A doxorubicin derivative based on mercapto-betaine modification, nano drug and preparation method thereof

A technology of nano-drugs and derivatives, applied in the field of biomedicine, can solve the problems of adriamycin, such as large toxic and side effects, long blood circulation time, and small toxic and side effects, and achieve fast drug release ability, excellent anti-tumor effect, and reduced toxicity. Effect

Active Publication Date: 2022-04-01
YANSHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This kind of nano-drug has the advantages of long blood circulation time, high drug loading capacity, small toxic and side effects, good pH value response, drug controlled release ability and good tumor inhibitory effect, which effectively solves the toxic and side effects of doxorubicin and the tumor target. Downside Disadvantages

Method used

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  • A doxorubicin derivative based on mercapto-betaine modification, nano drug and preparation method thereof
  • A doxorubicin derivative based on mercapto-betaine modification, nano drug and preparation method thereof
  • A doxorubicin derivative based on mercapto-betaine modification, nano drug and preparation method thereof

Examples

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Effect test

Embodiment 1

[0061] This embodiment provides a doxorubicin derivative modified by mercapto sulfobetaine, and nanomedicine formed by its self-assembly, mercapto sulfobetaine is selected from 3-((3-mercaptopropyl) dimethyl Ammonium) propane-1-sulfonate, its concrete structure is as follows, and concrete experimental procedure comprises:

[0062]

[0063] 3-((3-Mercaptopropyl)dimethylammonium)propane-1-sulfonate

[0064] (1) According to the molar ratio of mercaptosulfobetaine and 2-methacryloylhydrazide hydrogen bromide to the ratio of 1:2, mix 74.6mg of 2-methacrylohydrazide hydrogen bromide with 50mg of The mercaptolated sulfobetaine was dissolved in 5 mL of methanol solution and stirred for 10 min under nitrogen gas. After removing the nitrogen gas and sealing off the oxygen, it was placed in a 35°C water bath and stirred for 24 h. Rotate the reacted solution to dryness, then add 1mL volume of methanol to dissolve, drop the methanol solution into 9mL acetonitrile, then add 9mL ether, ...

Embodiment 2

[0074] Based on the thiol SB-hyd-DOX prepared in Example 1, this example provides a nanomedicine formed by mixing and self-assembling a mercaptosulfobetaine-modified doxorubicin derivative and paclitaxel. The specific experimental steps include:

[0075] According to the mass ratio of mercapto SB-hyd-DOX and paclitaxel of 1:0.2, mercapto SB-hyd-DOX and paclitaxel were respectively prepared as 5 mg / mL dimethyl sulfoxide solution, and the mercapto SB-hyd-DOX solution was taken separately 83 μL, paclitaxel solution 16.6 μL; the mass concentration of the solution after blending doxorubicin derivatives and paclitaxel is 5 mg / mL, after mixing well, add it dropwise into the phosphate buffer solution with pH 7.4 and stir to obtain thiol SB-hyd-DOX@ PTX self-assembled nanomedicine.

[0076] To characterize the prepared nanomedicine, such as Figure 11 Shown:

[0077] Figure 11 is the hydrodynamic particle size of thiol SB-hyd-DOX@PTX nanomedicine in phosphate buffer solution with p...

Embodiment 3

[0079] This embodiment provides a doxorubicin complex modified by mercaptocarboxybetaine, and nanomedicine formed by its self-assembly. The mercaptocarboxybetaine is selected from 2-((mercaptomethyl)dimethylammonium) ethyl Salt, the specific structure is as follows, and the specific experimental steps include:

[0080]

[0081] 2-((Mercaptomethyl)dimethylammonium)acetate

[0082] (1) Dissolve 50 mg of 2-methacrylohydrazide hydrogen bromide in 41.7 mg of The mercaptolated carboxybetaine was dissolved in 10mL of methanol solution, stirred for 10min with nitrogen gas, and reacted for 6h after removing the nitrogen gas and sealing the oxygen. The reacted solution was evaporated to dryness, and then 1 mL of methanol was added to dissolve it. Add the methanol solution dropwise to 9 mL of acetonitrile, then add 9 mL of ether, centrifuge to remove the lower precipitate, and dry to obtain 2-methacrylohydrazide hydrogen bromide-modified mercaptocarboxybetaine, that is, mercapto CB-...

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Abstract

The invention provides a doxorubicin derivative based on mercapto-betaine modification, a nano-medicine and a preparation method thereof, belonging to the field of biomedicine. The doxorubicin derivative has a structure of general formula (I), and its preparation method comprises: mixing and reacting mercapto-betaine and acrylohydrazide hydrogen bromide salt in a polar solvent, and obtaining a compound containing hydrazide bond by crystallization method betaine derivatives; then the betaine derivatives containing hydrazide bonds and doxorubicin hydrochloride are dissolved in polar solvents, trifluoroacetic acid is added as a catalyst and stirred for reaction, at the end of the reaction by dialysis and crystallization A doxorubicin derivative modified by thiol betaine was obtained. The particle size of this nano-medicine can be controlled at 20‑200nm, the drug loading capacity of doxorubicin is as high as 62.6%, the mouse tumor inhibition rate is as high as 93.2%, and the blood circulation time is long. In addition, the prepared nano-drugs also have good pH-responsive drug-controlled release capabilities and low toxic and side effects.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a doxorubicin derivative based on mercapto-betaine modification, a nano drug and a preparation method thereof. Background technique [0002] Cancer seriously threatens human life and health. Small molecule anticancer drugs (doxorubicin, paclitaxel and chlorin e6, etc.) have been used in the treatment of human cancer. However, these small-molecule anticancer drugs have defects such as low solubility and large toxic and side effects. Researchers have developed various types of nano-drug carriers to deliver small-molecule anti-cancer drugs to tumor tissues, improve the efficacy of small-molecule anti-cancer drugs, and overcome the above-mentioned problems. Nanomedicines with a particle size of 20-200nm can be targeted and enriched at tumor sites by utilizing high retention and high permeability effects. This targeting effect of nanomedicine is closely related to the hydrophilic layer s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K31/337A61K31/409A61K31/4745A61K31/519A61K31/704A61K45/06A61P35/00C07D309/14B82Y5/00
CPCA61K47/542A61K45/06A61K31/704A61K31/337A61K31/4745A61K31/409A61K31/519A61P35/00C07D309/14B82Y5/00A61K2300/00
Inventor 王龙刚崔天明梁莹李舒凯何蒙蒙
Owner YANSHAN UNIV
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