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Modified sodium alginate self-developing embolization microsphere and preparation method and application thereof

A technology of sodium alginate and embolizing microspheres, which is applied in the field of biomedicine, can solve the problems of long drug loading time, uneven dispersion of the developer, influence on tumor curative effect, etc., so as to improve the drug loading capacity and drug loading rate, and prolong the drug starting time. Effective time, reducing the effect of drug side effects

Active Publication Date: 2020-08-04
NKD PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, the microspheres (embolic materials) that are widely used in clinical practice are drug-loadable embolism microspheres, and the material used is polyvinyl alcohol, but the microspheres cannot achieve the effect of autoradiography, which is not conducive to the monitoring of clinical therapeutic effects.
Chinese patent CN107812232A discloses a developable carboxy-modified polyvinyl alcohol microsphere embolic agent and its preparation process, but its drug loading is small, the drug loading time is long, and there are disadvantages of non-degradability
In the above technology, the developer is dispersed by conventional stirring, which is prone to disadvantages such as uneven dispersion and agglomeration of the developer. In addition, the microspheres cannot achieve drug loading or only through physical blending, and the long-term effective release of the drug cannot be controlled. It has a great influence on the curative effect of tumor chemotherapy and embolization

Method used

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  • Modified sodium alginate self-developing embolization microsphere and preparation method and application thereof
  • Modified sodium alginate self-developing embolization microsphere and preparation method and application thereof
  • Modified sodium alginate self-developing embolization microsphere and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] In this example, modified sodium alginate self-imaging embolic microspheres were prepared and further drug-loaded according to the following method:

[0049] 1. Branching modification: add sodium alginate with a viscosity of 619mpa s to the acetone solution of dibromoethane, adjust the pH of the solution to 10, pre-react for 3 hours at 55°C, add pentaerythritol, pentaerythritol and sodium alginate The molar ratio of the repeating unit was 0.3:1. Stir the reaction at 80°C for 24 hours, add excess acetone solution, filter with suction, collect the precipitate, wash and dry to obtain branched and modified sodium alginate.

[0050] 2. Hydrophobic modification: add oleic acid and branched modified sodium alginate to N, N-dimethylformamide, add dicyclohexylcarbodiimide and 4-dimethylaminopyridine under stirring conditions , and reacted at room temperature for 24h to obtain hydrophobically modified sodium alginate. The molar ratio of oleic acid to the above sodium alginate re...

Embodiment 2-7

[0061] In Example 2-7, modified sodium alginate self-imaging embolic microspheres were prepared according to the method of Example 1 and further drug-loaded. The only difference lies in the raw materials and dosage during preparation, reaction conditions, developer mixing method and preparation electric field force The voltages are not exactly the same. In addition, the order of steps 2 and 3 was exchanged in Examples 6-7.

[0062] Specifically, the differences between Example 2-7 and Example 1 in the sodium alginate raw material in step 1, the concentration of the modified sodium alginate aqueous solution in step 4, the content of the developer, and the drug-loaded drug are shown in Table 1. See Table 2 for the differences between the amount of raw materials and the reaction conditions of Example 1 during chemical modification, and see Table 3 for the differences between the amount of raw materials and reaction conditions for hydrophobic modification and Example 1. See Table...

Embodiment 8

[0077] In this example, modified sodium alginate self-imaging embolic microspheres were prepared and further drug-loaded according to the following method:

[0078] 1. Branching modification: Add sodium alginate with a viscosity of 110mpa s to the acetone solution of dibromoethane, adjust the pH of the solution to 11, pre-react for 4 hours at 30°C, add glycerin, glycerin and sodium alginate The molar ratio of the repeating unit was 0.35:1, stirred and reacted at 100°C for 8 hours, added excess acetone solution, filtered with suction, collected the precipitate, washed and dried to obtain branched modified sodium alginate.

[0079] 2. Hydrophobic modification:

[0080] According to the molar ratio of 0.21:1, succinic anhydride and branched modified sodium alginate were added into dichloromethane, DMAP was added in sequence under magnetic stirring, and the temperature was raised to 35°C for 5 hours under nitrogen protection, and the filter cake was 35°C after suction filtration. ...

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Abstract

The invention relates to the technical field of biological medicines, and particularly discloses a modified sodium alginate self-developing embolization microsphere and a preparation method and application thereof. The modified sodium alginate self-developing embolization microsphere comprises modified sodium alginate and a developing agent, wherein the modified sodium alginate is sodium alginatewhich is firstly subjected to branching modification to introduce a plurality of hydroxyl groups and then subjected to hydrophobic modification and sulfonation modification, and the branching substitution rate of branching modification is 22-81%; the hydrophobic substitution rate of the hydrophobic modification is 5-32%; and the sulfonation substitution rate of sulfonation modification is 57-266%.When the embolization microsphere disclosed by the invention is used as a drug carrier, the drug loading capacity and the drug loading rate of a negatively charged drug can be remarkably improved, the drug release time can be delayed, and the burst release of the drug is reduced.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a modified sodium alginate self-imaging embolic microsphere and its preparation method and application. Background technique [0002] Arterial embolization is an important interventional therapy technique, which integrates medical imaging and clinical treatment and other disciplines, and is characterized by simplicity, safety, minimal invasiveness and few post-treatment complications. Transcatheter vascular embolization (TACE) is mainly to inject embolic agent into the blood vessel supplying the diseased target organ through the arterial or intravenous catheter, so as to occlude the blood vessel, interrupt the blood supply, and finally achieve the purpose of treatment. [0003] At present, the microspheres (embolic materials) widely used in clinical practice are drug-loadable embolization microspheres, and the material used is polyvinyl alcohol, but the microspheres cannot ac...

Claims

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Application Information

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IPC IPC(8): A61L24/00A61L24/08C08B37/04
CPCA61L24/001A61L24/08A61L24/0015C08B37/0084A61L2400/04C08L5/04
Inventor 冷鸿飞徐小雨谢辉王华明田圣涛陶秀梅陈鹏
Owner NKD PHARMA CO LTD
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