CA1091502A - Feed composition containing ronnel and antibiotic a3823 complex or factor and use thereof - Google Patents

Abstract

ABSTRACT

The invention concerns a composition for promoting animal nutrition and improved feed efficiency which com-prises 0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphoro-thioate and monensin in admixture with an edible solid.
The combination of phosphorothioate and monensin provides a synergistic nutritional response and improvement of feed efficiency.

Description

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~ rhis invention concerns a composition and method for promoting animal nutrition.
The composition of the invention comprises 0,0--dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate ~ (hereinafter called "phosphorothioate") and monensin in - admixture with an edible solid.
The method of the invention comprises intro-ducing into the diet of an animal in combination from 0.14 to 2.3 milligrams of monensin and from 0.5 to 4 milli-:
grams of 0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphoro-thioate per kilogram of body weight per day.
Generally, the composi-tion contains, by weight, from 0.01 to 3 0 parts of the phosphorothioate per one ~ part monensin. Preferably, the composition will contain ^`; 15 0.01 to 100, more preferably 0.1 to 20, and most preferably -~` 0.5 to 10 parts of the phosphorothioate per one part ~
.i:i ~` monensin.
The composition and method of the invention are ~i useful for promoting the growth, increasing milk and fiber .. .
production and improving the feed conversion efficiency, of livestock and poultry, especially those selected from cloven hoof ruminant animals, such as cattle or sheep, swine, and chickens. The invention further relates to the feed or feed additive supplement and feed addi-tive ~` 25 premix compositions containing the growth promoting sub-stances.
The invention more particularly relates to : ,. , : :
' the use of the phosphorothioate to overcome the depressed y feed intake previously observed upon the administration i 30 of the antibiotic monensin to livestock and poultry.
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109~S(32 The inventloll then relates to the use of said combination as synercJistic growth promotants, to feed compositions and feed addi-tive supplement compositions, lncluding growing mash for poultry, containing bo-th the : 5 components at appropriate dosage levels to be used in said method, and, to feed additive premixe~ and feedadditive concentrates employed in making up said compo-~ sitions.
U.S. Patent No. 3,501,568 describes monensin, ~ 10 where it is called A3823 complex, useful for treatment ~ of coccidiosis. As the patent explains, the production ~ of monensin by a fermentation process produces a mixture . of factors, all of which are useful. The monensin con-tains hydroxyl groups and can form physiologically accep~
.. 15 table alkali metal and alkaline earth metal salts, which ~:
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. include the sodium, potassium, lithium, cesium, rubidium, ~.~ barium, calcium and magnesium salts. Accordingly, the :; term "monensin" is used herein to refer to the various factors and the unresolved mixture of factors produced by fermentation, and the alkali metal and alkaline metal : salts.
The various factors of monensin are designated A, B, C and D.
The free acid form of factor A is a crystalline ::
compound having a melting point of 103 to 105C. The - sodium salt has a melting point of 267 to 269C. The .
.;, .
~ emperical formula of the free acid is C36H62Oll and the ~
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molecular weight thereof is 670. The semi-structural formula of factor A is:
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D9~5~

llO CH Cl-I CH

CH ~ o ~ CH3 . HO2C CH3 HO CH2OH
C~3 .
The sodium salt form of factor B has a melting point of about 227 to 228C. The molecular weight of the ` 10 crystalline free acid is 656. The semi-structural formula -~ is as follows:

~-~ HO CH CH

C ~ C~3 HO CH OH
-~ H2C ~ CH3 2 3 ;~
Factor C is a crystalline monocarboxylic acid having a molecular weight 684. The sodium salt melts ~ at 212 to 214C.
; Factor D is also a crystalline compound contain-. ing a carboxylic acid group and having a molecular weight .~ of 684. The sodium salt melts at 251 to 252C.
Monensin is obtained by culturing a Streptomyces . organism Stroptomyces cinnamonensis Okami ~NRRL B1588~ as , represented by a permanent deposit with the American Type -.~ Culture Collection at Washington~ D.C. that has been assigned the culture No. ATCC 15413. The use of the ~"~ ' n 18,247-F -3-,~."s .

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gl5~ i phosphorothioate for -the purpose of controlling parasites such as fl~as, flies, lice, ticks, screw-worms and cattle gr~bs as well as the helminthic parasites such as lung worms, stomach worms, or the gastrointestinal worms, attacking warm-blooded domestic animals is disclosed in U.S. Patent No. 2,811,480. The method of the patent com-prehends the administration of the phosphorothioate either topically or orally at a dosage rate in the range of 50 to 175 milligrams per kilogram of body weight depending ~ ....................................................................... . .
upon the phosphate ester selected and the parasite in-tended to be controlled. It is further taught that ~ `
;~ the treatment may be carried out in the form of multiple ~ dos~s over a period of several days in which case a -, daily dosage of from 5 to 25 milligrams per kilogram of ~- 15 body weight may be employed.
It has now been found that upon feeding to live-stock and poultry the phosphorothioate in combination with the monensin, the depressed feed intake observed on monen- ~ ~
sin-containing diets is overcome, and a highly desirable ~-combination of rapid weight gain and feed conversion ~`~ efficiency can be obtained. As a consequence, improved ... .
nutritional response evidenced by one or more of more `~
rapid weight gain and increased fiber production and/or `' milk production plus greater feed conversion efficiency is .,`~ . !
-;; 25 obtained on feeding an animal the combination of respec- -~
... . .
-~ tively from 0.14 to 2.3 milligrams of monensin and from i 0.5 to 2.5 mg of the phosphorothioate per kilogram of ;~
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body weight per day.

~;; The monensin and the phosphorothioate are con-, ~
~ 30 veniently inaorporated in a feed composition in appropriate ~
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amount to achieve the desired daily dosage of each in the amount of ration or supplement consumed reyularly, generally 5 to 100 grams (5.5 to 110 g.) of monensin and 3 to 350 grams (3.3 to 385 g.) of phosphorothioate per ton (metric ton) of balanced ration (dry matter basis, i.e. DMB), depending on the age and type of animal. These two nutritional response additives may also be incorporated in a mineral, protein or energy-type feed additive supplement in an appropriate amount -` of supplement the average animal is expected to consume each day on a daily basis.
For commercial use, it is convenient to provide a feed additive premix or concentrate containing the phosphoro-thioate and the monensin in a proportion such that a pre determined quantity of the premix to be added per ton of balanced ration DMB, for example, from 0.5 to 1000 pounds (0.225 to 450 kg.) of premix contains from 5 to 100 grams of .~ :
- monensin in addition to 3 to 200 grams of the phosphorothio-~ ate. The feed additive premix or concentrate consists of "'J the monensin and the phosphorothioate and a carrier such as soybean meal or ground corn or other edible feed grade mater-ial or innocuous diluent suitable for the livestock or poultry -~ animals. ;
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~ The following glossary defines terms in terminology -~ promulgated by the Association of American Feed Control Officials.
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The term "blocks" means agglomerated feed compressed into a solid mass cohesive enough to hold its form and weigh-.;
~'~ ing over two pounds (1 kg.), and generally weighing 30 to 50 :
pounds (13.5 to 22.5 kg.).
The terms "pellets" and "cubes" refer to agglomer-ated feed formed by compacting and forcing through die . . .
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SC)2 openings by a mechanical process and cutting the extrudate into appropriate short lengths. Cubes are made from Eeed forced through a square opening and cut into appropriate lengths. Pellets are generally made from feed forced through round or oval openings.
The term "carrier" refers to an edible material to which ingredients are added to facilitate uniform incorpor-ation of such ingredients int~ feeds. The active ingredient ` is absorbed, impregnated, or coated into or onto the edible - ~
material in such a way as to disperse and physically carry the active ingredient.
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The term "commercial feed" means all materials which -~ are distributed for use as feed or for mixing in feed, for - animals other than man, except:
: 15 ~1) Option A - unmixed seed, whole or .:
~` processed, made directly from the ~
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entire seed; Option B - unmixed or~;
` unprocessed whole seeds; ~
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(2) Hay, straw, stover, silage, cobs husks and hu11s (a) when unground, and (b) when unmixed with other ... .
; materials; ~`
` (3) Individual chemical compounds when not mixed with other materials.
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~:: 25 The term "concentrate" re~ers to a feed used ~
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'r` with another to improve the nutritive balance of the total and intended to be further diluted and mixed to -~ produce a supplement or a complete feed.
:'-The terms "feed" and "feedstuff" each refer to one or more edible materials which are consumed by , .
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animals (other than man) and contribute energy and/or nutrients to the animal's diet.
The term "diet" means a feed ingredient or mixture of ingredients including water, which is con-sumed by animals.
The phrase "feed additive premix" refers to an article that must be diluted for safe use in feed addl-- tive concentrate, a feed additive supplement or a com-plete feed. It contains, among other things, one or more additives in high concentrate in a suitable feed base such that up to 100 pounds (50 kg.) must be diluted to produce l ton (l metric ton) of complete feed. A feed ` additive premix contains additives at levels for which safety to the animal has not been demonstrated and/or which may result when fed undiluted in residues in the . .
edible products from food producing animals in excess of ` the safe levels established.
The phrase "feed additive concentrate" refers to an article intended to be further diluted to produce ,` 20 a complete feed or a feed additive supplement and is throughout most of the range not suitable for offering , . .
as a supplement or for offering free choice without di-lution. It contains, among other things, one or more additives in amounts in a suitable feed base such that -.~f 25 from lO0 to lO00 pounds (50 to 500 kg.) of concentrate ~ must be diluted to produce l ton (l metric ton) of a com-`; plete feed. ~ "feed additive concentrate" is unsafe if fed free choice or as a supplement because of danger to the health of the animal or because of the production of residues in the edible products from food producing animals in excess of the safe levels established.
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~he phrase "Eeed additive supplement" re~ers to an article for the diet of an animal which con-tains one or mor¢~ ~ood additives and is intended -to be (1) further diluted and mixed to produce a complete feed;
`~ 5 or (2) fed undiluted as a supplement to other feeds;or (3) offered free choice with other parts of the ra-tions separately available. A "feed additive supple-ment" is intended to be safe for the animal and to not produce unsafe residues in the edible products from ~-food producing animals if fed according to directions.
By "free choice" is meant a feeding system by which animals are given unlimited access to the separate components or groups of components consti-- tuting the diet.
"Ration" means the amount of the total feed which is provided to one animal over a 24 hour period.
The term "premix" refers to a uniform mix-` ture of one or more micro-ingredients with diluent . ~ .
and/or carrier. Premixes are used to facilitate uni- -form dispersion of the micro-ingredients in a larger mix.
The phrase "trace minerals" refers to mineral nutrients required by animals in micro amounts.
The term "vitamins" means organic compounds - 25 that function as parts of enzyme systems essential for the transmission of energy and the regulation of metabo-.7, lisms of the body of an animal.
Increasing the weight gain, wool production, the milk production in lactating animals, and feed con-version efficiency of livestock and poultry selected 18,247-F -8-. . , ~ . , ., : , s~2 from the clov~n hoof-ruminant animals, cattle and sheep, from swine, and from poultry, i5 an important objec-tive of this invention. E'or example, immature sheep, cattle and swine are commonly fed for ma~imum qrowth rate in feedlots and poultry such as chickens and turkeys in broiler pens, until they :reach a marketable weight.
When the desired weight is achieved, the animal is sold for slaughter. There is a normal feed intake for most ,.
- animals due to both physical and metabolic factors.
. ., It is important economicall~ that the animals achieve market weight in as short a tima as possible while consuming the least amount of feed necessary to achieve ~ such gain.
; It has been unexpectedly found th~at when the - 15 phosphorothioate is admixed with a monensin containing feed as specified herein and administered to ruminant animals, swine and poultry they more readily eat the feed so that the depressed feed intake characteristic of the ~ -:
monensin containing diet is overcome and as a consequence ~
feed intake is improved, substantial rates of weight gain ~ ~ -are observed while achieving suprising feed conversion . ., . ~
~ efficiency results. On using monensin and the phosphoro- -~
- thioate in combination the average daily qain obtained as ` well as the feed conversion efficiency is much better than ; 25 would be predicted from the characteristics of each nutri-tional response promotant administered alone, thus achieving ... .. . .
synergistic results The practical effect of this invention is to bring ruminant animals such as sheep or cattle, swine, and poultry promptly to market weigh-t with ",;
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: . . - ' :, ' : ' :: ::. ' . . ~ ' ' S~z surprisingLy reduced feed consumption, to obtain improved fiber (wool) production efficiency, and, in the case of lactating animals, greater milk production efficiency, when there is included in the diet, by way of the feed or feed additive supplement in the daily ration o~ such ~ animals, the active ingredients or growkh promotants, `- phosphorothioate and monensin. These materials are most - conveniently dispersed uniformly throughout the normal feed or feed additive supplement of the subject animal being fed in effective dosage levels. Although some of ` the benefits of each of monensin and phosphorothioate may -~ be obtained by feeding the ~wo growth promotants simul-taneously but in respectively different supplements or components of the daily diet, the depressed feed intake observed with monensin containing diets is not over- ~
- come. ;
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-~ Although the benefits of providing monensin and ~ phosphorothioate together in the diet are generally not `~ markedly noticeable in cloven hoofed ruminants during a :
feeding period shorter than 28 days, or 7 days in the - case of swine, or 3 days in the case of poultry, the improvement in nutritional response continues to be increasingly evident as providing of the combination continues for longer periods such as up to 56 days and further, up to 112 days or more in the case of cloven hoof ruminants, up to 25 days and preferably at least 60 days ,.~ - .
in the case of swine, up to 10 days, more preferably up . ~ .
;, to 25 days and most preferably at least 60 days or more `~ in the case of poultry. Occasional lapses of several days :", 30 or more without provision of the phosphorothioate are not , ~ 18,247-F -10-: . . ., : ,.

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harmful to the animal, but limit the beneficial effects largely to those days durinq which the growth promotants are supplied. Providing the combination of growth pro-motants during at least 75% and preferably at least 90%
j 5 of the days throughout a feeding period is considered to be "substantially every day" with respect to the feeding of livestock and poultry according to the present method.
The monensin and phosphorothioate can be mixed with conventional feed compositions. The feed compositions are then fed to the described livestock or poultry ani- -- mals according to methods well known to the agricultural ~-art. The use of the combination is particularly advan-tageous when incorporated into the normal feeds of meat-- 15 -producing animals, i.e., into growing and/or fattening ruminant feeds or swine or chicken feeds. In the case of wool producing or lactating animals, the diet into which the combination of growth promotants is advantage-ously incorporated according to the invention may be a -~;
high production diet or a good maintenance diet as may be selected by the animal husbandman or poultryman.
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The animal feeds most generally used in con-junction with t~e method of this invention are composed of various grain mixtures and/or roughage feeds such ;:
as hay, cottonseed hulls, rice hulls, silage or other high fiber feedstuffs commonly fed to meat, milk and/or :., .
wool-producing animals~ especially in cattle or sheep feeds. The feeds for swine and poultry will consist primarily of various grain mixtures plus the usual ad-; -,: ., ditaments such as bran meal, cottonseed meal, tankage `~ or alfalfa meals suitable for monogastric animals.
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The amount of monesin added and the amount of phosphorothioate added to feeds will vary depending on the age and type of animal. Very young animals that have been weaned or young poultry one or a few days old will have a lower feed consumption However, as the animal goes through a growth period to a fattening period, some-times called finishing, the feed consumption gradually increases, but generally falls in proportion to body weight.
Following are tabulations of feed intake for various sized and types of animals with accompanying computed ranges of monensin and phosphorothioate require-ments to be used in combination per ton of feed DMB
needed to provide the daily dosages set forth above. The average daily feed intake figures are from "1inical And Diagnostic Veterinary Toxicology", 2nd ed., William B. Buck, Gary D. Oswaler and Gary A. Van Gelder, Kendall/-- Hunt Publishing Company, Dubuque, Iowa.
;- Beef Cattle Phosphorothioate in Feed Grams Monensin in Feed ;- 20 % Feedper (metric) ton Grams per (metric) ., sody Wt. Intake/-Dosage (mg/kg) Ton Dosage (mg/kg) lbskg Body Wt. 0.5__ 4 0.1~4_ 2.3-;
300136 2.3 19.7 157.6 5.5 90.6 i (21.7) (173.7) (6.1) (99.8) `~ 450204 2.5 18.2 145 6 5 1 83.7 (20.0) (160 5)(5 6) (92.3) - 25 650295 2.4 18.9 151.2 5.3 86.9 ~ (20.8) (166.6) (5.8) (95.8) ;

`; 1000 454 2.1 21.6 172.8 6 1 99 4 ~ (23.8) (190.5)(6 7) (109.5) ,~ . .
Lactating Cattle 770 350 1.4 35~0 280.0 9.8 161.0 -~ (38.6) (308.6)(10.8) (177.5) 1760 800 1.2 40.0 320.0 11.2 184.0 ~ (44.0) (352.7)(12.3) (202.8) .~
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Non-Lactatin~ Dairy Cattle Phosphorothioate in Feed Grams Monensin in Feed ~ Feecl per (metric) ton Grams per (metric) bBo~y Wt. Bod~Wt. Dosage (mg/kq) Ton Dosage (mg/kg) ~ 770350 1.8 33.0 264.0 9.~ 15~8 - (36.4)t2gl.0) (10.1) (167.3) 1760800 1.6 28.0 224.0 7.8 128 8 (30.8)(246.9) ~8.6)(141 9) Lambs 59 27 4.5 10.0 80.0 2.8 46.0 (11.0) (88.2) (3.1) (50.7) ~- 99 45 3.9 11.6 92.8 3.3 53.4 (12.8)(102.3r (3.6) (58.8) Swine ~ -104.5 8.0 5.7 45.6 1.8 26.2 (6.3) (50.3) (2.0) (28.9) -~ . , 5022.7 6.4 7.1 56.8 2.0 32.7 ~; (7.8) (62.6) (2.2) (36.0) .. . .
10045 5.3 8.6 68.8 2.4 39.6 (9.5) (75.8) (2.6) (43.6) ~, 15068 4.5 10.1 80.8 2.8 46.5 (11.1) (89.0)(301) (51.2) 20090 4.0 11.4 91.2 3.2 52.4 (12.5)(100.5~ (3.5) (57.8) -'` Chickens ..... .
0.50.2314.0 3.2 25.6 0.9 1~.7 (3.5) (28.2) (1.0) (16.2) 1.00.4511.4 ~.0 32.0 1.1 18.4 (4.4) (35.3) (1.2) (20.3) 1.50.69 9.7 4.7 37.6 1.3 21.6 (5.2) (41.4) (1.4)(2308)

3.51.59 6.7 6.7 53.6 1.8 30.8 (7.4) (59.1)(2~0) (33.9) 5.52.50 5.0 9.1 72.8 2.6 41.8 (10.0) ~80.2) (2.9) (46.1) ., '.

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From the foregoing, it is apparent that cattle on a growing diet and weighing 300 to 1000 pounds tl36 to 454 kg.) will ordinarily be fed a diet, accor~ing to the invention, containing 18 to 173 grams per ton DMs ~20 to 190 g./metric ton) phosphorothioate and 5 to 100 grams per ton DMs (5.5 to 110 g./metric ton) monensin while cattle on a fattening diet will also be fed a feed con-taining the same amounts of phosphorothioate and monensin.
In each case, the concentrations will generally be some-what higher for heavier animals.
Maintenance diets fed lactating dairy cattle ~ should contain 35 to 320 g./ton (38.5 to 353 g./metric - ton) phosphorothioate and 9 to 184 g./ton (10 to 203 g./-metric ton) monensin depending on the size and feed intake of animal, while non-lactating dairy cattle should receive a feed containing 28 to 264 g./ton (30.8 to 291 g./metric ` ton) phosphorothioate and 7 to 152 g./ton (7.7 to 168 ~?`
g./metric ton) monensin. Accordingly, a preferred com- `;~
~` position of the invention contains from 30 to 360 g.
phosphorothioate and from 7 to 210 g. monensin per metric ton and the balance maintenance xuminant animal feed. -~
Lambs on dry feed will generally be fed a ration containing 10 to 93 g./ton (11 to 102 g./metric ton) phos-; phorothioate and 2 to 54 g./ton (2.2 to 60 g./metric ton) ` 25 monensin. Grower pigs may be fed a ration containing - 5ito 92 g./ton (5.5 to 101 g./metric ton) phosphorothioate - and 1 to 53 g./ton (1.1 to 58 g./metric ton) monensin, while swine in the fattening stage will also generally be supplied a similar ration.
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18,247-F -14-. -~l~91~2 E~oultry such as very small day old or older birds up through starter or grower staye will generally be fed a cc)mplete ration or mash containing 3 -to 73 g./ton (3.~ to 80 g./metric ton) phosphorothioate and 0.9 to 42 g./ton (1 to 46 g./metric ton) monensin, while poultry on a fattening diet will be fed a similar ration.
- For commercial use, the monensin and phosphoro-thioate are most readily and conveniently used as a feed additive premix or feed additive concentrate formulation in which the growth promotants are distributed uniformly throughout a standard organic or inorganic animal feed carrier in a concentrated form which is conveniently - packaged and shipped to the feed mixer. This premix -~ or concentrate is then in turn mixed uniformly with ~;
a normal diet for the animal as desired by the grower `' or the feed mixer. Examples of carriers for premix compositions are soybean meal, corn oil, ground corn, ~`
:: . ~ . -, barley, wheat, mineral mixtures contalning, e.g., ver~
miculite or diatomaceous earth, corn gluten meal, corn distillers solubles, soy flour, or other modestly priced edible ingredients. The active ingredient will be in amounts to satisfy the criteria set forth above for ;~
balanced feed rations.
In the case of feed additive premix, a pre-selected unit quantity thereof in the range of 0.5 to 100 pounds (0.25 to 50 kg.) will contain a preselected quantity of each of monensin and phosphorothioate in one of the ranges set forth for each above, depending on the -animals to be fed and will be suited to mix with the final feed or diet at the rate of one unit quantity per ton (metric ton) of feed.

' 18,247-F -15-9155~;~

Ill the case o~ ~eed addit:ive concentrate, a prl~selected unit quantity in the range of 100 to 1000 pounds (50 to 500 kg.) will :likewise contain a preselec-ted quantity of monensin and phosphorothioa-te in one of the ranges set ~orth above ~or each of the growth promotant.s and will be suited to mix with the final feed or diet at the rate of one unit quantity per ton ~metric ton) of feed.
The growth promotants may also be admixed with a suitable carrier such as an edible feed or feed component in the form of a feed additi~e supplement as that is defined hereinabove. Such a supplement may contain 0.1 to 10 percent by weight DMB phosphorothioate and 0.04 to 5 percent by weight D~ monensin. If to be ~.
fed free choice or as a supplement, the phosphorothioate and monensin concentrations are provided according to the anticipated daily consumption of the supplement to provide a daily dose of each of the promotants in one of the ranges specified herein.
A feed additive premix may contain 0.25 to 25 :~
weight percent phosphorothioate and 0.08 to 8 weight per-cent monensin and the balance an organic or inorganic feed carrier~
A mineral feed additive supplement may contain 5 to 6 weight percent phosphorothioate and 1.5 to 2 weight .;,, ;~ 25 percent monensin and the balance mineral supplement in-~ gredients and binders.
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`I A feed additive supplement, if to be used as .-:
. a supplement, may be a mineral, protein or energy sup-i:~ plement in the form of a li~uid, compressed or dry granular `~ 30 composition which can be free choice or self fed to ani mals.

~ 18,247-F -16-;' 1~3lS~

The animal diets may also contain hay, straw, si~age, cornstalks, cottonseed hulls, oats, barley and cereal brans, particularly for the ruminants; natural oils such as animal fat or cat-tle, fish oils, safflower oil, peanut oil, and cotton seed oil, antioxidants, minerals, vi-tamins, antibiotics, anthelmin-tics; and other appropriate medicaments.
- Examples of typically prepared ruminant ani-mal feeds are as follows:
Example_l Weight Percent Ingredlents (D.M. Basis) ~- Mixed Hay 40.0 Ground Yellow Corn 45.0 - Soybean Oil Meal 7.0 ; 15 Cane Molasses 7.0 Dicalcium Phosphate 0.5 :- Trace Mineral Salt 0.5 Vitamin A 300 IU/lb (660 IU/kgO) Vitamin D 150 IU/lb (330 IU/kg.) -~ 20 Phosphorothioate 18 to 173 grams/
ton of feed (20 to 190 g./metric ton) ;

Monensin 5 to 100 grams/
; ton of feed (5.5 ~ to 110 g./metric ton) - Such a feed typically contains 8 to 15 percent by weight moisture.
Example 2 Weight Percent Ingredients (D.M. Basis)_ Ground Shelled Corn 65.85 ~-Mixed Ground Hay 20.00 Dried ~lasses 6.00 :;
18,247-F -17-., .

~ll0~1502 Weight Percent Ingredients (D.M. Basis) Soybean Meal 6.00 Phosphorothioate 18 to 173 grams/
ton of feed (20 to - 190 g./metric ton) Monensin 5 to 100 grams/
, ton of feed (5.5 to 110 g~/metric ton) Trace Mineral Salt o.So Dicalcium Phosphate 0.40 Ground Limestone 0.70 Vitamin A (30,000 units/gm) 66.7 grams/ton (73.5 g./metric ton) Vitamin D2 (16,000,000 units/lb) 7.1 grams/ton (35,242 units/g.) (7.8 ./metric ton) Such a feed typically contains 3 to 15 percent by weight moisture.
~- 15 Example 3 An example of a suitable feed additive premix ~-~- is as follows:
::
Phosphorothioate 64 grams Monensin 30 grams :
Ground Yellow Corn (5-10~ moisture) 360 grams ,.:
Example 4 For use in the field for animals on range, the monensin and phosphorothioate combination may be ~ administered by means of salt or molasses blocks. A
; 25 typical blo~k may be prepared using the following compo-~ sitions:
.
Weight Percent Ingredients (D.M Basis) Dried Cane Molasses 30.2 i Ground Soybean Hulls 29.6 Phosphorothioate 6 `'~:

~' 18,247-F -18-:

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Weight Percent In~re:dients (D.M. Basis)_ Monensin 4.8 Granlllated Salt 25.9 Trac~ Minerals and Vitamins 0.24 Stabilized Animal Fat 1.3 Moisture 2.6 Example 5 If desired, monensin and phosphorothioate :-~ together may be administered as a part of a liquid animal feed supplement such as a supplement containing a nonprotein nitrogen source such as urea in admixture with molasses and other feed ingredients. Such a liquid : supplement may be prepared using the following conditions:
Weight Percent -~ 15 Ingredients (D M. Basis?
- Molasses 79.90 ` Water 13.55 Phosphoric Acid, 85% Z.70 Ammonium Sulfate 2.00 Trace Minerals .50 Vitamin A, D & E .05 ; Salt 1.00 Phosphorothioate .20 - Monensin .10 :~ 100 . 00%
` 25 The following example demonstrates the marked . improvement in feed intake on combining phosphorothioate ~ and monensin in the diet as well as showing the further increase in average daily gain over phosphorothioate and the further increase in feed conversion efficiency over monensin on feeding the combination to beef cattle.
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1 8 . ? 47-F -19-~IL09~502 Exanple 6 24 Angus X Hereford Cross Heifers weighing ap-proximately 415 pounds (188 kg.) each were ear-tagged, weighed, and treated for grubs and helminths. These ani-mals were then allotted to treatment groups of 6 animals each and placed into individual feeding pens. Feed was offered to the cattle at maximum ad libitum intake on a daily basis. All discarded feed was weighed on a suc-ceeding day post-feeding, recorded, and then discarded.
Water was supplied ad libitum. Health and care were under the supervision of qualified personnel. All pens were washed on a daily basis.
~- Animals were weighed at 28 day intervals. Weight gain, feed conversion, and feed intake data~were calculated at each interval or until the experiment was terminated 111 days after initiation.
All the animals were fed the following basal ~- diet consisting of:

Weight Percent Ingredients ~D.M. sasis) Cottonseed Hulls 30.00 Ground Corn 40.40 Alfalfa Meal 12.70 Soybean Oil Meal 10.00 Molasses 5.25 Salt 0 50 Calcium Carbonate 0.40 Sodium Tripolyphosphate 0.25 Magnesium Oxide 0.30 Vitamins and Trace Minerals 0.20 100.00 .
18,247-F -20~

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A comparison group of animals was fed the basal diet having admixed therewith 30 g./ton (33 g./metric ton) monensin. (Group 1) A second comparison group was fed the basal diet having admixed therewith 80 g./ton (88 g./metric ton) phosphorothioate. (Group 2) A third group of six animals was fed according to the invention, the said basal diet having admixed therewith 30 grams per ton (33 g./
metric ton) of monensin and 80 grams per ton (88 g./metric ton) phosphorothioate. (Group 3) The fourth group of six animals served as controls and received the basal diet ~ without further additions. The results of the feeding ;~ study are tabulated as follows:
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The results listed for the comparisons in group 2 are based on data from just 5 animals, the 6th animal having given clearly spurious and anomalous results.
~he data in the table demonstrate that the addition of monensin and phosphorothioate in combination improve average daily gain by 11.1 percent when compared to the controls. The improvement is almost 14O2 percent when compared to monensin alone and 6.4 percent when com-pared to phosphoxothioate alone. Similar improvements are noted for the improvement in feed conversions.
- ~ Example 7 In the following chick feeding experiment, monensin and phosphorothioate are added in combination , . .
- 15 to the following rye grain basal diet which is illustra-- tive of poultry diets for broilers, i.e. rapidly growing ~`~
birds for meat production.
Ingredient Weight Percent ; -. .
Rye Grain 55a 00 .,~ ,; .
Soybean meal27.00 ~:-" , .
- Herring Fishmeal 5 ~ 00 ' l .
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Dried Whey 1.00 Dehydrated Alfalfa 1.25 ~' 25 Salt 0.22 .
`~ Animal Fat 4.00 Dicalcium Phosphate 0.50 Ground Limestone 0.67 .~, Vitamin Pr~mix 0.25 Trace Mineral Premix 0O05 ,::
DL-Methionine0.06 `:
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lrhis diet without modification was fed -to a control qroup of 12 broiler-type day-old chicks.
Another grc~up of 12 broiler-type day-old chicks were fed according to the invention the above lis-t of diet which had admixed therewith -the combination of 50 g./ton (55 g./metric ton) phosphorothioate and 100 g./ton (110 g./metric ton) monensin. The chicks were individually ~` weighed and were fed for a total of 11 days. Feed and water were supplied ad libitum. Normal care and management of the facilities were observed. At the termination of the 11 day trial period, the birds were each individually weighed and the following data were calculated:

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Wllen compared to the controls, the chicks fed accol~ding to the invention were 5.7 percent heavier and consumed the 7.6 percent less feed to accomplish the heavier gain.
: 5 While the amounts o:E monensln and phosphorothioateto be employed according to the invention have been set forth hereinabove in broad ranges it is more preferred to utilize in the combination monensin in a dosage range of 0.5 to 1.2 mg/kg body weight and most preferably from 0.7 to 1 mg/kg of body weight. In the combination it is also more preferred to use the phosphorothioate in the dosage range of 1 to 2.5 mg/kg of body weight and most preferred to use about 2 mg/kg of body weight.
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Claims (11)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A composition for promoting animal nutrition which comprises 0,0-dimethyl 0-(2,4,5-trichlorophenyl)-phosphorothioate and monensin in admixture with an edible solid.

2. A composition as defined in Claim 1 which contains by weight, from 0.01 to 320 parts 0,0-dimethyl 0-(2,4,5-trichlorophenyl)phosphorothioate per one part monensin.

3. A composition as defined in Claim 1 which con-tains by weight from 0.01 to 100 parts 0,0-dimethyl 0-(2,4,5-trichlorophenyl)phosphorothioate per one part monensin.

4. A composition as defined in Claim 1 which con-tains by weight from 0.1 to 20 parts 0,0-dimethyl 0-(2,4,5-trichlorophenyl)phosphorothioate per one part monensin.

5. A composition as defined in Claim 1 which con-tains by weight from 0.5 to 10 parts 0,0-dimethyl 0-(2,4,5-trichlorophenyl)phosphorothioate per one part monensin.

6. A composition as defined in Claim 1 which con-tains from 20 to 190 g. 0,0-dimethyl 0-(2,4,5-trichlorophenyl)-phosphorothioate and from 5.5 to 110 g. monensin per metric ton and the balance ruminant animal feed.

7. A composition as defined in Claim 6 which contains from 30 to 360 g. 0,0-dimethyl 0-(2,4,5-trichloro-phenyl)phosphorothioate and from 7 to 210 g. monensin per metric ton and the feed is a maintenance diet ruminant animal feed.

8. A composition as defined in Claim 1 which con-tains from 5.5 to 101 g. 0,0-dimethyl 0-(2,4,5-trichloro-phenyl)phosphorothioate and from 1.1 to 58 g. monensin per metric ton and the balance a feed for swine.

9. A composition as defined in Claim 1 which contains from 3.3 to 80 g. 0,0-dimethyl 0-(2,4,5-trichloro-phenyl)phosphorothioate and from 1 to 46 g. monensin per metric ton and the balance a feed for poultry.

10. A composition as defined in Claim 1 which is a feed additive premix containing from 0.25 to 25 weight percent 0,0-dimethyl 0-(2,4,5-trichlorophenyl)phosphoro-thioate and from 0.08 to 8 weight percent monensin and the balance an organic or inorganic feed carrier.

11. A composition as defined in Claim 1 which is a mineral feed additive supplement containing from 5 to 6 weight percent 0,0-dimethyl 0-(2,4,5-trichlorophenyl)-phosphorothioate and from 1.5 to 2 weight percent monensin and the balance mineral supplement ingredients and binders.