A kind of toltrazuril inclusion compound freeze-dried powder and preparation method thereof

Abstract

The invention discloses toltrazuril inclusion compound lyophilized powder. The toltrazuril inclusion compound lyophilized powder is obtained by adopting sulfobutyl ether-beta-cyclodextrin to perform inclusion on toltrazuril and then carrying out a lyophilization process. A preparation method of the toltrazuril inclusion compound lyophilized powder concretely comprises the following steps: dissolving the toltrazuril by an organic solvent to obtain an organic solution of the toltrazuril; adding the organic solution of the toltrazuril into an aqueous solution of the sulfobutyl ether-beta-cyclodextrin, and magnetically stirring for carrying out a reaction; carrying out rotary evaporation on the materials obtained after the reaction so as to remove the organic solvent, then filtering by using amicrofiltration membrane and drying to obtain a toltrazuril inclusion compound; carrying out the lyophilization process to obtain the toltrazuril inclusion compound lyophilized powder. According to the preparation method, the sulfobutyl ether-beta-cyclodextrin is adopted to perform inclusion on the toltrazuril, so that the solubility of the indissolvable drug-the toltrazuril is improved; by adopting the lyophilization process, the stability and bioavailability of the toltrazuril are improved; the toltrazuril inclusion compound lyophilized powder enriches the preparations of antiparasitic drugs.

Description

technical field

[0001] The present invention relates to an inclusion compound and the technical field of preparation thereof, in particular to a freeze-dried powder of Toltrazuril inclusion compound and a preparation method thereof. Background technique

[0002] Toltrazuril (tohrazuril) is a triazinone anticoccidial drug developed by Bayer AG in the 1980s. Its trade name is Baycox, and it is called toltrazuril solution in China. The drug can effectively kill a variety of protozoa including coccidia. It is a highly effective anticoccidial drug with a very wide anti-coccidian spectrum, low toxicity, and slow drug resistance. It is widely used in livestock and poultry coccidia at home and abroad. Disease prevention and treatment.

[0003] The dosage forms of toltrazuril are mainly powder and drinking water, but their water solubility is poor. During use, due to its low concentration and poor stability of toltrazuril, it is prone to precipitation and discoloration, which greatl...

Examples

Embodiment 1

[0092] Step 1, dissolving Toltrazuril in an organic solvent to obtain an organic solution of Toltrazuril; the organic solvent is methanol, and the volume concentration is 30%;

[0093] In step 2, the organic solution of toltrazuril obtained in step 1 is added to the aqueous solution of sulfobutyl ether-β-cyclodextrin, and the mass ratio of toltrazuril to sulfobutyl ether-β-cyclodextrin is 2: 1. Magnetic stirring reaction at 300r / min and 60°C for 4h;

[0094] In step 3, the substance reacted in step 2 is rotated to evaporate the organic solvent, then filtered through a 0.45 μm microporous membrane, and dried to obtain the inclusion compound of toltrazuril;

[0095] Step 4: Pre-freeze the toltrazuril inclusion compound obtained in step 3 to -35°C for 3 hours, then freeze at -75°C for 10 hours, freeze-dry at -50°C for 24 hours, and finally heat up to 30°C for drying After 5 hours, the lyophilized powder of Toltrazuril inclusion compound was obtained.

Embodiment 2

[0097] Step 1, dissolving Toltrazuril in an organic solvent to obtain an organic solution of Toltrazuril; the organic solvent is ethanol, and the volume concentration is 30%;

[0098] In step 2, the organic solution of toltrazuril obtained in step 1 is added to the aqueous solution of sulfobutyl ether-β-cyclodextrin, and the mass ratio of toltrazuril to sulfobutyl ether-β-cyclodextrin is 3: 1. Magnetic stirring reaction at 350r / min and 50°C for 5h;

[0099] In step 3, the substance reacted in step 2 is rotated to evaporate the organic solvent, then filtered through a 0.45 μm microporous membrane, and dried to obtain the inclusion compound of toltrazuril;

[0100] Step 4: Pre-freeze the toltrazuril inclusion compound obtained in step 3 to -40°C for 5 hours, then freeze at -80°C for 12 hours, freeze-dry at -55°C for 22 hours, and finally raise the temperature to 35°C for drying After 4 hours, the lyophilized powder of Toltrazuril inclusion compound was obtained.

Embodiment 3

[0102] Step 1, dissolving Toltrazuril in an organic solvent to obtain an organic solution of Toltrazuril; the organic solvent is methanol, and the volume concentration is 40%;

[0103] In step 2, the organic solution of toltrazuril obtained in step 1 is added to the aqueous solution of sulfobutyl ether-β-cyclodextrin, and the mass ratio of toltrazuril to sulfobutyl ether-β-cyclodextrin is 4: 1. Magnetic stirring reaction at 400r / min and 30°C for 6h;

[0104] In step 3, the substance reacted in step 2 is rotated to evaporate the organic solvent, then filtered through a 0.45 μm microporous membrane, and dried to obtain the inclusion compound of toltrazuril;

[0105] Step 4: Pre-freeze the toltrazuril inclusion compound obtained in step 3 to -45°C for 4 hours, then freeze at -85°C for 11 hours, freeze-dry at -52°C for 21 hours, and finally heat up to 32°C for drying After 4.5 hours, the lyophilized powder of Toltrazuril inclusion compound was obtained.

technical field

[0001] The present invention relates to an inclusion compound and the technical field of preparation thereof, in particular to a freeze-dried powder of Toltrazuril inclusion compound and a preparation method thereof. Background technique

[0002] Toltrazuril (tohrazuril) is a triazinone anticoccidial drug developed by Bayer AG in the 1980s. Its trade name is Baycox, and it is called toltrazuril solution in China. The drug can effectively kill a variety of protozoa including coccidia. It is a highly effective anticoccidial drug with a very wide anti-coccidian spectrum, low toxicity, and slow drug resistance. It is widely used in livestock and poultry coccidia at home and abroad. Disease prevention and treatment.

[0003] The dosage forms of toltrazuril are mainly powder and drinking water, but their water solubility is poor. During use, due to its low concentration and poor stability of toltrazuril, it is prone to precipitation and discoloration, which greatl...

Examples

Embodiment 1

[0092] Step 1, dissolving Toltrazuril in an organic solvent to obtain an organic solution of Toltrazuril; the organic solvent is methanol, and the volume concentration is 30%;

[0093] In step 2, the organic solution of toltrazuril obtained in step 1 is added to the aqueous solution of sulfobutyl ether-β-cyclodextrin, and the mass ratio of toltrazuril to sulfobutyl ether-β-cyclodextrin is 2: 1. Magnetic stirring reaction at 300r / min and 60°C for 4h;

[0094] In step 3, the substance reacted in step 2 is rotated to evaporate the organic solvent, then filtered through a 0.45 μm microporous membrane, and dried to obtain the inclusion compound of toltrazuril;

[0095] Step 4: Pre-freeze the toltrazuril inclusion compound obtained in step 3 to -35°C for 3 hours, then freeze at -75°C for 10 hours, freeze-dry at -50°C for 24 hours, and finally heat up to 30°C for drying After 5 hours, the lyophilized powder of Toltrazuril inclusion compound was obtained.

Embodiment 2

[0097] Step 1, dissolving Toltrazuril in an organic solvent to obtain an organic solution of Toltrazuril; the organic solvent is ethanol, and the volume concentration is 30%;

[0098] In step 2, the organic solution of toltrazuril obtained in step 1 is added to the aqueous solution of sulfobutyl ether-β-cyclodextrin, and the mass ratio of toltrazuril to sulfobutyl ether-β-cyclodextrin is 3: 1. Magnetic stirring reaction at 350r / min and 50°C for 5h;

[0099] In step 3, the substance reacted in step 2 is rotated to evaporate the organic solvent, then filtered through a 0.45 μm microporous membrane, and dried to obtain the inclusion compound of toltrazuril;

[0100] Step 4: Pre-freeze the toltrazuril inclusion compound obtained in step 3 to -40°C for 5 hours, then freeze at -80°C for 12 hours, freeze-dry at -55°C for 22 hours, and finally raise the temperature to 35°C for drying After 4 hours, the lyophilized powder of Toltrazuril inclusion compound was obtained.

Embodiment 3

[0102] Step 1, dissolving Toltrazuril in an organic solvent to obtain an organic solution of Toltrazuril; the organic solvent is methanol, and the volume concentration is 40%;

[0103] In step 2, the organic solution of toltrazuril obtained in step 1 is added to the aqueous solution of sulfobutyl ether-β-cyclodextrin, and the mass ratio of toltrazuril to sulfobutyl ether-β-cyclodextrin is 4: 1. Magnetic stirring reaction at 400r / min and 30°C for 6h;

[0104] In step 3, the substance reacted in step 2 is rotated to evaporate the organic solvent, then filtered through a 0.45 μm microporous membrane, and dried to obtain the inclusion compound of toltrazuril;

[0105] Step 4: Pre-freeze the toltrazuril inclusion compound obtained in step 3 to -45°C for 4 hours, then freeze at -85°C for 11 hours, freeze-dry at -52°C for 21 hours, and finally heat up to 32°C for drying After 4.5 hours, the lyophilized powder of Toltrazuril inclusion compound was obtained.

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