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A kind of bmp-2/ppla microsphere and preparation method thereof

A BMP-2, microsphere technology, applied in microcapsules, pharmaceutical formulations, peptide/protein components, etc., can solve the problems of unstable microspheres, different particle sizes of microspheres, short half-life, etc. Adhesion, diversified administration routes, simple and easy-to-control effects

Active Publication Date: 2020-10-02
SHANDONG UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as a protein drug, BMP-2 has the common disadvantages of protein drugs: poor biological stability, short half-life, diffuses or degrades with body fluids soon after entering the human body, cannot exert long-acting effects at the application site, and cannot reach expected treatment effect
For example, the Chinese patent application "a preparation method of PELA / BMP-2 microspheres" (CN104511019A) has prepared microspheres with good smoothness and good fluidity, but the disadvantage is that the use of ultrasonic method will lead to different particle sizes of microspheres , making the prepared microspheres unstable, and the phacoemulsification operation is difficult to control, which easily leads to microsphere rupture and protein denaturation
[0006] In addition, clinical non-injectable solid stents, that is, surgically implanted stents, porous stents (or nanofibrous stents) integrated with growth factors or chemicals in advance or before use, are mostly in the shape of thin films, sheets shape, block, etc., due to its large size and certain rigidity, it must be implanted through surgery, and the operation is complicated

Method used

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  • A kind of bmp-2/ppla microsphere and preparation method thereof
  • A kind of bmp-2/ppla microsphere and preparation method thereof
  • A kind of bmp-2/ppla microsphere and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1: Preparation of BMP-2-PPLA-MS

[0038](1) Weigh a certain mass of PPLA and dissolve it in dichloromethane, shake and dissolve with a vortex machine, and prepare a solution with a PPLA concentration of 90 mg / ml. Take a certain volume of PPLA (molecular weight is 50000Da) solution and place it in the EP tube, add BMP-2 protein stock solution (concentration is 0.55mg / ml), control the volume ratio of BMP-2 protein stock solution and PPLA solution added to be 1: 5. Use a homogenizer to emulsify for the first time in an ice bath environment, with a shear speed of 15000 rpm and a time of 20 s, to obtain colostrum.

[0039] (2) Weigh a certain mass of PVA and dissolve it in a certain volume of distilled water, swell overnight and stir to dissolve or heat to 80 to 90°C to dissolve, configure it as a solution with a PVA mass fraction of 4%, cool to room temperature after the dissolution is complete, and Add a certain volume of PVA solution to the colostrum obtained ...

Embodiment 2

[0052] Embodiment 2: Preparation of BMP-2-PPLA-MS

[0053] (1) Weigh a certain mass of PPLA and dissolve it in dichloromethane, shake and dissolve with a vortex machine, and prepare a solution with a PPLA concentration of 95 mg / ml. Take a certain volume of PPLA (molecular weight is 50000Da) solution and place it in the EP tube, add BMP-2 protein stock solution (concentration is 0.55mg / ml), control the volume ratio of BMP-2 protein stock solution and PPLA solution added to be 1: 5. Use a homogenizer to emulsify for the first time in an ice bath environment with a shearing speed of 16,000 rpm and a time of 15 s to obtain colostrum.

[0054] (2) Weigh a certain mass of PVA and dissolve it in a certain volume of distilled water, swell overnight and stir to dissolve or heat to 80 to 90°C to dissolve, configure it as a solution with a PVA mass fraction of 4%, cool to room temperature after the dissolution is complete, and Add a certain volume of PVA solution to the colostrum obtain...

Embodiment 3

[0058] Embodiment 3: the preparation of BMP-2-PPLA-MS

[0059] (1) Weigh a certain amount of PPLA and dissolve it in dichloromethane, shake and dissolve with a vortex machine, and prepare a solution with a PPLA concentration of 85 mg / ml. Take a certain volume of PPLA (molecular weight is 50000Da) solution and place it in the EP tube, add BMP-2 protein stock solution (concentration is 0.55mg / ml), control the volume ratio of BMP-2 protein stock solution and PPLA solution added to be 1: 5. Use a homogenizer to emulsify for the first time in an ice bath environment with a shear speed of 14000 rpm and a time of 25 s to obtain colostrum.

[0060] (2) Weigh a certain mass of PVA and dissolve it in a certain volume of distilled water, swell overnight and stir to dissolve or heat to 80 to 90°C to dissolve, configure it as a solution with a PVA mass fraction of 4%, cool to room temperature after the dissolution is complete, and Add a certain volume of PVA solution to the colostrum obta...

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Abstract

The invention discloses BMP-2 / PPLA (bone morphogenetic protein-2 / polylactic acid and polyethylene glycol block copolymer) microspheres and a preparation method thereof. The method comprises stages as follows: a stage of preparing an initial emulsion by dissolving or dispersing BMP-2 in an emulsion phase with PPLA dissolved; a stage of preparing a compound emulsion by dispersing the initial emulsion in a PVA solution; a stage of preparing the microspheres encapsulated with BMP-2 after an organic solvent in the compound emulsion is removed. The PPLA is taken as a supporter material, BMP-2 is subjected to entrapment with a compound emulsion solvent evaporation method, and the microspheres are prepared; the obtained microspheres have smooth surfaces, uniform sizes and high stability and can be used for local injection administration, so that BMP-2 acts on application parts in a long-acting and stable manner, and bone growth is promoted.

Description

technical field [0001] The invention relates to the technical field of preparation of bone repair materials, in particular to a BMP-2 / PPLA microsphere and a preparation method thereof. Background technique [0002] Bone defect refers to the destruction of the structural integrity of the bone, which is a common clinical disease. Trauma, infection, tumor, surgical debridement of osteomyelitis, and various congenital diseases are the main causes of bone defects. Conventional surgical treatment often brings unbearable pain to patients, and the therapeutic effect is unpredictable, which often leads to the occurrence of nonunion. The main means of clinical treatment of bone defects is autologous bone grafting or allogeneic bone grafting, and bone growth factors are needed to promote the healing of bone defects. [0003] Bone morphogenetic protein-2 (bone morphogenetic protein-2, BMP-2) is an earlier researched bone growth factor, which has a strong osteogenic effect, can induce ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/18A61K9/50A61K47/34A61P19/08
CPCA61K9/0019A61K9/5031A61K9/5089A61K38/1875
Inventor 林贵梅宋燕媚俸小芊李玥史岩彬
Owner SHANDONG UNIV
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