WO2018169051A1 - Procédé de revêtement de ballonnet - Google Patents

Procédé de revêtement de ballonnet Download PDF

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Publication number
WO2018169051A1
WO2018169051A1 PCT/JP2018/010470 JP2018010470W WO2018169051A1 WO 2018169051 A1 WO2018169051 A1 WO 2018169051A1 JP 2018010470 W JP2018010470 W JP 2018010470W WO 2018169051 A1 WO2018169051 A1 WO 2018169051A1
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WIPO (PCT)
Prior art keywords
balloon
crystal
supply unit
drug
coating
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PCT/JP2018/010470
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English (en)
Japanese (ja)
Inventor
古市英資
黒崎靖夫
Original Assignee
テルモ株式会社
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Publication date
Application filed by テルモ株式会社 filed Critical テルモ株式会社
Priority to JP2019506297A priority Critical patent/JP6955548B2/ja
Publication of WO2018169051A1 publication Critical patent/WO2018169051A1/fr

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    • 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

Definitions

  • the present invention relates to a method of coating a drug on the balloon surface of a balloon catheter.
  • Balloon catheters are widely used to improve lesions (stenosis) occurring in living body lumens.
  • the balloon catheter usually includes a long catheter shaft and a balloon that is provided on the distal end side of the catheter shaft and is expandable in the radial direction. By expanding the deflated balloon after reaching a target location in the body via a thin living body lumen, the lesioned part can be expanded.
  • the endothelial cells may overgrow and develop new stenosis (restenosis) in the lesion.
  • a drug-eluting balloon Drug Eluting Ballon: DEB
  • DEB Drug Eluting Ballon
  • Examples of methods for forming a coating layer containing a drug on a balloon include a spray method, a drop method, and a stringing method.
  • the spray method is a method in which a coating liquid containing a drug is sprayed in a mist form from a nozzle that does not contact the balloon, and then the coating liquid is dried to form a coating layer on the surface of the balloon.
  • the drop method is a method of forming a coating layer on the surface of the balloon by dropping the coating liquid from a nozzle that does not contact the balloon and then drying the coating liquid.
  • the thread drawing method is a method in which a coating liquid is supplied onto the surface of the balloon via a thread or the like that contacts the balloon, and then the coating liquid is dried to form a coating layer on the surface of the balloon.
  • the entire surface of the balloon is moved by moving the nozzle, thread, and other devices for supplying the coating liquid in the axial direction of the balloon while rotating the balloon.
  • a coating solution can be applied to the substrate (for example, see Patent Document 1).
  • the formulation of solvent type, ratio, amount, etc. of the coating solution, coating method, coating parameters such as temperature and flow rate, etc. It is necessary to control precisely.
  • the present invention has been made to solve the above-described problems, and an object of the present invention is to provide a balloon coating method for forming uniform crystals on the balloon surface without being affected by external factors.
  • the balloon coating method according to the present invention for achieving the above object is a balloon coating method for forming a coating layer on the surface of the balloon in a catheter having a balloon at the tip of a shaft, Supplying and applying a coating liquid containing a drug from a first supply unit to the surface of the balloon while rotating the catheter about the axis of the shaft; and While the rotation of the catheter is maintained, before the coating solution dries, the crystallization inducer is supplied from the second supply unit to the surface of the balloon to which the coating solution has been applied, and is applied for crystallization.
  • a step that prompts Have
  • the crystal inducer is added after a certain time from the application of the coating solution, the crystal formation rate can be made constant over the entire surface of the balloon. For this reason, crystallization can proceed under certain conditions without being influenced by external factors. Thereby, variation in crystal shape can be suppressed, and crystals having a certain shape and size can be stably formed on the surface of the balloon.
  • the balloon coating method of the present invention includes a step of volatilizing the solvent of the coating liquid and the crystal inducer after the crystal inducer is applied to the surface of the balloon to produce drug crystals. For this reason, since the solvent and the crystal inducer volatilize after the crystal is generated by the crystal inducer, the drug can be crystallized regardless of the volatilization conditions of the solvent and the crystal inducer, and the balloon can be used regardless of external factors. It is possible to form drug crystals that are uniformly dispersed on the surface.
  • the first supply unit and the second supply unit are spaced apart from each other at a predetermined interval in the axial direction of the balloon, and the first supply unit moves in parallel with the liquid in relation to the surface of the balloon. Apply. Thereby, the time from the application of the coating solution to the addition of the crystal inducer can be made constant throughout the balloon.
  • the distance between the first supply unit and the second supply unit in the axial direction of the balloon is adjusted, and then the liquid is supplied from the first supply unit and the second supply unit to the surface of the balloon. Since the time from the application of the coating solution to the application of the crystal inducer can be changed, the shape and size of the drug crystals formed on the surface of the balloon can be adjusted.
  • the crystal inducer is a poor solvent for the drug. Thereby, the crystal
  • the drug contained in the coating solution is rapamycin, paclitaxel, docetaxel, or everolimus, restenosis of the stenosis in the blood vessel can be satisfactorily suppressed.
  • the crystal inducer is water, heptane, or a mixture thereof, the solubility of paclitaxel in the crystal inducer is low, so that the crystal formation of paclitaxel can be effectively promoted.
  • the solvent contained in the coating solution is either dimethyl sulfoxide or N, N-dimethylacetamide
  • the crystal inducer is any of acetonitrile, alcohols, acetone, tetrahydrofuran, and water.
  • the crystal inducer is miscible with the solvent contained in the coating solution, and the solubility of the water-insoluble drug is less than or not soluble in the solvent contained in the coating solution or a mixture thereof. can do.
  • the solvent contained in the coating liquid is any one of acetonitrile, alcohols, acetone, and tetrahydrofuran, and the crystal inducer is either water or heptane.
  • the crystal inducer is miscible with the solvent contained in the coating solution, and the solubility of the water-insoluble drug is less than or not soluble in the solvent contained in the coating solution or a mixture thereof. can do.
  • FIG. 8 is a cross-sectional view of a state before the balloon is folded (FIG. 7A), a state in which blades are formed on the balloon (FIG. 7B), and a state in which the balloon is folded (FIG. 7C). It is sectional drawing which shows the state which expanded the stenosis part of the blood vessel with the balloon catheter.
  • the catheter 1 includes a long shaft 10, a balloon 11 provided at the tip of the shaft 10, a coat layer 30 containing a drug provided on the outer surface of the balloon 11, and the shaft 10. And a hub 12 fixed to the base end of the head.
  • the shaft 10 includes an outer tube 20 that is a tube having an open front end and a base end, and an inner tube 21 that is a tube disposed inside the outer tube 20.
  • the inner tube 21 is housed in the hollow interior of the outer tube 20, and the shaft 10 has a double tube structure at the tip.
  • the hollow interior of the inner tube 21 is a guide wire lumen 23 through which the guide wire is inserted.
  • an expansion lumen 22 through which the expansion fluid of the balloon 11 is circulated is formed inside the hollow of the outer tube 20 and outside the inner tube 21.
  • the inner tube 21 opens to the outside at the opening 24.
  • the inner tube 21 protrudes further to the distal end side than the distal end of the outer tube 20.
  • the balloon 11 has a proximal end portion fixed to the distal end portion of the outer tube 20, and a distal end portion fixed to the distal end portion of the inner tube 21. Thereby, the inside of the balloon 11 communicates with the expansion lumen 22.
  • the balloon 11 can be expanded by injecting the expansion fluid into the balloon 11 via the expansion lumen 22.
  • the expansion fluid may be a gas or a liquid.
  • a gas such as helium gas, CO 2 gas, O 2 gas, N 2 gas, or Ar gas, or a liquid such as physiological saline or a contrast agent can be used.
  • a cylindrical straight portion 11a (expanded portion) having the same outer diameter when expanded is formed in the central portion in the axial direction of the balloon 11, and the outer diameter gradually increases on both sides of the straight portion 11a in the axial direction.
  • a taper portion 11b that changes to is formed.
  • medical agent is formed in the whole outer surface of the straight part 11a.
  • the range in which the coating layer 30 is formed in the balloon 11 is not limited to the straight portion 11a, but may include at least a part of the tapered portion 11b in addition to the straight portion 11a, or one of the straight portions 11a. It may be only part.
  • the hub 12 is formed with a proximal end opening 40 that communicates with the expansion lumen 22 of the outer tube 20 and functions as a port through which expansion fluid flows in and out.
  • the length of the balloon 11 in the axial direction is not particularly limited, but is preferably 5 to 500 mm, more preferably 10 to 300 mm, and still more preferably 20 to 200 mm.
  • the outer diameter when the balloon 11 is expanded is not particularly limited, but is preferably 1 to 10 mm, more preferably 2 to 8 mm.
  • the outer surface before the coating layer 30 of the balloon 11 is formed is smooth and non-porous.
  • the outer surface of the balloon 11 before the coating layer 30 is formed may have minute holes that do not penetrate the membrane.
  • the outer surface of the balloon 11 before the coating layer 30 is formed may have both a smooth and non-porous range and a range with a minute hole that does not penetrate the membrane.
  • the size of the minute holes is, for example, 0.1 to 5 ⁇ m in diameter and 0.1 to 10 ⁇ m in depth, and may have one or a plurality of holes for one crystal.
  • the size of the minute holes is, for example, a diameter of 5 to 500 ⁇ m and a depth of 0.1 to 50 ⁇ m, and one hole or a plurality of crystals may be included for one hole.
  • the balloon 11 has a certain degree of flexibility so that it can be expanded when it reaches a blood vessel, tissue, etc., and has a certain degree of hardness so that the drug can be released from the coat layer 30 on its outer surface.
  • the balloon 11 is made of metal or resin, but at least the outer surface of the balloon 11 on which the coat layer 30 is provided is preferably made of resin.
  • the constituent material of at least the outer surface of the balloon 11 is, for example, a polyolefin such as polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or a mixture of two or more of these, soft poly
  • a thermoplastic resin such as vinyl chloride resin, polyamide, polyamide elastomer, nylon elastomer, polyester, polyester elastomer, polyurethane, fluororesin, silicone rubber, latex rubber, or the like can be used.
  • polyamides are preferable. That is, at least a part of the outer surface of the balloon 11 that coats the drug is a polyamide.
  • the polyamide is not particularly limited as long as it is a polymer having an amide bond.
  • polytetramethylene adipamide nylon 46
  • polycaprolactam nylon 6
  • polyhexamethylene adipamide nylon 66
  • Homopolymers such as polyhexamethylene sebacamide (nylon 610), polyhexamethylene dodecamide (nylon 612), polyundecanolactam (nylon 11), polydodecanolactam (nylon 12), caprolactam / lauryl lactam copolymer Polymer (nylon 6/12), caprolactam / aminoundecanoic acid copolymer (nylon 6/11), caprolactam / ⁇ -aminononanoic acid copolymer (nylon 6/9), caprolactam / hexamethylene diammonium adipate copolymer ( Nylon 6/66 Copolymers such as a copolymer of adipic acid and meta-x
  • polyamide elastomer which is a block copolymer having nylon 6, nylon 66, nylon 11, nylon 12 or the like as a hard segment and polyalkylene glycol, polyether or aliphatic polyester as a soft segment is also a material of the balloon 11.
  • Used as The said polyamides may be used individually by 1 type, and may use 2 or more types together.
  • the balloon 11 preferably has a smooth surface of polyamide.
  • the coating layer 30 is formed on the outer surface of the balloon 11 directly or via a pretreatment layer such as a primer layer by a method described later. As shown in FIG. 3, the coat layer 30 extends with an additive 110 (excipient) containing a water-soluble low-molecular compound disposed in a layered manner on the outer surface of the balloon 11 and an independent long axis. And a water-insoluble drug crystal 111.
  • the end of drug crystal 111 may be in direct contact with the outer surface of balloon 11, but additive 110 is present between the end of drug crystal 111 and the outer surface of balloon 11 without being in direct contact. May be.
  • the end portion of the drug crystal 111 may be positioned on the surface of the layer of the additive 110 and the drug crystal 111 may protrude from the additive 110.
  • the plurality of drug crystals 111 may be regularly arranged on the outer surface of the balloon 11. Alternatively, the plurality of drug crystals 111 may be irregularly arranged on the outer surface of the balloon 11.
  • the amount of the drug contained in the coat layer 30 is not particularly limited, but is 0.1 ⁇ g / mm 2 to 10 ⁇ g / mm 2 , preferably 0.5 ⁇ g / mm 2 to 5 ⁇ g / mm 2 , more preferably 0.5 ⁇ g. / Mm 2 to 3.5 ⁇ g / mm 2 , more preferably 1.0 ⁇ g / mm 2 to 3 ⁇ g / mm 2 .
  • the amount of crystals of the coat layer 30 is not particularly limited, but is preferably 5 to 500,000 [crystal / (10 ⁇ m 2 )] (number of crystals per 10 ⁇ m 2 ), more preferably 50 to 50,000 [crystal / (10 ⁇ m 2 )], more preferably 500 to 5,000 [crystal / (10 ⁇ m 2 )].
  • the drug crystal 111 may have a form having independent long axes. Further, the drug crystal 111 may be other morphological types.
  • the plurality of drug crystals 111 may be present in a state where they are combined, or may be present in contact with a plurality of adjacent drug crystals 111 forming different angles.
  • the plurality of drug crystals 111 may be positioned on the balloon surface with a space (a space not including a crystal). There may be both a plurality of drug crystals 111 in a combined state and a plurality of drug crystals 111 independent from each other on the surface of the balloon 11.
  • the plurality of drug crystals 111 may be arranged in a brush shape in a circumferential shape having different major axis directions.
  • Each of the drug crystals 111 exists independently, has a certain length, and one end (base end) of the length portion is fixed to the additive 110 or the balloon 11.
  • the drug crystal 111 does not form a complex structure with the adjacent drug crystal 111 and is not connected.
  • the major axis of the crystal is almost linear.
  • the drug crystal 111 forms a predetermined angle with respect to the surface with which the base where the major axes intersect is in contact.
  • the drug crystals 111 stand independently without contacting each other.
  • the base of the drug crystal 111 may be in contact with another base on the base material of the balloon 11.
  • the base part of the drug crystal 111 may be independent on the base material of the balloon 11 without contacting with another base part.
  • the drug crystal 111 may be hollow or solid. Both the hollow drug crystal 111 and the solid drug crystal 111 may exist on the surface of the balloon 11. When the drug crystal 111 is hollow, at least the tip thereof is hollow.
  • the cross section of drug crystal 111 in a plane perpendicular to the major axis of drug crystal 111 (perpendicular) has a hollow shape.
  • the drug crystal 111 having the hollow has a polygonal cross section of the drug crystal 111 in a plane (perpendicular) perpendicular to the long axis.
  • the polygon is, for example, a triangle, a tetragon, a pentagon, or a hexagon.
  • the drug crystal 111 has a distal end (or distal end surface) and a proximal end (or proximal end surface), and a side surface between the distal end (or distal end surface) and the proximal end (or proximal end surface) is a plurality of substantially flat surfaces. It is formed as a configured long polyhedron.
  • This crystal form type (hollow elongated body crystal form type) constitutes the whole or at least a part of a certain plane on the surface in contact with the base.
  • the length in the major axis direction of the drug crystal 111 having a major axis is preferably 5 ⁇ m to 20 ⁇ m, more preferably 9 ⁇ m to 11 ⁇ m, and even more preferably around 10 ⁇ m.
  • the diameter of the drug crystal 111 having a long axis is preferably 0.01 ⁇ m to 5 ⁇ m, more preferably 0.05 ⁇ m to 4 ⁇ m, and still more preferably 0.1 ⁇ m to 3 ⁇ m. Examples of combinations of length and diameter in the long axis direction of the drug crystal 111 having a long axis include a combination having a diameter of 0.01 to 5 ⁇ m when the length is 5 ⁇ m to 20 ⁇ m and a length of 5 to 20 ⁇ m.
  • Examples include combinations having a diameter of 0.05 to 4 ⁇ m, and combinations having a diameter of 0.1 to 3 ⁇ m when the length is 5 to 20 ⁇ m.
  • the drug crystal 111 having the long axis is linear in the long axis direction, but may be curved. Both the linear drug crystal 111 and the curved drug crystal 111 may exist on the surface of the balloon 11.
  • the above-mentioned crystal form type having a crystal having a long axis is 50% by volume or more, more preferably 70% by volume or more with respect to the entire drug crystal on the outer surface of the balloon 11.
  • the drug crystal 111 which is a crystal particle having a long axis is formed so as to stand on the outer surface of the balloon 11 or the additive 110.
  • the additive 110 is present in the region where the drug crystal 111 is present, and may not be present in the region where the drug crystal 111 is absent.
  • the additive 110 is distributed in the space between the plurality of drug crystals 111 that stand.
  • the ratio of the substance constituting the coat layer 30 is preferably such that the water-insoluble drug crystal 111 occupies a larger volume than the additive 110.
  • Additive 110 does not form a matrix.
  • the matrix is a layer in which a relatively high-molecular substance (polymer or the like) is continuously formed, forms a network-like three-dimensional structure, and has a fine space therein. Therefore, the water-insoluble drug constituting the crystal is not attached to the matrix material.
  • the water-insoluble drug constituting the crystal is not embedded in the matrix material.
  • the additive 110 may form a matrix.
  • the additive 110 is coated on the outer surface of the balloon 11 while being dissolved in a solvent, and then dried to form a layer.
  • the additive 110 is amorphous.
  • the additive 110 may be crystal particles.
  • Additive 110 may be present as a mixture of amorphous and crystalline particles.
  • the additive 110 in FIG. 3 is in the state of crystalline particles and / or particulate amorphous. Alternatively, the additive 110 may be in a film-like amorphous state.
  • the additive 110 is formed as a layer containing a water-insoluble drug. Alternatively, the additive 110 may be formed as a separate layer that does not contain a water-insoluble drug.
  • the thickness of the additive 110 is 0.1 to 5 ⁇ m, preferably 0.3 to 3 ⁇ m, more preferably 0.5 to 2 ⁇ m.
  • the layer containing the long crystalline form type drug crystal 111 has low toxicity and high stenosis-inhibiting effect when delivered into the body.
  • a water-insoluble drug containing a hollow long crystalline form is effective because it has good permeability to the tissue and good solubility because one unit of the crystal becomes small when the drug moves into the tissue. It can act to suppress stenosis.
  • toxicity is low because the drug hardly remains in the tissue as a large mass.
  • the layer containing the drug crystal 111 having a long crystal form type has a small crystal size (length in the major axis direction) that moves to the tissue of about 10 ⁇ m. Therefore, it acts uniformly on the affected part of the lesion and increases tissue permeability. Furthermore, since the size of the transferred drug crystal 111 is small, an excessive amount of drug does not remain in the affected part for an excessive period of time, so that it is possible to exhibit a high stenosis suppressing effect without developing toxicity. Think.
  • the drug coated on the outer surface of the balloon 11 may include an amorphous type.
  • the drug crystal 111 and the amorphous may be arranged so as to have regularity in the coat layer 30. Alternatively, crystals and amorphous materials may be arranged irregularly.
  • a coating liquid is applied to the surface of the balloon 11 by the balloon coating apparatus 2, and the applied coating liquid is dried to form a large number of water-insoluble drug crystals extending with independent long axes. .
  • the balloon coating apparatus 2 can form the coat layer 30 on the balloon 11.
  • the balloon coating apparatus 2 includes a rotation mechanism 50 that rotates the catheter 1 and a support base 70 that supports the catheter 1.
  • the balloon coating apparatus 2 further includes a tube-like first supply unit 92 for applying a coating liquid containing a drug on the surface of the balloon 11 and a tube-like second supply unit 97 for applying a crystal inducer.
  • the rotation mechanism 50 holds the hub 12 of the catheter 1 and rotates the catheter 1 around the axis of the shaft 10 by a drive source such as a built-in motor.
  • a drive source such as a built-in motor.
  • the core material 51 is inserted and held in the guide wire lumen 23, and the core material 51 prevents the coating liquid from flowing into the guide wire lumen 23.
  • a three-way cock that can open and close the flow path is connected to the proximal end opening 40 of the hub 12 in order to operate the flow of fluid to the expansion lumen 22.
  • the support base 70 includes a tubular proximal end support portion 71 that accommodates the shaft 10 and rotatably supports the shaft 10, and a distal end side support portion 72 that rotatably supports the core material 51. Note that the tip side support portion 72 may rotatably support the tip portion of the shaft 10 instead of the core material 51 if possible.
  • the moving mechanism 60 includes a moving table 61 that can move linearly in a direction parallel to the axis of the balloon 11, and a first tube fixing unit to which the first supply unit 92 and the second supply unit 97 are fixed. 62 and a second tube fixing portion 63.
  • the moving table 61 can move linearly by a driving source such as a built-in motor. As the moving table 61 moves, the first supply unit 92 and the second supply unit 97 move linearly in a direction parallel to the axis of the shaft 10.
  • the first supply container 90 and the second supply container 95 of the application mechanism 80 are placed on the moving table 61, and these are linearly moved in both directions along the axis.
  • the application mechanism 80 supplies a coating liquid application unit 81 that supplies and applies a coating liquid to be applied first to the surface of the balloon 11, and a crystal that supplies and applies a crystal inducer that is applied to the surface of the balloon 11 after application of the coating liquid.
  • an inducer application part 82 includes a first supply container 90 that stores the coating liquid, a first liquid supply pump 91 that supplies the coating liquid at an arbitrary liquid supply amount, and a first liquid application unit that applies the coating liquid to the balloon 11. 1 supply unit 92.
  • the crystal inducer application unit 82 includes a second supply container 95 that stores the crystal inducer, a second liquid supply pump 96 that supplies the crystal inducer in an arbitrary liquid supply amount, and the crystal inducer for the balloon 11. And a second supply unit 97 for applying to the substrate.
  • the first liquid feeding pump 91 and the second liquid feeding pump 96 are, for example, syringe pumps, and are controlled by the control unit 100.
  • the first liquid feed pump 91 sucks the coating liquid from the first supply container 90 through the suction pipe 93 and supplies the coating liquid to the first supply unit 92 through the supply pipe 94 at an arbitrary liquid feed amount. Can be supplied.
  • the second liquid feed pump 96 sucks the crystal inducer from the second supply container 95 through the suction pipe 98 and sends the crystal inducer to the second supply unit 97 through the supply pipe 99. Can be supplied in quantity.
  • the first liquid feeding pump 90 and the second liquid feeding pump 95 are installed on the moving table 61.
  • the first liquid delivery pump 90 and the second liquid delivery pump 95 are not limited to syringe pumps as long as they can deliver a coating liquid or a crystal inducer, and are, for example, a tube pump or a high-pressure pump for spraying. May be.
  • the first supply unit 92 communicates with the supply pipe 94 and discharges the coating liquid supplied from the first liquid feed pump 91 through the supply pipe 94 to the surface of the balloon 11.
  • the first supply unit 92 is a circular tubular member. An upper end of the first supply unit 92 is fixed to the first tube fixing unit 62. Further, the first supply unit 92 is formed with a first discharge port 92a extending vertically downward from the first tube fixing unit 62 and opening at the lower end.
  • the second supply unit 97 communicates with the supply pipe 99 and discharges or sprays the crystal inducer supplied from the second liquid feeding pump 96 through the supply pipe 99 onto the surface of the balloon 11.
  • the second supply unit 97 is a circular tubular member.
  • the second supply unit 97 has an upper end fixed to the second tube fixing unit 63.
  • the second supply unit 97 is formed with a second discharge port or spray port 97a that extends vertically downward from the second tube fixing unit 63 and opens at the lower end.
  • the first supply unit 92 and the second supply unit 97 move the moving table 61 to move the catheter 1 together with the first liquid feeding pump 91 and the second liquid feeding pump 96 installed on the moving table 61. It can move linearly in both directions along the axial center direction.
  • the first supply unit 92 and the second supply unit 97 are separated from each other with a predetermined interval in the axial direction of the balloon 11, and the interval is maintained even when moving by the moving table 61.
  • the 1st supply part 92 and the 2nd supply part 97 may not be circular as long as a coating liquid and a crystal inducer can be supplied.
  • the first supply unit 92 and the second supply unit 97 do not extend in the vertical direction as long as the coating liquid and the crystal inducer can be discharged or sprayed from the discharge ports or the spray ports 92a and 97a. Also good.
  • the first supply unit 92 and the second supply unit 97 are arranged so as not to contact the surface of the balloon 11.
  • the material of the first supply unit 92 and the second supply unit 97 various materials that are flexible or hard can be used.
  • the first supply unit 92 and the second supply unit 97 may be disposed so as to contact the surface of the balloon 11.
  • the material of the first supply unit 92 and the second supply unit 97 is flexible so that the contact load on the balloon 11 can be reduced and the change in the contact position accompanying the rotation of the balloon 11 can be absorbed by bending.
  • the material of the first supply unit 92 and the second supply unit 97 is flexible so that the contact load on the balloon 11 can be reduced and the change in the contact position accompanying the rotation of the balloon 11 can be absorbed by bending.
  • the material of the first supply unit 92 and the second supply unit 97 is flexible so that the contact load on the balloon 11 can be reduced and the change in the contact position accompanying the rotation of the balloon 11 can be absorbed by bending.
  • the constituent materials of the first supply unit 92 and the second supply unit 97 are, for example, polyolefins such as polyethylene and polypropylene, cyclic polyolefins, polyesters, polyamides, polyurethanes, PTFE (polytetrafluoroethylene), ETFE (tetrafluoroethylene ⁇ Fluorine resin such as ethylene copolymer), PFA (tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer), FEP (tetrafluoroethylene / hexafluoropropylene copolymer), etc. can be applied. There is no particular limitation as long as it can be deformed.
  • the constituent material of the second supply unit 97 is a metal such as brass or stainless steel or a resin such as polypropylene, polyvinyl chloride, or polyvinylidene fluoride. Can be applied.
  • the outer diameters of the first supply unit 92 and the second supply unit 97 are not particularly limited, but for example, 0.1 mm to 5.0 mm, preferably 0.15 mm to 3.0 mm, more preferably 0.3 mm to 2 .5 mm.
  • the inner diameters of the first supply unit 92 and the second supply unit 97 are not particularly limited, but are, for example, 0.05 mm to 3.0 mm, preferably 0.1 mm to 2.0 mm, and more preferably 0.15 mm to 1.mm. 5 mm.
  • the lengths of the first supply unit 92 and the second supply unit 97 are not particularly limited, but may be a length within 5 times the balloon diameter, for example, 1.0 mm to 50 mm, preferably 3 mm to 40 mm.
  • the spray diameter of the second supply unit 97 is not particularly limited, but for example 0.1 mm to 10.0 mm, preferably 0.1 mm to 7.0 mm.
  • the spray angle is not particularly limited, but is, for example, 0 ° to 120 °, more preferably 0 ° to 90 °.
  • the control unit 100 is configured by a computer, for example, and comprehensively controls the rotation mechanism 50, the movement mechanism 60, and the coating mechanism 80. Therefore, the control unit 100 determines the rotational speed of the balloon 11, the moving speed of the first supply unit 92 and the second supply unit 97 in the axial direction relative to the balloon 11, the first supply unit 92 and the second supply unit. The discharge speed of the coating liquid and the crystal inducer from 97 or the spraying flow rate when spraying can be comprehensively controlled.
  • the coating liquid supplied to the surface of the balloon 11 by the first supply unit 92 is a solution or suspension containing the constituent material of the coat layer 30 and contains a water-insoluble drug, an excipient, an organic solvent, and water. Yes. After the coating liquid is supplied to the surface of the balloon 11, the organic solvent and water are volatilized, so that a large number of water-insoluble drug crystals extending on the surface of the balloon 11 with independent long axes are formed. A coat layer 30 having a scale is formed.
  • the viscosity of the coating solution is 0.2 to 1500 cP, preferably 0.2 to 500 cP, more preferably 0.2 to 100 cP.
  • Water-insoluble drug means a drug that is insoluble or sparingly soluble in water. Specifically, the solubility in water is less than 5 mg / mL at pH 5-8. Its solubility may be less than 1 mg / mL and even less than 0.1 mg / mL. Water-insoluble drugs include fat-soluble drugs.
  • examples of some preferred water-insoluble drugs include immunosuppressants, such as cyclosporines including cyclosporine, immunoactive agents such as rapamycin, anticancer agents such as paclitaxel, antiviral or antibacterial agents, anti-neoplastic agents, Analgesics and anti-inflammatory agents, antibiotics, antiepileptics, anxiolytics, antiparalytic agents, antagonists, neuron blocking agents, anticholinergics and cholinergic agents, antimuscarinic and muscarinic agents, antiadrenergic agents, Contains antiarrhythmic, antihypertensive, hormonal and nutritional agents.
  • immunosuppressants such as cyclosporines including cyclosporine, immunoactive agents such as rapamycin, anticancer agents such as paclitaxel, antiviral or antibacterial agents, anti-neoplastic agents, Analgesics and anti-inflammatory agents, antibiotics, antiepileptics, anxiolytics, antiparalytic agents, antagonist
  • Water-insoluble drugs are preferably paclitaxel and paclitaxel derivatives, taxanes, docetaxel and rapamycin and rapamycin derivatives, such as biolimus A9, pimecrolimus, everolimus, zotarolimus, tacrolimus, fasudil and epothilone, paclitaxel and rapamycin, especially docetaxel, and evelimel.
  • rapamycin, paclitaxel, docetaxel and everolimus include analogs and / or derivatives thereof as long as they have the same medicinal effect.
  • paclitaxel and docetaxel are in an analog relationship.
  • Rapamycin and everolimus are in a derivative relationship. Of these, paclitaxel is more preferred.
  • Additive 110 contains a water-soluble low-molecular compound.
  • the molecular weight of the water-soluble low molecular weight compound is 50 to 2000, preferably 50 to 1000, more preferably 50 to 500, and further preferably 50 to 200.
  • the water-soluble low molecular weight compound is preferably 5 to 10,000 parts by weight, more preferably 5 to 200 parts by weight, and still more preferably 8 to 150 parts by weight with respect to 100 parts by weight of the water-insoluble drug.
  • the constituent materials of water-soluble low molecular weight compounds are serine ethyl ester, citrate ester, polysorbate, water-soluble polymer, sugar, contrast agent, amino acid ester, glycerol ester of short-chain monocarboxylic acid, pharmaceutically acceptable salt and interface An activator or the like, or a mixture of two or more of these can be used.
  • the water-soluble low molecular weight compound has a hydrophilic group and a hydrophobic group and is characterized by being dissolved in water.
  • the water-soluble low molecular weight compound is preferably non-swellable or hardly swellable.
  • the additive 110 is preferably amorphous on the balloon 11.
  • the additive 110 containing a water-soluble low-molecular compound has an effect of uniformly dispersing the water-insoluble drug on the outer surface of the balloon 11. Furthermore, since the additive 110 is easily dissolved when the balloon 11 is expanded in the blood vessel, the drug crystal 111 of the water-insoluble drug on the outer surface of the balloon 11 is easily released, and the drug crystal 111 adheres to the blood vessel. Has the effect of increasing the amount.
  • Additive 110 is preferably not a hydrogel. Since the additive 110 is a low molecular weight compound, it dissolves quickly without swelling when in contact with an aqueous solution.
  • the additive 110 is easily dissolved when the balloon 11 is expanded in the blood vessel, the particles of the water-insoluble drug crystal 111 on the outer surface of the balloon 11 are easily released. It has the effect of increasing the amount of adhesion.
  • the additive 110 is a matrix made of a contrast agent such as Ultravist (registered trademark)
  • crystal particles are embedded in the matrix, and crystals are not generated from the base material of the balloon 11 toward the outside of the matrix.
  • the drug crystal 111 of the present embodiment can extend from the surface of the base material of the balloon 11 to the outside of the additive 110.
  • the solvent contained in the coating liquid is a solvent capable of dissolving the water-insoluble drug or a mixture containing the same.
  • a solvent is not particularly limited, but tetrahydrofuran, acetone, glycerin, ethanol, methanol, dichloromethane, hexane, ethyl acetate, water, among them tetrahydrofuran, ethanol, acetone, water, and some of these are preferable. .
  • a combination of tetrahydrofuran and water, tetrahydrofuran and ethanol and water, tetrahydrofuran and acetone and water, acetone and ethanol and water, tetrahydrofuran, acetone, ethanol, and water can be used.
  • the crystal inducer supplied to the surface of the balloon 11 by the second supply unit 97 is a substance that generates a crystal of a drug contained in the coating solution, and is miscible with the solvent contained in the coating solution.
  • the solubility of the water-insoluble drug is less than that of the solvent contained in the solution or a mixture thereof, or is not soluble.
  • Examples of such a crystal inducer include a solvent corresponding to a poor solvent in which the solubility of the drug contained in the coating liquid is small. When a poor solvent is added to the coating liquid, the solvent dissolving the drug contained in the coating liquid and the poor solvent are dissolved together, the solubility of the drug as a solute is lowered, and the drug is precipitated as crystals. Further, it is desirable that the crystal inducer does not volatilize and remain after the drug is crystallized. Specifically, water, heptane, or a mixture thereof can be used as the substance having such properties.
  • the solvent and the crystal inducer contained in the coating liquid need to be a combination in which the drug is precipitated by the poor solvent addition method, and typically includes a combination of tetrahydrofuran and water.
  • the water-insoluble drug is paclitaxel and the solvent contained in the coating liquid is dimethyl sulfoxide or N, N-dimethylacetamide
  • examples of the crystal inducer include acetonitrile, alcohols, acetone, tetrahydrofuran, and water.
  • examples of the crystal inducer include water and heptane.
  • a combination in which the solvent contained in the coating liquid is tetrahydrofuran, acetone, and ethanol and the crystal inducer is water can be mentioned.
  • a combination in which the solvent contained in the coating liquid is dimethyl sulfoxide and the crystal inducer is acetone and water can be mentioned.
  • Other combinations are also possible.
  • an expansion fluid is supplied into the balloon 11 through a three-way cock connected to the proximal end opening 40 of the hub 12.
  • the three-way cock is operated to seal the expansion lumen 22, and the state where the balloon 11 is expanded is maintained.
  • the balloon 11 is expanded at a pressure (for example, 4 atmospheres) lower than the pressure (for example, 8 atmospheres) at the time of use in the blood vessel.
  • the catheter 1 is rotatably installed on the support base 70, and the hub 12 is connected to the rotation mechanism 50.
  • the position of the moving table 61 is adjusted to position the first supply unit 92 with respect to the balloon 11.
  • the first discharge port 92 a of the first supply unit 92 is positioned so as to be close to the position on the most distal end side where the coating layer 30 is formed in the balloon 11.
  • the first supply unit 92 that applies the coating liquid to the balloon 11 is located closer to the base end side of the balloon 11 than the second supply unit 97 that applies the crystal inducer to the balloon 11. Therefore, in this state, the second supply unit 97 is located on the distal end side from the position on the most distal end side where the coating layer 30 is formed in the balloon 11 and is not opposed to the balloon 11.
  • the rotating mechanism 50 rotates the catheter 1 in the axial direction of the shaft 10 and moves the moving table 61 while moving the coating liquid from the first supply unit 92 toward the balloon 11.
  • the discharge amount of the coating liquid is adjusted by the first liquid feed pump 91.
  • the first supply unit 92 is moved from the distal end side of the balloon 11 toward the proximal end side by the moving table 61.
  • the coating liquid is applied to the surface of the balloon 11 while drawing a spiral.
  • the second supply unit 97 moves together with the first supply unit 92 while keeping the distance of the first supply unit 92 in the axial direction of the balloon 11 constant.
  • the second supply unit 97 located on the distal end side of the balloon 11 from the first supply unit 92 reaches the area where the coat layer 30 is formed, as shown in FIG.
  • the discharge of the crystal inducer toward the balloon 11 is started.
  • the discharge amount or spray flow rate of the crystal inducer is adjusted by the second liquid feeding pump 96.
  • the second supply unit 97 When the second supply unit 97 reaches the position where the coating solution is applied by the first supply unit 92, the coating solution is not dried and the drug is not crystallized. In this state, the crystal inducer is discharged or sprayed from the second supply unit 97 to be applied repeatedly. By adding a crystal inducer to the coating liquid, crystals of the drug contained in the coating liquid are generated.
  • the crystal inducer By applying the crystal inducer to the surface of the balloon 11 so as to follow the application of the coating liquid, the crystal inducer is added after a certain time from the application of the coating liquid.
  • the crystal formation rate can be kept constant. For this reason, crystallization can proceed under certain conditions without being affected by external factors such as temperature in the manufacturing room, air flow, variation in procedure, and individual differences in the coating liquid and balloon 11. Thereby, variation in crystal shape can be suppressed, and crystals having a certain shape and size can be stably formed on the surface of the balloon 11.
  • the shape and size of the crystals formed on the surface of the balloon 11 are the distance between the first supply unit 92 and the second supply unit 97 in the axial direction of the balloon 11, the type of crystal inducer, the discharge amount, or the spray amount. Can be adjusted.
  • the moving speed of the first supply unit 92 and the second supply unit 97 is not particularly limited, but for example 0.01 to 2 mm / sec, preferably 0.03 to 1.5 mm / sec, more preferably 0.05. ⁇ 1.0 mm / sec.
  • the discharge amounts of the coating liquid and the crystal inducer from the first supply unit 92 and the second supply unit 97 are not particularly limited, but are, for example, 0.01 to 1.5 ⁇ L / sec, preferably 0.01 to 1.. 0 ⁇ L / sec, more preferably 0.03 to 0.8 ⁇ L / sec.
  • the spray flow rate from the second supply unit 97 is not particularly limited, but is, for example, 0.1 to 5.0 mL / sec, preferably 0.8. 1 to 1.0 ⁇ L / sec, more preferably 0.1 to 0.5 mL / sec.
  • the rotation speed of the balloon 11 is not particularly limited, but is, for example, 10 to 300 rpm, preferably 30 to 250 rpm, and more preferably 50 to 200 rpm.
  • the diameter of the balloon 11 when applying the coating solution and the crystal inducer is not particularly limited, but is, for example, 1 to 10 mm, preferably 2 to 7 mm.
  • the coating solution is applied to the surface of the balloon 11
  • the crystal inducer is applied to the surface of the balloon 11
  • the organic solvent that is the solvent of the coating solution and the crystal inducer dissolve in each other, and the solubility of the drug decreases.
  • the drug precipitates and crystals grow from the crystal nucleus.
  • the solvent contained in the coating solution is volatilized.
  • the time from application of the coating solution to crystal growth depends on external factors such as temperature in the case of precipitation due to volatilization of the organic solvent. By adding the agent, crystals are generated regardless of external factors.
  • a morphological form of drug crystal including a plurality of drug crystals 111 each having an independent long axis is formed on the surface of the balloon 11.
  • the drug crystal 111 in this state stands with respect to the surface of the balloon 11.
  • the proximal end of the drug crystal 111 may be located on the surface of the balloon 11, the surface of the additive 110, or the inside thereof.
  • the first supply unit 92 and the second supply unit 97 are gradually moved along the axial direction of the balloon 11 while rotating the balloon 11, so that the surface of the balloon 11 is moved toward the axial direction.
  • the coat layer 30 is formed gradually. After the coating layer 30 having the drug crystal 111 is formed in the entire range where the coating layer 30 is to be formed in the balloon 11, the rotation mechanism 50, the moving mechanism 60, and the coating mechanism 80 are stopped.
  • the catheter 1 is removed from the balloon coating apparatus 2 and the coating of the balloon 11 is completed.
  • the balloon 11 has a substantially circular cross section with the expansion fluid injected therein. From this state, the balloon 11 is formed with the protruding blade portion 120, and as shown in FIG. 7 (b), the blade outer portion 120 b constituting the outer surface of the blade portion 120 and the inner portion of the blade portion 120. A blade inner portion 120a constituting the side surface and an intermediate portion 120c located between the blade outer portion 120b and the blade inner portion 120a are formed. From this state, as shown in FIG.7 (c), the blade
  • the blade inner portion 120a and the intermediate portion 120c are overlapped and contacted, and an overlapping portion 121 is formed in which the outer surfaces of the balloon 11 are opposed to each other. And a part of intermediate part 120c and the blade
  • the region on the tip end side of the root side space portion 122 of the blade portion 120 is in close contact with the intermediate portion 120c.
  • the ratio of the circumferential length of the base side space portion 122 to the circumferential length of the blade portion 120 is in the range of 1 to 95%.
  • the blade outer portion 120b of the balloon 11 receives a pressing force that rubs in the circumferential direction from a blade for folding the balloon 11, and is further heated. As a result, the long drug crystal 111 provided on the blade outer side portion 120 b falls on the surface of the balloon 11 and is easy to sleep. It is not necessary for all of the drug crystal 111 to fall asleep.
  • the drug crystal 111 is difficult to sleep.
  • the drug crystal 111 is Easy to receive pressure. Therefore, in this region, the drug crystal 111 falls down and tends to sleep.
  • Example 1 a drug-eluting balloon 11 is produced by a crystal inducer dropping method.
  • a catheter 1 having a balloon 11 size of 6.0 mm in diameter and 200 mm in length was prepared.
  • the material of the balloon 11 that is the expansion portion is nylon elastomer.
  • the balloon 11 expanded with the coating solution was coated so that the amount of paclitaxel was about 3 ⁇ g / mm 2 .
  • a dispensing tube (first supply unit 92) having an opening at the foremost end and formed of polyethylene is used as the catheter. 1 was moved from the lateral direction (horizontal direction) with respect to 1, and a part of the side surface of the tip of the dispensing tube was installed so as to contact along the outer surface of the balloon 11. And the metal nozzle (2nd supply part 97) for dripping heptane was installed in the reverse direction of the advancing direction of the dispensing tube for discharging a coating solution so that the surface of the balloon 11 may not be contacted.
  • the catheter 1 was rotated about the axis of the balloon 11 in the opposite direction (reverse direction) to the discharge direction of the medicine. While maintaining the rotation, the coating solution is discharged from the distal end opening (first discharge port 92a) of the dispensing tube while constantly contacting the outer surface of the balloon 11 with the side surface of the distal end of the dispensing tube. Heptane was dropped from the tip of a metal nozzle to the coating solution thus formed. The moving speed of the dispensing tube and the metal nozzle in the axial direction of the balloon 11 and the rotation speed of the balloon 11 are adjusted, and at the start of rotation, the coating solution is discharged at 0.547 ⁇ L / sec. Heptane was discharged at 0.055 ⁇ L / sec and added dropwise to the coated coating solution. Thereafter, the balloon 11 after coating was dried to produce a drug-eluting balloon 11.
  • Example 2 the balloon 11 is produced by a crystal inducer spraying method.
  • a catheter 1 having a balloon 11 size of 6.0 mm in diameter and 200 mm in length was prepared.
  • the material of the balloon 11 that is the expansion portion is nylon elastomer.
  • the expanded balloon 11 was coated with the coating solution so that the amount of paclitaxel was about 3 ⁇ g / mm 2 .
  • a dispensing tube (first supply unit 92) having an opening at the foremost end and formed of polyethylene is used as the catheter. 1 was moved from the lateral direction (horizontal direction) with respect to 1, and a part of the side surface of the tip of the dispensing tube was installed so as to contact along the outer surface of the balloon 11. And the spray (2nd supply part 97) for spraying water was installed in the reverse direction of the advancing direction of the dispensing tube for discharging a coating solution so that the surface of the balloon 11 may not be contacted. In this state, the catheter 1 was rotated about the axis of the balloon 11 in the opposite direction (reverse direction) to the discharge direction of the medicine.
  • the coating solution is discharged from the distal end opening (first discharge port 92a) of the dispensing tube while constantly contacting the outer surface of the balloon 11 with the side surface of the distal end of the dispensing tube. Water was sprayed from the spray onto the resulting coating solution. The moving speed of the dispensing tube and spray in the axial direction of the balloon 11 and the rotation speed of the balloon 11 are adjusted, and at the start of rotation, the coating solution is discharged at 0.547 ⁇ L / sec. Water was sprayed onto the coating solution thus formed at a spray flow rate of 0.138 mL / sec. Thereafter, the balloon 11 after coating was dried to produce a drug-eluting balloon 11.
  • the surgeon punctures a blood vessel from the skin by a known method such as the Seldinger method, and places an introducer (not shown).
  • the guide wire 200 (see FIG. 8) is inserted into the guide wire lumen 23.
  • the guide wire 200 and the catheter 1 are inserted into the blood vessel from the inside of the introducer.
  • the catheter 1 is advanced while the guide wire 200 is advanced, and the balloon 11 reaches the stenosis.
  • a guiding catheter may be used to reach the catheter 1 to the stenosis 300.
  • a predetermined amount of expansion fluid is injected from the proximal end opening 40 of the hub 12 using an inflator or a syringe, and the expansion fluid is fed into the balloon 11 through the expansion lumen 22.
  • the folded balloon 11 is expanded, and the narrowed portion 300 is pushed and expanded by the balloon 11.
  • the coat layer 30 provided on the outer surface of the balloon 11 contacts the narrowed portion 300.
  • the drug crystal 111 is delivered to the living body while the additive 110 that is a water-soluble low-molecular compound contained in the coat layer 30 is gradually or quickly dissolved.
  • the drug crystal 111 of the coat layer 30 is uniformly formed by the manufacturing method described above. For this reason, a medicine can be made to act satisfactorily on a living body without variation.
  • the expansion fluid is sucked and discharged from the proximal end opening 40 of the hub 12, and the balloon 11 is contracted and folded. Thereafter, the guide wire 200 and the catheter 1 are removed from the blood vessel via the introducer, and the procedure is completed.
  • the balloon coating method according to the present embodiment is a balloon coating method in which the coat layer 30 is formed on the surface of the balloon 11 in the catheter 1 having the balloon 11 at the distal end portion of the shaft 10.
  • the coating liquid containing the drug is supplied from the first supply unit 92 to the surface of the balloon 11 while rotating around the axis of the axis 10, and the coating liquid is maintained while the rotation of the catheter 1 is maintained.
  • the crystal inducer is added after a certain time from the application of the coating liquid, the crystal formation rate can be made constant over the entire surface of the balloon 11. For this reason, crystallization can proceed under certain conditions without being influenced by external factors. Thereby, variation in crystal shape can be suppressed, and crystals having a certain shape and size can be stably formed on the surface of the balloon 11.
  • the balloon coating method of the present embodiment includes a step of volatilizing the solvent of the coating liquid and the crystal inducer after applying a crystal inducer to the surface of the balloon 11 to generate a drug crystal.
  • the solvent and the crystal inducer volatilize after the crystal is generated by the crystal inducer, the drug can be crystallized regardless of the volatilization conditions of the solvent and the crystal inducer, and the balloon can be used regardless of external factors. It is possible to form drug crystals uniformly dispersed on the surface of 11.
  • first supply unit 92 and the second supply unit 97 are spaced apart from each other at a predetermined interval in the axial direction of the balloon 11, and the first supply unit 92 moves in parallel in advance, with respect to the surface of the balloon 11. Apply the solution. Thereby, the time from the application of the coating solution to the addition of the crystal inducer can be made constant throughout the balloon 11.
  • the distance between the first supply unit 92 and the second supply unit 97 in the axial direction of the balloon 11 is adjusted, and then the first supply unit 92 and the second supply unit 97 to the surface of the balloon 11. If the liquid is applied, the time from application of the coating liquid to application of the crystal inducer can be changed, so that the shape and size of the drug crystals formed on the surface of the balloon 11 can be adjusted. .
  • the crystal inducer is a poor solvent for the drug.
  • medical agent is promoted by adding a crystal inducer to a coating liquid.
  • the drug contained in the coating solution is rapamycin, paclitaxel, docetaxel, or everolimus, restenosis of the stenosis in the blood vessel can be satisfactorily suppressed.
  • the crystal inducer is water, heptane, or a mixture thereof, the solubility of paclitaxel in the crystal inducer is low, and thus the crystal formation of paclitaxel can be effectively promoted.
  • the solvent contained in the coating solution is either dimethyl sulfoxide or N, N-dimethylacetamide
  • the crystal inducer is any one of acetonitrile, alcohols, acetone, tetrahydrofuran, and water.
  • the crystal inducer is miscible with the solvent contained in the coating solution, and the solubility of the water-insoluble drug is less than or not soluble in the solvent contained in the coating solution or a mixture thereof. can do.
  • the solvent contained in the coating liquid is any one of acetonitrile, alcohols, acetone, and tetrahydrofuran, and the crystal inducer is either water or heptane.
  • the crystal inducer is miscible with the solvent contained in the coating solution, and the solubility of the water-insoluble drug is less than or not soluble in the solvent contained in the coating solution or a mixture thereof. can do.
  • the present invention is not limited to the above-described embodiment, and various modifications can be made by those skilled in the art within the technical idea of the present invention.
  • the above-described balloon catheter 10 is a rapid exchange type, but may be an over-the-wire type.
  • the first supply unit 92 that supplies the coating liquid and the second supply unit 97 that supplies the crystal inducer are moved integrally by the moving table 61.
  • the supply unit 92 and the second supply unit 97 may move independently. Even in this case, the crystal inducer is applied to the surface of the balloon 11 before the coating solution is dried.
  • the 1st supply part 92 and the 2nd supply part 97 may be arrange
  • the method of applying the coating liquid and the crystal inducer is not limited to the above-described embodiment, and other methods such as a spray method and a string drawing method can be used.

Abstract

La présente invention concerne un procédé de revêtement de ballonnet dans lequel des cristaux uniformes sont formés sur une surface de ballonnet sans être affectés par des facteurs externes. L'invention concerne un procédé de revêtement de ballonnet pour former une couche de revêtement (30) sur la surface d'un ballonnet (11) dans un cathéter (1) comportant le ballonnet (11) à l'extrémité distale d'une tige (10), le procédé de revêtement de ballonnet comportant une étape pour distribuer et appliquer une solution de revêtement qui contient un médicament d'une première partie d'alimentation (92) à la surface du ballonnet (11) tout en faisant tourner le cathéter (1) autour de l'axe de la tige (10), et une étape de distribution et d'application d'un inducteur de cristallisation depuis une deuxième partie d'alimentation (97) sur la surface du ballonnet 11 sur lequel la solution de revêtement a été appliquée et l'induction de la cristallisation avant que la solution de revêtement ne sèche tandis que la rotation du cathéter 1 est maintenue.
PCT/JP2018/010470 2017-03-16 2018-03-16 Procédé de revêtement de ballonnet WO2018169051A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011525849A (ja) * 2008-06-25 2011-09-29 ボストン サイエンティフィック サイムド，インコーポレイテッド 治療剤を含む医療機器
JP2013192755A (ja) * 2012-03-21 2013-09-30 Japan Lifeline Co Ltd 薬剤投与バルーンカテーテルおよびその製造方法
JP2014200269A (ja) * 2013-04-01 2014-10-27 テルモ株式会社 バルーンコーティング方法
WO2015151876A1 (fr) * 2014-04-01 2015-10-08 テルモ株式会社 Procédé de revêtement de ballonnet
WO2016118923A1 (fr) * 2015-01-22 2016-07-28 Intersect Ent, Inc. Ballonnet enduit de médicament

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2874824C (fr) * 2012-06-01 2021-10-26 Surmodics, Inc. Appareil et methode de revetement de catheters a ballonnet

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011525849A (ja) * 2008-06-25 2011-09-29 ボストン サイエンティフィック サイムド，インコーポレイテッド 治療剤を含む医療機器
JP2013192755A (ja) * 2012-03-21 2013-09-30 Japan Lifeline Co Ltd 薬剤投与バルーンカテーテルおよびその製造方法
JP2014200269A (ja) * 2013-04-01 2014-10-27 テルモ株式会社 バルーンコーティング方法
WO2015151876A1 (fr) * 2014-04-01 2015-10-08 テルモ株式会社 Procédé de revêtement de ballonnet
WO2016118923A1 (fr) * 2015-01-22 2016-07-28 Intersect Ent, Inc. Ballonnet enduit de médicament

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