MXPA00011736A - Semi-solid aqueous preparations for oral applications of toltrazuril sulphone - Google Patents

Abstract

The present invention relates to toltrazuril sulphone pastes containing an active substance in a concentration of 0.1-20 wt.%and a particle size of 1 - 10.10-6 m, polyacrylic acids with a degree of polymerisation of approximately 3.106 in a concentration of 0.1-5 wt.%, in addition to preservatives and moisturizers, whereby the rest consists of water, amounting to a total of 100%.

Description

SEMISOLID AQUEOUS PREPARATIONS FOR ORAL APPLICATION OF TOLTRAZURIL-SULFONE Field of the Invention The present invention relates to aqueous preparations, semisolid, for oral application, containing as active component l-methyl-3- [4- [(trifluorhyl) sulfonyl] phenoxy] -m-tolyl] -s-triazine-2 , 4, 6 (1H, 3H, 5H) -trione (= Tol trazuril-sulfone).

Background of the Invention Toltrazuril-sulfone is used as an active product in agents against coccidiosis and similar diseases in animals (US-P 4 219 552, DE-P 2 718 799). Such agents are usually solutions of the active products, which are administered to the animals through drinking water, after dilution with water (EP-A 116 175). Such agents are also powders and granules which are mixed with the feed of untreated animals. REF .: 12 352"A, In those cases in which the active product is only hardly soluble in water, aqueous suspensions of the active product are prepared with the use of suitable suspending agents. For this the active product is micronized in a wet milling process and mixed with the suspending agent and water. Starting from such suspensions, semisolid or pasty preparations are then prepared by the addition of thickening agents. The micronizing of Tol trazur il-sul fona in the wet milling process leads to a product that can not be further processed. The manufacture of a stable suspension of Tol trazuril-sul phona therefore can not be achieved with the usual methods. Thus, the usual production of a paste containing Toltrazuri-1-sulfone as an active product could not be achieved with the usual methods. In the case of a micronization of the Tol trazur il-sul-fona in the dry process, particle sizes of the active product which only allow a stable aqueous suspension of the active product using very high concentrations of suspending agents should be expected.

However, direct administration agents should be manufactured without additional dilution, YJ such as for example oral pastes, with the least possible amount of additives. A paste, conventionally manufactured, of Toltrazuril-sulfone, however, would have, besides thickening agents, a high content of suspending agents.

Description of the Invention The present invention relates to a paste for oral administration of Tol trazuril-sulphone, characterized in that a) the active product is presented with a size of grain of 1.10"6 m and a maximum grain size of 50.10" 6 m in a concentration of 0.1-20% by weight, b) polyacrylic acids, with an acrylic acid content of 56 to 68% by weight and with A molecular weight of about 3.10"6, which are neutralized with alkaline or alkaline earth bases, are present in a concentration of 0.1-5% by weight, c) if necessary, agents for the maintenance of moisture at a concentration of 5 to 30% by weight d) If appropriate, preservatives are present in a concentration of 0.01 to 0.5% by weight, e) and the rest up to 100% by weight is made up of water.

The active compound is preferably contained in the formulations according to the invention, in concentrations by weight of 5% by weight to 20% by weight, particularly preferably 10% by weight, up to 15% by weight. The polyacrylic acids are preferably neutralized with hydroxides or alkali carbonates. The polyacrylic acids are contained in the formulation according to the invention in concentrations by weight of 0.2% up to 1%, preferably 0.5%. These can be obtained commercially and are known in the medical books for example under the trade name Carb 934 P.

The preferred preservatives will be esters of para-hydroxybenzoic acid (parabens) _______ «3B_«,. such as methyl 4-hydroxybenzoate, ethyl 4-hydroxybenzoate or propyl 4-hydroxybenzoate. The preservatives can be used individually or in combination for sufficient preservation. These are usually contained in concentrations of 0.01-0.5% by weight. Optionally the formulation may also contain moisture maintenance agents such as, for example, glycerin or 1.2-10 propylene glycol. The agents for the maintenance of moisture are used in concentrations by weight of 5% to 30%, preferably 10% to 20%. The active product is present with a grain size of 1 to 10.10"6 m, preferably 15 up to 5.10 'm, The maximum of the grain sizes is 50.10 m, preferably 30.10" d m. The desired grain size distribution of the active product is obtained by dry milling. For this purpose, 20 kg of active compound per hour are micronized in a flat cylindrical air jet mill under a pressure of 5 to 6 bar with compressed air. - ">« "'' •« AIÜ ». -._-_, -. '".»! • »« _, »..... j__C.

The agent according to the invention is obtained by mixing together the individual components. This can be modified in terms of its consistency by increasing or decreasing the proportion in water. A pasty consistency is desirable. This allows the oral administration of the agent with suitable applicators such as syringes, tubes, spatulas, etc. The agents according to the invention are especially suitable for combating coccidiosis and similar diseases in a large number of mammals such as horses (horses, donkeys, etc.), ruminants (cows, lambs, goats, camelids, etc.), pigs , dogs, cats, rabbits, rodents or other mammals. The treatment can reach all age groups. By coccidiosis and similar diseases should be understood infections with infection states of types of various species, such as for example Eimeria, Isospora, Cas toisospora, Sarkocystis, Toxoplasma, Neospora or Cryptosporidien. The treated animals can be final hosts or intermediate hosts. The resulting diseases are diverse (for example diarrheal diseases in many coccidiosis, disorders of the locomotor system in the case of EPM, abortions, etc.). Therefore, the application recommendations are very diverse. In general, doses of up to 30 mg of active compound are effective for each body weight, either once or several times. The pasta can also be mixed with animal feed.

Example 1 Paste for oral application or for mixing with the feed.

Composition: Toltrazuril-sulfone 15 g Polyacrylic acid 0.5 g Sodium hydroxide 0.1 g 1, 2-Propylene glycol 20 g Propylparaben 0.02 g Methylparaben 0.14 g Water q. s. 100 g The components are stirred together, forming an aqueous, semi-solid preparation that can be packaged in corresponding applicators.

It is noted that in relation to this date, the method known to the applicant, to carry out the aforementioned invention, is that which is clear from the present description of the invention.

INVENTION Having described the invention as above, property is claimed as contained in the following: fifteen twenty -i- *

Claims (3)

R E I V I N D I C A C I O N S

1. Orally administrable Toltrazuril-sulfone paste, characterized in that a) the active product is presented with a grain size of 1-10.10-6 m and a maximum grain size of 50.10 ~ 6 m in a concentration of 0.1-20% by weight , b) polyacrylic acids, with an acrylic acid content of 56 to 68% by weight and with a molecular weight of approximately 3.10"6, which are neutralized with alkaline or alkaline bases, are present in a concentration of 0.1. - 5% by weight, c) if necessary, agents for the maintenance of moisture at a concentration of 5 to 30% by weight are present d) if necessary preservatives are present in a concentration of 0.01 to 0.5% in weight, e) and the rest up to 100% by weight is made up of water.

2. Use of the paste according to claim 1, for the oral treatment of cocci fHwsis diseases in animals.

3. Process for obtaining the pastes according to claim 1, characterized in that the active product is micronized and mixed with the other components. . t i. »*. írttio