tumors such as oral cancer, brain tumors; or chronic hepatitis due to hepatitis B or C virus, HIV, influenza, etc.
  • infectious diseases such as digestive organ cancers such as colon cancer and stomach cancer, myeloma, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, eclampsia cancer
  • lung cancer Can be applied to cancer or malignant tumors such as oral cancer, brain tumors; or chronic hepatitis due to hepatitis B or C virus, HIV
  • an auxiliary active substance for use in immunotherapy comprising the above-described rod-shaped cell activator.
  • the auxiliary activator is a substance that is administered into the living body together with the rod cells in order to induce the activation of the rod cells during the immunotherapy, and is included as one component of the pharmaceutical composition. May be.
  • the diseases targeted by immunotherapy are not particularly limited.
  • gastrointestinal cancers such as colon cancer and gastric cancer, myeloma, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, uterine cancer, lung cancer It can be applied to cancers or malignant tumors such as oral cancer and brain tumor; or chronic hepatitis due to hepatitis B or C virus, HIV and influenza.
  • 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 drug, a quasi-drug, a component of a 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-shaped 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 rod cells activated by the method of the present invention have a high IL-12 production ability, they strongly promote the activity of Thl cells through IL 12 production and have a high therapeutic effect on the disease or It is thought to exert a preventive effect.
  • FIG. 1 An example of a test result comparing the ability of the mesimacob extract and the PSK to activate the rod-shaped cell activity.
  • FIG. 2 is an example of test results comparing the ability to produce interleukin 12 in rodent cells activated by Meshimakobu extract and PSK.
  • Meshimakobu extract was prepared by the following procedure. 25 g of Meshimakobu fruit body powder with a particle size of 100 ⁇ m or less prepared by pulverizing Meshimakobu fruit body was suspended in 500 ml of distilled water and subjected to ultrasonic crushing treatment at 35 ° C for 30 minutes. . The treated solution was centrifuged at a high speed to remove the precipitate, and the obtained filtrate was lyophilized to obtain a Meshimakobu extract. The resulting extract of Meshimakobu was 5-20% of the original fruit body powder.
  • Heteroline blood was collected from peripheral blood of healthy individuals, and RosetteSep Humon monocyte Enrichment Using a cocktail kit (Stemcell), monocytes were prepared according to the protocol attached to the kit, and a cell suspension was prepared in RPMI1640 medium (sigma, containing 10% FBS) at 5xl0 5 cells / 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. This was cultured at 37 ° C, 5% CO for 3 days. Be careful not to suck the cells after 3 days.
  • RPMI1640 medium sigma, containing 10% FBS
  • 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. This was cultured
  • RPMI 1640 medium (sigma, containing 10% FBS) 300 / z L was added. Further, GM-CSF (Peprotech) and IL-4 (Peprotech) were added at 40 ng / ml, and further cultured for 3 days (6 days in total) to induce immature rod cells. 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 and confirmed with a flow cytometer (Beckman Coulter Epics XL).
  • the immature rod cells prepared as described above were supplemented with Meshimakobu extract and PSK to a final concentration of 200 ⁇ g / ml, and cultured at 37 ° C., 5% CO for 2 days. 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
  • Immature rod cells were induced from human peripheral blood in the same manner as in Example 2.
  • Messimacob extract and PSK were added to a final concentration of 200 g / ml, and the cells were cultured at 37 ° C., 5% CO for 24 hours. Also, 37 ° C without any addition as a control
  • the cells were cultured for 24 hours under 5% CO conditions. After 24 hours, each culture supernatant is collected and stored in the culture supernatant.
  • the amount of IL-12 was measured with an ELISA kit (Biosource) according to the kit protocol. The result is shown in figure 2.

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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 Phellinus linteus. 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/JP2005/004066 2004-09-30 2005-03-09 Activateur de cellules dendritiques WO2006006271A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004-288654 2004-09-30
JP2004288654 2004-09-30

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Publication Number Publication Date
WO2006006271A1 true WO2006006271A1 (fr) 2006-01-19

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003327541A (ja) * 2002-05-13 2003-11-19 Oubiken:Kk インターロイキン１２産生促進組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003327541A (ja) * 2002-05-13 2003-11-19 Oubiken:Kk インターロイキン１２産生促進組成物

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
PARK S.-K. ET AL: "Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 312, 2003, pages 449 - 452, XP004473292 *
TAKADA S. ET AL: "Hito Masshoketsu Yudo Jujyo Saibo no Bunka o Sokushin Suru Phellinus linteus no Seibun ni Tsuite", THE JAPANESE SOCIETY OF PHARMACOGNOSY NENKAI KOEN YOSHISHU, vol. 51, 9 August 2004 (2004-08-09), pages 199, XP002996079 *
TOGASHI K. ET AL: "Phelinus linteus no Men'eki Fukatsu Kassei Seibun ni Tsuite", THE JAPANESE SOCIETY OF PHARMACOGNOSY NENKAI KOEN YOSHISHU, vol. 50, 2003, pages 85, XP002996080 *

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