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Core-shell type pre-charged chemotherapy medicine embolization microsphere and preparation method thereof

A chemotherapy drug and embolization microsphere technology, applied in the field of biomedicine, can solve the problems of reducing local efficacy, increasing adverse reactions, high drug loss rate, etc., to achieve the effect of changing distribution and kinetics, improving bioavailability, and reducing side effects

Inactive Publication Date: 2018-11-02
ENERGY RES INST OF SHANDONG ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method has two major defects: ① local deposition of lipiodol emulsion sometimes cannot achieve satisfactory results, and as time goes on, the cytotoxic effect of chemotherapy drugs on tumor tissue also decreases; ② traditional Drug carriers are lipids, and chemotherapy drugs are water-soluble, such traditional emulsions cause rapid release of chemotherapy drugs into the bloodstream, thereby rapidly entering the systemic circulation, increasing systemic adverse reactions and reducing local efficacy
The invention patent uses mechanical agitation to prepare microsphere embolism. The method lacks effective control of the particle size of the microspheres. The particle size distribution of the obtained microspheres is relatively wide. Blockage of blood vessels that do not require embolization
In addition, the drug is added dropwise during the preparation process, and the drug loss rate is relatively high

Method used

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  • Core-shell type pre-charged chemotherapy medicine embolization microsphere and preparation method thereof
  • Core-shell type pre-charged chemotherapy medicine embolization microsphere and preparation method thereof
  • Core-shell type pre-charged chemotherapy medicine embolization microsphere and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Example 1: Core-shell prepacked paclitaxel embolization microspheres and their preparation

[0069] select figure 1 (A) co-flow micro-scale channel, preparing O / W / O double emulsion micro-droplets, wherein, θ1=90°, θ2=90°; the diameter of the inner oil phase fluid channel 1 in the micro-scale channel is 200 microns, and the middle The diameter of the water phase fluid channel 2 is 200 microns, the diameter of the collection micro channel 4 is 250 microns; the diameter of the outer oil phase fluid channel 3 is 250 microns, and the diameter of the collection micro channel 5 is 400 microns.

[0070]The inner oil phase is a dichloromethane solution containing 8% PLGA, in which 400 μg / mL paclitaxel is dissolved; the middle water phase is a mixed aqueous solution of 1.5% sodium alginate and 2% polyvinyl alcohol, and the outer oil phase is a solution containing 2% EM90. Liquid paraffin oil. The inner oil phase, the middle water phase and the outer oil phase were pumped into c...

Embodiment 2

[0072] Example 2: Core-shell prepacked ginsenoside embolization microspheres and their preparation

[0073] The micro-scale channel is as described in Example 1 to prepare O / W / O double emulsion micro-droplets. The difference is that the diameter of the inner oil phase fluid channel 1 in the microscale channel is 150 microns, the diameter of the middle water phase fluid channel 2 is 150 microns, the diameter of the collection micro channel 4 is 200 microns; the diameter of the outer oil phase fluid channel 3 is 200 microns, The collection microchannel 5 has a diameter of 300 microns.

[0074] The inner oil phase is selected from dimethyl carbonate solution containing 6% PLGA, in which 30 μg / ml ginsenoside is dissolved; Polyvinyl alcohol mixed aqueous solution, the outer oil phase is selected from soybean oil containing 2% DC749. The inner oil phase, middle water phase and outer oil phase were pumped into channels 1, 2, and 3 at constant flow rates of 0.7 mL / h, 3.0 mL / h, and 6...

Embodiment 3

[0076] Example 3: Core-shell prepacked doxorubicin embolization microspheres and their preparation

[0077] select figure 1 (B) Micro-scale channel of flow-focusing structure to prepare W / O / W double-emulsion droplets. The outlet diameter of the aqueous phase fluid channel 7 in the micro-scale channel is 50 microns, and the inlet diameter of the collection micro channel 10 is 120 microns.

[0078] The inner water phase is a mixed aqueous solution of 20% PEG and 2% sodium alginate, and 200 μg / mL of doxorubicin is dissolved in it; the middle oil phase is made of dodecane containing 2% EM90, and the outer water phase is 4% polyvinyl alcohol aqueous solution . The inner water phase, the middle oil phase and the outer water phase were pumped into channels 7, 8, and 9 at constant flow rates of 0.8 mL / h, 2.0 mL / h, and 13.0 mL / h, respectively. Double emulsion micro-droplets are generated at the intersection of channels 7 and 10.

[0079] The droplets were collected and added to a 5...

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Abstract

The invention provides a core-shell type pre-charged chemotherapy medicine embolization microsphere and a preparation method thereof. The method comprises the following steps of using water / oil / water(W / O / W) complex emulsion type or oil / water / oil (O / W / O) complex emulsion type emulsified micro liquid drips as templates; coating tiny liquid drips containing medicine into outer layer liquid drips; high molecular polymers in the inner and outer layer liquid drips are converted through measures such as physical measures and chemical measures to form an inner layer core and an outer layer shell. Theformed core-shell structure medicine microsphere is formed by polymers of two-layer structures; the inner core contains medicine; the outer shell is favorable for maintaining the activity of the inner core medicine; the stable medicine release is realized; the sudden release is prevented; the safety is enhanced. The medicine carried microsphere prepared by the method has the advantages that the particle diameter range is 10 to 1000 micrometers; the sphere degree is good; the particle diameter is uniform; (the dimension deviation is 5 percent); the medicine encapsulation rate is high; the structure / carried medicine is controllable; meanwhile, the preparation method of the pre-charged chemotherapy medicine embolization microsphere can provide a novel idea for the clinic application study ofthe transcatheter arterial embolization.

Description

technical field [0001] The invention relates to a preparation process of a core-shell prepacked chemotherapeutic drug microsphere embolic agent, belonging to the field of biomedicine. Background technique [0002] Transcatheter vascular embolization (Transarterial embolization, TAE) is the selective injection of embolic agents into the target blood vessels of the lesion to block the blood supply, so as to achieve the purpose of inhibiting tumor growth, eliminating the function of vascular lesions and stopping bleeding. In 1981, Kato first proposed chemoembolization, or transcatheter arterial chemoembolization (Transarterialchemoembolization, TACE), this method is to combine drugs and embolic agents, with both embolization and drug dual effects, more effective. Traditional TACE is commonly used lipiodol plus doxorubicin, cisplatin or other chemotherapeutic drugs mixed administration. However, this method has two major defects: ① local deposition of lipiodol emulsion sometime...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L24/06A61L24/08A61L24/10A61L24/00
CPCA61L24/0015A61L24/06A61L24/08A61L24/104A61L2430/36
Inventor 李艳王立秋侯延进田寒梅王建梅孔湉湉许敏
Owner ENERGY RES INST OF SHANDONG ACAD OF SCI
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