Patent Publication Number: US-2017354524-A1

Title: Multilayer balloons

Description:
This application claims the benefit of U.S. Provisional Application No. 62/347,118, entitled, “MULTILAYER BALLOON OPTIMIZING MATERIAL CAPABILITIES,” which was filed on Jun. 8, 2016 and is incorporated by reference herein in its entirety. 
    
    
     TECHNICAL FIELD 
     This disclosure relates to medical devices including balloons. 
     BACKGROUND 
     Catheters may be used in intravascular procedures or other procedures to facilitate minimally invasive access to a target site. For example, an angioplasty catheter may include balloons mounted to the catheter that may be advanced to the target site and inflated to clear or compress a blockage, for example a stenosis. As another example, a stent delivery catheter may include a stent positioned over a balloon, which may be inflated to deploy the stent. 
     SUMMARY 
     Example medical devices include multilayer balloons are described herein. In some examples, an example balloon includes an inner layer, and an outer layer coextruded on the inner layer. The outer layer has a maximum radial ratio that is lower than that of the inner layer. 
     Clause 1: In some examples, a medical device includes a balloon inflatable to an inflated configuration. The balloon includes an inner layer and an outer layer coextruded on the inner layer. The outer layer has a maximum radial ratio that is lower than that of the inner layer. 
     Clause 2: In some examples of the medical device of clause 1, the inner layer has a first maximum radial ratio of up to 8.5, and the outer layer has a second maximum radial ratio of up to 6.5. 
     Clause 3: In some examples of the medical device of clauses 1 or 2, the inner layer includes a first material having a first glass transition temperature, and the outer layer includes a second material having a second glass transition temperature higher than the first glass transition temperature. 
     Clause 4: In some examples of the medical device of any one of clauses 1 to 3, the inner layer has a lower Shore durometer hardness than that of the outer layer. 
     Clause 5: In some examples of the medical device of any one of clauses 1 to 4, the inner layer is more flexible than the outer layer. 
     Clause 6: In some examples of the medical device of any one of clauses 1 to 5, the balloon has a wall thickness of less than 0.0635 mm (0.0025 inches). 
     Clause 7: In some examples of the medical device of clause 6, the balloon has a burst pressure of at least 1013 kPa (10 atmospheres). 
     Clause 8: In some examples of the medical device of clause 7, the balloon has a burst pressure of at least 4053 kPa (40 atmospheres). 
     Clause 9: In some examples of the medical device of any one of clauses 1 to 8, the inner layer has a lower stiffness than the outer layer. 
     Clause 10: In some examples of the medical device of any one of clauses 1 to 9, the outer layer includes a biaxially oriented thermoplastic. 
     Clause 11: In some examples of the medical device of clause 10, the biaxially oriented thermoplastic includes one or more of a polyamide, a nylon 12, a nylon 6/12, a nylon 610, a nylon 612, or a nylon 1010, a polyester, a polyethelene terephthalate, or a polyurethane. 
     Clause 12: In some examples of the medical device of any one of clauses 1 to 11, at least one of the inner layer or the outer layer includes a thermoplastic elastomer. 
     Clause 13: In some examples of the medical device of clause 12, the thermoplastic elastomer includes a polyether block amide (PEBA). 
     Clause 14: In some examples, a system includes the medical device of any one of clauses 1 to 13 and a second medical device secured to the balloon. 
     Clause 15: In some examples of the system of clause 14, the second medical device includes a stent crimped to the balloon. 
     Clause 16: In some examples, the medical device of any one of clauses 1 to 15 further includes an elongated member. The balloon is mounted to the elongated member, and the elongated member includes a catheter body. 
     Clause 17: In some examples, a medical device includes a balloon inflatable to an inflated configuration. The balloon includes an inner layer and an outer layer coextruded on the inner layer. The inner layer includes a first material having a first glass transition temperature. The outer layer includes a second material having a second glass transition temperature higher than the first glass transition temperature. The balloon has a wall thickness of less than 0.0635 mm (0.0025 inches), and a burst pressure of at least 4053 kPa (40 atmospheres). 
     Clause 18: In some examples of the medical device of clause 17, the inner layer has a first maximum radial ratio of up to 8.5, and the outer layer has a second maximum radial ratio of up to 6.5. 
     Clause 19: In some examples, a method includes coextruding an outer layer on an inner layer to form an elongated tube, the outer layer has a maximum radial ratio that is lower than that of the inner layer; and forming a balloon by at least expanding the elongated tube within a mold defining a predetermined outer diameter of the balloon. 
     Clause 20: In some examples of the method of clause 19, forming the balloon further includes molding the inner layer and the outer layer over a scaffold. 
     Clause 21: In some examples of the method of clause 19 or 20, forming the balloon further includes heat-setting the balloon. 
     Clause 22: In some examples, the method of any one of clauses 19 to 21 further includes securing a medical device to the balloon. 
     Clause 23: In some examples of the method of clause 22, securing the medical device to the balloon includes crimping a stent to the balloon. 
     Clause 24: In some examples, a method includes introducing a balloon into vasculature of a patient, and after introducing the balloon into the vasculature, pressurizing the balloon to an operational pressure. The balloon includes an outer layer coextruded on an inner layer, the outer layer having a maximum radial ratio that is lower than that of the inner layer. 
     Clause 25: In some examples, the method of clause 24 further includes, after pressurizing the balloon, deflating the balloon, and withdrawing the balloon from the vasculature. 
     Clause 26: In some examples of the method of claim  24  or  25 , the balloon may be any one of the balloons of clauses 1 to 18. 
     The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic and conceptual side view of an example medical device including an elongated member and a balloon. 
         FIG. 2  is a schematic and conceptual partial side view of the example medical device of  FIG. 1  further including a second medical device secured to the balloon. 
         FIG. 3  is a schematic and conceptual cross-sectional view of the balloon of  FIG. 1 , in an inflated configuration, where the cross-section is taken in a direction orthogonal to a longitudinal axis of the medical device. 
         FIG. 4  is a schematic and conceptual cross-sectional view of a mold including a tube being inflated to form the balloon of  FIG. 3 . 
         FIG. 5  is a flow diagram illustrating an example technique for preparing an example balloon. 
         FIG. 6  is a flow diagram illustrating an example technique for using an example balloon in a procedure. 
         FIG. 7  is a graph illustrating a relationship between burst pressure and wall thickness for an example single layer balloon. 
         FIG. 8A  is a histogram illustrating wall thicknesses of a sample population of double layer balloons. 
         FIG. 8B  is a histogram illustrating burst pressures a sample population of double layer balloons. 
         FIG. 8C  is a histogram illustrating outer diameters of a sample population of double layer balloons. 
         FIG. 9  is a graph illustrating probability of burst at different pressures for balloons subjected to cycling. 
     
    
    
     DETAILED DESCRIPTION 
     The disclosure describes multilayer balloons having a relatively high burst resistance at a relatively lower wall thickness compared to single layer balloons, and example techniques for forming and using multilayer balloons. 
       FIG. 1  is a schematic and conceptual side view of an example medical device  10  including an elongated member  12  and a balloon  14  mounted closer to a distal tip  16  of elongated member  12  than a proximal end of elongate member  12 . A hub  18  connected to the proximal end of elongated member  12  may allow elongated member  12  to be manipulated, advanced, or retracted, and may provide ports for communicating with lumens defined by elongated member  12 . For example, hub  18  may include an inflation arm  20  that may be connected to a source of inflating fluid to deliver inflating fluid through an inflation lumen port  22  to inflate balloon  14 , or deflate balloon  14  by withdrawing the inflating fluid. In some examples, hub  18  may include an adapter  24  configured to receive a guidewire through a guidewire lumen in elongated member  12  (not shown). In some examples, elongated member  12  may include a catheter body, for example, a balloon catheter, and hub  18  may include a catheter hub. In some examples, medical device  10  may include a rapid-exchange balloon catheter system. 
     Elongated member  12  may be advanced to a target site, for example, through a body lumen such as a blood vessel of a patient. In some examples, distal tip  16  may be introduced into the vasculature of the patient through an incision or opening, followed by a shaft of elongated member  12 . Elongated member  12  may be advanced through the body lumen, for example, over a guidewire or another guide member (e.g., a guide catheter) introduced through adapter  24  of hub  18 . In some examples, balloon  14  may be maintained in an uninflated or partly inflated configuration while advancing elongated member  12  through the vasculature. When elongated member  12  is sufficiently advanced, for example, such that balloon  14  is adjacent the target site, inflating fluid may be delivered through inflation lumen port  22  to inflate balloon  14  to an inflated configuration at the target site. 
     Balloon  14  is illustrated in an inflated configuration in  FIG. 1 . In some examples, inflation of balloon  14  may result in expansion of the vasculature, or removal of blockage, for example, clots, debris, or fat at the target site. The inflating fluid may subsequently be withdrawn through inflation lumen port  22  to result in deflation of balloon  14 , and deflated balloon  14  may be withdrawn through the vasculature by retracting elongated member  12 . 
     In some examples, balloon  14  may include one or more radiopaque markers  17 . For example, radiopaque marker  17  may include one or more radiopaque bands disposed about balloon  14 , such as one marker  17  adjacent the proximal end of balloon  14  and another marker  17  adjacent a distal end of balloon  14 , as shown in  FIG. 1 . Radiopaque marker  17  may allow a clinician to observe balloon  14  using suitable radioimaging techniques during a medical procedure, for example, while advancing or retracting balloon  14  with elongated member  12 . 
     In some examples, medical device  10  may include a second medical device  26 .  FIG. 2  is a schematic and conceptual partial side view of medical device  10  of  FIG. 1  further including second medical device  26  positioned over (e.g., co-axial with) balloon  14 , and, in some examples, secured to balloon  14 . 
     In some examples, as illustrated in  FIG. 2 , second medical device  26  may include a stent crimped to balloon  14 . Balloon  14  is illustrated in an uninflated configuration in  FIG. 2 , with the stent in an unexpanded configuration ready for deployment. In examples in which second medical device  26  is secured to balloon  14 , second medical device  26  may be advanced with balloon  14  to the target site, and balloon  14  may be inflated to deploy second medical device  26 . For example, in examples in which second medical device  26  includes a stent, inflation of balloon  14  may expand the stent to an expanded state to scaffold a region of the vasculature adjacent the stent. After deploying second medical device  26  at a target site within the patient and subsequently partially or fully deflating balloon  14 , second medical device  26  may remain in a deployed configuration at the target site, and only balloon  14  can be withdrawn from the patient. In other examples, second medical device  26  may be withdrawn with balloon  14  after balloon  14  is partly or completely deflated. 
     As shown in  FIG. 1 , balloon  14  may be defined by a balloon wall  15 , which includes more than one layer, such that balloon  14  is a multilayer balloon. An example balloon  14  and balloon wall  15  are described with reference to  FIG. 3 , which illustrates a schematic and cross-sectional view of balloon  14 , the cross-section A-A being taken in a direction orthogonal to a longitudinal axis of elongated member  12  in  FIG. 1 . 
       FIG. 3  is a schematic and conceptual cross-sectional view of balloon  14  of  FIG. 1 , in an inflated configuration. Balloon wall  15  includes outer layer  32  and inner layer  34 . In some examples, outer layer  32  defines an outermost or exterior surface of balloon  14 , while inner layer  34  defines an innermost or interior surface of balloon  14 . However, in some examples, balloon  14  may include one or more additional layers, such as one or more intermediate layers between outer layer  32  and inner layer  34 , one or more layers internal to inner layer  34 , or one or more layers external to outer layer  32 . In addition, in some examples, one or more coatings or surface treatments may be applied to outer layer  32 , such as, but not limited to, a lubricious coating, a lubricious surface treatment, or a therapeutic agent (e.g., an anti-restenotic agent). 
     While in the examples shown in  FIG. 3 , balloon  14  is illustrated as having two layers, in other examples, balloon  14  may have any number of additional layers. In some examples, one or more tie layers may be provided between adjacent layers of balloon  14 . A tie layer is a layer that may tie or bond adjacent layers together, for example, layers that may be incompatibly or have low joinability or adhesion. For example, one or more tie layers may be coextruded with other layers of balloon  14  to facilitate bonding of the other layers to each other. In some examples, a tie layer may include one or more materials described with reference to outer layer  32  or inner layer  34 . 
     While in the example shown in  FIG. 3 , balloon  14  is illustrated having a circular cross-section, in other examples, balloon  14  may have any suitable shape, configuration, or cross-sectional shape. In some examples, balloon  14  may have a geometrically similar shape in an uninflated and an inflated configuration. For example, balloon  14  may be cylindrical in both uninflated and inflated configurations. In some examples, balloon  14  may have different shapes in uninflated and inflated configurations. For example, balloon  14  may be folded or otherwise have a compact uninflated configuration and may define a cylindrical or another shape in an inflated configuration. 
     Outer layer  32  and inner layer  34  may be formed of an inflatable material, for example, a polymer material that reversibly expands when subject to an inflation pressure. Outer layer  32  and inner layer  34  may have different compositions, which may provide outer layer  32  and inner layer  34  with relative differences in one or more of maximum radial ratio, compliance, stiffness, or hardness. These differences may affect properties of balloon  14 , such as burst resistance, and deliverability, as described in the disclosure. 
     The maximum radial ratio of a layer of balloon  14  may depend on the orientability of the layer. In some examples described herein, one or more layers of balloon  14  may include one or more polymeric materials. A layer including a polymeric material may exhibit an internal orientation, for example, an orientation arising from alignment of polymer chains along substantially the same direction. For example, when a polymeric material is heated to a temperature above the glass transition temperature of the polymeric material, polymer chains in the material may substantially realign along a direction in response to stress applied along that direction. If the polymeric material is then cooled sufficiently rapidly to prevent relaxation of the polymeric chains, the alignment of the polymeric chains will be maintained. Such alignment may increase the crystallinity within a polymeric material. For example, the crystallinity of a region of a polymeric material may be indicative of the extent of orientation within that region, a relatively higher crystallinity being indicative of a relatively higher orientation. The orientation or crystallinity may be determined using any suitable technique, for example, by x-ray diffraction, birefringence analysis, or the so-called Chrysler test. 
     The internal orientation within outer layer  32  or inner layer  34  of balloon  14  may be affected by the heat, pressure, and stretching used to form balloon  14 . In some examples, balloon  14  may be formed by expanding a tube including outer layer  32  and inner layer  34  in a mold while subjecting the tube to predetermined pressure, temperature, and radial or axial stretching. The respective internal orientations of outer layer  32  and inner layer  34  of balloon  14  may affect properties such as compliance and burst pressure of balloon  14 . 
     The orientation of a layer of balloon  14  may be characterized in terms of a radial ratio of the layer. The radial ratio of a layer of balloon  14  is a ratio of the outer diameter of a fully expanded tube including the layer in the mold to the inner diameter of the layer (before expanding the tube in the mold during formation of balloon  14  from the tube). For example, if the outer diameter of the fully expanded tube is OD expanded , and if the inner diameter of the tube before the expansion is ID initial , then the radial ratio RR can be determined as RR=OD expanded /ID initial . In some examples, the outer diameter of the fully expanded tube may be substantially the same as an inner diameter defined by the mold which constrains the tube as it is expanded (which can also be referred to as “blown”). While the radial ratio of a layer of balloon  14  may depend on the conditions under which balloon  14  was formed, the radial ratio may be indicative of the structural configuration of the layer after forming balloon  14 , for example, the degree of orientation of material within the layer. For example, a layer having a relatively higher radial ratio may exhibit higher orientation compared to another layer having a relatively lower radial ratio. 
     A maximum radial ratio of a layer is the highest radial ratio to which a layer may be expanded before it ruptures or tears during expanding. For example, if the outer diameter at which the expanded layer begins to rupture during the formation of balloon  14  from the tube is OD rupture , and if the inner diameter of the tube before the expansion is ID initial , then the maximum radial ratio RR max  can be determined as RR max =OD rupture /ID initial . The maximum radial ratio RR max  that a layer of balloon  14  is capable of enduring depends on the composition of the layer. For example, a layer having a particular composition may rupture or tear if the layer is expanded beyond a maximum radial ratio during formation of balloon  14  from the tube. A layer that has a relatively higher orientability can sustain a relatively greater expansion, because such a layer exhibits a higher degree of realignment of polymer chains, allowing for more expansion without rupture or tearing. Thus, a higher maximum radial ratio is indicative of a higher orientability, because a layer with a relatively higher maximum radial ratio can be blown to a relatively higher radial ratio without compromising the structural integrity of the layer of the balloon during expanding. 
     The radial ratio RR to which a layer of balloon  14  is actually subjected to without rupture or tearing during forming of the balloon may be any predetermined radial ratio RR less than the maximum radial ratio RR max . While the radial ratio of a layer of balloon  14  prepared by expanding a tube including the layer in a mold depends on the inner diameter defined by the mold, the maximum radial ratio of the layer is independent of the inner diameter defined by the mold. The maximum radial ratio of the layer depends on the thickness and the composition of the layer in the tube before the tube is expanded to form the balloon. 
     The burst resistance and ease of inflation of balloon  14  during use (e.g., during a medical procedure) may depend on the relative maximum radial ratios of outer layer  32  and inner layer  34 . For example, balloon  14  may include outer layer  32  having a maximum radial ratio that is lower than the maximum radial ratio of inner layer  34 . In some such examples, balloon  14  may have the same wall thickness as a single layer balloon, but have a relatively higher burst strength than the single layer balloon. A higher burst strength of a balloon can result in an ability to withstand higher inflation pressures. Alternatively, in some such examples, balloon  14  may have a wall thickness less than a walk thickness of a single layer balloon, while having the same or similar burst strength as the single-layer balloon. For example, a single layer balloon including GRILAMID L25 (a film extrusion grade of polyimide (nylon) 12, available from EMS-Grivory, Domat/Ems, Switzerland) may require a wall thickness of about 0.2667 mm (0.0105 inches) to achieve a burst pressure of about 4255.6 kPa (42 atmospheres), and balloon  14  including two or more layers (for example, outer layer  32  including GRILAMID L25, and inner layer  34  including PEBAX 7033 (a thermoplastic elastomer made of flexible polyether and rigid polyamide, available from Arkema, Paris, France) may achieve the same burst pressure with a significantly lower wall thickness such as about 0.0584 mm (0.0023 inches). For a given wall thickness, balloon  14  may have a higher burst strength than a multilayer balloon that does not include an outer layer having a maximum radial ratio that is lower than a maximum radial ratio of an inner layer. 
     A maximum radial ratio RR max  of a layer of balloon  14  can be determined as RR max =OD rupture /ID initial , where OD rupture  is the outer diameter of balloon  14  at which the expanded layer begins to rupture during the formation of balloon  14 , and where ID initial  is the initial inner diameter of the layer before expansion to form balloon  14 . In some examples, outer layer  32  may have a maximum radial ratio lower than that of inner layer  34 . For example, inner layer  34  may have a first maximum radial ratio, and outer layer  32  may have a second maximum radial ratio lower than the first maximum radial ratio. The first maximum radial ratio may be determined by the ratio RR max =OD rupture /ID initial  for inner layer  34 . The second maximum radial ratio may be determined by the ratio RR max =OD rupture /ID initial  for outer layer  32 . In some examples, the first maximum radial ratio may be greater than 2, 3, 4, 5, 6, 7, or 8, and the second maximum radial ratio may be greater than 1, 2, 3, 4, 5, or 6. For example, when the first maximum radial ratio of inner layer  34  is 6, the second radial ratio of outer layer  32  may be 5. In such an example, outer layer  32  having RR max =5 is capable of expanding during forming balloon  14  to provide balloon with an outer diameter of up to 5 times that of initial inner diameter ID initial  of outer layer  32  (without exhibiting rupture or tearing during the formation of balloon  14 ). Similarly, in such an example, inner layer  34  having RR max =6 is capable of expanding during forming balloon  14  to provide balloon with an outer diameter of up to 6 times that of initial inner diameter ID initial  of inner layer  34  (without exhibiting rupture or tearing during the formation of balloon  14 ). In some examples, the first maximum radial ratio of inner layer  34  may be up to 8.5, and the second maximum radial ratio of outer layer  32  may be up to 6.5. In some examples, the first maximum radial ratio of inner layer  34  may be higher than the second maximum radial ratio of outer layer  32  by at least 0.2, or 0.5, or 1, or 1.5, or 2. 
     Outer layer  32  and inner layer  34  may be formed from materials having different compositions to provide the different maximum radial ratios. Without being bound by theory, a material having a relatively lower glass transition temperature or lower melt temperature may be more orientable, and may have a higher maximum radial ratio, than a material having a relatively higher glass transition temperature or melt temperature. For example, inner layer  34  may include a first material having a first glass transition temperature, and outer layer  32  may include a second material having a second glass transition temperature higher than the first glass transition temperature. 
     In the case of polymeric materials, the glass transition temperature of a material may be indicative of the hardness or the stiffness of the material. Without being bound by theory, a layer having one or both of a lower hardness, a lower stiffness, or higher flexibility, relative to another layer may have a higher maximum radial ratio than the other layer. The hardness of a balloon layer may be the resistance of the layer to local deformation (for example, fracture, cracking, or tearing) initiated at a surface region. The stiffness of a balloon layer may be the resistance of the balloon layer to deformation by an applied force or pressure, and is indicative of the propensity of the layer to return to an original shape after the applied force or pressure is removed. 
     In some examples, a relatively higher glass transition temperature may be indicative of higher hardness. A material having a relatively lower glass transition temperature or a relatively lower melting temperature may be relatively softer than a material having a relatively higher glass transition temperature or a relatively higher melting temperature. A softer material may be able to endure a higher radial ratio, for example, by having a higher maximum radial ratio than a harder material. In these examples, inner layer  34  may include a material having a glass transition temperature or a melting temperature respectively lower than the glass transition temperature or the melting temperature of outer layer  32  by at least about 10° C. to about 30° C. or greater, such as by at least about 10° C., 15° C., about 20° C., or about 30° C. 
     While the relative hardness of different materials can be compared in terms of their glass transition temperatures, hardness may also be evaluated in terms of Shore hardness established using a durometer. The shore hardness may include Shore A hardness (for relatively softer materials) or Shore D hardness (for relatively harder materials) as appropriate. In some examples, inner layer  34  has a lower Shore durometer hardness than that of outer layer  32 . For example, outer layer  32  may have a hardness of about 74 Shore D, and inner layer  34  may have a hardness of about 40 Shore D, although layers  32 ,  34  may have other Shore durometer hardnesses in other examples. The Shore durometer hardness may be determined using a durometer and one or both of the Shore A hardness scale or the Shore D hardness scale. In some examples, inner layer  34  is more flexible than outer layer  32 . In some examples, inner layer  34  has a lower stiffness than outer layer  32 . 
     The compliance of a balloon layer is the degree or extent to which a balloon expands in response to inflation pressure. A relatively compliant layer (also called a compliant layer herein) is a layer including a material that inflates, deflates or deforms without resulting in mechanical failure of the material. A compliant layer, for example, a layer including a polyether block amide (PEBA) may exhibit stretching in response to an inflationary pressure. In contrast, a non-compliant layer, for example, a layer including a high density polyethylene (HDPE) may exhibit reduced or relatively no stretching compared to a compliant layer. Thus, a non-compliant layer may be a layer that has lower flexibility, lower softness, higher rigidity, or non-compliance to expansion or inflation compared to a compliant layer, for example, resulting in mechanical failure of the material in response to inflation or deformation beyond a predetermined threshold. 
     Whether a layer is compliant or non-compliant may depend on the composition, hardness, and dimensions, for example, thickness, of the layer. Compliance may be measured, for example, by measuring radial expansion of a layer as a ratio of inflation pressure. In some examples, a compliant layer may exhibit an expansion greater than about 10 millimeters/atmospheres (mm/atm), or greater than about 20 millimeters/atmospheres, or greater than about 50 millimeters/atmospheres. In some examples, a non-compliant layer may exhibit an expansion lower than about 0.02 mm/atm, or lower than about 0.01 mm/atm, or lower than about 0.001 mm/atm. A semi-compliant layer may exhibit an expansion greater than about 0.02 mm/atm and less than about 10 mm/atm. In some examples, inner layer  34  may include a compliant or a semi-compliant layer. In some examples, inner layer  34  may be more compliant than outer layer  32 . 
     The layers of balloon  14  may be formed from any suitable materials that provide the properties described herein. In some examples, one or both of outer layer  32  and inner layer  34 , or another layer of balloon  14 , may include one or more of a thermoplastic, an elastomer, or an elastomeric thermoplastic. In some examples, one or both of outer layer  32  and inner layer  34 , or another layer of balloon  14 , may include one or more of acrylonitrile-butadiene styrene (ABS), polyamides, for example, nylons, polyamide 6 (PA 6), or polyamide 66 (PA 66), polycarbonates (PC), polyethylenes (for example, high density polyethylenes (HDPE) or low density polyethylenes (LDPE)), poly(methyl methacrylate) (PMMA), polyoxymethylene (POM), polypropylenes (PP), polystyrenes (PS), polybutylene terephthalate (PBT), styrene acrylonitrile resin (SAN), thermoplastic elastomers (TPE) (for example, polyether block amides (PEBAs)), polyphenylene sulfide (PPS), polyetheretherketones (PEEK), polyurethanes, polyesters, or blends, copolymers, or coextrusions thereof. For example, one or more of outer layer  32  and inner layer  34  may include sublayers, for example, coextruded layers. In some examples, the TPEs (or PEBAs) may include materials sold under the PEBAX® brand name (Arkema, Paris, France) or VESTAMID (Evonik Industries, Essen, Germany). In some examples, the thermoplastic may include materials sold under the GRILAMID® brand name (EMS-Grivory, Domat/Ems, Switzerland), which includes amide thermoplastics. 
     In examples in which balloon  14  includes coextruded outer layer  32  and inner layer  34 , outer layer  32  and inner layer  34  may be fused to each other at respective interfaces as a result of the coextrusion. The fusion may help outer layer  32  and inner layer  34  resist delamination from each other, e.g., during inflation of balloon  14  during a medical procedure. 
     In some examples, outer layer  32  includes a biaxially oriented thermoplastic. For example, the biaxially oriented thermoplastic may include one or more of a polyamide, a nylon 12, a nylon 6/12, a nylon 610, a nylon 612, or a nylon 1010, a polyester, a polyethelene terephthalate, or a polyurethane. In some examples, one or both of outer layer  32  and inner layer  34  includes a thermoplastic elastomer. For example, the thermoplastic elastomer may include a polyether block amide (PEBA). Any suitable combination of materials may be used for outer layer  32  and inner layer  34 . For example, outer layer  32  may include PEBAX 7033 when inner layer  34  includes PEBAX 6333, outer layer  32  may include PEBAX 6333 when inner layer  34  includes PEBAX 5533, or outer layer  32  may include PEBAX 7433 when inner layer  34  includes PEBAX 4033. In some examples, outer layer  32  includes GRILAMID L25 and inner layer  34  includes PEBAX 7033. In such examples, outer layer  32  may have a maximum radial ratio of at least about 5 or 6, and inner layer  34  may have a maximum radial ratio of at least about 6 or 7. In some examples in which outer layer  32  includes GRILAMID L25 and inner layer  34  includes PEBAX 7033, the ratio of the tensile strength (for example, ultimate tensile strength) of the inner layer to that of the outer layer is about 1.75, while achieving a burst pressure (for example, 4255.65 kPA, or 42 atm) similar to the burst pressure of a single layer balloon including GRILAMID 25, and while having a wall thickness (for example, 0.0584 mm, or 0.0023 inches) that is 4.5 times thinner than the wall thickness of the single layer balloon. 
     Outer layer  32  and inner layer  34  may have any suitable thickness subject to the wall thickness of wall  15  of balloon  14  and to the respective radial ratios of outer layer  32  and inner layer  34 . In some examples, inner layer  34  may have a thickness that is between 5% and 50% of the thickness of wall  15  (“T” in  FIG. 3 ). In some examples, the thicknesses for outer layer  32  and inner layer  34  may vary within respective ranges, for example, between 10% and 40% of thickness T of wall  15  for inner layer  34 , and between 60% and 90% of thickness T of wall  15  for outer layer  32 . The relative thicknesses of outer layer  32  and inner layer  34  may depend on materials and performance requirements. The wall thickness T of wall  15  is the shortest distance between the exterior surface of balloon  14  and the interior surface of balloon  14 . For example, the wall thickness T is half the difference between the outer diameter of balloon  14  and the inner diameter of balloon  14 . Thus, the wall thickness may be measured across wall  15  along any line extending through a center of balloon  14 , or along a line extending along a normal to a surface of balloon  14 . In some examples, balloon  14  has a wall thickness of less than 0.0635 mm (0.0025 inches). For example, balloon  14  may have a wall thickness of less than 0.05842 mm (0.0023 inches), or less than 0.0508 mm (0.002 inches), or less than 0.0381 mm (0.0015 inches), or less than 0.0254 mm (0.0010 inches). In some examples, balloon  14  has a burst pressure of at least 1013.25 kPa (10 atmospheres, atm). For example, balloon  14  may have a burst pressure of at least 1519.88 kPa (15 atm), or at least 2026.5 kPa (20 atm), or at least 2533.13 kPa (25 atm), or at least 3039.75 kPa (30 atm), or at least 4053 kPa (40 atm), or at least 4255.65 kPa (42 atm). Balloon  14  may have the aforementioned burst pressures in examples in which balloon has the wall thickness of less than 0.0635 mm (0.0025 inches). For example, balloon  14  may have a thickness of less than or equal to 0.05842 mm (0.0023 inches) and a burst pressure of at least 4053 kPa (40 atm). 
     In some examples, a compliance of a layer of balloon  14  may be reduced by adding components, for example, reinforcing material or fibers that resist stretching or inflation. For example, one or both of outer layer  32  or inner layer  34  may include one or more reinforcing components, materials, or fibers. In some examples, the reinforcing components may include one or more of glass, metal, alloy, carbon, or polymers. 
     The multilayer configuration of balloon  14  shown in  FIG. 3  may exhibit higher burst or puncture resistance compared to a single layer balloon having the same respective effective wall thickness as respective balloon wall  15  of balloon  14 . Thus, example multilayer balloons according to the disclosure may be used in procedures where robustness and puncture-resistance of balloons is desired, while having relatively lower wall thickness. 
     Balloon  14 , as well as other example multilayer balloons according to the disclosure, including an outer layer and an inner layer having a higher maximum radial ratio than that of the outer layer can be formed using any suitable technique. For example, balloon  14  may be formed using any suitable mold assembly, for example, a mold assembly including mold  38  shown in  FIG. 4 .  FIG. 4  is a schematic and conceptual cross-sectional view of mold  38 , in which a tube  13  can be expanded to form balloon  14  of  FIG. 3 . Tube  13  is positioned within mold  38  in the example shown in  FIG. 4 . A mold assembly (not shown) including mold  38  may be used to form balloon  14  from tube  13 , for example, by expanding tube  13  under predetermined conditions (e.g., predetermined conditions of temperature, pressure, and stretching) within mold  38  of the mold assembly. Thus, tube  13  is a structure from which balloon  14  may be formed. 
     Mold  38  is substantially rigid, and an inner surface  39  of mold  38  constrains tube  13  as it is expanded under the predetermined conditions of temperature, pressure, and stretching. Mold  38  may be formed of any suitable material including one or more of a metal, an alloy, a ceramic, a glass, or a plastic, or another rigid material capable of constraining the expansion of tube  13  beyond mold inner diameter ID m . Mold  38  defines the shape of balloon  14  formed by expanding tube  13 . In some examples, mold  38  may be substantially cylindrical, and tube  13  expanded within cylindrical mold  38  may form a substantially cylindrical balloon  14 . However, mold  38  may have any suitable shape complementary to a target shape of balloon  14  formed from tube  13 . For example, one or more portions of mold  38  may define conical surfaces, or dome-shaped surfaces, or other curved or flat surfaces to respectively define conical, dome-shaped, or other curved or flat surfaces of balloon  14 . In some examples, the ends of mold  38  may define conical portions, and the portion of mold  38  extending between the ends may define a cylindrical portion. Mold  38  may also include a substrate, for example a mandrel, on which tube  13  may extruded or positioned and held during expansion within mold  38 . 
     Prior to being expanded within mold  38 , tube  13  may include an initial configuration of outer layer  32  and inner layer  34 . In an initial configuration (prior to expansion within mold  38 ), tube  13  includes coextruded outer layer  32  and inner layer  34  in an unblown or non-stretched configuration. In the initial configuration shown in  FIG. 4 , outer layer  32  has a first inner diameter ID 1 , and inner layer  34  has a second inner diameter ID 2 . Mold  38  defines an inner surface  39  having a mold inner diameter ID m . 
       FIG. 5  is a flow diagram illustrating an example technique for manufacturing balloon  14 . The example technique of  FIG. 5  is described with reference to mold  38  of  FIG. 4 . However, the example technique of  FIG. 5  may be implemented using any suitable mold. In some examples, the example technique of  FIG. 5  may include coextruding outer layer  32  on inner layer  34  ( 40 ). For example, respective heated, flowable, or molten compositions for outer layer  32  and inner layer  34  may be coextruded from an extrusion die onto a substrate, for example, a mandrel. Coextrusion of multiple layers may result in a uniform balloon structure. For example, coextruding layers of balloon  14  simultaneously may provide respective layers with a substantially uniform layer thickness and thus uniform thickness of wall  15  along a length of balloon  14 . In some examples, providing a uniform thickness to wall  15  may provide balloon  14  with a substantially uniform diameter along a longitudinal axis in an inflated configuration. 
     The example technique of  FIG. 5  may include coextruding tube  13  including outer layer  32  and inner layer  34 . In other examples, outer layer  32  and inner layer  34  may be coextruded as a multilayer sheet, for example, by coextruding onto a flat substrate, and tube  13  may be subsequently formed from the sheet. 
     In other examples of the technique shown in  FIG. 5 , outer layer  32  and inner layer  34  may be sequentially extruded. In some examples, a pair of layers may be coextruded, followed by extrusion of another layer. For example, outer layer  32  and inner layer  34  may be coextruded, followed by extrusion of another layer on the coextruded structure. In some examples, inner layer  34  may be extruded, followed by extrusion of outer layer  32  on inner layer  34 . In some examples, the order of layers during extrusion or coextrusion may be different from the order of layers in balloon  14 . For example, in examples in which balloon  14  includes three or more layers, pairs or groups of layers may be coextruded, and reordered, stacked or otherwise combined in a mold followed by pressurizing in the mold to eventually form balloon  14 . 
     Balloon  14  may be formed from multilayer tube  13  or a multilayer sheet including outer layer  32  and inner layer  34  ( 42 ). For example, tube  13  may be placed or secured in mold  38  configured to provide the shape of balloon  14 , as shown in  FIG. 4 . Tube  13  may be blown by applying pressure in addition to axial or radial stretching, so that tube  13  expands to occupy the periphery of the mold and contacts inner surface  39 . Tube  13  may be heated to a temperature greater than one or both of the respective glass transition temperatures of outer layer  32 , or inner layer  34 , or another suitable temperature, to soften tube  13 . Blown tube  13  may expand to an outer diameter substantially the same as mold inner diameter ID m  defined by mold  38  before tube  13  is cooled or otherwise cured or solidified. The ratio ID m /ID 1  may define a radial ratio of outer layer  32 , and the ratio ID m /ID 2  may define a radial ratio of inner layer  34 . As described in the disclosure, the ratio of inner diameter ID 2  of tube  13  to the mold inner diameter ID m  may be linked to the respective internal orientations within outer layer  32  and inner layer  34  in the final balloon  14 . One or more of ID m , ID 1 , or ID 2  may be selected such that the respective radial ratios of outer layer  32  and inner layer  34  are less than the respective maximum radial ratios of outer layer  32  and inner layer  34 , for example, to prevent premature rupture, tearing, or burst of balloon  14  during manufacture of balloon  14 . 
     In some examples, the respective compositions for outer layer  32  and inner layer  34  may be directly coextruded into mold  38 , so that balloon  14  is shaped during coextrusion. In some examples, one or both of inner layer  34  or outer layer  32  may be extruded onto a reinforcing substrate, for example, a reinforcing fabric, an or an arrangement of reinforcing components or fibers. In some examples, reinforcing components may be introducing during the coextrusion. 
     The coextruding ( 40 ) may include stretching balloon  14 , for example, one or both of axial or radial stretching. For example, a region or side of balloon  14  may be intermittently heated or stretched during or after the coextruding. In some examples, the stretching may include double stretching, or stretching balloon  14  from two sides. In some examples, the stretching may include a primary stretching at a first pressure followed by a secondary stretching at a second pressure. The stretching may promote a uniform wall thickness and promote uniform inflation of balloon  14 . 
     In some examples, the example technique of  FIG. 5  includes heat-setting balloon  14  ( 44 ). In some examples, heat-setting may include annealing, for example, heating and maintaining balloon  14  at a predetermined temperature for a predetermined period of time. The predetermined temperature may be near or above a melt transition of one or both of outer layer  32  or inner layer  34 , or near or above a glass transition temperature of one or more polymers in one or both of outer layer  32  or inner layer  34 . Heat-setting may help remove creases, wrinkles, or marks from surfaces of balloon  14 , and may further provide a uniform thickness to a wall of balloon  14 , for example, wall  15  of balloon  14 . For example, heat-setting may also be used to control the wall thickness of wall  15  of balloon  14 . 
     Heat-setting may be performed using any suitable technique. For example, balloon  14  may be heated in mold  38 , such that the heat-setting may provide a permanent set or shape for balloon  14 . Heat-setting may be used to control compliance of one or both of outer layer  32  or inner layer  34 , or overall compliance and burst resistance of balloon  14 . In some examples, the configuration of balloon  14  as molded and heat-set may correspond to an uninflated configuration of balloon  14 . In some examples, the configuration of balloon  14  as molded and heat-set may correspond to an inflated configuration of balloon  14 . 
     In some examples, the example technique of  FIG. 5  may further include securing second medical device  26  to balloon  14 . For example, in examples in which second medical device  26  includes a stent, securing second medical device  26  to the balloon may include crimping the stent to balloon  14 . 
     In some examples, the example technique of  FIG. 5  may further include mounting balloon  14  to elongated member  12  ( 46 ). For example, elongated member  12  may include a catheter body, and balloon  14  may be mounted to the catheter body. 
     While the example technique of  FIG. 5  may be used to prepare balloon  14 , other techniques for forming balloon  14  may be used in other examples. 
       FIG. 6  is a flow diagram illustrating an example technique for using balloon  14  in a procedure. In some examples, the example technique of  FIG. 6  includes introducing balloon  14  into vasculature of a patient ( 50 ). For example, distal tip  16  of elongated member  12  may be introduced at an incision or body opening and into the vasculature, followed by the shaft of elongated member  12  carrying balloon  14 . In some examples, introducing balloon  14  into the vasculature ( 50 ) may include advancing balloon  14  carried on elongated member  12  over a guidewire or other guide member through the vasculature to a target site within the vasculature. In examples in which balloon  14  includes radiopaque marker  17 , a clinician may use radiopaque marker  17  to visualize the position of balloon  14  relative to the target site within the vasculature, for example, by radioimaging. 
     After balloon  14  arrives at the target site, balloon  14  may be inflated, such as by pressurizing the balloon to an operational pressure ( 52 ). The operational pressure may be a pressure sufficient to inflate balloon  14  to an operational dimension, for example, an operational diameter. For example, the operational diameter may be an average diameter of balloon  14  in an inflated configuration that is sufficient to expand, clear, or scaffold a region of the vasculature adjacent the target site. In some examples, the operational diameter may be a diameter sufficient to deploy second medical device  26  at the target size, for example, by causing second medical device  26  to expand, move, or decouple from balloon  14  or elongated member  12 , and occupy the target site. 
     In some examples, the example technique of  FIG. 6  includes, after the pressurizing ( 52 ), deflating balloon  14  ( 54 ). A clinician may, for example, withdraw inflating fluid from inflating lumen port  22  to cause balloon  14  to depressurize and contract, shrink, collapse, fold, or otherwise attain a compact configuration allowing safe withdrawal of balloon  14   a  from the vasculature. After deflating balloon  14  ( 54 ), the clinician may withdraw balloon  14  from the vasculature ( 56 ). For example, elongated member  12  carrying balloon  14  may be withdrawn from the vasculature. 
     While the example technique of  FIG. 6  is described with respect to the vasculature, the example technique of  FIG. 6  may be used to advance and deploy balloon  14  at a target site within any body lumen accessible through a body opening or incision. Thus, an example technique for using balloon  14  has been described with reference to  FIG. 6 . 
     Thus, the disclosure describes multilayer balloons with higher burst resistance at lower wall thicknesses compared to single layer balloons, and techniques for forming and using multilayer balloons. Balloons having a higher burst pressure may be more robust than balloons having relatively lower burst pressure, for example, by resisting rupture or tearing during transport to or deployment at the target site. In some examples, achieving the high burst pressure with relatively low wall thickness may provide example balloons according to the disclosure with increased deliverability to a target site within a patient, for example, a target site within vasculature of the patient. For example, providing a low wall thickness may allow the balloon to be relatively low profile and flexible, enabling the balloon to conform to bends and exhibit relatively low resistance to travel through tortuous paths of the vasculature. Providing a smaller wall thickness may also reduce the profile of the balloon, allowing the balloon to be deployed through relatively narrow lumens of the vasculature or other anatomical features. 
     In some examples, providing an inner layer with a higher maximum radial ratio than an outer layer in a balloon may provide the inner layer with increased flexibility or compliance to stretching, which may result in increased deliverability of the balloon. However, if the balloon only includes a single layer having a relatively high maximum radial ratio, then the balloon may inflate beyond a target inflation diameter. The target inflation diameter may be selected to, for example, help avoid undesirable distention of a blood vessel. In contrast, in a multi-layer balloon, providing an outer layer having a lower maximum radial ratio may help constrain inflation of the balloon to within predetermined target inflation diameters. For example, providing the outer layer of a multilayer balloon with a lower maximum radial ratio may make the outer layer relatively harder and less compliant than the inner layer, and the outer layer may resist and prevent inflation of the balloon beyond the target inflation diameter. Thus, in some examples, even if a clinician attempts to exert relatively high inflation pressure on an example balloon according to the disclosure, the balloon may not exhibit significant change in the diameter beyond the target inflation diameter. 
     The example multilayer balloons described herein may be a part of any suitable medical device, and can be used for any suitable medical procedure, such as, but not limited to, angioplasty (e.g., plain balloon angioplasty (POBA)), stent delivery, heart valve delivery, other dilatation uses, vascular occlusion, and the like. 
     EXAMPLES 
     Comparative Example 1 
     The relation between pressure at burst and wall thickness for single layer balloons was evaluated. The balloons included nylon 12 material (Grilamid L25, available from EMS-Grivory, Domat/Ems, Switzerland). Balloons having different wall thicknesses were inflated until they burst, and the pressure at burst was recorded for each balloon. The results are shown in  FIG. 7 .  FIG. 7  is a graph illustrating a relationship between burst pressure and wall thickness for sample single layer balloons. As seen in  FIG. 7 , an increase in the burst pressure requires an increase in the wall thickness. Extrapolation indicates that a balloon wall thickness of 0.2667 mm (0.0105 inches) would be required to achieve a burst pressure of 4255.65 kPa (42 atmospheres). 
     Example 1 
     The relation between pressure at burst and wall thickness for double layer balloons was evaluated. The balloons included an inner layer of PEBAX 7033 (available from Arkema, King of Prussia, Pa.) and an outer layer of Grilamid L25. A number of example balloons were prepared by expanding a tube including the inner layer and the outer layer in a mold.  FIG. 8A  is a histogram illustrating wall thicknesses of a sample population of the double layer balloons.  FIG. 8B  is a histogram illustrating burst pressures of a sample population of the double layer balloons.  FIG. 8C  is a histogram illustrating outer diameters of a sample population of double layer balloons. 
     As respectively seen in  FIGS. 8A, 8B, and 8C , the mean double wall thickness (DWT) of the population was 0.0584 mm (0.0023 inches), the mean burst pressure was 42 atmospheres, and the mean outer diameter (OD) was 2.652 mm (0.1044 inches). Thus, a double wall thickness of 0.0584 mm (0.0023) inches was sufficient to achieve a burst pressure of 4255.65 kPa (42 atmospheres), which was significantly thinner than the wall thickness of 0.2667 mm (0.0105 inches) of the single layer balloon of COMPARATIVE EXAMPLE 1 required for a similar burst pressure. 
     Example 2 
     The effect of subjecting balloons to different pressure cycles was evaluated.  FIG. 9  is a graph illustrating probability of burst at different pressures for balloons subjected to cycling. Accelerated life testing (ALT) may be used to estimate the fatigue life of a balloon upon repeated inflation/deflation at a set pressure. Burst may be an indicator of the fatigue capability. ALT may be used to determine a statistical confidence level in the balloon meeting a certain number of cycles at certain pressure levels. As seen in  FIG. 9 , the multilayer balloon of EXAMPLE 1 is capable of sustaining 28 inflation/deflation cycles at 3141 kPa (31 Atmosphere, atm). 
     Various examples have been described. These and other examples are within the scope of the following claims.