NL2028362B1 - Composition for improving calcium and phosphorus regulation in poultry and uses thereof - Google Patents

Composition for improving calcium and phosphorus regulation in poultry and uses thereof Download PDF

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NL2028362B1
NL2028362B1 NL2028362A NL2028362A NL2028362B1 NL 2028362 B1 NL2028362 B1 NL 2028362B1 NL 2028362 A NL2028362 A NL 2028362A NL 2028362 A NL2028362 A NL 2028362A NL 2028362 B1 NL2028362 B1 NL 2028362B1
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calcium
composition
poultry
phytase
compositions
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NL2028362A
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Vulders Carly
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Intracare Bv
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/59Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/5939,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/105Aliphatic or alicyclic compounds
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/111Aromatic compounds
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/174Vitamins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/189Enzymes
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/20Inorganic substances, e.g. oligoelements
    • A23K20/24Compounds of alkaline earth metals, e.g. magnesium
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/20Inorganic substances, e.g. oligoelements
    • A23K20/26Compounds containing phosphorus
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/70Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75Feeding-stuffs specially adapted for particular animals for birds for poultry
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/08Oxides; Hydroxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10Carbonates; Bicarbonates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/465Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y301/00Hydrolases acting on ester bonds (3.1)
    • C12Y301/03Phosphoric monoester hydrolases (3.1.3)
    • C12Y301/030264-Phytase (3.1.3.26), i.e. 6-phytase
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/16Hydrolases (3) acting on ester bonds (3.1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y301/00Hydrolases acting on ester bonds (3.1)
    • C12Y301/03Phosphoric monoester hydrolases (3.1.3)

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  • Animal Husbandry (AREA)
  • Food Science & Technology (AREA)
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  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Birds (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • General Engineering & Computer Science (AREA)
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Abstract

The present application relates to orally administrable compositions comprising vitamin Ds, a calcium source and a phytase suitable for improving the calcium and phosphorus regulation and for reinforcing the eggshell quality in poultry. More particularly, the compositions are added to the drinking water of the poultry. Also methods to improve the calcium and phosphorus regulation and eggshell quality in poultry by administering said composition are disclosed.

Description

COMPOSITION FOR IMPROVING CALCIUM AND PHOSPHORUS REGULATION IN POULTRY AND USES THEREOF
FIELD OF THE INVENTION The present application relates generally to orally administrable compositions for improving the calcium and phosphorus regulation and for reinforcing the eggshell quality in poultry. Also methods to improve the calcium and phosphor regulation and eggshell quality in poultry by administering said composition are disclosed.
BACKGROUND OF THE INVENTION Optimal intestinal absorption of fundamental minerals and nutrients is essential to achieve full economic potential of modern layer poultry farming. Nutritional elements, such as vitamin Da, calcium and phosphorus, play a crucial role in the musculoskeletal integrity of the animals as well as in the development process of the eggshell. A drop in quality of the eggshells, and in particular, of the mechanical resistance of the eggshells, has given rise to a substantial increase in the percentage of broken, cracked or microcracked eggs, giving rise to a substantial loss in the product during transportation. Moreover, the reduction in quality of the eggshells requires the breeder to reduce the productive life of the laying poultry because this decrease in quality shows up most particularly after the 60” week of the life of the laying poultry.
Among the various nutritional factors that are necessary for proper eggshell formation in poultry, calcium and phosphorus probably play the most important role, because both calcium phosphorus are highly involved in the formation of the eggshell. Furthermore, it is well established that also for laying hens vitamin Dj is key to the maintenance of calcium homeostasis by stimulating its absorption and uptake.
Low availability of phosphorus in plant-based poultry diets has led to inorganic phosphorus supplementation of the poultry diets. Owing to phosphorus being one of the most expensive nutrients in poultry diets, increasing inorganic phosphorus in the diet, also increases feed cost. Furthermore, due to the public concern surrounding the contribution of phosphorus from animal excreta to environmental pollution, the industry is attempting to reduce phosphorus levels in commercial layer diets by reducing the margin of safety of this nutrient in feed formulation. Exogenous phytases have been used in poultry diets to liberate phosphorus and other minerals such as calcium, to reduce phosphorus pollution in poultry excreta and to reduce feed cost since they reduce the need for high levels of phosphorus in the feed. Nevertheless, so far, research studies have been focused on broilers only, but very little work has been carried out on laying hens.
SUMMARY Provided herein are compositions, more particularly orally administrable compositions for improving the calcium and phosphorus regulation and for reinforcing the eggshell quality in poultry. More particularly orally administrable compositions are provided comprising vitamin Ds, a calcium source and a phytase. Also provided are those compositions for use in treatment and/or prevention of a disturbed calcium and phosphorus regulation and for preventing a reduced quality of the eggshell in poultry. The compositions are particularly suitable for improving the eggshell quality in poultry. The applicants have found that compositions comprising vitamin D3, a combination of an inorganic and organic calcium salt as calcium source and a stabilized phytase provide synergistic effects on the calcium and phosphorus regulation in poultry thereby improving the musculoskeletal integrity of the animals and improving the eggshell quality of poultry. The present application thus provides an orally administrable composition comprising vitamin Ds or a derivative or analogue thereof, a calcium source and a stabilized phytase. In particular embodiments, the orally administrable composition comprises at least 200 1U/}; preferably at least 400 IU/1, vitamin Ds or a derivative or analogue thereof. In particular embodiments, the calcium source is an organic calcium salt, an inorganic calcium salt, or a combination thereof, or any hydrates thereof. In particular embodiments, the calcium source is a combination of an organic calcium salt and an inorganic calcium salt, or any hydrates thereof. In particular embodiments, the composition comprises a phytase that is selected from type A phytase or type B phytase. In some embodiments, the phytase is a fungal phytase, such as a phytase derived from the Aspergillus niger (A. niger) fungal strain. In some embodiments, the phytase is a bacterial phytase, such as a phytase derived from Escherichia coli (E. coli}. The application also provides the orally administrable composition as disclosed herein for use in treatment and/or prevention of a disturbed calcium and phosphorus regulation in poultry. In some embodiments, the orally administrable composition as disclosed herein is provided for use in the prevention of a reduced eggshell quality of poultry. In a further aspect, methods are provided for maintaining a normal calcium and phosphorus regulation in poultry wherein the orally administrable composition as disclosed herein is provided to the poultry.
In still another aspect, methods are provided for maintaining and/or improving the eggshell quality of poultry by administering the orally administrable composition as disclosed herein to the poultry. In particular embodiments, the orally administrable composition as disclosed herein is administered via the drinking water to the poultry. Particularly, the composition is administered via the drinking water to the poultry in a dilution of from 0.1 to 10% v/v; more preferably in a dilution of from 0.01% to 1% v/v. In particular embodiments, the orally administrable composition as disclosed herein is provided to the poultry during at least 3 consecutive days; preferably during at feast 3 consecutive days wherein the composition is provided continuously or ad libitum to the poultry. in some further embodiments, the composition as disclosed herein is provided ad libitum to the poultry for 3 to 7 consecutive days per week. In particular embodiments, the poultry is selected from layer poultry, parent stock or broilers. Even more preferred, the poultry is layer poultry. In particular embodiments, the poultry is selected from chicken, ducks, or quails.
BRIEF DESCRIPTION OF DRAWINGS Figure 1. Percentage of damaged eggs in a commercial layer farm after treatment with a composition comprising vitamin Dj, calcium chloride, calcium gluconate monohydrate and phytase. The composition was provided in the drinking water of layer hens from the age of 60 weeks. The arrow indicates the start of administration of the composition comprising vitamin D3, calcium chloride, calcium gluconate monohydrate and phytase. The straight line represents the trend of percentage of damaged eggs prior to the use of the composition. Figure 2. Comparison of the damaged egg rates in hens treated with the composition comprising vitamin D3, calcium chloride, calcium gluconate monohydrate and phytase, and a control group that did not receive the composition. 60-week old animals were treated during 11 days with the composition or with a control solution and the % of damaged eggs was evaluated.
DESCRIPTION OF EMBODIMENTS As used herein, the singular forms “a”, “an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.
The terms “comprising”, “comprises” and “comprised of” as used herein are synonymous with “including”, “includes” or “containing”, “contains”, and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. The terms also encompass “consisting of” and “consisting essentially of”, which enjoy well-established meanings in patent terminology.
The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints.
The terms “about” or “approximately” as used herein when referring to a measurable value such asa parameter, an amount, a temporal duration, and the like, are meant to encompass variations of and from the specified value, such as variations of +/-10% or less, preferably +/-5% or less, more preferably +/-1% or less, and still more preferably +/-0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. it is to be understood that the value to which the modifier “about” refers is itself also specifically, and preferably, disclosed.
Whereas the terms “one or more” or “at least one”, such as one or more members or at least one member of a group of members, is clear per se, by means of further exemplification, the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any 23, 24, 25, 26 or >7 etc. of said members, and up to all said members. In another example, “one or more” or “at least one” may refer to 1, 2, 3, 4, 5, 6, 7 or more.
The discussion of the background to the invention herein is included to explain the context of the invention. This is not to be taken as an admission that any of the material referred to was published, known, or part of the common general knowledge in any country as of the priority date of any of the claims, Throughout this disclosure, various publications, patents and published patent specifications are referenced by an identifying citation. All documents cited in the present specification are hereby incorporated by reference in their entirety. In particular, the teachings or sections of such documents herein specifically referred to are incorporated by reference.
Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the invention. When specific terms are defined in connection with a particular aspect of the invention or a particular embodiment of the invention, such connotation is meant to apply throughout this specification, i.e., also in the context of other aspects or embodiments of the invention, unless otherwise defined.
In the following passages, different aspects or embodiments of the invention are defined in more detail. Each aspect or embodiment so defined may be combined with any other aspect(s) or 5 embodiment(s) unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
Reference throughout this specification to “one embodiment”, “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the appended claims, any of the claimed embodiments can be used in any combination.
The present invention is based on the observation that administration of vitamin D3 in combination with a calcium source and a stabilized phytase to poultry improved the calcium and phosphorus regulation in the animals, thereby also improving musculoskeletal integrity and eggshell quality.
The inventors here demonstrate that by administration of a novel mixture of vitamin Ds, a calcium source and a stabilized phytase, the calcium and phosphorus regulation in the animals is synergistically improved. More specifically, by improving the calcium and phosphorus regulation, the musculoskeletal strength and integrity of the animals is improved, which contributes to the development and maintenance of a robust musculoskeletal system. After all, gait abnormalities and leg disorders are known as important issues found in poultry and egg production. These issues provide a welfare concern because lame birds may be incapable of reaching feed and water, are in pain and might become restricted in performance of natural behaviours. In broiler production systems with fast growing genetics, an increased prevalence of lameness is observed which varies from minor reduced capability to carry weight up to total immobility. Evidently, musculoskeletal problems also lead to reduced egg productivity of layer poultry.
By improving the calcium and phosphor regulation in poultry, the compositions and methods as disclosed herein also improve the eggshell quality of the poultry. Although the process for the development of the eggshell is not yet fully known, it has nevertheless been shown that nutritional elements, in particular calcium, phosphorus and vitamin Ds, in the feed of laying poultry could have beneficial effects on the functional properties of the shell. As shown in the examples herein, the inventors have now found that administration of the combination of vitamin D3, a stabilized phytase and calcium gluconate and calcium chloride as calcium source, reduced the presence of egg damage in layer poultry. The compositions and methods as disclosed herein therefore also provide an economic benefit by reducing the egg breakage and cracking rates and by increasing the yield.
An additional advantage of the compositions as disclosed herein is that the composition does not form a biofilm, which makes it particularly suitable for administration by way of the drinking water of animals. More specifically, the compositions as disclosed herein comprise no or only limited amounts of substances that may facilitate the formation of biofilms at the inner lining of drinking water systems, such as organic molecules and/or oils.
Accordingly, a first aspect of the application provides an orally administrable composition comprising vitamin Ds or a derivative or analogue thereof, a calcium source and a phytase.
The compositions envisaged herein thus comprise vitamin D; or a derivative or analogue thereof. Vitamin Ds, also known as cholecalciferol, is the inactive form of vitamin D that can be ingested through dietary intake or be generated endogenously in the skin of animals exposed to UV light. In the liver, vitamin Dj is converted into the active 25-hydroxyvitamin D; by hydroxylation, followed by conversion into 1,25-dihydroxyvitamin Ds, also known as 1,25-dihydroxycholecalciferol, calcitriol, or 12(0H}2D3, which is transported via the blood to its classic target organs, namely the intestine, kidney and bones. In the composition as envisage herein, vitamin D3, or any derivative or analogue is present. The derivatives or analogues can be selected from calcitriol, calcipotriol, or any other derivative or analogue of vitamin D; known in the art. In preferred embodiments, the orally administrable composition comprises vitamin Ds.
In particular embodiments, the compositions envisaged herein comprise at least 200 1U/! vitamin D3 or a derivative or analogue thereof; particularly at least 400 IU/l vitamin D or a derivative or analogue thereof. In further preferred embodiments, the compositions comprise in between 400 IU/l and 1000 1U/1 vitamin D; or a derivative or analogue thereof; in particular in between 500 U/l and 800 IU/I vitamin D3 or a derivative or analogue thereof. For example, the compositions envisaged herein comprise 400 1U/], 450 1U/1, 500 1U/1, 550 IU/I, 600 1/1, 650 1U/1, 700 13/1, 750 IU/l or 800 1U/! vitamin D3 or a derivative or analogue thereof. In some embodiments, the composition comprises in between
550 1U/l and 650 IU/I vitamin Ds or a derivative or analogue thereof, such as for example 550 IU/l, 560 10/1, 570 10/1, 580 tU/1, 590 1U/I, 600 1U/1, 610 1U/1, 620 U/l, 630 1U/1, 640 1U/1 or 650 IU/I vitamin D3 or a derivative or analogue thereof.
in particular embodiments, in the preparation of the orally administrable compositions as disclosed herein, the vitamin Ds, or a derivative or analogue thereof is added to the orally administrable compositions from a stock solution comprising about 10 MIU vitamin D3 or derivative or analogue thereof in a vegetable oil, such as for example corn oil, soybean oil or sunflower oil. Preferably, the vitamin D3, or derivative or analogue thereof, stock solution comprises about 10 MiU vitamin Ds; or derivative or analogue thereof in soybean oil.
The orally administrable composition as disclosed herein also comprises a calcium source. In particular, the calcium source is an organic calcium salt or a hydrate thereof, an inorganic calcium salt or a hydrate thereof, or a combination of an inorganic and organic calcium salt, or any hydrates thereof. Inorganic calcium salts in the composition envisaged herein can be selected from the group comprising calcium chloride, calcium phosphate, calcium sulfate, calcium oxide, calcium hydroxide, and calcium carbonate, or any hydrates thereof. Preferably, the inorganic calcium salt is calcium chloride. Organic calcium salts in the composition envisaged herein can be selected from the group comprising calcium gluconate, calcium pyruvate, calcium acetate, calcium benzoate, calcium L- threonate, or any hydrates thereof. Preferably, the organic salt is calcium gluconate or calcium gluconate hydrate.
In particular embodiments, the compositions as disclosed herein comprise in between 5% m/v and 15% m/v of a calcium salt; preferably in between 7% m/v and 12% m/v of a calcium salt, wherein the calcium salt is an organic calcium salt, an inorganic calcium salt, or a combination of an inorganic or organic calcium salt or any hydrates thereof. For example, the compositions as disclosed herein may comprise 7% m/v, 7.5% m/v, 8% m/v, 8.5% m/v, 9% m/v, 9.5% m/v, 10% m/v, 10.5% m/v, 11% m/v,
11.5% m/v, 12% m/v, of a calcium salt that is selected from an organic calcium salt, an inorganic calcium salt, or a combination of an inorganic or organic calcium salt or any hydrates thereof.
In particular embodiments, the compositions as disclosed herein comprise an inorganic calcium salt as calcium source. In further preferred embodiments, the compositions comprise in between 5% m/v and 15% m/v of the inorganic calcium salt or hydrate thereof; in particular in between 7% m/v and 12% m/v of the inorganic calcium salt. Thus, in some embodiments, the compositions comprise 7% m/v, 7.5% m/v, 8% m/v, 8.5% m/v, 9% m/v, 9.5% m/v, 10% m/v, 10.5% m/v, 11% m/v, 11.5% m/v, 12% m/v of inorganic calcium salt or hydrate thereof. In particular embodiments, the inorganic calcium salt is selected from calcium chloride, calcium phosphate, calcium sulfate, calcium oxide, calcium hydroxide, and calcium carbonate, or any hydrates thereof.
In particular preferred embodiments, the inorganic calcium salt is calcium chloride.
Thus, in particular embodiments, the inorganic calcium salt selected from calcium chloride, calcium phosphate, calcium sulphate, calcium oxide, calcium hydroxide, and calcium carbonate, or any hydrate thereof is present in between 5% m/v and 15% m/v; preferably in between 7% m/v and 12% m/v, in the composition as disclosed herein.
In preferred embodiments, the composition comprises calcium chloride as inorganic calcium - salt that is present in between 5% m/v and 15% m/v; preferably in between 7% m/v and 12% m/v, in the composition as disclosed herein.
In particular embodiments, the compositions as disclosed herein comprise an organic calcium salt as calcium source.
In further preferred embodiments, the compositions comprise in between 5% m/v and 15% m/v of the organic calcium salt or hydrate thereof; in particular in between 7% m/v and 12% m/v of the organic calcium salt.
Thus, in some embodiments, the compositions comprise 7% m/v, 7.5% m/v, 8% m/v, 8.5% m/v, 9% m/v, 9.5% m/v, 10% m/v, 10.5% m/v, 11% m/v, 11.5% m/v, 12% m/v of organic calcium salt or hydrate thereof.
In particular embodiments, the organic calcium salt is selected from calcium gluconate, calcium pyruvate, calcium acetate, calcium benzoate, calcium L-threonate, or any hydrates thereof.
Preferably, the organic salt is calcium gluconate or calcium gluconate hydrate.
Thus, in particular embodiments, the organic calcium salt selected from calcium gluconate, calcium pyruvate, calcium acetate, calcium benzoate, calcium L-threonate, or any hydrates thereof is present in between 5% m/v and 15% m/v; preferably in between 7% m/v and 12% m/v, in the composition as disclosed herein.
In particular embodiments, the compositions as disclosed herein comprise a combination of an inorganic calcium salt or hydrate thereof and an organic calcium salt or hydrate thereof as calcium source.
In further preferred embodiments, the compositions comprise in between 0.1% m/v and 2% m/v; preferably in between 0.3% m/v and 1% m/v, of an organic calcium salt or hydrate thereof, in combination with 4.7% m/v to 14% m/v; preferably with 4.9% m/v to 13% m/v, of a inorganic calcium salt or hydrate thereof.
In particular further embodiments, the composition as disclosed herein comprises 7% m/v to 12% m/v calcium chloride in combination with 0.3% m/v to 1% m/v calcium gluconate monohydrate as calcium source.
The compositions envisaged herein further comprise a phytase. in some embodiments, the phytase is a fungal phytase or a bacterial phytase.
In some further embodiments, the phytase is a fungal phytase derived from A. niger or from Peniophora lycii; preferably the phytase that is derived from the A. niger fungal strain.
In some other embodiments, the phytase is derived from bacteria, such as E. col, Citrobacter braakii or Buttiauxella spp.
In some embodiments, the phytase is a recombinant phytase.
In some embodiments, the phytase is a recombinant phytase produced by the Aspergillys niger fungal strain. The bacterial or fungal phytase as used herein can be produced in several producing organisms, such as A. niger, Trichoderma reesei, Asperigillus oryzae, Pichia pastoris, or Schizosaccharomyces pombe. In some embodiments, the phytase is a recombinant fungal or bacterial phytase produced in a producing organism selected from A. niger, Trichoderma reesei, Asperigillus oryzae, Pichia pastoris, or Schizosaccharomyces pombe. In some preferred embodiments, the phytase is a fungal phytase produced in A. niger.
Phytate, a salt complex of myo-inositol-1,2,3,4,5,6-hexakisdihydrogenphosphate, is a phosphorus storage compound in plants, which accounts for approximately two-thirds of the total phosphorus in plant ingredients. In chicken, phytate is not well used as a source of phosphorus because of limited endogenous phytase in the digestive tract of poultry. Administration of phytase to poultry animals increases the amount of plant phosphorus available to the animals and reduces the amount of inorganic phosphorus that needs to be added to the diet, resulting in substantial savings on feed costs. In specific embodiments, the orally administrable composition as disclosed herein comprises phytase in a range from about 10000 FTU to about 100000 FTU per kg composition, wherein FTU (phytase activity unit) is defined as the amount of phytase that liberates 1 micromole of inorganic phosphorus per minute from 0.0051 mol/l sodium phytate at 37°C and pH 5.5. In preferred embodiments, the orally administrable composition as disclosed herein comprises from phytase in a range from about 25000 FTU/kg to about 75000 FTU/kg composition, wherein FTU is defined as the amount of phytase that liberates 1 micromole of inorganic phosphorus per minute from 0.0051 mol/l sodium phytate at 37°C and pH 5.5. For example, the orally administrable compositions as disclosed herein comprises 30000 FTU/kg, 35000 FTU/kg, 40000 FTU/kg, 45000 FTU/kg, 50000 FTU/kg, 55000 FTU/kg, 60000 FTU/kg, 70000 FTU/kg or 75000 FTU/kg phytase.
In specific embodiments, the orally administrable composition as disclosed herein comprises at least 200 1U/}; preferably at least 400 1U/} vitamin D3 or a derivative or analogue thereof; in combination with 5% m/v to 15% m/v of a calcium salt and 10000 FTU/kg to 100000 FTU/kg phytase. The inventors have found that this specific ratio of vitamin Ds, calcium salt and phytase, allows dosing at a ratio which ensures the synergistic effect between these compound without significant side-effects. More specifically, the composition comprises in between 500 1U/} and 800 1U/! vitamin D3 or a derivative or analogue thereof, in combination with 7% m/v to 13% m/v of a inorganic and organic calcium salt, and 25000 FTU/kg to 75000 FTU/kg phytase. Even further, the composition as envisaged herein comprises in between 500 1U/l and 800 IU/l vitamin D3 or a derivative or analogue thereof, in combination with
7% m/v to 12% m/v of an inorganic calcium salt, in particular calcium chloride, and 0.3% m/v to 1% m/v of an organic calcium salt, in particular calcium gluconate monohydrate, and 25000 FTU/kg to 75000 FTU/kg phytase.
The orally administered compositions as envisaged are water soluble compositions, with the vitamin Ds, the one or more calcium salts and the phytase being suspended in a liquid, in particular in water.
In particular embodiments, the compositions as envisaged herein may further comprise other nutritional or mineral elements, such as for example kalium, natrium or magnesium sources.
For example, the compositions envisaged herein may comprise kalium sorbate, natrium benzoate and/or magnesium chloride, or any hydrate thereof.
In particular embodiments, the compositions envisaged herein comprise nitric acid.
In particular embodiments, the compositions envisaged herein comprise an emulsifier, for example a synthethic emulsifier such as glyceryl polyethylene glycol ricinoleate.
The composition as envisaged herein is an orally administrable composition, in particular a liquid orally administrable composition.
In preferred embodiments, the composition is added to the drinking water of poultry.
Other modes of administration can also be envisaged, such as for example addition of the composition to the feed.
For example, the composition can be added to the feed of the poultry.
The inventors of the present application specifically found that the compositions as envisaged herein particularly affect and improve the calcium and phosphorus regulation in poultry, thereby improving the musculoskeletal integrity of the animals as well as the eggshell quality while limiting negative side effects.
The present application therefore further provides the orally administrable composition as envisaged herein for use in the treatment and/or prevention of a disturbed calcium and phosphorus regulation in poultry.
As used herein, a disturbed calcium and phosphorus regulation is to be understood as any deviation from the normal physiological levels of calcium and phosphorus in the body that may lead to pathological effects and symptoms.
The compositions as envisaged herein are therefore for use in the improvement and normalization of the calcium and phosphorus regulation and for normalization of the calcium and phosphorus levels in the blood of the poultry.
Improvement of calcium and phosphorus regulation also refers to normalizing the absorption of dietary calcium and phosphorus by the small intestine and reabsorption of calcium by the kidneys.
In particular embodiments, the compositions as used herein are provided for use in preventing a reduced eggshell quality of poultry.
The compositions are further provided for reinforcing the eggshell of poultry. Indeed, by improving the calcium and phosphorus regulation in the animals, the compositions as disclosed herein reinforce the eggshells of the poultry, thereby improving their quality. The compositions as disclosed herein can also be applied in a preventive setting, used for preventing a decreased in the eggshell quality. Due to their effect on the eggshell quality and strength, the compositions are particularly useful to improve the mechanical resistance of the eggs of the poultry, thereby reducing the egg breakage rates and egg cracking rates.
In a further aspect, a method for maintaining a normal calcium and phosphorus regulation in poultry is provided, said method comprising administering to the poultry the composition as envisaged herein.
As used herein, maintaining a normal calcium and phosphorus regulation is to be understood as maintaining normal physiological levels of calcium and phosphorus in the body and maintaining the physiological absorption levels of dietary calcium and phosphorus by the small intestine and reabsorption levels of calcium by the kidneys.
In another aspect, a method for maintaining and/or improving the quality of the eggshell of poultry is disclosed as well as a method for preventing a reduced quality of the eggshell of poultry, wherein the compositions according to any of the embodiments as disclosed herein is administered to the poultry. By administering the compositions as envisaged herein to the poultry, in particular to laying poultry, it is possible to reinforce eggshells and to lower the egg breakage rate and the egg cracking rate compared with the case of not administering the same. The compositions according to the invention may administered to any birds without restriction. They can be added to the feed or to the drinking water of the animals. Preferably, the compositions as envisaged herein are added to the drinking water of the poultry.
The compositions as envisaged herein are thus typically provided as orally administrable compositions, meaning that they can be administered orally to the animals. Accordingly, the compositions as disclosed herein are liquid compositions.
In particular embodiments, the compositions as envisaged herein are thus administered via the drinking water of the poultry. By administering the composition via the drinking water, the animals have ad libitum access to the composition. In some particular embodiments, the compositions as envisaged herein are administered via the drinking water of the poultry in a dilution of from 0.1 to 10% v/v; more preferably in a dilution of from 0.01% to 1% v/v.
The compositions may be administered once daily or multiple times daily, for example two, three, or four times per day. In particular and preferred embodiments, the compositions are provided continuously and ad libitum to the animals, in particular via the drinking water.
In particular embodiments, the compositions as disclosed herein are ad libitum administered to the poultry during at least 3 consecutive days, such as during 3 days, during 4 days, during 5 days, during 6 days, during 7 days, or even during more than 7 days.
In particular embodiments, the compositions as disclosed herein are administered to the poultry for atleast 3 consecutive days per week; preferably for 3 to 7 consecutive days per week. For example, the compositions as disclosed herein can be administered for 3 days, followed by a 4-days period without administration of the composition, or for 4 days followed by a 3-days period without administration of the composition, or for 5 days followed by a 2-days period without administration of the composition, or for 6 days followed by one day without administration of the composition. This treatment regimen can further be applied for 1 week, for 2 weeks, for 3 weeks, for 4 weeks, or even for more than 4 weeks, During periods of challenge, such as disturbed calcium and phosphorus regulation or moderately or severely reduced eggshell quality, it is envisaged to administer the compositions as disclosed herein for several consecutive days, preferably for at least 3 consecutive days, such as for 3 to 7 consecutive days. In particular embodiments, the compositions may be administered for several weeks.
In particular embodiments, when the compositions are intended to be administered in a preventive setting, such as to maintain normal calcium and phosphorus blood levels, or to maintain the eggshell quality of the poultry, compositions are administered once a week for one, two, three, four or even more than four weeks. In other particular embodiments, the compositions as envisaged herein may be administered in a preventive setting for 3 to 7 days a week, such as for example in broilers.
The term “poultry” as used in the present application refers to chickens, home-bred chickens, silk fowls, turkeys, wild ducks, quails, ducks, guinea fowls, pheasants, crossbread of wild and domestic ducks, geese, ostriches, and the like The present invention is preferably applied to chickens, ducks and/or quails; even more preferably to chickens.
In particular embodiments, the poultry is selected from layer poultry, parent stock or broilers. In some further preferred embodiments, the poultry is selected from layer poultry, parent stock or broilers of chicken, ducks and/or quails. In still some further embodiments, the poultry is selected from layer chicken, parent stock chicken and/or broiler chickens. In some preferred embodiments, the invention is applied to laying hens bred for the purpose of producing chicken eggs. There is no particular limitation as to the kinds of chickens. lt is apparent that there have been provided in accordance with the invention products, methods, and uses, that provide for substantial advantages as set forth above. While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, modifications, and variations as follows in the spirit and broad scope of the appended claims. The above aspects and embodiments are further supported by the following non-limiting examples.
EXAMPLES Materials and methods The percentage of damaged eggs was evaluated in two separate flocks of a commercial layer farm, each comprising 14000 laying hens per house. Laying hens were from the Novagen breed, and during treatment they had an age in between 47 to 65 weeks. The hens were housed in a caged laying system with 14000 hens per house. In one housing system, the flock of laying hens was only administered the normal drinking water. In the other housing system, the laying hens received the composition according to the invention in their drinking water. More specifically, the composition comprising vitamin D3 (400-600 U/L}, 5% m/v to 15% m/v of a calcium source comprising calcium chloride and calcium gluconate monohydrate and 25000 FTU/kg to 75000 FTU/kg phytase was administered to the laying hens in a dilution of 0.1% in their drinking water, and the composition was administered for 3 consecutive days per week during 6 weeks (starting at week 60, indicated by the arrow in Figure 1).
Results As can be observed in Figure 1, the percentage of damaged eggs rises at an average rate of about 0.2% every week. However, administration of the composition as used herein reduced the percentage of damaged eggs by about 0.2-0.4% according to the trend for this flock. Remarkably, at the start of the administration of the composition (black arrow in Figure 1), the flock had an average age of about 60 weeks, concluding that the composition reduced the eggshell damage even in animals that are becoming older. When the percentage of damaged eggs in the treated hens was compared to the hens that only received normal drinking water, also a reduction of egg damage could be observed (Figure 2). More specifically, the average percentage of damaged eggs in the control group after 11 days is 1.63%,
whereas the average percentage of damaged eggs in the treated group after 11 days was 1.22%, showing a difference of 0.41% in the damaged egg rates.

Claims (15)

CONCLUSIESCONCLUSIONS 1. Een oraal toedienbare samenstelling omvattende vitamine Da of een afgeleide stof of analoog hiervan, een calcium bron en een fytase.An orally administrable composition comprising vitamin Da or a derivative or analogue thereof, a calcium source and a phytase. 2. De samenstelling volgens conclusie 1 waarbij de samenstelling ten minste 200 IU/l vitamine Da of een afgeleide stof of analoog hiervan bevat; bij voorkeur ten minste 400 {U/l vitamine Ds; of een afgeleide stof of analoog hiervan.The composition according to claim 1, wherein the composition contains at least 200 IU/l vitamin Da or a derivative or analogue thereof; preferably at least 400 {U/l vitamin Ds; or a derivative or analogue thereof. 3. De samenstelling volgens conclusie 1 of 2 waarbij de calcium bron een organisch calcium zout, een anorganisch calcium zout of een combinatie van een organisch en een anorganisch calcium zout is.The composition according to claim 1 or 2 wherein the calcium source is an organic calcium salt, an inorganic calcium salt or a combination of an organic and an inorganic calcium salt. 4. De samenstelling volgens conclusie 3 waarbij het organisch calcium zout geselecteerd wordt uit de groep omvattende calcium chloride, calcium fosfaat, calcium sulfaat, calcium oxide, calcium hydroxide en calcium carbonaat, of een hydraat hiervan.The composition of claim 3 wherein the organic calcium salt is selected from the group comprising calcium chloride, calcium phosphate, calcium sulfate, calcium oxide, calcium hydroxide and calcium carbonate, or a hydrate thereof. 5. De samenstelling volgens conclusie 3 waarbij het organisch calcium zout geselecteerd wordt uit de groep omvattende calcium gluconaat, calcium pyruvaat, calcium acetaat, calcium benzoaat, calcium L-threonaat, of een hydraat hiervan.The composition of claim 3 wherein the organic calcium salt is selected from the group comprising calcium gluconate, calcium pyruvate, calcium acetate, calcium benzoate, calcium L-threonate, or a hydrate thereof. 6. De samenstelling volgens eender welke voorgaande conclusie waarbij de calcium bron een combinatie is van een organisch calcium zout en een anorganisch calcium zout, of een hydraat hiervan; bij voorkeur een combinatie van calcium chloride en calcium gluconaat monohydraat.The composition of any preceding claim wherein the calcium source is a combination of an organic calcium salt and an inorganic calcium salt, or a hydrate thereof; preferably a combination of calcium chloride and calcium gluconate monohydrate. 7. De samenstelling volgens eender welke voorgaande conclusie waarbij het fytase afkomstig is van de Aspergillus niger schimmel.The composition of any preceding claim wherein the phytase is from the Aspergillus niger fungus. 8. De samenstelling volgens eender welke voorgaande conclusie, voor gebruik in de behandeling en/of preventie van een verstoorde calcium en fosfor regulatie in gevogelte.The composition according to any preceding claim, for use in the treatment and/or prevention of disturbed calcium and phosphorus regulation in poultry. 9. De samenstelling volgens eender welke voorgaande conclusies 1 tot 7 voor gebruik in de preventie van een verminderde eierschaalkwaliteit in gevogelte.The composition according to any one of claims 1 to 7 for use in the prevention of reduced eggshell quality in poultry. 10. Een methode voor het behoud van een normale calcium en fosfor regulatie in gevogelte, deze methode omvattende het toedienen van een samenstelling volgens eender welke voorgaande conclusie 1 tot 7 aan gevogelte.A method for maintaining normal calcium and phosphorus regulation in poultry, said method comprising administering a composition according to any one of claims 1 to 7 to poultry. 11. Een methode voor het behoud en/of de verbetering van de eierschaalkwaliteit in gevogelte en/of het verhinderen van een verminderde eierschaalkwaliteit in gevogelte, deze methode omvattende het toedienen van een samenstelling volgens eender welke voorgaande conclusie 1 tot 7 aan gevogelte.A method for preserving and/or improving eggshell quality in poultry and/or preventing reduced eggshell quality in poultry, said method comprising administering a composition according to any one of claims 1 to 7 to poultry. 12. De samenstelling voor gebruik volgens conclusies 8 of 9, of de methode volgens conclusies 10 of 11 waarbij de samenstelling toegediend wordt via het drinkwater van het gevogelte; bij voorkeur waarbij de samenstelling toegediend wordt via het drinkwater van het gevogelte in een verdunning van 0.1% tot 10% v/v; nog meer bij voorkeur in een verdunning van 0.01% tot 1% v/v.The composition for use according to claims 8 or 9, or the method according to claims 10 or 11, wherein the composition is administered via the drinking water of the poultry; preferably wherein the composition is administered via the drinking water of the poultry in a dilution of 0.1% to 10% v/v; even more preferably in a dilution of 0.01% to 1% v/v. 13. De samenstelling voor gebruik volgens één van de conclusies 8, 9 of 12, of de methode volgens één van de conclusies 10 tot 12, waarin de samenstelling ad libitum wordt aangeboden aan het gevogelte gedurende ten minste 3 opeenvolgende dagen; bij voorkeur waarbij de samenstelling ad libitum wordt aangeboden gedurende 3 tot 7 opeenvolgende dagen; nog meer bij voorkeur waarbij de samenstelling ad libitum wordt aangeboden gedurende 3 tot 7 opeenvolgende dagen per week.The composition for use according to any one of claims 8, 9 or 12, or the method according to any one of claims 10 to 12, wherein the composition is presented ad libitum to the poultry for at least 3 consecutive days; preferably wherein the composition is presented ad libitum for 3 to 7 consecutive days; even more preferably wherein the composition is offered ad libitum during 3 to 7 consecutive days per week. 14. De samenstelling volgens één van de conclusies 1 tot 7, de samenstelling voor gebruik volgens één van de conclusies 8, 9, 12 of 13, of de methode volgens één van de conclusies 10 tot 13, waarbij het gevogelte geselecteerd wordt uit leghennen, kweek gevogelte, of mestkuikens.The composition according to any one of claims 1 to 7, the composition for use according to any one of claims 8, 9, 12 or 13, or the method according to any one of claims 10 to 13, wherein the poultry is selected from laying hens, raise poultry, or fattening chickens. 15. De samenstelling volgens één van de conclusies 1 tot 7 of 14, de samenstelling voor gebruik volgens één van de conclusies 8, 9, 12, 13 of 14, of de methode volgens één van de conclusies 10 tot 14, waarbij het gevogelte geselecteerd wordt uit kippen, eenden en kwartels.The composition according to any one of claims 1 to 7 or 14, the composition for use according to any one of claims 8, 9, 12, 13 or 14, or the method according to any one of claims 10 to 14, wherein the poultry is selected is made from chickens, ducks and quail.
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