CN109091702A - For the preparation method and product of body implanting material surface gelatine microsphere drug-loaded biological active coating and application - Google Patents
For the preparation method and product of body implanting material surface gelatine microsphere drug-loaded biological active coating and application Download PDFInfo
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- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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Abstract
The present invention relates to a kind of preparation methods for body implanting material surface gelatine microsphere drug-loaded biological active coating and products thereof and application, preparation method of the present invention be by chemical bond covalence graft gelatin in polyester material surface as first coating to increase the bonding force between coating and matrix, the gelatine microsphere for being loaded with drug is then chemically crosslinked bioactivity in gelatin coating surface as second coating to improve material.In the product that the method for the present invention obtains, gelatine microsphere drug-loaded biological active coating has coating and matrix bonding force strong, the features such as coating stable, good biocompatibility, high drugloading rate, the gelatin drug bearing microsphere coating not only overcomes the problem of the interface compatibility difference between synthesis macromolecule and natural polymer, and the drug with immunotherapy targeted autoantibody effect is firmly carried on implantable rack surface.Preparation method is simple by the present invention, and strong operability is at low cost, provides convenience for further production.
Description
Technical field
The present invention relates to a kind of preparation methods for body implanting material surface gelatine microsphere drug-loaded biological active coating
And products thereof and application, the invention belongs to nano biological medical coating Material Fields.
Background technique
It can be adhered to, be interacted with growth factor receptors, while cell-specific can be provided with the cell at implantation
Signal and the growth and differentiation of inducing cell are only ideal bio-medical timbering material.Polyester base material is a kind of with good
The degradable biomaterial of biocompatibility, is widely used in bone renovating bracket material and tissue engineering material etc..But
It is polyester base material shortage activity functional groups, it is difficult to cell signaling molecule is identified, to cause between cell and material
Cell compatibility is poor.Therefore, activation modification is carried out in polyester base material surface, guiding the proliferation of recipient cell, differentiation is very
It is necessary.Currently, being directed to the surface active of polyester base, most effective method is to carry out coating to material surface, with coating
Load bioactive substance.
For polymerization species bio-medical timbering material, there are mainly two types of coating processes, physical method and chemical method.Physics side
Method most typically passes through physisorption and coats biological activity protein or polypeptide in surface of polymer material, to improve material
Affinity between material and cell, the behaviors such as adhesiveness and guidance cell proliferation and differentiation.Physical method is the most simple and effective, still
Physics coating process is often to be easy hair by the interaction between Van der Waals force maintenance bioactive molecule and polymeric matrix
Raw mutually to separate, combination power is weak between the two, and coating is easy the culture in cell, falls off in digestion process, influences polymer
The bioactivity of material, so that long-term impact effect be not achieved.Chemical method is to introduce the surface of polymer material of biologically inert
The active function groups that can be reacted with large biological molecule.It is mainly carried out in three steps: introducing reactivity in surface of polymer material first
Functional group such as hydroxyl, carboxyl or amino etc.；Secondly, reactive functional groups are activated；Finally, by the reactive functional groups after activation
It is reacted with large biological molecule.Currently, to the chemical modification most study of polyester base class being Surface grafting reaction.According to the first step
The mode for introducing reactable functional group usually has plasma to cause (Li H, Xia Y, Wu J, He QY, Zhou
XZ, Lu G, Shang L, Boey F, Venkatraman SS, Zhang H. ACS Applied Materials &
Interfaces, 2012,4,687)；Ultraviolet radioactive causes (Ma ZW, Gao CY, Gong YH, Shen JC.
Biomaterials, 2005,26,1253) and basic hydrolysis (Xu FJ, Yang XC, Li CY, Yang WT.
Macromolecules, 2011,44,2371).
Gelatin is the product of part collagen hydrolysate, and isoelectric point has good biocompatibility in pH=5 or so,
Good biological degradability, while nontoxic, preparation is convenient, cheap, thus is widely used in pharmacy and medical industry.And
Gelatine microsphere is widely used in pharmaceutical carrier due to its special pattern and dimensional effect.When drug with it is gelatin-compounded
Afterwards, with the degradation of gelatin, it can achieve the effect of slow releasing pharmaceutical in vivo.Gelatin drug bearing microsphere is in following biology neck
It will be with very extensive application prospect in domain.But there is weak interaction force between natural polymer and synthesis macromolecule,
It is modern study project urgently to be solved that how ball-type natural macromolecular carriers are securely coated on to synthesis macromolecule surface.Cause
This, in the gelatin drug bearing microsphere coating research significance with higher of polyester material surface coating high stability and using valence
Value.
Summary of the invention
Low for existing degradable poly esters artificial implantation material bioactivity, bonding force is insufficient between coating and matrix,
The disadvantages of surface covering is unstable, it is an object of that present invention to provide one kind to carry medicine life for body implanting material surface gelatine microsphere
The preparation method of object active coating.
Another object of the present invention is: providing a kind of the micro- for body implanting material surface gelatin of above method preparation
Balloon borne medicine bioactivity coatings product.
Another object of the present invention is to: a kind of application of the said goods is provided.
The object of the invention is realized by following proposal: one kind is living for body implanting material surface gelatine microsphere drug-loaded biological
The preparation method of property coating, it is characterised in that by chemical bond covalence graft gelatin in polyester material surface as first coating
To increase the bonding force between coating and matrix, then the gelatine microsphere chemical crosslinking for being loaded with drug is made in gelatin coating surface
The preparation method for the bioactivity for being second coating to improve material, comprising the following steps:
(1) chemical graft process prepares gelatin first coating:
The polyester base thin slice of 1cm × 1cm is immersed in 20 mL ethyl alcohol: ultrasound 2 hours in water (v/v)=1:1, then with a large amount of water
Rinse, the thin slice cleaned is placed in the mixed solution of 1,6- hexamethylene diamine and isopropanol and reacts 5 min under 45 oC, go from
Sub- water cleans 12h, and vacuum drying for 24 hours, obtains amidized thin slice；Then it places it in 1, the 5- glutaraldehyde solution of 1 wt%,
3h is reacted at room temperature, and deionized water cleans 12h, and vacuum drying obtains aldehyde radical functionalization thin slice for 24 hours, above-mentioned processed thin slice is set
In 4 °C, concentration is that cross-linking reaction for 24 hours, impregnates 12h cleaning, vacuum drying is for 24 hours in distilled water in the gelatin solution of 1 ~ 10wt%
The polyester base thin slice of the gelatin coating of chemical graft process coating is obtained afterwards；
(2) emulsification condensation polymerization crosslinking method prepares gelatin drug bearing microsphere:
A certain amount of Gelatin is configured to the solution of 0.1 ~ 1wt% mass fraction in 40 °C of deionized water, will be wait load
Drug is dissolved in dimethyl sulfoxide (DMSO), is configured to the solution of 1 ~ 20 wt% mass fraction, is filled to above two solution
Drug solution is slowly added drop-wise in gelatin solution after point dissolution, is vigorously stirred to being mixed thoroughly；Corn oil heats in advance
To 40 °C, above-mentioned gelatin pharmaceutical mixed solution is added drop-wise in corn oil dropwise then, is stirred under the conditions of 500 ~ 10000 rpm
It mixes 5 ~ 30 minutes, after it is mixed well, is put into ice-water bath, continue that 1 ~ 5% crosslinking agent stirring 1 ~ 10 is added after stirring half an hour
Hour, it stands, until microballoon settles, outwells supernatant, remaining solid part sequentially adds a large amount of acetone, water, and ethyl alcohol is washed
Filtering, is finally washed, filtration drying with a large amount of clear water, obtains yellow powder particle -- gelatin drug bearing microsphere；
(3) chemical crosslink technique prepares gelatine microsphere and carries medicine second coating:
A series of mass fractions are configured in the gelatin drug bearing microsphere suspension of 1 ~ 50 mg/mL with dehydrated alcohol, are divided under ultrasound condition
After dissipating, the first layer gelatin coating surface of the drying prepared during taking 50 ~ 200 μ L microsphere suspensions to drop to above-mentioned (1) is placed in
Dry under 4 °C, after second layer gelatine microsphere coating is dry, then the crosslinking agent for being 1 ~ 5% with mass fraction impregnates above-mentioned sample,
So that gelatine microsphere and gelatin coating is carried out cross-linking reaction, increases interface cohesion of the gelatin drug bearing microsphere coating between gelatin coating
Power, immersion 10 ~ after sixty minutes, with washes of absolute alcohol sample 3 times, every time 10 minutes, remaining crosslinking agent in sample is removed, is applied
Layer bracket freeze-drying.
The Artificial Intervention degradable polyester sill is Poly L-lactic acid (PLLA), poly lactic-co-glycolic acid
(PLGA), one of polylactic acid-caprolactone (PLA-PCL), polylactic acid-trimethylene carbonate-glycolide (PLTG).
The carrying medicament is one of taxol, resveratrol, gentamicin, somatomedin.
The crosslinking agent is Geniposide, in glutaraldehyde, acetic anhydride, diglycidyl ether, pungent two methyl ester imidate
One kind.
The present invention provides one kind for body implanting material surface gelatine microsphere drug-loaded biological active coating, according to above-mentioned
One preparation method obtains.
A kind of application the present invention also provides gelatine microsphere drug-loaded biological active coating on body implanting material surface.
Gelatine microsphere drug-loaded biological active coating of the present invention has coating and matrix bonding force strong, coating stable, biofacies
The features such as capacitive is good, drugloading rate is high.It is a kind of effective ways that can be applied to biodegradable polyesters class material surface coating.
The present invention has the advantages that
(1) using degradable polyester base class synthesis macromolecule as matrix, natural polymer gelatin is connect by chemical grafting method
Then the gelatine microsphere for being loaded with drug is fixed on gelatin surface by crosslinking agent, is prepared by this method by branch in material surface
Gelatin drug bearing microsphere coating performance stablize, be not easy and matrix stripping, drugloading rate is high；
(2) gelatin drug bearing microsphere coating prepared by the present invention not only overcomes the interface between synthesis macromolecule and natural polymer
The problem of poor compatibility, and the drug with immunotherapy targeted autoantibody effect is firmly carried on implantable rack surface；
(3) preparation method is simple in the present invention, and strong operability is at low cost, can provide convenience for further production.
Detailed description of the invention
Fig. 1 is the surface SEM figure of chemical graft gelatin coating prepared by embodiment 1；
Fig. 2 is the FTIR figure during chemical graft gelatin prepared by embodiment 1；
Fig. 3 is the external dynamic degradation experiment of chemical graft gelatin prepared by embodiment 1；
Fig. 4 is the SEM figure before and after the load medicine of gelatine microsphere prepared by embodiment 1.
Specific embodiment
Below by way of specific embodiment, the technical scheme of the present invention will be further described.Embodiment below is to this
The further explanation of invention, and do not limit the scope of the invention.
Embodiment 1
Poly- (lactic acid-trimethylene carbonic ether-glycolide) the copolymer thin slice of 1cm × 1cm is immersed in 20 mL ethyl alcohol: water (v/
V) ultrasound 2 hours in=1:1, are then rinsed with a large amount of water, the thin slice cleaned are placed in 1,6- hexamethylene diamine/isopropanol=2.4g/
5 min are reacted in the mixed solution of 20mL under 45 oC, deionized water cleans 12h, and vacuum drying for 24 hours, obtains amidized thin
Piece；Then it places it in 1, the 5- glutaraldehyde solution of 1 wt%, reacts 3h at room temperature, deionized water cleans 12h, vacuum drying
Aldehyde radical functionalization thin slice is obtained for 24 hours, above-mentioned processed thin slice is placed in 4 °C, concentration is cross-linking reaction in the gelatin solution of 3 wt%
For 24 hours, 12h cleaning is impregnated in distilled water, vacuum drying obtains the poly- (lactic acid-of the gelatin coating of chemical graft process coating afterwards for 24 hours
Trimethylene carbonic ether-glycolide) thin slice.
2g Gelatin is configured to the solution of 2 wt% mass fractions, resveratrol is dissolved in 40 °C of deionized water
In dimethyl sulfoxide (DMSO), it is configured to the solution of 10 wt% mass fractions, after completely dissolution will to above two solution
Drug solution is slowly added drop-wise in gelatin solution, is vigorously stirred to being mixed thoroughly.Corn oil is previously heated to 40 °C, so
Above-mentioned gelatin pharmaceutical mixed solution is added drop-wise in corn oil dropwise afterwards, stirs 30 minutes under the conditions of 1000 rpm, is filled to it
Divide after mixing, be put into ice-water bath, continues that 3% crosslinking agent stirring 2 hours is added after stirring half an hour, stand, until microballoon sedimentation,
Outwell supernatant.Remaining solid part sequentially adds a large amount of acetone, water, and ethyl alcohol carries out washing filtering, is finally washed with a large amount of clear water
It washs, filtration drying, obtains yellow powder particle.
A series of mass fractions are configured in the gelatin drug bearing microsphere suspension of 1 ~ 50 mg/mL, in ultrasound condition with dehydrated alcohol
After lower dispersion, the first layer gelatin coating surface of the drying prepared during taking 100 μ L microsphere suspensions to drop to above-mentioned (1) is placed in
Dry under 4 °C, after second layer gelatine microsphere coating is dry, then the crosslinking agent for being 3% with mass fraction impregnates above-mentioned sample, makes
Gelatine microsphere and gelatin coating carry out cross-linking reaction, increase interface cohesion of the gelatin drug bearing microsphere coating between gelatin coating
Power after impregnating 30 minutes, with washes of absolute alcohol sample 3 times, every time 10 minutes, removes remaining crosslinking agent in sample, coating
Bracket freeze-drying.
Fig. 1 is that gelatin is coated on poly- (lactic acid-trimethylene carbonic ether-glycolide) matrix surface by chemical graft process
SEM figure.As seen from the figure, the coating surface dense uniform and smooth.
Fig. 2 is the FTIR figure in gelatin chemistry grafting process.As seen from the figure, the diaphragm after gelatin immersion coating is not only
There is infrared absorption peak identical with matrix, and in 1639 cm-1With 1541 cm-1There is amide in gelatin in placeBand and
AmideC-N stretching vibration peak in band, shows that gelatin grafts on matrix surface.
Fig. 3 is the external dynamic degradation lab diagram of chemical graft gelatin coating.As seen from the figure, pass through chemical graft process coating
Gelatin, its weight-loss ratio is only 34.2% ± 2.03% in 7 days degradation times, shows chemical graft gelatin coating stability
Height has degradation rate appropriate.
Fig. 4 is the SEM figure of (Fig. 4 B) after (Fig. 4 A) before gelatine microsphere load medicine and load medicine, and as seen from the figure, its is bright before not carrying medicine
The partial size of glue microballoon is 10 μm, and after resveratrol is added, the average grain diameter of gelatin resveratrol complex microsphere is 20 μm, grain
Diameter obviously increases, it was demonstrated that resveratrol is carried on inside gelatine microsphere.
Embodiment 2
Poly- (lactic acid-trimethylene carbonic ether-glycolide) the copolymer thin slice of 1cm × 1cm is immersed in 20 mL ethyl alcohol: water (v/
V) ultrasound 2 hours in=1:1, are then rinsed with a large amount of water, the thin slice cleaned are placed in 1,6- hexamethylene diamine/isopropanol=2.4g/
5 min are reacted in the mixed solution of 20mL under 45 oC, deionized water cleans 12h, and vacuum drying for 24 hours, obtains amidized thin
Piece；Then it places it in 1, the 5- glutaraldehyde solution of 1 wt%, reacts 3h at room temperature, deionized water cleans 12h, vacuum drying
Aldehyde radical functionalization thin slice is obtained for 24 hours, above-mentioned processed thin slice is placed in 4 °C, concentration is cross-linking reaction in the gelatin solution of 3 wt%
For 24 hours, 12h cleaning is impregnated in distilled water, vacuum drying obtains the poly- (lactic acid-of the gelatin coating of chemical graft process coating afterwards for 24 hours
Trimethylene carbonic ether-glycolide) thin slice.
2g Gelatin is configured to the solution of 2 wt% mass fractions, taxol is dissolved in 40 °C of deionized water
In dimethyl sulfoxide (DMSO), it is configured to the solution of 10 wt% mass fractions, to above two solution after completely dissolution by medicine
Object solution is slowly added drop-wise in gelatin solution, is vigorously stirred to being mixed thoroughly.Corn oil is previously heated to 40 °C, then
Above-mentioned gelatin pharmaceutical mixed solution is added drop-wise in corn oil dropwise, is stirred 30 minutes under the conditions of 1000 rpm, sufficiently to it
It after mixing, is put into ice-water bath, continues that 3% crosslinking agent stirring 2 hours is added after stirring half an hour, stand, until microballoon settles,
Fall supernatant.Remaining solid part sequentially adds a large amount of acetone, water, and ethyl alcohol carries out washing filtering, is finally washed with a large amount of clear water,
Filtration drying obtains yellow powder particle.
A series of mass fractions are configured in the gelatin drug bearing microsphere suspension of 1 ~ 50 mg/mL, in ultrasound condition with dehydrated alcohol
After lower dispersion, the first layer gelatin coating surface of the drying prepared during taking 100 μ L microsphere suspensions to drop to above-mentioned (1) is placed in
Dry under 4 °C, after second layer gelatine microsphere coating is dry, then the crosslinking agent for being 3% with mass fraction impregnates above-mentioned sample, makes
Gelatine microsphere and gelatin coating carry out cross-linking reaction, increase interface cohesion of the gelatin drug bearing microsphere coating between gelatin coating
Power after impregnating 30 minutes, with washes of absolute alcohol sample 3 times, every time 10 minutes, removes remaining crosslinking agent in sample, coating
Bracket freeze-drying.
Embodiment 3
Poly- (lactic acid-trimethylene carbonic ether-glycolide) the copolymer thin slice of 1cm × 1cm is immersed in 20 mL ethyl alcohol: water (v/
V) ultrasound 2 hours in=1:1, are then rinsed with a large amount of water, the thin slice cleaned are placed in 1,6- hexamethylene diamine/isopropanol=2.4g/
5 min are reacted in the mixed solution of 20mL under 45 oC, deionized water cleans 12h, and vacuum drying for 24 hours, obtains amidized thin
Piece；Then it places it in 1, the 5- glutaraldehyde solution of 1 wt%, reacts 3h at room temperature, deionized water cleans 12h, vacuum drying
Aldehyde radical functionalization thin slice is obtained for 24 hours, above-mentioned processed thin slice is placed in 4 °C, concentration is cross-linking reaction in the gelatin solution of 3 wt%
For 24 hours, 12h cleaning is impregnated in distilled water, vacuum drying obtains the poly- (lactic acid-of the gelatin coating of chemical graft process coating afterwards for 24 hours
Trimethylene carbonic ether-glycolide) thin slice.
2g Gelatin is configured to the solution of 2 wt% mass fractions, gentamicin is dissolved in 40 °C of deionized water
In dimethyl sulfoxide (DMSO), it is configured to the solution of 10 wt% mass fractions, after completely dissolution will to above two solution
Drug solution is slowly added drop-wise in gelatin solution, is vigorously stirred to being mixed thoroughly.Corn oil is previously heated to 40 °C, so
Above-mentioned gelatin pharmaceutical mixed solution is added drop-wise in corn oil dropwise afterwards, stirs 30 minutes under the conditions of 1000 rpm, is filled to it
Divide after mixing, be put into ice-water bath, continues that 3% crosslinking agent stirring 2 hours is added after stirring half an hour, stand, until microballoon sedimentation,
Outwell supernatant.Remaining solid part sequentially adds a large amount of acetone, water, and ethyl alcohol carries out washing filtering, is finally washed with a large amount of clear water
It washs, filtration drying, obtains yellow powder particle.
A series of mass fractions are configured in the gelatin drug bearing microsphere suspension of 1 ~ 50 mg/mL, in ultrasound condition with dehydrated alcohol
After lower dispersion, the first layer gelatin coating surface of the drying prepared during taking 100 μ L microsphere suspensions to drop to above-mentioned (1) is placed in
Dry under 4 °C, after second layer gelatine microsphere coating is dry, then the crosslinking agent for being 3% with mass fraction impregnates above-mentioned sample, makes
Gelatine microsphere and gelatin coating carry out cross-linking reaction, increase interface cohesion of the gelatin drug bearing microsphere coating between gelatin coating
Power after impregnating 30 minutes, with washes of absolute alcohol sample 3 times, every time 10 minutes, removes remaining crosslinking agent in sample, coating
Bracket freeze-drying.
Embodiment 4
Poly- (lactic acid-trimethylene carbonic ether-glycolide) the copolymer thin slice of 1cm × 1cm is immersed in 20 mL ethyl alcohol: water (v/
V) ultrasound 2 hours in=1:1, are then rinsed with a large amount of water, the thin slice cleaned are placed in 1,6- hexamethylene diamine/isopropanol=2.4g/
5 min are reacted in the mixed solution of 20mL under 45 oC, deionized water cleans 12h, and vacuum drying for 24 hours, obtains amidized thin
Piece；Then it places it in 1, the 5- glutaraldehyde solution of 1 wt%, reacts 3h at room temperature, deionized water cleans 12h, vacuum drying
Aldehyde radical functionalization thin slice is obtained for 24 hours, above-mentioned processed thin slice is placed in 4 °C, concentration is cross-linking reaction in the gelatin solution of 3 wt%
For 24 hours, 12h cleaning is impregnated in distilled water, vacuum drying obtains the poly- (lactic acid-of the gelatin coating of chemical graft process coating afterwards for 24 hours
Trimethylene carbonic ether-glycolide) thin slice.
2g Gelatin is configured to the solution of 2 wt% mass fractions in 40 °C of deionized water, and somatomedin is molten
Solution is configured to the solution of 10 wt% mass fractions, after completely dissolution to above two solution in dimethyl sulfoxide (DMSO)
Drug solution is slowly added drop-wise in gelatin solution, is vigorously stirred to being mixed thoroughly.Corn oil is previously heated to 40 °C,
Then above-mentioned gelatin pharmaceutical mixed solution is added drop-wise in corn oil dropwise, is stirred 30 minutes under the conditions of 1000 rpm, to it
It after mixing well, is put into ice-water bath, continues that 3% crosslinking agent stirring 2 hours is added after stirring half an hour, stand, until microballoon is heavy
Drop, outwells supernatant.Remaining solid part sequentially adds a large amount of acetone, water, and ethyl alcohol carries out washing filtering, finally with a large amount of clear water
Washing, filtration drying obtain yellow powder particle.
A series of mass fractions are configured in the gelatin drug bearing microsphere suspension of 1 ~ 50 mg/mL, in ultrasound condition with dehydrated alcohol
After lower dispersion, the first layer gelatin coating surface of the drying prepared during taking 100 μ L microsphere suspensions to drop to above-mentioned (1) is placed in
Dry under 4 °C, after second layer gelatine microsphere coating is dry, then the crosslinking agent for being 3% with mass fraction impregnates above-mentioned sample, makes
Gelatine microsphere and gelatin coating carry out cross-linking reaction, increase interface cohesion of the gelatin drug bearing microsphere coating between gelatin coating
Power after impregnating 30 minutes, with washes of absolute alcohol sample 3 times, every time 10 minutes, removes remaining crosslinking agent in sample, coating
Bracket freeze-drying.
Claims (6)
1. a kind of preparation method for body implanting material surface gelatine microsphere drug-loaded biological active coating, which is characterized in that
By chemical bond covalence graft gelatin in polyester material surface as first coating, the gelatine microsphere of drug then will be loaded with
Be crosslinking in gelatin coating surface as second coating, comprising the following steps:
(1) chemical graft process prepares gelatin first coating:
The polyester base thin slice of 1cm × 1cm is immersed in 20 mL ethyl alcohol: ultrasound 2 hours in water (v/v)=1:1, then with a large amount of water
It rinses, the polyester base thin slice cleaned is placed in the mixed solution of 1,6- hexamethylene diamine and isopropanol and reacts 5 under 45 oC
Min, deionized water clean 12h, and vacuum drying for 24 hours, obtains amidized polyester base thin slice；Then amidized polyester base is thin
Piece is placed in 1, the 5- glutaraldehyde solution of 1 wt%, reacts 3h at room temperature, and deionized water cleans 12h, and vacuum drying obtains aldehyde radical for 24 hours
Above-mentioned processed thin slice is placed in 4 °C by functionalization thin slice, concentration be in the gelatin solution of 1 ~ 10wt% cross-linking reaction for 24 hours, in
12h cleaning is impregnated in distilled water, vacuum drying obtains the polyester base thin slice of the gelatin coating of chemical graft process coating afterwards for 24 hours；
(2) emulsification condensation polymerization crosslinking method prepares gelatin drug bearing microsphere:
By Gelatin in 40 °C of deionized water, it is configured to the gelatin solution of 0.1 ~ 1wt% mass fraction；It will medicine be loaded
Object is dissolved in dimethyl sulfoxide (DMSO), is configured to the solution of 1 ~ 20 wt% mass fraction, abundant to above two solution
Drug solution is slowly added drop-wise in gelatin solution after dissolution, is vigorously stirred to being mixed thoroughly；Corn oil is previously heated to
40 °C, above-mentioned gelatin pharmaceutical mixed solution is added drop-wise in corn oil dropwise then, stirs 5 under the conditions of 500 ~ 10000 rpm
It ~ 30 minutes, after it is mixed well, is put into ice-water bath, it is small to continue addition 1 ~ 5% crosslinking agent stirring 1 ~ 10 after stirring half an hour
When, it stands, until microballoon settles, outwells supernatant, remaining solid part sequentially adds a large amount of acetone, water, and ethyl alcohol carries out washed
Filter, is finally washed, filtration drying with a large amount of clear water, obtains yellow powder particle, i.e. gelatin drug bearing microsphere；
(3) chemical crosslink technique prepares gelatine microsphere and carries medicine second coating
A series of mass fractions are configured in the gelatin drug bearing microsphere suspension of 1 ~ 50 mg/mL with dehydrated alcohol, are divided under ultrasound condition
After dissipating, the first layer gelatin coating surface of the drying prepared during taking 50 ~ 200 μ L microsphere suspensions to drop to above-mentioned (1) is placed in
Dry under 4 °C, after second layer gelatine microsphere coating is dry, then the crosslinking agent for being 1 ~ 5% with mass fraction impregnates above-mentioned sample,
So that gelatine microsphere and gelatin coating is carried out cross-linking reaction, increases the interface cohesion between gelatin drug bearing microsphere coating and gelatin coating
Power, immersion 10 ~ after sixty minutes, with washes of absolute alcohol sample 3 times, every time 10 minutes, remaining crosslinking agent in sample is removed, is applied
Layer bracket freeze-drying.
2. being used for the preparation side of body implanting material surface gelatine microsphere drug-loaded biological active coating according to claim 1
Method, it is characterised in that the Artificial Intervention degradable polyester sill is Poly L-lactic acid (PLLA), poly lactic-co-glycolic acid
(PLGA), one of polylactic acid-caprolactone (PLA-PCL), polylactic acid-trimethylene carbonate-glycolide (PLTG).
3. being used for the preparation side of body implanting material surface gelatine microsphere drug-loaded biological active coating according to claim 1
Method, it is characterised in that the carrying medicament is one of taxol, resveratrol, gentamicin, somatomedin.
4. being used for the preparation side of body implanting material surface gelatine microsphere drug-loaded biological active coating according to claim 1
Method, it is characterised in that the crosslinking agent is Geniposide, glutaraldehyde, acetic anhydride, diglycidyl ether, pungent two imidic acids first
One of ester.
5. one kind is used for body implanting material surface gelatine microsphere drug-loaded biological active coating, it is characterised in that according to claim
Any preparation method of 1-4 obtains.
6. a kind of application of the gelatine microsphere drug-loaded biological active coating on body implanting material surface according to claim 5.
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