CN104857570B - A kind of degradable zinc-containing alloy support and preparation method thereof - Google Patents
A kind of degradable zinc-containing alloy support and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to a kind of degradable zinc-containing alloy support and preparation method thereof, the support includes degradable Zr-based materials rest body, rest body surface is provided with the degradable polymer eluting coatings containing curative drug, and the rest body is drum type brake network structure.The preparation method includes, degradable Zr-based materials are processed into rest body 1)；2) surface preparation is carried out to rest body；3) electrobrightening process is carried out to rest body；4) stent surface coated carries the degradable high polymer material of curative drug after treatment.The support that the present invention is provided is because of the more superior decay resistance of matrix material kirsite in the excellent support for being implanted into 4 months supports maintained above, matrix surface is coated with the good polymer coating of biocompatibility, the compatibility for improving zinc-containing alloy is covered in rack surface beneficial to endotheliocyte, and controllable drug release, reducing burst drug release makes medicine slowly persistently keep finite concentration release, to reduce local inflammation after stenter to implant, restenosiss and thrombus in stents risk.
Description
Technical field
The present invention relates to a kind of biodegradation type metal rack and preparation method thereof, belongs to Implantable Medical Device
Technical field.
Background technology
Gruentzing has successfully carried out the first percutaneous transluminal coronary angioplasty within 1977, opens simple ball
Capsule dilation therapy cardiovascular epoch, this new technique for not opening breast terminated cardiac operation solely lead coronary blood fortune weight
The history built.Sigwart successfully implements coronary stent operation first within 1987, and substantial amounts of clinical experiment confirms hat
Arteries and veins stenter to implant can be prevented effectively from the medical drawback of simple balloon expandable, and being widely accepted becomes in Coronary Artery Disease Intervention Treatment history
Second milestone.Holding state can be kept for a long time in lesion locations after coronary artery stenting, can effectively solve the problem that
The danger of postoperative acute vascular occlusion, improves the safety of PTCA, and can improve the negativity of lesion vesselses and reinvent, make postoperative
In support, medium-long term restenosiss incidence rate is reduced to less than 15%, and angiocardiopathy stent has greatly been widened in coronary artery bracket implantation
The indication of interventional therapy.Since 2003, with the appearance of the bracket for eluting medicament with CYPHER and TAXUS as representative, and
Achieve gratifying effect in clinical practice, Drug inhibition smooth muscle cell proliferation with the medicine of reduction Restenosis wash
The de- support epoch arrive, and once the new focus that becomes angiocardiopathy stent interventional therapy is listed, bracket for eluting medicament both may be used
Playing as bare bracket prevents early stage blood vessel elasticity retraction effect after stent endoprosthesis, again can be because of the medicine of anti-proliferative drugs
Reason is acted on and reduces postoperative smooth muscle cell proliferation, is prevented because new intima is thickened and caused restenosiss, is become new and have
The breakthrough of milestone significance.
But the development of nearly 10 years, also exposes the short slab of drug stent, though such as bracket for eluting medicament be effectively reduced again it is narrow
Narrow generation, but postpone blood vessel endothelium healing, cause blood vessel to be difficult to reconstruction and complete endothelialization so that support is exposed to for a long time
In blood vessel, the generation of medium-long term thrombosis in support is increased.The support of clinical practice at present, it is impossible to degradable, longer-term persistence
In blood vessel wall, vasomotoricity is affected, increase local inflammation, restenosiss and thrombus in stents risk.However, preferable support
System should be compatible with arteria coronaria physiological structure and function, can not only improve the local blood supply of arteria coronaria, and can recover after its implantation
With keep the original function of blood vessel, biodegradable stent then can make blood vessel structure and functional rehabilitation in theory to naturalness, quilt
" the 4th technological innovation " of the coronary intervention being considered after PTCA, BMS, DES.In recent years, U.S. Abbott is public
Department and Biotronik companies of Germany achieve important breakthrough in Wholly-degradable field of stents, with BVS and AMS supports as representative
Degradable coronary artery bracket be expected to lead the 4th revolution of Coronary Artery Disease Intervention Treatment.Technological revolution brings coronary heart
On the one hand the new era of disease treatment, support interventional technique replace Traditional surgical treatment disease, there is provided a kind of wound is less
Treatment meanss, on the other hand make the reluctant disease of some traditional operations be able to satisfactory solution, support interventional technique is
Become the effective means for the treatment of coronary heart disease, be that extensive patients bring glad tidings.
Wholly-degradable coronary artery bracket opens the effect of a kind of " temporary stent ", and timbering material in interventional therapy
With good biocompatibility, effective vessel support is able to maintain that early stage lesion locations are inserted, in certain effect
Between after with degradable, thus can fundamentally overcome the shortcomings and complication of permanent metal support, and can
Preferably by the progressively degraded of biomaterial, carrying medicament, cell, realize that belongings Quality Control is released and slow release plays its effect,
Become the forward position focus of current Coronary Artery Disease Intervention Treatment both at home and abroad research.Two sides are focused in the research of Biodegradable scaffold at present
Face：Degradable macromolecule support and degradable metal support.
In terms of polymer support, the research trend of early stage can make tunica intima shape in from the slower support of degradation speed
Into complete, it is to avoid thrombosis occur, but degradation speed can affect the growth of blood vessel itself excessively slowly, and the inflammation for extending blood vessel wall is anti-
Should, while because macromolecule intensity is relatively low, its support can cause elastical retraction because of support force deficiency, which has limited which in thin vessels
The use in chamber；Biodegradable metals support has the mechanic properties of bare metal stent, can effectively prevent early stage to return
Contracting, and the not penetrability with X-ray have the degradable characteristic of polymer support concurrently, and are subject to that researchers' is extensive
Concern, the degradable metal support of research is mainly including ferroalloy support and magnesium alloy bracket at present.Such as patent CN
A kind of iron-based biodegradable stent of 101496910 A and CN 102228721 A publicities, 101708140 A of patent CN,
A kind of magnesium base degradable support of CN101468216 A and CN102488932 A publicities.
However, the biodegradable stent of current research still suffers from some drawbacks, its extensive application is limited.To degradable polymer
For support, also there are the poor difficult problem of development effect and still need and capture, except the carriage support L-Tyrosine Merlon of REVA is constituted
But itself development, is easy to the visualization of implantation process and Follow-up After, and other biodegradable stents is mostly special at one end heavy
The development mark of metal tantalum and itself does not develop, this will necessarily be fed row two stands para-position and connect bring difficulty using operation, limit
Its application in longer vascular lesion is made, while will also retain in vivo, as different as the tantalum of mark after scaffold degradation
Thing long-term existence；For degradable metal support, magnesium alloy bracket shows degradation speed faster, and ferroalloy support drops
Solution speed is slower, is unfavorable for the reconstruction of blood vessel itself, needs to control degradation speed and provides more appropriate support force to fit
Answer the process of positivity vascular remodeling.
Zinc is one of micro elements needed by human, and all physiological metabolism processes are participated in body, and zinc is except in various gold
Catalysis is played in category enzyme, transcription factor and other albumen or structure effect is outer, played also in the form of neurotransmitter or quenched sample
Its function.Metallic zinc compared to polymer have excellent mechanical property and can developability, while study finding with preferable
Biocompatibility, degradation property are excellent in magnesium base alloy, have potential researching value as biomedical metallic material.So
And, zinc-containing alloy is but rarely reported as degradable metal material, and literature searches of the Jing to prior art finds, D Vojt ě ch
Etc. the mechanical performance and corrosive nature that report Zn-Mg alloys, and its feasibility (Acta applied in orthopaedics implantation is inquired into
biomaterialia,2011,7(9):3515-3522)；PK Bowen etc. report implantation reality of the pure zinc in mice ventral aorta
Test, disclose its internal etching characteristic, pure Zn has been inquired into as the feasibility (Advanced of support metal material
Materials,2013,25(18):2577-2582), however, the design of the support of degradable zinc and its alloy but has no report.
The content of the invention
The purpose of the present invention is just being to provide the novel degradable Metal Substrate support being made with zinc and kirsite, to gram
Conventional metals bare bracket non-degradable in vivo is taken, is retained as foreign body for a long time and produce in vivo inflammatory stimulus reaction, can keep away again
Exempt from that degradable polymer support is not good in mechanics support performance and the medical science that do not possess development effect and bring is limited and can
Degraded iron-based support, magnesio scaffold degradation speed and tube chamber rebuild unmatched drawback, while can by carrying in rack surface
To suppress the medicine of smooth muscle cell proliferation, suppress neointimal hyperplasia, thicken, so as to reduce even by the pharmacotoxicological effect of medicine
Eliminate the generation of in-stent restenosis.
The object of the present invention is achieved like this：
A kind of novel degradable zinc-containing alloy support, including：Degradable Zr-based materials rest body；The rest body table
Face is provided with the degradable polymer eluting coatings containing curative drug；The rest body is drum type brake network structure.
Described rest body is preferably drum type brake network structure, shows preferable pliability, is easy to intervention to place, and
Radial support better performances, and because matrix material metallic zinc imparts the preferable developing performance of support, facilitate operation technique support
Intervention and postoperative tracking.
The degradable Zr-based materials are pure zinc or zinc-containing alloy；The zinc-containing alloy is preferably Zn-Mg alloys, Zn-Ca
Alloy, Zn-Sr alloys, Zn-Sn alloys, Zn-Mg-Mn alloys, Zn-Mg-Ca alloys, Zn-Mg-Sr alloys, Zn-Mg-Sn alloys,
One kind in Zn-Mg-Mn-Ca alloys, Zn-Mg-Ca-Sr alloys etc.；Further preferably the degradable Zr-based materials are Zn- (0
～1.5) %Ca alloys, Zn- (0～1.5) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Mn alloys, Zn- (0～
1.5) %Mg- (0～1) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Ca- (0～0.5) %Mn alloys, Zn- (0～
1.5) one kind in %Mg alloys or Zn- (0～1.5) %Mg- (0～1) %Ca alloys.
In the present invention, term " Zn-1%Mg alloys " implication refers to " Mg contents are 1% in alloy, balance of Zn "；Term
" Zn-1%Mg-0.5%Ca alloys " implication refers to " Mg contents are that 1%, Ca contents are 0.5% in alloy, balance of Zn ".Other
It is similar to therewith.
The degradable polymer eluting coatings containing curative drug that the rest body surface is arranged, wherein described drop
Depolymerization compound includes polylactic acid, PGA, condensing model, copolymer of poly lactic acid, polyglycolic acid, polyhydroxybutyrate valerate, poly-
The copolymer of one or more in the absorbable macromolecule materials such as cyanoacrylate, can also include collagen egg
In vain, one kind in the natural biodegradable polymer material such as gelatin, chitin, it might even be possible to be synthetic macromolecular material and day
The blend of right degradable high polymer material；Described curative drug can be that the medicine with anti-cell proliferation effect is thunderous
One or more in handkerchief mycin, paclitaxel, rheum emodin, curcumin etc. is combined；Preferred therapeutic medicine is rapamycin, preferably
Degradable polymer is polylactic acid, and preferred eluting coatings thickness is 10～50 μm.
The rest body surface is provided with the degradable polymer eluting coatings containing curative drug and can improve metal
The biocompatibility of bare bracket, covers in rack surface beneficial to endotheliocyte, and controllable drug release, reduces burst drug release
Medicine is made slowly persistently to keep finite concentration release, to reduce the incidence rate of acute, subacute stent thrombosis after stenter to implant.
The rest body degradable Zr-based materials of the present invention are considered from the biological effect angle of alloying element in design,
Alloying is carried out to human body beneficial element, comprehensive mechanical property is improved after processing, be drawn into pipe, using laser engraving
Bare bracket is formed, degradation property is excellent in magnesio support；Described rest body be drum type brake network structure, the design table of support
Reveal preferable pliability, be easy to intervention to place, and radial support better performances, and because matrix material metallic zinc imparts support
Preferably developing performance, facilitates the intervention of operation technique support and postoperative tracking；Meanwhile, apply in degradable zinc-containing alloy rack surface
One or more layers degradable polymer coating for containing curative drug is covered, designed degradable polymer coating can be improved
The biocompatibility of bare metal stent, covers in rack surface beneficial to endotheliocyte, and controllable drug release, reduces medicine
Prominent releasing makes medicine slowly persistently keep finite concentration release, to reduce the incidence rate of acute, subacute stent thrombosis after stenter to implant.
Present invention additionally comprises：
The preparation method of above-mentioned degradable zinc-containing alloy support, including：1) degradable Zr-based materials are processed into into support base
Body；2) pretreatment is carried out to rest body, processing residual and surface appurtenance is rejected；3) rest body is carried out at electrobrightening
Reason；4) to polishing after-poppet matrix surface degradable polymer eluting coatings of the coating containing curative drug.
The step 2) pretreatment is carried out to rest body, processing residual and surface appurtenance are rejected, including：A) to support
Matrix carries out mechanical treatment；B) pickling is carried out to the rest body after mechanical treatment or alkali cleaning is processed；C) to pickling or alkali cleaning
Rest body after process carries out ultrasound wave cleaning.Wherein, the mechanical treatment that a) carries out to rest body uses physics
Method, rejects processing hollow out residual burr etc..It is described that pickling or alkali cleaning process b) are carried out to the rest body after mechanical treatment, i.e.,
Cleaning treatment (under room temperature) is carried out during support is put into pickle or alkali wash water, the greasy dirt or oxide of rack surface etc. is removed miscellaneous
Matter.Described pickle is acetic acid and neutral sodium-salt mixed solution, can be acetic acid and the neutral sodium-salt such as Sodium Chloride or sodium nitrate
Blend solution, can clean at room temperature 3-5 minutes；Described alkali wash water is sodium hydroxide and alkaline sodium salt mixed solution, can
To be the blend solution of sodium hydroxide and the alkaline sodium salt such as sodium carbonate or sodium bicarbonate, can clean at room temperature 5-10 minutes.Institute
State the rest body after c) processing to pickling or alkali cleaning and carry out ultrasound wave cleaning and use clear water, usually pure water to process after
Support is cleaned, and removal is attached to the acid of rack surface or alkali liquor.
The step 3) rest body is carried out electrobrightening process will rest body be put into (hang on) and hold electrolysis
The electrolysis bath of liquid carries out electrobrightening process, and concrete technology is：DC voltage is 2.5～30V, and electric current is 0.2～10A, is electrolysed
Polishing time is 0.5～20 minute, and electrolysis temperature is 10～40 DEG C；The electrolyte is the alcoholic solution of acid, and the acid can be
Phosphoric acid or perchloric acid or its mixed liquor；The bath composition can be phosphoric acid and the volume ratio of dehydrated alcohol is 2～5: 5～2,
Can also be perchloric acid and the volume ratio of dehydrated alcohol is 1～4: 20, or can also be perchloric acid：Phosphoric acid：Dehydrated alcohol
Volume ratio is 1～5: 5～15: 24～40.Described electrolytic polishing process also includes carrying out purified water to polishing after-poppet
The step of cleaning treatment.
The step 4) to polishing after-poppet matrix surface degradable polymer eluting of the coating containing curative drug
The degradable polymer solution containing curative drug for configuring is coated by coating by methods such as spraying, dip-coating or electrostatic coatings
In zinc and kirsite rest body surface, preferred spraying coating process, the thickness for being preferably coated with degradable polymer eluting coatings is 10
～50 μm；More preferably coating layer thickness is 20～40 μm；
The degradable polymer solution containing curative drug is the above-mentioned macromolecule material for carrying above-mentioned curative drug
Material polymer-organic solvent solution, wherein macromolecular material polymer are preferably polylactic acid；The organic solvent is preferably chlorine
Imitative, dichloromethane, tetrafluoro hydrogen such as are muttered at the effumability organic solvent；Preferable organic solvent is chloroform；(thunderous handkerchief is mould for preferred agents
Element) it is 1～3: 9～27 with the mass ratio of macromolecular material polymer (such as polylactic acid), macromolecular material polymer is (such as poly- breast
Acid) it is 1～5: 20～50 with the volume ratio of organic solvent (such as chloroform)；Preferred agents are rapamycin；Preferred scheme is
The degradable polymer solution containing curative drug is the polylactic acid-chloroform uniform solution for carrying rapamycin, and thunder handkerchief is mould
Element is 1: 10 with the mass ratio of polylactic acid, and polylactic acid is 1: 20 with the volume ratio of chloroform.
The characteristics of support has temporary transient stand-up by made by biological degradable material, its metabolite to body without
Evil, it can provide necessary support for tube chamber in a short time, while and can avoid caused by metal rack longer-term persistence
Complication, can also carry various medicines and allogenic gene acts on pathological lumen, have become preventing and treating in-stent restenosis
And the research new direction of thrombus in stents.A kind of novel degradable zinc-containing alloy support proposed by the present invention it is advantageous that：
1st, from the composition design of matrix material, the biological effect of alloying element is paid the utmost attention to, selecting has to human body
Beneficial element carries out alloying, avoids the introducing of the alloy element with cytotoxicity and genotoxicity, and the zinc-base of preparation is closed
Golden hypotoxicity, good biocompatibility.
From the point of view of the biological effect angle of magnesium, magnesium ion (Mg2+) it is the second important cation in human body cell, to people
Body is harmless.In addition magnesium also has various special physiological functions, and it can activate internal various enzymes, suppress dysautonomia irritability,
The stability of nucleic acid structure is maintained, synthesis, muscle contraction and thermoregulation of vivo protein etc. is participated in.
From the point of view of the biological effect angle of manganese, manganese is the element favourable to cardiovascular, especially to safeguarding cell line grain
Body function is particularly significant.And normal brain function can be kept, moreover it is possible to normal sugar, lipid metabolism are maintained, improves the hemopoietic of body
Function.Manganese can also strengthen endocrine function, maintain thyroid normal function, promote the synthesis of gonadal hormone, adjust nerves reaction
Ability.
From the point of view of the biological effect angle of calcium, the calcium ion that calcium can maintain the normal physiological condition of cell intracellular is
Cell is to stimulating aitiogenic medium.Calcium and receptor calcium etc. adjust many important physiological functions of body, including skeleton jointly
The contraction of flesh and cardiac muscle, smooth muscle and nonmuscle cellses activity and the maintenance of neural excitation.Calcium also participates in Blood Coagulation Process.Mesh
The calbindin of front known at least 4 kinds of vitamin K dependents participates in Blood Coagulation Process, i.e., be only possible in the presence of calcium ion
Cascade reaction is completed, is finally made soluble fibrin original be changed into fibrin, is formed blood coagulation.
From the point of view of the biological effect angle of strontium, strontium is a kind of indispensable trace element of human body, be skeleton and
The normal ingredient of tooth, it is mainly closely related with the formation of skeleton to the function of human body；Its function and structure with blood vessel
Relation of also have is made, its mechanism of action is probably that strontium is absorbed with sodium competition in enteral, so as to reduce absorption of the human body to sodium, increases sodium
Excretion, play the role of prevention of cardiovascular disease etc..
2nd, biological medical degradable zinc-containing alloy support has controllable bio-absorbable degradation characteristic, will not as rustless steel,
The conventional metals support such as cobalt chromium, NiTi, after implantation as a nonabsorable foreign body long-term existence, to tissue produce it is very strong
Inflammatory reaction, and longer-term persistence is in wall of the lumen, affects tube chamber systolic and diastolic function, increases blood in local inflammation, restenosiss and support
Bolt risk；Described zinc-containing alloy corrosion characteristics in physiological environment are homogeneous corrosion, and support can be kept in the blood vessel for a long time
Holding state, effective support can effectively solve the problem that the danger of postoperative acute obliteration, it is to avoid degradable up to more than 4 months
Iron-based support, magnesio scaffold degradation speed and tube chamber rebuild unmatched drawback, beneficial to the reconstruction of tube chamber itself；Compared to can drop
Depolymerization polymer scaffold, described zinc-base support have preferable developing performance, facilitate the intervention of operation technique support and postoperative tracking,
And the support force for providing more suitably adapts to the process of positivity tube chamber reconstruct.
3rd, the zinc-containing alloy rack surface that the present invention is provided is the degradable polymerization that one or more layers contains curative drug
Thing coating, biocompatibility preferably, are remarkably improved the compatibility of zinc-containing alloy support, can anticoagulation anti-proliferate, reduce anxious
Property thrombosis and vascular inflammation reaction, beneficial to endotheliocyte rack surface cover；Curative drug is uniform in the polymer simultaneously
Blending, is capable of achieving the controllable release of medicine, and reducing burst drug release makes medicine slowly persistently keep finite concentration release, to reduce
The incidence rate of acute after stenter to implant, subacute stent thrombosis.
A kind of degradable zinc-containing alloy support preparation method that the present invention is provided, its method are easy, electrolytic polishing process peace
Entirely, the degradable zinc-containing alloy support that adopting said method can be prepared can be intravascular stent, trachea bracket, esophageal stents appear, intestinal
Support, biliary tract rack or urethra rack etc..
Description of the drawings
The specific embodiment of the present invention will be described in detail with reference to Figure of description.
Fig. 1 is a kind of flow chart of degradable zinc-containing alloy support its preparation method that the present invention is provided.
Specific embodiment
Embodiments of the invention are given below, and the present invention is further described, rather than limits the scope of the present invention.
A kind of novel degradable zinc-containing alloy support in the present invention, including：Degradable Zr-based materials rest body；It is described
Rest body surface is provided with the degradable polymer eluting coatings containing curative drug；The rest body is that drum type brake is netted
Structure.Wherein, rest body material is selected to the beneficial unit of human body in design from the biological effect angle consideration of alloying element
Element carries out alloying, and comprehensive mechanical property is improved after processing, is drawn into pipe, forms bare bracket using laser engraving, degraded
Excellent performance is in magnesio support；The degradable Zr-based materials are pure zinc or zinc-containing alloy；The zinc-containing alloy is preferably Zn-Mg
Alloy, Zn-Ca alloys, Zn-Sr alloys, Zn-Sn alloys, Zn-Mg-Mn alloys, Zn-Mg-Ca alloys, Zn-Mg-Sr alloys, Zn-
One kind in Mg-Sn alloys, Zn-Mg-Mn-Ca alloys, Zn-Mg-Ca-Sr alloys etc.；The further preferred degradable zinc-base
Material be Zn- (0～1.5) %Ca alloys, Zn- (0～1.5) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Mn alloys,
Zn- (0～1.5) %Mg- (0～1) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Ca- (0～0.5) %Mn alloys,
One kind in Zn- (0～1.5) %Mg alloys or Zn- (0～1.5) %Mg- (0～1) %Ca alloys.
Described rest body is preferably drum type brake network structure, and the design show of support goes out preferable pliability, is easy to
Intervention is placed, and radial support better performances, and because matrix material metallic zinc imparts the preferable developing performance of support, facilitates handss
Art operation support intervention and postoperative tracking；Meanwhile, in degradable Zr-based materials rest body surface-coated, one or more layers contains
The degradable polymer eluting coatings of curative drug, described degradable polymer include polylactic acid, PGA, polyacids
The artificial synthesized degradable high score such as acid anhydride, copolymer of poly lactic acid, polyglycolic acid, polyhydroxybutyrate valerate, polybutylcyanoacrylate
The copolymer of one or more in sub- material, can be with natural biodegradable polymers such as including collagen, gelatin or chitins
One kind in material, or even should also include the blending of the absorbable macromolecule material and natural biodegradable polymer material
Thing；Designed degradable polymer coating can improve the biocompatibility of bare metal stent, beneficial to endotheliocyte in support
Surface covers, and controllable drug release, and reducing burst drug release makes medicine slowly persistently keep finite concentration release, to reduce
The incidence rate of acute after stenter to implant, subacute stent thrombosis.
A kind of flow process of the degradable zinc-containing alloy support its preparation method of the embodiment of the present invention as shown in figure 1, including with
Lower step：
1) degradable Zr-based materials are processed into into rest body；Described Zr-based materials are pure zinc or Zn-base alloy structure
Into intravascular stent, trachea bracket, esophageal stents appear, intestinal stent, biliary tract rack or urethra rack matrix etc. can be processed into.
2) rest body carries out pretreatment, rejects processing residual and surface appurtenance；Including a) carrying out machine to rest body
Tool process；B) pickling is carried out to the rest body after mechanical treatment or alkali cleaning is processed；Propping up after c) processing to pickling or alkali cleaning
Frame matrix carries out ultrasound wave cleaning.
Described carries out mechanical treatment step to rest body, i.e., using the method for physics, reject processing hollow out residual hair
Thorn etc..
Described carries out pickling or alkali cleaning process step to the rest body after mechanical treatment, will support be put into pickle
Or cleaning treatment (under room temperature) in alkali wash water, is carried out, remove the impurity such as the greasy dirt or oxide of rack surface.
Described pickle is acetic acid and neutral sodium-salt mixed solution, can be acetic acid and the neutrality such as Sodium Chloride or sodium nitrate
The blend solution of sodium salt, can be cleaned 3-5 minutes at room temperature；Described alkali wash water mixes molten with alkaline sodium salt for sodium hydroxide
Liquid, can be the blend solution of sodium hydroxide and the alkaline sodium salt such as sodium carbonate or sodium bicarbonate, can clean 5-10 point at room temperature
Clock.
Described carries out ultrasound wave cleaning step, i.e., using clear water, one to the rest body after pickling or alkali cleaning process
As to be pure water clean to processing after-poppet, removal is attached to the acid of rack surface or alkali liquor.
3) electrobrightening process is carried out to rest body, will rest body hang on and hold the electrolysis bath of electrolyte and carry out
Electrobrightening process.
Concrete technology is：DC voltage is 2.5～30V, and electric current is 0.2～10A, and the electrobrightening time is 0.5～20 point
Clock, electrolysis temperature are 10～40 DEG C.
The electrolyte is the alcoholic solution of acid, and the acid can be phosphoric acid or perchloric acid or its mixed liquor；The electrolyte
It is 2～5: 5～2, or the volume ratio of perchloric acid and dehydrated alcohol that composition can be phosphoric acid with the volume ratio of dehydrated alcohol
For 1～4: 20, or can also be perchloric acid：Phosphoric acid：The volume ratio of dehydrated alcohol is 1～5: 5～15: 24～40.
The step 3) rest body is carried out electrobrightening process also include carrying out purified water to polishing after-poppet
The step of cleaning treatment, i.e., using clear water, usually pure water is cleaned to processing after-poppet, and removal is attached to rack surface
Ion.
4) to polishing after-poppet matrix surface degradable polymer eluting coatings of the coating containing curative drug, i.e.,
The degradable polymer solution containing curative drug for configuring is coated in by zinc-base by methods such as spraying, dip-coating, electrostatic coatings
Stock support matrix surface.It is preferred that spraying coating process, the thickness for being preferably coated with degradable polymer eluting coatings is 10～50 μm；
The degradable polymer includes polylactic acid, PGA, condensing model, copolymer of poly lactic acid, polyglycolic acid, poly-
The copolymer of one or more in the absorbable macromolecule materials such as hydroxybutyric acid pentyl ester, polybutylcyanoacrylate；Also
With one or more in the natural biodegradable polymer material such as including collagen, gelatin, chitin, or even can also include people
The blend of work synthesized degradable macromolecular material and natural biodegradable polymer material；Described curative drug can be tool
Have one or more in medicine such as rapamycin, paclitaxel, rheum emodin, curcumin etc. of anti-cell proliferation effect and be combined, it is excellent
Elect rapamycin as.
The degradable polymer solution containing curative drug is the above-mentioned macromolecule material for carrying above-mentioned curative drug
Material polymer-organic solvent solution, wherein macromolecular material polymer are preferably polylactic acid；The organic solvent is preferably chlorine
Imitative, dichloromethane, tetrafluoro hydrogen such as are muttered at the effumability organic solvent；Preferred solvent is chloroform；Preferred agents are rapamycin；
It is preferred that rapamycin is 1～3: 9～27 with the mass ratio of polylactic acid, polylactic acid is 1～5 with the volume ratio of chloroform:
20～50.
It is the poly- breast for carrying rapamycin that preferred scheme is the degradable polymer solution containing curative drug
Acid-chloroform uniform solution, rapamycin are 1: 10 with the mass ratio of polylactic acid, and polylactic acid is 1: 20 with the volume ratio of chloroform.
It is an unexpected discovery of the invention that when selection degradable Zr-based materials are Zn-1%Mg alloys or Zn-1%Mg-0.5%Ca
Alloy, macromolecular material polymer is polylactic acid, curative drug is rapamycin, it is organic molten to prepare degradable polymer solution
When agent is 20～40 μm for the thickness of chloroform and medication coat, support of the present invention is slow in degradation speed, biocompatibility and medicine
Release etc. aspect with especially excellent performance.
A kind of degradable zinc-containing alloy support of the present invention and preparation method thereof preferred embodiment is given below.
Embodiment 1
A kind of novel degradable zinc-containing alloy support in the present invention, including degradable Zr-based materials rest body and support
Matrix surface is provided with the degradable polymer eluting coatings containing curative drug；Wherein degradable Zr-based materials are Zn-1%Mg
Alloy, curative drug are rapamycin, and degradable polymer is polylactic acid, prepare degradable polymer solution organic solvent and are
Chloroform, eluting coatings thickness are 30 μm.
Embodiment 2
A kind of novel degradable zinc-containing alloy support in the present invention, including degradable Zr-based materials rest body and support
Matrix surface is provided with the degradable polymer eluting coatings containing curative drug.Wherein degradable Zr-based materials are Zn-1%
Mg-0.5%Ca alloys, curative drug are rapamycin, and degradable polymer is polylactic acid, prepares degradable polymer solution
Organic solvent is chloroform, and eluting coatings thickness is 30 μm.
Embodiment 3
Described in embodiment 1, the preparation method of novel degradable zinc-containing alloy support, comprises the following steps：
1) degradable Zr-based materials are processed into into rest body；Composition is selected to be material based on Zn-1%Mg alloys,
Capillary micro-pipe is drawn into, intravascular stent matrix is made using laser engraving.
2) rest body carries out pretreatment, rejects processing residual and surface appurtenance；
Specifically include a) above-mentioned rest body is first rejected under optical loupes and process clout and obvious burr；B) with
Immersed into the mixing pickle of acetic acid and sodium nitrate afterwards, pickling processes 5min under room temperature, wherein pickle composition are 40ml/L
Acetic acid and 10g/L sodium nitrate, balance of pure water；C) again rest body is placed in clear water and is cleaned with ultrasonic washing unit
10min。
3) electrobrightening process is carried out to rest body
The rest body that pretreatment is finished is put into electrobrightening in the electrolysis bath for fill electrolyte and processes after being dried, specifically
Electrolytic polishing process is：DC voltage is 10V, and electric current is 1A, and the electrobrightening time is 3min, and electrolysis temperature is for 40 DEG C and uses
Constant water bath box temperature control；Electrolyte is mixed acid alcoholic solution, and Ju Ti Pei Fang is perchloric acid: phosphoric acid: dehydrated alcohol volume ratio is 1:
13∶26；Subsequently it is cleaned by ultrasonic to processing after-poppet using pure water, to remove the acid ion for being attached to rack surface.
4) to polishing after-poppet matrix surface degradable polymer eluting coatings of the coating containing curative drug；
Spray treatment is carried out by being fixed on after the rest body dried after polishing on support Ultrasonic spraying machine, its
In, the mass ratio of the polylactic acid-chloroform uniform solution for carrying rapamycin, rapamycin and polylactic acid is contained with propeller
For 1: 10, polylactic acid is 1: 20 with the volume ratio of chloroform；Spraying after-poppet is put in vacuum drying oven in 37 DEG C of freeze-day with constant temperature
24h, to remove the organic solvent of remnants.
Embodiment 4
Described in embodiment 2, the preparation method of novel degradable zinc-containing alloy support, comprises the following steps：
1) degradable Zr-based materials are processed into into rest body；
Select composition to be material based on Zn-1%Mg-0.5%Ca alloys, be drawn into capillary micro-pipe, carved using laser
Scribe into intravascular stent matrix.
2) rest body carries out pretreatment, rejects processing residual and surface appurtenance；
Specifically include a) first to reject under optical loupes and process clout and obvious burr；B) it is subsequently dipped to sodium hydroxide
In the mixing alkali wash water of sodium carbonate, under room temperature alkali cleaning process 5min, wherein alkali wash water composition for 10g/L sodium hydroxide and
The sodium carbonate of 10g/L, balance of pure water；C) again rest body is placed in clear water 10min is cleaned with ultrasonic washing unit.
3) electrobrightening process is carried out to rest body
The rest body that pretreatment is finished is put into electrobrightening in the electrolysis bath for fill electrolyte and processes after being dried, specifically
Electrolytic polishing process is：DC voltage is 15V, and electric current is 2A, and the electrobrightening time is 5min, and electrolysis temperature is for 40 DEG C and uses
Constant water bath box temperature control, electrolyte prescription are 350ml：The phosphoric acid alcoholic solution of 650ml ratios；After pure water is subsequently used to process
Support is cleaned by ultrasonic, to remove the ion for being attached to rack surface.
4) to polishing after-poppet matrix surface degradable polymer eluting coatings of the coating containing curative drug；
Spray treatment is carried out by being fixed on after the rest body dried after polishing on support Ultrasonic spraying machine, its
In, the mass ratio of the polylactic acid-chloroform uniform solution for carrying rapamycin, rapamycin and polylactic acid is contained with propeller
For 1:10, polylactic acid is 1 with the volume ratio of chloroform:20；Spraying after-poppet is put in vacuum drying oven in 37 DEG C of freeze-day with constant temperature
24h, to remove the organic solvent of remnants.
Embodiment 5-10 6 embodiment degradable zinc-containing alloy support preparation methoies are with embodiment 3, respective design parameter
As shown in table 1.
Contrast experiment
Radial stress when regulation deflection is 10% in 1* experiments.
2* data are quoted from Journal of Materials Science:Materials in Medicine,2013,24
(3):713-724.
3* quoted from The Lancet, 2013,381 (9869):836-844.
4* quoted from International journal of cardiology, 2013,167 (1):11-21.
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (5)
1. a kind of degradable zinc-containing alloy support, it is characterised in that include：Degradable Zr-based materials rest body；The support base
Body surface face is provided with the degradable polymer eluting coatings containing curative drug；The rest body is drum type brake network structure；
The degradable Zr-based materials are Zn- (0～1.5) %Ca alloys, Zn- (0～1.5) %Sn alloys, Zn- (0～1.5) %Mg-
(0～1) %Mn alloys, Zn- (0～1.5) %Mg- (0～1) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Ca- (0～
0.5) one kind in %Mn alloys, Zn- (0～1.5) %Mg alloys or Zn- (0～1.5) %Mg- (0～1) %Ca alloys；It is described
Degradable polymer is polylactic acid；The curative drug is rapamycin；The thickness of the eluting coatings is 10～50 μm；With
Chloroform prepares PLA solution for solvent, and polylactic acid is 1～5: 20～50 with the mass volume ratio of chloroform；Rapamycin and poly- breast
The mass ratio of acid is 1～3: 9～27.
2. degradable zinc-containing alloy support according to claim 1, it is characterised in that the degradable Zr-based materials are Zn-
1%Mg alloys or Zn-1%Mg-0.5%Ca alloys；The thickness of the eluting coatings is 30 μm；The mass body of polylactic acid and chloroform
Product is than being 1: 20；Rapamycin is 1: 10 with the mass ratio of polylactic acid.
3. degradable zinc-containing alloy support according to claim 1, it is characterised in that the degradable Zr-based materials are Zn-
1%Ca alloys, Zn-1%Sn alloys, Zn-1%Mg-0.5%Mn alloys, Zn-1%Mg-0.5%Sn alloys or Zn-1%Mg-
0.5%Ca-0.1%Mn；The thickness of the eluting coatings is 30 μm；Polylactic acid is 1: 20 with the mass volume ratio of chloroform；Thunder handkerchief
Mycin is 1: 10 with the mass ratio of polylactic acid.
4. the preparation method of the arbitrary degradable zinc-containing alloy support of claim 1-3, including：1) by degradable Zr-based materials
It is processed into rest body；2) pretreatment is carried out to rest body, processing residual and surface appurtenance is rejected；3) rest body is entered
The process of row electrobrightening；4) polishing after-poppet matrix surface degradable polymer eluting of the coating containing curative drug is applied
Layer；
The step 2) include：Pickling or alkali cleaning process step are carried out to the rest body after mechanical treatment；The pickle is
Acetic acid and Sodium Chloride or the blend solution of sodium nitrate；Described alkali wash water is that sodium hydroxide is molten with sodium carbonate or sodium bicarbonate blending
Liquid；
The step 3) it is that rest body is put into electrolyte to carry out electrobrightening process：DC voltage be 2.5～30V, electric current
For 0.2～10A, the electrobrightening time is 0.5～20 minute, and electrolysis temperature is 10～40 DEG C；The electrolyte is the anhydrous of acid
Ethanol solution, the acid are phosphoric acid or perchloric acid or its mixed liquor；The electrolyte is phosphoric acid and the volume ratio of dehydrated alcohol is 2
～5: 5～2, or the volume ratio of perchloric acid and dehydrated alcohol is 1～4: 20, or perchloric acid: phosphoric acid: dehydrated alcohol
Volume ratio is 1～5: 5～15: 24～40.
5. the preparation method of degradable zinc-containing alloy support according to claim 4, it is characterised in that step 4) it is to configure
The degradable polymer solution containing curative drug rest body table is coated in by spraying, dip-coating or electrostatic coating method
Face.
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| CN106693043B (en) * | 2015-11-18 | 2020-06-16 | 先健科技(深圳)有限公司 | Absorbable iron-based alloy implanted medical instrument and preparation method thereof |
| CN105925847B (en) * | 2016-05-12 | 2018-06-29 | 管仁国 | A kind of biodegradable zinc-base metal material and the ureterectasia stent obtained using the material |
| CN106048707B (en) * | 2016-06-29 | 2018-09-28 | 西北有色金属研究院 | A kind of surface treatment method of medical degradable metal intervention support |
| CN107496993B (en) * | 2017-01-12 | 2022-10-11 | 乐普（北京）医疗器械股份有限公司 | Medical degradable implantable metal material |
| CN107519539A (en) * | 2017-09-11 | 2017-12-29 | 乐普（北京）医疗器械股份有限公司 | A kind of medical degradable Zn-base alloy and its intravascular stent product |
| CN107670121A (en) * | 2017-11-09 | 2018-02-09 | 北京赛铂医药科技有限公司 | A kind of absorbable stent and preparation method thereof |
| CN109966563B (en) * | 2017-12-28 | 2021-08-03 | 元心科技(深圳)有限公司 | Implanted medicine carrying device |
| CN108815589A (en) * | 2018-03-27 | 2018-11-16 | 乐普（北京）医疗器械股份有限公司 | A kind of medical degradable zinc-containing alloy intravascular stent product |
| CN109128064B (en) * | 2018-09-21 | 2020-04-28 | 北京科技大学 | Biodegradable Zn-Na series zinc alloy and preparation method thereof |
| CN109939271B (en) * | 2019-04-11 | 2021-10-15 | 赵亚芳 | Coating structure of medical biodegradable zinc alloy stent and preparation method thereof |
| CN110934621A (en) * | 2019-12-10 | 2020-03-31 | 贺迎坤 | Degradable blood flow guiding device |
| CN113116595B (en) * | 2019-12-30 | 2022-06-21 | 元心科技(深圳)有限公司 | Absorbable iron-based instrument |
| CN113491796B (en) * | 2020-04-07 | 2022-11-18 | 元心科技(深圳)有限公司 | Zinc-containing medical devices |
| CN113599035A (en) * | 2021-09-02 | 2021-11-05 | 东莞颠覆产品设计有限公司 | Support and application |
| CN114059146A (en) * | 2021-11-16 | 2022-02-18 | 湖南华耀百奥医疗科技有限公司 | Surface treatment method of degradable metal osseointegration implant |
| CN114657418A (en) * | 2021-12-27 | 2022-06-24 | 中国科学院宁波材料技术与工程研究所 | Alloy and preparation method and application thereof |
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