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Self-solidified microspheres and preparation method and application thereof

A self-curing, microsphere technology, applied in cosmetic preparations, fixed on/in organic carriers, pharmaceutical formulations, etc., can solve the problem of reducing the uniformity of microsphere particle size, difficulty in droplet shedding, slow emulsification speed, etc. problems, to achieve the effect of maintaining activity, facilitating diffusion, and the preparation method is simple and mild

Active Publication Date: 2013-01-09
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, when preparing microspheres with a particle size of less than 10 microns, the membrane pore size used is very small (usually less than 3 microns), and the emulsification speed is still very slow even at a higher transmembrane pressure, especially when the temperature sensitive The emulsification speed is slower when the viscosity is higher, and the higher viscosity will make it difficult for the generated droplets to fall off the membrane surface, requiring a longer emulsification process
Increasing the pressure can increase the emulsification speed to a certain extent, but too much pressure will reduce the uniformity of the particle size of the microspheres

Method used

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  • Self-solidified microspheres and preparation method and application thereof
  • Self-solidified microspheres and preparation method and application thereof
  • Self-solidified microspheres and preparation method and application thereof

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preparation example Construction

[0059] The method for preparing the above-mentioned self-curing microspheres of the present invention comprises the steps of:

[0060] (1) Provide a solution of a temperature-sensitive material added with a biologically active substance or a functional component as a dispersed phase;

[0061] The active substance or functional ingredient must be completely dissolved or uniformly dispersed in the dispersed phase in step 1, and the functional ingredient can be selected from proteins, polypeptides, enzymes, vaccines, cells, genes, hormones, antibiotics, anticancer drugs One or more of animal and plant extracts and their mixtures, the concentration of functional components in the dispersed phase is 0-10g / mL. The concentration of the functional components in step 1 may be 0 g / mL, and blank microspheres are prepared at this time.

[0062] In some embodiments of the method of the present invention, the solution of the thermosensitive material in step 1 is chitosan-glycerophosphate m...

Embodiment 1

[0094] Hydrophobic modification of the membrane: soak the hydrophilic SPG membrane with a pore size of 1.4 μm in the mixed oil phase of liquid paraffin and petroleum ether (petroleum ether boiling range is 60-90°C, volume ratio 5:7) overnight to make the membrane pores Fully moist.

[0095] Dispersed phase preparation: temperature sensitive material selects chitosan-glycerophosphate system, and its preparation method is: accurately weigh a certain amount of chitosan and dissolve in 9mL acetic acid solution (0.1mol / L), make it under magnetic stirring Fully dissolve to obtain chitosan acetic acid solution; another certain amount of sodium glycerophosphate is dissolved in 1mL deionized water. After the chitosan acetic acid solution and the sodium glycerophosphate solution were incubated at 4°C for 10 minutes, the sodium glycerophosphate solution was slowly added dropwise to the chitosan acetic acid solution, and magnetically stirred (300 rpm, 10 minutes) to mix them evenly. The ...

Embodiment 2

[0099] Chitosan microspheres are prepared using the same device and method as in Example 1, wherein the difference is that the membrane aperture of the SPG membrane used is 10.2 microns, and the hydrophobic modification step of the membrane is: the hydrophilic SPG membrane is placed in pure water at normal temperature Sonicate for 30 minutes, then put into 3% (V / V) modifier KP-18C (origin: Japan) aqueous solution, then depressurize (vacuum degree: 0.5MPa) sonicate for 2h, and then heat at 120°C for 4h.

[0100] Dispersed phase: the concentration of chitosan in the dispersed phase is 0.8wt.%, the concentration of sodium glycerophosphate in the dispersed phase is 8.0wt.%, the solvent is a hydrochloric acid solution of 0.1mol / L, and its LCST is 60°C.

[0101] Continuous phase: The continuous phase is a mixture (volume ratio of 2:1) of liquid paraffin and petroleum ether (the boiling range of petroleum ether is 90-120°C), the emulsifier is polyoxyethylene hydrogenated castor oil, a...

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Abstract

The invention provides self-cured microspheres, which are prepared from a temperature-sensitive material with a lower critical soluble temperature, wherein the average particle size of the self-cured microspheres is in the range of 50nm to 100 microns, and the particle size distribution coefficient of the self-cured microspheres is smaller than 20%. The self-cured microspheres are prepared by thefollowing steps of: 1) providing a solution of the temperature-sensitive material added with bioactive substances or functional components as a dispersed phase; 2) providing emulsifying agent dissolved solvents which are dispersed and are insoluble with each other as continuous phases; 3) dispersing the dispersed phase in step 1) into the continuous phases in step 2) to obtain a pre-emulsion; 4) enabling the pre-emulsion in step 3) to pass through a microporous membrane for one time or a plurality of times under a pressure to obtain an emulsion; 5) heating the emulsion in step 4) to above thelower critical soluble temperature of the adopted temperature-sensitive material, so that liquid drops are cured to obtain the microspheres. The self-cured microspheres is suitable for serving as carriers of bioactive substances.

Description

technical field [0001] The invention relates to the field of drug carriers in the fields of medicine, biochemical industry and the like. [0002] In particular, the present invention relates to self-curing microspheres. [0003] The present invention also relates to a preparation method of the above-mentioned self-curing microspheres. [0004] The present invention also relates to the application of the self-curing microsphere as a bioactive material carrier. Background technique [0005] In the fields of medicine, biochemical industry, cosmetics, health products, and tissue engineering, biologically active substances are often used, such as proteins, polypeptides and other biological macromolecular substances with large molecular weight and complex spatial structure. Such substances are easily destroyed by complex physiological environments, especially a large number of enzymes, during drug delivery. In order to solve this problem, people have mainly used injections for ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/36A61K47/34A61K47/38A61K8/02A61K8/73A61K8/86A61K8/81C12N11/04
Inventor 马光辉吴颉吴有斌苏志国王月琦
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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