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Preparation method and products of danofloxacin mesylate liposome

A technology of dafloxacin mesylate lipid and dafloxacin mesylate, which is applied in the preparation of dafloxacin mesylate lung-targeted liposomes and the field of preparation of veterinary drugs, and can solve the production process Complicated, expensive, nephrotoxic and other problems, to achieve the effect of good dispersion, good stability and long efficacy

Inactive Publication Date: 2011-10-19
NORTHEAST AGRICULTURAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with other third-generation quinolones, danofloxacin has milder adverse reactions, but it also has certain neurotoxicity, hepatotoxicity and nephrotoxicity, and there are problems such as high price and complicated production process.

Method used

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  • Preparation method and products of danofloxacin mesylate liposome
  • Preparation method and products of danofloxacin mesylate liposome
  • Preparation method and products of danofloxacin mesylate liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The preparation of embodiment 1 dafloxacin mesylate liposome of the present invention

[0023] Egg yolk lecithin (EPC) and cholesterol (CH) with a weight ratio of 3:2 and 2.6% stearylamide (SA) of the two weights were thoroughly mixed, dissolved with anhydrous ether, and then evaporated under reduced pressure on a rotary basis. Remove the ether to obtain a uniform translucent phospholipid film. After vacuum drying for 24 hours, add 250mmol / L ammonium sulfate solution to elute. The resulting blank liposomes are sized through a 3μm microporous filter membrane and dialyzed 3 times with 150mmol / L NaCl solution at room temperature. , 24 hours each time; take the blank liposomes after dialysis, add 10mg / mL dafloxacin mesylate solution, the ratio of drug to lipid is 2:5, adjust the pH value with 100mmol / L NaOH solution, and then place it at 35 Incubate in a water bath at ℃ for 15 minutes, quantify with PBS solution, and use the freeze-thaw method to filter the suspension with ...

Embodiment 2

[0025] The preparation of embodiment 2 dafloxacin mesylate liposomes of the present invention

[0026] Egg yolk lecithin (EPC) and cholesterol (CH) with a weight ratio of 4:3 and 2.8% stearylamide (SA) of the two weights were thoroughly mixed, dissolved in anhydrous ether, and then evaporated under reduced pressure on a rotary basis. Remove the ether to obtain a uniform translucent phospholipid film. After vacuum drying for 32 hours, add 280mmol / L ammonium sulfate solution to elute. The obtained blank liposomes are sized through a 3μm microporous filter membrane and dialyzed 3 times with 150mmol / L NaCl solution at room temperature. , each time for 32 hours; take the blank liposome after dialysis, add 10mg / mL dafloxacin mesylate liquid, the ratio of drug to lipid is 2:6, adjust the pH value with 100mmol / L NaOH solution, and then place it at 37 Incubate in a water bath at ℃ for 12 minutes, quantify with PBS solution, and use the freeze-thaw method to filter the suspension with a...

Embodiment 3

[0028] Embodiment 3 The preparation of dafloxacin mesylate liposome of the present invention

[0029]Egg yolk lecithin (EPC) and cholesterol (CH) with a weight ratio of 3:2.5 and stearamide (SA) of 3.0% by weight of the two were thoroughly mixed, dissolved in anhydrous ether, and evaporated under reduced pressure on a rotary basis. Remove the ether to obtain a uniform translucent phospholipid film. After vacuum drying for 24 hours, add 200mmol / L ammonium sulfate solution to elute. The resulting blank liposomes are sized through a 3μm microporous filter membrane and dialyzed 3 times with 150mmol / L NaCl solution at room temperature. , 24 hours each time; take the blank liposome after dialysis, add 10mg / mL dafloxacin mesylate liquid, the ratio of drug to lipid is 2:3, adjust the pH value with 100mmol / L NaOH solution, and then place it at 35 Incubate in a water bath at ℃ for 15 minutes, quantify with PBS solution, and use the freeze-thaw method to filter the suspension with a 3 μm...

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Abstract

The invention provides a preparation method and products of danofloxacin mesylate liposome. The preparation method comprises the following steps: (1) adopting the ammonium sulfate gradient method to prepare blank liposome; and (2) adding danofloxacin mesylate liquor in the blank liposome, using water bath for incubation, filtrating, and performing repeated freeze thawing to the filtrate by using the freeze and thawing method to obtain the danofloxacin mesylate liposome. The finished liposome prepared by the preparation method of the invention is milky semitransparent mixed suspension which appears as spherical or nearly globose small vesicles with regular shape, good dispersity and uniform grain size under an electron microscope; the entrapment rate of the liposome is above 90% and the liposome has good stability; the pharmacokinetic and pharmacodynamic properties of the liposome are better than that of conventional dosage forms and the liposome is characterized by slow release, long acting and high lung-targeting.

Description

technical field [0001] The invention relates to a preparation method of veterinary medicine, in particular to a preparation method of dafloxacin mesylate lung-targeted liposome and its product, belonging to the field of veterinary medicine. Background technique [0002] The lipid system refers to the microvesicles formed by encapsulating drugs in lipid bilayers, also known as lipid globules or liquid crystal microcapsules, which belong to the microparticle drug delivery system. Its main components are phospholipids (such as phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid), phosphatidylserine, etc. As a new type of drug-targeted preparation, liposomes can improve the physical and chemical properties of drugs, enhance the directivity and retention of drugs to target tissues, improve the distribution of drugs in local tissues, and reduce drug dosage and treatment Cost, reduce drug toxicity to normal cells and improve bioavailability, etc. In the late 1960s, R...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K31/4709A61K47/28A61P11/00A61P31/04
Inventor 李继昌丁良君姜晓文张秀英王春仁柳影李丽
Owner NORTHEAST AGRICULTURAL UNIVERSITY
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