CN102526813A - Surface-modified metal stent and preparation method thereof - Google Patents
Surface-modified metal stent and preparation method thereof Download PDFInfo
- Publication number
- CN102526813A CN102526813A CN2012100461136A CN201210046113A CN102526813A CN 102526813 A CN102526813 A CN 102526813A CN 2012100461136 A CN2012100461136 A CN 2012100461136A CN 201210046113 A CN201210046113 A CN 201210046113A CN 102526813 A CN102526813 A CN 102526813A
- Authority
- CN
- China
- Prior art keywords
- metal rack
- solution
- metal
- initiator
- inert polymer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The invention provides a surface-modified metal stent and a preparation method thereof. The surface of the metal stent is coated with an epsilon-lysine grafting inert polymer layer, wherein the hydrophilic inert polymer is polymethylacrylic acid-2-hydroxyl-ethyl ester or polymethylacrylic acid oligomeric gylcol ester. The epsilon-lysine grafting inert polymer layer on the surface of the surface-modified metal stent provided by the invention can effectively repel the adsorption of non-specific protein on the surface of the materials on one hand; on the other hand, the polymer comprises abundant lysine molecular structures, so that the efficiency of the combination between the surface of the metal stent and plasminogen is improved, a fibrinolytic system is rapidly activated and then the purpose of dissolving primary thrombosis is reached. Therefore, the surface-modified metal stent can avoid the formation of thrombosis to a great extent and quickly dissolve the primary thrombosis even primary thrombosis is formed in the later period, thereby improving the use security of the metal stent and prolonging the service life of the metal stent.
Description
Technical field
The present invention relates to the coronary stent field, particularly a kind of finishing metal rack and preparation method thereof.
Background technology
Coronary heart disease is the abbreviation of coronary heart disease.Because the metabolism of body inner lipid is undesired; Lipid calmness in the blood is on the tremulous pulse film of otherwise smooth; On endarterium, form similar medicated porridge shape, pile up the white speckle that forms by lipid material, white speckle appends to increase and can cause lumen of artery narrow, and blood flow is obstructed; Cause heart ischemia, produce angina pectoris.In recent years, coronary heart disease has become one of the most serious disease of harm humans health, and its M & M all presents ascendant trend year by year.Therefore, the treatment for coronary heart disease more and more receives people's attention.
At present the prefered method of coronary heart disease interventional therapy is the coronary stent implantation, and it is a puncture vessel at first, and conduit is moved ahead in blood vessel, arrives the coronary ostium place; Then with special transfer system with slits to the position that need lay; Place, withdraw from conduit at last.With respect to other interventional therapy method, the coronary stent implantation has that wound is little, misery less, recover fast, can repeat and art in advantages such as risk is less relatively.
Coronary stent is a critical component of implementing the coronary stent art, and existing coronary stent mainly contains two kinds: first kind is bare metal stent, and second kind is bracket for eluting medicament (DES).Wherein, the major defect of bare metal stent is the restenosis rate height after the dispensing support portions.This is because the mechanical damage that when support is implanted, blood vessel wall is caused causes tissue inflammation easily, induces to produce thrombosis in the acute or subacute support, causes neointimal hyperplasia, thereby causes restenosis.Bracket for eluting medicament can significantly reduce the incidence rate of restenosis behind the percutaneous coronary intervention, improves patient's quality of life, obtains clinically using comparatively widely.But show through clinical test results: relative with bare metal stent, though bracket for eluting medicament can reduce restenosis and target vessel is rebuild, significantly increase stent thrombosis formation in late period.
In order to improve the performance of above-mentioned support, naked metal support surface is carried out functional modification, improve its surface biological compatibility, anti-tampon has become the important behave that promotes coronary stent implantation application development in the formation of rack surface.Usually be at rack surface fixing heparin (Journal of Biomedical Materials Research 2008 to the most frequently used method of metal support surface anticoagulation modification; 86A; 648-661), (Biomaterials 2010 for the recombined human tropoelastin; 31,8332-8340) wait bioactive molecule.Though these methods can be prevented the formation of tampon at rack surface to a certain extent, in the later stage use, still can inevitably produce thrombosis.
Summary of the invention
The technical problem that the present invention solves is to provide a kind of finishing metal rack and preparation method thereof, has preventing thrombosis function preferably by the finishing metal rack of method preparation, in case and thrombosis also have thrombolytic effect.
In view of this, the present invention provides a kind of method for preparing of finishing metal rack, comprising:
A), metal rack carried out hydroxylating handle, obtain the hydroxylating metal rack;
B), said hydroxylating metal rack is placed 3-aminopropyl triethoxysilane solution, obtain the amination metal rack;
C), said amination metal rack is placed initiator solution, obtain the metal rack that the surface is fixed with initiator, said initiator is 2-bromo isobutyl acylbromide or chloracetyl chloride;
D), at 0 ℃～100 ℃, under the inert gas shielding, catalyst, part and said surface are fixed with under the condition that the metal rack of initiator exists, monomer generation radical polymerization obtains inert polymer modified metal support; Said monomer is methacrylic acid-2-hydroxy methacrylate or methacrylic acid oligomeric ethylene glycol ester;
E), under inert gas shielding, said inert polymer modified metal support is carried out the terminal hydroxy group activation; Place the ε-lysine solution of tert-butyl group oxygen carbonyl-protection to carry out graft reaction the metal rack after the activation, remove protection after the reaction and handle, obtain the finishing metal rack.
Preferably, the processing time of step a is 1min～20min.
Preferably, said hydroxylating processing is specially one or both in the following mode:
Place the mixed solution of hydrogen peroxide and concentrated sulphuric acid to handle metal rack;
Metal rack placed carry out oxygen plasma treatment.
Preferably, the concentration expressed in percentage by volume of said 3-aminopropyl triethoxysilane solution is 0.5%～5%.
Preferably, the concentration expressed in percentage by volume of said initiator solution is 1%～10%.
Preferably, the processing time of step c is 3h～24h.
Preferably, said catalyst is cuprous bromide, Cu-lyt., copper chloride-ascorbic acid system or copper bromide-ascorbic acid system.
Preferably, said part is 2, the 2-bipyridyl.
Preferably; Said removing protects processing to be specially: place trifluoroacetic acid solution to carry out deprotection reaction the metal rack behind the graft reaction; The concentration expressed in percentage by volume of said trifluoroacetic acid solution is 25%～30%, and the temperature of said deprotection reaction is 15 ℃～25 ℃.
Accordingly, the present invention also provides a kind of finishing metal rack, and said metal support surface is covered with ε-lysine grafting inert polymer layer; Said hydrophilic inert polymer is polymethacrylate-2-hydroxy-ethyl ester or polymethylacrylic acid oligomeric ethylene glycol ester.
The present invention provides a kind of method for preparing of finishing support; This method is that metal rack is carried out hydroxylating and amination modified back fixedly initiator successively; Utilize this initiator to prepare the inert polymer layer through atom transfer radical polymerization method then at metal support surface; Again inert polymer is carried out grafting ε-lysine after the terminal hydroxy group activation at last, obtain the surface mount that ε-lysine grafting inert polymer is modified thus.With respect to prior art; The metal support surface of method for preparing of the present invention is covered with ε-lysine grafting inert polymer and repaiies layer; This polymer can effectively repel the absorption of nonspecific proteins matter at material surface on the one hand, therefore can prevent that to a certain extent tampon forms at metal support surface; On the other hand; Above-mentioned inert polymer is a pectinate texture; The polymer of this structure comprises abundant lysine molecular structure, thereby has improved the efficient of metal support surface combination plasminogen, and then the quick active fibrinolytic system; Activate the intravital antithrombotic of machine from the bionics angle and form passage, reach the purpose of the nascent thrombosis of dissolving thus.Therefore the finishing metal rack of preparation not only can prevent to form thrombosis to a great extent according to the method described above, also can dissolve fast even the later stage forms nascent thrombosis, improves the safety that metal rack uses and increases the service life.
Description of drawings
Fig. 1 is the absorption collection of illustrative plates of L605 cochrome material in the fibrinogen solution of 1mg/mL before and after embodiment 1 finishing;
Fig. 2 is the absorption collection of illustrative plates of L605 cochrome material in the human serum albumin solution of 1mg/mL before and after embodiment 1 finishing;
Fig. 3 is the L605 cochrome material before and after embodiment 1 finishing adsorbs plasminogen in blood plasma an enzyme linked immunological absorption collection of illustrative plates;
Fig. 4 is the thrombus performance test collection of illustrative plates of the L605 cochrome material before and after embodiment 1 finishing.
The specific embodiment
In order further to understand the present invention, below in conjunction with embodiment the preferred embodiment of the invention is described, describe just to further specifying feature and advantage of the present invention but should be appreciated that these, rather than to the restriction of claim of the present invention.
The embodiment of the invention discloses a kind of method for preparing of finishing metal rack, comprise the steps:
A), metal rack carried out hydroxylating handle, obtain the hydroxylating metal rack;
B), said hydroxylating metal rack is placed 3-aminopropyl triethoxysilane solution, obtain the amination metal rack;
C), said amination metal rack is placed initiator solution, obtain the metal rack that the surface is fixed with initiator, said initiator is 2-bromo isobutyl acylbromide or chloracetyl chloride;
D), at 0 ℃～100 ℃, under the inert gas shielding, catalyst, part and said surface are fixed with under the condition that the metal rack of initiator exists, monomer generation radical polymerization obtains inert polymer modified metal support; Said monomer is methacrylic acid-2-hydroxy methacrylate, methacrylic acid oligomeric ethylene glycol ester;
E), under inert gas shielding, said inert polymer modified metal support is carried out the terminal hydroxy group activation; Place the ε-lysine solution of tert-butyl group oxygen carbonyl-protection to carry out graft reaction the metal rack after the activation, remove protection after the reaction and handle, obtain the finishing metal rack.
Can know by such scheme; The present invention carries out after hydroxylating, the amination metal rack at the fixing initiator of metal support surface successively; Utilize the ATRP principle to form the inert polymer layer then in the metal support surface polymerization; On the inert polymer molecule segment, introduce ε-lysine at last, obtain having the metal rack that dissolving is nascent thrombosis function thus.
Wherein, step a carries out hydroxylated step with metal rack, metal rack is carried out hydroxylated purpose be: insert hydroxyl at metal support surface, make it can carry out follow-up amination step.Concrete, hydroxylating is handled and is preferably adopted in the following following mode one or both:
Place the mixed solution of hydrogen peroxide and concentrated sulphuric acid to handle metal rack;
Metal rack placed carry out oxygen plasma treatment.
More preferably carry out in order to improve hydroxylating efficient: carry out oxygen plasma treatment again after placing the mixed solution of hydrogen peroxide and concentrated sulphuric acid to handle metal rack according to following mode.
The present invention preferably controls hydrogen peroxide and the concentrated sulphuric acid mixed solution processing time is 1min～20min, more preferably 15min～20min.Vitriolic concentration expressed in percentage by volume is preferably 70%～75% in use hydrogen peroxide and the concentrated sulphuric acid mixed solution.
According to step a can obtain surface hydroxylation metal rack.Carry out amination according to step b then and handle, the purpose of carrying out the amination processing is to be convenient to the step of follow-up fixedly initiator.This step is specially the hydroxylating metal rack that step a is made and places 3-aminopropyl triethoxysilane solution, and the hydroxyl of 3-aminopropyl triethoxysilane solution and metal support surface reacts, and makes metal support surface be fixed with amino thus.3-aminopropyl triethoxysilane solution according to the invention is that the 3-aminopropyl triethoxysilane is dissolved in the solution that obtains behind the organic solvent, and organic solvent is preferably toluene.
Step b preferably carries out under 0 ℃～100 ℃ condition.The concentration expressed in percentage by volume of the 3-aminopropyl triethoxysilane solution that uses is preferably 0.5%～5%; If 3-aminopropyl triethoxysilane solution concentration is low excessively; Its density that is grafted on rack surface is lower, and then causes the density of fixing initiator lower, influences efficiency of initiation.If excessive concentration, the 3-aminopropyl triethoxysilane of its surface grafting has reached saturated, and residual volume is too high in the solution, causes the wasting of resources.
Metal support surface through after the step b processing is connected to amino; Then need be according to the fixing step of initiator of step c; The effect of carrying out steps d is to make in follow-up polyreaction, under action of evocating, can form the inert polymer layer at metal support surface.This step is specially the amination metal rack that step c is made and places initiator solution, and initiator solution according to the invention is meant initiator is dissolved in the solution that obtains behind the organic solvent that organic solvent is preferably dichloromethane.Above-mentioned initiator is 2-bromo isobutyl acylbromide or chloracetyl chloride.The amino on this step reaction medium-height trestle surface and the acylbromide in the initiator or acyl chlorides react, and slough a part hydrogen bromide or hydrogen chloride, form amido link, realize the fixing of initiator thus.The concentration expressed in percentage by volume of initiator solution is preferably 1%～10%, and initiator solution concentration is low excessively, and its surface grafting density is lower, and then influences efficiency of initiation; If excessive concentration, the initiator of its surface grafting has reached saturated, and residual volume is too high in the solution, causes the wasting of resources.The time of this step process is preferably 3h～24h.
Steps d is the process for preparing the inert polymer layer at metal support surface; ATRP takes place in monomer methacrylic acid-2-hydroxy methacrylate or methacrylic acid oligomeric ethylene glycol ester under catalyst, part and action of evocating, form hydrophilic inert polymer polymethacrylate-2-hydroxy-ethyl ester or polymethylacrylic acid oligomeric ethylene glycol ester.Catalyst that this step is used and part can adopt synthetic middle catalyst and the part that uses of above-mentioned two kinds of polymer well known to those skilled in the art.As preferred version, catalyst is preferably cuprous bromide, Cu-lyt., copper chloride-ascorbic acid system or copper bromide-ascorbic acid system.Part is preferably 2, the 2-bipyridyl.Thus, metal support surface forms the inert polymer layer, and above-mentioned inert polymer can effectively repel the absorption of nonspecific proteins matter at material surface, therefore can prevent that to a certain extent tampon forms at metal support surface.
In addition; Above-mentioned inert polymer is a pectinate texture; The polymer of this structure comprises abundant side chain, the hydroxyl of side chain terminal can highdensity covalent bond lysine molecule behind chemical activation, thereby has improved the efficient that metal support surface combines plasminogen; And then the quick active fibrinolytic system, reach the purpose of dissolving nascent thrombosis.
Step e is the step of inert polymer being carried out terminal hydroxy group activation and covalence graft ε-lysine.Concrete; At first need inert polymer modified metal support be carried out the activation of terminal hydroxy group, this activation step preferably carries out according to following mode: the inert polymer modified metal is propped up be placed on the priming reaction that carries out terminal hydroxy group in the succinum imines carbonic diester solution.Abundant in order to guarantee activation, soak time preferably is set to 4h～12h.
Place the ε-lysine solution of tert-butyl group oxygen carbonyl-protection to carry out graft reaction metal rack again after the terminal hydroxy group activation, the response time preferably is made as 12h～24h.Use the purpose of the ε-lysine of tert-butyl group oxygen carbonyl-protection to be: at first the epsilon-amino with lysine protects; Be fixed on the support through alpha-amido and the butanimide radical reaction that is fixed on the surface then, again tert-butyl group oxygen carbonyl removed at last epsilon-amino is come out.Guarantee that epsilon-amino and carboxyl in the lysine molecule expose simultaneously, performance combines with the specificity of plasminogen.
Remove protection behind the graft reaction again and handle, obtain having the metal rack of the nascent thrombosis function of dissolving thus.Removing the protection processing specifically preferably carries out according to following mode: place trifluoroacetic acid solution to carry out deprotection reaction the metal rack behind the graft reaction, the temperature of deprotection reaction is 15 ℃～25 ℃.As more preferably scheme, the concentration expressed in percentage by volume of trifluoroacetic acid is 25～30% in the trifluoroacetic acid solution.For the impurity of removing rack surface also can be with obtaining that the finishing metal rack is washed again and dry.
Can know by The above results; The present invention carries out after hydroxylating and the amination fixedly initiator to metal rack successively; Utilize this initiator to prepare the inert polymer layer at metal support surface then through the ATRP principle; Again inert polymer is carried out grafting ε-lysine after the terminal hydroxy group activation at last, obtain the surface mount that ε-lysine grafting inert polymer is modified thus.With respect to prior art; The metal support surface of method for preparing of the present invention is covered with ε-lysine grafting inert polymer and repaiies layer; This polymer can effectively repel the absorption of nonspecific proteins matter at material surface on the one hand, therefore can prevent that to a certain extent tampon forms at metal support surface; On the other hand; Above-mentioned inert polymer is a pectinate texture; The polymer of this structure comprises abundant lysine molecule, thereby has improved the efficient of metal support surface combination plasminogen, and then the quick active fibrinolytic system; Activate the intravital antithrombotic of machine from the bionics angle and form passage, reach the purpose of the nascent thrombosis of dissolving thus.Therefore the finishing metal rack of preparation not only can prevent to form thrombosis to a great extent according to the method described above, also can dissolve fast even the later stage forms nascent thrombosis, improves the safety that metal rack uses and increases the service life.
The present invention also provides a kind of finishing metal rack, and this metal support surface is covered with ε-lysine grafting inert polymer layer; Said hydrophilic inert polymer is polymethylacrylic acid-2-hydroxyl-ethyl ester or polymethylacrylic acid oligomeric ethylene glycol ester.This finishing metal rack can prepare according to the method described above.
The ε of modification rack surface provided by the invention-lysine grafting inert polymer is repaiied layer, can effectively repel the absorption of nonspecific proteins matter at material surface on the one hand; On the other hand, this decorative layer comprises abundant lysine molecular structure, thereby has improved the efficient that metal support surface combines plasminogen, can the quick active fibrinolytic system, reach the purpose of the nascent thrombosis of dissolving thus.Therefore above-mentioned finishing metal rack not only can prevent to form thrombosis to a great extent, also can dissolve fast even the later stage forms nascent thrombosis, improves the safety that metal rack uses and increases the service life.
In order further to understand the present invention, below in conjunction with embodiment metal rack with the nascent thrombosis function of dissolving provided by the invention and preparation method thereof to be described, protection scope of the present invention is not limited by the following examples.
1, the surperficial fixedly initiator of L605 cochrome timbering material
L605 propped up be placed in the mixed solution that is mixed by 9mL hydrogen peroxide (30%) and 21mL concentrated sulphuric acid (98%), soaked 15 minutes under the room temperature, reaction finishes after big water gaging ultrasonic cleaning, nitrogen dry up; Be placed on then in the oxygen plasma that power is 100W and handled 2 minutes, obtain the L605 timbering material of surface hydroxylation.
The L605 of surface hydroxylation propped up be placed in dry toluene (20mL) solution that contains 0.4mL 3-aminopropyl triethoxysilane, 80 ℃ of reactions 18 hours, reaction finishes after toluene, water, acetone ultrasonic cleaning successively, obtains the L605 support of surface amination.
The support of surface amination is put into anhydrous methylene chloride (20mL) solution that contains 1mL bromine isobutyl acylbromide and 1mL triethylamine; Reaction is 18 hours under the room temperature; Reaction finishes after dichloromethane, water, acetone ultrasonic cleaning successively obtain the L605 support that the surface is fixed with initiator.
2, L605 cochrome timbering material surface grafting polymerization 2-hydroxyethyl methacrylate
With 1.3g 2-hydroxyethyl methacrylate, 12.5mg 2,2-bipyridyl, 6.82mgCuCl
22H
2The L605 metal rack that O, 7.05mg ascorbic acid, 5mL methanol, 5mL water and surface are fixed with initiator places the 50mL reaction bulb, under nitrogen protection, and room temperature reaction 10 hours.After reaction is accomplished, support is taken out, obtain the L605 timbering material of polymethylacrylic acid 2-hydroxy methacrylate graft modification through methanol, water washing, drying.
3, L605 cochrome timbering material surface chemistry bonding ε-lysine
0.256g succinum imines carbonic diester and 0.14mL triethylamine are dissolved in the 20mL anhydrous acetonitrile; The L605 support that then step 2 is obtained joins in this solution; Under nitrogen protection, room temperature reaction took out after 6 hours, after fully cleaning and dry up with nitrogen with dry acetonitrile; Put into 10mL concentration rapidly and be in the PBS (pH=8.3) of ε-lysine of tert-butyl group oxygen carbonyl-protection of 5mg/mL, react and use distilled water wash after 24 hours.With reaction in the trifluoroacetic acid aqueous solution of washed support immersion 25% 1.5 hours, water fully cleaned to guarantee the pickling of remnants is fallen.
Adopt x-ray photoelectron power spectrum (XPS) that the chemical composition on modification front and back support surface is characterized, test result is listed in table 1.
Support a in the table 1 representes the unmodified support; Support b～e support is represented according to the L605 support of the surface amination of present embodiment method preparation, the L605 support that the surface is fixed with initiator, the L605 support of polymethacrylate-2-hydroxy-ethyl ester graft modification and the L605 support that ε-lysine grafting inert polymer layer is modified.
Table 1 X-ray photoelectron spectroscopic analysis result
| Test event | C1s | O1s | Si2p | N1s | Br3d | C∶O |
| Support a | 36.7 | 9.34 | 2.56 | 0.27 | - | 3.9 |
| Support b | 28.7 | 13.69 | 4.18 | 1.15 | - | 2.1 |
| Support c | 31.42 | 13.41 | 1.94 | 1.28 | 0.22 | 2.3 |
| Support d | 34.17 | 12.55 | 1.2 | 0.81 | 0.09 | 2.7 |
| Support e | 35.27 | 11.6 | 1.2 | 0.96 | - | 3.0 |
Can be known that by table 1 interpretation of result the L605 surface is after the 3-aminopropyl triethoxysilane is modified, the content of Si2p, N1s increases to some extent, shows that its successful group has been contained in the hydroxylating rack surface.Behind the amination rack surface and 2-bromo isobutyryl bromine reaction after the 3-aminopropyl triethoxysilane is modified, the appearance of Br3d characteristic peak shows that initiator 2-bromo isobutyl acylbromide successfully has been fixed on the amination rack surface.Be fixed with the rack surface generation atom transition free radical polymerization reaction of initiator when methacrylic acid-2-hydroxy methacrylate monomer after; Because polymethacrylate-2-hydroxy-ethyl ester is grafted on substrate surface equably; The C constituent content obviously increases, and the content of elements such as Si, N, Br descends to some extent.When lysine is fixed on rack surface through the terminal activation hydroxyl of polymethacrylate-2-hydroxy-ethyl ester; Its C/O is increased to 3.04 than by 2.72; The N constituent content also is increased to 0.96 from 0.81; This is consistent with the situation of change that lysine molecule grafting front and back support surface chemistry is in theory formed, show the lysine molecule success be grafted on material surface.
The L605 support (L605-PHEMA-Lys) that the L605 support (L605-PHEMA) and the ε-lysine grafting inert polymer layer of unmodified support (L605), the graft modification of polymethylacrylic acid 2-hydroxy methacrylate are modified carries out the adsorption test of Fibrinogen, human serum albumin and plasminogen respectively.Be illustrated in figure 1 as the absorption collection of illustrative plates of L605 cochrome material in the fibrinogen solution of 1mg/mL of embodiment 1 finishing front and back.Be illustrated in figure 2 as the absorption collection of illustrative plates of L605 cochrome material in human albumin's solution of 1mg/mL of embodiment 1 finishing front and back.The L605 cochrome material that is illustrated in figure 3 as embodiment 1 finishing front and back adsorbs the enzyme linked immunological absorption collection of illustrative plates of plasminogen in blood plasma.
Be illustrated in figure 4 as before modifying and the thrombus performance test collection of illustrative plates of the L605 cochrome material after modifying.Curve 1 expression unmodified cochrome material among Fig. 2, the L605 support that the ε-lysine grafting inert polymer layer of curve 2 this enforcement of expression preparations is modified.
Can be known by Fig. 2～4: the modification support of present embodiment preparation can either effectively repel the absorption of nonspecific proteins matter, can combine plasminogen by specificity again, and nascent thrombosis is had dissolution.
1, the fixing initiator of 316L stainless steel stent material surface
316LSS propped up to be placed in the oxygen plasma that power is 100W handled 2 minutes, obtain the 316L timbering material of surface hydroxylation.The 316LSS of surface hydroxylation propped up be placed in dry toluene (20mL) solution that contains 0.4mL 3-aminopropyl triethoxysilane, 80 ℃ of reactions 18 hours, reaction finishes after toluene, water, acetone ultrasonic cleaning successively, obtains the 316L support of surface amination.The support of surface amination is put into anhydrous methylene chloride (20mL) solution that contains 1mL chloracetyl chloride and 1mL triethylamine; Reaction is 24 hours under the room temperature; Reaction finishes after dichloromethane, water, acetone ultrasonic cleaning successively obtain the 316LSS support that the surface is fixed with initiator.
2,316LSS timbering material surface grafting polymerization 2-hydroxyethyl methacrylate
With 2.148g 2-hydroxyethyl methacrylate, 62.5mg 2,2-bipyridyl, 6.82mgCuBr, 1.6mL methanol, 0.4mL water and the surperficial 316LSS that is fixed with initiator prop up and are placed in the 50mL reaction bulb, under nitrogen protection, and room temperature reaction 10 hours.After reaction is accomplished, support is taken out, obtain the 316LSS timbering material of polymethylacrylic acid 2-hydroxy methacrylate graft modification through methanol, water washing, drying.
3,316LSS timbering material surface chemistry bonding ε-lysine
0.256g succinum imines carbonic diester and 0.14mL triethylamine are dissolved in the 20mL anhydrous acetonitrile; The 316L support that then step 2 is obtained joins in this solution; Under nitrogen protection, room temperature reaction took out after 6 hours, after fully cleaning and dry up with nitrogen with dry acetonitrile; Put into 10mL concentration rapidly and be in the PBS (pH=8.3) of ε-lysine of tert-butyl group oxygen carbonyl-protection of 5mg/mL, react and use distilled water wash after 24 hours.With reaction in the trifluoroacetic acid aqueous solution of washed support immersion 30% 1.5 hours, water fully cleaned to guarantee the pickling of remnants is fallen.
Embodiment 3
1, the fixing initiator of nick-eltitanium alloy stent material surface
Nick-eltitanium alloy stent placed by 9mL hydrogen peroxide (30%) and 21mL concentrated sulphuric acid (98%) mix solution, soaked 10 minutes under the room temperature, reaction finishes after big water gaging ultrasonic cleaning, nitrogen dry up.With being placed in dry toluene (20mL) solution that contains 0.4mL 3-aminopropyl triethoxysilane of surface hydroxylation, 80 ℃ of reactions 24 hours, reaction finishes after toluene, water, acetone ultrasonic cleaning successively obtain the surface and has amino nick-eltitanium alloy stent.The support of surface amination is put into anhydrous methylene chloride (20mL) solution that contains 1mL bromine isobutyl acylbromide and 1mL triethylamine; Reaction is 12 hours under the room temperature; Reaction finishes after dichloromethane, water, acetone ultrasonic cleaning successively obtain the nick-eltitanium alloy stent that the surface is fixed with initiator.
2, nick-eltitanium alloy stent material surface glycerol polymerization methacrylic acid oligomeric ethylene glycol ester
With 2.64g methacrylic acid oligomeric ethylene glycol ester, 12.5mg 2,2-bipyridyl, 6.82mgCuCl
22H
2The nick-eltitanium alloy stent that O, 7.05mg ascorbic acid, 5mL methanol, 5mL water and surface are fixed with initiator places the 50mL reaction bulb, under nitrogen protection, and room temperature reaction 6 hours.After reaction is accomplished, support is taken out, obtain the nick-eltitanium alloy stent material of polymethylacrylic acid oligomeric ethylene glycol ester graft modification through methanol, water washing, drying.
3, nick-eltitanium alloy stent material surface chemical bonding ε-lysine
0.51g p-nitrophenyl chloroformate ester and 0.36mL triethylamine are dissolved in the 10mL anhydrous acetonitrile; The support that then step 2 is obtained joins in this solution; Under nitrogen protection, room temperature reaction took out after 12 hours, after fully cleaning and dry up with nitrogen with dry acetonitrile; Put into 10mL concentration rapidly and be in the PBS (pH=8.3) of ε-lysine of tert-butyl group oxygen carbonyl-protection of 5mg/mL, react and use distilled water wash after 24 hours.With reaction in the trifluoroacetic acid aqueous solution of washed support immersion 25% 1.5 hours, water fully cleaned to guarantee the pickling of remnants is fallen.
Modification support with present embodiment 1～3 preparation immerses in the blood plasma respectively, and makes blood plasma force to form thrombosis, and the thrombosis of observing in the blood plasma after 40 minutes is all dissolved.
The explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof.Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of claim of the present invention.
To the above-mentioned explanation of the disclosed embodiments, make this area professional and technical personnel can realize or use the present invention.Multiple modification to these embodiment will be conspicuous concerning those skilled in the art, and defined General Principle can realize under the situation that does not break away from the spirit or scope of the present invention in other embodiments among this paper.Therefore, the present invention will can not be restricted to these embodiment shown in this paper, but will meet and principle disclosed herein and features of novelty the wideest corresponding to scope.
Claims (10)
1. the method for preparing of a finishing metal rack comprises:
A), metal rack carried out hydroxylating handle, obtain the hydroxylating metal rack;
B), said hydroxylating metal rack is placed 3-aminopropyl triethoxysilane solution, obtain the amination metal rack;
C), said amination metal rack is placed initiator solution, obtain the metal rack that the surface is fixed with initiator, said initiator is 2-bromo isobutyl acylbromide or chloracetyl chloride;
D), at 0 ℃～100 ℃, under the inert gas shielding, catalyst, part and said surface are fixed with under the condition that the metal rack of initiator exists, monomer generation radical polymerization obtains inert polymer modified metal support; Said monomer is methacrylic acid-2-hydroxy methacrylate or methacrylic acid oligomeric ethylene glycol ester;
E), under inert gas shielding, said inert polymer modified metal support is carried out the terminal hydroxy group activation; Place the ε-lysine solution of tert-butyl group oxygen carbonyl-protection to carry out graft reaction the metal rack after the activation, remove protection after the reaction and handle, obtain the finishing metal rack.
2. method for preparing according to claim 1 is characterized in that, the processing time of step a is 1min～20min.
3. method for preparing according to claim 1 is characterized in that, said hydroxylating processing is specially one or both in the following mode:
Place the mixed solution of hydrogen peroxide and concentrated sulphuric acid to handle metal rack;
Metal rack placed carry out oxygen plasma treatment.
4. method for preparing according to claim 1 is characterized in that, the concentration expressed in percentage by volume of said 3-aminopropyl triethoxysilane solution is 0.5%～5%.
5. method for preparing according to claim 1 is characterized in that, the concentration expressed in percentage by volume of said initiator solution is 1%～10%.
6. method for preparing according to claim 1 is characterized in that, the processing time of step c is 3h～24h.
7. method for preparing according to claim 1 is characterized in that, said catalyst is cuprous bromide, Cu-lyt., copper chloride-ascorbic acid system or copper bromide-ascorbic acid system.
8. method for preparing according to claim 1 is characterized in that, said part is 2, the 2-bipyridyl.
9. method for preparing according to claim 1; It is characterized in that; Said removing protects processing to be specially: place trifluoroacetic acid solution to carry out deprotection reaction the metal rack behind the graft reaction; The concentration expressed in percentage by volume of said trifluoroacetic acid solution is 25%～30%, and the temperature of said deprotection reaction is 15 ℃～25 ℃.
10. a finishing metal rack is characterized in that, said metal support surface is covered with ε-lysine grafting inert polymer layer; Said hydrophilic inert polymer is polymethacrylate-2-hydroxy-ethyl ester or polymethylacrylic acid oligomeric ethylene glycol ester.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210046113.6A CN102526813B (en) | 2012-02-27 | 2012-02-27 | Surface-modified metal stent and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210046113.6A CN102526813B (en) | 2012-02-27 | 2012-02-27 | Surface-modified metal stent and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102526813A true CN102526813A (en) | 2012-07-04 |
| CN102526813B CN102526813B (en) | 2014-04-30 |
Family
ID=46335616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210046113.6A Active CN102526813B (en) | 2012-02-27 | 2012-02-27 | Surface-modified metal stent and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102526813B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102743788A (en) * | 2012-07-06 | 2012-10-24 | 淮阴工学院 | Method for performing surface treatment on material for boosting cell growth and resisting biological pollution |
| CN109013233A (en) * | 2018-08-03 | 2018-12-18 | 武汉理工大学 | A method of quaternary ammonium salt coating is prepared in metal surface using self assembly |
| CN110358128A (en) * | 2019-07-04 | 2019-10-22 | 苏州贝蒂克生物技术有限公司 | A kind of method that polymer surfaces are amido modified and its apparent relevance can characterizing method |
| WO2021104296A1 (en) * | 2019-11-26 | 2021-06-03 | 上海微创医疗器械（集团）有限公司 | Drug-loaded implanted medical device and preparation method therefor |
| CN114904060A (en) * | 2022-05-30 | 2022-08-16 | 浙江大学 | Medical catheter containing anti-adhesion layer and preparation method thereof |
| CN115246910A (en) * | 2022-04-29 | 2022-10-28 | 上海微密医疗科技有限公司 | Synthesis method and application of polymer |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060034888A1 (en) * | 2004-07-30 | 2006-02-16 | Advanced Cardiovascular Systems, Inc. | Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages |
| US20060074191A1 (en) * | 2004-10-06 | 2006-04-06 | Desnoyer Jessica R | Blends of poly(ester amide) polymers |
| CN1791437A (en) * | 2003-05-16 | 2006-06-21 | 布卢薄膜有限责任公司 | Medical implants comprising biocompatible coatings |
| CN101942105A (en) * | 2010-09-03 | 2011-01-12 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
| CN101962422A (en) * | 2010-08-06 | 2011-02-02 | 浙江大学 | Cardiovascular stent coating material with endothelial cell selectivity and preparation and application method thereof |
-
2012
- 2012-02-27 CN CN201210046113.6A patent/CN102526813B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1791437A (en) * | 2003-05-16 | 2006-06-21 | 布卢薄膜有限责任公司 | Medical implants comprising biocompatible coatings |
| US20060034888A1 (en) * | 2004-07-30 | 2006-02-16 | Advanced Cardiovascular Systems, Inc. | Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages |
| US20060074191A1 (en) * | 2004-10-06 | 2006-04-06 | Desnoyer Jessica R | Blends of poly(ester amide) polymers |
| CN101962422A (en) * | 2010-08-06 | 2011-02-02 | 浙江大学 | Cardiovascular stent coating material with endothelial cell selectivity and preparation and application method thereof |
| CN101942105A (en) * | 2010-09-03 | 2011-01-12 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李鑫 等: "新型抗凝血材料表面的制备", 《2011年全国高分子学术论文报告会论文摘要集》, 28 September 2011 (2011-09-28), pages 669 - 057 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102743788A (en) * | 2012-07-06 | 2012-10-24 | 淮阴工学院 | Method for performing surface treatment on material for boosting cell growth and resisting biological pollution |
| CN109013233A (en) * | 2018-08-03 | 2018-12-18 | 武汉理工大学 | A method of quaternary ammonium salt coating is prepared in metal surface using self assembly |
| CN110358128A (en) * | 2019-07-04 | 2019-10-22 | 苏州贝蒂克生物技术有限公司 | A kind of method that polymer surfaces are amido modified and its apparent relevance can characterizing method |
| CN110358128B (en) * | 2019-07-04 | 2021-09-14 | 苏州贝蒂克生物技术有限公司 | Method for modifying amino group on surface of polymer and characterization method of surface related performance of polymer |
| WO2021104296A1 (en) * | 2019-11-26 | 2021-06-03 | 上海微创医疗器械（集团）有限公司 | Drug-loaded implanted medical device and preparation method therefor |
| CN115246910A (en) * | 2022-04-29 | 2022-10-28 | 上海微密医疗科技有限公司 | Synthesis method and application of polymer |
| CN114904060A (en) * | 2022-05-30 | 2022-08-16 | 浙江大学 | Medical catheter containing anti-adhesion layer and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102526813B (en) | 2014-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102526813B (en) | Surface-modified metal stent and preparation method thereof | |
| Li et al. | Lysine-PEG-modified polyurethane as a fibrinolytic surface: effect of PEG chain length on protein interactions, platelet interactions and clot lysis | |
| US9284409B2 (en) | Endoprosthesis having a non-fouling surface | |
| McPherson et al. | Grafting of PEO to glass, nitinol, and pyrolytic carbon surfaces by γ irradiation | |
| JP6435863B2 (en) | Antithrombotic material | |
| US20020009535A1 (en) | Superoxide dismutase or superoxide dismutase mimic coating for an intracorporeal medical device | |
| Yuan et al. | Site-directed immobilization of antibodies onto blood contacting grafts for enhanced endothelial cell adhesion and proliferation | |
| JP2005517490A (en) | Composite stent with polymeric covering and bioactive coating | |
| CN101080247A (en) | Biomaterials carrying cyclodextrines having improved absorption properties and used for the progressive and delayed release of therapeutic molecules | |
| CN101357241B (en) | CD34 antibody or CD133 antibody surface orientation fixing method of titanium and titanium alloy cardiovascular implantation device | |
| WO2005118020A1 (en) | Surface coating comprising bioactive compound | |
| TW200835521A (en) | A method of treating hair | |
| WO2013152713A1 (en) | Drug balloon based on hydrogen-bond interaction and coating method therefor | |
| CN101942105B (en) | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof | |
| CN102671637A (en) | Biomimetic specific immune adsorption material with PAMAM (Polyamidoamine) as spacer arm, and preparation method and application thereof | |
| Li et al. | Endothelial mimetic multifunctional surfaces fabricated via polydopamine mediated copper immobilization | |
| JPWO2016159243A1 (en) | Antithrombotic metal material | |
| CN104177641B (en) | A kind of method for preparing lubricating coating in medical polyvinyl material surface | |
| CN101264327A (en) | Magnetic target carrier system | |
| CN100435861C (en) | Method for preparing drug or gene carried stent | |
| JP4832290B2 (en) | Drug / gene eluting stent | |
| CN103830777A (en) | REDV modification novel biodegradable coronary artery coating support | |
| CN114904062B (en) | Vascular stent with selective biological functionalization and preparation method thereof | |
| CN104492395B (en) | Bionical immunoadsorbent with PAMAM as spacerarm and preparation method and application | |
| CN113426423B (en) | Adsorbent for removing LDL (low density lipoprotein) by extracorporeal blood circulation, preparation method thereof and perfusion device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220407 Address after: 215123 building 26, Dongjing industrial building, No. 1, Jintian Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province Patentee after: JIANGSU BIOSURF BIOTECH Co.,Ltd. Address before: 215123 No. 199 benevolence Road, Suzhou Industrial Park, Jiangsu, China Patentee before: SOOCHOW University |
|
| TR01 | Transfer of patent right |