CN116999680A

CN116999680A - Drug shock wave balloon catheter

Info

Publication number: CN116999680A
Application number: CN202310469165.2A
Authority: CN
Inventors: 宋精忠; 曹瀚文; 胡军; 刘斌
Original assignee: Sonosemi Medical Co Ltd
Current assignee: Sonosemi Medical Co Ltd
Priority date: 2023-04-23
Filing date: 2023-04-23
Publication date: 2023-11-07

Abstract

The invention relates to a drug shock wave balloon catheter, which comprises an outer tube, an inner tube, a tail end tube, a balloon, at least one shock wave emitting device and a notch wire; the inner tube is arranged in the inner cavity of the outer tube, and the distal end of the inner tube penetrates out of the outer tube and is fixedly connected with the tail end tube; the balloon is wrapped outside the inner tube, and two ends of the balloon are respectively connected with the distal end of the outer tube and the proximal end of the tail end tube in a sealing way; the inner part of the balloon is provided with a containing cavity, a liquid filling channel which can be communicated with the containing cavity in the balloon is formed between the outer tube and the inner tube, liquid medium can be conveyed into the containing cavity in the balloon through the liquid filling channel, and the shock wave transmitting device is arranged in the balloon; the notch wire is arranged on the outer surface of the balloon, the notch wire is provided with a treatment surface, the treatment surface is away from the outer side surface of the balloon, a groove is formed in the treatment surface, and a treatment medicine is sprayed in the groove. The invention can promote the release of the medicine in the groove by matching with the energy of the impact wave, thereby reducing the loss in the medicine transportation process and increasing the release rate of the medicine to the affected part.

Description

Drug shock wave balloon catheter

Technical Field

The invention relates to the technical field of medical instruments, in particular to a drug shock wave balloon catheter.

Background

The Drug Coated Balloon (DCB) is widely applied to various cardiovascular stenosis diseases because of the combination of mechanical dilatation and drug treatment. At present, paclitaxel is the most common antiproliferative drug for DCB, but the paclitaxel has high cytotoxicity, the current DCB drug transfer rate is extremely low, the loss in the conveying process is extremely high, taking a Lutonix balloon of Bard company and an IN.PACT balloon of Medunli company as examples, the drug transfer rates are only 5% and 1%, and the drug loss in the conveying process is as high as 81%. Combining the two points, there is a high dose, high density of antiproliferative drug needed in DCB, which risks increasing mortality.

In order to solve the problem of low transfer rate of DCB drugs in the delivery process, the problem is solved currently by arranging a large-dose and high-density antiproliferative drug on DCB or arranging a double-layer drug carrying balloon, but the related method still has the problems of overhigh cost, increased operation difficulty and difficulty in being suitable for most patients.

Based on this, there is a need to provide an improved drug shock wave balloon catheter to reduce drug loss during delivery in cardiovascular stenosis and vascular calcification, improve drug release efficiency, and further increase drug transfer efficiency to achieve the desired therapeutic effect.

Disclosure of Invention

The invention solves the problems that: the problems of large drug loss and low drug release rate and transfer efficiency in the drug shock wave balloon catheter conveying process in the prior art are solved.

(II) technical scheme

A drug shock wave balloon catheter comprises an outer tube, an inner tube, a tail end tube, a balloon, at least one shock wave emitting device and a notch wire;

the inner tube is arranged in the inner cavity of the outer tube, and the distal end of the inner tube penetrates out of the outer tube and is fixedly connected with the tail end tube;

the balloon is wrapped outside the inner tube, and two ends of the balloon are respectively connected with the distal end of the outer tube and the proximal end of the tail end tube in a sealing way;

an accommodating cavity is formed in the balloon, a liquid filling channel which can be communicated with the accommodating cavity in the balloon is formed between the outer tube and the inner tube, and physiological saline or contrast medium can be conveyed into the accommodating cavity in the balloon through the liquid filling channel;

the shock wave transmitting device is arranged inside the balloon;

the notch wire is arranged on the outer surface of the balloon, the notch wire is provided with a treatment surface, the treatment surface is away from the outer side surface of the balloon, a groove is formed in the treatment surface, and a treatment medicine is sprayed in the groove.

According to one embodiment of the invention, the score wire is a ductile wire;

when the balloon is in a contracted state, the notch wire is in a contracted state and is attached to the inner tube along with the balloon, and when the balloon is in a filling state, the notch wire is in an extending state and is attached to the outer side face of the balloon.

According to one embodiment of the invention, the grooved wire has a continuous wave structure;

when the balloon is in a contracted state, the wavy structure of the notch wire is in a contracted state and is attached to the inner tube along with the balloon, and when the balloon is in a filling state, the wavy structure of the notch wire is in a stretched state and is attached to the outer side face of the balloon.

According to one embodiment of the invention, the grooving wires are provided in a plurality, and the grooving wires are attached to the outer surface of the balloon along the radial direction or the axial direction of the balloon.

According to one embodiment of the invention, the notch wires are provided with a plurality of notch wires, the notch wires are woven to form a net sleeve structure wrapped outside the balloon, and two ends of the net sleeve structure are respectively fixed at two opposite ends of the balloon.

According to one embodiment of the invention, the radial cross section of the scored wire is circular, semicircular, oval, arcuate, rectangular or irregular polygonal.

According to one embodiment of the invention, the grooves extend along the length of the score wire, and the radial cross section of the grooves is arched, semicircular or rectangular.

According to one embodiment of the invention, the ratio of the maximum width of the score wire to the maximum width of the groove ranges from 1.2 to 2;

the bottom of the groove is positioned at the position of 1/3 to 2/3 of the height of the notch wire.

According to one embodiment of the present invention, the therapeutic drug comprises a drug microcapsule comprising a shell and a pharmaceutically active ingredient enclosed in the shell;

the shell is made of at least one of degradable polyester, degradable polyanhydride, degradable polyamino acid and complexing agent; the degradable polyester is any one or at least two physical blend of polylactic acid, polyglycolic acid, poly succinate, poly beta-hydroxybutyrate, polycaprolactone, polyethylene glycol adipate, poly valerate, polyhydroxyalkyl alcohol ester and poly malate; and/or, a copolymer of at least two of the monomers forming polylactic acid, polyglycolic acid, poly succinate, poly beta-hydroxybutyrate, polycaprolactone, polyethylene adipate, poly valerate, polyhydroxyalkyl alcohol esters, and poly malate; the degradable polyanhydride is at least one of polyglycolic anhydride, polysuccinic anhydride, polyadipic anhydride, polysebacic anhydride, polydodecyl anhydride, polycycloic anhydride, polymalic anhydride, polysuccinic anhydride, polytartaric anhydride, polyitaconic anhydride and polymaleic anhydride; and/or the degradable polyanhydride is selected from at least one of monomers forming polyethylene glycol anhydride, poly succinic anhydride, poly adipic anhydride, poly sebacic anhydride, poly dodecaanhydride, poly citric anhydride, poly malic anhydride, poly succinic anhydride, poly tartaric anhydride, poly itaconic anhydride and poly maleic anhydride and at least one of monomers forming polylactic acid, poly glycollic acid, polycaprolactone, poly succinic acid ester, poly beta-hydroxybutyrate, poly glycol adipate and poly hydroxybutyrate valerate;

the degradable polyamino acid is at least one of polylysine, polyaspartic acid, polycysteine, methionine, ornithine, glycine and glutamic acid;

the complexing agent is 8-hydroxyquinoline, 8-hydroxyquinaldine, 4, 5-dihydroxybenzene-1, 3-disulfonic acid sodium salt, 4- [3, 5-dihydroxybenzene-1H-1, 2, 4-triazole ] -benzoic acid, 8-mercaptoquinoline, thioglycollic acid, 5-methyl-2-mercaptobenzoic acid methyl ester, ethylenediamine, triethylenetetramine, ethylenediamine tetraacetic acid tetrasodium salt, N' - [5- [ [4- [ [5- (acetamido) amyl ] amino ] -1, 4-dioxybutyl ] hydroxylamine ] amyl ] -N- (5-aminopentyl) -N-hydroxysuccinamide, phenanthroline, bipyridine, porphyrin, porphine, chlorophyll, hemoglobin, 1, 2-dimethyl-3-hydroxy-4-pyridone 1-nitroso-2-naphthol, 1-nitroso-2-naphthol-6-sodium sulfonate, sulfosalicylic acid, 8-hydroxyquinoline-5-sulfonic acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphate, polyphosphoric acid, sodium pyrophosphate, sodium hexametaphosphate, ammonium polyphosphate, potassium diethylenetriamine pentamethylphosphonate, sodium ethylenediamine tetramethylene phosphonate, oxalic acid, tartaric acid, malic acid, succinic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, nitrilotriacetic acid, diethylenetriamine pentacarboxylic acid, alginic acid, glutamic acid, aspartic acid, ornithine, lysine, potassium citrate, calcium citrate, glyceryl citrate, citric acid, at least one of acetylsalicylic acid and sulfosalicylamide

The medicine active component comprises paclitaxel and derivatives thereof, rapamycin and derivatives thereof;

the particle size of the drug microcapsule is 1 to 10 μm.

According to one embodiment of the present invention, the positive sound pressure peak value of the shock wave emitted by the shock wave emitting device on the surface of the balloon is 1 to 10MPa.

The invention has the beneficial effects that:

the invention provides a drug shock wave balloon catheter, which comprises an outer tube, an inner tube, a tail end tube, a balloon, at least one shock wave emitting device and a grooved wire; the inner tube is arranged in the inner cavity of the outer tube, and the distal end of the inner tube penetrates out of the outer tube and is fixedly connected with the tail end tube; the balloon is wrapped outside the inner tube, and two ends of the balloon are respectively connected with the distal end of the outer tube and the proximal end of the tail end tube in a sealing way; an accommodating cavity is formed in the balloon, a liquid filling channel which can be communicated with the accommodating cavity in the balloon is formed between the outer tube and the inner tube, and physiological saline or contrast agent is conveyed into the accommodating cavity in the balloon through the liquid filling channel; the shock wave transmitting device is arranged inside the balloon; the notch wire is arranged on the outer surface of the balloon and is provided with a treatment surface, the treatment surface is away from the outer side surface of the balloon, a groove is formed in the treatment surface, and a treatment medicine is sprayed in the groove.

According to the drug shock wave balloon catheter provided by the invention, as the surface of the balloon is provided with the notch wires, and then the drugs are stored in the grooves of the notch wires instead of the surface of the balloon, the loss of the drugs in the drug shock wave balloon catheter in the conveying process can be reduced in cardiovascular stenosis diseases and vascular calcification diseases, and then the release of the drugs in the grooves is promoted by matching with the shock wave energy, so that the loss in the drug conveying process is reduced, the release rate of the drugs to affected parts is increased, the drug transfer efficiency is increased, and the expected treatment effect is achieved.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.

Fig. 1 is a schematic perspective view of a drug shock wave balloon catheter according to example 1;

FIG. 2 is an enlarged view of area I-1 of FIG. 1;

FIG. 3 is a schematic view of the interior of a drug shock wave balloon catheter provided in example 1;

FIG. 4 is a schematic perspective view of a partially grooved wire according to example 5;

FIG. 5 is an axial cross-sectional view of the grooved wire of example 5;

FIG. 6 is an axial cross-sectional view of a grooved wire of example 4;

FIG. 7 is an axial cross-sectional view of a grooved wire of example 2;

FIG. 8 is an axial cross-sectional view of a grooved wire of example 1;

fig. 9 is a microscopic schematic of the drug microcapsule of example 1.

Icon: 1-end tube; 2-balloon; 3-grooving the silk; 4-an outer tube; 5-guiding the guide wire; 6-an inner tube; 7-developing ring; 8-a shock wave emitting device; 9-grooves; 10-a housing; 11-pharmaceutically active ingredient.

Detailed Description

The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

In the field of interventional medical devices, the end of the implanted medical device closer to the operator is generally referred to as the "proximal end", the end farther from the operator is generally referred to as the "distal end", and the "proximal end" and the "distal end" of any component of the medical device are defined according to this principle. "axial" generally refers to the longitudinal direction of a medical device when delivered, and "radial" generally refers to the direction of the medical device perpendicular to its "axial" direction, and defines the "axial" and "radial" directions of any component of the medical device in accordance with this principle.

As shown in fig. 1-9, one embodiment of the present invention provides a drug shock wave balloon catheter, a drug shock wave balloon catheter comprising an outer tube 4, an inner tube 6, a tip tube 1, a balloon 2, at least one shock wave emitting device 8 and a score wire 3; the inner tube 6 is arranged in the inner cavity of the outer tube 4, and the distal end of the inner tube 6 penetrates out of the outer tube 4 and is fixedly connected with the tail end tube; the balloon 2 is wrapped outside the inner tube 6, and two ends of the balloon 2 are respectively connected with the distal end of the outer tube 4 and the proximal end of the tail end tube 1 in a sealing way;

an accommodating cavity is formed in the balloon 2, a liquid filling channel which can be communicated with the accommodating cavity in the balloon 2 is formed between the outer tube 4 and the inner tube 6, and liquid medium is conveyed into the accommodating cavity in the balloon 2 through the liquid filling channel; the shock wave transmitting device 8 is arranged inside the balloon 2;

the notch wire 3 is arranged on the outer surface of the balloon 2, the notch wire 3 is provided with a treatment surface, the treatment surface is away from the outer side surface of the balloon 2, a groove 9 is formed in the treatment surface, and a treatment medicine is sprayed in the groove 9.

The drug shock wave balloon catheter provided by the invention is used for treating calcification lesions in the lumen of a human body, and comprises the following steps: the method comprises the steps of implanting a drug shock wave balloon catheter in a contracted state into a calcified lesion part, attaching a notch wire 3 to the surface of the contracted balloon 2, then conveying filling liquid medium into a containing cavity in the balloon 2 through a liquid filling channel, expanding the balloon 2 to be abutted against the wall of a human body lumen, attaching the notch wire 3 to the outer wall of the expanded balloon 2 and abutting against the wall of the human body lumen along with the outer wall of the balloon 2, applying high-voltage pulse to a shock wave transmitting device 8, generating a liquid-electricity effect in the balloon 2 by the shock wave transmitting device 8, converting electric energy into mechanical energy, outputting unfocused shock wave energy outwards, generating compressive stress and fracturing calcified plaques. Meanwhile, as the medicine is stored in the grooves 9 of the notch yarns 3 instead of the surface of the sacculus 2, the loss of the medicine in the conveying process of the medicine shock wave sacculus catheter can be reduced, the energy of the shock wave can also promote the release of the medicine in the grooves 9, the loss in the conveying process of the medicine is reduced, and the release rate of the medicine reaching an affected part is increased.

Preferably, the peak value of the positive sound pressure of the shock wave emitted by the shock wave emitting device 8 on the surface of the balloon 2 is in the range of 1 to 10MPa. According to the scheme, the endothelial gap can be widened on the basis of not damaging the cell membrane, the permeability of the cell membrane is increased, and meanwhile, the release of the medicine in the groove 9 is promoted, so that the cell achieves a better medicine absorption effect.

Preferably, since the morphology of the balloon 2 changes before and after filling, and the notch 3 needs to be attached to the surface of the balloon 2, the notch 3 should have a certain deformation capability, so as to satisfy that the length of the notch 3 increases with the increase of the surface of the balloon 2.

In the present invention, the material of the notch wire 3 is selected from metals, which may be pure metals or alloys, preferably nickel-titanium alloys.

In one embodiment of the invention, the score wire 3 is a ductile wire. Thus, when the balloon 2 is in the contracted state, the notch 3 is in the contracted state and attached to the catheter mechanism along with the balloon 2, and when the balloon 2 is in the inflated state, the notch 3 is in the extended state and attached to the outer side surface of the balloon 2.

It should be noted that, the notch wire 3 has two opposite surfaces, the first surface is a fixing surface, the second surface is a treatment surface, wherein the fixing surface is attached to the outer surface of the balloon 2, the treatment surface is away from the outer side surface of the balloon 2, a groove 9 is formed on the treatment surface, and a therapeutic drug is sprayed in the groove 9.

In the past, the therapeutic drug is directly sprayed on the outer surface of the balloon 2, so that the friction between the therapeutic drug on the outer surface of the balloon 2 and a blood vessel is large, the outer surface of the balloon 2 is smooth, the adhesive force of the therapeutic drug is poor, and the drug loss in the conveying process is large.

Compared with the existing scheme, in the embodiment, the friction between the therapeutic drug and the blood vessel can be effectively reduced by spraying the therapeutic drug into the grooves 9 of the notch wire 3, so that the drug loss in the conveying process can be reduced, and on the other hand, the adhesive force of the therapeutic drug sprayed on the grooves 9 of the notch wire 3 is better, so that the drug loss in the conveying process is further reduced.

Preferably, the outer tube 4 is coaxially sleeved outside the inner tube 6, the distal end of the outer tube 4 is in sealing connection with one end of the balloon 2, the distal end of the inner tube 6 penetrates through the outer tube 4 to enter the balloon 2, a containing cavity is formed inside the balloon 2, a liquid filling channel which can be communicated with the containing cavity in the balloon 2 is formed between the outer tube 4 and the inner tube 6, a liquid medium such as a mixed solution of normal saline and contrast agent is conveyed into the containing cavity in the balloon 2 through the liquid filling channel, and the guide wire 5 is guided to be inserted into the inner tube 6 and the outer tube 4.

Specifically, as shown in fig. 2 and 3, the inner tube 6 is used for passing through the finger guide wire 5, during operation, the catheter is delivered to the lesion site through the finger guide wire 5 by the inner tube 6, the outer tube 4 is connected with the head end of the balloon 2, the inner tube 6 axially penetrates through the balloon 2 along the balloon 2, and the liquid medium is delivered into the balloon 2 through the liquid filling channel between the outer tube 4 and the inner tube 6.

Preferably, 2 shock wave emitting devices 8 are further arranged in the balloon 2, the 2 shock wave emitting devices 8 are arranged on the outer surface of the inner tube 6, and the voltage of the shock wave emitting devices 8 is 2500V.

Preferably, referring to fig. 1, an end tube 1 is further disposed outside the end of the balloon 2, the end tube 1 is conical, an inner cavity is formed in the end tube 1, two openings are opposite, the diameters of the two openings are different, the diameter of the opening near the balloon 2 is larger than that of the opening far from the balloon 2, the end tube 1 is sleeved outside the end of the inner tube 6, namely, the end of the inner tube 6 is connected with the opening of the end tube 1 near the balloon 2, so that the inner cavity of the end tube 1 is butted with the tube cavity of the inner tube 6 to form a guide wire cavity, the guide wire cavity is used for penetrating a guide wire 5, and the end of the inner tube 6 is in sealing connection with a pin at the end of the balloon 2.

Preferably, in this embodiment, as shown in fig. 1, a plurality of filament-shaped notch filaments 3 are provided, and the plurality of notch filaments 3 are attached to the outer surface of the balloon 2 along the radial direction of the balloon 2, and the notch filaments 3 are equidistantly arranged. The ends of the notch 3 are fixed between the end tube 1 and the end pin of the balloon 2.

Further, the outer tube 4 is in sealing connection with the head end pin of the balloon 2, a space for circulating the substances of the filled balloon 2 is reserved between the inner tube 6 and the outer tube 4, and the head end of the notch wire 3 is fixed between the head end pin of the balloon 2 and the outer tube 4.

Optionally, the outer tube 4 and the head end pin of the balloon 2 are welded by laser, and the head end of the notch wire 3 is welded between the head end pin of the balloon and the outer tube 4 by laser.

Preferably, the notch wires 3 are provided with a plurality of notch wires 3, the notch wires 3 are woven to form a net sleeve structure wrapped outside the balloon 2, two ends of the net sleeve structure are respectively fixed at two opposite ends of the balloon 2, the proximal end of the net sleeve structure is fixedly connected with the distal end of the outer tube 4, the distal end of the net sleeve structure is fixedly connected with the proximal end of the tail end tube 1, the net sleeve structure has elasticity, and when the balloon 2 is in a contracted state, the net sleeve structure contracts and is attached to the balloon 2 and the inner tube 6; when the balloon 2 is in the inflated state, the mesh structure stretches and attaches to the outer wall of the balloon 2.

Alternatively, two ends of the net sleeve structure are respectively connected with the outer tube 4 and the tail end tube 1 by adopting a laser welding connection mode.

The present invention is not particularly limited with respect to the specific form of the mesh structure, and may be a mesh woven from a plurality of wires, or a sleeve formed by a plurality of wires circumferentially arranged outside the balloon along the axial direction.

In an alternative embodiment of the present invention, when the diameter of the balloon 2 is large, the notch 3 may be designed to be continuous wave, and the plurality of wavy notch 3 are attached to the outer side of the balloon 2 along the radial direction of the balloon 2, because the notch 3 is wave-shaped and has a length greater than that of the balloon 2, when the balloon 2 is inflated, the notch 3 has a buffer length and is not straightened, and when the balloon 2 is in a contracted state, the wavy notch 3 is in a contracted state and is attached to the outside of the balloon 2 and the inner tube 6.

In an alternative embodiment of the present invention, the score lines 3 may be designed to be continuous waves, and a plurality of wavy score lines 3 are attached to the outer side surface of the balloon 2 along the axial direction of the balloon 2.

In an alternative embodiment of the present invention, the notch wire 3 is provided with one notch wire, and the notch wire 3 is wound around the outer side surface of the balloon 2 around the axis of the balloon 2 to form a spiral notch wire 3.

Optionally, a plurality of notch wires 3 are provided, the plurality of notch wires 3 are sequentially wound around the axis of the balloon 2 on the outer side surface of the balloon 2, and the intervals between the notch wires 3 are the same, so that a plurality of spiral notch wires 3 are formed.

In the present invention, the radial cross section of the score wire 3 is circular, elliptical, arcuate, rectangular or irregular polygonal. It will be appreciated that the drug shock wave balloon catheter is better overall passability when the radial cross section of the score wire 3 is arcuate. When the radial cross section of the notch wire 3 is rectangular, the notch wire 3 has a better cutting effect on calcified plaque, is suitable for simple paths and large in vessel diameter, and has general severe calcified lesions on the trafficability requirements of balloon catheters.

In the present invention, the grooves 9 on the score line 3 extend along the length direction of the score line 3, and the position and length of the groove 9 on the score line 3 are not particularly limited, and the grooves 9 may extend through the entire length of the score line 3 or may be a plurality of groove bodies arranged at intervals in the length direction of the score line 3. In order to allow sufficient space for storing the drug, the portion of the score wire 3 provided with the groove 9 is at least 50% or more of the portion of the score wire 3 in contact with the surface of the balloon 2.

Preferably, in this embodiment, the grooves 9 on the score wire 3 extend continuously along the length of the score wire 3 except for portions at the proximal and distal ends of the balloon 2 for fixation with other components.

In some alternative embodiments, the groove 9 is centered in the width direction of the score wire 3.

In the present invention, the radial cross section of the groove 9 is rectangular or arcuate.

It will be appreciated that when the radial cross section of the recess 9 is arcuate, the medicament within the recess 9 is less prone to accumulation within the recess 9. The grooves 9 are rectangular in radial cross section and can carry more medicine.

It will be appreciated that the wider the groove 9, the correspondingly increased amount of drug is contained, but the finer the score wire 3 is on both sides, the greater the difficulty of processing and the higher the risk of breakage during treatment. In some alternative embodiments, the ratio of the maximum width of the score wire 3 to the maximum width of the groove 9 may range from 1.2 to 2, such as 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0, considering the combined difficulty of processing, risk of surgery, and total drug content of the individual score wires.

It will be appreciated that the deeper the groove 9, the thinner the bottom of the score wire 3, the more difficult the process and the higher the risk of breakage during the treatment. The shallower the groove 9, the less medicament the individual score wire 3 can accommodate. In some alternative embodiments, the bottom of the groove 9 is located at 1/3 to 2/3 of the height of the score wire 3, for example, 1/3, 2/5, 1/2, 3/5 or 2/3, considering the combined processing difficulty, surgical risk and total content of the single score wire drug.

The height of the notch wire 3 refers to the highest position of the cross section of the notch wire 3, and when the axial cross section of the notch wire 3 is rectangular, the height of the notch wire 3 is rectangular; when the axial cross section of the notch wire 3 is in a major arc shape, the height of the notch wire is the radius of the circle where the major arc shape is located.

Preferably, as shown in fig. 1, two developing rings 7 are further provided on the inner tube 6.

In some alternative embodiments, the drug stored in the groove 9 of the score wire 3 comprises a drug microcapsule, as shown in fig. 9, comprising a shell 10 and a drug active 11 enclosed in the shell 10. During treatment, the shock wave energy breaks the shell 10 of the drug microcapsule, releasing the drug active 11 enclosed therein, without losing the drug mass.

The diameter of the drug microcapsules is preferably 1 to 10 μm, and may be, for example, 1,2, 3, 4,5, 6, 7, 8, 9 or 10 μm.

The pharmaceutically active ingredient 11 is used for preventing, alleviating and/or treating diseases, and the skilled person can select the corresponding pharmaceutically active ingredient according to the desired affected area of the medical shock wave balloon catheter, according to the general therapeutic principles of the art, which the present invention is not limited to.

In some alternative embodiments, the pharmaceutically active ingredient comprises paclitaxel.

The shell 10 of the drug microcapsule has a wide range of materials, typically at least one of degradable polyester, degradable polyanhydride, degradable polyamino acid and complexing agent, and the materials of the shell have low manufacturing cost.

Specifically, the degradable polyester is any one or a physical blend of at least two of polylactic acid, polyglycolic acid, poly succinate, poly beta-hydroxybutyrate, polycaprolactone, polyethylene glycol adipate, poly valerate, polyhydroxyalkyl alcohol ester and poly malate;

or, the degradable polyester is a copolymer of at least two monomers from the group of monomers that form polylactic acid, polyglycolic acid, poly succinate, poly beta-hydroxybutyrate, polycaprolactone, polyethylene adipate, poly valerate, polyhydroxyalkyl alcohol esters, and poly malate.

Optionally, the degradable polyanhydride is at least one of polyglycolic anhydride, polysuccinic anhydride, polyadipic anhydride, polysebacic anhydride, polydodecyl anhydride, polycyitric anhydride, polymalic anhydride, polysuccinic anhydride, polytartaric anhydride, polyitaconic anhydride and polymaleic anhydride.

Or, the degradable polyanhydride is a copolymer formed by copolymerizing at least one of monomers forming the polyethylene glycol anhydride, the poly succinic anhydride, the poly adipic anhydride, the poly sebacic anhydride, the poly dodecaanhydride, the poly citric anhydride, the poly malic anhydride, the poly succinic anhydride, the poly tartaric anhydride, the poly itaconic anhydride and the poly maleic anhydride with at least one of monomers forming the polylactic acid, the poly glycolic acid, the polycaprolactone, the poly succinic acid ester, the poly (beta-hydroxybutyrate), the polyethylene glycol adipate and the polyhydroxybutyrate valerate.

The degradable polyamino acid is at least one of polylysine, polyaspartic acid, polycysteine, polymethine, polyornithine, polyglycine and polyglutamic acid.

The complexing agent is selected from 8-hydroxyquinoline, 8-hydroxyquinaldine, 4, 5-dihydroxybenzene-1, 3-disulfonic acid sodium salt, 4- [3, 5-dihydroxybenzene-1H-1, 2, 4-triazole ] -benzoic acid, 8-mercaptoquinoline, thioglycollic acid, methyl 5-methyl-2-mercaptobenzoate, ethylenediamine, triethylenetetramine, ethylenediamine tetraacetic acid tetrasodium salt, N' - [5- [ [4- [ [5- (acetamido) amyl ] amino ] -1, 4-dioxobutyl ] hydroxylamine ] pentyl ] -N- (5-aminopentyl) -N-hydroxysuccinamide, phenanthroline, bipyridine, porphyrin, porphine, chlorophyll, hemoglobin, 1, 2-dimethyl-3-hydroxy-4-pyridone 1-nitroso-2-naphthol, 1-nitroso-2-naphthol-6-sodium sulfonate, sulfosalicylic acid, 8-hydroxyquinoline-5-sulfonic acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphate, polyphosphoric acid, sodium pyrophosphate, sodium hexametaphosphate, ammonium polyphosphate, potassium diethylenetriamine pentamethylphosphonate, sodium ethylenediamine tetramethylene phosphonate, oxalic acid, tartaric acid, malic acid, succinic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, nitrilotriacetic acid, diethylenetriamine pentacarboxylic acid, alginic acid, glutamic acid, aspartic acid, ornithine, lysine, potassium citrate, calcium citrate, glyceryl citrate, citric acid, at least one of acetylsalicylic acid and sulfosalicylamide.

The preparation method of the drug microcapsule is preferably as follows: dissolving the material constituting the case 10 in an organic solvent; dispersing the pharmaceutically active ingredient 11 in distilled water; the auxiliary materials are dissolved in distilled water. The dissolved shell material solution is added to the active ingredient suspension and pre-emulsified by means of an ultrasonic cytobreaker. Then adding the pre-emulsion into the auxiliary material aqueous solution, and immediately placing into a rapid membrane emulsifier. After several extrusions through the ceramic microporous membrane tube at room temperature, the mixture was gently stirred until the organic phase was completely evaporated. And finally, centrifuging and freeze-drying to obtain a white powdery product.

The drug in the groove 9 of the score wire 3 may be optionally dissolved, dispersed or suspended in a solvent, and the solvent may be any pharmaceutically acceptable solvent, which is not limited in this regard.

When the drug in the grooves 9 of the score wire 3 is a drug microcapsule, the drug microcapsule is preferably suspended in a solvent, which preferably comprises an organic solvent, which may be, for example, but not limited to, PEG-2000 or ethanol. The pharmaceutical microcapsules suspended in the organic solvent are preferably sprayed into the grooves 9 of the score wire 3 using a spray coater.

According to the drug shock wave balloon catheter provided by the invention, the notch wire 3 is arranged outside the balloon 2, and the active drug is arranged in the notch wire 3, so that loss of the drug in the conveying process can be reduced, after the drug shock wave balloon catheter is implanted to a lesion part, after the shock wave transmitting device 8 generates shock waves, the drug can be gradually released under the action of the shock waves, and a better treatment effect is achieved.

The technical solution and technical effects of the present invention are further described below in connection with preferred embodiments.

Example 1

The embodiment provides a drug shock wave balloon catheter, and the three-dimensional structure is shown in fig. 1-3.

The drug shock wave balloon catheter comprises a balloon 2 and a catheter. The balloon 2 has a length of 12mm and a diameter of 3mm. The surface of the balloon 2 is adhered with a plurality of notch wires 3 in a straight line along the axial direction of the balloon 2, and the notch wires 3 in the embodiment are made of nickel-titanium alloy. The surface of the score wire 3 is provided with a groove 9 for storing a drug, which groove 9 is a continuous groove extending in the length direction of the score wire 3. The ends and head ends of the score line 3 are not provided with grooves 9. The axial cross section of the grooving wire 3 is preferably arc-shaped, and the axial cross section of the groove 9 is rectangular, as shown in fig. 4. The drug microcapsules are sprayed into the grooves 9 of the score wire 3.

The drug shock wave balloon catheter comprises an inner tube 6 and an outer tube 4, wherein the inner tube 6 is sleeved in the outer tube 4, as shown in figure 2. The inner tube 6 is used for passing the finger guide wire 5, and the catheter is delivered to the lesion through the finger guide wire 5 through the inner tube 6 during operation. The outer tube 4 is connected with the head end of the balloon 2, and the inner tube 6 penetrates through the interior of the balloon 2 along the axial direction of the balloon 2. A space for the flow of the substance filled in the balloon 2 is reserved between the inner tube 6 and the outer tube 4, and the substance filled in the balloon 2 is conveyed into the balloon 2 through the space between the outer tube 4 and the inner tube 6. The substance filling the balloon 2 may be selected from physiological saline or contrast agent. 2 shock wave emitting devices 8 are further arranged in the balloon 2, the 2 shock wave emitting devices 8 are arranged on the outer surface of the inner tube 6, and the voltage of the shock wave emitting devices 8 is 2500V.

The tail end of the inner tube 6 is in sealing connection with the tail end pin of the balloon, the tail end of the balloon 2 is also provided with a tail end tube 1, the tail end tube 1 is sleeved outside the tail end of the inner tube 6, and the tail end of the notch wire 3 is fixed between the tail end tube 1 and the tail end pin of the balloon; the tail end of the tail end tube 1, the tail end of the notch wire 3, the tail end pin of the balloon and the tail end of the inner tube 6 are welded by laser.

The outer tube 4 is connected with the balloon head end pin in a sealing way, a space for circulating substances of the filled balloon 2 is reserved between the joint of the outer tube 4 and the balloon head end pin and the outer wall of the inner tube 6, the head end of the notch wire 3 is fixed between the balloon head end pin and the outer tube 4, and the head end of the notch wire 3, the balloon head end pin and the outer tube 4 are welded by laser.

The drug shock wave balloon catheter provided by the embodiment is used for severe calcification lesions of coronary arteries. The drug shock wave balloon catheter is subjected to simulation treatment in an in-vitro calcified blood vessel model, and the drug loss rate in the conveying process is found to be 9%, the residual drug in the metal wire groove is found to be 88%, the drug transfer rate is found to be 61%, and the calcified blood vessel model is successfully fractured.

The drug active component 11 in the drug microcapsule of the embodiment is paclitaxel, the material of the shell 10 is polylactic acid-glycolic acid copolymer, the microcapsule structure is shown in fig. 5, and the preparation method is as follows:

0.8g of PLGA (polylactic acid-glycolic acid copolymer, 50/50, intrinsic viscosity 1.0 dl/g) was dissolved in 56g of methylene chloride. 0.2g of paclitaxel was dispersed in 10g of distilled water. 10g of PVA (polyvinyl alcohol, average molecular weight 2000) are dissolved in 1000ml of distilled water.

PLGA in dichloromethane was added to the paclitaxel suspension and pre-emulsified by ultrasonic cytoclasis for 1 min. The pre-emulsion was then added to the aqueous PVA solution and immediately placed into a fast film emulsifier. After 11 extrusions through a 5 μm ceramic microporous membrane tube at room temperature, the mixture was gently stirred until the organic phase was completely evaporated. And finally, centrifuging and freeze-drying to obtain a white powdery product. The prepared taxol microcapsule has a diameter of 3 μm and a drug content of 3 μg/mm ² 。

The paclitaxel microcapsules were suspended in PEG-2000/ethanol solvent and then spray coated.

Example 2

The drug shock wave balloon catheter provided in this embodiment is different from embodiment 1 only in that the notch wire 3 is different, the axial cross section of the notch wire 3 in this embodiment is preferably arc-shaped, and the axial cross section of the groove 9 is semicircular, as shown in fig. 6.

The drug shock wave balloon catheter provided by the embodiment is used for severe calcification lesions of coronary arteries. The drug shock wave balloon catheter is subjected to simulated treatment in an in-vitro calcified blood vessel model, and the drug loss rate in the conveying process is found to be 11%, the residual drug in the metal wire groove is found to be 86%, the drug transfer rate is found to be 62%, and the calcified blood vessel model is successfully fractured.

Example 3

The drug shock wave balloon catheter provided in this embodiment is different from embodiment 2 only in that the drug active ingredient in the drug microcapsule is rapamycin, and the drug sprayed in the notch wire 3 in this embodiment is a common drug coating. Specifically, rapamycin and polylactic acid are dissolved in ethyl acetate and sprayed into the groove 9 of the notch wire 3, and the medicine content is 3 mug/mm ² 。

The drug shock wave balloon catheter provided by the embodiment is used for severe calcification lesions of coronary arteries. The drug shock wave balloon catheter is subjected to simulated treatment in an in-vitro calcified blood vessel model, and the drug loss rate in the conveying process is found to be 30%, the residual drug in the metal wire groove is found to be 67%, the drug transfer rate is found to be 15%, and the calcified blood vessel model is successfully fractured.

Example 4

The balloon 2 of the drug shock wave balloon catheter provided by the embodiment has the nominal length of 30mm, the nominal diameter of 18mm, the axial cross section of the notch wire 3 is rectangular, and the axial cross section of the groove 9 is rectangular, as shown in fig. 7; 6 shock wave emitting devices 8 are arranged in the device, and the voltage is set to 3000V; the remainder was the same as in example 1.

The drug shock wave balloon catheter provided by the embodiment is used for the right ventricular outflow tract stenosis, the drug shock wave balloon catheter is subjected to simulation treatment in an in-vitro calcified blood vessel model, the drug loss rate in the conveying process is found to be 9%, the residual drug in a metal wire groove is found to be 89%, the drug transfer rate is found to be 62%, and the calcified model is successfully fractured.

Example 5

The balloon 2 of the drug shock wave balloon catheter provided by the embodiment has the nominal length of 30mm, the nominal diameter of 18mm, the axial cross section of the notch wire 3 is rectangular, and the axial cross section of the groove 9 is semicircular, as shown in fig. 8 and 9; 6 shock wave emitting devices 8 are arranged in the device, and the voltage is set to 3000V; the remainder was the same as in example 1.

The drug shock wave balloon catheter provided by the embodiment is used for the right ventricular outflow tract stenosis, the drug shock wave balloon catheter is subjected to simulation treatment in an in-vitro calcified blood vessel model, the drug loss rate in the conveying process is found to be 10%, the residual drug in a metal wire groove is found to be 88%, the drug transfer rate is found to be 63%, and the calcified model is successfully fractured.

Comparative example 1

The drug shock wave balloon catheter provided in this comparative example was not provided with the notch wire 3, and the drug microcapsule prepared according to the preparation method of example 1 was sprayed onto the surface of the balloon 2, and the rest was the same as in example 1.

The drug shock wave balloon catheter provided by the embodiment is used for severe calcification lesions of coronary arteries. The drug shock wave balloon catheter is subjected to simulated treatment in an in-vitro calcified blood vessel model, and the drug loss rate in the conveying process is found to be 53%, the residual drug in the metal wire groove is found to be 42%, the drug transfer rate is found to be 32%, and the calcified blood vessel model is successfully fractured.

Comparative example 2

The drug shock wave balloon catheter provided in this comparative example was not provided with notch 3, paclitaxel and polylactic acid were dissolved in ethyl acetate, sprayed onto the balloon surface, and drug content was 3 μg/mm ² The remainder was the same as in example 1.

The drug shock wave balloon catheter provided by the embodiment is used for severe calcification lesions of coronary arteries. The drug shock wave balloon catheter is subjected to simulated treatment in an in-vitro calcified blood vessel model, and the drug loss rate in the conveying process is found to be 85%, the residual drug in the metal wire groove is found to be 13%, the drug transfer rate is found to be 4%, and the calcified blood vessel model is successfully fractured.

The effects of examples 1 to 5 and comparative examples 1 to 2 are shown in the following table.

TABLE 1

As can be seen from the comparison results, the drug shock wave balloon catheter with the notch wire 3 has less drug loss in the conveying process than the drug shock wave balloon catheter without the notch wire 3; the residual medicine amount of the medicine shock wave balloon catheter with the notch wire 3 is larger than that of the medicine shock wave balloon catheter without the notch wire 3, and the medicine transfer rate of the medicine shock wave balloon catheter with the notch wire 3 is generally larger than that of the medicine shock wave balloon catheter without the notch wire 3.

In the description of the present invention, it should be noted that the azimuth or positional relationship indicated by the terms "upper", "lower", etc. are based on the azimuth or positional relationship shown in the drawings, and are merely for convenience of describing the present invention and simplifying the description, and are not indicative or implying that the apparatus or element in question must have a specific azimuth, be constructed and operated in a specific azimuth, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; the communication may be direct or indirect through an intermediate medium, or may be internal to two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art. Furthermore, in the description of the present invention, unless otherwise indicated, the meaning of "a plurality" is two or more.

The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.

Claims

1. A drug shock wave balloon catheter, which is characterized by comprising an outer tube (4), an inner tube (6), a tail end tube (1), a balloon (2), at least one shock wave emitting device (8) and a notch wire (3);

the inner tube (6) is arranged in the inner cavity of the outer tube (4), and the distal end of the inner tube (6) penetrates out of the outer tube (4) and is fixedly connected with the tail end tube;

the balloon (2) is wrapped outside the inner tube (6), and two ends of the balloon (2) are respectively connected with the distal end of the outer tube (4) and the proximal end of the tail end tube (1) in a sealing manner;

a containing cavity is formed in the balloon (2), a liquid filling channel which can be communicated with the containing cavity in the balloon (2) is formed between the outer tube (4) and the inner tube (6), and liquid medium can be conveyed into the containing cavity in the balloon (2) through the liquid filling channel;

the shock wave transmitting device (8) is arranged inside the balloon (2);

the groove cutting wire (3) is arranged on the outer surface of the balloon (2), the groove cutting wire (3) is provided with a treatment surface, the treatment surface is away from the outer side surface of the balloon (2), a groove (9) is formed in the treatment surface, and a treatment medicine is sprayed in the groove (9).

2. A medical shock wave balloon catheter according to claim 1, wherein the score wire (3) is a ductile wire;

when the balloon (2) is in a contracted state, the notch wire (3) is in a contracted state and is attached to the inner tube (6) along with the balloon (2), and when the balloon (2) is in a filling state, the notch wire (3) is in an extending state and is attached to the outer side face of the balloon (2).

3. A medical shock wave balloon catheter according to claim 1, wherein the score wire (3) is of a continuous wave-like structure;

when the balloon (2) is in a contracted state, the wavy structure of the notch wire (3) is in a contracted state and is attached to the inner tube (6) along with the balloon (2), and when the balloon (2) is in a filling state, the wavy structure of the notch wire (3) is in a stretching state and is attached to the outer side face of the balloon (2).

4. A medical shock wave balloon catheter according to claim 2 or 3, characterized in that the score wires (3) are provided in a plurality, the score wires (3) being attached to the outer surface of the balloon (2) in the radial or axial direction of the balloon (2).

5. A medical shock wave balloon catheter according to claim 2 or 3, wherein the grooving wires (3) are provided in plurality, the grooving wires (3) are woven to form a net sleeve structure wrapped outside the balloon (2), and two ends of the net sleeve structure are respectively fixed at two opposite ends of the balloon (2).

6. A medical shock wave balloon catheter according to claim 5, wherein the radial cross section of the score wire (3) is circular, semi-circular, oval, arcuate, rectangular or irregular polygonal.

7. A medical shock wave balloon catheter according to claim 6, wherein the grooves (9) extend in the length direction of the score wire (3), the radial cross section of the grooves (9) being arcuate, semi-circular or rectangular.

8. A drug shock wave balloon catheter according to claim 7, characterized in that the ratio of the maximum width of the score wire (3) to the maximum width of the groove (9) is in the range of 1.2 to 2;

the bottom of the groove (9) is positioned at the position of 1/3 to 2/3 of the height of the notch wire (3).

9. A drug balloon catheter according to claim 1, characterized in that the therapeutic drug comprises drug microcapsules comprising a housing (10) and a drug active (11) enclosed in the housing (10);

the shell (10) is made of at least one of degradable polyester, degradable polyanhydride, degradable polyamino acid and complexing agent; the degradable polyester is any one or at least two physical blend of polylactic acid, polyglycolic acid, poly succinate, poly beta-hydroxybutyrate, polycaprolactone, polyethylene glycol adipate, poly valerate, polyhydroxyalkyl alcohol ester and poly malate; and/or, a copolymer of at least two of the monomers forming polylactic acid, polyglycolic acid, poly succinate, poly beta-hydroxybutyrate, polycaprolactone, polyethylene adipate, poly valerate, polyhydroxyalkyl alcohol esters, and poly malate; the degradable polyanhydride is at least one of polyglycolic anhydride, polysuccinic anhydride, polyadipic anhydride, polysebacic anhydride, polydodecyl anhydride, polycycloic anhydride, polymalic anhydride, polysuccinic anhydride, polytartaric anhydride, polyitaconic anhydride and polymaleic anhydride; and/or the degradable polyanhydride is selected from at least one of monomers forming polyethylene glycol anhydride, poly succinic anhydride, poly adipic anhydride, poly sebacic anhydride, poly dodecaanhydride, poly citric anhydride, poly malic anhydride, poly succinic anhydride, poly tartaric anhydride, poly itaconic anhydride and poly maleic anhydride and at least one of monomers forming polylactic acid, poly glycollic acid, polycaprolactone, poly succinic acid ester, poly beta-hydroxybutyrate, poly glycol adipate and poly hydroxybutyrate valerate;

The pharmaceutical active ingredient (11) comprises paclitaxel and derivatives thereof, rapamycin and derivatives thereof;

the particle size of the drug microcapsule is 1 to 10 μm.

10. A medical shock wave balloon catheter according to claim 9, characterized in that the shock wave emitted by the shock wave emitting means (8) has a positive sound pressure peak value of 1 to 10MPa at the surface of the balloon (2).