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A simple method for preparing plga microspheres with uniform particle size

A particle size and microsphere technology, applied in the field of PLGA microspheres, can solve the problems of high rotation speed, poor repeatability of results, uneven particle size, etc., and achieve the effects of uniform particle size distribution, high enrichment yield and simple equipment

Active Publication Date: 2018-03-06
INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Stirring emulsification method is relatively cheap and simple, and the particle size is controlled by stirring speed and time, but because the force of the liquid is very uneven during the emulsification process, the formed particle size is very uneven
Although microspheres of comparable size can be enriched to a certain extent by differential centrifugation, the yield of enriched microspheres is very low (<30%) due to the wide particle size distribution of microspheres.
In addition, using this method to prepare small-sized microspheres requires a very high rotational speed. For example, obtaining 1-2 μm microspheres requires a stirring speed of nearly 10,000 rpm, which requires more professional equipment; ultrasonic emulsification is generally used to prepare nano-scale microspheres , not suitable for the preparation of micron-sized microspheres; the spray drying method not only requires special equipment, but also has poor particle size uniformity; the membrane emulsification method obtains PLGA particles with better uniformity, but the cost of professional equipment and consumables is high
Due to the above-mentioned limitations of existing methods, the quality and uniformity of PLGA microspheres prepared in many studies are not good, and the repeatability of the results is poor; while PLGA microspheres with better uniformity can only be completed in more professional laboratories

Method used

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  • A simple method for preparing plga microspheres with uniform particle size
  • A simple method for preparing plga microspheres with uniform particle size
  • A simple method for preparing plga microspheres with uniform particle size

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Preparation of PLGA Microspheres Assisted by Glass Beads

[0025] (1) Preparation of the oil phase: Weigh 0.6g of PLGA, dissolve it in 10mL of dichloromethane, and prepare a 6% PLGA solution;

[0026] (2) Preparation of PVA aqueous solution: Weigh 2.5g of PVA solid, add it into 100mL distilled water, heat and stir to fully dissolve, and prepare 2.5% PVA aqueous solution;

[0027] (3) Glass bead assisted emulsification: In glass bottles of appropriate size, add 10 mL of 2.5% PVA solution to each bottle, and disperse 1 mL of 6% PLGA oil phase solution, then add a magnetic stirrer rotor and several 4- Glass beads with a diameter of 6 mm were stirred for 3 hours at 400 rpm, 800 rpm, and 1000 rpm, respectively;

[0028] (4) Volatility of the organic solvent: after the glass bead-assisted emulsification is completed, the glass bead is taken out and stirred at a low speed for 12-24 hours to fully volatilize the dichloromethane organic solvent;

[0029] (5) Collect...

Embodiment 2

[0032] Example 2: Enrichment of PLGA microspheres with uniform particle size

[0033] In this example, PLGA microspheres prepared by emulsifying at 1000 rpm for 1 hour were used as samples to enrich PLGA microspheres with uniform particle size, the main purpose of which was to enrich and prepare microspheres with a diameter of 2-3 μm.

[0034] (1) Preparation of the oil phase: Weigh 0.6g of PLGA, dissolve it in 10mL of dichloromethane, and prepare a 6% PLGA solution;

[0035] (2) Preparation of PVA aqueous solution: Weigh 2.5g of PVA solid, add it into 100mL distilled water, heat and stir to fully dissolve, and prepare 2.5% PVA aqueous solution;

[0036] (3) Glass bead assisted emulsification: In glass bottles of appropriate size, add 10 mL of 2.5% PVA solution to each bottle, and disperse 1 mL of 6% PLGA oil phase solution, then add a magnetic stirrer rotor and several 4- 6mm diameter glass beads, stirred at 1000 rpm for 1 hour;

[0037] (4) Volatility of the organic solven...

Embodiment 3

[0042] Example 3: Preparation of PLGA drug-loaded microspheres encapsulating rifampin drug and 2-3 μm particle size

[0043] (1) Preparation of the oil phase: Weigh 0.6g PLGA and 0.05g rifampicin and dissolve them together in 10mL of dichloromethane to prepare a solution containing 6% PLGA and 0.5% rifampicin;

[0044] (2) Preparation of PVA aqueous solution: Weigh 2.5g of PVA solid, add it into 100mL distilled water, heat and stir to fully dissolve, and prepare 2.5% PVA aqueous solution;

[0045] (3) Glass bead assisted emulsification: In a glass bottle of appropriate size, add 10mL of 2.5% PVA solution to each bottle, and disperse 1mL of 6% PLGA oil phase solution in it, then add a magnetic stirrer rotor and several 5 - Glass beads with a diameter of 6 mm, stirred for 1 hour at 1000 rpm;

[0046] (4) Volatilization of organic solvents: after glass bead-assisted emulsification is completed, take out glass beads and stir at a low speed for 12-24 hours to fully volatilize the ...

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Abstract

The invention provides an improved stirring emulsification method for preparing PLGA microspheres with uniform particle size. The particle size distribution of the microspheres prepared by the method is relatively narrow, and the PLGA microspheres with uniform particle size can be obtained with a high yield through simple centrifugal enrichment. The preparation process is as follows: dissolving PLGA in dichloromethane as the oil phase, using the PVA solution as the water phase, dispersing the oil phase into the water phase in a certain proportion, adding several glass beads with a diameter of 2‑8mm to assist emulsification, and then Stirring and emulsification under a magnetic stirrer; PLGA microspheres with uniform particle size were obtained by volatilization of organic solvents, washing, and enrichment by differential centrifugation.

Description

technical field [0001] The invention relates to a preparation process of polymer microspheres, in particular to PLGA microspheres with uniform particle size distribution, and belongs to the technical field of biomedical materials. Background technique [0002] Polylactic acid hydroxylactic acid (PLGA) is a biodegradable polymer material that can eventually degrade into carbon dioxide and water in the body. It is safe, non-toxic and has good biocompatibility. It is regarded as an excellent medical material and has been approved by the United States. Food and Drug Administration (FDA) approved for clinical use. Microsphere carriers prepared from PLGA materials have important uses in the field of biomedicine and have been extensively studied, including drug delivery, antibody preparation, vaccine adjuvants, etc. At present, the FDA has approved a variety of pharmaceutical preparations based on PLGA microspheres to enter the clinic, such as LupronDeport and so on. In 2009, my ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/32A61K31/395
Inventor 刘志强冯晓燕张贺秋段翠密修冰水张旭辉杨锡琴阙海萍
Owner INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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