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Antibacterial/healing-promoting double-drug delivery system, pharmaceutical composition as well as preparation method and application of antibacterial/healing-promoting double-drug delivery system

A delivery system and polymer technology, applied in the direction of drug combination, antibacterial drugs, pharmaceutical formulations, etc., can solve the problems of short drug retention time, high biological toxicity of preparations, and low bioavailability, so as to improve bioavailability and operation Convenience and the effect of prolonging the residence time

Pending Publication Date: 2022-03-25
CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the cleavage of the specific polypeptide sequence by the enzyme is used to release the drug, thereby playing an intelligent regulatory role; however, the polypeptide specifically recognized by the MMP-2 enzyme needs to be modified into hyaluronic acid containing the polypeptide, and the steps are cumbersome and the preparation process is complicated.
[0007] The methods for promoting wound healing disclosed in the above-mentioned documents have the problems of high biological toxicity of the preparation, complicated steps, short maintenance time of the drug in the wound, and low bioavailability.

Method used

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  • Antibacterial/healing-promoting double-drug delivery system, pharmaceutical composition as well as preparation method and application of antibacterial/healing-promoting double-drug delivery system
  • Antibacterial/healing-promoting double-drug delivery system, pharmaceutical composition as well as preparation method and application of antibacterial/healing-promoting double-drug delivery system
  • Antibacterial/healing-promoting double-drug delivery system, pharmaceutical composition as well as preparation method and application of antibacterial/healing-promoting double-drug delivery system

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0154] This embodiment provides an antibacterial / healing-promoting dual-drug delivery system. The preparation method of the antibacterial / healing-promoting dual-drug delivery system includes the following steps:

[0155] (1) The reaction formula of the polymer modified by the MMP-9 responsive peptide is as follows:

[0156]

[0157] The preparation method of the MMP-9 responsive peptide modified polymer specifically comprises the following steps:

[0158] (a) 9.6 μmol of MMP-9-responsive PVGLIG was dissolved in 1 mL of methanol to obtain solution A; 12 μmol of DSPE-Mal was dissolved in 2 mL of chloroform to obtain solution B;

[0159] (b) Mix solution A and solution B obtained in step (a), react at 40° C. for 4 hours, and remove the solvent to obtain an intermediate product;

[0160] (c) The intermediate product obtained in step (b), 13.2 μmol mPEG2k-NH 2 , 24 μmol EDC, 1.2 μmol DMAP and 3 mL chloroform were mixed, reacted at 40 ° C for 4 hours, concentrated to remove the...

Embodiment 2

[0166] This embodiment provides an antibacterial / healing-promoting dual-drug delivery system. The preparation method of the antibacterial / healing-promoting dual-drug delivery system includes the following steps:

[0167] (1) The reaction formula of the polymer modified by the MMP-9 responsive peptide is as follows:

[0168]

[0169] The preparation method of the MMP-9 responsive peptide modified polymer specifically comprises the following steps:

[0170] (a) 9 μmol of MMP-9-responsive PVGLIG was dissolved in 1 mL of methanol to obtain solution A; 12 μmol of DSPE-Mal was dissolved in 2 mL of chloroform to obtain solution B;

[0171] (b) Mix solution A and solution B obtained in step (a), react at 38° C. for 4.2 hours, and remove the solvent to obtain an intermediate product;

[0172] (c) The intermediate product obtained in step (b), 13 μmol mPEG2k-NH 2 , 25 μmol EDC, 1.3 μmol DMAP, and 3 mL chloroform were mixed, reacted at 38 ° C for 4.2 h, concentrated to remove the so...

Embodiment 3

[0178] This embodiment provides an antibacterial / healing-promoting dual-drug delivery system. The preparation method of the antibacterial / healing-promoting dual-drug delivery system includes the following steps:

[0179] (1) The reaction formula of the polymer modified by the MMP-9 responsive peptide is as follows:

[0180]

[0181] The preparation method of the MMP-9 responsive peptide modified polymer specifically comprises the following steps:

[0182] (a) 10 μmol of MMP-9-responsive PVGLIG was dissolved in 1 mL of methanol to obtain solution A; 12 μmol of DSPE-Mal was dissolved in 2 mL of chloroform to obtain solution B;

[0183] (b) Mix solution A and solution B obtained in step (a), react at 42° C. for 3.8 hours, and remove the solvent to obtain an intermediate product;

[0184] (c) The intermediate product obtained in step (b), 13.5 μmol mPEG2k-NH 2 , 23 μmol EDC, 1.1 μmol DMAP, and 3 mL chloroform were mixed, reacted at 42 ° C for 3.8 h, concentrated to remove the...

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Abstract

The invention provides an antibacterial / healing-promoting double-drug delivery system, a pharmaceutical composition as well as a preparation method and application of the antibacterial / healing-promoting double-drug delivery system. An outer layer of the antibacterial / healing-promoting dual drug delivery system comprises a hydrophilic chain segment, an inner core comprises a hydrophobic chain segment, and an MMP-9 responsive peptide is embedded between the hydrophilic chain segment and the hydrophobic chain segment. The antibacterial / healing-promoting double-drug delivery system provided by the invention can respond to the environment of a chronic wound difficult to heal, so that hydrophobic drugs are enriched at the wound, the hydrophobic drugs can be promoted to enter cells, and pathogenic bacteria in the cells are effectively killed; besides, the double-drug delivery system further comprises EGFR targeting peptide connected to the tail end of the hydrophilic chain segment, endocytosis of epithelial cells to the drug delivery system can be increased, so that the amount of the drug entering the epithelial cells is increased, and the drug can more effectively remove bacteria invading the epithelial cells.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to an antibacterial / healing-promoting dual drug delivery system, a pharmaceutical composition, a preparation method and application thereof. Background technique [0002] Trauma is the destruction of tissues or organs caused by mechanical factors on the human body, and is often accompanied by damage to important organs, with more loss of blood or plasma, severe hypoxia, acidosis, and massive tissue necrosis. These strong stimuli promote tissue degeneration, thereby accelerating the rate of metabolic changes, leading to shock, acute renal failure, sepsis, sepsis and other serious complications. In the face of such wounds, the treatment and repair of the damaged parts will be carried out after the rescue. In the process of wound tissue healing, it is often accompanied by infection and adhesion. To address these problems, antibiotics, anti-adhesion film, and hemostatic pro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/62A61K9/06A61K31/12A61K31/496A61K47/42A61P17/02A61P31/04C08G65/335C08G81/00
CPCA61K47/62A61K47/42A61K31/12A61K31/496A61K9/06A61P31/04A61P17/02C08G65/3356C08G81/00
Inventor 马晓溦朱奎沈建忠赵谦陈莹娴韩军华
Owner CHINA AGRI UNIV
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