CN107595806A - The Nano chitosan of quick adjustment drug releasing rate - Google Patents
The Nano chitosan of quick adjustment drug releasing rate Download PDFInfo
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- CN107595806A CN107595806A CN201710992941.1A CN201710992941A CN107595806A CN 107595806 A CN107595806 A CN 107595806A CN 201710992941 A CN201710992941 A CN 201710992941A CN 107595806 A CN107595806 A CN 107595806A
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- nano chitosan
- chitosan
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Abstract
Present invention relates to the Nano chitosan of quick adjustment drug releasing rate, kernel is Nano chitosan, outer layer is high molecular polymer clad, the high molecular polymer clad on Nano chitosan surface is uneven, and single some parts of Nano chitosan surface are enclosed with high molecular polymer clad, some parts do not wrap up high molecular polymer clad.
Description
Technical field
Present invention relates to the Nano chitosan of quick adjustment drug releasing rate.
Background technology
Nano chitosan is presently the most one of important nanometer technology product, is widely used in bio-pharmaceuticals, disease is examined
The various fields such as disconnected, purified treatment, environmental monitoring, paint, cosmetics.When Nano chitosan makees pharmaceutical carrier, it surpasses
Micro volume more easily passes tissue space, will be contained by capillary wall, gastric mucosa, intestinal mucosa even keratoderma
Medicine transport directly to targeting moiety, slowly release, reach the purpose of medicament slow release and target administration.The technology changes well
It has been apt to pharmaceutical properties, has solved the current problems for influenceing curative effect of medication, more and more closed by people on medicament slow release
Note.
Nano chitosan is presently the most one of important nanometer technology product, is widely used in bio-pharmaceuticals, disease is examined
The various fields such as disconnected, purified treatment, environmental monitoring, paint, cosmetics.When Nano chitosan makees pharmaceutical carrier, it surpasses
Micro volume more easily passes tissue space, will be contained by capillary wall, gastric mucosa, intestinal mucosa even keratoderma
Medicine transport directly to targeting moiety, slowly release, reach the purpose of medicament slow release and target administration.The technology changes well
It has been apt to pharmaceutical properties, has solved the current problems for influenceing curative effect of medication, more and more closed by people on medicament slow release
Note.
Chitosan（Chitosan）It is chitin deacetylated derivative, is distributed widely in shellfish, insect and portion
In part microorganism wall.It is the second largest polysaccharide for being only second to cellulose, resource very abundant.Because chitosan compares chitin
More superior bio characteristic, be widely used in biomedicine, chemical, food industry, cosmetics industry, light industry,
The field such as agriculture, environmentally friendly pollution treatment and microelectronics.One of focus as global development research.All kinds of chitosan products in China are most
For normal size chitosan, fail really to show the bioactivity of chitosan and the overall picture of excellent medical characteristics, and nanometer technology
Intervention be the approach to solve the above problems.
Research finds that the release behavior of medicine can be by microballoon outer surface, the parent of modified high molecular polymer covering layer
Hydrophobicity and thickness control.Hydrophilic and hydrophobic such as PEG-PLA is different and different because of the two molecular weight, therefore can be by using
The release behavior of PEG-PLA clads control medicine with different molecular weight.
But the release behavior of polymer covering layer control medicine is by polymer concentration, molecular weight, coating thickness etc.
The influence of many factors, therefore, in laboratory needing to find a kind of can quickly adjust releasing for polymer covering layer control medicine
The method for putting speed, in favor of studying under different pharmaceutical rate of release, the property of medicament-carried nano chitosan.
The content of the invention
In view of this, in order to solve the above problems, the present invention provides a kind of nanoshell of quick adjustment drug releasing rate
Glycan.
The Nano chitosan of quick adjustment drug releasing rate, kernel is Nano chitosan, and outer layer is high molecular polymer
Clad, it is characterized in that, the high molecular polymer clad on Nano chitosan surface is uneven, and single Nano chitosan table
Some parts of face are enclosed with high molecular polymer clad, some parts do not wrap up high molecular polymer clad.
Further, the nm of Nano chitosan diameter 400 after high molecular polymer clad is wrapped up.
Further, Nano chitosan envelop rate is 60-80%.
Further, the nm-300 nm of nuclear diameter 200 in Nano chitosan.
Further, high molecular polymer includes PEG and PLA-PEG either PEG or PLA-PEG or PLA-PEG-
PLA。
High molecular polymer is fine and close and surface porosity, and it discharges solution when the speed of internal drug is wrapped up with it
Concentration（Molecular weight）It is relevant with integument thickness.In order to obtain the integument of different rate of release, conventional art needs to adjust molten
Liquid molecular weight repeatedly is repeatedly carried out wrapping up.Often obtain once the integument of different rate of release, it is necessary to carry out once complete
The whole technique for making-carrying medicine-parcel outer layer from microballoon.It is and undesirable（Rate of release）Experiment product can only abandon,
Lose time and medicine.And the chemicals used when wrapping up is often poisonous, integument thickness is adjusted using multiple parcel
Technique, it is dangerous to experimenter.Using the integument of structure in the application, you can quick regulation integument rate of release.When
When needing to configure the integument of different rate of release, it need to only cause the high molecular polymer integument of Nano chitosan core surface
It is uneven, and single Nano chitosan core surface is locally enclosed with high molecular polymer, part does not wrap up high molecular polymerization
Thing.The now speed of the control internal drug release of integument, depending on situation is wrapped up on surface（The local medicine for having integument is released
Slow down, fast without the thin place release of integument or integument, therefore the rate of release of single particulate is changed）, modification
Parcel situation（Integument is uneven, part is enclosed with high molecular polymer, part is not wrapped up）Different releases can be produced
The integument of speed.
Brief description of the drawings
Fig. 1 is the structural representation of the present invention.
Embodiment
1.1 material
Chitosan (CS, molecular weight 5000Da, deacetylation 85%), Zhejiang Australia is emerging.DL- lipoic acids 99% (LA), tristearin
98% (SA) of acid, 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), n-hydroxysuccinimide
(NHS), dithiothreitol (DTT) (DTT), it is purchased from Aladdin reagent (China) Co., Ltd.Formic acid solution (concentration 88%),
Formalin (concentration 40%), absolute ethyl alcohol are that analysis is pure, purchased from Tianjin reagent wholesaling firm.
The preparation of 1.2 grafted chitosans
1g chitosans are taken to be dissolved in 70mL deionized waters, (mol ratio of the amino of stearic acid and chitosan is 0.2 by stearic acid:
1) it is dissolved in 35mL ethanol that (EDC and NHS and carboxyl mol ratio are 10 with 1.6g EDC and 0.95g NHS:1), room temperature
It is added dropwise to after lower pre-reaction 0.5h in the aqueous solution of chitosan, reacts 2d at 60 DEG C.After reaction terminates, product is in deionized water
Dialyse 2d, changes water-dialyzing daily 2 times, and the molecular cut off of bag filter is 3500Da.Tristearin is obtained after dialyzate freeze-drying
The chitosan (CS-SA) of acid modification.
By CS-SA through same method be grafted again lipoic acid (mol ratio of the amino of lipoic acid and chitosan be 0.2:1), obtain
End-product stearic acid and the chitosan (CS-SA-LA) of lipoic acid grafting.Whole lucifuge operation.
1.3 amino methylate
Grafted chitosan CS-SA-LA is dissolved in a certain amount of 88% aqueous formic acid, adds appropriate formalin (first
Aldehyde is respectively 0.25 with the free amino group mol ratio on grafted chitosan:1、1:1 and 100:1) it is anti-at 60 DEG C after, stirring
8 ~ 12h is answered, product deionized water dialysis 3d, changes water-dialyzing daily 3 times, the molecular cut off of bag filter is 3500Da.Thoroughly
The grafted chitosan (Me-CS-SA-LA) that end-product methylates is obtained after analysis liquid freeze-drying.
1.4 the preparation of modification of chitosan nano-particle
The preparation of nano-particle：Two kinds of each 10mg of modification of chitosan of CS-SA-LA and Me-CS-SA-LA are taken to be dispersed in 10mL respectively
In deionized water, magnetic agitation 3h, then ultrasound 10 times (each 6s, being spaced 1s) in ice-water bath, centrifuge under 6000r/min
20min, take supernatant to be freeze-dried, that is, obtain the nano-particle of two kinds of modification of chitosan.Whole lucifuge operation.
The crosslinking of nano-particle：Take modification of chitosan nano-particle CS-SA-LA to freeze sample to be scattered in secondary water again, it is dense
Spend for 0.2mg/mL.PH value is adjusted to 8.5 with 0.2mol/L PBS cushioning liquid (pH=9.0), then inflated with nitrogen 10min,
The DTT of the lipoic acid 10% (mol ratio) relative to grafting is added, 22h is reacted at room temperature under nitrogen environment, is then exposed to air
Middle dialysis 1d, extracellular fluid dialysis are secondary water, and water is changed 1 time per 5h.Dialyzed solution is freeze-dried again, that is, the modification shell being crosslinked gathers
Sugared nano-particle (Cross-linked CS-SA-LA).Whole lucifuge operation.
The modification of 1.4 modification of chitosan nano-particle outer surfaces
Nano chitosan powder is uniformly dispersed, is laid in smooth bright and clean and enough surface strength plane, then by another
Smooth bright and clean and enough hardness surface is pressed on Nano chitosan powder and pressurizeed, and adjusts moulding pressure, then dropwise
It is added dropwise macromolecule polymer solution around Nano chitosan powder, wetting, keeps under normal temperature being vented to solution evaporation complete
Finish.
Such as Fig. 1, kernel 1 is Nano chitosan, PEG and PLA-PEG integuments 2 because closely squeeze from each other when wrapping up
Pressure, so as to cause deep mixed breach 21 on the surface of integument 2.And single some parts of Nano chitosan surface are enclosed with
PEG and PLA-PEG clads 2, some parts 22 do not wrap up PEG and PLA-PEG clads 2.
Claims (5)
1. the quickly Nano chitosan of adjustment drug releasing rate, kernel is Nano chitosan, and outer layer is high molecular polymer bag
Coating, it is characterized in that, the high molecular polymer clad on Nano chitosan surface is uneven, and single Nano chitosan surface
Some parts are enclosed with high molecular polymer clad, some parts do not wrap up high molecular polymer clad.
2. the Nano chitosan of quick adjustment drug releasing rate as claimed in claim 1, it is characterized in that：Wrap up macromolecule
The nm of nuclear diameter 1000 in medicament-carried nano chitosan after PEG and PLA-PEG.
3. the Nano chitosan of quick adjustment drug releasing rate as claimed in claim 2, it is characterized in that：Nano chitosan bag
Envelope rate is 60-80%.
4. the Nano chitosan of quick adjustment drug releasing rate as claimed in claim 3, it is characterized in that：In Nano chitosan
The nm-800 nm of nuclear diameter 600.
5. the Nano chitosan of quick adjustment drug releasing rate as claimed in claim 4, it is characterized in that：High molecular polymer
Including PEG and PLA-PEG either PEG or PLA-PEG or PLA-PEG-PLA.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710992941.1A CN107595806A (en) | 2017-10-23 | 2017-10-23 | The Nano chitosan of quick adjustment drug releasing rate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710992941.1A CN107595806A (en) | 2017-10-23 | 2017-10-23 | The Nano chitosan of quick adjustment drug releasing rate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107595806A true CN107595806A (en) | 2018-01-19 |
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ID=61079287
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710992941.1A Withdrawn CN107595806A (en) | 2017-10-23 | 2017-10-23 | The Nano chitosan of quick adjustment drug releasing rate |
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| Country | Link |
|---|---|
| CN (1) | CN107595806A (en) |
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2017
- 2017-10-23 CN CN201710992941.1A patent/CN107595806A/en not_active Withdrawn
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Application publication date: 20180119 |