DE2525165A1 - CHICKEN FEED COMPOSITIONS FOR EGG-LAYING HENS - Google Patents

Description

LAWYERS

dr. JüP. r-: rr.-C! «*, v. waiter BEft Γ .5. June 1975

AiFRi :; - ¹ ■;. · ■■ ":» .1

DR. '... ".-J VyOLFP

DR. Ji. r ·. ■ ·. · .. ■ -. . ' νιί.

623 rk '.! .ν ,. _Λ "^" N-HüCHSf

Our no. 19 874 Ba / ki

The Upjohn Company Kalamazoo, Mich., V.St.A.

Chicken feed compositions for egg-laying hens

The poultry industry has recently made significant strides in addressing many of its problems. However, one area of concern in which it has had little success is in attempts to reduce the incidence of broken hen eggs. Nearly $ 5 to $ 8> of chicken eggs break prematurely, resulting in a loss of up to $ 100 million or more per year for egg producers. The reason for this premature breakage appears to be insufficient lime scale formation in the eggshell, resulting in the formation of eggshells that are too thin to withstand the forces exerted on them. It is known that

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Vitamin D, which affects the shell thickness of chicken eggs. Vitamin D, however, exercises little or no Effect on the thickness of the eggshells of certain hens. It also achieves the activity of vitamin D * in terms of increasing the thickness of eggshells to a height at which no further increase occurs, not even with extremely high doses of vitamin D ^

Recently, an active metabolite of vitamin D ~ has been isolated been. This metabolite, the 25-hydroxy derivative of vitamin D, is commonly known as 25-hydroxycholecaleiferol and referred to below as 25-HCC, has been shown to be a cure in serial experiments on rats of rickets (in the rat line rickets cure assay) and in tests carried out on young chicks to prevent Rickets proven to be more effective than vitamin D ~.

However, no specific attempts have been made to use 25-HCC in mature egg-laying chickens or other species apply. So far - because perhaps of even greater importance - only problems related to the formation of bone calcification, such as rickets and osteomalacia or in general membrane calcium transport, such as beef milk fever and hypoparathy * Roidism affecting humans has been treated.

Increasing the thickness of eggshells and curing or preventing bone conditions, such as rickets and Osteomalacia, are achieved through various physiological mechanisms of action. Dis substance necessary for the Increasing the shell thickness is responsible for calcium carbonate. The deposited substance with which successfully Various bone diseases can be treated is calcium hydroxyapatite, a complex mineral-like Salt of phosphorus, oxygen and calcium, which is not chemically related to carbonate. Also differ the organic matrices in which these substances are found

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are deposited, basically from each other. The organic matrix of eggshells is not made up of cells, but made up of amorphous protein platelets. The organic matrix of bones is shaped, living tissue and able to reproduce itself.

It has been found that 25-HGG and related compounds, which are further described below, have the property of increasing the shell thickness of chicken eggs. When given to hens, these compounds increase the shell thickness of the eggs of a substantial number of hens whose eggshells are less than or equal to 0.33 mm (0.013 inch) thick, a thickness that is considered critical since most of the breakage occurs Egg shells with a thickness of less than 0.33 mm occurs.

The invention thus relates to a feed formulation for Increasing the thickness of egg shells, and includes a chicken feed in combination with an egg shell thickness effectively increasing, but non-toxic, amount of one or more of the following compounds

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(b)

and or

(c)

worm

R = H or acyl "means,

wherein acyl is an acyl radical of a normal or inomerized Is carboxylic acid of 2 to about 8 carbon atoms, and

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R ¹ , R "and R" ¹ = H, OH or O-acyl,

wherein acyl has the meaning given above

Has,

but at least 2 of the substituents

R ¹ , R "and R"'should be hydrogen

and

when R ¹ , R "or R" ^{1 is} OH, R = H

should and

when R ¹ , R "or R" ^{1 is} O-acyl, R =

should be the same acyl and

R ^a = H or acyl,

wherein acyl has the meaning given above, and when R ^{a is} hydrogen, R should be hydrogen and when R ^{a is} acyl, R should be the same acyl.

When using the chicken feed composition to increase the Shell thickness of chicken eggs is given to hens a chicken feed in combination with the thickness of the egg shell effectively increasing, but non-toxic, amount of one or more of the above with respect to the composition components specified compounds, except that 25-hydroxycholecalciferol and its acylates are omitted are administered.

It has been found that the shell thickness of hen's eggs can be increased by adding 25-hydroxycholecalciferol, 24,25-dihydroxycholecalciferol, 25 _; 26-dihydroxycholecalciferol, 1,25-dihydroxycholecalciferol, 25-hydroxydihydrotachysterol, 3,25-hydroxyergocalciferol, 1- «^ .- hydroxycholecalciferol and their acylates.

The manufacture of the used in these compositions Connections and the use of such compositions takes place in a manner known per se. The manufacture of the not acylated compounds of the invention is described in

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Formula A.

25-HGC
24.25

25.26

R = R ^t = R ^II = R ^{l! L} = H
U.S. Patent 3,565,924

Dihydroxycholecalciferol - R = R ^ R ¹ · »= H,

R ^I! = OH

U.S. Patent 3,715,374

Dihydroxycholecalciferol - R = R '= R ^ff = H,

R "" = 0H

Biochemistry 9: 24: 4776-4780, 1970

Dihydroxycholecalciferol - R = R ¹ «= R ^f '» = H,

R '= 0H

Biochemistry 10: 14: 2799-2804, 1971

Formula B.
25th

Hydroxydihydrotachysterol, - R = H, Federation Proceeding 29: 2-687, 1970

Formula G
25th

Hydroxyergocaloiferol, R = H, Biochemistry 8: 9: 3515-3519, 1969

Formula D
1 oC

Hydroxycbolecalciferol, R = H

J. Am. Chem. Soc. 95: 8, 2748 (1973)

To prepare the acylated compounds of the invention, the non-acylated compounds given above are used with the acid anhydride or chloride of the desired Hydrocarbon carboxylic acid having 2 to 8 carbon atoms implemented in the manner indicated in Example 16 of BE-PS 747 492. Below are some examples specified for raw materials and end products.

25-Hydroxycholecalciferol gives with treatment with Acetic anhydride 25-hydroxycholecalciferol-3-acetate;

25-Hydroxycholecalciferol gives on treatment with butyryl chloride 25-Hydroxycholecalciferol-3-butyrate,

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25-Hydroxycholecalciferol gives "when treated with Octanoyl chloride SS-Hydroxycholecalciferol - ^ - octanoate;

24,25-dihydroxycholecalciferol gives when treated with ; Siganhydride 24,25-dihydroxycholecaleiferol-3,24-diacetate;

24,25-dihydroxycholecalciferol gives when treated with Isobutyryl chloride 24,25-dihydroxycholecalciferol-3,24-diisobutyrate;

25,26-Dihydroxycholecalciferol gives when treated with Propionic anhydride 25.26 dihydroxycholecalciferol-3,26-dipropionate;

# -, 25-Dihydroxycholecalciferol gives when treated with Valeric anhydride 1,25 dihydroxycholecalciferol-1,3-divalerate;

25-Hydroxydihydrotachysterol, gives with treatment

with acetic anhydride 25-hydroxydihydrotachysterol-, ' 3-acetate;

25-Hydroxyergocalciferol gives with treatment with Acetic anhydride 25-hydroxyergocalcifexol-3-acetate;

1cL-Hydroxycholecalciferol gives when treated with Propionyl chloride cholecalciferol ~ 1,3-dipropionate,

It is always possible to use the metabolites in the hydrated form is preferred. So z. B. the hydrate of 25-HCC versus the 25-HCC in non-hydrated Shape preferred. The production process is described in BE-PS 492 Example 8.

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The chicken feed with which the compounds of the invention

Consolidated represents a standard diet that on

egg-laying hens is fed. Below is an example of such a diet:

Laying formulation (fed ingredients after 20 weeks of age)

(Pounds)

Corn flour, No. yellow, ground

So bean meal $ 50> protein

Fish meal $ 65> protein

Leftover meat and bones 50 io protein

Corn distillates

dry soluble parts

Alfalfa flour 17% protein

Limestone, ground salt, iodized DL-methionine Vitamin premix

302.6 (667.5) 45.4 (100) 6.8 (15) 34 (75) 22.7 (50) 6.8 (15) 31.8 (70) 1.1 (2.5) 0.2 (0.5) 2.3 (5)

calculated composition

Protein, % 17.2

Calcium, % 3.4

The calcium level for egg-laying hens is known and important for the calcium formation in eggshells. Usually about 2.5 to about 5.5, preferably about 3.0 to about 4.0 % calcium, calculated as weight calcium per weight of feed formulation, is required. Is used with KaIk-

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ORIGfNAL INSPECTED

Worked mirror at the top of the range, one can Diet with increased strength and protein concentration "used will.

The active connection is before combination with the feed preferably provided with a coating to prevent degradation. This is particularly desirable when the active ingredient is used in the non-hydrated form. The coating can be any of the standard vitamin coatings to be used. For example, the crystalline compound can contain a solid antioxidant in such a large amount be coated so that only the crystal surfaces are covered with the substance. This is followed by drying of the crystals as described in US Pat. No. 3,110,783. Ea is also possible, however, a solid or liquid composition which contains the active substance, by adding Standard antioxidants such as tocopherol, propyl gallate, butylated hydroxyanisole or butylated hydroxytoluene, to stabilize.

The active substance can be mixed with the chicken feed formulation in the form of the pure compound or in combination with other feed components, in crystalline form, in solution or in suspension, as long as the substance is uniform present in the entire feed composition.

The active substance should be present in the feed formulation in an amount that increases the thickness of the eggshell but is non-toxic. The active substance can be used in as large a quantity as desired, as long as no toxic effects are observed. The smallest amount of active ingredient with which the desired results in terms of increasing the eggshell thickness are achieved is also the preferred amount in which the active ingredient is applied. With amounts of about 5 / yr to about 20 ag per 0.454 kg (Ib) feed formulation of 25-HCC, positive results are obtained with regard to the increase in eggshell

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thickness has been achieved, which Example 1 shows.

The feed formulation of the invention will "hens" normal feed intake, after which you get the desired Reinforcement of the eggshells "can be observed.

The invention is to be explained in more detail by the following examples. However, this should not result in any restrictions can be derived.

example 1

150 Hyline strain SGWL hens given feed containing a commercially available form of stabilized vitamin D, and the eggs with a shell thickness from less than 0.279 mn (0.011 inch) to more than 0.331 mm (0.015 inch) became uniform divided into six treatment groups, so that each treatment group has all representative values of different Shell thicknesses included. A basic feed formulation that was not supplemented with vitamin D was added daily either 25-HCC or vitamin D ,. This food gave then the hens. The daily formulation was used to prevent vitamin degradation. Cup changes and dimension of production were determined weekly. The chickens were put on this schedule for ten weeks.

The results from this experiment show that the shell thickness after administration of 25-HCC or vitamin D, increased by 0.025 mm to 0.076 mm (0.001 to 0.003 inches). The increase in egg shell thickness in hens treated with 25-HCC was at least as good as in hens treated with vitamin D. Egg production appeared after treatment with 25-HCC to be unchanged.

Tables I and II contain the data regarding the improvement in shell thickness in eggs from one given number of hens after administration of 25-HCC

_ ... ^ 5098 5 1/0838 or Vitamin D ^. _#

Table I.

Comparison of vitamin D and 25-HCC effects on hens
lay eggs with <0.33 mm (opi3 inch) shell.

Chicken-
group link /^g./454 g
(Ib) putter formulation number of
Hens that
C 0.33 mm
(0.013 inch)
thick sheep
len form number of
Hens with
improved
Shell limestone
education % of hens
with improved
Peel 1 Vitamin D, 10 Crystalline 16 6/16 37.5 cn
/ - ^ 2 Vitamin D, 10 Propylene
Glycol 14th 6/14 42.8 LD ι
CU 3 25-HGG 5 Propylene
Glycol 12th 9/12 75.0 • ^ I 4th 25-HCG 10 Propylene
Glycol 11 8/11 72.7 O
cc- 5 25-HGG 10 Crystalline 15th 13/15 86.6 U)
OC- 6th 25-HGC 20th Propylene
Glycol 11 9/11 81.8

Table II

Comparison of vitamin D and 25-HCC effects on hens
lay eggs with> 0.33 mm (0.013 inch) shell.

cn
MM » Chicken
group link /Ug./454 g
(Ib) putter formulation number of
Hens that
> 0.33 mm
(0.013 inch
thick sheep
len form number of
Hens with
improved
) Shell limestone
education % of hens
with improved
Peel O
co
00 1 Vitamin B, 10 Crystalline 6th 1/6 17.0 Ul 2 Vitamin D* 10 Propylene
Glycol 9 2/9 22.0 O
00
co 3 25-HCC 5 Propylene
Glycol 7th 4/7 56.5 00 4th 25-HCC 10 Crystalline 7th 4/7 56.5 5 25-HGG 10 Propylene
Glycol 6th 3/6 50.0 6th 25-HGG 20th Propylene
Glycol 8th 5/8 62.5

to ■ cn ro cn

The results of Tables I and II clearly show the surprising superiority of 25-HCG over vitamin D ^ in terms of improving the thickness of eggshells in a given number of hens. In cases where the eggshells were thinner than 0.33 mm (0.013 inch), which may be an indication of insufficient use of vitamin D ~ by the hens, the number of hens whose eggshell thickness was 25 with the administration was 25 -HCC increased, twice the number of hens treated with vitamin D. In addition, doses of 10 and 20 are ju g on the previously indicated level of vitamin DyAktivitat. In those cases where the eggshells were initially thicker than 0.33 mm (0.013 inch), the improvement in eggshell thickness achieved by the application of 25-HCO is even more pronounced. The number of hens whose eggshell thickness increased after administration of 25-HCC was nearly two and a half times the number of hens treated with vitamin D ^. Since these are apparently normal hens, these results cannot be explained by any known theory.

Although 5 JW g of 25-HCC was the lowest amount used in this experiment, this does not mean that the desired results in increasing the shell thickness of eggs cannot be obtained with even smaller amounts. Likewise, amounts greater than 20 / <g may be as effective, or perhaps even more effective, with no observable toxic effects.

Example 2

Chickens are physically separated from the chicken feed formulation with a source of calcium, such as oyster shells, and with that much 25-HCC impregnates that 3 / ^ g of 25-HCC per chicken per day gives, fed. The chickens ingest the oyster shells and absorb the 25-HCC from the digestive tract. Both

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eggs laid afterwards, the desired eggshell thickness "was observed.

Examples 3 and 4 illustrate further methods of administering the active component to egg-laying hens.

Example 3

A sufficient amount of 25-HCG to supply a chicken with about 3 jug of 25-HCC per day, taking into account the average water intake of the chicken per day, is measured and added to the water supply for the hen. To facilitate thorough dispersion, the 25-HGC can, if desired, be micronized and dissolved in a surfactant such as polysorbate 80 and measured into the water supply. The chickens consumed their normal amount of water including the 25-HGC. The desired eggshell thickness was observed in the eggs laid subsequently.

Example 4

A sufficient amount of 25-HCG, sufficient to provide a chicken with a 60-day supply of 25-HCC, is provided with an inert carrier, for example a mineral oil, combined and injected subcutaneously into the tissue of the wing. The 25-HCC is slowly released and absorbed. In the case of the eggs laid afterwards, the desired Shell thickness observed.

Example 5

In in Examples 1, 2, 3 and 4 indicated manner were 24,25-dihydroxycholecalciferol, 25-dihydroxycholecalciferol ₁ 26, 25-Hydroxyergocalciferol, 25-Hydroxydihydrotachysterolcr, 1 c * -, 25-Dihydroxycholecalcif erol, sov; ie 1oC-hydroxycholecalciferol given to egg-laying hens, with results similar to those of Examples 1, 2, 3 and 4 being obtained.

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" ¹⁵ " 2575165

Example 6

In the manner indicated in Examples 1, 2, 3 and 4 were 25-hydroxycholecalciferol-3-acetate, 25-hyaroxycholecalciferol-3-butyrate, 25-hydroxycholecalciferol-3-octanoate, 24,25-dihydroxycholecalciferol-3,24-diacetate, 24,25-dihydroxycholecalcif erol-3> 24-diisobutyrate, 25,26-dihydroxycholeealciferol-3,26-dipropionate, 1C ^, 25-dihydroxycholecalciferol-1,3-dipentanoate, 25-hydroxydihydrotachysterol, -3-acetate, 25-Hydroxyergocalciferol-3-acetate and 10 £ -Cholecalciferol-1,3-dipropionate given to egg-laying hens, with results similar to those in Examples 1, 2, 3 and 4 were achieved.

It should be noted that it is not known that the parent molecules of the metabolites of hydroxylated Dihydrotachysterol and ergocalciferol have the property of increasing the thickness of eggshells. Consequently in their special cases any effects to increase eggshell thickness were totally unexpected.

When using an acylate, the dosage amount should be based on its non-acylated parent molecule on a molar basis will. For example, about 1.6 / ^ g of 24,25-dihydroxycholecalciferol-3,24-dioctanoate, 1.0 / ^ g of 24,25-dihydroxycholecalciferol equivalent to.

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Claims (4)

Patent to sayings Chicken feed composition for egg-laying hens which, in combination with a chicken feed, is an effective but effective non-toxic amount of one or more eggshell thickness increasing compounds of the following Formulas contain: (c) and / or > R-cf 509551/08 38 "aOR ^a (d) wherein R = H or acyl, wherein acyl is an acyl radical of a normal or isomerized carboxylic acid with 2 to about 8 Carbon atoms is, and R ¹ , R "and R" ¹ = H, OH or O-acyl, wherein acyl has the meaning given above, but at least two of the substituents R ¹ , R ¹ * and R ¹ ·· should be hydrogen and if R ', R ¹¹ or R ^{111 is} OH, R = H and if R ¹ , R "or R ¹¹¹ O-acyl is, R = should be the same acyl and R ^a = H or acyl, wherein acyl has the meaning given above and whom and when R ^{a is} hydrogen, R should be hydrogen when R ^{a is} acyl, R is intended to be the same acyl. 2. Composition according to claim 1, characterized in that it is 1gL-hydroxycholecalciferol as the active ingredient or its acylates, the acyl group of which has 1 to 8 carbon atoms, inclusive. 3. Composition according to claim 1 or 2, characterized in that it is about 2.5 to about 5.5 # calcium per contains g (Ib) chicken feed. 4. Composition according to claims 1, 2 or 3, characterized in that it is about 5 / ig to about 20 / ^ g Contains active substance per 454 g (Ib) chicken feed. For: The Upjohn Company Ju Kalamazqto, Mich., V.St.A. Lk 509851/083 8 t Lawyer