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Polypeptide capable of forming PH response drug-loaded hydrogel through self-assembly, hydrogel and preparation method and application thereof

A self-assembly and hydrogel technology, applied in the field of biomedical materials and their preparation, can solve the problems of unsatisfactory drug absorption and distribution, poor bioavailability, fast metabolism, etc., and achieve good biodegradability and mechanical properties Good, reduce toxic and side effects

Active Publication Date: 2021-12-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Among them, there are many problems and deficiencies in traditional chemical drug therapy, such as fast metabolism, poor bioavailability, unsatisfactory drug absorption and distribution, poor selectivity, large toxic and side effects, etc., which have always been the limitations of cancer combination therapy

Method used

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  • Polypeptide capable of forming PH response drug-loaded hydrogel through self-assembly, hydrogel and preparation method and application thereof
  • Polypeptide capable of forming PH response drug-loaded hydrogel through self-assembly, hydrogel and preparation method and application thereof
  • Polypeptide capable of forming PH response drug-loaded hydrogel through self-assembly, hydrogel and preparation method and application thereof

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Experimental program
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Embodiment 1

[0030] Embodiment 1 (please supplement the specific consumption of following raw materials)

[0031] The polypeptide synthesis method described in the present invention is a conventional solid-phase synthesis method, that is, an insoluble resin is used as a solid-phase carrier, the C-terminus of the polypeptide chain is fixed on the resin, and amino acids are sequentially condensed from the C-terminal to the N-terminal to extend the polypeptide chain. .

[0032] 1. Peptide synthesis steps

[0033] In the first step, the first amino acid is covalently attached to the resin

[0034] Weigh 2g of 2-CTC resin (degree of substitution 0.9mmol / g) into a 150mL reactor, soak it in 50mL of DCM for 2h to make it swell, then wash the resin with 3 times the volume of the resin in DMF, and drain it, repeating this four times. The resin was drained and set aside. Weigh the first amino acid (4mmol) at the C-terminal into a 50mL centrifuge tube, add 20mL DMF to dissolve it, then add 2mL DIEA...

Embodiment 2

[0047] The synthesis method of the polypeptide is the same as in Example 1. Dissolve the synthesized polypeptide in deionized water, vortex until fully dissolved to obtain a polypeptide solution with a polypeptide concentration of 10 mg / ml, adjust the pH of the polypeptide solution to 7.4 with 0.5M NaOH solution, and let it stand at room temperature for 20 minutes to form a gel.

Embodiment 3

[0049] The synthesis method of the polypeptide is the same as in Example 1. Dissolve the synthesized polypeptide in deionized water, vortex until fully dissolved to obtain a polypeptide solution with a polypeptide concentration of 15 mg / ml, adjust the pH of the polypeptide solution to 7.4 with 0.5M NaOH solution, and let it stand at room temperature for 20 minutes to form a gel.

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Abstract

The invention discloses polypeptide capable of forming PH response drug-loaded hydrogel through self-assembly, hydrogel and a preparation method and application thereof. The polypeptide sequence is FOVVVEF, F is phenylalanine, O is ornithine, V is valine, and E is glutamic acid. Polypeptide with seven amino acids is synthesized through a solid-phase synthesis method, and the polypeptide is self-assembled to form the polypeptide hydrogel wrapping doxorubicin hydrochloride. The polypeptide has good biocompatibility, biodegradability and mechanical performance, can achieve a slow release effect after wrapping a drug, has high sensitivity to PH, and injects the drug-loaded gel to the periphery of a tumor in a tumor site in-situ injection mode; and under stimulation of an acidic tumor microenvironment, targeted slow-release drug delivery of anti-tumor drugs can be achieved, the chemotherapy effect is improved, the anti-tumor effect is improved, and toxic and side effects are reduced.

Description

technical field [0001] The invention relates to a biomedical material and its preparation method and use, in particular to a polypeptide capable of self-assembling to form a pH-responsive drug-loaded hydrogel, a hydrogel, its preparation method and its use. Background technique [0002] Currently, cancer treatments mainly include surgery, chemotherapy, and radiotherapy. Among them, there are many problems and deficiencies in the traditional chemical drug therapy, such as fast metabolism, poor bioavailability, unsatisfactory drug absorption and distribution, poor selectivity, large toxic and side effects, etc., which have always been the limitations of cancer combination therapy. In order to overcome the above shortcomings, more and more new drug-loaded materials have been developed. As a special drug carrier, polypeptide hydrogel has attracted great attention due to its excellent biocompatibility, controllable degradability and slow control. Injectable polypeptide hydrogel...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/08C07K1/06C07K1/04A61K31/704A61K9/06A61K47/42A61P35/00
CPCC07K7/06A61K31/704A61K9/06A61K47/42A61P35/00
Inventor 葛亮朱颖沈娟
Owner CHINA PHARM UNIV
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