CN106581785A - Intravascular stent and preparation method thereof - Google Patents

Intravascular stent and preparation method thereof Download PDF

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Publication number
CN106581785A
CN106581785A CN201610970699.3A CN201610970699A CN106581785A CN 106581785 A CN106581785 A CN 106581785A CN 201610970699 A CN201610970699 A CN 201610970699A CN 106581785 A CN106581785 A CN 106581785A
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CN
China
Prior art keywords
rapamycin
layer
drug
present
kynoar
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.)
Pending
Application number
CN201610970699.3A
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Chinese (zh)
Inventor
胡堃
余均武
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Huarui (fujian) Biological Technology Co Ltd
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Huarui (fujian) Biological Technology Co Ltd
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Priority to CN201610970699.3A priority Critical patent/CN106581785A/en
Publication of CN106581785A publication Critical patent/CN106581785A/en
Pending legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/08Materials for coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005Use of materials characterised by their function or physical properties
    • A61L33/0011Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/06Use of macromolecular materials
    • A61L33/08Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42Anti-thrombotic agents, anticoagulants, anti-platelet agents

Abstract

The present invention discloses an intravascular stent, which is characterized in that the outer side of a metal stent (4) is sequentially coated with a fixation layer (3), rapamycin and a polyvinylidene fluoride drug-loading layer (2). The present invention further relates to a method for preparing the intravascular stent. According to the present invention, through the slow release of rapamycin, the occurrence of the vascular restenosis can be effectively prevented.

Description

Intravascular stent and preparation method thereof
The application is the divisional application of No. 201410610806.2 applications for a patent for invention, and No. 201410610806.2 inventions are special It is entitled that profit is applied:Intravascular stent and preparation method thereof, the applying date is on November 04th, 2014, and the application retains 201410610806.2 the applying date of number application for a patent for invention.
Technical field
The present invention relates to a kind of intravascular stent and preparation method thereof.
Background technology
The Cerebral Haemorrhage Invasion Rate of China is high, is 120 people/100,000, occupies the 2nd, the world.And wherein up to 33% brain soldier In caused by cerebrovascular arteries are narrow, the at present narrow treatment of symptomatic cerebrovascular arteries is roughly divided into Drug therapy, outer Section treats and intravascular Interventional Treatment, but Drug therapy curative effect is poor, surgical risk is larger, therefore interventional therapy cerebrovascular The application of stricture of artery disease gradually increases.And intravascular Interventional Treatment is divided into simple balloon dilatation and cerebrovascular arteries Frame implantation.It is remaining that simple balloon dilatation easily forms acute inner membrance interlayer, arteriorrhexis, blood vessel elasticity retraction and postoperative stenosis The high complication of rate, limits its application in interventional therapy.Cerebrovascular arteries implantation support is obviously improved can blood flow, because This Endovascular Stent-assisted Angioplasty is the narrow maximally effective Therapeutic Method of current cerebrovascular arteries.
However, recently result shows, because cerebrovascular arteries smooth muscle cell content is high, such as substrate is transitioned into by vertebral artery Arterial smooth muscle cell content rises to 85% by 60%, and smooth muscle cell proliferation is acknowledged as causing narrow in support Principal element, therefore cerebrovascular arteries post stent implantation restenosis rate is far above arteria coronaria.Clinical study results also demonstrate that this is asked The seriousness of topic, the case of follow-up 32.4% occurs in that in-stent restenosis after cerebrovascular stent is implanted into 6 months, and apoplexy is answered after 1 year The rate of sending out is 13.9%.Also, it is often accompanied by the complication situations such as acute subacute stent thrombosis formation in stent implantation procedure to deposit .
The content of the invention
In order to be prevented effectively from present in prior art, restenosiss are susceptible to after cerebrovascular stent implantation, and are easily sent out The defects such as the acute subacute stent thrombosis formation of life, the present invention provides a kind of intravascular stent, can effectively prevent cerebrovascular stent to be implanted into The generation that afterwards restenosiss and acute subacute stent thrombosis are formed.
As one aspect of the present invention, be related to a kind of intravascular stent, the outside of metal rack 4 be sequentially coated with fixation layer 3, Rapamycin and Kynoar drug-loaded layer 2.Rapamycin and the surface of Kynoar drug-loaded layer 2 can also be coated with heparin load Medicine layer 1.The medicament contg of heparin drug-loaded layer is 0.7-1.0 μ g/mm.
Fixation layer 2 can be polyacrylate layer.Polyacrylic acid ester content is 8-10 μ g/mm.
Rapamycin with gather inclined ethylene fluoride mass ratio be:1:7-9, wherein, the content of rapamycin is in 15-20 μ g/ mm.Preferably, rapamycin is with the mass ratio for gathering inclined ethylene fluoride:1:8, wherein, the content of rapamycin is in 16 μ g/ mm。
As another aspect of the present invention, the method for being related to prepare above-mentioned intravascular stent, comprise the steps:
By polyacrylate-coated in metal rack outside;
Rapamycin is coated in polyacrylate layer surface and gather the mixture of inclined ethylene fluoride.
Can also comprise the steps:
Heparin layer is coated in rapamycin with poly- inclined ethylene fluoride layer surface.
Rapamycin with gather inclined ethylene fluoride mixture in, rapamycin with gather inclined ethylene fluoride mass ratio be:1: 7-9, wherein, in 15-20 μ g/mm, preferably rapamycin is the content of rapamycin with the mass ratio for gathering inclined ethylene fluoride:1: 8, wherein, the content of rapamycin is in 16 μ g/mm.
After such scheme, the present invention can at least realize following beneficial effect:
1st, by the slow release of rapamycin, the generation of vascular restenosiss is effectively prevented;
2nd, by the use of heparin, the formation of acute subacute stent thrombosis is effectively prevented;
3rd, by the use of polyacrylate, by active ingredient layer it is stable be fixed on intravascular stent inwall, support turn round It is difficult for drop-off in bent deformation process.
Description of the drawings
Fig. 1 is intravascular stent generalized section of the present invention.
1 is heparin drug-loaded layer;2 is rapamycin and Kynoar drug-loaded layer;3 is fixation layer;4 is metal rack.
Specific embodiment
Below in conjunction with the accompanying drawings the invention will be further described with specific embodiment, so that those skilled in the art can be with It is better understood from the present invention and can be practiced, but illustrated embodiment is not as a limitation of the invention.
Embodiment 1
As shown in figure 1, the intravascular stent that the present embodiment is provided, in the outside of metal rack 4 fixation layer 3, thunder is sequentially coated with Handkerchief mycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1.
Fixation layer 3 is that polyacrylate is sprayed or dip coating manner is coated on metal rack 4 and is formed, polyacrylic acid ester content For 8-10 μ g/mm, rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1 are bonded on metal rack 4.This Bright discovery, the fixation layer 3 obtained using polyacrylate-coated, possesses excellent binding ability, can firmly tie with metal rack 4 It is combined, and in mounting system subsequent machining technology and implements interventional therapy operation support in tortuous very thin Ink vessel transfusing operation During the medicine composite coating phenomenon such as do not ftracture, come off.
Rapamycin with gather inclined ethylene fluoride mass ratio be:1:7, wherein, the content of rapamycin is in 18 μ g/mm.Liver The medicament contg of element coating is in 0.7 μ g/mm.Rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1, with spray or Dip coating manner is sequentially coated on fixation layer 3.Medicine layer in the present invention possesses good biocompatibility.
The present embodiment provides rapamycin and possesses suppression in the reasonable scope, both with the medicament contg for gathering inclined ethylene fluoride layer Effect of cell propagation processed, and do not damage normal cell.Rapamycin can stably be discharged being implanted in 150 days by rule, effectively Prevent the generation of restenosiss.
In the present embodiment, heparin medication coat is being implanted in 1 month by rule release 70%, is all released in 50 days Finish, can effectively suppress acute subacute stent thrombosis to be formed.
Embodiment 2
As shown in figure 1, the intravascular stent that the present embodiment is provided, in the outside of metal rack 4 fixation layer 3, thunder is sequentially coated with Handkerchief mycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1.
Fixation layer 3 is that polyacrylate is sprayed or dip coating manner is coated on metal rack 4 and is formed, polyacrylic acid ester content For 8-10 μ g/mm, rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1 are bonded on metal rack 4.This Bright discovery, the fixation layer 3 obtained using polyacrylate-coated, possesses excellent binding ability, can firmly tie with metal rack 4 It is combined, and in mounting system subsequent machining technology and implements interventional therapy operation support in tortuous very thin Ink vessel transfusing operation During the medicine composite coating phenomenon such as do not ftracture, come off.
Rapamycin with gather inclined ethylene fluoride mass ratio be:1:8, wherein, the content of rapamycin is in 16 μ g/mm.Liver The medicament contg of element coating is in 0.8 μ g/mm.Rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1, with spray or Dip coating manner is sequentially coated on fixation layer 3.Medicine layer in the present invention possesses good biocompatibility.
The present embodiment provides rapamycin and possesses suppression in the reasonable scope, both with the medicament contg for gathering inclined ethylene fluoride layer Effect of cell propagation processed, and do not damage normal cell.Rapamycin can stably be discharged being implanted in 180 days by rule, effectively Prevent the generation of restenosiss.
In the present embodiment, heparin medication coat is being implanted in 1 month by rule release 70%, is all released in 50 days Finish, can effectively suppress acute subacute stent thrombosis to be formed.
Embodiment 3
As shown in figure 1, the intravascular stent that the present embodiment is provided, in the outside of metal rack 4 fixation layer 3, thunder is sequentially coated with Handkerchief mycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1.
Fixation layer 3 is that polyacrylate is sprayed or dip coating manner is coated on metal rack 4 and is formed, polyacrylic acid ester content For 8-10 μ g/mm, rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1 are bonded on metal rack 4.This Bright discovery, the fixation layer 3 obtained using polyacrylate-coated, possesses excellent binding ability, can firmly tie with metal rack 4 It is combined, and in mounting system subsequent machining technology and implements interventional therapy operation support in tortuous very thin Ink vessel transfusing operation During the medicine composite coating phenomenon such as do not ftracture, come off.
Rapamycin with gather inclined ethylene fluoride mass ratio be:1:7, wherein, the content of rapamycin is in 15 μ g/mm.Liver The medicament contg of element coating is in 0.7 μ g/mm.Rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1, with spray or Dip coating manner is sequentially coated on fixation layer 3.Medicine layer in the present invention possesses good biocompatibility.
The present embodiment provides rapamycin and possesses suppression in the reasonable scope, both with the medicament contg for gathering inclined ethylene fluoride layer Effect of cell propagation processed, and do not damage normal cell.Rapamycin can stably be discharged being implanted in 160 days by rule, effectively Prevent the generation of restenosiss.
In the present embodiment, heparin medication coat is being implanted in 1 month by rule release 70%, is all released in 50 days Finish, can effectively suppress acute subacute stent thrombosis to be formed.
Embodiment 4
As shown in figure 1, the intravascular stent that the present embodiment is provided, in the outside of metal rack 4 fixation layer 3, thunder is sequentially coated with Handkerchief mycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1.
Fixation layer 3 is that polyacrylate is sprayed or dip coating manner is coated on metal rack 4 and is formed, polyacrylic acid ester content For 8-10 μ g/mm, rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1 are bonded on metal rack 4.This Bright discovery, the fixation layer 3 obtained using polyacrylate-coated, possesses excellent binding ability, can firmly tie with metal rack 4 It is combined, and in mounting system subsequent machining technology and implements interventional therapy operation support in tortuous very thin Ink vessel transfusing operation During the medicine composite coating phenomenon such as do not ftracture, come off.
Rapamycin with gather inclined ethylene fluoride mass ratio be:1:9, wherein, the content of rapamycin is in 20 μ g/mm.Liver The medicament contg of element coating is in 1.0 μ g/mm.Rapamycin and Kynoar drug-loaded layer 2 and heparin drug-loaded layer 1, with spray or Dip coating manner is sequentially coated on fixation layer 3.Medicine layer in the present invention possesses good biocompatibility.
The present embodiment provides rapamycin and possesses suppression in the reasonable scope, both with the medicament contg for gathering inclined ethylene fluoride layer Effect of cell propagation processed, and do not damage normal cell.Rapamycin can stably be discharged being implanted in 170 days by rule, effectively Prevent the generation of restenosiss.
In the present embodiment, heparin medication coat is being implanted in 1 month by rule release 70%, is all released in 50 days Finish, can effectively suppress acute subacute stent thrombosis to be formed.
Embodiment described above is only the preferred embodiment lifted to absolutely prove the present invention, the protection model of the present invention Enclose not limited to this.Equivalent substitute or conversion that those skilled in the art are made on the basis of the present invention, in the present invention Protection domain within.Protection scope of the present invention is defined by claims.

Claims (1)

1. a kind of intravascular stent, it is characterised in that metal rack (4) outside is sequentially coated with fixation layer (3), rapamycin and poly- Vinylidene drug-loaded layer (2) and heparin drug-loaded layer (1), the fixation layer (3) is polyacrylic acid ester layer, and polyacrylic acid ester content is 8-10 μ g/mm, rapamycin is 1 with the mass ratio of Kynoar:8, wherein, the content of rapamycin is in 16 μ g/mm;
The intravascular stent is prepared by the following method:
By polyacrylate-coated in metal rack outside;
The mixture of rapamycin and Kynoar is coated in polyacrylate layer surface;
In rapamycin and Kynoar drug-loaded layer surface-coated heparin drug-loaded layer;
In the mixture of rapamycin and Kynoar, rapamycin is 1 with the mass ratio of Kynoar:8, wherein, thunder The content of handkerchief mycin is in 16 μ g/mm.
CN201610970699.3A 2014-11-04 2014-11-04 Intravascular stent and preparation method thereof Pending CN106581785A (en)

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Application Number Priority Date Filing Date Title
CN201610970699.3A CN106581785A (en) 2014-11-04 2014-11-04 Intravascular stent and preparation method thereof
CN201410610806.2A CN104383612A (en) 2014-11-04 2014-11-04 Vascular stent and preparation method thereof

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110665074A (en) * 2019-10-25 2020-01-10 福建长庚医疗生物科技有限公司 Heparin coating composition and preparation method thereof

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106264781A (en) * 2015-06-25 2017-01-04 李雷 The manufacture method of overlay film frame, system
CN106562838A (en) * 2015-10-09 2017-04-19 李道远 Novel cardiovascular stent
CN105559944B (en) * 2015-12-14 2016-11-09 李雷 Film-coated vascular support
CN105435314A (en) * 2015-12-14 2016-03-30 李雷 Preparation method of covered endovascular stent-graft
CN107049571A (en) * 2017-05-12 2017-08-18 微创神通医疗科技(上海)有限公司 A kind of vertebral artery stent and preparation method thereof

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Publication number Priority date Publication date Assignee Title
CN202146455U (en) * 2011-07-05 2012-02-22 张湘鲁 Cardiovascular composite medicine bracket
CN203436435U (en) * 2013-07-01 2014-02-19 雅伦生物科技(北京)有限公司 Cerebrovascular drug-eluting stent

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN202146455U (en) * 2011-07-05 2012-02-22 张湘鲁 Cardiovascular composite medicine bracket
CN203436435U (en) * 2013-07-01 2014-02-19 雅伦生物科技(北京)有限公司 Cerebrovascular drug-eluting stent

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110665074A (en) * 2019-10-25 2020-01-10 福建长庚医疗生物科技有限公司 Heparin coating composition and preparation method thereof

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Application publication date: 20170426