US20160256426A1 - Composition preventing necrotic enteritis in galloanserans - Google Patents

Composition preventing necrotic enteritis in galloanserans Download PDF

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Publication number
US20160256426A1
US20160256426A1 US15/029,230 US201415029230A US2016256426A1 US 20160256426 A1 US20160256426 A1 US 20160256426A1 US 201415029230 A US201415029230 A US 201415029230A US 2016256426 A1 US2016256426 A1 US 2016256426A1
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United States
Prior art keywords
glycerol ester
ester composition
weight
composition according
glyceryl
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Abandoned
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US15/029,230
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English (en)
Inventor
Filip Van Immerseel
Richard SYGALL
Karolien Van DRIESSCHE
Richard Ducatelle
Conrad Gerard SCHWARZER
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Perstorp AB
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Perstorp AB
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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • 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
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention refers to the use of a glycerol ester composition of at least one short chain fatty acid for preventing and/or alleviating necrotic enteritis in the gastric tract of galloanserans.
  • the glycerol ester composition comprises at least 75% by weight of glyceryl tributyrate, below 25% by weight of glyceryl dibutyrate and below 8% by weight of glyceryl monobutyrate.
  • the present invention also refers to the use of said composition for modulating the gut flora of galloanserans.
  • Necrotic enteritis is an acute infection affecting galloanserans.
  • Galloanserans are divided into the subgroups galliformes (landfowls) like chicken, turkey, grouse and pheasant, and anseriforms (waterfowls) like ducks, goose and swan.
  • Necrotic enteritis has become an emerging problem especially among poultry and is characterized by severe necroses of intestinal mucosa. The clinical illness is usually very short and often the only signs are a sudden increase in mortality. However, birds with depression, ruffled feathers, and diarrhea may also be seen. The gross lesions are primarily found in the small intestine (jejunum), which may be ballooned, friable, and contain a foul-smelling, brown fluid.
  • the causative agent is the gram-positive, obligate, anaerobic bacteria Clostridium perfringens. There are two primary C. perfringens types, A and C, associated with necrotic enteritis in galloanserans. Toxins produced by the bacteria cause damage to the small intestine, but also liver lesions, and mortality.
  • C perfringens is a nearly ubiquitous bacteria readily found in soil, dust, feces, feed, and used poultry litter. It is also a normal inhabitant of the intestines of healthy galloanserans.
  • necrotic enteritis depends on the presence of predisposing factors, such as mucosal damage caused by coccidial pathogens and feed containing high protein levels.
  • C. perfringens Because C. perfringens is nearly ubiquitous, it is important to prevent coccidiosis, as well as changes in the intestinal microflora that would promote its growth. This has earlier been accomplished by routinely adding antibiotics to the feed. However, since the ban of growth promoting antibiotics in the European Union in 2006, necrotic enteritis has become an emerging disease among, for instance, poultry. There is a great need for alternative methods to counteract this disease or malfunction.
  • the gut flora consists of a complex of microorganism species that live in the digestive tract.
  • gut is synonymous with intestinal and flora with microbiota and microflora.
  • the microorganisms perform a host of useful functions, such as fermenting unused energy substrates, training the immune system, preventing growth of harmful, pathogenic bacteria, regulating the development of the gut, producing vitamins for the host and producing hormones to direct the host to store fats.
  • some species are thought to be capable of causing diseases or malfunction by producing infection or increasing cancer risk for the host.
  • the present invention discloses the use of a glycerol ester composition for preventing and/or alleviating necrotic enteritis in the gastric tract of galloanserans, like chicken and turkey.
  • the use of said composition for modulating the gut flora of galloanserans is also disclosed.
  • Use of the composition according to the invention balances or normalizes the gut flora of galloanserans in such a way that the growth of pathogenic species is inhibited and diseases like necrotic enteritis are prevented.
  • One mechanism behind this effect is presently believed to be that the growth of helpful bacteria is favored and that this prevents the growth of pathogenic species by competing for nutrition and attachment sites to the epithelium of the colon.
  • butyric acid on gut health in poultry and other animals have been known for a long time.
  • Different distribution forms of butyric acid have also been explored, among them distributing butyric acid in the form of glycerol esters.
  • glyceryl monobutyrate as a feed-additive to promote animal gut health.
  • glycerol ester composition comprising mainly glyceryl tributyrate
  • the present invention refers to the use of a glycerol ester composition comprising a short chain fatty acid, which has proven to be an efficient way of preventing necrotic enteritis in galloanserans, such as broiler chicken.
  • the glycerol ester composition comprises at least 75% by weight of glyceryl tributyrate, below 25% by weight of glyceryl dibutyrate and below 8% by weight of glyceryl monobutyrate.
  • Butyric acid is known to have a positive effect on gut health in galloanserans.
  • the present invention shows that distributing the butyric acid mainly as glyceryl tributyrate is an efficient way of preventing necrotic enteritis in galloanserans, such as broiler chicken, and it has proven to be more efficient than distributing butyric acid mainly in the form of glyceryl monobutyrate.
  • the glycerol ester composition comprises at least 80% by weight of glyceryl tributyrate, below 20% by weight of glyceryl dibutyrate and below 5% by weight of glyceryl monobutyrate.
  • the glycerol ester composition comprises at least 85% by weight of glyceryl tributyrate, below 15% by weight of glyceryl dibutyrate and below 4% by weight of glyceryl monobutyrate.
  • the glycerol ester composition comprises at least 90% by weight of glyceryl tributyrate, below 10% by weight of glyceryl dibutyrate and below 2.5% by weight of glyceryl monobutyrate.
  • the amount of free butyric acid in the glycerol ester composition is below 1%, preferably below 0.5% and most preferably below 0.2% by weight. Keeping down the amount of free butyric acid also ensures that the pH in the glycerol ester composition is kept at a level where the glycerol ester will not undergo hydrolyzation into glycerol and free acid, hence, the product is kept stable.
  • the glycerol ester composition is adsorbed on an inert carrier, such as a silica carrier.
  • a silica carrier preferably comprises porous silica particles with an average particle size of 20-70 ⁇ m.
  • the glycerol ester composition is adsorbed on silica particles in a weight ratio of 50-80% glycerol ester and 20-50% silica particles.
  • the glycerol ester composition according to the present invention can be added to any commercially available feedstuffs for galloanserans.
  • the glycerol ester composition may be incorporated directly into commercially available feeds or fed supplementary to commercially available feeds.
  • the amount of glycerol ester composition fed to the galloanserans is from 0.05 to 1.5% by weight, preferably from 0.1 to 1.0% by weight of the galloanserans' daily feed ration.
  • the amount of said glycerol ester composition is administered over time intervals of 5-10 days and is decreased over a 1-5 week period.
  • the decrease of said amount is 20-50% of the amount given during the previous interval.
  • C. perfringens strain 56 The challenge strain used in the in vivo trials, C. perfringens strain 56, was isolated from the gut of a broiler chicken with necrotic lesions from a flock with weight gain problems and has been shown to be highly virulent in earlier in vivo trials.
  • the strain was classified as a type A strain (netB positive, beta-2 and enterotoxin negative) and produces moderate amounts of alpha toxin in vitro (Gholamiandehkordi et al., 2006).
  • the strain was grown for 24 h in Brain Heart Infusion broth (BHI, Oxoid, Basingstoke, England).
  • a ten-fold dose of the anticoccidial vaccine Paracox®-8 (Schering-Plough Animal Health, Brussels, Belgium), containing live, attenuated oocysts of Eimeria ( E. ) acervulina (two lines), E. brunetti, E. maxima, E. necatrix, E. praecox, E. mitis and E. tenella was used in this study.
  • Nobilis Gumboro D 78 vaccine (Schering-Plough Animal Health, Brussels, Belgium) was given in the drinking water.
  • the feed was provided by the Institute for Agricultural and Fisheries Research (ILVO). The tested products were mixed in the feed.
  • the Gumboro vaccine was given in the drinking water at day 16 in all groups. All groups were challenged orally one time a day with approximately 4.10 8 cfu C. perfringens strain 56 at days 17, 18, 19 and 20. At day 18 all birds were orally inoculated with a ten-fold dose of Paracox-8TM. At days 21, 22 and 23, 9 animals of each group were euthanized by intravenous sodium pentobarbital injection.
  • the GraphPad Prism Software, Inc was used to determine whether there were significant differences between groups. Statistical significance was determined at a P value of ⁇ 0.05.
  • Table 3 shows the number of birds with necrotic enteritis lesions for each group, at day 21, day 22 and day 23. Also, the total number of birds with lesions per group is shown.
  • glyceryl monobutyrate at the higher concentration is compared to the addition of glyceryl tributyrate, it is about the same weight of butyric acid that is added (making the assumption that glycerol and butyric acid have about the same molar weights).
  • glyceryl tributyrate gives a much better result (24% positive chicken in total for glyceryl tributyrate compared to 46% positive chicken in total for glyceryl monobutyrate at the higher concentration).
  • the embodiment example is to be construed as illustrative and not limiting in any way.
  • the glycerol ester composition may for example comprise a blend of glycerol esters of different short chain fatty acids, such as butyric acid, propionic acid and valeric acid. The dosage levels will then have to be calculated with respect to the total amount of glycerol esters.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Birds (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Food Science & Technology (AREA)
  • Animal Husbandry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Fodder In General (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Feed For Specific Animals (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
US15/029,230 2013-10-14 2014-10-06 Composition preventing necrotic enteritis in galloanserans Abandoned US20160256426A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE1300646-5 2013-10-14
SE1300646 2013-10-14
PCT/SE2014/000123 WO2015057121A1 (en) 2013-10-14 2014-10-06 Composition preventing necrotic enteritis in galloanserans

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US (2) US20160256426A1 (de)
EP (1) EP3057441B1 (de)
CN (1) CN105636452A (de)
BR (1) BR112016006934B1 (de)
EA (1) EA031937B1 (de)
ES (1) ES2666909T3 (de)
PL (1) PL3057441T3 (de)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111149919A (zh) * 2020-01-14 2020-05-15 湖南泰丰动物药业有限公司 一种禽用丁酸甘油酯复合物及其制备方法与应用
BE1031379B1 (nl) * 2023-08-28 2024-09-18 Hipeva Synergistische samenstelling omvattende boterzuur en agave-fructaan

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CN106107192B (zh) * 2016-06-23 2019-11-01 杭州康德权饲料有限公司 一种蛋禽饲料添加剂及其应用
WO2018052356A1 (en) * 2016-09-19 2018-03-22 Perstorp Ab A dietary supplement for balancing cholesterol.
CN107736614A (zh) * 2017-08-29 2018-02-27 上海市儿科医学研究所 含丁酸的营养制剂
CN107684554B (zh) * 2017-08-29 2019-02-22 上海市儿科医学研究所 丁酸类化合物在制备防治nec药物中的应用
EP3809869A1 (de) * 2018-06-22 2021-04-28 Basf Se Zusammensetzungen für tiere und verwendungen davon
WO2020226548A1 (en) * 2019-05-09 2020-11-12 Perstorp Ab Antioxidant composition for animal feed

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111149919A (zh) * 2020-01-14 2020-05-15 湖南泰丰动物药业有限公司 一种禽用丁酸甘油酯复合物及其制备方法与应用
BE1031379B1 (nl) * 2023-08-28 2024-09-18 Hipeva Synergistische samenstelling omvattende boterzuur en agave-fructaan

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Publication number Publication date
BR112016006934B1 (pt) 2020-11-17
EP3057441A1 (de) 2016-08-24
CN105636452A (zh) 2016-06-01
PL3057441T3 (pl) 2018-07-31
US20170087115A1 (en) 2017-03-30
BR112016006934A2 (pt) 2017-08-01
BR112016006934A8 (pt) 2020-02-27
EP3057441B1 (de) 2018-03-21
EA201690767A1 (ru) 2016-07-29
ES2666909T3 (es) 2018-05-08
WO2015057121A1 (en) 2015-04-23
US9877945B2 (en) 2018-01-30
EA031937B1 (ru) 2019-03-29
EP3057441A4 (de) 2017-04-12

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