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A diagnostic and therapeutic preparation with multiple stimuli-responsive drug controlled release function and its preparation method and application

A multi-stimuli-responsive, drug-controlled release technology, applied in the field of biomedical materials, can solve the problems of complex surface modification operations of polypyrrole, achieve the effects of improving biological safety, improving drug targeting, and solving complex surface modification processes

Active Publication Date: 2018-10-16
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] One of the objectives of the present invention is to provide a polypyrrole nanoparticle with gelatin as a stabilizer to improve the biological safety of polypyrrole, solve the problem of complex surface modification of polypyrrole, and at the same time endow the nanoparticle with gelatinase-sensitive drug control. ability to interpret

Method used

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  • A diagnostic and therapeutic preparation with multiple stimuli-responsive drug controlled release function and its preparation method and application
  • A diagnostic and therapeutic preparation with multiple stimuli-responsive drug controlled release function and its preparation method and application
  • A diagnostic and therapeutic preparation with multiple stimuli-responsive drug controlled release function and its preparation method and application

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Embodiment 1

[0034] A preparation scheme of a diagnostic and therapeutic preparation with multiple stimuli-responsive drug controlled release functions described in the present invention is shown in the attached figure 1 shown, including the following steps:

[0035] (1) Synthesis of polypyrrole nanoparticles with gelatin as a stabilizer: 500 mg of deep-water fish gelatin was added to 40 mL of water, heated and stirred at 50°C for 20 minutes to completely dissolve the gelatin. After cooling to room temperature, 0.82 g of ferric chloride hexahydrate was added to the solution, and stirring was continued at room temperature for 1 h. The solution was placed in an ice-water bath, 139 μL of pyrrole was slowly added dropwise to the solution, and the stirring was continued for 24 h. Polypyrrole nanoparticles were obtained by centrifugation at 17,000 g for 40 min, redispersed with deionized water, centrifuged, and washed three times to obtain pure polypyrrole nanoparticles. The mother liquor was s...

Embodiment 2

[0040] A preparation scheme of a diagnostic and therapeutic preparation with multiple stimuli-responsive drug controlled release functions described in the present invention is as follows:

[0041] (1) Preparation of carboxymethylcyclodextrin-modified gelatin: weigh monosubstituted carboxymethylcyclodextrin, dissolve it in deionized water, add 1-(3-dimethylaminopropyl)-3-ethylcarbodi Carboxyl groups were activated with imine hydrochloride and N-hydroxysulfosuccinimide, placed in a shaker for 15 minutes, and β-mercaptoethanol was added to terminate the reaction, and then dissolved in phosphate buffer (0.2 M, pH=8.0 ) deep-water fish gelatin, and continue shaking for 2 h. The reaction solution was added to a dialysis bag with a molecular cut-off of 2000 Da, dialyzed in pure water for 48 h, and the dialysate was constantly replaced, and finally pure carboxymethyl cyclodextrin-modified gelatin was obtained.

[0042] (2) Synthesis of polypyrrole nanoparticles with cyclodextrin-mod...

Embodiment 3

[0046] The evaluation of the photoacoustic imaging effect of a small animal in vivo photoacoustic imaging of a diagnosis and treatment preparation with multiple stimuli-responsive drug controlled release functions of the present invention mainly includes the following steps:

[0047] (1) Establishment of subcutaneous tumor model in nude mice: TPC-1 cells were injected into each nude mouse at 5×10 6 The amount of cells was inoculated subcutaneously on the outer thigh of BALB / c nude mice, and the nude mice were raised under SPF environment;

[0048] (2) The tumor size grows to about 200 mm 3 200 μL of 5 mg / mL of the preparation prepared in Example 1 was injected via the tail vein, and the photoacoustic signal of the tumor site was detected with a small animal photoacoustic imaging system before and after administration at different times.

[0049] The imaging results are attached image 3 As shown, after injection of the preparation, the photoacoustic signal at the tumor site ...

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Abstract

The invention discloses a diagnosis and treatment preparation with a multi-stimuli-responsive medicine controlled release function and a preparation method and application thereof. According to the prepared preparation, polypyrrole nano particles are used as a core and externally modified by a cyclodextrin-chemotherapeutics compound and a targeted group, and the preparation has the effects of multi-stimuli-responsive medicine controlled release, photoacoustic imaging and chemotherapeutic and photo-thermal combined treatment. According to the preparation, three medicine controlled release mechanisms including pH values, gelatinase and photo-thermal response are combined, and the selectivity of chemotherapeutics to tumors is improved; imaging and treatment are fused, in-vivo distribution ofthe preparation can be monitored in real time, and the laser radiation position, power and time during photo-thermal treatment are guided; and chemotherapeutics and photo-thermal treatment are combined, so that the tumor recurrence rate is effectively lowered. By means of the composite preparation, the diagnosis and treatment efficiency is effectively improved, the medical effect is improved, thetoxic and side effects are lowered, and the diagnosis and treatment preparation has good clinic application prospects.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a polypyrrole-cyclodextrin nanometer system for diagnosis and treatment with a multi-stimuli-responsive drug controlled release function and its preparation method and application. Background technique [0002] Chemotherapy is an important means of cancer treatment. However, after simple small molecule chemotherapy drugs enter the human body, they are rapidly metabolized and excreted by organs such as the liver and kidney, and their half-life and average residence time in the body are relatively short. Advanced drug delivery systems can solve this problem well. Loading chemotherapeutic drugs on nano drug carriers can greatly prolong the in vivo half-life of chemotherapeutic drugs, thereby increasing the drug efficacy. However, simple small-molecule chemotherapeutic drugs and common drug delivery systems still have the problems of insufficient tumor targeting and ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/61A61K41/00A61K49/22A61K47/64A61K47/69A61K47/68A61K45/06A61P35/00
Inventor 王凡梁晓龙马晓途李小达史继云姚美男邵楠张旭侯睿
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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