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Visual polyhydroxy polymer embolism microsphere and preparation method thereof

A technology of embolic microspheres and polymers, applied in the field of medical materials, can solve the problems of increased difficulty, cumbersome operation steps, and vascular stimulation, and achieve the effects of simple operation, reduced surgical risk, and good scalability

Active Publication Date: 2017-08-18
SUZHOU HENGRUI CALLISYN BIOLOGICAL MEDICINE TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to achieve better embolization and imaging effects, it is necessary to mix embolization microspheres and ethyliodol to form a stable suspension system during the process of adding ethyliodol, but such a combination is often unstable, which means that the injection combination The substance needs to be prepared immediately before injection, and the ethyliodol and embolic microspheres may be in different positions in the tissue after injection, which greatly increases the difficulty of the doctor's operation. At the same time, the use of contrast medium will also directly stimulate blood vessels. , bringing additional risk
[0006] WO2014 / 152488 describes a polymer microsphere (LC / DC- ) to activate preformed hydrogel beads by nucleophilic attack, and then covalently attach iodine-containing compounds to polymer microspheres to prepare visualization microspheres. This method prepares visualization microspheres by chemically modifying the surface of the microspheres, but the operation The steps are cumbersome, and due to the nature of the network structure of the microspheres and the large steric hindrance of the reaction, the preparation of the visualized microspheres requires a higher temperature (50°C) and a longer reaction time (more than 24h). more demanding
[0007] US2016 / 0193367 describes the surface chemical modification of a polymer microsphere under the catalysis of methanesulfonic acid and an acetal compound containing iodobenzene at 80°C. The prepared microsphere can be developed under X-ray, but Due to the network structure of the microspheres (lower reactivity), the reaction temperature is higher, which may adversely affect the physical properties of the microspheres such as size, sphericity, swelling and compressibility

Method used

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  • Visual polyhydroxy polymer embolism microsphere and preparation method thereof
  • Visual polyhydroxy polymer embolism microsphere and preparation method thereof
  • Visual polyhydroxy polymer embolism microsphere and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0037]

[0038] Slowly add 50 mL of dimethyl sulfoxide solution containing 419.0 g of 3,5-diiodo-4-aminobenzaldehyde dimethyl acetal into a four-necked reaction flask filled with aqueous sodium hydroxide solution (40 g, 300 mL), and stir to make the solution Uniform; Acryloyl chloride (99.5g) was slowly added dropwise, and the reaction was continued for 1 hour after the dropwise addition. Then add saturated sodium chloride solution (100mL) to the above solution, add ethyl acetate (2×200mL) for extraction, wash the organic phase with water (2×100mL), and concentrate the organic phase to obtain crude product purified by column chromatography to obtain Yellow oily product 3,5-diiodo-4-acrylamidobenzaldehyde dimethyl acetal 1 (300g), HPLC purity 99.0%, 1 HNMR [DMSO-d 6 ]:8.201(s,1H),7.541(s,2H),6.482-6.410(m,1H),6.172-6.124(m,1H),5.714-5.682(m,1H),5.490(s,1H), 3.252(s,6H).

Embodiment 2

[0040]

[0041] In a 2L four-necked reaction flask, add 1000g of water and a molecular weight of 5×10 4 ~8×10 4 150g of polyvinyl alcohol, heated to 96°C for 4 hours, cooled the fully dissolved polyvinyl alcohol solution to room temperature, and added 15.7g of 3,5-diiodo-4-acrylamidobenzaldehyde dimethyl acetal Dimethyl sulfoxide solution 10mL, concentrated hydrochloric acid 100mL, reacted for 3 hours, after the reaction was completed, 560g of 2.5M sodium hydroxide solution was added, and the collected crude product was concentrated to obtain 550g of a gel-like functionalized macromolecular intermediate with a viscosity of 3000cps. This intermediate 2 was kept for future use.

Embodiment 3

[0043]

[0044] In a 2L reaction flask, add sodium 2-acrylamide-2-methylpropanesulfonate (20.0g), potassium persulfate (12.0g) and water, mix and stir until the potassium persulfate is completely dissolved, and then add it into the functionalized The macromolecular intermediate (400g) was stirred evenly to obtain a macromolecular monomer solution, which was placed for subsequent use. Add butyl acetate (2.5L) and ethyl acetate solution (35g) of 10% butyl acetate cellulose in 5L reactor, feed nitrogen, system temperature rises to 63 ℃, add above-mentioned macromolecular monomer solution and four Methylethylenediamine (20 mL), then the reaction was stirred at 58°C for 3 hours. After the reaction, the reaction mixture was washed with butyl acetate and acetone successively, filtered with suction, and dried in vacuum to obtain polyvinyl alcohol embolism microspheres 3 (80 g).

[0045] After swelling and sieving, the embolism microspheres are round and plump, with smooth surface,...

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Abstract

The invention relates to a visual polyhydroxy polymer embolism microsphere and a preparation method thereof, belonging to the technical field of medical treatment materials. The visual embolism microsphere is prepared from functional macromolecules with biocompatibility and a cross-linking agent, namely an iodobenzene compound through cross-linking polymerization and is capable of reflecting or weakening X rays. The invention relates to a novel visual embolism microsphere in the technical field of medical materials and a preparation process of the novel visual embolism microsphere. According to the process, the defect that a contrast agent is added into a traditional surgical embolism process for developing is changed, the surgical risk is reduced, and convenience is provided for treating tumor diseases by virtue of a minimally invasive interventional therapy; the visual microsphere prepared by virtue of the preparation process is capable of reflecting or weakening the X rays and has good flexibility, elasticity and compression deformation property; and meanwhile, a traditional embolism microsphere needs to be dyed so as to guarantee that a doctor can conveniently observe in a surgical process, but the embolism microsphere prepared by virtue of the process is yellow and does not need to be dyed, so that the operation is simple and feasible.

Description

technical field [0001] The invention relates to a visualized polyhydroxy polymer embolic microsphere and a preparation method thereof, in particular to a preparation process of a visualized embolic microsphere with good deformation elasticity for minimally invasive interventional therapy for tumor diseases, belonging to the technical field of medical materials . Background technique [0002] In recent years, interventional embolization therapy has played an increasingly important role in clinical medicine, especially in the treatment of tumors rich in blood vessels such as liver cancer, kidney cancer, and uterine fibroids. The preferred alternative for treating tumors that cannot be surgically removed. At present, commonly used embolic materials for interventional embolization include microspheres, microcatheters, coils, silk threads, etc., and microspheres are highly targeted to specific tissues and organs, have good embolization effects, can be combined with chemotherapy ...

Claims

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Application Information

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IPC IPC(8): A61L24/06A61L24/04A61L24/08A61K9/16A61K47/32A61K47/10A61K47/36A61P35/00C08F16/06C08F8/30C08F8/36
CPCA61K9/1635A61K9/1641A61K9/1652A61L24/046A61L24/06A61L24/08A61L2300/416C08F8/36C08F16/06C08L29/04C08L71/02C08L3/02C08L5/08C08L1/284C08F8/30
Inventor 王鹤明柳小平汪青松徐伟春
Owner SUZHOU HENGRUI CALLISYN BIOLOGICAL MEDICINE TECH CO LTD
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