Polypeptide hydrogel loaded with small interfering RNA as well as preparation method and application of polypeptide hydrogel

A hydrogel, low-interference technology, applied in the direction of medical preparations, peptides, pharmaceutical formulations containing active ingredients, etc., can solve simple problems, achieve good histocompatibility, promote proliferation and migration, and promote wound healing. Effect

Active Publication Date: 2021-06-11
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to overcome in the prior art, the hydrogel dressing of current clinical application mostly is pure hydrogel matri...

Method used

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  • Polypeptide hydrogel loaded with small interfering RNA as well as preparation method and application of polypeptide hydrogel
  • Polypeptide hydrogel loaded with small interfering RNA as well as preparation method and application of polypeptide hydrogel
  • Polypeptide hydrogel loaded with small interfering RNA as well as preparation method and application of polypeptide hydrogel

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] A polypeptide The amino acid sequence of the polypeptide is SEQ ID NO: 1, the N-terminal of the polypeptide is acetylated with 2-naphthylacetic acid, the C-terminal contains two carboxyl groups, and the two carboxyl groups at one end are reserved: polypeptide GD7. A carboxyl group at the C-terminus is aminated as: GD7-NH 2 Its structure is as follows:

[0046]

[0047] The preparation method of GD7: synthesized by solid phase method.

[0048] GD7-NH 2 Preparation Methods: Synthesis by solid-phase method.

[0049] GD7 and GD7-NH2 were synthesized by Gill Biochemical (Shanghai) Co., Ltd.

[0050] Use analytical high-performance liquid chromatography to analyze, the gradient is 10-100, the time is 0-25 minutes, A pump is 100% acetonitrile plus 0.1% TFA, B pump is 100% water plus 0.1% TFA, sample injection analysis, search After the target peak, determine whether the mass spectrum is correct. After determining the target peak, give the corresponding gradient for prep...

Embodiment 2

[0052] A polypeptide hydrogel loaded with small interfering RNA, according to mass percentage, includes the following components:

[0053] GD7 or GD7-NH 2 : 0.2~0.6%;

[0054] G0-C14 / siRNA: 0.01~0.5%;

[0055] Solvent: 90-97%.

[0056] The preparation method of the above-mentioned polypeptide hydrogel loaded with small interfering RNA comprises the following steps:

[0057] (1) Dissolve GD7 or GD7-NH2 powder in ultrapure water, add a small amount of 1M NAOH solution to dissolve, vortex, and ultrasonic water bath to obtain a hydrogel solution;

[0058] (2) Cationic liposomes (G0-C14) were synthesized by ring-opening 1,2-epoxytetradecane to generate the 0th generation PAMAM dendrimers. The specific synthetic method refers to the literature: "X.Xu, J.Wu, S.Liu, P.E.Saw, W.Tao, Y.Li, L.Krygsman, S.Yegnasubramanian, A.M.De Marzo, J.Shi, C.J.Bieberich, O.C.Farokhzad, Small 2018,14,e1802565", "X.Xu, K.Xie, X.Q.Zhang, E.M.Pridgen, G.Y.Park, D.S.Cui, J.Shi, J.Wu, P.W.Kantoff, S.J....

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Abstract

The invention relates to the technical field of pharmaceutical chemistry, in particular to polypeptide hydrogel loaded with small interfering RNA and a preparation method and application of polypeptide hydrogel. The amino acid sequence of polypeptide is SEQ ID NO: 1, and the N end of the polypeptide is acetylated. After the polypeptide hydrogel is smeared on a wound, the retention rate of MMP-9siRNA compound on the wound can be effectively increased, use is convenient, and secondary mechanical damage to the wound can be avoided. The MMP-9siRNA is slowly released for a long time, and the function of the siRNA for inhibiting the MMP-9 is better played; an acidic and moist environment is provided, excessive alkaline exudate on the local part of a wound is neutralized and absorbed, the times of dressing change can be reduced, the discomfort or pain of a patient is reduced, the compliance of the patient is improved, and the healing of diabetic foot ulcer is promoted; and the polypeptide source and histocompatibility are good, no obvious toxic or side effect exists, the preparation condition is mild, the process is simple, operation is convenient, and industrial production can be achieved easily.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical chemistry, in particular to a polypeptide hydrogel loaded with small interfering RNA and its preparation method and application. Background technique [0002] The skin of diabetic patients is easily damaged, and it is difficult to heal after injury, and even leads to amputation of patients. This is a common and serious complication of diabetic patients, which brings a heavy burden to patients and society. Therefore, research on the treatment of diabetic foot ulcers is one of the key issues to be urgently solved clinically, and the use of dressings plays an extremely important role in the treatment of diabetic foot ulcers. [0003] Imbalances in extracellular matrix synthesis and degradation play an important role in diabetic skin damage and healing. Matrix metalloproteinase (matrix metalloproteinase, MMPs) system is a zinc-dependent endopeptidase family, which plays an important role in th...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K47/42A61K48/00A61K31/713A61K9/06A61P17/02
CPCC07K7/06A61K47/42A61K31/713A61K9/06A61P17/02
Inventor 严励许小丁任萌吴良燕蔡佩娥曾钢洪晓思陈彦博
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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