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Double-drug-loading self-healing hydrogel system and preparation method thereof

A dual drug-loading and hydrogel technology, which is applied in the direction of drug combinations, pharmaceutical formulations, and medical preparations of non-active ingredients, can solve the problems of clinical use restrictions, low oral activity, strong toxic and side effects, etc., and achieve short preparation cycles , good biocompatibility, and the effect of reducing toxic and side effects

Active Publication Date: 2017-08-08
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cisplatin is a complex of transition metal element platinum, and it is also a non-specific drug for the cell cycle. It has obvious inhibitory effect on cell proliferation. It is a broad-spectrum anticancer drug, but it has poor water solubility and low oral activity, especially toxic and side effects. Strong, resulting in greatly limited clinical use

Method used

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  • Double-drug-loading self-healing hydrogel system and preparation method thereof
  • Double-drug-loading self-healing hydrogel system and preparation method thereof
  • Double-drug-loading self-healing hydrogel system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] 1) Dissolve 10.000 g pullulan in 400 mL double-distilled water, and stir it with magnetic force to fully dissolve it;

[0030] 2) Add 10 mL of 232 mg / mL oxidant potassium periodate solution to the solution obtained in step 1) and react for 1.5 h;

[0031] 3) Add 0.72 mL glycerol to the solution obtained in step 2) and react for 15 min to terminate the oxidation reaction;

[0032] 4) Place the solution obtained in step 3) in a dialysis bag of MWCO 6000, and dialyze at 4°C for 3 days, during which time the water is changed every 6-8 hours;

[0033] 5) Vacuum freeze-dry the dialyzed solution for 3 days to obtain pure solid oxidized pullulan;

[0034] 6) Accurately weigh 1.000 g of the obtained oxidized pullulan, add 20 mL of double distilled water, and dissolve at 37°C;

[0035] 7) Add 30 mg cisplatin and 40 mg doxorubicin hydrochloride to the solution obtained in step 6), and fully dissolve at 37°C;

[0036] 8) Add 250 μL of 0.5 g / mL ε-polylysine aqueous solution to th...

Embodiment 2

[0041] 1) Dissolve 10.000 g pullulan in 400 mL double-distilled water, and stir it with magnetic force to fully dissolve it;

[0042] 2) Add 10 mL of 232 mg / mL oxidant potassium periodate solution to the solution obtained in step 1) and react for 1.5 h;

[0043] 3) Add 0.72 mL glycerol to the solution obtained in step 2) and react for 15 min to terminate the oxidation reaction;

[0044] 4) Place the solution obtained in step 3) in a dialysis bag of MWCO 6000, and dialyze at 4°C for 3 days, during which time the water is changed every 6-8 hours;

[0045] 5) Vacuum freeze-dry the dialyzed solution for 3 days to obtain pure solid oxidized pullulan;

[0046] 6) Accurately weigh 1.000 g of the obtained oxidized pullulan, add 20 mL of double distilled water, and dissolve at 37°C;

[0047] 7) Add 30 mg cisplatin and 40 mg doxorubicin hydrochloride to the solution obtained in step 6), and fully dissolve at 37°C;

[0048] 8) Add 350 μL of 0.5 g / mL ε-polylysine aqueous solution to the ...

Embodiment 3

[0053] 1) Dissolve 10.000 g pullulan in 400 mL double-distilled water, and stir it with magnetic force to fully dissolve it;

[0054] 2) Add 10 mL of 232 mg / mL oxidant potassium periodate solution to the solution obtained in step 1) and react for 1.5 h;

[0055] 3) Add 0.72 mL glycerol to the solution obtained in step 2) and react for 15 min to terminate the oxidation reaction;

[0056] 4) Place the solution obtained in step 3) in a dialysis bag of MWCO 6000, and dialyze at 4°C for 3 days, during which time the water is changed every 6-8 hours;

[0057] 5) Vacuum freeze-dry the dialyzed solution for 3 days to obtain pure solid oxidized pullulan;

[0058] 6) Accurately weigh 1.000 g of the obtained oxidized pullulan, add 20 mL of double distilled water, and dissolve at 37°C;

[0059] 7) Add 30 mg cisplatin and 40 mg doxorubicin hydrochloride to the solution obtained in step 6), and fully dissolve at 37°C;

[0060] 8) Add 50 μL of 0.5 g / mL ε-polylysine aqueous solution to the...

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Abstract

The invention discloses a double-drug-loading self-healing hydrogel system and a preparation method thereof. The preparation method comprises the steps of adopting oxidized pullulan, epsilon-polylysine and low molecular weight polyethyleneimine as raw materials, adding two anti-cancer drugs such as cis-platinum and doxorubicin hydrochloride while preparing a hydrogel, and generating dynamic imine linkage through Schiff base reaction and crosslinking to prepare the double-drug-loadingself-healinghydrogel system. The preparation method provided by the invention is simple to operate, and short in preparation period; the prepared hydrogel system has biocompatibility, syringeability and self-healing property, and is loaded with two drugs at the same time, so that combined chemotherapy can be carried out on malignant tumors through parenteral administration around the tumor, the drugs play tosynergistic effect, a curative effect is enhanced, and the drug toxicity and the drug resistance are reduced.

Description

technical field [0001] The invention belongs to the field of polymer drug carriers, and in particular relates to a double-loaded self-healing hydrogel system and a preparation method thereof. Background technique [0002] The occurrence and development of tumor is a complex process involving multiple steps and factors. At present, surgery, radiotherapy, and chemotherapy are still the main strategies for the treatment of malignant tumors. At the same time, biological treatments such as immunotherapy and gene therapy are emerging. Chemotherapy, which uses small molecule drugs to kill tumor cells, is gradually becoming an important component of comprehensive treatment for malignant tumors. part. However, drug resistance to chemotherapy is a major problem in the treatment of malignant tumors today, and it is also an important reason for the failure of comprehensive therapy. Of all the therapeutic agents available for chemotherapy, anthracyclines and platinum-based drugs are th...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K33/24A61K47/36A61P35/00C08B37/00C08J3/075A61K9/06A61K31/704
CPCA61K9/0019A61K31/704A61K33/24A61K47/36C08B37/0018C08J3/075C08J2377/04C08J2405/00C08J2479/02A61K2300/00
Inventor 程翠张秀丽游力军王家斌张其清
Owner FUZHOU UNIV
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