Biological responsiveness targeted double-drug slow-release carrier material and preparation method thereof

A slow-release carrier and responsive technology, which can be used in drug delivery, pharmaceutical formulations, medical preparations with inactive ingredients, etc. It can solve problems such as normal cell damage, toxic side effects, and lower drug utilization efficiency, and achieve good biological responsiveness. , the effect of easy degradation

Inactive Publication Date: 2016-09-21
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, human blood is a hydrophilic environment, and drugs are difficult to dissolve in blood, which poses a major challenge to the transportation and absorption of hydrophobic drugs.
At the same time, before the drug reaches the lesion, most of the drug has been released in advance, and the actual amount of the drug reaching the lesion is very small, which seriously reduces the utilization efficiency of the drug.
In addition, chemotherapy drugs have toxic side effects on normal cells, and the drugs released before reaching the lesion will cause great damage to normal cells

Method used

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  • Biological responsiveness targeted double-drug slow-release carrier material and preparation method thereof
  • Biological responsiveness targeted double-drug slow-release carrier material and preparation method thereof
  • Biological responsiveness targeted double-drug slow-release carrier material and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0039] A method for preparing a bioresponsive targeted dual-drug slow-release carrier material, comprising the following steps:

[0040](1) Synthesis of RAFT reagents:

[0041] a. Dissolve 2.5g KOH in 2.5mL H 2 Obtain KOH solution in O; Dissolve 10.1g dodecanethiol and 0.64g tetrabutylammonium bromide in 25mL acetone, then mix it with KOH solution;

[0042] b. Slowly add 2.6mL of carbon disulfide to the mixed solution obtained in step (a) dropwise, stir for 30 minutes, add 5mL of chloroform to it, and stir for another 10min; place the solution at 0°C, and add dropwise while stirring KOH solution (12.0g KOH dissolved in 10mL H 2 O), after the dropwise addition was completed, it was placed at room temperature and stirred overnight;

[0043] c. Add 60 mL of deionized water to the solution obtained in step (b), then add 10 mL of concentrated hydrochloric acid for acidification; the resulting product is vacuum-dried to obtain a solid product; recrystallized with isopropanol, and...

Embodiment 2

[0055] A method for preparing a bioresponsive targeted dual-drug slow-release carrier material, comprising the following steps:

[0056] (1) Synthesis of RAFT reagent: same as Example 1;

[0057] (2) Synthesis of PDSEMA:

[0058] (3) Preparation of amphiphilic single-chain polymer: Dissolve 90mg of RAFT reagent, 7g of PDSEMA, 4g of polyethylene glycol methacrylate (Mw 500) and 10mg of AIBN in 10mL of DMF, and use the freeze-thaw pump circulation method to purify and remove Gas more than 3 times; then seal the reaction mixture, put it into a preheated 70 ℃ oil bath for 12h; 5mL of dichloromethane, and then re-precipitated in 20mL of ether to obtain unreduced amphiphilic polymer single chain;

[0059] (4) Preparation of amphiphilic polymer nanospheres: Dissolve 10 mg of amphiphilic polymer single chain in 200 μL of acetone, slowly add DTT dropwise therein; stir for 10 minutes, add 1 mL of deionized water, and then stir overnight at room temperature , in contact with the air, ...

Embodiment 3

[0063] A method for preparing a bioresponsive targeted dual-drug slow-release carrier material, comprising the following steps:

[0064] (1) Synthesis of RAFT reagent: same as Example 1;

[0065] (2) Synthesis of PDSEMA:

[0066] (3) Preparation of amphiphilic polymer single chain: Dissolve 90mg of RAFT reagent, 5g of PDSEMA, 4g of polyethylene glycol methacrylate (Mw 500) and 10mg of AIBN in 10mL of DMF, and use the freeze-thaw pump circulation method to purify and remove Gas more than 3 times; then seal the reaction mixture, put it into a preheated 70 ℃ oil bath for 12h; 5mL of dichloromethane, and then re-precipitated in 20mL of ether to obtain unreduced amphiphilic polymer single chain;

[0067] (4) Preparation of amphiphilic polymer nanospheres: Dissolve 10 mg of amphiphilic polymer single chain in 200 μL of acetone, slowly add DTT dropwise therein; stir for 10 minutes, add 1 mL of deionized water, and then stir overnight at room temperature , in contact with the air, ...

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Abstract

The invention belongs to the field of targeted drug slow-release carrier materials, and particularly relates to a biological responsiveness targeted double-drug slow-release carrier material and a preparation method thereof. The biological responsiveness targeted double-drug slow-release carrier material is prepared from double-shell biological responsiveness nanometer microspheres; an inner shell of the material is prepared from nanometer microspheres formed by aggregating amphiphilic polymers; an outer shell of the material is mesoporous silica; the diameter of the inner shell is 160nm to 800nm; the mesoporous diameter of the mesoporous silica of the outer shell is 2 to 4nm. The amphiphilic polymer nanometer microspheres of the inner shell can provide load loci for a hydrophobic drug, and the mesoporous silica of the outer shell can provide load loci for a hydrophilic drug; hence, the biological responsiveness targeted double-drug slow-release carrier material can load two different drugs and realize slow release of the double drugs, so as to achieve the aim of double-drug synergy therapy.

Description

technical field [0001] The invention belongs to the field of targeted drug slow-release carrier materials, in particular to a bioresponsive targeted double-drug slow-release carrier material and a preparation method thereof. Background technique [0002] As the degree of social industrialization increases and environmental pollution becomes more and more serious, the human cancer rate increases year by year. At the same time, with the progress of social civilization, people pay more and more attention to their own quality of life and physical health. Therefore, the treatment of cancer has become an urgent problem for scientists and medical scientists since the 20th century. The current drugs for treating cancer are mainly composed of some hydrophobic organic molecules containing a large number of benzene rings or pyridine groups. However, human blood is a hydrophilic environment, and drugs are difficult to dissolve in blood, which poses a major challenge to the transportat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/32A61K47/04
CPCA61K9/0002A61K9/5115A61K9/5138
Inventor 阳晓宇范思宇胡执一别亚琦李宗鑫胡洁刘之状杨婧男苏宝连
Owner WUHAN UNIV OF TECH
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