CS273931B1 - Therapeutical preparation for veterinary application with erythromycin or tylosine content - Google Patents

Abstract

The solution concerns a medical preparation for veterinary containing bases of erythromycin or tylosin. Basic antibiotic is contained in the preparation together with appropriate organic acid and is completed with excipient. The effective application form is obtained by means of mixing in water or in environment containing water in predefined concentration.

Description

The invention relates to a medicament for veterinary use comprising erythromycin or tylosin.

Erythromycin is a macrolide antibiotic and has a broad antimicrobial spectrum. Tylosin is an antibiotic for veterinary use effective against serious swine diseases.

The use of these base antibiotics in veterinary medicinal products when administered in water or aqueous formulations is not effective because of the low solubility of the active ingredients.

Application water-soluble forms of erythromycin and tylosin are prepared in the form of addition salts with organic acids. These are produced by a separate technological process using additional raw materials, labor and other components of production costs. From the separately prepared water-soluble addition salt, the dosage form is prepared by incorporation into a suitable vehicle.

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In the case of erythromycin, MS. Spofa Vubivet ER and Erymykoin pulv. solub. containing erythromycin lactate and Abbott Gallimycin PF containing erythromycin thiocyanate. The preparation of water-soluble glucoheptonate is solved by US patent 2852429. The preparation of Elanco Tylan Solutie contains water-soluble tylosin tartrate.

It has now surprisingly been found that the active dosage form can be prepared using low soluble erythromycin or tylosin bases while incorporating a suitable organic acid into the premix, preferably citric or tartaric acid. Although the premix contains the base and the acid side by side, it is sufficiently stable, retaining flowability and other suitable technological properties. When applied in water or water containing media, it is in all respects equal to medicinal products containing separately prepared water-soluble salts of erythromycin or tylosin.

The subject of the invention is therefore a medicinal product for veterinary use containing from 1 to 50% by weight of erythromycir or tylosin base. based on the weight of the formulation, an organic acid such as citric or tartaric acid and a vehicle such as glucose or sucrose. The composition may also contain a pH correction agent such as sodium hydrogen phosphate or sodium citrate.

The stability of the dry mixture, the good water solubility, the stability of the prepared solution for use, the taste suitability and the absorbability of the active ingredient have been experimentally demonstrated. Clinical verification showed the same effect of the new product as that of the water-soluble antibiotic salt.

Stirring the product in water or water containing the environment results directly in the dosage form to be used according to the respective instructions.

The composition may also be combined with other agents, such as therapeutic agents, biofactors, flavor correctors or product stability enhancers.

The new type of erythromycin or tylosin-containing medicinal product saves considerable manufacturing costs for the separate preparation of the water-soluble salts of erythromycin or tylosin. In addition, it also contributes to environmental protection, since large amounts of toxic organic solvents are used in the preparation of water-soluble forms such as erythromycin lactate.

CS 273 931 Bl

These examples illustrate but do not limit the invention in any way.

Example 1

An erythromycin base containing IDO g (0.136 mol) erythromycin base, 12 g (0.0624 mol) citric acid monohydrate and 88B g glucose was prepared by homogenizing the ingredients in a bulk mixer.

Therapeutically applied, for example, in calves in 1 wt. concentration in the milk feed mixture or 0.2 wt. concentration in milk, water or tea for 7 days.

Example 2

A medicinal product containing tylosin base of 20 g (0.022 mol) tylosin base, g (0.02 mol) L - (+) tartaric acid, 0.1 g sodium hydrogen phosphate and 76.9 g sucrose was prepared by homogenizing the ingredients in a blender for loose materials.

The preparation is to be administered dissolved in water at a concentration corresponding to approximately 20 mg tylosin per kg live weight of pig.

Example 3

A medicinal product containing erythromycin base of 100 g (0.136 mol) erythromycin base, 12 g (0.0624 mol) citric acid monohydrate, 2 g sodium citrate and 886 g glucose was prepared by homogenizing the ingredients in a bulk mixer.

The application of the premix is the same as in Example 1.

In tabular form, for example, erythromycin stability in dry form, stability in drinking water and blood serum erythromycin levels are demonstrated. (The working name Vubivet ER solub is used for the premix of the invention.)

Monitoring of erythromycin stability in Vubivet ER solub. 10% wt. premix (dry form)

Vubivet ER solub. č.š. expected ERY concentration in g / kg time tracking result testace 1 week 100% Week 2 100% 1 month 100% 2nd month 100% 210788 100 g / kg 3rd month 100% 4th month 100% 8th month 100% 10th month 100% 12th month 100%

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Monitoring of erythromycin stability in drinking water

Vubivet ER solub. No expected ERY concentration in mg / ml monitoring time result testace 1 day 105% 2107G8 1,25 Day 2 100% Day 6 100% B. den 100% Erymykoin 1,25 1 day 105% Spof a Day 2 100 h pulv.solub. Day 6 100%

Layers premix erythromycin in the blood % in 1 wt. concentration calves serum after 7 doses of Vubivet ER solub. 10% wt. calf no. ERY levels in yug / ml 24 h. 24 h. 48 h. 24 h. before after the start after the start P ° end applications application application application 1 0 0.90 0.72 0 2 0 0.55 0.55 0 3 0 0.60 0.64 0 4 0 0.69 0.76 ’ 0 5 0 0.60 0.64 0

Erythromycin levels in broiler blood serum after continuous five-day application in drinking water of Vubivet ER solub.

broiler no. number of hours ERY levels in / µg / ml 1 in 24 h 0,089 5 .den 0,093 2 in 24 h 0,082 Day 5 0,094 3 in 24 h 0,075 Day 5 0,096 4 in 24 h 0,082 Day 5 0,086 5 in 24 h 0,075 Day 5 0,082 6 in 24 h 0,086 5.den 0,093

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Claims (2)

SUBJECT OF THE INVENTION Medicament for veterinary use comprising erythromycin or tylosin, characterized in that it contains etryhromycin or tylosin base in an amount of 1 to 50% by weight. based on the weight of the formulation, an organic acid such as citric or tartaric acid in an amount of 0.25 to 1.5 moles per mole of the base present and a vehicle such as glucose or sucrose. 2. The medicament of claim 1 comprising a pH correcting agent such as sodium hydrogen phosphate or sodium citrate.