HU206828B - Process for producing veterinary compositions containing benzimidazol derivatives as active components - Google Patents

Abstract

Anthelmintic granular compositions comprise as active ingredient 5 to 50% by weight a compound of the general formula I <IMAGE> - wherein X means -O-, -S-, -CO-, -SO-, -SO2- or a valence bond, R means a group of the general formula -NH-COOR<2> wherein R<2> is C1-4 alkyl, or a 4-thiazolyl-group, and R<1> means hydrogen, C1-4 alkyl or phenyl, and 5 to 30% by weight of one or more surfactants having more than 7 carbon atoms, 0.1 to 3% by weight of a polymer and appropriate other additives (such as gliding and colouring agents) to 100%.

Description

Description: 4 pages (including 1 page illustration)

HU 206 828 B

FIELD OF THE INVENTION The present invention relates to a process for the preparation of water-dispersible granules having a specific anthelmintic activity and containing a benzimidazole derivative of the Formula (I) or lyotropic liquid crystalline compositions thereof.

The compositions of the present invention are used in veterinary medicine.

In formula I, X is -S-,

R is -NH-COOR ² ,

^R1 is C1-4 alkyl, r 2 _e j] Designation _en C1-4 alkyl.

Vc compounds of formula (I) are known to have anthelmintic activity and are widely used in veterinary medicine (U.S. Pat. No. 3,915,986).

It is an object of the present invention to provide formulations which, when concentrated and diluted, exhibit good stability, good solubility in water, no sedimentation, and low viscosity.

It has now been found that the compositions of the present invention meet the above requirements:

- easy to administer,

- their buoyancy is extremely high, so that the resulting suspension does not have to be constantly mixed to dissolve the granulate in water to ensure an even distribution of the active ingredient.

- the active substance does not settle out, thus reducing the risk of toxicosis.

The compositions of the present invention may be prepared by providing 5 to 50% by weight of the active ingredient of formula (I)

- where in the formula

X, R, R ¹ and R ² are as defined in claim 1, containing from 5 to 30% by weight of surfactant (s) containing at least 8 carbon atoms, from 0.1 to 3% by weight of a polymer, characterized by curvature and fluid permeability. from 0.6 to 1.0, mixed with other inert veterinary adjuvants or excipients such as fillers, colorants and 100% by weight, and granulated in a known manner.

The compositions of the present invention preferably contain 5 (6) -propylthio-2-benzimidazolylmethylcarbamate as the active ingredient.

The surfactants in the compositions of the invention are ionic (anionic and cationic) and / or nonionic and / or amphoteric surfactants such as salts of carboxylic acids, such as fatty acid soaps; sulfates, such as alkyl sulfates, preferably sodium dodecyl sulfate; salts of sulfonic acids, such as alkyl benzene sulfonates; phosphates, such as alkyl phosphates and their salts; esters of ethoxylated fatty alcohols with inorganic acids (preferably sulfuric acid, phosphoric acid) and salts thereof; cationic ammonium salts such as cetyltrimethylammonium halides; quaternary nitrogen containing compounds such as N-alkylpyridinium salts; salts of alkyl amines or alkyl amide adducts with ethylene oxide, such as oxyethylated coconut fatty acid amide; non-ionic fatty acid esters of polyhydric alcohols, such as oxyethylated dianhydro-sorbitol stearates, o-phosphoric acid trialkyl esters; ethylene oxide adducts as fatty alcohol ethylene oxide adducts of fatty acid polyethylene glycol esters with alkyl phenols-ethylene oxide; preferably ethylene oxide adducts of alkylphenyl poly (glycol ether) alkylamines or alkylamides; poly (propylene glycols) with ethyleneoxyde; alkyl (polyethylene glycol reaches) -o-phosphoric acid triesters; choline salts of amines, preferably betaines or phosphoric acid slides.

Polyelectrolytes, neutral polymers, natural macromolecules and their derivatives, and polypeptides having a value of> 0.6 may be used.

Preferred polymers are e.g. polyvinylpyrrolidone (M = 18,000-25,000; a =

0.77-0.85 polyethylene oxide (M = 1000; a = 0.82) polyvinyl alcohol (M = 78,000; a = 0.77) poly (ethyleneimine) (Μ = 12,000; a = 0.89) poly (acrylic acid) -at (M = 500,000; a = 0.91) oligodextran (M = 2000; a = 0.60) polyethylene oxide-propylene oxide (M = 10,000; a =

0.84)

The granules of the invention are used in feed or dissolved in water.

The water-dispersible granules of the invention, when mixed with water, form a stable suspension having a lyotropic liquid crystal structure.

Accordingly, it is another object of the present invention to provide liquid crystalline compositions containing from 0.1 to 20% by weight of the water-dispersible granules of the invention and 100% by weight of water.

The lyotropic liquid crystalline compositions may optionally be prepared by mixing, in situ, water-dispersible granules at the site of use with an appropriate amount of the animals' drinking water.

Ready-to-use solutions contain 50-5000 ppm, preferably 500-1000 ppm of active ingredient.

The invention is illustrated by the following examples:

Examples:

1. Water dispersible granules:

The active ingredient and any excipients used are homogenized. A mixture of surfactant (s) and polymer is added in small portions to the homogenized material. After each addition, thorough homogenization is performed and the material is granulated in a known manner.

crowd%

a) 5 (6) -propylthio-2-benzimidazolylmethylcarbamate 21.00

Emulson AG (CO) 22 [polyoxyethylene (20) decyl alcohol

HU 206 828 B

HLB: 15.3 10.00 Oligodextran (M = 2000; a = 0.6) 1.0 Sucrose 68.00

2. Liotropic liquid crystalline composition

/ 1 crowd% the 2 crowd% the 3 crowd% agent 10.5 0.21 0.105 Emulsifiers AG (CO) 22 5.0 0.1 0.05 oligodextrán 0.5 0.01 0,005 saccharose 34 6.8 0.34 WATER ad 100 ad 100 ad 100

The above formulations exhibit a liquid crystalline structure 2 hours after dilution when examined with a polarization microscope (crossed polarizer and analyzer using Gypsum I. red plate).

3. (Comparative example)

5 (6) -propylthio-2-benzylidazolylmethylcarbamate 21.00

Emulson AG (CO) 22 10.00 sucrose 69.00

Formulations diluted as in Example 2 do not show a liquid crystalline structure 2 hours after dilution.

The physico-chemical properties of the compositions of the invention are as follows:

Example composition floating Ability bulk chemicals conc. in standard hard water In 30 minutes Within 2 hours First 10.5 78 72 0.21 80 YOU 0.105 80 72

Example composition floating Ability bulk chemicals conc. in standard hard water In 30 minutes Within 2 hours Third 10.5 65 43 0.21 60 40 0.105 60 40

Comparative test results show that the composition of the invention, when mixed with water, has a more uniform distribution due to its liquid crystalline structure than the known composition which does not have a liquid crystalline structure which does not contain the polymer of the invention.

Claims (2)

PATENT CLAIMS A process for the preparation of a compound of formula (I): X is -SR is -NH-COOR ² , R ¹ is C 1 -C 4 alkyl, R ² is C 1-4 alkyl group containing water-dispersible granulate, characterized in that 5-50% by weight (I) active compound of general formula - wherein X, R, R ¹ and R ² are as defined herein 5 to 30% by weight of surfactant (s) containing at least 8 carbon atoms, 0.1 to 3% by weight of polymer having a fineness and fluid permeability of from 0.6 to 1.0 - 100% by weight other inert veterinary excipients such as fillers, colorants, and the mixture is granulated in a known manner. A process for the preparation of a lyotropic liquid crystalline composition comprising mixing 0.1-20% by weight of the composition of claim 1 in an amount of 100% by weight in water.