CN114949373A - Method for preparing drug eluting balloon coating by overcoming surface tension of liquid - Google Patents
Method for preparing drug eluting balloon coating by overcoming surface tension of liquid Download PDFInfo
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- CN114949373A CN114949373A CN202210519026.1A CN202210519026A CN114949373A CN 114949373 A CN114949373 A CN 114949373A CN 202210519026 A CN202210519026 A CN 202210519026A CN 114949373 A CN114949373 A CN 114949373A
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- 239000003814 drug Substances 0.000 title claims abstract description 186
- 229940079593 drug Drugs 0.000 title claims abstract description 111
- 239000011248 coating agent Substances 0.000 title claims abstract description 68
- 238000000576 coating method Methods 0.000 title claims abstract description 68
- 239000007788 liquid Substances 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 63
- 238000005507 spraying Methods 0.000 claims abstract description 38
- 238000000889 atomisation Methods 0.000 claims abstract description 29
- 239000004744 fabric Substances 0.000 claims abstract description 13
- 229930012538 Paclitaxel Natural products 0.000 claims abstract description 12
- 229960001592 paclitaxel Drugs 0.000 claims abstract description 12
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims abstract description 12
- 238000003618 dip coating Methods 0.000 claims abstract description 9
- 238000007605 air drying Methods 0.000 claims abstract description 7
- 238000004140 cleaning Methods 0.000 claims abstract description 7
- 238000010828 elution Methods 0.000 claims abstract description 5
- 239000010410 layer Substances 0.000 claims description 24
- 239000011247 coating layer Substances 0.000 claims description 5
- 239000007921 spray Substances 0.000 claims description 5
- 239000004745 nonwoven fabric Substances 0.000 claims description 3
- 239000013078 crystal Substances 0.000 abstract description 10
- 238000004220 aggregation Methods 0.000 abstract description 4
- 230000002776 aggregation Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 43
- 210000005077 saccule Anatomy 0.000 description 23
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
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- 238000011068 loading method Methods 0.000 description 5
- 238000007664 blowing Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
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- 238000005303 weighing Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
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- 238000001556 precipitation Methods 0.000 description 2
- 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 2
- 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 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- JHWNWJKBPDFINM-UHFFFAOYSA-N Laurolactam Chemical compound O=C1CCCCCCCCCCCN1 JHWNWJKBPDFINM-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
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- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
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- 239000002775 capsule Substances 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 208000026758 coronary atherosclerosis Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
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- 238000000520 microinjection Methods 0.000 description 1
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- 239000002861 polymer material Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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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
- A61L29/04—Macromolecular materials
- A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- 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
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
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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
- 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
- A61L2300/608—Coatings having two or more layers
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
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Abstract
The invention provides a method for preparing a drug eluting balloon coating by overcoming the surface tension of liquid, belonging to the technical field of medical instruments and comprising the following steps; (1) dissolving paclitaxel in ethanol 1 solution to obtain drug coating solution; (2) cleaning the surface of the balloon by using dust-free cloth of ethanol 2 after the balloon is inflated, and airing the balloon; (3) coating a drug coating solution on the surface of the air-dried balloon by adopting any one of dip coating, smearing and spraying, wiping the surface of the balloon by using dust-free cloth after air drying to obtain the balloon coated with a layer of drug; (4) and putting the balloon coated with the layer of medicine into ultrasonic atomization equipment to perform ultrasonic atomization spraying on the medicine coating solution to obtain a balloon coated with two layers of medicine, namely a medicine elution balloon. The method can obviously improve the uniformity of the medicine on the surface of the balloon, prevent the aggregation of medicine liquid drops and the lumping of the medicine in the ultrasonic atomization spraying process, avoid the collapse of medicine crystals on the surface of the balloon and have low medicine folding loss rate.
Description
Technical Field
The invention belongs to the technical field of medical instruments, and particularly relates to a method for preparing a drug eluting balloon coating by overcoming the surface tension of liquid.
Background
In recent years, atherosclerosis obliterans of lower limbs and coronary atherosclerosis have become one of the most prevalent arterial diseases, and drug eluting balloons are a necessary trend in the development of interventional therapies for coronary lesions and have become widely used.
A drug eluting balloon, i.e., a balloon with a drug coating. Currently, drug-coated drugs are mainly lipophilic drugs such as: paclitaxel and rapamycin. The sacculus mainly comprises hydrophobic high polymer materials (polyvinyl chloride, polyethylene, polyurethane, nylon and polyethylene terephthalate). The physical methods for bonding the drug to the balloon surface at the present stage are mainly dip coating and spray coating. However, the current stage of the spraying process is mainly 'crystal theory', and the principle of drug crystallization is not drug precipitation caused by reduced solubility. The solvent volatilization process in the medicine solution is utilized in the spraying crystallization process, so that the medicine is separated out. However, the first prerequisite for crystallization of the drug is that the drug is dissolved in the solvent in the form of solute, which means that the drug is distributed on the surface of the balloon in the form of solute during the spraying process.
The main solvents commonly used in the prior art for carrying paclitaxel and rapamycin are methanol, acetone, ethanol and chloroform. Among these solvents, ethanol has the advantages of low toxicity, volatility and high medical safety. Ethanol is certainly the best solvent. However, ethanol is a hydrophobic and lipophilic solvent, and after a medicinal solution with the solvent being ethanol contacts the surface of the balloon, the medicinal liquid is contracted due to the surface tension of the liquid, and the medicinal liquid on the surface of the balloon forms liquid beads under the action of the surface tension of the liquid due to the fact that the liquid does not have good adhesion with the material of the balloon. After the liquid beads are dried, spot-shaped drug aggregation is formed on the surface of the balloon, the surface of the balloon is exposed, the drug cannot be crystallized, the drug folding loss rate is high, and the like.
Disclosure of Invention
In view of the above, the invention provides a method for preparing a drug-eluting balloon coating by overcoming liquid surface tension, which can significantly improve the uniformity of drugs on the surface of the balloon, and the compact drug coating can firmly combine with the drugs sprayed by subsequent ultrasonic atomization just like a 'foundation', so that drug liquid drops are prevented from being aggregated and the drugs are prevented from being lumpy in the ultrasonic atomization spraying process, drug crystal collapse on the surface of the balloon is avoided, and the drug folding loss rate is low.
The invention relates to a method for preparing a drug eluting balloon coating by overcoming the surface tension of a liquid, which comprises the following steps;
(1) preparing a drug coating solution; dissolving paclitaxel in 85% ethanol 1 solution to obtain drug coating solution with concentration of 15-50 mg/ml;
the balloon is made of nylon-12, and 85% ethanol has good adhesion with the surface of the balloon, so that the firmness of the balloon in the processes of folding, sleeving the balloon into a protective sleeve and conveying is guaranteed.
The lower concentration of the paclitaxel is 15-50 mg/ml, so that the drug can be crystallized on the surface of the balloon and the requirement of not blocking the spray head can be met. Meanwhile, the efficiency in the production process can be ensured under the concentration, and the spraying of the saccule with the common specification can be finished within 5 minutes.
(2) Pretreatment of the saccule; after 2-3ml of the balloon is inflated, cleaning the surface of the balloon by using dust-free cloth of 75% ethanol 2, and airing the balloon;
(3) coating a drug coating solution on the surface of the air-dried balloon by adopting any one of dip coating, smearing and spraying, and after air-drying, lightly wiping the surface of the balloon by using dust-free cloth to obtain the balloon coated with a layer of drugs;
dip-coating is to place the air-dried balloon in the drug coating solution for 5-10s and then take out; the spraying is to put the drug coating solution into a spraying gun and spray the drug coating solution to the air-dried balloon for 360 degrees; the smearing is to put the non-woven fabrics into the drug coating solution to be soaked and then wipe the air-dried saccule for 2-3 times.
(4) And putting the balloon coated with the layer of the medicine into ultrasonic atomization equipment for ultrasonic atomization spraying of a medicine coating solution, wherein the flow rate of the ultrasonic atomization spraying is 100-.
The principle of ultrasonic atomization spraying is that after a solution comes out of a micro-injection pump, the solution is fed along a liquid path pipe, after the solution reaches an ultrasonic atomization nozzle, liquid drops at the nozzle are atomized under the action of high-frequency sound waves, the atomized liquid drops fall on the surface of a carrier under the action of gravity and carrier gas, in the process, an organic solvent is volatilized rapidly, and a solute is adhered to the surface of the carrier. Meanwhile, the carrier is driven by the motor to do uniform horizontal and rotary motion, so that the coating on the surface of the whole carrier is uniformly covered. There can be very big impact force at ultrasonic atomization's in-process, the atomizing droplet that has the medicine coating solution can fill and level up the medicine carrying top layer of unevenness on the sacculus that scribbles the one deck medicine, then continue to carry out the load of medicine through ultrasonic atomization again, make the medicine load capacity on whole sacculus surface very even like this, medicine carrying layer thickness is even, in addition also have volatilizing of solvent at the in-process of atomizing spraying, the phenomenon that the later stage was dropped because the medicine volatilizees the coronary artery sacculus surface medicine carrying "skinning" that arouses in a large number fast like this has been avoided because of the solvent.
The basic principle of drug crystallization is the precipitation of drug with reduced solubility in solvents due to some reason. These factors may be temperature, solvent evaporation, solute concentration, etc. The crystallization of the drug requires that the drug be present in a liquid form. Because the medicine exists in a liquid form, the medicine is attached to the surface of the balloon in the spraying process, the solvent is volatilized to form medicine powder instead of crystallization, in addition, the medicine is built layer by layer on the surface of the balloon, the medicine exists in a liquid state, the medicine can collapse in the crystallization process, and the crystallized medicine is dissolved again to form the medicine powder. All can cause the crystallization instability of the drug on the surface of the saccule in the production process, and the contact between the final crystallization product and the saccule is not firm and is easy to fall off.
The invention adopts a mode of combining pre-coating and final coating to solve the problem of unstable crystallization of the medicine. In the invention, the first layer of medicine which is dipped, smeared and sprayed is unevenly distributed on the surface of the saccule, but white medicine crystals which are peeled off from the surface of the saccule are slightly wiped off after the medicine is dried after pretreatment, so that a relatively uniform and compact medicine coating layer is formed on the surface of the saccule. On one hand, the surface layer of the first compact medicine coating layer is provided with a plurality of pits, and the compact medicine coating layer is like a foundation which can be firmly combined with the medicine sprayed by the subsequent ultrasonic atomization, so that the medicine liquid drops in the spraying process are prevented from being gathered to form medicine speckles. On the other hand, even if the flow rate of the medicine sprayed subsequently is large, the crystallized medicine cannot be dissolved again and fall off, so that the medicine crystals on the surface of the balloon collapse. The pretreated balloon surface has a larger flow tolerance range, and the stability in the production process is improved. The medicine-carrying saccule prepared by the invention has uniform medicine crystal layer, can not cause the falling of a local medicine layer, has stable crystallized medicine layer in the operation process, is easy to operate in the next step, and has low medicine folding loss rate.
Drawings
Fig. 1 is an external view (0.7X times) of a balloon obtained in comparative example 1 according to an embodiment of the present invention;
fig. 2 is an appearance view (25X times) of the balloon obtained in comparative example 1 under a body microscope according to an embodiment of the present invention;
fig. 3 is an external view (0.7X times) of the drug eluting balloon obtained in example 1 according to the embodiment of the present invention;
fig. 4 is a crystal appearance (25X times) of the drug eluting balloon obtained in example 1 under a body microscope according to the embodiment of the present invention.
Fig. 5 is an external view (0.7X times) of the drug eluting balloon obtained in example 2 according to the embodiment of the present invention;
FIG. 6 is a graphical representation (0.7X times) of the appearance of the drug eluting balloon from example 3 in accordance with an embodiment of the present invention;
fig. 7 shows the drug crystal morphology (10000 times) of the drug eluting balloon obtained in example 1 under a scanning electron microscope.
Detailed Description
The present invention will be described in detail with reference to specific embodiments.
Example 1
A method for preparing a drug eluting balloon coating by overcoming the surface tension of a liquid, comprising the following steps;
(1) 85% ethanol, weighing 85ml absolute ethanol (medicinal grade), and adding 15ml ultrapure water to obtain 85% ethanol;
(2) preparing a drug coating solution; dissolving paclitaxel in 85% ethanol 1 solution, and dissolving with ultrasonic wave to obtain drug coating solution with concentration of 15 mg/ml;
(3) pretreatment of the saccule; connecting a finished coronary artery balloon product with the diameter of 4.0mm and the length of 20mm to a three-way valve, injecting 2ml of gas by using an injector, blowing up the balloon, and cleaning the surface of the balloon by using dust-free cloth of 75% ethanol 2 to obtain an air-dried balloon;
(4) placing the air-dried balloon in the drug coating solution for 5s, then taking out, coating the drug coating solution on the surface of the air-dried balloon, and after air-drying, lightly wiping the surface of the balloon with dust-free cloth to obtain the balloon coated with a layer of drug;
(5) and putting the balloon coated with the layer of the medicine into ultrasonic atomization equipment to perform ultrasonic atomization spraying of a medicine coating solution, wherein the flow rate of the ultrasonic atomization spraying is 100 mu l/min, the liquid amount is 220 mu l, and starting spraying to obtain the balloon coated with two layers of the medicine, namely the medicine elution balloon.
Detecting the drug-loading capacity of the saccule, washing the drug on the surface of the saccule with acetonitrile, and detecting the drug-loading capacity on the surface of the saccule according to the following chromatographic conditions;
the equipment used; high performance liquid chromatography type: agilent 1100; a chromatographic column: welch Ultimate XB-C18 (4.6X 150 mm,3 μm). Mobile phase: acetonitrile, purified water =65: 35; flow rate: 1 ml/min; temperature: at 40 ℃.
Example 2
A method for preparing a drug eluting balloon coating by overcoming the surface tension of a liquid, comprising the following steps;
(1) 85% ethanol, weighing 85ml absolute ethanol (medicinal grade), and adding 15ml ultrapure water to obtain 85% ethanol;
(2) preparing a drug coating solution; dissolving paclitaxel in 85% ethanol 1 solution, and dissolving with ultrasonic wave to obtain drug coating solution with concentration of 30 mg/ml;
(3) pretreatment of the saccule; connecting a coronary artery balloon finished product with the diameter of 4.0mm and the length of 20mm to a three-way valve, injecting 2.5ml of gas by using an injector, blowing up the balloon, and cleaning the surface of the balloon by using dust-free cloth of 75% ethanol 2 to obtain an air-dried balloon;
(4) putting the medicine coating solution into a spraying gun, spraying the medicine coating solution to the air-dried balloon for 360 degrees, coating the medicine coating solution on the surface of the air-dried balloon, and wiping the surface of the balloon lightly with dust-free cloth after air drying to obtain the balloon coated with a layer of medicine;
(5) and putting the saccule coated with the layer of medicine into ultrasonic atomization equipment to carry out ultrasonic atomization spraying on the medicine coating solution, wherein the flow rate of the ultrasonic atomization spraying is 120 mu l/min, the liquid amount is 220 mu l, and the spraying is started to obtain the saccule coated with two layers of medicine, namely the medicine elution saccule.
Example 3
A method for preparing a drug eluting balloon coating by overcoming the surface tension of a liquid, comprising the following steps;
(1) 85% ethanol, weighing 85ml absolute ethanol (medicinal grade), and adding 15ml ultrapure water to obtain 85% ethanol;
(2) preparing a drug coating solution; dissolving paclitaxel in 85% ethanol 1 solution, and dissolving with ultrasonic wave to obtain drug coating solution with concentration of 50 mg/ml;
(3) pretreatment of the saccule; connecting a finished coronary artery balloon product with the diameter of 4.0mm and the length of 20mm to a three-way valve, injecting 3ml of gas by using an injector, blowing up the balloon, and cleaning the surface of the balloon by using dust-free cloth of 75% ethanol 2 to obtain an air-dried balloon;
(4) placing the non-woven fabric into a drug coating solution for soaking, wiping the air-dried balloon for 2-3 times, coating the drug coating solution on the surface of the air-dried balloon, and wiping the surface of the balloon lightly with dust-free cloth after air-drying to obtain the balloon coated with a layer of drug;
(5) and putting the balloon coated with the layer of the medicine into ultrasonic atomization equipment to perform ultrasonic atomization spraying of a medicine coating solution, wherein the flow rate of the ultrasonic atomization spraying is 140 mu l/min, the liquid amount is 220 mu l, and starting spraying to obtain the balloon coated with two layers of the medicine, namely the medicine elution balloon.
Example 4
This example is the same as example 1 except that dip coating in this example was to place the aired balloon in the drug coating solution for 6 s.
Example 5
This example is the same as example 1 except that dip coating in this example was to place the aired balloon in the drug coating solution for 10 s.
Example 6
This example is the same as example 1 except that dip coating in this example was to place the aired balloon in the drug coating solution for 8 s.
Comparative example 1
A method for preparing a drug eluting balloon coating by overcoming the surface tension of a liquid, comprising the following steps;
(1) preparing a drug coating solution; dissolving paclitaxel in 85% ethanol 1 solution, and dissolving with ultrasonic wave to obtain drug coating solution with concentration of 15 mg/ml;
(2) pretreatment of the saccule; connecting a coronary artery balloon finished product with the diameter of 4.0mm and the length of 20mm to a three-way valve, injecting 3ml of gas by using an injector, blowing up the balloon, and cleaning the surface of the balloon by using dust-free cloth of 75% ethanol 2 to obtain an air-dried balloon;
(3) and putting the balloon into ultrasonic atomization equipment for ultrasonic atomization spraying of a drug coating solution, wherein the flow rate of the ultrasonic atomization spraying is 140 mul/min, and the liquid amount is 220 mul, and starting spraying to obtain the drug-coated balloon.
From fig. 1 and 2, it can be seen that the balloon directly sprayed is lumpy in appearance because the drug is not firmly attached to the balloon surface and the droplets are collected by the surface tension of the liquid. After aggregation, the medicine solution loses the solvent and is dried to form the lumpy medicine.
The medicine on the surface of the balloon after direct spraying is not obvious or has less crystallization, and the sprayed medicine liquid forms liquid drops under the action of surface tension. The aggregation of the liquid drops leads to the crystallization failure or the dissolution of the crystals, and the ultrasonic atomization spraying loses the original effect. The liquid medicine is directly dried on the surface of the saccule to form medicine block powder.
Comparing fig. 3-6 with fig. 1 and 2, the balloon surface drug prepared by the method of the invention is firmly combined with the drug, overcomes the action of surface tension of the liquid and can not be contracted to form liquid drops. The liquid medicine is uniformly distributed on the surface of the saccule. The medicine is uniformly distributed on the surface of the saccule, the nozzle reciprocates to spray the medicine solution on the surface of the saccule, and the crystal grows layer by layer along with the reciprocating motion of the nozzle.
The surface drug loading of the capsules in examples 1 to 6 of the present invention and comparative example 1 was as follows;
the above data show that the balloon drug loading is firm and stable in the present invention.
The results of the folding loss rate and the balloon drug release rate test in examples 1 to 6 and comparative example 1 are as follows;
folding loss rate = (average drug load-folded drug load)/average drug load
Release Rate = (folded drug loading-residual amount)/folded drug loading
From the above data, it can be seen that the drug on the surface of the balloon in comparative example 1 has a higher folding loss rate, i.e. the loss rate is higher during folding, and the balloon is not firmly bonded with the drug. The directly sprayed drug balloon can not ensure whether the drug dose on the balloon surface reaching the lesion is effective or not in clinical application. In addition, the drug drop from the surface of the directly sprayed drug in the human body transportation process can cause the increase of the harm of the paclitaxel to other organs. The drug-loaded balloon prepared by the method is firmly combined with drugs, ensures that the balloon reaches the lesion position and still has higher effective concentration, and can reduce the harm of paclitaxel to other organs.
The surface of the drug eluting balloon prepared by the method has high release rate. Provides possibility for inhibiting the restenosis of the blood vessel by the drug balloon. In contrast to the directly sprayed drug balloon of comparative example 1, the release rate was only 61.59%, and it was not possible to ensure that the effective drug concentration was released to the vessel wall.
Claims (8)
1. A method for preparing a drug eluting balloon coating by overcoming the surface tension of a liquid is characterized by comprising the following steps;
(1) dissolving paclitaxel in ethanol 1 solution to obtain drug coating solution;
(2) cleaning the surface of the balloon by using dust-free cloth of ethanol 2 after the balloon is inflated, and airing the balloon;
(3) coating a drug coating solution on the surface of the air-dried balloon by adopting any one of dip coating, smearing and spraying, wiping the surface of the balloon by using dust-free cloth after air drying to obtain the balloon coated with a layer of drug;
(4) and putting the balloon coated with the layer of medicine into ultrasonic atomization equipment to perform ultrasonic atomization spraying on the medicine coating solution to obtain a balloon coated with two layers of medicine, namely a medicine elution balloon.
2. The method of preparing a drug eluting balloon coating against liquid surface tension of claim 1, wherein the concentration of the drug coating solution is 15-50 mg/ml.
3. The method for preparing a drug eluting balloon coating against liquid surface tension of claim 1, wherein the ethanol 1 is 85% ethanol and the ethanol 2 is 75% ethanol.
4. The method for preparing drug eluting balloon coating against liquid surface tension as claimed in claim 1, wherein the flow rate of the ultrasonic atomization spraying is 100-.
5. The method for preparing a drug-eluting balloon coating layer against the surface tension of a liquid according to claim 1, wherein the dip coating in step (3) is to place the air-drying balloon in the drug coating solution for 5-10s and then take out.
6. The method for preparing a drug eluting balloon coating against liquid surface tension according to claim 1, wherein the spraying of step (3) is to spray the drug coating solution into a spray gun to the air-dried balloon for 360 °.
7. The method for preparing a drug eluting balloon coating layer by overcoming the surface tension of a liquid according to claim 1, wherein the smearing in the step (3) is to wipe the air-dried balloon 2-3 times after the non-woven fabric is soaked in the drug coating solution.
8. The method for preparing a drug eluting balloon coating against the surface tension of a liquid according to claim 1, wherein the balloon is inflated with 2-3ml of gas in step (2).
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| Application Number | Priority Date | Filing Date | Title |
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| CN202210519026.1A CN114949373A (en) | 2022-05-13 | 2022-05-13 | Method for preparing drug eluting balloon coating by overcoming surface tension of liquid |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202210519026.1A CN114949373A (en) | 2022-05-13 | 2022-05-13 | Method for preparing drug eluting balloon coating by overcoming surface tension of liquid |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070212394A1 (en) * | 2006-03-10 | 2007-09-13 | Cook Incorporated | Taxane coatings for implantable medical devices |
| US20100049296A1 (en) * | 2008-08-22 | 2010-02-25 | Med Institute, Inc. | Implantable medical device coatings with biodegradable elastomer and releasable taxane agent |
| CN109481827A (en) * | 2018-11-05 | 2019-03-19 | 南京友德邦医疗科技有限公司 | A kind of medicine eluting balloon catheter and preparation method thereof |
| CN109954198A (en) * | 2017-12-25 | 2019-07-02 | 先健科技(深圳)有限公司 | Medicinal balloon and preparation method thereof |
-
2022
- 2022-05-13 CN CN202210519026.1A patent/CN114949373A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070212394A1 (en) * | 2006-03-10 | 2007-09-13 | Cook Incorporated | Taxane coatings for implantable medical devices |
| US20100049296A1 (en) * | 2008-08-22 | 2010-02-25 | Med Institute, Inc. | Implantable medical device coatings with biodegradable elastomer and releasable taxane agent |
| CN109954198A (en) * | 2017-12-25 | 2019-07-02 | 先健科技(深圳)有限公司 | Medicinal balloon and preparation method thereof |
| CN109481827A (en) * | 2018-11-05 | 2019-03-19 | 南京友德邦医疗科技有限公司 | A kind of medicine eluting balloon catheter and preparation method thereof |
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Application publication date: 20220830 |