Daptomycin for injection and preparation method thereof

A technology of daptomycin and dehydrated daptomycin, which is applied in the directions of medical preparations containing active ingredients, pharmaceutical formulations, peptide/protein components, etc., can solve problems such as unfavorable industrial scale production, low product content, poor clarity, etc. problem, to achieve the effect of reducing solvent consumption, high purity and fast reconstitution speed

Active Publication Date: 2022-04-15
NORTH CHINA PHARMA COMPANY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to provide a kind of daptomycin for injection and its preparation method, to solve the problems existing in the prior art that are not conducive to industrial scale production, low product content, many impurities, poor color, clarity, etc.

Method used

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  • Daptomycin for injection and preparation method thereof
  • Daptomycin for injection and preparation method thereof
  • Daptomycin for injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Step (1): Introduce 30L of daptomycin filtrate with a titer of 1026u / mL into an ion exchange resin (about 4L in volume) with a diameter of about 10cm for enrichment and adsorption, wash with pure water, and elute with 0.01M NaCl, Finally, desorb with 1M NaCl; collect the desorbed solution with a titer greater than 1000u / mL and combine them. The volume of the final solution was 14L, the content of daptomycin was 1550u / mL, and the yield was 70.5%.

[0058] Step (2): Ultrafiltration of the analysis solution obtained in step (1) with a 30KD ultrafiltration membrane, and the above operating temperatures are all controlled below 20°C. 22 L of filtrate was obtained, with a titer of 940u / mL. The yield was 95.3%.

[0059] Step (3): The filtrate obtained in step (2) is introduced into a macroporous adsorption resin (about 3 L in volume) with a diameter of about 8 cm for adsorption, washed with pure water, eluted with 15% ethanol, and then washed with 35% ethanol The ethanol wa...

Embodiment 2

[0069] Step (1): Introduce 30L of daptomycin filtrate with a titer of 1026u / mL into an ion exchange resin (about 4L in volume) with a diameter of about 10cm for enrichment and adsorption, wash with pure water, and elute with 0.5M NaCl, Finally, desorb with 5M NaCl; collect the desorbed solution with a titer greater than 1000u / mL and combine them. The volume of the final solution was 12L, the content of daptomycin was 1784u / mL, and the yield was 71.4%.

[0070] Step (2): Ultrafiltration of the analysis solution obtained in step (1) with a 30KD ultrafiltration membrane, and the above operating temperatures are all controlled below 20°C. 20L of the filtrate was obtained with a titer of 1007u / mL. The yield was 94.1%.

[0071] Step (3): import the filtrate obtained in step (2) into a macroporous adsorption resin (about 3 L in volume) with a diameter of about 8 cm for adsorption, wash with pure water, elute with 25% ethanol, and then use 45 % ethanol was used for desorption, the ...

Embodiment 3

[0081] Step (1): Introduce 30L of daptomycin filtrate with a titer of 1026u / mL into an ion exchange resin (about 4L in volume) with a diameter of about 10cm for enrichment and adsorption, wash with pure water, and elute with 0.32M NaCl, Finally, desorb with 2.7M NaCl; collect the desorbed solution with a titer greater than 1000u / mL and combine them. The volume of the final analysis solution was 12L, the content of daptomycin was 1820u / mL, and the yield was 71.9%.

[0082] Step (2): Ultrafiltration of the analysis solution obtained in step (1) with a 30KD ultrafiltration membrane, and the above operating temperatures are all controlled below 20°C. Obtain 20L of filtrate, titer is 1020u / mL. The yield was 93.4%.

[0083] Step (3): The filtrate obtained in step (2) is introduced into a macroporous adsorption resin (about 3 L in volume) with a diameter of about 8 cm for adsorption, washed with pure water, eluted with 19% ethanol, and then washed with 40% ethanol The ethanol was ...

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Abstract

The invention provides daptomycin for injection and a preparation method thereof. The daptomycin for injection is prepared by sequentially separating and purifying through ion exchange resin, macroporous adsorption resin, polymer resin and C18 resin, and then crystallizing, redissolving, desalting and carrying out a specific freeze-drying process. The prepared product is high in purity, full in appearance, free of shrinkage and bubbling, porous, high in redissolving speed, low in residual moisture and light in color, and the content, clarity and stability are greatly improved. The quality and the stability of the product are far higher than those of the currently produced product, and the safety of clinical medication is improved. The preparation method is simple in process and more beneficial to industrial production, and has important theoretical significance and application value for production and clinical application of daptomycin for injection.

Description

technical field [0001] The invention relates to the technical field of daptomycin preparation, in particular to a daptomycin for injection and a preparation method thereof. Background technique [0002] Daptomycin is produced by the fermentation of Streptomyces roseospora, which is composed of a decane side chain and a tryptophan at the N-terminus of a cyclic β-amino acid peptide chain consisting of 13 amino acid residues. Acidic lipopeptide antibiotics are also the first cyclolipopeptide antibiotics successfully developed in the world. Daptomycin has a novel structure and a unique bactericidal mechanism. It can destroy the function of bacterial cell membranes in many aspects and kill Gram-positive bacteria. The effectiveness of the effect is long. In addition, daptomycin can quickly kill bacteria without autolysis of cells, and avoid inflammatory reactions caused by the release of teichoic acid, peptidoglycan and DNA, so it is safer than general anti-infective drugs. Dap...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/10A61K9/19A61P31/04
CPCY02A50/30
Inventor 程林沈梅李彦朴张天兵张志江随子华赵辉贾啸静张娴张慧明赵倩姜明星田鑫赵建强程启东刘雨鞠加学张涛毛兰恩赵颖
Owner NORTH CHINA PHARMA COMPANY
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