JP2011184803A - Radiopaque coating for biomedical device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical device having radiopaque coating with a sufficient thickness, which imparts a preferable X-ray contrast, biocompatibility and corrosion resistance. <P>SOLUTION: A medical device has a porous radiopaque coating that can withstand the high strain inherent in the use of such devices without delamination. A coating of Ta is applied to the medical device, such as a stent, by vapor deposition so that the thermomechanical properties of the stent are not adversely affected. The coating preferably has high emissivity. The coating is applied via a generally monoclinic coating agent or a low energy coating agent. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

Disclosure details

[Cross-reference to related applications]
This application claims the benefit of US Provisional Patent Application No. 60 / 579,577, filed June 14, 2004, and US Provisional Patent Application No. 60 / 555,7, filed March 23, 2004.
US patent application Ser. No. 11 / 087,90 filed Mar. 23, 2005, claiming benefit of 21
U.S. Provisional Patent Application No. 60/538, filed Jan. 22, 2004
No. 11/040, filed Jan. 21, 2005, claiming the benefit of No. 749,
This is a partial continuation application of No. 433. These patent documents are hereby incorporated by reference in their entirety for some or all purposes.

(Field of the Invention)
The present invention relates to a medical device.

BACKGROUND OF THE INVENTION
Stents have become a vital device in the treatment of cardiovascular disease. A stent is a small mesh “scaffold” that can be placed in an artery and patency the artery to maintain sufficient blood flow. Generally, a stent is introduced into a patient's organ through the brachial artery or femoral artery and delivered to a predetermined location using a catheter and a guide wire. This minimally invasive procedure
It is an alternative to surgery and has gained widespread use today because it offers significant benefits in terms of patient care and cost.

To deploy the stent, it is a fraction of the normal diameter so that it can be delivered to the desired location.
Must be compressed to Thus, many stents and guidewires are formed from a nickel titanium alloy known as Nitinol, which has special superelastic and shape memory properties. Both of these properties are due to the fact that nitinol is present in the martensite phase below the first transformation temperature known as M _f and in the austenite phase higher than the second transformation temperature known as A _f. to cause. Both M _f and A _f can be manipulated by the ratio of nickel to titanium in the alloy and the heat treatment of the material. In the martensite phase, nitinol has high ductility and can be easily deformed, whereas in the austenite phase, it has a high elastic modulus. When stress is applied, it becomes a kind of martensitic material at a temperature higher than A _f , and when the stress is removed, this material returns to its original shape. This provides a very high elasticity of Nitinol, called superelastic properties, i.e. pseudoelasticity. Furthermore, when Nitinol is deformed by being lowered to a temperature below M _f , it returns to its original shape when the temperature rises above A _f . This is the shape memory characteristic.

Stents with superelastic and shape memory properties can be placed so that they can be compressed to a small diameter and moved into place before returning to full size. By choosing an alloy composition that has an A _f that is lower than normal body temperature, the stent remains expanded with great force once deployed. Surprisingly, nitinol is usually 8% during this procedure.
It must withstand distortion.

Stents and similar intraluminal devices can also be formed from materials such as stainless steel or other metal alloys. Such metals do not have shape memory or superelastic properties,
Stents made from such materials must also withstand significant strain deformation during use.

FIG. 1 illustrates one of a number of stent designs that can be used to facilitate this compression and expansion. This design uses a ring-type “strut” 12. Each strut has a corrugated structure that allows it to contract to a small diameter. A bridge 14, also called a node, connects the struts. This bridge 14 must also be bent in use. Various other types of expandable shapes, such as spiral designs, braided designs, woven designs, and coils, are known in the art and used for various purposes.

One problem with stents formed from Nitinol and various other alloys is that the X-ray absorption is relatively weak because the atomic number of the metal used is often small. Thus, a normal sized stent is difficult or impossible to view with x-rays when maneuvering and in place. Such a device is called radiolucent.
Many advantages are obtained when the stent is visible with X-rays. For example, so-called radiopacity allows the stent to be accurately placed initially, and once the stent is in place, changes in shape that can reflect medically important symptoms can be identified. .

Various methods for imparting radiopacity to a stent or portion thereof have been disclosed in the prior art. In such prior art, the stent cavity is filled with a radiopaque material (US Pat. Nos. 6,635,082, 6,641,607) and radiopaque markers are attached to the stent ( US Pat. Nos. 6,293,966 and 6,312,452
No. 6, No. 6,334,871, No. 6,361,557, No. 6,402,777
No. 6,497,671, No. 6,503,271, No. 6,554,854), a stent containing a multilayer material with different radiopacity (US Pat. No. 6,638, 301, 6,620,192), including a radiopaque structural element in the stent (US Pat. Nos. 6,464,723, 6,471,721, 6,540,774). No. 6,585,757, 6,652,579), coated with a binder containing radiopaque particles (US Pat. No. 6,355,058), and the radiopaque of the stent A method of spray coating a functional material (US Pat. No. 6,616,765) is included.

All these prior art methods of imparting radiopacity to a stent greatly increase manufacturing costs and complexity and / or impart radiopacity to only a portion of the stent. The most efficient method is simply to apply a conformal coating of sufficiently dense radiopaque material to all surfaces of the stent. Such a coating must have a sufficient thickness to provide good X-ray contrast, biocompatibility, and corrosion resistance. More difficultly, however, such coatings can withstand extreme strains in use without cracking and debonding, and are sufficient to maintain the important thermomechanical properties of the stent. Must have ductility. In addition, such coatings must withstand the constant expansion and contraction of the stent caused by the expansion and contraction of blood vessels in the heartbeat.

Sputtering, thermal evaporation, and cathodic arc evaporation (cathodic)
High density conformal coatings of radiopaque materials such as gold, platinum, tantalum, and tungsten can be applied by physical vapor deposition methods such as arc deposition). Physical vapor deposition is widely used and reliable. However, coatings formed by such methods usually cannot adhere well to substrates that experience up to 8% strain, as required herein. This problem is related to US Pat. No. 6,1
74,329, mentioning the need to apply a protective coating over the radiopaque coating to prevent the radiopaque coating from peeling off during use of the stent.

Another important limitation of radiopaque coatings deposited by physical vapor deposition is the temperature sensitivity of nitinol and other stent materials. As described above, the shape memory biomedical device is formed with a value of _Af slightly lower than the normal body temperature. Nitinol
Increasing the temperature too high for an excessively long time increases the _Af value of nitinol,
Sustained temperatures above 00 ° C. to 400 ° C. adversely affect _Af values commonly used for stents. Similarly, stainless steel can degrade if it is raised to excessively high temperatures.
Other stent materials will also be adversely affected. Thus, the history of stent time and temperature during coating is extremely important. In the prior art, it is customary in such cases to directly control the temperature of the substrate, especially with a very low thermal mass, such as a stent. This is usually done by placing the substrate in thermal contact with a large mass or heat sink whose temperature is controlled. This method is known as direct temperature control. Due to the shape and structure of the stent, it is difficult to directly control the temperature of the stent during coating. In addition, because the portion of the stent that contacts the heat sink is not coated, it is difficult to interpret the resulting radiograph.

Accordingly, there is a need in the art for a biomedical device having a radiopaque coating that is thick enough to provide good X-ray contrast, biocompatibility, and corrosion resistance. Furthermore, the coating must be sufficiently ductile to withstand extreme strains in use without cracking or peeling and to maintain the thermomechanical properties of the device.

[Summary of the Invention]
The present invention relates to a medical device having a radiopaque outer coating that can withstand the strain caused by the use of the device without delamination.

A medical device according to the present invention can include a body comprising at least a portion of a nickel titanium alloy or other suitable material and a Ta coating disposed on at least a portion of the body. The Ta coating is thick enough so that the medical device is radiopaque and can withstand the strains that result from the use of the device without delamination. The Ta coating can consist of a bcc crystalline phase or a tetragonal crystalline phase. The thickness of the Ta coating is preferably in the range of about 3 μm to 10 μm. The medical device can be, for example, a stent or a guide wire. Such a coating is preferably porous. Such coatings are applied either by a generally oblique coating flux or a low energy coating bundle.

A method for depositing a Ta layer on a medical device, comprising maintaining a background pressure of an inert gas in a sputter coating system including a Ta sputter target, and applying a voltage to the Ta target to cause sputtering. Sputtering for a given time to form a coating of the desired thickness, wherein the Ta layer preferably has a visible spectral emissivity of at least 80%. The medical device is preferably not directly heated or cooled, but indirectly controls the equilibrium temperature of the medical device during deposition by this method. This equilibrium temperature is preferably in the range of 150 ° C to 450 ° C.
During this method, an AC or DC voltage can be applied to the medical device constantly or as a pulse. The medical device can be precleaned by applying an initial high voltage, preferably in the range of 100V to 500V, over a first time, preferably in the range of 1 minute to 20 minutes. Over a given time, preferably 1 to 3 hours, preferably 50V to 20
A second low voltage in the range of 0V can be applied. Preferably, the inert gas is Ar
, Kr, and Xe. Preferably, a deposition rate of 1 μm / hour to 4 μm / hour is obtained depending on the voltage at the target. This target is preferably a cylinder or a plate.

The medical device includes a body having an outer layer and a radiopaque coating disposed on at least a portion of the outer layer. This coating is applied using physical vapor deposition techniques.

These and other features, aspects, and advantages of the present invention will become better understood from the following description, appended claims, and accompanying drawings.

[Detailed explanation]
The present invention relates to a medical device having a radiopaque outer coating that can withstand the strains that occur during use of the medical device without peeling off.

Tantalum is an attractive material for radiopaque coatings in this application because of its high atomic number, biomedical inertness, and corrosion resistance. However, other materials such as, but not limited to, platinum, gold, or tungsten can be used. 3μ
It has been found that satisfactory X-ray contrast can be sufficiently obtained with a Ta coating having a thickness of m to 10 μm. However, since Ta has a melting point of approximately 3000 ° C., all coating steps are performed at a low homologous temperature to maintain the stent _Af value described above.
temperature) (ratio of deposition temperature (Kelvin) to melting temperature of the coating material). In the field of physical vapor deposition, it is well known that coating properties often decrease when the homologous coating temperature is low. Nevertheless, it has unexpectedly been found that radiopaque Ta coatings deposited under appropriate conditions can withstand the inherent strains of stent use without unacceptable delamination.

Of further note is the fact that such adhesive coatings can be deposited at high speed without directly affecting the temperature of the stent without substantially affecting _Af . Since the normal body temperature is 37 ° C., the A _f value after coating should be lower than 37 ° C. so that the thermomechanical properties of nitinol are not impaired. The lower the A _f value after coating, the more desirable.

In the case of an insulated substrate, the equilibrium temperature depends on factors such as the heat of condensation of the coating material, the energy of the atoms impinging on the substrate, the coating rate, the radiative cooling of the surrounding chamber, and the thermal mass of the substrate. Surprisingly, this energy balance allows high speed coating of temperature sensitive low mass materials such as stents without increasing the temperature beyond an acceptable range. The coating process is significantly simplified when direct temperature management of the stent is no longer required. This is a particularly important element of the manufacturing process.

The present invention relates to coatings that impart radiopacity to biomedical devices, including intraluminal biomedical devices, and that resist the extremely large strains inherent in the use of such devices without unacceptable delamination. Specifically, the present invention relates to a Ta coating having such characteristics and a method for applying the Ta coating that does not adversely affect the thermomechanical characteristics of the stent.

An unstable cylindrical magnetron sputtering system (unbalanced cylindric) disclosed in US Pat. No. 6,497,803 B2, which is hereby incorporated by reference.
The coating was deposited using an al magnetron sputtering system). 2 and 3
Illustrates the setup. Two Ts, each 34cm in diameter and 10cm in height
aThe target 20 was used 10 cm apart. These are 40 kHz DC power or AC
It was driven using electric power. Xenon or krypton was used as the sputtering gas. The total power to both cathodes is 2 kW or 4 kW, and -50 is applied to the stent during coating.
V or -150V bias was applied. Other devices known to those skilled in the art, such as vacuum pumps, power supplies, gas flow meters, and pressure gauges, have been omitted in FIGS. 2 and 3 for clarity.

In each coating experiment, the stent 22 was placed in one of the three positions shown in FIGS.

In position A, the stent was secured to a 10 cm diameter fixture 24 rotating about a vertical axis about 7 cm away from the cathode centerline. The vertical position of the stent was at the center of the upper cathode. Finally, each stent was periodically rotated about its own vertical axis by a small “kicker” in a manner well known in the art.

In position B, the stent 22 was supported on an axis of rotation about 7 cm away from the chamber centerline.
The vertical position of the stent was at the center of the upper cathode.

In position C, stent 22 was secured to a 10 cm diameter fixture or plate 24 that rotates about a vertical axis about 7 cm away from the cathode centerline. The vertical position of the stent is at the center of the chamber, midway between the upper and lower cathodes. Finally, each stent was periodically rotated by a “kicker” about its own vertical axis.

Prior to coating, the stents were cleaned with a warm water soluble detergent in an ultrasonic bath. 0.5 pounds of Crest 270 Cleaner (Crest Ultrasonics, Inc.) for 1 gallon of water
And diluted at 55 ° C. This ultrasonic cleaning was performed for 10 minutes. The stents were then rinsed in tap water sonicated for 2 minutes and rinsed in deionized water sonicated for 2 minutes. The stent was then dried with nitrogen and further dried with hot air. It has been found that the method of cleaning the stent is extremely important. When the stent was ultrasonically cleaned with acetone and isopropyl alcohol, residues were found on the stent that could cause poor adhesion. Such residue would be material left after the electropolishing process, which is often performed using an aqueous solution.

The Ta sputtering target is the power and pressure used in certain coating experiments,
Pretreated for 10 minutes. During this step, the stent was isolated from the target with a shutter. This preheating allows the stent to be further degassed and approach the actual coating step temperature. After opening the shutter, the coating time was adjusted so that a coating with a thickness of about 10 μm was obtained. It takes 2 hours and 15 minutes with 4kW power, 2k
It took 4 hours and 30 minutes with W power. These are coating speeds that are well tolerated as a manufacturing process. The stent was not directly heated or cooled in any way during deposition. These time and temperature histories were determined entirely by the coating process.

FIG. 4 illustrates a cross-section of conformal coating Ta40 on strut 12, shown as a coating about 10 μm thick. Stents coated with this method were evaluated in several ways. First, in order to confirm whether there was peeling or peeling when the tape was peeled off, the stent was pressed against the adhesive tape. The stent was then bent to the maximum and examined for delamination. In either case, the stent was bent at least 3 times and in some cases 10 times. Finally, the _Af value of the stent was measured using a water bath to determine the temperature at which the stent returns to its original shape.

Table 1 summarizes the results of this experiment. The level of exfoliation at positions A and B and the A _f values were very similar in the experiment, and these were averaged to the values in the table. The level of peeling was classified according to the following criteria.
Level 5: Stripping of coating area about 10% or more Level 4: Stripping of coating area in the range of about 5% to 10% Level 3: Stripping of the coating area in the range of about 1% to 5% Level 2: About Peeling of coating area in the range of 0.1% to 1% Level 1: Peeling may be observed, but peeling of coating area less than about 0.1% Level 0: Peeling is not observed

The allowable peeling level varies depending on the application, but the peeling level 2 to 0 is considered as the allowable range.

From the results for positions A and B, it was found that the main factor determining adhesion was the bias voltage. With a bias of -150V, better overall adhesion is obtained than with a bias of -50V. This is consistent with many literature reports that in many applications, good adhesion is obtained with high substrate bias. However, a high temperature is generated at a given power, as determined by the A _f value.

An important exception that a high bias is required to obtain good adhesion is Experiment 5, in particular, which has the lowest A _f value and excellent adhesion. Furthermore, the appearance of the coating of Experiment 5 was visually noticeable black. This suggests a very high visible spectral emissivity characteristic of so-called black bodies. As shown in the graph of FIG.
The reflectance is measured to be about 0.5% at a wavelength of 400 nm and about 1.10% at a wavelength of 700 nm.
Is rising. Since this base material does not transmit a large amount of radiation, the relationship r + a = 1 can be used. Where r is the reflectance of the coating and a is the absorption of the coating. Therefore, in this case, the absorption rate is about 99%. Because absorption and emissivity are the same (eg, Sears and Zamansky, “University
Physics 3rd edition (Addison Wesl
ey), 1964, pp. 376-378)), which is an emissivity of the visible spectrum of about 99% or more.

The combination of extremely low A _f values and excellent adhesion is surprising. While not being bound by this explanation, one possibility consistent with the observed results is that the coating is highly porous. A low homologous temperature (ratio of substrate temperature (Kelvin) in the coating to melting point of the coating material) is known to produce an open columnar coating structure. Those skilled in the art will understand that the porous coatings described herein are sometimes referred to as zone 1 coatings for materials to be sputtered and deposited (eg, by John Thornton). , "High Rate T
hick Film Growth) ", Annual Review of Materials Science (Ann.
Rev. Mater. Sci.), 1977, pages 239-260).

The observed black appearance may be the result of an extreme porous coating. It is also known in the art that such a configuration is associated with very low coating stress since the coating is not of sufficient density. However, even if this explanation is correct, the excellent adhesion is a great surprise. In general, the coating conditions that result in such a porous coating result in extremely low adhesion, and the coating can be actively bent without signs of flaking.

Another possible reason for obtaining a high emissivity coating is that the radiant cooling of the stent during coating is more efficient than the radiative cooling of a low emissivity glossy surface, thereby reducing the low coating temperature. The fact that maintenance is helped.

Further, US patent application Ser. No. 11 / 040,4, which is hereby incorporated by reference.
As disclosed in US Pat. No. 33, the sputtered Ta typically has two crystalline phases: tetragonal (known as β phase) or body-centered cubic (bcc) (known as α phase). It exists as one of Since the α phase of Ta is significantly more ductile than the β phase, it can withstand greater strain. Therefore, Ta α phase would be more preferred for the present invention. FIG.
Is an X-ray diffraction pattern of a coating formed under the conditions of Experiment 5 above, indicating that the coating is alpha tantalum. Ta in Kr or Xe using substrate bias
In sputtering, it is known in the art that an alpha phase is deposited. For example, “Surface and Coatings Technology 1”
46-147 "(2001, p344-350). However, none of the prior art or our experience has shown that an αTa coating with a thickness of 10 μm can withstand the extremely large strains that occur with the use of a stent without delamination or coating defects. Also, the prior art does not show that αTa can be deposited in such an open porous structure.

An open porous structure has other advantages. For example, microcavities in the coating can include drugs or other substances that elute gradually over time. In this field
Currently, drug eluting coatings on stents are formed using polymeric materials. The porous inorganic coating can form a drug eluting stent that does not require a polymer overcoat.

Surprisingly, all of the stents at position C shown in FIG. 3 achieved the same or better adhesion than positions A and B regardless of the conditions. Table 2 illustrates this surprising result (NA indicates a coating experiment for which no data was available at that location). The stent at position C always had little or no peeling, even under coating conditions where there was significant peeling of the stent at position A or B. As can be seen from Table 2, this is true for a wide range of coating conditions. The A _f value of the stent at position C is comparable to the A _f value of the stent at other positions, and in the case of AC coating, the A _f value of the stent at position C may be significantly lower. The stent at position C (experiment numbers 2 and 3) sputter coated in Kr with a pressure of about 0.45 Pa (3.4 mTorr), a bias of −150 V and 2 kW AC power, has a metallic appearance. , A _f value is in the range of 38 ° C to 42 ° C. At a pressure of about 0.45 Pa (3.4 mTorr), 2 kW DC power, −50 V bias,
A stent coated with Kr at position C (Experiment 8) has a black appearance and A
_{The f} value was only 24 ° C. The A _f value at 24 ° C. is not substantially different from the A _f value before coating. Both metallic and black samples have excellent adhesion. The fact that at position C a virtually always favorable adhesion and _Af value was obtained was unexpected.

The stent at position C is generally more oblique than the stent at position A or position B.
que) to receive a lower energy coating bundle. By oblique coating bundles is meant that the majority of the depositing atoms arrive in a direction other than substantially perpendicular to the surface to be coated. Some of the atoms that reach the surface of the stent at position C from the upper and lower targets can be coated without significant energy loss or loss of directionality due to collision with the background sputter gas. Reach the surface. Most of these atoms come from the portion of the target proximate to the stent shown in FIGS. 2 and 3, creating a diagonal coating bundle. Other atoms collide with the background gas and lose energy and direction before reaching the substrate surface. Such atoms generally come from portions of the target that are remotely located to form a low energy coating bundle.

Before the energy is reduced to the energy of the background gas, Ta atoms are about 0.45 Pa (
(3.4 mTorr) The average distance traveled through Ar is about 15 cm to 30 cm,
Calculated by Westwood (by WD Westwood)
“Calculation of deposit in diode sputtering system
ion rates in diode sputtering systems), Journal of Vacuum Science and Technology, Vol. 15, 1978, p. 1). (This distance is somewhat shorter in Kr, and the exact value depends on the initial energy of Ta atoms.) Our cylindrical target has an inner diameter of about 34 cm.
Therefore, the substrate (positions A and B) placed in the plane of the target receives more normally incident atoms with higher energy than the substrate placed between the targets (position C).

Due to the geometry of the cylindrical magnetron arrangement shown in FIGS.
Ensure that the atoms that reach the surface of the stent at a relatively oblique angle or with a relatively low energy. In general, a sputtering atom has several electrons V (e
V) Leave the target surface with an average kinetic energy. As described by Westwood, after several collisions with the background gas, the sputtering atoms lose most of their kinetic energy. Sputtering atoms having an average energy of about 1 eV or less due to low energy are described. The Westwood calculation can be used to estimate the target spacing relative to the substrate needed to achieve this low average energy for a given sputtering pressure. Furthermore, as is well known to those skilled in the art, atoms deposited by evaporation have an average energy of less than about 1 eV when leaving the evaporation source. Thus, in the case of vapor deposited coating, there is no need to scatter gas in the chamber to obtain a low energy coating bundle.

In short, as shown in FIGS. 2 and 3, when the stent is close to the target and the arriving Ta atoms lose little energy, the atoms arrive at an oblique angle. If the arrival angle is not so inclined when the stent approaches the center of the chamber, since the stent is away from the target surface, the reaching Ta atoms are absorbed by collision with the gas. Is lost.

When atoms during physical vapor deposition reach the substrate surface with low energy or tilt angle, compared to a coating formed from atoms that reach a nearly normal incidence angle or high energy,
It is widely known in the art to have low density coatings. Low substrate bias (
The black appearance of the DC low power coating deposited in Experiment 5 of Table 1 and Experiment 8 of Table 2 is believed to be a result of the considerable porosity of the coating. Normally, low density physical vapor deposition coatings are considered undesirable, but conditions that result in relatively low density or porous coatings have been found to give very favorable results to the present invention.

Additional evidence that the geometry of the coating was important was confirmed in the following experiment.
Using the fixture shown in FIGS. 2 and 3, at position C, a number of coatings in Kr at a pressure of about 0.45 Pa (3.4 mTorr), 2 kW DC power, −50 V bias Went. As described above, the stent was rotated about the vertical rod and about the vertical axis of the stent itself. A stent coated in this manner is matte black at the bottom but slightly glossy at the top. In contrast, as shown in FIG. 7, under the same conditions, except that the second plate 24 is placed on the stent, the stent 2
When the coating was applied to 2, the stent became a uniform black from the bottom to the top.

The non-uniform appearance obtained at position C using the fixture shown in FIGS. 2 and 3 suggests that the coating structure depends on the detailed positional relationship of the stent and sputter target relative to each other. Yes. As noted above, when the stent is in the position Ci shown in FIG. 7, the stent is very oblique inciden from the adjacent target portion.
The material that receives the material at ce) and arrives from the rest of the target must travel a long distance. Therefore, all coating bundles have a high angle (high ang
le) or travel a fairly long distance and lose energy and directionality in collision with the sputtering gas. However, the position Cii where the stent is shown in FIG.
The stent is coated at a slightly less oblique angle from all directions. In the configuration shown in FIG. 3, at position C, the lower portion of the stent is shielded from more direct energy flux from the bottom target by the plate holding the stent, while the upper portion of the stent is shielded from the upper target. It is not shielded from the more direct coating bundle from the bottom of the stent. As shown in FIG. 7, by providing a plate above the stent, more direct coating bundles are shielded in all parts of the stent, and the coating material has a relatively high incidence incidence.
Or after being scattered by the background gas and losing energy and directionality, the coating material arrives. The plate above the stent provides positional symmetry and the coating formed on the stent is a uniform black throughout.

Other methods can be used to place and move the substrate in the chamber to achieve results similar to those described above, and such methods are within the scope of the present invention. In another experiment, three stents were placed as shown in FIGS. All three stents 22 were fixed at their respective positions in the chamber and rotated around their respective vertical axes during the coating experiment. The innermost stent is 3 cm from the cathode centerline, the middle stent is 7 cm from the cathode centerline, and the outermost stent is 11 cm from the cathode centerline.
cm apart. Deposition is 2 kW DC power, about 0.45 Pa (3.4 mTorr) Kr
The pressure was applied and the stent was biased at -50V. These are the same conditions used in Experiment 8 in Table 2. All three stents had a matte black appearance and excellent adhesion was confirmed in the test. Thus, located at virtually every radial position within the cathode,
Stents rotated about their respective vertical axes can be satisfactorily coated when placed axially between targets.

Although less preferred, other methods include using a large target away from the substrate or tilting the incident coating to reduce the energy of the atoms reached by collision, but with this method, The pressure of the sputtering gas increases.

Sputtering is performed under conditions where gas flows continuously. That is, since sputtering gas is introduced into the chamber at a constant rate and exhausted from the chamber at the same rate, the pressure becomes constant and the gas in the chamber is continuously purged. This flow is necessary to remove unwanted gases such as water vapor generated from the system during coating. Such unwanted gases can be incorporated into the growing coating and adversely affect its properties.

High vacuum pumps used for sputtering, such as diffusion pumps, turbomolecular pumps, and cryogenic pumps, have a limited allowable pressure at their openings. Therefore, it is well known that in order to obtain high sputtering pressure, it is necessary to place a restriction at the pump opening that "squeezes" such a pump, ie the pressure of the chamber is significantly higher than the pressure of the pump. ing. Such “throttle” inevitably reduces the gas flow through the chamber, ie the gas throughput. Surprisingly, it has been found that at high gas throughputs, the adhesion of the coating is improved.

In one experiment, using a cylindrical magnetron cathode with an inner diameter of 19 cm and a length of 10 cm,
The stent was coated with Ta in Ar at a sputtering pressure of about 3.99 Pa (30 millitorr). In order to obtain this pressure, it was necessary to squeeze the turbomolecular high vacuum pump of the vacuum system. The Ar flow rate during this coating was approximately 84 Pa (0.63 Torr) -L / sec, consistent with a throttled pumping speed of 21 L / sec. The stent was placed in the center of the cathode about 9 cm away from the target surface. The cathode sputtering power is 20
It was set to 0W. According to Westwood's calculations, before reaching the thermal motion speed, it is about 3.99 Pa (
The average distance of Ta atoms moving in Ar at 30 mTorr varies depending on the initial energy, but is in the range of 1.7 cm to 3.4 cm. Thus, under such coating conditions, a very low density coating should be obtained. This is the case for coated stents with a black appearance. However, the adhesion of the coating is
It was very low.

In another experiment, the stent was coated at location C using two cathodes with a diameter of 34 cm, as shown in FIGS. This sputtering gas is about 0.4.
The pressure was Kr of 5 Pa (3.4 mTorr). A 2 kW DC power, a −50 V substrate bias, and the conditions of Experiment 8 in Table 2 were used. The flow rate of Kr was 28 cm ³ / min (standard cubic centimeters per minute), that is, about 48 Pa (0.36 Torr) -L / sec. At a pressure of about 0.45 Pa (3.4 mTorr), this corresponds to a squeezed pumping speed of 104 L / s during coating. All of the resulting black coatings had a level 1 to 3 peel when tested. Next, the position of the pump throttle is changed, and the flow rate of Kr is set to 200 cm ³ / min (standard state conversion), that is, about 337 Pa (2
. 53 torr) -L / sec. At the same power, pressure, and bias level as before,
The stent was coated at the C position. The only difference is that the pumping speed squeezed during coating is 744 L / sec. In this case, when the coating was inspected, there was no peeling or cracking. A scanning electron micrograph of the surface of the coating applied to the polished stainless steel surface under such conditions is shown in FIG. The open porosity of the coating can be clearly seen.

From the above results, it has been concluded that sufficient adhesion cannot be obtained with a low gas throughput, which is usually required when obtaining a high sputtering pressure. Sputtering pressure and system geometry ensure that the coating bundle reaches the substrate surface at a large angle of incidence, or the sputtering atoms travel a distance sufficiently away from the target to significantly reduce energy before reaching the substrate surface. Must be selected.

As shown, the geometry of the cylindrical magnetron can achieve this in an efficient manner, but the same result can be achieved using a planar target. The same result can be achieved using a planar target. In the case of a planar target, it is necessary to sufficiently separate the substrate from the target surface so that the distance between the target and the substrate is sufficiently separated. Alternatively, the substrate can be placed to the side of the planar target so that the coating material arrives at a large angle of incidence. This configuration is illustrated in FIG. Of course, in the case of a planar target 50, the coating material will be used inefficiently due to the position of the stent 22 shown. Nevertheless, FIG. 10 illustrates how the method of the present invention can be used with geometries other than cylindrical magnetrons.

It was found that the initial coating conditions affect the microstructure and crystalline phase of the coating but maintain excellent adhesion. In one experiment, a stent was placed at location C in the setup shown in FIG. 7 using a 34 cm diameter target. With the shutter closed, two Ta targets were applied at a Kr pressure of 3.6 mT, 200 cm ³ / min (
It was operated at 2 kW (1 kW each) at a Kr flow rate in terms of standard conditions. After 5 minutes, with the shutter closed, -200V applied to the stent to plasma clean the Ta target.
The voltage of was applied. After another 5 minutes, the shutter was opened, and coating was started with a -200V bias applied to the stent. When these conditions were maintained for 2 minutes, the stent voltage dropped to -50V and under these conditions the coating was deposited for 180 minutes. No delamination was observed on these stents.

Except for the first 5 minutes of plasma cleaning and 2 minutes of sputtering with a bias of -200 V, the conditions in the above example are the same as the conditions that produced the structure and bcc crystal phase shown in FIG. FIG. 12 shows that the microstructure has been altered by the initial conditions.
It is an atomic force microscope photograph of the obtained coating. The features in FIG. 11 and FIG.
Both are similar and porous coatings, but from close analysis, the structure of FIG.
It was found that the size was from nm to 200 nm, and the structure of FIG. 12 was about twice as large. Furthermore, the X-ray diffraction pattern of FIG. 13 shows that the crystal phase of this coating shown in FIG. 12 is mainly tetragonal and that bcc exists in part. The reflectance of this coating progressed from about 11% at a wavelength of 400 nm to about 17% at a wavelength of 700 nm.

While not being bound by this description, it has come to consider that a crucial factor in the excellent adhesion of the present coating is a porous structure promoted by oblique incidence and / or low energy deposition.

Although the present invention has been described in considerable detail using certain preferred forms, other forms are possible. For example, devices other than stents can be coated with Ta or another radiopaque material. Accordingly, the concept and scope of the appended claims should not be limited to the description of the preferred form disclosed herein.

All features disclosed in this specification, including the appended claims, abstract, and accompanying drawings, and all steps in all disclosed methods and processes, are at least part of such features and / or Or it can be combined in any combination except when the steps are mutually exclusive. All features disclosed in this specification, including the appended claims, abstract, and accompanying drawings, are replaced with alternative features serving the same, equivalent, or similar purpose unless otherwise indicated. be able to. Thus, unless expressly stated otherwise, all features disclosed are only examples of a generic series of equivalent or similar features.

All elements in the claims that do not expressly define "means" for performing a specific function or "steps" for performing a specific function are described in 35 USC 112. It should not be construed as “means” or “step”.

Embodiment
(1) In medical devices,
(A) a body at least partially comprising a radiolucent material;
(B) a porous Ta coating provided on at least a portion of the body;
Including
The Ta coating has sufficient thickness so that the medical device is radiopaque and can withstand distortions that occur during use of the medical device without unacceptable flaking;
The Ta coating is applied to the body by one of a generally oblique coating flux or a low energy coating bundle;
Medical device.
(2) In the medical device according to the embodiment (1),
The Ta coating is a medical device mainly composed of a bcc crystal phase.
(3) In the medical device according to the embodiment (1),
The thickness of the Ta coating is a medical device in the range of about 3 μm to 10 μm.
(4) In the medical device according to the embodiment (1),
The medical device is a stent.
(5) In the medical device according to embodiment (1),
The medical device is a guide wire.

(6) In the medical device according to the embodiment (1),
The medical device is an intracavitary device.
(7) In the medical device according to the embodiment (1),
The Ta coating is applied to the body by physical vapor deposition.
(8) In the medical device according to embodiment (7),
The physical vapor deposition includes sputtering, cathodic arc deposition,
Or a medical device comprising one selected from the group consisting of thermal evaporation.
(9) In the medical device according to the embodiment (1),
A material that elutes over time during the Ta coating;
A medical device.
(10) In a method for depositing a Ta layer on a medical device,
(A) maintaining a background pressure of inert gas in a sputter coating system comprising at least one Ta sputter target;
(B) applying a voltage to the Ta target to cause sputtering;
(C) sputtering for a given time to form a coating of the desired thickness;
Including
The Ta layer has a visible spectral emissivity of at least 80%;
The Ta layer is applied to the medical device by one of a generally oblique coating bundle or a low energy coating bundle;
Method.

(11) In the method according to embodiment (10),
A method in which the equilibrium temperature of the medical device during deposition is indirectly controlled by the method.
(12) In the method according to embodiment (10),
The method wherein the equilibrium temperature is in the range of 150 ° C to 450 ° C.
(13) In the method according to embodiment (10),
Applying a voltage to the medical device during the method.
(14) In the method according to embodiment (13),
The voltage includes an initial high voltage for precleaning the medical device during a first time period,
Method.
(15) In the method according to embodiment (14),
The method wherein the initial high voltage ranges from 100V to 500V.

(16) In the method according to embodiment (14),
The method wherein the first time ranges from 1 minute to 20 minutes.
(17) In the method according to embodiment (13),
The method, wherein the voltage comprises a second low voltage applied for a second time.
(18) In the method according to embodiment (17),
The method wherein the low voltage ranges from 10V to 100V.
(19) In the method according to embodiment (17),
The method wherein the second time ranges from 1 hour to 5 hours.
(20) In the method according to embodiment (10),
The method, wherein the inert gas is selected from the group comprising Ar, Kr, and Xe.

(21) In the method according to embodiment (10),
The method wherein the voltage produces a deposition rate of 1 μm / hour to 5 μm / hour.
(22) In the method according to embodiment (10),
The method, wherein the Ta layer is porous.
(23) In the method according to embodiment (22),
Introducing a material capable of eluting over time into the pores of the Ta layer;
Further comprising a method.
(24) In a medical device,
(A) a body having an outer layer;
(B) a radiopaque coating provided on at least a portion of the outer layer;
Including
The coating is applied by one of a generally oblique coating bundle or a low energy coating bundle using physical vapor deposition;
Medical device.
(25) In a medical device,
(A) a body at least partially comprising a radiolucent material;
(B) Ta coating provided on at least a part of the main body;
Including
The Ta coating can withstand distortions that occur during use of the medical device without unacceptable flaking,
The Ta coating is applied to the body by one of a generally oblique coating bundle or a low energy coating bundle;
Medical device.

1 illustrates a prior art stent. FIG. It is a top view of Ta target which surrounds a stent. FIG. 3 is a side cross-sectional view of a Ta target surrounding the stent of FIG. 2. 2 is a cross-sectional view of a conformal coating of Ta provided on a strut 12 of a stent. FIG. 4 is a graph showing reflectivity versus wavelength for a Ta coating formed in accordance with the present invention. 4 is a graph showing an X-ray diffraction pattern of a Ta coating formed according to the present invention. 4 is a cross-sectional side view of a target surrounding a stent at position C in FIG. 3 with a plate disposed over the stent. FIG. It is a top view of Ta target which surrounds a stent. FIG. 9 is a side cross-sectional view of a Ta target surrounding the stent of FIG. 8. FIG. 3 is a side elevation view of a stent disposed in the vicinity of a planar target with a large incident angle. It is a scanning electron micrograph of the surface of Ta coating applied to the surface of polished stainless steel. 4 is an atomic force micrograph of a Ta coating formed in accordance with another preferred embodiment of the present invention and applied to a polished nitinol substrate. 4 is a graph showing an X-ray diffraction pattern of a coating formed according to another preferred embodiment of the present invention.

Claims (25)

In medical devices,
(A) a body at least partially comprising a radiolucent material;
(B) a porous Ta coating provided on at least a portion of the body;
Including
The Ta coating has sufficient thickness so that the medical device is radiopaque and can withstand distortions that occur during use of the medical device without unacceptable flaking;
The Ta coating is applied to the body by one of a generally monoclinic coating or a low energy coating;
Medical device. The medical device according to claim 1, wherein
The Ta coating is a medical device mainly composed of a bcc crystal phase. The medical device according to claim 1, wherein
The thickness of the Ta coating is a medical device in the range of about 3 μm to 10 μm. The medical device according to claim 1, wherein
The medical device is a stent. The medical device according to claim 1, wherein
The medical device is a guide wire. The medical device according to claim 1, wherein
The medical device is an intracavitary device. The medical device according to claim 1, wherein
The Ta coating is applied to the body by physical vapor deposition. The medical device according to claim 7, wherein
The physical vapor deposition method includes a medical device including one selected from the group consisting of sputtering, cathodic arc vapor deposition, or thermal vapor deposition. The medical device according to claim 1, wherein
A material that elutes over time during the Ta coating;
A medical device. In a method for depositing a Ta layer on a medical device,
(A) maintaining a background pressure of an inert gas in a sputter coating system comprising at least one Ta sputter target;
(B) applying a voltage to the Ta target to cause sputtering;
(C) sputtering for a given time to form a coating of the desired thickness;
Including
The Ta layer has a visible spectral emissivity of at least 80%;
The Ta layer is applied to the medical device by one of a generally monoclinic coating or a low energy coating;
Method. The method of claim 10, wherein
A method in which the equilibrium temperature of the medical device during deposition is indirectly controlled by the method. The method of claim 10, wherein
The method wherein the equilibrium temperature is in the range of 150 ° C to 450 ° C. The method of claim 10, wherein
Applying a voltage to the medical device during the method. The method of claim 13, wherein
The voltage includes an initial high voltage for precleaning the medical device during a first time period,
Method. 15. The method of claim 14, wherein
The method wherein the initial high voltage ranges from 100V to 500V. 15. The method of claim 14, wherein
The method wherein the first time ranges from 1 minute to 20 minutes. The method of claim 13, wherein
The method, wherein the voltage comprises a second low voltage applied for a second time. The method of claim 17, wherein
The method wherein the low voltage ranges from 10V to 100V. The method of claim 17, wherein
The method wherein the second time ranges from 1 hour to 5 hours. The method of claim 10, wherein
The method, wherein the inert gas is selected from the group comprising Ar, Kr, and Xe. The method of claim 10, wherein
The method wherein the voltage produces a deposition rate of 1 μm / hour to 5 μm / hour. The method of claim 10, wherein
The method, wherein the Ta layer is porous. 23. The method of claim 22, wherein
Introducing a material capable of eluting over time into the pores of the Ta layer;
Further comprising a method. In medical devices,
(A) a body having an outer layer;
(B) a radiopaque coating provided on at least a portion of the outer layer;
Including
The coating is applied by one of a generally monoclinic coating or a low energy coating using physical vapor deposition;
Medical device. In medical devices,
(A) a body at least partially comprising a radiolucent material;
(B) Ta coating provided on at least a part of the main body;
Including
The Ta coating can withstand distortions that occur during use of the medical device without unacceptable flaking,
The Ta coating is applied to the body by one of a generally monoclinic coating or a low energy coating;
Medical device.