WO2014033490A1 - Produits de prévention contre des germes pathogènes, et leur procédé d'utilisation - Google Patents

Produits de prévention contre des germes pathogènes, et leur procédé d'utilisation Download PDF

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Publication number
WO2014033490A1
WO2014033490A1 PCT/HU2012/000088 HU2012000088W WO2014033490A1 WO 2014033490 A1 WO2014033490 A1 WO 2014033490A1 HU 2012000088 W HU2012000088 W HU 2012000088W WO 2014033490 A1 WO2014033490 A1 WO 2014033490A1
Authority
WO
WIPO (PCT)
Prior art keywords
product
methylglyoxal
mixed
product according
feed
Prior art date
Application number
PCT/HU2012/000088
Other languages
English (en)
Inventor
István Géza HUTÁS
Original Assignee
PHARMATÉKA Kutató, Fejlesztö és Szolgátató Kft.
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 PHARMATÉKA Kutató, Fejlesztö és Szolgátató Kft. filed Critical PHARMATÉKA Kutató, Fejlesztö és Szolgátató Kft.
Publication of WO2014033490A1 publication Critical patent/WO2014033490A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/105—Aliphatic or alicyclic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/121—Ketones acyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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

Definitions

  • the subject of the invention is a group of preventive products to be used against pathogenic germs, and the method for using these products, each product is being a special combined additive for preventive purposes, which could be used as additive or supplementary material in animal feed to produce products primarily for preventing and treating bacterial infection of poultry, which selectively inhibit the propagation of pathogenic germs that generate endo and exo toxins.
  • the livestock is exposed to various bacterial infections during animal husbandry as a result of the circumstances the animals are kept. It is known in veterinary practice that certain pathogenic germs are obligate anaerobes that are associated with the living cells and animal species. Other germs can often play a characteristic role as carrier of disease, and these bacteria cause strong physiological symptoms in the human body. The first symptoms appear as a characteristic chock effect in the tissue with attack peristaltic clinical picture. The wall of the bowel exhibits an oedematous condition. Within a couple of days the pathogenic germs enter the vein system and paralyse the immune system, causing a so called blood poisoning.
  • a critical situation can occur, if the bacterium body contains antitoxins, because these toxins escape (as a result of cell destruction) when antibiotics are used, and they cause strong toxic effect on parenchymal internal organs, the liver and the kidney. At the same time, their haemolysing ability leads to internal bleeding, and often causes the death of the infected organism.
  • the pathogenic germs are so called "intelligent" organisms, that can adapt quickly, and they can destroy one another also, usually the more aggressive one gets dominance, and the resistance to medication can also be attributed to this biochemical mechanism.
  • the defence against pathogenic germs is a complex tasks.
  • the most important mode is the preventive protection, which should be multiple faceted. It is necessary to combine preventive material with multiple components, which can be used in a given case for pharmaceutical treatment while continuously dosing the preventive products.
  • Pathogenic germs and moulds remain viable for a long time among humid conditions, and they tend to propagate quickly when affected by heat. In countries having moderately warm climate - like Hungary - they remain viable even as long as half a year.
  • the contamination usually starts from below, from the external environment, from the bedding materials or from the gaps of the planking of stables from point-like locations.
  • the collateral effect caused by rodents contribute to the start of contamination, because these animals are carriers of pathogenic germs. If a centre of infection starts to propagate in a barn containing 10,000 animals, then over 50 % of the animals will be contaminated within one or two weeks.
  • the animals defecate in the bedding material, and then they walk into the fodder, feeder and water one after another.
  • the contamination spreads continuously, the pathogenic flagellar germs propagate by means of contact, which are very virulent as a result of the movement of the flagella. Therefore, it is very important to keep the number of pathogenic germs at properly low level in the bedding materials and in the feed.
  • the Hungarian patent application P 07 00745 published on 2009-07-28 describes "A product containing EDTA, its salts and its complexes for preventing and treating bacterial intestinal diseases of pigs, and for enhancing the effect of antibiotics administered in case of such diseases".
  • the solution described in this application is intended to be suitable for preventing and treating intestinal diseases of pig using ethylene diamine tetra acetic acid (EDTA) and its salts and complexes, as well as for enhancing the effect of antibiotics administered in case of such diseases.
  • EDTA ethylene diamine tetra acetic acid
  • the animal husbandry products containing salt and complexes of EDTA are also subject of the invention.
  • the patent document number EP0005346 describes enterochelin complexes, pharmaceutical products containing enterochelin complexes, as well as the procedures for producing these products.
  • the patent document number EP0597167 describes a veterinary product, that contains an antibiotic mixture of gentamicin and lincomycin as additive to the drinking water or to the feed, including the application for breeding pigs.
  • the patent document number GB2027590 describes parenteral product containing tiamuline.
  • the patent document number US4716173 describes a procedure for treating malaria with a single intervention.
  • the patent document number US2003194451 describes a pharmaceutical product to be used for preventing and treating gastrointestinal discinetic illnesses.
  • the patent document number WO2004080210 describes compositions of nutritional metals to be used for strengthening physiological small intestines and for preventing diarrhoea.
  • our aim was to develop such a new product, which is suitable for preventing and treating bacterial infection of poultry, with particular attention to the fact, that resistance to medicines (antibiotics) develops quickly, and their effectiveness diminishes.
  • methylglyoxal and its diacetate have not been used for elimination of germs in feed or during animal husbandry, e.g. for treating beddmg material or as additive in feed.
  • methylglyoxal and its diacetate we observed the unexpected effect that the propagation of pathogenic germs had been inhibited by the use of these compounds and compositions.
  • the methylglyoxal is a naturally occurring substance in the honey of certain bees, e.g. in the Manuka honey.
  • the invention is a preventive product against pathogenic germs, primarily for preventing and treating bacterial contamination of poultry, which is characterized by that, the product is prepared by homogenizing or blending methylglyoxal or its diacetate, i.e. methylglyoxal diacetate with some organic acids and/or in combination with Na salts of organic acids, and it is added to the drinking water of the animals and/or mixed in the feed, and in this way it is administered to the animals, and/or used for disinfecting the bedding materials.
  • methylglyoxal or its diacetate i.e. methylglyoxal diacetate with some organic acids and/or in combination with Na salts of organic acids
  • the product contains 10-1000 mg kg methylglyoxal or methylglyoxal-diacetate.
  • a 60 % aqueous solution of methylglyoxal, or powder methylglyoxal diacetate is used for its preparation.
  • organic acids are used as supplementary materials in the product, in the given case formic acid and/or ascorbic acid.
  • EDTA ethylene diamine tetra acetic acid
  • sodium acid is used in the product as supplementary material.
  • malic acid is used in the product as supplementary material.
  • lactic acid and/or tetra sodium salt of EDTA ethylene diamine tetra acetic acid
  • EDTA ethylene diamine tetra acetic acid
  • the product is made in the from of powder mixture, in which tartaric acid and/or tannic acid is used as organic acid.
  • the product is mixed into the bedding material for the purpose of disinfecting the bedding material with the following proportions:
  • the product is mixed into the bedding material for the purpose of disinfecting the bedding material with the following proportions:
  • the surface of the bedding material in the given case straw or wood chips, is treated with the product in the form of spray, and in the given case the methylglyoxal is applied as dissolved in isopropyl aldehyde.
  • the product is mixed into the feed for the application as an additive with the following proportions:
  • the essential oil mix is added in the feed as an additive with the following proportions: Mixed in 1000 g turkey feed
  • the product is added in the feed as an additive with the following proportions:
  • the product is mixed in the drinking water of the animals as an additive with proportions so that the concentration of methylglyoxal or methylglyoxal diacetal is 10-1000 mg/kg.
  • the product is mixed in the bedding material, and this way, the product performs its disinfecting and preventing action externally.
  • the product is mixed in feed, which is consumed by the animal, therefore, the product performs its disinfecting and preventive function through the intestinal system.
  • the advantage of the product according to the invention is that it is able to inhibit the propagation of certain virulent pathogenic germs among in vitro conditions with the synergetic combination of materials exhibiting inhibitory properties even among physiological conditions, so that it is possible to maintain a condition free from infection if a healthy immunological background is present. This is particularly important in case of poultry breeding, because the bacteria having zoonotic properties can often infect the human population too.
  • the product according to the invention and their application ensures the chance of breeding an infected animal without additional medicinal treatment and avoiding the development of resistance, if no new (or continuous) infection exists.
  • the product can be applied in two different ways:
  • the animal eats the product with the feed or drinks it with water, and other hand, the product is mixed in the bedding material to inhibit the propagation of bacteria.
  • the number of germs can be reduced by two orders of magnitude with the product according to the invention relative to the control. It means that the product can efficiently reduce the propagation of pathogenic germs.
  • the product according to the invention is used primarily for poultry, e.g. chicken, turkey, duck, goose, because salmonella does not occur so often in pigs. It can be used for any of poultry, both for the chicks and the hens. It is important to continuously disinfect the bedding material in addition to administering the product through the feed to the animals.
  • the product according to the invention is a combination, which reduces the number of bacteria and the symptoms caused by them, as well as the number of pathogenic bacteria, in the given case e.g. continuously controls salmonella, it does not allow extreme propagation of it.
  • the infantis bacterium type is characteristic in Hungary.
  • the typhi and entretis types occur frequently in other countries.
  • These bacteria require large amount of energy because of their movement, and they are very virulent.
  • the number of bacteria can reach millions in half an hour depending on the temperature. The higher the temperature, the quicker is the replication. They react quickly to all external effects.
  • the essential property of the product is that it controls the replication by blocking the energy level of bacteria in a physiological manner. When administered in preventive dosages it will not kill the bacteria.
  • the benefit of the preventive application is that it only controls the bacteria, and therefore no endotoxin is produced, and the harmful effect of toxins is avoided.
  • the major active ingredient of the product according to the invention is the methylglyoxal and the methylglyoxal diacetal, which we supplemented with adjuvant materials.
  • These materials include vitamin C, which itself has an antibacterial effect on salmonella.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Animal Husbandry (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Fodder In General (AREA)

Abstract

L'objet de la présente invention est un groupe de produits de prévention destiné à être utilisés contre des germes pathogènes, et le procédé d'utilisation de ces produits, chaque produit étant un additif combiné spécial dans des fins de prévention, qui pourraient être utilisés comme matière additionnelle ou supplémentaire dans les aliments pour animaux pour produire des produits principalement pour la prévention et le traitement d'une infection bactérienne de la volaille, qui inhibent sélectivement la propagation de germes pathogènes qui génèrent des endo- et des exotoxines. Le produit selon l'invention est approprié principalement pour la prévention et le traitement d'une contamination bactérienne de la volaille. Il est caractérisé en ce que le produit est préparé par l'homogénéisation ou le mélange de méthylglyoxal ou de son diacétate, à savoir le diacétate de méthylglyoxal, avec certains acides organiques et/ou en combinaison avec des sels de Na d'acides organiques. Au cours du procédé selon l'invention, le produit est ajouté à l'eau de boisson des animaux et/ou mélangé dans l'alimentation, et de cette façon, il est administré aux animaux et/ou utilisé pour désinfecter les matières de litière.
PCT/HU2012/000088 2012-08-30 2012-08-31 Produits de prévention contre des germes pathogènes, et leur procédé d'utilisation WO2014033490A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU1200500A HU230466B1 (hu) 2012-08-30 2012-08-30 Metilglioxált vagy metilglioxál-diacetált és szerves savakat és/vagy szerves savak Na sóját tartalmazó, patogén csíra ellenes preventív készítmény alkalmazása baromfiak almozásához használt alom fertőtlenítésére
HUP1200500 2012-08-30

Publications (1)

Publication Number Publication Date
WO2014033490A1 true WO2014033490A1 (fr) 2014-03-06

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WO (1) WO2014033490A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115176907B (zh) * 2022-07-25 2023-12-22 安徽粮牧农业科技有限公司 一种反刍动物用发酵饲料及其制作方法

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4048299A (en) * 1969-09-05 1977-09-13 William Wrigley, Jr. Co. Anticaries confectionaries and oral health products
EP0005346A1 (fr) 1978-05-05 1979-11-14 National Research Development Corporation Complexes d'entérocheline, compositions pharmaceutiques les contenant et un procédé pour leur préparation
GB2027590A (en) 1978-08-14 1980-02-27 Squibb & Sons Inc Parenteral compositions containing tiamulin
US4716173A (en) 1985-02-06 1987-12-29 Aida Salatinjants Method of treatment of malaria by one time interference
EP0597167A1 (fr) 1992-11-08 1994-05-18 LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d., Ljubljana Composition vétérinaire contenant un mélange antibiotique de gentamicine et lincomycine comme additif pour l'eau potable ou pour la nourriture pour animaux et son utilisation dans l'élevage de porcs
US20030194451A1 (en) 2002-04-12 2003-10-16 Pangenomics Co., Ltd. Crude drug composition for preventing and treating gastrointestinal dyskinetic diseases
WO2004080210A1 (fr) 2003-03-14 2004-09-23 Boehringer Ingelheim Danmark A/S Compositions a base de metaux alimentaires destinees a soutenir le developpement physiologique des intestins et a prevenir la diarrhee
WO2009066117A1 (fr) 2007-11-22 2009-05-28 Pharmateka Kiskereskedelmi Bt Utilisation de l'edta et de ses dérivés pour la prévention et le traitement de maladies intestinales bactériennes des porcs et pour l'augmentation des effets d'antibiotiques exercés dans de telles maladies
WO2010044042A1 (fr) * 2008-10-14 2010-04-22 Manuka Health New Zealand Limited Compositions antimicrobiennes
WO2010082846A1 (fr) * 2008-12-24 2010-07-22 Comvita New Zealand Limited Formulations médicales et nutritionnelles

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4048299A (en) * 1969-09-05 1977-09-13 William Wrigley, Jr. Co. Anticaries confectionaries and oral health products
EP0005346A1 (fr) 1978-05-05 1979-11-14 National Research Development Corporation Complexes d'entérocheline, compositions pharmaceutiques les contenant et un procédé pour leur préparation
GB2027590A (en) 1978-08-14 1980-02-27 Squibb & Sons Inc Parenteral compositions containing tiamulin
US4716173A (en) 1985-02-06 1987-12-29 Aida Salatinjants Method of treatment of malaria by one time interference
EP0597167A1 (fr) 1992-11-08 1994-05-18 LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d., Ljubljana Composition vétérinaire contenant un mélange antibiotique de gentamicine et lincomycine comme additif pour l'eau potable ou pour la nourriture pour animaux et son utilisation dans l'élevage de porcs
US20030194451A1 (en) 2002-04-12 2003-10-16 Pangenomics Co., Ltd. Crude drug composition for preventing and treating gastrointestinal dyskinetic diseases
WO2004080210A1 (fr) 2003-03-14 2004-09-23 Boehringer Ingelheim Danmark A/S Compositions a base de metaux alimentaires destinees a soutenir le developpement physiologique des intestins et a prevenir la diarrhee
WO2009066117A1 (fr) 2007-11-22 2009-05-28 Pharmateka Kiskereskedelmi Bt Utilisation de l'edta et de ses dérivés pour la prévention et le traitement de maladies intestinales bactériennes des porcs et pour l'augmentation des effets d'antibiotiques exercés dans de telles maladies
HUP0700745A2 (en) 2007-11-22 2009-07-28 Pharmateka Bt Use of edta its salts and complexes for the prevention and treatment of bacterial intestinal swine diseases and for enhancement of efficiency of antibiotics in curing such illnesses
EP2224918A1 (fr) 2007-11-22 2010-09-08 PHARMATÉKA Gyártó és Kereskedelmi BT Utilisation de l'edta et de ses dérivés pour la prévention et le traitement de maladies intestinales bactériennes des porcs et pour l'augmentation des effets d'antibiotiques exercés dans de telles maladies
EA201000854A1 (ru) 2007-11-22 2010-12-30 Фарматека Дьярто Эш Керешкедельми Бт Применение эдта и ее солей для профилактики и лечения дизентерии свиней и усиления эффектов антибиотиков, проявляющихся при этом заболевании
WO2010044042A1 (fr) * 2008-10-14 2010-04-22 Manuka Health New Zealand Limited Compositions antimicrobiennes
WO2010082846A1 (fr) * 2008-12-24 2010-07-22 Comvita New Zealand Limited Formulations médicales et nutritionnelles

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CAMPBELL ET AL: "Methylglyoxal and other carbohydrate metabolites induce lanthanum-sensitive Ca<2+> transients and inhibit growth in E. coli", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, ACADEMIC PRESS, US, vol. 468, no. 1, 14 November 2007 (2007-11-14), pages 107 - 113, XP022344721, ISSN: 0003-9861, DOI: 10.1016/J.ABB.2007.09.006 *
MALETTA ANNE B ET AL: "Effect of Coffee Filtrate, Methylglyoxal, Glyoxal, and Caffeine on Salmonella Typhimurium and S. Enteritidis Survival in Ground Chicken Breasts", JOURNAL OF FOOD SCIENCE, vol. 77, no. 2, February 2012 (2012-02-01), pages M135 - M141, XP002694084 *
TALUKDAR ET AL: "Further testing of antiviral activity of methylglyoxal urgently needed", MEDICAL HYPOTHESES, EDEN PRESS, PENRITH, US, vol. 67, no. 3, 1 January 2006 (2006-01-01), pages 673 - 674, XP005513897, ISSN: 0306-9877, DOI: 10.1016/J.MEHY.2006.04.005 *

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Publication number Publication date
HUP1200500A2 (en) 2014-03-28
HU230466B1 (hu) 2016-07-28

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