CN105816921A - Bionic vascular stent and preparation method thereof - Google Patents
Bionic vascular stent and preparation method thereof Download PDFInfo
- Publication number
- CN105816921A CN105816921A CN201610248782.XA CN201610248782A CN105816921A CN 105816921 A CN105816921 A CN 105816921A CN 201610248782 A CN201610248782 A CN 201610248782A CN 105816921 A CN105816921 A CN 105816921A
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- stent
- redv
- bionical
- intravascular stent
- polypeptide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
Abstract
The invention belongs to the field of high polymer materials and biomedical engineering, and particularly relates to a bionic vascular stent and a preparation method thereof. The bionic vascular stent comprises a bare stent for supporting, a drug-loaded degradable polymer coating, and a polymer coating containing a phosphorylcholine group and an Arg-Clu-Asp-Val (REDV) polypeptide (or molecules, capable of specifically combining endothelial cells and endothelial progenitor cells, of a CD34 antibody, a CD133 antibody and the like). The stent is applied to a vascular disease position; the degradable polymer coating on the outer wall of the stent gradually releases the loaded drug and inhibits vascular smooth muscle proliferation to prevent vascular restenosis after the stent is implanted; the polarity of the stent platform can be changed by the phosphorylcholine group in the coating at the inner side of the stent; the biocompatibility of the stent surface is improved; adhesive growth of the endothelial cells and the endothelial progenitor cells can be promoted by specific recognition sites of the endothelial cells/endothelial progenitor cells of REDV and the like; and the endothelialization progress of the stent surface is accelerated.
Description
Technical field
The invention belongs to macromolecular material and biomedical engineering field, be specifically related to a kind of bionical intravascular stent and system thereof
Preparation Method.
Background technology
Coronary atherosclerotic heart disease is coronary artery generation atherosclerotic lesion and causes blood vessel
Chamber stenosis or occlusion, causes myocardial ischemia, anoxia or heart disease that is downright bad and that cause, is commonly referred to as " coronary heart disease ".2013
Being published in the Disease Spectrum research of " lancet " China to show, Chinese population cause of the death front three is apoplexy, ischemic heart desease successively
And chronic obstructive pulmonary disease, wherein front two accounts for about the 90% of whole cardiovascular diseases (including cerebrovascular), and therefore cardiovascular diseases is China
The severe challenge that public health and healthy cause are faced.
It is percutaneous coronary artery intervention (PCI) and and arteria coronaria currently for the treatment means that coronary heart disease is maximally efficient
Bypass graft (CABG), wherein, PCI because of its wound little, painful little, post-operative recovery is fast, the feature such as evident in efficacy and be subject to
Extensive concern.Since first bare mental stents (BMS) in 1985 inserts human body, solved list support Successful treatment with interventional
The difficult problem that pure balloon expandable epoch restenosis rate is the highest, becomes the Main Means of clinical treatment.Bracket for eluting medicament
(DrugEluting Stent, DES) in 2002 come out, compared with BMS, DES in different types of coronary artery pathological changes all
Having significant advantage, percutaneous coronary intervention (pci) (PCI) postoperative restenosis incidence rate reduces to from 10%～the 35% of the BMS epoch
Less than 10%, reduce Revascularization rate.But when DES starts to be widely used in clinic, advanced thrombus shape in support
The problem but emersion water surface become.Its mechanism includes that blood vessel is the completeest to high response, the support endothelialization of drug/polymer coating
Complete and adherent bad etc..Medicine greatly suppresses intercellular membrane hypertrophy during the degraded of polymer discharges, and props up reducing
Frame is implanted and is also caused while restenosis problem cell to climb skin reducing and support is difficult to and the problem such as blood vessel wall well healing.
Although extending duplex may reduce the generation of advanced thrombus in support the antiplatelet course for the treatment of, but bring hemorrhage risk simultaneously.
Series of risk after stenter to implant also exist in intracranial vessel, peripheral blood vessel (as kidney sound affectionately, intracranial sound
Affectionately, artery of lower extremity and vein, digestive tract arteriovenous, liver and pulmonary vascular etc.).How to improve support blood compatibility,
Promote the endotheliocyte covering to support, be to solve the key issue of risk after stenter to implant.
Cell membrane is mainly with phospholipid bilayer for membrane structure skeleton, and the outer surface of film is mainly made up of lecithin, and ovum
The function of phospholipid is mostly derived from its hydrophilic Phosphorylcholine group (Phosphoryl Choline, PC), based on bionics,
Y. Kadoma et al. in last century the mid-80 propose the concept of imitative membrane structure, design has synthesized 2 monomethyl propylene
Trimethylammonium Phosphorylcholine (MPC), by itself and hydrophobic monomer copolymerization
Obtain amphipathic copolymer, to reach to imitate membrane structure and the purpose of function.MPC copolymer is by the phosphinylidyne gallbladder of polarity
Alkali end group and nonpolar alkane molecule chain composition, therefore it is easily formed the microstructure similar to cell membrane, there is good biology
The compatibility and surface wettability.More Free water is contained on the surface that this kind of MPC copolymer is modified, and is formed at material surface and combines
It is hydrated layer closely, can effectively suppress protein adsorption and cell adhesion, show good biocompatibility.
Arginine-glutamic acid-aspartic acid-valine (Arg-Glu-Asp-Val, REDV): REDV is fibronectin
An active amino acid sequence on white III CS site, can integrated element α4β1Specific recognition, and integrin alpha4β1Main expression
In endotheliocyte (ECs)/endothelial progenitor cells (EPCs), thus REDV can endotheliocyte, fibroblast, smooth muscle cell and
Specifically promoting sticking and growth of endotheliocyte in platelet, REDV also can suppress hematoblastic sticking in addition.REDV's
This characteristic so that it is the surface that can be used for biomaterial is modified, to set up the high selective function interface of endotheliocyte.
Summary of the invention
Goal of the invention: it is an object of the invention to overcome the deficiencies in the prior art, it is provided that a kind of bionical intravascular stent and
Its preparation method.First there is the Phosphorylcholine family macromolecule coating of biomimetic features in the preparation of bare bracket inner cavity surface and there is spy
The functional coating of anisogamy endotheliocyte and endothelial progenitor cells is (containing REDV, CD34Antibody, CD133Antibody etc.), then propping up
Frame outer surface prepares medicine carrying degradable polymer coating.
The purpose preparing functional coating inside support is to increase outside the blood compatibility of endovascular stent, specific adsorption
Endothelial progenitor cells in all blood or endotheliocyte, thus promote the endotheliocyte covering to support, promote endothelium reparation；?
Stent outer prepares blood vessel that the purpose of medicine carrying degradable polymer coating is to prevent to be caused by smooth muscle cell proliferation again
Narrow.
Technical scheme: the present invention is achieved by the following technical solutions, the present invention includes the bare bracket for supporting, painting
It is overlying on the Phosphorylcholine family macromolecule coating of bare bracket inner cavity surface and there is the REDV coating of specific adsorption, and being coated on
The medicine carrying degradable polymer coating of rack outer surface.
Described Phosphorylcholine family macromolecule coating by 2 methacryloxyethyl Phosphorylcholines with have the most hydrophobic
Working substance copolymerization forms, and has the material of certain hydrophobic interaction in methyl acrylic ester, polylactic acid and modifier thereof
One or more.
The described polymeric coating layer containing REDV polypeptide is formed with the substance reaction containing active function groups by REDV polypeptide,
Active function groups includes one or more in carboxyl, amino, anhydride, acyl chlorides or ester group.
Regulation, containing Phosphorylcholine macromolecule and the high molecular ratio of the polypeptide containing REDV, can realize regulating between PC and REDV
Ratio, this proportional numerical value is 0.05 ~ 20.
The described thickness containing the polymeric coating layer of Phosphorylcholine group is 0.1 ~ 3 micron, macromolecule containing REDV polypeptide is coated with
The thickness of layer is 0.1 ~ 3 micron, the thickness of medicine carrying degradable polymer coating is 1 ~ 10 micron.
The preparation method of a kind of bionical intravascular stent, comprises the following steps:
1. after using ultrasonic cleaning bare bracket, drying for standby；
2. the macromolecule containing Phosphorylcholine group is joined in solvent with the macromolecule containing REDV polypeptide and mix homogeneously, then will
It is sprayed on the inner surface of bare bracket, and after drying at room temperature, vacuum drying hour again, i.e. can get inner cavity surface and contain phosphinylidyne gallbladder
The polymer coating of the bionical promotion endothelialization of alkali and REDV polypeptide；
3. use special process, prepare asymmetric medicine carrying degradable polymer coating, it may be assumed that drug-carried coat is only distributed in support appearance
Face.
Beneficial effect: by this stent applications lesion locations, medicine carrying of rack outer surface in implanted patients with coronary heart disease body
Degradable polymer coating is gradually degraded and is discharged loaded medicine, and the blood vessel that suppression Ink vessel transfusing proliferation of smooth muscle causes is the narrowest
Narrow；Phosphorylcholine family macromolecule coating and the REDV polypeptide polymeric coating layer of support inner cavity surface have excellent bio-compatible
Property, the imitative membrane structure of Phosphorylcholine group can be that metal rack provides more preferable biocompatibility, prevents protein
With biomolecule in the nonspecific action of material surface, REDV group endotheliocyte, fibroblast, smooth muscle cell and
Platelet specifically promotes sticking and growth of endotheliocyte, promotes support endothelialization, it is provided that preferably curative effect and long term
Safety.
Accompanying drawing explanation
Fig. 1 is the effect schematic diagram with the coating bracket promoting endothelial effect.
Fig. 2 coating is in the distribution situation of a frame peripheral.
Below in conjunction with specific embodiment, such scheme is described further.Should be understood that these embodiments are for this is described
Bright and be not limited to limit the scope of the present invention.The implementation condition used in embodiment can be done into one according to the condition of concrete producer
Successive step, not marked implementation condition is usually the condition in normal experiment.
Embodiment 1: the present embodiment chooses 316L rustless steel arteria coronaria bare bracket, drying for standby after ultrasonic cleaning；Take first
2 methacryloxyethyl Phosphorylcholine 3.0g, are dissolved in 8. 6g methacrylic acid second vinegar, add light trigger
0.01g, irradiates under uviol lamp about 5 minutes and makes reaction carry out completely.
Take product 0.05g and the 0.05g lactic-co-glycolic acid of above-mentioned reaction, be dissolved in suitable solvent, profit
By the mode of ultrasonic spraying, mixture being sprayed at support inner cavity surface, first drying at room temperature 12 hours, then vacuum drying 24 is little
Time, dried bare bracket being placed in the REDV solution of 500 μ g/ml, room temperature reaction takes out after 24 hours and is dried；It is special to use
Technique, prepares asymmetric medicine carrying degradable polymer coating at rack outer surface.
Embodiment 2: the present embodiment chooses degradable polylactic acid bracket, drying for standby after ultrasonic cleaning；Take glycerophosphoryl
Choline 3.0g, adds initiator 0.01g, catalyst 0.005g, lactide 15g, Acetic acid, hydroxy-, bimol. cyclic ester 5g, tube sealing polymerization 16 after evacuation
Hour, then take out, purify standby.
Take product 0.05g and the 0.05g lactic-co-glycolic acid of above-mentioned reaction, be dissolved in suitable solvent, profit
By the mode of ultrasonic spraying, mixture being sprayed at support inner cavity surface, first drying at room temperature 12 hours, then vacuum drying 24 is little
Time, dried being placed in the REDV solution of 500 μ g/ml, room temperature reaction takes out after 24 hours and is dried；Use special work
Skill, prepares asymmetric medicine carrying degradable polymer coating at rack outer surface.
Claims (10)
1. a bionical intravascular stent, it is characterised in that include the bare bracket for supporting, height containing Phosphorylcholine (PC) group
Molecular coatings, containing REDV polypeptide or the polymeric coating layer of other endothelium (ancestral) cell recognition molecule and medicine carrying degradable polymer
Coating.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that described
Bare bracket can be metal non-degradable support (material therefor includes but not limited to 316L rustless steel, cochrome), degradable
Metal rack (material therefor includes but not limited to zinc and zinc-containing alloy, magnesium and magnesium based alloys, ferrum and ferrous alloy), degradable poly
Polymer scaffold (material therefor includes but not limited to polylactic acid, polycaprolactone).
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that described
Medicine carrying degradable polymer coating include medicine and degradable high polymer material, described degradable high polymer material include but not only
It is limited to lactic-co-glycolic acid, polylactic acid, PEG polylactic acid and PEG lactic-co-glycolic acid；Described medicine
Thing includes rapamycin and derivant, paclitaxel and derivant thereof, ciclosporin and derivant thereof, and other has suppression carefully
One or more in the medicine of born of the same parents' proliferation function.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that described
The polymeric coating layer containing Phosphorylcholine group by 2 methacryloxyethyl Phosphorylcholines, glyceryl phosphoryl choline or
One or more of Semen Allii Tuberosi choline, form with having certain hydrophobic interaction material copolymerization；The described thing with certain hydrophobic interaction
Matter includes but not limited to one or more in methyl acrylic ester, polylactic acid and modifier thereof.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that phosphorous
2 methacryloxyethyl Phosphorylcholines or glyceryl phosphoryl choline or Semen Allii Tuberosi choline in the polymeric coating layer of phatidylcholine group
Mass percent be 0.001% ~ 50%.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that described
The polymeric coating layer containing REDV polypeptide formed with the substance reaction containing active function groups by REDV polypeptide, active function groups bag
Include one or more in carboxyl, amino, anhydride, acyl chlorides or ester group.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that contains
In the polymeric coating layer of REDV polypeptide REDV(or other can specific binding endotheliocyte/endothelial progenitor cells) percent mass
Ratio is 0.001-50%.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that regulation
Containing Phosphorylcholine macromolecule and the high molecular ratio of the polypeptide containing REDV, can realize regulating the ratio between PC and REDV, this ratio
Number of cases value is 0.05 ~ 20.
The most according to claim 1 have the bionical intravascular stent promoting endothelial effect, it is characterised in that described
Thickness containing the polymeric coating layer of Phosphorylcholine group is 0.1 ~ 3 micron, thickness containing the polymeric coating layer of REDV polypeptide is 0.1
~ 3 microns, the thickness of medicine carrying degradable polymer coating be 1 ~ 10 micron.
The preparation method with the bionical intravascular stent promoting endothelial effect the most according to claim 1, it is special
Levy and be to comprise the following steps:
1. after using ultrasonic cleaning bare bracket, drying for standby；
2. will contain the macromolecule of Phosphorylcholine group (or other choline components) and the macromolecule containing REDV polypeptide or other
Specific molecular joins mix homogeneously in solvent, is then sprayed or be immersed in the inner surface of bare bracket, dry through hatching
The technique such as dry, i.e. can get inner cavity surface and contains the polymer coating of Phosphorylcholine and the bionical promotion endothelialization of REDV polypeptide；
3. use the techniques such as special spraying and immersion, prepare asymmetric medicine carrying degradable polymer coating, it may be assumed that drug-carried coat only divides
It is distributed in rack outer surface.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610248782.XA CN105816921A (en) | 2016-04-20 | 2016-04-20 | Bionic vascular stent and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610248782.XA CN105816921A (en) | 2016-04-20 | 2016-04-20 | Bionic vascular stent and preparation method thereof |
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Family
ID=56526283
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| CN201610248782.XA Pending CN105816921A (en) | 2016-04-20 | 2016-04-20 | Bionic vascular stent and preparation method thereof |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107411845A (en) * | 2016-09-14 | 2017-12-01 | 四川蓝光英诺生物科技股份有限公司 | Lumen organization's construct, lumen organization's structure preparation and its device |
| CN108014379A (en) * | 2017-03-22 | 2018-05-11 | 中国科学院金属研究所 | A kind of surface modifying method for improving magnesium alloy blood vessel rack corrosion resisting property |
| CN109971015A (en) * | 2019-04-03 | 2019-07-05 | 苏州大学 | Dewatering and artificial blood vessel of a kind of bacteria cellulose film and preparation method thereof |
| CN110675717A (en) * | 2019-10-10 | 2020-01-10 | 吉林大学 | Bionic equipment for simulating vascular stenosis and thrombus |
| CN113274557A (en) * | 2021-04-30 | 2021-08-20 | 上海大学 | Drug-loaded vascular stent tectorial membrane with unilateral drug release capability and preparation method thereof |
| CN113648114A (en) * | 2021-08-25 | 2021-11-16 | 心凯诺医疗科技(上海)有限公司 | Coated stent and preparation method thereof |
| CN114225115A (en) * | 2021-09-27 | 2022-03-25 | 南开大学 | Nondestructive modified blood vessel substitute containing living cells and preparation method thereof |
| CN114796627A (en) * | 2022-05-19 | 2022-07-29 | 东莞市人民医院 | Double-sided intravascular stent based on albumin and preparation method thereof |
| CN114870102A (en) * | 2022-05-18 | 2022-08-09 | 东莞市人民医院 | Double-sided intravascular stent with nitric oxide catalytic release function 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107411845A (en) * | 2016-09-14 | 2017-12-01 | 四川蓝光英诺生物科技股份有限公司 | Lumen organization's construct, lumen organization's structure preparation and its device |
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| CN109971015B (en) * | 2019-04-03 | 2022-02-08 | 苏州大学 | Dehydration method of bacterial cellulose membrane, artificial blood vessel and preparation method of artificial blood vessel |
| CN109971015A (en) * | 2019-04-03 | 2019-07-05 | 苏州大学 | Dewatering and artificial blood vessel of a kind of bacteria cellulose film and preparation method thereof |
| CN110675717A (en) * | 2019-10-10 | 2020-01-10 | 吉林大学 | Bionic equipment for simulating vascular stenosis and thrombus |
| CN113274557A (en) * | 2021-04-30 | 2021-08-20 | 上海大学 | Drug-loaded vascular stent tectorial membrane with unilateral drug release capability and preparation method thereof |
| CN113648114A (en) * | 2021-08-25 | 2021-11-16 | 心凯诺医疗科技(上海)有限公司 | Coated stent and preparation method thereof |
| CN113648114B (en) * | 2021-08-25 | 2022-06-24 | 心凯诺医疗科技(上海)有限公司 | Coated stent and preparation method thereof |
| CN114225115A (en) * | 2021-09-27 | 2022-03-25 | 南开大学 | Nondestructive modified blood vessel substitute containing living cells 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 |
| CN114870102A (en) * | 2022-05-18 | 2022-08-09 | 东莞市人民医院 | Double-sided intravascular stent with nitric oxide catalytic release function and preparation method thereof |
| CN114870102B (en) * | 2022-05-18 | 2023-08-25 | 东莞市人民医院 | Double-sided vascular stent with nitric oxide catalytic release function and preparation method thereof |
| CN114796627A (en) * | 2022-05-19 | 2022-07-29 | 东莞市人民医院 | Double-sided intravascular stent based on albumin and preparation method thereof |
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