CN107550889A - The Nanometer Insulin chitosan of quick adjustment drug releasing rate - Google Patents
The Nanometer Insulin chitosan of quick adjustment drug releasing rate Download PDFInfo
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- CN107550889A CN107550889A CN201710994000.1A CN201710994000A CN107550889A CN 107550889 A CN107550889 A CN 107550889A CN 201710994000 A CN201710994000 A CN 201710994000A CN 107550889 A CN107550889 A CN 107550889A
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- chitosan
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Abstract
Present invention relates to the Nanometer Insulin chitosan of quick adjustment drug releasing rate, kernel is Nanometer Insulin chitosan, outer layer is high molecular polymer clad, the high molecular polymer clad on Nanometer Insulin chitosan surface is uneven, and single some parts of Nanometer Insulin 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 Nanometer Insulin-chitosan of quick adjustment drug releasing rate.
Background technology
Insulin is by endogenous or exogenous material such as glucose, lactose, ribose, essence by the beta Cell of islet in pancreas
The stimulation of propylhomoserin, hyperglycemic factor etc. and a kind of proteohormone secreted.Insulin is that swashing for blood glucose is uniquely reduced in body
Element, while promote glycogen, fat, protein synthesis.Exogenous insulin is mainly used to treat diabetes.
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 nanometer pancreas of quick adjustment drug releasing rate
Island element-chitosan.
Nanometer Insulin-chitosan of quick adjustment drug releasing rate, kernel are Nanometer Insulin-chitosan, outer layer
For high molecular polymer clad, it is characterized in that, the high molecular polymer clad height on Nanometer Insulin-chitosan surface is not
It is flat, and single Nanometer Insulin-some parts of chitosan surface are enclosed with high molecular polymer clad, some parts are not wrapped up
High molecular polymer clad.
Further, Nanometer Insulin-nm of chitosan diameter 400 after high molecular polymer clad is wrapped up.
Further, Nanometer Insulin-chitosan envelop rate is 60-80%.
Further, the nm-300 nm of nuclear diameter 200 in Nanometer Insulin-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 are modified the preparation of insulin-chitin nanometer
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, by neutral insulin:Chitosan is about 1:Insulin is dissolved in chitosan-acetic acid solution by 40.Magnetic agitation
3h, then ultrasound 10 times (each 6s, being spaced 1s) in ice-water bath, 20min is centrifuged under 6000r/min, takes supernatant freezing dry
It is dry, that is, obtain the nano-particle of two kinds of modified insulin-chitosans.Whole lucifuge operation.
The crosslinking of nano-particle:The lyophilized samples of modified insulin-chitin nanometer CS-SA-LA are taken to be scattered in again secondary
In water, concentration 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, then exposes
Dialysed 1d in air, and extracellular fluid dialysis are secondary water, and water is changed 1 time per 5h.Dialyzed solution is freeze-dried again, that is, what is be crosslinked changes
Property insulin-chitin nanometer (Cross-linked CS-SA-LA).Whole lucifuge operation.
1.4 are modified the modification of insulin-chitin nanometer outer surface
Nanometer Insulin-Chitosan powder is uniformly dispersed, is laid in smooth bright and clean and enough surface strength plane, then will
Another smooth bright and clean and enough hardness surface is pressed on Nano chitosan powder and pressurizeed, and adjusts moulding pressure, so
It is added dropwise macromolecule polymer solution around Nanometer Insulin-Chitosan powder dropwise afterwards, wetting, keeps ventilation under normal temperature
Finished to solution evaporation.
Such as Fig. 1, kernel 1 is Nanometer Insulin-chitosan, PEG and PLA-PEG integuments 2 are because when wrapping up from each other
Squeezed tight, so as to cause deep mixed breach 21 on the surface of integument 2.And some parts of single Nano chitosan surface are wrapped
It is wrapped with PEG and PLA-PEG clads 2, some parts 22 do not wrap up PEG and PLA-PEG clads 2.
Claims (5)
1. quickly Nanometer Insulin-chitosan of adjustment drug releasing rate, kernel is Nanometer Insulin-chitosan, and outer layer is
High molecular polymer clad, it is characterized in that, the high molecular polymer clad height on Nanometer Insulin-chitosan surface is not
It is flat, and single Nanometer Insulin-some parts of chitosan surface are enclosed with high molecular polymer clad, some parts are not wrapped up
High molecular polymer clad.
2. Nanometer Insulin-chitosan of quick adjustment drug releasing rate as claimed in claim 1, it is characterized in that:Parcel
Load medicine after macromolecule PEG and PLA-PEG receives the nm of nuclear diameter 1000 in insulin-rice chitosan.
3. Nanometer Insulin-chitosan of quick adjustment drug releasing rate as claimed in claim 2, it is characterized in that:Nanometer
Insulin-chitosan envelop rate is 60-80%.
4. Nanometer Insulin-chitosan of quick adjustment drug releasing rate as claimed in claim 3, it is characterized in that:Nanometer
The nm-800 nm of nuclear diameter 600 in chitosan.
5. Nanometer Insulin-chitosan of quick adjustment drug releasing rate as claimed in claim 4, it is characterized in that:High score
Sub- polymer includes PEG and PLA-PEG either PEG or PLA-PEG or PLA-PEG-PLA.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108371708A (en) * | 2018-02-02 | 2018-08-07 | 中山大学 | A kind of oral insulin nanoparticle formulations and preparation method thereof |
CN108434120A (en) * | 2018-03-26 | 2018-08-24 | 湘潭大学 | A kind of oral insulin nano particle and preparation method thereof |
-
2017
- 2017-10-23 CN CN201710994000.1A patent/CN107550889A/en not_active Withdrawn
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108371708A (en) * | 2018-02-02 | 2018-08-07 | 中山大学 | A kind of oral insulin nanoparticle formulations and preparation method thereof |
CN108434120A (en) * | 2018-03-26 | 2018-08-24 | 湘潭大学 | A kind of oral insulin nano particle and preparation method thereof |
CN108434120B (en) * | 2018-03-26 | 2020-02-07 | 湘潭大学 | Oral insulin nano-particles and preparation method thereof |
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