WO2006006272A1 - Activateur de cellules dendritiques - Google Patents

Activateur de cellules dendritiques Download PDF

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Publication number
WO2006006272A1
WO2006006272A1 PCT/JP2005/004067 JP2005004067W WO2006006272A1 WO 2006006272 A1 WO2006006272 A1 WO 2006006272A1 JP 2005004067 W JP2005004067 W JP 2005004067W WO 2006006272 A1 WO2006006272 A1 WO 2006006272A1
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WO
WIPO (PCT)
Prior art keywords
rod
cells
shaped cell
cell activator
extract
Prior art date
Application number
PCT/JP2005/004067
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English (en)
Japanese (ja)
Inventor
Yasunori Matsui
Yoshihiro Yamaguchi
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 WO2006006272A1 publication Critical patent/WO2006006272A1/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
    • A61K36/062—Ascomycota
    • A61K36/066—Clavicipitaceae
    • A61K36/068—Cordyceps
    • 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

Definitions

  • the present application relates to a rod-shaped cell activator comprising a Cordyceps extract or a fraction thereof, particularly a rod-shaped cell maturation promoter. Furthermore, the present invention relates to an oral intake composition, pharmaceutical composition, 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 ability to activate T cells.
  • rod cells present in lymphoid organs are called mature rod cells because they have a strong ability to activate T cells.
  • Such functional differences are due to increased expression of cell adhesion and costimulatory molecules (eg, CD40, CD54, CD58, CD80 and CD86) in addition to MHC (major histocompatibility complex) molecules and It is caused by changes in the production capacity of cytokines such as chemokines.
  • cell adhesion and costimulatory molecules eg, CD40, CD54, CD58, CD80 and CD86
  • MHC major histocompatibility complex
  • the rod-shaped cells also have a structure with strong adhesion and high motility due to reorganization of the cytoskeleton, and begin to move to the lymph nodes.
  • the rod-like cells promote the activity of T cells by producing 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 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).
  • Cordyceps is a collective term for mushrooms arising from insects and the like, and is positioned as a genus of the Ascomycota fungus' Aperidomycetes ⁇ Ergotaceae.
  • Cordyceps s inensis (Berkely) Saccardo is a mushroom that parasitizes lepidopterous bat larvae and is distributed in the alpine belts of China, Cambodia, Nepal, the Himalayas, and 3000-4000 m above sea level. In China, it has been handed down as a traditional Chinese medicine for immortality and tonic. Recent studies have reported various physiological activities of the components contained in Cordyceps sinensis (Non-patent Document 7: Biol. Pharm. Bull.
  • Non-Patent Document 8 Biol. Pharm. Bull. 16th, 12th, 1993, 1291-129 3
  • Non-patent 9 Phytochemistry, 51st, 1999, 891-898 page.
  • Cordyceps sinensis extract particularly Cordycesbus sinensis extract, which has any effect on rod-shaped 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
  • 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 Biol. Pharm. Bull. No. 22, No. 9, 1999, 966-970
  • Non-Patent Document 8 Biol. Pharm. Bull. No. 16, No. 12, 1993, No. 1291—pages 1293
  • Non-Patent Document 9 Phytochemistry, 51st, 1999, 891-898
  • the present invention was completed by discovering that an extract of Cordycesbus sinensis has a rod-like cell activating action.
  • An object of the present invention is to provide an extract derived from Cordyceps sinensis having a rod-like cell activation action, and a rod-like cell activator, immunostimulant, composition for oral intake, pharmaceutical composition containing the extract, It is to provide food compositions, foods and beverages.
  • a rod-shaped cell activator comprising an extract of Cordyceps sinensis.
  • activation of rod cells means that some function of rod cells is enhanced, or the amount of molecules such as proteins expressed in rod cells is amplified.
  • the meaning of the term includes, for example, promoting maturation of rod cells, enhancing antigen uptake ability, enhancing antigen presentation ability, and enhancing T lymphocyte stimulation ability.
  • Adhesion molecule Z co-stimulatory molecules eg, CD40, CD54, CD58, CD80, CD86, etc.
  • site 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 C and hepatitis C virus, HIV, influenza, and the like.
  • the extract of Cordyceps sinensis in the present invention may be an extract of fruit bodies and Z or mycelium.
  • the extract is preferably prepared using an extract of the mycelium of Cordyceps sinensis, particularly preferably in the state of the mycelium in the previous stage of the edible fruit body.
  • Cordyceps sinensis may be produced by culture or collected from nature.
  • mycelium obtained by culturing Cordyceps sinensis bacteria in a solid medium can be used.
  • the extract of Cordyceps sinensis used in the present invention can be prepared by a method known in the art. For example, a solid medium containing mycelium is pulverized and decomposed in the presence of water and an enzyme.
  • the extract obtained in this way can be used.
  • a solvent used for the preparation of the extract 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 from here.
  • the Cordyceps sinensis extract thus obtained has a carbohydrate content of 1-50%, preferably 5-20% (wZw) by the carbohydrate analysis by the phenol-sulfuric acid method, and the protein by the protein analysis by the Lowry method.
  • the Cordyceps sinensis extract in the present invention may be a fraction obtained from the extract.
  • the fractionation method may be a method commonly used in the technical field to which the present invention belongs. Examples of the fractionation method include fractionation by extraction using an arbitrary solvent, gel filtration force, ram chromatography. , Fractionation using an ion exchange column, and silica gel column chromatography.
  • 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 concentrated solution, a viscous substance or a solid obtained by concentration and Z or freeze-drying as a soluble fraction. be able to.
  • spikeder cell activator generally refers to an action that enhances the function of a rod cell by acting on the rod cell, or a rod cell. It means a drug that has the effect of amplifying the amount of the substance expressed in the cell or inside the 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 components, for example, one or more pharmaceutically acceptable excipients, disintegrants, diluents, lubricants, and dressings.
  • Flavoring agent, coloring agent, sweetener, flavoring agent, suspending agent, wetting agent, emulsifying agent, dispersing agent, adjuvant, prevention It may include preservatives, buffers, binders, stabilizers, coating agents, and the like.
  • 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.
  • Cordycebus sinensis mycelium extract was originally used as a food and herbal medicine and has little concern for hyperplasia! / It is a relatively safe substance, so it can be administered at high concentrations as needed It is.
  • Cordyceps extract is generally used at a dose of 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, for example, other rod-like cell activators, immunostimulators, anticancer agents, antitumor agents, anti-infective agents, etc. It can also be used in combination with drugs.
  • 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 (eg, CD83) specific to mature rod cells 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 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 for use in activating rod-shaped cells in vitro is, in an amount, 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; or chronic hepatitis due to hepatitis B or C virus, HIV, influenza, etc. Can be applied to.
  • the auxiliary activator of the present invention can contain various commonly used components, 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. It can be selected appropriately.
  • 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.
  • an auxiliary activator 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-shaped cells in order to induce the activation of the rod-shaped cells during immunotherapy, and is included as one component of the pharmaceutical composition. Also good.
  • diseases targeted for immunotherapy are not particularly limited.
  • gastrointestinal cancer such as colon cancer and gastric cancer, myeloma, liver cancer, leukemia, melanoma, prostate cancer, breast cancer, uterine cancer
  • cancers such as lung cancer, oral cancer, brain tumor or malignant tumors; or chronic hepatitis due to hepatitis B or C virus, HIV, influenza and other infections.
  • a food composition comprising the above-described rod-shaped cell activator.
  • the food composition of the present invention includes a liquid beverage such as a functional beverage.
  • the food The product composition can be used as a functional food, as well as a quasi-drug, a food and drink component, and 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 the present specification includes, but is not limited to, inorganic components such as iron and calcium, various vitamins, dietary fibers such as oligosaccharides and chitosan, proteins such as soybean extract, lipids such as lecithin, It contains saccharides such as sucrose and lactose, and plant extracts such as shiitake mushrooms.
  • inorganic components such as iron and calcium
  • various vitamins such as dietary fibers such as oligosaccharides and chitosan
  • proteins such as soybean extract
  • lipids such as lecithin
  • It contains saccharides such as sucrose and lactose
  • 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 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.
  • Cordycebus sinensis extract (hereinafter also referred to as “corticus extract”) was prepared by the following procedure.
  • Cordycebus sinensis mycelium was liquid cultured at 15-18 ° C in a medium obtained by adding glucose solution to corn powder extract, koji powder extract, and soybean powder extract. After culturing, the mycelium was separated by high-speed centrifugation and dried with a laminar flow dryer to obtain Cordyceps sinensis mycelium powder.
  • 2 L of distilled water was added and extracted at 90-95 ° C for 4 hours. The extract was filtered, and the filtrate was concentrated under reduced pressure to obtain Cordyceps extract powder. The recovery rate was about 30% in terms of mycelium powder force conversion.
  • Healthy human peripheral blood was Nono phosphorus bled f a, RosetteSep Humon monocyte Enrichment cocktail kit (Stemcell, Inc.) using monocytes adjust the protocol as the kit, RPMI1640 medium (sigma, 10% FBS-containing) to 5xl0 5 cells
  • 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. This was cultured at 37 ° C, 5% CO for 3 days. Be careful not to suck the cells after 3 days.
  • 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 with a flow cytometer (Beckman Coulter Epics XL) for confirmation.
  • Cordyceps extract and PSK were added 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
  • Cell surface costimulatory factors CD40, CD80, CD86 protein and mature rod cell specific marker CD83 protein expression levels of anti-CD40 antibody FITC label, anti-CD80 antibody PE label, anti-CD86 antibody PC5 label Measurement was performed with a flow cytometer (Beckman Coulter Epics XL) using Peprotech and anti-CD83 antibody FITC labeling (Peprotech). The results are shown in Figure 1.
  • Example 3 Measurement of IL-12-producing ability of human rod-like cells activated by Cordyceps extract
  • immature rod-like cells were induced from human peripheral blood.
  • Cordyceps extract and PSK were added to the prepared immature rod cells so that the final concentration was 200 g / ml, and the cells were cultured at 37 ° C., 5% CO for 24 hours.
  • 37 ° C without any addition 37 ° C without any addition
  • 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.
  • FIG. 1 An example of test results comparing the ability of Cordyceps mycelium extract and PSK to activate rod-shaped cells.
  • FIG. 2 Inter-mouth of rod-shaped cells activated by Cordyceps mycelium extract and PSK It is an example of a test result comparing the production capacity of IKIN-12.

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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 Cordyceps sinensis. 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/JP2005/004067 2004-09-30 2005-03-09 Activateur de cellules dendritiques WO2006006272A1 (fr)

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JP2004-288570 2004-09-30
JP2004288570 2004-09-30

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106010977A (zh) * 2016-05-25 2016-10-12 浙江农林大学 中国被毛孢人工侵染蝙蝠蛾幼虫的方法

Non-Patent Citations (6)

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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 *
KUO Y ET AL: "Regulation of bronchoalveolar lavage fluids cell function by the immunomodulatory agents from Cordyceps sinensis.", LIFE SCIENCES., vol. 68, no. 9, 2001, pages 1067 - 1082, XP002996081 *
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YAMAGUCHI Y ET AL: "Tochunatsukusa Kinshitai Tatorui no Cytokine Sansei koshin Oyobi Koshuyo Sayo.", THE JAPANESE SOCIETY OF NUTRITION AND FOOD SCIENCE., vol. 58, 1 April 2004 (2004-04-01), pages 179, XP002996082 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106010977A (zh) * 2016-05-25 2016-10-12 浙江农林大学 中国被毛孢人工侵染蝙蝠蛾幼虫的方法

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