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Preparation method and application of mesoporous calcium carbonate pharmaceutical composition modified by hyaluronic acid

A technology of hyaluronic acid modification and hyaluronic acid, applied in the field of medicine, can solve the problems of low tumor targeting and poor water dispersibility, and achieve the effects of simple preparation process, low production cost, and huge economic and social benefits.

Active Publication Date: 2019-04-30
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still some limitations in the application of small molecule sonosensitizers, such as low tumor targeting and poor water dispersibility.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The preparation method of the mesoporous calcium carbonate pharmaceutical composition modified by hyaluronic acid of the present invention comprises the following steps:

[0021] (1) Add 0.66g of CaCl 2 Dissolved in 1000ml water, configured as CaCl 2 solution; 0.63g of Na 2 CO 3 Dissolved in 1000ml water, configured as Na 2 CO 3 Solution: Dissolve 2.5g of soluble starch in 1000ml of water to form a soluble starch solution;

[0022] (2) The CaCl configured in step (1) 2 Mix 125ml of solution with 125ml of soluble starch solution, stir for 30min, then add 125ml of Na 2 CO 3 The solution was vigorously stirred for 15 minutes and left to stand for 24 hours; centrifuged at 12,000 rpm for 5-10 minutes to obtain a precipitate, which was redissolved in ultrapure water, then centrifuged and redissolved, and repeated twice, freeze-dried to obtain mesoporous calcium carbonate nanoparticles MCC;

[0023] (3) Ultrasonically disperse 170mg of mesoporous calcium carbonate nano...

Embodiment 2

[0028] The preparation method of the mesoporous calcium carbonate pharmaceutical composition modified by hyaluronic acid of the present invention comprises the following steps:

[0029] (1) Add 0.6g of CaCl 2 Dissolved in 1000ml water, configured as CaCl 2 solution; 0.6g of Na 2 CO 3 Dissolved in 1000ml water, configured as Na 2 CO 3 Solution: Dissolve 2 g of soluble starch in 1000 ml of water to form a soluble starch solution;

[0030] (2) The CaCl configured in step (1) 2 Mix 100ml of solution with 100ml of soluble starch solution, stir for 20min, then add 100ml of Na 2 CO 3The solution was vigorously stirred for 10 minutes and left to stand for 22 hours; centrifuged at 12,000 rpm for 5 minutes to obtain a precipitate, which was redissolved in ultrapure water, then centrifuged and redissolved, and repeated twice, freeze-dried to obtain mesoporous calcium carbonate nanoparticles MCC;

[0031] (3) Ultrasonic disperse 140mg of mesoporous calcium carbonate nanoparticles ...

Embodiment 3

[0036] The preparation method of the mesoporous calcium carbonate pharmaceutical composition modified by hyaluronic acid of the present invention comprises the following steps:

[0037] (1) Add 0.7g of CaCl 2 Dissolved in 1000ml water, configured as CaCl 2 solution; 0.7g of Na 2 CO 3 Dissolved in 1000ml water, configured as Na 2 CO 3 Solution: Dissolve 3 g of soluble starch in 1000 ml of water to form a soluble starch solution;

[0038] (2) The CaCl configured in step (1) 2 Mix 150ml of solution with 150ml of soluble starch solution, stir for 40min, then add 150ml of Na 2 CO 3 The solution was vigorously stirred for 20 minutes, and left to stand for 26 hours; centrifuged at 12,000 rpm for 10 minutes to obtain a precipitate, which was redissolved in ultrapure water, centrifuged and redissolved again, and so repeated 3 times, freeze-dried to obtain mesoporous calcium carbonate nanoparticles MCC;

[0039] (3) Ultrasonically disperse 200mg of mesoporous calcium carbonate n...

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Abstract

The invention relates to a preparation method and applications of a mesoporous calcium carbonate medicinal composition modified by hyaluronic acid, for effectively simultaneously realizing targeting, controlled release and ultrasonic therapy and ultrasonic imaging combination, and further realizing diagnosis and treatment integration on cancer. The technical scheme is as follows: the preparation method comprises the following steps: modifying hyaluronic acid on aminated calcium carbonate obtained by reacting mesoporous calcium carbonate and 3-aminopropyl triethoxysilane, and then loading a micromolecular sonosensitizer, thus obtaining the mesoporous calcium carbonate medicinal composition modified by hyaluronic acid. The preparation method has the advantages that a preparation process is simple, a method is stable and reliable, the production cost is low, and the prepared mesoporous calcium carbonate modified by hyaluronic acid and the medicinal composition of mesoporous calcium carbonate simultaneously have the efficacies of tumor targeting, in vitro and in vivo double-stimulation (in acid environment and under high-intensity focused ultrasonic condition) sensitive medicine release, sonodynamic therapy and ultrasonic imaging combined diagnosis and treatment integration, belong to an innovation in tumor treatment medicines, and have enormous economic and social benefits.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation method and application of a hyaluronic acid-modified mesoporous calcium carbonate pharmaceutical composition. Background technique [0002] At present, ultrasonic imaging technology has been widely used in the field of clinical medicine due to its advantages of non-invasive, non-radiation, cheap, dynamic real-time, diverse diagnostic parameters and engineering flexibility, and has become an effective means of medical examination and imaging diagnosis of diseases. In order to improve the resolution and contrast of ordinary ultrasound images, it is necessary to introduce a class of reagents that can significantly enhance medical ultrasound detection signals—ultrasound contrast agents. As a drug reservoir, mesoporous calcium carbonate nanoparticles (MCC) have a unique mesoporous structure that can load small molecule drugs and have a very high drug-loading capacity. In additio...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K47/36A61K47/02A61K41/00A61P35/00
CPCA61K9/0019A61K9/0024A61K9/0053A61K41/0033A61K47/02A61K47/36A61K49/221
Inventor 张振中冯倩华侯琳张媛媛
Owner ZHENGZHOU UNIV
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