Preparation method of volume controllable PLGA microsphere

A PLGA and microsphere technology, applied in prosthesis, pharmaceutical formulations, medical science and other directions, can solve the problems such as the inability to flexibly control the size of PLGA microspheres, increase the complexity and cost of the preparation process, and the unchangeable particle size of PLGA microspheres, etc. To achieve the effect of reducing adverse reactions, protecting from damage, reducing drug toxicity and irritation

Active Publication Date: 2019-06-18
SHANGHAI UNIV OF T C M
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  • Claims
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Problems solved by technology

However, the size of the PLGA microspheres obtained by this method cannot be flexibly regulated, because the size of the PLGA microspheres depends on the size of the initial emulsified droplets formed in the emulsion preparation stage. Once the emulsion preparation is completed, the particle size of the PLGA microspheres generated after extraction will be unchangeable
[0009] Although the existing supercritical fluid emulsion extraction method can prepare PLGA microspheres with good formability and good stability, there is a disadvantage that the particle size of PLGA microspheres depends entirely on the initial emulsified droplets, and its size cannot be adjusted. The size of the initial emulsified droplets is not easy to control and is not intuitive, which will increase the complexity and cost of the preparation process

Method used

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  • Preparation method of volume controllable PLGA microsphere
  • Preparation method of volume controllable PLGA microsphere
  • Preparation method of volume controllable PLGA microsphere

Examples

Experimental program
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Effect test

Embodiment 1

[0051] Embodiment 1 supercritical fluid emulsion extraction method prepares PLGA microsphere

[0052] The common preparation methods of PLGA microspheres include the traditional emulsification solvent evaporation method and the emerging supercritical fluid injection method and supercritical fluid emulsion extraction method. This example uses the supercritical fluid emulsion extraction method as the preparation method to illustrate the PLGA microspheres. Ball preparation process.

[0053] Preparation of PLGA emulsion: 100 mg of PLGA (LA / GA=75 / 25, Mw50k) was weighed and dissolved in 10 ml of dichloromethane at room temperature as the oil phase. Dissolve PVA (Mw 20k-30k) in deionized water as the water phase. 10ml oil phase is dripped in 40ml water phase, under the action of the high-speed shear machine of 10000rpm, form the colostrum of coarse dispersion system under rotating speed; W-type PLGA emulsion.

[0054] Preparation of PLGA microsphere suspension: First, while heatin...

Embodiment 2

[0057] Example 2 Supercritical fluid water injection method to prepare volume-controllable PLGA microspheres

[0058] The PLGA microsphere suspension prepared in Example 1 is placed in the supercritical kettle 7, while the supercritical kettle 7 is heated and heated, the liquid carbon dioxide in the carbon dioxide steel cylinder 1 is condensed by the low temperature constant temperature tank of the condenser 2, and then passed through the high pressure After the pump 3 is compressed to the pressure-stabilizing tank, the pressure-stabilizing tank is preheated by the preheater 4, and then pumped into the supercritical kettle 7 through the outer channel of the coaxial two-flow nozzle to increase the pressure in the supercritical kettle 7. After the temperature and pressure in 7 rise to the preset supercritical temperature of 35°C and pressure of 10MPa, stabilize for a period of time, close the outlet valve and inlet valve of the supercritical kettle 7, and form airtight supercriti...

Embodiment 3

[0060] Example 3 Investigation of Pressure Factors of Supercritical Fluid Water Injection Method

[0061] The present embodiment supercritical fluid water injection method is the same as embodiment 2, keeps the supercritical temperature in the supercritical kettle 7 constant, and the swelling time is constant, and investigates with pressure (0MPa, 10MPa, 15MPa, 20MPa) as a single factor variable, According to the preparation method of Example 1, a PLGA microsphere suspension with a particle size of 0.1 to 1 μm was prepared, and it was used as a sample of this example, and the results were as follows image 3 shown. Electron micrograph of unswollen PLGA microsphere suspension under 0MPa pressure image 3 As shown in (A), the particle size of PLGA microspheres is 0.1-1 μm; the electron micrograph of PLGA microsphere suspension after swelling under 10MPa supercritical pressure condition is as follows image 3 As shown in (B), the particle size of PLGA microspheres is 1-4 μm; th...

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Abstract

Belonging to the field of macromolecule materials, the invention in particular relates to a preparation method of a volume controllable PLGA (poly(lactic-co-glycolic acid)) microsphere. The preparation method of the volume controllable PLGA microsphere includes: placing a PLGA microsphere suspension in a supercritical kettle for formation of supercritical carbon dioxide, and swelling the PLGA microsphere with supercritical carbon dioxide dissolved in water. In the process of preparing the PLGA microsphere by the preparation method provided by the invention, by adjusting the supercritical process factors (like temperature, pressure, etc.), the molecular weight of PLGA, the ratio of LA and GA in PLGA and other influence factors, the particle size of the PLGA microsphere can be flexibly controlled. The PLGA microsphere prepared by the method provided by the invention has uniform size, no aggregation bonding, hollow interior structure, and increasable microsphere particle size, specific surface area and pore diameter, and provides ideas for different applications in pharmaceutical and medical fields.

Description

technical field [0001] The invention belongs to the field of polymer materials, and in particular relates to a volume-controllable PLGA microsphere, its preparation method and application. Background technique [0002] Poly(lactic-co-glycolic acid), PLGA is randomly polymerized from lactic acid (LA) and glycolic acid (GA). Molecular organic compounds have good biocompatibility, non-toxicity, good encapsulation and film-forming properties, and are widely used in pharmaceuticals, medical engineering materials and modern industrial fields. [0003] The microsphere system prepared by polylactic acid-glycolic acid copolymer can protect the drug from damage, deliver the drug to certain special tissues, delay / control the release of the drug, prolong the drug action time, and reduce the toxicity and irritation of the drug. The advantages of PLGA microspheres have become a research hotspot for targeted sustained and controlled release drug carriers. [0004] Polylactic acid-glycoli...

Claims

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Application Information

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IPC IPC(8): C08J7/02A61K9/16A61K9/72A61L27/18A61L27/50C08L67/04
CPCY02P20/54
Inventor 冯年平党蓓蕾
Owner SHANGHAI UNIV OF T C M
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