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Method for preparing florfenicol-chitosan/long-chain carboxylic acid nano-micelle freeze-dried powder

A long-chain carboxylic acid and nano-micelle technology, which is applied in freeze-drying transportation, powder transportation, pharmaceutical formulations, etc., can solve the problems of low bioavailability of common preparations, high cost of use, wide application, and difficulty in forming complexes. Achieve huge social and economic benefits, wide applicability, good research and development and application prospects

Inactive Publication Date: 2018-08-10
QINGDAO UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, florfenicol is almost insoluble in water, only soluble in some organic solvents, and its common preparations have low bioavailability and high cost of use, which limits its wide application.
[0003] Studies have shown that for insoluble or lipophilic drugs, methods such as salt formation, ultrafine pulverization, and complex formation can be used to change the physical and chemical properties of the drug to improve the solubility and dissolution rate of the drug, but these methods have certain limitations. For example, neutral compounds are not suitable for making salts, and the ultrafine powder of drugs obtained by ultrafine grinding will reduce the stability of drugs, and some drugs are difficult to form complexes, etc.

Method used

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  • Method for preparing florfenicol-chitosan/long-chain carboxylic acid nano-micelle freeze-dried powder
  • Method for preparing florfenicol-chitosan/long-chain carboxylic acid nano-micelle freeze-dried powder
  • Method for preparing florfenicol-chitosan/long-chain carboxylic acid nano-micelle freeze-dried powder

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038]First, polyvinyl alcohol-grafted aminopolysaccharide was added into deionized water to completely dissolve to obtain solution I, and then palmitic acid was added to ethanol to dissolve to obtain solution II, and solution I and solution II were mixed, and then the probe was ultrasonically treated and injected into the solution. Wherein add DCC, HOBt catalyst, DCC and HOBT are mixed according to mass ratio (1-3):(2-6), select DCC and HOBT to mix according to mass ratio 1:2 in this embodiment, add pH adjustment reagent to control system acidity and alkalinity pH 1. Control the ultrasonic output power to 10w, the ultrasonic time to 12s, the interval time to 4s, and the number of ultrasonics to 150 times; by controlling the reaction temperature at 5°C and the reaction time at 2h, the polyvinyl alcohol-grafted aminopolysaccharide-palmitic acid self-assembled nanomicelles and The catalyst mixture is separated, dialyzed, freeze-dried and washed to obtain polyvinyl alcohol-grafted...

Embodiment 2

[0040] First add amino polysaccharide to deionized water to completely dissolve to prepare solution I, then add conjugated linoleic acid to dissolve in low-concentration acetic acid to prepare solution II, mix solution I and solution II, then perform ultrasonic treatment on the probe and inject Wherein add EDC, NHS catalyst, EDC and NHS mix according to mass ratio (1-3):(2-6), choose EDC and NHS mix according to mass ratio 2:5 in this embodiment, add pH adjusting reagent control system pH 6. Control the ultrasonic output power to 100w, the ultrasonic time to 10s, the interval time to 10s, and the number of ultrasonics to 100 times; by controlling the reaction temperature to 35°C and the reaction time to 1.5h, amino polysaccharide-conjugated linoleic acid self-assembled nanomicelles and catalysts can be obtained The mixed solution was separated, dialyzed, freeze-dried and washed to obtain aminopolysaccharide-conjugated linoleic acid nanomicelles. Add it to low-concentration ace...

Embodiment 3

[0046] First add the amino polysaccharide quaternary ammonium salt into deionized water to completely dissolve to obtain solution I, then add cis-15-tetradecenoic acid to dissolve in isopropanol to obtain solution II, and mix solution I and solution II , then carry out probe sonication and add PyBop, DIEA catalyst wherein, PyBop and DIEA are mixed according to mass ratio (1-3):(2-6), select PyBop and DIEA to mix according to mass ratio 1:3 in this embodiment, Add a pH adjusting reagent to control the pH of the system to 12, control the ultrasonic output power to 50w, the ultrasonic time to 8s, the interval time to 10s, and the number of ultrasonics to 100 times; by controlling the reaction temperature to 50°C and the reaction time to 1.8h, the amino polysaccharide-cis-15- The mixed solution of tetracosenoic acid self-assembled nanometer micelles and catalyst is separated, dialyzed, freeze-dried and washed to obtain aminopolysaccharide-cis-15-tetracosenoic acid nanometer micelle...

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Abstract

The invention discloses a method for preparing florfenicol-chitosan / long-chain carboxylic acid nano-micelle freeze-dried powder. The method comprises the following steps of (1) dissolving to obtain asolution I of chitosan derivatives; 2) dissolving the long-chain carboxylic acid to prepare a solution II; (3) mixing the solution I and the solution II, adding a catalyst, controlling the pH of a system, and reacting under ultrasonic conditions to obtain a mixing solution of the chitosan-long-chain carboxylic acid self-assembled nano-micelle and the catalyst; (4) making the mixing solution subjected to centrifugation, dialysis treatment, freeze-drying and washing to obtain the chitosan-long-chain carboxylic acid nanomicelle; (5) mixing the chitosan-long-chain carboxylic acid nano-micelle withflorfenicol under the ultrasonic conditions, and filtering and drying to obtain a solid product of the florfenicol-chitosan / long-chain carboxylic acid nano-micelle. The method has the advantages of convenient operation, stability, abundant raw material sources and the like. The self-assembly and ultrasonic pulverization method is adopted, so that the micelle is more dense and the performance is more stable, and the economic development potential is good.

Description

technical field [0001] The invention belongs to the technical field of new drug research and development, and in particular relates to a method for preparing florfenicol-chitosan / long-chain carboxylic acid nano-micelle freeze-dried powder. Background technique [0002] Florfenicol (Flo) is a new generation of chloramphenicol-type animal-specific broad-spectrum antibiotics. It has strong antibacterial activity against a variety of Gram-positive bacteria, Gram-negative bacteria and mycoplasma. Multocida, Pasteurella multocida, and Actinobacillus pleuropneumoniae are highly sensitive, and Florfenicol can pass through the blood-brain barrier and has a good therapeutic effect on animal bacterial meningitis. In vitro tests show that the antibacterial activity of florfenicol is significantly better than that of chloramphenicol, tetracycline, and ampicillin, and it has broad application prospects in the prevention and treatment of animal diseases. However, florfenicol is almost ins...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K47/54A61K9/19A61K9/107A61K31/165A61P31/04
CPCA61K47/542A61K47/61A61P31/04A61K9/1075A61K9/19A61K31/165
Inventor 宋益民齐晓丹贾喜乐李媛媛周莉罗尚满华潘爱红
Owner QINGDAO UNIV OF SCI & TECH
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