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Fenton reagent and adriamycin co-transport targeting nanocarrier and preparation method thereof

A Fenton’s reagent and nanocarrier technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of co-transportation of Fenton’s reagent and doxorubicin. Carrier preparation method and other issues, to achieve stable release rate, high encapsulation rate and drug loading rate, and fast release rate

Active Publication Date: 2019-11-22
QILU UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, there is no effective Fenton's reagent and doxorubicin co-transport targeting nanocarriers and better preparation methods

Method used

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  • Fenton reagent and adriamycin co-transport targeting nanocarrier and preparation method thereof
  • Fenton reagent and adriamycin co-transport targeting nanocarrier and preparation method thereof
  • Fenton reagent and adriamycin co-transport targeting nanocarrier and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] The preparation of embodiment 1 CA-OH and Fc-OH

[0063] Preparation of CA-OH:

[0064] 1) In a 100 mL eggplant-shaped bottle, dissolve 12 mmol cinnamaldehyde and 15.6 mmol trimethylolethane in 12 mL toluene, and dissolve the above raw materials in a magnetic stirring oil bath.

[0065] 2) After the raw materials are completely dissolved, add 0.12 mmol catalyst p -TsOH, stirred and reacted at 90° C. for 10 h.

[0066] 3) After the reaction, toluene was removed by rotary evaporation at 45°C to obtain a yellow viscous substance, namely the product acetal;

[0067] with dichloromethane (CH 2 Cl 2 ) After dissolving the yellow sticky substance completely, add an appropriate amount of 200-300 mesh chromatographic silica gel powder to mix the sample, and add 3 drops of triethylamine during the sample mixing process to prevent the acetal decomposition of the product.

[0068] 4) Carry out column chromatography separation and purification

[0069] The column press agent i...

Embodiment 2

[0082] The preparation of embodiment 2CA-SA-COOH and Fc-SA-COOH

[0083] Preparation of CA-SA-COOH:

[0084] 1) In a 100 mL eggplant-shaped flask, 2.15 mmol of CA-OH synthesized in Example 1 and 3.23 mmol of dry succinic anhydride were dissolved in 5 mL of butanone, and the raw materials were dissolved in a magnetic stirring oil bath.

[0085]2) After the raw materials are completely dissolved, add 0.5 mL acid-binding agent triethylamine (TEA), condense and reflux, and stir the reaction at 80°C for 12 hours.

[0086] 3) After the reaction, butanone was removed by rotary evaporation at 40°C, and the reaction solution was mixed with silica gel powder into powder, and 3 drops of triethylamine were added during the sample mixing process.

[0087] 4) Carry out column chromatography separation and purification

[0088] The pressure column agent is made of petroleum ether and triethylamine in a volume ratio of 60:1, and the eluent is CH 2 Cl 2 、CH 3 OH was compounded at a volume...

Embodiment 3

[0101] The preparation of embodiment 3FA-PEG-COOH

[0102] 1) In a 50 mL eggplant-shaped bottle, mix 0.258 mmol FA·H 2 O and 0.258 mmol EDC·HCl were dissolved in 10 mL DMSO and stirred on a magnetic stirrer for 3 h to activate the g-carboxyl group of FA molecules.

[0103] 2) The activated FA solution was added dropwise to a solution containing 0.172 mmol NH 2 -PEG-COOH in 5 mL DMSO solution, with strong magnetic stirring drop by drop, and stirred at 65 °C for 24 h.

[0104] 3) After the reaction, the reaction solution was dialyzed in DMSO with an average molecular weight cut-off of 300 for 12 hours to remove excess FA molecules, and then dialyzed with distilled water for one day (changing the water several times) to remove the product of the activator EDC and DMSO.

[0105] 4) Finally, 0.3543 g of yellow solid FA-PEG-COOH was obtained by freeze-drying, with a yield of 85%.

[0106] Example 3 The reaction equation for the synthesis of FA-PEG-COOH is attached Figure 12 sho...

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Abstract

The invention discloses a fenton reagent and adriamycin co-transport targeting nanocarrier and a preparation method thereof. The method includes the steps of preparing CA-OH and Fc-OH, preparing CA-SA-COOH and Fc-SA-COOH, preparing FA-PEG-COOH, preparing CA and Fc-g-Pullulan, preparing CA, Fc and FA-g-Pullulan, and preparing DOX-loaded CFFP NPs. According to the preparation method, a hydrophobic chain segment containing a fenton reagent and a hydrophilic folic acid chain segment modified pullulan grafted copolymer with a targeting function are used for self-assembling and wrapping the anti-tumor treatment drug adriamycin, and the fenton reagent and adriamycin co-transport targeting nanocarrier is prepared. The nanocarrier and the preparation method eliminate the limitation in the aspects of the targeting property of an active oxygen generator and single active oxygen efficient treatment in the prior art.

Description

technical field [0001] The invention belongs to the technical field of medical polymer drug delivery and release, and specifically relates to a Fenton reagent and doxorubicin co-transport targeting nanocarrier and a preparation method thereof. Background technique [0002] Malignant tumors are currently one of the major diseases that endanger human health. Chemotherapy and combined treatment with other therapies are currently the main means of clinical treatment of tumors. [0003] Chemotherapy is an important method for clinical treatment of tumors, but chemotherapeutic drugs have high toxicity and side effects, and are easy to cause drug resistance. Therefore, how to reduce the toxic and side effects of drugs while improving the therapeutic effect of tumors has become a major research topic. [0004] Reactive oxygen species (ROS) widely exist in the human body and have high oxidative capacity. After enrichment, ROS can quickly oxidize enzymes, proteins and DNA related to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/36A61K31/704A61K33/00A61P35/00
CPCA61K9/1075A61K31/704A61K33/00A61K47/36A61P35/00A61K2300/00
Inventor 张海涛赛福涛马上鸿曲建波王建勇
Owner QILU UNIV OF TECH
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