EP1536809A1 - Use of fermented wheat germ extract as anti-inflammatory agent - Google Patents

Use of fermented wheat germ extract as anti-inflammatory agent

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Publication number
EP1536809A1
EP1536809A1 EP03784303A EP03784303A EP1536809A1 EP 1536809 A1 EP1536809 A1 EP 1536809A1 EP 03784303 A EP03784303 A EP 03784303A EP 03784303 A EP03784303 A EP 03784303A EP 1536809 A1 EP1536809 A1 EP 1536809A1
Authority
EP
European Patent Office
Prior art keywords
avemar
day
inflammatory
wheat germ
treatment
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.)
Withdrawn
Application number
EP03784303A
Other languages
German (de)
English (en)
French (fr)
Inventor
Máté HIDVEGI
Akos Resetar
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP1536809A1 publication Critical patent/EP1536809A1/en
Withdrawn legal-status Critical Current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
    • A61K36/18—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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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Mycology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP03784303A 2002-08-09 2003-08-08 Use of fermented wheat germ extract as anti-inflammatory agent Withdrawn EP1536809A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
HU0202638 2002-08-09
HU0202638A HUP0202638A3 (en) 2002-08-09 2002-08-09 Use of fermented wheat-germ extract for preparation of antiphlogistic compositions
PCT/HU2003/000065 WO2004014406A1 (en) 2002-08-09 2003-08-08 Use of fermented wheat germ extract as anti-inflammatory agent

Publications (1)

Publication Number Publication Date
EP1536809A1 true EP1536809A1 (en) 2005-06-08

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ID=89980690

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EP03784303A Withdrawn EP1536809A1 (en) 2002-08-09 2003-08-08 Use of fermented wheat germ extract as anti-inflammatory agent

Country Status (15)

Country Link
EP (1) EP1536809A1 (ja)
JP (1) JP2006501214A (ja)
KR (1) KR20050059066A (ja)
CN (1) CN1674924A (ja)
AU (1) AU2003255854A1 (ja)
BR (1) BR0313589A (ja)
CA (1) CA2494744A1 (ja)
EA (1) EA007844B1 (ja)
HR (1) HRP20050114A2 (ja)
HU (1) HUP0202638A3 (ja)
IL (1) IL166732A0 (ja)
MX (1) MXPA05001469A (ja)
NO (1) NO20051168L (ja)
PL (1) PL375391A1 (ja)
WO (1) WO2004014406A1 (ja)

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FR2908998A1 (fr) * 2006-11-24 2008-05-30 Bao Quoc Ho Nouveau produit enzymatique et son utilisation.
HUP0900614A2 (en) 2009-09-29 2011-05-30 Mate Dr Hidvegi Preparation comprising dehydrated, fermented material with amorphous crystaline structure and process for its production
WO2010135580A2 (en) * 2009-05-20 2010-11-25 The Regents Of The University Of California Fermented wheat germ proteins (fwgp) for the treatment of cancer
US20120164132A1 (en) * 2010-08-02 2012-06-28 Mate Hidvegi Anticancer and immunomodulating molecules and fractions containing said molecules, and process for preparing said fractions and said molecules from fermented vegetal material, and their uses
GB201108560D0 (en) 2011-05-20 2011-07-06 3 Ch Ltd Use of fermented wheat germ in the treatment of inflammatory bowel disease
GB201110746D0 (en) 2011-06-23 2011-08-10 Biropharma Uk Ltd Wheat germ derived material
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 (ko) * 2016-05-11 2017-11-16 씨제이제일제당 (주) 밀배아 발효물의 추출물을 유효성분으로 함유하는 피부 주름 개선 외용제 조성물
KR101955111B1 (ko) * 2016-09-23 2019-03-07 씨제이제일제당 (주) 밀배아 발효물의 추출물을 유효성분으로 함유하는 피부진정 외용제 조성물

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HU223344B1 (hu) * 1997-08-13 2004-06-28 Máté Hidvégi Immunstimuláns és metasztázist gátló fermentált, szárított anyag, ezt tartalmazó gyógyszerkészítmények, eljárás az előállítására és alkalmazásai

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Title
GYÖRGY FALKAY ET AL.: "Fermented wheat germ extract (Avemar) Inhibits adjuvants arthritis", CONFERENCE OF THE ONCOLOGY ASSOCIATION, 22 November 2001 (2001-11-22) - 24 November 2001 (2001-11-24), BUDAPEST, pages 1 - 22, XP003016919
See also references of WO2004014406A1
TELEKES ANDRAS AND HIDVEGI MATE: "Avemar's effect mechanism (part2) - immunological effects", NÖGYOGYASZATI ONKOLOGIA, vol. 6, 2001, BUDAPEST, HU, pages 1-4, 40 - 41, XP003016918

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HUP0202638A3 (en) 2007-08-28
PL375391A1 (en) 2005-11-28
HUP0202638A2 (hu) 2004-06-28
CN1674924A (zh) 2005-09-28
MXPA05001469A (es) 2005-06-06
CA2494744A1 (en) 2004-02-19
NO20051168L (no) 2005-03-04
BR0313589A (pt) 2005-07-12
EA007844B1 (ru) 2007-02-27
WO2004014406A1 (en) 2004-02-19
IL166732A0 (en) 2006-01-15
EA200500326A1 (ru) 2005-06-30
JP2006501214A (ja) 2006-01-12
HRP20050114A2 (en) 2005-10-31
HU0202638D0 (ja) 2002-10-28
KR20050059066A (ko) 2005-06-17
AU2003255854A1 (en) 2004-02-25

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