CN106265683A - A kind of preparation method with the pathogenic bacterium biomembrane new inhibitor wearing film targeting characteristic - Google Patents
A kind of preparation method with the pathogenic bacterium biomembrane new inhibitor wearing film targeting characteristic Download PDFInfo
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- CN106265683A CN106265683A CN201610825038.1A CN201610825038A CN106265683A CN 106265683 A CN106265683 A CN 106265683A CN 201610825038 A CN201610825038 A CN 201610825038A CN 106265683 A CN106265683 A CN 106265683A
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- dspe
- peg5000
- pathogenic bacterium
- aptamer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- General Health & Medical Sciences (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A kind of preparation method with the pathogenic bacterium biomembrane new inhibitor wearing film targeting characteristic, first it is respectively adopted cell-penetrating peptide TAT and pathogenic bacterium aptamers modifies DSPE PEG5000, then use DSPE PEG to encapsulate 3 kinds and there is synergistic natural phenolic compound, prepare novel nano liposome, have and wear the feature such as film, targeting, significantly enhance the antibacterial of natural phenolic composition and antibiont film effect, it is possible to be effective against multiple drug-resistant bacteria, effectively remove pathogenic bacterium biomembrane.
Description
Technical field
The invention belongs to natural product field, the present invention relates to nanorize targeting modification natural constituents and prepare bacterial biof iotalm
The method of natural inhibitor.
Background technology
At present, the drug resistance problems of various malignant bacterias is increasingly severe, and the strong of food safety and people in serious threat
Health, especially bacterial biof iotalm, more higher than planktonic bacteria drug resistance, endanger bigger.In recent years, natural phenolic compound is antibacterial
Activity causes the attention of people, is not easily formed drug resistance, and side effect is less, has a extensive future.By target administration, nanometer
Nexus liposome modifications etc., are expected to improve the antibacterial of phenolic compound and antibiont film activity further.Thus keep away further
Exempt from the drug resistance of antibacterial and the untoward reaction of medicine, expand it in the clinical and application of other field.
Cell-penetrating peptide is the popular target base of research at present, is primarily due to cell-penetrating peptide and not only self can pass through various kinds of cell
Film, but also the exogenous macromole that can effectively carry Radix Achyranthis Bidentatae bigger than its relative molecular mass enters living cells, this high efficiency
Cell-penetrating peptide host cell is not had notable toxic and side effects.Aptamers (Aptamer) is that one obtains through in-vitro screening technology
The oligonucleotide sequence (RNA or DNA) arrived, has strict identification ability and the affinity of height, aptamers with corresponding part
Have high specific, target molecule is wide, be prone to the advantages such as external synthesis and modification.
In recent years, nanometer liposome has become the study hotspot in the field such as pharmacy and molecular biology as carrier.Lipid
Body as carrier have slow releasing pharmaceutical, extend action time, targeted, enhancing pharmaceutically active, reduce drug dose, avoid resistance to
There is, reduce the advantages such as the damage of normal tissue in the property of medicine.
Summary of the invention
A kind of preparation method with the pathogenic bacterium biomembrane new inhibitor wearing film targeting characteristic, its characterization step is:
Take DSPE-PEG5000 to be dissolved in right amount in ultra-pure water, with the carboxyl site of EDC activation DSPE-PEG5000, then press
DSPE-PEG5000 is that 1:1-5:1 adds TAT with the mol ratio of cell-penetrating peptide TAT, reacts 5-8h, forms compound DSPE-
PEG5000-TAT；Cross-linked by EDC, by the aptamer of DSPE-PEG5000 Yu certain pathogenic bacterium specific binding
(Aptamer) reaction, forms DSPE-PEG5000-Aptamer；
DSPE-PEG2000,40-60 DEG C of decompression rotary evaporation film forming is dissolved with chloroform；By DSPE-PEG5000-TAT with
DSPE-PEG5000-Aptamer is 1:1-1:3 mixing according to mass ratio, and this mixture taking 1 part of quality is dissolved in PBS buffering
In liquid, add 3-7 part quality phenolic compound compositions, phenolic compound compositions consist of P-coumaric acid, caffeic acid
And ursolic acid, it is sufficiently mixed；Being subsequently adding the DSPE-PEG2000 of the film forming of 15-20 part quality, 40-65 DEG C of concussion processes
1-4h, then processes 1-10min by this suspension ice-bath ultrasonic, extruded the microporous filter membrane of aperture 0.45 μm, and must have and wear film
The polyphenol nanometer liposome of targeting characteristic.
This beneficial effect of the invention: use novel nano polyphenol liposome prepared by the method, due to the modification of aptamers,
Can be specifically bound on target pathogenic bacterium and biomembrane thereof, accurate targeting；Cell-penetrating peptide is the most also used to be repaiied
Decorations such that it is able to promote that antimicrobial component enters in bacterial cell, significantly enhance antibacterial effect；3rd, use and there is collaborative resisting
3 kinds of natural phenolic compounds of bacterium effect act on jointly, and antibacterial activity and antibiont film ability are greatly enhanced；4th, employing is received
Mizhi plastid is as carrier, it is possible to ensures natural phenolic composition targeted to target pathogenic bacterium, and has slow release effect, energy
Enough extend the action time of phenolic compound, further enhance the antibacterial of phenols component and antibiont film effect, be conducive to simultaneously
Avoid drug resistance further, reduce other antibacterials and the injury of normal structure.Based on multiple advantage, prepared by this invention novel
Nanometer polyphenol liposome can effectively kill multiple drug-resistant bacteria, it is possible to the formation of suppression bacterial biof iotalm, destroys and high-efficient cleaning removes
Ripe pathogenic bacterium biomembrane, it is possible to the antibacterial ability of phenolic compound is improved decades of times.
Detailed description of the invention
Embodiment 1
Take 2g DSPE-PEG5000 to be dissolved in ultra-pure water, with the carboxyl site of EDC activation DSPE-PEG5000, then add
Enter cell-penetrating peptide TAT of 0.0003 mole, react 6h, form compound DSPE-PEG5000-TAT；Cross-linked by EDC, by DSPE-
PEG5000 reacts with the aptamer (Aptamer) of certain pathogenic bacterium specific binding, forms DSPE-PEG5000-
Aptamer；
DSPE-PEG2000 is dissolved, 60 DEG C of decompression rotary evaporation film forming with chloroform；By DSPE-PEG5000-TAT and DSPE-
PEG5000-Aptamer is 1:1 mixing according to mass ratio, takes this mixture of 2g and is dissolved in PBS, adds 7.5g phenols
Compound composition, phenolic compound compositions consist of P-coumaric acid 2.5g, caffeic acid 2.5g and ursolic acid 2.5g, fully
Mixing；Being subsequently adding the DSPE-PEG2000 of the film forming of 38g, 55 DEG C of concussions process 2h, then by this suspension ice-bath ultrasonic
Process 5min, extruded the microporous filter membrane of aperture 0.45 μm, and must have the polyphenol nanometer liposome wearing film targeting characteristic.
Embodiment 2
Take DSPE-PEG5000 to be dissolved in right amount in ultra-pure water, with the carboxyl site of EDC activation DSPE-PEG5000, then press
DSPE-PEG5000 is that 3:1 adds TAT with the mol ratio of cell-penetrating peptide TAT, reacts 7h, forms compound DSPE-PEG5000-
TAT；Cross-linked by EDC, DSPE-PEG5000 is anti-with the aptamer (Aptamer) of certain pathogenic bacterium specific binding
Should, form DSPE-PEG5000-Aptamer.
DSPE-PEG2000 is dissolved, 45 DEG C of decompression rotary evaporation film forming with chloroform；By DSPE-PEG5000-TAT and DSPE-
PEG5000-Aptamer is 1:1.5 mixing according to mass ratio, takes this mixture of 3g and is dissolved in PBS, adds the phenol of 9g
Compounds compositions, phenolic compound compositions consist of P-coumaric acid 3g, caffeic acid 3g and ursolic acid 3g, the most mixed
Close；Being subsequently adding the DSPE-PEG2000 of 60g film forming, 60 DEG C of concussions process 3h, then this suspension ice-bath ultrasonic are processed
8min, extruded the microporous filter membrane of aperture 0.45 μm, must have the polyphenol nanometer liposome wearing film targeting characteristic.
Embodiment 3
Take DSPE-PEG5000 to be dissolved in right amount in ultra-pure water, with the carboxyl site of EDC activation DSPE-PEG5000, then press
DSPE-PEG5000 is that 1:1 adds TAT with the mol ratio of cell-penetrating peptide TAT, reacts 5h, forms compound DSPE-PEG5000-
TAT；Cross-linked by EDC, DSPE-PEG5000 is anti-with the aptamer (Aptamer) of certain pathogenic bacterium specific binding
Should, form DSPE-PEG5000-Aptamer.
DSPE-PEG2000 is dissolved, 51 DEG C of decompression rotary evaporation film forming with chloroform；By DSPE-PEG5000-TAT and DSPE-
PEG5000-Aptamer is 1:2 mixing according to mass ratio, and this mixture taking 0.5g is dissolved in PBS, adds 2g's
Phenolic compound compositions, phenolic compound compositions consist of P-coumaric acid 0.6g, caffeic acid 0.7g and ursolic acid 0.7g,
It is sufficiently mixed；Being subsequently adding the DSPE-PEG2000 of the film forming of 9.5g, 63 DEG C of concussions process 1.5h, then by this suspension ice
Bath supersound process 6min, extruded the microporous filter membrane of aperture 0.45 μm, must have the polyphenol nano-lipid wearing film targeting characteristic
Body.
Claims (1)
1. having a preparation method for the pathogenic bacterium biomembrane new inhibitor wearing film targeting characteristic, its characterization step is:
(1) take DSPE-PEG5000 to be dissolved in right amount in ultra-pure water, with the carboxyl site of EDC activation DSPE-PEG5000, then press
DSPE-PEG5000 is that 1:1-5:1 adds TAT with the mol ratio of cell-penetrating peptide TAT, reacts 5-8h, forms compound DSPE-
PEG5000-TAT；Cross-linked by EDC, by the aptamer of DSPE-PEG5000 Yu certain pathogenic bacterium specific binding
(Aptamer) reaction, forms DSPE-PEG5000-Aptamer；
(2) DSPE-PEG2000,40-60 DEG C of decompression rotary evaporation film forming are dissolved with chloroform；By DSPE-PEG5000-TAT with
DSPE-PEG5000-Aptamer is 1:1-1:3 mixing according to mass ratio, and this mixture taking 1 part of quality is dissolved in PBS buffering
In liquid, add 3-7 part quality phenolic compound compositions, phenolic compound compositions consist of P-coumaric acid, caffeic acid
And ursolic acid, it is sufficiently mixed；Being subsequently adding the DSPE-PEG2000 of the film forming of 15-20 part quality, 40-65 DEG C of concussion processes
1-4h, then processes 1-10min by this suspension ice-bath ultrasonic, extruded the microporous filter membrane of aperture 0.45 μm, and must have and wear film
The polyphenol nanometer liposome of targeting characteristic.
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| CN201610825038.1A CN106265683A (en) | 2016-09-14 | 2016-09-14 | A kind of preparation method with the pathogenic bacterium biomembrane new inhibitor wearing film targeting characteristic |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113546162A (en) * | 2021-05-31 | 2021-10-26 | 江苏省农业科学院 | Mycoplasma vaccine and preparation method thereof |
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| CN113546162B (en) * | 2021-05-31 | 2023-07-18 | 江苏省农业科学院 | Mycoplasma vaccine and preparation method thereof |
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Application publication date: 20170104 |
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