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Porous calcium phosphate support loaded microsphere composite material, as well as preparation method and application thereof

A technology of porous calcium phosphate and loaded microspheres, which is applied in the field of medicine to achieve the effect of reducing recurrence and treating bone and joint tuberculosis

Inactive Publication Date: 2019-03-08
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a porous calcium phosphate scaffold-loaded microsphere composite material, which overcomes the deficiency that the existing topical medication cannot maintain an effective bactericidal concentration of anti-tuberculosis drugs in the residual cavity for a long time

Method used

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  • Porous calcium phosphate support loaded microsphere composite material, as well as preparation method and application thereof
  • Porous calcium phosphate support loaded microsphere composite material, as well as preparation method and application thereof
  • Porous calcium phosphate support loaded microsphere composite material, as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] 3D printing of porous β-TCP scaffold and determination of its porosity

[0075] 1.1 3D printing of porous β-TCP scaffold

[0076] The porous β-TCP model to be printed is constructed by computer-aided design (CAD). Figure 1-1 to Figure 1-3 As shown, the use of β-tricalcium phosphate powder with a particle size of 2 μm, dilute citric acid, potassium dihydrogen phosphate, silicon dioxide, zinc oxide, and paraffin microspheres with a diameter of 2-8 μm (by mass percentage, the proportion is 55: 2.5:22.5:10:6.5:3.5), to prepare printing ink. A 750μm nozzle is selected, the walking speed is 100mm / min, the thickness of each layer is 750μm, and the intervals between layers on the X, Y, and Z axes are all 400μm. After spraying the β-TCP solution by the 3D-Bioplotter printer, the β-TCP stent was sintered at a constant temperature of 1100°C for 2 hours, and finally the finished product such as diagram 2-1 and Figure 2-2 shown. The cylindrical scaffold with a pore size of 4...

Embodiment 2

[0088] Preparation method and in vitro release of isoniazid and rifampicin sustained-release microspheres

[0089] 2.1 Preparation method of isoniazid and rifampicin sustained-release microspheres

[0090] Weigh 20 mg of isoniazid, 15 mg of rifampicin, 60 mg of PLGA and 600 mg of PVA (polyvinyl alcohol), put 600 mg of PVA into a small beaker and add 30 ml of ultrapure water, heat bath until PVA is completely dissolved, and use it as an adhesive for later use; The process of making microspheres by emulsion solvent evaporation method is as follows: Figure 4 As shown, isoniazid was added to 2ml of ultrapure water, vortexed for 3 minutes to mix well, and used as the water phase for later use; 2ml of dichloromethane was added to rifampicin and PLGA, and used as the oil phase for later use. Put the above into the refrigerator at 4°C for 1 hour, add the water phase to the oil phase, mix, homogenize, emulsify, accelerate the reaction, etc. through the ultrasonic breaker, then quickl...

Embodiment 3

[0096] PLGA anti-tuberculosis drug sustained-release microspheres loaded into porous β-TCP scaffold

[0097] Shake and stir the double-distilled water solution of PLGA anti-tuberculosis drug slow-release microspheres, mix the microspheres and add them to flat-bottomed centrifuge tubes, and place a piece of 3D printed porous β-TCP in the bottom of each centrifuge tube. Start the centrifuge, set the rotation speed to 4000rpm, and process for 15 minutes. After centrifugation, the PLGA anti-tuberculosis drug slow-release microspheres can enter all pores of the porous β-TCP scaffold until saturated. After centrifugation, discard the liquid and excess microspheres, then add 10% gelatin solution to the tube, and centrifuge at low speed for 15 minutes again. Capable of binding microspheres within the pores of porous β-TCP. After 24 hours of freeze-drying treatment, the 3D printed porous β-TCP loaded PLGA anti-tuberculosis drug sustained-release microsphere composite material was fina...

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Abstract

The invention provides a porous calcium phosphate support loaded microsphere composite material, as well as a preparation method and application thereof. The porous calcium phosphate support loaded microsphere composite material comprises a porous calcium phosphate support, wherein a polylactic acid-glycolic acid copolymer microsphere is loaded in each hole of the porous calcium phosphate supportand the polylactic acid-glycolic acid copolymer microsphere coats one or more antituberculosis drugs. The experiment proves that the porous calcium phosphate support loaded microsphere composite material has a filling bone remodeling and bone inducing osteogenesis function, further has an effect of locally continuously and three-dimensionally slowly releasing the antituberculosis drugs, and achieves an effect of treating osteoarticular tuberculosis and reducing recurrence. The invention further provides the preparation method and the application of the porous calcium phosphate support loaded microsphere composite material.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a porous calcium phosphate scaffold-loaded microsphere composite material and a preparation method and application thereof. Background technique [0002] There are about 20 million tuberculosis patients in the world, and the incidence rate is on the rise. There are about 5 million in my country. Among all tuberculosis patients, about 10-15% are extrapulmonary tuberculosis, and bone and joint tuberculosis accounts for the first place in extrapulmonary tuberculosis. Combination drugs can improve the efficacy of anti-tuberculosis and reduce the emergence of drug-resistant bacteria. Systemic chemotherapy with triple or more anti-tuberculosis drugs requires more than 10 months, and even ultra-short-course chemotherapy for bone and joint tuberculosis requires at least 6-8 months. However, in the treatment of bone tuberculosis, due to poor blood supply in the lesion area ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K47/02A61K47/34A61K47/42A61K31/4409A61K31/496A61P31/06A61P19/02A61P19/08
CPCA61K9/19A61K31/4409A61K31/496A61K47/02A61K47/34A61K47/42A61P19/02A61P19/08A61P31/06A61K2300/00
Inventor 何晓乐刘军王晓明甄诚王燕甄平马永海李旭升杨巧巧周胜虎王伟
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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