WO2013097717A1

WO2013097717A1 - Drug-eluting balloon tube

Info

Publication number: WO2013097717A1
Application number: PCT/CN2012/087528
Authority: WO
Inventors: 李孝秀; 谢志永; 郭芳; 卢惠娜; 张滢涛; 孙芳华; 常孟琪; 罗七一
Original assignee: 上海微创医疗器械（集团）有限公司
Priority date: 2011-12-27
Filing date: 2012-12-26
Publication date: 2013-07-04
Also published as: CN102512747A

Abstract

A drug-eluting balloon tube comprises a balloon tube body and a drug coating (7). The balloon tube body comprises a balloon (1), and a plurality of grooves (6) is disposed on the outer surface of the balloon (1). The drug coating (7) is applied on groove portions and planar portions at the outer surface of the balloon (1). The grooves (6), when the balloon (1) is inflated, turn into inverted convexes. The drug-eluting balloon tube is not only capable of carrying more drugs and reducing the loss of drugs during the conveyance, but also is capable of directly discharging drugs that stay inside the grooves into the blood under the effect of the inverted convexes, so as to accelerate the release of drugs and increase the concentration of drugs at a target position, so that the drugs can quickly concentrate and act on the target position to better prevent the blood vessel tissue at the target position from regeneration and restenosis.

Description

Drug eluting balloon catheter

The invention relates to the field of medical devices. More specifically, the present invention relates to a drug lavage balloon catheter. Background technique

Since the 1970s, intraluminal balloon angioplasty has been widely used to treat stenosis caused by atherosclerosis. Although the immediate therapeutic effect of balloon angioplasty is satisfactory, the incidence of surgical complications, especially restenosis, is high, limiting its widespread clinical application. Endovascular stenting is the implantation of a stent at the stenosis site while the balloon is dilating. The stent is resistant to vascular stratification and restenosis caused by elastic retraction, which can significantly reduce the acute or subacute ischemic complications of interventional therapy. However, the insertion of the stent stimulates the migration of vascular smooth muscle cells and proliferates in a large amount, causing intimal hyperplasia of the blood vessels, resulting in in-stent restenosis.

In 2001, rapamycin and paclitaxel drug-eluting stents were successfully used clinically and were extremely successful in treating in-stent restenosis, demonstrating the potential of drug-eluting stents for the treatment of restenosis. However, many years of clinical analysis found that drug stent coatings may have some adverse effects, such as delayed thrombosis that can lead to patient death and chronic inflammatory reactions from bio-inert polymers. Drug-coated balloons are an emerging means of endovascular treatment in recent years, which avoids endothelialization disorders caused by continuous drug contact, drug-coated balloons or drug-coated balloon-based bare metal stents. A good prospect. Since the launch of the first generation of drug-eluting balloon catheters (SeQuent Please), a variety of drug-eluting balloon catheters have been developed and marketed in Europe. Existing drug-eluting balloon dilatation catheters are typically coated with a drug coating on the outer surface of a flat balloon (see Patent Application No. 200910084768.0, a drug-loaded balloon dilatation catheter) And the patent application No. 200710150413.8, "drug coating applied to the surface of a balloon catheter balloon to relieve vascular restenosis", and generally pays more attention to the selection of a drug coated on the outer surface of the balloon. The amount of drug that can be loaded on the outer surface of the flat balloon is limited, not only due to contact with the blood vessel wall and blood during transportation, but also the drug release rate is slow. Although a skilled person has proposed a drug-eluting balloon catheter having a concave-convex non-flat structure for the purpose of increasing the drug loading amount (see the patent application No. 201010121627.4, the "drug balloon catheter and its preparation method"), but The uneven structure of the unevenness is rigid and thick, although it is possible to increase the drug loading amount and reduce the amount of loss during transportation by holding the drug in the concave portion, but the concave portion, especially the deep portion of the concave portion, is retained after being transported to the target position. The drug is less prone to release quickly and does not accelerate drug release. Therefore, there is a need to provide a drug eluting balloon catheter that not only increases drug loading, reduces the loss of coated drug during catheter delivery, but also accelerates drug release at the target site. Summary of the invention

In order to solve the above technical problems, the present invention provides a drug eluting balloon catheter comprising a balloon catheter body and a drug coating, the balloon catheter body comprising a balloon, and the balloon has a plurality of outer surfaces The groove, and the drug coating is coated on the groove portion and the flat portion of the outer surface of the balloon, characterized in that the groove is converted into a reverse projection after the balloon is filled. Preferably, the shape of the groove is circular and/or elliptical. Wherein, the grooves may be arranged in an array. Preferably, the material of the balloon is a medical polymer material. Preferably, the medical polymer material is a polyamide-based polymer material, a modified polyamide polymer material, or a polymer composite material. Furthermore, the grooves can also be in the form of strips. Preferably, the volume of each groove is uniform. Preferably, the groove can be obtained by integrally blow molding the balloon by changing the structure of the balloon molding die. Preferably, the drug coating comprises a drug-loading layer comprising a drug carrier and an active drug. Preferably, the drug carrier is primarily a hydrophilic organic substance which promotes drug elution and promotes penetration of the drug into the diseased vascular tissue at the target site. Preferably, the pharmaceutical carrier used in the present invention means a water-soluble organic substance containing one or more functional groups of a hydroxyl group, an amino group, an amide group, a sulfonic acid group, a carboxylic acid group, a carboxylic acid group, and an ether bond. Preferably, the pharmaceutical carrier is selected from the group consisting of urea, gluconolactone, sorbitol, dipropanolamine hexanoline, glucose, fructose, polysaccharide, low molecular weight chitosan, and polyethylene glycol having a molecular weight of 4000-8000. One or more of an alcohol, a hydroxyl group-containing hydrophilic monomer polymer. Preferably, the active drug is selected from one or more of an anticancer drug, an anticoagulant, a microbial immunosuppressive agent, and other anti-restenosis drugs. The anticancer drug is selected from the group consisting of methotrexate, anthraquinone, pyrimidine, plant alkaloid, epothilone, tripterygium wilfordii compound, antibiotic (especially actinomycin-D), hormone, antibody treatment One or more of cancer drugs. Preferably, the plant alkali anticancer drug is paclitaxel. The anticoagulant is selected from one or more of heparin, aspirin, hirudin, colchicine, antiplatelet GP lI b/IIIa receptor antagonist, said antiplatelet GP lI b/IIIa The receptor antagonist is selected from one or more of tirofiban, abciximab, and eptifibatide. The microbial immunosuppressive agent is selected from the group consisting of cyclosporine A, tacrolimus and homologues, desperin, enzymatic phenolic acid ester, rapamycin and its derivatives, strain of strain Streptomyces FR900520, chain Mold strains FR900523, daclizumab, valeramide, claramycin, sclarin, lycopene 25c, tranilast, myriocin, cyclosporine, bracemycin, mycophenol One or more of acid, brefeldin A, ketone corticosteroid. The other anti-restenosis drug is selected from the group consisting of bamastat, a metalloproteinase inhibitor, 17 beta-estradiol, a NO donor, 2-chlorodeoxyadenosine, 2-deoxy-assisin, Fingolimo De, mycophenolate sodium, cyclosporin A derivative ISA (TX) 247, acesulfabate, celecoxib, basiliximab, antithymocyte, everolimus, methotrexate, endo One or more of lar, cyclophosphamide, benzoquina sodium, leflunomide, and imidazolyl. Preferably, the drug coating may be applied to the groove portion and the flat portion of the outer surface of the balloon by spraying or dipping. The drug eluting balloon catheter according to the present invention has the following beneficial effects: 1) providing a groove on the outer surface of the balloon, which can not only carry more drugs, but also reduce the loss of the drug during transportation; When the balloon is filled and expanded at the target position, the groove is converted into a reverse protrusion after the balloon is filled, whereby the drug stored in the groove is directly dumped and thrown under the action of the reverse protrusion. The diseased vascular tissue at the target position accelerates the release of the drug and increases the concentration of the drug at the target site, thereby enabling concentration and rapid action on the target site, and better preventing proliferation and restenosis of the vascular tissue at the target site. DRAWINGS

In order to more clearly describe the technical solution of the present invention, a brief description will be made below with reference to the accompanying drawings. It will be apparent that these figures are only some of the specific embodiments of the drug eluting balloon catheters described herein. The structure of the biodegradable stent of the present invention includes but is not limited to the following The figure. 1 is a schematic partial cross-sectional view of a drug eluting balloon catheter in accordance with an embodiment of the present invention;

2 is a schematic illustration of a balloon structure of a drug eluting balloon catheter in accordance with an embodiment of the present invention;

3 is a cross-sectional view of a balloon of another drug eluting balloon catheter prior to loading a drug, in accordance with an embodiment of the present invention.

4 is a cross-sectional view of a balloon of another drug eluting balloon catheter after loading a drug, in accordance with an embodiment of the present invention.

Figure 5 is a cross-sectional view of a balloon of another drug eluting balloon catheter after inflation and expansion, in accordance with an embodiment of the present invention. detailed description

In order to further understand the present invention, the preferred embodiments of the present invention will be described below in conjunction with the embodiments. These descriptions are only illustrative of the features and advantages of the invention and are not intended to limit the scope of the invention. 1 is a schematic cross-sectional view of a drug eluting balloon catheter in accordance with an embodiment of the present invention. As shown in FIG. 1, the drug eluting balloon catheter comprises a balloon catheter body and a drug coating 7, the balloon catheter body comprising: a balloon 1, an inner tube 2, a delivery rod 3 and a connector 4, wherein The tube 2 is placed inside the delivery rod 3 and the balloon 1 for passing through a guide wire (not shown); the delivery rod 3 is for delivering the balloon 1 to the target position along the guide wire; the balloon 1 is connected to The distal end of the delivery rod 3; the connector 4 is disposed at the proximal end of the delivery rod 3 for piercing the guidewire and filling the balloon 1 as needed. Although a specific structure of a drug eluting balloon catheter is shown in Fig. 1, other structures composed of a balloon catheter body and a drug coating 7 are also suitable. A development mark 5 may be provided on the surface of the inner tube 2 for developing the position of the balloon in the cardiovascular structure by radiography to ensure positioning and filling of the balloon at the target position. As shown in FIG. 2 to FIG. 3, the outer surface of the balloon 1 is provided with a plurality of grooves 6, and the groove 6 The shape is circular and/or elliptical and can be arrayed. Although not shown in the drawings, the groove 6 may also be in the form of a strip. The volume of the plurality of grooves 6 on the outer surface of the balloon 1 is uniform. The groove can be obtained by integrally blow molding the balloon by changing the structure of the balloon molding die. A layer of drug coating 7 is applied by dipping or spraying on the grooved portion and the flat portion of the outer surface of the balloon, as shown in FIG. The drug coating 7 comprises a drug carrying layer comprising a drug carrier and an active drug. The drug carrier is mainly a water-soluble organic substance. When the balloon is filled and expanded and contacted with vascular tissue, the drug carrier can be rapidly dissolved in the blood, thereby promoting rapid release of the drug. In addition, according to the actual situation, the release rate of the drug in the drug coating can be adjusted by adjusting the proportional relationship between the active drug and the drug carrier. In the embodiment of the present invention, the drug carrier may employ a water-soluble organic substance containing one or more functional groups of a hydroxyl group, an amino group, an amide group, a sulfonic acid group, a carboxylic acid group, a carboxylic acid group, and an ether bond. More preferably, the pharmaceutical carrier may be selected from the group consisting of urea, gluconolactone, sorbitol, dipropanolamine hexanoline, glucose, fructose, polysaccharide, low molecular weight chitosan, and a molecular weight of 4000-8000. One or more of ethylene glycol and a methoxy-containing hydrophilic monomer polymer. In addition, the active drug in the drug coating 7 may be selected from one or more of an anticancer drug, an anticoagulant, a microbial immunosuppressive agent, and other anti-restenosis drugs. Among them, the anticancer drug may be selected from the group consisting of methotrexate, anthraquinone, pyrimidine, plant alkali (especially paclitaxel), epothilone, tripterygium series compound, antibiotic (especially actinomycin-D) ), one or more of hormones, antibody cancer drugs. Preferably, the anticoagulant drug is selected from the group consisting of heparin, aspirin, hirudin, colchicine, and an antiplatelet GP lI b/IIIa receptor antagonist. Preferably, the anti-platelet GP lI b/IIIa receptor antagonist is selected from the group of tirofiban

(tirofiban), one or more of abciximab, eptifibatide. Preferably, the microbial immunosuppressive agent is selected from the group consisting of cyclosporin A (CsA), tacrolimus and homolog (FK506), 15-deoxyspergualin, and enzymatic phenolic acid (MMF) ), Rapamycin and its derivatives, Streptomyces strain FR900520, Streptomyces strain FR900523, daclizumab, depsidomycin, Kanglemycin C, spergualin, prodigiosin 25-c, tranilast, myriocin, cyclosporine C , one or more of bredinin, mycophenolic acid, brefeldin A, ketone corticosteroids. Preferably, the other anti-restenosis drug may be selected from the group consisting of batimastat, metalloproteinase inhibitor, 17 beta-estradiol, NO donor, 2-chlorodeoxyadenosine, 2-deoxycoformycin, fingolimod (FTY-720), mycophenolate sodium (Myfortic), ISA(TX)247 (cyclosporin A derivative), acebec (AGI-1096), Zenapax, Simulect, Thymoglobulin, Enverolimus, Methotrexate, Neola Neoral, Cyclophosphamide (Brequinar Sodium), Leflunomide^Mizoribine. After the balloon is delivered to the target site, the balloon is filled and expanded. The stenotic blood vessel at the target position is expanded, and at this time, under the action of the pressure difference between the inside and the outside of the balloon, the shape of the groove can be changed from a concave shape to a reverse convex shape. Preferably, the material of the balloon is medically high. Molecular material. Preferably, the medical polymer material is a polyamide polymer Material, modified polyamide polymer material or polymer composite material. As shown in Fig. 5, through the deformation of the groove, the drug originally left in the groove is directly dumped to the diseased blood vessel tissue at the target position, accelerating the drug. Released, and the drug concentration at the target position is increased. As can be seen from the above technical solution, the drug eluting balloon catheter according to the embodiment of the present invention can carry more drugs while reducing the number of drugs provided on the surface of the balloon. The loss of the drug during transport, and the groove is converted into a reverse bulge after the balloon is filled, and the drug can be quickly concentrated to the target position to better prevent proliferation and restenosis of the vascular tissue at the target position. The description of the embodiments is only to assist in understanding the core idea of the present invention. It should be noted that those skilled in the art can also make several improvements to the degradable stent of the present invention without departing from the principles of the present invention. Modifications, but such modifications and modifications are also intended to fall within the scope of the appended claims.

Claims

Claim

A drug eluting balloon catheter comprising a balloon catheter body and a drug coating, the balloon catheter body comprising a balloon, the balloon having a plurality of grooves on an outer surface thereof, and in the balloon The drug coating is coated on the groove portion and the flat portion of the outer surface, and the groove is converted into a reverse projection after the balloon is filled.

2. The drug eluting balloon catheter of claim 1, wherein the groove is circular and/or elliptical in shape.

3. The drug eluting balloon catheter of claim 1 or 2, wherein the grooves are arranged in an array.

4. The drug eluting balloon catheter of claim 1, wherein the material of the balloon is a medical polymer material.

The drug eluting balloon catheter according to claim 4, wherein the medical polymer material is a polyamide-based polymer material, a modified polyamide polymer material or a polymer composite material.

6. The drug eluting balloon catheter of claim 1, wherein the groove is in the form of a strip.

7. The drug eluting balloon catheter of claim 1, wherein the volume of each of the grooves is uniform.

8. The drug eluting balloon catheter of claim 1 wherein said groove is integrally formed by blow molding with a balloon.

9. The drug eluting balloon catheter of claim 1, wherein the drug coating comprises a drug loading layer comprising a drug carrier and an active drug.

10. The drug eluting balloon catheter of claim 9, wherein the drug carrier is a hydrophilic organic material.

1 1. The drug eluting balloon catheter according to claim 10, wherein the pharmaceutical carrier is one or more of a hydroxyl group, an amino group, an amide group, a sulfonic acid group, a carboxylic acid group, a carboxylic acid group, and an ether bond. A functional group of readily soluble organic matter.

12. The drug eluting balloon catheter of claim 11, wherein the pharmaceutical carrier is selected from the group consisting of urea, gluconolactone, sorbitol, dipropanol hexyl citrate, glucose, fructose, polysaccharide, low One or more of a molecular weight chitosan, a polyethylene glycol having a molecular weight of 4000-8000, and a hydroxyl group-containing hydrophilic monomer polymer.

13. The drug eluting balloon catheter of claim 9, wherein the active drug is selected from one or more of an anticancer drug, an anticoagulant, a microbial immunosuppressive agent, and other anti-restenosis drugs. .

The drug eluting balloon catheter according to claim 13, wherein the anticancer drug is selected from the group consisting of methotrexate, anthraquinone, pyrimidine, plant alkaloid, epothilone, and tripterygium One or more of a compound, an antibiotic, a hormone, and an antibody cancer drug.

The drug eluting balloon catheter according to claim 14, wherein the alkaloid anticancer drug is paclitaxel.

16. The drug eluting balloon catheter of claim 13, wherein the anticoagulant is selected from the group consisting of heparin, aspirin, hirudin, colchicine, and an antiplatelet GP lI b/IIIa receptor antagonist. One or more.

The drug eluting balloon catheter according to claim 16, wherein the anti-platelet GP lI b/IIIa receptor antagonist is selected from the group consisting of tirofiban, abciximab, and eptifibatide One or more.

18. The drug eluting balloon catheter of claim 13, wherein the microbial immunosuppressive agent is selected from the group consisting of cyclosporine A, tacrolimus and homologs, desperatin, enzymatic phenolic acid ester , rapamycin and its derivatives, strain FR900520 of Streptomyces species, strain FR900523 of Streptomyces species, daclizumab, valeramide, claramycin C, sclarin, lycopene 25c, tranus One or more of special, globulin, cyclosporine, brevisin, mycophenolic acid, brefeldin A, ketone corticosteroid.

19. The drug eluting balloon catheter of claim 13, wherein the other anti-restenosis drug is selected from the group consisting of: bamastat, a metalloproteinase inhibitor, 17 beta-estradiol, a NO donor, 2- Chloro deoxyadenosine, 2-deoxy-assisin, fingolimod, mycophenolate sodium, cyclosporin A derivative ISA (TX) 247, acesulfabate, celecoxib, basiliximab One or more of antithymocyte globulin, everolimus, methotrexate, endolol, cyclophosphamide, benzoquina sodium, leflunomide, and imidazophene.

20. The drug eluting balloon catheter of claim 1, wherein the drug coating is applied to the groove portion and the flat portion of the outer surface of the balloon by spraying or dipping.