MXPA99011708A

MXPA99011708A - Increased radiopacity of peripheral cateter tube and cent

Info

Publication number: MXPA99011708A
Application number: MXPA/A/1999/011708A
Authority: MX
Inventors: C Onwumere Fidelis; D Solomon Donald
Original assignee: Ethicon Inc
Priority date: 1998-12-31
Filing date: 1999-12-14
Publication date: 2000-12-06

Abstract

A medical implant, tube and method for providing increased intensity of X-ray detection in catheters, stents, vascular grafts or other tubular implants, in one aspect the medical implant includes a visually transparent radiopaque polymer and a filling material having a radiopaque component

Description

INCREASED RADIOPACITY OF PERIPHERAL AND CENTRAL CATHETER TUBE BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The invention relates generally to medical implants and more particularly to medical implants including medical tubes for catheters, stents and other devices.

BACKGROUND OF THE INVENTION In certain medical procedures, medical implants are placed on the body. These implants include catheters inserted into passages, blood vessels or body cavities to pass fluids, drain fluids, perform medical examinations, etc. A stent is a second type of medical implant that is used to keep an orifice or body cavity open during skin grafting or to provide support for tubular structures, for example, during or after an anastomosis. It is generally desired that medical implants, such as catheters and stents, be radiographically opaque, so that their precise location, within the host body, can be detected by X-ray examination. Furthermore, it is advantageous that such medical implants are optically or visually transparent, so that a flow of fluid from one side to another of them can be observed. Many tubular shaped medical implants, such as catheters and stents, are made from a polymeric base. Suitable polymers are those that can be configured into tubular shapes that are, particularly in the case of catheters, flexible enough to be routed or snaked to a location in the body. In the case of a peripherally inserted central catheter (PICC), for example, the catheter tube is routed or snaked, in one case, through a vein in the patient's neck or arm into the superior vena cava of the patient's heart . The tube should be flexible enough to be routed in this way without causing trauma to the patient. The polymer chosen as well as the medical implant must also have sufficient strength when configured in a tube so that the lumen does not collapse in a passage or hole. Even, the tube must be resistant to folding or twisting to ensure a continuous passage. Polyurethane based polymers are a popular choice for polymers for medical implants, because certain polyurethanes have the beneficial properties indicated. In general, polyurethanes are condensation products of reactions between diisocyanate (diisocyanate compounds having one or two functionalities) and soft block polyols. Typically, the polyurethanes are combined with aromatic or aliphatic diols or diamines of low molecular weight as chain extenders to impart the useful properties of flexibility, strength and kink resistance. Low molecular weight diols include butanediol, pentanediol, hexanediol, heptanediol, benzene-dimethanol, hydroquinone-diethanol and ethylene glycol. The addition of diamine-based chain extenders forms a class of polyurethanes commonly known as polyurethaneureas. Suitable diamines include ethylenediamine, butanediamine, propandiamine and pentanediamine. An additional feature of the polyurethanes with the diol or diamine chain extenders is that the catheters or stents formed from these materials are typically optically or visually transparent making these polymer matrices excellent compounds for medical implants.

However, unfortunately, these polyurethanes are generally not radiopaque. Radiopaque medical implants, such as catheters, including radiopaque polyurethanes have been developed. Generally, these radiopaque polymer structures are of two forms. A first form of radiopaque polymer incorporates a radiopaque filler or pigment material. Typical fillers include barium sulfate (BaSO), bismuth subcarbonate or certain metals such as tungsten (W). Other radiopaque fillers are pigments that are incorporated into a polymer tube include bismuth oxychloride and other bismuth salts such as bismuth subnitrate (basic bismuth nitrate) and bismuth oxide (See patent E.U.A. No. 3618,614). A drawback of the polymers with incorporated filler material is that, although such polymers are radiopaque, the filler material tends to render the polymer non-transparent. A second form of radiopaque polymer useful in medical implants incorporates a halogenated chain extender in the polymer matrix. In the patents E.U.A. Nos. 4,722,344; 5,177,710 and 5,346,981 examples of these types of polymers are described. The preferred halogen in these patents is bromine (Br). Polymers that incorporate a brominated chain extender in the polymer matrix generally yield a tube that is radiopaque and optical or visually transparent. In order to properly impart the useful radiopaque properties, the halogen-extended chain polymer, such as a bromine-extended chain polymer, must have a minimum amount of halogen (for example bromine) to impart radiopacity to the polymer. Experimental studies show that, for example, the minimum amount of bromine in a polyurethane-based polymer useful as a catheter is approximately 15 percent. Amounts less than this tend to make the tube difficult to detect with X-rays. A second problem with halogen-extended chain polymers is that the maximum amount of halogen that can be incorporated into the polymer is limited. Experimental studies show that polymers having, for example, a bromine concentration greater than 30% are too rigid to be used as a medical implant, such as a catheter tube. Accordingly, the radiopacity of the tube is limited by the amount of bromine that can be incorporated into the polymer matrix without degrading the properties of the tube made from such a polymer. As indicated above, certain halogen-extended chain polymers offer both radiopacity and optical transparency. However, to properly maintain the superior properties demonstrated by the conventional thermoplastic polyurethane elastomer with non-halogenated chain extenders, the amounts of halogen must be strictly limited. It would be desirable, in certain cases, to have a halogen-extended chain polymer with a radiopaque property that is not limited by the amount of bromine that is incorporated into the polymer matrix. What is needed is a combination that can maximize the radiopacity of the implant without increasing the halogen concentration of the polymer beyond that which could adversely affect the physical characteristics of the medical implant.

BRIEF DESCRIPTION OF THE INVENTION A method and apparatus for providing increased radiopacity to a polymer while retaining its desired rigidity or flexibility. In one embodiment, a medical implant such as a tube comprising a visually transparent radiopaque polymer and a radiopacific filling material having a radiopaque component is produced.

BRIEF DESCRIPTION OF THE DRAWINGS Figures 1, 2, 3 and 4 are cross sections of the tube of alternative embodiments of the invention.

DETAILED DESCRIPTION OF THE INVENTION In order to produce medical implants, catheters, stents, vascular grafts and the like, it is important to obtain a balance between radiopacity, optical transparency and the flexible or manageable properties of the composition to form an effective material. The natural balance of increasing one of these properties at the potential expense of the other becomes clear from the antecedent technique and the antecedents, presenting significant limitations. The invention relates to a radiopaque tube comprising a visually transparent radiopaque polymer and a radiopaque filler material useful as a medical implant such as a catheter, stent, vascular graft or a similar device. In one embodiment, the visually transparent radiopaque polymer comprises a polyurethane including a diisocyanate, a polyol, and a chain extender, which contains between 10-30 wt.% Bromine concentration. The filler material contains a radiopaque agent which may be, for example, barium sulfate, bismuth subcarbonate, tungsten or other material. In one embodiment, the filler material is combined with the radiopaque polymer in a tube by combining the filler material and the polymer and extruding them into a unitary tube. Figure 1 shows a cross section of a tube where the combination of radiopaque polymer and filler material is arranged circumferentially to form the tube 20 defining the lumen 30. In one embodiment, the filler material, for example, is material of barium sulfate filler or bismuth subcarbonate, which provides radiopacity to the final apparatus (eg, tube). One way of making a medical implant such as a medical tube is to combine the filling material as a powder with pieces of transparent radiopaque polymer and process the combination by a twin screw extruder to form pellets. The pellets are extruded after conformity with conventional extrusion techniques to form the medical implant shown in Figure 1. In another embodiment, the filler material includes filler and polymer material (eg, thermoplastic polyurethane) and is coextruded with a amount of radiopaque polymer visually transparent. The tube of Figure 1 can be extruded from polymer pellets containing the filler material (filled polymer) and polymer pellets containing the visually transparent radiopaque polymer using an extruder. To make the polymer pellets of the filling material, the filling material (for example, barium sulfate, bismuth subcarbonate, etc.) can be added in the form of a powder with pieces of polymer and processed by a twin screw extruder to form the filled polymer pellets. Although the advantage of a substantial increase in radiopacity is provided, when combined with the polymer, the filler material in the tube resulting from the invention will tend to limit the optical transparency of the polymer. This can be overcome by various modalities which provide at least one visually transparent radiopaque polymer window, which is free of filler material, coextruded to produce a segment of optical or visually transparent cross section of the tube. Figures 2-4 illustrate various embodiments formed by combining the visually transparent radiopaque polymer (for example brominated polyurethane) with a filled polymer filled material (filled thermoplastic polyurethane and / or filled brominated polyurethane). Figure 2 shows a cross section of tube having filling material (filled polymer) disposed through tube 20. A visually transparent radiopaque polymer window is co-extruded as segment 10 allowing visual observation of the fluid flowing within the lumen 30 of the tube. In other modalities, multiple windows may be added, whenever desired, in separate segments along the circumferential circumference of the tube, which nevertheless extend longitudinally, parallel to the general direction of flow within the lumen. In Figure 3 one such example of multiple window composition is illustrated. Each embodiment illustrated by Figure 2 and Figure 3 can be co-extruded using two extruders, an extruder for the visually transparent radiopaque polymer and a second extruder for the filler material, which, in these embodiments, is a filled polymer. In Figure 3, the particular extrusion can be divided to form multiple windows that appear longitudinally as strips along the length of the tube. It is contemplated that the additional embodiments of various window arrangements are within the scope and scope of the invention. Figure 4 shows an embodiment resulting from the coextrusion of the visually transparent radiopaque polymer that does not have filler material and the filler material (filled polymer). In Figure 4, the filling material (filled polymer is mostly isolated and concentrated in one or more segments 40 disposed within the tube, which in other conditions is visually transparent, of for example brominated polymer 10. When the tube is viewed in the longitudinal direction, the segments 40 of the filling material tend to form one or more stripes of varying size which generally extend longitudinally along some portion of the tube, substantially parallel to the direction of flow within the lumen. This modality allows the specific placement of radiopaque segments, although they are potentially optically obstruent (filled polymer) so as to allow observation of the flow of the fluid while retaining the upper radiopacity of the segments, appearing as strips within the tube, where they are arranged concentrated amounts of the filling material, as with the modality of figure 3, a A coextrusion using two extruders with separate extrusions can form the pattern into strips. The visually transparent radiopaque polymer is prepared in accordance with the polymerization procedures known in the art. In certain embodiments, the polymer is a brominated polyurethane which is prepared in accordance with the methods described in U.S. Patent Nos. 5,346,981, 5,177,170 and 4,722,344. An example of a suitable polyurethane comprises a diisocyanate, a polyol and a brominated chain extender. Suitable diisocyanates include, but are not limited to, trans-1,4-cyclohexane diisocyanate, methylenebis-diphenyldiisocyanate and methylenebis-dicyclohexanediisocyanate. Suitable polyols include but are not limited to, polytetrahydrofuran, polyethylene glycol, ethylene glycol-b-propylene glycol-b-ethylene glycol, polyester diol and polyester carbonate diol. Suitable brominated chain extenders include, but are not limited to, bromobisphenol-A-diethanol (for example tetrabromobisphenol-A-diethanol), brominated hydroquinone-diethanol, brominated benzene-diethanol and brominated biphenyoxidietanol. Where the visually clear radiopaque polymer is a polyurethane, the concentration of bromine in the polymer is typically less than about 30% by weight of the polymer due to! potential effect that high levels of bromine have on polymer properties, and potential stoichiometric limitations for binding additional bromine to the polymer. The appropriate filler material such as the filling material of the medical implant of the invention includes, but is not limited to, barium sulfate, certain bismuth compounds including bismuth subcarbonate and bismuth oxychloride, and certain metals having radiopaque properties including tungsten . As indicated above, the appropriate fillers can be combined directly with the visually transparent radiopaque polymer (for example thermoplastic polyurethane containing brominated chain extenders) to form the tube shown, for example, in Figure 1. Alternatively, appropriate fillers can be combined with a radiopaque or non-radiopaque polymer to form a filled polymer. The filled polymer can then be combined with a visually transparent radiopaque polymer to form the tube shown, for example in Figures 1-4. Non-radiopaque polymers suitable for the filler material include, but are not limited to, the above-mentioned thermoplastic polyurethanes with the desired elastomeric properties (eg, polyurethanes, or polyurethaneurea, extended chain with diols or low molecular weight diamines respectively). Suitable radiopaque polymers include, but are not limited to, polyurethanes having brominated chain extenders such as those described above with reference to the visually clear radiopaque polymer.

In particular embodiments wherein the visually transparent radiopaque polymer is a brominated polyurethane and is combined with a radiopaque or non-radiopaque filled polyurethane filler material, a resulting medical implant, i.e. tube, will have a percentage of filler material (i.e. , filled polyurethane) of between 35% and 65% by weight. Typical weight ratios of brominated polyurethane to filled polyurethane include 50:50, 55:45, 60:40, 65:35. It will be appreciated that the weight ratios will vary depending on, among other considerations, the desired level of radiopacity of the resulting medical implant and whether the filled polymer is formed of a radiopaque polymer. The addition of the radiopacific filler material (either as a filler material only with the visually clear radiopaque polymer or as a filler material combined with a radiopaque or non-radiopaque polymer) substantially increases the X-ray intensity of the resulting tube without affecting the properties of the polymer. Its flexibility and its elastomeric properties are generally retained. The typical proportions of the filler material used vary depending on the particular type. For example, for the bismuth subcarbonate, the percentage of filler material by weight of the entire tube is between 15 and 30% when combined with a polyurethane polymer. Barium sulfate can be used in a concentration between 18-35%, although, in certain coextrusion processes, it can be increased up to 45%. The tungsten-based radiopacifying filler material is commonly used in a percentage of tube weight concentration of between 15-25%. The foregoing detailed description focused on the combination of a polymer and a filler. It will be appreciated that additional polymers or additives can be combined with the polymer and filler material to, in certain cases, further enhance the properties of the final composition including a medical implant. For example, the polyurethane can be combined with other medical grade polymers such as polyether amide, polyether ester and thermoplastic elastomers that do not have a urethane base. In the foregoing detailed description, the invention is described with reference to specific embodiments thereof. However, it will be apparent that various modifications and changes may be made thereto without departing from the broad scope and scope of the invention as set forth in the claims. Therefore, the specification and drawings should be considered in an illustrative rather than restrictive sense.

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A medical implant comprising: a radiopaque polymer visually transparent; and a filler material having a radiopaque component.

2. The medical implant according to claim 1, further characterized in that the visually transparent radiopaque polymer is a first polymer and the radiopacific filling material comprises a second polymer.

3. The medical implant according to claim 2, further characterized in that the second polymer is brominated.

4. The medical implant according to claim 1, further characterized in that the filling material comprises a filling material selected from the group consisting of barium sulfate, bismuth subcarbonate and tungsten.

5. The medical implant according to claim 1, further characterized in that the polymer is a polyurethane.

6. The medical implant according to claim 1, further characterized in that the polymer comprises a polyol.

7. - The medical implant according to claim 1, further characterized in that the polymer comprises a brominated chain extender that can react with the isocyanate.

8. The medical implant according to claim 7, further characterized in that the concentration of bromine is approximately between 10% and 30% by weight of the medical implant.

9. The medical implant according to claim 1, further characterized in that the filling material is barium sulfate in a range between about 18% to 45% by weight of the medical implant.

10. The medical implant according to claim 1, further characterized in that the radiopaque component of the filling material is a bismuth compound in a range between approximately 15% and 30% by weight of the medical implant.

11. The medical implant according to claim 1, further characterized in that the radiopaque component of the filling material is tungsten in a range between approximately 15% and 25% by weight of the medical implant.

12. A tube comprising: a radiopaque polymer visually transparent; and a radiopacific filler material having a radiopaque component.

13. The tube according to claim 12, further characterized in that the visually transparent radiopaque polymer is a first polymer and the radiopacific filler material comprises a second polymer.

14. The tube according to claim 13, further characterized in that the second polymer is brominated.

15. The tube according to claim 12, further characterized in that the filling material comprises filling material selected from the group consisting of barium sulfate, bismuth subcarbonate and tungsten.

16. The tube according to claim 12, further characterized in that the polymer is a polyurethane.

17. The tube according to claim 12, further characterized in that the polymer comprises a polyol.

18. The tube according to claim 12, further characterized in that the polymer comprises a brominated chain extender that can react with the isocyanate.

19. The tube according to claim 18, further characterized in that the bromine concentration is approximately between 10% and 30% by weight of the tube.

20. The tube according to claim 12, further characterized in that radiopaque component of the filling material is barium sulfate in a range between about 18% and 45% by weight of the tube.

21. The tube according to claim 12, further characterized in that the radiopaque component of the filling material is a bismuth compound in a range between approximately 15% and 30% by weight of the tube.

22. The tube according to claim 12, further characterized in that the radiopaque component of the filling material is tungsten in a range between approximately 15% and 25% by weight of the tube.

23.- A method that comprises: combining a visually transparent radiopaque polymer; and a radiopaque filling material; and forming the combination in a medical implant.

24. The method according to claim 23, further characterized in that the visually transparent radiopaque polymer is a first polymer and the radiopaque filling material comprises a second polymer.

25. The method according to claim 24, further characterized in that the second polymer is brominated.

26. The method according to claim 23, further characterized in that the radiopaque visually transparent polymer is a radiopaque brominated polyurethane.

27. The method according to claim 23, further characterized in that the polymer is a first portion and the method further comprises: coextruding a second portion of the polymer.

28. - The method according to claim 23, further characterized in that the polymer is a first portion and the method further comprises: coextruding a second portion of the polymer so that it substantially isolates and encompasses at least one segment of the polymer-material combination of filling inside the polymer.

29. The method according to claim 27, further characterized in that the step of coextruding also comprises configuring a tube wherein the polymer-filler material combination is longitudinally arranged with a portion of the tube.

30. The method according to claim 29, further characterized in that the longitudinal arrangement of the combination first portion of the polymer-filler material forms coextensive strips with a portion of the tube.