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Tumor-targeted nanometer compound, preparing method and application of compound to acoustic-power-mediated precise tumor treatment

A nanocomposite, tumor targeting technology, applied in the field of pharmaceutical preparations, can solve the problems of difficult to maximize enrichment of drugs, and achieve the effects of maximized enrichment, good long-circulation properties, and good sonodynamic anti-tumor effect.

Active Publication Date: 2019-07-12
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

SDT has attracted more and more attention in the field of tumor treatment due to its advantages of local precision and minimal invasiveness, no damage to normal tissues, etc. Sono-chemotherapy remains a major challenge in cancer treatment

Method used

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  • Tumor-targeted nanometer compound, preparing method and application of compound to acoustic-power-mediated precise tumor treatment
  • Tumor-targeted nanometer compound, preparing method and application of compound to acoustic-power-mediated precise tumor treatment
  • Tumor-targeted nanometer compound, preparing method and application of compound to acoustic-power-mediated precise tumor treatment

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0039] (1) Preparation of PCH

[0040] Place the methanol solution (10mg / mL) of PAMAM-G5.0 (300mg) in a single-necked flask, spin dry by rotary evaporation (evaporating temperature is 30~37℃, remove methanol), add anhydrous dimethylmethylene Sulfone (DMSO) re-dissolved. Dissolve succinic anhydride (600 mg) in anhydrous DMSO to obtain a 22 mg / mL succinic anhydride solution, which was added dropwise to the above single-neck flask, and stirred at room temperature for 24 hours. The reaction system uses a dialysis bag with Mw=3500Da to be dialyzed in deionized water for 3 days. The liquid in the dialysis bag is freeze-dried to obtain the product PAMAM-COOH (PCH). The Fourier infrared spectrometer is used to use solid potassium bromide powder as the diluent , The infrared spectrum of the product is analyzed by the tablet test, see figure 1 , The test result shows that at 1257cm -1 The characteristic peak of PCH appears at the place. At the same time, the product is tested by hydrogen...

example 1

[0043] (1) Dissolve 10 mg of PCH prepared in (1) in 2 mL of deionized water, and sonicate for 5 min in a water bath (20~25℃) to fully dissolve; dissolve 1 mg of ICG (molecular weight: 774.96) in 2 mL of deionized water After the water was added dropwise to the PCH solution, the mixed system was placed in an ultrasonic disintegrator, the ultrasonic intensity was set to 220W, ultrasonic for 3min, and then the free ICG was removed by centrifugation using an ultrafiltration tube (Mw=10kDa), and then freeze-dried to obtain PCI (ie PCH with ICG internal load);

[0044] (2) The surface of PCH is negatively charged, while the surface of the anti-tumor drug Dox is positively charged. The two can adsorb Dox on the surface of PCH through electrostatic adsorption. Therefore, 1mg Dox (molecular weight 579.99) was dissolved in 1mL of deionized water and added to the PCI (5mg) aqueous solution, stirred at room temperature for 24h, and then centrifuged with an ultrafiltration tube (Mw=10kDa) to ...

example 2

[0047] (1) Take 10mg of PCH prepared in (1) and dissolve it in 2mL of deionized water, sonicate it in a water bath (20~25℃) for 5min to fully dissolve; dissolve 2mg of ICG (molecular weight: 774.96) in 2mL of deionized water After the water was added dropwise to the PCH solution, the mixed system was placed in an ultrasonic disruptor, the ultrasonic intensity was set to 220W, ultrasonic for 3min, and then the free ICG was removed by centrifugation with an ultrafiltration tube (Mw=10kDa), and then freeze-dried to obtain PCI;

[0048] (2) Dissolve 2mg Dox (molecular weight 579.99) in 1mL deionized water and add it to PCI (10mg) aqueous solution, stir at room temperature for 24h, then use ultrafiltration tube (Mw=10kDa) to remove free Dox by centrifugation and freeze-dry to obtain PCID;

[0049] (3) Dissolve 3mg HA (6.4kDa) in 1mL deionized water and add it to the PCID (8mg) aqueous solution, stir at room temperature for 4h, then use an ultrafiltration tube (Mw=10kDa) to centrifuge to...

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Abstract

The invention discloses a tumor-targeted nanometer compound, a preparing method and application of the compound to acoustic-power-mediated precise tumor treatment. The nanometer compound comprises compound nanoparticles wrapped by hyaluronic acid. A preparing method of the compound nanoparticles includes the steps of converting part of amino groups on the surface of a dendrimer PAMAM into carboxylgroups through succinic anhydride, and compounding the dendrimer PAMAM with a sensitizer (indocyanine green), an anti-tumor medicine (doxorubicin) and hyaluronic acid. The nanometer compound has a good acoustic power anti-tumor effect, the sensitizer and the anti-tumor medicine have a good synergistic effect in treatment, and the nanometer compound is suitable for noninvasive / minimally invasive tumor treatment.

Description

Technical field [0001] The invention belongs to the field of pharmaceutical preparations, and specifically relates to a tumor-targeting nanocomposite, a preparation method and its application in sonodynamic therapy. Background technique [0002] Chemotherapy is currently an important means to treat tumors in addition to surgery, but the clinical benefits brought by different modes of administration and doses are quite different, and due to the different time lags in the adhesion, distribution, and metabolism of drugs, it is very It is difficult to deliver the appropriate concentration of drug to the target area of ​​the lesion at the correct time. In addition, the real-time drug concentration in the tumor is much lower than the effective dose, which causes pharmacokinetic tolerance, which is the main reason for the failure of chemotherapy. Exploring how to improve the bioavailability of chemotherapeutics and reduce the serious side effects and drug resistance in the body has bec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/34A61K47/36A61P35/00A61K31/704
CPCA61K31/704A61K41/0033A61K47/34A61K47/36A61P35/00A61K2300/00
Inventor 万明习吴鹏英乔晓阳
Owner XI AN JIAOTONG UNIV
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