Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Alginic acid-adriamycin amycin bonding medicine and preparation method thereof

A technology of doxorubicin hydrochloride and alginic acid, which is applied in the direction of pharmaceutical formulations, antineoplastic drugs, drug combinations, etc., can solve the problems of lack of release of doxorubicin, poor biocompatibility, cumbersome preparation process, etc., and achieve good biological activity and Effects of biocompatibility, slow release, and stable performance

Active Publication Date: 2014-03-19
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The Chinese patent whose publication number is CN102406946A discloses a kind of macromolecular bonded drug, first, polyethylene glycol monomethyl ether, carboxylated doxorubicin derivatives, 1-(3-dimethylaminopropyl)-3-ethyl Carbodiimide hydrochloride and N-hydroxysuccinimide react in an organic solvent to obtain a reaction mixture, and then add poly (L-lysine) or chitosan to the reaction mixture to obtain Polymer doxorubicin-bonded drug; Chinese patent publication No. 101234205A discloses a polymer doxorubicin-bonded drug with targeting function, which is assembled by mixing two polyethylene glycol-polylactic acid block copolymers The polylactic acid chain end of the first polyethylene glycol-polylactic acid block copolymer is connected with doxorubicin, and the polyethylene glycol chain end of the second polyethylene glycol-polylactic acid block copolymer is connected with There is lactose, which has a sustained release function; lactose has a targeting function, which can realize the targeted delivery of doxorubicin, so the doxorubicin-bonded drug can be released slowly in tumor tissue; however, the above two bonded drugs are due to The chemical bond between the bonded polymer compound and the drug molecule is too stable, so there are problems such as low drug loading and lack of intelligence in the release of doxorubicin
Biomaterials (Vol.31, p1360-1371, 2010) disclosed a carboxyl group modified by polyethylene glycol monomethyl ether and cis-3-carboxyglutaconic anhydride on the surface amino groups of polyamide-amine dendrimers The polymer doxorubicin-bonded drug obtained by doxorubicin can be quickly released under the acidic conditions of tumor tissues and cells, thereby realizing the intelligence of drug release, but the carrier used in the bonded drug The material is a polyamide-amine dendrimer, and its preparation process is cumbersome and its biocompatibility is poor, which is not conducive to the practical application of the bonded drug.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Alginic acid-adriamycin amycin bonding medicine and preparation method thereof
  • Alginic acid-adriamycin amycin bonding medicine and preparation method thereof
  • Alginic acid-adriamycin amycin bonding medicine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0030] The invention also provides a preparation method of the alginic acid-doxorubicin bond medicine, which comprises:

[0031] Mixing and reacting the buffer solution in which doxorubicin hydrochloride is dissolved with alginic acid to obtain the alginic acid-doxorubicin bond drug having the structure of formula (I);

[0032] Alternatively, the buffer solution in which doxorubicin hydrochloride is dissolved is mixed and reacted with alginic acid and sodium cyanoborohydride to obtain an alginic acid-doxorubicin bond drug having a structure of formula (II).

[0033] The alginic acid-doxorubicin bond drug with the structure of formula (I) is prepared according to the following method:

[0034] First, doxorubicin hydrochloride is dissolved in a buffer solution to obtain a mixed solution; the doxorubicin hydrochloride has the structure shown in formula (III):

[0035]

[0036] The buffer solution is preferably an acetate buffer solution, specifically a sodium acetate-acetic acid buffer sol...

Embodiment 1～8

[0056] Prepare the acetate buffer solution with pH=5. Measure 5 mL of each buffer solution and place them in 8 round-bottom flasks. Add 0.05 g of doxorubicin hydrochloride to each flask. After stirring and dissolving in the dark, According to the dosage ratio in Table 1, add alginic acid and sodium cyanoborohydride to each flask. The number average molecular weight of the alginic acid is 3141 g.mol -1 , And then seal each reaction bottle, follow the reaction conditions in Table 1, and react for 52 hours in the dark. After the reaction, adjust the pH of each reaction solution to 7.4 with sodium bicarbonate solution, and then dialyze with a dialysis bag with a molecular weight cut-off of 7000 Dalton for 48 hours. After filtration After freeze-drying, the alginic acid-doxorubicin-conjugated drugs were obtained. The experimental results are shown in Table 1. Table 1 shows the reaction conditions and yields of the alginic acid-doxorubicin-conjugated drugs prepared in Examples 1-8 of t...

Embodiment 9～16

[0062] Prepare the acetate buffer solution with pH=5, and place 5 mL of each buffer solution in 8 round-bottom flasks. According to the ratio in Table 2, add doxorubicin hydrochloride to each flask, avoid light After stirring and dissolving, add alginic acid and sodium cyanoborohydride to each flask according to the dosage ratio in Table 2. The number average molecular weight of the alginic acid is 3141g.mol -1 , And then seal each reaction flask, and react for 52 hours at 40°C in the dark. After the reaction, adjust the pH of each reaction solution to 7.4 with sodium bicarbonate solution, and then dialyze with a dialysis bag with a molecular weight cut-off of 7000 Dalton for 48 hours, filter and freeze-dry to obtain respectively Alginic acid-doxorubicin bond drugs, the experimental results are shown in Table 2. Table 2 shows the reaction conditions and yields of the alginic acid-doxorubicin bond drugs prepared in Examples 9-16 of the present invention, where i represents alginic...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Number average molecular weightaaaaaaaaaa
Login to View More

Abstract

The invention provides an alginic acid-adriamycin amycin bonding medicine which has a structure shown in a formula (I) or (II), wherein n is degree of polymerization of alginic acid, and n is greater than or equal to 7 but less than or equal to 1507. The alginic acid-adriamycin amycin bonding medicine is prepared by taking alginic acid, sodium cyanoborohydride and adriamycin amycin as raw materials. As the raw material alginic acid ahs good bioactivity and biocompatibility, the alginic acid-adriamycin amycin prepared has good bioactivity and biocompatibility. Meanwhile, alginic acid and adriamycin amycin are connected through oxime bonds, and can be quickly released in a tumor tissue or cell under a lower pH value condition, so that the pesticide effect is enhanced. The reductive alginic acid-adriamycin amycin bonding medicine with the structure shown in the formula (II) further has a more stable performance, is more slowly to release adriamycin amycin, and reaches an ideal long-acting treatment.

Description

Technical field [0001] The present invention relates to the technical field of chemical bond drugs, in particular to an alginic acid-doxorubicin bond drug and a preparation method thereof. Background technique [0002] Doxorubicin, also known as 1,4-hydroxydaunorubicin, 1,4-hydroxyn-diamycin, doxorubicin, and hydroxyerythrubicin, is an anthracycline antibiotic with a high-efficiency and broad-spectrum anti-tumor The drug is a kind of cell cycle non-specific drug and has the strongest effect on S phase. It mainly acts by inserting cell DNA, thereby triggering topoisomerase II to destroy the tertiary structure of DNA. So far, doxorubicin is considered to be a powerful clinical chemotherapeutic drug, which mainly treats solid tumors such as liver cancer, lung cancer, gastric cancer, breast cancer, ovarian cancer, bladder cancer, and thyroid cancer. [0003] At present, clinically, doxorubicin chemotherapy is mainly administered through intravenous administration. However, the drug is...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K47/48A61K31/704A61P35/00
Inventor 丁建勋许维国庄秀丽陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com