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Method for preparing protein-polysaccharide vitreum slow release microsphere by using low-temperature aqueous-aqueous phase emulsion

A slow-release technology of microspheres and proteins, applied in pharmaceutical formulations, drug delivery, etc., can solve problems such as aggregation

Inactive Publication Date: 2007-02-07
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some protein molecules may interact with polyelectrolytes, causing aggregation

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: Preparation of microspheres

[0029] 1. Preparation of protein-polysaccharide vitreous

[0030] Prepare 10% polyethylene glycol and 10% polysaccharide aqueous solutions with ultrapure water, accurately weigh 10 g of PEG and 10 g of polysaccharide water into a 100 ml beaker, add 90 g of water, and then place the two beakers on heating Magnetic stirring for 30min, after the PEG and 10% polysaccharide are all dissolved, take it out and cool it for later use. Use an electronic balance to accurately weigh 800 mg of protein and dissolve it in 7.2 ml of water for later use.

[0031] ① Under the condition of 0℃-4℃, put the above-mentioned polysaccharide, protein and PEG aqueous solution in volume ratio of 1:1:5, 1:1:10, 1:1:20, 1:1:40 in a vial Vortex for 30s-60s to mix well to form a water phase-water phase emulsion; or weigh according to the mass ratio of polysaccharide and PEG as 1:1:5, 1:1:10, 1:1:20, 1:1:40 In the vial, mix well and then add water to dissolve, and t...

Embodiment 2

[0042] Implementation Example 2: Preparation of controlled release and sustained release PLGA microspheres

[0043] 1. Prepare the protein-polysaccharide vitreous body according to the method of Example 1

[0044] 2. Preparation of microspheres loaded with protein-polysaccharide vitreous

[0045] Weigh 100 mg of polylactic acid-polyglycolic acid (PLGA) and fully dissolve it in 1 ml of acetonitrile under the action of a vortex mixer, then weigh 10 mg of one-step particles into the acetonitrile solution, and fully disperse it under magnetic stirring . Add 200ml of cottonseed oil surfactant span80 to a certain amount of the outer oil phase solution, and mix it thoroughly with an electric stirrer at 200 rpm. The acetonitrile solution with one-step particles was added dropwise to the stirring outer oil phase solution, stirred and solidified for 5 hours, and filtered with suction. The obtained microsphere particles were washed three times with 50ml petroleum ether, dried under reduced p...

Embodiment 3

[0047] Example 3: Preparation of glass body temperature-sensitive gel loaded with protein-polysaccharide

[0048] 1. Preparation of apopolysaccharide vitreous body according to the method of Example 1

[0049] 2. Preparation of protein-polysaccharide vitreous thermosensitive fluid-colloid

[0050] Weigh 10 mg of protein-polysaccharide vitreous particles, uniformly disperse them in 0.5 g of PLGA-PEG-PLGA aqueous solution at 4°C, the concentration of PLGA-PEG-PLGA is 20% (W / W), magnetically stir for 15 minutes at 1800 rpm , Fully stir to make the protein-polysaccharide vitreous particles uniformly dispersed in the PLGA-PEG-PLGA solution, and the resulting suspension uniformly dispersed in PLGA-PEG-PLGA is heated to 37°C to solidify for in vitro release. The clinical application is now available for immediate use.

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PUM

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Abstract

The invention discloses a protein-polysaccharide glass slow releasing microball preparing method of low-temperature water phase-water phase emulsion, which comprises the following steps: allocating water-phase-water-phase emulsion; freezing the emulsion; freeze-drying the sample to obtain the protein-polysaccharide glass; dispersing the micro-particle of protein-polysaccharide in the primary emulsion of oil-soluble macromolecular solution; forming water-in-oil in the water-phase; or forming primary emulsion to decompose macromolecular solution; spraying to dry; adding addictive in the gel; fitting for peptide, antibody or grease body agent.

Description

Technical field [0001] The invention relates to a preparation method in the field of biotechnology. In particular, it is a method for preparing protein-polysaccharide vitreous sustained-release microspheres by low-temperature water-water emulsion. Background technique [0002] Due to poor absorption and short half-life in the body, most protein drugs need to be administered by frequent injections. In order to reduce the frequency of such injections, since the 1970s, the development of sustained-release dosage forms of such drugs has attracted a lot of attention from scientists in the field, and it is still a topic that is still being tackled. However, a large amount of scientific research investment has not achieved the expected results. So far, there has not been a successful product (the only sustained-release protein drug formulation-recombinant human growth hormone), which failed soon after it was launched and was withdrawn from the market. The main obstacle that technology c...

Claims

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Application Information

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IPC IPC(8): A61K9/64
Inventor 袁伟恩金拓吴飞
Owner SHANGHAI JIAO TONG UNIV
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