CN114504723A - Polymer balloon and preparation method thereof - Google Patents
Polymer balloon and preparation method thereof Download PDFInfo
- Publication number
- CN114504723A CN114504723A CN202111584389.5A CN202111584389A CN114504723A CN 114504723 A CN114504723 A CN 114504723A CN 202111584389 A CN202111584389 A CN 202111584389A CN 114504723 A CN114504723 A CN 114504723A
- Authority
- CN
- China
- Prior art keywords
- balloon
- nano
- polymer
- micro
- array microstructure
- 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
Links
- 229920000642 polymer Polymers 0.000 title claims abstract description 179
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 94
- 239000002086 nanomaterial Substances 0.000 claims abstract description 93
- 238000000034 method Methods 0.000 claims abstract description 26
- 238000001727 in vivo Methods 0.000 claims abstract description 5
- 238000012377 drug delivery Methods 0.000 claims abstract description 3
- 239000012043 crude product Substances 0.000 claims description 71
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 62
- 239000002245 particle Substances 0.000 claims description 46
- 239000000243 solution Substances 0.000 claims description 36
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 35
- 230000003647 oxidation Effects 0.000 claims description 35
- 238000007254 oxidation reaction Methods 0.000 claims description 35
- 239000010936 titanium Substances 0.000 claims description 35
- 229910052719 titanium Inorganic materials 0.000 claims description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 239000000047 product Substances 0.000 claims description 34
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 31
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 238000009826 distribution Methods 0.000 claims description 20
- 239000011259 mixed solution Substances 0.000 claims description 20
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 16
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 claims description 16
- 238000005498 polishing Methods 0.000 claims description 15
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 14
- 229910052782 aluminium Inorganic materials 0.000 claims description 14
- 230000003213 activating effect Effects 0.000 claims description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 238000000465 moulding Methods 0.000 claims description 11
- 238000002791 soaking Methods 0.000 claims description 10
- 150000007522 mineralic acids Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 229920001169 thermoplastic Polymers 0.000 claims description 8
- 229910052786 argon Inorganic materials 0.000 claims description 6
- 230000001678 irradiating effect Effects 0.000 claims description 6
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- 238000004140 cleaning Methods 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000004416 thermosoftening plastic Substances 0.000 claims description 3
- 238000010104 thermoplastic forming Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 57
- 238000011068 loading method Methods 0.000 abstract description 15
- 239000012729 immediate-release (IR) formulation Substances 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 7
- 210000004351 coronary vessel Anatomy 0.000 abstract description 4
- 238000000071 blow moulding Methods 0.000 description 21
- 238000005406 washing Methods 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 13
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 12
- 238000005507 spraying Methods 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 239000002105 nanoparticle Substances 0.000 description 11
- 210000005077 saccule Anatomy 0.000 description 11
- 238000007493 shaping process Methods 0.000 description 10
- 239000004411 aluminium Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- -1 polyethylene Polymers 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229920000299 Nylon 12 Polymers 0.000 description 6
- 238000005868 electrolysis reaction Methods 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 238000011056 performance test Methods 0.000 description 6
- MLXDKRSDUJLNAB-UHFFFAOYSA-N triethoxy(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)silane Chemical compound CCO[Si](OCC)(OCC)CCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F MLXDKRSDUJLNAB-UHFFFAOYSA-N 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 238000003618 dip coating Methods 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 4
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 4
- 229960002930 sirolimus Drugs 0.000 description 4
- 238000004381 surface treatment Methods 0.000 description 4
- 208000031481 Pathologic Constriction Diseases 0.000 description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 3
- 238000000889 atomisation Methods 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 3
- 239000002861 polymer material Substances 0.000 description 3
- 238000009991 scouring Methods 0.000 description 3
- 229910000077 silane Inorganic materials 0.000 description 3
- 230000036262 stenosis Effects 0.000 description 3
- 208000037804 stenosis Diseases 0.000 description 3
- 206010056489 Coronary artery restenosis Diseases 0.000 description 2
- JHWNWJKBPDFINM-UHFFFAOYSA-N Laurolactam Chemical compound O=C1CCCCCCCCCCCN1 JHWNWJKBPDFINM-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 238000007743 anodising Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 238000010924 continuous production Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000009740 moulding (composite fabrication) Methods 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000003856 thermoforming Methods 0.000 description 2
- 201000000054 Coronary Restenosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 206010040007 Sense of oppression Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- KKDAVNZSOWTBKR-UHFFFAOYSA-N ethanol trichloro(octadecyl)silane Chemical compound CCO.CCCCCCCCCCCCCCCCCC[Si](Cl)(Cl)Cl KKDAVNZSOWTBKR-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000037891 myocardial injury Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000002321 radial artery Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/1027—Making of balloon catheters
- A61M25/1029—Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/1027—Making of balloon catheters
- A61M25/1029—Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
- A61M2025/1031—Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Anesthesiology (AREA)
- Child & Adolescent Psychology (AREA)
- Biophysics (AREA)
- Pulmonology (AREA)
- Manufacturing & Machinery (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Materials For Medical Uses (AREA)
Abstract
The application provides a polymer balloon and a preparation method thereof, wherein the outer surface of the polymer balloon is provided with a micro-nano structure, and the polymer balloon is used for conveying drugs in vivo. The polymer balloon can be applied to serve as a medical balloon, for example, the polymer balloon can be used as a drug delivery balloon for coronary artery, and the micro-nano structure on the surface of the polymer balloon can adsorb drugs, so that the drug adhesion is improved, the loss rate of the drugs in the treatment process is reduced, the specific surface area of the polymer balloon is increased by the micro-nano structure, the contact area of the drugs is increased, the drug loading amount is increased, the stability and the loading amount of the drugs on the surface of the polymer balloon are improved, and the immediate release capacity of the drugs is improved.
Description
Technical Field
The application belongs to the technical field of surface processing of polymer materials, and particularly relates to a polymer balloon and a preparation method thereof.
Background
Myocardial infarction is an acute cardiac condition that results in a disturbance in the blood circulation of the myocardium and may cause myocardial injury, and the immediate cause is the complete occlusion of the coronary arteries. Without timely treatment, myocardial infarction is prone to death, and the most common treatment for myocardial infarction is balloon angioplasty.
The catheter is directly connected to the artery by puncture and catheterization of femoral artery or radial artery, contrast agent is injected along the catheter to clearly identify the artery stenosis part, the catheter with the saccule is sent into the stenosis section, pressurization and expansion are carried out, the stenosis lumen is enlarged, and the blood flow is smooth. However, balloon angioplasty is less advanced, and some patients develop coronary restenosis due to thickening of the vessel wall, resulting in recurrence of myocardial infarction. Through research, the balloon and the stent which are used as interventional therapy instruments are coated with specific medicines, so that the vascular intimal hyperplasia is resisted, the postoperative inflammatory reaction is relieved, the probability of coronary artery restenosis can be effectively reduced, and the prognosis effect of patients is improved.
The existing balloon stent drug loading technology carries drug on the smooth surface of the balloon by a spraying or dip-coating mode, and the drug loading loss is easily caused by blood flow scouring in the interventional therapy process when the drug loading is limited, so that the drug application effect is finally influenced.
Disclosure of Invention
Based on this, the application provides a polymer sacculus, the surface of polymer sacculus has micro-nano structure, and when its application was used as medical sacculus, can effectively improve the drug loading rate to reduce the medicine carrying loss rate in the use, improve medicine immediate release rate, in order to solve the medical sacculus medicine carrying that exists among the prior art and lose easily, immediate release rate is low, influences the technical problem who gives medicine to the poor free of charge effect.
The application also provides a preparation method of the polymer balloon, according to the material characteristics, the preparation process is optimized, so that the surface of the polymer balloon has a micro-nano structure, the preparation effect is good, and the process operation is suitable for industrial popularization.
The utility model provides a polymer sacculus, the surface of polymer sacculus has micro-nano structure, and polymer sacculus is used for the internal transport of medicine.
Optionally, the nanostructure comprises a plurality of nano-columnar particles, the nano-columnar particles being distributed in a vertical manner.
Optionally, the diameter of the nano columnar particles is 20-400 nm.
Optionally, the distribution density of the nano columnar particles of the micro-nano structure is 3-50 particles/mm2。
Optionally, the height of the micro-nano structure is 1-12 μm.
Optionally, the polymeric balloon is made of a thermoplastic polymer.
A method of making a polymeric balloon for in vivo delivery of a drug, the method comprising the steps of:
providing a mold, wherein the mold is provided with a balloon molding cavity, and the surface of the cavity wall of the balloon molding cavity is provided with a nano array microstructure for forming a nano microstructure;
and providing a polymer tube body, and placing the polymer tube body in a balloon forming cavity for thermoplastic forming treatment to obtain the polymer balloon with the surface having the micro-nano structure.
Optionally, the method for obtaining the polymer balloon with the micro-nano structure on the surface by placing the polymer tube body in the balloon forming cavity for thermoforming comprises the following steps:
and placing the polymer tube body in a balloon forming cavity, and performing blow molding treatment on the polymer tube body to obtain the polymer balloon with the surface having the micro-nano structure.
Optionally, the temperature of the blow molding treatment is 120-180 ℃, the pressurizing pressure is 5-15 atm, and the pressure maintaining time is 2-20 min.
A mould for preparing any polymer sacculus is a pure aluminum product, the mould is provided with a sacculus forming cavity, the cavity wall of the sacculus forming cavity is provided with a nano array microstructure, and the nano array microstructure on the surface of the sacculus forming cavity is prepared by adopting an anodic oxidation method.
Optionally, the mold comprises two half molds, wherein one sides of the two half molds opposite to each other are respectively provided with a groove, after the two half molds are closed, the two grooves jointly form a balloon forming cavity, and the preparation method of the half molds comprises the following steps:
carrying out electrolytic polishing on the half mould to obtain a first-stage rough product of the half mould;
placing the first-stage crude product in an inorganic acid solution, taking the first-stage crude product as an anode and titanium as a cathode, and performing reaction under the conditions that the voltage is 145-155V, and the current density is 6-20 mA/cm2At a temperature of 8 ℃ to 12 ℃ to carry out the second stepPerforming primary anodic oxidation to obtain a second-stage rough product of the half mould;
immersing the second-order crude product into a mixed solution of phosphoric acid and chromic acid, cleaning in a water bath at 65-75 ℃, and then cleaning with water to obtain a third-order crude product;
immersing the third-order crude product in an inorganic acid solution, taking the third-order crude product as a positive electrode and titanium as a negative electrode, and performing the treatment under the conditions that the voltage is 145-155V, the current density is 6-20 mA/cm2And carrying out second anodic oxidation at the temperature of 8-12 ℃ to obtain the half mould with the surface provided with the nano array microstructure, wherein the nano array microstructure is distributed on the surface of the groove.
Optionally, the inorganic acid solution is a phosphoric acid or sulfuric acid solution; and/or the mixed solution of phosphoric acid and chromic acid is a mixed solution of 5 wt% -7 wt% of phosphoric acid and 1.0 wt% -2.3 wt% of chromic acid.
Optionally, the method of electropolishing a mold half comprises the steps of: placing the half-mould into a mixed solution of perchloric acid and ethanol, and electrolyzing at the voltage of 16-18V and the temperature of 8-12 ℃ by taking the half-mould as an anode and titanium as a cathode.
Alternatively, in the mixed solution of perchloric acid and ethanol, the volume ratio of perchloric acid to ethanol is 1: (4-8).
Optionally, after the step of obtaining the mold half with the nano-array microstructure on the surface, the method further comprises the following steps: and carrying out surface treatment on the nano-array microstructure of the half mold.
Optionally, the method for surface treatment of the nano-array microstructure of the mold half comprises the following steps:
activating the nano array microstructure on the surface of the groove to enable the nano array microstructure to have hydrophilicity;
and (3) placing the half mold into an ethanol solution of a release agent for soaking, drying and forming a release agent layer on the surface of the nano array microstructure.
Optionally, the specific operation of the nano-array microstructure for activating the groove surface is as follows: and irradiating the nano array microstructure on the surface of the groove by adopting ultraviolet light, or exposing the nano array microstructure on the surface of the groove in ozone atmosphere, or bombarding the nano array microstructure on the surface of the groove by adopting argon low-temperature plasma.
Optionally, the mass content of the release agent in the ethanol solution of the release agent is 1% to 2%.
Optionally, the release agent is a hydrophobic oleophobic silane.
1. The polymer balloon surface provided by the application has a micro-nano structure, and can be applied as a medical balloon, such as a drug delivery balloon for coronary artery of heart, because the micro-nano structure on the surface of the polymer balloon generates an adsorption effect on drugs, the drug adhesion is improved, the loss rate of the drugs in the treatment process is reduced, and the micro-nano structure increases the specific surface area of the polymer balloon and increases the contact area of the drugs, so that the drug loading rate is increased, the stability and the loading capacity of the drugs on the surface of the polymer balloon are improved, and meanwhile, the immediate release rate of the drugs can be improved;
2. according to the preparation method of the polymer balloon, the mold with the nano array microstructure is utilized to form the controllable micro-nano structure on the surface of the polymer material, the production process has the advantages of continuous production and small influence on the size accuracy of a product, and the mold with the nano array microstructure on the surface is used for completely re-engraving the nano array microstructure on the surface of the mold and forming the micro-nano structure on the curved surface of the polymer balloon.
Drawings
The invention will be further described with reference to the accompanying drawings and examples, in which:
fig. 1 is a scanning electron micrograph of the nanostructures on the surface of a polymer balloon of example 3 of the present application;
FIG. 2 is a scanning electron micrograph of the nanostructure of the surface of the mold half of example 3 of the present application.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present application clearer, the present application is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application.
The embodiment of the application provides a polymer sacculus, and the outer surface of the polymer sacculus is provided with a micro-nano structure.
The polymer balloon surface has a micro-nano structure, and can be applied as a medical balloon for medicine in vivo delivery, such as a medicine delivery balloon for heart coronary artery, because the micro-nano structure on the surface of the polymer balloon generates an adsorption effect on the medicine, the medicine adhesive force is improved, the loss rate of the medicine in the treatment process is reduced, in addition, the micro-nano structure increases the specific surface area of the polymer balloon, the contactable area of the medicine is increased, the medicine carrying amount is increased, the stability and the carrying amount of the medicine on the surface of the polymer balloon are improved, and meanwhile, the immediate release rate of the medicine can also be improved.
In the embodiments of the present application, the nanostructure refers to a minute structure having a size of 500nm or less, which includes nanoparticles and/or nano-sized pores.
In this application embodiment, micro-nano structure includes a plurality of nanometer columnar granule, and nanometer columnar granule is vertical form and distributes, extends outward from polymer sacculus body promptly and erects. When the polymer balloon is used as a medical balloon, a medicine is sprayed on the surface of the micro-nano structure, gaps are formed between nano columnar particles in the micro-nano structure and the nano columnar particles, and the medicine can be attached to the side surfaces and the top surfaces of the nano columnar particles in the micro-nano structure, so that the attachment area of the medicine is increased; before the polymer balloon is expanded, certain resistance exists between particles due to gaps between the particles, so that the friction of blood vessels and the scouring of blood flow to the medicine are reduced, and the medicine loss rate is reduced; after the polymer saccule is expanded, the nano columnar particles in the micro-nano structure are almost leveled, so that the specific surface area of the polymer saccule is increased, the medicine can be quickly released, and the medicine release rate is improved.
The diameter of the nano columnar particles is the columnar diameter of the particles, and understandably, under the condition of the same height and distribution density, the larger the diameter of the nano columnar particles is, the larger the surface area of the surface of the polymer balloon is, the larger the drug-carrying area is, and the larger the specific surface area is after the polymer balloon is expanded, the higher the drug immediate release rate is. However, if the diameter of the nano-columnar particles is too large, such as larger than 400nm, the gaps between the particles may be smaller compared to the smaller diameter of the nano-columnar particles, thereby increasing the drug adhesion resistance; if the diameter of the nano columnar particles is too small, for example, less than 20nm, the increase in the surface area of the polymer balloon is small and the increase in the drug loading amount and the drug immediate release rate is small if the distribution density is small. Therefore, in practice, the diameter of the nano-columnar particles can be selected to be 20-400 nm.
It can be understood that, under the condition of the same average particle size and height, the larger the distribution density of the nano columnar particles, the larger the specific surface area of the polymer balloon, the larger the drug-carrying area, the smaller the gaps between the particles, the larger the scouring resistance and the smaller the drug loss rate. However, if the distribution density of the nano columnar particles is too large, for example, more than 50 particles/mm2When the particles are too dense, the resistance of the medicine adhered to the surface of the polymer balloon is increased, which is not beneficial to spraying the medicine; if the density of the distribution of the nano-columnar particles is too small, e.g. less than 3 particles/mm2In the case of a small diameter of the nano columnar particles, the improvement of the drug loading rate, the drug loss rate and the immediate drug release rate is not significant. Therefore, when the method is implemented, the distribution density of the nano columnar particles of the micro-nano structure can be selected to be 3-50 particles/mm2。
The height of the micro-nano structure is the height of the micro-nano structure protruding relative to the smooth surface of the polymer balloon, and the height of the micro-nano structure is also the height of the nano columnar particles. It can be understood that the height of the micro-nano structure also affects an important parameter of the surface area increase of the polymer balloon, and under the condition of the same diameter and distribution density, the higher the height of the micro-nano structure is, the larger the surface area of the polymer balloon is, the more the drug can be carried, the larger the resistance of the drug to be washed, and the lower the drug loss rate is. However, if the height of the micro-nano structure is too large, such as greater than 12 μm, when the polymer balloon is expanded, the nano columnar particles are difficult to flatten, that is, the polymer balloon needs to be expanded to have a larger volume to flatten the nano columnar particles, which may increase the difficulty in use, and in addition, when the height of the micro-nano structure is greater than 12 μm, the difficulty and cost of processing are high, which is not favorable for popularization and use; if the height of the micro-nano structure is too small, such as less than 1 μm, if the distribution density is small and the diameter of the particles is small, the surface of the polymer balloon is close to a smooth surface, the drug loading rate is not obviously improved, the improvement on the reduction of the drug loss rate is small, the specific surface area of the polymer balloon is slightly increased after the polymer balloon is expanded and expanded, and the improvement on the drug loading rate, the drug loss rate and the immediate drug release rate is small. Therefore, the height of the micro-nano structure can be selected to be 1-12 mu m in implementation.
The polymer balloon in the embodiment of the application is made of thermoplastic polymers, for example, the thermoplastic polymers can be, but are not limited to, polyethylene, polypropylene, polyamide, polycarbonate, polyurethane and the like, the thermoplastic polymers have good processing formability, can be softened at a characteristic temperature, are good in forming stability after being cooled, and are beneficial to forming a stable micro-nano structure on the surface of the polymer balloon.
The embodiment of the application also provides a preparation method of the polymer balloon, which comprises the following steps:
s100: and providing a mold, wherein the mold is provided with a balloon molding cavity, and the surface of the cavity wall of the balloon molding cavity is provided with a nano-array microstructure.
Optionally, the mold in the embodiment of the present application is a pure aluminum product, a nano array microstructure for forming a micro-nano structure is provided on a cavity wall surface of the balloon molding cavity, the nano array microstructure is manufactured by an anodic oxidation method, and alumina nanoparticles having column holes are formed on the cavity wall surface of the balloon molding cavity by anodic oxidation to form the nano array microstructure. The balloon forming cavity is used for thermoplastic processing and forming of polymers in the subsequent process, and limits the forming of the polymers, so that the polymers have the function of forming a balloon in a preset shape.
It can be understood that the micro-nano structure may be distributed only on the cavity wall surface of the balloon molding cavity, or may be completely distributed on the outer surface of the entire mold, including the cavity wall surface of the balloon molding cavity.
Optionally, the mold comprises two half molds, wherein the opposite sides of the two half molds are respectively provided with a groove, and after the two half molds are closed tightly, the two grooves jointly form a balloon forming cavity.
The preparation method of the half mould comprises the following steps:
s10: and (4) carrying out electrolytic polishing on the half mould to obtain a first-stage rough product of the half mould.
The method for electrolytic polishing of the half mold comprises the following steps: and (3) placing the half mould into a mixed solution of perchloric acid and ethanol, and carrying out electrolytic polishing under the conditions that the voltage is 16-18V and the temperature is 8-12 ℃ by taking the half mould as an anode and titanium as a cathode for about 5 min.
And (3) carrying out electrolytic polishing on the half mould to remove alumina or other impurities possibly existing on the surface, and enabling the surface of the half mould to be smooth and clean, thereby being beneficial to carrying out anodic oxidation treatment subsequently.
Alternatively, in the mixed solution of perchloric acid and ethanol, the volume ratio of perchloric acid to ethanol is 1: (4-8), the polishing effect is good, and the surface of the half mold cannot be blackened.
S20: placing the first-stage crude product in an inorganic acid solution, taking the first-stage crude product as a positive electrode and titanium as a negative electrode, and performing the treatment under the conditions that the voltage is 145-155V, and the current density is 6-20 mA/cm2And carrying out first anodic oxidation at the temperature of 8-12 ℃ to obtain a second-stage rough product of the half mould.
Optionally, the electrolysis time of the first anodic oxidation is 50-120 min, and a proper electrolysis time is selected according to the height of the required nano-array microstructure layer.
The inorganic acid solution can be phosphoric acid or sulfuric acid water solution, the concentration of the phosphoric acid solution is 0.1-0.2 mol/L, and the concentration of the sulfuric acid solution is 0.1-0.2 mol/L.
S30: and (3) immersing the second-order crude product into a mixed solution of phosphoric acid and chromic acid, washing in a water bath at 65-75 ℃, and then washing with water to obtain a third-order crude product.
Alternatively, the mixed solution of phosphoric acid and chromic acid is a mixed solution of 5 wt% to 7 wt% of phosphoric acid and 1.0 wt% to 2.3 wt% of chromic acid, can corrode and wash away the alumina on the surface of the half mold, and can not corrode and damage the aluminum material of the half mold.
S40: immersing the third-order crude product in an inorganic acid solution, taking the third-order crude product as an anode and titanium as a cathode, and performing reaction under the conditions that the voltage is 145-155V, the current density is 6-20 mA/cm2And carrying out second anodic oxidation at the temperature of 8-12 ℃ to obtain the half mould with the surface provided with the nano array microstructure, wherein the nano array microstructure is distributed on the surface of the groove.
Optionally, the electrolysis time of the second anodic oxidation is 30-240 min, and a proper electrolysis time is selected according to the actual height requirement of the alumina nano structure.
The inorganic acid solution can be phosphoric acid or sulfuric acid water solution, the concentration of the phosphoric acid solution is 0.1-0.2 mol/L, and the concentration of the sulfuric acid solution is 0.1-0.2 mol/L.
Optionally, during the electropolishing, the first anodizing and the second anodizing, distances between the half mold and the titanium are all 6.5-8 cm, the fixed distance is mainly used for controlling the electrolysis degree and the current density, when the distance between the half mold and the titanium is greater than 8cm, the current density may be greatly reduced, and when the distance between the half mold and the titanium is less than 6.5cm, a breakdown may occur.
According to the embodiment of the application, regularly distributed alumina nano structures can be generated on the surface of a half mold through two times of anodic oxidation, the alumina nano particles are subjected to the first anodic oxidation, irregularly arranged alumina nano particles are generated on the surface of the half mold, the half mold is cleaned by adopting a mixed solution of phosphoric acid and chromic acid, the alumina nano particles generated by the first anodic oxidation are completely cleaned, a plurality of irregular pits can be generated on the surface of the cleaned half mold due to the fact that the alumina nano particles generated by the first anodic oxidation are irregularly distributed, regularly distributed hexagonal prism-shaped alumina nano particles are generated under the guidance of the pits during the second anodic oxidation, each alumina nano particle is provided with a column hole, a nano array microstructure is formed, and the alumina nano particles and the column holes are in columnar vertical distribution.
In some embodiments of the present application, the height of the nano-array microstructure on the surface of the half mold is 10 to 30 μm, i.e., the height of the alumina nanoparticles is 10 to 30 μm, the diameter of the pillar holes is 30 to 400nm, and the distribution density of the pillar holes is 10 to 30 μmIs 3 to 50 pieces/mm2。
In the embodiment of the present application, after the step of S40, the following step of S50 is further included:
and carrying out surface treatment on the nano-array microstructure of the half mold.
Optionally, the method for surface treatment of the nano-array microstructure of the mold half comprises the following steps:
the nano array microstructure on the surface of the groove is activated, so that the nano array microstructure has hydrophilicity, and the release agent can be better attached to the nano array microstructure.
Optionally, the method for activating the nano-array microstructure on the surface of the groove comprises the following steps:
the nano array microstructure on the surface of the groove is irradiated by ultraviolet light, or exposed in ozone atmosphere, or bombarded by argon low-temperature plasma, so that the nano array microstructure has hydrophilicity.
And (3) placing the half mold into an ethanol solution of a release agent for soaking, drying and forming a release agent layer on the surface of the nano array microstructure. And (3) soaking the half mold in an ethanol solution of a release agent, drying at the temperature of 100-130 ℃ to completely volatilize the ethanol, and forming a release agent film to be attached to the surface of the nano array microstructure to form a release agent layer.
Optionally, the mass content of the release agent in the ethanol solution of the release agent is 1-2%, which is beneficial to volatilization of ethanol and does not influence film formation of the release agent.
Considering that the nano array microstructure has a curved surface and is small in size, the release agent needs to have both hydrophobic and oleophobic properties and wettability, the hydrophobic and oleophobic properties are beneficial to smooth release of a subsequent polymer balloon, and the wettability enables the release agent to be uniformly attached to the surface of the nano array microstructure. Alternatively, the release agent is a hydrophobic oleophobic silane such as octadodecyl trichlorosilane, polydimethylsiloxane, perfluorosiloxane, or the like; the perfluorosiloxane may be, for example, 1H,2H, 2H-perfluorodecyltriethoxysilane or the like. The silane release agents and the polymer of the saccule do not react or adhere, and the polymer saccule can be smoothly released after being processed.
According to the preparation method of the mold, the property that the mold is a pure aluminum product is utilized, An Aluminum Oxide (AAO) nano array microstructure can be generated on the surface of the pure aluminum mold through an anodic oxidation method, and a structural basis is provided for the polymer balloon re-etching micro-nano structure.
S200: providing a polymer tube body, and placing the polymer tube body in a balloon forming cavity for hot plastic forming treatment to obtain the polymer balloon with the surface having the micro-nano structure.
Optionally, the method of placing the polymer in the balloon molding cavity for thermoforming comprises the steps of: and (3) placing the polymer pipe body in a balloon forming cavity, and performing blow molding treatment on the polymer pipe body to obtain a polymer product with a micro-nano structure on the surface.
Optionally, the temperature of the blow molding treatment is 120-180 ℃, the pressurizing pressure is 5-15 atm, and the pressure maintaining time is 2-20 min.
The polymer is expanded by the blow molding and forms the polymer utricule, after the heating, the surface of polymer utricule softens gradually, to the inside pressurization of polymer utricule, the surface oppression sacculus shaping chamber cavity wall's nanometer array microstructure of polymer utricule, in the column hole of the nanometer array microstructure of sacculus shaping chamber is crowded into to polymer utricule partial surface, produces deformation, forms the nanometer columnar particle that the same array distributes with the column hole on the surface of polymer utricule, makes the polymer sacculus that has micro-nano structure on the surface. The nano-array microstructure on the wall of the balloon forming cavity and the micro-nano structure on the surface of the polymer balloon are mutually in a male-female mode, and the shapes of the micro-array microstructure and the micro-nano structure are complementary.
According to the preparation method of the polymer balloon, the mold with the nano array microstructure is utilized to form the controllable micro-nano structure on the surface of the polymer material, the production process has the advantages of continuous production and small influence on the size accuracy of a product, and the nano array microstructure on the surface of the mold can be completely repeatedly engraved and the micro-nano structure on the curved surface of the polymer balloon can be formed through the mold with the nano array microstructure on the surface.
The polymer balloon and the preparation method thereof, and the performance of the polymer balloon are illustrated by the following examples.
Example 1
The polymer sacculus of this application embodiment adopts polyethylene to make, and polymer sacculus surface has micro-nano structure, and micro-nano structure's height is 5 mu m, and the diameter of nanometer column granule is 50 ~ 102nm, and the distribution density is 23/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 4, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7cm, and carrying out electrolytic polishing under the conditions that the voltage is 16V and the temperature is 12 ℃ for 5min to obtain a first-order crude product of the half-mould.
S20: placing the first-order crude product in an aqueous solution (0.2mol/L) of sulfuric acid, taking the first-order crude product as a positive electrode, titanium as a negative electrode, and under the condition that the voltage is 145V, the distance between the positive electrode and the negative electrode is 7cm, and the current density is 10mA/cm2And carrying out first anodic oxidation at the temperature of 10 ℃ for 80min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 6.5 percent of phosphoric acid and 1.8 percent of chromic acid, washing the second-stage crude product in a water bath at 65-68 ℃, and then washing the second-stage crude product with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution (0.2mol/L) of sulfuric acid, taking the third-order crude product as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7cm, the voltage is 145V, and the current density is 10mA/cm2And carrying out second anodic oxidation at the temperature of 10 ℃ for 30min to obtain a half mold with a nano array microstructure on the surface, wherein the nano array microstructure covers the grooveThe height of the nano-array microstructure is 10 μm.
S50: and activating the nano array microstructure on the surface of the groove, and irradiating the nano array microstructure on the surface of the groove by adopting ultraviolet light to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 1 wt% of 1H,1H,2H, 2H-perfluorodecyl triethoxysilane ethanol solution for soaking for 2 days, drying at the temperature of 120 ℃, and forming a release agent layer on the surface of the nano array microstructure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and performing blow molding treatment on the polymer tube body, wherein the temperature of the blow molding treatment is 160 ℃, the pressure is 10atm, and the pressure maintaining time is 12min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Example 2
The polymer balloon is made of polycarbonate, the surface of the polymer balloon is provided with a micro-nano structure, the height of the micro-nano structure is 7 micrometers, the diameter of nano columnar particles is 40-85 nm, and the distribution density is 5 particles/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 5, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 6.5cm, and carrying out electrolytic polishing under the conditions that the voltage is 17V and the temperature is 9 ℃ for 6min to obtain a first-order rough product of the half-mould.
S20: placing the first-order crude product in an aqueous solution (0.15mol/L) of sulfuric acid, taking the first-order crude product as a positive electrode, titanium as a negative electrode, the distance between the positive electrode and the negative electrode being 8cm, the voltage being 148V, and the current density being 12mA/cm2And carrying out first anodic oxidation at the temperature of 8 ℃ for 70min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 7 wt% phosphoric acid and 2.2 wt% chromic acid, washing in a water bath at 65-68 ℃, and then washing with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution of sulfuric acid (0.15mol/L), taking the third-order crude product as a positive electrode, titanium as a negative electrode, and taking the distance between the positive electrode and the negative electrode as 6.5cm, wherein the voltage is 148V, and the current density is 12mA/cm2And carrying out second anodic oxidation at the temperature of 8 ℃ for 70min to obtain a half mold with a nano array microstructure on the surface, wherein the nano array microstructure covers the surface of the groove, and the height of the nano array microstructure is 12 micrometers.
S50: and activating the nano array microstructure on the surface of the groove, and bombarding the nano array microstructure on the surface of the groove by argon low-temperature plasma to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 2 wt% of 1H,1H,2H, 2H-perfluorodecyl triethoxysilane ethanol solution for soaking for 2 days, drying at the temperature of 120 ℃, and forming a release agent layer on the surface of the nano array microstructure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and performing blow molding treatment on the polymer tube body, wherein the temperature of the blow molding treatment is 180 ℃, the pressure is 5atm, and the pressure maintaining time is 10min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Example 3
The polymer sacculus of this application embodiment adopts polyamide 12 (nylon 12) to make, and polymer surface has micro-nano structure, and micro-nano structure's height is 10 mu m, and the diameter of nanometer column granule is 100 ~ 150nm, and distribution density is 35/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 4, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7cm, and carrying out electrolytic polishing under the conditions that the voltage is 18V and the temperature is 11 ℃ for 5min to obtain a first-stage rough product of the half-mould.
S20: placing the first-stage crude product in phosphoric acid aqueous solution (0.2mol/L), taking the first-stage crude product as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7cm, the voltage is 150V, and the current density is 15mA/cm2And carrying out first anodic oxidation at the temperature of 12 ℃ for 50min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 6 wt% phosphoric acid and 1.8 wt% chromic acid, washing in a water bath at 65-70 ℃, and then washing with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution (0.2mol/L) of phosphoric acid, taking the third-order crude product as a positive electrode, titanium as a negative electrode, the distance between the positive electrode and the negative electrode is 7cm, the voltage is 150V, and the current density is 15mA/cm2And carrying out second anodic oxidation at the temperature of 12 ℃ for 120min to obtain the half mold with the surface provided with the nano-array microstructure, wherein the nano-array microstructure covers the surface of the groove, and the height of the nano-array microstructure is 20 micrometers.
S50: and activating the nano array microstructure on the surface of the groove, and irradiating the nano array microstructure on the surface of the groove by adopting ultraviolet light to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 1.5 wt% of 1H,1H,2H, 2H-perfluorodecyl triethoxysilane ethanol solution for soaking for 2 days, drying at the temperature of 130 ℃, and forming a release agent layer on the surface of the nano array microstructure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and performing blow molding treatment on the polymer tube body, wherein the temperature of the blow molding treatment is 140 ℃, the pressure is 10atm, and the pressure holding time is 5min, so as to obtain a polymer balloon with a micro-nano structure on the surface, and the micro-nano structure on the surface of the polymer balloon is shown in fig. 2.
Example 4
The polymer balloon is made of polyamide 12, the surface of the polymer balloon is provided with a micro-nano structure, the height of the micro-nano structure is 6 micrometers, the diameter of nano columnar particles is 95-130 nm, and the distribution density is 37 particles/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 4.5, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7.2cm, and carrying out electrolytic polishing under the conditions that the voltage is 17V and the temperature is 10 ℃ for 5min to obtain a first-stage rough product of the half-mould.
S20: placing the first-stage crude product in sulfuric acid water solution (0.17mol/L), taking the first-stage crude product as a positive electrode and titanium as a negative electrode, wherein the distance between the positive electrode and the negative electrode is 7.5cm, the voltage is 150V, and the current density is 20mA/cm2And carrying out first anodic oxidation at the temperature of 12 ℃ for 110min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 6 wt% phosphoric acid and 1.5 wt% chromic acid, washing in a water bath at 68-70 ℃, and then washing with water to obtain a third-stage crude product.
S40: the third-stage crude product was immersed in an aqueous solution of sulfuric acid (0.17mol/L) to obtain a third-stage crude productThe three-order crude product is a positive electrode, titanium is a negative electrode, the distance between the positive electrode and the negative electrode is 7.5cm, the voltage is 150V, and the current density is 20mA/cm2And carrying out second anodic oxidation at the temperature of 12 ℃, wherein the electrolysis time is 240min, so as to obtain the half mold with the nano array microstructure on the surface, wherein the nano array microstructure covers the surface of the groove, and the height of the nano array microstructure is 30 micrometers.
S50: and activating the nano array microstructure on the surface of the groove, and bombarding the nano array microstructure on the surface of the groove by argon low-temperature plasma to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 1 wt% of 1H,1H,2H, 2H-perfluorodecyl triethoxysilane ethanol solution for soaking for 2 days, drying at the temperature of 110 ℃, and forming a release agent layer on the surface of the nano array microstructure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and performing blow molding treatment on the polymer tube body, wherein the temperature of the blow molding treatment is 150 ℃, the pressure is 8atm, and the pressure maintaining time is 10min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Example 5
The polymer sacculus of this application embodiment adopts polypropylene to make, and polymer sacculus surface has micro-nano structure, and micro-nano structure's height is 8 mu m, and the diameter of nanometer column granule is 200 ~ 220nm, and distribution density is 17/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 6, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 8cm, and carrying out electrolytic polishing under the conditions that the voltage is 16V and the temperature is 9.5 ℃ for 7min to obtain a first-stage rough product of the half-mould.
S20: placing the first-stage crude product in phosphoric acid water solution (0.2mol/L), taking the first-stage crude product as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 8cm, the voltage is 152V, and the current density is 18mA/cm2And carrying out first anodic oxidation at the temperature of 9 ℃ for 120min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 7 wt% phosphoric acid and 1.5 wt% chromic acid, washing in a water bath at 70-75 ℃, and then washing with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution (0.2mol/L) of phosphoric acid, taking the third-order crude product as a positive electrode, titanium as a negative electrode, and taking the distance between the positive electrode and the negative electrode as 8cm, wherein the voltage is 152V, and the current density is 18mA/cm2And carrying out second anodic oxidation at the temperature of 9 ℃ for 200min to obtain the half mold with the surface provided with the nano-array microstructure, wherein the nano-array microstructure covers the surface of the groove, and the height of the nano-array microstructure is 23 μm.
S50: and activating the nano array microstructure on the surface of the groove, and irradiating the nano array microstructure on the surface of the groove by adopting ultraviolet light to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into a 1 wt% octadecyl trichlorosilane ethanol solution to be soaked for 2.5 days, drying at the temperature of 130 ℃, and forming a release agent layer on the surface of the nano array microstructure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a forming cavity, and performing blow molding on the polymer tube body, wherein the temperature of the blow molding is 170 ℃, the pressure is 7atm, and the pressure maintaining time is 20min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Example 6
The polymer balloon of the embodiment of the application adopts polyimideThe surface of the polymer balloon is provided with a micro-nano structure, the height of the micro-nano structure is 5 micrometers, the diameter of the nano columnar particles is 260-300 nm, and the distribution density is 31 particles/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 5, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7cm, and carrying out electrolytic polishing under the conditions of 18V of voltage and 10 ℃ for 8min to obtain a first-stage crude product of the half-mould.
S20: placing the first-stage crude product in phosphoric acid water solution (0.2mol/L), taking the first-stage crude product as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 7cm, the voltage is 149V, and the current density is 15mA/cm2And carrying out first anodic oxidation at the temperature of 9 ℃ for 60min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 7 wt% phosphoric acid and 2 wt% chromic acid, washing in a water bath at 70-75 ℃, and then washing with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution (0.2mol/L) of phosphoric acid, taking the third-order crude product as a positive electrode, titanium as a negative electrode, the distance between the positive electrode and the negative electrode is 7cm, the voltage is 149V, and the current density is 15mA/cm2And carrying out second anodic oxidation at the temperature of 9 ℃ for 50min to obtain a half mold with a nano array microstructure on the surface, wherein the nano array microstructure covers the surface of the groove, and the height of the nano array microstructure is 13 mu m.
S50: and activating the nano array microstructure on the surface of the groove, and exposing the nano array microstructure on the surface of the groove in ozone atmosphere to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 1 wt% of 1H,1H,2H, 2H-perfluorodecyl triethoxysilane ethanol solution for soaking for 2 days, drying at the temperature of 100 ℃, and forming a release agent layer on the surface of the nano array microstructure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and performing blow molding treatment on the polymer tube body, wherein the temperature of the blow molding treatment is 145 ℃, the pressure is 15atm, and the pressure maintaining time is 3min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Example 7
The polymer sacculus of this application embodiment adopts polyurethane to make, and polymer sacculus surface has micro-nano structure, and micro-nano structure's height is 3 mu m, and the diameter of nanometer column granule is 320 ~ 380nm, and distribution density is 19/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 8, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 6.8cm, and carrying out electrolytic polishing for 7min under the conditions that the voltage is 18V and the temperature is 10 ℃ to obtain a first-order crude product of the half-mould.
S20: placing the first-stage crude product in phosphoric acid water solution (0.16mol/L), taking the first-stage crude product as a positive electrode and titanium as a negative electrode, wherein the distance between the positive electrode and the negative electrode is 7.1cm, the voltage is 155V, and the current density is 9mA/cm2And carrying out first anodic oxidation at the temperature of 10 ℃ for 100min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 6 wt% phosphoric acid and 1.8 wt% chromic acid, washing in a water bath at 65-70 ℃, and then washing with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution of phosphoric acid (0.16mol/L), taking the third-order crude product as a positive electrode, titanium as a negative electrode, and the distance between the positive electrode and the negative electrode is 7.1cm, and the current density is 9mA/cm under the condition that the voltage is 155V and the current density is 9mA/cm2And carrying out second anodic oxidation at the temperature of 10 ℃ for 90min to obtain a half mold with a nano array microstructure on the surface, wherein the nano array microstructure covers the surface of the groove, and the height of the nano array microstructure is 14 micrometers.
S50: and activating the nano array microstructure on the surface of the groove, and irradiating the nano array microstructure on the surface of the groove by adopting ultraviolet light to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 2 wt% of 1H,1H,2H, 2H-perfluorodecyl triethoxysilane ethanol solution for soaking for 2 days, drying at the temperature of 130 ℃, and forming a release agent layer on the surface of the nano structure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and carrying out blow molding on the polymer tube body, wherein the blow molding temperature is 120 ℃, the pressure is 15atm, and the pressure maintaining time is 2min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Example 8
The polymer balloon is made of polyamide 12, the surface of the polymer balloon is provided with a micro-nano structure, the height of the micro-nano structure is 3 micrometers, the diameter of nano columnar particles is 255-310 nm, and the distribution density is 35 particles/mm2。
The mould of this application embodiment is pure aluminium product, and the mould includes two half moulds, and the relative one side of two half moulds is seted up flutedly respectively, and two half moulds close the back, and two recesses constitute sacculus shaping chamber jointly.
The preparation method of the polymer balloon comprises the following steps:
s10: placing the half mould into a mould with a volume ratio of 1: 7, taking the half-mould as an anode and titanium as a cathode, wherein the distance between the anode and the cathode is 8cm, and carrying out electrolytic polishing under the conditions that the voltage is 16V and the temperature is 8 ℃ for about 5min to obtain a first-order crude product of the half-mould.
S20: placing the first-order crude product in phosphoric acid water solution (0.1mol/L), taking the first-order crude product as an anode, titanium as a cathode, the distance between the anode and the cathode is 8cm, the voltage is 155V, and the current density is 6mA/cm2And carrying out first anodic oxidation at the temperature of 10 ℃ for 105min to obtain a second-stage rough product of the half mould.
S30: and (3) immersing the second-stage crude product into a mixed solution of 5 wt% phosphoric acid and 1.2 wt% chromic acid, washing in a water bath at 72-75 ℃, and then washing with water to obtain a third-stage crude product.
S40: immersing the third-order crude product in an aqueous solution (0.1mol/L) of phosphoric acid, taking the third-order crude product as a positive electrode, titanium as a negative electrode, and taking the distance between the positive electrode and the negative electrode as 8cm, wherein the voltage is 155V, and the current density is 6mA/cm2And carrying out second anodic oxidation at the temperature of 10 ℃ for 100min to obtain the half mold with the surface provided with the nano-array microstructure, wherein the nano-array microstructure covers the surface of the groove, and the height of the nano-array microstructure is 18 micrometers.
S50: and activating the nano array microstructure on the surface of the groove, and bombarding the nano array microstructure on the surface of the groove by argon low-temperature plasma to ensure that the nano array microstructure has hydrophilicity.
S60: and (3) placing the half mold into 1.5 wt% of polydimethylsiloxane ethanol solution to be soaked for 2 days, drying at the temperature of 100 ℃, and forming a release agent layer on the surface of the nano structure to obtain the half mold.
S100: the two half molds are closed tightly, and the two grooves jointly form a balloon forming cavity.
S200: providing a polymer tube body, placing the polymer tube body in a balloon forming cavity, and carrying out blow molding on the polymer tube body, wherein the blow molding temperature is 140 ℃, the pressure is 12atm, and the pressure maintaining time is 2min, so that the polymer balloon with the micro-nano structure on the surface is obtained.
Comparative example
The polymer balloon is prepared from polyamide 12 (nylon 12), and the surface of the polymer balloon is smooth.
Performance test (one): drug load testing
And spraying rapamycin medicaments on the polymer balloons of the examples 1-8 and the comparative example according to the same spraying process parameters to prepare 5 medicament-coated polymer balloon catheters with the specification of 3.0 multiplied by 20mm, and carrying out qualitative and quantitative detection on the coating medicaments by using acetonitrile as an extraction solvent and using a high performance liquid chromatography after the rapamycin medicaments are attached to the surfaces of the polymer balloons, wherein the polymer balloon adopting a dip coating mode for spraying the medicaments is the comparative example 1, and the polymer balloon adopting ultrasonic atomization for spraying the medicaments is the comparative example 2. Two replicates of each sample were run. Chromatographic conditions and system applicability test: bonding with octadecyl alkane as filler; mixing acetonitrile: water (70:30) as the mobile phase; column temperature: 40 ℃; flow rate: 1 mL/min; and (3) checking wavelength: 277 nm; the theoretical plate number is not lower than 1500 calculated according to rapamycin peak.
The calculation formula is as follows:
w is the total dose of the balloon, mu g; c1-content of test solution drug, μ g/mL; v1-constant volume, mL; s-balloon surface area, mm2(ii) a Q-balloon drug content, μ g/mm2。
The test results are shown in table 1.
TABLE 1
From the results, the polymer balloon catheter is treated by the AAO nanostructure of the application, the original dip-coating mode is adopted to attach the medicine, the drug-loading rate of the balloon is improved by 20-50% compared with that of the balloon which is not treated by the AAO, and even if the ultrasonic atomization spraying mode optimized by the spraying technology is adopted, the drug-loading rate of the balloon can be improved by 9.5-25% compared with that of the balloon which is not treated by the AAO. The polymer balloon surface of the invention has a micro-nano structure, can effectively improve the drug loading of the polymer balloon, and has great significance in reducing the loss of high-value drugs and the use safety of the drugs.
Performance test (ii): loss and release rate testing
Spraying the polymer balloons of the examples 1-8 and the comparative example 1 with the same spraying process parameters with rapamycins, preparing 5 balloon catheters with the drug coating, wherein each group is 3.0 multiplied by 20mm in specification, after the rapamycin drugs are attached to the surfaces of the polymer balloons, selecting a simulated blood vessel with the same diameter according to the diameter of the polymer balloon, penetrating the guide catheter and the guide wire into the simulated blood vessel, filling the pipeline with release liquid, taking a set of drug-coated balloon catheter sample, pushing the polymer balloon into the guide catheter through the guide wire within 60s, after the polymer balloon is pushed to a preset position, the balloon catheter is taken out to cut off the position of the polymer balloon, the content of the drug left on the polymer balloon is tested according to a performance test method, and the initial result W of the drug content is tested by combining the performance test method.0(μ g), loss rate testing was performed and two replicates were run for each sample. The following formula is used for calculation:
C2-balloon surface residual drug content, μ g/mL; v2-volume to volume, mL; w is total balloon dose, μ g.
When the polymer saccule is pushed toAfter the position is reached, the polymer saccule is pressurized and expanded by using an inflation pressure pump according to a saccule catheter compliance table, the drug coating part of the polymer saccule is ensured to be fully attached to the inner wall of the simulated blood vessel, and the pressure is maintained for 60 +/-2 seconds. Immediately taking out the polymer saccule after pressure relief, and carrying out the content W of the drug left on the saccule according to the performance test (I)2(μ g) and combined with the initial result W of the drug content0(μ g), loss rate results from performance test (II) S, drug release rate test was performed, and each sample was run in duplicate. The following formula is used for calculation:
the test results are shown in table 2.
TABLE 2
According to the results, compared with the original medicament attached by a dip-coating method without AAO treatment, the polymer balloon treated by AAO of the invention is simulated to be used clinically, the medicament loss rate is reduced by 25-50% compared with that without AAO treatment, and the medicament release rate is improved by 10-20%; even if the ultrasonic atomization spraying mode after the spraying technology is optimized is adopted, the medicine loss rate can be reduced by 40-60% compared with that of the medicine without AAO treatment, and the medicine release rate is improved by 10-20%. The polymer balloon surface of the invention has a micro-nano structure, which can remarkably improve the technical problems of high drug loss rate, low release rate and the like faced by the current drug balloon.
The above description is only exemplary of the present application and should not be taken as limiting the present application, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present application should be included in the protection scope of the present application.
Claims (10)
1. A polymeric balloon, characterized in that: the outer surface of the polymer balloon is provided with a micro-nano structure, and the polymer balloon is used for conveying the medicine in vivo.
2. The polymer balloon of claim 1, wherein: the micro-nano structure comprises a plurality of nano columnar particles which are vertically distributed.
3. The polymer balloon of claim 1, wherein: the micro-nano structure comprises a plurality of nano columnar particles, and the diameter of each nano columnar particle is 20-400 nm; and/or the distribution density of the micro-nano structure is 3-50/mm2。
4. The polymer balloon of claim 1, wherein: the height of the micro-nano structure is 1-12 mu m; and/or the polymer balloon is made of thermoplastic polymer.
5. A method for preparing a polymer balloon, which is characterized in that: the polymer balloon is used for in vivo drug delivery, and the preparation method comprises the following steps:
providing a mold, wherein the mold is provided with a balloon molding cavity, and the surface of the cavity wall of the balloon molding cavity is provided with a nano array microstructure for forming a micro-nano structure;
and providing a polymer tube body, and placing the polymer tube body in the balloon forming cavity for thermoplastic forming treatment to obtain the polymer balloon with the surface having the micro-nano structure.
6. The method of making a polymeric balloon of claim 5, wherein: the temperature of the thermoplastic treatment is 120-180 ℃, the pressure of the thermoplastic treatment is 5-15 atm, and the pressure maintaining time is 2-20 min.
7. The method of making a polymeric balloon of claim 5, wherein: the mold is a pure aluminum product, the mold is provided with a balloon forming cavity, the cavity wall of the balloon forming cavity is provided with a nano-array microstructure for forming a micro-nano structure, and the nano-array microstructure on the surface of the balloon forming cavity is prepared by an anodic oxidation method.
8. The method of making a polymeric balloon of claim 7, wherein: the mold comprises two half molds, wherein one sides of the two half molds, which are opposite to each other, are respectively provided with a groove, after the two half molds are closed, the two grooves jointly form the balloon forming cavity, and the preparation method of the half molds comprises the following steps:
carrying out electrolytic polishing on the half mould to obtain a first-stage rough product of the half mould;
placing the first-order coarse product in an inorganic acid solution, taking the first-order coarse product as an anode and titanium as a cathode, and controlling the voltage to be 145-155V and the current density to be 6-20 mA/cm2Carrying out first anodic oxidation at the temperature of 8-12 ℃ to obtain a second-stage crude product of the half mould;
immersing the second-order crude product into a mixed solution of phosphoric acid and chromic acid, cleaning in a water bath at 65-75 ℃, and then cleaning with water to obtain a third-order crude product;
immersing the third-order crude product in an inorganic acid solution, taking the third-order crude product as an anode and titanium as a cathode, and performing reaction under the conditions that the voltage is 145-155V, and the current density is 6-20 mA/cm2And carrying out second anodic oxidation at the temperature of 8-12 ℃ to obtain the half mold with the surface provided with the nano array microstructure, wherein the nano array microstructure is distributed on the surface of the groove.
9. The method of making a polymeric balloon of claim 8, wherein: after the step of obtaining the mold half with the nano-array microstructure on the surface, the method further comprises the following steps:
activating the nano array microstructure on the surface of the groove to enable the nano array microstructure to have hydrophilicity;
and (3) soaking the half mold in an ethanol solution of a release agent, and drying to form a release agent layer on the surface of the nano structure.
10. The method of making a polymeric balloon of claim 9, wherein: the method for activating the nano-structure on the surface of the groove comprises the following steps:
and irradiating the nano structure on the surface of the groove by adopting ultraviolet light, or exposing the nano array microstructure on the surface of the groove in ozone atmosphere, or bombarding the nano array microstructure on the surface of the groove by adopting argon low-temperature plasma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111584389.5A CN114504723A (en) | 2021-12-22 | 2021-12-22 | Polymer balloon and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111584389.5A CN114504723A (en) | 2021-12-22 | 2021-12-22 | Polymer balloon and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114504723A true CN114504723A (en) | 2022-05-17 |
Family
ID=81547453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111584389.5A Pending CN114504723A (en) | 2021-12-22 | 2021-12-22 | Polymer balloon and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114504723A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115054737A (en) * | 2022-06-27 | 2022-09-16 | 中国科学院金属研究所 | Nickel-titanium alloy intravascular stent surface coating for promoting endothelialization and preparation method thereof |
Citations (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020094427A1 (en) * | 2001-01-16 | 2002-07-18 | Edwards Christopher M. | Thermoplastic composite reinforced thermoform and blow-molded article |
| US20060229712A1 (en) * | 2005-04-12 | 2006-10-12 | Advanced Cardiovascular Systems, Inc. | Method of stent mounting to form a balloon catheter having improved retention of a drug delivery stent |
| CN1874799A (en) * | 2003-10-14 | 2006-12-06 | 库比医药公司 | Medical device with electrospun nanofibers |
| US20110022027A1 (en) * | 2008-03-12 | 2011-01-27 | Hosokawa Micron Corporation | Drug-eluting catheter and method of manufacturing the same |
| CN102844473A (en) * | 2010-03-25 | 2012-12-26 | 三菱丽阳株式会社 | Method of producing anodized alumina, examination device and examination method thereof |
| CN102892930A (en) * | 2010-03-25 | 2013-01-23 | 三菱丽阳株式会社 | Anodizing device, treatment tank, method for producing roll-shaped mold for imprinting, and method for producing article having plurality of protruding parts on surface |
| US20130261548A1 (en) * | 2012-03-27 | 2013-10-03 | Cook Medical Technologies Llc | Medical balloon with particles therein |
| CN104056341A (en) * | 2014-06-24 | 2014-09-24 | 深圳市金瑞凯利生物科技有限公司 | Medicament balloon and preparation method thereof |
| CN104651904A (en) * | 2015-01-30 | 2015-05-27 | 北京大学 | Preparation method of anodic-aluminum-oxide-based nano imprinting template |
| CN105473094A (en) * | 2013-08-22 | 2016-04-06 | 波士顿科学国际有限公司 | Medical balloon with patterned concave wall profile |
| CN107206218A (en) * | 2015-05-15 | 2017-09-26 | 尼普洛株式会社 | balloon catheter |
| CN108030995A (en) * | 2017-12-22 | 2018-05-15 | 鼎科医疗技术（苏州）有限公司 | medicinal balloon processing method |
| CN110241450A (en) * | 2019-07-19 | 2019-09-17 | 广东工业大学 | A kind of porous anodized aluminum template and its preparation method and application |
| CN110323285A (en) * | 2019-04-30 | 2019-10-11 | 山东大学 | A kind of multi-function membrane and the preparation method and application thereof based on micro-nano compound structure and coating |
| CN111132720A (en) * | 2014-10-16 | 2020-05-08 | W.L.戈尔及同仁股份有限公司 | Blow molded composite apparatus and method |
| CN111825783A (en) * | 2020-07-01 | 2020-10-27 | 清华大学深圳国际研究生院 | Polymer material with micro-nano hierarchical structure and preparation method thereof |
| CN112618922A (en) * | 2020-12-30 | 2021-04-09 | 上海心至医疗科技有限公司 | Preparation method of drug balloon, prepared drug balloon and application thereof |
| CN112721352A (en) * | 2020-12-30 | 2021-04-30 | 中南大学 | Preparation method of metal-plastic mixed structural part based on secondary anodic oxidation method |
| CN113427784A (en) * | 2021-06-29 | 2021-09-24 | 伊索曼(中山)医疗器械有限公司 | Manufacturing method of medical balloon surface bulge and medical balloon |
-
2021
- 2021-12-22 CN CN202111584389.5A patent/CN114504723A/en active Pending
Patent Citations (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020094427A1 (en) * | 2001-01-16 | 2002-07-18 | Edwards Christopher M. | Thermoplastic composite reinforced thermoform and blow-molded article |
| CN1874799A (en) * | 2003-10-14 | 2006-12-06 | 库比医药公司 | Medical device with electrospun nanofibers |
| US20060229712A1 (en) * | 2005-04-12 | 2006-10-12 | Advanced Cardiovascular Systems, Inc. | Method of stent mounting to form a balloon catheter having improved retention of a drug delivery stent |
| US20110022027A1 (en) * | 2008-03-12 | 2011-01-27 | Hosokawa Micron Corporation | Drug-eluting catheter and method of manufacturing the same |
| CN102844473A (en) * | 2010-03-25 | 2012-12-26 | 三菱丽阳株式会社 | Method of producing anodized alumina, examination device and examination method thereof |
| CN102892930A (en) * | 2010-03-25 | 2013-01-23 | 三菱丽阳株式会社 | Anodizing device, treatment tank, method for producing roll-shaped mold for imprinting, and method for producing article having plurality of protruding parts on surface |
| US20130261548A1 (en) * | 2012-03-27 | 2013-10-03 | Cook Medical Technologies Llc | Medical balloon with particles therein |
| CN105473094A (en) * | 2013-08-22 | 2016-04-06 | 波士顿科学国际有限公司 | Medical balloon with patterned concave wall profile |
| CN104056341A (en) * | 2014-06-24 | 2014-09-24 | 深圳市金瑞凯利生物科技有限公司 | Medicament balloon and preparation method thereof |
| CN111132720A (en) * | 2014-10-16 | 2020-05-08 | W.L.戈尔及同仁股份有限公司 | Blow molded composite apparatus and method |
| CN104651904A (en) * | 2015-01-30 | 2015-05-27 | 北京大学 | Preparation method of anodic-aluminum-oxide-based nano imprinting template |
| CN107206218A (en) * | 2015-05-15 | 2017-09-26 | 尼普洛株式会社 | balloon catheter |
| CN108030995A (en) * | 2017-12-22 | 2018-05-15 | 鼎科医疗技术（苏州）有限公司 | medicinal balloon processing method |
| CN110323285A (en) * | 2019-04-30 | 2019-10-11 | 山东大学 | A kind of multi-function membrane and the preparation method and application thereof based on micro-nano compound structure and coating |
| CN110241450A (en) * | 2019-07-19 | 2019-09-17 | 广东工业大学 | A kind of porous anodized aluminum template and its preparation method and application |
| CN111825783A (en) * | 2020-07-01 | 2020-10-27 | 清华大学深圳国际研究生院 | Polymer material with micro-nano hierarchical structure and preparation method thereof |
| CN112618922A (en) * | 2020-12-30 | 2021-04-09 | 上海心至医疗科技有限公司 | Preparation method of drug balloon, prepared drug balloon and application thereof |
| CN112721352A (en) * | 2020-12-30 | 2021-04-30 | 中南大学 | Preparation method of metal-plastic mixed structural part based on secondary anodic oxidation method |
| CN113427784A (en) * | 2021-06-29 | 2021-09-24 | 伊索曼(中山)医疗器械有限公司 | Manufacturing method of medical balloon surface bulge and medical balloon |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115054737A (en) * | 2022-06-27 | 2022-09-16 | 中国科学院金属研究所 | Nickel-titanium alloy intravascular stent surface coating for promoting endothelialization and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jiang et al. | Surface functionalization–a new functional dimension added to 3D printing | |
| EP2146757B1 (en) | Stents with drug reservoir layer and methods of making and using the same | |
| CN104558658B (en) | In the method for interposing catheter surface prepares coating, interposing catheter and intervention apparatus | |
| CN103800987B (en) | Medical balloon and preparation method thereof | |
| CN200980748Y (en) | Porous drug release structure of a drug eluting device | |
| JP2009542359A (en) | Medical device with selective covering | |
| JP2016508776A (en) | Substrate coating | |
| JP2010536431A (en) | Medical device having a sol-gel ceramic region with molded submicron surface features | |
| CN101199873A (en) | Nanometer-level hole drug release structure for drug eluting instrument and preparation method thereof | |
| CN114504723A (en) | Polymer balloon and preparation method thereof | |
| CN101161299A (en) | Hole and polymer-loaded drug release structure and preparation method thereof | |
| CN112770900A (en) | Antibacterial material, laminate, antibacterial laminate, medical member, method for producing antibacterial material, method for producing antibacterial laminate, and antibacterial method | |
| CN111671983A (en) | Biomedical material and preparation method thereof | |
| CN101229396A (en) | A kind of vascular stent and preparation method thereof | |
| CN101721753A (en) | Absorbable magnesium alloy bracket of inorganic and organic antiseptic biocompatible composite coating and preparation method thereof | |
| CN1569270B (en) | Method for preparing cardiovascular drug eluting stent | |
| CN113648114A (en) | Coated stent and preparation method thereof | |
| CN111803252B (en) | Stainless steel, preparation method thereof and drug eluting stent | |
| JP2014530058A (en) | Intervention medical device and manufacturing method thereof | |
| JP5217026B2 (en) | Stent and manufacturing method thereof | |
| CN203017550U (en) | Medical balloon | |
| CN204600790U (en) | Medicine slow-release magnesium alloy bracket | |
| JP7275269B2 (en) | Medical tube body and its preparation method | |
| CN114425126A (en) | Preparation method of medical balloon and medical balloon | |
| CN104177641B (en) | A kind of method for preparing lubricating coating in medical polyvinyl material surface |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220517 |
|
| RJ01 | Rejection of invention patent application after publication |