High-drug-loading degradable alginate sulfate vascular embolization microspheres and preparation method and application thereof

An alginic acid sulfate, embolizing microsphere technology, applied in the application, medical science, surgery and other directions, can solve the problems of non-degradable pharmaceutical raw materials, difficult to balance the embolization/degradation function, and the degradation speed is too fast, and achieve excellent biocompatibility and degradability, improving drug loading performance, and the effect of large specific surface area

Pending Publication Date: 2021-12-03
OCEAN UNIV OF CHINA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the drug-loaded microsphere products on the market are all non-degradable microspheres, and there are two core problems: ①Due to the limitation of raw materials and process, the content of drug-loaded groups is very limited, and it is difficult to meet the actual needs of more complex interventional embolization therapy ;②The drug release mechanism is the elution effect of the surrounding solution (such as blood, interstitial fluid). Because the raw materials are not degradable and cannot be released, the release function of drug-loaded microspheres is jointly restricted. The development of new drug-loaded embolic microspheres with larger drug-loadin

Method used

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  • High-drug-loading degradable alginate sulfate vascular embolization microspheres and preparation method and application thereof
  • High-drug-loading degradable alginate sulfate vascular embolization microspheres and preparation method and application thereof
  • High-drug-loading degradable alginate sulfate vascular embolization microspheres and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] A preparation method of highly drug-loaded degradable alginate sulfate vascular embolism microspheres, comprising the following steps:

[0042] (1) Water phase preparation: add 3.0 g of alginic acid sulfate into 15 mL of deionized water, dissolve evenly, adjust the pH to 11.0 with 2 mol / L NaOH solution, and set aside.

[0043] (2) Oil phase preparation: Add 4.5g Span60 to 300mL soybean oil, stir at 85°C until Span60 is completely dissolved, and set aside.

[0044] (3) Preparation of alginate sulfate microspheres: Add the prepared water phase to the oil phase at a speed of 10mL / min, and the stirring speed is 500r / min. After adding the water phase, add 9mL epichlorohydrin, React at 70°C for 4 hours; screen out the microspheres, wash with petroleum ether, ethyl acetate, and absolute ethanol three times, and vacuum-dry at 50°C to obtain alginate sulfate microspheres.

[0045] Such as figure 1 As shown, the alginate sulfate microspheres prepared by the present invention ha...

Embodiment 2

[0054] A preparation method of highly drug-loaded degradable alginate sulfate vascular embolism microspheres, comprising the following steps:

[0055] (1) Water phase preparation: Add 4.5g of alginic acid sulfate into 15mL of deionized water, dissolve evenly, adjust the pH to 11.0 with 2mol / L NaOH solution, and set aside.

[0056] (2) Preparation of oil phase: Add 4.5 g of Span60 and 0.5 g of Tween 60 to 300 mL of soybean oil, stir at 85 °C until the emulsifier is completely dissolved, and set aside.

[0057] (3) Preparation of alginic acid sulfate microspheres: Add the prepared water phase to the oil phase at a speed of 10mL / min, and the stirring speed is 500r / min. After adding the water phase, add 18mL epichlorohydrin, React at 85°C for 4 hours; sieve out the microspheres, wash with petroleum ether, ethyl acetate, and absolute ethanol three times, and vacuum-dry at 50°C to obtain alginate sulfate microspheres.

[0058] (4) Dissolve the drug in pure water, put the alginate s...

Embodiment 3

[0064] A preparation method of highly drug-loaded degradable alginate sulfate vascular embolism microspheres, comprising the following steps:

[0065] (1) Water phase preparation: Add 1.5g of alginic acid sulfate into 15mL of deionized water, dissolve evenly, adjust the pH to 8.0 with 2mol / L NaOH solution, and set aside.

[0066] (2) Oil phase preparation: Add 0.3 g of Span80 to 300 mL of sunflower oil, stir at 60°C until the emulsifier is completely dissolved, and set aside.

[0067] (3) Preparation of alginic acid sulfate microspheres: Add the prepared water phase to the oil phase at a rate of 0.1mL / min, where the stirring speed is 300r / min, and add 1.5mL epoxy chloride after the water phase is added Propane, reacted at 60°C for 2 hours; sieved the microspheres, washed them repeatedly with petroleum ether, ethyl acetate, and absolute ethanol respectively, and dried them in vacuum at 60°C to obtain alginic acid sulfate microspheres.

[0068] (4) Dissolve the drug in pure wat...

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Abstract

The invention discloses a preparation method of high-drug-loading degradable alginate sulfate vascular embolization microspheres. The preparation method comprises the following steps of: S01, preparing an aqueous phase; S02, preparing an oil phase; S03, preparing alginate sulfate microspheres; and S04, preparing drug-loaded alginate sulfate embolization microspheres. The invention also discloses the high-drug-loading degradable alginate sulfate vascular embolization microspheres obtained by the preparation method of the high-drug-loading degradable alginate sulfate vascular embolization microspheres and application of the high-drug-loading degradable alginate sulfate vascular embolization microspheres in preparation of an embolization agent for transcatheter arterial chemoembolization treatment. The alginate sulfate vascular embolization microspheres disclosed by the invention have good biocompatibility and are biodegradable, and the degradation product is safe and non-toxic. The preparation method has the advantages of simplicity and convenience in operation, high repeatability, mild conditions and the like, the prepared microspheres are uniform and controllable in particle size, and the vascular embolization microspheres prepared by the invention have good application prospects in the field of tumor interventional therapy.

Description

technical field [0001] The invention relates to a highly drug-loaded degradable alginate sulfate vascular embolization microsphere, a preparation method and application thereof, and belongs to the technical field of biomedical materials. Background technique [0002] Transcatheter Arterial Chemoembolization (TACE) refers to the controlled injection of embolic materials into the supply vessels of diseased organs through intra-arterial catheters, causing occlusion and interruption of blood supply, in order to control bleeding and treat tumors. and vascular lesions and techniques for eliminating diseased organs. TACE is mostly used clinically in the treatment of malignant tumors that are difficult to interfere with conventional therapies (such as surgery and chemotherapy). Taking liver cancer as an example, its clinical treatment methods are very limited, as follows: ①Surgery is the first choice for liver cancer treatment, but due to the complex physiological structure of the ...

Claims

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Application Information

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IPC IPC(8): A61L24/08A61L24/00
CPCA61L24/08A61L24/001A61L24/0015A61L2300/416C08L5/04
Inventor 卢乾张鹏杨文哲杨雪管华诗
Owner OCEAN UNIV OF CHINA
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