CZ20023429A3 - Isolation method of salinomycin from fermented soil - Google Patents

Abstract

The present solution refers to a method of isolating salinomycin for the purpose of obtaining a granulated product. The purpose aforementioned is reached by a method for isolating salinomycin from the fermentation broth according to the invention, the nature of which consists in that the fermentation broth of salinomycin is adjusted to an acidic pH range. A suitable inert filtration aid such as diatomaceous earth, zeolites, wood flour or a mixture thereof is added in an amount of 5 to 20 wt % referred to the weight of the fermentation broth. The biomass is separated by filtration, granulated and dried in a fluid bed drier. The dry granules are ground and sieved to a required particle size.

Description

METHOD OF INSULATION OF SALINOMYCIN FROM PHARMACEUTICAL SOIL

Technical field

The invention relates to a process for the isolation of salinomycin to obtain a granular product.

BACKGROUND OF THE INVENTION

Salinomycin feed grade is prepared by spray drying fermented soils together with an anti-caking agent and a filler, or isolated to a pure form after separation of the biomass by extraction, concentration and purification by recrystallization of the crude product. Isolation into pure mold is demanding and production costs and machinery and equipment of operation (see US Pat. No. 4,212,942 US Pat. No. 4,137,247). For use of salinomycin as a veterinary drug or as a growth promoter, it is not necessary to prepare the pure form. After fermentation and treatment, the soil can be directly dried together with anti-caking agents and can be concentrated on an evaporator before drying (see U.S. Pat. No. 4,395,491). The fermented broth of salinomycin contains a number of ballast substances which cause problems after drying in a spray drier. The solids clump together and form lumps that can no longer be processed. The main cause of agglomerate formation is the fat content. The fats contained in solids are particularly evident when the product is processed at high temperatures, moisture and mechanical stress. The product from the spray dryer is very dusty and needs to be granulated (see US Pat. No. 5,529,911). Granulation can be carried out directly in a combined fluid bed spray drier, or as an additional insulation step, either dry or wet. It has been found that a granular solid can be isolated from salinomycin fermented soil without agglomeration and clumping.

SUMMARY OF THE INVENTION

The above mentioned disadvantages are eliminated by the process of isolation of salinomycin from the fermentation broth according to the invention, which consists in that the fermented broth is adjusted to an acidic pH range of 4 to 5 and the inert broth is further added to the treated broth.

Preferably a diatomaceous earth, zeolite, wood flour, or a mixture thereof in an amount of 5 to 20% by volume of fermented soil, whereupon the biomass is separated by filtration and the biomass thus separated is subjected to a granulation process and dried in a fluid drying oven and the product obtained is ground and adjusted by sieving.

By this process it is possible to produce a product which does not agglomerate solids. The advantage is that the active substances are in the acidic pH range of the biomass cells and thus the separated filtrate obtained by this process can be discharged for aerobic treatment into a biological waste water treatment plant. Another advantage is that the biomass obtained has a higher dry matter content than the fermented soil and thus less energy is consumed to dry it than the entire fermented soil.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

The fermented broth obtained by femnentation of Streptomyces albus (CCM 4719) had a pH of 6.1 after 128 hours of cultivation and a salinomycin content of 18.4 g / kg. 527 kg of fermented soil was adjusted to pH 4.0 by addition of 10% HCl. Wood flour was added to the treated fermented soil in an amount of 8% by weight of the fermented soil. Filtration on a rotary vacuum filter packed with wood flour yielded 119.7 kg of biomass and 460.7 kg of a filtrate with salinomycin content below 0.01%, which after neutralization proceeded to aerobic wastewater treatment. The separated biomass was passed through a granulator to a fluid-bed dryer, where 74.2 kg of product containing 12.3% salinomycin were dried.

Example 2

The fermented broth obtained by fermentation of Streptomyces albus (CCM 4719) had a pH of 6.0 after 120 hours of cultivation and a salinomycin content of 22.6 g / kg. 589 kg of fermented soil was adjusted to pH 5.0 by addition of 10% HCl. Zeolite and diatomaceous earth were added to the treated fermented soil in an amount of 15% by weight of the fermented soil. Filtration on a kieselguhr rotary vacuum filter yielded 184.7 kg of biomass and 495.6 kg of salinomycin-containing filtrate

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The separated biomass was passed through a granulator to a fluidized bed dryer where 106.5 kg of product containing 12.1% salinomycin were dried.

Example 3

The fermented broth obtained by fermentation of Streptomyces albus (CCM 4719) had a pH of 6.2 and a salinomycin content of 17.1 g / kg after 124 hours of culture. The pH was adjusted to 7-8 by the addition of NaOH solution. The fermented soil thus treated was heated to 60 ° C and after cooling the pH was adjusted to dilute hydrochloric acid as in Example 1. To 524 kg of the treated fermented soil was added zeolite in 20% by weight of fermented soil. Filtration on a rotary vacuum filter packed with diatomaceous earth yielded 184.7 kg of biomass and 495.6 kg of filtrate with salinomycin content below 0.001%. The filtrate disposal, as in the first example, separated biomass was passed through a granulator to a fluidized bed dryer, where 80.7 kg of product containing 10.9% salinomycin were dried.

Example 4

The fermentation broth obtained by fermentation of Streptomyces albus (CCM 4719) had a pH of 6.3 and a salinomycin content of 15.5 g / kg after 120 hours of culture. 566.6 kg of fermented soil was adjusted to pH 4.7 by addition of 10% HCl. Kieselguhr was added to the treated fermented soil in an amount of 5% by weight of the fermented soil. Filtration on a rotary vacuum filter packed with diatomaceous earth yielded 100.7 kg of biomass and 500.6 kg of low salinomycin filtrate, which after neutralization proceeded to aerobic wastewater treatment. The separated biomass was passed through a granulator to a fluidized bed dryer, where 68.4 kg of dry product were dried. The salinomycin content of the product is 12.8%.

Industrial use

Salinomycin is used as an anticoccidial drug in veterinary medicine and as a growth stimulator in livestock nutrition.

Claims (1)

PATENT CLAIMS Method for the isolation of salinomycin from fermented soil, characterized in that the fermented soil is adjusted to an acidic pH of 4 to 5 and to the treated soil is further added an inert filtering agent, preferably diatomaceous earth, zeolites, wood flour or a mixture thereof in an amount 5 to 20% by volume of fermented soil, whereupon the biomass is separated by filtration and the biomass thus separated is subjected to a granulation process and dried in a fluid-bed dryer, and the product obtained is ground and sieved.