JP2005349202A - Instrument and method for delivering therapeutic agent into tissue - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an instrument and a method for efficiently and simultaneously delivering a therapeutic agent through two or more puncture regions in a controlled form into a specified part of a blood vessel such as an adventita layer. <P>SOLUTION: This instrument for delivering a therapeutic agent into tissue includes: a long body 202; a first balloon 230 in the body, which is expandable from a crushed position to an expanded position; and a second balloon 235 expandable from the crushed position to an expanded position. The second balloon has a plurality of apertures 237. A therapeutic agent 500 is disposed in the second balloon. A plurality of micro-projecting parts 250 are disposed on the surface of the second balloon for penetrating tissue 300. When the first balloon is expanded from the crushed position to the expanded position, the second balloon is expanded from the crushed position to the expanded position to dispose the two or more micro-projecting parts into tissue, and the therapeutic agent is supplied from the second balloon through the two or more apertures into the tissue. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention generally relates to an apparatus and method for introducing a drug for introducing a drug, and more particularly, a tissue for introducing a drug into a desired layer in a tissue such as an outer membrane layer of a blood vessel. The present invention relates to a new and beneficial device and method for introducing drugs into the body.

  Obstructive atherosclerotic disease is a difficult health problem that approaches our current society. The disease is the result of the deposition of fatty substances, adipocytes, and connective tissue inside the walls of the arteries. As such deposition increases or accumulates, the inner diameter of the artery narrows, thereby restricting blood flow through the artery. This disease, which narrows the opening or lumen of the artery, is known as atherosclerosis, and the accumulation of deposition is known as the lesion.

  One surgical technique that is currently widely used to treat obstructions caused by atherosclerosis is a surgical technique known as coronary artery bypass grafting (bypass surgery). Although bypass has been moderately successful in treating atherosclerosis, bypass is invasive and traumatic to the patient.

  One more recently developed less invasive and less traumatic surgical technique is coronary angioplasty. Coronary angioplasty and general angioplasty are surgical procedures in which a balloon is placed inside the artery at the site of accumulation or lesion and inflated to expand the atheromatous lesion and open the narrowed area of the artery. is there. To advance the balloon toward the lesion, the balloon is attached to the distal end of a smaller diameter catheter and the catheter includes means for inflating the balloon from the other end. The catheter is steered or “steered” through the patient's blood vessel toward the lesion site with the balloon deflated. Once the deflated balloon is properly placed in the lesion, the balloon is then inflated to expand the narrowed area.

  Although angioplasty has been quite successful in treating coronary artery disease, the narrowest stenosis of the treated site often occurs about three to six months after surgery. It is believed that the primary factor causing the most stenosis is the healing that occurs after the injury caused by the intervention of balloon dilatation surgery. Stenosis is very similar to scar formation after vascular surgery in that the histological results are in a similar form. This histological reaction is called intimal myopathy. The process of intimal myopathy involves the smooth muscle cells moving through the inner elastic lamina to the lumen of the blood vessel and proliferating in the lumen. The end result is a thickening of the vessel wall. Over time, such vessel wall thickening reoccludes or restenosis the vessel at clinically important points. Therefore, the blood flow flowing through the blood vessel is reduced to a flow rate comparable to that before the angioplasty is performed. The occurrence of such a decrease in blood flow appears to occur with a probability of about 30% to 35% after angioplasty at that specified site of the coronary artery.

  Several other surgical procedures have been attempted to affect the occurrence or rate of restenosis after intervention at the lesion site of the coronary artery. These surgical procedures include using lasers, mechanical atherectomy instruments, heated balloons, and metal implantable stents. Although each of these surgical techniques has had some success in treating early lesions, every surgical technique has the same problem of restenosis with a similar or greater incidence. Current estimates of restenosis at the lesion site using these alternative surgical techniques are in the range of 40% to 50%. In any case using these other surgical techniques, the restenosis occurs roughly from March to June after surgery.

  Thus, it can be seen that the healing lesion area leading to this restenosis is independent of the type of interventional surgical technique used. Rather, healing leading to restenosis is a physiological response to any type of trauma given to the lesion area. Because of this physiological response independent of the type of interventional surgical procedure, the potentially best way to treat restenosis is like drugs that target biochemical events that occur after surgery. Many doctors feel that this may be a method using pharmacological means.

  To date, most pharmacological attempts use drugs that are orally or intravenously injected throughout the body in the hope of affecting small lesion sites in the arteries. This type of pharmacological treatment is known as "systemic treatment". Drugs that have been tried in human clinical practice include heparin, calcium channel blockers, angiotensin converting enzyme inhibitors, omega-3 fatty acids, and growth peptides. Other drugs of interest that may not have been attempted in human clinical practice include thromboxane synthetase inhibitor, serotonin, growth factor inhibitor, angiopeptin Growth factor analogues such as, antogonists, HMG-CoA reductase inhibitors, platelet derived growth factor, inflammatory cell factor, platelet aggregation inhibitor, thrombin inhibitor such as hirudin or its analogues, etc. .

  Efficacy with most of these drugs is in in vitro cell culture studies or animal studies. These studies have shown some effect on the proliferation and migration of smooth muscle cells, a major component of intimal myopathy that occurs in lesions that cause restenosis. However, to date, none of the introduction of systemic drugs to humans has shown a noticeable effect on the occurrence of restenosis.

  None of these drugs have been fully successful in clinical trials against humans in vivo, but one or another of these drugs is locally and locally It remains widely felt that when specifically introduced into a lesion, it may still reduce the proliferative response. One challenge with systemic methods is the inability to locally introduce drugs at concentrations high enough to affect physiological responses. In vitro or in vivo animal studies that have shown some success, high concentrations of drug were used. Thus, it is believed that if a drug is introduced at a specific site rather than systemically, the drug will be introduced at a concentration sufficient to actually affect the physiological response.

  The reason that many of these drugs have not been used at higher concentrations for humans in vivo is that many of the drugs may exhibit undesirable side effects. Thus, when a high concentration of drug is administered systemically, the high concentration of drug may have undesirable physiological effects. Therefore, if the drug can be applied locally to the vessel wall at a high concentration while minimizing the amount of systemic drug, it can inhibit proliferation that causes restenosis and at the same time have any undesirable systemic effects. The desired result of preventing may be obtained.

  There are several other methods known to date for identifying a site and allowing a drug to be introduced into that site. One approach currently contemplated is to use a perforated or sweaty balloon. For example, one drug delivery device is described by Wolinsky, H., et al., “Use of a perforated balloon catheter to introduce concentrated heparin into the walls of normal dog arteries, 15 JACC475 ( Use of a Perforated Balloon Catheter to Deliver Concentrated Heparin Into the Wall of a Normal Canine Artery, 15 JACC475) ”(February 1990). This device is a percutaneous transluminal coronary angioplasty (PTCA) balloon in which a plurality of micropores are provided in the balloon to introduce a drug while the balloon is inflated. The drug is incorporated into the fluid used to inflate the balloon.

  The problem with instruments that can be used, such as those disclosed by Warinsky et al., Is that they substantially block blood flow through the target vessel during the surgical procedure. Therefore, these instruments are only used for a fairly short period of time (typically 1 or 2 minutes) that is the same as the period of expansion in actual angioplasty.

  Other usable drug introduction devices include, for example, Patent Document 1 (US Pat. No. 4,824,436: Warinsky) and Patent Document 2 (US Pat. No. 4,636,195: Warinsky). Is disclosed. These instruments are directed to double occlusion catheters where the balloon is inflated on the proximal and distal sides of the accumulation or lesion to form a space for injecting medication. This double occlusion balloon catheter creates a space for injecting drugs separately from the blood flow. However, this device is also used only for a short period of time because it prevents blood flow.

  In these types of instruments where the balloon is inflated within a blood vessel, several means for providing perfusion through the catheter itself become important. Such devices need to have a wide tolerance for the period during which the drug is introduced. Devices that occlude blood flow may not provide the necessary tolerance. Basic research on biochemical and physiological events shows that the first event begins immediately after the trauma and continues intensely over several hours, so the drug delivery device begins several hours after the intervention. It is desirable that the drug can be introduced over a period of 1 to 2 days. The study also points out that the first event later produces a tandem event that ultimately leads to intimal thickening. These accumulations or lesions are not apparent for months, so if such initial events can be suppressed, blocked or even promoted, subsequent tandem events can be altered and intimal thickening Can be reduced as a whole.

  Several devices have been designed that allow drugs to be introduced locally while providing enhanced perfusion capability. For example, some known drug delivery catheters provide an inflatable perfusion lumen that provides a significantly larger perfusion area than previous drug delivery catheters. The disclosed catheter and method also provide a drug introduction pocket located at the outer periphery of the perfusion lumen. The drug introduction pocket allows a drug to be introduced by specifying a site over a long period of time.

  However, all of the drug introduction devices described above must remain in the blood vessel while the drug is being administered. It would be desirable to have a method of introducing a drug locally without the need for the drug introduction device to remain in the blood vessel.

  To this end, several methods have been proposed in which drugs are introduced by surgical procedures that are introduced outside the blood vessel to be treated. Several studies have shown that drug administration (periarterial drug administration) by implanting a controlled release device that surrounds a blood vessel with drugs such as heparin ethylene vinyl acetate significantly prevents restenosis in arterial trauma models Has been shown to do. For example, “Proc. Natl. Acad. Sci. USA., 87, 3773 (1990)” by Edelman et al., And “J. Clin. Invest., 39, 65 (1992)” by Edelman et al. Is referenced. In these types of surgical procedures, access to the blood vessel is achieved by surgically cutting the desired location of the blood vessel. The drug is then held in the desired position by wrapping the blood vessel with a band or cuff filled with the drug. Periarterial drug administration has shown some initial success in animal models, but the obvious disadvantage that this surgical technique used to introduce a band or cuff is very invasive have.

  In addition, depending on the specific disease, it is known in the medical field that fluid drugs are injected directly into the blood vessel walls of the patient's cardiovascular system to obtain beneficial results. For example, one such application is the administration of drugs to the walls of the arteries that inhibit or prevent restenosis from arterial plaque. However, any surgical procedure that involves injecting fluid medication directly into the vessel wall requires several factors to be considered. First, the surgical procedure must be safe. For example, due to the toxic nature of some drugs, the surgical procedure must ensure that a minimal amount of drug is always washed out into the bloodstream and not actually injected into the vessel wall. Second, a device for injecting a drug into the wall of a blood vessel must be accurate in its introduction capability and reliable in operation.

  Several instruments have been proposed for the purpose of injecting fluid medication directly into the vessel wall. One type of drug introduction device is disclosed in US Pat. No. 5,538,504 (US Pat. No. 5,538,504). The instrument is a catheter with a single needle at the distal end that is curved to define a U-shape. An inflatable balloon is contained within the catheter for deploying a needle through the catheter window and into the blood vessel.

  Another example of such a device is US Pat. No. 5,354,279, issued to Hofling as invention “Plural Needle Injection Catheter”. )It is described in. The specific instrument disclosed in this invention uses a pre-bent hollow needle that extends from the catheter and punctures the vessel wall. The extended needle is then used to inject fluid medication.

  U.S. Pat. No. 5,354,279 describes a needle to engage a resilient inner hose with a surrounding vessel wall or even puncture the vessel wall to be expanded like a balloon. It is also disclosed that it can be used to move outward. Further, Patent Document 5 (US Pat. No. 5,364,356) was granted for another invention “Sleeve Catheter” to Hofling. The second patent granted to this hoffling uses a sleeve that is expanded with a balloon that introduces a fluid drug into the vessel wall. More particularly, this device for the hoffling includes a reconfigurable sleeve that is expanded by an inflatable balloon. When the sleeve is expanded, it is intended that the opening formed in the sleeve expands to release fluid drug to the surface of the vessel wall.

  Still another example of a device for administering a drug to the blood vessel wall is disclosed in Patent Document 6 (Barath et al. Invented "Catheter Device for Intramural Delivery of Catheter Device for Intramural Delivery of Therapeutic Agents) "is disclosed in U.S. Pat. No. 5,112,305. The same device is disclosed in Patent Document 7 (invented by Ballas et al. "Catheter Device and Method for Using Catheter Device and Method for Introducing Protein Kinase C and Tyrosine Protein Kinase Inhibitor to Prevent Restenosis After Balloon Angioplasty") US Pat. No. 5,242,397) entitled “Method of Use for Intramural Delivery of Protein Kinase C and Tyrosine Protein Kinase Inhibitors to Prevent Restenosis after Ballon Angioplasty)”. More specifically, the device disclosed by Ballas et al. Uses a balloon that first requires the balloon to be slowly filled with a drug in order to inflate the balloon and place the balloon surface against the vessel wall. . Following this initial slow drug filling, the balloon is rapidly filled with the drug to reconstruct the tubular extension on the surface of the balloon and inject the drug through the tubular extension into the vessel wall.

Another device for injecting a fluid medicament is disclosed in US Pat. No. 5,681,281. This device is a catheter with a plurality of lumens attached with inflatable PET balloons. A plurality of injectors are attached directly to a sleeve attached directly to the outer surface of the balloon. Each injector has a base plate and a hollow protrusion protruding from the base plate. The hollow protrusion is formed with a flow path for pumping fluid drug from the injection chamber to the vessel wall through the opening of the sleeve.
U.S. Pat. No. 4,824,436 (columns 2-4, Fig. 1) U.S. Pat. No. 4,636,195 (columns 2-4, FIG. 1) US Pat. No. 5,538,504 (columns 6-11, FIG. 1) US Pat. No. 5,354,279 (columns 4-8, FIG. 1) US Pat. No. 5,364,356 (columns 3-4, FIG. 1) US Pat. No. 5,112,305 (columns 2-4, FIG. 1) US Pat. No. 5,242,397 (columns 4-6, FIG. 2A) US Pat. No. 5,681,281 (columns 4-7, FIG. 2)

  To date, there are no known devices and methods for efficiently and simultaneously introducing therapeutic agents through multiple puncture sites in a controlled manner to a specific portion of a blood vessel, such as the adventitia layer.

  The present invention is directed to devices for introducing therapeutic agents into tissues and methods of use thereof. While the devices and methods according to the present invention can be used in any tissue that requires treatment with one or more therapeutic agents, the present invention is intended to introduce one or more therapeutic agents into the walls of blood vessels. It is particularly beneficial, and more particularly useful for introducing one or more therapeutic agents into the outer membrane or outer membrane layer of a blood vessel.

In certain embodiments, the invention is directed to an instrument for introducing a therapeutic agent into tissue, the instrument comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions A portion is deployed in the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures.

  The second balloon is a pressurized reservoir in which the therapeutic agent is housed. The second balloon is arranged circumferentially around the first balloon. Further, the second balloon is disposed near the distal end of the elongated body of the instrument.

  Furthermore, in some embodiments, the plurality of microprojections are arranged in an array. Furthermore, the array of microprojections is made of a metal, preferably a thin sheet of material such as titanium. Furthermore, the array of microprojections has a plurality of openings through the array, the plurality of openings being disposed adjacent to the plurality of openings in the second balloon for introducing a therapeutic agent.

  In addition, the instrument includes an outer sheath that is movably arranged to cover the distal end of the instrument if necessary.

In another embodiment according to the present invention, the present invention is directed to a catheter for introducing a therapeutic agent into tissue, the catheter comprising:
A flexible long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions A portion is deployed in the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures.

  The second balloon is a pressurized reservoir in which the therapeutic agent is housed. The second balloon is arranged circumferentially around the first balloon. In addition, the second balloon is disposed near the distal end of the elongated body of the catheter.

  Furthermore, in some embodiments, the plurality of microprojections are arranged in an array. Furthermore, the array of microprojections is made of a metal, preferably a thin sheet of material such as titanium. In addition, the array of microprojections has a plurality of openings, the plurality of openings being disposed adjacent to the plurality of apertures of the second balloon for introducing a therapeutic agent.

  In addition, the catheter includes an outer sheath that is movably disposed to cover the distal end of the instrument if necessary.

Furthermore, the present invention is also directed to a method for introducing a therapeutic agent into a tissue. In one embodiment according to the present invention, the method comprises:
Providing a device for introducing a therapeutic agent into tissue, the device comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing a device for introducing the therapeutic agent into the tissue, wherein a portion is deployed in the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures When,
Placing the device adjacent to a tissue site;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the tissue at the site.

  The method further comprises the step of supplying a first fluid medium into the first balloon to expand the first balloon.

Another embodiment according to the present invention is directed to a method of introducing a therapeutic agent into the wall of a blood vessel. The method is
Providing a device for introducing a therapeutic agent into tissue, the device comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing a device for introducing the therapeutic agent into the tissue, wherein a portion is deployed in the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures When,
Placing the device adjacent to a site of the blood vessel wall;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the blood vessel wall at the site.

  The method further comprises the step of supplying a first fluid medium into the first balloon to expand the first balloon. In addition, the method further includes the step of placing the device in the blood vessel before introducing the therapeutic agent into the vessel wall.

  In addition, the method further comprises introducing a therapeutic agent into the vessel wall. More specifically, the therapeutic agent is introduced into the outer membrane layer of the blood vessel.

In another embodiment in accordance with the invention, the invention is directed to a method of introducing a therapeutic agent into tissue, the method comprising:
Providing a catheter for introducing a therapeutic agent into tissue, the catheter comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing the catheter, wherein a portion is deployed in tissue and the therapeutic agent is delivered from the second balloon into the tissue through the plurality of apertures;
Placing the catheter adjacent to the tissue site;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the tissue at the site.

  The method further comprises the step of supplying a first fluid medium into the first balloon to expand the first balloon.

In another embodiment according to the present invention, the present invention is directed to a method of introducing a therapeutic agent into the wall of a blood vessel, the method comprising:
Providing a catheter for introducing a therapeutic agent into tissue, the catheter comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing the catheter, wherein a portion is deployed in tissue and the therapeutic agent is delivered from the second balloon into the tissue through the plurality of apertures;
Placing the catheter adjacent to a portion of the vessel wall;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the blood vessel wall at the site.

  The method further comprises the step of supplying a first fluid medium into the first balloon to expand the first balloon. In addition, the method further comprises the step of placing the catheter in the blood vessel before introducing the therapeutic agent into the vessel wall. In addition, the method further comprises introducing a therapeutic agent into the vascular layer. More specifically, the method further comprises introducing a therapeutic agent into the outer membrane layer of the blood vessel.

  The novel features of the invention are set forth with particularity in the appended claims. The invention itself, however, will be understood by reference to the following detailed description considered in conjunction with the accompanying drawings in terms of both structure and method of operation, together with other objects and advantages of the invention.

  According to the present invention, there is an effect that a therapeutic agent can be efficiently and simultaneously introduced through a plurality of puncture sites in a controlled manner in a specific part of a blood vessel such as an outer membrane layer.

  The present invention is directed to both devices and methods for introducing therapeutic agents into tissue. The instrument according to the present invention is generally designated by the reference numeral 200 as best shown in FIGS. FIG. 1 shows a device 200 (eg, a catheter) with a flexible elongated catheter body or inner sleeve 202. As shown in FIG. 1, the body 202 of the catheter 200 has a distal end 210 that extends to the distal tip 215. The body 202 of the catheter 200 includes both a proximal end (not shown) and a distal end 210 that extends to the distal tip 215. A first expandable member, such as an inflatable balloon or inner balloon 230 is secured to the inner sleeve or body 202 at the distal end 210 of the catheter 200. As will be appreciated by those skilled in the art, the first expandable member or inner balloon 230 is inflated using a pressurized fluid medium 400, such as a hydraulic or pneumatic fluid, for example. Expandable and expandable from a collapsed or closed position or structure to an open or expanded position or structure.

  The second expandable member or outer balloon 235 is a pressurized reservoir in which the therapeutic agent 500 is contained or stored. The outer balloon 235 is circumferentially arranged around the inner balloon 230 and is disposed at the distal end 210 of the body 202, as long as the outer balloon 235 is aligned with the inner balloon 230. It may be located at any desired location or portion of the body 202.

  By way of example, the outer balloon 235 is present in any fluid medium, such as liquid, when contained within the outer balloon 235 and is coated directly onto the microprojections 250 and (if necessary) the array 245 itself. In some cases, one or more therapeutic agents and / or agents (drugs) 500 are stored that are present in a dry form, such as a powder form. Therapeutic agents and / or agents (drugs) 500 include, but are not limited to, vinca alkaloids (eg, vinblastine, vincristine, and vinorelbine), paclitaxel, epidipodophyllotoxins (eg, etoposide) , Teniposide, antibiotics (dactinomycin (actinomycin D), daunorubicin, doxorubicin, and idarubicin), anthracycline, mitozantrone, bleomycin, plicamycin (mitromycin), and mitomycin, Anti-proliferative / anti-mitotic agents, including natural products such as enzymes (L-asparaginase that contrasts L-asparagine and rejects cells that are not capable of synthesizing its own asparagine); G ( P) antiplatelet agents such as IIbIIIa inhibitors and vitronectin receptor antagonists; nitrogen mustard (mechloretamine, cyclophosphamide and its analogs, melphalan, chlorambucil), ethylenimines and methylmelamine (hexamethylmelamine and Anti-proliferative / anti-mitotic alkylating agents such as thiotepa), alkylsulfonate-busulfan, nitrosoureas (carmustine (BCNU) and analogues, streptozocin), trazenes-dacarbazine (DTIC); Folic acid analogs (methotrexate), pyrimidine analogs (fluorouracil, floxuridine, and cytarabine), purine analogs and related inhibitors (mercaptopurine, thioguanine, pentostatin) And anti-proliferative / anti-mitotic antimetabolites such as 2-chlorodeoxyadenosine (cladribine); platinum coordination compounds (cisplatin, carboplatin), procarbazine, hydroxyurea, mitoten, aminogluteti Imidos; hormones (eg estrogens); anticoagulants (heparin, synthetic heparin salts, and other thrombin inhibitors); fibrinolytic agents (such as tissue plasminogen activator, streptokinase, and urokinase), aspirin, dipyridamole, ticlopidine ( ticlopidine, clopidogrel, abciximam; antiimigratory, antisecretory (breveldin); corticosteroids (cortisol, cortisone, fludrocortisone, prednisone) Prednisolone, 6α-methylprednisolone, triamcinolone, betamethasone, and dexamethasone), non-steroidal agents (eg salicylic acid derivatives such as aspirin; para-aminophenol derivatives such as acetaminophen; indoleacetic acid and indenacetic acid (indomethacin, sulindac, Etodalac, hetroarylacetic acid (tolmethine, diclofenac, and ketorolac), arylpropionic acid (ibuprofen and derivatives), anthranilic acid (mefenamic acid and meclofenamic acid), enolic acid (piroxicam, tenoxicam, phenylbutazone) , Oxyphenthatrazone, Nabumetone, Gold compounds (Auranofin, Gold thioglucose, Gold thio Anti-inflammatory drugs such as sodium angonate)))); immunosuppressants: (cyclosporine, tacrolimus (FK-506), sirolimus (rapamycin)), azathioprine, mycophenolate mofetil (Mycophenolate mofetil)); blood vessel-derived drugs: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), erythropoietin, angiotensin receptor blocker; nitric oxide donor; antisense Oligonucleotides and combinations thereof; cell cycle inhibitors, mTOR inhibitors, growth factor signal transduction kinase inhibitors, and the like.

  In addition, therapeutic agents or drugs 500 can include nucleotides, nucleic acids (such as DNA and RNA), amino acids, peptides, proteins, factors, cells, extracellular substrates such as fibers (collagen and elastin), proteoglycans, glycoproteins, It is also defined to include lipids.

  Outer balloon 235 has a plurality of apertures 237 that allow therapeutic agent 500 to be delivered from device 200 in a regulated and effective form as described in more detail below.

  In addition, a plurality of microprojections 250 directly puncture and penetrate tissue at any desired depth to form microchannels in the perforated tissue based on the interaction of inner balloon 230 and outer balloon 235. Therefore, it is disposed adjacent to the opening 237. Thus, when the inner balloon 230 is inflated with the fluid medium 400, the inner balloon 230 is expanded from its collapsed position to its expanded position. Then, when the inner balloon 230 is inflated and expanded, a new flow of the therapeutic agent 500 at a specific flow rate is formed by the microprojection 250 formed from the pressurized drug reservoir, that is, the outer balloon 235 through the opening 237 of the outer balloon 235. Supplied in the road.

  According to the invention, the microprojection 250 consists of a piercing element having a projection length of less than 1000 μm. In another embodiment, the piercing element 250 has a protruding length of less than 500 μm, more preferably less than 250 μm. The minute protrusion 250 has a width substantially in the range of 25 μm to 500 μm, and has a thickness substantially in the range of 10 μm to 100 μm. The microprojections may be formed in various shapes such as needles, blades, pins, punches, and combinations thereof.

  The microprojections 250 are from a plurality of microprojections 250 arranged in a particular arrangement (eg, the arrangement of row and column microprojections 250) to pierce blood vessel wall 300 and access outer membrane layer 310. Are arranged in an array 245 such as an array 245 of microprojections. The microprojection array 245 is formed by etching or punching a plurality of microprojections 250 from a thin sheet-like material (such as metal) to fold or bend the microprojections 250 out of the plane of the sheet-like material. It can be made by forming a configuration as shown in FIG. A plurality of openings 257 are made adjacent to each of the microprojections 250 within the sheet-like array 245. The array 245 is secured to the surface of the outer balloon 235, such as the outer surface (or the inner surface) of the outer balloon 235 such that the openings 257 of the array 245 are in fluid communication with the apertures 237 of the outer balloon 235. ing. Thus, in this embodiment, the microprojection array 245 is in the form of a thin titanium screen. The metal sheet-like array 245 is not continuous, and the array 245 can be expanded, for example, the metal sheet array 245 can be expanded with the outer balloon 235 and the inner balloon 230 expanded, respectively, with microprojections 250 and It is not placed around the outer circumference of the outer balloon 235 or inner balloon 230 to allow the drug 500 to be deployed. Alternatively, the array 245 may be in the form of a stent with grooves or openings that allow it to expand when deployed within the vessel 300. Thus, a Nitinol-deployed instrument or balloon (which may be a single balloon in this embodiment) may be deployed after a surgical procedure, for example, by deploying a stent into the blood vessel 300 to deliver the drug 500. A material that is suitable for forming a stent so that it can be easily collapsed and removed after introduction into a blood vessel. The array of microprojections 245 is formed with microprojections along each edge as disclosed in US Pat. No. 6,050,988, which is hereby incorporated by reference in its entirety. It may be formed by another known method such as forming one or more strips.

  As shown in FIG. 3, in one embodiment of the array of microprojections 245 used in the present invention, the array of microprojections 245 comprises a plurality of microprojections 250 in a particular arrangement. And the microprojections 250 preferably extend from the array 245 at an angle of substantially 90 degrees.

  In accordance with the present invention, the array 245 may be directly coupled to the outer surface of the outer balloon 235. The openings 257 in the array 245 overlap the perforations or openings 237 in the outer balloon 235. In this embodiment, the minute protrusion 250 is formed by etching, punching, or laser cutting a thin metal sheet (titanium sheet or the like) or a thin film of nickel / titanium and bending the minute protrusion from the plane of the sheet. It is formed by forming the portion 245. The array 245 may comprise any number of desirable microprojections 250 arranged in any number of rows and columns. As an example, FIGS. 1 and 2 show an array 245 consisting of five rows of microprojections 250 and FIG. 3 shows an array 245 consisting of four rows.

In one embodiment of the invention, the microprojection array 245 has a microprojection density of at least substantially 10 / cm ² , more preferably at least substantially 50 / cm ² to 2000 / cm ^2. cm ² . Preferably, the number of openings 257 per unit area through which the drug passes is substantially 10 / cm ² or more and substantially less than 2000 / cm ² .

  As shown, the microprojections 250 preferably have a projection length of less than 1000 μm. In one embodiment, the microprojection 250 has a projection length of less than 500 μm, more preferably a projection length of less than 250 μm. The minute protrusion 250 has a width substantially in the range of 25 μm to 500 μm, and has a thickness substantially in the range of 10 μm to 100 μm.

  Microprojection array 245 and microprojections 250 may be fabricated from a variety of metals such as stainless steel, titanium, nickel-titanium alloys, or similarly biocompatible materials such as polymeric materials. Preferably, the array of microprojections 245 and microprojections 250 are made from titanium.

  In accordance with the present invention, the microprojection array 245 and microprojections 250 may be made from a non-conductive material such as a polymer. Alternatively, the microprojection array 245 can be a non-conductive material such as Pyrene, a hydrophobic material such as Teflon, silicon, or other low It may be coated with an energy material. The above hydrophobic materials and associated base (eg, photoresist) layers are described in US Patent Application No. 60 / 484,142, which is hereby incorporated by reference.

  The microprojection array 245 that can be used in the present invention includes, but is not limited to, US Pat. No. 6,083,196, US Pat. There are members disclosed in US Pat. No. 6,091,975 and US 2002/0016562.

  Another microprojection array 245 and microprojection 250 that can be used in the present invention is described in US Pat. No. 5,879,326, which is hereby incorporated by reference in its entirety. There are arrays and microprojections formed by etching silicon using such silicon chip etching methods or by plastic molding using etched micromolds.

  Further, the microprotrusion 250 includes a microprotrusion 250 coated with a biocompatible coating. In accordance with the present invention, the biocompatible coating may partially or entirely cover each microprojection 250. For example, the biocompatible coating may be formed on the microprojection 250 as a dry pattern coating. The biocompatible coating may be applied before or after the microprojections 250 are formed. In addition, the biocompatible coating may also include one or more therapeutic agents or drugs 500 for introduction into the vessel wall 300, more specifically for introduction directly into the outer membrane layer 310 of the vessel 300.

  In accordance with the present invention, the biocompatible coating may be applied to the microprojections by various known methods. Preferably, the biocompatible coating is applied only to the portion of the microprojection array 245 and the microprojection 250 that perforates the blood vessel 300.

  One such known coating method is dip coating. The dip coating can be said to be a method of coating the microprojections by partially or fully immersing the microprojections 250 (as described below) in a coating solution containing a therapeutic agent or drug 500. By using a partial dipping method, the coating can be applied only to the tips of the minute protrusions.

  Another coating method includes roller coating, and this roller coating similarly uses a roller coating mechanism that applies a film only to the tip of the minute protrusion 250. The roller coating method is disclosed in US patent application Ser. No. 10 / 099,604 (Patent Application Publication No. 2002/0132054), which is hereby incorporated by reference in its entirety. As described in detail in the above patent application, the disclosed roller application method provides a smooth coating that does not easily peel off the microprojections 250 while piercing the blood vessel 300.

  Outer sheath 240 is made of a polymeric material such as polyethylene and is optionally used as a releasably placed cover for the distal end 210 of the catheter and instruments such as blood vessels 300 and microprojections 250. Serves as an additional protection to protect the 200 components and to prevent the therapeutic agent 500 from leaking out of the distal end 210 of the catheter. The cover (outer sheath) 240 not only provides protection as described above, but also deploys the microprojection 250 unimpeded when the microprojection 250 is positioned at the desired location of the microprojection at the tissue site. In order to be able to exit, it is movably positioned or movably disposed from the distal end 210 of the catheter.

  The method of using the catheter 200 and the method of introducing the therapeutic agent 500 according to the present invention includes the step of initially locating the patient's body for introducing the therapeutic agent 500 at a number of adjacent sites in the tissue. Once the desired introduction site or location is identified, the catheter 200 is inserted into the blood vessel 300 of the patient's body. The catheter 200 is used to pass through the blood vessel 300 until the desired location is reached, where the distal end 210 of the catheter 200 is placed at the desired location within the blood vessel 300. Cover 240 (if used) is removed from distal end 210 before expanding inner balloon 230. At this point, the microprojection array 250 is deployed by expanding or inflating with the fluid medium 400 to expand the inner balloon 230 to an open or expanded position.

  When the inner balloon 230 is inflated by the fluid medium 400, the inner balloon 230 is expanded from its collapsed position to its expanded position. Then, when the inner balloon 230 is inflated and expanded, the microprotrusion 250 is advanced into the blood vessel 300 to the desired puncture depth, for example, to a desired layer of the blood vessel 300, such as the adventitia layer 310, for example. A microchannel is formed in 300 and the outer membrane layer 310. A specific flow of therapeutic agent 500 is delivered from the pressurized drug reservoir or outer balloon 235 through the aperture 237 of the outer balloon 235 into the newly formed microchannels of the blood vessel 300 and outer membrane layer 310.

  After the therapeutic agent 500 is delivered, the inner balloon 230 is collapsed, for example, by deflating the expandable member (inner balloon), and the array of microprotrusions 250 is withdrawn into the catheter body 202, thereby causing the catheter 200. Are removed from both the deployment site of the blood vessel 300 and the patient's body.

  As best shown in FIG. 2, a method of introducing one or more therapeutic agents 500 using an instrument 200 according to the present invention is shown. By way of example, the target tissue undergoing therapeutic treatment is a blood vessel 300, more specifically a layer of the blood vessel wall 300, such as the outer membrane layer 310. Thus, a site within blood vessel 300 (surface or interior of the vessel wall) is identified for receiving therapeutic agent 500 in a simultaneous delivery mode adjusted at a plurality of separate and adjacent puncture sites. Accordingly, the distal end 210 of the catheter 200 is expanded with the fluid medium 400 such that the inner balloon 230 is expanded and moved from its collapsed position or collapsed configuration to its expanded position or expanded configuration. To the vessel site 300 to be transluminated. Thus, when the inner balloon 230 is inflated with the fluid medium 400, the outer balloon 235 that acts as a pressurized reservoir for the therapeutic agent 500 also expands at the same rate as the expansion of the inner balloon 230, ie in proportion to the inner balloon 230. . Accordingly, the array 245 of microprojections 250 is advanced outwardly and away from the longitudinal axis of the distal end 210 of the catheter body 202, while simultaneously perforating the vessel wall 300 at the perforation tip of each microprojection 250. And puncture. As the microprojection 250 advances through the vessel wall 300 to a desired depth, i.e., to a desired layer such as the outer membrane layer 310, a microchannel is formed in the vessel wall 300 and the inner balloon 230 is collapsed by the fluid medium 400. The therapeutic agent 500 delivered through the apertures or perforations 237 in the outer balloon 235 and the apertures 257 in the array 245 when directed or moved from the extended position to the expanded position is directed and flowed.

  Because the inner balloon 230 is inflated or expanded at a specific inflation rate, the therapeutic agent 500 is delivered through the outer balloon 235 from the distal end 210 of the instrument 200 at a delivery rate proportional to the inflation rate of the inner balloon 230. At this time, the therapeutic agent 500 flows from the perforation 230 of the outer balloon 235 through the opening 257 of the microprojection 245, and moves along the fluid channel along the microchannel formed in the blood vessel wall 300. It flows into the outer membrane layer 310 as shown.

  Accordingly, the therapeutic agent 500 is introduced into the outer membrane layer 310 of the blood vessel 300 while being adjusted and supplied simultaneously at a plurality of adjacent sites corresponding to the plurality of microprojections 250 of the array 245. Thus, a one-time application of therapeutic agent 500 using device 200 is particularly beneficial for simultaneously accessing and treating multiple adjacent sites of outer membrane layer 310 of blood vessel 300.

Specific embodiments of the present invention are as follows.
(1) A device for introducing a therapeutic agent into a tissue,
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions A device for introducing a therapeutic agent into a tissue, wherein the therapeutic agent is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures.
(2) The instrument according to the above embodiment (1), wherein the second balloon is arranged circumferentially around the first balloon.
(3) The instrument of embodiment (2) above, wherein the second balloon is disposed near the distal end of the elongated body.
(4) The instrument according to the above embodiment (3), in which a plurality of microprojections are arranged as an array.
(5) The device according to embodiment (4), wherein the arrangement is made from thin sheets or films.

(6) The instrument according to the embodiment (5), which has a plurality of openings through which the array passes.
(7) The instrument according to the above embodiment (6), wherein the plurality of openings are arranged adjacent to the plurality of openings of the second balloon.
(8) The instrument of embodiment (7) above, wherein the array is made from a thin sheet or film made of metal.
(9) The instrument according to the embodiment (8), wherein the metal is made of titanium or nickel / titanium.
(10) The device according to the above embodiment (4), wherein the device comprises a catheter.

(11) The instrument of embodiment (10) above, wherein the second balloon and array are located at the distal end of the catheter.
(12) The instrument of embodiment (11), further comprising an outer sheath removably disposed over the distal end of the catheter.
(13) A catheter for introducing a therapeutic agent into tissue,
Flexible and long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions A catheter for introducing a therapeutic agent into the tissue, wherein the therapeutic agent is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures.
(14) The catheter according to the above embodiment (13), wherein the second balloon is arranged circumferentially around the first balloon.
(15) The catheter according to embodiment (14), wherein the second balloon is disposed near the distal end of the elongated body.

(16) The catheter according to the above embodiment (15), wherein a plurality of microprojections are arranged as an array.
(17) The catheter according to the embodiment (16), wherein the array is made of a thin sheet or film.
(18) The catheter according to the embodiment (17), which has a plurality of openings through which the array passes.
(19) The catheter according to the above embodiment (18), wherein the plurality of openings are arranged adjacent to the plurality of openings of the second balloon.
(20) The catheter according to the embodiment (19), wherein the array is made from a thin sheet or film made of metal.

(21) The catheter according to the embodiment (20), wherein the metal is titanium or nickel-titanium.
(22) The catheter according to embodiment (16), wherein the second balloon and the array are disposed at the distal end of the catheter.
(23) The catheter according to the above embodiment (11), further comprising an outer sheath removably disposed over the distal end of the catheter.
(24) A method of introducing a therapeutic agent into a tissue,
A process for providing a device for introducing a therapeutic agent into tissue, the device comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of microprojections Providing a device for introducing the therapeutic agent into the tissue, wherein the device is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures;
Placing the device adjacent to a site in the tissue;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the tissue at the site.
(25) The method according to embodiment (24), further comprising the step of supplying a first fluid medium into the first balloon to expand the first balloon.

(26) A method for introducing a therapeutic agent into the wall of a blood vessel,
A process for providing a device for introducing a therapeutic agent into tissue, the device comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing a device for introducing the therapeutic agent into the tissue, wherein the device is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures;
Placing the device adjacent to a site of the blood vessel wall;
Introducing the therapeutic agent into the blood vessel wall by expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the blood vessel wall at the site. how to.
(27) The method according to embodiment (26), further comprising the step of supplying a first fluid medium into the first balloon to expand the first balloon.
(28) The method according to embodiment (27), further comprising the step of placing the device in the blood vessel before introducing the therapeutic agent into the vessel wall.
(29) The method according to embodiment (28), further comprising the step of introducing a therapeutic agent into the blood vessel layer.
(30) The method according to the above embodiment (29), further comprising the step of introducing a therapeutic agent into the outer membrane layer of the blood vessel.

(31) A method for introducing a therapeutic agent into a tissue,
Providing a catheter for introducing a therapeutic agent into tissue, wherein the catheter comprises:
A long body,
A first balloon in the body movable from a collapsed position to an expanded position;
A second balloon in the body that is movable from a collapsed position to an expanded position and has a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing a catheter for introducing the therapeutic agent into the tissue, wherein the catheter is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures;
Placing the catheter adjacent to a site in the tissue;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the tissue at the site.
(32) The method according to embodiment (31), further comprising supplying a first fluid medium into the first balloon to expand the first balloon.
(33) A method for introducing a therapeutic agent into the wall of a blood vessel,
Providing a catheter for introducing a therapeutic agent into tissue, wherein the catheter comprises:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions Providing a catheter for introducing the therapeutic agent into the tissue, wherein the catheter is deployed in the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures;
Placing the catheter adjacent to a site within the vessel wall;
Expanding the first balloon from the collapsed position to the expanded position and supplying the therapeutic agent into the blood vessel wall at the site to introduce the therapeutic agent into the blood vessel wall how to.
(34) The method according to the embodiment (33), further comprising supplying a first fluid medium into the first balloon to expand the first balloon.
(35) The method according to the above embodiment (34), further comprising the step of placing the catheter in the blood vessel before introducing the therapeutic agent into the blood vessel wall.

(36) The method according to the above embodiment (35), further comprising the step of introducing a therapeutic agent into the blood vessel layer.
(37) The method according to the above embodiment (36), further comprising the step of introducing a therapeutic agent into the outer membrane layer of the blood vessel.

  Since the above details are preferred embodiments of the present invention, variations and modifications may be made to the embodiments described herein based on the disclosed principles of the present invention without departing from the scope of the invention. It is understood that this is sometimes the case.

  While preferred embodiments of the invention have been illustrated and described herein, it will be apparent to those skilled in the art that such embodiments have been described for purposes of illustration only. Various modifications, changes and substitutions will now occur to those skilled in the art without departing from the invention. Accordingly, it is intended that the invention be limited only by the spirit and scope of the appended claims.

  The present invention can be used to introduce one or more therapeutic agents simultaneously at a plurality of adjacent sites.

FIG. 6 is a perspective view of a portion of a device for introducing a therapeutic agent according to the present invention with a microprojection. 2 is a cross-sectional view of the distal end of an instrument for introducing a therapeutic agent into a particular layer of tissue according to the present invention of FIG. It is a schematic diagram of the arrangement | sequence of the micro protrusion part of the instrument based on this invention of FIG.

Explanation of symbols

200 Instrument 202 Catheter body 210 Distal end 215 Distal tip 230 First expandable member 235 Outer balloon 237 Opening 240 Outer sheath 245 Array
250 Minute protrusion 257 Opening 300 Blood vessel 310 Outer membrane layer 400 Fluid medium 500 Therapeutic agent

Claims (24)

A device for introducing a therapeutic agent into a tissue,
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions A device for introducing a therapeutic agent into a tissue, wherein the therapeutic agent is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures. The instrument of claim 1, wherein the second balloon is circumferentially disposed about the first balloon. The instrument of claim 2, wherein the second balloon is disposed near the distal end of the elongated body. The instrument of claim 3, wherein the plurality of microprojections are arranged in an array. The instrument of claim 4, wherein the array is made from a thin sheet or film. The instrument of claim 5, wherein the array has a plurality of apertures therethrough. The instrument of claim 6, wherein the plurality of apertures are disposed adjacent to the plurality of apertures in the second balloon. 8. An instrument according to claim 7, wherein the array is made from a thin sheet or film of metal. The instrument of claim 8, wherein the metal comprises titanium or nickel-titanium. The instrument of claim 4, wherein the instrument comprises a catheter. The instrument of claim 10, wherein the second balloon and the array are disposed at the distal end of the catheter. The instrument of claim 11, further comprising an outer sheath removably disposed over the distal end of the catheter. A catheter for introducing a therapeutic agent into a tissue,
Flexible and long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of minute protrusions A catheter for introducing a therapeutic agent into the tissue, wherein the therapeutic agent is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures. The catheter of claim 13, wherein the second balloon is disposed circumferentially around the first balloon. The catheter of claim 14, wherein the second balloon is disposed near the distal end of the elongated body. The catheter according to claim 15, wherein the plurality of microprojections are arranged as an array. The catheter of claim 16, wherein the array is made from a thin sheet or film. The catheter of claim 17, having a plurality of openings through which the array passes. The catheter of claim 18, wherein the plurality of openings are disposed adjacent to the plurality of apertures in the second balloon. The catheter of claim 19, wherein the array is made from a thin sheet or film of metal. The catheter of claim 20, wherein the metal comprises titanium or nickel-titanium. The catheter of claim 16, wherein the second balloon and the array are disposed at the distal end of the catheter. The catheter of claim 11, further comprising an outer sheath removably disposed over the distal end of the catheter. A method of introducing a therapeutic agent into a tissue,
A process for providing a device for introducing a therapeutic agent into tissue, the device comprising:
A long body,
A first balloon in the body that is expandable from a collapsed position to an expanded position;
A second balloon in the body that is expandable from a collapsed position to an expanded position and includes a plurality of apertures;
A therapeutic agent in the second balloon;
A plurality of microprojections arranged on the surface of the second balloon for puncturing tissue,
When the first balloon is expanded from the collapsed position to the expanded position, the second balloon is expanded from the collapsed position to the expanded position, and the plurality of microprojections Providing a device for introducing the therapeutic agent into the tissue, wherein the device is deployed into the tissue and the therapeutic agent is supplied from the second balloon into the tissue through the plurality of apertures;
Placing the device adjacent to a site in the tissue;
Expanding the first balloon from the collapsed position to the expanded position and introducing the therapeutic agent into the tissue at the site.

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