PH-reduction dual-response polymer embolization agent for tumor catheter-free embolization and synthesis thereof

An embolic agent and double-response technology, which is applied in the field of polymer embolic agent and its synthesis for pH-reduction dual-response tumor catheter-free embolization, can solve problems such as gelation in the tube, simplify the operation process and requirements, and increase compliance , the effect of reducing height requirements

Active Publication Date: 2020-01-21
NORTHWEST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Some intelligent polymer embolic agents that can be gelled in situ, represented by temperature-sensitive polymers, have u

Method used

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  • PH-reduction dual-response polymer embolization agent for tumor catheter-free embolization and synthesis thereof
  • PH-reduction dual-response polymer embolization agent for tumor catheter-free embolization and synthesis thereof
  • PH-reduction dual-response polymer embolization agent for tumor catheter-free embolization and synthesis thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Add 1g of newly prepared L-threonine NCA to a 50mL three-necked flask, dissolve in 3mL redistilled 1,4-dioxane, and 2 Add 2.835 mg of piperazine under protective conditions to carry out the polymerization reaction. After the polymerization reaction is completed, add ethanol to obtain a white precipitate, centrifuge, and wash the white precipitate with ethanol and ether for 2 to 3 times, and dry it in vacuum at 40°C for 24 hours. White poly (L-threonine) (PLGThr) was obtained. Add 0.4 g of PLGThr to a 50 mL three-necked flask, suspend it in 2 mL of 1,4-dioxane, and 2 Added newly prepared L-glutamic acid-5-benzyl ester-NCA (BLG-NCA) and L-cysteine ​​NCA (LCys-NCA) under protective conditions, reacted for 72 hours, and precipitated with absolute ethanol to obtain a white solid as poly (L-glutamic acid-5-benzyl ester-L-cysteine)-poly(L-threonine)-poly(L-glutamic acid-5-benzyl ester-L-cysteine)( P(BLG-LCys)-PLGThr-P(BLG-LCys)), filtered, and then added to a round-bottomed ...

Embodiment 2

[0060] Add 0.8g of fresh L-threonine NCA to a 50mL three-necked flask, dissolve it with 3mL redistilled 1,4-dioxane, and 2 Add 0.42 mL of 1,4-cyclohexanediamine in 1,4-dioxane solution with a mass volume concentration of 5.4 mg / mL under protective conditions, react at room temperature for 48 hours, add ethanol to obtain a white precipitate, centrifuge, wash with ethanol, ether Wash 2-3 times, and dry in vacuum at 40°C for 24 hours to obtain white poly(L-threonine) (PLGThr); add 0.4 g of PLGThr into a 50 mL three-necked flask and suspend it in 2 mL of 1 ,4-dioxane, in N 2 Add 0.35g of fresh L-glutamic acid-5-benzyl ester-NCA (BLG-NCA) and 0.28g of L-tyrosine NCA (LTyr-NCA) under protective conditions, react at 35°C for 48 h, and use anhydrous Ethanol precipitation, the solid white obtained is poly(L-glutamic acid-5-benzyl ester-L-tyrosine)-poly(L-threonine)-poly(L-glutamic acid-5-benzyl ester- L-Tyrosine) (P(BLG-LTyr)-PLGThr-P(BLG-LTyr)), filtered, and then added to a round-b...

Embodiment 3

[0065] Add 2mL of triethylamine and 1,4-dioxane mixed solution in 50mL three-necked flask, the volume ratio of triethylamine and 1,4-dioxane in this mixed solution is 25: 1, in N 2 Add 0.35g of newly prepared L-glutamic acid-5-benzyl ester-NCA (BLG-NCA) and 0.20g of L-cysteine ​​NCA (LCys-NCA) under protective conditions, react at 35°C for 48 h, and use Precipitate with water and ethanol, the obtained white solid is poly(L-glutamic acid-5-benzyl ester-L-cysteine) [P(BLG-LCys)], wash with ethanol and ether three times respectively, and CIA at 40°C Vacuum dried for 24h. Add 0.5g of P(BLG-LCys) into a 50 mL three-neck flask filled with 5 mL of DMF, dissolve it, and 2 Add 0.25g polyethylene glycol 1000 and 2mL hydrogen bromide aqueous solution under protective conditions, and reflux at 80°C for 8h; add hydrochloric acid aqueous solution with a pH value of 2 to obtain a large amount of white precipitate, filter, and then add 30 mL of the mixed solution to the round bottom In the ...

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Abstract

The invention discloses a pH-reduction dual-response polymer embolization agent for tumor catheter-free embolization and synthesis thereof. The embolization agent is a linear triblock polymer; the pHand reduction stimulation response chain segment is formed by copolymerization of a monomer unit with a carboxyl side group and a monomer unit with a sulfydryl side group in the same structure, or isformed by copolymerization of a monomer unit with a carboxyl side group, a monomer unit with a sulfydryl side group and a monomer unit with a phenolic hydroxyl side group in the same structure. Then the polymer and sulfydryl-containing water-soluble small molecules are oxidized by using an oxidant to form disulfide bonds; and B is a hydrophilic polymer chain segment. An initiator initiates the monomers to polymerize into a pH-responsive adjustable polymer by the initiator; oxidation is performed to construct a disulfide bond with reduction response; and the pH-reduction dual-response polymer embolization agent for tumor catheter-free embolization. The embolization agent can respond to tumor reducibility and a subacid microenvironment to generate gelation transformation, so that the vascular embolization effect on tumors is realized.

Description

technical field [0001] The invention belongs to the technical field of biomedical embolic agents, and relates to a pH-reduction dual response polymer embolic agent for catheter-free embolization of tumors and a synthesis method thereof. Background technique [0002] With the continuous development of technology and medical technology, great progress has been made in the development of medical methods and drugs for tumor treatment, but tumor is still one of the diseases with the highest morbidity and mortality in the world. Tumor treatment methods in the prior art, such as chemoradiotherapy or surgical treatment, often have many disadvantages such as damage to normal tissues, difficulty in completely removing tumor tissues, or other side effects and complications. Therefore, highly selective and precise treatment methods aimed at the special microenvironment of tumors have emerged rapidly in recent years. Transcatheter Arterial Embolization (TAE) is a new method of clinical ...

Claims

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Application Information

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IPC IPC(8): C08G69/42C08G69/10C08G69/44C08F8/34C08F293/00C08F220/04A61L24/04A61L24/00
CPCC08G69/42C08G69/10C08G69/44C08F8/34C08F293/005C08F220/04A61L24/046A61L24/0015A61L2400/06C08L77/04C08L53/00
Inventor 路德待陈正鹏于莉莉陈铭枢李芸菲
Owner NORTHWEST NORMAL UNIVERSITY
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