WO2002096264A2

WO2002096264A2 - Single lumen balloon catheter having chemical-resistant or adherence-resistant balloon section.

Info

Publication number: WO2002096264A2
Application number: PCT/US2002/015875
Authority: WO
Inventors: Ivan Sepetka; Maureen Bensing; Diana M. Sanchez; Richard A. Helkowski; Christopher Ken; Mark Deem; Maria Aboytes; Hanson S. Gifford Iii
Original assignee: Concentric Medical, Inc.
Priority date: 2001-05-25
Filing date: 2002-05-16
Publication date: 2002-12-05
Also published as: AU2002344216A1; WO2002096264A9; WO2002096264A3

Abstract

This invention is a surgical device. In particular, it is low profile, single lumen catheter (130) preferably having a movable seal (140) or seat that allows the balloon (138) to be inflated by sealing against the movable guidewire (160) or against itself. An additional variation of the invention includes a non-removable guidewire (160) situated in the catheter body (130) in such a way to provide or add stiffness to the otherwise flexible distal section of the catheter (130) during a procedure. An enhanced strain relief transition joint between significantly stiffer proximal section (136) and the more flexible distal section (132) is provided. Finally, methods of using the inventive balloon catheter are also shown. The balloon (406) is preferably produced of one or more materials that are resistant to components of chemical vaso-occclusive compositions (414) or are resistant to adherence to those compositions.

Description

SINGLE LUMEN BALLOON CATHETER HAVING CHEMICAL- RESISTANT OR ADHERENCE-RESISTANT BALLOON SECTION

FIELD OF THE INVENTION

0001 This invention is a surgical device. In particular, it is a low profile, single lumen balloon catheter preferably having a movable seal or seat that allows the balloon to be inflated by sealing against the movable guidewire or against itself. An additional variation of the invention includes a non-removable guidewire situated in the catheter body in such a way to provide or add stiffness to the otherwise flexible distal section of the catheter during a procedure. An enhanced strain relief transition joint between the significantly stiffer proximal section and the more flexible distal section is provided. The catheter may be used in any service, but it is especially useful when sized and selected as a microcatheter in neurovascular procedures. Also, methods of using the inventive balloon catheter are also shown. The balloon is preferably produced of one or more materials that are resistant to components of chemical vaso-occlusive compositions or are resistant to adherence to those compositions.

BACKGROUND OF THE INVENTION

0002 This invention relates generally to medical balloon catheters, their structures, and methods of using them. In particular, the present invention relates to the construction of both large and small diameter, typically braid-reinforced balloon catheters having controlled flexibility, a soft distal tip and a typically elastomeric balloon near the distal tip for the partial or total occlusion of a vessel. This catheter uses a movable seal to direct fluid to or to bleed fluid from the balloon. The inventive catheter may be used for a wide variety of medical applications, such as interventional cardiological, peripheral, or neuroradiology procedures, but are particularly useful in intercranial selective catheterization.

0003 Medical catheters are used for a variety of purposes, including interventional therapy, drug delivery, diagnosis, perfusion, and the like. Catheters for each of these purposes may be introduced to the target sites within a patient's body by guiding the catheter through the vascular system, and a wide variety of specific catheter designs have been proposed for different uses.

0004 Of particular interest to the present invention are large lumen balloon catheters used in supporting procedures, in turn, using small diameter tubular access catheters. Such procedures include diagnostic and interventional neurological techniques, such as the imaging and treatment of aneurysms, tumors, arteriovenous malformations, fistulas, and the like. Practical treatment of embolic stroke is novel.

0005 The neurological vasculature places a number of requirements on the small catheters that may be used. The catheters should be quite small. The blood vessels in the brain are frequently as small as several millimeters, or less, requiring that the intervening catheters have an outside diameter as small as one French (0.33 millimeters). In addition to small size, the brain vasculature is highly tortuous, requiring that neurological catheters be very flexible, particularly at their distal ends, to pass through the regions of tortuosity. The blood vessels of the brain are quite fragile, so it is desirable that the catheter have a soft, non-traumatic exterior to prevent injury.

0006 The advent of interventional radiology and its sub-practice, interventional neuroradiology, as a viable treatment alternatives in various regions of the body having tortuous vasculature often surrounded by soft organs, has produced demands on catheterization equipment not placed on devices used in PCTA and PTA. The need for significantly smaller diameter devices and particularly those which have variable flexibility and are able to resist kinking is significant. 0007 Typical of the single lumen balloon catheter devices found in the literature are U.S. Pat. No. 5,776,099, to Tremulis; U.S. Pat. No. 6,074, 407, to Levine et al; U.S. Pat. Nos. 6,096,055, 5,683,410, and 5,304,198, all to Samson; U.S. Pat. No. 6,017,323, to Chee; U.S. Pat. No. 6,193,686, to Estrada et al; U.S. Pat. No. 6,090,126, to Burns; and U.S. Pat. No. 5,364,354, to Walker et al.

0008 Additionally, various chemical vaso-occlusive compositions are available. These materials are introduced into the vascular site to be occluded and via either a chemical reaction or a dilution of the carrier solvent, an occluding mass is formed. Such materials, examples of which are described below, include: (A.) modified cyanoacrylate compositions; (B.) partially hydrolyzed polyvinyl acetate initially in an ethanol solvent; (C.) biocompatible polymer compositions containing, e.g., cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid, and their mixtures in biocompatible solvents such as DMSO, acetone, ethanol, ethyl lactate, etc.

0009 Examples of modified cyanoacrylate compositions may be found in U.S. Pat No. 6,037,366 to Krall. The composition is a cyanoacrylate which involves mixing two separate containers of the material immediately prior to administration of the material into the arteriovenous malformation (ANM) by catheter. Such a composition may contain seven ingredients which are divided into two parts prior to mixture and use.

0010 Part I consists of a cyanoacrylate liquid monomer containing pure phosphoric acid (250 ppm) hydroquinone (100 ppm) and P-methoxyphenol (1200 ppm). It is believed that this composition is stable and unchanging for over two years. The container in which Part I is stored requires cleaning and preparation before such stability can be achieved. The liquid monomer of choice for this usage is 2- hexyl cyanoacrylate. Part II consists of pure powdered gold (5. +-.3 microns), a small amount of prepolymerized polymer of the same cyanoacrylate and ethyl myristate. Any of the large chain fatty acid esters will work to replace ethyl myristate so long as they are liquids. The pre-polymerized polymers of cyanoacrylate are unstable and change their structures and properties even in the solid state. The change is exponential and therefore the polymer must be used within a limited amount of time before deterioration occurs. The polymer is prepared by addition of part 1 to a rapidly stirring weak bicarbonate-water solution. The addition must be added drop-wise to avoid unpolymerized masses from forming. The solid polymer is washed thoroughly with pure water to remove any traces of bicarbonate, then washed thoroughly with pure ethanol to remove the water. Methanol dries rapidly and when the polymer is further dried at a high reduced pressure for 16-18 hours, it is considered dry. The polymer must be used in the next step within 24 hours to obtain consistent results in the final product. This mixture must be sterilized within 72 hours from the time of preparation.

0011 Part II is sterilized with ethylene oxide gas with the stopper held in an open position. Ethylene oxide is an alkylating agent and after sterilization the prepolymerized polymer is stable. Hence, the stability and sterilization of part 2 are carried out simultaneously. The sterilized samples of Part II are capped in a clean room under sterile handling conditions. The pre-polymerized polymer can be stabled by treatment with any of the strong alkylating agents, like ethylene oxide, ketene, etc. It is stated that this composition of matter has good cohesion as well as adequate adhesion to function well for ANMs and other similar uses within the vascular tree. The cohesion keeps the material together during the time required for it to polymerize. The adhesion makes it stick to the artery walls. The polymerized device will cause a modest but desirable inflammatory response in the treated tissues. 0012 A formulation for arteriovenous malformations and tumors is as follows:

Part I (Ml)

2-Hexyl Cyanoacrylate

999,550 ppm

Hydroquinone 100 ppm p-Methoxyphenol 100 ppm

Pure Phosphoric Acid 250 ppm

Part II (M2)

Pure Gold 1.0000 g

Pure Ethyl Myristate 0.5000 g

FMS* 0.0200 g

*FMS is a specially prepared polymer of 2-hexyl cyanoacrylate and must be used within 24 hours of preparation or will change and be unusable. Further, it must be sterilized within 72 hours.

0013 Examples of partially hydrolyzed polyvinyl acetates initially in an ethanol solvent are described in U.S. Pat No. 5,925,683 to Park et al and U.S. Pat No. 6,160,025 to Slaikeu et al. According to these patents, the composition comprises a mixture or solution of a.) partially hydrolyzed polyvinylacetate (PNAc) and b.) a pharmaceutically acceptable carrier solvent. The carrier solvent is selected so that it dissolves the partially hydrolyzed PVAc polymer, is acceptable for introduction into the human body with a minimum of side effects, and upon contact with blood or other body fluids precipitates from solution to form occlusive aggregates of the polymer. These compositions may also contain a dissolved or suspended radio-opacifier.

0014 Several variables which appear to control the overall efficacy of the precursor solution as an embolizing agent include: 1) the ratio of hydrolyzed PVAc to PVAc in the precursor solution, 2) the MW of the partially hydrolyzed PVAc, and

3) the concentration of hydrolyzed PVAc and PVAc in the carrier solvent. Also affecting the efficacy of the use of the inventive composition is the type and concentration of radio-opacifiers used in the composition.

0015 Partially Hydrolyzed PVAc Polymers (PVAc) is a polymer whose backbone chain is hydrophobic but the side chain, the acetate group, is moderately hydrophilic. The hydrophilicity can be increased via transformation of the acetate group into an alcohol. If the hydrophilicity of the polymer is increased too far, however, and too many alcoholic groups are introduced, the polymer itself becomes soluble in blood and thus does not effectively function as an embolic material. Conversely, if the hydrophobicity of the polymer is not decreased, the polymer is not sufficiently soluble in solvents which are both miscible in blood and safe for use in the human body. The theoretical best solvent for our system is water because of its safety. Minimizing the amount of any solvent other than water is desirable. Solvents such as ethanol that are acceptable from a safety point of view do have independent and undesirable side effects when used in too high a concentration. Thus careful control of the hydrolysis ratio is desirable. Hydrolysis of about 15-30% of the acetate groups appears to be most effective. Said another way, the ratio of acetate groups to hydrolyzed acetate (alcoholic) sites is in the range of 2.0 to 6.0 and preferably is between 2.3 and 5.6. 0016 Hydrolysis of PVAc takes place according to the following reaction:

-(-CH₂- - CH-)-_n- + H₂O

OCOC

- - -(-CH₂- - CH-)-_n- + CH₃COOH

OH

0017 The reaction is reasonably fast and is an equilibrium reaction. The end point or degree of hydrolysis may be controlled by addition of specific amounts of the secondary hydrolysis product—the acetic acid. Since the composition is to be used in the human body, it is preferred to hydrolyze the PVAc feedstock in ethanol using an acidic catalyst such as HC1. Heat should be added to the reaction vessel only to the extent necessary to dissolve the PVAc. Excessive heat causes a side reaction (apparently an elimination reaction) resulting in a slightly orange tinge in the resulting partially hydrolyzed product. In any event, the reaction may be carried out in the following way: PVAc is dissolved in an aqueous efhanolic solvent system, an appropriate amount of equilibrium-limiting acetic acid (the reaction product) is added, and the acidic catalyst is added. At 25.degree. C, the reaction is typically complete in less than about two days.

0018 The course of the reaction may be monitored using standard analytical techniques, e.g., titration using standardized NaOH solutions of the product solution (in acetone) with the remaining NaOH titrated to neutrality with a standardized HC1 solution.

0019 Once the desired level of hydrolysis is achieved, the partially hydrolyzed PVAc may be separated by precipitation in water. The precipitated product is typically then washed. The product may then be dried using vacuum (so to prevent heat degradation) and, in doing so, remove any remaining solvent.

0020 Once the partially hydrolyzed PVAc has been dried and stripped of solvent, it is dissolved in a suitable solvent for use as an occludant precursor. Appropriate solvents are pharmaceutically acceptable in nature and are typically polar, substantially non-toxic, and water miscible. Various suitable alcohols, ethers, amides, and glycols and their mixtures with each other or with water will be apparent to the worker of ordinary skill in this art. In general, the solvent or solvent system must be able to completely dissolve the partially hydrolyzed PVAc and upon introduction of that solution to a mammalian site containing an aqueous medium (naturally occurring or artificially introduced) allow the dissolved partially hydrolyzed PVAc to fall out of solution and form an agglomerate. Although many of these generically provided solvent systems would be suitable in certain situations where strong solvents would accelerate the occlusion activity of the partially hydrolyzed PVAc, e.g., where denaturing localized tissue would enhance the ultimate activity of causing tumor atrophy, an especially useful solvent system for the dissolution of partially hydrolyzed PVAc is a mixture of ethanol and water. Aqueous ethanolic solutions containing less than about 30% ethanol (by volume) do not dissolve the preferred partially hydrolyzed PVAc very well and solutions containing more than about 55% do not maintain most generally available non-ionic radio- opaque contrast media with efficiency. Consequently, the optimum solution for the preferred partially hydrolyzed PVAc polymers is an aqueous ethanolic solution containing between about 30% and 55% ethanol (by volume). It has been found that for the preferred embolic agent precursors discussed elsewhere herein, the higher range of ethanol concentration (e.g., 45% to 55%) is desirable because such solvent concentrations maintain the polymer in solution even in cold operating theaters. The inventive composition should be warmed prior to introduction into the body.

0021 Because these compositions are desirably used in regions of the vasculature which are both very tortuous and in which the vessel lumen are very narrow, the catheters through which these compositions are placed must be quite small. To allow ease of injection and to minimize the danger of immobilizing normal vessels around the desired treatment site, the viscosity of the inventive solution should be minimized, consistent with the other requirements noted herein. Because the viscosity of a polymer solution is very sensitive to polymer molecular weight (MW.sub.w), particularly at high polymer concentration, the MW of the polymer should be less than about 500,000. However, when the MW decreases, the polymer becomes increasingly soluble in water. Consequently, at lower MW, there is a chance that low molecular weight polymer would dissolve away from the precipitated polymer and act as a toxin. Therefore, it is desirable for the polymer to have a MW at least about than 10,000. The desired range is 10,000 to 500,000. The preferable MW is in the range of 50,000-100,000.

0022 The concentration of polymer also affects both the viscosity of the solution as well as the precipitation behavior of the polymer. Principally because of the high viscosity of polymer solutions at high polymer concentration is quite unwieldy, partially hydrolyzed PVAc concentrations of less than 30% are preferred for immobilization. If the polymer concentration is lower, we have found that the polymer tends to fragment into small pieces when introduced into the bloodstream due to high stress from the blood flow. There is an increased chance for the precipitated polymer to pass the malformation site and to end up in the lungs. Therefore, we have found that about 7.5-30% polymer solutions are suitable for embolization. That is to say that "weight % polymer" is calculated based on the overall solution content (solvent, water, diluents, radio-opacifiers, etc.). It has been found that a small amount of a commercial buffer (pH 7) at a rate of around 10 mg/100 ml solution is desirable.

0023 The partially hydrolyzed PVAc is soluble in an aqueous ethanolic solution containing far less ethanol than would be required for a similar PVAc polymer in the non-hydrolyzed condition. Aqueous ethanolic solutions of the partially hydrolyzed PVAc are able to dissolve higher loads of radio-opacifiers such as metrizamide (see, U.S. Pat. No. 3,701,771) or iopromide (see, U.S. Pat No. 4,364,921). Metrizamide is sold in a dilute form as "Amipaque" by Winthrop-Breon Laboratories, a division of Sterling Drug Inc. Iopromide is often sold in a dilute form under the tradename "Ultravist".

0024 Examples of biocompatible polymer compositions containing, e.g., cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid, and their mixtures in biocompatible solvents such as DMSO, acetone, ethanol, ethyl lactate, etc. are described in U.S. Pat No. 5,580,568 to Greff et al; U.S. Pat No. 5,695,480 to Evans et al; U.S. Pat. No. 5,667,767 to Greff et al; U.S. Pat No. 5,830,178 to Jones et al; and U.S. Pat. No. 6,051,607 to Greff et al. 0025 The '568 patent is directed to embolizing compositions comprising cellulose diacetate (having an acetyl content of from about 31 to about 40 weight percent). Moreover, it is directed to embolizing compositions comprising cellulose diacetate and a contrast agent selected from the group consisting of tantalum, tantalum oxide and barium sulfate provide compatible embolizing/contrast agent combinations. Accordingly, one embolizing composition comprises: (a) from about 2.5 to about 8.0 weight percent of a cellulose diacetate embolizing agent wherein said cellulose diacetate has an acetyl content of from about 31 to about 40 weight percent; (b) from about 10 to about 40 weight percent of a water insoluble contrast agent selected from the group consisting of tantalum, tantalum oxide and barium sulfate; (c) from about 52 to about 87.5 weight percent of a biocompatible solvent wherein the weight percent of the cellulose acetate, water insoluble contrast agent and biocompatible solvent is based on the total weight of the complete composition. In a preferred embodiment, the number average molecular weight of the cellulose diacetate composition is from about 25,000 to about 100,000 more preferably from about 50,000 to about 75,000 and still more preferably from about 58,000 to 64,000. The weight average molecular weight of the cellulose diacetate composition is preferably from about 50,000 to 200,000 and more preferably from about 100,000 to about 180,000. Preferably, the biocompatible solvent is dimethylsulfoxide.

0026 The compositions are prepared by conventional methods whereby each of the components is added and the resulting composition mixed together until the overall composition is substantially homogeneous. Specifically, sufficient amounts of the cellulose diacetate polymer are added to the biocompatible solvent to achieve the effective concentration for the complete embolizing composition. Preferably, the embolizing composition will comprise from about 2.5 to about 8.0 weight percent of the cellulose diacetate polymer composition based on the total weight of the embolizing composition and more preferably from about 4 to about 5.2 weight percent. If necessary, gentle heating and stirring can be used to effect dissolution of. the copolymer into the biocompatible solvent, e.g., 12 hours at 50 .degree. C.

0027 Sufficient amounts of the contrast agent are then added to the biocompatible solvent to achieve the effective concentration for the complete embolizing composition. Preferably, the embolizing composition will comprise from about 10 to about 40 weight percent of the contrast agent and more preferably from about 20 to about 40 weight percent and even more preferably 35 weight percent. Insofar as the contrast agent is not soluble in the biocompatible solvent, stirring is employed to effect homogeneity of the resulting suspension. In order to enhance formation of the suspension, the particle size of the contrast agent is preferably maintained at about 10 um or less and more preferably at from about 1 to about 5 um (e.g., an average size of about 2 um).

0028 The particular order of addition of components to the biocompatible solvent is not critical and stirring of the resulting suspension is conducted as necessary to achieve homogeneity of the composition. Preferably, mixing/stirring of the composition is conducted under an anhydrous atmosphere at ambient pressure. The resulting composition is heat sterilized and then stored preferably in sealed amber bottles or vials until needed.

0029 The '480 patent is directed to embolic compositions which can be consistently visualized during catheter delivery of the composition. Specifically, it has been found that fluoroscopic visualization of the embolic composition can be consistently achieved by employing a water insoluble contrast agent having an average particle size of about 10 um or less. It is stated that during catheter delivery of embolic compositions having average particle sizes of greater than 10 um, a portion of the contrast agent is not maintained in the embolic composition as delivered to the vascular site due to, for example, settling of the water insoluble contrast agent from suspension either before and/or during catheter delivery, adherence of the large particle size contract agents to the walls of the catheter delivery system, and the like. It is further stated that the narrow passages of the catheter delivery system coupled with the delivery protocol which requires that the contrast agent be maintained in suspension for prolonged periods of time aggravates this situation and that it is this failure to maintain a minimum amount of contrast agent in the injected embolic composition which leads to inconsistent fluoroscopic visualization during catheter delivery. Accordingly, one composition comprises: (a) from about 2.5 to about 8.0 weight percent of a biocompatible polymer; (b) from about 10 to about 40 weight percent of a water insoluble, biocompatible contrast agent having an average particle size of about 10 um or less; and (c) from about 52 to about 87.5 weight percent of a biocompatible solvent wherein the weight percent of the polymer, contrast agent and biocompatible solvent is based on the total weight of the complete composition. The biocompatible polymer composition can be replaced with a biocompatible prepolymer composition containing a biocompatible prepolymer. In this embodiment, a composition comprises: (a) a biocompatible prepolymer; (b) a biocompatible, water insoluble contrast agent having an average particle size of about 10 um or less; and (c) optionally, a biocompatible solvent.

0030 In a preferred embodiment, the water insoluble, biocompatible contrast agent is selected from the group consisting of barium sulfate, tantalum powder and tantalum oxide. In still a further preferred embodiment, the biocompatible solvent is dimethylsulfoxide (DMSO), ethanol or acetone.

0031 The polymer or prepolymer compositions employed may be prepared by conventional methods whereby each of the components is added and the resulting composition mixed together until the overall composition is substantially homogeneous.

0032 For example, polymer compositions can be prepared by adding sufficient amounts of the biocompatible polymer to the biocompatible solvent to achieve the effective concentration for the polymer composition. Preferably, the polymer composition will comprise from about 2.5 to about 8.0 weight percent of the biocompatible polymer composition based on the total weight of the polymer composition and more preferably from about 4 to about 5.2 weight percent. If necessary, gentle heating and stirring can be used to effect dissolution of the biocompatible polymer into the biocompatible solvent, e.g., 12 hours at 50.degree. C.

0033 Sufficient amounts of the contrast agent are then added to the biocompatible solvent as described above.

0034 In one preferred embodiment, the appropriate particle size of the contrast agent is prepared, for example, by fractionation. In such an embodiment, a water insoluble contrast agent such as tantalum having an average particle size of less than about 20 microns is added to an organic liquid such as ethanol (absolute) preferably in a clean environment. Agitation of the resulting suspension followed by settling for approximately 40 seconds permits the larger particles to settle faster. Removal of the upper portion of the organic liquid followed by separation of the liquid from the particles results in a reduction of the particle size which is confirmed under an optical microscope. The process is optionally repeated until a desired average particle size is reached.

0035 The particular order of addition of components to the biocompatible solvent is not critical and stirring of the resulting suspension is conducted as necessary to achieve homogeneity of the composition. Preferably, mixing/stirring of the composition is conducted under an anhydrous atmosphere at ambient pressure. The resulting composition is heat sterilized and then stored preferably in sealed amber bottles or vials until needed.

0036 Each of the polymers recited herein is commercially available but can also be prepared by methods well known in the art. For example, polymers are typically prepared by conventional techniques such as radical, thermal, UV, .gamma, irradiation, or electron beam induced polymerization employing, as necessary, a polymerization catalyst or polymerization initiator to provide for the polymer composition. The specific manner of polymerization is not critical and the polymerization techniques employed do not form a part of this invention. In order to maintain solubility in the biocompatible solvent, these polymers are preferably not cross-linked.

0037 Prepolymer compositions can be prepared by adding sufficient amounts of the contrast agent to the solution (e.g., liquid prepolymer) to achieve the effective concentration for the complete polymer composition. Preferably, the prepolymer composition will comprise from about 10 to about 40 weight percent of the contrast agent and more preferably from about 20 to about 40 weight percent and even more preferably about 30 weight percent. When the contrast agent is not soluble in the biocompatible prepolymer composition, stirring is employed to effect homogeneity of the resulting suspension. In order to enhance formation of the suspension, the particle size of the contrast agent is preferably maintained at about 10 um or less and more preferably at from about 1 to about 5 um (e.g., an average size of about 2 um).

0038 When the prepolymer is liquid (as in the case of polyurethanes), the use of a biocompatible solvent is not absolutely necessary but may be preferred to provide for an appropriate viscosity, etc. in the embolic composition. Preferably, when employed, the biocompatible solvent will comprise from about 30 to about 90 weight percent of the biocompatible prepolymer composition based on the total weight of the prepolymer composition and more preferably from about 60 to about 80 weight percent. When a biocompatible solvent is employed, the prepolymeric composition typically comprises from about 10 to about 50 weight percent of the prepolymer based on the total weight of the composition.

0039 In another example, the prepolymer is cyanoacrylate which is preferably employed in the absence of a biocompatible solvent. When so employed, the cyanoacrylate adhesive is selected to have a viscosity of from about 5 to about 20 centipoise at 20.degree. C. 0040 The '767 patent is directed to an injectable liquid embolizing composition comprising an ethylene vinyl alcohol copolymer dissolved in dimethylsulfoxide or other suitable biocompatible solvent and a water insoluble contrast agent selected from tantalum, tantalum oxide, or barium sulfate. Accordingly, one composition comprises: (a) from about 2.5 to about 8 weight percent of an ethylene vinyl alcohol copolymer embolizing agent; (b) from about 10 to about 40 weight percent of a water insoluble contrast agent selected from the group consisting of tantalum, tantalum oxide and barium sulfate; (c) from about 52 to about 87.5 weight percent of a biocompatible solvent wherein the weight percent of each of the components is based on the total weight of the complete composition.

0041 The molecular weight of the ethylene vinyl alcohol copolymer composition may be selected such that a solution of 6 weight percent of the ethylene vinyl alcohol composition, 35 weight percent of a tantalum contrast agent in DMSO has a viscosity equal to or less than 60 centipoise at 20 degree. C. and more preferably 40 centipoise or less at 20 degree. C. In another preferred embodiment, the ethylene vinyl alcohol copolymer composition comprises from about 25 to about 60 mole percent of ethylene and from about 40 to about 75 mole percent of vinyl alcohol. Preferably, the biocompatible solvent is dimethylsulfoxide. The compositions are prepared by conventional methods and as described above.

0042 The '178 patent is directed to a method of catheter delivery of the embolizing composition comprising DMSO or concentrated ethanol. It is stated that mammalian vasospasms arising from the intra- vascular delivery of the embolic solvent is concentration dependent at the in vivo injection site and that such vasospasms can be inhibited by controlling the injection rate of the embolic solvent such that its in vivo concentration does not exceed that required to initiate vasospasms. Accordingly, one method for intra- vascular delivery to a mammal of an embolic composition while inhibiting vasospasms in the mammal which method comprises: (a) selecting an embolic composition comprising a biocompatible, water insoluble polymer and an embolic solvent; and (b) intra- vascularly injecting the composition selected in (a) above into the mammal at a flow rate such that the concentration of the embolic solvent in a given blood volume is maintained at a level insufficient to initiate vasospasms. In a particularly preferred aspect, the embolic composition further comprises a contrast agent and preferably a water insoluble contrast agent.

0043 The polymer or compositions employed in the methods of this invention are prepared by conventional methods whereby each of the components is added and the resulting composition mixed together until the overall composition is substantially homogeneous. For example, polymer compositions can be prepared by adding sufficient amounts of the biocompatible polymer to the embolic solvent to achieve the effective concentration for the polymer composition. Preferably, the polymer composition will comprise from about 2.5 to about 8.0 weight percent of the biocompatible polymer composition based on the total weight of the polymer composition and more preferably from about 4 to about 5.2 weight percent. If necessary, gentle heating and stirring can be used to effect dissolution of the biocompatible polymer into the embolic solvent, e.g., 12 hours at 50 degree. C.

0044 A contrast agent may be added to the solvent as described above. Again, the particular order of addition of components to the embolic solvent is not critical and stirring of the resulting suspension is conducted as necessary to achieve homogeneity of the composition. Preferably, mixing/stirring of the composition is conducted under an anhydrous atmosphere at ambient pressure. The resulting composition is heat sterilized and then stored preferably in sealed clear or amber bottles or vials until needed.

0045 The polymers recited herein are typically commercially available but can also be prepared by methods well known in the art. For example, polymers are typically prepared by conventional techniques such as radical, thermal, UV, .gamma, irradiation, or electron beam induced polymerization employing, as necessary, a polymerization catalyst or polymerization initiator to provide for the polymer composition. The specific manner of polymerization is not critical and the polymerization techniques employed do not form a part of this invention. In order to maintain solubility in the embolic solvent, these polymers are preferably not cross- linked.

0046 The '607 patent is directed in part to the use of ethyl lactate as the embolic solvent which allows for sufficient solubility of biocompatible polymer in the embolizing composition while producing a composition which is fully biocompatible and without undesirable toxic side effects. Because lactate occurs naturally in the body, it is non-toxic when infused in a vessel. Accordingly, a composition comprises a biocompatible polymer and ethyl lactate, wherein the polymer has a solubility of at least 0.04 g/mL at 20.degree. C. in ethyl lactate. Compositions comprising cellulose acetates and, particularly, cellulose diacetate as the polymer are preferred, as are compositions comprising a contrast agent, more particularly an insoluble contrast agent, and, most particularly a contrast agent with an average particle size of 1 to 10 um. In one of its method aspects, this is directed to a method for embolizing a blood vessel by delivering via a catheter into said blood vessel a composition comprising a biocompatible polymer and ethyl lactate, wherein the polymer has a solubility of at least 0.04 g/mL at 20. degree. C. in ethyl lactate under conditions where a precipitate is formed, which precipitate embolizes the blood vessel.

0047 The polymer compositions employed in the methods of this invention are prepared by conventional methods whereby each of the components is added and the resulting composition mixed together until the overall composition is substantially homogeneous.

0048 The biocompatible embolic solvent used in this example is ethyl lactate. Ethyl lactate is degraded into lactic acid and ethanol. These degradation products occur naturally in the body, making ethyl lactate fully biocompatible. This is in contrast with DMSO which is a foreign substance which must be detoxified by the liver to eliminate it from the body.

0049 For example, polymer compositions can be prepared by adding sufficient amounts of the biocompatible polymer to the ethyl lactate solvent to achieve the effective concentration for the polymer composition. Preferably, the polymer composition will comprise from about 2.5 to about 8.0 weight percent of the biocompatible polymer composition based on the total weight of the polymer composition and more preferably from about 4 to about 7.0 weight percent. If necessary, gentle heating and stirring can be used to effect dissolution of the biocompatible polymer into the biocompatible ethyl lactate solvent, e.g., 12 hours at

50 degree. C.

0050 When a contrast agent is used, sufficient amounts of the contrast agent may be added to the solvent to achieve the effective concentration for the complete composition as described above. Also, the particular order of addition of components to the ethyl lactate is not critical and stirring of the resulting suspension is conducted as necessary to achieve homogeneity of the composition. Preferably, mixing/stirring of the composition is conducted under an anhydrous atmosphere at ambient pressure. The resulting composition is preferably heat sterilized and then stored preferably in sealed amber bottles or vials until needed.

0051 Each of the polymers recited herein is commercially available but can also be prepared by methods well known in the art. For example, polymers are typically prepared by conventional techniques such as radical, thermal, UV, .gamma, irradiation, or electron beam induced polymerization employing, as necessary, a polymerization catalyst or polymerization initiator to provide for the polymer composition. The specific manner of polymerization is not critical and the polymerization techniques employed do not form a part of this invention. In order to maintain solubility in the ethyl lactate, these polymers are preferably not cross-linked. 0052 Retention of these vaso occlusive materials in a chosen site, such as an aneurysm, until the desired occluding mass is formed, can be challenging.

0053 None of the cited art suggests the structure found in the inventive catheter nor the inventive balloon makeup.

SUMMARY OF THE INVENTION

0010 This invention has several variations. It desirably includes a low profile balloon catheter for use with a removable guide wire and is made up of a catheter body having a distal end, a proximal end, and a passageway for inflation of a balloon at the distal end of the inflation lumen. The balloon is located near said distal end and is filled with a fluid when a movable seal cooperates to seal the inflation passageway and, of course, fluid is introduced into the passageway. The balloon may be compliant.

0011 There are several variations of the seal. One seal is inflatable and employs a fluid supply lumen independent of the balloon inflation passageway. It may be situated within the passageway and upon inflation of the seal closes against the removable guide wire.

0012 Another variation is both self-closing and sealable against the removable guide wire when that guide wire passes through the movable seal. That variation of the seal may be distal of the balloon and, indeed, may be an extension, perhaps an everted extension, of the balloon.

0013 The seal assemblage of this invention may include an auxiliary seal for initially sealing the passageway against the guide wire while the balloon itself uses its own distal end to form the seal. The distal end closes both against the guide wire and is self-closing against itself upon introduction of a fluid into the balloon.

0014 In another variation, the seal is closed and permits inflation of the balloon when fluid is introduced into the fluid passageway. When the seal is penetrated by the guide wire, the inflation fluid passes through the seal and the balloon deflates. The seal may have a mating surface that is adapted to cooperate with the guide wire to provide openings in the seal adjacent to the guide wire. That mating surface may be sinusoidal or another suitable shape.

0015 The balloon catheter has a catheter shaft and the proximal section of that shaft typically is different in many aspects from the distal section. For instance, the proximal section may have a diameter larger than that of the distal section or may have a different flexibility.

0016 The balloon catheter may be used for a variety of purposes. The catheter may be of a flexibility, length, and diameter appropriate for a neurovascular microcatheter or for a guide catheter or other selected balloon catheter style.

0017 Another variation of the inventive low profile balloon catheter involves a generally non-removable guide wire and a seal to fill the balloon. The guide wire may be adapted to provide selectable axial stiffness to the flexible distal section of the catheter. The stiffness of the guide wire may be continuously and incrementally variable. The guide wire may have a variable diameter. The proximal portion of said catheter may be a hypotube.

0018 Another aspect of the invention involves a strain relief joint between a first comparatively stiff section adjacent a second comparatively flexible section, perhaps both tubing members. The first stiff section may have a diameter different than that of the second flexible section. The joint includes a corkscrew-shaped component wound over the joint that adheres to both the first and to said second sections. The first and second sections may be polymeric. Preferred are joints at least partially wrapped by a metallic ribbon of stainless steel or a superelastic alloy. It is desirable to adhere the metallic ribbon and the corkscrew-shaped component to the tubing sections via a first molten and then-solidified polymer. One or more shrink-wrapped polymeric coverings over the joints are desired.

0002 Finally, the balloon may be enclosed in a separate sack-like structure to allow its use with reactive or sticky vaso-occlusive materials. The balloon itself may be layered with such protective materials. The material of construction for the balloon may be selected from materials chosen to be resistant to the components (particularly any solvents or plasticizers) found in the chemical vaso-occlusive materials.

BRIEF DESCRIPTION OF THE DRAWINGS

0020 Figure 1 shows a view of the inventive catheter.

0021 Figure 2 shows in partial cross-section a variation of the inventive balloon catheter.

0022 Figure 3 shows in partial cross-section, details of the distal tip of the inventive balloon catheter.

0023 Figure 4 A shows, in partial cross-section, details of the distal tip of the inventive balloon catheter having an inflatable seal.

0024 Figure 4B shows, in cross section, the variation shown in Figure 4A. 0025 Figure 4C shows a partial longitudinal cross section of the variation of the catheter shown in Figures 4A and 4B with the seal inflated.

0026 Figures 5 A, 5B, and 5C show a variation of the inventive catheter in which the balloon is variously sealing against the introduced guidewire and against itself. Figure 5 A shows the balloon in a deflated condition. Figure 5B shows the balloon in an inflated condition with the seal seated against the guidewire. Figure 5C shows the balloon inflated against itself rather than against the guidewire.

0027 Figures 6A, 6B, 6C, and 6D show variations of the balloon catheter having a seal distal on the balloon and formed of material extending from the balloon. Figure 6A shows the instance in which the balloon is not inflated. Figure 6B shows the seal closed against the guidewire with the balloon inflated. Figure 6C shows the balloon inflated with the seal self-closing. Figure 6D shows a variation of the seal having a single layer of seal material in contrast to the everted, multilayer design of Figures 6A, 6B, and 6C.

0028 Figures 7 A - 7F show a version of the balloon catheter having a self- closing distal seal which is only opened by introduction of a guidewire through the seal. Figure 7A shows a deflated balloon prior to the introduction of inflation fluid. Figure 7B shows an end view of the Figure 7 A variation. Figure 7C shows a deflated balloon with a guidewire penetrating the distal seal. Figure 7D shows an end view of that instance. Figure 7E shows the balloon inflated and the end seal closed. Figure 7F shows an end view of the instance shown in Figure 7E.

0029 Figure 8 shows a variation of the inventive balloon catheter having a captive guidewire.

0030 Figure 9 shows another variation of that shown in Figure 8. 0031 Figure 10A shows a cross section of a balloon having a non-reactive, non-sticking shield.

0032 Figure 10B shows a cross section of a laminated balloon having a non- reactive, non-sticking outer surface.

0012 Figure 11 depicts a procedure for occluding an aneurysm using a balloon section or balloon catheter made according to the invention.

DESCRIPTION OF THE INVENTION

0034 Figure 1 shows a generic layout of the inventive catheter (100). Specifically, catheter (100) has a catheter body (102) which has one or more catheter sections typically having different flexibility. The proximal portion (104) of the catheter body is desirably quite stiff and the more distal portion (106) of the catheter body is, by comparison, significantly more flexible. The inflatable membrane or balloon (108) is quite distal on the catheter (100). Guidewire (110) having a distal tip is shown in the Figure. The guidewire (110) may be removable and is adapted to cooperate with seals found interior to the lumen catheter body (102) to inflate the balloon (108). At the proximal end of the balloon catheter may be found the proximal end (112) of the guidewire (110) and a torquer (114) for torquing or twisting the guidewire for its movement through the vasculature.

0035 Typical fluid connections are also used. For instance, a fluid connector (116), e.g., a "Luer-Lok", for introduction of the balloon inflation fluid is also shown.

0036 The overall length of the inventive catheter (100) preferably is in the range of 100 to 225 cm, preferably 175 to 210 cm. Since the preferable use of this inventive balloon catheter is in the neurovasculature, the diameter of the catheter body distally is 25 to 40 mils, preferably 30 to 35 mils. Where the catheter body is stepped, the diameter of the more proximal section preferably is 40 mils to 55 mils, most preferably 45 to 50 mils in diameter. The axial length of the balloon (108) desirably is 10 to 25 mm, more preferably 10 to 20 mm, and perhaps most preferably but not necessarily about 15 mm in length. The length of the more flexible distal section (106) is preferably from 15 to 40 cm in length, more preferably 15 to 25 cm, and most preferably about 20 cm in length. The more proximal section may be made up of one or more subsections of varying construction, and perhaps differing stiffness, but in any event makes up the rest of the overall catheter length.

0037 Figure 2 shows in partial cross-section an inventive catheter (130) having a highly desirable construction of catheter body (132) with more flexible distal section (134) and a stiffer proximal section (136). A balloon (138) in inflated condition is also shown, as is seal (140). A movable guidewire, that is necessary for inflation of the balloon as shown, has been removed for a more thorough explanation of the construction of the catheter body (130).

0038 In this variation, the most proximal portion of the proximal section involves a quite stiff inner layer (142) quite desirably of a material such as polyaryletheretherketone (PEEK) and variations of such ketone-based resins such as PEKK, PEKEKK, and the like. Polysulphones, including polyethersulphones, and polyphenylsulphones and various members of the Nylon family may be used. A metallic tube such as a hypotube is also suitable. Just distal of proximal inner liner (142) is an inner liner (144), preferably of material which is intermediate in flexibility between the inner liner (142) and distal section (134). Typical of such a material would be high density polyethylene (HDPE). Thermoplastics such as HDPE are desirable in that junction between larger proximal section and the smaller diameter distal section (136) may be easily fabricated.

0039 In this desired variation, substantially all or a significant portion of the catheter assembly (130) is covered by an irradiated shrink-wrap layer (146) of shrink- wrap of polyolefin or other similar material such as low density polyethylene (LDPE). An auxiliary covering of another shrink-wrap of polyolefin (148) (such as LDPE or LLDPE) may also be seen in the Figure 2 depiction. The auxiliary or outer covering (148) is placed over a majority of or all of the proximal section of catheter assembly (130) to provide additional stiffness to the proximal portion and to provide stability and some initial measure strain resistance to the junction between proximal portion (136) and distal portion (132).

0040 Further, this variation of the inventive catheter utilizes an anti-kinking member (150). The variation shown here includes a ribbon coil which is desirably continuous for a significant length of the catheter, desirably for the total length. Any of the ribbon and wire discussed here may be variously metallic (e.g., stainless steels or superelastic alloys such as nitinol) or polymeric. The polymers may be single phase, e.g., such as monofilament line, or multiple strands bundled or woven together. These components may be made of a mixture of materials, e.g., super- elastic alloy and stainless steel components or of LCPs. Preferred because of cost, strength, and ready availability are the stainless steels (SS304, SS306, SS308, SS316, SS318, etc.) and tungsten alloys. Especially preferred is stainless steel and, in particular, SS304-V. In certain applications, particularly in smaller diameter devices, more malleable metals and alloys, e.g., gold, platinum, palladium, rhodium, etc. may occasionally be, but then in combination with other materials for strength. A platinum alloy with a few percent of tungsten is sometimes used because of its high radio-opacity.

0041 When using a super-elastic alloy in any of the component tubing members, an additional step may be desirable to preserve the shape of the stiffening braid or coil. For instance, after a structure such as a coil has been wound or a braid has been woven, some heat treatment may be desirable. Braids and coils that are not treated this way may unravel during subsequent handling or may undertake changes in diameter or spacing during that handling. In any event, the braids or coils are placed on a heat-resistant mandrel and placed in an oven at a temperature of, e.g., 500° to 932°F, particularly 650° to 750°F, for a few minutes. This treatment may anneal the material in the constituent ribbon or wire but in any event provides it with a predictable shape for subsequent assembly steps. After heat-treatment, the braid or coil retains its shape and most importantly the alloy should retain its super-elastic properties.

0042 The antikinking member (150) preferably is formed from ribbons of stainless steel, superelastic alloys such as nitinol, or polymeric constructs. Although the braid may alternatively be formed from a round or oval profiled wire, a ribbon is preferred because of the overall lower profile attainable for an enhanced amount of kink resistance. The ribbon is preferably less than 1.5 mil in thickness, more preferably 0.7 mils to 1.5 mils, most preferably about 1 mil. The width desirably is 2.5 mils to 7.5 mils in width, more preferably about 5 mils.

0043 By "braid" here, we mean that the braid components are woven radially in and out as they progress axially down the braid structure. This is to contrast with the use of the term "braid" with co-woven coils merely laid one on top of the other in differing "handed-ness.".

0044 Returning to the discussion of the anti-kinking member (150), the anti-kinking member (150) may also suitably be a wire of suitable cross-section, e.g., round or oval or square. It need not be wound from one end of the catheter to the other, over the junctions between regions of different diameter, but it is desirable to do so. Anti- kinking members (150) may simply be multiple coils co- wound at the same time. Other variations include braids and multiple coils wound in opposite directions. The single layer ribbon coil is highly desirable because of the ease of assembly in placing the coil upon a catheter subassembly, particularly when the catheter subassembly has a variety of diameters. The other advantages include a high measure of kink- resistance even with an extremely low profile.

0045 The joint between the stiff proximal section (136) and the significantly more flexible distal section (132), as shown, incorporates an exceptional amount of strain relief without being bulky. In particular, the joint involves the stiffest inner member (142), perhaps the transition section (144) and the soft flexible covering (134). Central to the strain-resisting feature is the use of a corkscrew shaped section of material (152) that extends over the joint. In the event a coil or other similar strain relief device is employed, the added high strength corkscrew (152) is desirably placed between the turns of the anti-kinking device (150). Of course, the outer layers of shrink-wrap tubing (134 and 148) are also desirable in providing strength to this joint.

0046 Distally on the variation in Figure 2 may be found the balloon (138) access passageways (154) and tip seal (140). The balloon (138) is desirably of a highly compliant polymeric material, preferably an elastomeric stretchable material such as silicone rubber, latex rubber, polyvinylchloride (PVC), chloroprene, or isoprene. Radiopaque markers both (156) proximal of the balloon and (158) distal of the balloon (138) are also shown. In this variation, each of these markers (156, 158) is shown to be coils of a radiopaque material such as platinum or alloys of platinum/iridium and other suitable materials.

0047 As is apparent from the Figure 2 drawing, when seal (140) is closed, e.g., by introduction of a closely fitting guidewire, introduction of fluid through the open lumen of catheter (130) will cause fluid to flow through orifices (154) and expand balloon (138).

0048 Figure 3 shows guidewire (160) in contact with and closing seal (140) thereby causing balloon (138) to expand upon introduction of fluid into lumen (162). 0049 Figures 4A, 4B, and 4C show a variation of the inventive catheter in which the seal (164) is expandable. A separate inflation lumen (166) is also shown. The benefits of this variation are many. Specifically, the guidewire (160) is free to move both longitudinally and without significant friction from the seal during placement of the catheter using that guidewire (160). Once the seal (164) is inflated as is shown in Figure 4C, the lumen (162) is tightly and controllably closed for use in inflating balloon (138). Depending upon the design, annular inflatable seal (164) may "freeze" the guidewire (160) in place allowing the catheter - guidewire assembly to move easily as a single unit.

0050 Figures 5A through 5C show another variation of the inventive catheter (200). The distal tip including balloon (202) is also shown in Figures 5 A - 5C. In this variation, the balloon material is attached at the end of a stiffer tubular member (204) at, e.g., joint (206). Although the joint is shown here to be a butt-joint, the joint may be other joint structures as is appropriate for this kind of balloon assembly. This variation also uses an everted balloon (202) that folds back and is attached to the distal tubular member (204) at joint area (208). Finally, an auxiliary seal region (210) is implemented in this variation. The primary seal is the distal region of the balloon (212) as will be explained in more detail with regard to Figure 5C. Inflation fluid flows from the annular space (214) through the orifices (216) into the chamber of the balloon (202).

0051 Figure 5A shows the balloon in a deflated condition prior to the time inflation fluid is introduced through orifices (216). Auxiliary seal (210), however closes the annular space (214) to substantial flow of inflation fluid other than into the balloon. Figure 5B shows the balloon (202) in an inflated condition. It should be noted that the distal regions of the balloon (212) act as the primary seal and are closed against guidewire (160). 0052 Figure 5C shows the inflated balloon (202) with the guidewire (160) withdrawn from contact with the balloon (212) and the auxiliary seal region (210). Auxiliary seal (210) may be either compliant and in the form of an elastomeric ring much like a small rubber band or may be a properly sized rigid ring of a metal or other suitable material. In any event, primary seal region (212) remains closed and both the inflation of and deflation of the balloon are then controllable only by withdrawal of or introduction of fluid from annular space (214).

0053 Figures 6A and 6B show two versions of the inventive catheter in which the seal regions are located distally of the balloon and are normally closed. These variations permit sealing of distal seal (250 in Figures 6 A, 6B, 6C and 252 in Figure 6D) and also seal upon the included guidewire (160).

0054 Figure 6A shows a deflated balloon (254) having a distal seal region (250). The seal region (250) is everted in that it is folded back upon itself but retains an orifice (256) through which guidewire (160) may pass. In this variation, inflation fluid flows out of distal tip (258) of catheter body (260). Seal region (250) is self sealing and upon introduction of fluid through the catheter, will inflate whether the guidewire (160) is present in seal (250) or not. Similarly, as may be seen in Figure 6C, withdrawal of the guidewire from seal region (250) will not cause deflation of balloon (254). Production of small everted seals such as that shown in (250), is reasonably simple in that the open end may be simply rolled back and, e.g., glued to itself to form one or more layers of balloon material in that region. Figure 6D shows an alternative seal region (252) that involves only a single layer of material.

0055 Figures 7 A through 7F show still another variation of the inventive catheter (280). In this variation, guidewire (160) is used in cooperation with the shape of the seal region or mating surfaces in such a way that introduction of guidewire (160) into the seal surface will permit the balloon to be deflated. 0056 Figure 7A shows deflated balloon (284) prior to introduction of inflation fluid to the balloon and, the presence of guidewire (160). Figure 7B shows an end view of catheter with its convoluted or sinusoidal seal mating surface (282).

0057 In Figure 7C, guidewire (160) has been extended through seal mating surface (282) creating a number of openings (286) along the outer surface of guidewire (160). Fluid flows through these openings for deflation of the balloon. The protuberances of seal region (282) push against guidewire (160) to enhance the opening flow spaces (286). It is desirable that the material in the seal region (282) have a bit higher stiffness than the material of the surrounding balloon to allow for creation of the flow areas (286).

0058 Figure 7E shows a partial side view of the inflated balloon (284) as sealed by seal region (282).

0059 Figure 7F shows an end view of the inflated device (280) as otherwise shown in Figure 7E.

0060 Figures 8 and 9 show an additional variation of the inventive catheter (300). This variation includes a guide wire or core wire (302) that preferably is ground in such a way so to allow its use in conjunction with the surrounding catheter body (304) as a guide wire. More particularly, the core wire (302) is not removable from catheter body (304) during normal usage. The function of the core wire (302), in addition to its utility as a way for the device to be used in a "guiding" fashion, is that the core wire may be used to provide a measure of additional stiffness by an axial "pulling" on core wire (302). By controlling the overall flexibility of the device by twisting knob (308), the flexibility may be incrementally and continuously varied. It is highly desirable that the adjustment component (308) be configured in such a way that it does not transmit torque to core wire (302). The ball and socket joint at (310) is one way to prevent substantial torque from being transmitted to core wire (302). The annular region (312) for passage of inflation fluid from fluid import fitting (314) to balloon (316) is isolated by seal (318) at proximal end and seal (320) at the distal end. Other desirable features of this particular variation include the use of radio- opaque marker coils (322) coincident with and proximal of balloon (316) and a shapeable radio-opaque coil (324) distal of balloon (316). Desirable, but not required, is the flat region (326) of core wire (302) to allow an initial manual bending of the tip of the device for usage as a guide wire.

0061 The other functional structure of this variation of the guide wire may generally be as shown above with respect to the other catheter bodies. The use of anti-kinking or stiffener members (328) (flat wound ribbon coil) and a wire coil (330) may be as discussed above. The polymeric materials forming the desirably stiffer proximal end (332) and the more flexible materials making up distal end (334) may also be as discussed above. Similarly, the inflatable balloon (316) may be produced from the materials discussed above and those otherwise used in compliant balloons in this art.

0062 It is preferable that the balloons used in this device be compliant, that is, elastic in that typically they are used in the vasculature of the brain and high pressure is not always desired. The diameter of the balloons, once inflated, may also be controlled with such a balloon design. However, fixed diameter balloons are certainly within the scope of this invention, just not preferred.

0063 Figure 9 shows variation (350) of the device shown in Figure 8, with the exception that the stiffening of the guide wire by axial or longitudinal movement of that core wire (352) is more pronounced and not as finely adjustable as is the variation in Figure 8. Simply pulling on knob (354) will produce stiffening of the distal end of the catheter (350). Otherwise, the device is as described above. 0064 One of the uses of this device will be in the placement of vasoocclusive devices and materials in aneurysms. Vasoocclusive coils and the like (such as the Guglielmi Detachable Coil or "GDC") are well-known and widely used. However, it is also highly desirable to include other occluding materials such as cyanoacrylates and partially hydrolyzed polyvinyl acetate and the like in such aneurysms, particularly when the aneurysm is a wide-necked one. However, it is not always easy to maintain continuous or sticky or reactive media such as cyanoacrylate glues in a wide-mouth aneurysm. The inventive catheter is ideal for maintaining these materials in the aneurysm until they are effective in occluding the aneurysm, but the balloon and its environs are desirably inactive with regard to the occluding material.

0065 Figures 10A and 10B show two such variations.

0066. Figure 10A shows a balloon (380) of the type discussed at length above. Exterior to the balloon is a sack or enclosure (382) made of a material which variously does not react with nor stick to nor is degraded by the chemical occlusion- forming material placed in an aneurysm. Such an enclosure (382) is desirably a very thin, e.g., 0.025 mil to 0.15 mil wall thickness. Appropriate materials include, for instance, many of the polyfluorocarbons (polytetrafluoroethylene (PTFE or TFE), ethylene-chlorofluoroefhylene (ECTFE), fluorinated ethylene propylene (FEP), polychlorotrifluoroefhylene (PCTFE), polyvinylfluoride (PVF), or polyvinylidenefluoride (PVDF)). The preferred material is PTFE, and the especially preferred material is expanded polytetrafluoroethylene (ePTFE) such as is sold by the Gore Company as GORETEX or by CR. Bard's subsidiary, Impra, Inc. The ePTFE material may need filling in some instance because of its porosity. Other materials such as polyethylene (particularly LDPE, LLDPE, HDPE), polypropylene, and polyamides (the Nylons) their mixtures and co-polymers may be appropriate selections depending upon the material to be used in forming the occlusion. Most of these materials are not elastomeric, however, and consequently the balloon materials and its enclosing sack should be chosen with care.

0067 Figure 10B shows a similar balloon (384) but one having a laminated structure with an outer non-reactant, non-adherent layer and an inner polymeric layer (388) which may be compliant or not.

0068 Finally, the balloon itself (when used in a procedure not requiring a compliant balloon) may be made from materials such as polyolefins, e.g., polyethylene, polypropylene, and their respective copolymers, mixtures, and alloys, or the polyfluorocarbons listed above or other polymers suitable for resisting chemicals found in chemical vaso-occlusive materials.

0069 When used in an occluding procedure requiring a compliant balloon, the balloon may be made of materials such as various Silicones to resist degradation by the included plasticizers or solvents and the like.

0070 One variation of this invention includes the combination of a.) balloons of compositions suitably chosen to resist degradation of the material making up the balloon with a chemical occluding material and b.) that chemical occluding material composition and its components or reactants. The chemical occluding materials include those listed above in the Background of the Invention, the precursor materials (as appropriate), and the occluding masses as eventually formed. The patents listed above in the Background of the Invention are incorporated by reference. This combination may be either a kit to be used by a physician to form an occluding mass in a chosen body site or the combination as present in the body as found during the procedure, e.g., the balloon (inflated or not) perhaps sealing an aneurysm and the occluding mass in that aneurysm.

0071 Figure 11 shows a generic procedure for using a balloon section, balloon, or balloon catheter such as described above in occluding a vascular site such as an aneurysm or AVM. Step (a) shows the approach of a balloon catheter (400) made according to one or more aspects of the invention approaching an aneurysm (402) having a mouth (404) opening into an artery. A delivery catheter (406) is also shown approaching the aneurysm mouth (404). The balloon catheter (400) also has optional radio-opaque markers showing the ends of the balloon section and a marker (410) showing the distal end (410) of the catheter (400). In step (b), the delivery catheter (406) has been inserted through the aneurysm mouth (404) and into aneurysm (402). The balloon (412) has been inflated at least to close the aneurysm mouth (404) and perhaps the artery lumen. Occluding material (414) is shown to be leaving delivery catheter (406). Step (c) shows the occluding material (414) to be filling aneurysm (402) and the delivery catheter (406) having been retracted from the aneurysm mouth (404). Balloon (412) remains inflated until the occluding material (414) has set. In this step, the balloon (412) is in contact with the occluding material (414) and has not ruptured nor deteriorated. This combination is a variation of the invention. Finally, in step (d), balloon catheter (400) and delivery catheter (406) are shown during withdrawal from the aneurysm treatment site. The occluding material (414) is intact.

EXAMPLE

0072 We tested a variety of materials potentially useful as balloons to check for resistance to the material found in Krall — U.S. Pat No. 6,037,366.

Materials:

MIS Grapevine Balloon

Concentric Balloon Guide 7.4f

Concentric Balloon Guide 9f

PE Balloon

ITC SI Balloon

Dipped Silicon 29.6 solids

.018' ID x .004" wall Material MED-4120 Durometer 20

Ethyl Myristate

Neuracryl Al

Neuracryl A2 Test Procedure:

The test embolic solution was prepared by mixing 1.25cc of Neuracryl Al into Neuracryl A2 (1.632 g.). The balloons were prepared using standard procedures using saline as inflation media. The balloons were placed in the described solution.

See table below for solution description and time in solution.

* Balloon was checked after 2 hrs in the Neuracryl and there was no change. The balloon was placed back in to the Neuracryl for 18 additional hrs. The balloon was cast in the solidified Neuracryl, the balloon was dissected to examine, the internal walls of the balloon looked inflated and had no signs of any damage.

NOTE:

Balloons were tested in 100% ethyl myristate because ethyl myristate is mixed with the embolic agent. The trade name was Neuracryl Al .

TEST RESULTS:

This test showed the PE balloon was more resistant than any of the other materials, however, this material was not as compliant as the other balloon materials used for this test. The next most resistant are the silicone balloons and, in particular, the dipped silicone balloons.

0073 This invention has been described in reference to various illustrative embodiments. However, this description is not intended to be construed in a limiting sense. Various modifications and combinations of the illustrations, as well as other embodiments of the invention, will be apparent to those persons skilled in the art upon reference to the description. It is therefore intended to be appended to claims encompassing any such modifications or embodiments.

0074 Each specifically cited patent or article is specifically incorporated by reference.

Claims

0024 WE CLAIM AS OUR INVENTION:

1. A low profile balloon catheter for use with a removable guide wire comprising: a catheter body having a distal end, a proximal end, and a passageway for inflation of a balloon at the distal end of the inflation lumen, said balloon located near said distal end, and a movable seal adapted to cooperatively seal said passageway and to inflate said balloon upon introduction of fluid into said passageway.

2. The catheter of claim 1 wherein the movable seal is inflatable by a fluid supply lumen independent of said inflation passageway.

3. The catheter of claim 2 where the movable seal is situated within said passageway and upon inflation of said seal closes against said removable guide wire.

4. The catheter of claim 1 wherein the movable seal is both self-closing and sealable against the removable guide wire when said guide wire passes through said movable seal.

5. The catheter of claim 4 where said seal is distal of said balloon.

6. The catheter of claim 5 where said seal is a continuous extension of said balloon.

7. The catheter of claim 6 where said seal is an everted extension of said balloon.

8. The catheter of claim 1 further comprising an auxiliary seal for initially sealing said passageway against said guide wire and where the balloon includes a distal end forming said seal, both against said guide wire and self-closing against itself upon introduction of a fluid into said balloon.

9. The catheter of claim 1 where said seal is adapted to close said passageway and inflate said balloon when said guide wire does not pass through said seal and when fluid is introduced into said passageway and said seal is adapted to allow passage of fluid through said seal and deflation of said balloon when said guide wire passes through the seal.

10. The catheter of claim 9 where the seal has a mating surface adapted to cooperate with said guide wire to provide openings in said seal adjacent said guide wire.

11. The catheter of claim 10 wherein said mating surface is sinusoidal.

12. The catheter of claim 1 wherein the balloon is compliant.

13. The catheter of claim 1 wherein the catheter body has a catheter shaft with a proximal section different that said distal section.

14. The catheter of claim 13 where the proximal section has a larger diameter than the distal section.

15. The balloon catheter of claim 1 wherein said catheter is of a flexibility, length, and diameter appropriate for a neurovascular microcatheter.

16. The balloon catheter of claim 1 wherein said catheter is of a flexibility, length, and diameter appropriate for a guide catheter.

17. The balloon catheter of claim 1 wherein said balloon has an outer surface substantially non-reactive with and non-adherent to chemical vaso-occlussive materials.

18. The balloon catheter of claim 17 wherein said outer surface comprises one or more polyfluorocarbons selected from the group consisting of polytetrafluoroethylene (PTFE or TFE), ethylene-chlorofluoroethylene (ECTFE), fluorinated ethylene propylene (FEP), polychlorotrifluoroethylene (PCTFE), polyvinylfluoride (PVF), and polyvinylidenefluoride (PVDF).

19. A low profile balloon catheter comprising: a catheter body having a distal end, a proximal end, a flexible distal section, and a passageway for inflation of a balloon at a distal end of the inflatable lumen, an inflatable balloon located near said distal end, a non-removable guide wire, a seal situated in said passageway adapted to seal against said guide wire for inflation of said balloon upon introduction of fluid into said passageway, and said guide wire extending distally of that seal.

20. The catheter of claim 19 wherein the guide wire is adapted to provide axial stiffness to said flexible distal section.

21. The catheter of claim 20 wherein the stiffness of the guide wire is continuously and incrementally variable.

22. The catheter of claim 19 where the guide wire has a variable diameter.

23. The catheter of claim 19 where the proximal portion of said catheter is a hypotube.

24. The catheter of claim 19 wherein said catheter is of a flexibility, length, and diameter appropriate for a neurovascular microcatheter.

25. The catheter of claim 19 wherein said catheter is of a flexibility, length, and diameter appropriate for a guide catheter.

26. A strain relief joint between a first comparatively stiff section adjacent, a second comparatively flexible section comprising said first stiff section, said flexible second section joined to said first section at a joint, and a corkscrew-shaped component wound over said joint and adherent both to said first and to said second sections.

27. The strain relief joint of claim 26 wherein said first and second sections are tubing members.

28. The joint of claim 27 where the first and second sections are polymeric.

29. The joint of claim 28 wherein said joint is at least partially wrapped by a metallic ribbon.

30. The joint of claim 29 wherein the metallic ribbon comprises stainless steel alloy.

31. The joint of claim 30 where the first stiff section has a diameter different than the second flexible section.

32. The joint of claim 31 where the metallic ribbon and the corkscrew-shaped component are adherent to the tubing sections via a molten and solidified polymer.

33. The joint of claim 31 further comprising one or more shrink-wrapped polymeric coverings.

34. In combination, an inflatable balloon assembly comprising an inflatable member having an outer surface substantially non-reactive with and non-adherent to chemical vaso-occlusive materials in combination with one or more of the chemical vaso-occlusive materials.

35. The combination of claim 34 where the inflatable balloon assembly further comprises a sack enclosing said inflatable member composed of a material substantially non-reactive with and non-adherent to the chemical vaso-occlusive materials.

36. The combination of claim 34 where the inflatable member comprises a layered material having an exterior layer of the substantially non-reactive and non- adherent material.

37. The combination of claim 34 where the substantially non-reactive and non-adherent material comprises ePTFE.

38. The combination of claim 34 where the inflatable member comprises one or more polyfluorocarbons selected from the group consisting of polytetrafluoroethylene (PTFE or TFE), ethylene-chlorofluoroethylene (ECTFE), fluorinated ethylene propylene (FEP), polychlorotrifluoroethylene (PCTFE), polyvinylfluoride (PVF), and polyvinylidenefluoride (PVDF).

39. The combination of claim 34 where the inflatable member comprises a silicone.

40. The combination of claim 39 where the inflatable member comprises one or more polyolefms, and their copolymers, mixtures, and alloys.

41. The combination of claim 40 where the inflatable member comprises one or more polyolefms selected from the group consisting of polyethylene and polypropylene.

42. The combination of claim 34 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials selected from the group consisting of modified cyanoacrylate compositions; partially hydrolyzed polyvinyl acetate initially in an ethanol solvent; and biocompatible polymer compositions.

43. The combination of claim 34 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials, said chemical vaso-occlusive materials being modified cyanoacrylate compositions.

44. The combination of claim 34 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials, said chemical vaso-occlusive materials being partially hydrolyzed polyvinyl acetates initially in an ethanol solvent.

45. The combination of claim 34 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials, said chemical vaso-occlusive materials being biocompatible polymer compositions.

46. The combination of claim 34 where the chemical vaso-occlusive material is selected from the group consisting of modified cyanoacrylate compositions; partially hydrolyzed polyvinyl acetate initially in an ethanol solvent; and biocompatible polymer compositions.

47. The combination of claim 34 where the chemical vaso-occlusive material is a modified cyanoacrylate composition.

48. The combination of claim 34 where the chemical vaso-occlusive material is a partially hydrolyzed polyvinyl acetate initially in an ethanol solvent.

49. The combination of claim 34 where the chemical vaso-occlusive material is a biocompatible polymer composition comprising a biocompatible polymer component and a biocompatible solvent, said biocompatible polymer component selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid.

50. A method for introducing a chemical vaso-occlusive material to a selected site in the human body comprising the steps of: a.) introducing a chemical vaso-occlusive material to a selected site in the human body, and b.) placing an inflatable balloon assembly comprising an inflatable member having an outer surface substantially non-reactive with and non-adherent to the chemical vaso-occlusive materials in contact with the chemical vaso-occlusive material.

51. The method of claim 50 further including the step of inflating the inflatable member.

52. The method of claim 50 further including the step of deflating the inflatable member.

53. The method of claim 50 where the inflatable member comprises one or more polyfluorocarbons selected from the group consisting of polytetrafluoroethylene (PTFE or TFE), ethylene-chlorofluoroethylene (ECTFE), fluorinated ethylene propylene (FEP), polychlorotrifluoroethylene (PCTFE), polyvinylfluoride (PVF), and polyvinylidenefluoride (PVDF).

54. The method of claim 50 where the inflatable member comprises a silicone.

55. The method of claim 50 where the inflatable member comprises one or more polyolefms, and their copolymers, mixtures, and alloys.

56. The method of claim 50 where the inflatable member comprises one or more polyolefms selected from the group consisting of polyethylene and polypropylene.

57. The method of claim 50 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials selected from the group consisting of modified cyanoacrylate compositions; partially hydrolyzed polyvinyl acetate initially in an ethanol solvent; and biocompatible polymer compositions.

58. The method of claim 50 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials, said chemical vaso-occlusive materials being a modified cyanoacrylate composition,

59. The method of claim 50 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials, said chemical vaso-occlusive materials being a partially hydrolyzed polyvinyl acetate initially in an ethanol solvent.

60. The method of claim 50 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vasoocclusive materials, said chemical vaso-occlusive materials being a biocompatible polymer compositions.

61. The method of claim 50 where the chemical vaso-occlusive material is selected from the group consisting of modified cyanoacrylate compositions; partially hydrolyzed polyvinyl acetate initially in an ethanol solvent; and biocompatible polymer compositions.

62. The method of claim 50 where the chemical vaso-occlusive material is a modified cyanoacrylate composition.

63. The method of claim 50 where the chemical vaso-occlusive material is a partially hydrolyzed polyvinyl acetate initially in an ethanol solvent.

64. The method of claim 50 where the chemical vaso-occlusive material is a biocompatible polymer compositions comprising a biocompatible polymer component and a biocompatible solvent, said biocompatible polymer component selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid.

65. A balloon catheter section comprising an inflatable balloon assembly comprising an inflatable member having an outer surface substantially non-reactive with and non-adherent to chemical vaso-occlusive materials.

66. The balloon catheter section of claim 65 where the inflatable balloon assembly further comprises a sack enclosing said inflatable member composed of a material substantially non-reactive with and non-adherent to the chemical vasoocclusive materials.

67. The balloon catheter section of claim 65 where the inflatable member comprises a layered material having an exterior layer of the substantially non-reactive with and non-adherent material.

68. The balloon catheter section of claim 65 where the substantially non- reactive with and non-adherent material comprises ePTFE.

69. The balloon catheter section of claim 65 where the inflatable member comprises one or more polyfluorocarbons selected from the group consisting of polytetrafluoroethylene (PTFE or TFE), ethylene-chlorofluoroethylene (ECTFE), fluorinated ethylene propylene (FEP), polychlorotrifluoroethylene (PCTFE), polyvinylfluoride (PVF), and polyvinylidenefluoride (PVDF).

70. The balloon catheter section of claim 65 where the inflatable member comprises a silicone.

71. The balloon catheter section of claim 65 where the inflatable member comprises one or more polyolefms, and their copolymers, mixtures, and alloys.

72. The balloon catheter section of claim 71 where the inflatable member comprises one or more polyolefins selected from the group consisting of polyethylene and polypropylene.

73. The balloon catheter section of claim 65 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vaso-occlusive materials selected from the group consisting of modified cyanoacrylate compositions; partially hydrolyzed polyvinyl acetate initially in an ethanol solvent; and biocompatible polymer compositions.

74. The balloon catheter section of claim 65 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vaso-occlusive materials, said chemical vaso-occlusive materials being modified cyanoacrylate compositions.

75. The balloon catheter section of claim 65 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vaso-occlusive materials, said chemical vaso-occlusive materials being partially hydrolyzed polyvinyl acetates initially in an ethanol solvent.

76. The balloon catheter section of claim 65 where the inflatable member comprises one or more materials substantially non-reactive with and non-adherent to chemical vaso-occlusive materials, said chemical vaso-occlusive materials being a biocompatible polymer composition.

77. A balloon catheter for use with a removable guide wire comprising: a catheter body having a distal end, a proximal end, and a passageway for inflation of an inflatable member of a balloon catheter section at the distal end of the inflation lumen, said balloon catheter section as recited in any one of claims 65-76; and a movable seal adapted to cooperatively seal said passageway and to inflate said balloon upon introduction of fluid into said passageway.

78. The combination of claim 45 where the biocompatible polymer compositions comprise a biocompatible polymer component and a biocompatible solvent, said biocompatible polymer component selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid.

79. The combination of claim 78 where the biocompatible solvent is selected from the group consisting of DMSO, acetone, ethanol, ethyl lactate.

80. The combination of claim 49 where the biocompatible solvent is selected from the group consisting of DMSO, acetone, ethanol, ethyl lactate.

81. The method of claim 60 where the biocompatible polymer compositions comprise a biocompatible polymer component and a biocompatible solvent, said biocompatible polymer component selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid.

82. The method of claim 81 where the biocompatible solvent is selected from the group consisting of DMSO, acetone, ethanol, ethyl lactate.

83. The balloon catheter section of claim 76 where the biocompatible polymer composition comprises a biocompatible polymer component and a biocompatible solvent, said biocompatible polymer component selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyacrylates, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid.

84. The balloon catheter section of claim 83 where the biocompatible solvent is selected from the group consisting of DMSO, acetone, ethanol, ethyl lactate.