Medical instrument and device having echogenic markings

Abstract

The present invention relates to a medical device having an improved ultrasound visibility and a very smooth surface, to methods for producing the device according to the invention and to the application of the device in therapeutic and diagnostic interventions. The improved ultrasound visibility is achieved by bubbles or closed cavities in an inner polymer layer.

Claims

1. A medical device having an echogenic marking, the device comprising an element having a tubular shape, said element comprising an outer polymer layer and at least one inner polymer layer, and at least the outer polymer layer has a very smooth surface, wherein the outer polymer layer is transparent to laser radiation and at least one inner polymer layer contains laser additives comprised of laser absorbers and the echogenic marking is comprised of closed cavities or bubbles in the at least one inner layer containing laser additives, with the closed cavities or bubbles having been generated by the laser additives under the action of laser radiation.

2. The medical device having an echogenic marking according to claim 1, wherein the concentration of the laser absorbers in an inner layer is in the range from 0.05 to 1% by weight.

3. The medical device having an echogenic marking according to claim 1, wherein the laser absorbers are nanoscale.

4. The medical device having an echogenic marking according to claim 3, wherein the laser absorbers have particle sizes in the range of <300 nm.

5. The medical device having an echogenic marking according to claim 1, wherein the average roughness values R.sub.a of the surface of the outer layer, measured in accordance with DIN EN ISO 4287, of the marked and the unmarked regions deviate from one another by not more than 0.2 m.

6. The medical device having an echogenic marking according to claim 1, wherein the echogenic marking is present on large-area regions or in the form of small-area labels, patterns or markings.

7. The medical device having an echogenic marking according to claim 1, wherein the polymer layer outside the echogenic markings have a high transparency to visible light.

8. The medical device having an echogenic marking according to claim 1, wherein the number of bubbles or closed cavities in the marked areas is between 5 to 200 per mm.sup.2.

9. The medical device having an echogenic marking according to claim 1, wherein the bubbles or closed cavities have a diameter of 5 to 50 m and a virtually spherical shape.

10. The medical device having an echogenic marking according to claim 1, wherein the bubbles or closed cavities are gas-filled.

11. The medical device having an echogenic marking according to claim 1, wherein the device is a catheter, cannula, needle, stent, implant, dilator, balloon or marker.

12. The medical device having an echogenic marking according to claim 1, wherein said device further comprises an X-ray contrast agent.

13. A method for producing the medical device having an echogenic marking as claimed in claim 1 comprising (i) overlaying the inner layer containing laser additive with the outer layer that is transparent to laser radiation or embedding the inner layer containing laser additive between two outer layers; (ii) foaming areas within the inner layer containing laser additive by treating the tube with laser radiation, thereby causing the laser absorbers to generate closed cavities or vesicles within the inner layer.

14. The method as claimed in claim 13, wherein said overlaying step is selected from co-extruding, casting, shrink-wrapping, adhering or coating.

15. The method as claimed in claim 13, wherein said laser radiation has a wavelength of from 350 to 1,100 nm.

16. The method as claimed in claim 13, wherein the area is a label, pattern or marking.

17. The method as claimed in claim 13, wherein said method further comprises forming the inner layer by combining nanoscale absorber additives and polymer.

18. The method as claimed in claim 13, wherein said method further comprises filling one of the layers with an X-ray contrast agent.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0020] FIG. 1A is a schematic representation of a catheter produced according to the example;

[0021] FIG. 1B is a top view photograph of a catheter produced according to the example;

[0022] FIG. 2A is a scanning electron microscope (SEM) image of a cross-section of a catheter produced according to the example;

[0023] FIG. 2B is an SEM and of the surface of a catheter produced according to the example;

[0024] FIG. 3A is an ultrasound view of a catheter produced according to the example at a 0 position (a); and

[0025] FIG. 3B is an ultrasound view of a catheter produced according to the example at a 45 position (b).

DETAILED DESCRIPTION OF ADVANTAGEOUS EMBODIMENTS OF THE INVENTION

[0026] The invention is thus directed to a medical device having an echogenic marking, wherein the device comprises a flexible element having a tubular shape, said element comprising an outer polymer layer and at least one inner polymer layer, and at least the outer polymer layer has a very smooth surface, characterized in that the outer polymer layer is transparent to laser radiation and an inner polymer layer contains laser additives in the form of laser absorbers, wherein the echogenic marking is formed by closed cavities or bubbles in the inner layer, which are generated by the laser additives under the action of the laser radiation.

[0027] The flexible element preferably has an outer diameter of from 6 to 18 Charrire (2 mm to 6 mm) especially of from 2.5 mm to 5 mm. The wall thickness is preferably in a range of from 0.2 mm to 0.6 mm, especially from 0.25 mm to 0.4 mm. The flexible element is useful as an ultrasound detectable catheter.

[0028] In the method of foaming by means of laser, the organic compounds contained in the plastics are broken up, destroyed and vaporized by local heating. In this process, the carbon present in the plastic oxidizes to yield CO.sub.2 and forms gas bubbles. The cavities in the melt are firmly integrated in the material structure upon cooling of the material. Foaming is to be understood here to also mean the formation of a low number of bubbles at a relatively large distance from one another in the range of 5 to 200 per mm.sup.2.

[0029] The use of so-called chemical blowing agents is expressly dispensed with in the context of this invention. Chemical blowing agents evolve a gas at elevated temperature as a result of thermal decomposition and can thereby form a foam structure.

[0030] Such additives are usually characterized by physiologically unfriendly ingredients or decomposition products and not suitable for medical use. Moreover, the chemical blowing agents are not activated in a location-accurate manner.

[0031] For the heat input, a laser beam is directed to the surface to be foamed. By means of a computer-controlled optical system, rapidly deflectable laser pulses having the desired power can act specifically on the sites to be foamed.

[0032] The introduction of heat is exactly defined thermally and geometrically. Both large-area regions and small-area labels, patterns and markings can be foamed with high precision.

[0033] In the interaction with laser light, plastics differ from many other materials in that they absorb the energy to a different extent, depending on the wavelength of the light.

[0034] Most plastics are laser-transmissive, i.e. they show no interaction with the laser radiation, in the region of the NIR/IR wavelengths. To utilize the advantages of the laser, easily dispersed absorbers are introduced into specific layers of the catheter and thus ensure a positionally accurate introduction of heat upon irradiation. Preferably, the laser additives are introduced into an inner layer of the catheter and are always covered by an outer layer without laser additives. This feature, together with the elastic properties of the polymer layers, means that effects on surface roughness or surface unevennesses due to foam formation are negligible. By selection of suitable absorber substances with small particle size and small use amounts, it is possible to avoid negative influences on mechanical and optical properties as far as possible.

[0035] Nanoscale mixed metal oxides in particular, such as indium or antimony tin oxide, are suitable as absorber additives for transparent materials. Nanoscale absorber additives contribute to maintenance of transparency to visible light and achievement of a uniform size and distribution of the cavities, and this has an advantageous effect on the design of patterns or letterings and on ultrasound visibility.

[0036] For the foaming of plastic, cost-effective diode-pumped solid-state lasers and fibre lasers in the wavelength range of 1064 nm are available, as are similarly also used for marking and labelling. For even more exact markings and less thermal influence on the base material, it is also possible to use technically more complex instruments with wavelengths of only 532 nm or even 355 nm.

[0037] The markings according to the invention are characterized by a closed-pore structure, the cavities of which have a virtually spherical shape in the size range from 5 to 50 m and are only localized in the interior of the polymer layers of the catheter. By varying the additives and the laser parameters, such as power density, pulse frequency and deflection speed, it is possible to specifically set the foaming intensity. The parameters are chosen such that the desired pore size and pore number arises. Although ultrasound visibility increases with greater pore diameters, the size thereof can be limited depending on the wall thickness. It became apparent that just a pore number of 10-50 on an area of 1 mm.sup.2 brings about a sufficient improvement in marking visualization in ultrasound diagnostics.

[0038] A major aspect of the present invention is that the discrete echogenic markings are produced without changes in the nature of the surface of the catheters. The claimed catheters have the advantage that the entire surface, including the marked regions, have a consistent smooth nature which is solely determined by the catheter material and the extrusion conditions.

[0039] To avoid undesired surface changes due to the laser-induced foaming and due to open pores, what is proposed is to overlay the laser-sensitive layer with an additive-free, laser-transparent cover layer which is co-extruded or produced in some other way. In the preferred technology, the differing transmission behaviour of the layers is utilized in order to specifically trigger foam formation only in an inner layer. Besides the preferred design with 2 layers, the catheter can comprise yet further polymer layers. By embedding the laser-active layer between 2 laser-transparent layers, it is, for example, possible to ensure that the surface in the catheter lumen is also not influenced by the laser treatment. The elastic properties of the thermoplastic materials usually used for catheters, such as PEBAX, polyamide, thermoplastic polyurethane, polyethylene or soft PVC (polyvinyl chloride), ensure that the deformations in the foamed layer are not transferred up to the outer surfaces of the catheter. Since a thickness of <100 m of the cover layer is sufficient, it can usually be thinner than the foamed layer. As required for intravascular catheters according to DIN EN ISO 10555-1, the outer surface appears free of unevennesses and foreign bodies at 2.5 magnification. Surface analyses using digital 3D microscopy show that the average roughness values R.sub.a, measured in accordance with DIN EN ISO 4287:2010, of the marked and the unmarked regions deviate from one another by not more than 0.2 m.

[0040] Owing to the increased echogenicity of the markings, the medical instrument can be visually depicted with the aid of an ultrasound examination. The gas inclusions in the marked region bring about a stronger reflection of the sound waves, with the result that they are shown distinctly more brightly compared to the surrounding substances in the ultrasound image (B mode). The detectability of the catheter is thereby distinctly improved. Owing to a patterned design of the markings, simple distinguishing of endogenous structures is possible and a displacement, bend or twist is easily identifiable. Furthermore, the possibility arises of providing regions of particular interest with a scale by means of patterns and of highlighting said regions for subsequent manipulation of the catheter.

[0041] The angle-independent high scattering characteristics on the spherical gas inclusions means that a high image contrast is generated even in the case of an unfavourable inclined position of the device in relation to the incident ultrasound. In contrast to known solutions, the design according to the invention offers the advantage that an intensifying echogenicity is brought about especially with increasing angle of incidence.

[0042] By filling one of the polymer layers with an X-ray contrast agent, such as barium sulfate or iodine-containing contrast agent, it is also possible to combine the echogenic properties with a good X-ray visibility.

[0043] Besides the use on catheters, the claimed method can also be implemented on further medical devices used within a human body. These are especially cannulas, needles, stents, implants, dilators, balloons and markers. The necessary layers comprised of thermoplastic material can be generated by extrusion, casting, shrink-wrapping or adhesion of jackets or sleeves, or coatings with polymer solutions, melts or powders.

[0044] In what follows, the invention is elucidated on the basis of an exemplary embodiment. Further details, advantages and features of the invention are immediately apparent from the claims.

[0045] As noted above, in the drawings,

[0046] FIG. 1 shows a schematic representation (A) and a top view (B) of a catheter produced according to the example;

[0047] FIG. 2 shows SEM images of a cross-section (A) and of the surface (B) of a catheter produced according to the example

[0048] FIG. 3 shows an ultrasound view of a catheter produced according to the example at a 0 position (A) and 45 position (B).

[0049] FIG. 1A depicts the fundamental structure of a catheter 01 provided with echogenic markings 02. The catheter has two layers, wherein the two layers 03, 04 can consist either of the same polymer matrix or of different materials and the outer layer 03 contains no additives and the inner layer 04 is filled with a laser absorber at a low fraction of 0.05 to 1%. To achieve good transparency to visible light in the non-irradiated regions and a pore size and distribution in the irradiated regions that is as uniform as possible, preference is given to using laser absorbers with particle sizes <300 nm. Nanoscale laser absorber particles mean that the effectiveness of pattern generation, as measured by precision and delimitation of the contours, is optimized with minimum use of laser additive.

[0050] The gas bubbles 05 in the inner layer 04 are specifically generated by laser treatment. The laser absorbers mean that only the inner layer 04 is heated upon exposure to the laser radiation and that the formation of cavities 05 does not take effect at the surface. The outer unfilled cover layer 03 remains unchanged and can be realized with a relatively low layer thickness.

[0051] The travel path of the laser beam is programmed such that the pore structure arises in a localized manner only in the region 02 of the catheter that is to be marked. In the example depicted, the catheter contains striped markings 02 around the entire circumference. Owing to the arrangement of the stripes in groups having different numbers of stripes, an accurate assignment in the ultrasound image (FIGS. 3A and 3B) is possible.

[0052] The SEM image of a cross-section of an additivized layer 04 of a catheter, as depicted in FIG. 2A, shows that closed-pore cavities 05 in the size range of 5 to 50 m are formed. It is also clear that laser power decreases with increasing layer depth and that cavity size and number decrease as a result. The SEM image of the surface of a marked region of a two-layer catheter (FIG. 2B) confirms that the laser treatment does not cause any changes to the surface topography.

[0053] Ultrasound visibility was examined in a water bath at sonic angles of 0 (orthogonal angle) and 45 with a linear sonic head and a frequency of 10 MHz. To assess the contrast of the marking 10, 11 compared to unmarked regions 08, 09, the grey scale spectra of the individual image regions were compared with one another by means of a graphics program, with 100% black corresponding to a value of 0 and 100% white corresponding to a value of 255. In the ultrasound image, markings produced according to the invention stand out very well, with average brightness values of greater than 200, from the black background of the water and from the untreated regions of the catheter.

Example

[0054] This non-limiting example describes the production of an exemplary ultrasound marking according to the invention on a catheter.

[0055] A 2-layer catheter having an outer diameter of 3 mm, an outer layer thickness of 0.1 mm and an inner layer thickness of 0.3 mm was produced by means of a tube extrusion system. TPU of the type ELASTOLLAN 1180 A10 FC was used for both layers. For the inner layer, 1% of a master batch filled with a laser additive was premixed with the TPU granular material. The master batch, which was produced on the basis of TPU by compounding with an extruder, contained 10% of antimony-doped tin oxide with particle sizes in the range of 10 to 20 nm. The tube was cut to length and labelled using a pulsed Yb fibre laser from FOBA. The rectangular markings 02 (image 1) were programmed in the dimensions 13 mm and realized by double lasers after 180 rotation of the tube around the entire circumference of the tube. By choosing suitable laser parameters, both grey colouring and foaming were achieved at the marked sites 02. Owing to the grey colouring, the marking can also be visually identified by the human eye. Values applied in the laser processing were a pulse width of 120 ns at a frequency of 20 kHz with a pulse energy of 4.2 watts and a wavelength of 1064 nm. Images with a scanning electron microscope of the cross-sectional area and the surface of the catheter show that cavities having a diameter of 5 to 50 m are formed in the inner layer doped with laser additive and that the surface of the catheter remains smooth. The average number of cavities in this size range is approx. 100 per mm.sup.2. The surface topography was analysed using the 3D digital microscope VHX-6000. With an arithmetic average roughness value R.sub.a (DIN EN ISO 4287:2010) of 0.19 m, as ascertained over the entire width of the marking, and an averaged roughness depth R.sub.a of 1.7 m, there are no relevant differences in relation to the unmarked areas (i.e. R.sub.a: 0.16 m, R.sub.z: 1.6 m) of the catheter.

[0056] The sonographic properties were examined in a water bath and on a pork model using a DP-50 ultrasound diagnostic instrument from Mindray and a linear sonic head. FIGS. 3A and 3B show the ultrasound images of a catheter immersed in the water 07 at a 0 (3A) and 45 position (3B) in relation to the transmitted ultrasound. The following table gives an overview of the average brightness values of the various regions of the ultrasound image, as ascertained from a grey value histogram.

TABLE-US-00001 Region of the image Brightness value Water 07 1 Unmarked catheter region 0 08 41 Unmarked catheter region 45 09 32 Marking on catheter at 0 215 position 10 Marking on catheter at 45 242 position 11

[0057] Both the subjective visual observation and the digital analysis of the images provide evidence for the high degree of functionality of the echogenic markings. An increasing visibility can be determined with increasing angle of the ultrasound in relation to the position of the catheter.