Anthracycline antibiotic coupled nonlinear multi-block copolymer, and preparation method and application thereof

A technology of multi-block copolymers and antibiotics, applied in the direction of medical preparations, drug combinations, and pharmaceutical formulations of non-active ingredients, which can solve problems such as low solubility, limited application, and short half-life, and achieve easy dissolution and good therapeutic effect Effect

Active Publication Date: 2014-07-09
张雅珍
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Anthracycline antibiotics are currently widely used, but they often need to be turned into salts from a clinical point of view, such as doxorubicin. The common medicinal form is doxorubicin hydrochloride, which needs to be turned into hydrochloride. Its solubility is very low, it cannot be converted into salt form, so it cannot be used
After becoming hydrochloride, the pharmacodynamic function of doxorubicin is greatly reduced, so this brings great difficulties to clinical application.
[0004] Another disadvantage of anthracycline antibiotics is that due to their strong cytotoxicity, they are very toxic. They often have obvious bone marrow suppression about 10 days after use. After a week of use, they can show very obvious gastrointestinal tract Adverse reactions and cardiotoxicity, so the drug must be accurately calculated before it can be used, and the half-life of the drug is very short, which also limits the application

Method used

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  • Anthracycline antibiotic coupled nonlinear multi-block copolymer, and preparation method and application thereof
  • Anthracycline antibiotic coupled nonlinear multi-block copolymer, and preparation method and application thereof
  • Anthracycline antibiotic coupled nonlinear multi-block copolymer, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] 1) A mixture of 25 g of 1,6-bis(p-carboxyphenoxy)hexane in 500 ml of acetic anhydride is refluxed to form acetylated 1,6-bis(p-carboxyphenoxy)hexane;

[0055] 2) Mix 3 g of compound A, 51 mg of compound B, 165 mg of dicyclohexylcarbodiimide and 8 mg of pyridine, stir overnight at room temperature; then wash with ether and dry under vacuum to obtain a polymer;

[0056] 3) Mix the products of step 1) and step 2) into a flask, melt and polymerize under reduced pressure at 180°C for 1 hour; dissolve the polymer in chloroform after cooling to room temperature, wash with petroleum ether and dry;

[0057] 4) Put doxorubicin and the polymer of step 3 into 20ml dimethyl sulfoxide solution for 48 hours; then put it in an oven for 3 hours; at minus 10-20 degrees, ultrasonic for 15 minutes; homogenizer at high speed Stir for 1 minute, then put into 5% cholic acid solution and stir at 400 rpm for 2 hours; collect by centrifugation and freeze-dry to obtain the final product.

Embodiment 2

[0059] 1) A mixture of 30 g of 1,6-bis(p-carboxyphenoxy)hexane in 300 ml of acetic anhydride was refluxed to form acetylated 1,6-bis(p-carboxyphenoxy)hexane;

[0060] 2) 2.7 g of compound A, 29 mg of compound B, 130 mg of dicyclohexylcarbodiimide and 5 mg of pyridine were mixed, stirred overnight at room temperature; then washed with ether and dried under vacuum to obtain a polymer;

[0061] 3) Mix the products of step 1) and step 2) into a flask, melt and polymerize under reduced pressure at 150°C for 1 hour; dissolve the polymer in chloroform after cooling to room temperature, wash with petroleum ether and dry;

[0062] 4) Put pirarubicin and the polymer into a solution mixed with 5ml of ethanol and 5ml of dichloromethane; then put it in an oven for 24 hours; at minus 10-20 degrees, ultrasonic for 2 minutes; then homogenizer Stir at high speed for 2 minutes, put the product in 3% cholic acid solution and stir at 400 rpm for 2 hours; collect by centrifugation and freeze-dry t...

Embodiment 3

[0064] 1) A mixture of 1,6-bis(p-carboxyphenoxy)hexane 17 g in 500 ml acetic anhydride is refluxed to form acetylated 1,6-bis(p-carboxyphenoxy)hexane;

[0065] 2) 1.8 g of compound A, 26 mg of compound B, 90 mg of dicyclohexylcarbodiimide and 4 mg of pyridine were mixed with 10 ml of chloroform, stirred overnight at room temperature; then washed with ether and dried under vacuum to obtain a polymer;

[0066] 3) Mix the products of step 1) and step 2) into a flask, melt and polymerize under reduced pressure at 170°C for 1 hour; dissolve the polymer in chloroform after cooling to room temperature, wash with petroleum ether and dry;

[0067] 4) Put arubicin and the polymer of step 3 into a solution mixed with 10ml of dichloromethane and 6ml of dimethyl sulfoxide; then put it in an oven to dry for 1 hour; at minus 20-30 degrees, ultrasonic 1 minute, then high-speed stirring with a homogenizer for 5 minutes, the product was put into 2% cholic acid solution and stirred at 400 rpm fo...

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Abstract

The invention discloses a new compound anthracycline antibiotic coupled nonlinear multi-block copolymer, and a preparation method and an application thereof. The anthracycline antibiotic coupled nonlinear multi-block copolymer has better effects on treatment of oculopathy compared with other forms of drugs or medicaments.

Description

technical field [0001] The invention discloses a novel compound anthracycline antibiotic coupling nonlinear multi-block copolymer, as well as a preparation method and application. Background technique [0002] Anthracyclines are antimitotic and extremely cytotoxic drugs. Doxorubicin can successfully inhibit a variety of malignancies, including acute leukemia, lymphoma, soft tissue and osteosarcoma, childhood malignancies, and adult solid tumors. Its mechanism of action is that the drug can penetrate into the cell and bind to the chromosome. The planar loop in the drug structure is inserted between base pairs to form a complex with DNA, which seriously interferes with DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis. However, the concentration of doxorubicin required to produce an antiproliferative effect through this mechanism is higher than the concentration of the drug at the tumor site in clinical treatment. In addition, anthracycline antibiotics are a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G67/04C08G65/48A61K47/48A61K31/704A61P27/02A61P9/10
Inventor 张雅珍李铁力白毅
Owner 张雅珍
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