Super elastic alloy guide wire.

ES 2 159 559 T3

DESCRIPTION

Super elastic alloy guide wire.

This invention is a surgical device. It is a guidewire for use in a catheter and is used to access the target site in a lumen system of a patient's body. The core of the guide wire is made of a high elasticity alloy, preferably a Ni-Ti alloy, which has specified phosphorus parameters, and is especially useful for accessing peripheral or soft tissue destinations. The guidewire of the invention includes coating the wire with a lubricating polymeric material to enhance its suitability for use within catheters and with the interior of the vascular lumen. The tip of the "necked" guide wire also forms a specific variant of the invention.

Catheters are increasingly used as a means of delivering diagnostic and therapeutic agents to internal sites within the human body that can be accessed through various lumen systems of the body, particularly through the vasculature. A catheter guide wire is used to guide the catheter through the flexes, loops, and leads that form the blood vessels within the body. One method of using a guidewire to direct the catheter through the twisted trajectories of these lumen systems involves the use of a torsional guidewire that is directed as a unit from a body access tip such as the femoral artery. to the region of tissue that contains the target site. The guidewire is topically bent at its distal end, and can be guided by reciprocating and advancing the guidewire along the small vessel path to the desired destination. Typically, the guidewire and catheter are advanced by alternately moving the guidewire along a distance in the path of the vessel, holding the guidewire in place, and then advancing the catheter along the axis. of the guidewire until it reaches the portion of the guidewire already advanced further into the human body.

The difficulty in accessing remote regions of the body, the periphery of the body, or soft tissues within the body such as the brain and the liver, is evident. The catheter and its related guidewire must both be flexible, to allow the combination to follow the complicated path through the tissue, yet it must be sufficiently rigid to allow the distal end of the catheter to be manipulated by the clinician from the site. external access. It is common for the catheter to be as long as a meter or more.

The catheter guide wires used to guide a catheter through the human vasculature have a number of constructions of varying flexibility. For example, US Patent Nos. 3,789,841; 4,545,390; and 4,619,274 show guidewires in which the distal end section of the wire tapers conically along its length to allow greater flexibility in that remote region of the guidewire. This is so, since the distant region is where the steepest turns are found. The tapered section of the wire is often included in a coil of wire, typically a platinum coil, to increase the column strength of the tapered wire section without significant loss of flexibility in that region and also to increase the strength of the tapered wire section. Radial capacity of the guidewire to allow fine manipulation of the guidewire through the vasculature.

Another effective guidewire design is found in US Patent No. 5,095,915 which shows a guidewire having at least two sections. The distal portion is encased in an elongated polymer sleeve having axially spaced notches to allow increased flexibility of flexing the sleeve.

Others have suggested the use of guidewires made from various superelastic alloys in an attempt to achieve some of the stated functional desires.

US Patent 4,925,445, in the name of Sakamoto et al., Suggests the use of a two-portion guidewire that has a body portion relatively high in stiffness and a distal end portion that is comparatively flexible. At least a portion of the body and the distant end portions are formed of super-elastic metal materials. Although a number of materials are suggested, including Ni-Ti alloys of 49 to 58% (atm) nickel, the patent expresses a strong preference for Ni-Ti alloys, in which the transformation between austentite and martensite is completed at a temperature of 10^°C or below. The reason given is that “for the guidewire to be useful in the human body, it must be in the range of 10^° to 20^°C due to anesthesia at a low body temperature ”. The human body temperature is typically around 37^°C.

ES 2 159 559 T3

Another document that describes a guide wire using a metal alloy having the same composition as a Ni-Ti super-elastic alloy is WO91 / 15152 (in the name of Sahatjian et al., And owned by Boston Scientific Corp .). That description suggests a guide wire made from the precursor of the Ni-Ti elastomeric alloy. Super-elastic alloys of this type are made topically by stamping an ingot of the precursor alloy, while simultaneously heating it. In the unstressed state at room temperature, such superelastic materials occur in the austenite crystalline phase and, after stress application, show tensioon-induced austenite-martensite (SIM) crystalline transformations (SIM) that produce stress behavior. nonlinear elastic. On the other hand, it is said that the guide wires described in that published application should not be subjected to heating during the drawing process. The wires are cold drawn and great efforts are made to ensure that the alloy remains well below 300 F during each stage of its manufacture. This temperature control is maintained during the guidewire grinding step to form several of its tapered sections.

US Patent 4,665,906 suggests the use of tensioon-induced martensite (SIM) alloys as constituents in a variety of different medical devices. Such devices are said to include catheters and cannulas.

US Patent 4,969,890 to Sugita et al., Suggests the production of a catheter having a main body equipped with a shape memory alloy element, and having a liquid injection means to deliver a hot liquid to allow the shape memory alloy element to regain its original configuration after it has been heated by the fluid.

US Patent 4,984,581 to Stice suggests a guidewire having a core of a shape memory alloy, the guidewire utilizing the two-way memory properties of the alloy to provide movement both tip deviation and guidewire rotation in response to a controlled chest stimulus. The controlled chest stimulus in this case is provided through the application of an alternating current RF. The selected alloy is an alloy that has a transition temperature between 36 ° C and 45 ° C. The temperature of 36 ° C is chosen due to the temperature of the human body; the 45 ° C temperature is chosen because operation at higher temperatures could be destructive to body tissue, particularly to some proteones in the body.

US Patent 4,991,602 to Amplatz et al. upon which claim 1 is based, suggests a flexible guide wire made from a shape memory alloy such as the nickel-titanium alloy known as nitinol. The guide wire is a wire that has an individual diameter along its middle course, is tapered towards each end, and has a cord or ball at each of these ends. The cordoon or ball is selected to allow ease of movement through the catheter within the vasculature. The guidewire is symmetrical, so a clinician cannot make a big choice in determining which end of the guidewire to insert into the catheter. The patent suggests that coils of wire wound on the tip of the guidewire are undesirable. The patent further suggests the use of a polymeric coating (PTFE) and an anticoagulant. The patent does not suggest that any particular type of shape memory alloy or phosphical or chemical variations of these alloys are in any way advantageous.

Another catheter guide wire using Ni-Ti alloys is described in US Patent No.^° 5,069,226, to Yamauchi, et al., Yamauchi et al. describe a catheter guide wire that uses a Ni-Ti alloy that additionally contains some iron, but is topically heat treated at a temperature of about 400^° to 500^°C to provide an extreme section showing pseudo-elasticity at a temperature of approximately 37^°C and plasticity at a temperature below about 80^°C. A variation is that only the extreme portion is plastic at temperatures below 80^°C.

United States Patent N^° 5,171,383, to Sagae, et al. shows a guidewire produced from a super-elastic alloy which is then subjected to a thermal treatment, so that the flexibility is sequentially increased from its proximal portion to its distant end portions. A thermoplastic coating or coil spring can be placed over the distal portion of the wire material. Generally speaking, the guidewire near end portion maintains a comparatively high stiffness and the distal end portion is very flexible. The extreme close section is said in the claims to have a yield stress

ES 2 159 559 T3 approximately five to seven kg / mm² and an intermediate portion of the guidewire is said in the claims to have a yield stress of about 11 to 12 kg / mm.².

European Published Patent Application 0.515.201-A1 also describes a guide wire produced at least in part from a super-elastic alloy. The publication describes a guidewire in which the most distant portion can be bent or curved into a physician-desired configuration immediately prior to use in a surgical procedure. The guide wire, next to the guide tip, is made of a super-elastic alloy. Although nickel-titanium alloys are said to be the most desirable of the class shown in that description, no particular phosphoric description of these alloys is disclosed that is more desirable than the others.

European Published Patent Application 0,519,604-A2 similarly describes a guidewire that can be produced from a super-elastic material such as nitinol. The core of the guide wire is covered with a plastic jacket, one portion of which may be hydrophilic and the other portion

Examples of Ni-Ti alloys are described in US Patent Nos. 3,174,851;

3,351,463; and 3,753,700.

None of these descriptions suggest the guidewire composition or configuration described below.

In accordance with the present invention, a suitable guidewire is provided to guide a catheter into a body lumen, the guidewire comprising an elongated flexible metal wire core of a super-elastic alloy, at least one portion being clad. of the guide wire with a lubricating polymeric material and a bonding layer being arranged between the polymeric coating and the core, where when measured in a stress-strain test at 6% strain, the alloy has an upper level (UP) of 517 ± 68.9 MPa (75 ± 10 ksi) and a lower level (LP) of 172.4 ± 51.7 MPA (25 ± 7.5 ksi) measured at 3% formation and has a residual strain (RS) of less than 0.25%.

A highly desirable variation of the guidewire of the invention comprises a long wire having a proximal section, an intermediate section, and a distant section. The guide wire can additionally have an eccentricity ratio of 1 ± 10^-4. The far end section is topically the most flexible of the sections and is at least about three centimeters long. Desirably, the flexible distal end section is tapered and is covered by a coil assembly that connects to the distal end of the guidewire at its distal tip. The coil assembly may be attached to the distal tip by soldering, perhaps then electroplating or coating the distal end section with a malleable or solderable metal, such as gold. The guidewire assembly can be coated with a polymer or other material to enhance its ability to pass through the lumen of the catheter. A lubricating polymer is placed on a "bonding" layer. The bonding layer may be a retroactively wound tubing or plasma deposition or it may be a dip or spray coating of a suitable material. The bonding layer can also be radio opaque.

The guidewire of this invention may be of a composite material, in which a distant portion of the core is a super-elastic alloy of the type described below and the closest section or sections are of another material or configuration, for example, stainless steel wire or bar, stainless steel hypotube, super-elastic alloy tube, carbon fiber tube, etc.

Ideally, there are one or more radiopaque markers placed on the guidewire, eg, at its distal tip and potentially along the length of the midsection. These markers can be used both to improve the radiopacity of the guidewire and its ability to transmit torque from the near end to the far end while maintaining a desired flexibility.

A specific variation of the guidewire of the invention includes a section of the distal guidewire having a smaller diameter "neck" or portion surrounded by larger diameter areas allowing the secure welding of a tape or wire within a coil assembly that extends beyond the distal end of the guidewire core. The included wire or tape can be bent or configured prior to insertion of the guide wire into the catheter to facilitate

ES 2 159 559 T3 the movement of the guidewire through twists in the vasculature.

Another physical variation of this invention involves the use of notches in the guidewire to improve flexibility in these sections without sacrificing the columnar strength of the guidewire.

This invention also includes a catheter apparatus made of the guidewire core and a thin-walled catheter designed to be advanced along the guidewire through the vasculature to place it in a desired location.

Brief description of the drawings

Figure 1 shows a schematic side view (not to scale) of the main components of the guidewire of the invention.

Figure 2 is a side view, in partial section, of the guidewire according to this invention, having a distal portion of a highly elastic alloy.

Figure 3 is a side view, in partial section, of an embodiment of the distal tip of the device of Figure 1.

Figure 4 is a side view, in partial section, of a second embodiment of the distal tip of the device of Figure 1.

Figure 5A is a partial sectional side view of a third embodiment of the distal tip of the device of Figure 1.

Figure 5B is a top view, in partial section, of the embodiment shown in Figure 5A.

Figure 6 is a partial side view of a midsection joint in the guidewire of the invention.

Figure 7 shows a stress-strain diagram for a Ni-Ti alloy representing objective criteria for the selection of alloys for the guidewire of the invention.

Description of the invention

Figure 1 shows an enlarged side view of a guidewire made in accordance with a highly desirable variation of the guidewire of the invention (100). The guide wire (100) is made of the wire core formed of a flexible torsional wire filament material, of the alloys described below, and has a total length typically between about 50 and 300 centimeters. The proximal section (102) preferably has a uniform diameter (along its length) of about 0.25 to 0.63 mm (0.010 to 0.025 inches), preferably 0.25 to 0.46 mm (0.010 to 0.018 inches). The relatively more flexible distal section (104) extends 3 to 30 centimeters or more from the distal end of the guidewire (100). There may be a midsection (106) that has an intermediate diameter between the diameter of the two portions of the wire that join the midsection. The midsection 106 may be continuously tapered, it may have a number of tapered sections or sections of different diameters, or it may be of a uniform diameter along its length. If the middle section (106) is of a generally uniform diameter, the core of the guidewire will form a downward neck as seen in (108). The distal section (104) of the guide wire (100) typically has an end cap (110), a coil of fine wire (112), and a solder joint (114). The fine wire coil 112 can be radiopaque and made of materials including, but not limited to, platinum and its alloys. The specific variations of the invention of the distant section (104) are described below. The end cap (110) may be radiopaque to allow knowledge of the position of the coil (112) during the process of inserting the catheter and traversing the guidewire through the vasculature. All or part of the proximal section of the guide wire (102) and of the middle section (106) and of the distant section (104) is coated with a thin layer (116) of polymeric material to improve its lubricity without affecting its shape. The flexibility or conformability of the guide wire is adversely affected.

Figure 2 shows a variation of the guidewire of the invention which is a composite material, for example, a remote portion of the guidewire core is produced from the specific alloy and

ES 2 159 559 T3 the composite material is of another material or configuration. In particular, the composite guide wire (140) is formed of a proximal section (142) which is a small diameter tube section of, for example, a suitable stainless steel or high elasticity alloy, such as that described. somewhere here. The tubular proximal section (142) is secured by welding or gluing or by other joining method suitable for the materials involved in the gasket (144) to a distal section (146) extending to the distal end of the composite guide wire assembly. (140). The distal tip (148) of the catheter assembly (140) may be of the same configuration as otherwise described herein. The catheter assembly can be coated (150) with polymeric material, as desired.

Figure 3 shows a partial section of an embodiment of the remote section (104) and the remote end of the intermediate section (106). The core of the metallic guide wire is shown partially coated with polymer (116) and a malleable metal coating (118) on the tapered portion of the distal tip. The malleable metal can be selected from suitable radiopaque materials, such as gold or other materials that can be readily welded, such as silver, platinum, palladium, rhodium, and alloys of the foregoing. The tip also includes a radiopaque coil (112) which is delimited at its proximal end by a solder joint (114) and is joined with the end of the guide wire at (110). Radiopaque coil 112 can be made of known suitable materials, such as platinum, palladium, rhodium, silver, gold, and their alloys. An alloy containing platinum, and a small amount of tungsten, is preferred. The distal and proximal ends of coil 112 can be secured to the core wire by tin soldering.

Figure 4 shows a partial section of another embodiment of the distal section (104) of the guide wire of the invention. In this embodiment, the metal guidewire core has a proximal tapered portion (120), a distal tapered section (122) with a solder joint (114) separating the two sections, and a constant diameter (124). The distal tip 124 may have a constant diameter typically between about 0.05 and 0.13 mm (0.002 and 0.005 inches), preferably about 0.08 mm (0.003 inches). The distal tip (124) is preferably between about 1 and 5 cm in length, preferably about 2 cm, but the constant diameter portion extends to at least about 25% of the distance between the solder joint (128) and the solder joint (114). This constant diameter section marginally strengthens the distal tip assembly for improved control. The entire distal section (104) is desirably between about 20 and 50 cm, preferably about 25 cm in length. The maximum diameter of the proximal tapering portion (120) of the guidewire core is typically between 0.13 and 0.51 mm (0.005 and 0.020 inches), preferably about 0.25 mm (0.010 inches). The distally tapered portion (122) and distal tip (124) are again shown with a malleable metal coating (118), such that the distally tapered portion (122) and distal tip (124) remain bent afterwards. of training by the doctor. In this embodiment, the coil of fine wire (112) is delimited at its proximal end by a solder joint (114) and at its distal end by an end cap (110). The end cap (110) is connected to the guide wire by means of a metal tape (126). The tape 126 can be made of stainless steel, platinum, palladium, rhodium, silver, gold, tungsten, and their alloys or other materials that are plastics and that are easily welded. The tape (126) is welded to the coil of fine wire (112) and to the distal tip (124) of the distal section (104) of the guide wire at a solder joint (128), such that the end cap (110) is secured against coil of fine wire (112).

Figures 5A and 5B show yet another embodiment of the distal section (104) of the guidewire (100) of the invention. Figure 5A shows a side view, partially in section, of the guide wire of the invention. The coil of fine wire (112) may be bounded by a polymer adhesive (136) that bonds the coil (112) to the core wire and an end cap (110) and additionally secured to the core of guide wire by a gasket. welding (128). In this embodiment, the distal section (104) of the guide wire again comprises a tapered portion (120) that is proximal to the polymer adhesive (136) and a tapered portion (122) that is distal to the adhesive of polymer (136). The distal section (104) also comprises a smaller diameter portion (130) or "neck" that can be surrounded by the optional inner coil (132). The inner coil 132 can be made of a suitable metal material, preferably one that is easy to weld and preferably radiopaque. It is preferably platinum or stainless steel. One way to produce the neck (130) is to flatten the distal portion of the guide wire (134) distal toward the neck, so that the resulting space (134) is no longer circular in cross section but rectangular in configuration. This can be more easily visualized in Figure 5B, since the figure shows a sectional top view of the guidewire shown in Figure 5A. As in the previously described embodiments, the end cap (110) is secured to the guide wire by a tape.

ES 2 159 559 T3 metallic (126). The solder joint (128) secures the guide wire core to the inner helical coil (132) which secures the end cap (110) through the tape (126) and further secures the outer fine wire coil (112) . This configuration is especially valuable for use with guide wire materials that cannot be easily welded. The solder joint does not need to adhere to the guide wire, yet the inner coil (132), the tape (126), and the outer fine wire coil (112) are all maintained as a single integral unit and have no no ability to slide proximally or distantly on the guidewire assembly.

In the embodiment described with reference to Figures 5A and 5B, suitable materials for the tape are stainless steel, platinum, palladium, rhodium, and the like.

Figure 6 is a partial side view of a midsection joint in the guidewire of the invention. In many variations of the guidewire of the invention, various sections of the nucleus are joined by tapered sections, as seen at (160). This means that the guidewire core is significantly stiffer at the proximal end of the choanically tapered joint (160). We have found that it is sometimes desirable to notch 162 at that proximal end to decrease the overall stiffness of the guidewire at that junction and yet retain columnar strength.

Guide Wire Core

This guide wire is typically used in a catheter that is made of an elongated tubular element having proximal and distal ends. The catheter is (again) approximately 50 to 300 centimeters in length, typically between approximately 100 and 200 centimeters in length. Often the tubular catheter element has a relatively stiffened proximal section that extends along a greater portion of the catheter's length and one or more relatively flexible distal sections that provide the catheter with greater ability to locate the guide wire. through curves and turns encountered as the catheter is advanced through tortuous trajectories found in the vasculature. The construction of a suitable catheter assembly having differential flexibility along its length is described in US Patent No. 4,739,768.

We have found that certain alloys, particularly Ni-Ti alloys, retain their super-elastic properties during passage through the vasculature and yet are flexible enough to allow the clinician to use the guidewire with improved "feel" or feedback and yet does not “jerk” during use. That is, as a guidewire is twisted, it stores energy during a twist and releases it precipitously as it "snaps" to quickly recover stored tension. Preferred alloys do not incur significant unrecovered deformation in use. We have also found that if the eccentricity of the wire, that is, the deviation of the cross section of the guidewire with respect to the "roundness" (particularly in the midsection) is kept very low, the guidewire is much easier to guide or direct through the vasculature.

The material used in the guidewires of this invention are shape memory alloys that exhibit super-elastic / pseudo-elastic shape recovery characteristics. These alloys are known. See, for example, United States Patents No.^° 3,174,851 and 3,351,463 as well as 3,753,700; however, the '700 patent describes a less desirable material, due to higher moduli of the material due to increased iron content. These metals are characterized by their ability to be transformed from an austenitic crystal structure to a tensioan-induced martensatic (SIM) structure at certain temperatures, and elastically return to the austenitic structure when the tension is removed. These alternating crystalline structures provide the alloy with its super-elastic properties. One well-known alloy of this type, nitinol, is a nickel-titanium alloy. It is readily available commercially and undergoes austenite-SIM-austenite transformation in a variety of temperature ranges between -20^°Cy30^°C.

These alloys are especially suitable because of their ability to elastically recover almost completely to the initial configuration once the tensioan is removed. Typically, there is little plastic deformation, even at relatively high deformations. This allows the guidewire to undertake substantial flexions as it passes through the body vasculature, and to return, however, to its original configuration once the flexion has been traversed without retaining any indication of a buckling or flexion. However, the tips shown are often sufficiently plastic that the initial tip formation is retained. However, compared to

ES 2 159 559 T3 similar stainless steel guidewires, less force needs to be exerted against the inner walls of the vessels to deform the guidewire of the invention along the desired path through the blood vessel, thus decreasing trauma to inside the blood vessel and reducing friction against the coaxial catheter.

A guidewire, as it passes through the vasculature to its destination, can undergo numerous bends and loops. The desire to improve the ease with which a guidewire can be twisted to allow the flexed distal tip to enter a desired bypass of the vasculature cannot be overstated. We have found that an important factor in improving such ease of use, ie, improving the controllability of the guide wires, is to control the eccentricity of the cross section of the middle portion of the guide wire. We have found that keeping the middle portion of the guide wire (106 in figure 1) up to an eccentricity ratio of 1 ± 10^-4, the guidewire is significantly more controllable than that which falls outside of this ratio. By "eccentricity" we mean that at any point along the guidewire the ratio of the largest diameter in that cross section to the smallest diameter of the wire in that cross section.

To achieve these results of high strength and improved control while allowing feedback to the attending physician during use, we have found the following alloy fossil parameters to be important. In a stress-strain test as shown in a stress-strain diagram such as that found in figure 7, the stress found at the midpoint of the upper level (UP) (measured, for example, at approximately 3% strain when the extreme point of the test is approximately 6% strain) it should be in the range of 517 MPa (75 ksi (thousand pounds per square inch) ± 68.9 MPa (10ksi) and preferably in the range of 517 Mpa ± 34.5 Mpa (75 ksi ± 5 ksi). Additionally, this material should show a lower level (LP) of 172.4 ± 51.7 MPa (25 ± 7.5 ksi), preferably 137.9 ± 17.2 MPa (20 ± 2.5 ksi), measured at the midpoint of the lower level. The material has no more than about 0.25% residual strain (RS) (when tensioned to 6% strain and allowed to return) and preferably no more than about 0.15% residual strain.

The preferred material is nominally 50.6% ± 0.2% Ni and the remainder Ti. The alloy should contain no more than about 500 parts per million of either O, C, or N. Typically, such commercially available materials will be sequentially mixed, cast, formed, and co-worked separately at 30-40%, annealed, and drawn. .

By way of further explanation, Figure 7 shows a stylized stress-strain diagram showing the various parameters listed above and their measurement in that diagram. As stress is initially applied to a sample of the material, the strain is first proportional (a) until the phase change from austentite to martensite begins in (b). At the upper level (UP), the energy introduced with the applied voltage is stored during the formation of the quasi-stable martensite or stress-induced martensite (SIM) phase. After the substantial completion of the phase change, the stress-strain relationship again approaches a proportional relationship in (c). The tension is no longer applied when the deformation reaches 6%. The measured value (UP) is found at the midpoint between zero and 6% deformation, that is, at 3% deformation. If another terminal strain condition is chosen, for example 7%, the measured value of (UP) and (LP) will be at 3.5%.

Materials that have high UP values ​​produce guidewires that are quite strong and allow exceptional torque transmission, but cause a compromise in the resulting “linearity” of the guidewire. We have found that guidewires that have high UP values ​​in combination with high LP values ​​are not straight. These guide wires are difficult to use due to their tendency to "jerk" as they are turned. Again, that is, as a guidewire is turned, it stores energy during a twist and releases it rapidly. The difficulty of using such a jerky guidewire will be obvious. Materials that have UP values ​​as indicated above are suitable as guide wires.

Additionally, materials that have LP values ​​that are high, again, are not straight. Lowering the LP value compromises the ability of the guidewire to transmit torque, but improves the ease with which a straight guidewire can be produced. Lowering the LP value too far, however, results in a guidewire that, although round, has a poor touch response. Feels a bit "fuzzy" and "thick" during use. The LP values ​​provided above allow for excellent torque transmission, linearity, and valuable touch response.

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The residual strain values ​​described above define a material that does not buckle or otherwise retain a "fit" or configuration after tension during use as a guidewire.

Example

In each case, the following procedure was used in the production of data represented in the table below: commercial Ni-Ti alloy wires having a nominal composition of 50.6% Ni and the remainder Ti, and diameters of 3.3mm, 4.1mm, or 4.6mm (0.13 ", 0.16", or 0.18 ") were stressed at room temperature. In each case, the values ​​for transmission temperature, RS, UP, and LP were measured. Additionally, several of the indicated wires were inserted into a U-shaped Tygon tube and rotated to allow qualitative evaluation of the roundness and tactile response of the wires. Comments on that answer are also in the table below.

<td></td><td>Comparison / Invention (C / I)</td><td>UP</td><td>LP</td><td>RS (%)</td><td>A * T ° C</td><td>Qualitative rotation test</td>

<td> 1'</td><td>I</td><td>513.5 Mpa (74.48 Ksi)</td><td>216.8 MPa (31.45 ksi)</td><td> 0,06</td><td> -11</td><td>Uniform rotation, good feeling</td>

<td> 2^{1 2}</td><td>I</td><td>530.4 MPa (76.94 ksi)</td><td>130.3 MPa (18.9 ksi)</td><td> 0,121</td><td> -8</td><td>Uniform rotation, good feeling</td>

<td> 3³</td><td>I</td><td>495.8 MPa (71.92 ksi)</td><td>165.9 MPa (24.06 ksi)</td><td> 0,10</td><td> 13,5</td><td>Uniform</td>

<td> 4⁴</td><td>C</td><td>539.4 MPa (78.24 ksi)</td><td>405.5 MPa (58.82 ksi)</td><td> 0,20</td><td> -9</td><td>Very sharp turn, sharp movement</td>

<td> 5⁵</td><td>C</td><td>439.8 MPa (63.80 ksi)</td><td>91.3 MPa (13.25 ksi)</td><td> 0,2</td><td> 12,5</td><td>Smooth spin, responsive feel</td>

<td> 6⁶</td><td>C</td><td>401.9 MPa (58.30 ksi)</td><td>91.8 MPa (13.31 ksi)</td><td> 0,0</td><td> -12</td><td>Turned tightly, sensitive feeling</td>

<td> 7⁷</td><td>C</td><td> -</td><td> -</td><td> -</td><td> -</td><td>Hard to turn</td>

¹ Commercially available from US Nitinol, Inc.

² Commercially available from Special Metals, Inc.

³ Commercially available from Shape Metal Alloys, Inc.

⁴ Commercially available as a plaostic coated (0.13 ") 3.3mm guide wire from Fuji Terumo, Inc.

⁵ Commercially available from ITI.

⁶ Commercially available from Metal Tek * Measured at room temperature with no applied voltage.

These data describe both guidewires made in accordance with the invention and comparative guidewires. Additionally, they show that guidewire made of topical stainless steel alloy is very difficult to turn using the qualitative test described above.

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Guide Wire Core Liners

To be in accordance with the present invention, all or part of the guidewire core is covered or lined with one or more layers of a polymeric material. The coating is typically applied to improve the lubricity of the guidewire nucleus as it passes through the catheter lumen or vascular walls.

Lining materials

Coating of at least a portion of the core of the guidewire can be achieved by dipping or spraying or by similar process with materials such as polysulfones, polyfluorocarbons (such as TEFLON), polyolefins such as polyethylene, polypropylene, polyetersters (including polyamides such as NYLON's), and polyurethanes; their blends and copolymers such as polyether block amides (eg PEBAX).

It is often desirable to use a coating such as that described above on the proximal portion of the guidewire and a coating as described below on the most distant sections. Any mixture of coatings placed variously on the guidewire is acceptable as it is chosen for manual work.

The guidewire core can also be at least partially covered with other hydrophilic polymers including here those that are made from monomers, such as ethylene ioxide and its higher homologues; 2-vinyl pyridine; N-vinylpyrrolidone; polyethylene glycol acrylates, such as mono-alkoxy polyethylene glycol mono (meth) acrylates, including mono-methoxy triethylene glycol mono (meth) acrylate, mono-methoxy tetraethylene glycol mono (meth) acrylate, polyethylene glycol mono (meth) acrylate; other hydrophilic acrylates such as

2-hydroxyethylmethacrylate, glycerylmethacrylate; acrylic acid and its salts; acrylamide and acrylonitrile; Acrylamidomethylpropane sulphoinic acid and its cellulose salts, cellulose derivatives such as methyl cellulose, ethyl cellulose, carboxymethyl cellulose, cyanoethyl cellulose, cellulose acetate, polysaccharides such as amylose, pectin, amylopectin, alginic acid, and reticulated heparin maleic anhydride; aldehydes. These monomers can be formed into homopolymers or block or random copolymers. The use of oligoimers of these monoimers in the coating of the guidewire for further polymerization is also an alternative. Preferred precursors include ethylene ioxide; 2-vinyl pyridine; N-vinylpyrrolidone and acrylic acid and its salts; acrylamide and polymerized acrylonitrile (with or without substantial crosslinking) in homopolymers, or in random or block copolymers.

Additionally, hydrophobic monomers can be included in the polymeric coating material in an amount in excess of about 30% by weight of the resulting copolymer, as long as the hydrophilic nature of the resulting copolymer is not substantially compromised. Suitable monomers include ethylene, propylene, styrene derivatives, alkylmethacrylates, vinyl chloride, vinylidene chloride, methacrylonitrile, and vinyl acetate. Ethylene, propylene, styrene, and styrene derivatives are preferred.

The polymeric coating can be cross-linked using various techniques, for example, by light, such as ultraviolet light, heat, or ionization radiation, or by peroxides or azo compounds such as acetyl peroxide, cumyl peroxide, propionyl peroxide, benzoyl peroxide, or the like. . A polyfunctional monoimer such as divinylbenzene, ethylene glycol dimethacrylate, trimethylol propane, pentaerythritol di- (or tri- or tetra-) methacrylate, diethylene glycol, or polyethylene glycol dimethacrylate, and similar multifunctional monoimers capable of crosslinking the above-described monomers and polymers.

The polymers or oligíomers applied using the procedure described below are activated or functionalized with photoactive or radiation active groups to allow the reaction of the polymers or oligoimers with the underlying polymeric surface. Suitable activating groups include benzophenone, thioxanthone, and the like; acetophenone and its derivatives specified as:

Ph

C = 0 ^|

R¹ -CR^{3 |}_R2

ES 2 159 559 T3 where

R¹ is H, R² is OH, R³ is Ph; or

R¹ is H, R² is an alkoxy group including -OCH3, -OC2H3, R³ is Ph; or R¹ = R² = an alkoxy group, R³ is Ph; or R¹ = R² = an alkoxy group, R³ it's H; or

R¹ = R² = Cl, R³ is H or Cl.

Other known activators are suitable.

The polymeric coating can then be articulated with the substrate using known and appropriate techniques selected on the basis of the chosen activators, eg, by ultraviolet light, heating, ionization radiation. Crosslinking with the enumerated polyomers or oligoomers can be achieved by the use of peroxides or azo compounds, such as acetyl peroxide, cumyl peroxide, propionyl peroxide, benzoyl peroxide, or the like. A polyfunctional monoomer such as divinylbenzene, ethylene glycol dimethacrylate, trimethylolpropane, pentaerythritol di- (or tri- or tetra-) methacrylate, diethylene glycol, or polyethylene glycol dimethacrylate, and similar multi-functional monomers capable of crosslinking the above-described polyomers and oligomers is also appropriate for this invention.

The polymeric coating can be applied to the guidewire by any variety of methods, for example, by spraying a solution or suspension of the polyomers or oligoomers of the monomers onto the guidewire core or by dipping it into the solution or suspension. The initiators can be included in the solution or applied in a separate step. The guidewire can be dried sequentially or simultaneously to remove the solvent after application of the polymer or oligoomer to the guidewire and crosslinked.

The solution or suspension should be very dilute, since only a very thin layer of polymer should be applied. We have found that an amount of oligoomer or polymer in a solvent between 0.25% and 5.0% (by weight), 0.5 to 2.0% (by weight) is preferred, it is excellent for thin coating and complete of the resulting polymer. The preferred solvents for this process when using the preferred polyomers and process are water, low molecular weight alcohols, and ethers, especially methanol, propanol, isopropanol, ethanol, and mixtures thereof. Other water-miscible solvents, eg, tetrahydrofuran, methylene dichloride, methyl ethyl ketone, dimethylacetate, ethyl acetate, etc., are suitable for the indicated polymers and should be chosen according to the characteristics of the polymer; They should be polar due to the hydrophilic nature of the polyomers and oligoomers but, due to the reactivity of the end groups of these materials, the known rapid cooling effects caused by oxygen, hydroxyl groups and the like must be recognized by the user of this process when polyomers and solvent systems are chosen.

Particularly preferred as a coating for the guidewire cores described herein are phosphor mixtures of homo-oligoomers of at least one of polyethylene oxide; poly 2-vinyl pyridine; polyvinylpyrrolidone, polyacrylic acid, polyacrylamide, and polyacrylonitrile. The catheter bodies or substrates are spray or dip coated, dried, and preferably irradiated to produce a polymerized and cross-linked polymeric surface of the indicated oligoomers.

The lubricating hydrophilic coating is preferably produced using generally simultaneous crosslinking and solvent removal operations. The coating is applied at a rate that allows the solution to “roll”, for example, the formation of a visibly uniform layer without “runs”. In an immersion operation for use with most polymeric substrates, including those listed below, optimal coating speeds are at a linear removal rate between 0.6 and 5 cm / s (0.25 and 2 , 0 inches / second), preferably between 1.3 and 2.5 cm / s (0.5 and 1.0 inches / second).

Solvent evaporation operations can be carried out using a suitable heating chamber to keep the surface at a temperature between 25^°C and the vitreous transition temperature (Tg) of the underlying substrate. Preferred temperatures are 50^°C to 125^°C. Preferred masses for the preferred and indicated solvent systems are in the range of 75^° to 110^°C.

ES 2 159 559 T3

Ultraviolet light sources can be used to crosslink the polymeric precursors on the substrate. Movement through an irradiation chamber having an ultraviolet light source at 90-375 nm (preferably 300-350 nm) having an irradiation density of 50-300 mW / cm is desirable.² (preferably 150-250 mW / cm²) for a period of three to seven seconds. The passage of a guidewire core through the chamber at a speed of 0.6 to 5 cm / s (0.25 to 2.0 inches / second) (preferably 1.3 to 2.5 cm / s 0.5 to 1.0 inch / second) on a camera that is 7.6 to 22.9 cm (three to nine inches) in length is adequate. When ionizing radiation is used, a radiation density of 1 to 100 kRads / cm² (preferably 20 to 50 kRads / cm²) can be applied to the solution or suspension on the polymeric substrate.

The exceptional durability of the resulting coating is produced by repeating the dipping / solvent removal / irradiation steps up to five times. Two to four repetitions are preferred. Tie layers

To be in accordance with the present invention, a "bonding" layer is provided between the outer polymeric surface and the guidewire core to improve overall adhesion of the outer polymeric surface to the core. Of course, these materials must be able to tolerate the various other solvents, cleaners, sterilization procedures, etc. in which the guide wire and its components are placed during other stages of production.

The choice of materials for bonding layers of this type is determined by their functionality. Specifically, materials are chosen for their affinity or toughness to the hydrophilic coating or polymeric lubricant. Clearly, the bonding layer material must be flexible and strong. The material should be extrudable and preferably easily transformed into the shrink tube for mounting on the guidewire through heating. We have found that various NYLON's, polyethylene, polystyrene, polyurethane, and preferably polyethylene terephthalate (PET) make excellent bonding layers. These tube materials can also be formulated to include radiopaque materials, such as barium sulfate, bismuth trioexide, bismuth carbonate, tungsten, tantalum, or the like.

As noted above, an easily achievable way of applying a bonding coat is by hot retracting the tube onto the guidewire. The guidewire core is simply inserted into a suitable size tube - often with a small amount of a "caulk" at either end to seal the tube against invasion of fluids or non-sterile materials from under the tube. The tube is cut to the required length and heated until it is small enough in size. The resulting tube tie layer is desirably between about 0.064 and 0.381 mm (0.0025 and 0.015 inches) thick. The thinnest layers are typically made of polyurethane or PET. The lubricating polymer layer is then placed on the outer surface of the retracted tube.

Another method of preparing or pretreating guidewires prior to receiving a backcoat of a polymer, preferably a polymer that is lubricating, biocompatible, and hydrophilic, is through the use of a plasma stream to deposit a hydrocarbon or fluorocarbon residue. The procedure is described as follows: the core of the guide wire is placed in a plasma chamber and cleaned with an oxygen plasma acid. The guidewire core is then exposed to a hydrocarbon plasma to deposit a plasma polymerized bonding layer on the guidewire core to complete the pretreatment. The hydrocarbon plasma may comprise lower molecular weight (or gaseous) alkanes, such as methane, ethane, propane, isobutane, butane, or the like; lower molecular weight alkenes, such as ethene, propene, isobutene, butene or the like or; Gaseous hydrocarbons such as tetrafluoromethane, trichlorofluoromethane, dichlorodifluoromethane, trifluorochloromethane, tetrafluoroethylene, trichlorofluoroethylene, dichlorodifluoroethylene, trifluorochlorethylene and other such materials. Mixtures of these materials are also acceptable. The bonding layer apparently provides CC bonds for covalent bonding subsequent to the outer hydrophilic polymer coating. Preferred flow rates for the hydrocarbon within the plasma chamber are in the range of 500 cc / min to 2000 cc / min. and the residence time of the guidewire in the chamber is in the range of 1-20 minutes, depending on the chosen hydrocarbon and the operating parameters of the plasma chamber. Power settings for the plasma chamber are preferably in the range of 200 W to 1500 W.

A plasma-produced hydrocarbon residue bonding layer having a thickness on the order of 10A thick is disposed between the core and the cladding. This process typically produces layers of hydrocarbon residue less than about 1000A thick, and typically less.

ES 2 159 559 T3 of 100A. The unioan layer effectively bonds the outer layer to the guidewire core while adding very little additional mass to the guidewire. Guidewires made in accordance with this invention therefore avoid the problems of maneuverability and sizing of prior art guidewires.

The pretreated guide wire can be coated with a polymer using a procedure as described above. For example, the pretreated guidewire can be immersed in a solution of a photoactive hydrophilic polymer system, ie, a latently photoreactive binding group covalently attached to a hydrophilic polymer. After drying, the coated guide wire is hardened by exposing it to UV light. UV light activates the reactive group latently in the photoactive polymer system to form covalent bonds with crosslinked CC bonds in the hydrocarbon residue unioan layer. The dipping and curing steps are repeated with sufficient frequency preferably, typically twice, to achieve the appropriate thickness of the hydrophilic coating layer.

A highly preferred variation of the invention involves a metal core guide wire, preferably 0.254 to 0.635 mm (0.010 to 0.25 ") thick of stainless steel or nitinol. The outer surface of the guidewire is a biocompatible coating of a polyacrylamide / polyvinylpyrrolidone mixture adhered to a photoactive bonding agent. The preferred coating is made from a blend of Bio-Metric Systems PA03 and PV05 (or PV01) bonding system according to the Examples below.

The photoactive hydrophilic polymer system of this preferred embodiment is a blend of Bio-Metric Systems PA03 polyacrylamide / binder system and Bio-Metric Systems PV05 polyvinylpyrrolidone system. The polyacrylamide system provides lubricity, and the polyvinylpyrrolidone system provides both lubricity and adhesion for durability. The exact proportions of the two systems can be varied to suit the application. As an alternative, however, the hydrophilic biocompatible coating can be polyacrylamide alone, polyvinylpyrrolidone alone, polyethylene oxide, or any suitable coating known in the art. Additionally, a coating of heparin, albumin, or other proteans can be deposited onto the hydrophilic coating in a manner known in the art to provide additional biocompatibility characteristics.

The guide wire or other device can be cleaned using argan plasma acid instead of oxygen plasma acid. The thickness of the plasma polymerized bonding layer can also be varied without departing from the scope of this invention.

The following examples are further illustrative of the articles of this invention. The invention is not limited to these examples.

Example

A 0.41mm (0.016 ") diameter nitinol guide wire was placed in a Plasma Etch MK II plasma chamber and flushed with an oxygen plasma for 10 minutes. The methane flow at a rate of 2000 cc / min. It will be admitted into the chamber, and the chamber is operated at a power setting of 400 W for 2 minutes to deposit a hydrocarbon residue on the surface of the wire. All of the wire, except about 15 mm (six inches), was immersed in a photocrosslinkable polyvinylpyrrolidone / polyacrylamide (PVP / PA) solution of a mixture of 67% BSI PV01 and 33% BSI PA03. The coated guide wire will then be dried and exposed to ultraviolet light (325 nm) for 8 seconds. The immersion, drying, and exposure steps were repeated several times. When wetted, the resulting wire felt lubricating and would require less force to push through a 0.457mm (0.018 ") ID catheter than an uncoated wire.

Example

A 0.406 mm (0.016 ") diameter nitinol guide wire is placed in a Plasma Etch MK II plasma chamber and cleaned with an oxygen plasma for 10 minutes. The methane flow at a rate of 1500 cc / min. It will be admitted into the chamber, and the chamber is operated at a power setting of 600 W for 5 minutes to plasma treat the methane within a hydrocarbon residue on the surface of the wire. All of the wire, except about 15 cm (six inches), was immersed in a photocrosslinkable polyvinyl pyrrolidone / polyacrylamide (PVP / PA) solution consisting essentially of a mixture of 50% BSI PV01 and 50% BSI PA03. The coated guide wire was then dried and exposed to ultraviolet light (325 nm) for 8 seconds. The stages were repeated

ES 2 159 559 T3 of immersion, drying, and exposure. When wet, the resulting wire felt lubricating, and it would take less force to be pushed through a 0.457mm (0.018 ") ID catheter than an uncoated wire.

Example

A 0.406 mm (0.016 ") diameter nitinol guide wire was placed in a Plasma Etch MK II plasma chamber and cleaned with an oxygen plasma for 10 minutes. The ethane flow at a rate of 900 cc / min. It will be admitted into the chamber, and the chamber is operated at a power setting of 600W for 10 minutes to deposit a hydrocarbon residue on the surface of the wire. All of the wire, except approximately 15 cm (six inches), was immersed in a photoretractable solution of polyvinylpyrrolidone / polyacrylamide (PVP / PA) of a mixture of 33% BSI PV01 and 67% BSI PA03. The coated guide wire was then dried and exposed to ultraviolet light (325 nm) for 8 seconds. The dipping, drying, and exposing steps were repeated twice. When wet, the resulting wire will feel lubricating and less force is required to be pushed through a 0.457mm (0.0182) ID catheter than a coated wire.

Although preferred embodiments of the present invention have been described, it should be understood that various changes, adaptations, and modifications can be made herein without departing from the scope of the claims that follow.