WO2024120532A1 - 利用球囊实现药物输送的装置、给药装置及微创医学系统 - Google Patents
利用球囊实现药物输送的装置、给药装置及微创医学系统 Download PDFInfo
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- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229920002725 thermoplastic elastomer Polymers 0.000 description 1
- 229920002803 thermoplastic polyurethane Polymers 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 208000006601 tracheal stenosis Diseases 0.000 description 1
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M29/00—Dilators with or without means for introducing media, e.g. remedies
- A61M29/02—Dilators made of swellable material
-
- 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
-
- 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
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
Definitions
- the present invention relates to the technical field of medical devices, and in particular to a device for delivering drugs using a balloon, a drug delivery device and a minimally invasive medical system.
- Balloon catheters have been used to improve lesions (stenosis) in biological lumens.
- Balloon catheters usually include a long shaft and a radially expandable balloon disposed at the front end of the shaft. The lesion can be expanded by expanding the deflated balloon to the target site in the body through the narrow biological lumen.
- a drug eluting balloon (DEB) is used, in which the outer surface of the balloon is coated with a drug for inhibiting stenosis.
- the drug eluting balloon expands to release the drug coated on the outer surface to the lesion instantly, which can move the drug to the biological tissue, thereby inhibiting restenosis.
- the limited release time makes the effective release rate of the drug less than 10%, and the low effective transfer rate of the drug is also the direction and difficulty of this technology to be improved.
- the perfusion balloon is a porous balloon, which injects the drug into the surface of the inner wall of the blood vessel through micropores by injection, and also transfers the drug to the lower part of the inner wall of the blood vessel by tissue absorption.
- the purpose of the present invention is to solve the above-mentioned problem and to provide a device, a drug delivery device and a minimally invasive medical system using a balloon.
- the present invention provides a device for drug delivery using a balloon, comprising: a delivery catheter, multiple puncture components and a balloon component, wherein:
- the delivery catheter has a proximal portion and a distal portion, and includes a first channel for delivering drugs and a second channel for circulation and pressure relief, which are not connected to each other. At least the first channel near the distal portion is a multi-lumen structure, and the multi-lumen structure includes a plurality of independent drug delivery channels for delivering drugs.
- each group of puncture components includes at least one puncture structure and a drug delivery cavity
- the puncture structure includes a puncture portion and a drug release hole
- the drug release hole in the group is connected to the drug delivery cavity
- the drug delivery cavity is connected to the corresponding drug delivery channel
- the balloon assembly comprises at least one balloon, which is connected to the distal end of the second channel and is configured to change between a folded configuration and an expanded configuration.
- the multiple groups of puncture components are separately enclosed in the balloon.
- the balloon is expanded by pressurizing the second channel to put it in the expanded configuration.
- the expansion of the balloon drives the puncture parts of the multiple groups of puncture components to protrude.
- the drug is configured to be delivered to the target area through multiple drug delivery channels, the drug delivery cavity corresponding to each drug delivery channel, and the drug release hole connected to the drug delivery cavity under the action of external force.
- the balloon assembly further comprises a guide catheter, the distal end of the balloon is connected to the guide catheter to seal the distal end of the balloon, and the proximal end of the balloon is connected to the guide catheter in a sealed or unsealed manner;
- the balloon is folded to form a plurality of pairs of folding wings, which are arranged circumferentially along the guide catheter, and each pair of folding wings arranged opposite to each other forms a folding wing space, and the puncture assemblies of these groups are respectively accommodated in the adapted folding wing spaces, and the plurality of pairs of folding wings are evenly arranged circumferentially of the balloon;
- the drug delivery cavity further comprises a base, the upper surface of the base and other peripheral surfaces form a relatively fixed drug delivery cavity, the upper surface of the base is provided with a through hole connected with the drug release hole along the length direction of the balloon, the puncture structure is fixedly arranged on the upper surface of the base, and the drug release hole is connected with the drug delivery cavity through the through hole; more preferably, the height H of the folding wing space is not less than the sum of the height h2 of the base and the height h1 of the puncture structure;
- the base is made of hard material; preferably, the base is made of metal material, polymer material or ceramic material; preferably, the upper surface of the base is made of metal material, polymer material or ceramic material;
- the cross section of the base is a hollow structure; more preferably, the cross section of the base is a hollow circle, a hollow ellipse, a hollow rectangle, a hollow polygon or a contoured hollow structure; preferably, the outer contour of the base is a contoured hollow structure with an arc, and the curvature of the contoured hollow structure is consistent with the curvature of the balloon;
- the drug delivery cavity is arranged on the outer surface of the balloon, and the other outer peripheral surfaces of the base include a lower surface, the lower surface is fixed to the outer surface of the balloon, and in the unfolded configuration, as the balloon expands, the base is driven to move outward, thereby driving the puncture portion arranged on the upper surface of the base to protrude; or, the drug delivery cavity is arranged on the inner surface of the balloon, the base is arranged inside the inner surface of the balloon, the upper surface of the base is fixedly fitted with the inner surface of the balloon, a hole for the puncture structure to pass through is provided on the balloon, and the puncture structure is protruded from the inner surface of the balloon through which the puncture structure passes, and in the folded configuration, the protruding puncture structure is arranged in the folding wing space formed by the folding wing; in the unfolded configuration, as the balloon expands, the base is driven to move outward, thereby driving the protruding puncture structure to extend out of the folding wing space, and
- each group of puncture assemblies are arranged along the circumference of the guide catheter;
- the height of the folding wing space should be no less than the protruding height of the puncture structure protruding from the inner surface of the balloon;
- the base and the balloon are connected by pasting or welding after plasma treatment;
- the ends of the folded wings on both sides of the puncture structure are at an equal distance from the puncture structure;
- each group of puncture side components is symmetrically arranged;
- each group of puncture components has multiple puncture structures, which are arranged at intervals along the length direction of the base, the top of the puncture part is pointed, and the end of the puncture part is surrounded to form the drug release hole;
- each puncture structure in each group of puncture components is equidistantly distributed;
- the multiple groups of puncture components are three or four groups;
- the delivery catheter is further provided with a pressure-charging and pressure-releasing control unit and a drug delivery control unit, the flow pressure-charging and pressure-releasing channel formed by the second channel and the balloon is controlled by the pressure-charging and pressure-releasing control unit, and the first channel and the balloon are respectively controlled by the drug delivery control unit;
- the first channel is provided with a first Luer interface, and the first Luer interface is connected to the catheter lumens corresponding to the multiple drug delivery channels through a catheter;
- a groove is provided along the radial direction of the second channel, and the groove is extended along the axial direction of the second channel, and the groove is used to accommodate the first channel, so that the radial size of the non-balloon part of the device is smaller; preferably, the radius of the groove is not less than the outer diameter of the first channel; preferably, the depth of the groove may be not less than the outer radius of the first channel; preferably, the device further comprises a catheter hub, which is connected to the first channel and is used to deliver drugs, and preferably, the catheter hub is a double Luer connector (2-Way Hub) or a three-Way Hub (3-Way Hub) or even a multi-Luer connector design; a Luer connector on the catheter hub can be connected to a valve, a connector, a syringe or a pressure filler, through which a special drug is given to the infusion channel, and the drug is a designated drug system;
- a pressure inflation and deflation control unit and a drug delivery control unit are also provided on the delivery catheter, and the pressure inflation and deflation channel formed by the second channel and the balloon and the drug delivery channel are controlled by the pressure inflation and deflation control unit and the drug delivery control unit respectively.
- the puncture portion has a puncture wall, a puncture cavity and a puncture surface
- the puncture surface is the surface at the top of the puncture portion, that is, the surface that produces the puncture effect when piercing the tissue
- the puncture surface is a plane, and the angle a between the puncture surface and the plane perpendicular to the axial direction of the puncture structure is 5 to 85°
- the puncture surface is a conical surface, and the angle a of the conical surface is 25 to 75°
- the puncture surface is a concave surface, a convex surface or a multi-prism surface
- the outer part of the puncture wall is cylindrical, conical, cylindrical at the bottom and conical at the top, or stepped, and correspondingly, the puncture cavity is cylindrical, conical or stepped ladder-shaped; preferably, the inside of the puncture wall is ladder-shaped, and the closer to the top, the smaller the radial dimension inside, so as to increase the pressure of drug
- the exterior of the puncture wall is a surface extending along the axial direction of the balloon
- the puncture cavity is a gap formed along the puncture wall
- the cross section of the puncture wall is two triangles arranged opposite to each other
- the middle of the puncture wall is the puncture cavity
- the drug release hole is an elongated opening or a slot-shaped opening; preferably, the drug release hole opens along the axial direction of the puncture portion; preferably, the drug release hole opens along the radial direction of the puncture portion; preferably, the opening of the drug release hole faces an angle direction between the axial direction and the radial direction; preferably, on the same puncture portion, there are one or more drug release holes;
- the drug release hole is circular, elliptical, rectangular or polygonal in shape
- the puncture portion is made of a hard material, and the hard material is a polymer material, a ceramic material or a metal material;
- the cross-section of the drug delivery cavity is circular, elliptical, triangular, rectangular or polygonal;
- the height h1 of the puncture portion is between 0.1 and 1.5 mm, and the height of the drug delivery cavity is between 0.1 and 0.5 mm; preferably, the ratio of the wall thickness T of the drug delivery cavity to the outer diameter D (transverse dimension W) is 0.06 to 0.8, preferably, the ratio of the wall thickness T of the drug delivery cavity to the outer diameter D (transverse dimension W) is 0.06 to 0.8, preferably, the ratio of the wall thickness T of the drug delivery cavity to the outer diameter D (transverse dimension W) is 0.05 to 0.45; preferably, the puncture portion and the drug delivery cavity are connected by welding or bonding; preferably, the distance between each puncture portion is less than the radial dimension of the puncture portion; preferably, the distance between each puncture portion is 0.5 to 5 mm; preferably, the distance is 1 to 2 mm;
- the base is a tube body with a cylindrical structure, and the base is made of a hard material;
- the upper surface of the base connected to the puncture portion is made of hard material, and the other surface parts are made of flexible material to form a hose;
- the base is a plate-like structure
- the length of the plate-like structure is less than the axial length of the balloon
- the width of the plate-like structure is not less than the diameter of the drug delivery cavity of the puncture assembly
- the thickness of the plate-like structure is not less than the wall thickness of the drug delivery cavity of the puncture assembly
- the plate-like structure also has a curvature, and the surface of the plate-like structure in contact with the balloon has a curvature facing the balloon, thereby enabling the plate-like structure to be more tightly connected to the balloon;
- the curvature of the arc of the plate-like structure toward the balloon is consistent with the curvature of the balloon
- the base is a plate-like structure
- the drug delivery cavity further comprises a drug delivery catheter
- the base is arranged on the drug delivery catheter
- the drug delivery catheter of the puncture assembly includes a hard catheter and a soft catheter, the hard catheter and the soft catheter are arranged in sections and at intervals, and the puncture structure is arranged on the hard catheter;
- the number of soft catheters is one less than the number of rigid catheters
- the soft catheter can be bent, and can be arranged to extend non-axially on the surface of the balloon;
- the hard catheter of the front section and the hard catheter of the rear section are arranged in different circumferential directions of the balloon to form a staggered arrangement;
- the drug delivery cavity is connected to the first channel; the outer diameter of the first channel is matched with the inner diameter of the drug delivery cavity; or, the inner diameter of the first channel is matched with the outer diameter of the drug delivery cavity;
- the first channel is made of soft material or hard material
- the folding wings do not overlap; when the diameter of the balloon is 2-6 mm, the folding wings are 3-5 pairs; when the diameter of the balloon is 4-12 mm, the folding wings are 5-6 pairs; when the diameter of the balloon is 10-30 mm, the folding wings are 6-12 pairs;
- the upper surface of the base is fixedly fitted with the inner surface of the balloon, at least part of the puncture structure protrudes from the inner surface of the balloon, and in the folded configuration, the protruding puncture structure is arranged in the accommodating space formed by the folding wings; in the unfolded configuration, as the balloon expands, the base is driven to move outward, driving the protruding puncture structure to extend out of the accommodating space, and the accommodating space becomes smaller or expands and disappears;
- each puncture assembly is a pair of puncture blades, the pair of puncture blades are arranged along the length direction of the base, and the pair of puncture blades are arranged to form a long strip of the drug release hole;
- the pair of puncture blades are arranged to extend along the length direction of the balloon; the blades are wide at the bottom and narrow at the top, and the blade head is located at the top; the aspect ratio of the blades is 0.05 to 1; the aspect ratio of the blades is 0.1 to 0.25;
- the height H of the folding wing space is between 0.5 and 2.0 mm; preferably, the folding wings are 3 to 6 pairs; preferably, when the balloon is in the expanded configuration, the puncture force of the puncture structure is ⁇ 0.7N;
- the balloon is a cylindrical structure with two ends of constricted openings; preferably, the balloon is a structure formed by connecting two cylinders with two ends of constricted openings, that is, the balloon comprises a first balloon and a second balloon, the first balloon is connected to the second balloon, and both the first balloon and the second balloon are cylindrical structures with two ends of constricted openings; the first balloon is closer to the distal end of the device than the second balloon, and the maximum diameter of the first balloon is smaller than the maximum diameter of the second balloon; the puncture assembly can be arranged on the first balloon and/or the second balloon; preferably, the puncture assembly is arranged on the second balloon;
- the balloon includes a third balloon and a second balloon
- the third balloon is a cylindrical balloon with a constricted end
- the second balloon is a cylindrical balloon with constricted ends
- one end of the cylindrical balloon is connected and communicated with the constricted end of the cylindrical balloon of the second balloon
- the puncture assembly or the drug release assembly is arranged on the third balloon and/or the second balloon; preferably, the size of the third balloon is 5 to 12 mm;
- the wall thickness T of the drug delivery cavity of the puncture assembly is 0.05-0.2 mm, the diameter D is 0.25-0.75 mm, and the width W is 0.3-0.8 mm.
- the present invention also provides a device for drug delivery using a balloon, comprising: a delivery catheter, at least one set of drug release components and a balloon component, wherein:
- the delivery catheter has a proximal portion and a distal portion, and includes a first channel for delivering drugs and a second channel for circulation and pressure relief, which are not connected to each other. At least the first channel near the distal portion is a multi-lumen structure, and the multi-lumen structure includes a plurality of independent drug delivery channels for delivering drugs.
- the drug release component comprises at least one release structure and a drug delivery cavity, wherein the release structure comprises at least a drug delivery hole, and the drug delivery holes in the group are connected to the drug delivery cavity;
- the balloon assembly comprises at least one balloon, which is configured to change between a folded configuration and an unfolded configuration by means of inflation and deflation; in the folded configuration, the drug release components are individually enclosed in the balloon; in the unfolded configuration, the expansion force of the balloon drives the drug release components to move to a preset target area, and the drug is delivered to the target area through the drug administration channel by applying a corresponding control force alone.
- the drug release components are multiple groups, and the groups of drug release components are respectively controlled by multiple drug delivery control units or the same drug delivery control unit to control the movement of the drug;
- the drug delivery cavity further comprises a drug delivery cavity and a drug delivery hole, the first channel and the drug release component are arranged on the inner surface of the balloon, the drug release hole is located on the balloon, and the drug release hole is connected with the drug delivery cavity through the drug delivery hole; more preferably, the drug delivery hole and the drug release hole have the same size; or, the first channel and the drug release component are arranged on the inner surface of the balloon;
- the first channel and the drug release component are arranged on the outer surface of the balloon, and the drug release hole is communicated with the drug delivery cavity;
- the pressure of the balloon is in the range of 3 to 30 atm;
- the drug release holes of the drug release component when the first channel and the drug release component are arranged on the outer surface of the balloon, when the drug release holes of the drug release component are a row of hole structures, the drug release holes face the direction of balloon expansion; or, the direction of the drug release holes forms a certain angle with the direction of balloon expansion; when the drug release holes of the drug release component are a multi-row hole structure, the axial directions of the holes in each row of hole structures have an angle;
- the radial dimension of the drug delivery cavity is larger than the diameter of the drug delivery hole
- the inner diameter of the drug delivery cavity is ⁇ 1 ⁇ m, preferably, the inner diameter of the drug delivery cavity is ⁇ 3 ⁇ m; preferably, the inner diameter of the drug delivery cavity is ⁇ 0.1 mm; preferably, the inner diameter of the drug delivery cavity is ⁇ 0.3 mm; more preferably, the inner diameter of the drug delivery cavity is ⁇ 0.5 mm, more preferably, the inner diameter size range of the drug delivery hole is about 2 ⁇ m-500 ⁇ m, preferably 2 ⁇ m-200 ⁇ m, more preferably 50-150 ⁇ m; the inner/outer diameter ratio of the drug delivery cavity is 0.1-0.9, more preferably, the inner/outer diameter ratio of the drug delivery cavity is 0.4-0.8; the inner diameter of the drug delivery hole is smaller than the inner diameter of the drug delivery cavity; preferably, the inner diameter of the drug delivery hole is less than 0.5 times the inner diameter of the drug delivery cavity, and the inner diameter of the drug delivery hole is ⁇ 0.01 mm;
- the drug release component is a hollow silk thread, and the hollow silk thread is provided with a drug release hole;
- the spacing between each drug release hole is 0.1-1 mm, preferably, 0.25-0.75 mm; preferably, the cross section of the drug delivery cavity is a circular or triangular hollow tube; when the drug delivery cavity is circular, the drug delivery holes on the drug delivery cavity are preferably oriented in the direction of the balloon expansion; preferably, there is a certain angle between the drug delivery holes on the drug delivery cavity and the direction of the balloon expansion; when the drug delivery holes of the drug release component are a multi-row hole structure, there is an angle between the axial directions of the holes in each row of hole structures; preferably, there are multiple drug delivery holes in the same circumferential direction of the drug delivery cavity;
- the drug release assembly comprises a hard catheter and a soft catheter, wherein the hard catheter provides a fixed lumen required for the release structure, and the soft catheter is provided to provide flexibility for the drug delivery catheter;
- the drug delivery catheter of the drug release assembly includes a hard catheter and a soft catheter, and the hard catheter and the soft catheter are arranged in sections and at intervals; preferably, the number of the soft catheters is one less than the number of the hard catheters;
- the puncture structure is disposed on a hard catheter
- the hard catheter of the front section and the hard catheter of the rear section are arranged in different circumferential directions of the balloon to form a staggered arrangement;
- the size of the hard catheter and the axial size of the soft catheter are 0.5 to 20 mm;
- both sides of the triangular column preferably have drug release holes
- the drug release component is a triangular hollow tube, that is, the outer surface shape of the drug delivery cavity is a triangular cylinder, one of the corners of the triangular cylinder is arranged toward the radial outside of the balloon, and one end of the corner toward the radial outside of the balloon is defined as the entry end, and the drug release hole is arranged at the entry end of the drug delivery cavity;
- the drug release holes are evenly or unevenly arranged along the axial direction of the drug delivery cavity of the triangular hollow tube;
- the drug release component is a triangular hollow tube, that is, the outer surface of the drug delivery cavity is a triangular cylinder, and the drug release hole is arranged at a combination of the cut-in end and the two side walls of the triangular hollow tube; preferably, along the axial direction of the drug release component, the axial position of the drug release hole arranged at the cut-in end and the axial position of the drug release hole arranged at the two side walls of the triangular hollow tube are the same or different;
- the size of each drug delivery hole is uniformly set; preferably, along the drug delivery cavity of the triangular hollow tube, from the proximal end to the distal end, the size of each drug delivery hole gradually increases or decreases; preferably, along the axial direction of the drug delivery cavity of the triangular hollow tube, from the proximal end to the distal end, the size of each drug delivery hole gradually increases;
- the height of the outer dimension of the drug delivery cavity is 0.1-1.0 mm, and more preferably, the height of the outer dimension of the drug delivery cavity is 0.3-0.7 mm; preferably, the wall thickness of the drug delivery cavity is 0.01-0.1 mm, and more preferably, the wall thickness of the drug delivery cavity is 0.03-0.07 mm; preferably, the length of the drug delivery cavity is 5-50 mm; preferably, the inner cavity vertex angle (angle of the cut-in end) of the triangle of the drug delivery cavity is 10-80°; preferably, the non-inner cavity vertex angle of the drug delivery cavity is 10-70°;
- the diameter of the drug release holes is 0.01-0.2 mm; preferably, the diameter of the drug release holes is 0.05-0.15 mm; preferably, the spacing between the drug release holes is between 0.05 mm and 7 mm;
- a sharp corner is extended along the radial direction of the balloon, that is, in the extension direction of the cutting end, to form a micro-convex corner, and the micro-convex corner is extended along the axial direction of the cutting end; preferably, the end of the micro-convex corner is edged or not edged;
- the inner surface of the drug delivery cavity is in the shape of a triangular lumen, a circular lumen, a rectangular lumen, a polygonal lumen or a special-shaped lumen;
- the shape of the inner surface of the drug delivery cavity is a triangular lumen
- the cross section of the drug delivery cavity is designed to have a cavity with a sharp angle on the basis of a triangle and is extended in the direction of the cut-in end to form a quasi-triangular hollow tube.
- the shape of the cross section of the quasi-triangular hollow tube is consistent with the shape of the cross section of the outer surface of the drug delivery cavity containing the micro-convex angle;
- the material of the drug release component is resin, ceramic, stainless steel, nylon, degradable polymer or a combination of these materials; preferably, the material of the ceramic is aluminum oxide, zirconium oxide, magnesium oxide, calcium phosphate or a combination of these materials;
- the drug release component adopts an ultra-precision micro-nano 3D printing process, preferably, a sintering process, more preferably, laser sintering or high-temperature sintering;
- the release structure further comprises a base, the upper surface of the base and other peripheral surfaces form the drug delivery cavity, the upper surface of the base is provided with a through hole connected to the drug delivery hole along the length direction of the balloon, and the drug delivery hole is connected to the drug delivery cavity through the through hole;
- the balloon is a cylindrical structure with two ends of constricted openings; preferably, the balloon is a structure formed by connecting two cylinders with two ends of constricted openings, that is, the balloon includes a first balloon and a second balloon, the first balloon is connected to the second balloon, and the first balloon and the second balloon are both cylindrical structures with two ends of constricted openings; the first balloon is closer to the distal end of the device than the second balloon, and the maximum diameter of the first balloon is smaller than the maximum diameter of the second balloon; the drug release component can be arranged on the first balloon and/or the second balloon; preferably, the drug release component is arranged on the second balloon;
- the balloon includes a third balloon and a second balloon
- the third balloon is a cylindrical balloon with a constricted end
- the second balloon is a cylindrical balloon with constricted ends
- one end of the cylinder of the third balloon is connected and communicated with the constricted end of the cylinder of the second balloon
- the drug release component is arranged on the third balloon and/or the second balloon; preferably, the expanded diameter of the third balloon is 5-20 mm;
- the wall thickness T of the drug delivery cavity of the drug release component is 0.05-0.2 mm, the diameter D is 0.25-0.75 mm, and the width W is 0.3-0.8 mm.
- the present invention also provides a drug delivery device, comprising: a delivery catheter, the delivery catheter having a proximal portion and a distal portion, the drug delivery catheter comprising a pressure-charging and pressure-releasing cavity, the drug release assembly comprising a drug delivery cavity, the drug delivery cavity and the pressure-charging and pressure-releasing cavity using the same cavity;
- At least one group of drug release components comprising at least one release structure and a drug delivery cavity, the release structure comprising a drug delivery hole, the drug delivery hole in the group being connected to the drug delivery cavity;
- the balloon assembly comprises at least one balloon, which is configured to change between a folded configuration and an unfolded configuration by means of inflation and deflation; in the folded configuration, the drug release components are individually enclosed in the balloon; in the unfolded configuration, the expansion force of the balloon drives the drug release components to move to a preset target area, and the drug is delivered to the target area through the drug administration channel by applying a corresponding control force alone.
- the release structure further comprises a puncture portion
- the chamber is used to be filled with a drug carrier of the drug and/or a liquid of the drug
- the liquid is configured to be used for circulation, pressure relief and drug administration, the liquid fills the balloon to drive the balloon to expand, so that the balloon is in an expanded configuration, and the liquid is administered through the drug administration channel by applying a corresponding control force alone;
- the release structure further comprises a base, the base is plate-shaped, and the puncture portion is arranged on the base; preferably, the base and all the release structures are integrally formed; preferably, the material of the release structure and the base can be processed from at least one of high molecular polymer, inorganic silicon, metal and other materials; preferably, the outer diameter of the release structure is larger than the inner diameter of the base, and the inner diameter of the release structure is smaller than the inner diameter of the base; preferably, the base is located on the outer surface of the balloon or the inner surface of the balloon;
- the top of the puncture portion is pointed, and the end is arranged to form the drug release hole, and there are multiple puncture portions, which are arranged at intervals along the length direction of the base;
- the puncture portion is a pair of puncture blades, and the pair of puncture blades are arranged along the length direction of the base, and the pair of puncture blades are arranged to surround the drug release hole in a long strip.
- the balloon assembly further comprises a guide catheter, and the balloon is sealably attached to the guide catheter.
- the balloon is folded to form a plurality of folding wings, which are arranged along the circumference of the guide catheter, and each pair of folding wings arranged opposite to each other forms a folding wing space, and the drug release components are respectively accommodated in the adapted folding wing spaces;
- the drug release components are configured to implant the drug into the target area or inject the drug into the target area;
- the balloon is a cylindrical structure with two ends of constricted openings; preferably, the balloon is a structure formed by connecting two cylinders with two ends of constricted openings, that is, the balloon includes a first balloon and a second balloon, the first balloon is connected to the second balloon, and the first balloon and the second balloon are both cylindrical structures with two ends of constricted openings; the first balloon is closer to the distal end of the device than the second balloon, and the maximum diameter of the first balloon is smaller than the maximum diameter of the second balloon; the drug release component can be arranged on the first balloon and/or the second balloon; preferably, the drug release component is arranged on the second balloon;
- the balloon includes a third balloon and a second balloon
- the third balloon is a cylinder with a constricted end
- the second balloon is a cylinder with constricted ends
- one end of the cylinder of the third balloon is connected and communicated with the constricted end of the cylinder of the second balloon
- the drug release component is arranged on the third balloon and/or the second balloon; preferably, the expansion diameter of the third balloon is 5 to 20 mm.
- a layer of structure is coated on the drug delivery device.
- the coating is a drug coating.
- the drug coating and the drug delivered in the drug delivery device are the same drug or different drugs.
- the present invention also provides a drug delivery device, which is used for dilating the prostatic urethra.
- the device includes a balloon, which includes a balloon structure near the distal end and a balloon structure near the proximal end that are internally connected.
- the balloon structure near the distal end is used to be at least arranged at the position of the bladder neck to widen the bladder neck;
- the balloon structure near the proximal end is used to be at least arranged at the position of the prostatic urethra to widen the prostatic urethra;
- the maximum diameter of the balloon structure near the distal end is smaller than the maximum diameter of the balloon structure near the distal end, so that the size of the bladder neck widened by the balloon structure near the distal end is smaller than the size of the prostatic urethra widened by the balloon structure near the distal end;
- a puncture component, a drug release component and/or a drug coating are arranged on at least part of the structure of the balloon structure near the
- the balloon structure near the distal end is a first balloon
- the balloon structure near the proximal end is a second balloon.
- Both the first balloon and the second balloon are cylindrical structures with narrowed ends.
- the first balloon is used to be at least arranged at the position of the bladder neck to widen the bladder neck
- the second balloon is used to be at least arranged at the position of the prostatic urethra to widen the prostatic urethra.
- the maximum diameter of the first balloon is smaller than the maximum diameter of the second balloon, so that the size of the bladder neck widened by the first balloon is smaller than the size of the prostatic urethra widened by the second balloon.
- the puncture assembly, the drug release assembly and/or the drug coating can be arranged on the first balloon and/or the second balloon;
- the balloon structure near the distal end is a third balloon
- the balloon structure near the proximal end is a second balloon
- the third balloon is a cylindrical shape with a constricted end
- the second balloon is a cylindrical shape with constricted ends
- one end of the cylindrical shape of the third balloon is connected and communicated with the constricted end of the cylindrical shape of the second balloon
- the third balloon is used to be at least arranged at the position of the bladder neck, or at least arranged at the bladder neck and the connection between the bladder neck and the urethra to widen the bladder neck and its periphery
- the second balloon is used to be at least arranged at the position of the prostatic urethra to widen the prostatic urethra
- the maximum diameter of the third balloon is smaller than the maximum diameter of the second balloon, so that the size of the bladder neck opened by the third balloon is smaller than the size of the prostatic urethra opened by the second balloon; preferably, the puncture component, the drug release component
- the present invention provides a drug system, which includes drug particles and/or drug carriers, wherein the drug particles and/or the drug carriers can be mixed with a solution to form a drug solution, and the drug solution is delivered to a target tissue location;
- the drug particles are drug crystals, and the drug crystals are transported to tissues to achieve sustained drug release.
- the drug particles have a particle size of 1 to 1000 ⁇ m, preferably 150 ⁇ m, and more preferably 1 to 50 ⁇ m.
- the sustained release period of the drug crystals is from one week to six months.
- the drug carrier is a drug sustained-release microsphere made by mixing a degradable polymer material with a drug
- the diameter of the drug sustained-release microsphere is 1 to 1000 ⁇ m, preferably, the diameter of the drug sustained-release microsphere is 1 to 150 ⁇ m, more preferably, the diameter of the drug sustained-release microsphere is 1 to 50 ⁇ m
- the sustained-release period is 1 week to 6 months;
- the drug carrier has pores, the pores contain drugs, the drugs are slowly released from the pores, the diameter of the drug carrier is 1 to 1000 ⁇ m, preferably, the diameter of the drug carrier is 1 to 150 ⁇ m, more preferably, the diameter of the drug carrier is 1 to 50 ⁇ m; the sustained release period is 1 week to 6 months;
- the polymer degradable material used in the drug carrier includes: one of polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), carbon dioxide polymer (PPC), polybutylene succinate (PBS), fatty aromatic polyester Ecoflex (PBAT), polytrimethylene terephthalate (PPT), poly- ⁇ -hydroxyalkanoate (PHA), poly- ⁇ -caprolactone (PCL), polydioxanone (PPDO), or a copolymer or blend of any multiple polymers thereof;
- PLA polylactic acid
- PLGA polylactic acid-glycolic acid copolymer
- PPC carbon dioxide polymer
- PBS polybutylene succinate
- PBAT fatty aromatic polyester Ecoflex
- PPT polytrimethylene terephthalate
- PHA poly- ⁇ -hydroxyalkanoate
- PCL poly- ⁇ -caprolactone
- PPDO polydioxanone
- the drug system is a drug particle, or a drug carrier, or a drug carrier or composition containing drug particles, which includes one or more therapeutic substances, diagnostic substances, a drug, a therapeutic composition, a diagnostic composition, a physiologically active agent, a biochemically active agent, one or more living cells, DNA, RNA, nucleic acid, a cell carrier for delivering genetic material to a target site, an anti-inflammatory agent, an anti-restenosis agent, a cell proliferation inhibitor, a smooth muscle proliferation inhibitor, paclitaxel, rapamycin, everolimus, a vasoactive agent, a vasodilator, a vasoconstrictor, an antibiotic, an anticoagulant, a platelet aggregation inhibitor, an antifibrotic agent, an alpha reductase inhibitor, a pharmaceutically acceptable carrier, a lipid-based carrier, and any combination thereof;
- a coating layer is provided on the drug carrier, the drug is provided in the coating layer to form a sustained release, and the coating layer can be dissolved; the sustained release period is 1 week to 6 months;
- the drug carrier is spherical, rod-shaped or sheet-shaped; preferably, the drug crystal is spherical, polygonal, rod-shaped or sheet-shaped;
- the drugs in the drug system are: mometasone furoate, prednisolone, triamcinolone acetonide, methylprednisone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
- the present invention also provides a medical minimally invasive system, comprising any one of the above devices, and comprising the above drug system; preferably, the device includes a drug delivery control unit, and the drug delivery control unit can be configured to load the delivery force of the drug to control the delivery of the drug to the target area through the drug delivery channel; preferably, the diameter of the drug release hole is larger than the diameter of the drug system.
- the present invention has the following advantages:
- Efficient drug delivery capability Compared with drug-coated balloons (DCBs), drugs will not be lost during catheter delivery, and drugs can be injected in precise doses and multiple times.
- DCBs drug-coated balloons
- the microneedle has a circumferential distribution structure and no directionality. This means that the doctor does not need to adjust the position of the catheter during the operation.
- the drug can be evenly absorbed on the blood vessel wall to achieve the expected clinical effect.
- FIG1A is a schematic diagram of a device for drug delivery using a balloon provided in the first embodiment
- FIG1B is a cross-sectional view of the device for drug delivery using a balloon taken along the line A-A in FIG1A ;
- FIG2A is a schematic diagram of a device for drug delivery using a balloon provided in the first embodiment
- FIG2B is a cross-sectional view of the device for drug delivery using a balloon in FIG2A in a certain direction;
- FIG2C is a cross-sectional view of the device for drug delivery using a balloon in FIG2A in a folded state
- FIG2D is a cross-sectional view of another device for drug delivery using a balloon according to Embodiment 1 in a folded state;
- FIG3 is a schematic diagram of drug delivery and drug delivery of the device for drug delivery using a balloon in FIG2A ;
- FIG4A is a diagram showing the structure of a puncture assembly
- FIG4B is a structure of another puncture assembly
- FIG4C is a structure of another puncture assembly
- FIG5A is a schematic diagram of another puncture assembly provided in the first embodiment
- FIG5B is a schematic diagram of another puncture assembly provided in the first embodiment
- FIG5C is a schematic diagram of another puncture assembly provided in the first embodiment
- FIG5D is a diagram showing the deployment of another puncture assembly provided in the first embodiment along the circumferential direction of the balloon;
- FIG5E is a schematic diagram of the positional relationship between another puncture assembly and a balloon provided in the first embodiment
- FIG6A is a schematic diagram of a device for drug delivery using a balloon provided in the second embodiment
- FIG6B is a cross-sectional view of the device for drug delivery using a balloon in FIG6A in a folded state
- FIG7 is a schematic diagram of a device for drug delivery using a balloon provided in the third embodiment.
- FIG8A is a schematic diagram of a drug delivery device provided in Example 4.
- FIG8B is a schematic diagram of another drug delivery device provided in the fourth embodiment.
- FIG9 is a schematic diagram of a drug delivery device provided in Embodiment 5.
- FIG10 is a schematic diagram of another drug delivery device provided in Example 5.
- FIG11 is an exemplary diagram of a drug delivery device provided in Embodiment 6;
- FIG12 is a schematic diagram of tissue after in vitro injection of the esophageal balloon device of Example 8.
- FIG13 is a schematic diagram of a prostatic urethra device provided in Embodiment 8.
- FIG14 is a schematic diagram of another prostatic urethra device provided in the eighth embodiment.
- FIG15 is a schematic diagram of tissues after in vitro injection using the prostatic urethral device of Example 9;
- FIG16 is a schematic diagram of the overall structure of the injection balloon of the tenth embodiment.
- FIG17A is a schematic cross-sectional view of the balloon portion of the injection balloon of the tenth embodiment
- FIG17B is a schematic cross-sectional view of a balloon portion of another injection balloon of the tenth embodiment
- FIG17C is a schematic cross-sectional view of a balloon portion of another injection balloon of the tenth embodiment
- FIG18A is a schematic diagram of the injection balloon of the tenth embodiment
- FIG18B is a schematic diagram of another injection balloon according to the tenth embodiment.
- FIG18C is a schematic diagram of another injection balloon according to the tenth embodiment.
- FIG19 is a schematic diagram of a drug release assembly of the injection balloon shown in FIG18 ;
- FIG20 is a schematic diagram of the overall structure of another injection balloon according to the tenth embodiment.
- FIG21A is a schematic diagram of an example of a drug carrier provided in Example 11.
- FIG21B is a schematic diagram of a second example of a drug carrier provided in Example 11.
- FIG22A is a schematic diagram of a drug release assembly of a drug delivery device provided in Example 5.
- FIG22B is a schematic diagram of a cross-section of the drug release assembly shown in FIG22A ;
- FIG22C is a schematic diagram of a longitudinal section of the drug release assembly shown in FIG22B ;
- FIG23A is another schematic diagram of the drug release component of the drug delivery device provided in the fifth embodiment.
- FIG23B is a schematic diagram of a cross-section of the drug release assembly shown in FIG23A;
- FIG. 23C is a schematic diagram of a longitudinal cross-section of the drug release assembly shown in FIG. 23B .
- 1-delivery catheter 11-first channel, 111-drug delivery channel, 12-second channel, 121-groove;
- 2-puncture assembly 21-puncture structure, 211-puncture part, 2111-puncture wall, 2112-puncture cavity, 2113-puncture plane, 212-drug release hole, 213-puncture blade, 2131-drug release part, 22-drug delivery cavity, 221-base, 2211-through hole, 222-drug delivery catheter, 2221-hard catheter, 2222-soft catheter;
- 3-balloon assembly 31-balloon, 311-folding wing, 312-folding wing space, 32-guiding catheter;
- 4-drug release component 41-release structure, 411-drug release hole, 42-drug delivery cavity, 421-drug delivery cavity, 422-drug delivery hole, 423-cut end, 4231-micro-convex corner;
- 6-drug release component 61-release structure, 611-puncture part, 612-drug release hole, 63-base;
- the terms “installed”, “connected” and “connected” should be understood in a broad sense.
- it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, or it can be internal communication between two components.
- the “distal end” herein is the end away from the operator, and the “proximal end” is the end close to the operator.
- the earliest existing drug delivery catheters for delivering drugs to blood vessels have a balloon-like structure.
- the balloon When the balloon is inflated, the The outer surface is in contact with the inner surface of the blood vessel, and some drugs or therapeutic compositions can be delivered to the blood vessel wall.
- the drug delivery can be by adhering some drugs or therapeutic compositions to the inner membrane layer when in contact with the drug-coated outer surface of the balloon, or by dissolving the drug in the blood and diffusing it to the inner membrane layer, wherein the drug can play a biological therapeutic role, reducing or preventing the proliferation of vascular epithelial cells and the restenosis of the treated blood vessel site caused thereby.
- a common problem of such prior art drug delivery catheters is that during the process of the catheter being inserted into the vascular system and the catheter moving in the vascular system to reach the treatment site, the drug or therapeutic composition coated on the outer surface of the balloon is exposed to the blood contained in the vascular system, which may cause some drugs or active ingredients in the therapeutic composition to dissolve or disperse in the blood before the balloon reaches the desired treatment site.
- the double balloon structure mentioned in the prior art one balloon is used to deliver drugs, and the other balloon expands or contracts during inflation and decompression.
- the applicant found that the balloon used to deliver drugs in the double-balloon structure can expand or contract, and the balloon under the pressure of inflation and deflation can also expand or contract.
- Precision control is divided into the following types: controlling the area of drug delivery, controlling the amount of drug delivered (i.e., the effective transfer rate of the drug), and controlling the target depth of drug delivery to the target area.
- the core of our inventors is to achieve the latter two types of precision control.
- This preliminary core idea is: the balloon is configured to change between the folded configuration and the unfolded configuration through a pressure-relief channel and a drug-releasing hole that communicates with the drug-delivery cavity to form a drug delivery channel, and the two are two independent channels that are not connected to each other and are controlled separately.
- the drug release component In the folded configuration, the drug release component is attached to the balloon; in the unfolded configuration, the expansion force of the balloon drives the drug release component to move to the pre-set target area, and the drug is delivered to the target area through an independent drug delivery channel by applying the corresponding control force alone.
- the advantage of this core idea is that there is no need to set up double balloons, and only one balloon can achieve the effect of precise drug delivery.
- Multiple drug delivery channels can be set, and the movement of the drug is controlled by a drug delivery control unit, and the drug delivery to different depths of the target area can be controlled by adjusting the magnitude of the force.
- Multiple drug delivery channels can be set up, and different drug delivery control units can be used to control the movement of the drug in each drug delivery channel.
- Different drugs can be input, different drugs can be controlled to enter different areas, different depths of drugs can be controlled to enter different areas, and different times of administration of different drugs (different doses) can be controlled.
- the injection of drugs can be precise and multiple times.
- one of the above precise control methods can be selected for control.
- the drug of the present application is a broad concept.
- the drug can be a drug body or composition containing a drug, which includes one or more therapeutic substances, diagnostic substances, a drug, a therapeutic composition, a diagnostic composition, a physiologically active agent, a biochemically active agent, one or more living cells, DNA, RNA, nucleic acid, a cell carrier for delivering genetic material to a target site, an anti-inflammatory agent, an anti-restenosis agent, a cell proliferation inhibitor, a smooth muscle hyperplasia inhibitor, paclitaxel, rapamycin, everolimus, vasoactive agents, vasodilators, vasoconstrictors, antibiotics, anticoagulants, platelet aggregation inhibitors, antifibrotic agents, pharmaceutically acceptable carriers, lipid-based carriers and any combination thereof.
- the drug can also be an alpha reductase inhibitor, for example, finasteride, dutasteride.
- the drug can be a spherical particle with a diameter of 1 to 1000 ⁇ m, a sustained-release drug-loaded rod or sheet, and the drug delivery control unit can be configured to load the delivery force of the drug to control the drug delivery through the drug delivery channel to the target area and/or the depth corresponding to the target area.
- drug-loaded microspheres or sheets can continuously perform drug release functions. The release cycle can be as long as 1 week to 6 months, and it is continuously controllable.
- the spherical particles, sustained-release drug-loaded rods or sheets are made of degradable emulsified polymers. Specifically, there are pores in these spherical particles, sustained-release drug-loaded rods or sheets, and the drugs are carried in these pores, or the spherical particles are sustained-release drugs made by mixing drugs with polymer materials, or the spherical particles are a drug crystal, thereby achieving sustained release of the drug.
- Figure 1A is a schematic diagram of the device for drug delivery using a balloon provided in the present embodiment
- Figure 1B is a cross-sectional view of the A-A portion of the device for drug delivery using a balloon in Figure 1A
- Figure 2A is a schematic diagram of the device for drug delivery using a balloon provided in the present embodiment
- Figure 2B is a cross-sectional view of the device for drug delivery using a balloon in Figure 2A in a certain direction
- Figure 2C is a cross-sectional view of the device for drug delivery using a balloon in Figure 2A in a folded state
- Figure 2D is a cross-sectional view of another device for drug delivery using a balloon in a folded state of the present embodiment
- Figure 3 is a schematic diagram of drug delivery and liquid delivery of the device for drug delivery using a balloon in Figure 2A.
- the first embodiment provides a device for drug delivery using a balloon, wherein the device comprises a delivery catheter 1 , a plurality of puncture components 2 and a balloon component 3 .
- the delivery catheter 1 has a proximal portion and a distal portion.
- the delivery catheter 1 includes a first channel 11 for delivering drugs and a second channel 12 for circulation and pressure relief.
- the first channel 11 near the distal part is a multi-chamber structure, and the multi-chamber structure includes a plurality of independent drug delivery channels 111 for delivering drugs.
- the first channel 11 or the drug delivery channel 111 can be controlled to connect a syringe with a scale or an additional auxiliary device to achieve accurate drug delivery.
- a drug delivery control unit can be preferably provided on the first channel 11.
- the drug delivery control unit can be one, connected to the three drug delivery channels through the same connecting tube, and the drug is pressed into the three drug delivery channels through a connecting tube.
- the drug delivery control unit can individually control different pressure values and the timing and duration of force.
- a charging and releasing pressure control unit can be provided on the second channel 12.
- the second channel 12 can be a connecting tube, and the charging and releasing pressure control unit is connected to the second channel 12, and liquid is used to realize charging and releasing pressure.
- the control of charging and releasing pressure can adopt conventional technologies such as charging and releasing pressure valves, which will not be repeated here.
- the distal portion of the first channel 11 is, for example, three or four independent drug delivery channels 111, and the proximal portions of these drug delivery channels 111 can be connected in one cavity, or can be independently arranged.
- the first channel 11 is a plurality of drug delivery channels 111 that are independently arranged.
- a first Luer interface is also provided on the first channel 11, and the first Luer interface is connected to the catheter cavities corresponding to the plurality of drug delivery channels through a catheter.
- the outer diameter or inner diameter of the first channel 11 is smaller than the outer diameter or inner diameter of the second channel 12.
- the inner diameter of each first channel 11 is smaller than 1/N times the inner diameter of the second channel 12.
- each group of puncture components 2 includes at least one puncture structure 21 and a drug delivery cavity 22.
- the puncture structure 21 includes a puncture portion 211 and a drug release hole 212.
- the drug release hole 212 in the group is connected to the drug delivery cavity 22, and the drug delivery cavity 22 is connected to the corresponding drug delivery channel 111.
- the puncture portion 211 pierces the tissue, and then the drug solution can be injected into the tissue, preventing the loss of the drug solution, achieving accurate drug release, and improving the treatment efficiency. It also allows the drug to be accurately delivered to the target area, providing the necessary conditions for the quantitative, constant speed, constant pressure and other delivery of the drug.
- the puncture components 2 are three or four groups to match the drug delivery channel 111.
- the puncture structure 21 and the drug delivery cavity 22 of the puncture component 2 can be a variety of structures, which will be described in detail below.
- the combination of the puncture component 2 and the balloon 31 can also be in a variety of forms, which will be described in detail below.
- the drug delivery cavity 2 may be a tube formed of metal material, and its cross section may be circular, rectangular, triangular, polygonal or other shapes.
- the balloon assembly 3 includes at least one balloon 31.
- the balloon 31 may be a compliant balloon, a non-compliant balloon or a semi-compliant balloon.
- the balloon assembly 3 further includes a guide catheter 32.
- the distal end of the balloon 31 is connected to the guide catheter 32 to seal the distal end of the balloon 31.
- the proximal end of the balloon 31 is sealed or unsealed connected to the guide catheter 32.
- the guide catheter 32 is spaced apart from the second channel 12.
- the guide catheter 32 is arranged inside the second channel 12.
- the axial direction of the guide catheter 32 is arranged parallel to the axial direction of the second channel 12.
- the proximal end of the guide catheter 32 is the proximal end of the device.
- the proximal end of the balloon 31 is connected to the distal end portion of the second channel 12, and the inner cavity of the balloon 31 is connected to the second channel 12.
- the balloon 31 is configured to change between a folded configuration and an expanded configuration. As shown in FIG2C , in the folded configuration, multiple groups of puncture components 2 are independently enclosed in the balloon 31, so that the puncture components 2 can be individually enclosed in the balloon 31 to prevent each group of puncture components 2 from affecting each other. By pressurizing the second channel 12 to expand the balloon 31 so that it is in the expanded configuration, the expansion of the balloon 31 drives the puncture parts 211 of the multiple groups of puncture components 2 to bulge.
- the drug is configured to be delivered to the target area through multiple drug delivery channels 111, the drug delivery cavity 22 corresponding to each drug delivery channel 111, and the drug release hole 212 connected to the drug delivery cavity 22 by an external force (the external force can be a force controlled by the drug delivery control unit).
- the balloon 31 has a balloon lumen 9 and a balloon outer portion.
- the balloon outer portion of the balloon 31 can be folded to form multiple pairs of folding wings 311, which are arranged circumferentially along the guide catheter 32, and each pair of relatively arranged folding wings 311 forms a folding wing space 312, and the puncture components 2 of these groups are respectively accommodated in these adapted folding wing spaces 312. As shown in FIG.
- the balloon outer portion is folded into three pairs of folding wings 311, for example, and these folding wings 311 are respectively arranged circumferentially around the guide catheter 32, so that the puncture components 2 of these groups can be arranged along the circumferential direction, so that the orientation of the puncture components 2 on the device can be non-directional, which makes it unnecessary for the doctor to adjust the position of the catheter during the operation, greatly reducing the difficulty of the doctor's operation and improving the treatment efficiency.
- the drug In the circumferential direction along the tissue cavity (target position), the drug can be uniformly absorbed, thereby achieving the expected clinical effect.
- a group of puncture components 2 corresponds to a folding wing space 312, and in the folded state, a group of puncture components 2 is folded in the corresponding folding wing space 312.
- the balloon can be made to have shape memory during the manufacturing process, that is, when the manufacturing is completed, the balloon has the shape memory of the folded wing space 312.
- the balloon lumen 9 is connected to the second channel 12. When pressurized, the balloon lumen 9 is filled with liquid to control the expansion of the outer surface of the balloon. When depressurized, the balloon lumen 9 is depressurized and the balloon is folded.
- the drug delivery cavity 22 includes a base 221, and the upper surface of the base 221 and other peripheral surfaces (other peripheral surfaces refer to peripheral surfaces that do not include the upper surface) form a relatively fixed drug delivery cavity.
- the upper surface of the base 221 is provided with a through hole 2211 connected to the drug release hole 212 along the length direction of the balloon 31.
- the puncture structure 21 is fixedly arranged on the upper surface of the base 221, and the drug release hole 212 is connected to the drug delivery cavity through the through hole 2211.
- the base 221 can be made of metal, which is not flexible, and the size of the space is relatively fixed.
- the base 221 is not limited to metal materials, and it can be a hard and non-deformable material such as ceramic materials, stainless steel materials or polymer materials.
- the upper surface of the base 221 is made of a hard material, such as a metal material, to ensure that when the balloon 31 is expanded, each puncture structure 21 can be protruded with the same pressure.
- the cross section of the base 221 can be a hollow circular, hollow rectangular or other hollow cavity. It should be understood that the upper surface of the base 221 and the other peripheral surfaces can be integrally formed, for example, it can be the same tube, such as a circular tube, a triangular tube, etc.
- the cross-section of the base is a hollow structure; more preferably, the cross-section of the base is a hollow circle, a hollow ellipse, a hollow rectangle, a hollow polygon or a contoured hollow structure; preferably, the outer contour of the base is a contoured hollow structure with an arc, and the curvature of the contoured hollow structure is consistent with the curvature of the balloon, thereby reducing the outer diameter of the device and ensuring the space of the internal hollow structure, thereby ensuring the flow rate of drug delivery.
- the drug delivery cavity 22 is disposed on the outer surface of the balloon 31.
- the other peripheral surfaces of the base 221 include a lower surface, which is fixedly attached to the outer surface of the balloon 31, and when in the unfolded configuration, as the balloon 31 expands, the base 221 is driven to move outward, thereby driving the puncture portion 211 disposed on the upper surface of the base 221 to protrude.
- the base 221 and the balloon 31 are connected in the form of pasting to ensure the stability of the connection between the base 221 and the balloon 31.
- the height H of the folding wing space 312 should not be less than the sum of the height h2 of the base 221 and the height h1 of the puncture structure 21.
- This design makes the entire balloon catheter radially small in the folded state, while ensuring that the balloon can be smoothly transported and that the puncture structure 21 is not damaged, and is applicable to more scenarios.
- the ends of the folding wings 311 (each group of folding wings 311) on both sides of the puncture structure 21 are at an equal distance from the puncture structure 21, so that during the delivery of the device, the circumferential force of the balloon 31 is uniform, the delivery stability is good, and the puncture structure 21 can be better protected from being damaged or tilted.
- the folding wings 311 of each group are symmetrically arranged, and each group of the side-piercing components 2 is symmetrically arranged, further ensuring the circumferential force uniformity of the balloon 31.
- each group of puncture components 2 has a plurality of puncture structures 21, which are spaced apart along the length direction of the base 221, the top of the puncture portion 21 is pointed, and the end of the puncture portion 21 is arranged to form the drug release hole 212.
- each puncture structure 21 in each group of puncture components 2 is equidistantly distributed.
- a pressure inflation and relief control unit and a drug delivery control unit are also provided on the delivery catheter, and the flow pressure inflation and relief channel composed of the second channel 12 and the balloon 31 is controlled by the pressure inflation and relief control unit, and the first channel 11 and the balloon 31 are controlled separately by the drug delivery control unit.
- a first Luer interface is provided on the first channel 11, and the first Luer interface is connected to the catheter lumens corresponding to the multiple drug delivery channels through a catheter.
- a groove 121 is provided along the radial direction of the second channel 12, and the groove 121 is extended along the axial direction of the second channel 12, and the groove 121 is used to accommodate the first channel 11, so that the radial size of the non-balloon part of the device is smaller.
- the radius of the groove 121 is not less than the outer diameter of the first channel 11.
- the depth of the groove 121 may be not less than the outer radius of the first channel 11, so that when the first channel 11 is accommodated in the groove 121, its structure is more stable and the integrity is better.
- the depth of the groove 121 can be set to be greater than the outer radius of the first channel 11 according to actual needs.
- the number of the grooves 121 is not limited. In actual use, the first channel 11 can be placed at the groove 121, or it may not be placed at the groove 121. If the first channel 11 is not placed at the groove 121, it is also within the protection scope of the present invention.
- the device can be used to deliver a drug carrier 100, which contains a drug.
- the drug carrier 100 When the drug carrier 100 is injected into a tissue, the drug carrier 100 can slowly release the drug in the tissue, thereby achieving the purpose of continuously treating the tissue.
- the radial dimension of the puncture assembly of the device is larger than the radial dimension of the drug carrier 100, for example, the diameter of the puncture assembly is larger than the diameter of the drug carrier 100, thereby enabling the drug carrier 100 to enter the tissue through the puncture assembly.
- the radial dimension of the puncture assembly is larger than 1000 ⁇ m, preferably, larger than 200 ⁇ m.
- the puncture structure 21 includes a puncture portion 211 and a drug release hole 212 , wherein the puncture portion 211 has a puncture wall 2111 , a puncture cavity 2112 , and a puncture surface 2113 .
- the puncture surface 2113 is the top surface of the puncture portion 211, that is, the surface that produces the puncture effect when puncturing the tissue.
- the puncture surface 2113 may be a plane, and the angle a between the puncture surface 2113 and the plane perpendicular to the axis of the puncture structure 211 is 5 to 85°, so as to better penetrate the tissue.
- the puncture surface 2113 may also be a surface with a certain curvature, such as a concave surface or a convex surface.
- the puncture surface 2113 may also be a conical surface, and the angle a of the conical surface is 25 to 75°.
- the puncture surface 2113 may also be a polygonal cylindrical surface to match actual usage requirements.
- the outside of the puncture wall 2111 may be cylindrical, conical, cylindrical at the bottom and conical at the top, or stepped. As shown in FIG. 4C , inside the puncture wall 2111, along its axial direction, its thickness does not change, so that the puncture assembly is evenly stressed during the puncture process and the drug delivery pressure remains unchanged during the delivery process.
- the thickness of the inside of the puncture wall 2111 gradually decreases along its axial direction, for example, the taper formed by the thickness reduction is 0 to 10°, thereby making the top size of the puncture portion 211 smaller, or its thickness gradually increases, so that the size of the puncture cavity 2112 gradually decreases, thereby increasing the delivery pressure during drug delivery, thereby increasing the injection pressure.
- the inside of the puncture wall 2111 is stepped, and the closer to the top, the smaller the radial size inside, so that the pressure of drug delivery can be increased in a step-by-step manner.
- the puncture cavity 2112 may be cylindrical, conical or stepped.
- the ratio of the inner radial dimension to the outer radial dimension of the puncture wall 2111 is 0.2 to 0.8, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, etc.
- the inner radial dimension of the puncture wall 2111 is 0.2 mm, 0.5 mm or 0.8 mm, and its outer radial dimension can be 1 mm.
- the inner radial dimension of the puncture wall 2111 is 0.8 mm, and its outer radial dimension can also be 1.5 mm, 2 mm, 4 mm, etc.
- the inner diameter of the puncture wall 2111 ranges from about 2 ⁇ m to 500 ⁇ m, preferably 2 ⁇ m to 200 ⁇ m, more preferably 50 to 150 ⁇ m, for example, about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150 ⁇ m, etc.
- the outside of the puncture wall 2111 can also be a surface extending along the axial direction of the balloon, and the puncture cavity is a gap formed along the puncture wall.
- the cross-section of the puncture wall is two triangles arranged opposite to each other, and the middle of the puncture wall is the puncture cavity. Please refer to Example 3 for details.
- the number of puncture parts 211 can be set according to actual conditions, and can be arranged longitudinally along the balloon, or circumferentially, etc. In this way, the number of puncture parts 211 is large, which increases the breadth and density of their distribution, and can achieve simultaneous drug administration at multiple points at the same time, improve the uniformity of drug administration, make treatment more effective, and achieve a better therapeutic effect of preventing restenosis.
- the drug release hole 212 can be opened along the axial direction of the puncture portion 211, as shown in FIG4A, or can be opened along the radial direction of the puncture portion 211, or the opening angle of the drug release hole 212 can be any angle, and the opening of the drug release hole 212 faces the angle direction between the axial direction and the radial direction.
- the opening can be one or more, for example, as shown in FIG4B, the opening in the radial direction is 2-4.
- the drug release hole 212 can be circular, elliptical, rectangular or other polygonal shapes.
- the drug release hole can be an elongated opening, a slot-shaped opening, etc. Such openings can be arranged in longitudinal rows at intervals along the length direction of the base 221, or can not be arranged in longitudinal rows.
- the number of rows can be any suitable number in the range of 2-30 rows (but in some embodiments, the number of rows higher than 30 can also be used), according to needs, in particular, can be set according to the size of the opening, according to the type and chemical/physical properties, size and depth of entry into the target area of the drug or therapeutic composition, etc.
- the material of the puncture portion 211 can be made of a hard material, such as a metal material, and more preferably, it can be a nickel-titanium alloy, stainless steel, cobalt-chromium alloy, etc. More preferably, it can be a polymer material, including: nylon, ABS, resin, PEEK, TPE, TPU, PLA, photoresist, etc., and biopolymer materials such as silk fibroin.
- Metal materials can be made by laser etching, machining, pickling, polishing, grinding and other processes to form a sharp edge; polymer materials can be made by 3D printing, which has the advantages of high precision and fast processing speed. Polymer materials can also be made by mold casting/demolding, which has the advantages of high strength and mass production. More preferably, the material of the puncture portion 211 can also be a ceramic material, etc.
- the puncture portion 211 is connected to the medication cavity 22, and the cross-section of the medication cavity 22 can be circular, elliptical, triangular, rectangular or polygonal. More preferably, the height h1 of the puncture portion 211 is between 0.1 and 1.5 mm, and the height h2 of the medication cavity 22 is between 0.1 and 0.5 mm.
- the ratio of the wall thickness T of the medication cavity 22 to the outer diameter D (transverse dimension W) is 0.06 to 0.8, and preferably, the ratio of the wall thickness T of the medication cavity 22 to the outer diameter D (transverse dimension W) is 0.05 to 0.45.
- the puncture portion 211 and the drug delivery cavity 22 can be connected by welding or bonding.
- the distance between each puncture portion 211 is preferably smaller than the radial dimension of the puncture portion. More preferably, the distance between each puncture portion 211 is preferably 0.5 to 5 mm, preferably 1 to 2 mm, so that the injected drug can be evenly distributed in the tissue.
- the drug delivery cavity 22, such as the base 221 can be made of a hard material such as metal, polymer or ceramic, to provide a basis for the puncture structure 21 to penetrate the tissue evenly.
- the base 221 is, for example, a tube, and the base 221 is a cylindrical structure, and the entire cylindrical structure is made of hard materials such as metal, polymer material or ceramic.
- the length of the base 221 is less than the axial length of the balloon 31.
- the upper surface portion of the base 221 connected to the puncture portion 2 is made of hard material, and the other surface portions are made of flexible material to form a hose.
- the drug delivery cavity 22 and the balloon 31 are fixed to the balloon surface by adhesive curing and are evenly arranged in the circumferential direction.
- the connecting part is a hard material such as metal
- plasma treatment can be performed first, or by grinding, and then welding or gluing.
- the connecting part is a flexible hose, it is connected by welding or gluing.
- the structure of the drug delivery cavity 22 can be cylindrical, elliptical, rectangular, triangular or polygonal structure.
- the base 221 is, for example, a plate-like structure, and the drug delivery cavity 22 also includes a drug delivery catheter 222, and the base 221 can be arranged on the drug delivery catheter 222, such as pasting.
- the length of the plate-like structure is less than the axial length of the balloon 31, the width of the plate-like structure is not less than the diameter of the drug delivery cavity 22 of the puncture assembly 2, and the thickness of the plate-like structure is not less than the wall thickness of the drug delivery cavity 22 of the puncture assembly 2.
- the plate-like structure may also have a curvature, for example, the surface of the plate-like structure in contact with the balloon 31 has a curvature toward the balloon 31, so that the plate-like structure can be more tightly connected to the balloon 31.
- the curvature of the curvature of the plate-like structure toward the balloon 31 is consistent with the curvature of the balloon 31.
- the outer contour of the base is a contoured hollow structure with a curvature, and the curvature of the contoured hollow structure is consistent with the curvature of the balloon; the balloon folding can bury the puncture assembly between two folded balloon wings through a customized device to avoid scratching the blood vessel when the device is transported.
- the original folded state of the balloon can be achieved through the balloon folding wings. Due to the memory of the balloon folding, the balloon will return to the folded state after the balloon is depressurized. In this way, it can be ensured that the balloon effectively covers each group of puncture components.
- the drug delivery catheter 222 of the puncture assembly 2 includes a hard catheter 2221 and a soft catheter 2222, and the hard catheter 2221 and the soft catheter 2222 are arranged in sections and at intervals. For example, two sections of hard catheters 2221 and one section of soft catheter 2222 are included. Of course, the number of hard catheters and soft catheters is not limited. Preferably, the number of soft catheters 2222 is one less than the number of hard catheters 2221.
- the puncture structure 21 is preferably arranged on the hard catheter 2221, so that the hard catheter can provide the hardness and strength required for the puncture assembly 2 to penetrate the tissue.
- the setting of the soft catheter 2222 provides flexibility for the drug delivery catheter 22, improves the passability of the device, and facilitates the delivery of the device.
- the soft catheter 2222 can be bent, and it can be arranged on the surface of the balloon 31 in a non-axial extension; the setting of the soft catheter 2222 also provides a prerequisite for the misalignment setting of the puncture assembly 2.
- the hard catheter 2222 of the front section and the hard catheter 2222 of the rear section are different in the circumferential direction of the balloon 31 (FIG. 5D is a schematic diagram of the expansion of the drug delivery catheter 22 arranged circumferentially along the balloon 31), so as to form a staggered arrangement.
- the solid line indicates that one section of the hard catheter 2221 is arranged circumferentially at a certain angle
- the dotted line indicates that another section of the hard catheter 2221 is arranged circumferentially at another angle.
- the drug release component 4 can have a hard catheter and a soft catheter, and the hard catheter provides a fixed lumen required by the release structure 41 (61).
- the scheme of the drug release component 4 can refer to the structure of the puncture component 2, which will not be repeated here.
- the drug delivery cavity 22 is connected to the first channel 11.
- the outer diameter of the first channel 11 is matched with the inner diameter of the drug delivery cavity 22; or, the inner diameter of the first channel 11 is matched with the outer diameter of the drug delivery cavity 22.
- the puncture assembly 2 in the connection between the puncture assembly 2 and the balloon 31, can be arranged outside the balloon 31, specifically in the first embodiment. It can also be arranged inside the balloon 31, specifically in the second embodiment.
- a charging and releasing pressure control unit and a drug delivery control unit are also arranged on the delivery catheter, and the flow charging and releasing pressure channel composed of the second channel and the balloon and the drug delivery channel are controlled by the charging and releasing pressure control unit and the drug delivery control unit respectively.
- the charging and releasing pressure control unit and the drug delivery control unit can control the magnitude of the force by a pump or the like, or the magnitude of the force can be manually controlled by medical personnel.
- the balloon When the balloon is in a folded state, the balloon covers each group of puncture components; when the balloon is in an expanded state, the balloon expands, driving each group of puncture components to protrude from the balloon. In this way, the balloon can be delivered to the lesion when it is in a folded state. Since the balloon is in a folded state and covers each group of puncture components, the blood vessels will not be damaged during the intervention process; and after the balloon is depressurized, the balloon returns to a folded state, driving each group of puncture components to withdraw from the target area and cover each group of puncture components, avoiding damage to the tissue during the withdrawal of the balloon, and also avoiding each group of puncture components from remaining in the tissue, thereby improving the safety of the operation process. It can be understood that when the balloon is fully expanded, as the balloon expands, the additional drug delivery channel passes through the drug release hole and is injected into the target area through the drug release channel to complete the drug delivery.
- the liquid is configured for circulation, pressure filling and release, and for drug administration.
- the liquid can be physiological saline with added drugs or drug carriers, but it is certainly not limited to physiological saline.
- the separation between two liquids that will not mix is called “liquid-liquid phase separation", which is crucial to the function of many proteins.
- liquid-liquid phase separation can be applied in the device.
- the "liquid-drug phase separation” principle is used to separate the liquid and the drug or drug carrier, that is, the liquid and the drug or drug carrier are first injected into the chamber through one or more channels. If the density of the drug or drug carrier is lighter than that of the liquid, the liquid containing more drug or drug carrier content is ejected from the drug release component and transported to the target area by applying a corresponding control force alone.
- This section elaborates on the shape, material, size of the first channel 11, the combination of the first channel 11 and the drug delivery cavity 22, the positional relationship between the first channel 11 and the second channel 12, etc., but the first channel 11 is not limited to these. As long as the structure can achieve drug delivery, it is within the scope of this application.
- the first channel 11 is used to deliver the drug (it should be understood that the drug can be a liquid medicine) from the proximal end of the first channel 11 to the distal end.
- the first channel 11 is a multi-cavity structure at least near the distal end, and the multi-cavity structure includes a plurality of independent drug delivery channels 111 for delivering drugs.
- the first channel 11 can be a plurality of independent drug delivery channels, and the drug delivery channels are independent from the proximal end to the distal end.
- the drugs can be input from the drug delivery channels respectively to achieve separate drug administration.
- the radial size and axial size of each drug delivery channel are consistent, thereby providing conditions for achieving drug delivery at the same rate and pressure.
- the completely independent drug delivery channels can also have inconsistent radial or axial sizes, thereby making the pressure and rate of drug delivery different.
- the part of the first channel 11 near the proximal end includes a general channel, and the part near the distal end is divided into a plurality of independent drug delivery channels 111. When it is necessary to deliver drugs, the drugs are input from the general channel, and the drugs are then output through the independent drug delivery channels 111.
- the material of the first channel 11 is preferably a hose material, such as one or a combination of elastomers such as polyamide, polyimide, block polyether amide, polyvinyl chloride, silicone, etc., and the above materials are not limited in actual use.
- the first channel 11 can also be a hard material.
- the hard material can include metal materials, polymer materials, and ceramic materials.
- the balloon assembly can be a rapid exchange structure or a coaxial structure: the rapid exchange structure has a side hole for the guide wire; the coaxial structure consists of single-lumen or multi-lumen tubes of the same or different lengths, and the manufacturing process is relatively simple.
- the materials of the balloon assembly are mainly: polymer plastics, metal parts, and hydrophilic coatings, etc. Its manufacturing process includes but is not limited to: stretch blow molding, coaxial extrusion, laser/thermal welding, injection molding, and adhesive processes, etc.
- the connector may include two or three Luer ports, each of which has an independent chamber and can be fixed to the end of the catheter by mold injection or gluing.
- the chambers in the Luer ports are simultaneously and separately connected to the drug delivery channel; and an additional chamber is provided to be connected to the pressure infusion channel, which are independent of each other and do not interfere with each other.
- the folding wings do not overlap.
- the folding wings are 3-5 pairs; when the diameter of the balloon is 4-12 mm, the folding wings are 5-6 pairs; when the diameter of the balloon is 10-30 mm, the folding wings are 6-12 pairs.
- Figure 6A is a schematic diagram of a device for drug delivery using a balloon provided in the second embodiment
- Figure 6B is a cross-sectional view of the device for drug delivery using a balloon in Figure 6A in a folded state.
- the difference between the second embodiment and the first embodiment is that the structure of the device for delivering drugs by using a balloon is different, and further, the combination of the puncture assembly and the balloon is different.
- the same parts of the device in the second embodiment and the first embodiment are not described again, and only the differences are described below.
- the drug delivery cavity 22 is arranged on the inner surface of the balloon 31.
- the base 221 is arranged inside the inner surface of the balloon 31.
- the upper surface of the base 221 is fixedly fitted with the inner surface of the balloon 31, and a hole for the puncture structure 21 to pass through is arranged on the balloon 31, and the puncture structure 21 passes through the hole and is protruded from the inner surface of the balloon 31.
- the protruding puncture structure 21 is arranged in the folding wing space 312 formed by the folding wing; in the unfolded configuration, as the balloon 31 expands, the base 221 is driven to move outward, thereby driving the protruding puncture structure 21 to extend out of the folding wing space 312, and the folding wing space 312 becomes smaller or expands and disappears.
- the height H of the folding wing space 312 should be no less than the protruding height h3 of the puncture structure 21 protruding from the inner surface of the balloon 31.
- the bases 221 of each group of puncture components 2 are arranged circumferentially along the guide catheter 32. In the folded configuration, the bases 221 are supported by the guide catheter 32; in the expanded configuration, the bases 221 are driven away from the guide catheter 32 as the balloon 31 expands.
- FIG. 7 is a schematic diagram of a device for drug delivery using a balloon provided in the third embodiment.
- the difference between the third embodiment and the first and second embodiments is that the structure of the device for delivering the drug by using the balloon is different, and further, the structure of the puncture assembly is different.
- the same parts as in the second embodiment are not described again, and only the differences are described below.
- the puncture structure 21 of each group of puncture components 2 is a pair of puncture blades 213.
- the pair of puncture blades 213 are respectively composed of two long blades, which are respectively installed on the base and surround a long drug release hole 2131, thereby improving the drug delivery efficiency. In addition, due to the good integrity of the blades, the blades are not easy to fall off, thereby reducing the risk of the puncture component falling into the tissue.
- the pair of puncture blades 213 are extended along the length direction of the balloon 31, and the length of the puncture blades 213 can be set according to actual needs.
- the blade has a structure with a wide bottom and a narrow top, and the blade head is located at the upper end.
- the aspect ratio of the blade is 0.05 to 1, and preferably, the aspect ratio of the blade is 0.1 to 0.25.
- FIG. 8A is a schematic diagram of a drug delivery device provided in the fourth embodiment
- FIG. 8B is a schematic diagram of another drug delivery device provided in the fourth embodiment.
- the difference between the fourth embodiment and the fifth embodiment is that the drug delivery device of the fourth embodiment does not include the first channel and the drug delivery cavity, and the release structure of the drug delivery component is a raised through hole.
- the difference between the fourth embodiment and the first to third embodiments is that the drug delivery device of the fourth embodiment does not include the first channel and the drug delivery cavity. The same parts of the device of the fourth embodiment and the first embodiment are not described again, and only the differences are described below.
- the drug delivery device provided in the fourth embodiment includes: a delivery catheter (not shown in FIG. 8 ), at least one group of drug release components 6 and a balloon component 7 .
- the drug release component 6 includes at least one release structure 61 and a drug delivery cavity 62, wherein the release structure 61 includes a puncture portion 611 and a drug delivery hole 612, wherein the drug delivery hole 611 in the group is connected to the drug delivery cavity 62.
- the drug delivery cavity 62 and the pressure-charging and decompression cavity use the same chamber.
- the chamber is used to fill the drug carrier of the drug and/or the liquid of the drug, and the liquid is configured to circulate for pressure-charging and decompression and for drug delivery.
- the liquid fills the balloon to drive the balloon to expand, so that the balloon is in an expanded configuration.
- the release structure 61 and the base 63 can be fixed as one by adhesives, welding and other processes, and then can be directly fixed on the outer wall or inner surface of the balloon 71 by adhesives, welding and other processes, and then a drug release channel is opened on the release structure 61 and a through hole is opened on the base 63 at one time by laser drilling, so as to ensure the stability of the subsequent drug release process.
- the base 63 is located on the outer surface of the balloon 31.
- the base 63 can be a plate-like substrate.
- the base 63 is not limited to a plate-like substrate, and only has the function of installing or fixing the release structure 61.
- the base 63 can be made integrally with the release structure 61, or separately.
- the balloon assembly 7 at least comprises a balloon 71, and the balloon 71 is configured to change between a folded configuration and an unfolded configuration by a pressure-inflating and pressure-releasing process; in the folded configuration, the drug release components are separately enclosed in the balloon; in the unfolded configuration, the expansion force of the balloon 71 drives the drug release component 6 to move to a preset target area, and the drug is delivered to the target area through the drug delivery channel by applying a corresponding control force alone.
- the folded configuration and the unfolded configuration can be specifically referred to the description in the first embodiment.
- FIG. 8B which is different from FIG. 8A in that the base 63 can be located inside the balloon 31, the upper surface of the base 63 is fixedly fitted with the inner surface of the balloon 71, and the release structure 61 in the drug release assembly 6 protrudes from the inner surface of the balloon 71.
- the protruding release structure 61 is arranged in the accommodation space formed by the folded wings; in the unfolded configuration, as the balloon 71 expands, the release structure 61 moves outward, thereby driving the protruding release structure 61 to extend out of the accommodation space, and the accommodation space becomes smaller or expands and disappears.
- the liquid is configured for circulation, pressure relief and drug administration.
- the liquid can be saline with drugs or drug carriers added, but it is certainly not limited to saline.
- the pressure charging and discharging channel and the drug administration channel are two independent channels that are not interconnected and are controlled separately, and the drug release components are multiple groups, and the movement of the drug is controlled by multiple drug delivery control units or the same drug delivery control unit.
- the pressure filling and release channel and the drug delivery channel use the same chamber
- the drug release components are multiple groups
- the chamber contains a drug carrier of the drug or a liquid of the composition
- the liquid is configured to be used for circulation for pressure filling and release and for drug delivery
- the liquid fills the balloon to drive the balloon to expand, so that the balloon is in an expanded configuration
- the liquid is delivered through the drug delivery channel by applying a corresponding control force alone.
- the balloon assembly further comprises a guide catheter, the balloon is sealably attached to the guide catheter, the balloon is folded to form a plurality of folding wings, which are arranged circumferentially along the guide catheter, each pair of folding wings arranged opposite to each other forms a folding wing space, and the drug release components are respectively accommodated in the adapted folding wing spaces.
- a guide catheter the balloon is sealably attached to the guide catheter, the balloon is folded to form a plurality of folding wings, which are arranged circumferentially along the guide catheter, each pair of folding wings arranged opposite to each other forms a folding wing space, and the drug release components are respectively accommodated in the adapted folding wing spaces.
- the drug release components are configured to implant the drug into the target area or inject the drug into the target area.
- the top of the puncture portion is pointed, and the end is arranged to form the drug-releasing hole.
- Figure 9 is a schematic diagram of a drug delivery device provided in the fifth embodiment
- Figure 10 is a schematic diagram of another drug delivery device provided in the fifth embodiment.
- the drug release component 4 of the device for drug delivery using a balloon provided in the fifth embodiment does not include a puncture structure.
- the same parts of the device in the fifth embodiment as those in the other embodiments will not be described again, and only the differences will be described below.
- the fifth embodiment provides a drug delivery device, including: a delivery catheter (not shown in FIG. 9 ), at least one group of drug release components 4 and a balloon component 5 .
- the delivery catheter has a proximal portion and a distal portion, and includes a first channel (not shown in FIG. 9 ) for delivering drugs and a second channel (not shown in FIG. 9 ) for circulation and pressure relief, which are not connected to each other.
- At least the first channel near the distal portion is a multi-lumen structure, and the multi-lumen structure includes multiple independent drug delivery channels for delivering drugs.
- the drug release component 4 includes at least one release structure 41 and a drug delivery cavity 42, and the release structure 41 includes at least a drug delivery hole 411, and the drug delivery hole 411 in the group is connected to the drug delivery cavity 42.
- the drug delivery cavity 42 also includes a drug delivery cavity 421 and a drug delivery hole 422, and the drug delivery hole 411 is connected to the drug delivery cavity 421 through the drug delivery hole 422.
- the drug delivery hole 411 is located on the balloon 51.
- the drug delivery hole 411 is used as a drug delivery hole on the drug delivery cavity 42.
- the drug delivery hole 422 is the same size as the drug delivery hole 411, thereby facilitating drug delivery.
- the sizes of the drug delivery hole 422 and the drug delivery hole 411 may be different, and are set according to actual needs.
- the radial size of the drug delivery cavity 421 is greater than the diameter of the drug delivery hole 422, thereby ensuring the stability of the drug delivery pressure.
- the inner diameter of the dosing cavity 421 is ⁇ 0.1mm, such as 0.2, 0.3, 0.4, etc.; preferably, the inner diameter of the dosing cavity 421 is ⁇ 0.3mm; more preferably, the inner diameter of the dosing cavity 421 is ⁇ 0.5mm, such as 0.6, 0.7, 0.8, etc.
- the ratio of the inner/outer diameter of the dosing cavity 421 is 0.1-0.9, more preferably, the ratio of the inner/outer diameter of the dosing cavity 421 is 0.4-0.8.
- the inner diameter of the dosing hole 422 is smaller than the inner diameter of the dosing cavity 421.
- the inner diameter of the dosing hole 422 is less than 0.5 times the inner diameter of the dosing cavity 421, and the inner diameter of the dosing hole 422 is even less than 0.01mm.
- the inner diameter size range of the drug delivery hole 422 is about 2 ⁇ m-500 ⁇ m, preferably 2 ⁇ m-200 ⁇ m, more preferably 50-150 ⁇ m, for example, it can be 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150 ⁇ m, etc., of course, it can also be smaller or larger than these sizes.
- those skilled in the art can set the size of the drug delivery cavity 421 and the drug delivery hole 422 according to actual conditions. Those skilled in the art can determine the drug injection pressure during drug delivery according to the selection of the size of the drug delivery cavity 421 and the drug delivery hole 422, combined with the delivery force of the drug delivery.
- the balloon assembly 5 includes at least one balloon 51, and the balloon 51 is configured to change between a folded configuration and an unfolded configuration by a pressure release.
- the drug release assembly 4 is separately enclosed in the balloon 51.
- the expansion force of the balloon 51 drives the drug release assembly 4 to move to a pre-set target area, and the drug is delivered to the target area through the independent drug delivery channel by applying a corresponding control force separately.
- the folded configuration and the unfolded configuration can be specifically referred to the description in Example 1.
- the first channel and the drug release component 4 can be arranged on the inner surface of the balloon 51.
- the drug solution can have a separate channel, the concentration of the drug solution can be controlled, and the release rate can be controlled.
- the first channel and the drug release component 4 can be arranged on the outer surface of the balloon 51, and the drug release hole 411 is connected to the drug delivery cavity 42.
- the drug release component 4 adheres to and compresses the tissue, and closely adheres to the tissue, because the compressed tissue is affected by stress concentration, and when the drug is released at this position, the drug can be better penetrated into the tissue.
- the drug release component 4 can be a hollow silk thread, and the hollow silk thread is provided with a drug release hole.
- the inner diameter of the drug delivery cavity 42 is ⁇ 0.1mm, for example, 0.2, 0.3, 0.4, etc.; preferably, the inner diameter of the drug delivery cavity 42 is ⁇ 0.3mm; more preferably, the inner diameter of the drug delivery cavity 42 is ⁇ 0.5mm, for example, 0.6, 0.7, 0.8, etc.
- the ratio of the inner/outer diameter of the drug delivery cavity 42 is 0.1 to 0.9, and more preferably, the ratio of the inner/outer diameter of the drug delivery cavity 42 is 0.4 to 0.8.
- the inner diameter of the drug release hole 411 is smaller than the inner diameter of the drug delivery cavity 42.
- the inner diameter of the drug release hole 411 is smaller than 0.5 times the inner diameter of the drug delivery cavity 42.
- the spacing between each drug release hole 411 is 0.1 to 1 mm, preferably 0.25 to 0.75 mm. For example, 0.25mm, 0.3mm, 0.4mm, 0.45mm, 0.5mm, 0.6mm, etc. Of course, the drug release hole 411 can also be greater than 1mm.
- the cross section of the drug delivery cavity 42 can be a circular or triangular hollow tube. When the drug delivery cavity 42 is circular, the drug release hole 411 on the drug delivery cavity 42 is preferably oriented in the direction of the expansion of the balloon 51. Of course, in other embodiments, the drug release hole 411 on the drug delivery cavity 42 may be at a certain angle to the direction of the expansion of the balloon 51.
- both sides of the triangular column preferably have drug release holes 411.
- drug release holes 411 for example, two drug release holes 411, so that two rows of drug release holes 411 are formed on the drug delivery cavity 42, thereby increasing the channel for drug release and increasing the amount of drug intake.
- the drug release component 4 is a triangular hollow tube, that is, the outer surface shape of the drug delivery cavity 42 is a triangular cylinder, and one of the corners of the triangular cylinder is arranged toward the radial outside of the balloon 51.
- the end of the angle facing the radial outside of the balloon is defined as the incision end 423.
- the drug release hole 411 is arranged at the incision end 423 of the drug delivery cavity 42.
- the triangular hollow tube has a stronger ability to penetrate the tissue, and can even penetrate the diseased tissue completely, so that when the drug is released, it can be released in the diseased tissue, thereby improving the efficiency of drug delivery.
- the drug release hole 411 is arranged at the incision end 423 of the triangular hollow tube.
- its height along the radial direction of the balloon can be reduced by 20% to 30%, making the size smaller and the overall passability of the device good.
- People in the field know that in the field of intervention, any slight change in a narrow tissue cavity will provide a breakthrough in the technology of the field.
- the triangular hollow tube has high processing precision, short processing cycle, can be formed in one step, no additional process (such as welding, cutting, etc.), low cost, good processability, reduced manufacturing cost, improved overall quality of the device, and convenient for mass production.
- the setting of the cutting end 423 can play a role in stress concentration and promote targeted drug release. For example, it can also cut off the elastic membrane of the inner wall of the blood vessel and reduce the effect of postoperative vascular lumen rebound.
- the drug release component 4 is a triangular hollow tube, that is, the outer surface of the drug delivery cavity 42 is a triangular cylinder, and the drug release hole 411 can be a combination of being arranged at the cut-in end 423 and being arranged on the two side walls of the triangular hollow tube.
- the axial position of the drug release hole 411 arranged at the cut-in end 423 is the same as or different from the axial position of the two side walls of the triangular hollow tube. In this way, the lateral diffusion distribution of the drug liquid is more uniform than that of the unidirectional hole.
- the drug release holes 411 can be arranged uniformly or unevenly along the axial direction of the drug delivery cavity 42 of the triangular hollow tube, thereby providing a prerequisite for quantitative drug delivery.
- the drug release holes 411 can be arranged uniformly.
- the drug release holes 411 can be arranged unevenly.
- the density of the drug release holes 411 can be greater than the positions on both sides of the axial direction of the balloon that do not contact the lesion.
- the size of each drug release hole 411 can be uniform. Please refer to Figure 22C and Figure 23C.
- the size of each drug release hole 411 can be gradually enlarged or reduced.
- the size of each drug release hole 411 gradually increases, so that the liquid discharge of the drug release component 4 is more uniform.
- the specific reason is that in the drug delivery cavity 42, the closer to the distal end, the greater the liquid flow resistance, and the drug release hole 411 becomes appropriately larger to facilitate the outflow of the drug solution, so that the pressure relief of the drug release hole 411 (the drug release hole near the distal end) is as consistent as possible with the pressure relief of the previous drug release hole (the drug release hole near the proximal end), thereby ensuring a more uniform liquid discharge.
- the total length of the device is relatively long and thin, and the size of the drug delivery cavity 42 has a great influence on the liquid flow resistance.
- the gradually changing diameter of the drug release hole 411 is set in the drug delivery cavity 42 to overcome the technical difficulty of uneven liquid discharge.
- Table A is the measurement table of drug release hole equal diameter-released drug amount
- the drug release holes 411 are numbered 1 to 5 along the proximal end to the distal end of the drug delivery cavity 42 .
- Table B is a measurement table of drug release amount as the diameter of the drug release hole increases
- the drug release holes 411 are numbered 1 to 5 along the proximal end to the distal end of the drug delivery cavity 42 .
- Table C is a measurement table of drug release hole diameter change-drug release amount
- the drug release holes 411 are numbered from 1 to 7 along the proximal end to the distal end of the drug delivery cavity 42 .
- the diameter of the drug release holes is uniformly set, and the amount of drug released from the drug release holes is getting smaller and smaller, and the maximum difference in drug amount can reach 0.96uL.
- Table B from the proximal to the distal end, the diameter of the drug release holes increases, the difference in the amount of drug released decreases, the amount of drug released tends to be uniform, and the trend of the amount of drug released gradually decreases.
- the hole 4 (number 3) and the hole 5 (number 5) in the middle of the drug release hole can have a larger drug output, and the drug output at the two ends is smaller.
- uniform liquid discharge cannot be achieved, the middle position of the balloon is in the closest contact with the middle position of the lesion, and the treatment effect is good.
- the size of the drug delivery cavity 42 has a specific setting, thereby meeting the use of a specific scene.
- the height of the outer dimension of the drug delivery cavity 42 is 0.1-1.0mm (in the cross-sectional triangle, the surface attached to the balloon is the bottom surface, and the direction from the bottom surface to the incision end is the height direction), for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 and 1.0mm.
- the height of the outer dimension of the drug delivery cavity 42 is 0.3-0.7mm.
- the wall thickness of the drug delivery cavity 42 is 0.01-0.1mm, for example, 0.01, 0.03, 0.05, 0.07, 0.1mm. Preferably, the wall thickness of the drug delivery cavity 42 is 0.03-0.07mm.
- the length of the drug delivery cavity 42 is 5-50mm.
- the triangular inner cavity vertex angle (angle of the cut end) of the drug delivery cavity 42 is 10-80°, for example, 10°, 20°, 30°, 40°, 50°, 60°, 70°, 80°.
- the non-inner cavity vertex angle of the drug delivery cavity 42 is 10-70°, for example, 10°, 20°, 30°, 40°, 50°, 60°, 70°.
- the diameter of the drug release hole 411 may be 0.01-0.2 mm, for example, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2 mm.
- the diameter of the drug release hole 411 may be 0.05-0.15 mm.
- the spacing between the drug release holes 411 is between 0.05 mm and 7 mm, for example 0.05, 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 4.2, 4.4, 4.6, 4.8, 5, 5.2, 5.4, 5.6, 5.8, 6, 6.2, 6.4, 6.6, 6.8, 7 mm.
- a sharp angle is extended along the radial direction of the balloon 51, that is, in the extending direction of the cutting end 423, to form a micro-convex angle 4231, and the micro-convex angle 4231 is extended along the axial direction of the cutting end.
- the micro-convex angle 4231 is used to provide a relatively sharp end, and the micro-convex angle 4231 can also improve the hardness and rigidity of the tissue, making it easier for the drug release component 4 to penetrate the diseased tissue.
- the end of the micro-convex angle 4231 can be sharpened or not.
- the inner surface shape of the drug delivery cavity 42 can be a triangular lumen, a circular lumen, a rectangular lumen, a polygonal lumen or a special-shaped lumen.
- the shape of the inner surface of the drug delivery cavity 42 is a triangular lumen
- the cross section of the drug delivery cavity 42 is extended along the direction of the cut-in end to design a cavity with a sharp corner on the basis of the triangle, forming a triangular hollow tube.
- the shape of the cross section of the triangular hollow tube is consistent with the shape of the cross section of the outer surface of the drug delivery cavity containing the micro-convex corner, and the cavity is also used for liquid delivery. It should be understood that even if the cut-in end 423 has an extended micro-convex corner 4231, the drug release component 4 is opened on the micro-convex corner 4231 of the cut-in end 423, which is convenient for drug output.
- the triangular hollow tube is designed to be variable in size.
- the size of the triangular hollow tube gradually decreases, thereby making the liquid discharge more Even.
- the cavity wall of the triangular hollow tube can be of equal size or of variable size.
- the thickness of the triangular side wall does not change, or gradually widens or narrows, along the radial extension direction of the balloon.
- the side wall can gradually widen along the radial extension direction of the balloon.
- the side wall can gradually narrow along the radial extension direction of the balloon.
- the volume of the drug delivery cavity 42 can remain unchanged while the drug release component 4 penetrates the diseased tissue, which is convenient for the management of liquid medicine delivery.
- the pressure, volume and other parameters of the delivery will not be affected by the change in the volume of the drug delivery cavity 42.
- the drug release hole 41 can be a circular hole, an elliptical hole, a square hole, a rectangular hole, a triangular hole, a special-shaped hole, or a combination of any of these holes, and is specifically set according to the drug release amount and the drug release pressure.
- the drug release component 4 such as the triangular hollow tube or the quasi-triangular hollow tube, is made of resin, ceramic, stainless steel, nylon, degradable polymer or a combination of these materials.
- the ceramic material may be, for example, aluminum oxide, zirconium oxide, magnesium oxide, calcium phosphate or a combination of these materials, so that the component (triangular hollow tube) has good biocompatibility, mechanical strength that meets clinical requirements, and good manufacturability, and is convenient for mass production.
- the drug release component such as the triangular hollow tube and the quasi-triangular hollow tube, adopts ultra-precision micro-nano 3D printing technology.
- a sintering process is adopted, and more preferably, laser sintering or high-temperature sintering is adopted.
- commonly used materials are resins, stainless steel, etc., but due to the limitations of material properties, their processing accuracy is poor.
- the ceramic sintering process solves the problem of poor accuracy. Therefore, combining materials and processes, the control of accuracy is higher, and the error range of 2 to 5 ⁇ m can be achieved, which meets the requirements of controllable accuracy.
- the drug release component 4 can be one group or multiple groups.
- the groups of drug release components 4 control the movement of the drug through multiple drug delivery control units or the same drug delivery control unit, so that the movement force of the drug can be controlled separately.
- the release structure can only include the drug release hole 411, and the force of the drug movement passing through the drug release hole 411 can be controlled to control the force of the drug entering the target area.
- the aperture size of the drug release hole is set from small to large, which is more convenient to control the force of the drug entering the target area.
- the balloon assembly may also include a guide catheter (not shown in Figure 9), the balloon 51 is sealingly attached to the guide catheter, and the balloon 51 is folded to form a plurality of folding wings, which are arranged circumferentially along the guide catheter. Each pair of relatively arranged folding wings forms a folding wing space, and the drug release components are respectively accommodated in the folding wing spaces.
- the drug release components 4 are configured to implant or inject drugs into the target area.
- the release structure also includes a base, the upper surface of the base and other peripheral surfaces form the drug delivery cavity, the upper surface of the base is provided with a through hole connected to the drug delivery hole along the length direction of the balloon, and the drug delivery hole is connected to the drug delivery cavity through the through hole.
- the drug release component can be directly implanted into the target area or injected into the target area by the external force.
- FIG. 11 is an exemplary diagram of the drug delivery device provided in the sixth embodiment.
- the drug delivery device provided in the sixth embodiment is a coating structure, such as a drug coating, coated on the device of the first to fifth embodiments.
- the drug may be coated on the surface of the balloon, the puncture component (or the drug release component), or both.
- the drug and the drug coating can simultaneously treat the diseased part (such as a diseased blood vessel) in both the surface and point dimensions.
- the dotted line is used to indicate that the device has a coating structure on the outside, which does not represent the actual coating structure.
- the thickness of the coating structure, drug concentration and other parameters can be set according to actual conditions.
- the thickness and drug concentration of the coating can be matched with the drug solution to achieve drug therapy.
- the drug of the coating can be one drug, and the drug delivered by the balloon puncture component or the drug release component is another drug. The difference between the two drugs can be matched with each other, thereby achieving drug-assisted therapy.
- a method for achieving drug delivery, using the above device to achieve precise drug delivery comprises the following steps:
- the second channel is pressurized to expand the balloon so that the balloon is in the deployed configuration: the expansion of the balloon drives the puncture portion of the puncture assembly to bulge; or the expansion of the balloon drives the drug release assembly to cling to the tissue at the target location;
- the drugs are delivered through one or more drug delivery channels, each drug delivery channel corresponds to a drug delivery cavity,
- the drug release holes connected to the drug delivery cavity are respectively delivered to the target area.
- the balloon can be configured such that after rotating to a preset position, the drug is delivered to the target area once or multiple times through multiple drug delivery channels, the drug delivery cavity corresponding to each drug delivery channel, and the drug release holes connected to the drug delivery cavity.
- the balloon After the balloon is depressurized, the balloon returns to a folded state, driving the puncture structure to withdraw from the target area and cover the puncture structure.
- the device or drug delivery device using a balloon can be used in areas with narrow body cavities, including vascular stenosis, urethral stenosis, ureteral stenosis, esophageal stenosis, prostatic urethral stenosis, urinary tract stenosis, urethral stenosis, ureteral stenosis, coronary artery stenosis, tracheal stenosis, bronchial stenosis, achalasia stenosis, stent stenosis, sinus stenosis, gastric stenosis, small intestine stenosis, duodenal stenosis, jejunal stenosis, ileal stenosis, colon stenosis, rectal stenosis, large intestine stenosis, biliary stenosis, arteriovenous fistula
- Esophageal cancer is one of the most common malignant tumors. Endoscopic submucosal dissection (ESD) is widely used in the treatment of esophageal cancer due to its minimal trauma and few complications. However, ESD can cause scar fibrous tissue hyperplasia, which can lead to a smaller diameter of the digestive tract lumen, i.e., esophageal stenosis, and affect the normal passage of digestive tract contents.
- ESD Endoscopic submucosal dissection
- Endoscopic balloon dilatation can prevent and treat esophageal stenosis after ESD.
- patients with severe stenosis still need to undergo multiple balloon dilatation EBDs.
- Repeated dilatation usually has an unimpressive prognosis. Therefore, the present invention provides a device and treatment method: combining balloon dilatation and drug injection together, thereby greatly reducing the number of EBDs and providing more choices of injectable drugs.
- the injected drugs include but are not limited to: glucocorticoids, such as: prednisolone, triamcinolone acetonide, methylprednisone, betamethasone, beclomethasone dipropionate, prednisolone, hydrocortisone, dexamethasone, etc.
- glucocorticoids such as: prednisolone, triamcinolone acetonide, methylprednisone, betamethasone, beclomethasone dipropionate, prednisolone, hydrocortisone, dexamethasone, etc.
- This embodiment eight also provides an esophageal balloon device, which includes the device for drug delivery using a balloon as described above. It should be understood that the esophageal balloon device can use any device in the above embodiments one to six. This embodiment eight schematically uses the device provided in embodiment one for illustration, and reference can be made to FIG1 for this purpose.
- the esophageal balloon device comprises: a delivery catheter 1 , a plurality of puncture components 2 and a balloon component 3 .
- the inner diameter of the first channel in the delivery catheter 1 is 0.1-0.5 mm. If the inner diameter is too small, the flow resistance will be too large, which is not conducive to drug delivery.
- the puncture assembly 2 is preferably 3-6 groups.
- the corresponding folding wings are 3 to 6 pairs; multiple groups of puncture assemblies 2 are arranged along the circumference of the balloon 31, so that the device does not have high requirements for directionality during puncture, as long as it can be placed in the lesion site, it can meet the treatment requirements and improve the treatment efficiency.
- the diameter of the balloon is selected to be 6 to 15 mm, so that the balloon 31 can drive the puncture assembly 2 to pierce the esophageal wall when expanding.
- the height of the puncture assembly 2 is 0.5 to 1.7 mm, so that the puncture assembly 2 can pierce the esophageal wall and achieve effective drug injection. It is well known to those skilled in the art that the probability of circumferential lesions in esophageal lesions is very high. This device can achieve the situation that the esophagus can be expanded and the circumferential lesions can be treated in one implantation treatment. In terms of treatment effect, it can treat 3/4 and more circumferential lesions.
- Each group of puncture assemblies 2 preferably includes 6-18 puncture structures 21. In this way, at least 18 injection points are set to achieve uniform injection and efficient drug delivery. Compared with single-point injection in traditional esophageal surgery, it reduces the reflux of drug liquid.
- the outer surface of the balloon and the inner wall of the esophagus are in close contact, which prevents the reflux of drug liquid, achieves the effect of precise injection, and greatly improves the treatment efficiency.
- the height of the puncture component 2 is 0.5-1.7 mm. Within this range, the puncture component 21 can effectively penetrate the mucosa and submucosal layer of the esophagus (mucosa and submucosal layer 0.5-1.5 mm), and will not penetrate the blood vessels in the esophagus.
- the puncture component 2 of this embodiment is combined with the target anatomy to improve the permeability of the drug.
- the distance between each puncture structure 21 is 2.5-15 mm, so that the drug can be fully utilized and the utilization rate of the drug can be improved.
- the length of the balloon 31 in the balloon assembly 3 is preferably 45 to 80 mm.
- the number of folding wings 311 of the balloon 31 is 6 or 8, that is, 3 to 4 groups of folding wings.
- the outer diameter of the balloon 31 is less than 3.2 mm.
- the balloon is preferably a compliant balloon. More preferably, it is a three-stage expansion balloon. In this way, the device can be adapted to the esophagus, providing a prerequisite for effective drug delivery and ensuring the safety and effectiveness of its use.
- the height H of the folding wing space is between 0.5 and 2.0 mm, for example 0.5, 1, 1.5, 2 mm, so that the circumferential size of the balloon can be minimized while covering the puncture assembly.
- the total amount of drug injected through the first channel is 120 mg. It should be understood that the 120 mg may represent The concentration of the drug liquid is 10-20 mg/ml; the total injection volume of the drug liquid is 6-12 ml; the injection volume of each puncture structure is 0.1-0.3 ml. In this way, the drug release rate is higher than 87%, which is more than 8 times higher than the prior art. In other embodiments, the total injection volume of the drug can be 100, 110, 130, 140 mg, etc.
- the total number of puncture structures of the esophageal balloon device is greater than 18, and the injection time of the esophageal balloon device is less than 1.5 minutes, thereby greatly reducing the time it takes to implant the esophageal balloon device in the esophagus, improving treatment efficiency, and reducing the pain of patients.
- the puncture force of the puncture structure is ⁇ 0.7N.
- the puncture force of the device can be ⁇ 0.7N by setting parameters such as diameter-pressure, injection volume, and total injection volume, and its safety and effectiveness are guaranteed under the premise that the puncture structure can penetrate the tissue.
- the esophageal balloon device in this embodiment uses a drug carrier for treatment, and the drug carrier has a sustained release function, which can be sustained for 1 week to 6 months.
- the sustained release period is 1 to 12 weeks. More preferably, the sustained release period can be adaptively selected according to the condition of the disease, thereby achieving the effect of sustained release treatment.
- the sustained release period can be adaptively selected according to the condition of the disease, thereby achieving the effect of sustained release treatment.
- the injected drugs include but are not limited to: glucocorticoids, such as: mometasone furoate, prednisolone, triamcinolone acetonide, methylprednisone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, dexamethasone, etc.
- glucocorticoids such as: mometasone furoate, prednisolone, triamcinolone acetonide, methylprednisone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, dexamethasone, etc.
- the esophageal balloon device also includes a catheter hub, which is connected to the first channel and is used to deliver drugs.
- the catheter hub is a 2-Way Hub or a 3-Way Hub or even a multi-Luer connector design; a Luer connector on the catheter hub can be connected to a valve, a connector, a syringe or a pressure inflator, through which a special drug is given to the infusion channel, and the drug is a designated drug system.
- Esophageal balloon sample 1 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 6-8mm, a balloon length of 45mm, an outer diameter of 2.8mm, 6 folding wings, 3 groups of puncture components, 6 needles in each row, and a puncture structure height of 0.5mm.
- Esophageal balloon sample 2 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 8-10mm, a balloon length of 50mm, an outer diameter of 2.8mm, 6 folding wings, 3 groups of puncture components, 7 needles in each row, and a puncture structure height of 0.8mm.
- Esophageal balloon sample 3-1 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 10-12mm, a balloon length of 60mm, an outer diameter of 3mm, 6 folding wings, 3 groups of puncture components, 6 needles in each row, and a puncture structure height of 1mm.
- Esophageal balloon sample 3-2 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 10-12mm, a balloon length of 60mm, an outer diameter of 3mm, 8 folding wings, 4 groups of puncture components, 6 needles in each row, and a puncture structure height of 1mm.
- Esophageal balloon sample 3-3 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 10-12mm, a balloon length of 60mm, an outer diameter of 3mm, 8 folding wings, 4 groups of puncture components, 7 needles in each row, and a puncture structure height of 1mm.
- Esophageal balloon sample 4 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 12-15mm, a balloon length of 70mm, an outer diameter of 3.2mm, 8 folding wings, 4 groups of puncture components, 10 needles in each row, and a puncture structure height of 1.3mm.
- Esophageal balloon sample 5 The balloon is a compliant three-stage dilatation balloon with a balloon diameter of 15-18mm, a balloon length of 80mm, an outer diameter of 3.2mm, 12 folding wings, 6 groups of puncture components, 18 needles in each row, and a puncture structure height of 1.7mm.
- the esophageal balloon device of the present application reaches 8-11 atm under three-stage expansion, achieving good expansion and preventing drug reflux.
- the puncture force of the device is ⁇ 0.7N, ensuring its safety and effectiveness under the premise that the puncture structure can penetrate the tissue.
- the injected drug is triamcinolone acetonide (TA).
- TA triamcinolone acetonide
- the total injection volume of the drug liquid is 6-12 ml, and the amount of the injected drug liquid for each puncture structure is 0.1-0.3 ml.
- the concentration of the drug liquid is 10-20 mg/ml, and the total injection volume of the drug is 120 mg.
- the device of the present application can save 25 times of time compared to the single-point injection technology in the prior art, thus greatly improving the treatment efficiency.
- FIG12 shows a schematic diagram of tissue after in vitro injection using the esophageal balloon device of this embodiment.
- This embodiment uses the tissue of the esophagus of a pig and uses the esophageal balloon sample 3-1 to conduct in vitro tissue experiments. Using colored saline (blue) to simulate the drug solution, the balloon sample is slowly expanded to 8atm, and the pressure is maintained constant. Then 1.5ml of liquid is slowly injected. In the figure, the blue liquid in the subcutaneous tissue is the drug liquid, which means that the injected drug has entered the lower layer of the esophageal mucosa.
- Drug extraction rate amount of drug before injection into tissue/amount of drug before injection into device ⁇ 100%.
- the tissue is the tissue of the esophagus of a pig, and the drug used is triamcinolone acetonide (TA).
- TA triamcinolone acetonide
- the drug carrier is made of PLA material, and the drug is a glucocorticoid drug.
- the embodiment of this case injects the drug (preferably sustained-release drug microspheres) into the esophageal tissue by microneedle injection.
- the drug transfer rate i.e., the drug content in the tissue
- HPLC high performance liquid chromatography
- the esophageal balloon device used in this application adopts a single-layer balloon structure, which is easier to inject drugs than a double-layer balloon, and can achieve quantitative injection under very small thrust.
- the esophageal balloon device of this application can be used for injection without the use of a pump, and can be directly performed manually, thereby achieving a small amount of injection.
- TUCBDP Transurethral columnar balloon dilatation of the prostate
- the balloon component of the balloon catheter can be composed of multiple balloons, or a multi-chamber balloon.
- the drug can be selected from: paclitaxel, rapamycin, ⁇ -reductase inhibitors (e.g., finasteride, dutasteride) or their sustained-release drug microspheres.
- non-vascular cavities or non-vascular stenosis it also includes those blood-free channels in the airways, sinuses, trachea (bronchi), colon, bile duct, stomach, small intestine, duodenum, jejunum, ileum, rectum, large intestine, urinary tract, prostate, urethra, ureter and other non-vascular cavities.
- This embodiment nine also provides a prostatic urethra dilation device, which includes a device or drug delivery device that uses a balloon as described above. It should be understood that the prostatic balloon device can use any device in the above embodiments one to six. This embodiment nine schematically uses the device provided in embodiment one for illustration, and reference can be made to Figure 1 for this purpose.
- the prostatic urethra dilation device comprises: a delivery catheter 1, a plurality of puncture components 2 and a balloon component 3.
- the inner diameter of the first channel in the delivery catheter 1 is 0.1-0.5 mm. If the inner diameter is too small, the flow resistance will be too large, which is not conducive to drug delivery.
- the puncture assembly 2 is preferably 6 to 12 groups. Multiple groups of puncture components 2 are arranged along the circumference of the balloon 31, so that the device does not require high directionality during puncture, and can meet the treatment requirements as long as it can be placed in the lesion site.
- Each group of puncture components 2 preferably includes 6-18 puncture structures 21, and the distance between each puncture structure 21 is 2.5-15mm. In this way, at least 18 injection points are set to achieve uniform injection and efficient drug delivery, which reduces the backflow of drug liquid.
- the device of the present application has high drug transfer rate, drug output rate, and high treatment efficiency.
- the height of the puncture component 2 is 1-2mm, preferably greater than or equal to 1.5mm. Within this range, the puncture component 21 can effectively pierce the prostatic urethra. Such a setting allows the drug system (such as a drug solution or a drug carrier) to directly enter the tissue, thereby improving the efficiency of treatment.
- the drug carrier can also be delivered through the puncture component 21, and the drug carrier can be slowly released in the tissue, thereby ensuring that the drug in the drug carrier can be continuously released without causing a single injection volume that is too large to affect the tissue, or causing the drug to be lost due to an excessive injection volume.
- the length of the balloon 31 in the balloon assembly 3 is preferably 30 to 45 mm.
- the diameter of the balloon 31 is about 5 to 50 mm, preferably 25 to 30 mm, for example 5, 10, 15, 18, 20, 22, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50.
- the balloon diameter can be independently within this range or any range of a specific size.
- the folding wings 311 of the balloon 31 are 12 or 24, that is, 6 to 12 groups of folding wings.
- the outer diameter of the balloon 31 is less than 7 mm, and preferably, it is matched with a 21Fr mirror sheath when used.
- the balloon is preferably a compliant balloon, which can increase the balloon diameter by 2-3%. In this way, the device can be adapted to the prostatic urethra, providing a prerequisite for effective drug delivery and ensuring the safety and effectiveness of its use.
- the total amount of drug injected each time is 2-20 mg, preferably 3-8 mg, such as 3, 4, 5, 6, 7, 8 mg, and the injection dose is less than 12.5 ml/each puncture structure, preferably less than 0.5 ml/each puncture structure.
- this embodiment further provides a prostatic urethra dilation device, the device comprising a balloon 31, the balloon 31 comprising an internally connected balloon structure near the distal end (refer to 31a or 31c) and a balloon structure near the proximal end (refer to 31b), the balloon structure near the distal end is used to be at least arranged at the position of the bladder neck to widen the bladder neck.
- the balloon structure near the proximal end is used to be at least arranged at the position of the prostatic urethra to widen the prostatic urethra.
- the maximum diameter of the balloon structure near the distal end is smaller than the maximum diameter of the balloon structure near the distal end, so that the size of the bladder neck widened by the balloon structure near the distal end is smaller than the size of the prostatic urethra widened by the balloon structure near the distal end, thereby avoiding urine reflux caused by excessive expansion of the bladder neck, resulting in difficulty in urination.
- the prostatic urethra dilation device of this embodiment solves the technical problems of urine reflux and urinary difficulty in clinical practice by combining the anatomical structure of the prostatic urethra and bladder neck, the clinical needs of doctors and medical research, and by setting balloon structures of different radial sizes that are connected in the same manner.
- a puncture component, a drug release component and/or a drug coating are provided on at least part of the structure of the balloon structure near the distal end and/or the balloon structure near the proximal end to achieve drug administration of the balloon.
- the expansion pressure of the balloon 31 during operation is not less than 1.5 atm.
- 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, etc. to provide an effective expansion pressure for the balloon 31 under the condition of variable diameter.
- the expansion pressure of the balloon 31 during operation is 4-6 atm, thereby achieving precise expansion.
- the axial extent length of the drug coating, puncture component or drug release component may be greater than the length of the lesion to be treated, and may be less than the length of the lesion to be treated.
- the length of the balloon 31 is greater than the length of the lesion to be treated.
- the balloon structure near the distal end and the balloon structure near the proximal end of the balloon can be cylindrical structures with two ends of contraction. More preferably, as shown in FIG13 , the balloon structure near the distal end is the first balloon 31a, and the balloon structure near the proximal end is the second balloon 31b, that is, the balloon 31 includes the first balloon 31a and the second balloon 31b, the first balloon 31a is connected to the second balloon 31b, and the first balloon 31a and the second balloon 31b are both cylindrical structures with two ends of contraction.
- the first balloon 31a is used to be at least arranged at the position of the bladder neck to widen the bladder neck.
- the second balloon 32b is used to be at least arranged at the position of the prostatic urethra to widen the prostatic urethra.
- the first balloon 31a is closer to the distal end of the device than the second balloon 31b, and the maximum diameter of the first balloon 31a is smaller than the maximum diameter of the second balloon 32b, so that the size of the bladder neck opened by the first balloon 31a is smaller than the size of the prostatic urethra opened by the second balloon 32b, thereby avoiding urine reflux caused by excessive expansion of the bladder neck, resulting in urinary difficulties.
- the maximum diameter of the first balloon 31a is smaller than the maximum diameter of the second balloon 32b, so that the size of the bladder neck opened by the first balloon 31a is smaller than the size of the prostatic urethra opened by the second balloon.
- the puncture assembly, the drug release assembly and/or the drug coating can be arranged on the first balloon 31a and/or the second balloon 31b.
- the puncture assembly 2, the drug release assembly and/or the drug coating are arranged on the second balloon 31b.
- this embodiment further provides a prostatic urethral dilation device, wherein the balloon structure near the distal end is a third balloon 31c, and the balloon structure near the proximal end is a second balloon 31b.
- the balloons include the third balloon 31c and the second balloon 31b.
- the third balloon 31c is a cylindrical shape with a constricted end, and the second balloon 31b is a cylindrical shape with two constricted ends.
- the third balloon 31c is a cylindrical balloon with a constricted end, and one end of the cylindrical balloon 31c is connected and communicated with the constricted end of the cylindrical balloon 31b.
- the third balloon 31c is used to be at least arranged at the position of the bladder neck, or at least arranged at the bladder neck and the connection between the bladder neck and the urethra to widen the bladder neck and its surroundings.
- the second balloon 32b is used to be at least arranged at the position of the prostatic urethra to widen the prostatic urethra.
- the maximum diameter of the third balloon 31c is smaller than the maximum diameter of the second balloon 31b, so that the size of the bladder neck widened by the third balloon 31c is smaller than the size of the prostatic urethra widened by the second balloon 32b, thereby avoiding urine reflux caused by excessive expansion of the bladder neck, resulting in difficulty in urination.
- the puncture assembly, the drug release assembly or the drug coating are arranged on the third balloon 31c and/or the second balloon 31b. In this way, the third balloon 31c can be arranged at the connection for expanding the bladder and the prostatic urethra.
- the expanded diameter of the second balloon 31b is 20-50mm, for example, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 40, 50mm, etc.
- the length of the second balloon 31b is 20-80mm, for example, 20, 25, 30, 31, 32, 33, 34, 35, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80mm, etc.
- it is 30-50mm.
- the expansion diameter of the third balloon 31c is 5-20mm, for example, it can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20mm, to achieve effective expansion.
- the length of the third balloon 31c is 20-50mm, for example, it can be 20, 25, 30, 31, 32, 33, 34, 35, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50mm.
- it is 30-40mm.
- the wall thickness T of the drug delivery cavity 22 of the puncture assembly can be 0.05-0.2mm, the diameter D is 0.25-0.75mm, or the width W is 0.3-0.8mm.
- the drug can be selected from: paclitaxel, rapamycin, ⁇ -reductase inhibitors (eg, finasteride, dutasteride), sustained-release drug microspheres, and antibiotic drugs.
- Prostatic urethral dilation device sample 1 device diameter 25mm, device treatment length 20mm, balloon passing outer diameter 5.5mm, device folding wing number 12 pieces, puncture components are 6 groups, each group has 6 needles, and the height of the puncture structure is 1.5mm.
- Prostatic urethral dilation device sample 2 device diameter 26mm, device treatment length 30mm, balloon passing outer diameter 5.5mm, device folding wing number 12 pieces, puncture components are 6 groups, each group has 6 needles, and the height of the puncture structure is 1.5mm.
- Prostatic urethral dilation device sample 3-1 device diameter 27mm, device treatment length 40mm, balloon passing outer diameter 6mm, device folding wing number 16 pieces, puncture components are 8 groups, each group has 8 needles, and the height of the puncture structure is 1.5mm.
- Prostatic urethral dilation device sample 3-2 device diameter 27mm, device treatment length 40mm, balloon passing outer diameter 6mm, device folding wing number 16 pieces, puncture components are 10 groups, each group has 9 needles, and the height of the puncture structure is 1.5mm.
- Prostatic urethral dilation device sample 3-3 device diameter 27mm, device treatment length 40mm, balloon passing outer diameter 6mm, device folding wing number 16 pieces, puncture components are 10 groups, each group has 10 needles, and the height of the puncture structure is 1.5mm.
- Prostatic urethral dilation device sample 4 device diameter 28mm, device treatment length 50mm, balloon passing outer diameter 7mm, device folding wing number 24 pieces, puncture components are 12 groups, each group has 10 needles, and the height of the puncture structure is 1mm.
- Prostatic urethral dilation device sample 5 device diameter 30mm, device treatment length 50mm, balloon passing outer diameter 7mm, device folding wing number 24 pieces, puncture components are 12 groups, each group has 11 needles, and the height of the puncture structure is 1mm.
- the device of the present application can save time and greatly improve the treatment efficiency.
- FIG15 is a schematic diagram showing the test results of in vitro tissue puncture and injection using the prostate balloon device of Example 9.
- the material used is porcine prostate tissue.
- the blue liquid in the subcutaneous tissue is the drug liquid, which means that the injected drug has entered the lower layer of the esophageal mucosa.
- Drug extraction rate amount of drug before injection into tissue/amount of drug before injection into device ⁇ 100%.
- the drug preferably sustained-release drug microspheres
- the drug transfer rate is measured by high performance liquid chromatography (HPLC) to reach more than 80%, which can achieve the effect of long-term inhibition of tissue proliferation.
- the microneedles in this case are more numerous (at least 18 injection points) and are distributed circumferentially, so all doses can be injected at once; compared with the single-point injection of traditional esophageal surgery, the efficiency is higher. For example, if a single-point injection takes 0.5 minutes, 50 needles take 25 minutes; in this case, it only takes 1-1.5 minutes to complete the injection of the drug solution.
- Percutaneous transluminal coronary angioplasty is used to open blocked coronary arteries, unblock blood circulation, and maintain normal hemodynamic characteristics.
- the doctor uses the injection balloon provided in this embodiment to keep the blood vessels open to reduce the risk of restenosis and elastic retraction.
- the puncture assembly of the injection balloon is used to pierce the intima, and the drug or sustained-release drug is directly injected into the intima or media of the blood vessel to achieve long-term inhibition of neointimal hyperplasia, thereby reducing the probability of late lumen loss or restenosis.
- DCB drug-releasing balloon
- This embodiment is also applicable to percutaneous transluminal angioplasty (PTA).
- PTA percutaneous transluminal angioplasty
- the device provided by Example 1 to Example 11 can reduce the probability of restenosis.
- Figure 16 is a schematic diagram of the overall structure of the injection balloon of the present embodiment 10;
- Figure 17A is a schematic diagram of the cross-section of the balloon portion of the injection balloon of the present embodiment 10;
- Figure 17B is a schematic diagram of the cross-section of the balloon portion of another injection balloon of the present embodiment 10;
- Figure 17C is a schematic diagram of the cross-section of the balloon portion of another injection balloon of the present embodiment 10;
- Figure 18A is a schematic diagram of the injection balloon of the present embodiment 10;
- Figure 18B is a schematic diagram of another injection balloon of the present embodiment 10;
- Figure 18C is a schematic diagram of another injection balloon of the present embodiment 10;
- Figure 19 is a schematic diagram of a drug release component of the present embodiment 10;
- Figure 20 is a schematic diagram of the overall structure of another injection balloon of the present embodiment 10.
- Figure 9 is a schematic diagram of the drug delivery device provided in the present embodiment 5;
- Figure 10 is a schematic diagram of another drug delivery device provided in the present embodiment 5.
- This embodiment ten also provides an injection balloon, which is a device for drug delivery using a balloon as described above. It should be understood that the injection balloon provided in this embodiment can adopt any of the devices in the above-mentioned embodiments one to six.
- This embodiment ten schematically uses the device provided in embodiment five for illustration. It should be understood that in the device of embodiment five, such as a drug release component, when the drug delivery cavity is a triangular hollow tube or a quasi-triangular hollow tube, the device can be used in percutaneous transluminal coronary angioplasty (PTCA) and percutaneous transluminal angioplasty (PTA) to treat coronary or peripheral vascular stenosis.
- PTCA percutaneous transluminal coronary angioplasty
- PTA percutaneous transluminal angioplasty
- the injection balloon can be a quick exchange structure, which includes a developing ring, a connecting tube, a hypotube and a catheter seat in addition to the above components.
- the catheter seat is a 2-Way Hub design. This structure can improve the passability of the entire catheter in the blood vessel.
- the injection balloon comprises a delivery catheter (not shown in FIG. 9 ), at least one group of drug release components 4 and a balloon component 5.
- the balloon specifications are: diameter 1.2-14 mm, length 10-80 mm, and the drug release components 4 can be one row, two rows, three rows, four rows, six rows, etc.
- the delivery catheter has a proximal portion and a distal portion, and the delivery catheter comprises a first channel for delivering drugs (not shown in FIG. 9 ) and a second channel for circulation, filling and releasing pressure (not shown in FIG. 9 ) that are not connected to each other, and at least in the first channel near the distal portion,
- the multi-lumen structure comprises a plurality of independent drug delivery channels for delivering drugs.
- the drug release component 4 includes at least one release structure 41 and a drug delivery cavity 42, and the release structure 41 includes at least a drug delivery hole 411, and the drug delivery hole 411 in the group is connected to the drug delivery cavity 42.
- the drug delivery cavity 42 also includes a drug delivery cavity 421 and a drug delivery hole 422, and the drug delivery hole 411 is connected to the drug delivery cavity 421 through the drug delivery hole 422.
- the first channel and the drug release component 4 can be arranged on the outer surface of the balloon 51, or the first channel and the drug release component 4 can also be arranged on the inner surface of the balloon 51.
- the drug delivery hole 411 and the drug delivery hole 422 are represented as one structure.
- the drug delivery hole 411 is a hole arranged on the balloon 51.
- the injection balloon also includes a puncture portion, which is connected to the drug delivery hole 411, and the puncture portion is a needle-shaped structure. The contents of the puncture part can be referred to the above description and will not be repeated here.
- the first channel and the drug release component 4 can be arranged on the outer surface of the balloon 51.
- the drug release component 4 can be a hollow thread, and a drug release hole 411 is arranged on the hollow thread.
- the inner diameter of the drug delivery cavity 42 is ⁇ 1 ⁇ m, for example, 2, 3, 4 ⁇ m, etc.; preferably, the inner diameter of the drug delivery cavity 42 is ⁇ 3 ⁇ m; more preferably, the inner diameter of the drug delivery cavity 42 is ⁇ 0.1mm, for example, 0.2, 0.3, 0.4mm, etc.
- the ratio of the inner/outer diameter of the drug delivery cavity 42 is 0.1 to 0.9, and more preferably, the ratio of the inner/outer diameter of the drug delivery cavity 42 is 0.4 to 0.8.
- the inner diameter of the drug release hole 411 is smaller than the inner diameter of the drug delivery cavity 42.
- the inner diameter of the drug release hole 411 is less than 0.5 times the inner diameter of the drug delivery cavity 42.
- the spacing between each drug release hole 411 is 0.1 to 1 mm, preferably 0.25 to 0.75 mm, for example, 0.25 mm, 0.3 mm, 0.4 mm, 0.45 mm, 0.5 mm, 0.6 mm, etc.
- the drug release hole 411 can also be larger than 1 mm.
- the drug delivery cavity 42 can be a circular or triangular hollow tube.
- the outer diameter of the circular hollow tube can be 0.20 to 0.34 mm. As shown in FIG.
- the drug release hole 411 on the drug delivery cavity 42 is preferably oriented in the direction of expansion of the balloon 51.
- the drug release hole 411 on the drug delivery cavity 42 can be at a certain angle to the direction of expansion of the balloon 51, for example, the direction of expansion of the balloon is the radial direction of the balloon, and the axial direction of the drug release hole is at a certain angle to the radial direction of the balloon. For example, an acute angle.
- the drug release holes may be arranged in a row of hole structures along the axial direction of the drug delivery cavity 42, or may be arranged in two or three rows of hole structures.
- the drug release holes 411 in the same circumferential direction of the drug delivery cavity 42, there are a plurality of drug release holes 411, that is, when the drug release holes of the drug delivery component are multi-row hole structures, there is an angle between the axial directions of the holes in each row of hole structures, for example, there are two (or two rows) of drug release holes 411, so that two rows of drug release holes 411 are formed on the drug delivery cavity 42, thereby increasing the channel for drug release and thus increasing the amount of drug intake.
- the direction of the two rows of holes is toward the outside of the balloon, and is at a certain angle of 5 to 30° with the normal direction of the balloon.
- the drug delivery component 4 is a triangular hollow structure, one face of the triangular hollow structure is connected to the balloon, and the other two faces of the triangular hollow structure have drug release holes respectively. That is, when the cross section of the drug delivery cavity 42 is a triangle, the two sides of the triangular cylinder preferably have drug release holes 411. As shown in FIG. 19 , when the drug delivery cavity 42 is a triangular hollow tube, the openings of the triangular hollow tube are double-rowed, and the openings are located on both sides of the top edge of the hollow tube.
- the outer diameter of the triangular hollow tube can be 0.20-0.34 mm.
- the distance between each drug-releasing hole 411 is at least 0.5 mm.
- the injection balloon also includes a puncture portion, which is connected to the drug release hole 411 and has a needle-like structure.
- the height of the puncture portion is 0.1mm-2mm, and preferably, the height of the puncture portion is less than 0.5mm.
- the height of the microneedle is adjusted according to different parts, so that the microneedle only pierces the inner membrane or the middle membrane of the inner wall without piercing the tube wall, reducing the doctor's operating risk and ensuring the safety of the patient.
- the diameter of the end of the microneedle close to the balloon is larger than the diameter of the needle tip, so that it is convenient for the needle tip of the microneedle to pierce the inner wall and ensure the stability of the connection between the microneedle and the balloon or the base.
- a balloon with a puncture component can be used for the treatment of intravascular diseases (balloon specifications: diameter 1.2-14mm, length 10-200mm) and the treatment of non-intravascular diseases (balloon specifications: diameter 5-50mm, length 20-200mm); the size of the puncture component is: height 0.1-2.0mm, diameter 10 ⁇ m-500 ⁇ m, which can improve the efficiency of drug delivery.
- the pressure of the balloon 52 is less than 3 to 30 atm, so that the pressure of the balloon 52 is not too high to cause endothelial tearing, and at the same time, effective treatment and drug delivery can be achieved.
- the injection balloon further comprises a drug coating
- the drug in the drug coating may be the same as or different from the drug transported in the first channel.
- Example 6 See Section 6.
- the injection balloon includes a catheter hub, which is connected to the first channel for delivering drugs.
- the catheter hub is designed as a double Luer connector (2-Way Hub) or a three-Way Hub (3-Way Hub) or even a multiple Luer connector; a Luer connector on the catheter hub can be connected to a valve, a connector, a syringe or a pressure inflator, through which a special drug is given to the infusion channel, and the drug is a designated drug system.
- the balloon catheter can also be a full exchange structure.
- the inner tube, outer tube, balloon and drug administration notch structure also includes a developing ring and a catheter hub.
- the shadow ring is set in the balloon, and the catheter seat is a special 3-Way Hub design, as shown in Figure 20.
- This structure can improve the maneuverability of the catheter in the blood vessel.
- the injection balloon of this embodiment 10 is suitable for a universal balloon filler, which is connected to the drug interface on the catheter seat, and a special drug is given to the infusion channel through it.
- the drug is a specified drug system, such as a specified drug solution, or a specified drug microsphere.
- the drug release component 4 may have a hard catheter and a soft catheter, and the hard catheter provides a fixed lumen required by the release structure 41 (61).
- the scheme of the drug release component 4 may refer to the structure shown in Figures 5B to 5E.
- the drug delivery catheter of the drug release component 4 includes a hard catheter and a soft catheter, and the hard catheter and the soft catheter are arranged in sections and at intervals. For example, it includes two sections of hard catheters and one section of soft catheter.
- the number of hard catheters and soft catheters is not limited.
- the number of soft catheters is one less than the number of hard catheters.
- the puncture structure is preferably arranged on the hard catheter.
- the setting of the soft catheter provides flexibility for the drug delivery catheter, improves the passability of the device, and facilitates the delivery of the device.
- the setting of the soft catheter also provides a prerequisite for the misaligned setting of the drug release component 4.
- the hard catheter of the front section and the hard catheter of the rear section are in different circumferential directions of the balloon 51 (Fig. 5D is a schematic diagram of the expansion of the drug delivery catheter arranged circumferentially along the balloon 51) to form a staggered arrangement.
- Fig. 5D is a schematic diagram of the expansion of the drug delivery catheter arranged circumferentially along the balloon 51
- the solid line indicates that one section of the hard catheter is arranged circumferentially at a certain angle
- the dotted line indicates that another section of the hard catheter is arranged circumferentially at another angle.
- the drug release component 4 can be staggered in different circumferential directions along a drug delivery catheter in the circumferential direction of the longer balloon 51, thereby making the circumferential drug delivery uniform and improving the injection efficiency.
- the size of the hard catheter preferably, the axial size of the soft catheter is 0.5 to 20 mm.
- This embodiment ten also provides an injection balloon sustained-release system, which includes an injection balloon as described in any of the above items and a drug system, wherein the drug system includes drug particles and/or drug carriers; the drug particles can be dissolved in tissue fluid, and the drug particles are dissolved into drug liquid, and the drug liquid escapes from the drug carrier in the tissue to achieve sustained release.
- the injection balloon used in the injection balloon sustained-release system includes a puncture portion, and the drug system enters the interior of the tissue through the puncture portion, thereby achieving 1 week to 6 months of drug sustained release.
- the radial dimension of the drug outlet hole of the puncture portion is larger than the radial dimension of the drug carrier.
- the injection balloon provided in this embodiment improves the drug transfer rate by setting a separate first channel. At the same time, due to the specific setting of the drug release hole, precise drug delivery can be achieved. In addition, it has a small requirement for the balloon inflation pressure, and the pressure of drug injection will not be affected by the balloon inflation pressure. It can also achieve targeted drug delivery and multiple drug delivery.
- Tables 1 and 2 show the test results of drugs implanted into blood vessels using the drug system of this embodiment.
- the drug particles are made of Sirolimus
- the drug carrier adopts a PLA substrate, and Sirolimus drug is carried in the drug carrier.
- Table 1 is a comparison table of drug extraction rate and tissue drug content rate of the drug system provided in this embodiment
- Table 2 is a comparison table of drug effective time of the drug system provided in this embodiment
- the drug transfer rate will reach more than 79%, which can achieve the effect of long-term inhibition of tissue proliferation.
- FIG. 21A is a schematic diagram of an example of a drug system provided in the eleventh embodiment of the present invention
- FIG. 21B is a schematic diagram of a second example of a drug system provided in the eleventh embodiment of the present invention.
- the eleventh embodiment provides a drug system, which is delivered by the device of the first to tenth embodiments, thereby delivering the drug system to a target location, and the drug is delivered to the target location, thereby achieving the corresponding therapeutic effect of the drug.
- the drug system may be drug particles and/or drug carriers 100, and the drug particles and/or drug carriers may be mixed with a solution to form a drug solution, and the drug solution is delivered to the target tissue location.
- the drug carrier 100 has pores, and the pores may hold drugs, such as drug particles.
- the drug carrier 100 is delivered to the target tissue.
- the drug particles may be dissolved in the tissue fluid, such as saline.
- the drug particles are dissolved into drug liquid, and the drug liquid escapes from the drug carrier 100 in the tissue to achieve sustained release.
- the drug particles are crystalline drug crystals, and the drug crystals are delivered to the tissue to achieve sustained release of the drug.
- the particle size of the drug particles is 1 to 1000 ⁇ m, preferably, the particle size of the drug particles is 1 to 150 ⁇ m, more preferably, the particle size of the drug particles is 1 to 50 ⁇ m, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 ⁇ m, etc.; the sustained release period of the drug crystals is from one week to 6 months. It should be understood that the sustained release of the drug is related to the content of the drug, the molecular structure and molecular weight of the drug carrier, the porosity of the drug carrier, etc.
- the applicant obtained an ideal sustained-release drug by screening the molecular structure, molecular weight (i.e., the material selected by the drug) of the drug carrier, and the porosity of the drug.
- the sustained release period can be from 1 week to 6 months.
- the drug particles are mixed with a delivery fluid (such as saline, etc.) to form a suspension and then delivered to the target tissue.
- a delivery fluid such as saline, etc.
- the rate and dosage of the drug delivery can refer to the above description. It is understandable that the drug particles can be a broad concept of drugs, for example, the drug can be a drug for treating luminal stenosis.
- the drug can be a drug body or composition containing a drug, which includes one or more therapeutic substances, diagnostic substances, a drug, a therapeutic composition, a diagnostic composition, a physiologically active agent, a biochemically active agent, one or more living cells, DNA, RNA, nucleic acids, cell carriers for delivering genetic material to the target site, anti-inflammatory agents, an anti-restenosis agent, a cell proliferation inhibitor, a smooth muscle hyperplasia inhibitor, paclitaxel, rapamycin, everolimus, vasoactive agents, vasodilators, vasoconstrictors, antibiotics, anticoagulants, platelet aggregation inhibitors, antifibrotic agents, pharmaceutically acceptable carriers, lipid-based carriers and any combination thereof.
- the drug can also be an alpha reductase inhibitor, for example, finasteride, dutasteride.
- the drug carrier is a drug sustained-release microsphere made of a biodegradable polymer material mixed with a drug
- the diameter of the drug sustained-release microsphere is 1 to 1000 ⁇ m.
- the diameter of the drug sustained-release microsphere is 1 to 150 ⁇ m, for example, it can be about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150 ⁇ m, etc. More preferably, the diameter of the drug sustained-release microsphere is 1 to 50 ⁇ m, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 ⁇ m, etc.; the sustained-release period is 1 week to 6 months.
- the drug carrier has pores, the pores contain drugs, the drugs are slowly released from the pores, the diameter of the drug carrier is 1 to 1000 ⁇ m, preferably, the diameter of the drug carrier is 1 to 150 ⁇ m, more preferably, the diameter of the drug carrier is 1 to 50 ⁇ m, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 ⁇ m, etc.; the sustained release period is 1 week to 6 months.
- the drug carrier 100 has a plurality of micropores 101, and the micropores 101 are arranged as through holes or non-through holes on the drug carrier 100, so as to accommodate the drugs.
- the size of the micropores 101 is smaller than the size of the drugs.
- the drug carrier can also be made of drug sustained-release microspheres made of a mixture of polymer degradable materials and drugs.
- the drugs are in the tissue, because the drug concentration in the drug sustained-release microspheres is high, and the drugs can be released.
- the drug delivery control unit can be configured to load the delivery force on the spherical particles to control the delivery of the spherical particles to the target area through the drug delivery channel, and/or control the duration of delivery to the target area, and/or control the depth of delivery to the target area.
- the material of the drug carrier can be a polymer biodegradable material.
- the polymer biodegradable material includes but is not limited to: polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), carbon dioxide polymer (PPC), polybutylene succinate (PBS), fatty aromatic polyester Ecoflex (PBAT), polytrimethylene terephthalate (PPT), poly- ⁇ -hydroxyalkanoate (PHA), poly- ⁇ -caprolactone (PCL), polydioxanone (PPDO), or any copolymer or blend of any of the polymers thereof.
- PPA polylactic acid
- PLGA polylactic acid-glycolic acid copolymer
- PPC carbon dioxide polymer
- PBS polybutylene succinate
- PBAT fatty aromatic polyester Ecoflex
- PPT polytrimethylene terephthalate
- PHA poly- ⁇ -hydroxyalkanoate
- PCL poly- ⁇ -caprolactone
- PPDO polydioxanone
- the content of each component is 0 to 100%.
- the shape of the drug carrier can also be other structures, not limited to spherical.
- the drug carrier can be a sustained-release drug-loaded rod or sheet
- the drug delivery control unit can configure the delivery force loaded on the sustained-release drug-loaded rod or sheet to control the delivery of the sustained-release drug-loaded rod or sheet to the target area through the drug delivery channel
- the material of the rod or sheet can be a polymer biodegradable material. The setting of the rod and sheet is based on the actual drug delivery requirements.
- a coating layer may be provided on the drug carrier, and the drug is provided in the coating layer.
- the coating layer can be dissolved, thereby achieving sustained release of the drug carrier, and the sustained release period is 1 week to 6 months.
- the drug carrier is in the shape of a sphere, a rod or a sheet; preferably, the drug crystal is in the shape of a sphere, a polygon, a rod or a sheet.
- the drug carrier 100 can continuously perform the drug release function, and its release period is between 1 week and 6 months.
- the diameter of the drug release hole is larger than the diameter of the drug system, thereby facilitating the output of the drug system.
- Tables 1 and 2 show the test results of drugs implanted into the prostate gland using the drug system of this embodiment.
- the drug particles are made of Sirolimus
- the drug carrier adopts a PLA substrate, and Sirolimus drug is carried in the drug carrier.
- Table 1 is a comparison table of drug extraction rate and tissue drug content rate of the drug system provided in this embodiment
- Table 2 is a comparison table of drug effective time of the drug system provided in this embodiment
- This embodiment uses the device of embodiment 9 for injection, and its injection pressure is injection balloon, and its injection rate is injection balloon, so as to inject drug particles or drug carriers into the prostate gland.
- the drug transfer rate will reach more than 80%, and the effect of long-term inhibition of tissue proliferation can be achieved.
- the present embodiment 12 provides a minimally invasive medical system, including any one of the devices described in embodiments 1 to 10, and the drug system described in embodiment 11. That is, the devices in the above embodiments 1 to 10 are used to deliver the drug system described in the present embodiment 11, so that drug delivery is achieved through the device, and then the delivery of the drug is achieved, thereby providing a prerequisite for the sustained release of the drug system.
- any one of the devices in Embodiments 1 to 10 comprises a drug delivery control unit, and the drug delivery control unit can be configured to control the delivery force loaded to the drug to control the delivery of the drug to the target area through the drug delivery channel.
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Abstract
一种利用球囊（31、71）实现药物输送的装置，包括：输送导管（1）、多组穿刺组件（2）以及球囊组件（3、7），其中：输送导管（1）包括互不连通的用于输送药物的第一通道（11）和用于充泄压的第二通道（12），至少在靠近远端部分的第一通道（11）为多腔结构，多腔结构包含输送药物用的多个独立药物输送通道（111）；多组穿刺组件（2）中，每一组穿刺组件（2）包括至少一穿刺结构（21）和给药腔体（22），穿刺结构（21）包括穿刺部（211、611）及释药孔（212、612），该每一组穿刺组件（2）中释药孔（212、612）连通给药腔体（22），给药腔体（22）与对应的药物输送通道（111）连通。如此，可以提高药物输送效率。
Description
本发明涉及医疗器械技术领域，尤其涉及一种利用球囊实现药物输送的装置、给药装置及微创医学系统。
近年来，为了改善产生于生物体管腔内的病变部(狭窄部)而使用球囊导管。球囊导管通常包括长条的轴部和设于轴部的前端侧且能向径向扩张的球囊，通过使收缩的球囊经由细生物体管腔到达体内的目的部位后扩张，由此能够扩开病变部。
最近，使用在球囊的外表面涂敷了用于抑制狭窄的药物的药物洗脱球囊(Drug Eluting Balloon；DEB)。药物洗脱球囊通过扩张而将涂敷于外表面的药物瞬时向病变部释放，能够使药物向生物体组织移动，由此，能够抑制再狭窄。然而，有限的释放时间使得药物有效释放率不到10％，药物的有效转移率低，也是这一技术有待改进的方向和难点。灌注球囊是一种多孔的球囊，以注射给药的方式通过微孔将药物注射在血管内壁表面，也是通过组织吸收的方式将药物转移至血管内壁以下。然而其存在以下缺点：1)球囊压力较小，扩张压力不够；2)药物的有效转移率仍然不高。此外，在药物治疗方面，药物注射入组织中之后，由于短时间内输入较多的药物，一方面，在高浓度高含量的药物下，不是组织的最佳治疗浓度，另一方面，药物治疗的时间段，治疗效果不佳。同时，由于现有的装置中，没有实现周向分布的结构，治疗时，对球囊方向的放置要求高，使得医生使用不便，降低了治疗效率。
因此，亟需开发出一种提高药物转载能力、实现可持续的治疗且操作方便的装置。
发明内容
本发明的目的在于解决上述问题而提供的一种利用球囊实现药物输送的装置、给药装置及微创医学系统。
为解决上述技术问题，本发明提供一种利用球囊实现药物输送的装置，包括：输送导管、多组穿刺组件以及球囊组件，其中：
所述输送导管具有近端部分和远端部分，所述输送导管包括互不连通的用于输送药物的第一通道和用于流通充泄压用的第二通道，至少在靠近远端部分的所述第一通道为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道；
多组穿刺组件中，每一组穿刺组件包括至少一穿刺结构和给药腔体，所述穿刺结构包括穿刺部及释药孔，该组中所述释药孔连通所述给药腔体，所述给药腔体与对应的所述药物输送通道连通；
球囊组件：至少包含一球囊，所述球囊与所述第二通道的远端部分连通，并且所述球囊被配置为在折叠构型和展开构型之间变化，所述折叠构型下所述多组穿刺组件分别单独包附在所述球囊中；通过给所述第二通道充压作用于所述球囊膨胀使其处于所述展开构型，所述球囊的膨胀带动所述多组穿刺组件的穿刺部凸出，所述药物被配置为在外力作用下分别通过多个药物输送通道、每一药物输送通道对应的给药腔体、所述给药腔体连通的所述释药孔输送至目标区域。
可选的，所述球囊组件还包括导引导管，所述球囊的远端与所述导引导管连接，以密封所述球囊的远端，所述球囊的近端与所述导引导管密封或者不密封连接；所述球囊折叠形成多对折叠翼，其沿着所述导引导管周向设置，每对相对设置的折叠翼形成一折叠翼空间，该些组的所述穿刺组件分别容置在该些适配的所述折叠翼空间内，多对所述折叠翼均匀排布于所述球囊的周向；
优选的，所述给药腔体还包括一基座，所述基座的上表面和其它外周面形成相对固定的给药腔，所述基座的上表面沿着所述球囊的长度方向开设与所述释药孔连通的贯通孔，所述穿刺结构固定设置在所述基座的上表面上，所述释药孔通过所述贯通孔与所述给药腔连通；更优的，设置的所述折叠翼空间的高度H不小于所述基座的高度h2和所述穿刺结构的高度h1之和；
优选的，所述基座采用硬质材料制成；优选的，所述基座采用金属材料、高分子材料或者陶瓷材料制成；优选的，所述基座的上表面采用金属材质、高分子材料或者陶瓷材料；
优选的，所述基座的横截面为空心结构；更优选的，所述基座的横截面为空心圆形、空心椭圆、空心矩形、空心多边形或者仿形空心结构；优选的，所述基座其外轮廓呈具有一弧度的仿形空心结构，所述仿形空心结构的曲率与球囊的曲率一致；
优选的，所述给药腔体设置于所述球囊的外表面，所述基座其它外周面包含下表面，所述下表面固定于所述球囊的外表面，并且在展开构型时随着所述球囊的膨胀，带动所述基座向外运动，以此带动所述基座的上表面设置的所述穿刺部凸出；或者，所述给药腔体设置于所述球囊的内表面上，所述基座设置在所述球囊的内表面内，所述基座的上表面与所述球囊内表面固定贴合设置，所述球囊上设置有供所述穿刺结构穿出的孔，所述穿刺结构穿出所述孔凸设于所述球囊的内表面，在折叠构型下，凸设出来的所述穿刺结构设置在折叠翼形成的折叠翼空间内；在展开构型下，随着所述球囊的膨胀，带动基座向外运动，从而带动凸设出来的穿刺结构伸出折叠翼空间，折叠翼空间变小或被膨胀消失；
优选的，每一组穿刺组件的所述基座分别沿着导引导管周向布置；
更优的，设置的所述折叠翼空间的高度应不小于凸设出所述球囊内表面的所述穿刺结构的凸伸高度；
优选的，所述基座与所述球囊粘贴或者等离子处理后焊接连接；
优选的，沿装置的轴向，穿刺结构两侧的折叠翼的端部距离穿刺结构的距离相等；
优选的，沿装置的周向，各个组的折叠翼对称设置，每组穿侧组件对称设置；优选的，每一组穿刺组件的所述穿刺结构为多个，且沿着所述基座的长度方向间隔设置，所述穿刺部的顶部呈尖部，所述穿刺部的端部围设成所述释药孔；优选的，每组所述穿刺组件中的每个穿刺结构等距分布；所述多组穿刺组件为三组或四组；
优选的，所述输送导管上还设置充泄压控制单元和输药控制单元，所述第二通道与所述球囊组成的流通充泄压用通道通过所述充泄压控制单元控制，第一通道与所述球囊通过所述输药控制单各自控制；所述第一通道设置第一鲁尔接口，第一鲁尔接口通过一导管分别连接多个药物输送通道所对应的导管腔；
优选的，沿所述第二通道的径向设置有凹槽，所述凹槽沿第二通道的轴向延伸设置，所述凹槽用于容纳所述第一通道，以使得所述装置的非球囊部分的径向尺寸更小；优选的，所述凹槽的半径不小于所述第一通道的外径；优选的，所述凹槽的深度可以不小于所述第一通道的外半径；优选的，所述装置还包括导管座(Hub)，导管座与第一通道连接，用于输送药物，优选的，所述导管座为双鲁尔接头(2-Way Hub)或者三鲁尔接头(3-Way Hub)甚至多鲁尔接头的设计；导管座上的一个鲁尔接头可以与阀、连接器、注射器或压力充盈器相连接，通过其向输液通道中给定特殊的药物，该药物为指定的药物系统；
优选的，所述输送导管上还设置充泄压控制单元和输药控制单元，所述第二通道与所述球囊组成的流通充泄压用通道与所述药物输送通道分别通过所述充泄压控制单元和所述输药控制单各自控制。
可选的，所述穿刺部具有穿刺壁体、穿刺腔体以及穿刺面，所述穿刺面为所述穿刺部的顶部的面，即刺入组织时，产生刺入作用的面；所述穿刺面为一平面，所述穿刺面与垂直于所述穿刺结构的轴向的平面呈的角度a呈5～85°；优选的，所述穿刺面为一圆锥面，所述圆锥面的角度a呈25～75°；优选的，所述穿刺面为一凹面、凸面或者多棱柱面；优选的，所述穿刺壁体的外部呈圆柱形、呈圆锥形、底部圆柱形顶部圆锥形、或者呈阶梯状，相适配的，所述穿刺腔体呈圆柱形、呈圆锥形或者阶梯状；优选的，穿刺壁体的内部呈阶梯状，越靠近顶部，其内部的径向尺寸越小，进而能够呈阶梯式的增加药物输送的压力；优选的，在所述穿刺壁体的内部，沿其轴向，其厚度不变化；优选的，在所述穿刺壁体的内部，沿穿刺壁体的轴向，其厚度逐渐减小，厚度减小形成的锥度为0～10°；优选的，所述穿刺壁体的内径向尺寸与外径向尺寸之比为0.2～0.8；优选的，所述穿刺壁体的内径尺寸范围在约在2μm-500μm之间，更优的2μm-200μm，更优选为50-150μm；
优选的，所述穿刺壁体的外部是沿球囊的轴向延展的面，所述穿刺腔体为沿着所述穿刺壁体形成一缝隙，所述穿刺壁体的横截面呈两个三角形相对的布设，所述穿刺壁体的中间呈所述穿刺腔体；所述释药孔是细长开口或者槽状开口；优选的，所述释药孔沿所述穿刺部的轴向开口；优选的，所述释药孔沿所述穿刺部的径向开口；优选的，所述释药孔的开口朝向在轴向和径向之间的角度方向；优选的，在同一个穿刺部上，所述释药孔为一个或者多个；
优选的，所述释药孔是圆形、椭圆形、矩形或者多边形形状；
优选的，所述穿刺部的材质为硬质材质，所述硬质材料为高分子材料、陶瓷材料或者金属材料；
优选的，所述给药腔体的横截面为圆形、椭圆形、三角形、矩形或者多边形；
优选的，所述穿刺部的高度h1在0.1～1.5mm之间，给药腔体的高度在0.1～0.5mm之间；优选的，所述给药腔体的壁厚T与外径D(横向尺寸W)之比为0.06～0.8，优选的，给药腔体的壁厚T与外径D(横向尺寸W)之比为0.06～0.8，优选的，给药腔体的壁厚T与外径D(横向尺寸W)之比为0.05～0.45；优选的，所述穿刺部与给药腔体采用焊接或者粘接的方式连接；优选的，各个穿刺部之间的距离小于穿刺部的径向尺寸；优选的，各个穿刺部之间的距离为0.5～5mm；优选的，距离为1～2mm；
优选的，所述基座为一管体，呈圆柱形结构，所述基座为硬质材质制成；
优选的，所述基座与所述穿刺部连接的上表面的部分采用硬质材料，其他的表面的部分采用柔性材质以形成软管；
优选的，所述基座为一板状结构，板状结构的长度小于所述球囊的轴向长度，所述板状结构的宽度不小于穿刺组件的给药腔体的直径，所述板状结构的厚度不小于穿刺组件的给药腔体的壁厚；
优选的，所述板状结构还具有弧度，所述板状结构与球囊接触的表面具有朝向球囊的弧度，进而使得板状结构能够与球囊的连接更加紧密；
优选的，板状结构朝向球囊的弧度的曲率与球囊的曲率一致；
优选的，所述基座是一板状结构，所述给药腔还包括给药导管，所述基座设置于给药导管上；
优选的，沿所述球囊的轴向，穿刺组件的给药导管包括硬质导管与软质导管，硬质导管与软质导管分段间隔设置，穿刺结构设置于硬质导管上；
优选的，软质导管的数量比硬质导管的数量少一个；
优选的，软质导管能够发生弯曲，其能够在球囊的表面非轴向的延伸设置；
优选的，沿所述球囊的周向，前一段的硬质导管与后一段的硬质导管在球囊的周向方向不同，以形成错位布设；
优选的，所述给药腔体与第一通道连接；第一通道外径与给药腔体的内径适配；或者，第一通道的内径与给药腔体的外径适配；
优选的，所述第一通道采用软质材质或者硬质材质制成；
优选的，所述折叠翼之间不重叠；当球囊的直径在2～6mm时，所述折叠翼为3～5对；当球囊的直径在4～12mm时，所述折叠翼为5～6对；当球囊的直径在10～30mm时，所述折叠翼为6～12对；
优选的，所述基座的上表面与所述球囊内表面固定贴合设置，所述穿刺结构中至少部分结构凸设出所述球囊内表面，所述折叠构型下，凸设出来的所述穿刺结构设置在所述折叠翼形成的所述容置空间内；在所述展开构型下，随着所述球囊的膨胀，带动所述基座向外运动，带动所述凸设出来的所述穿刺结构伸出所述容置空间，所述容置空间变小或被膨胀消失；
优选的，每一组穿刺组件的所述穿刺结构为一对穿刺刀片，所述该对穿刺刀片沿着所述基座的长度方向设置，所述一对穿刺刀片围设成一长条状的所述释药孔；
优选的，该对穿刺刀片沿着球囊的长度方向延伸设置；所述刀片呈底部宽上端窄的结构，刀头部分位于上端；所述刀片的横纵比为0.05～1；刀片的横纵比对0.1～0.25；
优选的，所述折叠翼空间的高度H在0.5～2.0mm之间；优选的，所述折叠翼为3～6对；优选的，所述球囊在展开构型下，所述穿刺结构的穿刺力≤0.7N；
优选的，所述球囊为两端缩口的圆柱形结构；优选的，所述球囊为两个两端缩口的圆柱形连接形成的结构，即所述球囊包括第一球囊以及第二球囊，所述第一球囊与第二球囊连通，第一球囊与第二球囊均为两端缩口的圆柱形结构；所述第一球囊相比第二球囊更加靠近所述装置的远端，所述第一球囊的最大直径小于所述第二球囊的最大直径；所述穿刺组件可以设置于第一球囊和/或第二球囊上；优选的，所述穿刺组件设置于所述第二球囊上；
或者，所述球囊包括第三球囊与第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通；所述穿刺组件或者所述药物释放组件设置于第三球囊和/或第二球囊；优选的，所述第三球囊的尺寸为5～12mm；
优选的，所述穿刺组件的所述给药腔体的壁厚T为0.05～0.2mm，直径D为0.25～0.75mm，宽度W为0.3～0.8mm。
本发明还提供一种利用球囊实现药物输送的装置，包括：输送导管、至少一组药物释放组件以及球囊组件，其中：
所述输送导管具有近端部分和远端部分，所述输送导管包括互不连通的用于输送药物的第一通道和用于流通充泄压用的第二通道，至少在靠近远端部分的所述第一通道为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道；
所述药物释放组件包括至少一释放结构和给药腔体，所述释放结构至少包括释药孔，该组中所述释药孔连通所述给药腔体；
球囊组件：至少包含一球囊，所述球囊通过一充泄压被配置为在折叠构型和展开构型之间变化；所述折叠构型下，所述药物释放组件分别单独被包附在所述球囊中；所述展开构型下，所述球囊的膨胀力带动所述药物释放组件运动至预先设定的目标区域，所述药物通过单独施加对应控制力，经过所述给药通道输送至目标区域。
可选的，所述药物释放组件为多组，该些组药物释放组件分别通过多个输药控制单元或同一个输药控制单元控制药物的运动；
优选的，所述给药腔体还包括给药腔和给药孔，所述第一通道与所述药物释放组件设置在球囊的内表面，所述释药孔位于所述球囊上，所述释药孔通过给药孔与给药腔连通；更优的，所述给药孔与所述释药孔的尺寸相同；或者，所述第一通道与所述药物释放组件设置在球囊的内表面；
优选的，所述第一通道与所述药物释放组件设置在球囊的外表面，所述释药孔与给药腔连通；
优选的，所述球囊充压时，所述球囊的压力在3～30atm范围内；
优选的，当所述第一通道与所述药物释放组件设置在球囊的外表面时，当所述药物释放组件的释药孔为一排孔结构时，所述释药孔朝向所述球囊膨胀的方向；或者，所述释药孔的朝向与所述球囊膨胀的方向呈一定角度；当所述药物释放组件的释药孔为多排孔结构时，每排孔结构的孔轴向的朝向之间具有夹角；
优选的，所述给药腔的径向尺寸大于所述给药孔的直径；
优选的，给药腔体的内径≥1μm，优选的，给药腔的内径≥3μm；优选的，所述给药腔的内径≥0.1mm；优选的，给药腔的内径≥0.3mm；更优的，给药腔的内径≥0.5mm，更优的，所述给药孔的内径尺寸范围在约在2μm-500μm之间，优选为2μm-200μm，更优选为50-150μm；所述给药腔的内/外径之比为0.1～0.9，更优的，给药腔的内/外径之比为0.4～0.8；所述给药孔的内径小于所述给药腔的内径；优选的，给药孔的内径小于给药腔的内径的0.5倍，给药孔的内径≤0.01mm；
优选的，所述药物释放组件是一空心丝线，所述空心丝线上设置有释药孔；
优选的，每个释药孔之间的间距为0.1～1mm，优选的，为0.25～0.75mm；优选的，所述给药腔体的横截面是圆形或者三角形的中空管材；当给药腔体是圆形时，所述给药腔体上的释药孔优选朝向所述球囊膨胀的方向；优选的，所述给药腔体上的释药孔与球囊膨胀的方向存在一定的夹角；当所述药物释放组件的释药孔为多排孔结构时，每排孔结构的孔轴向的朝向之间具有夹角；优选的，在给药腔体的同一周向方向上，分别具有多个释药孔；
优选的，所述药物释放组件具有硬质导管与软质导管，所述硬质导管提供释放结构所需要的固定的管腔，所述软质导管的设置为给药导管提供柔性；
优选的，沿所述球囊的轴向，药物释放组件的给药导管包括硬质导管与软质导管，硬质导管与软质导管分段间隔设置；优选的，软质导管的数量比硬质导管的数量少一个；
优选的，所述穿刺结构设置于硬质导管上；
优选的，沿所述球囊的周向，前一段的硬质导管与后一段的硬质导管在球囊的周向方向不同，以形成错位布设；
优选的，硬质导管的尺寸与软质导管的轴向尺寸为0.5～20mm；
优选的，当给药腔体的横截面是三角形时，三角形柱体的两个侧面优选均具有释药孔；
优选的，所述药物释放组件为三角形中空管，即给药腔体的外表面形状是三角形柱体，所述三角形柱体的其中一个角朝向球囊的径向外侧布设，将朝向球囊的径向外侧的角的一端定义为切入端，所述释药孔设置于所述给药腔体的切入端；
优选的，所述释药孔沿着三角形中空管的给药腔体的轴向均匀的或者不均匀的布设；
优选的，所述药物释放组件为三角形中空管，即给药腔体的外表面是三角形柱体，所述释药孔设置于切入端与设置于所述三角形中空管的两个侧壁上的组合；优选的，沿药物释放组件的轴向，释药孔设置于切入端的轴向与设置于三角形中空管的两个侧壁的轴向位置相同或者不同；
优选的，沿所述三角形中空管的给药腔体，每个所述释药孔的大小为均一设置；优选的，沿所述三角形中空管的给药腔体，由近端至远端，每个所述释药孔的大小逐渐变大或者变小；优选的，沿所述三角形中空管的给药腔体的轴向，由近端至远端，每个所述释药孔的大小逐渐变大；
优选的，当给药腔体的外表面的横截面呈三角形结构，所述给药腔体的外尺寸的高度为0.1-1.0mm，更优的，所述给药腔体的外尺寸的高度为0.3-0.7mm；优选的，所述给药腔体的壁厚为0.01-0.1mm，更优的，所述给药腔体的壁厚为0.03-0.07mm；优选的，所述给药腔体的长度为5-50mm；优选的，所述给药腔体的三角形的内腔顶角(切入端的角)为10-80°；优选的，所述给药腔体的非内腔顶角为10-70°；
优选的，所述释药孔的孔径为0.01-0.2mm；优选的，所述释药孔的孔径为0.05-0.15mm；优选的，所述释药孔的间距在0.05mm与7mm之间；
优选的，沿所述球囊的径向方向，即在所述切入端的延伸方向延伸设置尖角，以形成一微凸角，所述微凸角沿切入端的轴向延伸设置；优选的，所述微凸角的端头开刃或者不开刃；
较佳的，所述给药腔体的内表面形状为三角形管腔、圆形管腔、矩形管腔、多边形管腔或者异型管腔；
优选的，所述给药腔体的内表面的形状为三角形管腔；
优选的，当所述药物释放组件设置有所述微凸角时，所述给药腔体的横截面在三角形的基础上，沿切入端的方向延伸设计具有尖角的空腔，形成类三角形中空管，优选的，所述类三角形中空管的横截面的形状与含有微凸角的给药腔体的外表面的横截面的形状一致；
优选的，所述药物释放组件采用的材料为树脂、陶瓷、不锈钢、尼龙，可降解聚合物或者这几种材料的组合；优选的，所述陶瓷的材料为氧化铝、氧化锆、氧化镁、磷酸钙或者这几种材料的组合；
优选的，所述药物释放组件采用超精密微纳3D打印工艺，优选的，采用烧结工艺，更优的，采用激光烧结或者高温烧结；
优选的，释放结构还包括一基座，基座的上表面和其它外周面形成所述给药腔体，所述基座的上表面沿着所述球囊长度方向开设与释药孔连通的贯通孔，所述释药孔通过贯通孔与所述给药腔体连通；
优选的，所述球囊为两端缩口的圆柱形结构；优选的，所述球囊为两个两端缩口的圆柱形连接形成的结构，即所述球囊包括第一球囊以及第二球囊，所述第一球囊与第二球囊连通，第一球囊与第二球囊均为两端缩口的圆柱形结构；所述第一球囊相比第二球囊更加靠近所述装置的远端，所述第一球囊的最大直径小于所述第二球囊的最大直径；所述药物释放组件可以设置于第一球囊和/或第二球囊上；优选的，所述药物释放组件设置于所述第二球囊上；
或者，所述球囊包括第三球囊与第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通；所述药物释放组件设置于第三球囊和/或第二球囊；优选的，所述第三球囊的扩张直径为5-20mm；
优选的，所述药物释放组件的所述给药腔体的壁厚T为0.05～0.2mm，直径D为0.25～0.75mm，宽度W为0.3～0.8mm。
本发明还提供一种给药装置，包括：输送导管，所述输送导管具有近端部分和远端部分，所述输药导管包括充泄压腔体，所述药物释放组件包括给药腔体，所述给药腔体与充泄压腔体采用同一个腔室；
至少一组药物释放组件，所述药物释放组件包括至少一释放结构和给药腔体，所述释放结构包括释药孔，该组中所述释药孔连通所述给药腔体；
球囊组件：至少包含一球囊，所述球囊通过一充泄压被配置为在折叠构型和展开构型之间变化；所述折叠构型下，所述药物释放组件分别单独被包附在所述球囊中；所述展开构型下，所述球囊的膨胀力带动所述药物释放组件运动至预先设定的目标区域，所述药物通过单独施加对应控制力，经过所述给药通道输送至目标区域。
可选的，所述释放结构还包括穿刺部，所述腔室用于充盈药物的药物载体和/或药物的液体，所述液体被配置用于流通充泄压用和用于给药用，所述液体充满所述球囊来带动所述球囊膨胀，使所述球囊处于展开构型，所述液体通过单独施加对应控制力，通过所述给药通道实现给药；
优选的，释放结构还包括一基座，所述基座呈板状，所述穿刺部设置于所述基座上；优选的，基座与所有的释放结构一体成型；优选的，所述释放结构与基座的材质可由高分子聚合物、无机硅、金属等材料中的至少一种加工而成；优选的，释放结构的外径大于基座的内径，所述释放结构的内径小于基座的内径；优选的，所述基座位于所述球囊的外表面或者所述球囊的内表面；
优选的，所述穿刺部的顶部呈尖部，端部围设成所述释药孔，所述穿刺部为多个，且沿着所述基座的长度方向间隔设置；
优选的，所述穿刺部为一对穿刺刀片，所述该对穿刺刀片沿着所述基座的长度方向设置，所述对穿刺刀片围设成一长条状的所述释药孔。
优选的，所述球囊组件还包括导引导管，所述球囊密封附接在所述导引导管上，
所述球囊折叠形成多个折叠翼，其沿着所述导引导管周向设置，每对相对设置的折叠翼形成一折叠翼空间，所述该些药物释放组件分别容置在该些适配的所述折叠翼空间内；
优选的，所述该些药物释放组件被配置为所述将药物植入所述目标区域或注射入所述目标区域；
优选的，所述球囊为两端缩口的圆柱形结构；优选的，所述球囊为两个两端缩口的圆柱形连接形成的结构，即所述球囊包括第一球囊以及第二球囊，所述第一球囊与第二球囊连通，第一球囊与第二球囊均为两端缩口的圆柱形结构；所述第一球囊相比第二球囊更加靠近所述装置的远端，所述第一球囊的最大直径小于所述第二球囊的最大直径；所述药物释放组件可以设置于第一球囊和/或第二球囊上；优选的，所述药物释放组件设置于所述第二球囊上；
或者，所述球囊包括第三球囊与第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通；所述药物释放组件设置于第三球囊和/或第二球囊；优选的，所述第三球囊的扩张直径为5～20mm。
优选的，所述给药装置上涂覆一层结构，优选的，所述涂层是药物涂层，优选的，所述药物涂层与所述给药装置中输送的药物为同一种药物或者不同种药物。
本发明还提供一种给药装置，所述给药装置用于前列腺尿道扩张，所述装置包括球囊，所述球囊包括内部相连通的靠近远端的球囊结构与靠近近端的球囊结构，所述靠近远端的球囊结构用于至少设置于膀胱颈的位置，以阔开膀胱颈；所述靠近近端的球囊结构用于至少设置于前列腺尿道的位置，以阔开前列腺尿道；所述靠近远端的球囊结构的最大直径小于靠近远端的球囊结构的最大直径，以使得靠近远端的球囊结构所阔开的膀胱颈的尺寸小于靠近远端的球囊结构所阔开的前列腺尿道的尺寸；优选的，靠近远端的球囊结构和/或靠近近端的球囊结构的至少部分结构上设置穿刺组件、药物释放组件和/或药物涂层，以实现球囊的给药；优选的，所述球囊在工作时的扩张压力不小于1.5atm；优选的，药物涂层、穿刺组件或者药物释放组件的轴向范围长度可以大于病变部位待治疗的长度；优选的，所述球囊的长度大于病变部位待治疗的长；
优选的，所述靠近远端的球囊结构为第一球囊，所述靠近近端的球囊结构为第二球囊，所述第一球囊与第二球囊均为两端缩口的圆柱形结构，所述第一球囊用于至少设置于膀胱颈的位置，以阔开膀胱颈，所述第二球囊用于至少设置于前列腺尿道的位置，以阔开前列腺尿道，所述第一球囊的最大直径小于第二球囊的最大直径，以使得第一球囊所阔开的膀胱颈的尺寸小于第二球囊所阔开的前列腺尿道的尺寸；优选的，所述穿刺组件、所述药物释放组件和/或者药物涂层可以设置于第一球囊和/或第二球囊上；
优选的，靠近远端的球囊结构为第三球囊，靠近近端的球囊结构为第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通，所述第三球囊用于至少设置于膀胱颈的位置，或者至少设置于膀胱颈以及膀胱颈与尿道的连接部位，以阔开膀胱颈及其周边，所述第二球囊用于至少设置于前列腺尿道的位置，以阔开前列腺尿道，所述第三球囊的最大直径小于第二球囊的最大直径，以使得第三球囊所阔开的膀胱颈的尺寸小于第二球囊所阔开的前列腺尿道的尺寸；优选的，所述穿刺组件、所述药物释放组件或者药物涂层设置于第三球囊和/或第二球囊；优选的，所述第二球囊的扩张直径为20-50mm；优选的，所述第二球囊的长度为20-80mm，优选的，所述第三球囊的扩张直径为5-20mm；优选的，所述第三球囊的长度为20-50mm。
本发明提供一种药物系统，所述药物系统包括药物颗粒和/或药物载体，所述药物颗粒和/或所述药物载体能够与一溶液混合形成药液，药液被输送至目标组织位置；
优选的，所述药物颗粒为药物晶体，所述药物晶体被输送至组织中能够实现药物缓释，所述药物颗粒的粒径为1～1000μm，优选的，所述药物颗粒的粒径为150μm，更优选的，所述药物颗粒的粒径为1～50μm；所述药物晶体的缓释周期在一周至6个月；
优选的，所述药物载体为可降解高分子材料与药物混合制成药物缓释微球，所述药物缓释微球的直径在1～1000μm，优选的，所述药物缓释微球的直径为1～150μm，更优选的，所述药物缓释微球的直径为1～50μm；所述缓释周期在1周至6个月；
优选的，所述药物载体具有孔隙，所述孔隙中容载药物，所述药物从孔隙中缓释，所述药物载体的直径在1～1000μm，优选的，所述药物载体的的直径为1～150μm，更优选的，所述药物载体的直径为1～50μm；所述缓释周期在1周至6个月；
优选的，所述药物载体中采用的高分子可降解材料包括：聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、二氧化碳聚合物(PPC)、聚丁二酸丁二醇酯(PBS)、脂肪芳香聚酯Ecoflex(PBAT)、聚对苯二甲酸丙二醇酯(PPT)、聚β-羟基烷酸酯(PHA)、聚ε-己内酯(PCL)、聚对二氧环己酮(PPDO)中的一种，或者是其中任意多种的聚合物的共聚物或者共混物；
优选的，所述药物系统为药物颗粒、或者药物载体、或者包含药物颗粒的药物载体或组合物，其包括一种或多种治疗物质、诊断物质、一种药物、一种治疗组合物、一种诊断组合物、生理活性剂、一种生物化学活性剂、一个或多个活细胞、DNA、RNA、核酸、用于将遗传物质递送到目标部位中的细胞载体、抗炎剂、一种抗再狭窄剂、一种细胞增殖抑制剂、平滑肌增生抑制剂、紫杉醇、雷帕霉素、依维莫司、血管活性剂、血管扩张剂、血管收缩剂、抗生素、抗凝剂、血小板凝集抑制剂、抗纤维化剂、α还原酶抑制剂、药学上可接受的载体、脂质基载体及其任意组合；
优选的，所述药物载体上设置一包覆层，药物设置在包覆层内，以形成缓释，包覆层能够被溶解；所述缓释周期在1周至6个月；
优选的，所述药物载体为球状、棒材或者片材；优选的，所述药物晶体为球状、多边形状、棒材或者片材；
优选的，所述药物系统中的药物为：糠酸莫米松、强的松龙、曲安奈德、甲泼尼松、倍他米松、丙酸倍氯米松、泼尼松龙、氢化可的松、地塞米松。
为解决上述技术问题，本发明还提供一种医学微创系统，包括如上的任一项装置，以及包括如上所述的药物系统；优选的，所述装置包括输药控制单元，所述输药控制单元可配置加载到所述药物的输送力大小，以控制所述药物通过所述药物输送通道输送至所述目标区域；优选的，所述释药孔的直径大于所述药物系统的直径。
与现有技术相比，本发明有以下优点：
1、高效的药物转载能力：和涂药球囊(DCB)相比，药物不会在导管输送的过程中损失，且药物的注射是可以精准剂量的、多次的。
2、可持续的治疗效果：除单一药物以外、载药物微球有持续地药物释放功能。其释放周期可达1周至6个月之久，并持续可控。
3、手术操作简便：微针的周向分布结构，无方向性。这使医生在手术过程中无需调整导管的位置。药物可以在血管壁上被均匀地吸收，达到预期临床效果。
本领域的普通技术人员将会理解，提供的附图用于更好地理解本发明，而不对本发明的范围构成任何限定。其中：
图1A为本实施例一提供的利用球囊实现药物输送的装置的示意图；
图1B为图1A中的利用球囊实现药物输送的装置的A-A部位的剖视图；
图2A为本实施例一提供的利用球囊实现药物输送的装置的示意图；
图2B为图2A中的利用球囊实现药物输送的装置的某一方向的剖视图；
图2C为图2A中的利用球囊实现药物输送的装置的折叠状态的剖视图；
图2D为实施例一的另一种利用球囊实现药物输送的装置的折叠状态的剖视图；
图3为图2A中的利用球囊实现药物输送的装置的药物输送与药物输送的示意图；
图4A为穿刺组件的结构；
图4B为另一种穿刺组件的结构；
图4C为另一种穿刺组件的结构；
图5A为本实施例一提供另一种穿刺组件的示意图；
图5B为本实施例一提供的另一种穿刺组件的示意图；
图5C为本实施例一提供的另一种穿刺组件的示意图；
图5D为本实施例一提供的另一种穿刺组件沿球囊周向的展开；
图5E为本实施例一提供的另一种穿刺组件与球囊的位置关系的示意图；
图6A为本实施例二提供的利用球囊实现药物输送的装置示意图；
图6B为图6A中的利用球囊实现药物输送的装置的折叠状态的剖视图；
图7为本实施例三提供的利用球囊实现药物输送的装置的示意图；
图8A为本实施例四提供的给药装置的示意图；
图8B为本实施例四提供的另一种给药装置的示意图；
图9为本实施例五提供的给药装置的示意图；
图10为本实施例五提供的另一种给药装置的示意图；
图11为本实施例六提供的给药装置的示例图；
图12为采用本实施例八的食道球囊装置进行体外注射后的组织示意图；
图13为本实施例八提供的前列腺尿道装置的示意图；
图14为本实施例八提供的另一种前列腺尿道装置的示意图；
图15为采用本实施例九的前列腺尿道装置进行体外注射后的组织示意图；
图16为本实施例十的注射球囊的整体结构的示意图；
图17A为本实施例十的注射球囊的球囊部分的横截面示意图；
图17B为本实施例十的另一种注射球囊的球囊部分的横截面示意图；
图17C为本实施例十的另一种注射球囊的球囊部分的横截面示意图；
图18A为本实施例十的注射球囊的示意图；
图18B为本实施例十的另一种注射球囊的示意图；
图18C为本实施例十的另一种注射球囊的示意图；
图19为图18所示的注射球囊的药物释放组件的示意图；
图20为本实施例十的另一种注射球囊的整体结构的示意图；
图21A为本实施例十一提供药物载体的一种实例示意图；
图21B为本实施例十一提供药物载体的第二种实例示意图；
图22A为本实施例五提供的给药装置的药物释放组件的示意图；
图22B为图22A所示的药物释放组件的横截面的示意图；
[根据细则91更正 23.01.2024]
图22C为图22B所示的药物释放组件的纵截面的示意图；
图22C为图22B所示的药物释放组件的纵截面的示意图；
图23A为本实施例五提供给药装置的药物释放组件的另一示意图；
图23B为图23A所示的药物释放组件的横截面的示意图；
图23C为图23B所示的药物释放组件的纵截面的示意图。
附图中：
1-输送导管，11-第一通道，111-药物输送通道，12-第二通道，121-凹槽；
2-穿刺组件，21-穿刺结构，211-穿刺部，2111-穿刺壁体，2112-穿刺腔体，2113-穿刺平面，212-释药孔，213-穿刺刀片，2131-释药部，22-给药腔体，221-基座，2211-贯通孔，222-给药导管，2221-硬质导管，2222-软质导管；
3-球囊组件，31-球囊，311-折叠翼，312-折叠翼空间，32-导引导管；
4-药物释放组件，41-释放结构，411-释药孔，42-给药腔体，421-给药腔，422-给药孔，423-切入端，4231-微凸角；
5-球囊组件，51-球囊，
6-药物释放组件，61-释放结构，611-穿刺部，612-释药孔，63-基座；
7-球囊组件，71-球囊；
10-涂层结构；
H-折叠翼空间的高度，h1-穿刺结构的高度，h2-给药腔体的高度；
100-药物载体，101-微孔。
以下通过特定的具体实例说明本发明的实施方式，本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用，本说明书中的各项细节也可以基于不同观点与应用，在没有背离本发明的精神下进行各种修饰或改变。需要理解的是，术语“中心”、“纵向”、“横向”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本发明和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本发明的限制。此外，术语“第一”、“第二”等仅用于描述目的，而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此，限定有“第一”、“第二”等的特征可以明示或者隐含地包括一个或者更多个该特征。在本发明的描述中，除非另有说明，“多个”的含义是两个或两个以上。
需要说明的是，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以通过具体情况理解上述术语在本发明中的具体含义。本文中的“远端”为远离操作者的一端，“近端”为靠近操作者的一端。下文中的“装置”指代“利用球囊实现药物输送的装置”。
首先，本申请人先阐明本申请的创作过程。
现有最早给血管供药的药物输送导管有呈球囊状的结构。当球囊充压时，球囊的
外表面与血管的内表面接触，并且可以将一些药物或治疗组合物递送到血管壁。递送药物可以是通过在与球囊的药物涂覆的外表面接触时，将一些药物或治疗组合物粘附到内膜层，或者通过溶解血液中药物向内膜层扩散，其中药物可以起到生物治疗作用，减少或防止血管上皮细胞的增生和由此引起的治疗血管部位的再狭窄。这种现有技术的药物输送导管的一个共同问题是，在导管插入脉管系统和导管在脉管系统内移动以到达治疗部位的过程中，包覆球囊外表面的药物或治疗组合物暴露于脉管系统中所含的血液中，这可能导致治疗组合物中的一些药物或活性成分在球囊到达所需治疗部位之前溶解或分散在血液中。为此，现有技术中提到的双球囊结构，一个球囊用来输送药物，另一个球囊在充泄压时膨胀或收缩。本申请人经过多次思考后发现，双球囊结构中用来输送药物的球囊存在膨胀或收缩，而充泄压力作用的球囊也可以膨胀或收缩，这种现有技术的结构制作复杂且成本高，而且用来输送药物的球囊很难控制输送药物的力，无法真正做到精准控制的功效。将精准控制分为以下几种：控制药物输送的区域、控制输送药物量(即药的有效转移率)、控制药物输送至目标区域的目标深度，我司发明人的核心就是希望能够达到后两种所说的精准控制。
为此，本申请人经过多次思考和多次验证后得知，将药物输送导管的功能分为：将药物进行输送、将药物输送至目标区域。本申请人考虑到设置一被折叠球囊，球囊展开状态下将药物输送至目标区域，并且通过设置单独的药物输送通道输送药物，这种初步核心思路为：球囊通过一充泄压被配置为在折叠构型和展开构型之间变化，流通充泄压的充泄压通道和释药孔连通给药腔体而形成的给药通道，两者为互不连通且单独控制的两个独立通道。折叠构型下，药物释放组件包附在所述球囊中；展开构型下，球囊的膨胀力带动药物释放组件运动至预先设定的目标区域，药物通过单独施加对应控制力，经过独立的给药通道输送至目标区域。这种核心思路的好处是不需要设置双球囊、只要一个球囊就可以实现精准给药的功效。给药通道可以设置多个，用一个输药控制单元控制所述药物的运动，并且通过调节力的大小可以控制药物输送至目标区域的不同的深度。给药通道可以设置多个，可以用不同的输药控制单元控制所述药物在每一个给药通道中的运动，可以输入不同药物、控制不同输入的药物进不同的区域、控制药物进不同的区域深度、控制不同输入的药物(不同药量)不同次数的给药。这种方式，药物的注射是可以精准剂量的、多次的。以上仅是一个举例说明，在实例操作时，可以选择上述其中一种精准控制方式进行控制。
另外，还需要说明的是，本申请的药物是一种广义的概念。药物可以为包含药物的药物体或组合物，其包括一种或多种治疗物质、诊断物质、一种药物、一种治疗组合物、一种诊断组合物、生理活性剂、一种生物化学活性剂、一个或多个活细胞、DNA、RNA、核酸、用于将遗传物质递送到目标部位中的细胞载体、抗炎剂、一种抗再狭窄剂、一种细胞增殖抑制剂、平滑肌增生抑制剂、紫杉醇、雷帕霉素、依维莫司、血管活性剂、血管扩张剂、血管收缩剂、抗生素、抗凝剂、血小板凝集抑制剂、抗纤维化剂、药学上可接受的载体、脂质基载体及其任意组合。此外，所述药物还可以是α还原酶抑制剂，例如，非那雄胺、度他雄胺。比如，药物可以为直径为1～1000μm的球形微粒、缓释载药棒材或片材，输药控制单元可配置加载到药物的输送力大小，以控制药物通过药物输送通道输送至目标区域、和/或目标区域对应的深度。除单一药物以外、载药物微球或片材等可持续地进行药物释放功能。其释放周期可达1周至6个月之久，并持续可控。需理解，所述球形微粒、缓释载药棒材或者片材，采用可降解的乳化聚合物制成，具体的，这些球形微粒、缓释载药棒材或者片材中存在孔隙，药物被承载于这些孔隙中，或者，所述球形微粒是药物与高分子材料混合制得的缓释药物，或者，所述球形微粒是一种药物结晶体，进而实现药物的缓释。
【实施例一】
请参阅图1至图3，图1A为本实施例一提供的利用球囊实现药物输送的装置的示意图；图1B为图1A中的利用球囊实现药物输送的装置的A-A部位的剖视图；图2A为本实施例一提供的利用球囊实现药物输送的装置的示意图；图2B为图2A中的利用球囊实现药物输送的装置的某一方向的剖视图；图2C为图2A中的利用球囊实现药物输送的装置的折叠状态的剖视图；图2D为实施例一的另一种利用球囊实现药物输送的装置的折叠状态的剖视图；图3为图2A中的利用球囊实现药物输送的装置的药物输送与液体输送的示意图。
本实施例一提供一种利用球囊实现药物输送的装置。所述装置包括：输送导管1、多组穿刺组件2以及球囊组件3。
请参阅图1A与图1B所示，输送导管1具有近端部分和远端部分。输送导管1包括互不连通的用于输送药物的第一通道11和用于流通充泄压用的第二通道12。至少
在靠近远端部分的所述第一通道11为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道111。如此，可以通过控制第一通道11或者药物输送通道111连接一个带刻度的注射器或额外的辅助装置，实现药物的精准输送。例如，第一通道11上优选可以设置输药控制单元。输药控制单元可以为一个，通过同一个连接管连接至三个药物输送通道，药物通过一个连接管压入三个药物输送通道。当然，输药控制单元可以为三个，分别通过各自的连接管连接至三个药物输送通道，这种情况下输药控制单元可以单独控制不同的压力值及发力的时机、持续时间等。第二通道12上可以设置充泄压控制单元。第二通道12可以为连接管，充泄压控制单元与第二通道12相连，采用液体实现充泄压。充泄压的控制可以采用充泄压阀等常规技术，本文在此不再赘述。第一通道11的远端部分例如为三个或者四个独立的药物输送通道111，这几个药物输送通道111的近端部分可以连通在一个腔道中，也可以分别独立的设置，例如，第一通道11是分别独立设置的多个药物输送通道111。第一通道11上还设置第一鲁尔接口，第一鲁尔接口通过一导管分别连接多个药物输送通道所对应的导管腔。优选的，所述第一通道11的外径或者内径小于第二通道12的外径或者内径。优选的，当所述装置包括N个第一通道11(或者包括N个药物输送通道111)时，每个第一通道11的内径小于第二通道12的内径的1/N倍。
请参阅图1A、图2A与图2B所示，多组穿刺组件2中，每一组穿刺组件2包括至少一穿刺结构21和给药腔体22。穿刺结构21包括穿刺部211及释药孔212，该组中释药孔212连通给药腔体22，给药腔体22与对应的药物输送通道111连通。使用时，穿刺部211刺入组织中，进而能够将药液注射至组织中，防止药液的损失，实现精准释药，提高治疗效率。还使得药物可以被精准的输送至目标区域，对药物的定量、定速、定压力等输送提供必要条件。在本实施例一中，所述穿刺组件2为三组或者四组，以与药物输送通道111匹配。所述穿刺组件2的穿刺结构21、给药腔体22可以是多种结构，下文中将进行详细描述。所述穿刺组件2与球囊31的组合方式也可以是多种形式，下文将进行详细的描述。给药腔体2可以采用金属材质形成的管，其横截面可以是圆形、矩形、三角形、多边形等其他形状。
请参阅图1至图3，球囊组件3至少包括一球囊31。球囊31可以是顺应性球囊、非顺应性球囊或者半顺应性球囊。优选的，球囊组件3还包括一导引导管32。所述球囊31的远端与导引导管32连接，以密封所述球囊31的远端。球囊31的近端与导引导管32密封或者不密封连接。当其密封连接时，如图1B所示，所述导引导管32与第二通道12间隔设置。当其不密封连接时，所述导引导管32设置于所述第二通道12的内部。导引导管32的轴向与所述第二通道12的轴向平行设置。导引导管32的近端为所述装置的近端。所述球囊31的近端与第二通道12的远端部分连接，球囊31的内腔与第二通道12连通。值得注意的是，球囊31被配置为在折叠构型和展开构型之间变化。如图2C所示，折叠构型下，多组穿刺组件2分别独立包附在球囊31中，可以使得穿刺组件2能够被单独包覆于球囊31中，防止每组穿刺组件2之间相互影响。通过给第二通道12充压作用于球囊31膨胀使其处于展开构型，球囊31的膨胀带动多组穿刺组件2的穿刺部211凸出。如图3所示，药物被配置为通过外力(外力可以是输药控制单元控制的力)分别通过多个药物输送通道111、每一药物输送通道111对应的给药腔体22、给药腔体22连通的释药孔212输送至目标区域。
优选的，球囊31具有球囊内腔9和球囊外表部。球囊31的球囊外表部可以折叠形成多对折叠翼311，其沿着所述导引导管32周向设置，每对相对设置的折叠翼311形成一折叠翼空间312，该些组的所述穿刺组件2分别容置在该些适配的所述折叠翼空间312内。如图2C所示，在本实施例中，球囊外表部例如折叠成三对折叠翼311，这些折叠翼311分别周向设置在导引导管32的四周，以使得该些组的穿刺组件2能够沿着周向布局，如此可以使得装置上的穿刺组件2的朝向无方向性，这使医生在手术过程中无需调整导管的位置，大大降低了医生的操作难度，提高治疗效率。在沿组织腔(目标位置)的周向，药物可以被均匀地吸收，进而达到预期临床效果。一组穿刺组件2对应一折叠翼空间312，折叠状态下，一组穿刺组件2折叠在对应的折叠翼空间312内。一般来说，球囊在工艺制作时可以让球囊有形状记忆性，即，制作完成时，球囊具有折叠翼空间312的形状记忆性。球囊内腔9与第二通道12连接。充压时球囊内腔9充满液体以控制球囊外表部展开。泄压时球囊内腔9泄压，球囊折叠。
优选的，给药腔体22包括一基座221，基座221的上表面和其它外周面(其它外周面是指不包含上表面的外周面)形成相对固定的给药腔，基座221的上表面沿着球囊31的长度方向开设与释药孔212连通的贯通孔2211，穿刺结构21固定设置在基座221的上表面上，释药孔212通过贯通孔2211与给药腔连通。基座221可以用金属制成，其不具有柔性，空间的大小相对固定。当输药控制单元控制的外力通过基座221、
贯通孔2211和释药孔212进行给药操作时，由于基座221、贯通孔2211和释药孔212的空间相对固定，通道大小不会有大的变化，这样的设置，可以使得输药控制单元控制的外力更好控制，具有更高的精度，给药量更精准。当然，在其他的实施例中，所述基座221不限为金属材料，其可以是陶瓷材料、不锈钢材料或者高分子材料等硬质的不易变形的材质。或者，在其他实施例中，所述基座221的上表面采用硬质材料制成，例如金属材质，保证在球囊31膨胀时，每个穿刺结构21能够以相同大小的压力凸出。基座221的横截面可以是空心圆形、空心矩形或其它形状的空心腔体。需理解，所述基座221的上表面与其他外周面可以是一体成形的，例如其可以是同一个管，例如圆形管、三角形管等。
优选的，所述基座的横截面为空心结构；更优选的，所述基座的横截面为空心圆形、空心椭圆、空心矩形、空心多边形或者仿形空心结构；优选的，所述基座其外轮廓呈具有一弧度的仿形空心结构，所述仿形空心结构的曲率与球囊的曲率一致，进而能够减小装置的通过外径还能够保证内部空心结构的空间，保证药物输送的流量。
优选的，如图2A与图2B所示，给药腔体22设置于球囊31的外表面。具体的，基座221的其它外周面包含下表面，下表面固定贴设于球囊31的外表面，并且在展开构型时随着球囊31的膨胀，带动基座221向外运动，以此带动基座221的上表面设置的穿刺部211凸出。所述基座221与球囊31采用粘贴的形式连接，保证基座221与球囊31连接的稳固性。
请参阅图2C，设置的折叠翼空间312的高度H应不小于基座221的高度h2和穿刺结构21的高度h1之和，这种设计使得整个球囊导管折叠状态下径向小，同时还能够保证球囊能够被顺利的输送，还能够保证穿刺结构21不被破坏，适用的场景更多。优选的，沿装置的轴向，穿刺结构21两侧的折叠翼311(每组折叠翼311)的端部距离穿刺结构21的距离相等，进而使得装置在输送过程中，球囊31的周向受力均匀，输送稳定性好，也能够更好的保护穿刺结构21不易破坏或者不易发生歪斜。同样的，沿装置的周向，各个组的折叠翼311对称设置，每组穿侧组件2对称设置，进一步保证球囊31的周向的受力均匀性。
优选的，每一组穿刺组件2的所述穿刺结构21为多个，且沿着所述基座221的长度方向间隔设置，所述穿刺部21的顶部呈尖部，所述穿刺部21的端部围设成所述释药孔212。优选的，每组穿刺组件2中的每个穿刺结构21等距分布。
优选的，所述输送导管上还设置充泄压控制单元和输药控制单元(图中未示出)，所述第二通道12与所述球囊31组成的流通充泄压用通道通过所述充泄压控制单元控制，第一通道11与所述球囊31通过所述输药控制单各自控制。
优选的，所述第一通道11上设置第一鲁尔接口，第一鲁尔接口通过一导管分别连接多个药物输送通道所对应的导管腔。
优选的，如图1B所示，沿所述第二通道12的径向设置有凹槽121，所述凹槽121沿第二通道12的轴向延伸设置，所述凹槽121用于容纳所述第一通道11，以使得所述装置的非球囊部分的径向尺寸更小。并且，这样设置，可以使得第一通道11能够距离第二通道12的轴线更近，弯曲半径减小，使得整体的柔顺性更好。进一步的，所述凹槽121的半径不小于所述第一通道11的外径。进一步的，所述凹槽121的深度可以不小于所述第一通道11的外半径，进而使得第一通道11容置于凹槽121中时，其结构更加稳定，整体性更好。当然，所述凹槽121的深度可以根据实际需求设置为大于第一通道11的外半径。所述凹槽121的数量不做限制。在实际使用时，第一通道11可以放置于凹槽121处，也可以不用放置在凹槽121处。若第一通道11不放置于凹槽121处，也在本发明的保护范围中。
优选的，所述装置能够用于输送药物载体100，药物载体100中含有药物，当药物载体100被注射至组织中时，所述药物载体100能够在组织中缓释药物，进而实现持续治疗组织的目的。进一步的，所述装置的穿刺组件的径向尺寸大于所述药物载体100的径向尺寸，例如穿刺组件的直径大于所述药物载体100的直径，进而使得药物载体100能够通过穿刺组件进入组织中。优选的，所述穿刺组件的径向尺寸大于1000μm，优选的，大于200μm。
穿刺组件
本部分将对穿刺结构的形状、材质、尺寸以及穿刺结构与给药腔体22的结合等方案进行展开阐述，但是穿刺结构并不限定于此，只要能够实现刺入组织的结构，均在本申请的范围内。
请参考图2B、图4A至图4C所示，所述穿刺结构21包括穿刺部211以及释药孔212，所述穿刺部211具有穿刺壁体2111、穿刺腔体2112、穿刺面2113。其中，所述
穿刺面2113为所述穿刺部211的顶部的面，即刺入组织时，产生刺入作用的面。
[根据细则91更正 23.01.2024]
优选的，如图4A与图4C所示，所述穿刺面2113可以是一个平面，所述穿刺面2113与垂直于穿刺结构211的轴向的平面的角度a呈5～85°，以更好的刺入组织。例如，当角度a为5°时，其顶部呈尖部，端部围设成一释药孔。当然，所述穿刺面2113还可以是具有一定弧度的面，例如凹面或者凸面等。如图4B所示，所述穿刺面2113还可以是圆锥面，所述圆锥面的角度a呈25～75°。所述穿刺面2113还可以是多棱柱面，以匹配实际使用需求。
优选的，如图4A与图4C所示，所述穿刺面2113可以是一个平面，所述穿刺面2113与垂直于穿刺结构211的轴向的平面的角度a呈5～85°，以更好的刺入组织。例如，当角度a为5°时，其顶部呈尖部，端部围设成一释药孔。当然，所述穿刺面2113还可以是具有一定弧度的面，例如凹面或者凸面等。如图4B所示，所述穿刺面2113还可以是圆锥面，所述圆锥面的角度a呈25～75°。所述穿刺面2113还可以是多棱柱面，以匹配实际使用需求。
[根据细则91更正 23.01.2024]
优选的，所述穿刺壁体2111的外部可以呈圆柱形、呈圆锥形、底部圆柱形顶部圆锥形、或者呈阶梯状。如图4C所示，在所述穿刺壁体2111的内部，沿其轴向，其厚度不变化，以使得在穿刺过程中穿刺组件受力均匀、药物从输送过程中输送压力不变。或者，穿刺壁体2111的内部，沿其轴向的厚度逐渐减小，例如厚度减小形成的锥度为0～10°，进而使得穿刺部211的顶部尺寸更小，或者其厚度逐渐增加，使得穿刺腔体2112的尺寸逐渐减小，进而增加药物输送中的输送压力，进而增加注射压力。或者，穿刺壁体2111的内部呈阶梯状，越靠近顶部，其内部的径向尺寸越小，进而能够呈阶梯式的增加药物输送的压力。相适配的，所述穿刺腔体2112可以呈圆柱形、圆锥形或者阶梯状等。所述穿刺壁体2111的内径向尺寸与外径向尺寸之比为0.2～0.8，例如是0.2、0.3、0.4、0.5、0.6、0.7、0.8等。例如，所述穿刺壁体2111的内径向尺寸为0.2mm、0.5mm或者0.8mm，其外径向尺寸可以是1mm。穿刺壁体2111的内径向尺寸为0.8mm，其外径向尺寸还可以是1.5mm、2mm、4mm等。优选的，所述穿刺壁体2111的内径尺寸范围在约在2μm-500μm之间，优选为2μm-200μm，更优选为50-150μm，例如可以约是50、60、70、80、90、100、110、120、130、140、150μm等，当然，还可以在小于或大于这些尺寸。可选的，所述穿刺壁体2111的外部还可以是沿球囊的轴向延展的面，所述穿刺腔体为沿着所述穿刺壁体形成一缝隙，所述穿刺壁体的横截面呈两个三角形相对的布设，所述穿刺壁体的中间呈所述穿刺腔体，具体可参考实施例三。
穿刺部211的数量，可以根据实际进行设置，其可以是沿球囊纵向排布，也可以是周向排布等。如此，穿刺部211的数量众多，提高了其分布的广度和密度，可实现同一时间多点位的同时给药，提升给药的均匀性，治疗更加有效，可达到更好的防止再次狭窄的治疗效果。
[根据细则91更正 23.01.2024]
优选的，所述释药孔212可以沿所述穿刺部211的轴向开口，如图4A所示，也可以沿所述穿刺部211的径向开口，或者，释药孔212的开口的角度可以是任意一角度，所述释药孔212的开口朝向在轴向和径向之间的角度方向。朝向轴向、径向或者任意角度开口时，所述开口可以是一个或者多个，例如，如图4B所示，朝向径向的开口是2-4个。所述释药孔212可以是圆形、椭圆形、矩形或者其他多边形形状等。所述释药孔可以是细长开口、槽状开口等。这样的开口可以沿着基座221的长度方向间隔排列成纵向排，也可以不排列成纵向排，排的数量(如果使用的话)可以是2-30排范围内的任何合适的数量(但是在一些实施例中也可以使用高于30的排的数量)，根据需要，特别是，根据开口的大小可以设置，根据药物或治疗组合物的类型和化学/物理特性、大小及进入目标区域深度等来设置。
优选的，所述释药孔212可以沿所述穿刺部211的轴向开口，如图4A所示，也可以沿所述穿刺部211的径向开口，或者，释药孔212的开口的角度可以是任意一角度，所述释药孔212的开口朝向在轴向和径向之间的角度方向。朝向轴向、径向或者任意角度开口时，所述开口可以是一个或者多个，例如，如图4B所示，朝向径向的开口是2-4个。所述释药孔212可以是圆形、椭圆形、矩形或者其他多边形形状等。所述释药孔可以是细长开口、槽状开口等。这样的开口可以沿着基座221的长度方向间隔排列成纵向排，也可以不排列成纵向排，排的数量(如果使用的话)可以是2-30排范围内的任何合适的数量(但是在一些实施例中也可以使用高于30的排的数量)，根据需要，特别是，根据开口的大小可以设置，根据药物或治疗组合物的类型和化学/物理特性、大小及进入目标区域深度等来设置。
[根据细则91更正 23.01.2024]
优选的，所述穿刺部211的材质可以是硬质的材料制成，例如是金属材料制成，更优选的，可以是镍钛合金、不锈钢材质、钴铬合金等。更优选的，可以是高分子材质，包括：尼龙、ABS、树脂、PEEK、TPE、TPU、PLA、光刻胶等，以及丝素蛋白等生物高分子材料。金属材料可以通过激光刻蚀、机加工、酸洗、抛光、研磨等工序制作，成尖或形成锋利的刃口；高分子材料可以通过3D打印方式制作，优点是精度高、加工速度快。高分子材料也可以通过模具浇铸/脱模的方式制作，优点是强度高、可批量生产。更优选的，所述穿刺部211的材质还可以是陶瓷材料等。
优选的，所述穿刺部211的材质可以是硬质的材料制成，例如是金属材料制成，更优选的，可以是镍钛合金、不锈钢材质、钴铬合金等。更优选的，可以是高分子材质，包括：尼龙、ABS、树脂、PEEK、TPE、TPU、PLA、光刻胶等，以及丝素蛋白等生物高分子材料。金属材料可以通过激光刻蚀、机加工、酸洗、抛光、研磨等工序制作，成尖或形成锋利的刃口；高分子材料可以通过3D打印方式制作，优点是精度高、加工速度快。高分子材料也可以通过模具浇铸/脱模的方式制作，优点是强度高、可批量生产。更优选的，所述穿刺部211的材质还可以是陶瓷材料等。
[根据细则91更正 23.01.2024]
优选的，所述穿刺部211与给药腔体22连接，所述给药腔体22的横截面可以是圆形、椭圆形、三角形、矩形或者多边形等。更佳的，所述穿刺部211的高度h1在0.1～1.5mm之间，给药腔体22的高度h2在0.1～0.5mm之间。所述给药腔体22的壁厚T与外径D(横向尺寸W)之比为0.06～0.8，优选的，给药腔体22的壁厚T与外径D(横向尺寸W)之比为0.05～0.45。
优选的，所述穿刺部211与给药腔体22连接，所述给药腔体22的横截面可以是圆形、椭圆形、三角形、矩形或者多边形等。更佳的，所述穿刺部211的高度h1在0.1～1.5mm之间，给药腔体22的高度h2在0.1～0.5mm之间。所述给药腔体22的壁厚T与外径D(横向尺寸W)之比为0.06～0.8，优选的，给药腔体22的壁厚T与外径D(横向尺寸W)之比为0.05～0.45。
优选的，所述穿刺部211与给药腔体22可以采用焊接、粘接的方式连接。各个穿刺部211之间的距离优选小于穿刺部的径向尺寸。更优选的，各个穿刺部2之间的距离优选为0.5～5mm，优选的，可以是1～2mm，可以使得注射药物能够均匀的分布于组织中。
优选的，所述给药腔体22，例如基座221，可以采用金属材质、高分子材质或者陶瓷等硬质材料，为穿刺结构21能够受力均匀的刺入组织中提供基础。在本实施例中，
所述基座221例如是一管体，基座221呈圆柱形结构，整个圆柱形结构均采用金属材质、高分子材质或者陶瓷等等硬质材料制成。基座221的长度小于所述球囊31的轴向的长度。在另一实施例中，基座221与穿刺部2连接的上表面的部分采用硬质材料，其他的表面的部分采用柔性材质以形成软管。给药腔体22与球囊31采用胶粘固化的方式固定在球囊表面，并在周向上均匀排列。当连接部分为金属等硬质材料时，可以先进行等离子处理，或者通过打磨的方式，再进行焊接或者胶粘连接。当连接部分为柔性软管时，采用焊接或者胶粘方式连接。所述给药腔体22的结构可以是圆柱形、椭圆形、矩形、三角形或者多边形体结构。请参考图5A，所述基座221例如是一板状结构，所述给药腔22还包括给药导管222，所述基座221可以设置于给药导管222上，例如粘贴。板状结构的长度小于所述球囊31的轴向长度，所述板状结构的宽度不小于穿刺组件2的给药腔体22的直径，所述板状结构的厚度不小于穿刺组件2的给药腔体22的壁厚。更佳的，所述板状结构还可以具有弧度，例如，所述板状结构与球囊31接触的表面具有朝向球囊31的弧度，进而使得板状结构能够与球囊31的连接更加紧密。例如，板状结构朝向球囊31的弧度的曲率与球囊31的曲率一致。优选的，所述基座其外轮廓呈具有一弧度的仿形空心结构，所述仿形空心结构的曲率与球囊的曲率一致；球囊折叠可以通过定制设备将穿刺组件埋藏在两片折叠后的球囊翼片之间，避免在输送器械时划伤血管。本实施例中，可通过球囊折叠翼实现球囊的原始折叠状态，由于球囊折叠的记忆性，在球囊泄压后，球囊会恢复折叠状态，如此，可保证球囊有效地覆盖包覆每一组穿刺组件。
优选的，如图5B与图5C所示，沿所述球囊31的轴向，穿刺组件2的给药导管222包括硬质导管2221与软质导管2222，硬质导管2221与软质导管2222分段间隔设置。例如，包括两段硬质导管2221和一段软质导管2222。当然，硬质导管与软质导管的数量不做限制。优选的，软质导管2222的数量比硬质导管2221的数量少一个。穿刺结构21优选设置于硬质导管2221上，这样硬质导管能够提供穿刺组件2刺入组织时所需的硬度与强度。所述软质导管2222的设置为给药导管22提供柔性，提高装置的通过性，便于装置的输送。另外，软质导管2222能够发生弯曲，其能够在球囊31的表面非轴向的延伸设置；软质导管2222的设置还外穿刺组件2的错位设置提供前提条件。优选的，如图5D-图5E所示，沿所述球囊31的周向，前一段的硬质导管2222与后一段的硬质导管2222在球囊31的周向方向不同(图5D为沿球囊31周向布设的给药导管22的展开示意图)，以形成错位布设。在图5D中，实线表示其中一段硬质导管2221在某一个角度周向布设，虚线表示其中另一段硬质导管2221在另一个角度周向布设。如此设置，可以使得在较长的球囊31的周向方向上，沿一个给药导管，穿刺组件2能够错位在不同的周向，进而使得周向给药均匀，提高注射效率。同理的，所述药物释放组件4可以具有硬质导管与软质导管，硬质导管提供释放结构41(61)所需要的固定的管腔。药物释放组件4的方案可以参考穿刺组件2的结构，本文在此不再赘述。
优选的，所述给药腔体22与第一通道11连接。例如，第一通道11外径与给药腔体22的内径适配；或者，第一通道11的内径与给药腔体22的外径适配。
优选的，穿刺组件2与球囊31的连接中，穿刺组件2可以设置于球囊31的外部，具体可本实施例一。也可以设置于球囊31的内部，具体可参考实施例二。输送导管上还设置充泄压控制单元和输药控制单元，第二通道与球囊组成的流通充泄压用通道与药物输送通道分别通过充泄压控制单元和输药控制单元各自控制。充泄压控制单元和输药控制单元可以由泵等控制其给力的大小，也可以医务人员手动控制其力的大小。
当球囊处于折叠状态时，球囊处于包覆每一组穿刺组件；当球囊处于展开状态时，球囊膨胀，带动每一组穿刺组件凸出于球囊。如此，可在球囊处于折叠状态时，将球囊输送入病灶处，由于球囊处于折叠状态且覆盖每一组穿刺组件，介入过程中不会损伤血管；且在球囊泄压后，球囊恢复折叠状态，带动每一组穿刺组件撤出目标区域并覆盖包覆每一组穿刺组件，避免球囊撤出过程中损伤组织，也可避免每一组穿刺组件留在组织中，提升操作过程的安全性。可以理解，当球囊完全展开后，随着球囊的膨胀，药物额外的给药通道通过释药孔并经由释药通道注射进入目标区域，完成给药。
液体被配置用于流通充泄压用和用于给药用，液体可以是加了药物或药物载体的生理盐水，当然也并不局于生理盐水。还有，不会混合的两种液体(如油和水)之间的分离被称为“液-液相分离”，这对许多蛋白质的功能至关重要。本申请人还发现可以将“液-液相分离”在该装置中应用。利用“液-液相分离”原理将“液-药相分离”，即，液体和药物或药物载体相分离，先通过一个或多个通道将液体和药物或药物载体打入腔室中。如药物或药物载体的密度相对于液体较轻，通过一定单独施加对应控制力，将包含更多药物或药物载体含量的液体从药物释放组件打出，输送至目标区域。
输送导管
本部分将第一通道11的形状、材质、尺寸以及第一通道11与给药腔体22的结合，第一通道11与第二通道12之间的位置关系等方案进行展开阐述，但是第一通道11并不限定于此，只要是能够实现输送药物的结构，均在本申请的范围内。
第一通道11用于将药物(需理解，所述药物可以是药液)从第一通道11的近端输送至远端。第一通道11至少在靠近远端部分的所述第一通道11为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道111。例如，所述第一通道11可以是多个独立的药物输送通道，及药物输送通道从近端至远端都是独立的。在输送药物的过程中，可以分别将药物从药物输送通道输入，实现分别给药。优选的，采用完全独立的输送药物的方式时，每个药物输送通道的径向尺寸、轴向尺寸一致，进而为实现同速率同压力的药物输送提供条件。当然，为了适应治疗需求，完全独立的药物输送通道还可以径向尺寸或者轴向尺寸不一致，进而使得药物输送的压力、速率不同。再例如，所述第一通道11靠近近端的部分包括一个总的通道、靠近远端部分为多个独立的药物输送通道111，当需要输送药物时，将药物从总的通道输入，药物再通过分别独立的药物输送通道111输出。
第一通道11的材质优选是软管材质，例如是聚酰胺、聚酰亚胺、嵌段聚醚酰胺、聚氯酯、硅胶等弹性体中的一种或者组合，实际使用时不限定以上材质。第一通道11还可以是硬质材质。本申请中，所述硬质材质可以包括金属材料、高分子材料以及陶瓷材料等。
球囊组件
球囊组件可以是快速交换结构或同轴结构：快速交换结构的管体设置有一个侧孔，可通过导丝；同轴结构的管体由长度相同或不同的单腔或多腔管组成，制作工艺相对简单。球囊组件的材料主要是：高分子塑料、金属件、以及亲水涂层等，其制作工艺包括但不限于：拉伸吹塑成型、共轴挤出、激光/热焊接、注塑成型、以及胶粘工艺等。
连接件可以含两个或三个鲁尔接口，每个接口有独立的腔室，并可通过模具注塑或胶粘的方式固定在导管末端。在实施例一中，鲁尔接口中的腔体同时且分别和药物输送通道连通；而设置额外的腔体和压力输液通道连通，它们相互独立，互不干涉。
折叠翼
优选的，所述折叠翼之间不重叠。当球囊的直径在2～6mm时，所述折叠翼为3～5对；当球囊的直径在4～12mm时，所述折叠翼为5～6对；当球囊的直径在10～30mm时，所述折叠翼为6～12对。
【实施例二】
请参考图6A至图6B，图6A为本实施例二提供的利用球囊实现药物输送的装置示意图；图6B为图6A中的利用球囊实现药物输送的装置的折叠状态的剖视图。
本实施例二与实施例一的区别在于，输送利用球囊实现药物输送的装置的结构不同，进一步的，所述穿刺组件与球囊的结合方式不同。本实施例二的装置与实施例一中相同部分不再叙述，以下仅针对不同点进行描述。
如图6A与图6B所示，与实施例一不同的是，给药腔体22设置于球囊31的内表面上。具体的，基座221设置在球囊31的内表面内。基座221的上表面与球囊31内表面固定贴合设置，球囊31上设置有供穿刺结构21穿出的孔，穿刺结构21穿出所述孔凸设于球囊31的内表面。折叠构型下，凸设出来的穿刺结构21设置在折叠翼形成的折叠翼空间312内；在展开构型下，随着球囊31的膨胀，带动基座221向外运动，从而带动凸设出来的穿刺结构21伸出折叠翼空间312，折叠翼空间312变小或被膨胀消失。
如图6A所示，设置的折叠翼空间312的高度H应不小于凸设出球囊31内表面的穿刺结构21的凸伸高度h3。每一组穿刺组件2的基座221分别沿着导引导管32周向布置，在折叠构型下，基座221通过导引导管32以实现支撑；在展开构型下，随着球囊31的膨胀带动所述基座221远离导引导管32。
【实施例三】
请参考图7，图7为本实施例三提供的利用球囊实现药物输送的装置的示意图。
本实施例三与实施例一、实施例二的区别在于，输送利用球囊实现药物输送的装置的结构不同，进一步的，所述穿刺组件的结构不同。本实施例三的装置与实施例一、
实施例二中相同部分不再叙述，以下仅针对不同点进行描述。
请参阅图7，每一组穿刺组件2的穿刺结构21为一对穿刺刀片213。该对穿刺刀片213分别由两片长条状的刀片组成，两片刀片分别安装在基座上，围设成一长条状的释药孔2131，进而提高给药效率。此外，由于刀片的整体性好，刀片不易脱落，进而降低穿刺组件落入组织中的风险。该对穿刺刀片213沿着球囊31的长度方向延伸设置，所述穿刺刀片213的长度可以根据实际需求设定。所述刀片呈底部宽上端窄的结构，刀头部分位于上端。所述刀片的横纵比为0.05～1，优选的，刀片的横纵比对0.1～0.25。
【实施例四】
请参考图8A至图8B，图8A为本实施例四提供的给药装置的示意图；图8B为本实施例四提供的另一种给药装置的示意图。
本实施例四与实施例五的区别在于，本实施例四的给药装置不包含第一通道及给药腔体，药物释放组件的释放结构为凸起通孔。本实施例四与实施例一至实施例三的区别在于，本实施例四的给药装置不包含第一通道以及给药腔体。本实施例四的装置与实施例一中相同部分不再叙述，以下仅针对不同点进行描述。
本实施例四提供的给药装置，包括：输送导管(图8未示出)、至少一组药物释放组件6以及球囊组件7。
所述药物释放组件6包括至少一释放结构61和给药腔体62，所述释放结构61包括穿刺部611与释药孔612，该组中所述释药孔611连通所述给药腔体62。需理解，在本实施例中，所述给药腔体62与充泄压腔体采用同一个腔室。腔室用于充盈药物的药物载体和/或药物的液体，液体被配置用于流通充泄压用和用于给药用，液体充满球囊来带动球囊膨胀，使球囊处于展开构型，液体通过单独施加对应控制力，通过给药通道(如实施例一的释药孔连通给腔室，腔室与对应的第二通道12连通)实现给药。优选的，所述药物释放组件6还包括基座63，所述基座63呈板状，所述穿刺部611设置于所述基座上；优选的，基座63与所有的释放结构61一体成型。所述释放结构61与基座63的材质可由高分子聚合物、无机硅、金属等材料中的至少一种加工而成。优选的，释放结构61的外径大于基座63的内径，释放结构61的内径小于基座63的内径。当然，释放结构61和基座63可通过粘结剂、焊接等工艺固定为一体，然后可再通过粘结剂、焊接等工艺直接固定安装在球囊71的外侧壁或内表面上，然后通过激光打孔一次性在释放结构61上开设出释药通道、在基座63上开设于贯穿孔、可保证后续释药过程的稳定性。在图8A中，基座63位于球囊31的外表面。基座63可以是一板状的基板。当然，在其他实施例中，基座63可以不限于板状的基板，只有用于安装或固定释放结构61的功效即可。基座63可以和释放结构61一体制成，也可以分别制成。
球囊组件7：至少包含一球囊71，所述球囊71通过一充泄压被配置为在折叠构型和展开构型之间变化；所述折叠构型下，所述药物释放组件分别单独被包附在所述球囊中；所述展开构型下，所述球囊71的膨胀力带动所述药物释放组件6运动至预先设定的目标区域，所述药物通过单独施加对应控制力，经过所述给药通道输送至目标区域。折叠构型、展开构型具体可参考实施例一中的描述。
请参阅图8B，与图8A不同之处在于，基座63可以位于球囊31内，基座63的上表面与球囊71内表面固定贴合设置，药物释放组件6中的释放结构61凸设出球囊71的内表面，折叠构型下，凸设出来的释放结构61设置在折叠翼形成的容置空间内；在展开构型下，随着球囊71的膨胀，释放结构61向外运动，从而带动凸设出来的释放结构61伸出容置空间，容置空间变小或被膨胀消失。同理，液体被配置用于流通充泄压用和用于给药用，液体可以是加了药物或药物载体的生理盐水，当然也并不局于生理盐水。
优选的，所述充泄压通道和给药通道为互不连通且单独控制的两个独立通道，所述药物释放组件为多组，该些组药物释放组件分别通过多个输药控制单元或同一个输药控制单元控制所述药物的运动。
优选的，所述充泄压通道和所述给药通道采用同一个腔室，所述药物释放组件为多组，所述腔室包含药物的药物载体或组合物的液体，所述液体被配置用于流通充泄压用和用于给药用，所述液体充满所述球囊来带动所述球囊膨胀，使所述球囊处于展开构型，所述液体通过单独施加对应控制力，通过所述给药通道实现给药。
优选的，所述球囊组件还包括导引导管，所述球囊密封附接在所述导引导管上，所述球囊折叠形成多个折叠翼，其沿着所述导引导管周向设置，每对相对设置的折叠翼形成一折叠翼空间，所述该些药物释放组件分别容置在该些适配的所述折叠翼空间
内。
优选的，所述该些药物释放组件被配置为所述将药物植入所述目标区域或注射入所述目标区域。
优选的，所述穿刺部的顶部呈尖部，端部围设成所述释药孔，所述穿刺部为多个，且沿着所述基座的长度方向间隔设置。
优选的，，所述穿刺部为一对穿刺刀片，所述该对穿刺刀片沿着所述基座的长度方向设置，所述对穿刺刀片围设成一长条状的所述释药孔。同样的，该包括刀片的设置，具体可参考实施例三，在此不再赘述。
【实施例五】
请参考图9至图10，图9为本实施例五提供的给药装置的示意图；图10为本实施例五提供的另一种给药装置的示意图。
本实施例五与上述实施例一至实施例三的区别在于，本实施例五提供的利用球囊实现药物输送的装置的药物释放组件4不包括穿刺结构。本实施例五的装置与其他实施例的相同部分不再叙述，以下仅针对不同点进行描述。
本实施例五提供一种给药装置，包括：输送导管(图9未示出)、至少一组药物释放组件4以及球囊组件5。
所述输送导管具有近端部分和远端部分，所述输送导管包括互不连通的用于输送药物的第一通道(图9未示出)和用于流通充泄压用的第二通道(图9未示出)，至少在靠近远端部分的所述第一通道为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道。
所述药物释放组件4包括至少一释放结构41和给药腔体42，所述释放结构41至少包括释药孔411，该组中所述释药孔411连通所述给药腔体42。优选的，当释放组件4位于所述球囊51的内部时，所述给药腔体42还包括给药腔421和给药孔422，释药孔411通过给药孔422与给药腔421连通，此时，所述释药孔411位于所述球囊51上。在其他的实施例中，当所述释放组件4位于所述球囊51的外部时，所述释药孔411作为给药腔体42上的给药孔。优选的，所述给药孔422与释药孔411的尺寸相同，进而便于药物输送。当然，在其他的实施例中，所述给药孔422与释药孔411的尺寸大小可以不同，根据实际需求进行设置。进一步的，所述给药腔421的径向尺寸大于所述给药孔422的直径，进而保证药物的输送压力的稳定性。给药腔421的内径≥0.1mm，例如是0.2、0.3、0.4等；优选的，给药腔421的内径≥0.3mm；更优的，给药腔421的内径≥0.5mm，例如是0.6、0.7、0.8等。给药腔421的内/外径之比为0.1～0.9，更优的，给药腔421的内/外径之比为0.4～0.8。给药孔422的内径小于给药腔421的内径，优选的，给药孔422的内径小于给药腔421的内径的0.5倍，给药孔422的内径甚至达到0.01mm以下。优选的，所述给药孔422的内径尺寸范围在约在2μm-500μm之间，优选为2μm-200μm，更优选为50-150μm，例如可以是50、60、70、80、90、100、110、120、130、140、150μm等，当然，还可以在小于或大于这些尺寸。或者，本领域技术人员可以根据实际情况，对给药腔421与给药孔422的尺寸进行设置。本领域技术人员可以根据给药腔421、给药孔422尺寸的选择，结合药物输送的输送力，确定药物输出时的药物注射压力等。
球囊组件5至少包含一球囊51，所述球囊51通过一充泄压被配置为在折叠构型和展开构型之间变化。所述折叠构型下，所述药物释放组件4分别单独被包附在所述球囊51中。所述展开构型下，所述球囊51的膨胀力带动所述药物释放组件4运动至预先设定的目标区域，所述药物通过单独施加对应控制力，经过独立的所述给药通道输送至目标区域。折叠构型、展开构型具体可参考实施例一中的描述。
优选的，如图9所示，所述第一通道与所述药物释放组件4可以设置在球囊51的内表面。如此可以使得药物药液具有单独的通道，药液的浓度可控，释放速率可控。
优选的，如图10所示，所述第一通道与所述药物释放组件4可以设置在球囊51的外表面，所述释药孔411与给药腔42连通。所述球囊51展开膨胀时，所述药物释放组件4贴合并压迫组织，与组织实现紧密贴合，因为受压迫的组织受到应力集中的影响，当在此部位，药物进行释放时，能够更好地将药物渗透到组织中去。优选的，所述药物释放组件4可以是一空心丝线，空心丝线上设置有释药孔。给药腔体42的内径≥0.1mm，例如是0.2、0.3、0.4等；优选的，给药腔体42的内径≥0.3mm；更优的，给药腔体42的内径≥0.5mm，例如是0.6、0.7、0.8等。给药腔体42的内/外径之比为0.1～0.9，更优的，给药腔体42的内/外径之比为0.4～0.8。优选的，释药孔411的内径小于给药腔体42的内径，优选的，释药孔411的内径小于给药腔体42的内径的0.5倍。每个释药孔411之间的间距为0.1～1mm，优选的，为0.25～0.75mm，例如，
0.25mm、0.3mm、0.4mm、0.45mm、0.5mm、0.6mm等。当然，所述释药孔411还可以大于1mm。所述给药腔体42的横截面可以是圆形或者三角形中空管材。当给药腔体42是圆形时，所述给药腔体42上的释药孔411优选朝向所述球囊51膨胀的方向。当然，在其他的实施例中，所述给药腔体42上的释药孔411可以是与球囊51膨胀的方向存在一定的夹角。进一步的，在给药腔体42的同一周向方向上，分别具有多个释药孔411，例如是两个释药孔411，如此在给药腔体42上形成两列释药孔411，进而增加了药物释放的通道进而增加了进药量。当给药腔体42的横截面是三角形时，三角形柱体的两个侧面优选均具有释药孔411。具体可参考下文实施例十的内容。
进一步的，如图22A-图22C所示，所述药物释放组件4为三角形中空管，即给药腔体42的外表面形状是三角形柱体，三角形柱体的其中一个角朝向球囊51的径向外侧布设。将朝向球囊的径向外侧的角的一端定义为切入端423。所述释药孔411设置于所述给药腔体42的切入端423。三角形中空管相比于圆形中空管，三角形中空管刺入组织的能力更强，甚至可以全部刺入病变组织中，使得药物释放时，就能够在病变组织中释放，进而提高了药物输送的效率。在三角形中空管的切入端423设置释药孔411，相比于具有穿刺部设置于药液输送通道的设计，其沿球囊径向的高度可降低20％～30％，使得尺寸更小，装置的整体通过性好，本领域人员都知道，对介入领域，在狭小的组织腔中，任何细微的变化，都会对本领域技术提供突破性的进展。并且，相比穿刺结构，三角形中空管的加工精度高，加工周期短，可以一次成型，无附加工艺(例如采用焊接、切割等工艺)，且成本低等，可加工性好，降低了制造成本，提高了装置整体的质量，便于批量化生产。切入端423的设置，可以起到应力集中，促进靶向释药的作用，例如，还能够切断血管内壁的弹力膜，减少术后血管管腔再回弹的作用。
进一步的，请继续参考图22A，所述药物释放组件4为三角形中空管，即给药腔体42的外表面是三角形柱体，所述释药孔411可以是设置于切入端423与设置于所述三角形中空管的两个侧壁上的组合。优选的，沿药物释放组件4的轴向，释药孔411设置于切入端423的轴向与设置于三角形中空管的两个侧壁的轴向位置相同或者不同。如此，药物液体的横向扩散分布比单向孔的更加均匀。
进一步的，所述释药孔411可以沿着三角形中空管的给药腔体42的轴向均匀的或者不均匀的布设，进而为定量给药提供前提条件。例如，当病变部位的长度大于球囊的轴向的长度时，释药孔411可以均匀布设。当病变部位的长度小于球囊的轴向长度时，释药孔411可以不均匀布设，例如，球囊的轴向中间部位贴合病变部位时，释药孔411可以设置的密度大于球囊的轴向的两侧非接触病变部位的位置。
进一步的，沿所述三角形中空管的给药腔体42，每个所述释药孔411的大小可以是均一的。请参考图22C与图23C，沿所述三角形中空管的给药腔体42，由近端至远端，每个所述释药孔411的大小可以是逐渐变大或者变小的。优选的，沿所述给药腔体42的轴向，由近端至远端(近端表示靠近操作端的一侧、远端表示远离操作端的一侧)，每个所述释药孔411的大小逐渐变大，以使得药物释放组件4出液更加均匀。具体理由为，在给药腔体42中，越靠近远端，液体流阻越大，释药孔411适当变大，便于药液流出，使得该释药孔411(靠近远端一侧的释药孔)的卸压与前一个释药孔(靠近近端一侧的释药孔)的卸压尽量保持一致，进而保证出液更加均匀。需理解，在本领域中，装置的总长度较长且细，给药腔体42的尺寸对液体流阻影响很大，释药孔411的逐渐变径的设置于给药腔体42，克服了液体出液不均匀的技术困难。
表A为释药孔等径-释放药量的测量表
备注：表A中，释药孔411沿给药腔体42近端至远端，释药孔411的编号依次为1至5。
表B为释药孔直径依次变大-释放药量的测量表
备注：表B中，释药孔411沿给药腔体42近端至远端，释药孔411的编号依次为1至5。
表C为释药孔变径-释放药量的测量表
备注：表C中，释药孔411沿给药腔体42近端至远端，释药孔411的编号依次为1至7。
如表A可知，释药孔的直径均一设置，释药孔释放的药量越来越少，药量的最大差值可达0.96uL。由表B可知，沿近端至远端，释药孔直径之间变大，释放的药量差异变小，出药量趋于均匀，释放药量呈逐渐变小的趋势变缓。
由表C可知，通过调节孔大小，使得远端的孔比近端孔大，可以使得释药孔的中间部位的孔4(编号3)、孔5(编号5)有较大的出药量，两端较小的出药量，尽管无法实现均匀出液，但是球囊的中间位置与病变部位的中间部位接触最为紧密，治疗效果佳。
进一步的，当给药腔体42的外表面的横截面呈三角形结构，所述给药腔体42的尺寸具有特定的设置，进而满足特定场景的使用。例如，所述给药腔体42的外尺寸的高度为0.1-1.0mm(横截面三角形中，贴附球囊的面为底面，底面至切入端的方向为高度方向)，例如为0.1、0.2、0.3、0.4、0.5、0.6、0.7、0.8、0.9以及1.0mm。优选的，所述给药腔体42的外尺寸的高度为0.3-0.7mm。所述给药腔体42的壁厚为0.01-0.1mm，例如是0.01、0.03、0.05、0.07、0.1mm。优选的，所述给药腔体42的壁厚为0.03-0.07mm。所述给药腔体42的长度为5-50mm。给药腔体42的三角形的内腔顶角(切入端的角)为10-80°，例如是10°、20°、30°、40°、50°、60°、70°、80°。给药腔体42的非内腔顶角为10-70°，例如10°、20°、30°、40°、50°、60°、70°。
进一步的，所述释药孔411的孔径可以是0.01-0.2mm，例如是0.01、0.02、0.03、0.04、0.05、0.06、0.07、0.08、0.09、0.1、0.11、0.12、0.13、0.14、0.15、0.16、0.17、0.18、0.19、0.2mm。优选的，所述释药孔411的孔径可以是0.05-0.15mm。所述释药孔411的间距在0.05mm与7mm之间，例如是0.05、0.2、0.4、0.6、0.8、1、1.2、1.4、1.6、1.8、2、2.2、2.4、2.6、2.8、3、3.2、3.4、3.6、3.8、4、4.2、4.4、4.6、4.8、5、5.2、5.4、5.6、5.8、6、6.2、6.4、6.6、6.8、7mm。
进一步的，沿所述球囊51的径向方向，即在所述切入端423的延伸方向延伸设置尖角，以形成一微凸角4231，所述微凸角4231沿切入端的轴向延伸设置，所述微凸角4231用于提供相对尖锐的端头，微凸角4231还能够提高其刺入组织的硬度和刚性，更加便于药物释放组件4刺入病变组织。优选的，所述微凸角4231的端头可以开刃也可以不开刃设计。
较佳的，所述给药腔体42的内表面形状可以是三角形管腔、圆形管腔、矩形管腔、多边形管腔或者异型管腔。
优选的，所述给药腔体42的内表面的形状是三角形管腔；
进一步的，当所述药物释放组件4设置有所述微凸角4231时，所述给药腔体42的横截面在三角形的基础上，沿切入端的方向延伸设计具有尖角的空腔，形成类三角形中空管。所述类三角形中空管的横截面的形状与含有微凸角的给药腔体的外表面的横截面的形状一致，所述空腔同样供液体输送。需理解，即使切入端423有延伸设计的微凸角4231，药物释放组件4开设于切入端423的微凸角4231上，便于药物输出。
进一步的，沿所述药物释放组件4的轴向，所述三角形中空管呈变尺寸设计。优选的，沿近端至远端的方向，所述三角形中空管的尺寸逐渐变小，进而使得出液更加
均匀。
进一步的，三角形中空管的腔壁体可以是等尺寸的，还可以是变尺寸的设计。例如，所述三角形的侧壁体，沿球囊的径向的延伸方向，所述侧壁体厚度不变化、或者逐渐变宽或者变窄。当三角形中空管的外壁的侧壁对应的两个角大于60°时，沿球囊的径向的延伸方向，所述侧壁体可以逐渐变宽。当三角形中空管的外壁的侧壁对应的两个角小于60度时，沿球囊的径向的延伸方向，所述测壁体可以逐渐变窄。如此，可以使得药物释放组件4刺入病变组织的同时给药腔体42的容积不变，便于药液输送的管理，例如，不会因为给药腔体42容积的变化而影响输送的压力、体积等参数。
进一步的，所述释药孔41可以是圆孔、椭圆孔、方形孔、矩形孔、三角形孔、异型孔或者其中任何一种孔的组合。具体根据药物释放量以及药物释放压力进行设定。
进一步的，所述药物释放组件4，例如所述三角形中空管、类三角形中空管，采用的材料为树脂、陶瓷、不锈钢、尼龙、可降解聚合物或者这几种材料的组合等。作为优选，陶瓷材料例如可以是氧化铝、氧化锆、氧化镁、磷酸钙或者可以是这几种材料的组合等，如此使得该部件(三角形中空管)具有生物相容性好，满足临床需求的机械强度，以及良好的可制造加工性，便于批量生产。
进一步的，所述药物释放组件，例如所述三角形中空管、类三角形中空管，采用超精密微纳3D打印技术。优选的，采用烧结工艺，更优的，采用激光烧结或者高温烧结。在现有的3D打印技术领域常用的材料是树脂、不锈钢等，但是受限于材料属性，其加工的精度差。陶瓷烧结这一工艺解决了精度差的问题。因此，结合材料与工艺，其对于精度的控制更高，可以达到2～5μm的误差范围，达到了精度可控的要求。
在本实例中，药物释放组件4可以是一组或多组。药物释放组件4为多组时，该些组药物释放组件4分别通过多个输药控制单元或同一个输药控制单元控制药物的运动，这样可以单独控制药物的运动力。释放结构可以只包括释药孔411，控制可以药物的运动力穿过释药孔411的力即可控制药物进入目标区域的力。优选的，所述释药孔的孔径从小到大的孔径大小设置，更方便控制药物进入目标区域的力。
本实例中，球囊组件还可以包括导引导管(图9未示出)，球囊51密封附接在导引导管上，球囊51折叠形成多个折叠翼，其沿着导引导管周向设置，每对相对设置的折叠翼形成一折叠翼空间，该些药物释放组件分别容置在该些所述折叠翼空间内。
该些药物释放组件4被配置为将药物植入所述目标区域或注射入所述目标区域。释放结构还包括一基座，基座的上表面和其它外周面形成所述给药腔体，所述基座的上表面沿着所述球囊长度方向开设与释药孔连通的贯通孔，所述释药孔通过贯通孔与所述给药腔体连通。
请参阅图9，在给药通道不设置穿刺结构的方案中，当输药控制单元给出的外力足够可控时，可以通过外力直接将药物释放组件植入所述目标区域或注射入所述目标区域。
本实施例提供的利用球囊实现药物输送的装置的其他结构，可参考上文的利用球囊实现药物输送的装置的内容，具体不再展开描述。
【实施例六】
请参阅图11，图11为本实施例六提供的给药装置的示例图。
本实施例六提供的给药装置，其是在实施例1至实施例五的装置上涂覆一层涂层结构，例如是药物涂层。其可以是在球囊的表面涂覆药物，可以是在穿刺组件(或者药物释放组件)上涂层药物，也可以同时涂覆。该药物和药涂层可以同时在面和点两个维度对病变部位(如病变血管)进行治疗作用。当然，在图11中，为了便于示意，采用虚线示意装置外部具有一层涂层结构，并不代表真实涂层结构。
所述涂层结构的厚度、药量浓度等参数可以根据实际情况进行设置。例如，所述涂层的厚度与药量浓度可以与药物药液匹配在一起实现药物治疗。再者，所述涂层的药物可以是一种药物，所述通过球囊穿刺组件或者药物释放组件输送的是另外一种药物。两种药物的不同，相互匹配，进而实现了药物协助治疗。
【实施例七】
一种实现药物输送的方法，采用上述的装置来实现精准药物输送，包括以下步骤：
配置所述球囊为折叠构型；
球囊被引导至目标位置后，
通过给第二通道充压作用于球囊膨胀使其处于所述展开构型：球囊的膨胀带动穿刺组件的穿刺部凸出；或者，球囊的膨胀带动药物释放组件紧贴目标位置的组织；
药物分别通过一个或者多个药物输送通道、每一药物输送通道对应的给药腔体、
给药腔体连通的所述释药孔各自输送至目标区域。
球囊可以被配置为转动至一预设位置后，药物分别通过多个药物输送通道、每一药物输送通道对应的给药腔体、给药腔体连通的释药孔一次或多次输送至目标区域。
在球囊泄压后，所述球囊恢复折叠状态，带动穿刺结构撤出目标区域并包覆穿刺结构。
以上任意实施例提供的利用球囊实现药物输送的装置或者给药装置均可以用于体腔狭窄的部位，体腔狭窄其包括血管狭窄、尿道狭窄、输尿管狭窄、食道狭窄、前列腺尿道狭窄、泌尿道狭窄、尿道狭窄、输尿管狭窄、冠状动脉狭窄、气管狭窄、支气管狭窄、贲门失弛缓症狭窄、支架狭窄、窦狭窄、胃狭窄、小肠狭窄、十二指肠狭窄、空肠狭窄、回肠狭窄、结肠狭窄、直肠狭窄、大肠狭窄、胆道狭窄、动静脉内瘘吻合口以及其他非血管强中的没有血液的通道等。
下文将以食道狭窄、前列腺腺体狭窄、血管狭窄、冠状动脉血管狭窄为例进行展开阐述。
【实施例八】
食管癌是常见的恶性肿瘤之一。内镜下黏膜剥离术(ESD)因创伤小，并发症少而被广泛应用于治疗食管癌疾病。然而，ESD术后会引起瘢痕纤维组织增生从而导致消化道管腔直径变小，即食管狭窄，并影响消化道内容物正常通过。
内镜下球囊扩张术(EBD)可预防并治疗ESD术后食管狭窄。然而，狭窄严重者仍需进行多次球囊扩张术EBD。反复扩张，预后通常不明显。因此，本发明专利提供了一种器械和治疗方式：将球囊扩张和药物注射结合再一起，从而大大减少EBD的次数，也提供了更多可注射药物的选择。本实施例中，所注射药物包括但不限于：糖皮质激素，如：强的松龙、曲安奈德、甲泼尼松、倍他米松、丙酸倍氯米松、泼尼松龙、氢化可的松、地塞米松等。
本实施例八还提供一种食道球囊装置，所述食道球囊装置包括如上所述的利用球囊实现药物输送的装置。需理解，所述食道球囊装置可以采用上述实施例一至六中的任一项装置。本实施例八示意性的采用实施例一提供的装置进行阐述，据此可参考图1。
所述食道球囊装置包括：输送导管1、多组穿刺组件2以及球囊组件3。
输送导管1中的第一通道的内径为0.1～0.5mm，若内径太小，流阻过大，不利于药物输送。
根据食道的解剖结构及特征，本申请中，所述穿刺组件2优选为3-6组。对应的所述折叠翼为3～6对；多组穿刺组件2沿球囊31的周向排布，使得装置在穿刺时，对方向性要求不高，只要能够放置于病变部位即可满足治疗要求，提高治疗效率。根据食道的结构特定的选择所述球囊的直径为6～15mm，进而使得球囊31在扩张时能够带动穿刺组件2刺入食道壁中。所述穿刺组件2的高度为0.5～1.7mm，进而使得穿刺组件2能够刺入食道壁进而实现有效的药物注射。本领域技术人员都知道，食道病变中周向病变的概率很大，本装置能够实现在一次植入治疗中，即可以扩张食道，又能够治疗周向上的病变的情况，治疗效果上其可以治疗3/4及以上的周向病变。每组穿刺组件2优选包括6-18个穿刺结构21。如此，设置至少18个注射点，可以实现均匀注射，实现药物的高效输送，相比传统的食道手术中的单点注射，其减少了药物液体的反流，同时，因为球囊31的扩张，球囊外表面和食道内壁紧贴着，阻止了药物液体的反流，达到了精准注射的效果，大大提高了治疗效率。此外，相比涂药的球囊，其能够将药物直接注射至病变部位，提高了药物的输送效率(请参考表3)。进一步的，所述穿刺组件2的高度为0.5～1.7mm，在该范围内，穿刺组件21能够有效的穿透食道的黏膜以及黏膜下层(黏膜及黏膜下层0.5～1.5mm)，同时不至于穿透食道部位的血管，本实施例的穿刺组件2与目标解剖学结合，可以提高药物的渗透率。优选的，每个穿刺结构21之间的距离为2.5～15mm，进而能够使得药物被充分利用，提高药物的利用率。
球囊组件3中球囊31的长度优选为45～80mm。球囊31的折叠翼311为6或者8个，即为3～4组折叠翼。球囊31的通过外径小于3.2mm。所述球囊优选为顺应性球囊。更优选的，为三级扩张球囊。如此，实现了所述装置能够适配于食道，为有效输送药物提供前提条件，保障其使用的安全性、有效性。优选的，所述折叠翼空间的高度H在0.5～2.0mm之间，例如是0.5、1、1.5、2mm，进而可以在包覆穿刺组件的前提下，尽量减少球囊的周向尺寸。
通过所述第一通道的药物总注射量为120mg，需理解，所述120mg可以表示
120mg偏高或者偏低的范围；药物液体的浓度为10～20mg/ml；药物液体的总注射量为6～12ml；每个穿刺结构的注射量为0.1～0.3ml。如此，使得药物释放率高于87％，相比现有技术，药物释放提高了8倍多。在其他的实施例中，所述药物的总注射量可以是100、110、130、140mg等。
所述食道球囊装置的总的穿刺结构的个数大于18个，所述食道球囊装置的注射时间小于1.5分钟，进而大大降低了食道球囊装置植入食道中的时间，提高了治疗效率，降低了患者的痛苦。
优选的，所述球囊在展开构型下，所述穿刺结构的穿刺力≤0.7N。通过这样的设置，可以保证本实施例装置在植入食道装置中，保证不会对食道形成较大的损伤，同时还能管够达到有效输送药物的目的。例如，本实施例可以通过直径-压力、注射量、总注射量等参数的设置，使得装置的穿刺力≤0.7N，在穿刺结构能够刺入组织的前提下，保证了其安全性、有效性。
此外，由于治疗效果佳、治疗效率高，进而避免了多次球囊扩张的治疗，在食道狭窄的治疗上提供了质的改变。此外，本实施例中的食道球囊装置采用药物载体治疗，药物载体具有缓释功能，可以缓释1周至6个月之久，。优选的，缓释周期为1～12周。更优选的，缓释周期可以根据病症的情况适应性的选择缓释时间，进而达到缓释治疗的效果。无需进行多次球囊扩张治疗。同时，为医患提供了良好的治疗环境。
本实施例中，所注射药物包括但不限于：糖皮质激素，如：糠酸莫米松、强的松龙、曲安奈德、甲泼尼松、倍他米松、丙酸倍氯米松、泼尼松龙、氢化可的松、地塞米松等。
优选的，所述食道球囊装置还包括导管座(Hub)，导管座与第一通道连接，用于输送药物，优选的，所述导管座为双鲁尔接头(2-Way Hub)或者三鲁尔接头(3-Way Hub)甚至多鲁尔接头的设计；导管座上的一个鲁尔接头可以与阀、连接器、注射器或压力充盈器相连接，通过其向输液通道中给定特殊的药物，该药物为指定的药物系统。
试验验证
食道球囊样品1：球囊为顺应性的三级扩张球囊，球囊直径6～8mm、球囊长度45mm、球囊通过外径2.8mm、球囊折叠翼片数6片、穿刺组件为3组、每排6个针、穿刺结构的高度0.5mm。
食道球囊样品2：球囊为顺应性的三级扩张球囊，球囊直径8～10mm、球囊长度50mm、球囊通过外径2.8mm、球囊折叠翼片数6片、穿刺组件为3组、每排7个针、穿刺结构的高度0.8mm。
食道球囊样品3-1：球囊为顺应性的三级扩张球囊，球囊直径10～12mm、球囊长度60mm、球囊通过外径3mm、球囊折叠翼片数6片、穿刺组件为3组、每排6个针、穿刺结构的高度1mm。
食道球囊样品3-2：球囊为顺应性的三级扩张球囊，球囊直径10～12mm、球囊长度60mm、球囊通过外径3mm、球囊折叠翼片数8片、穿刺组件为4组、每排6个针、穿刺结构的高度1mm。
食道球囊样品3-3：球囊为顺应性的三级扩张球囊，球囊直径10～12mm、球囊长度60mm、球囊通过外径3mm、球囊折叠翼片数8片、穿刺组件为4组、每排7个针、穿刺结构的高度1mm。
食道球囊样品4：球囊为顺应性的三级扩张球囊，球囊直径12～15mm、球囊长度70mm、球囊通过外径3.2mm、球囊折叠翼片数8片、穿刺组件为4组、每排10个针、穿刺结构的高度1.3mm。
食道球囊样品5：球囊为顺应性的三级扩张球囊，球囊直径15～18mm、球囊长度80mm、球囊通过外径3.2mm、球囊折叠翼片数12片、穿刺组件为6组、每排18个针、穿刺结构的高度1.7mm。
表1本实施例八的食道球囊的直径-压力对应表
表2本实施例八的食道球囊的药物注射量
本申请的食道球囊装置，在三级扩张下达到8～11atm，实现了良好的扩张及阻止药液反流。通过直径-压力、注射量、总注射量等参数的设置，使得装置的穿刺力≤0.7N，在穿刺结构能够刺入组织的前提下，保证了其安全性、有效性。
在本实施例中，所述注射的药物是曲安奈德(TA)。所述药物液体的总注射量6-12ml，每个穿刺结构的注射药液的量为0.1～0.3ml。药物液体的浓度为10～20mg/ml，药物总的注射量为120mg。
表3食道手术单点注射与本申请食道球囊装置治疗时间对比表
由图3可知，本申请的装置，相比现有技术中单点注射的技术，能够节约25倍的时间，大大提高了治疗效率。
图12示出了采用本实施例的食道球囊装置进行体外注射后的组织示意图。本实施例采用猪的食道的组织，采用食道球囊样品3-1进行体外的组织实验。采用有色的生理盐水(蓝色)模拟药液，将球囊样品缓慢扩张到8atm，维持压力不变。再缓慢注射1.5ml液体。图中，皮下组织中的蓝色的液体为药物液体，即表示被注射的药物进入了食管黏膜的下层。
表4本申请的食道球囊装置的样品3-1的出药率以及组织含药率
出药率＝打入组织前的药量/打入装置前的药量×100％。
所述组织表示猪的食道的组织，采用的药物为曲安奈德(TA)。所述药物载体微球中，药物载体采用PLA材质，药物为糖皮质激素类的药。
本案实施例通过微针注射的方式，将药物(更优的缓释药物微球)注射入食道组织。采用高效液相色谱法(HPLC)测得，药物转移率(即组织含药率)将达到＞80％以上，可实现长期抑制组织增生的效果。此外，本申请采用的食道球囊装置，采用了单层球囊的结构，相比于双层球囊，能够便于药物注射，能够在很小的推力作用下实现定量注射。另，采用本申请的食道球囊装置进行注射，可以不采用泵进行注射，直接手动进行，进而实现了少量的注射。
【实施例九】
目前对于前列腺增生(BPH)所有术式均为切除增生腺体组织，对于欲保留前列腺器官的患者无公认的有效手段。经尿道柱状球囊前列腺扩开术(TUCBDP)是近年来出现的一种治疗BPH的新技术，可以保留腺体，手术时间更短，安全性更高。然而，对于治疗良性前列腺增生BPH的中至重度下尿路症状，及其安全性、有效性的研究仍在进行中。本实施例为治疗BPH提供了另一种治疗选择。所述球囊导管的球囊部件可由多球囊组成，或多腔球囊组成。所述药物可选择：紫杉醇、雷帕霉素、α还原酶抑制剂(例如，非那雄胺、度他雄胺)或它们的缓释药物微球。
另外，除上述非血管腔道或非血管狭窄外，还包括气道、窦、气管(支气管)、结肠、胆道、胃、小肠、十二指肠、空肠、回肠、直肠、大肠、泌尿道、前列腺、尿道、输尿管和其它非血管腔中的那些没有血液的通道。
本实施例九还提供一种前列腺尿道扩张装置，所述前列腺尿道扩张装置包括如上所述的利用球囊实现药物输送的装置或者给药装置。需理解，所述前列腺球囊装置可以采用上述实施例一至六中的任一项装置。本实施例九示意性的采用实施例一提供的装置进行阐述，据此可参考图1。
所述前列腺尿道扩张装置包括：输送导管1、多组穿刺组件2以及球囊组件3。
输送导管1中的第一通道的内径为0.1～0.5mm，若内径太小，流阻过大，不利于药物输送。
根据前列腺尿道的解剖结构及特征，本申请中，所述穿刺组件2优选为6～12组。
多组穿刺组件2沿球囊31的周向排布，使得装置在穿刺时，对方向性要求不高，只要能够放置于病变部位即可满足治疗要求。每组穿刺组件2优选包括6-18个穿刺结构21，每个穿刺结构21之间的距离为2.5～15mm。如此，设置至少18个注射点，可以实现均匀注射，实现药物的高效输送，其减少了药物液体的反流，同时，因为球囊的扩张，球囊外表面和组织内壁紧贴着，阻止了药物液体的反流，达到了精准注射的效果，大大提高了治疗效率。此外，相比药物涂层的球囊，本申请的装置药物转移率、出药率高，治疗效率高。进一步的，所述穿刺组件2的高度为1～2mm，优选为大于等于1.5mm，在该范围内，穿刺组件21能够有效的刺入前列腺尿道。如此设置，使得药物系统(例如是药物药液或者药物载体)能够直接的进入组织中，提高治疗的效率。还可以通过穿刺组件21输送药物载体，药物载体在组织中实现缓释，进而保证药物载体中的药物能够持续的被释放，不会导致单次注射量过大影响组织，或者不会使得因为注射量过大而使得药物流失。
球囊组件3中球囊31的长度优选为30～45mm。球囊31的直径约为5～50mm，优选的，为25～30mm，例如是5、10、15、18、20、22、24、25、26、27、28、29、30、35、40、45、50。球囊直径可以独立的在该范围内或特定尺寸中的任一个范围内。球囊31的折叠翼311为12或者24个，即为6～12组折叠翼。球囊31的通过外径小于7mm，优选的，使用时匹配21Fr镜鞘。所述球囊优选为顺应性球囊，可以使球囊直径具有2-3％的增幅。如此，实现了所述装置能够适配于前列腺尿道，为有效输送药物提供前提条件，保障其使用的安全性、有效性。
每次注射药物的总量为2～20mg，优选的，3～8mg，例如3、4、5、6、7、8mg，注射剂量为小于12.5ml/每个穿刺结构，优选的，小于0.5ml/每个穿刺结构。
如图13与图14所示，本实施例还提供一种前列腺尿道扩张装置，所述装置包括球囊31，所述球囊31包括内部相连通的靠近远端的球囊结构(可参考31a或31c)与靠近近端的球囊结构(可参考31b)，所述靠近远端的球囊结构用于至少设置于膀胱颈的位置，以阔开膀胱颈。所述靠近近端的球囊结构用于至少设置于前列腺尿道的位置，以阔开前列腺尿道。所述靠近远端的球囊结构的最大直径小于靠近远端的球囊结构的最大直径，以使得靠近远端的球囊结构所阔开的膀胱颈的尺寸小于靠近远端的球囊结构所阔开的前列腺尿道的尺寸，进而避免因为膀胱颈被过分扩大会引起尿液回流，导致小便不畅。相比于现有技术中采用球状的球囊或者等径的圆柱形球囊，本实施例的前列腺尿道扩张装置，通过结合前列腺尿道及膀胱颈的解剖结构、医生临床需求以及医学研究，通过设置相同连通的不同径向尺寸的球囊结构，其解决了临床中尿液回流、小便不畅技术问题。优选的，靠近远端的球囊结构和/或靠近近端的球囊结构的至少部分结构上设置穿刺组件、药物释放组件和/或药物涂层，以实现球囊的给药。
优选的，所述球囊31在工作时的扩张压力不小于1.5atm。例如1.5、2、2.5、3、3.5、4、4.5、5、5.5、6、6.5、7、7.5、8等，以提供在球囊31在变径条件下的有效的实现扩张的压力。更优的，所述球囊31在工作时的扩张压力为4-6atm，进而实现精准的扩张。
优选的，药物涂层、穿刺组件或者药物释放组件的轴向范围长度可以大于病变部位待治疗的长度，可以小于病变部位待治疗的长度。
优选的，所述球囊31的长度大于病变部位待治疗的长度。
优选的，如图13所示，，所述球囊的靠近远端的球囊结构与靠近近端的球囊结构可以为两端缩口的圆柱形结构。更优选的，如图13所示，靠近远端的球囊结构为第一球囊31a，靠近近端的球囊结构为第二球囊31b，即所述球囊31包括第一球囊31a以及第二球囊31b，所述第一球囊31a与第二球囊31b连通，第一球囊31a与第二球囊31b均为两端缩口的圆柱形结构。所述第一球囊31a用于至少设置于膀胱颈的位置，以阔开膀胱颈。所述第二球囊32b用于至少设置于前列腺尿道的位置，以阔开前列腺尿道。优选的，所述第一球囊31a相比第二球囊31b更加靠近所述装置的远端，所述第一球囊31a的最大直径小于所述第二球囊32b的最大直径，以使得第一球囊31a所阔开的膀胱颈的尺寸小于第二球囊32b所阔开的前列腺尿道的尺寸，进而避免因为膀胱颈被过分扩大会引起尿液回流，导致小便不畅。所述第一球囊31a的最大直径小于第二球囊32b的最大直径，以使得第一球囊31a所阔开的膀胱颈的尺寸小于第二球囊所阔开的前列腺尿道的尺寸。优选的，所述穿刺组件、所述药物释放组件和/或者药物涂层可以设置于第一球囊31a和/或第二球囊31b上。在图13中，所述穿刺组件2、所述药物释放组件和/或者药物涂层设置于所述第二球囊31b上。
如图14所示，本实施例还提供一种前列腺尿道扩张装置，其中，靠近远端的球囊结构为第三球囊31c，靠近近端的球囊结构为第二球囊31b，所述球囊包括第三球囊31c与第二球囊31b，所述第三球囊31c为一端缩口的圆柱形，第二球囊31b为两
端缩口的圆柱形，第三球囊31c的圆柱形一端与第二球囊31b的圆柱形的缩口连接并连通。可理解的，所述第三球囊31c用于至少设置于膀胱颈的位置，或者至少设置于膀胱颈以及膀胱颈与尿道的连接部位，以阔开膀胱颈及其周边。所述第二球囊32b用于至少设置于前列腺尿道的位置，以阔开前列腺尿道。所述第三球囊31c的最大直径小于第二球囊31b的最大直径，以使得第三球囊31c所阔开的膀胱颈的尺寸小于第二球囊32b所阔开的前列腺尿道的尺寸，进而避免因为膀胱颈被过分扩大会引起尿液回流，导致小便不畅。所述穿刺组件、所述药物释放组件或者药物涂层设置于第三球囊31c和/或第二球囊31b。如此，可以将第三球囊31c设置于用于扩张膀胱和前列腺尿道的连接处。
优选的，所述第二球囊31b的扩张直径为20-50mm，例如可以为20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、40、50mm等。优选的，所述第二球囊31b的长度为20-80mm，例如可以为20、25、30、31、32、33、34、35、40、41、42、43、44、45、46、47、48、49、50、55、60、65、70、75、80mm等。优选为30-50mm。
优选的，所述第三球囊31c的扩张直径为5-20mm，例如可以是5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20mm，以实现有效扩张。优选的，所述第三球囊31c的长度为20-50mm，例如可以为20、25、30、31、32、33、34、35、40、41、42、43、44、45、46、47、48、49、50mm。优选为30-40mm。优选的，如图4A至4C所示，所述穿刺组件的所述给药腔体22的壁厚T可以是0.05～0.2mm，直径D是0.25～0.75mm，或者宽度W是0.3～0.8mm。
优选的，所述药物可选择：紫杉醇、雷帕霉素、α还原酶抑制剂(例如，非那雄胺、度他雄胺)、缓释药物微球以及抗生素药物。
试验验证
前列腺尿道扩张装置样品1：装置直径25mm、装置治疗长度20mm、球囊通过外径5.5mm、装置折叠翼片数12片、穿刺组件为6组、每组6个针、穿刺结构的高度1.5mm。
前列腺尿道扩张装置样品2：装置直径26mm、装置治疗长度30mm、球囊通过外径5.5mm、装置折叠翼片数12片、穿刺组件为6组、每组6个针、穿刺结构的高度1.5mm。
前列腺尿道扩张装置样品3-1：装置直径27mm、装置治疗长度40mm、球囊通过外径6mm、装置折叠翼片数16片、穿刺组件为8组、每组8个针、穿刺结构的高度1.5mm。
前列腺尿道扩张装置样品3-2：装置直径27mm、装置治疗长度40mm、球囊通过外径6mm、装置折叠翼片数16片、穿刺组件为10组、每组9个针、穿刺结构的高度1.5mm。
前列腺尿道扩张装置样品3-3：装置直径27mm、装置治疗长度40mm、球囊通过外径6mm、装置折叠翼片数16片、穿刺组件为10组、每组10个针、穿刺结构的高度1.5mm。
前列腺尿道扩张装置样品4：装置直径28mm、装置治疗长度50mm、球囊通过外径7mm、装置折叠翼片数24片、穿刺组件为12组、每组10个针、穿刺结构的高度1mm。
前列腺尿道扩张装置样品5：装置直径30mm、装置治疗长度50mm、球囊通过外径7mm、装置折叠翼片数24片、穿刺组件为12组、每组11个针、穿刺结构的高度1mm。
表1本实施例九的前列腺尿道扩张装置的药物注射量
表2与本申请前列腺尿道扩张装置治疗时间对比表
本申请的装置，相比涂药球囊，能够节约时间，大大提高了治疗效率。
图15示出了采用本实施例九的前列腺球囊装置进行体外组织穿刺、注射的试验结果示意图。采用猪的前列腺组织的材料。图中，皮下组织中的蓝色的液体为药物液体，即表示被注射的药物进入了食管黏膜的下层。
表3本申请的前列腺尿道扩张装置的样品3-1的出药率以及组织含药
出药率＝打入组织前的药量/打入装置前的药量×100％。
本实施例通过微针注射的方式，将药物(更优的缓释药物微球)注射入前列腺腺体。采用高效液相色谱法(HPLC)测得，药物转移率将达到＞80％以上，可实现长期抑制组织增生的效果。
其次，本案件技术的微针数量较多(至少18个注射点)且周向分布，可以一次性注射所有剂量；相比传统食道手术的单点注射效率更高。例：单点注射需要0.5分钟的话，50针需要25min；本案只需要1-1.5min完成注射药液的操作。
再次，传统单点注射，有药液返流的情况；由于球囊在压力下与前列腺尿道壁紧密贴合，本案在球囊扩张的同时也阻止了药液返流，达到了精确注射、药物转移率高的效果。
【实施例十】
经皮冠状动脉腔内成形术(PTCA)，以打开阻塞的心脏冠状动脉，使血液循环畅通，维持正常的血流动力学特征。在PTCA的治疗过程中，医生通过本实施例提供的注射球囊，以保持血管开放以降低再狭窄及弹性回缩的风险。通过注射球囊的穿刺组件刺入内膜，将药物或缓释药物直接注射进入血管内膜或中膜，达到长期抑制新生内膜增生，从而减少晚期管腔丢失或再狭窄的几率。与传统药物释放球囊(DCB)相比，大大提高了药物转移率。本实施例同样适用于经皮腔内血管成形术(PTA)。针对冠脉或外周血管狭窄，通过实施例一至实施例十一提供的装置，可以减少再狭窄的发生概率。
请参考图16至图20以及图9、图10，图16为本实施例十的注射球囊的整体结构的示意图；图17A为本实施例十的注射球囊的球囊部分的横截面示意图；图17B为本实施例十的另一种注射球囊的球囊部分的横截面示意图；图17C为本实施例十的另一种注射球囊的球囊部分的横截面示意图；图18A为本实施例十的注射球囊的示意图；图18B为本实施例十的另一种注射球囊的示意图；图18C为本实施例十的另一种注射球囊的示意图；图19为本实施例十的一种药物释放组件的示意图；图20为本实施例十的另一种注射球囊的整体结构的示意图。图9为本实施例五提供的给药装置的示意图；图10为本实施例五提供的另一种给药装置的示意图。
本实施例十还提供一种注射球囊，其如上所述的利用球囊实现药物输送的装置。需理解，本实施例提供的注射球囊，可以采用上述实施例一至实施例六中的任一项装置。本实施例十示意性的采用实施例五提供的装置进行阐述。需理解，所述实施例五的装置，例如药物释放组件中，给药腔体为三角形中空管或者类三角形中空管时，该装置可以用于经皮冠状动脉腔内成形术(PTCA)、经皮腔内血管成形术(PTA)中，治疗的冠脉或外周血管狭窄。
本实施例中，如图16所示，注射球囊可以为快速交换结构，除上述部件外，还包括显影环、连接管、海波管和导管座，导管座为2-Way Hub的设计。该结构可以提高整体导管在血管中的通过性。
所述注射球囊，包括输送导管(图9未示出)、至少一组药物释放组件4以及球囊组件5。优选的，如图18A至图18C所示，球囊规格：直径1.2-14mm、长度10-80mm，药物释放组件4可以是一排、两排、三排、四排、六排等。所述输送导管具有近端部分和远端部分，所述输送导管包括互不连通的用于输送药物的第一通道(图9未示出)和用于流通充泄压用的第二通道(图9未示出)，至少在靠近远端部分的所述第一通道
为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道。
所述药物释放组件4包括至少一释放结构41和给药腔体42，所述释放结构41至少包括释药孔411，该组中所述释药孔411连通所述给药腔体42。优选的，所述给药腔体42还包括给药腔421和给药孔422，释药孔411通过给药孔422与给药腔421连通。需理解，所述第一通道与所述药物释放组件4可以设置在球囊51的外表面，或者，所述第一通道与所述药物释放组件4也可以设置在球囊51的内表面。当所述第一通道与所述药物释放组件4可以设置在球囊51的外表面时，所述释药孔411与给药孔422表示为一个结构。当所述第一通道与所述药物释放组件4也可以设置在球囊51的内表面时，所述释药孔411为设置在球囊51上的孔。较佳的，所述注射球囊还包括穿刺部，所述穿刺部与所述释药孔411连通，所述穿刺部呈针状结构。所述穿刺部的内容可参考上文描述，此处不在赘述。
所述第一通道与所述药物释放组件4可以设置在球囊51的外表面。优选的，所述药物释放组件4可以是一空心丝线，空心丝线上设置有释药孔411。给药腔体42的内径≥1μm，例如是2、3、4μm等；优选的，给药腔体42的内径≥3μm；更优的，给药腔体42的内径≥0.1mm，例如是0.2、0.3、0.4mm等。给药腔体42的内/外径之比为0.1～0.9，更优的，给药腔体42的内/外径之比为0.4～0.8。释药孔411的内径小于给药腔体42的内径，优选的，释药孔411的内径小于给药腔体42的内径的0.5倍。每个释药孔411之间的间距为0.1～1mm，优选的，为0.25～0.75mm，例如，0.25mm、0.3mm、0.4mm、0.45mm、0.5mm、0.6mm等。当然，所述释药孔411还可以大于1mm。所述给药腔体42的可以是圆形或者三角形中空管。所述圆形的空心管的外径可以是0.20～0.34mm。如图18A所示，当给药腔体42是圆形时，所述给药腔体42上的释药孔411优选朝向所述球囊51膨胀的方向。当然，在其他的实施例中，如图18B所示，所述给药腔体42上的释药孔411可以是与球囊51膨胀的方向存在一定的夹角，例如球囊膨胀的方向为球囊的径向方向，所述释药孔的轴向与球囊的径向呈一定夹角。例如呈锐角。所述释药孔可以是沿着给药腔体42的轴向呈一排孔结构布设，可以是两排或者三排孔结构布设。进一步的，如图18C所示，在给药腔体42的同一周向方向上，分别具有多个释药孔411，即当所述药物释放组件的释药孔为多排孔结构时，每排孔结构的孔轴向的朝向之间具有夹角，例如是两个(或者两排)释药孔411，如此在给药腔体42上形成两列释药孔411，进而增加了药物释放的通道进而增加了进药量。两列孔的方向朝向球囊的外侧，和球囊的法向呈一定角度5～30°。所述药物释放组件4为三角形空心结构，所述三角形空心结构的一个面与所述球囊连接，所述三角形空心结构的另外两个面分别具有释药孔。即当给药腔体42的横截面是三角形时，三角形柱体的两个侧面优选均具有释药孔411。如图19所示，所示给药腔体42是三角形的空心管时，三角形空心管的开孔则为双排，开孔位于空心管顶边的两侧，三角形空心管的外径可以为0.20～0.34mm。
在本实施例中，每个释药孔411之间的间距至少为0.5mm。
较佳的，所述注射球囊还包括穿刺部，所述穿刺部与所述释药孔411连通，所述穿刺部呈针状结构。穿刺部的高度为0.1mm-2mm，优选的，穿刺部的高度小于0.5mm。根据不同部位调整微针的高度，如此可保证微针只是刺入内壁的内膜或中膜，而不会刺穿管壁，减小医生的操作风险，并保障患者的安全。可以理解，微针靠近球囊的端部直径大于针尖的直径，如此，既方便微针的针尖刺入内壁，也可保证微针与球囊或基座之间的连接稳固。
本申请中，带有穿刺组件的球囊可以应用于血管内疾病的治疗(球囊规格：直径1.2-14mm、长度10-200mm)和非血管内疾病的治疗(球囊规格：直径5-50mm、长度20-200mm)；所述穿刺组件的尺寸为：高0.1-2.0mm、直径10μm-500μm，进而可以提高药物输送的效率。
优选的，所述球囊52冲压时，球囊52的压力在小于3～30atm范围内，进而可以使得球囊52的压力不至于过大而引起内皮撕裂，同时，还能够实现有效的治疗与输送药物。
优选的，所述注射球囊还包括药物涂层，所述药物涂层的药物可以与所述第一通道中输送的药物相同或者不同。具体可参考实施例六。
优选的，所述注射球囊包括导管座(Hub)，导管座与第一通道连接，用于输送药物，优选的，所述导管座为双鲁尔接头(2-Way Hub)或者三鲁尔接头(3-Way Hub)甚至多鲁尔接头的设计；导管座上的一个鲁尔接头可以与阀、连接器、注射器或压力充盈器相连接，通过其向输液通道中给定特殊的药物，该药物为指定的药物系统。
进一步的，所述注射球囊除快速交换结构外，所述球囊导管也可以为全程交换结构。除内管、外管、球囊和给药刻痕结构外，还包括显影环和导管座(Hub)，所述显
影环设置于球囊中，导管座为特殊的3-Way Hub设计，如图20所示。该结构可以提高导管在血管中的操控性。本实施例十的注射球囊适用通用的球囊充盈器，球囊充盈器与导管座上的药物接口相连接，通过其向输液通道中给定特殊的药物，该药物为指定的药物系统，例如指定的药液，也可以为指定的药物微球。
优选的，所述药物释放组件4可以具有硬质导管与软质导管，硬质导管提供释放结构41(61)所需要的固定的管腔。药物释放组件4的方案可以参考如图5B至图5E所示的结构。沿所述球囊31的轴向，药物释放组件4的给药导管包括硬质导管与软质导管，硬质导管与软质导管分段间隔设置。例如，包括两段硬质导管和一段软质导管。当然，硬质导管与软质导管的数量不做限制。优选的，软质导管的数量比硬质导管的数量少一个。穿刺结构优选设置于硬质导管上。所述软质导管的设置为给药导管提供柔性，提高装置的通过性，便于装置的输送。另外，软质导管的设置还外药物释放组件4的错位设置提供前提条件。优选的，如图5D-图5E所示，沿所述球囊31的周向，前一段的硬质导管与后一段的硬质导管在球囊51的周向方向不同(图5D为沿球囊51周向布设的给药导管的展开示意图)，以形成错位布设。在图5D中，实线表示其中一段硬质导管在某一个角度周向布设，虚线表示其中另一段硬质导管在另一个角度周向布设。如此设置，可以使得在较长的球囊51的周向方向上，沿一个给药导管，药物释放组件4能够错位在不同的周向，进而使得周向给药均匀，提高注射效率。优选的，硬质导管的尺寸，优选的，软质导管的轴向尺寸为0.5～20mm。
本实施例十还提供一种注射球囊缓释系统，其包括如上任一项所述的注射球囊以及药物系统，所述药物系统包括药物颗粒和/或药物载体；药物颗粒在组织液中能够被溶解，药物颗粒被溶解为药物液体，药物液体在组织中从药物载体中逸出进而实现缓释。进一步的，所述注射球囊缓释系统采用的注射球囊包含有穿刺部，药物系统通过穿刺部进入组织的内部，进而实现1周～6个月的药物缓释。优选的，所述穿刺部的出药孔的径向尺寸大于药物载体的径向尺寸。
本实施例提供的注射球囊，通过设置单独的第一通道，提高了药物的转移率，同时，由于释药孔的特定设置，可以实现精准给药，并且，其对球囊的膨胀压力要求小，不会因为球囊膨胀的压力大小而影响药物注射的压力；还可以实现靶向给药，也可以多次给药。
试验验证
表1与表2为采用本实施例的药物系统被植入血管中的药物的试验结果。
组织：血管
药物颗粒采用Sirolimus药
药物载体采用PLA基材，药物载体中承载Sirolimus药。
表1为本实施例提供的药物系统的出药率与组织含药率的对照表
表2为本实施例提供的药物系统的药物有效时间的对照表
药物转移率将达到＞79％以上，可实现长期抑制组织增生的效果。
【实施例十一】
请参阅21A至图21B，图21A为本实施例十一提供药物系统的一种实例示意图；图21B为本实施例十一提供药物系统的第二种实例示意图。
本实施例十一提供一种药物系统，所述药物系统采用本实施例一至实施例十的装置进行输送，进而实现将药物系统输送至目标位置，药物被输送于目标位置之中，进而实现药物相应的治疗效果。
所述药物系统可以是药物颗粒和/或药物载体100，所述药物颗粒和/或所述药物载体能够与一溶液混合形成药液，药液被输送至目标组织位置。所述药物载体100具有孔隙，所述孔隙能够容载药物，例如药物颗粒，药物载体100被输送至目标组织中，需理解，药物颗粒在组织液中能够被溶解，例如被生理盐水溶解，药物颗粒被溶解为药物液体，药物液体在组织中从药物载体100中逸出进而实现缓释。优选的，所述药物颗粒为结晶态的药物晶体，所述药物晶体被输送至组织中能够实现药物缓释，所述
药物颗粒的粒径为1～1000μm，优选的，所述药物颗粒的粒径为1～150μm，更优选的，所述药物颗粒的粒径为1～50μm，例如1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50μm等；所述药物晶体的缓释周期在一周至6个月。需理解，药物的缓释与药物的含量、药物载体的分子结构、分子量、药物载体的孔隙率等有关。本实施例中，申请人通过筛选药物载体的分子结构、分子量(即药物所选的材质)，以及药物的孔隙率得到了理想的缓释药物。缓释周期可以在1周至6个月。
当所述药物系统采用药物颗粒时，药物颗粒通过输送液(例如生理盐水等)混合形成混悬液进而输送至目标组织中。所述药物输送的速率，药量可参考上文描述。可理解的，所述药物颗粒可以是一种广义的药物的概念，，例如，所述药物可以是治疗腔道狭窄的药物。可选的，药物可以为包含药物的药物体或组合物，其包括一种或多种治疗物质、诊断物质、一种药物、一种治疗组合物、一种诊断组合物、生理活性剂、一种生物化学活性剂、一个或多个活细胞、DNA、RNA、核酸、用于将遗传物质递送到目标部位中的细胞载体、抗炎剂、一种抗再狭窄剂、一种细胞增殖抑制剂、平滑肌增生抑制剂、紫杉醇、雷帕霉素、依维莫司、血管活性剂、血管扩张剂、血管收缩剂、抗生素、抗凝剂、血小板凝集抑制剂、抗纤维化剂、药学上可接受的载体、脂质基载体及其任意组合。此外，所述药物还可以是α还原酶抑制剂，例如，非那雄胺、度他雄胺。
请参阅图21A，优选的，所述药物载体为可降解高分子材料与药物混合制成药物缓释微球，所述药物缓释微球的直径在1～1000μm，优选的，所述药物缓释微球的直径为1～150μm，例如，可以约为50、60、70、80、90、100、110、120、130、140、150μm等，更优选的，所述药物缓释微球的直径为1～50μm，例如1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50μm等；所述缓释周期在1周至6个月。优选的，所述药物载体具有孔隙，所述孔隙中容载药物，所述药物从孔隙中缓释，所述药物载体的直径在1～1000μm，优选的，所述药物载体的的直径为1～150μm，更优选的，所述药物载体的直径为1～50μm，例如1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50μm等；所述缓释周期在1周至6个月。较佳的，药物载体100上具有若干微孔101，所述微孔101在药物载体100上为通孔或者不通孔的设置，进而能够容纳药物。当然，在其他的实施例中，所述微孔101的尺寸小于药物的尺寸即可。优选的，所述药物载体提还可以采用高分子可降解材料与药物混合制成的药物缓释微球，药物在组织中，因为药物缓释微球中的药物浓度高，进而可以使得药物释放出来。采用实施例一至实施例十中的装置输送药物载体时，相比于输送药物颗粒，所需要的输送效率高、输药控制单元可配置加载到球形微粒上的输送力大小，以控制将球形微粒通过药物输送通道输送至目标区域、和/或控制输送至目标区域的持续时间、和/或控制输送至目标区域的深度。药物载体的材料可以为高分子生物可降解材料。高分子生物可降解材料包括且不限于：聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、二氧化碳聚合物(PPC)、聚丁二酸丁二醇酯(PBS)、脂肪芳香聚酯Ecoflex(PBAT)、聚对苯二甲酸丙二醇酯(PPT)、聚β-羟基烷酸酯(PHA)、聚ε-己内酯(PCL)、聚对二氧环己酮(PPDO)中的一种，或者是其中任意多种的聚合物的共聚物或者共混物等。优选的，在任意多种的聚合物的共混物中，每个组分的含量为0～100％。
请参阅图21B，药物载体的形状还可以其他的结构，不限于球状。例如，药物载体可以为缓释载药棒材或片材，输药控制单元可配置加载到缓释载药棒材或片材上的输送力大小，以控制将缓释载药棒材或片材通过药物输送通道输送至目标区域，棒材或片材的材料可以为高分子生物可降解材料。棒材和片材的设置，是根据实际的载药需求进行的设置。
优选的，所述药物载体上还可以设置一包覆层，药物设置在包覆层内。包覆层能够被溶解，进而实现药物载体的缓释，所述缓释周期在1周至6个月。
优选的，所述药物载体为球状、棒材或者片材；优选的，所述药物晶体为球状、多边形状、棒材或者片材。
所述药物载体100可持续地进行药物释放功能。其释放周期在1周至6个月之间。
优选的，所述释药孔的直径大于所述药物系统的直径，进而便于药物系统的输出。
试验验证
表1与表2为采用本实施例的药物系统被植入前列腺腺体的药物的试验结果。
组织：前列腺腺体
药物颗粒采用Sirolimus药
药物载体采用PLA基材，药物载体中承载Sirolimus药。
表1为本实施例提供的药物系统的出药率与组织含药率的对照表
表2为本实施例提供的药物系统的药物有效时间的对照表
本实施例通过采用实施例九的装置进行注射，其注射压力注射球囊，注射速率注射球囊方式，将药物颗粒或者药物载体注射入前列腺腺体。药物转移率将达到＞80％以上，可实现长期抑制组织增生的效果。
【实施例十二】
本实施例十二提供一种医学微创系统，包括实施例一至实施例十所述的任一项装置，以及包括实施例十一所述的药物系统。即，上述实施例一至实施例十中的装置，用于输送本实施例十一所述的药物系统，如此，通过该装置实现了药物输送，进而实现了该药物的输送，进而为药物系统的缓释提供前提条件。
优选的，所述实施例一至实施例十中的任意一项装置包括输药控制单元，所述输药控制单元可配置加载到所述药物的输送力大小，以控制所述药物通过所述药物输送通道输送至所述目标区域。
Claims (10)
- 一种利用球囊实现药物输送的装置，其特征在于，包括：输送导管、多组穿刺组件以及球囊组件，其中：所述输送导管具有近端部分和远端部分，所述输送导管包括互不连通的用于输送药物的第一通道和用于流通充泄压用的第二通道，至少在靠近远端部分的所述第一通道为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道；多组穿刺组件中，每一组穿刺组件包括至少一穿刺结构和给药腔体，所述穿刺结构包括穿刺部及释药孔，该组中所述释药孔连通所述给药腔体，所述给药腔体与对应的所述药物输送通道连通；球囊组件：至少包含一球囊，所述球囊与所述第二通道的远端部分连通，并且所述球囊被配置为在折叠构型和展开构型之间变化，所述折叠构型下所述多组穿刺组件分别单独包附在所述球囊中；通过给所述第二通道充压作用于所述球囊膨胀使其处于所述展开构型，所述球囊的膨胀带动所述多组穿刺组件的穿刺部凸出，所述药物被配置为在外力作用下分别通过多个药物输送通道、每一药物输送通道对应的给药腔体、所述给药腔体连通的所述释药孔输送至目标区域。
- 如权利要求1所述的利用球囊实现药物输送的装置，其特征在于，所述球囊组件还包括导引导管，所述球囊的远端与所述导引导管连接，以密封所述球囊的远端，所述球囊的近端与所述导引导管密封或者不密封连接；所述球囊折叠形成多对折叠翼，其沿着所述导引导管周向设置，每对相对设置的折叠翼形成一折叠翼空间，该些组的所述穿刺组件分别容置在该些适配的所述折叠翼空间内，多对所述折叠翼均匀排布于所述球囊的周向；优选的，所述给药腔体还包括一基座，所述基座的上表面和其它外周面形成相对固定的给药腔，所述基座的上表面沿着所述球囊的长度方向开设与所述释药孔连通的贯通孔，所述穿刺结构固定设置在所述基座的上表面上，所述释药孔通过所述贯通孔与所述给药腔连通；更优的，设置的所述折叠翼空间的高度H不小于所述基座的高度h2和所述穿刺结构的高度h1之和；优选的，所述基座采用硬质材料制成；优选的，所述基座采用金属材料、 高分子材料或者陶瓷材料制成；优选的，所述基座的上表面采用金属材质、高分子材料或者陶瓷材料；优选的，所述基座的横截面为空心结构；更优选的，所述基座的横截面为空心圆形、空心椭圆、空心矩形、空心多边形或者仿形空心结构；优选的，所述基座其外轮廓呈具有一弧度的仿形空心结构，所述仿形空心结构的曲率与球囊的曲率一致；优选的，所述给药腔体设置于所述球囊的外表面，所述基座其它外周面包含下表面，所述下表面固定于所述球囊的外表面，并且在展开构型时随着所述球囊的膨胀，带动所述基座向外运动，以此带动所述基座的上表面设置的所述穿刺部凸出；或者，所述给药腔体设置于所述球囊的内表面上，所述基座设置在所述球囊的内表面内，所述基座的上表面与所述球囊内表面固定贴合设置，所述球囊上设置有供所述穿刺结构穿出的孔，所述穿刺结构穿出所述孔凸设于所述球囊的内表面，在折叠构型下，凸设出来的所述穿刺结构设置在折叠翼形成的折叠翼空间内；在展开构型下，随着所述球囊的膨胀，带动基座向外运动，从而带动凸设出来的穿刺结构伸出折叠翼空间，折叠翼空间变小或被膨胀消失；优选的，每一组穿刺组件的所述基座分别沿着导引导管周向布置；更优的，设置的所述折叠翼空间的高度应不小于凸设出所述球囊内表面的所述穿刺结构的凸伸高度；优选的，所述基座与所述球囊粘贴或者等离子处理后焊接连接；优选的，沿装置的轴向，穿刺结构两侧的折叠翼的端部距离穿刺结构的距离相等；优选的，沿装置的周向，各个组的折叠翼对称设置，每组穿侧组件对称设置；优选的，每一组穿刺组件的所述穿刺结构为多个，且沿着所述基座的长度方向间隔设置，所述穿刺部的顶部呈尖部，所述穿刺部的端部围设成所述释药孔；优选的，每组所述穿刺组件中的每个穿刺结构等距分布；所述多组穿刺组件为三组或四组；优选的，所述输送导管上还设置充泄压控制单元和输药控制单元，所述第二通道与所述球囊组成的流通充泄压用通道通过所述充泄压控制单元控制，第一通道与所述球囊通过所述输药控制单各自控制；所述第一通道设置第一 鲁尔接口，第一鲁尔接口通过一导管分别连接多个药物输送通道所对应的导管腔；优选的，沿所述第二通道的径向设置有凹槽，所述凹槽沿第二通道的轴向延伸设置，所述凹槽用于容纳所述第一通道，以使得所述装置的非球囊部分的径向尺寸更小；优选的，所述凹槽的半径不小于所述第一通道的外径；优选的，所述凹槽的深度可以不小于所述第一通道的外半径；优选的，所述装置还包括导管座(Hub)，导管座与第一通道连接，用于输送药物，优选的，所述导管座为双鲁尔接头(2-Way Hub)或者三鲁尔接头(3-Way Hub)甚至多鲁尔接头的设计；导管座上的一个鲁尔接头可以与阀、连接器、注射器或压力充盈器相连接，通过其向输液通道中给定特殊的药物，该药物为指定的药物系统；优选的，所述输送导管上还设置充泄压控制单元和输药控制单元，所述第二通道与所述球囊组成的流通充泄压用通道与所述药物输送通道分别通过所述充泄压控制单元和所述输药控制单各自控制。
- 如权利要求1所述的利用球囊实现药物输送的装置，其特征在于，所述穿刺部具有穿刺壁体、穿刺腔体以及穿刺面，所述穿刺面为所述穿刺部的顶部的面，即刺入组织时，产生刺入作用的面；所述穿刺面为一平面，所述穿刺面与垂直于所述穿刺结构的轴向的平面呈的角度a呈5～85°；优选的，所述穿刺面为一圆锥面，所述圆锥面的角度a呈25～75°；优选的，所述穿刺面为一凹面、凸面或者多棱柱面；优选的，所述穿刺壁体的外部呈圆柱形、呈圆锥形、底部圆柱形顶部圆锥形、或者呈阶梯状，相适配的，所述穿刺腔体呈圆柱形、呈圆锥形或者阶梯状；优选的，穿刺壁体的内部呈阶梯状，越靠近顶部，其内部的径向尺寸越小，进而能够呈阶梯式的增加药物输送的压力；优选的，在所述穿刺壁体的内部，沿其轴向，其厚度不变化；优选的，在所述穿刺壁体的内部，沿穿刺壁体的轴向，其厚度逐渐减小，厚度减小形成的锥度为0～10°；优选的，所述穿刺壁体的内径向尺寸与外径向尺寸之比为0.2～0.8；优选的，所述穿刺壁体的内径尺寸范围在约在2μm-500μm之间，更优 的2μm-200μm，更优选为50-150μm；优选的，所述穿刺壁体的外部是沿球囊的轴向延展的面，所述穿刺腔体为沿着所述穿刺壁体形成一缝隙，所述穿刺壁体的横截面呈两个三角形相对的布设，所述穿刺壁体的中间呈所述穿刺腔体；所述释药孔是细长开口或者槽状开口；优选的，所述释药孔沿所述穿刺部的轴向开口；优选的，所述释药孔沿所述穿刺部的径向开口；优选的，所述释药孔的开口朝向在轴向和径向之间的角度方向；优选的，在同一个穿刺部上，所述释药孔为一个或者多个；优选的，所述释药孔是圆形、椭圆形、矩形或者多边形形状；优选的，所述穿刺部的材质为硬质材质，所述硬质材料为高分子材料、陶瓷材料或者金属材料；优选的，所述给药腔体的横截面为圆形、椭圆形、三角形、矩形或者多边形；优选的，所述穿刺部的高度h1在0.1～1.5mm之间，给药腔体的高度在0.1～0.5mm之间；优选的，所述给药腔体的壁厚T与外径D(横向尺寸W)之比为0.06～0.8，优选的，给药腔体的壁厚T与外径D(横向尺寸W)之比为0.06～0.8，优选的，给药腔体的壁厚T与外径D(横向尺寸W)之比为0.05～0.45；优选的，所述穿刺部与给药腔体采用焊接或者粘接的方式连接；优选的，各个穿刺部之间的距离小于穿刺部的径向尺寸；优选的，各个穿刺部之间的距离为0.5～5mm；优选的，距离为1～2mm；优选的，所述基座为一管体，呈圆柱形结构，所述基座为硬质材质制成；优选的，所述基座与所述穿刺部连接的上表面的部分采用硬质材料，其他的表面的部分采用柔性材质以形成软管；优选的，所述基座为一板状结构，板状结构的长度小于所述球囊的轴向长度，所述板状结构的宽度不小于穿刺组件的给药腔体的直径，所述板状结构的厚度不小于穿刺组件的给药腔体的壁厚；优选的，所述板状结构还具有弧度，所述板状结构与球囊接触的表面具有朝向球囊的弧度，进而使得板状结构能够与球囊的连接更加紧密；优选的，板状结构朝向球囊的弧度的曲率与球囊的曲率一致；优选的，所述基座是一板状结构，所述给药腔还包括给药导管，所述基座设置于给药导管上；优选的，沿所述球囊的轴向，穿刺组件的给药导管包括硬质导管与软质导管，硬质导管与软质导管分段间隔设置，穿刺结构设置于硬质导管上；优选的，软质导管的数量比硬质导管的数量少一个；优选的，软质导管能够发生弯曲，其能够在球囊的表面非轴向的延伸设置；优选的，沿所述球囊的周向，前一段的硬质导管与后一段的硬质导管在球囊的周向方向不同，以形成错位布设；优选的，所述给药腔体与第一通道连接；第一通道外径与给药腔体的内径适配；或者，第一通道的内径与给药腔体的外径适配；优选的，所述第一通道采用软质材质或者硬质材质制成；优选的，所述折叠翼之间不重叠；当球囊的直径在2～6mm时，所述折叠翼为3～5对；当球囊的直径在4～12mm时，所述折叠翼为5～6对；当球囊的直径在10～30mm时，所述折叠翼为6～12对；优选的，所述基座的上表面与所述球囊内表面固定贴合设置，所述穿刺结构中至少部分结构凸设出所述球囊内表面，所述折叠构型下，凸设出来的所述穿刺结构设置在所述折叠翼形成的所述容置空间内；在所述展开构型下，随着所述球囊的膨胀，带动所述基座向外运动，带动所述凸设出来的所述穿刺结构伸出所述容置空间，所述容置空间变小或被膨胀消失；优选的，每一组穿刺组件的所述穿刺结构为一对穿刺刀片，所述该对穿刺刀片沿着所述基座的长度方向设置，所述一对穿刺刀片围设成一长条状的所述释药孔；优选的，该对穿刺刀片沿着球囊的长度方向延伸设置；所述刀片呈底部宽上端窄的结构，刀头部分位于上端；所述刀片的横纵比为0.05～1；刀片的横纵比对0.1～0.25；优选的，所述折叠翼空间的高度H在0.5～2.0mm之间；优选的，所述折叠翼为3～6对；优选的，所述球囊在展开构型下，所述穿刺结构的穿刺力≤0.7N；优选的，所述球囊为两端缩口的圆柱形结构；优选的，所述球囊为两个 两端缩口的圆柱形连接形成的结构，即所述球囊包括第一球囊以及第二球囊，所述第一球囊与第二球囊连通，第一球囊与第二球囊均为两端缩口的圆柱形结构；所述第一球囊相比第二球囊更加靠近所述装置的远端，所述第一球囊的最大直径小于所述第二球囊的最大直径；所述穿刺组件可以设置于第一球囊和/或第二球囊上；优选的，所述穿刺组件设置于所述第二球囊上；或者，所述球囊包括第三球囊与第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通；所述穿刺组件或者所述药物释放组件设置于第三球囊和/或第二球囊；优选的，所述第三球囊的扩张直径为5～20mm；优选的，所述穿刺组件的所述给药腔体的壁厚T为0.05～0.2mm，直径D为0.25～0.75mm，宽度W为0.3～0.8mm。
- 一种利用球囊实现药物输送的装置，其特征在于，包括：输送导管、至少一组药物释放组件以及球囊组件，其中：所述输送导管具有近端部分和远端部分，所述输送导管包括互不连通的用于输送药物的第一通道和用于流通充泄压用的第二通道，至少在靠近远端部分的所述第一通道为多腔结构，所述多腔结构包含输送药物用的多个独立药物输送通道；所述药物释放组件包括至少一释放结构和给药腔体，所述释放结构至少包括释药孔，该组中所述释药孔连通所述给药腔体；球囊组件：至少包含一球囊，所述球囊通过一充泄压被配置为在折叠构型和展开构型之间变化；所述折叠构型下，所述药物释放组件分别单独被包附在所述球囊中；所述展开构型下，所述球囊的膨胀力带动所述药物释放组件运动至预先设定的目标区域，所述药物通过单独施加对应控制力，经过所述给药通道输送至目标区域。
- 如权利要求4所述的给药装置，其特征在于，所述药物释放组件为多组，该些组药物释放组件分别通过多个输药控制单元或同一个输药控制单元控制药物的运动；优选的，所述给药腔体还包括给药腔和给药孔，所述第一通道与所述药物释放组件设置在球囊的内表面，所述释药孔位于所述球囊上，所述释药孔通过给药孔与给药腔连通；更优的，所述给药孔与所述释药孔的尺寸相同； 或者，所述第一通道与所述药物释放组件设置在球囊的内表面；优选的，所述第一通道与所述药物释放组件设置在球囊的外表面，所述释药孔与给药腔连通；优选的，所述球囊充压时，所述球囊的压力在3～30atm范围内；优选的，当所述第一通道与所述药物释放组件设置在球囊的外表面时，当所述药物释放组件的释药孔为一排孔结构时，所述释药孔朝向所述球囊膨胀的方向；或者，所述释药孔的朝向与所述球囊膨胀的方向呈一定角度；当所述药物释放组件的释药孔为多排孔结构时，每排孔结构的孔轴向的朝向之间具有夹角；优选的，所述给药腔的径向尺寸大于所述给药孔的直径；优选的，给药腔体的内径≥1μm，优选的，给药腔的内径≥3μm；优选的，所述给药腔的内径≥0.1mm；优选的，给药腔的内径≥0.3mm；更优的，给药腔的内径≥0.5mm，更优的，所述给药孔的内径尺寸范围在约在2μm-500μm之间，优选为2μm-200μm，更优选为50-150μm；所述给药腔的内/外径之比为0.1～0.9，更优的，给药腔的内/外径之比为0.4～0.8；所述给药孔的内径小于所述给药腔的内径；优选的，给药孔的内径小于给药腔的内径的0.5倍，给药孔的内径≤0.01mm；优选的，所述药物释放组件是一空心丝线，所述空心丝线上设置有释药孔；优选的，每个释药孔之间的间距为0.1～1mm，优选的，为0.25～0.75mm；优选的，所述给药腔体的横截面是圆形或者三角形的中空管材；当给药腔体是圆形时，所述给药腔体上的释药孔优选朝向所述球囊膨胀的方向；优选的，所述给药腔体上的释药孔与球囊膨胀的方向存在一定的夹角；当所述药物释放组件的释药孔为多排孔结构时，每排孔结构的孔轴向的朝向之间具有夹角；优选的，在给药腔体的同一周向方向上，分别具有多个释药孔；优选的，所述药物释放组件具有硬质导管与软质导管，所述硬质导管提供释放结构所需要的固定的管腔，所述软质导管的设置为给药导管提供柔性；优选的，沿所述球囊的轴向，药物释放组件的给药导管包括硬质导管与软质导管，硬质导管与软质导管分段间隔设置；优选的，软质导管的数量比硬质导管的数量少一个；优选的，所述穿刺结构设置于硬质导管上；优选的，沿所述球囊的周向，前一段的硬质导管与后一段的硬质导管在球囊的周向方向不同，以形成错位布设；优选的，硬质导管的尺寸与软质导管的轴向尺寸为0.5～20mm；优选的，当给药腔体的横截面是三角形时，三角形柱体的两个侧面优选均具有释药孔；优选的，所述药物释放组件为三角形中空管，即给药腔体的外表面形状是三角形柱体，所述三角形柱体的其中一个角朝向球囊的径向外侧布设，将朝向球囊的径向外侧的角的一端定义为切入端，所述释药孔设置于所述给药腔体的切入端；优选的，所述释药孔沿着三角形中空管的给药腔体的轴向均匀的或者不均匀的布设；优选的，所述药物释放组件为三角形中空管，即给药腔体的外表面是三角形柱体，所述释药孔设置于切入端与设置于所述三角形中空管的两个侧壁上的组合；优选的，沿药物释放组件的轴向，释药孔设置于切入端的轴向与设置于三角形中空管的两个侧壁的轴向位置相同或者不同；优选的，沿所述三角形中空管的给药腔体，每个所述释药孔的大小为均一设置；优选的，沿所述三角形中空管的给药腔体，由近端至远端，每个所述释药孔的大小逐渐变大或者变小；优选的，沿所述三角形中空管的给药腔体的轴向，由近端至远端，每个所述释药孔的大小逐渐变大；优选的，当给药腔体的外表面的横截面呈三角形结构，所述给药腔体的外尺寸的高度为0.1-1.0mm，更优的，所述给药腔体的外尺寸的高度为0.3-0.7mm；优选的，所述给药腔体的壁厚为0.01-0.1mm，更优的，所述给药腔体的壁厚为0.03-0.07mm；优选的，所述给药腔体的长度为5-50mm；优选的，所述给药腔体的三角形的内腔顶角，即切入端的角为10-80°；优选的，所述给药腔体的非内腔顶角为10-70°；优选的，所述释药孔的孔径为0.01-0.2mm；优选的，所述释药孔的孔径为0.05-0.15mm；优选的，所述释药孔的间距在0.05mm与7mm之间；优选的，沿所述球囊的径向方向，即在所述切入端的延伸方向延伸设置尖角，以形成一微凸角，所述微凸角沿切入端的轴向延伸设置；优选的，所 述微凸角的端头开刃或者不开刃；较佳的，所述给药腔体的内表面形状为三角形管腔、圆形管腔、矩形管腔、多边形管腔或者异型管腔；优选的，所述给药腔体的内表面的形状为三角形管腔；优选的，当所述药物释放组件设置有所述微凸角时，所述给药腔体的横截面在三角形的基础上，沿切入端的方向延伸设计具有尖角的空腔，形成类三角形中空管，优选的，所述类三角形中空管的横截面的形状与含有微凸角的给药腔体的外表面的横截面的形状一致；优选的，所述药物释放组件采用的材料为树脂、陶瓷、不锈钢、尼龙，可降解聚合物或者这几种材料的组合；优选的，所述陶瓷的材料为氧化铝、氧化锆、氧化镁、磷酸钙或者这几种材料的组合；优选的，所述药物释放组件采用超精密微纳3D打印工艺，优选的，采用烧结工艺，更优的，采用激光烧结或者高温烧结；优选的，释放结构还包括一基座，基座的上表面和其它外周面形成所述给药腔体，所述基座的上表面沿着所述球囊长度方向开设与释药孔连通的贯通孔，所述释药孔通过贯通孔与所述给药腔体连通；优选的，所述球囊为两端缩口的圆柱形结构；优选的，所述球囊为两个两端缩口的圆柱形连接形成的结构，即所述球囊包括第一球囊以及第二球囊，所述第一球囊与第二球囊连通，第一球囊与第二球囊均为两端缩口的圆柱形结构；所述第一球囊相比第二球囊更加靠近所述装置的远端，所述第一球囊的最大直径小于所述第二球囊的最大直径；所述药物释放组件可以设置于第一球囊和/或第二球囊上；优选的，所述药物释放组件设置于所述第二球囊上；或者，所述球囊包括第三球囊与第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通；所述药物释放组件设置于第三球囊和/或第二球囊；优选的，所述第三球囊的扩张直径为5-20mm；优选的，所述药物释放组件的所述给药腔体的壁厚T为0.05～0.2mm，直径D为0.25～0.75mm，宽度W为0.3～0.8mm。
- 一种给药装置，其特征在于，包括：输送导管，所述输送导管具有近端部分和远端部分，所述输药导管包括充泄压腔体，所述药物释放组件包括给药腔体，所述给药腔体与充泄压腔体采用同一个腔室；至少一组药物释放组件，所述药物释放组件包括至少一释放结构和给药腔体，所述释放结构包括释药孔，该组中所述释药孔连通所述给药腔体；球囊组件：至少包含一球囊，所述球囊通过一充泄压被配置为在折叠构型和展开构型之间变化；所述折叠构型下，所述药物释放组件分别单独被包附在所述球囊中；所述展开构型下，所述球囊的膨胀力带动所述药物释放组件运动至预先设定的目标区域，所述药物通过单独施加对应控制力，经过所述给药通道输送至目标区域。
- 如权利要求6所述的给药装置，其特征在于，所述释放结构还包括穿刺部，所述腔室用于充盈药物的药物载体和/或药物的液体，所述液体被配置用于流通充泄压用和用于给药用，所述液体充满所述球囊来带动所述球囊膨胀，使所述球囊处于展开构型，所述液体通过单独施加对应控制力，通过所述给药通道实现给药；优选的，释放结构还包括一基座，所述基座呈板状，所述穿刺部设置于所述基座上；优选的，基座与所有的释放结构一体成型；优选的，所述释放结构与基座的材质可由高分子聚合物、无机硅、金属等材料中的至少一种加工而成；优选的，释放结构的外径大于基座的内径，所述释放结构的内径小于基座的内径；优选的，所述基座位于所述球囊的外表面或者所述球囊的内表面；优选的，所述穿刺部的顶部呈尖部，端部围设成所述释药孔，所述穿刺部为多个，且沿着所述基座的长度方向间隔设置；优选的，所述穿刺部为一对穿刺刀片，所述该对穿刺刀片沿着所述基座的长度方向设置，所述对穿刺刀片围设成一长条状的所述释药孔。优选的，所述球囊组件还包括导引导管，所述球囊密封附接在所述导引导管上，所述球囊折叠形成多个折叠翼，其沿着所述导引导管周向设置，每对相对设置的折叠翼形成一折叠翼空间，所述该些药物释放组件分别容置在该些适配的所述折叠翼空间内；优选的，所述该些药物释放组件被配置为所述将药物植入所述目标区域 或注射入所述目标区域；优选的，所述球囊为两端缩口的圆柱形结构；优选的，所述球囊为两个两端缩口的圆柱形连接形成的结构，即所述球囊包括第一球囊以及第二球囊，所述第一球囊与第二球囊连通，第一球囊与第二球囊均为两端缩口的圆柱形结构；所述第一球囊相比第二球囊更加靠近所述装置的远端，所述第一球囊的最大直径小于所述第二球囊的最大直径；所述药物释放组件可以设置于第一球囊和/或第二球囊上；优选的，所述药物释放组件设置于所述第二球囊上；或者，所述球囊包括第三球囊与第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通；所述药物释放组件设置于第三球囊和/或第二球囊；优选的，所述第三球囊的扩张直径为5～20mm。优选的，所述给药装置上涂覆一层结构，优选的，所述涂层是药物涂层，优选的，所述药物涂层与所述给药装置中输送的药物为同一种药物或者不同种药物。
- 一种给药装置，其特征在于，所述给药装置用于前列腺尿道扩张，所述装置包括球囊，所述球囊包括内部相连通的靠近远端的球囊结构与靠近近端的球囊结构，所述靠近远端的球囊结构用于至少设置于膀胱颈的位置，以阔开膀胱颈；所述靠近近端的球囊结构用于至少设置于前列腺尿道的位置，以阔开前列腺尿道；所述靠近远端的球囊结构的最大直径小于靠近远端的球囊结构的最大直径，以使得靠近远端的球囊结构所阔开的膀胱颈的尺寸小于靠近远端的球囊结构所阔开的前列腺尿道的尺寸；优选的，靠近远端的球囊结构和/或靠近近端的球囊结构的至少部分结构上设置穿刺组件、药物释放组件和/或药物涂层，以实现球囊的给药；优选的，所述球囊在工作时的扩张压力不小于1.5atm；优选的，药物涂层、穿刺组件或者药物释放组件的轴向范围长度可以大于病变部位待治疗的长度；优选的，所述球囊的长度大于病变部位待治疗的长；优选的，所述靠近远端的球囊结构为第一球囊，所述靠近近端的球囊结构为第二球囊，所述第一球囊与第二球囊均为两端缩口的圆柱形结构，所述第一球囊用于至少设置于膀胱颈的位置，以阔开膀胱颈，所述第二球囊用于 至少设置于前列腺尿道的位置，以阔开前列腺尿道，所述第一球囊的最大直径小于第二球囊的最大直径，以使得第一球囊所阔开的膀胱颈的尺寸小于第二球囊所阔开的前列腺尿道的尺寸；优选的，所述穿刺组件、所述药物释放组件和/或者药物涂层可以设置于第一球囊和/或第二球囊上；优选的，靠近远端的球囊结构为第三球囊，靠近近端的球囊结构为第二球囊，所述第三球囊为一端缩口的圆柱形，第二球囊为两端缩口的圆柱形，第三球囊的圆柱形一端与第二球囊的圆柱形的缩口连接并连通，所述第三球囊用于至少设置于膀胱颈的位置，或者至少设置于膀胱颈以及膀胱颈与尿道的连接部位，以阔开膀胱颈及其周边，所述第二球囊用于至少设置于前列腺尿道的位置，以阔开前列腺尿道，所述第三球囊的最大直径小于第二球囊的最大直径，以使得第三球囊所阔开的膀胱颈的尺寸小于第二球囊所阔开的前列腺尿道的尺寸；优选的，所述穿刺组件、所述药物释放组件或者药物涂层设置于第三球囊和/或第二球囊；优选的，所述第二球囊的扩张直径为20-50mm；优选的，所述第二球囊的长度为20-80mm，优选的，所述第三球囊的扩张直径为5-20mm；优选的，所述第三球囊的长度为20-50mm。
- 一种药物系统，其特征在于，所述药物系统包括药物颗粒和/或药物载体，所述药物颗粒和/或所述药物载体能够与一溶液混合形成药液，药液被输送至目标组织位置；优选的，所述药物颗粒为药物晶体，所述药物晶体被输送至组织中能够实现药物缓释，所述药物颗粒的粒径为1～1000μm，优选的，所述药物颗粒的粒径为150μm，更优选的，所述药物颗粒的粒径为1～50μm；所述药物晶体的缓释周期在一周至6个月；优选的，所述药物载体为可降解高分子材料与药物混合制成药物缓释微球，所述药物缓释微球的直径在1～1000μm，优选的，所述药物缓释微球的直径为1～150μm，更优选的，所述药物缓释微球的直径为1～50μm；所述缓释周期在1周至6个月；优选的，所述药物载体具有孔隙，所述孔隙中容载药物，所述药物从孔隙中缓释，所述药物载体的直径在1～1000μm，优选的，所述药物载体的的直径为1～150μm，更优选的，所述药物载体的直径为1～50μm；所述缓释周期在1周至6个月；优选的，所述药物载体中采用的高分子可降解材料包括：聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、二氧化碳聚合物(PPC)、聚丁二酸丁二醇酯(PBS)、脂肪芳香聚酯Ecoflex(PBAT)、聚对苯二甲酸丙二醇酯(PPT)、聚β-羟基烷酸酯(PHA)、聚ε-己内酯(PCL)、聚对二氧环己酮(PPDO)中的一种，或者是其中任意多种的聚合物的共聚物或者共混物；优选的，所述药物系统为药物颗粒、或者药物载体、或者包含药物颗粒的药物载体或组合物，其包括一种或多种治疗物质、诊断物质、一种药物、一种治疗组合物、一种诊断组合物、生理活性剂、一种生物化学活性剂、一个或多个活细胞、DNA、RNA、核酸、用于将遗传物质递送到目标部位中的细胞载体、抗炎剂、一种抗再狭窄剂、一种细胞增殖抑制剂、平滑肌增生抑制剂、紫杉醇、雷帕霉素、依维莫司、血管活性剂、血管扩张剂、血管收缩剂、抗生素、抗凝剂、血小板凝集抑制剂、抗纤维化剂、α还原酶抑制剂、药学上可接受的载体、脂质基载体及其任意组合；优选的，所述药物载体上设置一包覆层，药物设置在包覆层内，以形成缓释，包覆层能够被溶解；所述缓释周期在1周至6个月；优选的，所述药物载体为球状、棒材或者片材；优选的，所述药物晶体为球状、多边形状、棒材或者片材；优选的，所述药物系统中的药物为：糠酸莫米松、强的松龙、曲安奈德、甲泼尼松、倍他米松、丙酸倍氯米松、泼尼松龙、氢化可的松、地塞米松。
- 一种医学微创系统，包括权利要求1至8中的任一项装置，以及包括权利要求9中的药物系统；优选的，所述装置包括输药控制单元，所述输药控制单元可配置加载到所述药物的输送力大小，以控制所述药物通过所述药物输送通道输送至所述目标区域；优选的，所述释药孔的直径大于所述药物系统的直径。
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| JP2010273936A (ja) * | 2009-05-29 | 2010-12-09 | Tti Ellebeau Inc | バルーンカテーテル |
| CN208611569U (zh) * | 2018-01-04 | 2019-03-19 | 龙金 | 一种前列腺扩开导管及其装置 |
| CN113018660A (zh) * | 2021-03-16 | 2021-06-25 | 中国科学技术大学 | 一种用于介入给药的微针球囊 |
| CN114010917A (zh) * | 2021-11-05 | 2022-02-08 | 广东博迈医疗科技股份有限公司 | 双药物给药球囊 |
| CN114225185A (zh) * | 2021-11-05 | 2022-03-25 | 广东博迈医疗科技股份有限公司 | 给药球囊及给药装置 |
| CN114768057A (zh) * | 2022-04-09 | 2022-07-22 | 四川大学华西医院 | 一种载药的切割球囊导管 |
| CN117065189A (zh) * | 2022-12-09 | 2023-11-17 | 鑫易舟(上海)医疗器械有限公司 | 利用球囊实现药物输送的装置、给药装置及微创医学系统 |
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Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010273936A (ja) * | 2009-05-29 | 2010-12-09 | Tti Ellebeau Inc | バルーンカテーテル |
| CN208611569U (zh) * | 2018-01-04 | 2019-03-19 | 龙金 | 一种前列腺扩开导管及其装置 |
| CN113018660A (zh) * | 2021-03-16 | 2021-06-25 | 中国科学技术大学 | 一种用于介入给药的微针球囊 |
| CN114010917A (zh) * | 2021-11-05 | 2022-02-08 | 广东博迈医疗科技股份有限公司 | 双药物给药球囊 |
| CN114225185A (zh) * | 2021-11-05 | 2022-03-25 | 广东博迈医疗科技股份有限公司 | 给药球囊及给药装置 |
| CN114768057A (zh) * | 2022-04-09 | 2022-07-22 | 四川大学华西医院 | 一种载药的切割球囊导管 |
| CN117065189A (zh) * | 2022-12-09 | 2023-11-17 | 鑫易舟(上海)医疗器械有限公司 | 利用球囊实现药物输送的装置、给药装置及微创医学系统 |
| CN117224822A (zh) * | 2022-12-09 | 2023-12-15 | 鑫易舟(上海)医疗器械有限公司 | 前列腺尿道扩张装置 |
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| CN117224822A (zh) | 2023-12-15 |
| CN118178841A (zh) | 2024-06-14 |
| CN117065189A (zh) | 2023-11-17 |
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