CN104758087A - Drug sustained release magnesium alloy stent and preparation method thereof - Google Patents
Drug sustained release magnesium alloy stent and preparation method thereof Download PDFInfo
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- CN104758087A CN104758087A CN201510181904.3A CN201510181904A CN104758087A CN 104758087 A CN104758087 A CN 104758087A CN 201510181904 A CN201510181904 A CN 201510181904A CN 104758087 A CN104758087 A CN 104758087A
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Abstract
The invention discloses a drug sustained release magnesium alloy stent and a preparation method thereof. The drug sustained release magnesium alloy stent comprises a magnesium alloy stent backbone and composite coatings, and the composite coatings comprise a first coating covering the surface of the magnesium alloy stent backbone, a second coating covering the surface of the first coating and a third coating covering the surface of the second coating; the first coating is a silane coupling agent KH550 coating, the second coating is a DL-PLCL medicine carrying layer, and the third coating is a medicine carrying layer formed by at least one of PLGA and PLLA. According to the drug sustained release magnesium alloy stent and the preparation method thereof, the composite coatings can effectively separate the magnesium alloy stent backbone from an outside corrosive medium and can effectively increase the supporting time of the magnesium alloy stent in the body, the composite coatings are degradable coatings, and degradation products are harmless to a human body.
Description
Technical field
The present invention relates to technical field of medical instruments, particularly relate to a kind of medicine slow-release magnesium alloy bracket and preparation method thereof.
Background technology
Along with the development of modern medical service technology and being gradually improved of armarium, Interventional stent in the treatment has become a kind of Main Means getting involved cardiovascular therapy.But, the angiocarpy bracket of current clinical practice still based on the metal material of non-degradable, as rustless steel, cobalt-chromium alloy etc., these metal racks are all biologically inerts, long-term existence in vivo after implantation, has the risk causing thrombosis, needs of patients long-term taking anticoagulant for this reason.
Magnesium alloy bracket, as a kind of biodegradable stent, becomes a kind of development trend and the study hotspot of intravascular stent gradually.But magnesium alloy bracket corrosion degradation speed in blood/tissue pendular ring border is too fast, does not reach effective supporting time of clinical demand.For improving the decay resistance of magnesium alloy bracket, increasing magnesium alloy bracket effective supporting time in vivo, proposing the safeguard procedures of multiple magnesium alloy both at home and abroad.But, usually can introduce harmful material in magnesium alloy bracket in existing safeguard procedures, thus negative effect is produced to human body, affect therapeutic effect; Or processing step is more, be unfavorable for large-scale production.
Summary of the invention
The invention provides a kind of medicine slow-release magnesium alloy bracket prepared simply, to human non-toxic's evil, magnesium alloy bracket backbone and extraneous corrosive medium can be made to isolate, postpone the etching time starting point of magnesium alloy bracket in blood/tissue pendular ring border, add magnesium alloy bracket active time in vivo.Meanwhile, present invention also offers the preparation method of this medicine slow-release magnesium alloy bracket.
For achieving the above object, the present invention adopts following technical scheme:
A kind of medicine slow-release magnesium alloy bracket, comprise magnesium alloy bracket backbone and composite coating, described composite coating comprises the first coating covering described magnesium alloy bracket backbone surface, the second coating covering described first coating surface, and covers the 3rd coating of described second coating surface;
Wherein, described first coating is Silane coupling agent KH550 coating, and described second coating is DL-PLCL drug-loaded layer, the drug-loaded layer that described 3rd coating is formed at least one in PLGA and PLLA.
Wherein in an embodiment, the thickness of described first coating is 200nm ~ 1 μm, and the thickness of described second coating is 3 μm ~ 10 μm, and the thickness of described 3rd coating is 3 μm ~ 5 μm.
Wherein in an embodiment, described first coating is 1:10 ~ 1:20 with the ratio of the thickness of described second coating, and described second coating is 1:1 ~ 2:1 with the ratio of the thickness of described 3rd coating.
Wherein in an embodiment, the gross thickness of described composite coating is 6 μm ~ 15 μm.
Wherein in an embodiment, in described second coating and described 3rd coating, contained medicine is anti-restenosis drugs, antitumor drug, anticoagulant or anti-proliferative drug; And the quality of medicine contained in described second coating and described 3rd coating is respectively 30% ~ 40% of its place coating gross mass.
A preparation method for medicine slow-release magnesium alloy bracket, comprises the following steps:
S100: by magnesium alloy bracket backbone good for laser engraving through polishing after washing, then flood 0.25min ~ 5min in the first coating, do drying, cured after taking-up, obtains the magnesium alloy bracket that surface coverage has the first coating;
Wherein, described first coating comprises Silane coupling agent KH550, dehydrated alcohol and the first solvent, and described first solvent is water, and the volume ratio of described Silane coupling agent KH550, described dehydrated alcohol and described first solvent is 2 ~ 5:90 ~ 95:3 ~ 6;
S200: magnesium alloy bracket surface-coated second coating obtained in step S100, then does drying, cured, obtains the magnesium alloy bracket that surface coverage has the second coating;
Wherein, described second coating comprises DL-PLCL, the first carrying medicament and the second solvent, described second solvent is at least one in dichloromethane, chloroform and oxolane, and the quality sum of described DL-PLCL and described first carrying medicament is 0.2% ~ 2% of described second coating gross mass;
S300: magnesium alloy bracket surface-coated the 3rd coating obtained in step S200, then does drying, cured, obtains the magnesium alloy bracket that surface coverage has the 3rd coating;
Wherein, described 3rd coating comprises controlled release agent, the second carrying medicament and the 3rd solvent, described controlled release agent is at least one in PLGA and PLLA, described 3rd solvent is at least one in dichloromethane, chloroform and oxolane, and the quality sum of described controlled release agent and described second carrying medicament is 0.2% ~ 2% of described 3rd coating gross mass.
Wherein in an embodiment, in described second coating, the mass ratio of described DL-PLCL and described first carrying medicament is 7:3 ~ 6:4;
In described 3rd coating, the mass ratio of described controlled release agent and described second carrying medicament is 7:3 ~ 6:4.
Wherein in an embodiment, in step S100, described drying, cured step are: at room temperature dried by the magnesium alloy bracket after dipping in the first coating, then at 80 DEG C ~ 120 DEG C, sinter 15min ~ 60min.
Wherein in an embodiment, in step S200, described drying, cured step are: will be coated with magnesium alloy bracket vacuum drying 10h ~ 24h at 10 DEG C ~ 50 DEG C of the second coating, and then temperature will be adjusted to 50 DEG C ~ 170 DEG C, be incubated 5min ~ 120min under vacuum state.
Wherein in an embodiment, in step S300, described drying, cured step are: will be coated with magnesium alloy bracket vacuum drying 10h ~ 24h at 50 DEG C ~ 70 DEG C of the 3rd coating, and then temperature will be adjusted to 70 DEG C ~ 170 DEG C, be incubated 5min ~ 120min under vacuum state.
Beneficial effect of the present invention is as follows:
Medicine slow-release magnesium alloy bracket of the present invention is primarily of magnesium alloy bracket backbone and composite coating composition, wherein, composite coating comprises Silane coupling agent KH550 coating, DL-PLCL drug-loaded layer, and the drug-loaded layer to be formed by least one in PLGA and PLLA, magnesium alloy bracket backbone and corrosive medium can be isolated by this composite coating, effectively postpone the start time of magnesium alloy bracket backbone body internal corrosion in vivo; This composite coating is biodegradation coating simultaneously, successively can degrade in time in blood/tissue pendular ring border, catabolite is to human non-toxic's evil, and the medicine carried in coating can be absorbed by the body, there is good biocompatibility and anti-hamartoplasia ability, the requirement of clinical vascular support can be met; In addition, medicine slow-release magnesium alloy bracket of the present invention is easily prepared, and cost is lower, has higher market popularization value.
Accompanying drawing explanation
Fig. 1 is the cross section structure schematic diagram of medicine slow-release magnesium alloy bracket one embodiment of the present invention.
Detailed description of the invention
Below the specific embodiment of the present invention is described in detail.Should be understood that, detailed description of the invention described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
See Fig. 1, the invention provides a kind of medicine slow-release magnesium alloy bracket, it comprises magnesium alloy bracket backbone 100 and composite coating 200, this composite coating 200 comprises the first coating 210 covering magnesium alloy bracket backbone 100 surface, the second coating 220 covering the first coating 210 surface, and covers the 3rd coating 230 on the second coating 220 surface.In the present invention, the first coating 210 is Silane coupling agent KH550 coating, and the second coating 220 is DL-PLCL drug-loaded layer, the drug-loaded layer that the 3rd coating 230 is formed at least one in PLGA and PLLA.
Wherein, DL-PLCL is levorotatory lactide caprolactone copolymer, and PLGA is Poly(D,L-lactide-co-glycolide, and PLLA is Poly-L-lactic acid.
Drug-loaded layer refers in this coating and carries medicine, is described for the second coating 220, and the main body namely in the second coating 220 is carry medicine in DL-PLCL, DL-PLCL main body.Magnesium alloy bracket backbone 100 in the present invention can be ZK60 magnesium alloy bracket, also can be other magnesium alloy brackets, as AZ31B magnesium alloy bracket, AE21 magnesium alloy bracket etc.
In the present invention, first coating 210 i.e. Silane coupling agent KH550 coating directly contacts with magnesium alloy bracket backbone 100, due in Silane coupling agent KH550 containing two kinds of different active groups (amino and oxygen base), can be used for coupling organic polymer and inorganic molecule, therefore, the first coating 210 in the present invention can either be combined closely with inorganic magnesium alloy bracket backbone 100, can be cross-linked with each other with organic second coating 220 again, thus improve the binding ability of composite coating 200 and magnesium alloy bracket backbone 100, enhance the fastness between the first coating 210 and the second coating 220 and compactness simultaneously, and then reduce the degradation rate of composite coating 200 in blood/tissue pendular ring border, add effective supporting time of medicine slow-release magnesium alloy bracket of the present invention, simultaneously, the catabolite of Silane coupling agent KH550 is harmless, the depolymerization that can absorb water after chance water is small molecule monomer and metabolism.
Second coating 220 is the second layer protecting film of magnesium alloy bracket backbone 100, this coating is DL-PLCL drug-loaded layer, there is certain elasticity, toughness and stronger hydrophobicity, can keep after stent-expansion that rete is complete not to break, there is stronger deformability, before it is degraded to a certain degree, effectively can prevent the first coating 210 to absorb water depolymerization, postpone the etching time starting point of magnesium alloy bracket backbone 100; Meanwhile, this coating is drug-carried coat, can slow releasing medicine (contained medicine is generally anti-restenosis drugs, antitumor drug, anticoagulant or anti-proliferative drug) in degradation process, plays the effects such as the hyperplasia suppressing stent-expansion position.Wherein, DL-PLCL is degradable synthetic polymer, its catabolite to human non-toxic's evil, and degradation rate and the molecular weight of himself and copolymerization ratios closely related, can regulate according to actual needs.
3rd coating 230 is the outermost layer protecting film of magnesium alloy bracket backbone 100, the drug-loaded layer that this coating is formed at least one in PLGA and PLLA, and after implanting, this coating directly contacts with blood/tissue pendular ring border.This coating is in degradation process, and product, simultaneously can slow releasing medicine to human non-toxic's evil, play the effects such as Inhibiting proliferation, meanwhile, PLGA or PLLA can Drug controlled release speed, the effect of isolation can be played again, effectively prevent the adhesion of composite coating 200 and sacculus.
Medicine slow-release magnesium alloy bracket of the present invention, at the surface-coated composite coating 200 of magnesium alloy bracket backbone 100, after entering implant into body, magnesium alloy bracket backbone 100 and blood/tissue pendular ring border can effectively isolate by this composite coating 200, and composite coating 200 is successively degraded, stepsly lose protective action, effectively increase magnesium alloy bracket supporting time in vivo; The catabolite of this composite coating 200 is to human non-toxic's evil simultaneously, and the medicine carried in coating can be absorbed by the body, and has good biocompatibility and anti-hamartoplasia ability, can meet the requirement of clinical vascular support.
Preferably, the gross thickness of the composite coating 200 in the present invention is 6 μm ~ 15 μm.Composite coating 200 is blocked up, can increase the integral diameter of medicine slow-release magnesium alloy bracket of the present invention, thus is unfavorable for the implantation in blood vessel, and in stent-expansion process easy cracking and reduce the protective action of coating; Composite coating 200 is excessively thin, can cause degrading too fast and not reaching effective acting time of expection.Coating layer thickness in this embodiment can ensure the smooth implantable intravascular of support, and can play stronger protective action, extends the effective acting time of support in blood/tissue liquid.
Preferably, the thickness of the first coating 210 is 200nm ~ 1 μm, and the thickness of the second coating 220 is 3 μm ~ 10 μm, and the thickness of the 3rd coating 230 is 3 μm ~ 5 μm.Because each coating role is not quite similar, Main Function as the first coating 210 is adhesion second coating 220 and magnesium alloy bracket backbone 100, to strengthen overall fastness, play the effect of supplemental protective simultaneously, second coating 220 and the 3rd coating 230 pairs of magnesium alloy bracket backbones 100 play main protective action, discharge medicine simultaneously; Meanwhile, the degradation rate of each coating in blood/tissue pendular ring border is not identical yet, as the first coating 210 has degradation rate faster relative to the second coating 220 and the 3rd coating 230.Therefore, the thickness of each coating needs mutual coordinated, farthest could play the effect of composite coating 200.Coating layer thickness in present embodiment farthest can coordinate connection and the cooperation of each painting interlayer, greatly strengthen the adhesion between magnesium alloy bracket backbone 100 and composite coating 200, and serve stronger protective action, improve the effective acting time of magnesium alloy bracket in blood/tissue liquid, clinical requirement can be met.
Preferably, the ratio of the thickness of the first coating 210 and the second coating 220 is 1:10 ~ 1:20, and the ratio of the thickness of the second coating 220 and the 3rd coating 230 is 1:1 ~ 2:1.Under this ratio, can strengthen the adhesion of two painting interlayers of next-door neighbour, make composite coating 200 overall structure compacter, the fastness being coated with interlayer is stronger, enhances the total quality of medicine slow-release magnesium alloy bracket of the present invention.
In the present invention, in second coating 220 and the 3rd coating 230, contained medicine can be selected according to the actual needs of patient, as can be anti-restenosis drugs, antitumor drug, anticoagulant or anti-proliferative drug, and, second coating 220 can be identical with contained medicine in the 3rd coating 230, also can be different.As preferably, in the second coating 220 and the 3rd coating 230, contained medicine all can be rapamycin.
Preferably, as a kind of embodiment, the quality of medicine contained in the second coating 220 and the 3rd coating 230 is respectively 30% ~ 40% of its place coating gross mass.Under this content ratio, the effect of medicine can be played largely, good protective action can be played to magnesium alloy bracket backbone 100 again simultaneously, improve the comprehensive result of use of medicine slow-release magnesium alloy bracket of the present invention.
In addition, present invention also offers a kind of preparation method of medicine slow-release magnesium alloy bracket, utilize the method can prepare above-mentioned medicine slow-release magnesium alloy bracket, comprise the following steps:
S100: by magnesium alloy bracket backbone 100 good for laser engraving through polishing after washing, then flood 0.25min ~ 5min in the first coating, do drying, cured after taking-up, obtains the magnesium alloy bracket that surface coverage has the first coating.First coating comprises Silane coupling agent KH550, dehydrated alcohol and the first solvent, and wherein, the first solvent is water, and the volume ratio of Silane coupling agent KH550, dehydrated alcohol and water is 2 ~ 5:90 ~ 95:3 ~ 6.
In the present invention, the polishing mode of magnesium alloy bracket backbone 100 has multiple, is preferably electrochemical polish.
This step has prepared the first coating 210 (i.e. Silane coupling agent KH550 coating) on the surface of magnesium alloy bracket backbone 100.Wherein, the thickness of the first coating 210 and quality are all closely related with the concentration of Silane coupling agent KH550 in the first coating; when the excessive concentration of Silane coupling agent KH550; the coating formed easily ftractures in the process of drying, cured; the deformability of coating can be reduced simultaneously, easily ftracture when stent-expansion and do not have the protective effect of expection, therefore; in the present invention, the volume ratio of alkane coupling agent KH550 in the first coating is 2% ~ 5%.Preferably, the thickness of the first coating 210 is 200nm ~ 1 μm.
Preferably, as a kind of embodiment, concrete operations that are dry in step S100, cured are: at room temperature dried by the magnesium alloy bracket after dipping in the first coating, then at 80 DEG C ~ 120 DEG C, sinter 15min ~ 60min.This processing mode can effectively remove moisture and dehydrated alcohol, obtains comparatively fine and close Silane coupling agent KH550 coating.
S200: magnesium alloy bracket surface-coated second coating obtained in step S100, then drying, cured is done, obtain the magnesium alloy bracket that surface coverage has the second coating, wherein, second coating comprises DL-PLCL, the first carrying medicament and the second solvent, second solvent is at least one in dichloromethane, chloroform and oxolane, and the quality sum of DL-PLCL and the first carrying medicament is 0.2% ~ 2% of the second coating gross mass.
This step has prepared the second coating 220 (DL-PLCL drug-loaded layer) on magnesium alloy bracket backbone 100 surface, obtain the magnesium alloy bracket that surface coverage has duplex coating.In order to ensure the quality of the second coating 220, reach the protection effect of expection, the quality sum of DL-PLCL and the first carrying medicament is 0.2% ~ 2% of the second coating gross mass.Preferably, in order to take into account Drug therapy and the protection to magnesium alloy bracket backbone 100, the mass ratio of DL-PLCL and the first carrying medicament is 7:3 ~ 6:4.Wherein, the first carrying medicament is selected according to the state of an illness, can be anti-restenosis drugs, antitumor drug, anticoagulant or anti-proliferative drug.
The coating method of the second coating has multiple, as dip-coating, spraying, also can select other coating method.Preferably, the coating method of the second coating is preferably ultrasonic spraying, and which can obtain the second coating 220 of dense uniform after application, thus reliably extends the effective acting time of magnesium alloy bracket in blood/tissue liquid.
Wherein, the thickness of the second coating 220 and surface quality are all directly proportional to the amount of polymers (concentration and the flow parameter of the second coating) sprayed in coating time and unit interval, namely within the scope of suitable flow parameter, when using low concentration low discharge, extend coating time, can obtain and shorten the identical coating layer thickness of spray time and surface quality with using during high concentration high flow capacity.Preferably, the thickness of the second coating 220 is 3 μm ~ 10 μm.
Preferably, as a kind of embodiment, drying in step S200, cured step are: will be coated with magnesium alloy bracket more than vacuum drying 10h at 10 DEG C ~ 50 DEG C of the second coating, be preferably 10h ~ 24h, then temperature is adjusted to 50 DEG C ~ 170 DEG C, under vacuum state, is incubated 5min ~ 120min.Which effectively can remove the solvent in coating, and can make DL-PLCL melting after raised temperature, and then closes by the microchannel formed after solvent effusion, increases the compactness of the second coating 220, the rate of release of the medicine that slows down and the degradation rate of DL-PLCL.
S300: magnesium alloy bracket surface-coated the 3rd coating obtained in step S200, then drying, cured is done, obtain the magnesium alloy bracket that surface coverage has the 3rd coating, wherein, 3rd coating comprises controlled release agent, the second carrying medicament and the 3rd solvent, controlled release agent is at least one in PLGA and PLLA, and the 3rd solvent is at least one in dichloromethane, chloroform and oxolane, and the quality sum of controlled release agent and the second carrying medicament is 0.2% ~ 2% of the 3rd coating gross mass.
This step has prepared the 3rd coating 230 (drug-loaded layer that at least one in PLGA and PLLA is formed) on magnesium alloy bracket backbone 100 surface, obtain required medicine slow-release magnesium alloy bracket.Preferably, the thickness of the 3rd coating 230 is 3 μm ~ 5 μm.
In order to ensure the quality of the 3rd coating 230, reach the protection effect of expection, the quality sum of controlled release agent and the second carrying medicament is 0.2% ~ 2% of the 3rd coating gross mass.Preferably, in order to take into account Drug therapy and the protection to magnesium alloy bracket backbone 100, the mass ratio of controlled release agent and the second carrying medicament is 7:3 ~ 6:4.Wherein, the second carrying medicament is selected as required, can be anti-restenosis drugs, antitumor drug, anticoagulant or anti-proliferative drug, and the second carrying medicament can be identical with the first carrying medicament, also can be different.Preferably, the first carrying medicament and the second carrying medicament all select rapamycin.
Preferably, as a kind of embodiment, drying in step S300, cured step are: will be coated with magnesium alloy bracket more than vacuum drying 10h at 50 DEG C ~ 70 DEG C of the 3rd coating, be preferably 10h ~ 24h, then temperature is adjusted to 70 DEG C ~ 170 DEG C, under vacuum state, is incubated 5min ~ 120min.Which effectively can remove solvent, and increases the compactness of the 3rd coating 230.
The preparation method of medicine slow-release magnesium alloy bracket of the present invention, process is simple, and easily control, preparation cost is lower, and the medicine slow-release magnesium alloy bracket that available can be excellent, has higher market popularization value.
In order to understand the present invention better, below by specific embodiment, medicine slow-release magnesium alloy bracket of the present invention and preparation method thereof is further described.
Embodiment 1
(1) by ZK60 magnesium alloy bracket backbone good for laser engraving through polishing after washing, then be placed in the first coating and flood 0.25min, insert drying baker after drying under room temperature, at 120 DEG C, sinter 15min, obtain the magnesium alloy bracket that surface-coated has the first coating; Wherein, in the first coating, the volume ratio of each composition is: Silane coupling agent KH550: dehydrated alcohol: water=2:94:4, and the thickness of the first coating is 200nm;
(2) in ultrasonic spraying second coating in magnesium alloy bracket surface that step (1) obtains, then insert in vacuum drying oven, vacuum drying 12h at 30 DEG C, is then warming up to 80 DEG C, insulation 60min, obtains the magnesium alloy bracket that surface coverage has the second coating; Wherein, the second coating is made up of rapamycin, DL-PLCL and chloroform, and the mass ratio that the quality sum of rapamycin and DL-PLCL is 0.5%, DL-PLCL and rapamycin of the second coating gross mass is 7:3, and the thickness of the second coating is 4 μm;
(3) in magnesium alloy bracket surface ultrasonic spraying the 3rd coating that step (2) obtains, then insert in vacuum drying oven, vacuum drying 24h at 50 DEG C, is then warming up to 100 DEG C, insulation 90min, obtains the magnesium alloy bracket that surface coverage has the 3rd coating; Wherein, the 3rd coating is made up of PLGA, rapamycin and chloroform, and the mass ratio that the quality sum of rapamycin and PLGA is 1.5%, PLGA and rapamycin of the 3rd coating gross mass is 7:3, and the thickness of the 3rd coating is 4 μm.
Embodiment 2
(1) by AE21 magnesium alloy bracket backbone good for laser engraving through polishing after washing, be then placed in the first coating and flood 2min, after drying under room temperature, insert drying baker, at 80 DEG C, sinter 60min, obtain the magnesium alloy bracket that surface-coated has the first coating; Wherein, in the first coating, the volume ratio of each composition is: Silane coupling agent KH550: dehydrated alcohol: water=5:90:5, and the thickness of the first coating is 1 μm;
(2) in ultrasonic spraying second coating in magnesium alloy bracket surface that step (1) obtains, then insert in vacuum drying oven, vacuum drying 24h at 10 DEG C, is then warming up to 50 DEG C, insulation 120min, obtains the magnesium alloy bracket that surface coverage has the second coating; Wherein, the second coating is made up of paclitaxel, DL-PLCL and dichloromethane, and the mass ratio that the quality sum of paclitaxel and DL-PLCL is 2%, DL-PLCL and paclitaxel of the second coating gross mass is 6:4, and the thickness of the second coating is 10 μm;
(3) in magnesium alloy bracket surface ultrasonic spraying the 3rd coating that step (2) obtains, then insert in vacuum drying oven, vacuum drying 10h at 70 DEG C, is then warming up to 170 DEG C, insulation 5min, obtains the magnesium alloy bracket that surface coverage has the 3rd coating; Wherein, the 3rd coating is made up of PLLA, paclitaxel and dichloromethane, and the mass ratio that the quality sum of paclitaxel and PLLA is 2%, PLLA and paclitaxel of the 3rd coating gross mass is 7:3, and the thickness of the 3rd coating is 4 μm.
Embodiment 3
(1) by AM50 magnesium alloy bracket backbone good for laser engraving through polishing after washing, be then placed in the first coating and flood 5min, after drying under room temperature, insert drying baker, at 100 DEG C, sinter 30min, obtain the magnesium alloy bracket that surface-coated has the first coating; Wherein, in the first coating, the volume ratio of each composition is: Silane coupling agent KH550: dehydrated alcohol: water=2:95:3, and the thickness of the first coating is 300nm;
(2) in ultrasonic spraying second coating in magnesium alloy bracket surface that step (1) obtains, then insert in vacuum drying oven, vacuum drying 10h at 50 DEG C, is then warming up to 170 DEG C, insulation 5min, obtains the magnesium alloy bracket that surface coverage has the second coating; Wherein, the second coating is made up of rapamycin, DL-PLCL and oxolane, and the mass ratio that the quality sum of rapamycin and DL-PLCL is 0.2%, DL-PLCL and rapamycin of the second coating gross mass is 6.5:3.5, and the thickness of the second coating is 3 μm;
(3) in magnesium alloy bracket surface ultrasonic spraying the 3rd coating that step (2) obtains, then insert in vacuum drying oven, vacuum drying 14h at 60 DEG C, is then warming up to 70 DEG C, insulation 120min, obtains the magnesium alloy bracket that surface coverage has the 3rd coating; Wherein, the 3rd coating is made up of PLLA, rapamycin and oxolane, and the mass ratio that the quality sum of rapamycin and PLLA is 0.2%, PLLA and rapamycin of the 3rd coating gross mass is 6.5:3.5, and the thickness of the 3rd coating is 3 μm.
Embodiment 4
(1) by ZK21 magnesium alloy bracket backbone good for laser engraving through polishing after washing, be then placed in the first coating and flood 3min, after drying under room temperature, insert drying baker, at 90 DEG C, sinter 40min, obtain the magnesium alloy bracket that surface-coated has the first coating; Wherein, in the first coating, the volume ratio of each composition is: Silane coupling agent KH550: dehydrated alcohol: water=3:91:6, and the thickness of the first coating is 450nm;
(2) in ultrasonic spraying second coating in magnesium alloy bracket surface that step (1) obtains, then insert in vacuum drying oven, vacuum drying 16h at 40 DEG C, is then warming up to 100 DEG C, insulation 90min, obtains the magnesium alloy bracket that surface coverage has the second coating; Wherein, second coating is made up of hydroxy camptothecin, DL-PLCL, chloroform and dichloromethane, and the mass ratio that the quality sum of hydroxy camptothecin and DL-PLCL is 1%, DL-PLCL and hydroxy camptothecin of the second coating gross mass is 6.2:3.8, the thickness of the second coating is 8 μm;
(3) in magnesium alloy bracket surface ultrasonic spraying the 3rd coating that step (2) obtains, then insert in vacuum drying oven, vacuum drying 20h at 55 DEG C, is then warming up to 120 DEG C, insulation 20min, obtains the magnesium alloy bracket that surface coverage has the 3rd coating; Wherein, 3rd coating is made up of PLGA, PLLA, hydroxy camptothecin, chloroform and dichloromethane, and the quality sum of hydroxy camptothecin, PLGA and PLLA is 1% of the 3rd coating gross mass, the quality sum of PLGA and PLLA and the mass ratio of hydroxy camptothecin are 6.2:3.8, and the thickness of the 3rd coating is 4 μm.
Embodiment 5
(1) by ZK60 magnesium alloy bracket backbone good for laser engraving through polishing after washing, be then placed in the first coating and flood 4min, after drying under room temperature, insert drying baker, at 95 DEG C, sinter 45min, obtain the magnesium alloy bracket that surface-coated has the first coating; Wherein, in the first coating, the volume ratio of each composition is: Silane coupling agent KH550: dehydrated alcohol: water=3.5:91:5.5, and the thickness of the first coating is 420nm;
(2) in ultrasonic spraying second coating in magnesium alloy bracket surface that step (1) obtains, then insert in vacuum drying oven, vacuum drying 15h at 45 DEG C, is then warming up to 110 DEG C, insulation 10min, obtains the magnesium alloy bracket that surface coverage has the second coating; Wherein, the second coating is made up of rapamycin, DL-PLCL and chloroform, and the mass ratio that the quality sum of rapamycin and DL-PLCL is 1.2%, DL-PLCL and rapamycin of the second coating gross mass is 6.6:3.4, and the thickness of the second coating is 7 μm;
(3) in magnesium alloy bracket surface ultrasonic spraying the 3rd coating that step (2) obtains, then insert in vacuum drying oven, vacuum drying 18h at 58 DEG C, is then warming up to 130 DEG C, insulation 70min, obtains the magnesium alloy bracket that surface coverage has the 3rd coating; Wherein, the 3rd coating is made up of PLLA, paclitaxel and dichloromethane, and the quality sum of paclitaxel and PLLA is the quality of 1%, PLLA of the 3rd coating gross mass and the mass ratio of paclitaxel is 6.2:3.8, and the thickness of the 3rd coating is 5 μm.
The above embodiment only have expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. a medicine slow-release magnesium alloy bracket, it is characterized in that, comprise magnesium alloy bracket backbone and composite coating, described composite coating comprises the first coating covering described magnesium alloy bracket backbone surface, the second coating covering described first coating surface, and covers the 3rd coating of described second coating surface;
Wherein, described first coating is Silane coupling agent KH550 coating, and described second coating is DL-PLCL drug-loaded layer, the drug-loaded layer that described 3rd coating is formed at least one in PLGA and PLLA.
2. medicine slow-release magnesium alloy bracket according to claim 1, is characterized in that, the thickness of described first coating is 200nm ~ 1 μm, and the thickness of described second coating is 3 μm ~ 10 μm, and the thickness of described 3rd coating is 3 μm ~ 5 μm.
3. medicine slow-release magnesium alloy bracket according to claim 1, is characterized in that, described first coating is 1:10 ~ 1:20 with the ratio of the thickness of described second coating, and described second coating is 1:1 ~ 2:1 with the ratio of the thickness of described 3rd coating.
4. the medicine slow-release magnesium alloy bracket according to any one of claims 1 to 3, is characterized in that, the gross thickness of described composite coating is 6 μm ~ 15 μm.
5. medicine slow-release magnesium alloy bracket according to claim 1, is characterized in that, in described second coating and described 3rd coating, contained medicine is anti-restenosis drugs, antitumor drug, anticoagulant or anti-proliferative drug; And the quality of medicine contained in described second coating and described 3rd coating is respectively 30% ~ 40% of its place coating gross mass.
6. a preparation method for medicine slow-release magnesium alloy bracket, is characterized in that, comprises the following steps:
S100: by magnesium alloy bracket backbone good for laser engraving through polishing after washing, then flood 0.25min ~ 5min in the first coating, do drying, cured after taking-up, obtains the magnesium alloy bracket that surface coverage has the first coating;
Wherein, described first coating comprises Silane coupling agent KH550, dehydrated alcohol and the first solvent, and described first solvent is water, and the volume ratio of described Silane coupling agent KH550, described dehydrated alcohol and described first solvent is 2 ~ 5:90 ~ 95:3 ~ 6;
S200: magnesium alloy bracket surface-coated second coating obtained in step S100, then does drying, cured, obtains the magnesium alloy bracket that surface coverage has the second coating;
Wherein, described second coating comprises DL-PLCL, the first carrying medicament and the second solvent, described second solvent is at least one in dichloromethane, chloroform and oxolane, and the quality sum of described DL-PLCL and described first carrying medicament is 0.2% ~ 2% of described second coating gross mass;
S300: magnesium alloy bracket surface-coated the 3rd coating obtained in step S200, then does drying, cured, obtains the magnesium alloy bracket that surface coverage has the 3rd coating;
Wherein, described 3rd coating comprises controlled release agent, the second carrying medicament and the 3rd solvent, described controlled release agent is at least one in PLGA and PLLA, described 3rd solvent is at least one in dichloromethane, chloroform and oxolane, and the quality sum of described controlled release agent and described second carrying medicament is 0.2% ~ 2% of described 3rd coating gross mass.
7. the preparation method of medicine slow-release magnesium alloy bracket according to claim 6, is characterized in that, in described second coating, the mass ratio of described DL-PLCL and described first carrying medicament is 7:3 ~ 6:4;
In described 3rd coating, the mass ratio of described controlled release agent and described second carrying medicament is 7:3 ~ 6:4.
8. the preparation method of medicine slow-release magnesium alloy bracket according to claim 6, it is characterized in that, in step S100, described drying, cured step are: at room temperature dried by the magnesium alloy bracket after dipping in the first coating, then at 80 DEG C ~ 120 DEG C, sinter 15min ~ 60min.
9. the preparation method of medicine slow-release magnesium alloy bracket according to claim 6, it is characterized in that, in step S200, described drying, cured step are: will be coated with magnesium alloy bracket vacuum drying 10h ~ 24h at 10 DEG C ~ 50 DEG C of the second coating, then temperature is adjusted to 50 DEG C ~ 170 DEG C, under vacuum state, is incubated 5min ~ 120min.
10. the preparation method of the medicine slow-release magnesium alloy bracket according to any one of claim 6 ~ 9, it is characterized in that, in step S300, described drying, cured step are: will be coated with magnesium alloy bracket vacuum drying 10h ~ 24h at 50 DEG C ~ 70 DEG C of the 3rd coating, then temperature is adjusted to 70 DEG C ~ 170 DEG C, under vacuum state, is incubated 5min ~ 120min.
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| CN109771276A (en) * | 2019-01-22 | 2019-05-21 | 首都医科大学 | Acupuncture needle and preparation method thereof |
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