CN110201243A - A kind of combination drug coating foley's tube and preparation method thereof - Google Patents
A kind of combination drug coating foley's tube and preparation method thereof Download PDFInfo
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- CN110201243A CN110201243A CN201910613891.0A CN201910613891A CN110201243A CN 110201243 A CN110201243 A CN 110201243A CN 201910613891 A CN201910613891 A CN 201910613891A CN 110201243 A CN110201243 A CN 110201243A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61M25/1002—Balloon catheters characterised by balloon shape
-
- 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
- A61M25/1036—Making parts for balloon catheter systems, e.g. shafts or distal ends
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/43—Hormones, e.g. dexamethasone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
-
- 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
-
- 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
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
-
- 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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/02—General characteristics of the apparatus characterised by a particular materials
- A61M2205/0238—General characteristics of the apparatus characterised by a particular materials the material being a coating or protective layer
Abstract
The present invention relates to a kind of combination drug coating foley's tubes and preparation method thereof, belong to the field of medical instrument technology.A kind of combination drug coating foley's tube, including sacculus and the medication coat for being covered on balloon surface；Medication coat includes active medicine and carrier；Carrier includes low molecular weight carriers and high molecular weight carrier, and the mass ratio of active medicine and high molecular weight carrier in medication coat is 0.2~20, and the mass ratio of low molecular weight carriers and high molecular weight carrier is 0.5~10, and drugloading rate is 0.5~10ug/mm2.The present invention takes into account drug and quickly reprints and reduce transmission process loss.Guarantee the integrality of the coating of medicinal balloon；After drug is reprinted to vascular tissue, some drugs are temporarily fixed to not discharge in carrier, with the degradation and/or dissolution of high molecular weight carrier, drug is just gradually discharged, to extend the duration of drug in the tissue, for longer periods inhibit hyperblastosis, to reduce endovascular restenosis rate.
Description
Technical field
The present invention relates to a kind of combination drug coating foley's tubes and preparation method thereof, belong to the field of medical instrument technology.
Background technique
Percutaneous transluminal angio plasty (PTA) experienced bare ball capsule, bare mental stents, drug from 1970s so far
FirebirdTM, medicine-coated balloon stage.Wherein medicine-coated balloon (Drug Coated Balloon, DCB), one side medicine
Object can inhibit smooth muscle cell hyperplasia effectively to reduce restenosis incidence, on the other hand be not necessarily to Stent Implantation, thus
Reduce the inflammatory reaction of endangium, reduces Thrombosis in sten risk, shorten the duplex antiplatelet time, reduce
Bleeding risk.In addition, in the clinical research of coronary artery disease, DCB treatment in-stent restenosis, Small vessel,
Show better validity and safety when bifurcated lesions, and DCB apply also for High risk of bleeding patient, taking orally it is anti-
Solidifying drug or the patient for carrying out surgical operation in the recent period.DCB also takes in the primary narrow and in-stent restenosis for the treatment of peripheral blood vessel
Obtained preferable curative effect.DCB is just had become a hot topic of research with the advantage of its " intervening without implantation ".
First generation medicinal balloon is released so far from German B.Braun company, has the medicinal balloon of more companies both at home and abroad
At home and abroad list.The medicinal balloon of B.Braun company using contrast agent Iopromide as carrier and taxol together as
Rouge can be improved due to the water-wet behavior of Iopromide coated in treatment coronary artery reangiostenosis on foley's tube in medication coat
Soluble drug taxol to the reprinting rate of vascular tissue, ensure that the product in the validity of clinical use, but the coating structure
Medicinal balloon product during clinical use, there are certain complication rate, especially Iopromides to belong to larger
Hydrophilic molecule, the single use of this carrier makes to will appear during its clinical use that conveyance loss is serious, and coating generates
Particle is more, and particle is larger, causes the risk of downstream blood vessel blockage.Therefore, the changing for excipients in subsequent DCB exploitation
It quick is reprinted and the conveyance loss of drug is excessive and particle bring into there is still a need for lasting progress, need to take into account Balance Pharmaceuticals
Risk.
Application No. is the patents of CN200880001141.8, are related to a kind of for therapeutic agent to be delivered to the Medical treatment device of tissue
Tool.The medical instrument has a layer being covered on the outer surface of the medical instrument.The layer contains therapeutic agent and adds
Add agent.In certain embodiments, the additive has hydrophilic segment and the affine part of drug, wherein the affine portion of the drug
Be divided at least one of following part: hydrophobic part by hydrogen bond and the affine part of the therapeutic agent and passes through Van der Waals
Interaction and the affine part of the therapeutic agent.In embodiments, the additive is water-soluble.In other embodiment party
In case, the additive is at least one of surfactant and compound, and the molecular weight of the compound is 80-
750 or tool there are four the above hydroxyl group.Using the amphiphilic substance of hydrophilic and oleophilic, as carrier, liposoluble may be implemented in the patent
Transient equilibrium between property drug and vascular tissue's hydrophily, enables lipophilic drugs more preferably to contact reprinting with vascular tissue,
But the patent coating use carrier it is single, can't resolve drug quick release reprint and drug conveyance loss it is excessive with
And the contradiction between particle.
Application No. is the patent of CN201310732989.0, the drug coated balloon catheter being related to includes sacculus and is covered on
The medication coat of balloon surface.The medication coat includes active medicine and carrier；The active medicine is taxol, thunder pa is mould
Element, paclitaxel derivatives or rapamycin derivative；The carrier includes acylate and polyalcohol, in the medication coat
The mass ratio of active medicine and carrier is 0.2~100, and the mass ratio of the organic acid and polyalcohol is (0.2~5): 1.Drug
Acylate and polyalcohol in coating play a role jointly, prevent from being presented to target site prodrug in foley's tube and cross premature disconnection
It puts, drug is promoted to be absorbed from balloon surface quick release and by target tissue, not only can be reduced drug loss in transmission process but also have
Preferable drug reprints effect.
Application No. is the patents of CN201510124482.6, are related to a kind of medicine eluting balloon catheter, including conduit, sacculus
Ontology and balloon surface further include hydrophilelipophile bottom and drug-carried coat, and the hydrophilelipophile bottom is located above balloon surface,
Drug-carried coat is located at hydrophilelipophile substratum, and the drug-carried coat is made of polymer and drug.The medicament elution sacculus is led
Pipe has structure simple, and production process is simple, and drug loss is few in transmission process, and the drug on sacculus after intervention operation
The characteristics of less residue.The patent introduces a kind of composite coating structure, which is divided into hydrophilelipophile bottom and drug applies
Layer, the primer coating of hydrophilelipophile can help drug-carried coat to load to balloon surface and form stable coatings, reduce transmission process
Loss, but the pharmaceutical carrier of the coating is polymer, larger particle easy to form causes the risk of downstream blood vessel embolism.
The key difficulties of medicinal balloon coating be how to realize the combination of medication coat and balloon surface and drug to
Balance between vascular tissue's release reprinting.Stable bond between medication coat and balloon surface may be implemented medication coat and exist
Less loss in foley's tube transmission process reduces the influence to downstream blood vessel；Meanwhile drug is to the quick of vascular tissue
Release may be implemented greater proportion of drug reprinting and be adsorbed onto target vessel, reach the mesh for effectively inhibiting smooth muscle cell hyperplasia
, commercialized product coating structure and patent coating technology are difficult to realize take into account this two key performances at present, and therefore, having must
Novel composite coating is researched and developed to realize the balance of conveyance loss and quick release.In addition the prior art is all to rely on
The tissue absorption properties and crystallinity of drug itself go Drug controlled release to compare with drug stent, and the drug of medicinal balloon is released
The period put is shorter, this exactly leads to insufficient reason one of of the medicinal balloon in terms of inhibiting restenosis.
Summary of the invention
The present invention can not take into account the shortcomings that transmission process loss is quickly reprinted and reduced to drug for the prior art, solve
Certainly the technical issues of, is to provide a kind of NEW TYPE OF COMPOSITE coating, and the composite coating is with high molecular weight carrier and low molecular weight carriers group
Cooperation is pharmaceutical carrier and hyperblastosis drug is inhibited to form evenly dispersed coating.
To achieve the above object, the present invention uses following technical scheme.
A kind of combination drug coating foley's tube, which is characterized in that applied including sacculus and the drug for being covered on balloon surface
Layer；The medication coat includes active medicine and carrier；The active medicine be rapamycin, Zuo Tamosi, taxol, fill in
One or more of meter Song and its derivative；The carrier includes low molecular weight carriers and high molecular weight carrier, low molecular weight
The molecular weight of carrier is 50~2000Da, and the molecular weight of high molecular weight carrier is 400~40000Da, in the medication coat
The mass ratio of active medicine and high molecular weight carrier is 0.2~20, and low molecular weight carriers and the mass ratio of high molecular weight carrier are
0.5~10, the active medicine is 0.5~10ug/mm in the unit area drugloading rate of balloon surface2。
The low molecular weight carriers are selected from one of polyalcohol, phosphatide, acylate, Laurocapram, urea or several
Kind.
The polyalcohol includes being selected from one or more of polyethylene glycol, xylitol, mannitol, sorbierite, amino alcohol；
The phosphatide in phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylserine, phosphatidyl glycerol and phosphatidylinositols one
Kind is several；Acylate is selected from one of stearate, benzoate, oxalates, aspartate, nicotinate or several
Kind.
The molecular weight of the low molecular weight carriers is 50~200Da or 200~2000Da.
The high molecular weight carrier is selected from polyalcohol, polyester substance, poloxamer, Iopromide, polyvinylpyrrolidine
One or more of ketone, tween, molecular weight are 400~20000Da or 5000~40000Da.
The polyalcohol is one or more of polyethylene glycol and polysorbate；Polyester substance is selected from polylactic acid, gathers
Glycolic, polylactic-co-glycolic acid, poly butylene succinate, polyhydroxyalkanoate, polycaprolactone, polyadipate
One or more of glycol ester or polyhydroxybutyrate valerate copolymer.
The active medicine and high molecular weight carrier are present in combination drug coating in the form of composite particles, discontinuously
" island phase " structure, the partial size of each " island phase " structure is less than or equal to 20 μm.
The mass ratio of active medicine and high molecular weight carrier in " island phase " structure is 0.2~20, is higher than the ratio,
The medication amount of high molecular weight carrier encapsulating is less, can not maintain longer Tissue；Lower than the ratio, drug is big
High molecular weight carrier package is measured, drug release rate is slow, and drug is also unable to reach effective Tissue in short term.
The mass ratio of active medicine and high molecular weight carrier in the medication coat is 0.5~2, this ratio influences
The release of drug in " island phase " structure, and then Tissue is influenced, the mass ratio of drug and high molecular weight carrier is lower than
0.5, it may result in that drug release is slow, and to reach effective Tissue may need higher dose to maintain；
And ratio is higher than 2, then may be such that the drug of encapsulating is less, most of drug is caused to discharge in the early stage, can not maintain longer
The Tissue of phase (such as 60 days).The mass ratio of low molecular weight carriers and high molecular weight carrier is 1~5, low molecule loading gage
The purpose of body is to form continuous phase, and ratio is too low, and high molecular weight carrier can not form " the island phase " of dispersion, and de- carry of drug is caused to be stranded
It is difficult；Ratio is too high, and the buried drug that is not easy in low molecular weight carriers of drug/high molecular weight carrier can be made quickly to be transferred to
Tissue.The active medicine is preferably 0.5~4ug/mm in the unit area drugloading rate of balloon surface2, suitable drug/
Under carrier ratio and process conditions, the effect of the reprinting rate of drug and the sustained release of drug is promoted, the use of drug can be further decreased
It measures to 0.5~4ug/mm2。
High molecular weight carrier is combined closely with drug, is evenly dispersed into low molecular weight carriers, and " island phase " structure is formed,
Conducive to drug from the de- load on sacculus.
The conjugate of high molecular weight carrier and drug, which is mixed into the carrier of low molecular weight, forms heterogeneous system, macromolecule
The conjugate of loading gage body and drug is dispersed in continuous low molecular weight carriers, as being dispersed in ocean island, referred to as " island
Phase " structure.Coating is after reaching target position, balloon dilatation, and " marine facies " structure of low molecular weight carriers is soluble easily in water, so that
" island phase " can be downloaded in vascular tissue from idling de- on sacculus rapidly.On the other hand, its smaller specific surface area of the size of " island phase "
Bigger, the surface area of unit mass is bigger, also bigger with tissue contact surface product, to accelerate the suction-operated of vascular tissue；
And when the size of " island phase " is less than endangium gap, " island phase " substance can penetrate endangium or/and middle film, it is buried in
In blood vessel, so that drug be avoided to be lost by washing away for blood.
The present invention provides the preparation method of three kinds of medicine-coated balloons, as follows respectively:
Method one: a kind of medicine-coated balloon preparation method, this method comprises the following steps:
1) solution 1 for configuring high molecular weight carrier and drug, is sufficiently mixed；
2) solution 2 for configuring low molecular weight carriers, is sufficiently mixed；
3) solution 1 and solution 2 are mixed to get coating solution；
4) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
5) drug coated balloon catheter is obtained after coating is dry.
The preparation method is simple, easily operated, and technology stability is good.
Method two: a kind of medicine-coated balloon preparation method, this method comprises the following steps:
1) high molecular weight carrier and drug are dissolved into organic solvent, are sufficiently mixed to obtain solution 3；Wherein solvent is selected from
One of chloroform, methylene chloride, ethyl acetate, tetrahydrofuran, acetone and acetonitrile or multiple combinations.
2) low molecular weight carriers are dissolved in solvent, are sufficiently mixed to obtain solution 4；Wherein solvent is selected from methanol, ethyl alcohol, isopropyl
One of alcohol and water is a variety of；
3) polyvinylpyrrolidone or polyvinyl alcohol are dissolved in aqueous solution, obtain solution 5；
4) solution 3 is passed through into Ultrasonic spraying and stirs 1h or more into the solution 5 or water of high-speed stirred, then filtered, clearly
Wash and obtain after drying the drug bearing microsphere that partial size is no more than 20um；
5) drug bearing microsphere obtained in step 4) is mixed into solution 4 and obtains coating solution；
6) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
7) drug coated balloon catheter is obtained after coating is dry.
The drug bearing microsphere that the preparation method obtains can effective entrapped drug, the drug release of longer-term can be maintained.
Method three: a kind of medicine-coated balloon preparation method, this method comprises the following steps:
1) high molecular weight carrier and drug are dissolved into organic solvent, are sufficiently mixed to obtain solution 6；Wherein solvent is selected from
One of chloroform, methylene chloride, ethyl acetate, tetrahydrofuran, acetone and acetonitrile or multiple combinations, and macromolecule carrier
Insoluble in methanol, ethyl alcohol, isopropyl alcohol and water.
2) low molecular weight carriers are dissolved in solvent, are sufficiently mixed to obtain solution 7；Wherein solvent is selected from methanol, ethyl alcohol, isopropyl
One of alcohol and water is a variety of；
3) solution 6 is passed through into Ultrasonic spraying into the solution 7 of high-speed stirred, obtained suspended with drug bearing microsphere
Liquid, the solution are coating solution；
4) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
5) drug coated balloon catheter is obtained after coating is dry.
Method three is the optimization of preceding 2 kinds of methods, and not only preparation method is simple, but also high molecular weight carrier can be encapsulated preferably
Drug maintains longer drug release.
The principle of the present invention is as follows:
The present invention is mixed with low molecular weight carriers using high molecular weight carrier, wherein the characteristics of high molecular weight carrier be: 1.
The linear backbone of molecule is conducive to form drug package and constraint effect, forms stable coating, be 2. wrapped in it
Internal drug is gradually discharged with the gradually dissolution or degradation of high molecular weight carrier, is achieved the effect that medicament slow release, can also be kept away
Exempting from drug violent release causes local organization drug concentration beyond toxic concentration.
The characteristics of low molecular weight carriers is: 1. small molecule compound can be formed with drug molecule and/or medicinal composition
Evenly dispersed coating structure；2. good water solubility can quickly dissolve, achieve the purpose that drug is quickly carried from sacculus is de-；3. with
Tissue affinity is good, can promote the reprinting of drug.
Carrier by having the characteristics that both combines the composite coating structure to be formed and has the advantage that
1. medication coat is uniformly dispersed, stablize；
2. under the protective effect of high molecular weight carrier, coating stable, during conduit is delivered to target lesion position,
Drug loss is few；
3. high molecular weight carrier is combined closely with drug, it is evenly dispersed into low molecular weight carriers, forms " island phase " knot
Structure, conducive to drug from the de- load on sacculus.
4. low molecular weight carriers and inhibition hyperblastosis drug and/or medicinal composition form evenly dispersed coating knot
Structure, the dissolution of low molecular weight carriers are conducive to the disintegration of coating, so that drug on sacculus from quickly reprinting into tissue；
5. high molecular weight carrier is to the encapsulating effect of drug so that drug release period is longer, tissue drug concentration is maintained
Time is long.
Background technology part patent and the existing sacculus of marketed drug have two:
Firstly, drug reprinting rate is low, it is not higher than 5%, more drugs are lost in sacculus transmission process, a large amount of medicine
Object is washed to downstream blood vessel or organ；Therefore the reprinting rate for improving drug, on the one hand can effectively inhibit hyperplasia, it is another can
The initial drugloading rate of medicinal balloon is reduced, the medication amount for being washed and organizing to downstream is reduced, mitigates drug to downstream blood vessel or device
The toxic side effect of official.
Second, it is short to maintain the time for active drug concentration in tissue, is no more than 30 days, because the prior art is all by drug
The tissue absorption properties and crystallinity of itself go Drug controlled release to compare with drug stent, the drug release of medicinal balloon
Period is shorter, this exactly leads to insufficient reason one of of the medicinal balloon in terms of inhibiting restenosis.
Advantages of the present invention is as follows:
The carrier that the present invention designs includes high molecular weight carrier and low molecular weight carriers.The low molecular weight carriers are in coating
It can be embedded between drug molecule in solution, the dispersion that can promote drug in medication coat is more uniform, so that vascular tissue
It is come into full contact with drug, increases the reprinting rate of drug；It is easy to drug from sacculus after low molecular weight carriers dissolution in implantation process
Upper disengaging is reprinted to blood vessel, to improve reprinting rate；But in coating if low molecular weight carriers mass fraction too it is high will lead to it is defeated
Dose loss during sending is big, and this patent preferably goes out the ratio of low molecular weight carriers in molecular weight ranges and medicine coating carrier
Example.
High molecular weight carrier can sufficiently be combined with drug, conducive to the combination of drug and sacculus, guarantee medicine-coated balloon
Coating integrality；In addition after drug is reprinted to vascular tissue, some drugs are temporarily fixed to high molecular weight carrier
Internal and can not discharge, with the degradation and/or dissolution of high molecular weight carrier, drug is just gradually discharged, and is existed with extending drug
Duration in tissue, for longer periods inhibits hyperblastosis, to reduce endovascular restenosis rate.
Detailed description of the invention
Specific embodiments of the present invention will be described in further detail with reference to the accompanying drawing.
Fig. 1 shows the photo of island phase structure
Specific embodiment
Embodiment 1:
One, raw material:
1. drug: taxol；
2. low molecular weight carriers: mannitol, molecular weight 182；
3. high molecular weight carrier: PEG600, molecular weight 600；
4. purified water, medical grade ethyl alcohol.
Two, preparation method
1. configure high molecular weight carrier PEG600 and taxol ethanol solution, concentration 21mg/ml, wherein taxol with
The mass ratio of PEG600 is 20: 1, is sufficiently mixed to obtain solution 1；
2. configuring the aqueous solution of low molecular weight carriers mannitol, concentration 10mg/ml is sufficiently mixed to obtain solution 2；
3. the solution 2 of the solution 1 of 10ml and 1ml is mixed to get coating solution, wherein taxol and high molecular weight carrier
Mass ratio with low molecular weight carriers is 20: 1: 1；
4. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
5. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 2.5ug/mm2。
Embodiment 2:
One, raw material:
1. drug: rapamycin；
2. low molecular weight carriers: phosphatidyl choline, molecular weight 759；
3. high molecular weight carrier: poly lactide-glycolide acid (PLGA), molecular weight 20000；
4. purified water, medical level ethyl acetate, medical grade ethyl alcohol.
Two, preparation method
1. high molecular weight carrier PLGA and rapamycin are dissolved into ethyl acetate, concentration 20mg/ml, wherein thunder pa is mould
The mass ratio of element and PLGA are 1: 1, and solution 3 is obtained after being sufficiently mixed；
2. low molecular weight carriers phosphatidyl choline is dissolved in ethyl alcohol, concentration 10mg/ml, it is sufficiently mixed to obtain solution 4；
3. polyvinyl alcohol is soluble in water, obtain the poly-vinyl alcohol solution 5 of 1mg/ml；
4. by solution 3 by Ultrasonic spraying into the solution 5 of high-speed stirred, continue stir 2h, then filter, clean and
The drug bearing microsphere of PLGA/ rapamycin of the partial size no more than 20um is obtained after drying；
5. drug bearing microsphere obtained in step 4 to be mixed into the coating for obtaining that rapamycin concentrations are 10mg/ml in solution 4
Solution, rapamycin and high molecular weight carrier and the mass ratio of low molecular weight carriers are 1: 1: 1；
6. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
7. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 2.5ug/mm2。
Embodiment 3:
One, raw material:
1. drug: Zuo Tamosi；
2. low molecular weight carriers: PEG400, molecular weight 400；
3. high molecular weight carrier: poloxamer, molecular weight 3000；
4. medical grade ethyl alcohol.
Two, preparation method
1. configuring the ethanol solution of high molecular weight carrier poloxamer and Zuo Tamosi, concentration 12mg/ml, wherein helping him
The mass ratio of Mo Siyu poloxamer is 1: 5, is sufficiently mixed to obtain solution 1；
2. configuring the ethanol solution of low molecular weight carriers PEG400, concentration 10mg/ml is sufficiently mixed to obtain solution 2；
3. the solution 2 of the solution 1 of 10ml and 5ml is mixed to get coating solution, wherein Zuo Tamosi and macromolecule loading gage
Body and the mass ratio of low molecular weight carriers are 2: 10: 5；
4. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
5. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 10ug/mm2。
Embodiment 4:
One, raw material:
1. drug: dexamethasone；
2. low molecular weight carriers: xylitol, molecular weight 152；
3. high molecular weight carrier: Iopromide, molecular weight 791；
4. medical grade ethyl alcohol.
Two, preparation method
1. configure high molecular weight carrier Iopromide and dexamethasone ethanol solution, concentration 15mg/ml, wherein fill in
The mass ratio of meter Song Yu Iopromide is 1: 2, is sufficiently mixed to obtain solution 1；
2. configuring the ethanol solution of low molecular weight carriers xylitol, concentration 50mg/ml is sufficiently mixed to obtain solution 2；
3. the solution 2 of the solution 1 of 10ml and 10ml is mixed to get coating solution, wherein dexamethasone and macromolecule loading gage
Body and the mass ratio of low molecular weight carriers are 1: 2: 10；
4. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
5. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 4ug/mm2。
Embodiment 5:
One, raw material:
1. drug: taxol；
2. low molecular weight carriers: odium stearate, molecular weight 306；
3. high molecular weight carrier: polyvinylpyrrolidone, molecular weight 10000；
4. purified water, medical grade ethyl alcohol.
Two, preparation method
1. the ethanol solution of high molecular weight carrier polyvinylpyrrolidone and taxol is configured, concentration 15mg/ml, wherein
The mass ratio of taxol and polyvinylpyrrolidone is 2: 1, is sufficiently mixed to obtain solution 1；
2. configuring the aqueous solution of low molecular weight carriers odium stearate, concentration 40mg/ml is sufficiently mixed to obtain solution 2；
3. the solution 2 of the solution 1 of 10ml and 2.5ml is mixed to get coating solution, wherein taxol and macromolecule loading gage
Body and the mass ratio of low molecular weight carriers are 2: 1: 2；
4. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
5. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 1.5ug/mm2。
Embodiment 6:
One, raw material:
1. drug: taxol；
2. low molecular weight carriers: mannitol, molecular weight 182；
3. high molecular weight carrier: polysorbas20, molecular weight 1228；
4. medical grade ethyl alcohol.
Two, preparation method
1. configure high molecular weight carrier polysorbas20 and taxol ethanol solution, concentration 12mg/ml, wherein taxol with
The mass ratio of polysorbas20 is 5: 1, is sufficiently mixed to obtain solution 1；
2. configuring the ethanol solution of low molecular weight carriers PEG400, concentration 30mg/ml is sufficiently mixed to obtain solution 2；
3. the solution 2 of the solution 1 of 10ml and 1ml is mixed to get coating solution, wherein taxol and high molecular weight carrier
Mass ratio with low molecular weight carriers is 10: 2: 3；
4. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
5. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 1ug/mm2。
Embodiment 7:
One, raw material:
1. drug: taxol；
2. low molecular weight carriers: PEG2000, molecular weight 2000；
3. high molecular weight carrier: ploy DL lactic caid (PDLLA), molecular weight 40000；
4. medical grade ethyl alcohol, medical grade acetone.
Two, preparation method
1) high molecular weight carrier ploy DL lactic caid and taxol are dissolved into acetone, concentration 30mg/ml, wherein Japanese yew
The mass ratio of alcohol and PDLLA are 2: 1, are sufficiently mixed to obtain solution 6；
2) low molecular weight carriers PEG2000 is dissolved in ethyl alcohol, concentration is that 2mg/ml is sufficiently mixed to obtain solution 7；
3) 2ml solution 6 is passed through into Ultrasonic spraying into the 10ml solution 7 of high-speed stirred, obtained with drug bearing microsphere
Suspension, which is coating solution, and wherein the mass ratio of taxol and high molecular weight carrier and low molecular weight carriers is
10:5:5；
4) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
5) drug coated balloon catheter is obtained after coating is dry, the drugloading rate of sacculus unit external surface area is 0.5ug/mm2。
Comparative example:
One, raw material:
1. drug: taxol；
2. low molecular weight carriers: mannitol, molecular weight 182；
3. medical grade ethyl alcohol
Two, preparation method
1. configuring the ethanol solution of taxol and mannitol, concentration 9mg/ml, the wherein matter of rapamycin and mannitol
Amount is sufficiently mixed to obtain coating solution than being 8: 1；
2. coating solution is passed through Ultrasonic spraying to sacculus outer surface；
3. obtaining drug coated balloon catheter after coating is dry, the drugloading rate of sacculus unit external surface area is 5ug/mm2。
Embodiment 8: inside and outside test
One, material
Drug coated balloon catheter made from above-described embodiment 1-7 and comparative example carries out the survey of medicament residue rate and reprinting rate
Examination.
Two, method:
1. in-vitro simulated testing drug residual rate and reprinting rate method
In-vitro simulated test is carried out with pig coronary artery blood vessel simulation target vessel.Expand than 1.10~1.20 selections suitably according to crossing
Simulaed path is placed in constant temperature in 37 DEG C of water-bath by simulated blood vessel, and keeps the flow velocity of purified water in path in 300ml/min,
The foley's tube of preparation is inserted into simulation target vessel (the pig coronary artery blood vessel that dissection obtains) through simulaed path, sacculus is pressurized to
Then about 12atm, pressure maintaining 1min take out by foley's tube release and from in-vitro simulated test macro, continue to wash away target vessel
2min, the sacculus collecting target vessel tissue and withdrawing.It is tested on target vessel and sacculus respectively using high performance liquid chromatography (HPLC)
Remaining medicament contg, then compared with the initial dose of medicinal balloon and external reprinting rate and external medicament residue can be obtained
Rate.
Chromatographic condition:
1260 efficient liquid phase test macro of Agilent；
Chromatographic column: Agilent ZORBAX SB-C18 4.6 × 250mm, 5 μm；
Mobile phase: methanol: water: acetonitrile=23: 41: 36；
Column temperature: 30 DEG C；
Flow rate pump: 1.0ml/min；
Detection wavelength: 227nm UV detector.
2. the test method of Tissue
Medicine-coated balloon is respectively implanted in the femoral artery,superficial of healthy miniature pig, and marked, in scheduled follow-up
Time point puts to death animal, and dissection obtains the target vessel that medicine-coated balloon expands position, molten with the 0.1mol/L PBS containing heparin
Liquid (every 1000mlPBS 25000 unit containing heparin) slow rinse target vessel 3 times.
The moisture on target vessel surface is blotted, target vessel weight is then weighed；Recycle liquid chromatograph-mass spectrometer (LC-
MS the medicament contg in target vessel) is measured.
The test condition of LC-MS are as follows:
Liquid chromatogram instrument: 1200 type liquid chromatographic system of Agilent；
Mass spectrometer: the API4000 QTRAP type triple quadrupole bar tandem mass spectrometer of AB Sciex company；
Chromatographic column: the Venusil XBP C8 chromatographic column of Beaune Ai Jieer, size: 2.1 × 50mm, 5 μm；
Mobile phase condition: A phase (containing 0.1% aqueous formic acid), B phase (containing 0.1% formic acid acetonitrile solution), gradient is washed
It is de-；Column temperature: 30 DEG C；
Mass Spectrometry Conditions: ESI positive ion detection mode.
Three, experimental result
As it can be seen from table 1 compared with comparative example, using the medicine of high molecular weight carrier and low molecular weight carriers complex carrier
The external reprinting rate of object coating sacculus significantly improves；Effective Tissue to maintain the time also longer, it is contemplated that energy
Preferably play the role of long-term Inhibiting proliferation.
Table 1 is reprinted in vitro and in-vivo tissue drug concentration test experiments result
The series of detailed descriptions listed above only for feasible embodiment of the invention specifically
Protection scope bright, that they are not intended to limit the invention, those skilled in the art can be designed that a lot of other modification and
Embodiment, these modifications and implementations will be fallen within scope and spirit disclosed in the present application.More specifically, exist
The application discloses, in the range of drawings and claims, can building block to theme combination layout and/or layout carry out it is more
Kind variations and modifications.In addition to variations and improvements to the component parts and or layout, those skilled in the art are come
It says, other purposes also will be apparent.
Claims (10)
1. a kind of combination drug coating foley's tube, which is characterized in that including sacculus and the medication coat for being covered on balloon surface；
The medication coat includes active medicine and carrier；The active medicine be rapamycin, Zuo Tamosi, taxol, fill in rice
One or more of pine and its derivative；The carrier includes low molecular weight carriers and high molecular weight carrier, low molecule loading gage
The molecular weight of body is 50~2000Da, and the molecular weight of high molecular weight carrier is 400~40000Da, the work in the medication coat
Property drug and the mass ratio of high molecular weight carrier be 0.2~20, the mass ratio of low molecular weight carriers and high molecular weight carrier is 0.5
~10, the active medicine is 0.5~10ug/mm in the unit area drugloading rate of balloon surface2。
2. a kind of combination drug coating foley's tube according to claim 1, which is characterized in that the low molecular weight carriers
Selected from one or more of polyalcohol, phosphatide, acylate, Laurocapram, urea.
3. a kind of combination drug coating foley's tube according to claim 2, which is characterized in that the polyalcohol includes choosing
From one or more of polyethylene glycol, xylitol, mannitol, sorbierite, amino alcohol；The phosphatide be selected from phosphatidyl choline,
One or more of phosphatidyl-ethanolamine, phosphatidylserine, phosphatidyl glycerol and phosphatidylinositols；Acylate is selected from hard
One or more of resin acid salt, benzoate, oxalates, aspartate, nicotinate.
4. a kind of combination drug coating foley's tube according to claim 1, which is characterized in that the low molecular weight carriers
Molecular weight be 50~200Da or 200~2000Da.
5. a kind of combination drug coating foley's tube according to claim 1, which is characterized in that the high molecular weight carrier
Selected from one or more of polyalcohol, polyester substance, poloxamer, Iopromide, polyvinylpyrrolidone, tween, divide
Son amount is 400~20000Da or 5000~40000Da.
6. a kind of combination drug coating foley's tube according to claim 5, which is characterized in that the polyalcohol is poly- second
One or more of two pure and mild polysorbates；Ester be selected from polylactic acid, polyglycolic acid, polylactic-co-glycolic acid,
Poly butylene succinate, polyhydroxyalkanoate, polycaprolactone, polyethylene glycol adipate or polyhydroxybutyrate valerate
One or more of copolymer.
7. a kind of combination drug coating foley's tube according to claim 1, which is characterized in that the active medicine and height
Molecular weight carrier is present in combination drug coating in the form of composite particles, forms discontinuous " island phase " structure, each
The partial size of " island phase " structure is less than or equal to 20 μm.
8. a kind of combination drug coating foley's tube according to claim 7, which is characterized in that in " island phase " structure
Active medicine and high molecular weight carrier mass ratio be 0.2~20.
9. according to claim 1 to a kind of combination drug coating foley's tube described in any one of 8, which is characterized in that institute
The mass ratio for stating active medicine and high molecular weight carrier in medication coat is 0.5~2, low molecular weight carriers and macromolecule loading gage
The mass ratio of body is 1~5, and the active medicine is preferably 0.5~4ug/mm in the unit area drugloading rate of balloon surface2。
10. a kind of preparation method of combination drug coating foley's tube, feature described in any one of claim 1 to 9
It is, is any one following method:
Method one: a kind of medicine-coated balloon preparation method, this method comprises the following steps:
1) solution 1 for configuring high molecular weight carrier and drug, is sufficiently mixed；
2) solution 2 for configuring low molecular weight carriers, is sufficiently mixed；
3) solution 1 and solution 2 are mixed to get coating solution；
4) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
5) drug coated balloon catheter is obtained after coating is dry；
Method two: a kind of medicine-coated balloon preparation method, this method comprises the following steps:
1) high molecular weight carrier and drug are dissolved into organic solvent, are sufficiently mixed to obtain solution 3；Wherein solvent is selected from trichlorine
One of methane, methylene chloride, ethyl acetate, tetrahydrofuran, acetone and acetonitrile or multiple combinations.
2) low molecular weight carriers are dissolved in solvent, are sufficiently mixed to obtain solution 4；Wherein solvent be selected from methanol, ethyl alcohol, isopropanol and
One of water is a variety of；
3) polyvinylpyrrolidone or polyvinyl alcohol are dissolved in aqueous solution, obtain solution 5；
4) solution 3 is passed through into Ultrasonic spraying and stirs 1h or more into the solution 5 or water of high-speed stirred, then filtered, clean
With obtained after drying partial size be no more than 20um drug bearing microsphere；
5) drug bearing microsphere obtained in step 4) is mixed into solution 4 and obtains coating solution；
6) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
7) drug coated balloon catheter is obtained after coating is dry.
Method three: a kind of medicine-coated balloon preparation method, this method comprises the following steps:
1) high molecular weight carrier and drug are dissolved into organic solvent, are sufficiently mixed to obtain solution 6；Wherein solvent is selected from trichlorine
One of methane, methylene chloride, ethyl acetate, tetrahydrofuran, acetone and acetonitrile or multiple combinations, and macromolecule carrier is insoluble
In methanol, ethyl alcohol, isopropyl alcohol and water.
2) low molecular weight carriers are dissolved in solvent, are sufficiently mixed to obtain solution 7；Wherein solvent be selected from methanol, ethyl alcohol, isopropanol and
One of water is a variety of；
3) solution 6 is passed through into Ultrasonic spraying into the solution 7 of high-speed stirred, obtains the suspension with drug bearing microsphere, it should
Solution is coating solution；
4) coating solution is passed through into Ultrasonic spraying to sacculus outer surface；
5) drug coated balloon catheter is obtained after coating is dry.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110882473A (en) * | 2019-12-26 | 2020-03-17 | 科睿驰（深圳）医疗科技发展有限公司 | Medicinal balloon catheter and preparation method thereof |
| CN111035815A (en) * | 2020-01-10 | 2020-04-21 | 卢静 | Medical tracheal catheter, tracheal catheter coating and preparation method thereof |
| CN111298272A (en) * | 2020-03-11 | 2020-06-19 | 科塞尔医疗科技（苏州）有限公司 | Drug-coated balloon, preparation method thereof and drug-coated balloon dilatation catheter |
| CN111671982A (en) * | 2020-05-08 | 2020-09-18 | 北京永益润成科技有限公司 | Medicinal coating composition and preparation method thereof |
| CN113117220A (en) * | 2021-04-14 | 2021-07-16 | 深圳市赛禾医疗技术有限公司 | Medicine balloon catheter, medicine balloon catheter system and control method thereof |
| CN113813449A (en) * | 2021-08-30 | 2021-12-21 | 孟繁宇 | Preparation method of nanoparticle rapamycin drug-loaded coating balloon |
| CN114377278A (en) * | 2022-01-14 | 2022-04-22 | 浙江介尔欣医疗科技有限公司 | Medicine balloon and preparation method thereof |
| CN115957383A (en) * | 2021-10-12 | 2023-04-14 | 凯诺威医疗科技(武汉)有限公司 | Interventional medical instrument |
| CN116889651A (en) * | 2023-09-11 | 2023-10-17 | 苏州中天医疗器械科技有限公司 | Drug coating for drug coating balloon, and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106267377A (en) * | 2015-05-26 | 2017-01-04 | 先健科技(深圳)有限公司 | Drug coated balloon catheter |
| CN108295359A (en) * | 2016-12-30 | 2018-07-20 | 先健科技(深圳)有限公司 | Carry medicine instrument and preparation method thereof |
-
2019
- 2019-07-09 CN CN201910613891.0A patent/CN110201243B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106267377A (en) * | 2015-05-26 | 2017-01-04 | 先健科技(深圳)有限公司 | Drug coated balloon catheter |
| CN108295359A (en) * | 2016-12-30 | 2018-07-20 | 先健科技(深圳)有限公司 | Carry medicine instrument and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| GRABOW N,等: "A Biodegradable Balloon-expandable Stent for Interventional Applications in the Peripheral Vasculature - In vitro Feasibility", 《4TH EUROPEAN CONFERENCE OF THE INTERNATIONAL FEDERATION FOR MEDICAL AND BIOLOGICAL ENGINEERING》 * |
| LINCOFF AM，等: "Sustained local delivery of dexamethasone by a novel intravascular eluting stent to prevent restenosis in the porcine coronary injury model", 《JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110882473A (en) * | 2019-12-26 | 2020-03-17 | 科睿驰（深圳）医疗科技发展有限公司 | Medicinal balloon catheter and preparation method thereof |
| CN110882473B (en) * | 2019-12-26 | 2022-04-15 | 科睿驰（深圳）医疗科技发展有限公司 | Medicinal balloon catheter and preparation method thereof |
| CN111035815A (en) * | 2020-01-10 | 2020-04-21 | 卢静 | Medical tracheal catheter, tracheal catheter coating and preparation method thereof |
| CN111298272A (en) * | 2020-03-11 | 2020-06-19 | 科塞尔医疗科技（苏州）有限公司 | Drug-coated balloon, preparation method thereof and drug-coated balloon dilatation catheter |
| CN111671982A (en) * | 2020-05-08 | 2020-09-18 | 北京永益润成科技有限公司 | Medicinal coating composition and preparation method thereof |
| CN113117220A (en) * | 2021-04-14 | 2021-07-16 | 深圳市赛禾医疗技术有限公司 | Medicine balloon catheter, medicine balloon catheter system and control method thereof |
| WO2022217917A1 (en) * | 2021-04-14 | 2022-10-20 | 深圳市赛禾医疗技术有限公司 | Drug balloon catheter, and drug balloon catheter system and control method therefor |
| CN113813449A (en) * | 2021-08-30 | 2021-12-21 | 孟繁宇 | Preparation method of nanoparticle rapamycin drug-loaded coating balloon |
| CN115957383A (en) * | 2021-10-12 | 2023-04-14 | 凯诺威医疗科技(武汉)有限公司 | Interventional medical instrument |
| CN114377278A (en) * | 2022-01-14 | 2022-04-22 | 浙江介尔欣医疗科技有限公司 | Medicine balloon and preparation method thereof |
| CN116889651A (en) * | 2023-09-11 | 2023-10-17 | 苏州中天医疗器械科技有限公司 | Drug coating for drug coating balloon, and preparation method and application thereof |
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