CN111298274B

CN111298274B - Medicine balloon and using method thereof

Info

Publication number: CN111298274B
Application number: CN202010404681.3A
Authority: CN
Inventors: 祁勇翔; 罗雷; 聂芳芳; 李丹; 唐乃杰; 缪永生; 刘瑜
Original assignee: Shanghai Biomagic Medical Co ltd
Current assignee: Shanghai Biomagic Medical Co ltd
Priority date: 2020-05-14
Filing date: 2020-05-14
Publication date: 2020-09-22
Anticipated expiration: 2040-05-14
Also published as: CN111298274A

Abstract

The invention relates to the technical field of medical instruments and discloses a medicine balloon and a using method thereof. The drug balloon comprises a balloon catheter, the balloon catheter comprises a balloon body section and a liquid through pipe, two ends of the balloon body section are respectively connected with the liquid through pipe, and an inner cavity of the balloon body section is communicated with the liquid through pipe to form a liquid through cavity; the surface of the balloon body section is also provided with a blood flow cavity for blood to pass through, and the blood flow cavity is formed by the surrounding of the side wall of the liquid through cavity; micropores for the medicine microsphere preparation to pass through are distributed on the outer arc surface of the balloon body section. When the medicine balloon is pressurized, the blood flow cavity can supply blood in a blood vessel to pass through, so that sufficient downstream blood supply can be ensured, and myocardial ischemia caused by vessel occlusion is avoided; meanwhile, the sufficient contact action time between the surface of the balloon and the inner wall of the blood vessel is ensured, and the adhesion effect of the medicine on the target blood vessel wall is improved; through set up the micropore at sacculus body section and release the medicine microballon preparation to the vascular wall, can let the medicine more stably remain in the vascular wall effectively, long-term stable release.

Description

Medicine balloon and using method thereof

Technical Field

The invention relates to the technical field of medical instruments, in particular to a medicine balloon and a using method thereof.

Background

Cardiovascular and cerebrovascular diseases have become the first cause of death worldwide. At present, the following methods are mainly used for treating ischemic heart disease: drug-based basic therapies, coronary bypass-based surgical therapies, coronary stent-based interventions, and drug balloon-based interventions. The above treatments all have shown significant results in the treatment of coronary stenosis, but each still has some significant problems.

The coronary stent implantation is to deliver a stent system to a target area in a puncture intervention mode, expand a balloon to release a stent, open a stenotic lesion blood vessel, recover blood supply and treat ischemic heart disease. However, the stent is in the human body for a long time, the body can be stimulated to generate immune rejection, smooth muscle cells are excessively proliferated to cause thickening of an inner membrane, so that the loss of a lumen is caused, the patency rate of the lumen is reduced, the blood supply is influenced, and the life health and safety of a patient are threatened. Therefore, for the restenosis lesion in the stent, a secondary interventional operation needs to be performed on the patient, the restenosis lesion blood vessel is supported again, the blood flow is recovered, and the life of the patient is saved.

The appearance of the drug balloon solves the problems of the coronary stent to a certain extent, and the drug released from the balloon acts on primary stenosis and restenosis to inhibit smooth muscle cell hyperproliferation and ensure the smoothness of the lumen. After the operation is finished, the medicine balloon system is withdrawn from the body, so that the permanent implantation of the instrument is avoided, and the risks of stent fracture, long-term thrombus and the like are eliminated.

The traditional medicine balloon is characterized in that a medicine coating is coated on the surface of a naked balloon, and after the balloon is pressurized, medicines contained in the coating contact and act on the inner wall of a blood vessel to inhibit cell proliferation, so that the traditional medicine balloon has the function of resisting intimal hyperplasia, and the long-term lumen smoothness of the blood vessel is ensured. However, conventional drug balloons also present some serious problems during design and use. Firstly, the traditional medicine balloon seals a blood vessel after being expanded in the blood vessel, and blood flow cannot flow to the downstream, so that the downstream myocardial ischemia of coronary artery is caused, and the life of a patient is threatened. In order to reduce the problem of myocardial ischemia caused by artificial blood vessel closure as much as possible, the time for pressurizing the balloon is controlled within 1 minute. Simultaneously, reduce the time that the sacculus was pressurized and will directly influence the time of sacculus and vascular wall laminating, and then reduce the adhesion efficiency of medicine on the vascular surface, reduce the effective medicine content of vascular wall to influence the treatment effect of primary stenosis pathological change and restenosis pathological change. Secondly, the traditional medicine coating adopts a method of recrystallization after mixing the medicine and the carrier and is adhered to the surface of the saccule, when the saccule is pressurized, the crystallized coating is broken, the medicine is adhered to the blood vessel wall in a chip shape under the action of the carrier, the medicine is easy to fall off under the long-term impact of blood flow, and the long-term adhesion rate of the medicine is low. Moreover, in the process of delivery and release, the drug coating on the surface of the balloon can be partially peeled off under the action of blood flow impact and expansion pressure and then flows into blood, and partial coating can also be remained on the surface of the balloon when the balloon is withdrawn after pressure relief. Therefore, most of the medicine runs off in the operation process of the traditional medicine balloon, the amount of the medicine really acting on the blood vessel wall is small, the effective release rate of the medicine is low, and the treatment effect is influenced. Finally, the drug coating that is shed off by conventional balloons during expansion and release is not soluble in blood, will be present in the form of large particles, and with blood flow to the distal small vessels, there is a significant risk of occluding the distal vessels.

In summary, for primary stenosis and restenosis, how to develop a drug balloon, when the balloon is pressurized, enough blood supply is ensured, and myocardial ischemia caused by vessel occlusion is avoided or reduced; how to ensure that the balloon surface has sufficient contact action time with the inner wall of the blood vessel when the balloon is pressurized, and improve the adhesion effect of the medicine on the target vessel wall; how to develop a new drug and carrier combination and release mode, so that the drug and carrier are retained on the vessel wall in a more stable and effective mode, and the long-term stable release of the drug is ensured; how to avoid or reduce the falling of a medicine coating and the residue on the surface of the balloon when the balloon is used for conveying, pressurizing and pressure relief, and improve the effective release rate of the medicine; how to avoid or reduce large particles caused by coating falling off and avoid or reduce the occurrence of distal vascular embolism and acute myocardial infarction when the saccule is conveyed and pressurized is a problem which needs to be solved by the technicians in the field at present.

Disclosure of Invention

Based on the above, the present invention provides a drug balloon and a method for using the same, so as to solve the above technical problems in the prior art.

In order to achieve the purpose, the invention adopts the following technical scheme:

a medicine balloon comprises a balloon catheter, wherein the balloon catheter comprises a balloon body section and a liquid through pipe, two ends of the balloon body section are respectively connected with the liquid through pipe, and an inner cavity of the balloon body section is communicated with the liquid through pipe to form a liquid through cavity; the surface of the balloon body section is also provided with a blood flow cavity for blood to pass through, and the blood flow cavity is formed by the surrounding of the side wall of the liquid through cavity; micropores for the medicine microsphere preparation to pass through are distributed on the outer arc surface of the balloon body section.

As a preferable scheme of the drug balloon, the number n of the balloon body segments is 1-16, and the number of the blood flow cavities is equal to that of the balloon body segments.

As a preferable scheme of the medicine balloon, the balloon body segment is linearly arranged or spirally twisted along the axial direction of the liquid through pipe.

As a preferable scheme of the medicine balloon, the micropores are distributed in a linear array or a spiral torsion mode along the axial direction of the liquid through pipe.

As a preferred scheme of a medicine balloon, the number n of balloon body segments is 1, the cross section of the liquid through cavity is crescent, and the cross section of the blood flow cavity is circular with an opening.

As a preferable scheme of the drug balloon, the number n of the balloon body segments is 2-8, and the n balloon body segments are uniformly distributed in the circumferential direction; the cross section of the liquid through cavity is a round T-shaped structure with n bent parts uniformly distributed; the cross section of the blood flow cavity is of a special-shaped fan-shaped structure.

As a preferable scheme of the medicine balloon, the wall thickness of the balloon body section is 0.01-0.1mm, and the ear part thickness of the bent T-shaped structure is 0.3-0.5 mm.

As a preferable scheme of the medicine balloon, the sum of the sectional areas of the blood flow cavities accounts for more than 30% of the sectional area of the whole balloon body section.

As a preferable scheme of the medicine balloon, the proximal end of the liquid through tube is opened to allow liquid to pass through; the liquid through tube is closed at the far end and does not allow liquid to pass through.

As a preferable scheme of the drug balloon, the diameters of the micropores on the balloon body segment are the same, or the diameters of the micropores on the proximal end area of the balloon body segment and the distal end area of the balloon body segment are larger than the diameter of the micropores on the middle area of the balloon body segment.

As a preferable scheme of the drug balloon, the diameter of the micropores is 1-100 μm.

As a preferable scheme of the medicine balloon, in each row of micropores, the axial arrangement distance between every two adjacent micropores is 0.1-10 mm.

As a preferable scheme of the medicine balloon, when the balloon body section is spirally twisted along the axial direction of the liquid through pipe, the pitch of the spiral line of the balloon body section is 1-20 mm.

As a preferred embodiment of the drug balloon, the drug microsphere formulation comprises: the drug microsphere is in a suspension state in the working medium at room temperature, and the maximum size of the drug microsphere is smaller than the diameter of the micropore.

As a preferred embodiment of the drug balloon, the maximum size of the drug microspheres is less than 1/5 of the diameter of the micropores.

As a preferable scheme of the drug balloon, the drug microsphere is in a spherical structure, and the diameter of the drug microsphere is 1-990 nm.

As a preferred embodiment of the drug balloon, the drug microsphere comprises a drug and an excipient; the medicine is one or more of nimustine, carmustine, 5-fluorouracil, fluoroguanosine, gemcitabine, daunorubicin, doxorubicin, paclitaxel, vinblastine, topotecan, aminoglutethimide, sirolimus, everolimus, rapamycin and zotarolimus; the excipient is one or more of racemic polylactic acid, polyethylene glycol, magnesium stearate, iohexol, iopromide, urea, sorbitol, polysorbitol, polyoxyethylene polyoxypropylene ether block copolymer, trihexyl citrate, phospholipid, ropiperazine matrix, polylactic acid-glycolic acid copolymer, polyvinylpyrrolidone, cholesterol, vitamin E and vitamin E polyethylene glycol succinate.

A method of using a drug balloon as described in any of the above aspects, comprising the steps of:

s1: after the medicine saccule is released to a target lesion area, first preset pressure is applied to the saccule catheter through the medicine microballoon preparation, so that the medicine microballoon preparation flows into a saccule body section from the liquid through pipe and flows out of the medicine saccule through the micropores, and liquid drops are formed, grown and dropped periodically outside the medicine saccule;

s2: and applying a second preset pressure to the balloon catheter through the medicinal microsphere preparation, so that the medicinal microsphere preparation is jetted outwards at a high speed from the micropores to form a 'cavity effect', and the medicinal microspheres are embedded in target tissues in the blood vessel.

As a preferable scheme of the using method of the drug balloon, the first preset pressure is 1-8 atm.

As a preferable scheme of the using method of the drug balloon, the second preset pressure is 8-20 atm.

The invention has the beneficial effects that:

the balloon body section is communicated with the liquid through pipe to form a liquid through cavity for introducing the medicinal microsphere preparation into the balloon; the surface of the balloon body section is provided with a blood flow cavity for blood circulation in blood vessels in the operation process; micropores are distributed on the outer arc surface of the balloon body section and are used for enabling the drug microsphere preparation in the liquid through cavity to flow out or be ejected at high speed through the micropores, so that the drug microspheres can stably stay in target lesion tissues.

When the medicine balloon is pressurized, the blood flow cavity can supply blood in a blood vessel to pass through, so that sufficient downstream blood supply can be ensured, and myocardial ischemia caused by vessel occlusion is avoided; meanwhile, the balloon surface and the inner wall of the blood vessel have sufficient contact action time, and the adhesion effect of the medicine on the target blood vessel wall is improved. The invention releases the drug microsphere preparation to the vessel wall through the micropores arranged on the balloon body section, so that the drug can be more stably and effectively retained on the vessel wall, and the drug can be stably released for a long time. Moreover, when the drug balloon is used for conveying, pressurizing and pressure relief, the problems of falling off and residue of a drug coating do not exist, and the effective release rate of the drug is greatly improved; meanwhile, the problems of distal vascular embolism, acute myocardial infarction and the like caused by the falling of the coating are avoided.

In addition, the diameters of the micropores in the proximal end area of the balloon body section and the distal end area of the balloon body section in the embodiment of the invention are larger than the diameter of the micropores in the middle area of the balloon body section. The effect of the above differential aperture design lies in: firstly, when the balloon body section is initially formed, high temperature and high pressure are applied to the inside of a thin-wall polymer tube, and a main cylindrical balloon body section structure with two conical ends is formed under the limitation of an external balloon forming mold. In the process of forming the balloon, the temperature of the two ends of the balloon body section is lower relative to the middle part (only the balloon body section of the tube is heated, the temperature of the two ends close to the external environment is lower), the strength is higher, and the balloon body section cannot be completely expanded to the target diameter in a forming die under the conventional condition. That is, after the balloon body segment is blow molded at high temperature and high pressure, the diameters of the two ends are generally slightly smaller than the diameter of the middle portion. Under the condition that the volume of the material of the balloon body section is not changed (the length of the balloon body section is not changed in the forming process, such as lengthening or shortening), theoretically, the cross-sectional areas of the balloon body section are equal, the diameters of two ends of the balloon body section are small, the diameter of the middle section is large, and then the two end walls are thick and the middle wall is thin. If the micropore aperture that distributes at sacculus both ends and middle section is the same, because both ends wall thickness, also the micropore degree of depth is darker, the inside high-pressure liquid of sacculus just also longer through the route that micropore flowed out the sacculus, and external resistance is bigger, and the flow is littleer, so can guarantee through the micropore aperture at increase sacculus both ends that the flow is more balanced. Second, when the balloon is applied to a restenosis lesion, the proximal and distal end regions of the balloon body segment correspond to the proximal and distal end regions of the restenosis lesion. Clinically, these two regional restenosis pathological changes are more serious than middle section pathological changes (when stenosis pathological change is implanted the support for the first time, the near-end of support and distal end wave pole can stimulate the vascular wall that corresponds the region, the vascular inner wall in this region receives the stimulation, arouse a series of strong cellular reaction, arouse smooth muscle cell transitional proliferation, and this vascular region contains the support blank, do not have the powerful support of support, so the lumen is lost more obviously, the vessel diameter obviously reduces, hinder the blood flow), so also can guarantee more medicine supplies through the micropore aperture at increase sacculus both ends, guarantee that long-term lumen is unobstructed. Of course, in other embodiments, the diameters of the micropores may be the same throughout the balloon body segment, thereby simplifying the manufacturing process of the balloon body segment.

Drawings

Fig. 1 is a schematic structural diagram of a drug balloon provided in an embodiment of the present invention (the direction of the arrow indicates the direction of blood flow);

FIG. 2 is an enlarged view of a portion of FIG. 1 (the direction of the arrows indicate the direction of flow of the liquid medicine);

fig. 3 is a front view of a drug balloon provided in accordance with an embodiment of the present invention;

FIG. 4 is a view of the drug balloon of FIG. 3 in the direction A-A;

FIG. 5 is a schematic cross-sectional view of a drug balloon according to an embodiment of the present invention;

FIG. 6 is a schematic cross-sectional view of a drug balloon inserted into a blood vessel according to an embodiment of the present invention;

fig. 7 is a schematic structural diagram of a drug balloon provided in the second embodiment of the present invention (the direction of the arrow indicates the direction of blood flow);

FIG. 8 is an enlarged view of a portion of FIG. 7 (the direction of the arrows indicate the direction of flow of the medical fluid);

fig. 9 is a front view of a drug balloon provided in accordance with example two of the present invention;

FIG. 10 is a view of the drug balloon of FIG. 9 in the direction B-B;

fig. 11 is a schematic cross-sectional structural view of a drug balloon provided in the second embodiment of the present invention;

fig. 12 is a schematic cross-sectional structure diagram of a drug balloon interventional vessel provided by the second embodiment of the invention;

fig. 13 is a schematic structural diagram of a drug balloon provided in the third embodiment of the present invention (the direction of the arrow indicates the direction of blood flow);

FIG. 14 is an enlarged view of a portion of FIG. 13 (the direction of the arrows indicating the direction of flow of the medical fluid);

fig. 15 is a front view of a drug balloon provided in accordance with a third embodiment of the present invention;

FIG. 16 is a view of the drug balloon of FIG. 15 in the direction C-C;

fig. 17 is a schematic cross-sectional structural view of a drug balloon provided in the third embodiment of the present invention;

fig. 18 is a schematic cross-sectional structure view of a drug balloon interventional vessel provided by the third embodiment of the invention;

fig. 19 is a schematic structural view of a drug balloon provided in accordance with a fourth embodiment of the present invention (the direction of the arrows indicate the direction of blood flow);

FIG. 20 is an enlarged view of a portion of FIG. 19 (the direction of the arrows indicating the direction of flow of the medical fluid);

fig. 21 is a front view of a drug balloon provided in accordance with a fourth embodiment of the present invention;

FIG. 22 is a view of the drug balloon of FIG. 21 in the D-D direction;

fig. 23 is a schematic cross-sectional view of a drug balloon provided in accordance with a fourth embodiment of the present invention;

fig. 24 is a schematic cross-sectional view of a drug balloon inserted into a blood vessel according to the fourth embodiment of the present invention;

FIG. 25 is a schematic modeling diagram of finite element analysis of a blood flow chamber according to a first embodiment of the present invention;

FIG. 26 is a cloud view of a flow rate slice of a finite element analysis of a blood flow lumen according to a first embodiment of the present invention;

FIG. 27 is a velocity field arrow plot of a finite element analysis of a blood flow lumen according to a first embodiment of the present invention;

FIG. 28 is a cloud of pressure slices from a finite element analysis of a blood flow chamber according to a first embodiment of the invention;

FIG. 29 is a schematic modeling diagram of finite element analysis of the blood flow chamber according to the second embodiment of the present invention;

FIG. 30 is a cloud view of a flow rate slice of a finite element analysis of the blood flow lumen of the second embodiment of the present invention;

FIG. 31 is a velocity field arrow plot of a finite element analysis of the flow lumen of example two of the present invention;

FIG. 32 is a cloud of pressure slices from a finite element analysis of the blood flow chamber of the second embodiment of the present invention;

FIG. 33 is a schematic modeling diagram of finite element analysis of a blood flow lumen according to a third embodiment of the present invention;

FIG. 34 is a cloud image of a flow rate slice of a finite element analysis of the blood flow lumen of the third embodiment of the present invention;

FIG. 35 is a velocity field arrow plot of a finite element analysis of the blood flow lumen of the third embodiment of the present invention;

FIG. 36 is a cloud image of a pressure slice of a finite element analysis of the blood flow lumen of the third embodiment of the present invention;

FIG. 37 is a schematic modeling diagram of a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention;

FIG. 38 is a cloud of flow rate slices from a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention;

FIG. 39 is a velocity field volume arrow plot of a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention;

FIG. 40 is a cloud image of pressure slices from a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention.

In the figure:

1-vessel wall; 10-a drug balloon; 100-balloon catheter; 110-balloon body segment; 120-liquid through pipe; 130-the blood flow lumen; a 1-inlet; a 2-outlet; 140-a liquid through cavity; 1101-balloon segment side; 1102-balloon body segment outer arc surface; 1103-micropores; 1104-balloon body segment proximal end; 1105-the distal end of the balloon body segment; 1106-balloon body segment middle; 1201-liquid pipe extrados surface; 1202-proximal of the catheter; 1203-liquid tube distal end;

2-vessel wall; 20-a drug balloon; 200-a balloon catheter; 210-balloon body segment; 220-liquid through pipe; 230-the blood flow lumen; b 1-inlet; b 2-outlet; 240-liquid through cavity; 2101-balloon body segment side; 2102-balloon body segment outer arc; 2103-microwell; 2104-balloon body segment proximal end; 2105-balloon body segment distal end; 2106-balloon body segment middle; 2201-outer arc surface of liquid-passing pipe; 2202-proximal end of liquid conduit; 2203-a distal end of a liquid through tube;

3-vessel wall; 30-a drug balloon; 300-a balloon catheter; 310-balloon body segment; 320-liquid through pipe; 330-blood flow lumen; c 1-inlet; c 2-outlet; 340-liquid through cavity; 3101-inner arc surface of balloon body segment; 3102-outer arc surface of balloon body segment; 3103-microwells; 3104-balloon body segment proximal end; 3105-balloon body segment distal end; 3106-balloon body segment middle; 3202-proximal end of liquid-passing tube; 3203-distal end of liquid-passing tube;

4-vessel wall; 40-a drug balloon; 400-balloon catheter; 410-balloon body segment; 420-liquid through pipe; 430-the blood flow lumen; d 1-inlet; d 2-outlet; 440-a liquid through cavity; 4101-inner arc surface of balloon body segment; 4102-outer arc surface of balloon body segment; 4103-microwell; 4104-balloon body segment proximal end; 4105-balloon body segment distal end; 4106-balloon body segment middle; 4202-proximal end of liquid-conducting tube; 4203-distal end of liquid-passing tube.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings and examples. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting of the invention. It should be further noted that, for the convenience of description, only some of the structures related to the present invention are shown in the drawings, not all of the structures.

In the description of the present invention, unless expressly stated or limited otherwise, the terms "connected," "connected," and "fixed" are to be construed broadly, e.g., as meaning permanently connected, removably connected, or integral to one another; can be mechanically or electrically connected; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.

In the present invention, unless otherwise expressly stated or limited, "above" or "below" a first feature means that the first and second features are in direct contact, or that the first and second features are not in direct contact but are in contact with each other via another feature therebetween. Also, the first feature being "on," "above" and "over" the second feature includes the first feature being directly on and obliquely above the second feature, or merely indicating that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature includes the first feature being directly under and obliquely below the second feature, or simply meaning that the first feature is at a lesser elevation than the second feature.

In the description of the present embodiment, the terms "upper", "lower", "left", "right", and the like are used based on the orientations and positional relationships shown in the drawings only for convenience of description and simplification of operation, and do not indicate or imply that the referred device or element must have a specific orientation, be configured and operated in a specific orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first" and "second" are used only for descriptive purposes and are not intended to have a special meaning.

Example one

As shown in fig. 1-6, the present embodiment provides a drug balloon 10, comprising a balloon catheter 100, the balloon catheter 100 comprising a balloon body segment 110 and a liquid-communicating tube 120. One end of the balloon body segment 110 is connected to the proximal end 1202 of the liquid through tube, the other end of the balloon body segment 110 is connected to the distal end 1203 of the liquid through tube, and the inner cavity of the balloon body segment 110 is communicated with the liquid through tube 120 to form a liquid through cavity 140 for introducing a medical liquid for treating diseases into the balloon, wherein the medical liquid is preferably a drug microsphere preparation in this embodiment. The surface of balloon body segment 110 is further provided with a blood flow lumen 130 for blood circulation in a blood vessel during surgery, which blood flow lumen 130 is surrounded by the side walls of a through-flow lumen 140. In this embodiment, the balloon body segment 110 is preferably cylindrical, and a plurality of micropores 1103 are distributed on the outer arc surface 1102 of the balloon body segment, so as to enable the drug microsphere preparation in the fluid passage cavity 140 to flow out or be ejected at high speed through the micropores 1103, thereby enabling the drug microsphere to stably stay in the target lesion tissue.

When the medicinal balloon 10 is pressurized, the blood flow cavity 130 can supply blood in a blood vessel to pass through, so that sufficient downstream blood supply can be ensured, and myocardial ischemia caused by vessel occlusion is avoided; meanwhile, the balloon surface and the vessel wall 1 are ensured to have sufficient contact action time, and the adhesion effect of the medicine on the target vessel wall 1 is improved. According to the invention, the medicine microsphere preparation is released to the blood vessel wall 1 through the micropores 1103 arranged on the balloon body segment 110, so that the medicine can be more stably and effectively retained on the blood vessel wall 1, and the medicine can be stably released for a long time. Moreover, when the drug balloon 10 is used for conveying, pressurizing and pressure relief, the problems of falling off and residue of a drug coating do not exist, and the effective release rate of the drug is greatly improved; meanwhile, the problems of distal vascular embolism, acute myocardial infarction and the like caused by the falling of the coating are avoided.

The balloon body segment 110 in this embodiment is linearly arranged along the axial direction of the liquid through-tube 120, and correspondingly, the blood flow lumen 130 is also linearly arranged along the axial direction of the liquid through-tube 120. The greatest advantage of the straight arrangement is that the blood flow lumen 130 has the fastest flow rate, and the balloon is open to provide the best blood supply to the distal tissue. The number of balloon body segments 110 is preferably 4 (in other cases also other numbers, such as 2-16), and the number of blood flow lumens 130 is equal to the number of balloon body segments 110, also 4. Both ends of 4 sacculus body segments 110 all are connected with liquid through-

tube

120, and 4 sacculus body segments 110 are in the outside of liquid through-tube 120 along the circumferencial direction array distribution, and 4 sacculus body segments 110 have a public inner chamber, and this inner chamber and liquid through-tube 120 intercommunication to form liquid through cavity 140. To pressurize the lumen 140, the proximal end 1202 of the catheter is open in this embodiment to allow fluid to pass through, and the distal end 1203 of the catheter is closed to prevent fluid from passing through.

In the present embodiment, as shown in fig. 3-5, the cross-section of the fluid passage 140 in the pressurized state is a circle with 4T-shaped structures uniformly distributed thereon, where the circle represents the fluid passage tube 120 and the T-shaped structure represents the balloon body segment 110. The design of the T-shaped structure of buckling is mainly to increase the contact area between the outer arc surface 1102 of the balloon body section and the blood vessel wall 1 to the maximum extent, and guarantee the balloon opening effect and the drug release effect. Further, the wall thickness of the balloon body section 110 is 0.01-0.1mm, and the ear thickness of the bent T-shaped structure is 0.3-0.5mm, so that the balloon can be smoothly opened when being processed and used. A blood flow cavity 130 is formed between the side 1101 of the balloon body section and the extrados 1201 of the liquid through tube, and the cross section of the blood flow cavity 130 is of a special-shaped fan-shaped structure (i.e. the extrados of the fan-shaped structure is provided with an opening) so as to ensure that blood flow can be smoothly supplied to downstream myocardial tissues under the condition that the balloon is pressurized to work, thereby avoiding myocardial ischemia. The special-shaped fan-shaped opening structure is designed mainly from the processing angle, so that the design of a balloon forming mold is facilitated. It is known that, in a blood flow environment with a circular cross section, the closer the blood flow is to the vessel wall, the slower the flow velocity is, the higher the viscosity is, and the closer the blood flow is to the center position, the faster the flow velocity is, the lower the viscosity is. On the premise of ensuring that the balloon body segment outer arc surface 1102 is in sufficient contact with the blood vessel wall 1, the balloon part of the T-shaped structure for blocking the blood flow is designed to be as close to the blood vessel wall 1 as possible and to be as thick as possible, so that the flow rate of the blood flow blocked by the balloon part is low, the influence on the whole blood flow supply is minimal, and the blood volume passing through the blood flow cavity 130 is maximized.

Furthermore, the sum of the cross-sectional areas of the 4 blood flow cavities 130 in this embodiment accounts for more than 30% of the cross-sectional area of the whole balloon body segment 110, and the design basis is that it is generally considered clinically that the normal myocardial work of the human body in a quiet state can be ensured when the blood supply volume of the coronary blood vessel reaches 25% of the maximum theoretical blood flow supply. As described in the hemodynamic characteristics of coronary stenosis at page 26 of the second subsection of the third chapter, the 3 rd edition of coronary angiography, the stenosis of 75% or more can serve as an amplification point of resistance, and a stenosis of 75% in the cross-sectional area of the dog artery (corresponding to a 50% diameter stenosis) can cause a significant reduction in resting blood flow, and myocardial ischemia can occur in light activity, even at rest, as is also demonstrated in the coronary artery. The description of "the easy cause" on page 17 of chapter ii, third section of "coronary angiography and clinics, 3 rd edition" is divided into four stages, I stage, according to the degree of luminal stenosis caused by plaque: the stenosis of the lumen is below 25 percent; II stage: stenosis is 26% -50%; grade III: stenosis is 51% -75%; stage IV: stenosis is above 76%. "As can be seen, stenosis above 76% is already a level of the most severe stenosis, reflected also from the side, ensuring that more than 25% of the blood flow area across the cross-section is important for the patient. In the description of the representation and judgment of the degree of stenosis by coronary angiography, page 36 of the fourth section of the first chapter, 3 rd edition, the "degree of coronary stenosis" can be expressed as a percentage of the reduction of the diameter of the stenosis or as a percentage of the area of the stenosis, with a 50% reduction of the diameter of the stenosis corresponding to a 75% reduction of the cross-sectional area. Tubular artery stenosis >50% in diameter, and exercise may induce myocardial ischemia, and is considered a meaningful lesion ". That is, a reduction of 75% in stenosis area, motion that may induce myocardial ischemia, is a meaningful lesion, and it is important to ensure a blood flow area of greater than 25% across the cross-section. In view of the above, the sum of the sectional areas of the 4 blood flow cavities 130 accounts for more than 25% of the sectional area of the whole balloon body segment 110, and the normal blood flow supply to the downstream cardiomyocytes can be ensured, in this embodiment, the number is increased to more than 30%, and the patient experience is improved, and the patient safety is ensured.

Meanwhile, in the present embodiment, the ratio of the sum of the sectional areas of the 4 blood flow cavities 130 to the sectional area of the whole balloon body segment 110 is not set to be 25% to 30%, for the following reasons: clinically, 25% is the borderline of resting myocardial ischemia. However, there is individual variability among patients and ischemic symptoms may still appear even when the blood flow lumen area is 25% -30%. Therefore, the area of the blood flow cavity is increased to 30 percent of the cross section area of the blood vessel, which is equivalent to increase the safety factor of the operation, relieves the symptoms of myocardial ischemia of the patient and reduces the operation risk.

On the other hand, in terms of engineering, the blood flow cavity area is increased to be more than 30% of the blood vessel sectional area, so that the processing difficulty and the processing cost of the balloon forming die are reduced, and the structural precision of a balloon product is improved. Taking the example of a single circular lumen design, suppose S1=25% · S, S2=30% · S, where S is the vessel cross-sectional area, S1 is the cross-sectional area of the first lumen, and S2 is the cross-sectional area of the second lumen. S1= pi · (D1/2), S2= pi · (D2/2), then D2/D1 ≈ 1.1, wherein D1 and D2 respectively denote a diameter of the first kind of single circular blood flow cavity and a diameter of the second kind of single circular blood flow cavity. For a coronary balloon, a vessel diameter of 3.00mm is generally defined, and the diameter of the first blood flow lumen is 1.50mm, and the diameter of the second blood flow lumen is 1.65 mm. The forming of the blood flow cavity of the balloon depends on the mandrel-like convex structure on the balloon forming die, so that the processing difficulty of the mandrel-like structure with the diameter of 1.65mm is lower, the processing cost is lower, and the structure precision is higher on the premise that the processing equipment precision is the same (for example, the precision of 1.65 +/-0.02 mm is obviously higher than 1.50 +/-0.02 mm under the condition that the grinding machine can ensure the diameter size tolerance of +/-0.02 mm).

When the blood flow cavity is designed into four circular cross sections, taking a blood vessel with the diameter of 3.00mm as an example, the diameter of the blood flow cavity with the cross section area of 25% of the blood vessel is 0.75mm, the diameter of the blood flow cavity with the cross section area of 30% of the blood vessel is 0.82mm, and similarly, the mandrel-like structure on the balloon forming die of the blood flow cavity with the cross section area of 30% of the blood vessel is lower in processing difficulty and lower in processing cost, and the structure precision is higher on the premise that the precision of processing equipment is the same (for the same reason). In addition, the machining difficulty of the mandrel structure smaller than 1.0mm is very high, and the reduction of the diameter by 0.01mm brings very high machining difficulty, even the equipment cannot meet the precision requirement.

In addition, when the blood flow chamber was designed, still along with the design of the T type structure thickness of buckling on the sacculus body section etc. the blood flow chamber is littleer and must lead to the fact these originally further increases with regard to meticulous structure processing degree of difficulty, increases the processing cost, and the precision further reduces, influences the whole support performance and the blood flow condition of passing through of sacculus structure. In summary, the present embodiment preferably increases the ratio of the total area of the blood flow lumen to the cross-sectional area of the blood vessel to 30% or more.

Further, the plurality of micro holes 1103 of the present embodiment are uniformly arranged in a linear array along the axial direction of the liquid passing tube 120. Preferably, the present embodiment provides 1 row of micropores 1103 on each balloon body segment 110, i.e. the whole balloon catheter 100 is provided with 4 rows of micropores 1103. Further preferably, the diameter of the micropores 1103 in the area of the proximal 1104 and distal 1105 areas of the balloon body segment of the present embodiment is larger than the diameter of the micropores 1103 in the area of the middle 1106 area of the balloon body segment, so as to ensure pressure equalization throughout the balloon body segment 110.

The reasons for the above-mentioned differential pore size design are mainly two: firstly, when the balloon body section is initially formed, high temperature and high pressure are applied to the inside of a thin-wall polymer tube, and a main cylindrical balloon body section structure with two conical ends is formed under the limitation of an external balloon forming mold. In the process of forming the balloon, the temperature of the two ends of the balloon body section is lower relative to the middle part (only the balloon body section of the tube is heated, the temperature of the two ends close to the external environment is lower), the strength is higher, and the balloon body section cannot be completely expanded to the target diameter in a forming die under the conventional condition. That is, after the balloon body segment is blow molded at high temperature and high pressure, the diameters of the two ends are generally slightly smaller than the diameter of the middle portion. Under the condition that the volume of the material of the balloon body section is not changed (the length of the balloon body section is not changed in the forming process, such as lengthening or shortening), theoretically, the cross-sectional areas of the balloon body section are equal, the diameters of two ends of the balloon body section are small, the diameter of the middle section is large, and then the two end walls are thick and the middle wall is thin. If the micropore aperture that distributes at sacculus both ends and middle section is the same, because both ends wall thickness, also the micropore degree of depth is darker, the inside high-pressure liquid of sacculus just also longer through the route that micropore flowed out the sacculus, and external resistance is bigger, and the flow is littleer, so can guarantee through the micropore aperture at increase sacculus both ends that the flow is more balanced. Second, when the balloon is applied to a restenosis lesion, the balloon body segment proximal 1104 and balloon body segment distal 1105 regions correspond to the proximal and distal regions of the restenosis lesion. Clinically, these two regional restenosis pathological changes are more serious than middle section pathological changes (when stenosis pathological change is implanted the support for the first time, the near-end of support and distal end wave pole can stimulate the vascular wall that corresponds the region, the vascular inner wall in this region receives the stimulation, arouse a series of strong cellular reaction, arouse smooth muscle cell transitional proliferation, and this vascular region contains the support blank, do not have the powerful support of support, so the lumen is lost more obviously, the vessel diameter obviously reduces, hinder the blood flow), so also can guarantee more medicine supplies through the micropore aperture at increase sacculus both ends, guarantee that long-term lumen is unobstructed. Of course, in other embodiments, the diameters of the micropores 1103 on the entire balloon body segment 110 may be the same, thereby simplifying the manufacturing process of the balloon body segment 110. The micropores 1103 of this embodiment are cylindrical micropores having a diameter of 1 to 100 μm. The design basis of the diameter range is as follows: if the aperture is too small, the drug microspheres in the prior art cannot pass through the small holes smoothly; if the aperture is too large, the liquid flow is too large, the operation process is difficult to operate, meanwhile, the jet impact force under high pressure is too large, the blood vessel is easy to be damaged, and the balloon is easy to rupture under high pressure due to too large small holes. In each row of linearly arranged micro-holes 1103 in the present embodiment, the axial arrangement distance between adjacent micro-holes 1103 is 0.1-10 mm.

Preferably, the material of the balloon body segment 110 of this embodiment may be one or more of nylon, modified nylon, nylon elastomer and linear low density polyethylene. The balloon body segment 110 may be integrally blow molded or 3D printed, or the proximal end 1104, the middle 1106 and the distal end 1105 may be blow molded separately and then joined by laser welding or hot melt welding. The micro-holes 1103 can be formed by laser drilling several hundred micro-scale holes on the surface of the balloon body segment 110.

Further, the pharmaceutical microsphere formulation of the present embodiment comprises: the drug microspheres are in a suspension state in the working medium at room temperature and stably exist. Compared with the traditional medicine balloon, the surface of the medicine balloon is not provided with a medicine coating, so that the medicine loss is avoided in the balloon conveying and pressurizing opening processes, and meanwhile, the medicine microsphere carrier has better adhesion performance to the vessel wall 1, so that the medicine release efficiency is improved, and the toxicity of the medicine to the organism is reduced. Meanwhile, the occurrence of distal embolism and acute myocardial infarction caused by the falling of large particles of the drug coating is avoided.

The maximum size of the drug microspheres in this embodiment should be smaller than the diameter of the micropores 1103. It is noted that, in the whole fluid environment, the pressure inlet is the liquid through tube 120 of the balloon catheter 100, and the pressure outlet is only a plurality of micropores 1103 with a diameter of 1-100 μm. Under the action of pressure, a large number of drug microspheres can be gathered at the micropores 1103 along with the working medium, so that the maximum size of the drug microspheres is required to be smaller than the diameter of the micropores 1103, otherwise, the risk of blocking the micropores 1103 by the drug microspheres can occur. The drug microspheres in the embodiment are in a spherical structure, and under the action of liquid flow, the drug microspheres in the spherical structure move towards the micropores 1103, so that the drug microspheres are ensured to pass more smoothly.

Further, the maximum size of the drug microsphere is less than 1/5, which is the diameter of the micropores 1103. In a microsphere release test, a suspension of drug microspheres at a certain concentration is injected into the balloon, and the drug microspheres flow out or are ejected from the micropores along with liquid flow under the action of liquid pressure.

Specifically, in the test, the pore diameter D =2.5um of the micropores on the surface of the balloon,

syringes

1 and 2 are used to respectively suck microsphere suspensions with the drug concentration of 0.3mg/mL, aqueous needle filters with the filter pore diameters of 0.45um and 0.8um are respectively mounted on the heads of the

syringes

1 and 2, the syringe handles are pushed forward, the suspensions filtered by the filters are respectively labeled as suspension 1 and suspension 2, wherein the diameters of the microspheres in the suspension 1 are respectively smaller than 0.45um, that is, the maximum diameter of the microspheres in the suspension 1 is D1=0.45um, and the diameters of the microspheres in the suspension 2 are smaller than 0.8um, that is, the maximum diameter of the microspheres in the suspension 2 is D2=0.8um (the microspheres with the diameters larger than 0.45um and 0.8um are all filtered by the densely distributed pores on the filter heads). Then, the suspension 1 is injected into the balloon through an inflator under the working pressure of more than 8atm, the microspheres can flow out through a plurality of micropores on the surface of the balloon, the flow is stable and is similar to the flow when the liquid without the microspheres is injected; and the turbid liquid 2 is injected into the balloon through the filling device under the working pressure of more than 8atm, the microspheres can rapidly block micropores on the surface of the balloon, the flow is greatly reduced, and even the liquid cannot flow out. Therefore, even if the aperture of the micro-hole of the balloon is larger than 0.8um, the micro-hole of the micro-ball with the diameter of 0.8um can not be smoothly formed. The reason for this phenomenon is that a large number of drug microspheres can be gathered at the micropores 1103 along with the working medium during operation, and in real circumstances, the microspheres do not flow out one by one, but a plurality of microspheres pass through the micropores together, and the probability that the micropores are blocked by the large-diameter microspheres is greatly increased when the large-diameter microspheres are accumulated.

That is, the proportional relationship between the diameter of the micro-pores on the surface of the balloon and the diameter of the maximum microspheres in the filtered suspension is the key of the function test. D/D1 is equal to about 5, and D/D2 is equal to about 3: 1, the microspheres in the first group of proportional relations can smoothly pass through micropores on the surface of the balloon to realize a drug delivery function, and the microspheres in the second group of proportional relations cannot smoothly pass through micropores on the surface of the balloon to block the micropores, so that the drug delivery fails. Therefore, the present embodiment preferably sets the diameter ratio of the balloon micropores to the drug microspheres to be greater than 5: 1.

preferably, the drug microspheres have a diameter of 1-990 nm. The maximum diameter of the submicron-level drug microsphere is smaller than 1 micron, and compared with the bulk coating of the traditional drug balloon, under the condition that the total drug loading is the same, the sum of the surface areas of all the drug-loaded sub-microspheres is far larger than the surface area of the traditional drug balloon drug coating, namely the real contact area of the drug-loaded sub-microspheres and the blood vessel wall 1 is far larger than the bulk drug coating on the surface of the traditional drug balloon. The larger the real contact area with the vessel wall 1, the higher the overall adhesion efficiency of the drug on the vessel wall 1. Therefore, under the same condition of initial medicine total amount, compare with traditional medicine sacculus, the sub-microballon of medicine carrying can let target vascular wall 1 go up the medicine volume of adhesion more, and the drug concentration in the long-term tissue is higher, and the effect of restraining smooth muscle cell excessive proliferation is better, and the patency rate of long-term lumen is higher.

The drug microspheres of this embodiment comprise a drug and an excipient; the drug can be one or more of nimustine, carmustine, 5-fluorouracil, fluoroguanosine, gemcitabine, daunorubicin, doxorubicin, paclitaxel, vinblastine, topotecan, aminoglutethimide, sirolimus, everolimus, rapamycin and zotarolimus; the excipient can be one or more of racemic polylactic acid, polyethylene glycol, magnesium stearate, iohexol, iopromide, urea, sorbitol, polysorbitol, polyoxyethylene polyoxypropylene ether block copolymer, trihexyl citrate, phospholipid, matrix of ropiperazine, polylactic acid-glycolic acid copolymer, polyvinylpyrrolidone, cholesterol, vitamin E, and vitamin E polyethylene glycol succinate.

Further preferably, rapamycin is selected as the drug of this embodiment. When the drug microspheres are adhered or embedded on target pathological tissues, the drug rapamycin is gradually released from the microspheres and acts on cells on the inner wall of a blood vessel. Rapamycin is effective in inhibiting smooth muscle cell proliferation. The P12 carrier protein specially aiming at rapamycin is distributed on the intima of the blood vessel, and the specific carrier protein can transport and diffuse rapamycin molecules to the media membrane and the adventitia. Thus, rapamycin is uniformly distributed in all of the intima, media, and adventitia of the blood vessel wall 1, and the hyperproliferation of smooth muscle cells is suppressed for a long period of time. Rapamycin diffuses relatively slowly into the media and adventitia of the blood vessel, requiring a relatively long time, and the carrier needs to be stable over time to help fix the drug to the target tissue. The drug microsphere successfully overcomes the defect of slow diffusion speed of rapamycin by means of the release principle, ensures that the drug microsphere is in close contact with the blood vessel wall 1 within 1 minute (the traditional drug microsphere on the market at present uses paclitaxel as a drug instead of rapamycin, the main reason is that the paclitaxel has a fast diffusion speed in the blood vessel, the rapamycin is relatively slow, and the contact time of the drug microsphere and the blood vessel cannot exceed one minute so as to avoid the far-end myocardial ischemia caused by long-term blood vessel blockage, while the balloon catheter in the invention can allow more than 30% of blood flow to normally pass through, completely avoid the adverse symptoms of the far-end myocardial ischemia), and can stably fix the drug microsphere of the rapamycin on the surface of the tissue for a long time. In order to ensure the patency of the lumen, the concentration of the drug in the vascular tissue is generally required to be kept above 1ng/mg within 30 days. Rapamycin is mainly used as an immunosuppressant, and the blood drug concentration of rapamycin immediately when a drug stent and a drug balloon are used is less than one ten thousandth of the safe concentration of the drug.

Paclitaxel also inhibits smooth muscle cell proliferation. The tunica intima is also distributed with a microtubule structure specially aiming at the paclitaxel, and the carrier structure can also transport and diffuse the paclitaxel molecules on the tunica intima to the tunica media and the tunica adventitia. However, compared with the uniform diffusion of rapamycin, the concentration of paclitaxel in the media and outer membrane is lower than that in the inner membrane layer, and the distribution is not very uniform. The diffusion speed of the paclitaxel to the tunica media and the tunica adventitia of the blood vessel is relatively high, and the required time is short, so the paclitaxel can be widely applied to the traditional medicine balloon. The paclitaxel medicament is used as an anti-cancer medicament at the earliest time, has certain medicament toxicity, and the peak value of the blood concentration of the traditional paclitaxel medicament released by a balloon at home and abroad is one percent of the safe concentration of the medicament.

Example two

As shown in fig. 7-12, the present embodiment provides a drug balloon 20 comprising a balloon catheter 200, the balloon catheter 200 comprising a balloon body segment 210 and a catheter 220. One end of the balloon body section 210 is connected with the proximal end 2202 of the liquid through tube, the other end of the balloon body section 210 is connected with the distal end 2203 of the liquid through tube, and the inner cavity of the balloon body section 210 is communicated with the liquid through tube 220 to form a liquid through cavity 240 for introducing liquid medicine for treating diseases into the balloon, wherein the liquid medicine is preferably a drug microsphere preparation in the embodiment. The surface of balloon body segment 210 is further provided with a blood flow lumen 230 for blood circulation in a blood vessel during surgery, which blood flow lumen 230 is surrounded by the side walls of the access lumen 240. In this embodiment, the shape of the balloon body segment 210 is preferably cylindrical, and a plurality of micropores 2103 are distributed on the outer arc surface 2102 of the balloon body segment for allowing the drug microsphere preparation in the fluid passage 240 to flow out or be ejected at high speed through the micropores 2103, so that the drug microspheres can stably stay in the target lesion tissue.

In this embodiment, the balloon body segment 210 is helically twisted along the axial direction of the catheter 220, and accordingly, the blood flow lumen 230 is also helically twisted along the axial direction of the catheter 220. The pitch of the helically twisted trajectory helix of the balloon body segment 210 is preferably 1-20 mm. The structure of the helically twisted balloon body section 210 in this embodiment can ensure that when the balloon is pressurized, the balloon body section 210 has good support performance on the whole in the 360-degree direction of the circumference, and the linearly distributed balloon body sections are easily collapsed and toppled when the external force is unbalanced in the circumferential direction. In addition, plaques in the blood vessel are often linearly arranged along the axial direction, once the gaps between balloon body sections which are linearly arranged are positioned at the plaques, the balloons at the parts have almost no supporting capacity and cannot effectively support the plaque lesions; therefore, the present embodiment preferably employs a balloon body segment 210 that is helically twisted along the axial direction of the catheter 220. The number of balloon body segments 210 is preferably 4 (in other cases also other numbers, such as 2-16), and the number of blood flow lumens 230 is equal to the number of balloon body segments 210, also 4. Both ends of 4 sacculus body sections 210 all are connected with liquid through-

tube

220, and 4 sacculus body sections 210 are in the even array distribution of the outside of liquid through-tube 220 along the circumferencial direction, and 4 sacculus body sections 210 have a public inner chamber, and this inner chamber and liquid through-tube 220 intercommunication to form liquid through cavity 240. To pressurize lumen 240, in this embodiment, proximal lumen end 2202 is open to allow passage of liquid, and distal lumen end 2203 is closed to prevent passage of liquid.

In the present embodiment, as shown in fig. 9-11, the cross-section of the liquid-passing cavity 240 in the pressurized state is a circle with 4 bent T-shaped structures uniformly distributed thereon, where the circle represents the liquid-passing tube 220 and the bent T-shaped structures represent the balloon body segment 210. The design of the T-shaped structure of buckling is mainly to increase the contact area between the outer arc surface 2102 of the balloon body section and the vessel wall 2 to the maximum extent, and guarantee the balloon expanding effect and the drug releasing effect. Further, the wall thickness of the balloon body section 210 is 0.01-0.1mm, and the ear thickness of the bent T-shaped structure is 0.3-0.5mm, so that the balloon can be smoothly opened when being processed and used. A blood flow cavity 230 is formed between the side surface 2101 of the balloon body section and the outer arc surface 2201 of the liquid through pipe, and the section of the blood flow cavity 230 is of a special-shaped fan-shaped structure (i.e. the outer arc surface of the fan-shaped structure is provided with an opening) so as to ensure that blood flow can be smoothly supplied to downstream myocardial tissues under the condition that the balloon is pressurized to work, thereby avoiding myocardial ischemia. The special-shaped fan-shaped opening structure is designed mainly from the processing angle, so that the design of a balloon forming mold is facilitated. It is known that, in a blood flow environment with a circular cross section, the closer the blood flow is to the vessel wall, the slower the flow velocity is, the higher the viscosity is, and the closer the blood flow is to the center position, the faster the flow velocity is, the lower the viscosity is. On the premise of ensuring sufficient contact between the balloon body section outer arc surface 2102 and the blood vessel wall 2, the balloon part with the T-shaped structure for blocking the blood flow is designed to be as close to the blood vessel wall 2 as possible and to be as thick as possible, so that the flow rate of the blood flow blocked by the balloon part is low, the influence on the whole blood flow supply is minimal, and the blood volume passing through the blood flow cavity 230 is maximized. Further, in this embodiment, the sum of the cross-sectional areas of the 4 blood flow cavities 230 accounts for more than 30% of the cross-sectional area of the entire balloon body section 210, and the design basis thereof is the same as that in the first embodiment, and the details are not repeated in this embodiment.

Further, the plurality of micropores 2103 of the present embodiment are arranged spirally twisted in the axial direction of the liquid passing tube 220. Preferably, in the present embodiment, 1 row of micro holes 2103 is disposed on each balloon body segment 210, the spiral arrangement direction of the micro holes 2103 is the same as the spiral twisting direction of the balloon body segment 210, and the whole balloon catheter 200 is disposed with 4 rows of the micro holes 2103. For the blood flow cavity design which is spirally twisted along the central axis, micropores on the surface of the balloon are spirally twisted and distributed on the surface of the balloon, and the thread pitches of spiral tracks distributed on the micropores are the same as those of the spiral tracks spirally twisted in the blood flow cavity. The beneficial effects are two main points: firstly, for the surface of the saccule, the distances of the adjacent micropores in the circumferential direction are the same, and the distances of the adjacent micropores in the axial direction are the same, so that when the suspension of the drug microspheres is released from the micropores, the drug can be uniformly distributed, adhered or embedded into the inner wall of the blood vessel, and the tissue drug concentration of the target blood vessel is uniform and stable. Secondly, the thread pitch of the spiral track of the micropore distribution is the same as that of the spiral track of the blood flow cavity spiral torsion, so that the micropores can never be located in an undesirable area such as a blank opening area of the blood flow cavity in direct contact with a blood vessel wall or a boundary of a balloon body segment and the blank opening area. The use of a helically twisted pattern, such as a straight line or other pitch, will likely result in the formation of undesirable regions as described above during microporous processing. Because the micropores are usually realized by adopting a laser drilling mode, when the micropores are positioned in a blank opening area, no real micropores are formed due to the absence of a balloon material; when the micropores are located at the boundary of the balloon body section and the blank opening area, the pores are likely to be located on the wall of the blood flow cavity, so that the microspheres enter the blood flow cavity when the balloon is pressurized, and the drug utilization rate and the drug concentration of target vascular tissues are reduced.

It is further preferred that the diameter of the micro-holes 2103 in the area of the balloon body segment proximal 2104 and balloon body segment distal end 2105 is larger than the diameter of the micro-holes 2103 in the area of the balloon body segment middle 2106, so as to ensure pressure equalization throughout the balloon body segment 210. The design basis of the differential aperture is the same as that in the first embodiment, and the description of this embodiment is omitted. Of course, in other embodiments, the diameters of the micro-holes 2103 may be the same throughout the balloon body segment 210, thereby simplifying the manufacturing process of the balloon body segment 210. The micropores 2103 of this embodiment are cylindrical micropores having a diameter of 1 to 100. mu.m. The design basis of the diameter range is as follows: if the aperture is too small, the drug microspheres in the prior art cannot pass through the small holes smoothly; if the aperture is too large, the liquid flow is too large, the operation process is difficult to operate, meanwhile, the jet impact force under high pressure is too large, the blood vessel is easy to be damaged, and the balloon is easy to rupture under high pressure due to too large small holes. In each row of the micro-holes 2103 spirally and torsionally arranged in the embodiment, the axial arrangement distance between the adjacent micro-holes 2103 is 0.1-10 mm.

Further, other arrangement manners of the balloon catheter 200 and the drug microsphere preparation in the present embodiment are the same as those in the first embodiment, and are not described herein again.

EXAMPLE III

As shown in fig. 13-18, the present embodiment provides a drug balloon 30 comprising a balloon catheter 300, the balloon catheter 300 comprising a balloon body segment 310 and a catheter 320. One end of the balloon body segment 310 is connected to the proximal end 3202 of the liquid through tube, the other end of the balloon body segment 310 is connected to the distal end 3203 of the liquid through tube, and the inner cavity of the balloon body segment 310 is communicated with the liquid through tube 320 to form the liquid through cavity 340 for introducing a medical liquid for treating diseases into the balloon, wherein the medical liquid is preferably a drug microsphere preparation in this embodiment. The surface of balloon body segment 310 is further provided with a blood flow lumen 330 for blood circulation in a blood vessel during surgery, which blood flow lumen 330 is surrounded by the side walls of the access lumen 340. In this embodiment, the balloon body section 310 is preferably cylindrical, and a plurality of micropores 3103 are distributed on the outer arc surface 3102 of the balloon body section, so that the drug microsphere preparation in the fluid passage 340 flows out or is ejected at high speed through the micropores 3103, thereby stably staying in the target lesion tissue.

The balloon body segment 310 in this embodiment is linearly arranged along the axial direction of the catheter 320, and correspondingly, the blood flow lumen 330 is also linearly arranged along the axial direction of the catheter 320. The greatest advantage of the straight arrangement is that the blood flow lumen 330 has the fastest flow rate, and the balloon is open for optimal blood supply to the distal tissue. The number of balloon body segments 310 is preferably 1, and the number of blood flow lumens 330 is equal to the number of balloon body segments 310, also 1. To pressurize the lumen 340, the proximal end 3202 of the access tube is open in this embodiment to allow fluid to pass through, and the distal end 3203 of the access tube is closed to prevent fluid from passing through.

In the present embodiment, as shown in fig. 15-17, the cross-section of the balloon body segment 310 is crescent-shaped in the inflated state, i.e. the cross-section of the liquid passing lumen 340 is crescent-shaped. The crescent structure is designed to increase the contact area between the outer arc surface 3102 of the balloon body segment and the blood vessel wall 3 to the maximum extent, so that the balloon opening effect and the drug release effect are ensured. Further, the wall thickness of the balloon body section 310 is 0.01-0.1mm, and the thickness of both ends of the crescent structure is 0.3-0.5mm, so that the balloon can be smoothly opened during processing and using. The inner arc surface 3101 of the balloon body section surrounds to form a blood flow cavity 330, the cross section of the blood flow cavity 330 is a circular structure with an opening, the circular structure is eccentrically arranged relative to the center of the liquid through tube 320, and the opening on the circular structure is designed for facilitating the design of a balloon core sleeve and the molding processing of the balloon. The blood flow cavity 330 of the present embodiment can ensure that blood flow can also smoothly supply downstream myocardial tissue under the condition of balloon pressurization work, thereby avoiding myocardial ischemia. It is known that, in a blood flow environment with a circular cross section, the closer the blood flow is to the vessel wall, the slower the flow velocity is, the higher the viscosity is, and the closer the blood flow is to the center position, the faster the flow velocity is, the lower the viscosity is. On the premise of ensuring that the balloon body section outer arc surface 3102 is in full contact with the blood vessel wall 3, the design of the balloon part with the crescent structure for blocking the blood flow is as close as possible to the blood vessel wall 3 and the thickness is minimized, so that the flow rate of the blood flow blocked by the balloon part is low, the influence on the whole blood flow supply is minimal, and the blood volume passing through the blood flow cavity 330 is maximized. Further, the sectional area of the blood flow cavity 330 in this embodiment accounts for more than 30% of the sectional area of the entire balloon body section 310, and the design basis thereof is the same as that in the first embodiment, and the details are not repeated herein.

Further, the plurality of micropores 3103 of the present embodiment are arranged in a linear array along the axial direction of the liquid passing tube 320. Preferably, the balloon body segment 310 of the present embodiment is provided with 4 rows of micropores 3103. It is further preferred that the diameter of the micropores 3103 in the region of the proximal 3104 and distal 3105 of the balloon body segment of this embodiment is greater than the diameter of the micropores 3103 in the region of the middle 3106 of the balloon body segment, thereby ensuring pressure equalization throughout the balloon body segment 310. The design basis of the differential aperture is the same as that in the first embodiment, and the detailed description is omitted here. Of course, in other embodiments, the diameters of the micro holes 3103 may be the same throughout the balloon body segment 310, thereby simplifying the fabrication process of the balloon body segment 310. The micropores 3103 of this embodiment are columnar micropores having a diameter of 1 to 100. mu.m. The design basis of the diameter range is as follows: if the aperture is too small, the drug microspheres in the prior art cannot pass through the small holes smoothly; if the aperture is too large, the liquid flow is too large, the operation process is difficult to operate, meanwhile, the jet impact force under high pressure is too large, the blood vessel is easy to be damaged, and the balloon is easy to rupture under high pressure due to too large small holes. In each row of linearly arranged micro holes 3103 of the present embodiment, the axial arrangement distance between adjacent micro holes 3103 is 0.1-10 mm.

Further, other arrangement manners of the balloon catheter 300 and the drug microsphere preparation in this embodiment are the same as those in the first embodiment, and are not described herein again.

Example four

As shown in fig. 19-24, the present embodiment provides a drug balloon 40 comprising a balloon catheter 400, the balloon catheter 400 comprising a balloon body segment 410 and a catheter 420. One end of the balloon body segment 410 is connected to the proximal end 4202 of the liquid-passing tube, the other end of the balloon body segment 410 is connected to the distal end 4203 of the liquid-passing tube, and the inner cavity of the balloon body segment 410 is connected to the liquid-passing tube 420 to form a liquid-passing cavity 440 for passing a medical liquid for treating diseases, preferably a drug microsphere preparation in this embodiment. The surface of balloon body segment 410 is further provided with a blood flow lumen 430 for blood circulation within the vessel during the procedure, which blood flow lumen 430 is surrounded by the side walls of the access lumen 440. In this embodiment, the balloon body segment 410 is preferably cylindrical, and a plurality of micropores 4103 are distributed on the outer arc surface 4102 of the balloon body segment, so that the drug microsphere preparation in the fluid passage 440 flows out or is ejected at high speed through the micropores 4103, thereby stably staying the drug microsphere in the target lesion tissue.

The balloon body segment 410 in this embodiment is helically twisted along the axis of the catheter 420 and correspondingly the blood flow lumen 430 is also helically twisted along the axis of the catheter 420. The pitch of the helically twisted trajectory helix of the balloon body segment 410 is preferably 1-20 mm. In this embodiment, the structure of the balloon body section 410 spirally twisted along the axial direction can ensure that the balloon body section 410 has good support performance on the whole in the 360-degree direction of the circumference when being pressurized, and the linearly distributed balloon body sections are easy to collapse and topple when being unbalanced by external force in the circumferential direction. In addition, plaques in the blood vessel are often linearly arranged along the axial direction, once the gaps between balloon body sections which are linearly arranged are positioned at the plaques, the balloons at the parts have almost no supporting capacity and cannot effectively support the plaque lesions; thus, the present embodiment preferably employs a balloon body segment 410 that is helically twisted along the axial direction of the catheter 420. The number of balloon body segments 410 is preferably 1, and the number of blood flow lumens 430 is equal to the number of balloon body segments 410, also 1. To pressurize lumen 440, in this embodiment, proximal end 4202 is open to allow fluid to pass therethrough and distal end 4203 is closed to prevent fluid from passing therethrough.

As shown in fig. 21-23, in this embodiment, the cross-section of the balloon body segment 410 is crescent-shaped in the inflated state, i.e. the cross-section of the fluid lumen 440 is crescent-shaped. The design of crescent structure is mainly in order to the area of contact between at utmost increase sacculus body section extrados 4102 and the vascular wall 4, guarantees sacculus distraction effect and medicine release effect. Further, the wall thickness of the balloon body section 410 is 0.01-0.1mm, and the thickness of both ends of the crescent structure is 0.3-0.5mm, so that the balloon can be smoothly opened during processing and using. The intrados 4101 of the balloon body segment surrounds to form a blood flow cavity 430, the cross section of the blood flow cavity 430 is a circular structure with an opening, the circular structure is eccentrically arranged relative to the center of the liquid through tube 420, and the opening on the circular structure is designed for facilitating the design of the balloon core sleeve and the molding processing of the balloon. The blood flow cavity 430 of the present embodiment can ensure that blood flow can also smoothly supply downstream myocardial tissue under the condition of the pressurized work of the balloon, thereby avoiding myocardial ischemia. It is known that, in a blood flow environment with a circular cross section, the closer the blood flow is to the vessel wall, the slower the flow velocity is, the higher the viscosity is, and the closer the blood flow is to the center position, the faster the flow velocity is, the lower the viscosity is. On the premise of ensuring sufficient contact between the balloon body segment outer arc surface 4102 and the blood vessel wall 4, the balloon part with the crescent structure for obstructing blood flow is designed to be as close to the blood vessel wall 4 as possible and to be minimized in thickness, so that the blood flow obstructed by the balloon part is low in flow speed, the influence on the whole blood flow supply is minimal, and the blood volume passing through the blood flow cavity 430 is maximized. Further, the sectional area of the blood flow chamber 430 of this embodiment accounts for more than 30% of the sectional area of the entire balloon body section 410, and the design basis thereof is the same as that in the first embodiment, and the details are not repeated herein.

Further, the plurality of micropores 4103 of the present embodiment are arranged spirally twisted in the axial direction of the liquid passing tube 420. Preferably, the present embodiment spirally arranges four rows of micro-holes 4103 on the balloon body segment 410, i.e. the whole balloon catheter 400 is provided with four rows of micro-holes 4103. Further preferably, the diameter of the micro-holes 4103 in the area of the balloon body segment proximal end 4104 and the balloon body segment distal end 4105 is larger than the diameter of the micro-holes 4103 in the area of the balloon body segment middle part 4106, thereby ensuring pressure equalization throughout the balloon body segment 410. The design basis of the differential aperture is the same as that in the first embodiment, and the description of this embodiment is omitted. Of course, in other embodiments, the diameters of the micro-holes 4103 may be the same throughout the balloon body segment 410, thereby simplifying the manufacturing process of the balloon body segment 410. The micropores 4103 of this embodiment are cylindrical micropores having a diameter of 1 to 100 μm. The design basis of the diameter range is as follows: if the aperture is too small, the drug microspheres in the prior art cannot pass through the small holes smoothly; if the aperture is too large, the liquid flow is too large, the operation process is difficult to operate, meanwhile, the jet impact force under high pressure is too large, the blood vessel is easy to be damaged, and the balloon is easy to rupture under high pressure due to too large small holes. In each row of the micro-holes 4103 spirally twisted in this embodiment, the axial arrangement distance between the adjacent micro-holes 4103 is 0.1-10 mm.

Further, other arrangement manners of the balloon catheter 400 and the drug microsphere preparation in this embodiment are the same as those in the first embodiment, and are not described herein again.

EXAMPLE five

The embodiment provides a use method of the drug balloon according to any one of the first to fourth embodiments, which specifically includes the following steps:

s1: after the medicine saccule is released to a target lesion area, first preset pressure is applied to the saccule catheter through the medicine microballoon preparation, so that the medicine microballoon preparation flows into a saccule body section from the near end of the liquid through pipe and flows out of the medicine saccule through the micropores, and liquid drops are formed, grown and dropped periodically outside the medicine saccule;

in the step, the medicine balloon is injected with the medicine microsphere preparation to realize the pressurization of the medicine balloon, and the pressure is gradually increased to a first preset pressure, wherein the first preset pressure is preferably 1-8 atm. When the balloon is pressurized, the drug microsphere preparation gradually enters and fills the balloon body segment through the liquid through tube under the action of liquid high pressure above 1atm, wherein the drug microsphere also enters the balloon body segment along with the liquid flow direction. On the premise that the sealing performance of the system joint is good, liquid can flow to a low-pressure area outside the balloon from a high-pressure area inside the balloon body section along micropores distributed on the outer arc surface of the balloon body section. As the pressure increased, the periodic formation, growth and dripping of the droplets was seen outside the balloon. The drug microspheres flow out of the balloon along with the liquid flow through the micropores, and are adhered to and act on the plaque in the blood vessel and the inner wall of the blood vessel. It should be noted that, in this embodiment, when the first preset pressure reaches 3atm, a small amount of jet flow occurs in the liquid flowing out of the micropores, but the occurrence of droplets is still mainly at this stage.

In this step, the balloon catheter is continuously pressurized, and the pressure is further increased to a second predetermined pressure, preferably 8-20 atm. When the liquid pressure rises to be more than 8atm, the liquid form of the liquid in the saccule is changed after the liquid flows from the internal high-pressure area to the external low-pressure area of the saccule through the micropores, and a large amount of high-speed jet flow begins to appear. The high-speed jet flow ejected from the micropores strikes plaques and blood vessel walls in the blood vessel by virtue of the physical impact effect of the high-speed jet flow, and a large number of cavities are formed. The drug microspheres brought by the high-speed jet flow are embedded in the target tissues and directly act on plaques and vessel walls. Preferably, the second preset pressure is 10-14atm, and more preferably, the second preset pressure is 10-12 atm.

The drug microspheres in the slow liquid drops are attached to the surfaces of plaques and blood vessel walls in a carrier adhesion mode; even if it can stably adhere to the tissue surface, it is kept in contact with the flowing blood before the completion of neoendothelialization, and a part of the drug in the drug microspheres is released into the blood during this time, resulting in a decrease in the drug content in the tissue. And a part of the drug microspheres in the high-speed jet flow are embedded in the cavities inside the plaque and the blood vessel wall by the effect of the jet flow striking the plaque and the blood vessel wall. Compared with the mode that the drug microspheres are adhered to the surface of the tissue in slow-speed liquid drops, the drug microspheres in the high-speed jet flow are embedded in newly-opened cavities which are positioned in the tissue, so that the periphery of the drug microspheres can be well physically protected, the situation that the blood flow on the surface of the tissue is taken away by the blood flow under long-term flushing is avoided, the retention time of the drug microspheres in the tissue is greatly prolonged, the long-term tissue drug content is relatively increased, and the excessive proliferation of smooth muscle cells and the subsequent restenosis are inhibited for a long time. Compared with the slow liquid drops, the high-speed jet flow can also greatly increase the flow of the system, increase the amount of the medicine released in unit time, improve the medicine release speed, reduce the operation time of a surgeon and reduce the physical and mental burden of a patient.

The high-speed jet of the porous balloon also needs to reasonably control the pressure in clinical application, otherwise, certain risks exist. In clinical surgery, when the water jet scalpel is used for liver cutting, the high-speed jet flow is utilized to break and separate the target liver parenchyma tissue, and simultaneously, the densely distributed blood vessels at the liver cutting position are well preserved. Therefore, under the condition of proper pressure, the high-speed jet flow can well protect the blood vessel and can not cause the rupture and perforation of the blood vessel. Returning to the invention, the high-speed jet flow emitted from the micropores of the balloon has more remarkable effect on the plaque, can form a plurality of cavities, and has little damage to the blood vessel wall 1 with better elasticity. However, when the water jet cutter is applied to the industrial processing field, the water jet cutter can easily cut hard materials such as thick steel plates under the condition that the pressure is further increased. The liquid pressure in the present invention is required to ensure that the high-speed jet stream emitted from the micropores can effectively attack the plaque, and the pressure is not so great as to tear the blood vessel, even cause perforation and rupture of the blood vessel, so the present invention sets the pressure to be 8-20 atm.

In addition, the high-speed jet ejected from the micropores produces a powerful physical impact effect on the target tissue and simultaneously produces a "cavitation effect", namely, the high-speed jet generates a large amount of micro bubbles after impacting a liquid environment near the vascular plaque. The generated micro bubbles are in an unstable state and can be periodically changed, the pressure is suddenly large and suddenly small, the volume is suddenly large and suddenly small, and the temperature is suddenly high and suddenly low. These unstable bubbles can collapse after undergoing a large number of periodic changes, thereby generating a large number of micro-jets. These microjets act on the target tissue with some "erosion" effect, which creates a large number of closely spaced tiny "cavities". In the field of ships, a propeller rotating at a high speed acts on water, a large amount of high-speed fluid is generated near the propeller, and the high-speed fluid also generates a large amount of micro bubbles in the moving process and directly acts on the surface of the propeller to form a large amount of honeycomb-shaped micro 'cavities'. From the above, the high-speed jet flow can leave a remarkable "cavitation" effect even on high-strength metal materials, so that in order to ensure the safety of the intravascular use, the liquid pressure inside the balloon needs to be controlled, and the pressure is set to be 8-20 atm.

The physical impact of high-speed jet flow emitted by the micropores of the saccule and the 'cavity' effect act on the inner wall of the blood vessel and the plaque together, a plurality of cavities are formed on a target tissue, and then cellular tiny 'cavity' structures are densely distributed, so that the medicine microspheres can be more effectively and more stably embedded in the tissue. The human blood vessel is divided into 3 layers of structures, namely an inner membrane, a middle membrane and an outer membrane; the protrusions that obstruct blood flow in primary stenotic or occlusive lesions are mainly soft sticky liposome plaques and hard and brittle calcified plaques; the main disease in restenosis is hyperproliferation of smooth muscle cells. For soft lipid plaques, the high velocity jet can create tiny spaces inside the lipid plaque, injecting the liquid into the plaque, such that the drug microspheres are surrounded by the lipid plaque. For dense and hard calcified plaque, high-speed jet flow can cause the plaque to have crack gaps under the action of physical impact, and the cavitation further forms a large number of micro structures which are convenient for the fixation of the drug microspheres on the basis of the crack gaps, so that the drug microspheres can stably and firmly stay in the plaque. In the case of restenosis, some of the high velocity jets may even deliver drug microspheres into the interstices of the smooth muscle cells, directly acting on and consistently causing hyperproliferation of the smooth muscle cells that are stenotic and occluded. Therefore, the high-speed jet flow emitted by the micropores can directly convey the drug microspheres to the inside of the calcified plaque, the lipid plaque and the vascular tissue, so that the drug microspheres can stably exist in the plaque or the vascular tissue, the drug is slowly released for a long time, the excessive proliferation of smooth muscle cells is inhibited for a long time, and the occurrence of primary vascular stenosis and intravascular restenosis is avoided or reduced. Under the protection of vascular tissues and plaques, the drug loss caused by direct impact of the drug microspheres by blood flow is avoided, the drug amount released to blood when the drug microspheres are contacted with the blood is also reduced, and the drug content of the drug in target lesion tissues is ensured.

Experimental verification

As shown in fig. 25 to 40, the present invention also performed finite element analysis verification on four structures of the first to fourth embodiments. The purpose is as follows: the flow of liquid in the blood flow lumen of the four drug balloons was simulated by CFD hydrodynamic simulation. The method comprises the following steps: and establishing a mesh model for the liquid model by adopting Comsol5.0 finite element analysis software and adopting tetrahedral units. Applying a pressure to the inlet of the liquid, the pressure being 120 mmhg; a pressure of 80 mmhg was applied to the outlet of the liquid.

The results of the simulation experiments of the first to fourth embodiments of the present invention are as follows:

FIG. 25 is a schematic modeling diagram of finite element analysis of a blood flow chamber according to a first embodiment of the present invention. Referring to fig. 25, the blood flow lumen 130 of the drug balloon 10 in the first embodiment has a cross section of a special fan-shaped structure extending along a straight line. FIG. 26 is a cloud view of a flow rate slice of a finite element analysis of a blood flow lumen according to a first embodiment of the present invention. As shown in fig. 26, the flow velocity of the fluid in the blood flow chamber 130 of the first embodiment gradually decreases from the middle to the edge, i.e., the fluid flow velocity is highest at the center of the irregular sector-shaped cross section, the maximum flow velocity is 13.20m/s, and the flow velocity at the edge of the contour is the slowest. FIG. 27 is a velocity field arrow plot of a finite element analysis of a blood flow lumen according to a first embodiment of the present invention. As shown in FIG. 27, the larger the arrows indicate the faster the flow rate, i.e., the flow rate of the liquid at the center of the shaped fan section is greater than at the edges of the profile. FIG. 28 is a cloud image of pressure slices from a finite element analysis of a blood flow chamber according to a first embodiment of the present invention. As shown in fig. 28, the fluid pressure in the blood flow lumen 130 gradually decreases from the inlet a1 to the outlet a2, with a peak pressure of 159 KPa.

FIG. 29 is a schematic modeling diagram of finite element analysis of the blood flow chamber according to the second embodiment of the present invention. Referring to fig. 29, the blood flow lumen 230 of the drug balloon 20 in the second embodiment has a cross section of a special sector structure, which is twisted along a spiral direction. FIG. 30 is a cloud view of a flow rate slice of a finite element analysis of the blood flow lumen of the second embodiment of the present invention. As shown in fig. 30, in the blood flow chamber 230 of the second embodiment, the flow velocity of the liquid is the highest on the side close to the twisted trajectory in the central portion of the special-shaped fan-shaped cross section, and the maximum flow velocity is 5.19 m/s; the flow velocity at the edge of the profile is the slowest. FIG. 31 is a velocity field arrow plot of a finite element analysis of a blood flow lumen according to a second embodiment of the present invention. As shown in FIG. 31, the larger the arrows indicate the faster the flow velocity, i.e., the center of the shaped fan section is closer to the twisted trajectory portion than the edge of the profile. FIG. 32 is a cloud image of pressure slices from a finite element analysis of the blood flow chamber of the second embodiment of the present invention. As shown in fig. 32, the fluid pressure in the blood flow chamber 230 gradually decreases from the inlet b1 to the outlet b2, and the pressure peaks at 159 KPa.

FIG. 33 is a modeling diagram of finite element analysis of the blood flow lumen according to the third embodiment of the present invention. Referring to fig. 33, the blood flow lumen 330 of the drug balloon 30 in the third embodiment has a circular cross section with an opening, and extends in a straight line. FIG. 34 is a cloud image of a flow rate slice of a finite element analysis of a blood flow lumen according to a third embodiment of the present invention. As shown in FIG. 34, the flow velocity of the liquid in the blood flow chamber 330 of the third embodiment is gradually reduced from the middle to the edge, i.e., the liquid flow velocity is highest at the center of the circular cross section, the maximum flow velocity is 30.30m/s, and the flow velocity at the edge of the contour is slowest. FIG. 35 is a velocity field arrow plot of a finite element analysis of the blood flow lumen of example three in accordance with the present invention. As shown in fig. 35, the larger the arrows indicate the faster the flow rate, i.e., the greater the liquid flow rate at the center of the circular cross-section than at the edges of the profile. FIG. 36 is a cloud image of pressure slices from a finite element analysis of the blood flow lumen of example three of the present invention. As shown in fig. 36, the fluid pressure in the blood flow lumen 330 gradually decreases from the inlet c1 to the outlet c2, with a pressure peak of 158 KPa.

FIG. 37 is a schematic modeling diagram of a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention. Referring to fig. 37, the blood flow lumen 430 of the drug balloon 40 of the fourth embodiment is circular with an opening in cross section and is twisted in a helical direction. FIG. 38 is a cloud of flow rate slices from a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention. As shown in fig. 38, in the blood flow chamber 430 of the fourth embodiment, the flow velocity of the liquid is the highest on the side close to the twisted trajectory in the center portion of the circular cross section, and the maximum flow velocity is 19.30 m/s; the flow velocity at the edge of the profile is the slowest. FIG. 39 is a velocity field arrow plot of a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention. As shown in fig. 39, the larger the arrows indicate the faster the flow velocity, i.e., the center of the circular cross section is closer to the twisted trajectory portion than the edge of the contour. FIG. 40 is a cloud image of pressure slices from a finite element analysis of a blood flow lumen according to a fourth embodiment of the present invention. As shown in fig. 40, the fluid pressure in the blood flow lumen 430 gradually decreases from the inlet d1 to the outlet d2, with a peak pressure of 180 KPa. It is noted that there is a local pressure increase near the section d1 of the inlet due to the effect of the helical lumen fluid squeezing.

From the above, the blood flow cavity is a structure with a circular cross section and extending along a straight line direction, and has the fastest maximum flow rate and the most abundant blood supply. Compared with a structure extending in a straight line, a structure rotating in a spiral direction can play a certain speed reduction role on blood flow. Meanwhile, the flow velocity of the small special-shaped fan-shaped section is smaller than that of the large circular section. In addition, the fluid simulation results of the four structures show that the flow velocity of the area close to the pipe wall is low, and the low flow velocity of the circular pipe wall area is verified, so that the cross section of the liquid passing cavity is designed into a bent T-shaped structure to accord with the fluid mechanics principle.

And (4) analyzing results:

through CFD analysis, the circular cross-section structure in the third embodiment can be found to have the fastest liquid flow rate when passing through the fluid with the same pressure difference, namely, the blood volume passing through the blood flow cavity in unit time is the largest, and the blood supply for the far-end tissues is more sufficient. The structures of embodiment one, embodiment two and embodiment four have unique advantages in other respects.

Compared with a linear direction extending structure and a spiral direction twisting structure, the linear direction extending structure has the advantages of high blood flow velocity and good blood supply effect after the balloon is opened; the disadvantage is that the contact position of the single blood flow cavity and the vessel wall corresponds to a linear opening, and when the balloon is inflated, the outer surface of the balloon may be elliptical. Plaque in the blood vessel usually extends along the linear direction in the blood vessel, and once the linear plaque just corresponds to the linear opening position of the balloon, the supporting effect of the balloon on the plaque is influenced to a certain degree. And to the torsional structure of spiral direction, the position that the blood flow chamber and vascular wall contact corresponds the torsional opening of a heliciform, and the wholeness is better, avoids appearing surface circularity not enough at the expansion pathological change in-process, avoids meetting the direct long section embedding opening part's of linear plaque the condition.

Comparing the cross section of the blood flow cavity, the blood flow cavity in the first embodiment and the second embodiment adopts a special-shaped sector cross section with 4 circumferential arrays, and the blood flow cavity in the third embodiment and the fourth embodiment adopts a circular cross section eccentrically arranged with the liquid through pipe, and the structures have advantages and disadvantages respectively. Wherein, with the blood flow chamber of the circular cross-section of liquid pipe eccentric settings, the centre of a circle in blood flow chamber and the centre of a circle noncoincidence of blood vessel can find its blood flow velocity of flow fast through CFD analysis, and the sacculus is opened the back and is more abundant for distal end tissue blood supply. However, the direction of the blood flow center does not coincide with the normal blood flow center of the blood vessel, and the axis of the blood flowing out is offset from the axis of the original blood vessel, and a certain load is imposed on the downstream blood vessel wall on one side (the blood flow at the outflow end always impacts the blood vessel region relatively close to the blood flow lumen). The blood flow cavities with the special-shaped fan-shaped sections in the 4 circumferential arrays are adopted, and because the 4 blood flow cavities are circumferentially arrayed along the central axis of the blood vessel wall, after the blood in the downstream blood flow cavities is gathered, the central axis of the flowing-out blood is superposed with the axis of the original blood vessel, so that the blood flow state is the optimal blood flow state; although the blood flow is not as large as a circular cross-section, 4 blood flow lumens also guarantee the blood flow supply requirements. In addition, the positions of the blood flow cavities of the irregular fan-shaped sections arranged in the 4 circumferential arrays, which are contacted with the blood vessel wall, correspond to 4 openings, and the openings can also increase the nutrition for the blood vessel wall (namely, the blood flowing through the blood is required to provide nutrition for the growth and metabolism of the blood vessel wall cells).

It is to be noted that the foregoing is only illustrative of the preferred embodiments of the present invention and the technical principles employed. It will be understood by those skilled in the art that the present invention is not limited to the particular embodiments described herein, but is capable of various obvious changes, rearrangements and substitutions as will now become apparent to those skilled in the art without departing from the scope of the invention. Therefore, although the present invention has been described in greater detail by the above embodiments, the present invention is not limited to the above embodiments, and may include other equivalent embodiments without departing from the spirit of the present invention, and the scope of the present invention is determined by the scope of the appended claims.

Claims

1. A medicine balloon comprises a balloon catheter and is characterized in that the balloon catheter comprises a balloon body section and a liquid through pipe, two ends of the balloon body section are respectively connected with the liquid through pipe,

the number n of the balloon body sections is 2-8, the n balloon body sections are uniformly distributed and sequentially connected along the circumferential direction, the n balloon body sections are provided with a common inner cavity which is communicated with the liquid through pipe to form a liquid through cavity, and the cross section of the liquid through cavity is of a round and uniformly distributed n bent T-shaped structures;

the surface of the balloon body section is also provided with blood flow cavities for blood to pass through, the blood flow cavities are formed by surrounding the side walls of the liquid through cavities, the number of the blood flow cavities is equal to that of the balloon body section, the blood flow cavities and the balloon body section are sequentially and alternately arranged along the circumferential direction, the cross section of each blood flow cavity is of a special-shaped fan-shaped structure with an opening on an outer arc surface, and the sum of the cross sections of the blood flow cavities accounts for more than 30% of the cross section of the whole balloon body section;

micropores for the medicine microsphere preparation to pass through are distributed on the outer arc surface of the balloon body section; the diameters of the micropores of the balloon body segment proximal region and the balloon body segment distal region are greater than the diameter of the micropores of the balloon body segment middle region;

after the medicine saccule is released to a target area, first preset pressure is applied to the saccule catheter through the medicine microballoon preparation, so that the medicine microballoon preparation flows into a saccule body section from the near end of the liquid through pipe and flows out of the medicine saccule through the micropores, and liquid drops are formed, grown and dropped periodically outside the medicine saccule; then, a second preset pressure is applied to the balloon catheter through the drug microsphere preparation, so that the drug microsphere preparation is jetted outwards at a high speed from the micropores, a cavity effect is formed, and the drug microspheres are embedded in target tissues in the blood vessel.

2. The drug balloon of claim 1, wherein the balloon body segments are arranged linearly or helically twisted along the axis of the catheter.

3. The drug balloon of claim 2, wherein the micropores are distributed in a linear array or a helical twist along the axis of the liquid through tube.

4. A drug balloon according to claim 3, wherein the wall thickness of the balloon body segment is 0.01-0.1mm and the ear thickness of the T-shaped bend structure is 0.3-0.5 mm.

5. The drug balloon of any of claims 1-4, wherein the liquid conduit is open at a proximal end to allow passage of liquid; the liquid through tube is closed at the far end and does not allow liquid to pass through.

6. The drug balloon of any of claims 1-4, wherein the micropores have a diameter of 1-100 μm.

7. The drug balloon of claim 3 or 4, wherein the axial arrangement distance between adjacent micropores in each row of micropores is 0.1-10 mm.

8. A drug balloon according to any of claims 2-4, wherein the pitch of the helical line of the balloon body segment is 1-20mm when the balloon body segment is helically twisted along the axis of the catheter.

9. The drug balloon of any of claims 1-4, wherein the drug microsphere formulation comprises: the drug microsphere is in a suspension state in the working medium at room temperature, and the maximum size of the drug microsphere is smaller than the diameter of the micropore.

10. The drug balloon of claim 9, wherein the maximum dimension of the drug microspheres is less than 1/5 of the micropore diameter.

11. The drug balloon of claim 9, wherein the drug microspheres are spherical structures with a diameter of 1-990 nm.

12. The drug balloon of claim 9, wherein the drug microspheres comprise a drug and an excipient; the medicine is one or more of nimustine, carmustine, 5-fluorouracil, fluoroguanosine, gemcitabine, daunorubicin, doxorubicin, paclitaxel, vinblastine, topotecan, aminoglutethimide, sirolimus, everolimus, rapamycin and zotarolimus; the excipient is one or more of racemic polylactic acid, polyethylene glycol, magnesium stearate, iohexol, iopromide, urea, sorbitol, polysorbitol, polyoxyethylene polyoxypropylene ether block copolymer, trihexyl citrate, phospholipid, ropiperazine matrix, polylactic acid-glycolic acid copolymer, polyvinylpyrrolidone, cholesterol, vitamin E and vitamin E polyethylene glycol succinate.