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A pH-responsive and tumor-targeted anticancer drug carrier and preparation method thereof

An anticancer drug and tumor targeting technology, applied in the field of medicinal chemistry, can solve the problems of low drug loading rate and high only 19.2%, and achieve the effects of reducing drug resistance, obvious pH sensitivity, and easy operation.

Active Publication Date: 2021-10-01
TAIYUAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, Chen Qiuchi and others modified polyaspartic acid to obtain a targeting carrier capable of loading doxorubicin. However, the hydrophobic segment of this study used histidine, and the grafting rate reached only 17%, and the drug loading rate reached only 17%. 19.2%, low drug loading rate
Hima Bindu Ruttala et al. used aspartic acid, tyrosine and ethylene glycol to form a three-block copolymer carrier with pH response and redox effect, and loaded lonidamine and docetaxel at the same time, but still There is a problem of low drug loading rate, the highest is only 25%

Method used

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  • A pH-responsive and tumor-targeted anticancer drug carrier and preparation method thereof
  • A pH-responsive and tumor-targeted anticancer drug carrier and preparation method thereof
  • A pH-responsive and tumor-targeted anticancer drug carrier and preparation method thereof

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Embodiment 1

[0032] This embodiment provides a pH response and a tumor targeted dual drug anti-cancer carrier and a preparation method thereof, the preparation process figure 1 As shown, the specific steps are as follows:

[0033] (1) Preparation of polyteenaline-tyrosine graft (Pt): Weighing 0.36 G tyrosine to carry out 20 mL water for ultrasonic dispersion 20 min spare, and then take 0.8 g of polyteenine dissolution In 20 ml of water, 0.192 g of carbodiimide (EDC) was added to 0.115 g N-hydroxy succinimide (NHS) stirring reaction reaction for 40 min, and then added to the previously prepared tyrosine dispersion, stirred at 24 h. The unreacted tyrosine was removed by filtration, and the filtrate was dialyzed for three days, and then dried under 50 ° C. Grinding PT powder;

[0034] (2) Preparation of ethylenediamine - polyteenine - tyrosine (EPT): PT powder prepared by step (1) was dissolved in 30 ml of water, and 19.2 mg EDC and 14 mg NHS stirred reaction reaction 40 MIN, adding a drop of eth...

Embodiment 2

[0048] This embodiment provides a pH response and a tumor targeted dual drug anti-cancer carrier and a preparation method thereof, and the specific steps are as follows:

[0049] (1) Preparation of polyteenine-tyrosine graft (Pt): Weighing 0.108 G tyrosine to add 20 ml of water for ultrasonic dispersion 20 min spare, and separate 0.8 g of polyteenine dissolution In 50 ml of water, 0.038 g of carbon diimide (EDC) was added to 0.023 g N-hydroxy succinimide (NHS) stirring at 40 min, and then added to the previously prepared tyrosine dispersion, stirred at 24 h. The unreacted tyrosine was removed by filtration, and the filtrate was dialyzed for three days, and then dried under 50 ° C. Grinding PT powder;

[0050] (2) Preparation of ethylenediamine - polyteenine - tyrosine (EPT): PT powder prepared by step (1) was dissolved in water, and 3.8 mg EDC was added to 2.8 mg NHS stirring reaction 40 min. Heterdened ethylenediamine (EDA), stirred at a stirred reaction 24 h, three days by 2000 ...

Embodiment 3

[0055] This embodiment provides a pH response and a tumor targeted dual drug anti-cancer carrier and a preparation method thereof, and the specific steps are as follows:

[0056] (1) Preparation of polyteenine-tyrosine graft (Pt): Weighing 0.18 g of tyrosine to carry out 20 mL water for ultrasonic dispersion 20 min spare, and then take 0.8 g of polyteenine dissolution In 20 ml of water, 0.038 g of carbon diimide (EDC) was added to 0.023 g N-hydroxy succinimide (NHS) stirred by 40 min, and then the previously prepared tyrosine dispersion is added, and the reaction is stirred 24 h. The unreacted tyrosine was removed by filtration, and the filtrate was dialyzed for three days, and then dried under 50 ° C. Grinding PT powder;

[0057] (2) Preparation of ethylenediamine - polyteenine - tyrosine (EPT): PT powder prepared by step (1) was dissolved in water, and 3.8 mg EDC and 2.8 mg NHS stirred reaction reaction 40 MIN, adding a drop of ethylenediamine (EDA), stirring at 24 h, three days...

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Abstract

The invention discloses a pH-responsive and tumor-targeted anticancer drug carrier and a preparation method thereof. Polyaspartic acid (PASP) is used as a raw material, and tyrosine (Tyr) is grafted to polyaspartic acid (PASP) through amidation reaction. The aspartic acid side chain forms an amphiphilic polyaspartic acid-tyrosine graft, which can self-assemble in the aqueous phase to form nanomicelles. The aspartic acid side chain is grafted with ethylenediamine, and ethylenediamine is used as a bridge to graft hyaluronic acid (HA) as a targeting ligand, endowing the micelles with a targeting effect on cancer cells. Using curcumin as a hydrophobic drug model and doxorubicin hydrochloride as a hydrophilic drug model, the simultaneous loading of the two drugs is achieved with a high drug loading rate. The drug carrier has the following advantages: it can simultaneously load two drugs, has a high drug loading rate, has obvious pH response, has targeting ability to cancer cells, has good biocompatibility, is low in cost, and is easy to operate.

Description

Technical field [0001] The present invention relates to a pH response to a tumor-targeted anticancer drug carrier and a preparation method thereof, belonging to the field of medical chemistry. Background technique [0002] Cancer has always been one of the most terrible diseases that people smell, and due to the side effects of the drug in chemotherapy, it is critical to improve the specificity of the drug to cancer cells. The environmental pH around the cancer cell is relatively low to normal tissue cells, and there is excessively expressed specific receptor on the surface of cancer cells, such as a CD44 receptor specific to HA, which is not in normal tissue cells. Drug resistance of cancer cells is also one of the most headaches of people. [0003] The pharmaceutical carrier has been widely studied in anti-cancer drugs since discovered, which can utilize their own pH sensitivity and targeting to reduce drug-toxic side effects on human normal cells and improve drug utilization. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/34A61K47/36A61K31/704A61K31/12A61P35/00
CPCA61K9/1075A61K31/12A61K31/704A61K47/34A61K47/36A61P35/00A61K2300/00
Inventor 郭睿劼张杰李天杨侯文娟张耀东晏泓王慧芳牛宝龙
Owner TAIYUAN UNIV OF TECH