CS236862B2 - Admixture to fodder - Google Patents

Description

The present invention relates to feed additives or premixes for the manufacture of feeds comprising a suitable combination of active ingredients consisting of kitasamycin and 1,4-di-N-oxides of 2-methyl-3-carbamoylquinoxaline. The feed additives or premixes are used to stimulate growth and improve animal feed utilization.

Kitasamycin (cf. U.S. Pat. No. 3,535,309; The Merck Index, Ninth Edition) is known to be antimicrobially effective and is also used as an additive in feed. The 1,4-di-N-oxides of 2-methyl-3-carbamoylquinoxaline also include effective animal growth promoters (cf. German Patent 1670 935) such as 1,4-di-N-oxide N- (2-hydroxyethyl) of 2-methyl-3-quinoxaline carboxylic acid amide (olaquindox).

It has now been found that the combination of kitasamycin with 2-methyl-3-carbamoylquinoxaline 1,4-di-N-oxides, in particular 2-methyl-3-, N- (2-hydroxyethyl) amide 1,4-di-N-oxide. quinoxaline carboxylic acids lead to an improved effect in terms of stimulating the growth and recovery of animal feed that exceeds the sum effect.

The subject of the present invention is a feed additive or feed premix comprising an active ingredient combination consisting of kitasamycin and 1,4-di-N-oxides of 2-methyl-3-carbamoylquinoxaline of the formula I

in which

R ¹ is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or chloro,

R ² represents hydrogen or hydroxy, C 1-4 alkyl, mono- or dialkylamino having 1 to 4 carbon alkyl-substituted straight or branched alkyl group having 1 to 6 carbon atoms,

R ³ is hydrogen, and R ³ may have the meaning of R ² , wherein the meanings of the sym236862 of R ² and R ³ may be the same or different from each other and, when R ² and R ³ are alkyl, an amide nitrogen atom may be a component of a 5- or 6-membered heterocyclic ring system which optionally contains, in addition to the amide nitrogen atom, a further nitrogen atom or an oxygen atom, and the hydrogen atom on the additional nitrogen atom is optionally substituted by a C1 -C4 alkyl radical; is itself optionally optionally substituted by hydroxy, wherein the ratio of kitasamycin to the compounds of formula I is 1: 10 to 10: 1, preferably 1: 1.

When R ² and R ³ together are part of a heterocyclic ring system, the ring system of the amide nitrogen atom may contain an additional nitrogen atom or an oxygen atom, in the case of the 6-membered ring the additional heteroatom is preferably in the p-position to the amide and wherein the hydrogen atom on the additional nitrogen atom may be optionally substituted by a C 1 -C 4 alkyl radical, which itself may in turn be substituted by a hydroxy group.

Particularly preferred are active compound combinations which, in addition to kitasamycin, contain the N- (2-hydroxyethyl) -2-methyl-3-quinoxaline carboxamide 1,4-di-N-oxide.

The present invention also relates to the use of the feed additive according to the invention to stimulate growth and improve animal feed utilization.

The preparation of quinoxaline 1,4-di-N-oxides is also known from the literature cited above as the production of kitasamycin. For the purposes of this invention, kitasamycin is understood to mean both a mixture of biologically active ingredients as well as isolated individual ingredients and mixtures of two or more individual ingredients.

Examples of quinoxaline di-N-oxides to be used according to the invention include the following compounds:

example number formula

Table 1 Melting Point (° C) Appearance

172 light yellow crystals

208 light yellow crystals (decomposition)

136 light yellow crystals

.214 light yellow crystals (decomposition) example number formula melting point (° C) appearance

1, C 0 -NH-CH 2 CH 2 OC

209 (decomposition) pale yellow crystals

CO-NH-C (O) OCH3

135

141 pale yellow crystals pale yellow crystals

J CO-NH-C ^^^ θ

CHv

CO-N

218 (decomposition) pale yellow crystals

CH189 light yellow crystals

162

231 (decomposition) light yellow crystals light yellow crystals example number formula melting point (° C) appearance

203 light yellow crystals (decomposition)

O

183 yellow crystals

169 pink-red crystals

O

190 yellow crystals

yellow crystals.

yellow crystals

The feed additives according to the invention can be used in all animal husbandry sectors as a means to stimulate and accelerate growth as well as to improve the value of feed, both in healthy and sick animals.

The effectiveness of the combinations according to the invention is essentially independent of the species and sex of the animals. Of particular value are combinations of active compounds according to the invention in breeding and keeping young animals and mast animals. Animals in which the active compound combinations according to the invention can be used to promote and accelerate growth and to improve the value of the feed thereof include, for example, the following commercial and ornamental animals:

warm-blooded animals such as cattle, pigs, horses, sheep, goats, cats, dogs, rabbits, furry animals such as mink and chinchilla, poultry such as hens, geese, ducks, turkeys, pigeons, parrots and canaries and cold-blooded animals , such as fish such as carp, and reptiles such as snakes.

The amount of active compound combination to be administered to the animals in order to obtain the desired effect can be varied within a wide range due to the favorable properties of the active compounds.

This amount is preferably about 5 to 500, in particular 10 to 100 mg / kg body weight per day. The application period can vary from a few hours or days to several years. The appropriate amount of active ingredients as well as the corresponding duration of application depend, in particular, on the species, age, sex, health and behavior of the animals and can be readily ascertained by one skilled in the art.

The active compound combinations according to the invention are applied to the animals by conventional methods. The method of administration depends in particular on the species, behavior and health of the animals. Thus, administration can be performed once or several times a day at regular or irregular intervals orally or parenterally. In most cases, oral administration is preferred, particularly preferably at the same time as food or beverage intake.

The active compound combinations according to the invention can be administered as a pure mixture of substances or in the form of compositions, i.e. in admixture with non-toxic inert carriers of any kind, for example carriers, and in the formulations customary for nutritional preparations.

The active compound combinations according to the invention are applied, if appropriate, in the form of compositions together with pharmaceutically active substances, mineral salts, trace elements, vitamins, proteins, fats, colorants and / or flavorings in a suitable form.

Oral administration together with feed and / or drinking water may be recommended, with all or part of the feed and / or drinking water added to the active ingredient combinations as appropriate.

The active compound combination according to the invention is added to the feed and / or to the drinking water according to customary methods by simple mixing in the form of a pure mixture of substances, preferably in finely dispersed form or in the form of compositions in admixture with inedible non-toxic carriers.

The feed and / or the drinking water may contain the active compound combinations according to the invention, for example in a weight concentration of from about 5 to 500 ppm, in particular from 10 to 100 ppm. The optimum level of concentration of the active ingredients in the feed and / or drinking water depends in particular on the amount of feed and / or drinking water taken up by the animal and can be readily determined by one skilled in the art.

The nature of the feed and its composition is of immaterial importance. All commonly used or special feed compositions that contain preferably the usual balance necessary for balanced nutrition from energy and building materials including vitamins and minerals may be used. The feed may consist, for example, of plant substances such as hay, beet, grain, grain by-products, animal substances such as meat, fat, bone meal, fish products, and vitamins such as vitamin A, D-complex and B-corplex, from proteins, amino acids such as DL-methionine and inorganic substances such as lime and table salt.

The feed concentrates contain the active compound combinations according to the invention in addition to ingestible substances such as rye flour, soya flour or lime, optionally together with other nutrients and nutrients, as well as proteins, mineral salts and vitamins. They can be prepared by conventional mixing methods.

In premixtures and feed concentrates, the active compound combination may optionally also be protected by suitable means covering their surface, for example with non-toxic waxes or gelatin, against air, light and / or moisture.

An example of a chicken feed composition comprising a combination of active ingredients according to the invention:

200 g wheat, 340 g corn. 361 g of soya meal, 60 g of beef tallow, 15 g of dicalcium phosphate, 10 g of calcium carbonate, 4 g of iodinated table salt, 7.5 g of a mixture of vitamins and minerals and 2.5 g of the active ingredient premix provide 1 kg of feed.

Mixture of vitamins and minerals consisting of 600 IU of vitamin A, 100 IU vitamin D,., 10 mg of vitamin Ε, 1 mg of vitamin _K:> 3mg riboílavinu, 2 mg of pyridoxine, 20 mg of vitamin B _l2, 5mg kalciumpantothenátu, 30 mg nicotinic acid, 200 mg choline chloride, 200 mg of MnS0 _fourth H ₂ O.140 mg ZnSO ₄ . 7 H> 0.1, 100 mg of FeSO _4, 7 H ₂ O and 20 milligrams of CuSO ₄ . 5 H ₂ O.

The premix of the active ingredients comprises a combination of the active compounds according to the invention in the required amount, for example 100 mg and in addition 1 g of DL-methionine and enough soybean meal to produce 2.5 g of the premix.

An example of a composition of a feed for the production of pigs comprising a combination of active ingredients according to the invention:

630 g of feed grain meal (consisting of 200 g of maize, 150 g of barley meal,

150 g of oat meal and 130 g of wheat meal), 80 g of fish meal, 60 g of soy meal, 60 g of tapioca meal, 38 g of beer yeast, 50 g of a mixture of vitamins and minerals intended for pigs chickens), 30 g of flaxseed meal, 30 g of maize sebum, 10 g of soybean oil, 10 g of sugar cane molasses and 2 g of premix containing active substances (composition, for example, the same as in the case of animal feed) 1 kg of feed.

Said feed mixtures are preferably intended for the cultivation of chickens or pigs, or for feeding on feed, but may also be used in the same or similar composition for growing or feeding on the feed of other animals.

Numerous animal fattening experiments have been carried out with the feed additives of the invention and the following results have been achieved:

Example 1 and animal and feed characteristics:

al) piglet a2) number 30 a3) breed landrase - large white a4) sex male a5) age about 8 to 14 weeks a6) mass 17.5 to 45 kg a7) state good a8) feed Crude protein (least) 17.0% Crude fat 2.5% fiber 5,0 '% salt urea 0.5% (maximum) 0.0% fluorine (maximum) 0.01 o / o lysine 0,832% methionine 0.249% threonine 0.494% isoleucine methionine + 0,564 Ψο + cysteine 0.522 «/ o thryptophan 0,209% biotin 0,108% choline 0,110% calcium 1,035 «/ o phosphorus 0,790%

Folders:

wheat, barley, millet, bran, fish meal, soybean meal, cottonseed meal, sunflower seed meal, lysine, salt, limestone, 2RO, MnO, copper sulphate and ferrous sulphate, potassium iodide, vitamins A, D, E, Κ, B / 2, niazine, pantothenic acid.

(b) animal treatment:

The animals are treated in groups (five groups).

The starting weight for each group is the same.

ppm bl) olaquindox 50 b2) kitasamycin 50 b3) olaquindox + kitasamycin 25: 25 b4) olaquindox + kitasamycin 12.5: 12.5 b5) control (no active ingredients) -

(c) Evaluation:

Piglets are weighed daily. The daily weight gain and recovery of feed is determined. Weekly weighing and individual food intake are recorded.

(d) Result (weight gain g / denj

koncen- trace (ppm) average daily weight gain (g / day) dl) 50 593 d2) 50 562 d3) 25: 25 626 d4) 12.5: 12.5 560 d5) control 537

The synergistic effect of weight gain is significant.

ej Result (feed evaluation end - average value of feed evaluation (PPm) (g / g)

el) 2.52 e2) 2.64 e3) 2.44 e4) 2.66 e5) 2.72 Synergistic Effect in Feed Valuation · va is significant. Example 2 (a) Characteristics animal and feed: and l) piglet (a2) number 84 (a3) sex mixed a4) breed · landrase - big white (a5) age (Crossbreeding) Five weeks a6) weight 7 to 75 kg a7) condition good (a8) feed , 1: 2 '' ** '*

° / o raw protein - starter

kg / tonne wheat 730 fish meal 100 ALIGN! soya meal 120 sunflower meal 30 Prernix containing minerals and vitamins 10 vegetable oil 10

% crude protein - finisher kg / ton of wheat .804 fish meal; 125 sunflower meal -; 60 mineral mixture for vitamins t10 methionine 1

(b) Animal treatment:

dose, (ppm)

up to 40 kg up to 75 kg b1) olaquindox b2) kitasamycin 100 25 b3) olaquindox + kitasamycin 55 11 b4) control 25 + 22 25 + 11

(c) Evaluation:

Piglets are weighed at the beginning of the experiment and weighed at weekly or biweekly intervals until the end of the experiment.

Feed and mortality are recorded daily.

The back fat thickness is measured at the end of the experiment by ultrasound and the value is corrected to 75 kg body weight.

dj Result (weight gain g / day)

start up to 40 kg 40 kg to the end beginning to end dl) 499 641 573 d2) 508 574 522 d3) 517 624 568 d4) 460 593 531

(e) Result (feed evaluation) (g / g)

start up to 40 kg 40 kg to 75 kg beginning to end el) 2.30 3.10 2.74 a2) 2.28 3.17 2.74 a3) 2.15 2.80 2.48 e4) 2.41 3.18 2.81

(f) Result (back fat thickness)

back fat (mm) fi) 21.3 f2) 20.3 f 3) 20.7 f4) 21.6

Also in Example 2, a higher effect of the combination preparation according to the invention can be easily detected.

Claims (2)

SUBJECT A feed additive or feed premix comprising a combination of active ingredients consisting of kitasamycin and the 1,4-di-N-oxides of 2-methyl-3-carbamoylquinoxaline of the general formula I in which: R ^l represents hydrogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms or chlorine, R ² represents hydrogen or hydroxy, C 1-4 alkyl, mono- or dialkylamino having 1 to 4 the invention carbon alkyl-substituted straight or branched alkyl group having 1 to 6 carbon atoms, R ³ may be hydrogen and further may have a meaning of R ^2, wherein R ² and R ³ may be the same or different from each other, and in case R ² and R ³ are alkyl, these groups, together with the amide nitrogen atom to be sou-; part of a 5- or 6-membered heterocyclic ring system which optionally contains an additional nitrogen or oxygen atom in addition to the amide nitrogen atom, and the hydrogen atom on the additional nitrogen atom is optionally substituted with a C1-C4 alkyl radical, which itself is optionally again wherein the ratio of kitasamycin to the compounds of formula I is 1: 10 to 10: 1, preferably 1: 1. 2. An additive or premix according to claim 1 comprising a combination of active ingredients consisting of kitasamycin and N- (2-hydroxyethyl) -2-methyl-3-quinoxaline carboxamide 1,4-di-N-oxide.