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Preparation method of polyacrylic acid-tocopherol succinate self-assembly drug loading system for slow drug release

A technology of tocopheryl succinate and polyacrylic acid, which is applied in the field of material synthesis and biomedicine, can solve the problems of unsatisfactory efficacy and achieve the effect of simple preparation

Inactive Publication Date: 2019-06-14
CHANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinically, traditional chemotherapy is the most common treatment strategy, and its efficacy is still unsatisfactory due to the non-specific toxicity of drugs

Method used

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  • Preparation method of polyacrylic acid-tocopherol succinate self-assembly drug loading system for slow drug release
  • Preparation method of polyacrylic acid-tocopherol succinate self-assembly drug loading system for slow drug release
  • Preparation method of polyacrylic acid-tocopherol succinate self-assembly drug loading system for slow drug release

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] The preparation of polyacrylic acid-tocopheryl succinate self-assembled drug loading system includes the following steps:

[0024] (1) Mix 0.2g polyacrylic acid and 50mL pH value of 5.6 phosphate buffer solution, then add 0.247g N-hydroxysuccinimide and 0.411g 1-ethyl-(3-dimethylaminopropyl) carbon Diimine hydrochloride, stirred at room temperature 25°C for 1 hour; then added 1.4 g of cystamine hydrochloride, and continued to stir for 24 hours; dialyzed for three days to remove unreacted substances, then centrifuged to remove the precipitate, and freeze-dried the supernatant The cystamine-modified polyacrylic acid can be obtained immediately.

[0025] (2) Dissolve 30mg of tocopheryl succinate in 10mL of N,N-dimethylformamide, then add 6.5mg of N-hydroxysuccinimide and 10.9mg of 1-ethyl-(3-dimethyl Aminopropyl) carbodiimide hydrochloride, stirred at room temperature 25°C for 1 hour; then a certain amount of cystamine-modified polyacrylic acid prepared in step (1) was di...

Embodiment 2

[0030] Drug release in vitro at different pH values ​​involves the following steps:

[0031] The preparation process of the polyacrylic acid-tocopheryl succinate self-assembled drug-loading system is the same as that of Example 1.

[0032] (1) Weigh 20 mg of the drug-loaded composite material, place them in dialysis bags, and place the dialysis bags in 50 mL of phosphate buffer solution with different pH; magnetically stir at a temperature of 37°C to release the drug in vitro; The pH of the phosphate buffered saline was 5.6, 6.5 and 7.4 and the release was 24 hours.

[0033] (2) Take a sample every 1 hour for the first 4 hours, take a sample every 2 hours for 4 to 12 hours, and take a sample every 12 hours for 12 to 24 hours. Take 3 mL of solution for each sample, and measure the released formazan The amount of methotrexate was supplemented with 3 mL of fresh phosphate buffered saline solution; the concentration of methotrexate was measured at 302nm using an ultraviolet spect...

Embodiment 3

[0036] In vitro drug release under glutathione-stimulated conditions involves the following steps:

[0037] The preparation process of the polyacrylic acid-tocopheryl succinate self-assembled drug-loading system is the same as that of Example 1.

[0038] (1) Weigh 20 mg of the drug-loaded composite material and place it in a dialysis bag, put the dialysis bag in 50 mL of phosphate buffer solution with a pH of 5.6 and containing 10 mM glutathione, and perform magnetic stirring. Released for 24 hours.

[0039] (2) Take a sample every 1 hour for the first 4 hours, take a sample every 2 hours for 4 to 12 hours, and take a sample every 12 hours for 12 to 24 hours. Take 3 mL of solution for each sample, and measure the released formazan The amount of methotrexate was supplemented with 3 mL of fresh phosphate buffered saline solution; the concentration of methotrexate was measured at 302nm using an ultraviolet spectrophotometer, and the cumulative drug release percentage at differen...

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Abstract

The invention relates to a preparation method of a polyacrylic acid-tocopherol succinate self-assembly drug loading system for slow drug release. The preparation method comprises the following steps:preparing cystamine modified polyacrylic acid, preparing polyacrylic acid-tocopherol succinate and preparing drug-loading polyacrylic acid-tocopherol succinate. The preparation method has the advantages that the polyacrylic acid-tocopherol succinate self-assembly drug loading system is simple to prepare and can be prepared through two-step amidation reaction, the self-assembled drug loading systemhas dual sensitivity of pH and redox, and a drug can be slowly released through stimulation of pH and glutathione.

Description

technical field [0001] The invention relates to a preparation method of a polyacrylic acid-tocopherol succinate self-assembled drug-loading system that can be used for drug sustained release, and belongs to the fields of material synthesis and biomedicine. technical background [0002] Cancer has been the focus of global attention for decades. Clinically, traditional chemotherapy is the most common treatment strategy, but its efficacy is still unsatisfactory due to the nonspecific toxicity of drugs. To alleviate systemic toxicity and enhance therapeutic efficacy, nanotechnology has been greatly developed in oncology. Utilizing the self-assembly of amphiphilic polymers in aqueous solution, nanoparticles with a core-shell structure can be formed. Among them, the hydrophilic shell is used as a physical shield to prevent the interaction between nanoparticles and nanoparticles, thereby ensuring the stability of nanoparticles; the hydrophobic core uses lipophilic fragments to pr...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/32A61K31/519A61P35/00
Inventor 孔泳丁承强吴大同
Owner CHANGZHOU UNIV
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