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Mesoporous silicon dioxide-6-mercaptopurine-cisplatin nanoparticles as well as preparation, activity and application thereof

A technology of mesoporous silica and mercaptopurine, which is applied in the direction of active ingredients of heterocyclic compounds, medical preparations of non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of decreased survival rate and cure rate of cancer patients, Issues such as improving CDDP have not been achieved

Inactive Publication Date: 2018-02-13
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, none of these combination regimens has been able to achieve the goal of improving the survival and cure rates of cancer patients treated with CDDP and reducing systemic toxicity.

Method used

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  • Mesoporous silicon dioxide-6-mercaptopurine-cisplatin nanoparticles as well as preparation, activity and application thereof
  • Mesoporous silicon dioxide-6-mercaptopurine-cisplatin nanoparticles as well as preparation, activity and application thereof
  • Mesoporous silicon dioxide-6-mercaptopurine-cisplatin nanoparticles as well as preparation, activity and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1 prepares MSNS-6MP

[0022] 1. Preparation of MSNS

[0023] Dissolve 1g of cetyltrimethylammonium bromide (CTAB) in 480mL of distilled water, add 3.5mL of sodium hydroxide (2mol / L) under magnetic stirring, heat in an oil bath, and stabilize when the temperature in the flask reaches 80°C 1h, stir vigorously until the solution is clear and transparent, quickly add 5mL tetraethylorthosilicate (TEOS) and 1mL 3-mercaptopropyltrimethoxysilane (MPTMS), continue to react at 80°C for 2h under vigorous stirring, and then the reaction mixture passes through Wash with distilled water and ethanol three times respectively, dry in vacuum at 70°C for 24 hours, reflux with 350 mL of methanol (plus 7 mL of concentrated hydrochloric acid) for 24 hours, remove the surfactant template, wash with distilled water and ethanol three times, dry in vacuum at 70°C for 24 hours, and obtain 1.2 g surface Thiol-functionalized mesoporous silica nanoparticles (MSNS).

[0024] 2. Preparati...

Embodiment 2

[0026] Embodiment 2 prepares MSNS-6MP / CDDP

[0027] Dissolve 40 mg of CDDP in 5 mL of normal saline, add 300 mg of MSNS-6MP, protect from light, shake ultrasonically for 30 minutes, stir overnight at 37°C with magnetic force, dry in an oven at 37°C, filter with suction, wash away CDDP attached to the surface with normal saline, and vacuum at 37°C Dry to constant weight and repeat 3 times to obtain 330mg MSNS-6MP / CDDP. Gravimetric analysis showed that 300mg of MSNS-6MP / CDDP contained 30mg of CDDP.

Embodiment 3

[0028] Embodiment 3 measures the nanostructure of MSNS, MSNS-6MP and MSNS-6MP / CDDP

[0029] 1. Determination method The ethanol suspensions of MSNS, MSNS-6MP and MSNS-6MP / CDDP were prepared at a concentration of 500 μg / mL. 200 μL of the suspension was dropped on the surface of the scanning electron microscope glass, dried at 37°C, observed under the scanning electron microscope (S-4800, HITACHI, Japan), and the scanning electron microscope pictures were recorded. Take 50 μL of the suspension, drop them on the surface of the TEM copper grid, dry at 37°C, observe under the TEM (JEM-1230, JEOL, Japan), and record the TEM images.

[0030] 2. Measurement results from figure 2 It can be seen from the TEM images in that MSNS, MSNS-6MP and MSNS-6MP / CDDP are regular spheres with a diameter of about 100nm, and regular channels are distributed on the surface. From image 3 It can be seen from the scanning electron microscope images that MSNS, MSNS-6MP and MSNS-6MP / CDDP are all in a r...

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Abstract

The invention discloses a nano-scale mesoporous silica-6-mercaptopurine (6MP) / cisplatin (CDDP) nano-delivery system (MSNS-6MP / CDDP). Its preparation method is disclosed, that is, modifying mercapto groups on mesoporous silica, linking 6MP through disulfide bonds to form mesoporous silica nanoparticles (MSNS‑6MP) connected to 6MP, loading CDDP in the channel to form a link 6MP, CDDP-loaded mesoporous silica nanoparticles; disclosed its nanostructure; disclosed its role in inhibiting tumor growth in S180 mice, compared with conventional 6MP and CDDP combined application, MSNS‑6MP / CDDP significantly prolongs S180 Survival time of mice, improved efficacy and reduced systemic toxicity. Therefore, the invention discloses its application in the preparation of tumor treatment drugs, which has a good application prospect.

Description

technical field [0001] The invention relates to a mesoporous silica-6-mercaptopurine (6MP) / cisplatin (CDDP) nanoparticle (MSNN-6MP / CDDP). Its preparation method involves modifying mercapto groups on the surface of mesoporous silica nanoparticles to prepare mercapto-functionalized mesoporous silica nanoparticles (MSNN), and then the mercapto groups of MSNN are covalently combined with 6MP to form 6-mercaptopurine- Mercapto-modified mesoporous silica nanoparticles (MSNN-6MP), and finally loading cisplatin into the nanopores of MSNN-6MP to prepare nanoscale mesoporous silica-6-mercaptopurine / cisplatin nanoparticles (MSNN-6MP) -6MP / CDDP). Involved in its antitumor effect. Compared with the combined application of conventional 6MP and CDDP, MSNN-6MP / CDDP significantly prolongs the survival time of S180 mice, improves the curative effect and reduces the systemic toxicity of CDDP. Therefore, the present invention discloses the application of MSNN-6MP / CDDP in the preparation of ant...

Claims

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Application Information

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IPC IPC(8): A61K47/52A61K47/69A61K9/14A61K33/24A61K31/52A61P35/00
CPCA61K33/24A61K31/52A61K2300/00
Inventor 赵明彭师奇王玉记吕晓洁
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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