WO2004014406A1 - Utilisation d'extrait de germe de ble fermente comme agent anti-inflammatoire - Google Patents
Utilisation d'extrait de germe de ble fermente comme agent anti-inflammatoire Download PDFInfo
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- WO2004014406A1 WO2004014406A1 PCT/HU2003/000065 HU0300065W WO2004014406A1 WO 2004014406 A1 WO2004014406 A1 WO 2004014406A1 HU 0300065 W HU0300065 W HU 0300065W WO 2004014406 A1 WO2004014406 A1 WO 2004014406A1
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- Prior art keywords
- avemar
- day
- inflammatory
- wheat germ
- treatment
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- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
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- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
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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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to a new therapeutic application of a fermented wheat germ extract under the trade name Avemar®, more specifically to the use of Avemar® for the manufacture of pharmaceutical compositions useful as anti- inflammatory agent for preventing or treating or alleviating inflammatory conditions, particularly arthritis.
- Avemar® The production method as well as the immunostimulant and anti-metastatic effects of the fermented wheat germ extract (hereinafter referred to as Avemar®) are described in WO 99/08694.
- Avemar® the fermented wheat germ extract
- This substance can be obtained by fermenting wheat germ with Saccharomyces cerevisiae in an aqueous medium and drying the filtered liquid ferment.
- the obtained substance is characterized by its 2.6-dimetoxi-p-benzoquinone content representing approximately 0.4 mg/g dry substance.
- Avemar® can be applied for treating or preventing inflammatory diseases, particularly rheumatoid arthritis occuring in mammals including humans.
- Arthritis is a general denomination for a number of arthritic diseases, such as rheumatoid arthritis, bacterial arthritis, reactive arthritis, etc.
- Rheumatoid arthritis includes a large group of non-bacterial states, the most important symptoms of which are the inflammation and deformation of joints.
- classic rheumatoid arthritis affects a number of joints (polyarthritis) , but it can also be limited to a single joint ( onoarthritis) .
- the attack of an arthritic cartilage is only one of the factors deforming numerous cartilages and bones and destroying articular function. This disease affects the articular sheath, ligaments and the bone tissue as well. In the majority of cases, the disease is characterized by varying courses, including aggravation and improvement periods accompanying the entire lifetime; however, the articular deformation and systemic disability continuously deteriorate. Only about 10% of the patients is spontaneously recovered.
- anti-inflammatory agents such as steroids (prednisolon, dexamethasone) , non- steroidal anti-inflammatory drugs (NSAIDs) and anti-rheumatic drugs affecting the disease (DMARDs) .
- NSAID group involves salicilates, ibuprofen, fenoprofen, naproxen, piroxicam, tolmetine, indomethacine and others, e.g. cyclooxygenase enzyme inhibitors.
- chemotherapeutic drugs are characterized by little effectiveness and high toxicity.
- DMARD or SAAR anti-rheumatic drugs with prolonged effect
- D-penicillinamine gold salts
- chloroquine chloroquine
- asatioprine methotrexate
- cyclophosphamide a pharmaceutically acceptable carrier for reducing oxidative stress.
- these drugs are usually selected by professionals only in the second place when the patient's responses are less favourable to NSAIDs.
- These agents are usually applied in combination with NSAIDs.
- non-steroidal anti-inflammatory agents have also been developed for treating rheumatoid arthritis, including gamma-interferon and interleukin-6 antagonists, cyclosporine, PAF-antagonists, eicosapentaenoic acid (EPA) , somatostatine analogues, peptide derivatives and immune modulators.
- gamma-interferon and interleukin-6 antagonists including gamma-interferon and interleukin-6 antagonists, cyclosporine, PAF-antagonists, eicosapentaenoic acid (EPA) , somatostatine analogues, peptide derivatives and immune modulators.
- EPA eicosapentaenoic acid
- somatostatine analogues peptide derivatives and immune modulators.
- Hungarian patent No. 203044 describes a pharmaceutical preparation to ameliorate arthritis wherein the active agent is a herb extract.
- Avemar® adjuvant arthritis
- rats which is the most frequently used experimental model of human rheumatoid arthritis (RA) .
- RA rheumatoid arthritis
- the time and degree of AA development in rats depends on several factors, such as the triggering agent and its dose, the location of injection, the strain of experimental rat, etc.
- An acute inflammatory reaction primary response
- the degree of inflammation becomes constant (plateau effect) between the 6 th and .11 th days; then the intensity of the reaction further increases.
- An inflammatory reaction is generated on the non-injected foot pad as well (a secondary or immune-mediated response) on the 10 th to 12 th day following the injection.
- the inflammatory reaction that is, the increase in paw volume reaches the maximum on both the treated and the untreated foot pad between the 18 th and 21 th days.
- Figure 1 shows the effect of a 22-day p.o. treatment on AA
- Figure 2 shows the effect of a 22-day p.o. treatment on AA
- Figure 3 shows the effect of a 22-day p.o. treatment on AA on the 14 th day (injected foot pad)
- Figure 4 shows the effect of a 22-day p.o. treatment on AA on the 18 th day (injected foot pad)
- Figure 5 shows the effect of a 22-day p.o. treatment on AA on the 22 nd day (injected foot pad)
- Figure 6 shows the effect of a 22-day p.o. treatment on AA on the 14 th day (non-injected foot pad)
- Figure 7 shows the effect of a 22-day p.o. treatment on AA on the 18 th day (non-injected foot pad)
- Figure 8 shows the effect of a 22-day p.o.
- Figure 9 shows the effect of a 22-day p.o. treatment on the body weight of rats in function of time
- Figure 10 shows the effect of a 22-day p.o. treatment on the body weight of rats on the 22 nd day
- Figure 11 shows the effect of a 35-day p.o. treatment on AA
- Figure 12 shows the effect of a 35-day p.o. treatment on AA
- Figure 13 shows the effect of a 35-day p.o. treatment on AA on the 28 th day (injected foot pad)
- Figure 14 shows the effect of a 35-day p.o. treatment on AA on the 32 nd day (injected foot pad)
- Figure 15 shows the effect of a 35-day p.o. treatment on AA on the 35 th day (injected foot pad)
- Figure 16 shows the effect of a 35-day p.o. treatment on AA on the 28 th day (non-injected foot pad)
- Figure 17 shows the effect of a 35-day p.o. treatment on AA on the 32 nd day (non-injected foot pad)
- Figure 18 shows the effect of a 35-day p.o.
- Figure 19 shows the effect of a 35-day p.o. treatment on the body weight of rats in function of time
- Figure 20 shows the effect of a 35-day p.o. treatment on the body weight of rats on the 35 th day
- Figure 21 shows severe chronic inflammatory infiltration in the synovium and adjacent tissues of untreated rats presenting AA
- Figure 22 shows severe infiltration containing giant cells in the synovium of untreated rats presenting AA
- Figure 23 shows micro-abscesses within an inflammatory infiltration in the periarticular tissue of untreated rats presenting AA
- Figure 24 shows CD4 positive lymphocytes in the inflammatory infiltration found in the synovium of untreated rats presenting AA
- Figure 25 shows the lack of inflammatory infiltration in the synovial and perisynovial tissues of rats previously presenting AA and treated by Avemar.
- adjuvant arthritis was triggered in female Wistar rats by injecting 0.1 ml 0.5% killed Mycobacterium butyricum (Difco) suspended and homogenized in liquid paraffin under the skin of the sole of the right hind paw of the animals.
- the average initial body weight of the experimental animals was 138+5 g in the group treated for 22 days and 118+5 g in the group treated for 35 days.
- the body weight of the animals was measured by plethysmography during the treatment by Avemar®, together with the volume of the injected right leg and the non-injected left leg (to follow the changes of the primary and secondary reactions) on days 0, 1, 4, 7, 12, 14, 18 and 22 in the 22-day experiment and on days 0, 3, 7, 11, 15, 18, 21, 25, 28, 32 and 35 in the 35-day experiment.
- the inflammatory reaction was triggered on day 1 (22-day test) and on day 14 (35-day test) , respectively, after starting treatment by Avemar®.
- the following experimental groups and methods were applied in both experiments: 1. Control 2x1.0 ml/150 g (distilled water); 2. Avemar® 2x2.5 g/kg/day; 3. Avemar® 2x1.0 g/kg/day; 4.
- Avemar® manufactured by Biromedicina Pel., Budapest, Hungary
- dexamethasone solutions were always prepared and/or diluted immediately before the administration.
- Indomethacin manufactured by Chinoin Pharmaceutical and Chemical Works, Budapest, Hungary
- the various doses of Avemar® as well as indomethacin and dexamethasone were administered by gastric tube in 1.0 ml/150 g body weight twice a gay, i.e. the first half of the daily dose between 8.00 and 10.00 a.m. and the other half between 4.00 and 6.00 p.m.
- the control group received 1 ml/150 g distilled water.
- Results of the 22-day treatment are shown in Figures 1 to 10 and the results of the 35-day treatment in Figures 11 to 20.
- the results show that Avemar® can depending on the dose significantly inhibit the development of both the primary and the secondary inflammatory reactions in rats which supports its anti-inflammatory effect. Similarly to indomethacin and dexamethasone, Avemar® minimized adjuvant arthritis in a dose- dependent manner in the treated rats.
- the affected joints of the right hind foot pad together with the epiphyses of the bones and the surrounding fibrous and muscular tissues were fixed in buffered neutral 4% formalin. Decalcification was performed by using EDTA and the samples were embedded into paraffin. 8 ⁇ m thin longitudinal sections were cut and the sections were stained with hemotoxiline (H) and eosine (E) . In the selected positive control and in the treated cases an immunoperoxidase reaction was performed to show CD4 and CD8 positive T-lymphocytes. The used antibody was the product of Santa Cruz (Santa Cruz, CA, USA), applied in 1:100 dilution.
- Table 1 Semi-quantitative histological qualification of inflammatory infiltrates in AA rats untreated and treated by Avemar, indomethacin or dexamethasone
- Avemar® did not exert any toxic effect, including erosive gastritis and acute gastric ulcer (Report. Acute oral toxicity study of Avemar® in mice. Code: 9901. Univ. Vet. Sci., Dept . Pharmacol. Toxicol., Budapest, 1999; Acute oral toxicity study of Avemar® in rats. Code: 9902. Univ. Vet. Sci., Dept. Pharmacol. Toxicol., Budapest, 1999; Subacute oral toxicity study of Avemar®. Code: 0001. Univ. Vet. Sci., Dept. Pharmacol. Toxicol., Budapest, 2000). Furthermore, the preparation was not genotoxic in micronucleus tests of rat bone marrow.
- Avemar® may be a suitable therapeutic tool in the treatment of rheumatoid arthritis in humans.
- Other immunopathological diseases may also be considered in this respect.
- the 15 RA patients were administered a daily dose of 2 x 9 g water soluble granulated Avemar® (9 g in the morning and 9 g in the evening) .
- the patients were checked at the time of starting treatment and every month; their statistical evaluation was performed in months 6 and 12, respectively.
- ESR erythrocyte sedimentation rate
- Dexamethasone D Chloroquine: Ch HAQ: Health Assessment Questionnaire Methylprednisolone.: M Methotrexate : MTX Triamcinolone: T Cyclosporine : C Prednisolone : P Sulfasalazine : S
- the object of the present invention is the use of fermented wheat germ extract (Avemar®) for preparing pharmaceutical compositions for treating or preventing or alleviating inflammatory conditions.
- Avemar® can be applied to prepare pharmaceutical compositions useful for treating or preventing or alleviating arthritis, more preferably rheumatoid arthritis.
- a further object of the present invention is a process for preparing pharmaceutical compositions containing fermented wheat germ extract as an active ingredient comprising manufacturing said active ingredient with commonly used pharmaceutically additives to a pharmaceutical composition useful for treating or preventing or alleviating inflammatory diseases.
- Avemar® can be applied prferably together with other non-steroidai (NSAID) type anti- inflammatory agents, such as diclophenac, ibuprophen, piroxicam, tolmetin, etc.
- NSAID non-steroidai
- the dose of NSAID type drugs can be considerably reduced, which is a great advantage regarding the toxicity of these drugs.
- the co-administration with diclophenac allows reducing by 50% the quantity of both agents and attaining similar effects of improvement the same time.
- a further object of the present invention is the use of a fermented wheat germ extract (Avemar®) and another active ingredient, especially an anti-inflammatory agent for producing a medicament for treating or preventing or alleviating arthritis.
- a non- steroidal anti-inflammatory agent is preferably used as another anti-inflammatory agent.
- the present invention also relates to a combined pharmaceutical composition containing an effective amount of fermented wheat germ extract (Avemar®) in combination with another active ingredient, especially an anti-inflammatory agent and a pharmaceutically acceptable carrier.
- an effective amount of fermented wheat germ extract especially an anti-inflammatory agent and a pharmaceutically acceptable carrier.
- Preferable anti-inflammatory pharmaceutical compositions of the invention contain an effective dose of fermented wheat germ extract (Avemar®) and diclofenac.
- the active ingredient used in the present invention can be formulated in several oral and parenteral dosage forms and administered to treat and prevent rheumatoid arthritis.
- the active ingredient is present in about 5% to 95% by weight in the composition.
- the pharmaceutically acceptable excipients used for producing pharmaceutical compositions can be in solid or liquid phase.
- solid pharmaceutical compositions include powders, tablets, pills, capsules, cachets, rhomboid medicinal formulas, suppositories and dispersable granules.
- Solid compositions can include several additives such as thinners, flavors, soluble agents, lubricants, suspending agents, binders, preservatives, tablet desintegrators or encapsulating substances .
- the excipient is a finely powdered solid substance which constitutes a mixture with the finely dispersed active ingredient.
- a carrier possessing the required binding characteristics is mixed in proper proportion with the active ingredient and pressed to the required shape and size.
- powders and tablets contain the agent in 5% to 70%.
- suitable excipients include magnesium carbonate, magnesium stearate, talcum, sugar, lactose, pectin, dextrin, cyclodextrin, maltodextrin, starch, gelatine, tragacanta, methylcellulose, sodium carboxymethylcellulose, waxes of low melting point, cocoa butter, etc.
- the production involves the formulation of the active ingredient with the encapsulating substance as excipient, thereby a capsule is obtained in which the active ingredient with or without other carriers is surrounded by the excipient, which the latter being thus linked to the active ingredient.
- Cachets and rhomboid drug formulas are produced similarly. Tablets, powders, capsules, pills, cachets and rhomboid drug formulas can be applied for oral administration.
- waxes with low melting point e.g. a mix of fatty acid glycerides or cocoa butter are first melted and the active ingredient is homogeneously dispersed therein by mixing. Then the melted homogeneous mix is poured into suppository moulds of appropriate size, left to cool down and solidify.
- Liquid pharmaceutical preparations include solutions, suspensions, emulsions, syrups, and elixirs, such as aqueous or aqueous propylene glycol solutions.
- liquid pharmaceutical compositions can be formulated in an aqueous polyethylene glycol solution.
- Solutions suitable for oral administration can be produced by dissolving the active ingredient in water and adding appropriate colorants, flavors, stabilizers and coagulants.
- Suspensions suitable for oral administration can be produced by dispersing the finely ground active ingredient in water together with a viscous substance such as natural or synthetic rubbers, resin, methylcellulose, sodium carboxymethylcellulose and other well-known suspending agents.
- a viscous substance such as natural or synthetic rubbers, resin, methylcellulose, sodium carboxymethylcellulose and other well-known suspending agents.
- Solid pharmaceutical compositions also include those intended to be converted into liquid preparations shortly before use for oral administration.
- liquid pharmaceutical formulations include solutions, suspensions and emulsions.
- these pharmaceutical preparations may contain colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersing agents, coagulants, soluble agents and similar substances.
- Sterile compositions for parenteral administration can be preferably aqueous or non-aqueous solutions, suspensions or emulsions.
- solvents water, propylene glycol, some sort of polyethylene glycol, vegetable oils, such as olive oil, injectable organic esters, such as ethyl oleate.
- These compositions may also contain other auxiliaries, particularly lubricants, isotonising, emulgeating, dispersing and stabilizing agents.
- Sterilization can be performed in several ways, including aseptic filtration, inclusion of sterilizers into the composition, irradiation or heat treatment.
- Sterile solid compositions can also be prepared which can be solved in sterile water or any other injectable medium immediately before use.
- compositions are packaged in unit doses.
- the preparation is divided into unit doses, each containing a specific quantity of active ingredient.
- the unit dose form can be a packaged preparation where the packaging contains discrete quantities of the preparation, such as packaged tablets, capsules and powders in vials or ampoules.
- the unit dose form can also include capsules, tablets, cachets, rhomboid drugs or a certain number thereof included in packaging.
- the amount of the active ingredient can change or can be adjusted between 1 and 1000 mg, preferably between 10 and 100 mg in unit dose preparations in accordance with use and the potential of the active ingredient.
- Pharmaceutical compositions can also contain other compatible therapeutic agents, if necessary.
- the effective dose ' of the composition applied according to the present invention and the rate of dosage to prevent, suppress or hinder arthritis depend on a number of factors. Suitable doses should be obligatorily determined by professionals. In general, it is the attendant physician who specifies the proper dose depending on the age, body weight and any other individual factors of the person to be treated. Daily dose levels vary between about 0.1 and 1000 mg/kg body weight, preferably about 1 to 500 mg/kg/day and more preferably about 50 to 250 mg/kg/day. For safety reasons, the entire daily dose can be divided and administered in portions during the day, if necessary.
- the other agent can be selected from the following group: corticosteroids, anti-inflammatory agents, anti-rheumatic agents, immune suppressors, antimetabolites and immune modulators.
- corticosteroids anti-inflammatory agents
- anti-rheumatic agents anti-rheumatic agents
- immune suppressors antimetabolites
- immune modulators The list of the compounds pertaining to these categories can be found in the following manual: “Comprehensive Medical Chemistry", Pergamon Press, Oxford, 970-986 (1990) .
- This group includes, for example, sulfasalazine and aminosalycilates (anti-inflammatory agents) ; cyclosporine, FK-506 and rapamicine (immune suppressors) ; cyclophosphamide and methotrexate (anti- metabolites) ; dexamethazone, methylprednisolone, triamcinolone, prednisolone (steroids) ; and interferons (immune modulators) .
- Avemar® is applied in combination with one or more further agents, these can be packaged together or they can be administered in combination.
- the administration of one or more agents in combination with Avemar® is substantially performed simultaneously or subsequently. Professionals can determine the most suitable method of administration depending on the agents released, the results desired, the patient and the condition to be cured.
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Abstract
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03784303A EP1536809A1 (fr) | 2002-08-09 | 2003-08-08 | Utilisation d'extrait de germe de ble fermente comme agent anti-inflammatoire |
CA002494744A CA2494744A1 (fr) | 2002-08-09 | 2003-08-08 | Utilisation d'extrait de germe de ble fermente comme agent anti-inflammatoire |
BR0313589-6A BR0313589A (pt) | 2002-08-09 | 2003-08-08 | Uso de extrato de germe de trigo fermentado como agente antiinflamatório |
US10/522,131 US20050266106A1 (en) | 2002-07-22 | 2003-08-08 | Use of fermented wheat germ extract as anti-inflammatory agent |
JP2004527076A JP2006501214A (ja) | 2002-08-09 | 2003-08-08 | 発酵小麦胚芽抽出物の抗炎症剤としての使用 |
AU2003255854A AU2003255854A1 (en) | 2002-08-09 | 2003-08-08 | Use of fermented wheat germ extract as anti-inflammatory agent |
MXPA05001469A MXPA05001469A (es) | 2002-08-09 | 2003-08-08 | Uso de extracto de germen de trigo fermentado como agente anti-inflamatorio. |
EA200500326A EA007844B1 (ru) | 2002-08-09 | 2003-08-08 | Применение ферментированного экстракта проростков пшеницы в качестве противовоспалительного агента |
HR20050114A HRP20050114A2 (en) | 2002-08-09 | 2005-02-03 | Use of fermented wheat germ extract as anti-inflammatory agent |
IL16673205A IL166732A0 (en) | 2002-08-09 | 2005-02-07 | Use of fermented wheat germ extract as anti-inflammatory agent |
NO20051168A NO20051168L (no) | 2002-08-09 | 2005-03-04 | Anvendelse av fermentert hvetekimekstrakt som anti-inflammasjonsmiddel |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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HUP0202638 | 2002-08-09 | ||
HU0202638A HUP0202638A3 (en) | 2002-08-09 | 2002-08-09 | Use of fermented wheat-germ extract for preparation of antiphlogistic compositions |
Publications (1)
Publication Number | Publication Date |
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WO2004014406A1 true WO2004014406A1 (fr) | 2004-02-19 |
Family
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PCT/HU2003/000065 WO2004014406A1 (fr) | 2002-07-22 | 2003-08-08 | Utilisation d'extrait de germe de ble fermente comme agent anti-inflammatoire |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP1536809A1 (fr) |
JP (1) | JP2006501214A (fr) |
KR (1) | KR20050059066A (fr) |
CN (1) | CN1674924A (fr) |
AU (1) | AU2003255854A1 (fr) |
BR (1) | BR0313589A (fr) |
CA (1) | CA2494744A1 (fr) |
EA (1) | EA007844B1 (fr) |
HR (1) | HRP20050114A2 (fr) |
HU (1) | HUP0202638A3 (fr) |
IL (1) | IL166732A0 (fr) |
MX (1) | MXPA05001469A (fr) |
NO (1) | NO20051168L (fr) |
PL (1) | PL375391A1 (fr) |
WO (1) | WO2004014406A1 (fr) |
Cited By (6)
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FR2908998A1 (fr) * | 2006-11-24 | 2008-05-30 | Bao Quoc Ho | Nouveau produit enzymatique et son utilisation. |
WO2010100514A3 (fr) * | 2009-03-03 | 2010-10-28 | Hidvegi Mate | Composition pharmaceutique contenant une matière déshydratée, fermentée avec une structure cristalline amorphe |
WO2010135580A2 (fr) * | 2009-05-20 | 2010-11-25 | The Regents Of The University Of California | Protéines de germe de blé fermenté (fwgp) pour le traitement du cancer |
WO2012159988A1 (fr) | 2011-05-20 | 2012-11-29 | 3Ch Ltd | Utilisation de germe de blé fermenté dans le traitement de la maladie intestinale inflammatoire |
WO2012175594A1 (fr) | 2011-06-23 | 2012-12-27 | Biropharma Uk Ltd | Extrait de germe de blé obtenu par hydrolyse par protéase et utilisation médicale de cet extrait |
EP2600721A1 (fr) * | 2010-08-02 | 2013-06-12 | Mate Hidvegi | Molécules anticancéreuses et immunomodulatrices et fractions les renfermant |
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JP6115995B2 (ja) * | 2013-04-24 | 2017-04-19 | 株式会社日清製粉グループ本社 | 非酵素的糖化反応抑制剤 |
CN104381450A (zh) * | 2014-10-15 | 2015-03-04 | 张士远 | 治疗胃粘膜损伤的保健牛奶及其制备方法 |
WO2017196048A1 (fr) * | 2016-05-11 | 2017-11-16 | 씨제이제일제당 (주) | Composition à application externe pour soulager les rides de la peau, contenant un extrait de produit de germe de blé fermenté en tant qu'ingrédient actif |
KR101955111B1 (ko) * | 2016-09-23 | 2019-03-07 | 씨제이제일제당 (주) | 밀배아 발효물의 추출물을 유효성분으로 함유하는 피부진정 외용제 조성물 |
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2002
- 2002-08-09 HU HU0202638A patent/HUP0202638A3/hu unknown
-
2003
- 2003-08-08 BR BR0313589-6A patent/BR0313589A/pt not_active Application Discontinuation
- 2003-08-08 EA EA200500326A patent/EA007844B1/ru not_active IP Right Cessation
- 2003-08-08 MX MXPA05001469A patent/MXPA05001469A/es unknown
- 2003-08-08 JP JP2004527076A patent/JP2006501214A/ja active Pending
- 2003-08-08 WO PCT/HU2003/000065 patent/WO2004014406A1/fr not_active Application Discontinuation
- 2003-08-08 KR KR1020057002283A patent/KR20050059066A/ko not_active Application Discontinuation
- 2003-08-08 EP EP03784303A patent/EP1536809A1/fr not_active Withdrawn
- 2003-08-08 CN CNA038189003A patent/CN1674924A/zh active Pending
- 2003-08-08 PL PL03375391A patent/PL375391A1/xx not_active Application Discontinuation
- 2003-08-08 CA CA002494744A patent/CA2494744A1/fr not_active Abandoned
- 2003-08-08 AU AU2003255854A patent/AU2003255854A1/en not_active Abandoned
-
2005
- 2005-02-03 HR HR20050114A patent/HRP20050114A2/hr not_active Application Discontinuation
- 2005-02-07 IL IL16673205A patent/IL166732A0/xx unknown
- 2005-03-04 NO NO20051168A patent/NO20051168L/no not_active Application Discontinuation
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DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; KOBAYASHI, AKIO ET AL: "Manufacture of anti-inflammatory substances and benzoquinones and hydroxybiphenyls as inflammation inhibitors", XP002260816, retrieved from STN Database accession no. 1995:967539 * |
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HIDVÉGI M ET AL: "MSC, a new benzoquinone-containing natural product with antimetastatic effect.", CANCER BIOTHERAPY & RADIOPHARMACEUTICALS. UNITED STATES AUG 1999, vol. 14, no. 4, August 1999 (1999-08-01), pages 277 - 289, XP009020668, ISSN: 1084-9785 * |
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Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2908998A1 (fr) * | 2006-11-24 | 2008-05-30 | Bao Quoc Ho | Nouveau produit enzymatique et son utilisation. |
WO2010100514A3 (fr) * | 2009-03-03 | 2010-10-28 | Hidvegi Mate | Composition pharmaceutique contenant une matière déshydratée, fermentée avec une structure cristalline amorphe |
US8563050B2 (en) | 2009-03-03 | 2013-10-22 | Máté Hidvégi | Pharmaceutical composition containing a fermented, dehydrated material with amorphous crystalline structure |
WO2010135580A2 (fr) * | 2009-05-20 | 2010-11-25 | The Regents Of The University Of California | Protéines de germe de blé fermenté (fwgp) pour le traitement du cancer |
WO2010135580A3 (fr) * | 2009-05-20 | 2011-03-31 | The Regents Of The University Of California | Protéines de germe de blé fermenté (fwgp) pour le traitement du cancer |
US9480725B2 (en) | 2009-05-20 | 2016-11-01 | The Regents Of The University Of California | Fermented wheat germ proteins (FWGP) for the treatment of cancer |
EP2600721A1 (fr) * | 2010-08-02 | 2013-06-12 | Mate Hidvegi | Molécules anticancéreuses et immunomodulatrices et fractions les renfermant |
EP2600721A4 (fr) * | 2010-08-02 | 2014-07-02 | Mate Hidvegi | Molécules anticancéreuses et immunomodulatrices et fractions les renfermant |
WO2012159988A1 (fr) | 2011-05-20 | 2012-11-29 | 3Ch Ltd | Utilisation de germe de blé fermenté dans le traitement de la maladie intestinale inflammatoire |
WO2012175594A1 (fr) | 2011-06-23 | 2012-12-27 | Biropharma Uk Ltd | Extrait de germe de blé obtenu par hydrolyse par protéase et utilisation médicale de cet extrait |
Also Published As
Publication number | Publication date |
---|---|
EA200500326A1 (ru) | 2005-06-30 |
CN1674924A (zh) | 2005-09-28 |
KR20050059066A (ko) | 2005-06-17 |
JP2006501214A (ja) | 2006-01-12 |
CA2494744A1 (fr) | 2004-02-19 |
BR0313589A (pt) | 2005-07-12 |
EA007844B1 (ru) | 2007-02-27 |
HU0202638D0 (fr) | 2002-10-28 |
HUP0202638A3 (en) | 2007-08-28 |
PL375391A1 (en) | 2005-11-28 |
MXPA05001469A (es) | 2005-06-06 |
IL166732A0 (en) | 2006-01-15 |
HUP0202638A2 (hu) | 2004-06-28 |
HRP20050114A2 (en) | 2005-10-31 |
NO20051168L (no) | 2005-03-04 |
EP1536809A1 (fr) | 2005-06-08 |
AU2003255854A1 (en) | 2004-02-25 |
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