FR2908998A1 - Use of enzyme concentrate from cereal germ for therapeutic purposes to manufacture an anti inflammatory drug to treat arthritis and osteoarthritis - Google Patents

Use of enzyme concentrate from cereal germ for therapeutic purposes to manufacture an anti inflammatory drug to treat arthritis and osteoarthritis Download PDF

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FR2908998A1
FR2908998A1 FR0610317A FR0610317A FR2908998A1 FR 2908998 A1 FR2908998 A1 FR 2908998A1 FR 0610317 A FR0610317 A FR 0610317A FR 0610317 A FR0610317 A FR 0610317A FR 2908998 A1 FR2908998 A1 FR 2908998A1
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enzyme concentrate
enzyme
therapeutic purposes
therapeutic
cereal
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Bao Quoc Ho
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • 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]

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pain & Pain Management (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)

Abstract

Use of enzyme concentrate (I) from cereal germ for therapeutic purposes to manufacture an anti inflammatory drug, is claimed. An independent claim is included for the preparation of (I) comprising subjecting the cereal seeds to germination to break the cuticles, crushing after drying, contacting the obtained powder with water, draining in aqueous alcohol at low temperatures and precipitating the enzyme powder by denaturing followed by lyophilization. ACTIVITY : Antiinflammatory; Antiarthritic; Osteopathic. MECHANISM OF ACTION : None given.

Description

NOUVEAU PRODUIT ENZYMATIQUE ET SON UTILISATION La présente invention seNEW ENZYMATIC PRODUCT AND USE THEREOF

rapporte au domaine de la chirnie et plus particulièrement à celui de la biochimie. Elle a plus particulièrement pour objet l'utilisation d'un produit biologique extrait de céréales en vue de l'alimentation ou de la guérison des maladies d'origine inflammatoire. Elle a spécifiquement pour objet l'utilisation d'un concentré enzymatique tiré du germe de céréales en vue de la réalisation d'un médicament destiné à combattre les états d'inflammation chez l'homme ou l'animal.  relates to the field of chirnie and more particularly to that of biochemistry. More particularly, it relates to the use of an organic product extracted from cereals for the purpose of feeding or curing inflammatory diseases. It specifically relates to the use of an enzyme concentrate derived from the cereal germ for the production of a medicament for combating the inflammation states in humans or animals.

On connaissait déjà de nombreuses préparations médicamenteuses tirées du germe de céréales. C'est ainsi qu'on a mis en évidence les propriétés anti-inflammatoires et cicatrisantes de l'insaponifiable d'huile de germe de soja obtenu par traitement de l'huile par de la soude. Le produit ainsi obtenu contient principalement des stérols végétaux. On connaît également du brevet européen 1.536.809 au nom de HIDVEGI MATE et RESETAR AKOS (HU) l'utilisation en thérapeutique d'un extrait de germe de blé fermenté au moyen de souches de Saccharomyces cerevisiae, pour la fabrication d'un médicament utile comme agent anti-inflamratoire. On connaît encore l'utilisation d'une fraction insaponifiable de Zea mays pour le traitement des parodontoses (brevet coréen KR 2002/003413).  Numerous drug preparations from cereal germ were already known. Thus, the anti-inflammatory and healing properties of the unsaponifiable soybean oil obtained by treating the oil with sodium hydroxide have been demonstrated. The product thus obtained contains mainly plant sterols. Also known from European patent 1,536,809 in the name of HIDVEGI MATE and RESETAR AKOS (HU) the therapeutic use of a wheat germ extract fermented with strains of Saccharomyces cerevisiae, for the manufacture of a useful medicament as an anti-inflammatory agent. The use of an unsaponifiable fraction of Zea mays for the treatment of periodontal diseases is still known (Korean patent KR 2002/003413).

On connaît encore l'utilisation d'un extractum riche en sels minéraux de zinc, à partir de germes de céréales (EP 0858743 au nom de Nisshin Flour Milling Corp). Dans ce brevet, on montre que l'extraction du germe de céréale par de l'eau à une température de l'ordre de 70 en milieu légèrement acide amène la 2908998 2 mise en solution de protéines de bonne qualité, d'acides gras essentiels, de vitamines et de sels minéraux. Par concentration, on fait précipiter les sels minéraux qui sont principalement sous forme de phytates.  The use of an extractum rich in zinc mineral salts from cereal sprouts (EP 0858743 in the name of Nisshin Flour Milling Corp.) is still known. In this patent, it is shown that the extraction of the cereal germ with water at a temperature of the order of 70 in a slightly acidic medium leads to the solution of high quality proteins and essential fatty acids. , vitamins and minerals. By concentration, the mineral salts are precipitated which are mainly in the form of phytates.

5 Toutes ces références illlustratives de l'art antérieur sont complètement distinctes de la présente invention. Selon l'invention, il s'agit de l'utilisation à des fins thérapeutiques d'un concentré riche en enzymes multiples tiré des germes de céréales.All of these illlustrative references of the prior art are completely separate from the present invention. According to the invention, it concerns the therapeutic use of a concentrate rich in multiple enzymes derived from cereal germs.

10 Le concentré enzymatique est tiré de différentes graines de céréales (comme par exemple le blé, le riz ou le maïs) que l'on soumet à une mise en germination pour rompre les cuticules à un broyage après séchage pour obtenir une poudre que l'on met en contact avec de l'eau pendant plusieurs heures, on épuise à 15 l'alcool aqueux à basse température pour amener la précipitation de la poudre enzymatique par dénaturation que l'on sèche par lyophisation. L'alcool est ensuite évaporé par lyophilisation et le produit pulvérulent ainsi séparé contient essentiellement l'ensemble des enzymes du germe de céréales. L'utilisation comme solvant d'extraction de l'éthanol et plus particulièrement de l'éthanol 20 aqueux permet d'extraire les fractions enzymatiques sans entraîner de fraction protéique ni de fraction lipidique. L'extrait enzymatique est ainsi pratiquement dépourvu de l'huile de germe de céréales ; ce qui assure sa stabilité et sa conservation.The enzyme concentrate is derived from various cereal seeds (such as, for example, wheat, rice or maize) which are subjected to germination to break the cuticles upon grinding after drying to obtain a powder which the The mixture is contacted with water for several hours, and the aqueous alcohol is depleted at low temperature to cause precipitation of the enzymatic powder by denaturation which is dried by lyophilization. The alcohol is then evaporated by lyophilization and the pulverulent product thus separated essentially contains all the enzymes of the cereal germ. The use as extraction solvent of ethanol and more particularly of aqueous ethanol makes it possible to extract the enzymatic fractions without causing a protein fraction or a lipid fraction. The enzymatic extract is thus practically devoid of the grain germ oil; which ensures its stability and preservation.

25 L'extrait enzymatique contient près de 20 enzymes présents naturellement dans les céréales, notamment des amylases et principalement de l'a-amylase, des protéases et des lipases. L'extrait lyophilisé contient essentiellement le concentré d'enzymes avec la quantité minimale de substance de charge.The enzyme extract contains about 20 enzymes naturally present in cereals, including amylases and mainly α-amylase, proteases and lipases. The lyophilized extract essentially contains the enzyme concentrate with the minimum amount of filler.

30 Le solvant d'extraction est un mélange éthanolique contenant des pourcentages variés d'eau et d'éthanol. Un solvant approprié est celui qui contient de 20 à 80 d'éthanol et le reste étant de l'eau. Un solvant préféré est celui qui contient de 40 à 60 % d'éthanol, le reste étant de l'eau.The extraction solvent is an ethanolic mixture containing various percentages of water and ethanol. A suitable solvent is one that contains 20 to 80% ethanol and the balance is water. A preferred solvent is one which contains 40 to 60% ethanol, the balance being water.

2908998 3 En pratique, au départ de 1 kg de céréales, on recueille 15 à 25 % de mélange enzymatique et de préférence 20 mg environ. Ce mélange complexe d'enzymes possède des propriétés biologiques intéressantes et notamment des propriétés anti-inflammatoires.In practice, from 1 kg of cereals, 15 to 25% of enzymatic mixture is collected and preferably about 20 mg. This complex mixture of enzymes has interesting biological properties and in particular anti-inflammatory properties.

5 Ce mélange enzymatique est dépourvu de propriétés allergisantes et exempt de toute toxicité. II peut être administré par voie orale sous forme de comprimés, de dragées, de pilules, de gélules, de capsules molles ou durcies, de sachets de poudre, de cachets ou de granules éventuellement aromatisés ou édulcorés. Ces formes pharmaceutiques renferment de 25 à 100 mg de mélange 10 enzymatique inerte non toxique pharmaceutiquement acceptable en mélange ou en association avec un excipient ou un véhicule. Le mélange enzymatique selon l'invention est administré, dilué dans un excipient inerte non toxique, pharmaceutiquement acceptable à raison de 25 à 100 mg par 15 jour, de préférence de 40 à 60 mg par jour et principalement environ 50 mg par jour. En raison de son absence de toxicité, l'extrait enzymatique de germes de céréales peut être administré d'une manière prolongée, notamment pendant quinze jours, pour obtenir une sédation des phénomènes douloureux liés à l'inflammation.This enzymatic mixture lacks allergenic properties and is free of any toxicity. It may be administered orally in the form of tablets, lozenges, pills, capsules, soft or hard capsules, sachets of powder, cachets or granules, optionally flavored or sweetened. These dosage forms contain from 25 to 100 mg of non-toxic, pharmaceutically acceptable, inert enzymatic mixture admixed with or in association with an excipient or carrier. The enzymatic mixture according to the invention is administered, diluted in a non-toxic, pharmaceutically acceptable inert excipient at 25 to 100 mg per day, preferably 40 to 60 mg per day and mainly about 50 mg per day. Due to its lack of toxicity, the enzymatic extract of cereal germs can be administered in a prolonged manner, in particular for a fortnight, to obtain a sedation of the pain phenomena related to inflammation.

20 L'invention trouve un emploi comme médicament des troubles articulaires liés à des phénomènes d'inflammation comme l'arthrite ou l'arthrose. Les exemples suivants illustrent l'invention sans toutefois la limiter. Exemple I • Extrait lyophilisé de germe de blé 0,050 kg • Lactose 0,010 kg • Phosphate tricalcique 0,025 kg • Stéréate de magnésium 0,005 kg 25 Comprimés à base d'un extrait enzymatique de germe de blé : 30 2908998 4 • Talc 0,10 kg Exemple II 5 Gélules à base d'un extrait enzymatique de germe de blé : • Extrait lyophilisé de germe de blé 0,075 kg • Lactose 0,020 kg • Silice colloïdale 0,002 kg • Stéiréate de magnésium 0,048 kg 10 pour 1000 gélulesThe invention finds use as a medicament for joint disorders related to inflammation phenomena such as arthritis or osteoarthritis. The following examples illustrate the invention without limiting it. Example I • Freeze-dried extract of wheat germ 0.050 kg • Lactose 0.010 kg • Tricalcium phosphate 0.025 kg • Magnesium sterate 0.005 kg Enzyme-based tablets of wheat germ: 2908998 4 • Talc 0.10 kg Example II 5 Capsules based on an enzymatic extract of wheat germ: • Freeze-dried extract of wheat germ 0.075 kg • Lactose 0.020 kg • Colloidal silica 0.002 kg • Magnesium steairate 0.048 kg 10 per 1000 capsules

Claims (9)

REVENDICATIONS 1. Utilisation à des fins thérapeutiques d'un concentré enzymatique tiré du germe de céréales en vue de la réalisation d'un médicament anti-5 inflammatoire.  1. Therapeutic use of an enzyme concentrate derived from the cereal germ for the production of an anti-inflammatory drug. 2. Utilisation à des fins thérapeutiques selon la revendication 1 dans laquelle le concentré d'enzymes contient principalement des amylases, des protéases et des lipases.  The use for therapeutic purposes according to claim 1 wherein the enzyme concentrate contains mainly amylases, proteases and lipases. 3. Utilisation à des fins thérapeutiques selon la revendication 1 et la revendication 2 dans laquelle le concentré d'enzymes contient principalement de l'aûamylase. 15  The use for therapeutic purposes according to claim 1 and claim 2 wherein the enzyme concentrate contains mainly alamylase. 15 4. Utilisation à des fins thérapeutiques selon l'une des revendications 1 à 3 dans laquelle le concentré d'enzymes est reparti en compositions pharmaceutiques adaptées pour la voie orale.  4. Use for therapeutic purposes according to one of claims 1 to 3 wherein the enzyme concentrate is divided into pharmaceutical compositions adapted for the oral route. 5. Utilisation à des fins thérapeutiques selon l'une des revendications 20 précédentes dans laquelle les compositions pharmaceutiques adaptées pour la voie orale contiennent de 0,025 à 0,100 g de concentré d'enzymes par prise unitaire.  5. Therapeutic use according to one of the preceding claims wherein the pharmaceutical compositions adapted for the oral route contain from 0.025 to 0.100 g of enzyme concentrate per unit dose. 6. Utilisation à des fins thérapeutiques selon l'une des revendications 25 précédentes dans laquelle le concentré d'enzymes est additionné ou mis en mélange avec un excipient ou un véhicule inerte non toxique pharmaceutiquement acceptable.  6. Therapeutic use according to one of the preceding claims wherein the enzyme concentrate is added or mixed with a pharmaceutically acceptable excipient or non-toxic inert carrier. 7. Utilisation à des fins thérapeutiques selon l'une des revendications 30 précédentes dans laquelle on adrninistre le concentré d'enzymes à la dose journalière de 25 à 100 mg. 10 2908998 6  7. Therapeutic use according to one of the preceding claims, wherein the enzyme concentrate is administered at a daily dose of 25 to 100 mg. 10 2908998 6 8. Utilisation à des fins thérapeutiques selon la revendication 7 dans laquelle on administre le concentré enzymatique à la dose d'environ 50 mg par jour.  The use for therapeutic purposes of claim 7 wherein the enzyme concentrate is administered at a dose of about 50 mg per day. 9. Procédé de préparation du concentré enzymatique selon la revendication 1 dans lequel on soumet les graines de céréales à une mise en germination pour rompre les cuticules,,à un broyage après séchage, met en contact la poudre ainsi obtenue avec de l'eau, épuise à l'alcool aqueux à basse température et laisse précipiter la poudre d'enzymes par dénaturation puis la sèche par lyophilisation.  9. Process for preparing the enzyme concentrate according to claim 1, in which the cereal seeds are subjected to germination to break the cuticles, to a grinding after drying, bringing the powder thus obtained into contact with water. depleted with aqueous alcohol at low temperature and allowed to precipitate the enzyme powder by denaturation and then dried by lyophilization.
FR0610317A 2006-11-24 2006-11-24 Use of enzyme concentrate from cereal germ for therapeutic purposes to manufacture an anti inflammatory drug to treat arthritis and osteoarthritis Withdrawn FR2908998A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2693208A1 (en) * 1992-07-02 1994-01-07 Inocosm Laboratoires Prepn. of anti-radical enzyme compsn. for prodn. of super-oxide dismutase, peroxidase and catalase - by extn. with ethanol@ or methanol followed by recovery, re-extraction and vacuum drying.
FR2747044A1 (en) * 1996-04-03 1997-10-10 Coletica USE OF POST-GERMINATING VEGETABLE SEEDS AS A SOURCE OF SUPEROXIDE DISMUTASE AND COSMETIC, PHARMACEUTICAL OR AGRO-FOOD COMPOSITIONS CONTAINING SUCH SUPEROXIDE DISMUTASE VEGETABLE, AND METHOD OF EXTRACTING
WO2001041794A2 (en) * 1999-12-10 2001-06-14 Laboratoire Top-Pharm Activated amylase
EP1262167A1 (en) * 2001-06-01 2002-12-04 Cognis France S.A. Cosmetic preparations containing an extract from germinating plants
WO2004014406A1 (en) * 2002-08-09 2004-02-19 Hidvegi Mate Use of fermented wheat germ extract as anti-inflammatory agent

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2693208A1 (en) * 1992-07-02 1994-01-07 Inocosm Laboratoires Prepn. of anti-radical enzyme compsn. for prodn. of super-oxide dismutase, peroxidase and catalase - by extn. with ethanol@ or methanol followed by recovery, re-extraction and vacuum drying.
FR2747044A1 (en) * 1996-04-03 1997-10-10 Coletica USE OF POST-GERMINATING VEGETABLE SEEDS AS A SOURCE OF SUPEROXIDE DISMUTASE AND COSMETIC, PHARMACEUTICAL OR AGRO-FOOD COMPOSITIONS CONTAINING SUCH SUPEROXIDE DISMUTASE VEGETABLE, AND METHOD OF EXTRACTING
WO2001041794A2 (en) * 1999-12-10 2001-06-14 Laboratoire Top-Pharm Activated amylase
EP1262167A1 (en) * 2001-06-01 2002-12-04 Cognis France S.A. Cosmetic preparations containing an extract from germinating plants
WO2004014406A1 (en) * 2002-08-09 2004-02-19 Hidvegi Mate Use of fermented wheat germ extract as anti-inflammatory agent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SHARMA A ET AL: "Purification of Wheat Germ Amylase by Precipitation", PROTEIN EXPRESSION AND PURIFICATION, ACADEMIC PRESS, SAN DIEGO, CA, US, vol. 18, no. 1, February 2000 (2000-02-01), pages 111 - 114, XP004435588, ISSN: 1046-5928 *

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