DE1197737B - Animal feed, animal feed additive, poultry feed or poultry feed additive - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

Number:
File number:
Registration date:
Display day:

A23k

German class: 53 g - 4/04

1197 737 _: C25721IV a / 53g June 26, 1960 July 29, 1965

The present invention relates to animal feeds and animal feed additives useful in animal breeding, which are the new ethers of 18-hydroxy-3ß, 20a-yohimban-16-carboxylic acid esters the general formula

RiOOC

OR ₃

OR ₂

contain, in which Ri is a lower alkyl, alkoxyalkyl or dialkylaminoalkyl radical in which the lower alkyl group carrying the substituent separates the substituent from the ester oxygen atom by at least 2 carbon atoms, R2 a lower alkyl radical. R3 is a lower alkyl radical which is optionally substituted by lower alkoxy, alkyl mercapto or dialkylaminoalkyl groups. in which the substituted hydroxyl, mercapto or amino group is separated from the ether oxygen atom by at least 2 carbon atoms, or a phenyl lower alkyl radical, R4 and R5 are hydrogen or halogen atoms or lower alkyl or alkoxy groups, Re is a hydrogen atom or a lower alkyl group, as well as their N-oxides and salts of these compounds with acids, with the exception of racemic and optically active methyl 18-0-methyl reserpate and salts thereof, preferably in the optically active form corresponding to 1-reserpine.

The phenyl lower alkyl radical R3 can optionally be substituted in the phenyl radical by halogen atoms, lower alkyl, Alkoxy, haloalkyl or nitro or amino groups may be substituted.

Salts of the new compounds, including those of the N-oxides, are especially those of inorganic ones Acids, e.g. B. mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric or phosphoric acids, or of organic acids such as vinegar, propionic, Glycolic, milk. Pyrites, oxal, malon, Amber, maleic, fumaric, apple, wine, lemon, ascorbic, citracon. Hydroxymaleic or Dihydroxymaleic acid, or benzoin, phenylacetic, animal feed, animal feed additives, poultry feed or poultry feed additives

Applicant:

CIBA Aktiengesellschaft, Basel (Switzerland)

Representative:

Dipl.-Ing. E. Splanemann, patent attorney, Munich 2, Theatinerstr. 33/34

Named as inventor:

Michael Mullen Robison, Berkeley Heights, N. J .; Robert Armistead Lucas,

Mendham, N. J. (V. St. A.)

Claimed priority:

V. St. v. America July 29, 1959 (830187),

dated September 1, 1959

(837 357),

dated June 20, 1960 (37 097) - -

4 - amino - benzene-. 4 - hydroxybenzoic, anthranil, cinnamon, almond, salicylic, 4-amino-salicylic, 2-phenoxy-benzoic or 2-acetoxy-benzoic acid or methanesulfonic, ethanesulfonic. 2-hydroxyethanesulfone or p-toluenesulfonic acid. Mono- or poly salts are formed.

Regarding the fact that several asymmetric carbon atoms are involved in the structure of the new compounds are involved, the latter as mixtures of racemates. pure racemates or as optical antipodes.

It is known that pets are exposed to a variety of environmental factors, which in certain Cases of both undesirable growth retardation and a considerable increase in Can effect food intake.

More recently it has been shown that antibiotics. Chemotherapeutic agents, hormone-active agents or Rauwolfiadiester alkaloids influence the rearing of domestic animals favorably or the degree of Increase feed utilization.

It is also known to use Rauwolfia diester alkaloids, such as reserpine, for the treatment of animals. because dealing with pets, especially

509 628/121

especially poultry, for example during transport or vaccination. Pruning or killing is one thing of the main problems of the animal breeder and is often associated with damage, i. H. economic losses, tied together.

The preference of the Rauwolfia diester alkaloids over other natural or synthetic ones, the handling with means that facilitate animals or promote rearing is mainly based on the low level Dosage so that especially the meat of the so ίο when animals were traded, there was practically no trace of the compounds mentioned and therefore no reduction in quality entry. However, these advantages are also offset by certain disadvantages. For example, B. the the desired effect only occurs after several hours and extends over a longer period of time, often over days. Should z. B. the administration of the said alkaloids containing feed the To make it easier to catch the animals, this can only begin 4 to 6 hours after they have been fed will. On the other hand, the long duration of action can be cumulative in some cases Effects lead, which is particularly detrimental to the growth of the animals. Too strong Treatment of the animals counteracts normal feed intake. Furthermore, the Rauwolfiadiester alkaloids Practically insoluble in water, which is why it is suitable for administration with drinking water badly suited. However, this type of application is due to the simple possibility of dosing even distribution among all animals in a herd and especially good control options desirable. So z. B. by withdrawal of drinking water within a certain time and subsequent The addition of an aqueous solution of the compounds mentioned easily produces a uniform effect all members of the flock or herd can be achieved.

It was.nun found that the new compounds mentioned at the outset also have the good effect of Rauwolfia diester alkaloids. such as reserpine. In contrast to the latter, with their slow The new compounds unfold their onset and often undesirably long-lasting effects Effect much earlier and for a well-limited period of time. Their duration of action extends mostly not beyond 24 hours, d. that is, the effect has completely subsided after this time. In addition, the new compounds, especially their acid addition salts, are relatively soluble in water and therefore particularly suitable for administration with drinking water. So you are the well-known Rauwolfia diester alkaloids superior.

For domestic animals such as cattle, horses, sheep, goats or pigs, especially poultry, like chickens, turkeys. Geese or ducks, but also dogs, cats or parrots, thus occur shortly after administration of the feed containing the new compounds, the desired effect occurs, so that the animals- ζ. Β. easily captured and the work to be done can be carried out effortlessly without much fuss.

Furthermore, by administering the new compounds with the feed or the drinking water the handling of flocks or herds of the animals mentioned is made much easier. The most common Mass hysteria does not occur or is kept to a minimum, the slaughter of the animals is facilitated, the work of the staff decreased, his safety increased, and often by shy animals Damage caused can be avoided.

The aforementioned feed or feed additives can also be used for the purpose of better Administered food grade. Due to the well-limited duration of action of the active ingredients occur hardly any of the aforementioned cumulative effects.

It is useful to feed the active ingredients. to mix components or to dissolve them in the potion. The type of other components that occur in addition to the active ingredient depends on the type the animals fed with it, their age, the respective market price of the feed and more other factors. In general, feed is made up of carbohydrates, proteins, fats, minerals and containing vitamins, very beneficial. Suitable feed components are, for example, types of grain, such as rye, wheat, barley, oats, buckwheat, corn, sorghum or millet, and their Milled products such as wheat, groats, flakes, bran or flour, as well as grass, clover, alfalfa, cabbage or Hay, molasses, meat waste, fish, soybean, peanut or oil cake flour, cod liver oil, lime or Bone meal, iodized table salt, dicalcium phosphate or manganese sulfate, vitamins, e.g. B. A, B12 or D; Niacin, thiamine, riboflavin, calcium pantothenate, ascorbic acid or similar nutrient, mineral and vitamin supplements. The feed or feed additives can also have other valuable ones Contain components, e.g. B. butyloxy-toluene, methionine, antibiotics, e.g. B. Bacitracin, penicillins, tetracyclines, such as chloro- or oxytetracycline or erythromycin, or compounds with hormonal effects, like diethylstilboestrol or hexoestrol.

The feed additives mostly contain suitable carriers, e.g. B. lower wheat flours, starch, Sugars, such as cane or lactose, mannitol, sodium gluconate, or soybean extraction residues. You can also use buffers such as citric acid-sodium citrate, sodium acetate, phthalic acid-potassium phthalate, Benzoic acid sodium benzoate, lactic acid sodium lactate or fumaric acid-sodium fumarate, contain and / or complexing agents, such as ethylenediamine-tetraacetic acid or the sodium salt thereof, or other valuable substances such as antioxidants or stabilizers. You can get the new ones Compounds but also in solution or dispersion with drinking water or skimmed milk or in any administer other forms.

The aforementioned compounds used as active ingredients can, for. B. obtained by that the formula corresponding 17-lower alkoxy -18-hydroxy-3-epialloyohimbane -16-carboxylic acid esters, their N-oxides or salts of these compounds with diazo compounds of the general formula N2 - R3 ', in which R3' is the impure hydrogen atom reduced radical R3 means, reacts in the presence of strong inorganic Lewis acids and, if desired or necessary, the tertiary amines obtained are converted into the N-oxides and / or, if desired, converts the bases obtained into their salts or the N-oxides obtained, if appropriate, into the tertiary amines and / or salts in 'the free Converts connections.

It has been found that the active ingredient content of the feed is expedient between approximately 0.0005 and 0.01%, preferably between 0.002 and 0.004%, should be in order to facilitate the handling of animals.

I 197

Animal feed, which is supposed to bring about a better utilization of food, naturally has a lower value Active ingredient content on than the former. The difference in concentration is about two Powers of ten. Furthermore, the active ingredient content of the mentioned feed is also related to body weight of animals in relation to each other. Poultry, e.g. B. chickens, eat relatively more feed than cattle, like cattle or horses. Therefore, the concentration of the active ingredient in feed for poultry should be be less than that for cattle.

If the compounds mentioned at the outset are added to the drinking water, their amounts are expedient Concentration in about 0.0004 to 0.003% for ease of handling animals.

The active ingredient content of feed additives can of course fluctuate within wide limits, see above that there is no need for more detailed information.

The invention is described in more detail in the following example.

example 1

A feed mixture with 18-O-ethyl reserpic acid methyl ester hydrochloride as an active substance can be obtained as follows: *

Main ingredients (premix):

(-) - 18-O-ethyl-reserps acid methyl-

ester hydrochloride 22.00 g

Wheat middle flour 10 978.00 g

Total weight 11,000.00 g

Additives:

Corn flour, 1,082.875 g

Fat 80,000 g

Fish meal, 60% protein 100,000 g

Soybean meal, 50% protein ... 500,000 g

Gluten flour 100,000 g

Dried alfalfa flour 50,000 g

Soluble corn pulp ingredients 40,000 g

Calcium carbonate 28,000 g

Iodized sodium chloride 10,000 g

Vitamins A and D (1 000 000 A and

250,000 D / 0.454 kg) 4.000 g

Calcium pantothenate 0.250 g

Butyl oxytoluene 0.250 g

Choline chloride, 25% 2.500g

Riboflavin conc. (24 g / 0.454 kg) .. 0.125 g

Vitamin B12 (0.02 kg / 0.454 kg) 1,000 g

Methionine 0.500 g

Manganese sulfate 0.500 g

Total weight 2,000,000 g

55

The additives are mixed as follows: about half of the maize flour is poured into the mixer, add the rest of it, mixed with the heated, liquefied fat, and mix until for even distribution of the fat. Manganese sulfate, calcium carbonate and iodized are put on top Add sodium chloride while mixing the fish, soybean, alfalfa and gluten meal and the soluble corn pulp ingredients. After thorough mixing, vitamins A are added and D, calcium pantothenate, choline chloride, riboflavin, vitamin B12, methionine and butyl oxytoluene in this order and continue to mix until all ingredients are evenly distributed. Once this has been achieved, the well-mixed main ingredients are added in such an amount as to add one Concentration of 0.02 g "(-) - 18-O-ethylreserpic acid methyl ester hydrochloride per 100 g of feed mixture in an even mix-to be achieved.

In the case of feed for birds, it is advantageous to have a content of 0.005 to 0.1 g, expedient. from _: 0.02 to 0.04 g of (-) - 18-O-EthyI-ReserpsäuremetriyleSterhydrochlorid to choose per 1000 g of 'feed mixture'.

Example 2 feeding trial

For the feeding experiment, a feed is used which contains 18-O-ethyl reserps acid methyl ester meleate contains. Groups of twenty turkeys each are taken (variety B-B-bronze, ten male and ten female animals each). Age: 1 week at the beginning of the experiment. Duration of the attempt 6 weeks. The results are summarized in the following table:

substance
(in mg / kg
Lining), At first
weight
(ing) End
weight
(ing) total
feed- '
medium
need
(ing). Feed
discarded
management
factor*) Long shot
body
weight
increase control
0.400 133
133 1673
1684 4485
3639 "2.68
2.16 1540
1551

*) Feed conversion factor =

Total weight of the birds

In comparison with those of German Patent 1,045,772, e.g. B. last table on page 4, that the reserpine even with a slightly higher dose (0.5 mg / kg feed) only one Feed conversion factor of 2.50 results.

Claims (1)

Claim: Animal feed, animal feed additive, poultry feed or poultry feed additive, characterized by a content of about 0.0005 to 0.01% of ethers of 18-hydroxy-3 ^, 20a-yohimbane-16-carboxylic acid esters the general formula RiOOC- OR ₃ OR ₂ wherein Ri is a lower alkyl, alkoxyalkyl or dialkylaminoalkyl radical in which the substituents lower alkyl group carrying the substituents from the ester oxygen atom by at least 2 carbon atoms separate, R2 one lower alkyl radical, R3 even if necessary lower alkoxy, alkyl mercapto or dialkylaminoalkyl groups substituted lower alkyl radical, in which the substituted hydroxyl, mercapto or amino group of the ether oxygen atom is separated by at least 2 carbon atoms, or a phenyl lower alkyl radical, R4 and R5 Hydrogen or halogen atoms or lower alkyl or alkoxy groups, Re is a hydrogen atom or mean a lower alkyl group, as well as their N-oxides and salts of these compounds with acids, with the exception of racemic ones and optically active 18-O-methylreserpic acid methyl ester and their salts, preferably in the optical corresponding to 1-reserpine active form. Considered publications:
German interpretative document No. 1 045 772.