Preparation method of active targeting adriamycin amycin-amphipathic chondroitin sulfate micelle

A chondroitin sulfate and amphiphilic technology, which is applied in the field of active targeting doxorubicin-amphiphilic chondroitin sulfate micelles, can solve the problem of lack of targeted tumor cell drug resistance and lack of target for anti-tumor drugs. Tropism, lack of targeting of tumor cells, etc., to achieve good application prospects, easy to pass through, and less interaction

Inactive Publication Date: 2015-02-25
TAISHAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although doxorubicin is widely used clinically, it lacks targeting of tumor cells
Because it can act on tumor cells and normal growth cells at the same time, this leads to significant toxic and side effects on normal tissues and organs at conventional doses, mainly manifested as: inhibiting bone marrow, leading to cumulative cardiotoxicity, and even causing Heart failure, intolerable by the patient leading to treatment failure
In addition, tumor cells are prone to spontaneous and acquired resistance to doxorubicin
These factors undoubtedly limit the clinical efficacy of doxorubicin
[0005] The toxic and side effects of antineoplastic drugs are largely caused by the lack of targeting of the drug. At the same time, due to the lack of targeting and the drug resistance of tumor cells, the effective drug concentration in the lesion tumor cells under the conventional treatment dose is too high. Low

Method used

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  • Preparation method of active targeting adriamycin amycin-amphipathic chondroitin sulfate micelle
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  • Preparation method of active targeting adriamycin amycin-amphipathic chondroitin sulfate micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Synthesis of folic acid-linoleoyl-shark chondroitin sulfate and preparation of doxorubicin nanoparticles

[0046] 1. Synthesis of Linoleoyl-Shark Chondroitin Sulfate

[0047] 5g shark chondroitin sulfate ( M w: 20,000), 0.5g DMAP, 100mL formamide, stir and dissolve at 55°C, add 1.5g of linoleoyl chloride for esterification reaction, stir at 55°C for 1h, dialyze the reaction solution with deionized water for 48h (change the water once every 6h) , to remove DMAP and formamide. Continue dialysis in 95% ethanol solution for 48h to remove free linoleic acid. The yellowish product obtained after dialysis was washed twice with 5 mL of 95% ethanol, and dried in vacuo at 45°C. The obtained yellowish solid powder was linoleoyl-sarcochondroitin sulfate, and the substitution degree of linoleic acid was 4.8%.

[0048] 2. Synthesis of Folate-Linoleoyl-Shark Chondroitin Sulfate

[0049] Add 0.2g folic acid to 2mL DMSO, add 3 drops of triethylamine dropwise, stir to dis...

Embodiment 2

[0052] Example 2 Synthesis of folic acid-linoleoyl-low molecular weight porcine chondroitin sulfate and preparation of doxorubicin nanoparticles

[0053] 1. Synthesis of Linoleoyl-Low Molecular Weight Porcine Chondroitin Sulfate

[0054] 10g low molecular weight porcine chondroitin sulfate ( M w: 4,000), 1g DMAP, 100mL formamide, stir and dissolve at 55°C, add 3g of linoleoyl chloride for esterification reaction, stir at 55°C for 1h, dialyze the reaction solution with deionized water for 48h (change the water every 6h), remove DMAP and formamide. Continue dialysis in 95% ethanol solution for 48h to remove free linoleic acid. The yellowish product obtained after dialysis was washed twice with 5 mL of 95% ethanol, and dried in vacuum at 45°C. The obtained yellowish solid powder was linoleoyl-low molecular weight porcine sulfate, and the substitution degree of linoleic acid was 5.3%. .

[0055] 2. Synthesis of Folate-Linoleoyl-Low Molecular Weight Porcine Chondroitin Sulfat...

Embodiment 3

[0059] Example 3 Synthesis of folic acid-α-linolenoyl-low molecular weight porcine chondroitin sulfate and preparation of doxorubicin nanoparticles

[0060] 1. Synthesis of α-linolenoyl-low molecular weight porcine chondroitin sulfate

[0061] 5g low molecular weight porcine chondroitin sulfate ( M w: 4,000), 0.5g DMAP, 100mL formamide, stir and dissolve at 55°C, add 1.5g of α-linolenoyl chloride for esterification reaction, stir at 55°C for 1h, dialyze the reaction solution with deionized water for 48h (change the water once every 6h ), remove DMAP and formamide. Continue dialysis in 95% ethanol solution for 48h to remove free α-linolenic acid. The yellowish product obtained after dialysis was washed twice with 5 mL of 95% ethanol, and dried in vacuum at 45°C. The resulting yellowish solid powder was α-linolenoyl-low molecular weight porcine chondroitin sulfate. 5.2%.

[0062] 2. Synthesis of Folate-α-Linolenoyl-Low Molecular Weight Porcine Chondroitin Sulfate

[0063]...

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Abstract

The invention discloses a preparation method of an amphipathic polysaccharide-folic acid-fatty acyl-chondroitin sulfate which contains a folate-targeted group and takes an amphipathic of chondroitin sulfate as a hydrophilic chain segment and a long-chain fatty acid as a hydrophobic chain segment as well as an application thereof in the aspect of adriamycin amycin antitumor pharmaceutical preparations. The average molecular weight (Mw) of the folic acid-fatty acyl-chondroitin sulfate is 3100-53000Da. The general formula of the folic acid-fatty acyl-chondroitin sulfate is shown in the specification, wherein x which is the number of carbon atoms is an integer ranging from 10 to 22; y which is the number of double bonds is an integer ranging from 0 to 6; n is an integer ranging from 8 to 150; O-alkyl substitution degree is 5-50%; folic acid substitution degree is 0.5-2%.

Description

Technical field [0001] The present invention involves a preparation method for a folic acid receptor with orcylin receptor to target two human sulfate sulfate nanojamins. Background technique [0002] Ayimycin, also known as Doxorubicin, belongs to the rotten antitumor antibiotics and has a clinical history of more than forty years.The structure is as follows: [0003] [0004] The mechanism of gyrincin is to interact with topological enzyme II to form a DNA-topological enzyme II-pharmaceutical triple complex, inhibit RNA transcription and DNA copy, and use anti-tumor activity.Aytein is a broad -spectrum antitumor drug, which is mainly used to treat physical tumors, such as breast cancer, ovarian cancer, lung cancer, thyroid cancer, liver cancer, sarcoma, etc.Eycin can be applied alone or combined with other drugs.Although glimcin is widely used in clinical practice, it lacks targeted tumor cells.Because it can act on tumor cells and normal growth cells at the same time, this l...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K9/107A61K31/704A61P35/00
Inventor 肖玉良武夏明韩俊芬
Owner TAISHAN MEDICAL UNIV
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