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Radioactive embolization microsphere with core-shell structure and preparation method and application thereof

A core-shell structure, embolizing microsphere technology, applied in the field of medicine and medicine, can solve the problems of polymer chain breakage, leakage, radiation-sensitive normal organ damage, etc., and achieve the effect of good dispersion

Pending Publication Date: 2020-09-01
彭盛 +2
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

By encapsulating microspheres such as organic ligands of nuclides, a large nuclide carrying capacity can be achieved, and the nuclide carrying rate is between 10-30wt%, but this type of microspheres, in the neutron activation step, The surface structure and surface polymer material of polymer microspheres are easily damaged by neutron beams, resulting in polymer chain breakage, which causes the radionuclide wrapped between the polymers close to the surface of the microspheres to lose the polymer package and leak after injection. Damage to radiation-sensitive normal organs such as the kidneys

Method used

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  • Radioactive embolization microsphere with core-shell structure and preparation method and application thereof
  • Radioactive embolization microsphere with core-shell structure and preparation method and application thereof
  • Radioactive embolization microsphere with core-shell structure and preparation method and application thereof

Examples

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Embodiment 1

[0035] Embodiment 1 prepares embolization microspheres containing lutetium chloride

[0036] Weigh 2 g of lutetium chloride (LuCl 3 ) was dissolved in 1 ml of 0.5% w / v Pluronic F-68 in water. LuCl 3 The aqueous solution was added to 30ml of chloroform solution in which 2g of poly(lactide-glycolide) copolymer (PLGA) (molecular weight: ~20,000, Sigma, USA) was dissolved, placed on a magnetic stirrer and stirred at 2000rpm for 5min to obtain an emulsified liquid. Then, slowly add the above emulsion into 200ml of 2% (w / w) polyvinyl alcohol (PVA, molecular weight: 13,000-23,000, 87-89% hydrolyzed) aqueous solution and stir the above mixture at 1000rpm for 20h to obtain micro ball. Microspheres were collected by centrifugation and washed three times with double distilled water to remove excess PVA. Disperse the washed microspheres into 50 ml of cryoprotectant solution (25 mM glycerol, 0.5% w / v Pluronic F-127, 0.1% w / v sucrose, 3% w / v mannitol and 5% w / v polyethylene glycol 400...

Embodiment 2

[0039] Example 2 Preparation of Embolization Microspheres Containing Yttrium Phosphate Nanoparticles

[0040] 8.4mmol of yttrium chloride (YCl 3 , Sigma-Aldrich, USA) and phosphoric acid (H 3 PO 4 , Sigma-Aldrich, USA) was dissolved in 300 mL of double distilled water. With constant stirring, 150ml of 56mM NaOH solution was slowly added to the above-mentioned yttrium nitrate-phosphoric acid solution, and the stirring was continued for 20min to obtain an opaque suspension. The suspension was centrifuged at 4000 rpm for 5 min to collect the white precipitate. The precipitate was washed three times with double distilled water. In a vacuum environment, dry the above-mentioned yttrium phosphate nanoparticles. Weigh 2.0 g of yttrium phosphate nanoparticles into 10 ml of 0.2% w / v In the F-68 (ThermoFisher, USA) aqueous solution, the yttrium phosphate nanoparticles were uniformly dispersed in the aqueous solution by ultrasonication for more than 30 minutes, and then the larger ...

Embodiment 3

[0043] Example 3 Preparation of phospholipid-coated holmium acetylacetonate embolization microspheres

[0044] Measure 200 mg of dipalmitoylphosphatidylcholine (DPPC, Avanti, USA), 150 mg of dipalmitoylphosphatidylglycerol (DPPG, Avanti, USA) and 150 mg of distearoylphosphatidylethanolamine-polyethylene glycol with an analytical balance. Diol (DSPE-mPEG2000, Avanti, USA) was placed in a flask, 25ml of propylene glycol (Sigma-Aldrich, USA) and 25ml of glycerin (Sigma-Aldrich, USA) were added, and heated in a water bath at 65°C for 20min until the phospholipids were dissolved , then add 150ml of distilled water (65°C) and continue heating in a water bath at 65°C for 20min to obtain a homogeneous phospholipid solution, then cool to room temperature to obtain a phospholipid solution (2.5mg / ml).

[0045] Weigh 2 g of holmium acetylacetonate (HoAcAc, Sigma-Aldrich, USA) and add 3 ml of chloroform to dissolve. Add the chloroform solution to 15ml of the phospholipid solution (2.5mg / m...

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Abstract

The invention provides a radioactive embolization microsphere with a core-shell structure. The microsphere with the core-shell structure is formed by taking a biodegradable high polymer material as ashell and wrapping radionuclide as an inner core. According to the biodegradable radioactive embolization microsphere with the core-shell structure provided by the invention, radionuclide is wrapped in the microsphere by a biodegradable polymer shell with the thickness of 1-30 microns. Due to the fact that the polymer shell is thick and all radionuclides are located in the centers of the microspheres, damage to the surface layer of the polymer shell cannot cause leakage of the radionuclides. After the treatment is finished, the nuclide loses radioactivity, and the embolization microsphere is gradually dissolved due to the biodegradable characteristic of the shell, so that the blood vessel in the treatment area is dredged again. In addition, the microsphere with the core-shell structure hasa certain proportion of cavities (5%-80% v / v), and the overall density of the microsphere is closer to the density of water, so that the microsphere has better dispersity.

Description

technical field [0001] The invention belongs to the field of medicine and medicine, and in particular relates to a radioembolization microsphere with a core-shell structure and a preparation method and application thereof. Background technique [0002] Due to the unique blood supply of hepatocellular carcinoma (HCC), which is almost exclusively from the hepatic artery, whereas the blood supply of a normal liver consists of ~75% from the portal vein and ~25% from the hepatic artery, radionuclide-labeled microspheres can be passed through The hepatic artery that supplies blood to the liver cancer tissue selectively stays in the hepatocellular carcinoma area. The radionuclide release line carried by the microspheres is generally β-rays, and its action distance is generally several millimeters to more than ten millimeters, which can cause the death of surrounding tumor cells, but has little damage to normal liver cells far away from the microspheres . [0003] There are curren...

Claims

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Application Information

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IPC IPC(8): A61K51/12A61K51/06A61P35/00A61K103/10A61K101/02A61K103/32A61K103/36A61K103/00A61K103/20A61K103/30
CPCA61K51/1251A61K51/06A61P35/00
Inventor 彭盛张福君
Owner 彭盛
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