CS258130B2 - Fodder admixture - Google Patents

Abstract

The feed additive contains as effective component RS- (2-quinoxalinyl-1,4-dioxide) - (4‘- -oxo-2‘-thione-5‘-thiazolidinyl) methanol formulas I. The additive contains as an inert carrier the cereal substance in the desired form, oil plant, plant concentrate meal of animal origin. It also contains a mineral that contains silicon or calcium and / or aluminum. Feed additive increases weight gains in animals and improves use of feed.

Description

The present invention relates to feed additives which contain RS (2-quinoxalinyl-1,4-dioxide) - (4'-oxo-2'-thion-5'-thiazolidinyl) methanol as a newly prepared substance RS. in animals.

It is known in the art that some quinaxaline-1,4-dioxide compounds increase weight gain in animals. U.S. Patent 3,371,090 discloses Schiff bases of 2-formylquinoxaline-1,4-dioxide. Other quinoxaline-1,4-dioxide derivatives are disclosed in Belgian Patent No. 764,088, German Patent No. 1,670,935, United States Patent No. 3,344,022 and DOS Patent No. 2,354,252.

Feed additive according to the invention contains as active ingredient RS- (2-quinoxalinyl-l, 4-dioxide) - (4'-oxo-2'-thione-5'-thiazolidinyl) methanol of Formula I ¹ / ^u \

OH S Πμΐ í T | / i i

CH-Clh- c ----- i

O (1.1

The additive comprises, as an inert carrier, a cereal in the desired form, an oil plant, a vegetable concentrate, an animal meal. It further comprises a mineral which contains silicon or calcium and / or aluminum.

The compound of formula I contains an asymmetric carbon atom and can therefore exist in the form of a racemic mixture or enantiomers. The present invention includes within its scope both the racemic mixture and the enantiomers of the compound of formula I.

The compounds of formula I may form acid addition salts. Suitable inorganic acids, such as hydrochloric, hydrobromic, sulfuric, nitric, etc., or organic acids, such as lactic, malic, maleic, fumaric, tartaric, and the like can be used to form salts.

The novel compound of formula I, which is included in the feed compositions of the present invention, has the ability to increase weight gain in animals. It can therefore be used in livestock production.

The beneficial effect of increasing weight gain is documented for the novel compound of formula I in the following test. Pigs were used as test animals. Groups of six pigs were used for each dose and each experiment with six animals was repeated three times. Pigs from the test group were fed a diet containing 50 milligrams / kilogram of the compound of formula I. The animals of each test group received the same food and under the same conditions. Animals from the control group received the same feed but without the test compound of Formula I. The results obtained can be summarized as follows: The average daily weight gain relative to the control animals was

150.3%. The weight of feed required for a 1 kg weight gain relative to control animals was 72.0%.

From the above values, it can be seen that the weight gains of the animals fed the compound containing the compound of formula I are considerably higher than in the pigs of the control group. At the same time, the same weight gains can be achieved with substantially less feed if a small amount of the compound of formula I is added to the feed.

An important advantage of the compound of the invention is that the compound is excreted from the animal body in a substantially shorter time than the prior art quinoxaline-1,4-dioxide derivatives. This means that its retention time is considerably shorter. This is a significant advantage in terms of livestock production.

The toxicity of the compound of formula I is so low that it can practically be considered non-toxic to domestic animals.

The feed compositions may be in the forms commonly used in veterinary practice, for example in the form of tablets, dragees, capsules, and the like. These compositions may contain conventional inert carriers, diluents and additives and may be prepared by processes known per se from the pharmaceutical industry.

The production of feed compositions, in particular feed additives, consists in mixing a compound of formula I, or a biologically acceptable salt thereof, with suitable edible solid or liquid carriers or diluents and additives which are generally used in the manufacture of feed compositions.

Any carrier or diluent may be any vegetable or animal substance which is edible or serves as a feed. Most preferably, wheat groats, barley, rye, unground (beaten) flour, rice bran, wheat bran, soya flour, corn flour, bone meal, alfalfa flour, soya groats, meat meal, fish meal or the like may be used. mixtures of these substances. A particularly preferred carrier material according to the invention is a high protein defibrillated vegetable feed concentrate, for example a preparation known under the trade name Vepex.

As additives, for example, silicas, wetting agents, antioxidants, starch, calcium phosphate, calcium carbonate, sorbic acid and the like can be used. Wetting agents may be, for example, non-toxic oils, preferably soybean oil, corn oil or mineral oil. In addition, various alkylene glycols may be used for this purpose. The starch used may be wheat starch, corn starch or potato starch.

Biologically active ingredient content within these limits. In most cases, the concentrates may contain from about 5 to 80% by weight, preferably from about 10 to 80% by weight, in particular from 20 to 50% by weight of the biologically active ingredient of the formula I. The active ingredient content of the finished feed composition may range from about 1 to 80%. to 400 ppm, preferably from about 1.0 to about 100 ppm. Feed additives and concentrates may also contain conventional vitamins such as vitamin A, B1, B'k Bs, Be, Bi 2, E, K and trace elements such as manganese, iron, zinc, copper iodine.

The feed concentrates according to the invention can be used for animal production after dilution. In contrast, the feed can be used for feed purposes in animal production.

According to the present invention, the feed can be used to feed a variety of productive animals such as pigs, sheep, cattle and poultry, and is particularly suitable for use in pigs.

The novel compound RS- (2-quinoxalines 1-1,4-dioxide) - (4‘-oxo-2‘-thione-5‘-thiazolidinyl) methanol of formula I and its suitable acid addition salts are prepared by:

a) reacting 2-formylquinoxaline-1,4-dioxide with 4-oxothiazolidine-2-thione; or

b) oxidation of RS- (2-quinoxalinyl) - (4'-oxo-2'-thione-5-thiazolidinyl) methanol; or

c) reacting ethyl RS-2-chloro-3-hydroxy-3- (2‘-quinoxalinyl-1‘, 4‘-dioxide) propionate with ammonium dithiocarbamate; or

d) reacting RS- (2-quinoxalinyl-1,4-dioxide) - (4‘-oxo-2‘-imino-5‘-thiazolidinyl) methanol with carbon disulfide.

The compound of formula (i) obtained is then optionally converted into biologically acceptable acid addition salts. The preparation of these salts can be carried out in a conventional manner, for example by reacting a compound of formula I with an approximately equimolar amount of the corresponding acid in a suitable solvent.

The mixture of isomers obtained can be separated into the known methods. individual enantiomers. Separation may be accomplished using conventional separation procedures.

The starting materials for process a) and bj are known compounds or can be prepared by known methods. The starting material for process c) ethyl-RS-2-chloro-3-hydroxy-3- (2'-quinoxalinyl-1 ', 4'-dioxide) propionate can be prepared by reacting the compound 2-formylquinoxaline-1,4-dioxide with ethyl chloroacetate.

β

Further details of the present invention are evident from the following non-limiting examples.

The melting points given in the examples were determined in a Koffler apparatus.

Example 1

..

Preparation of RS- (2-quinoxalinyl-1,4-dioxide) N- (4‘-oxo-2‘-thione-5‘-thiazolidinyl) methanol

A mixture of 19.0 grams (0.1 mol) of 2-formylquinoxaline-1,4-dioxide, 13.3 grams (0.1 mol) of 4-oxo-thiazolidin-2-thione, 200 milliliters of isopropanol and 4 ml of a 10% aqueous sodium hydroxide solution was stirred at room temperature for 3 hours, and the mixture was cooled and filtered to give 30.7 g of the title compound (95% yield). Melting point: 294-293 ^° C.

Example 2

Preparation of RS - (2-quinoxalinyl-1,4-dioxide) - (4-oxo-2‘-thione-5‘-thiazolidinyl) methanol

According to this example, the mixture was

14.6 ml (0.05 mole) RS- {2-quinoxalinyl) - (4'-oxo-2'-thione-5'-thiazolidinyl) -methanol and 100 ml of 12% peracetic acid is stirred at 50 C for ^P 20 hours. The reaction mixture was neutralized by cooling with 10 N sodium hydroxide solution and then filtered. 13.1 g of the title compound are obtained, corresponding to a yield of 81%. The melting point of the product thus obtained was in the range of 293 to 294 ° C.

Example 3

Preparation of RS- (2-quinoxalinyl-1,4-dioxide) - (4‘-oxo-2'-thione-5‘-thiazolidinyl) methanol

According to this example, the mixture was

15.6 g (corresponding to 0.05 mol) of RS-2-chloro-3-hydroxy-3- (2'-quinoxalinyl-1 ', 4'-dioxide j-ethylpropionate), 5.5 g (0.05 mol) of dithiocarbamate The reaction mixture was mixed with 50 ml of 6 N hydrochloric acid and the mixture was briefly boiled, the reaction mixture was cooled and the product was filtered off. of this case δ

Example 6

According to this embodiment, a mixture was prepared as a feed additive for piglets, having the following composition:

10.5 g of the title compound are obtained, which corresponds to a yield of 65%. The melting point of the resulting product ranged from 293 to 294 ° C.

Example 4

Preparation of RS (2-quinoxalinyl-1,4-dioxide) - (4‘-oxo-2‘-thion-5‘-thiazolidinyl) methanol

6.1 g (corresponding to 0.02 mol) of RS - (2-quinoxalinyl-1,4-dioxide) - (4'-oxo-oxide) were heated in a sealed vessel at 160 ° C for 2 hours. 2'-imino-5-thiazolidinyl) methanol, 1.9 g (0.025 mol) of carbon disulphide and 50 ml of ethanol were then cooled and the product was filtered off to give 5.5 g of the title compound. corresponding to a yield of 85%.

the melting point of the product thus obtained ranged from 293 to 294 ° C. after- Example 5 According to this embodiment, it was at- prepared pig mixture, said mixture had the following composition: Folders Amount vitamin A 3 000 000 m. (international units] vitamin Ds 600 000 m. vitamin E 4 000 m. vitamin K3 400 mg vitamin Bi 600 mg vitamin B2 800 mg vitamin B3 2 000 mg vitamin Βδ 800 mg vitamin B12 10 mg niacin 4 000 mg choline chloride 60 000 mg biologically active ingredient according to Example 1 10 000 mg butylhydroxytoluene (antioxidant) 30 000 mg flavoring substances 8 000 mg sodium saccharate 30 000 mg trace elements: manganese 8 000 mg iron 30 000 mg zinc 20 000 mg copper 6 000 mg iodine 100 ALIGN! mg twice ground bran 1 000 G

This mixture of vitamins and trace elements was mixed with the basic feed at a concentration of 0.5 kg per 100 kilograms.

Ingredients Quantity

vitamin A 1 200 000 IU vitamin D3 300 000 IU vitamin E 2,000 m vitamin B2 600 mg vitamin B3 2000 mg vitamin B12 5 mg niacin 3000 mg choline chloride 40,000 mg biologically active ingredient according to Example 1 10,000 mg butylhydroxy toluene (antioxidant] 30,000 mg trace elements: manganese 6000 mg iron 10,000 mg zinc 15,000 mg copper 30,000 mg iodine 100 mg twice ground bran 1 000 g Melted mixture of vitamins and trace elements was mixed with the basic feed in centering 0.5 kilograms per 100 kilograms. Example 7 0.5 kilogram of the mixture that was ready to according to Example 5, mixed 100,0 kilogra- we basic feed that had the following- Composition: Component Quantity (kgj maize 37.6 barley 25.4 rye 6.0 oat 5.0 soybeans 13.0 fish meat (meal) 6.0 bran 2.4 fat powder 1.5 mixture of minerals' 1.0 lime (feed quality) 1.0 sodium chloride 0.5 biolizine 0.1 the mixture of Example 5 0.5 total weight 100.0 kg Content biologically active components in the

The resulting pig feed was 50 ppm in this example.

“The composition of the mixture of minerals was as follows:

250130

Component Quantity (%)

calcium pyrophosphate 55.0 f os fo ree uan va penny 40.0 calcium carbonate 5.0 Ex. k 1 and d 8 According to this example was 0,5 kilogram of the mixture, the karaoke was prepared by example- du 6, mixed with the basic mixture had the following composition: fodder that Component Quantity (kg) maize 25.0 wheat 34.0 extracted soybeans 18.0 milk powder 9.9 fish meal 4.0 yeast (feed quality) 2,0 fat powder mixture of minerals 3.4 according to Example 7 1,8 lime (feed quality) 1.0 Sodium chloride (feed quality) 0.4 the mixture of Example 6 0.5 total weight 100.0 kg

The biologically active ingredient content of the resulting pig feed was 50 ppm in this case.

Example 9

In this example, 40 kilograms of ground soybean meal was poured into a mixer, 3.1 kilograms of soybean oil was added with stirring, and the mixture was stirred until an oil coating formed on the solid particles. 9.1 kg of the biologically active ingredient prepared as described in Example 1 were added. The mixture was stirred until a homogeneous substance was formed. Finally, 9.0 kg of soybean oil was added and the mixture was again homogenized.

Example 10

0.5 kg of biologically active ingredient was prepared as described in the Example. 1 was added with stirring to 40 kg of corn flour and then 3.0 kg of propylene glycol was sprayed into the mixture. Then 1.4 kg of dicalcium phosphate was added and the mixture was homogenized.

Example 11

In this example, the procedure in the same manner as in Example 9 except that instead of soybean oil as wetting agent ¹ used in this case is butylene.

Example 12

50 kg of soybean meal, 6 kg of biologically active substance prepared according to Example 1, 0.5 kg of silica and 0.2 kg of calcium propionate were homogenized with 1.6 kg of soybean oil.

Example 13

According to an exemplary embodiment, a premix for pig fattening was prepared by mixing the following ingredients, the premix having the following composition:

Ingredients Quantity. of Example 1 5 grams of twice milled bran 1000 grams

Tat ^r> masterbatch was then admixed to the basic feed in a concentration of 0.5 kg per 100 kg.

Example 14

According to an exemplary embodiment, a premix for pig fattening was prepared by mixing the following ingredients, the premix having the following composition:

Quantity ’

Compounds? according to Example 1, 5 grams of twice milled crops of 1000 grams to feed stock at a concentration of 0.5 kilograms per 100 kilograms.

Example 15

0.5 kg of the premix prepared in Example 13 was admixed with 100 kg of the feed having the following composition to obtain a pig feed compound.

Ingredients Quantity

maize 37.6 kg barley 25.4 kg wheat 6,0 kg oat 5,0 kg soya 13,0 kg fish meal 6,0 kg bran 6,0 kg lime (feed quality) 1,0 kg total weight 100.0 kg Content of active substance in the premix, mentioned above the way it was used for fattening pigs was 50 ppm.

258120

Example 16

A feed for pigs was prepared by mixing 0.5 kg of the masterbatch prepared according to Example 14 and 100 kg of the basic feed of the following composition:

Folders Amount maize 33,0 kg wheat 33,0 kg extracted soy gods 18,0 kg milk powder: 10,0 kg fish meal 4,0 kg lime (feed quality) __________ 2,0 kg total weight 100.0 kg

The active ingredient content of the above premix was 50 ppm.

Example 17

400 kg of pre-ground soya flour were placed in a corresponding mixer, and 9.1 kg of the compound prepared according to Example 1 was added while stirring and stirring was continued until the mixture was homogenized.

Example 18

0.5 kg of the compound prepared according to Example 1 was added to 100 kg of corn flour with stirring, and 1 kg of dibasic calcium phosphate was added thereto, and the mixture was homogenized.

Example 19

50 kg of soya flour, 6 kg of the compound prepared according to Example 1 and 0.5 kg of silica (in the form of silicic acid) were mixed and homogenized.

Claims (9)

SUBJECT Feed additive for increasing weight gain in animals based on methylquinoxaline-1,4-dioxide derivatives, characterized in that it contains RS- (2-quinoxalinyl-1,4-dioxide) - (4'-oxo-) as an active ingredient 2'-thion-5'-thiazolidinylmethanol of the formula I and as an inert carrier it contains cereal in the desired form, an oil plant, a vegetable concentrate, a meal of animal origin, as well as a silicon or calcium containing mineral ε / or aluminum. 2. A feed additive according to claim 1, characterized in that it contains 5 to 80% by weight of the compound of the formula I as a premix. 3. A feed additive according to claim 1, characterized in that it contains flour, meal or bran of maize, barley, wheat or oat as cereals in the desired form. 4. The fodder sits according to items 1 to 2, characterized in that Lim contains soya flour or sunflower flour as an oil plant. A feed additive according to any one of claims 1 to 2, characterized in that it contains as a concentrate a defibrillated plant product with a high protein content. 6. The feed additive according to claim 1, characterized in that it contains meat meal, fish meal or bone meal as animal flour. A feed additive according to claim 1, characterized in that it contains a silicate compound or silicic acid or sand as a mineral. 8. A feed additive according to claim 1, characterized in that it contains a calcium compound, calcium phosphate or calcium carbonate as a mineral. 9. A feed additive according to claim 1, characterized in that it contains as a mineral a compound of aluminum, clay or kaolin.