U.S. patent application number 12/347217 was filed with the patent office on 2010-07-01 for biocompatible polycarbonate and radiopaque polymer compositions and methods of manufacturing medical devices with same.
Invention is credited to Xiaoping Guo, David P. Johnson, Richard E. Stehr.
Application Number | 20100168270 12/347217 |
Document ID | / |
Family ID | 42060546 |
Filed Date | 2010-07-01 |
United States Patent
Application |
20100168270 |
Kind Code |
A1 |
Guo; Xiaoping ; et
al. |
July 1, 2010 |
BIOCOMPATIBLE POLYCARBONATE AND RADIOPAQUE POLYMER COMPOSITIONS AND
METHODS OF MANUFACTURING MEDICAL DEVICES WITH SAME
Abstract
The invention relates to biocompatible polycarbonate/polyamide
polymer compositions for use in medical and surgical devices.
Additional additives, crosslinking agents, phosphites, and
optionally a radiopaque filler or fillers can be used to produce
the high performance compositions desired. The polymer compositions
have improved melt processability along with balanced or enhanced
physical and mechanical properties, especially when combined or
over-extruded onto or covering other polymer layers, such as soft
and/or flexible layers commonly used in medical device applications
and catheter tips, for example. The ability to incorporate
radiopaque compounds into these polymer compositions during melt
processing offers improved methods for monitoring and visualizing
medical devices when used inside the body and as well as improving
the operating characteristics of the medical device components
Inventors: |
Guo; Xiaoping; (Eden
Prairie, MN) ; Johnson; David P.; (Brooklyn Park,
MN) ; Stehr; Richard E.; (Stillwater, MN) |
Correspondence
Address: |
SJM/AFD-WILEY;Legal Department
One St. Jude Medical Drive
St. Paul
MN
55117-9913
US
|
Family ID: |
42060546 |
Appl. No.: |
12/347217 |
Filed: |
December 31, 2008 |
Current U.S.
Class: |
523/113 |
Current CPC
Class: |
C08L 33/10 20130101;
C08L 69/00 20130101; C08L 77/10 20130101; C08L 69/00 20130101; C08L
77/02 20130101; C08L 77/06 20130101; C08G 69/40 20130101; C08L
2666/20 20130101; C08K 5/353 20130101; C08L 2666/20 20130101 |
Class at
Publication: |
523/113 |
International
Class: |
A61F 2/06 20060101
A61F002/06 |
Claims
1. A biocompatible polymer composition comprising poly(bisphenol A
carbonate), homopolymer a polyamide or a polyamide-based
thermoplastic elastomer, and optionally an inorganic radiopaque
filler.
2. The polymer composition of claim 1, wherein the polyamide is an
aromatic polyamide.
3. The polymer composition of claim 1, wherein the polyamide is an
aliphatic polyamide.
4. The polymer composition of claim 3, wherein the aliphatic
polyamide is selected from: nylon-6,6; nylon-6; nylon-11; nylon-12;
and nylon 6T.
5. The polymer composition of claim 1, wherein the polyamide-based
thermoplastic elastomer is a poly(ether-block-amide) copolymer.
6. The polymer composition of claim 1, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
7. The polymer composition of claim 4, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
8. The polymer composition of claim 5, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
9. The polymer composition of claim 1, further comprising one or
more organic phosphites having the general structure: wherein R,
R1, and R2 are selected from: phenyl; substituted phenyl groups;
phenyl groups substituted by an alkyl group of 1 to 20 carbon atoms
in length.
10. The polymer composition of claim 9, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
11. The polymer composition of claim 1, further comprising one or
more functionalized polyolefins, thermoplastic olefins, and
thermoplastic olefins having an anhydride reactive group.
12. The polymer composition of claim 11, wherein the polyolefin or
olefin is selected from one or more of: maleic anhydride-grafted
polyethylene and polypropylene; maleated SBS
(styrene-butadien-styrene copolymer); maleated SIBS
(styrene-isobutylene-styrene); and maleated SIS
(styrene-isoprene-styrene copolymer).
13. The polymer composition of claim 12, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
14. The polymer composition of claim 1, further comprising a
functionalized polymer containing an epoxide group.
15. The polymer composition of claim 14, wherein the functionalized
polymer containing an epoxide group is one or more of:
ethylene-butyl acrylate-acrylic acid terpolymer with epoxide group;
and glycidal methacrylate (GMA).
16. The polymer composition of claim 15, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
17. The polymer of claim 1, further comprising or more oxazoline or
bis-oxazoline compounds having the following formula: ##STR00003##
wherein R5 is an alkylene group having 1 to 20 carbon atoms, or an
arylene group having 6 to 12 carbon atoms, or an alkylene-arylene
group having from 7 to 20 carbon atoms; R3 is selected from
hydrogen, or alkyl group having 1 to 20 carbons, or aryl group
having 6 to 12 carbon atoms, or alkyl-aryl group having 7 to 20
carbon atoms; and R4 is selected from hydrogen, alkyl group having
1 to 20 carbons, or aryl group having 6 to 12 carbon atoms, or
alkyl-aryl group having 7 to 20 carbon atoms.
18. The polymer composition of claim 17, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
19. The polymer compound of claim 1, wherein the polyamide
component is nylon-11.
20. The polymer composition of claim 19, wherein the poly(bisphenol
A carbonate) component is present from about 30 to about 90 wt %
and the nylon-11 is present from about 2 to about 5 wt. %.
21. The polymer composition of claim 20, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
22. The polymer compound of claim 1, wherein the polyamide
component is nylon-12.
23. The polymer composition of claim 22, wherein the poly(bisphenol
A carbonate) component is present from about 30 to about 90 wt %
and the nylon-12 is present at about to 2 to about 5 wt. %.
24. The polymer composition of claim 23, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
25. The polymer composition of claim 1, wherein the inorganic
radiopaque filler component is present and is barium sulfate.
26. The polymer composition of claim 25, wherein the barium sulfate
is loaded at about 5 to 60 wt. %.
27. The polymer composition of claim 25, wherein the barium sulfate
is loaded at about 10 to 40 wt. %.
28. The polymer composition of claim 1, further comprising
1,3-phenylenebisoxazoline.
29. The polymer composition of claim 28, wherein the
1,3-phenylenebisoxazoline is present at a concentration of about
0.2 to about 5 phr (parts per hundred resin).
30. The polymer composition of claim 28, wherein the
1,3-phenylenebisoxazoline is present at a concentration of about
0.5 to about 1.0 phr. parts per hundred resin).
31. The polymer composition of claim 28, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
32. The polymer composition of claim 1, further comprising a
maleated polyolefin.
33. The polymer composition of claim 32, wherein the concentration
of maleated polyolefin is about 2 to about 20 wt. %.
34. The polymer composition of claim 33, wherein the concentration
of maleated polyolefin is about 5 to about 10 wt. %.
35. The polymer composition of claim 32, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
36. The polymer composition of claim 1, further comprising a
glycidal methacrylate copolymer.
37. The polymer composition of claim 36, wherein the glycidal
methacrylate copolymer is present at a concentration of about 2 to
20 wt %.
38. The polymer composition of claim 36, wherein the glycidal
methacrylate copolymer is present at a concentration of about 5 to
10 wt %.
39. The polymer composition of claim 36, wherein an inorganic
radiopaque filler is present and is selected from one or more of:
barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth
trioxide, tantalum, and tungsten.
40. A method of producing a biocompatible, radiopaque polymer
composition comprising poly(bisphenol A carbonate), a polyamide,
and an inorganic radiopaque filler, the method comprising: dry
mixing the poly(bisphenol A carbonate) and polyamide; melting the
mixture and adding the inorganic radiopaque filler at temperatures
from about 220 to about 300.degree. C.
41. The method of claim 40, wherein the temperatures is from about
220 to about 260.degree. C.
42. The method of claim 40, further comprising adding a phosphite
to the polymer mixture, wherein the mixing is through an
extruder.
43. The method of claim 40, further comprising coating a medical or
surgical device or part thereof with the biocompatible, radiopaque
polymer composition.
44. A method of producing a biocompatible polymer composition
comprising a polycarbonate, a polyamide, and an inorganic
radiopaque filler, the method comprising: melting the polycarbonate
and the polyamide components together to form a mixture, and
optionally adding an inorganic radiopaque filler to the mixture.
Description
BACKGROUND OF THE INVENTION
[0001] a. Field of the Invention
[0002] The invention relates to radiopaque polymer compositions for
use in medical and surgical devices. The polymer compositions have
improved melt processability along with balanced or enhanced
physical and mechanical properties, especially when combined with
or over-extruded onto or covering other polymer layers, such as
soft and/or flexible layers commonly used in medical device
applications and catheter tips, for example. The ability to
incorporate radiopaque components allows improved methods for
monitoring and visualizing medical devices when used inside the
body and improves the operating characteristics of the medical
device components.
[0003] b. Background and Introduction to Invention
[0004] A growing number of surgical or medical procedures employ
devices and kits that rely on inserting a device, catheter, or tube
into the body and visualizing the placement or movement of the
device and/or its progress during a procedure. There is an
increasing need for developing radiopaque polymer compounds that
can be used for high performance catheter shafts employed in these
procedures. However, radiopaque compounds must be chemically
compatible with the thermoplastic elastomer or other polymer
selected for the flexible and soft medical devices or parts
thereof, such as catheter tips. For example, the catheter tip
materials can be composed of soft, polyamide-based thermoplastic
elastomers, polyester-based thermoplastic elastomers, thermoplastic
polyurethanes, or silicone-thermoplastic polyurethanes having low
durometers ranging from 25 D to 55 D. These soft polymer materials
may not have significant radiopaque properties and more
undesirably, they are largely lacking in the sufficient mechanical
strength properties required for making the slender body of a
catheter shaft, for example.
[0005] Polycarbonate (PC) resins are widely used and commercially
available. PC resins are selected primarily due to their superb
material toughness, thermal stability, and excellent mechanical
strength. However, polycarbonate has limited chemical resistance
and is characterized by a rapid solidification during melt
processing due to its amorphous nature. The latter property may
make it difficult to over-extrude PC on other layers by melt
processing. Also, high performance polycarbonate resins generally
have high viscosity due to high molecular weights, and generally
have to be extrusion-processed at temperatures as high as
270.degree. C., even up to 300.degree. C. This imposes limitations
on the types of processes and products that can be manufactured
from PC in combination with other polymer materials having lower
melt processing temperatures. Therefore, a number of limitations
exist in using pure PC resins for medical and surgical devices.
[0006] Accordingly, in one aspect, the invention addresses the need
for radiopaque polymers that can be used in medical and surgical
devices. In another aspect, the invention addresses the need for
polycarbonate resins that can be modified for use as a
high-performance polymer in medical and surgical devices and
methods. As explained more fully below, the polymer compositions of
the invention improve the melt processability of polycarbonate
resin along with various enhancements in physical and mechanical
performance when used for a variety of medical and surgical devices
and kits. In addition, the polymer compositions of the invention
can be used to improve the X-ray radiopacity, namely the ability to
visualize basic catheter and medical device parts or elements in
the human body.
BRIEF SUMMARY OF THE INVENTION
[0007] In one aspect, the invention addresses the use of a
radiopaque polymer composition to make at least a part of or an
element to a medical or surgical device, or a kit comprising such
medical or surgical devices. Incorporating the radiopaque polymer
compositions with new or existing designs and polymer layers allows
the devices to be more easily visualized during medical and
surgical procedures. In another aspect, a high performance polymer
composition where one of the base polymer resins is poly(bisphenol
A carbonate) or simply a polycarbonate (PC) and another component
is a polyamide resin. Various additives, stabilizers, crosslinking
agents, block copolymers, and other biocompatible components can be
mixed with the base polymer resins. An inorganic radiopaque filler
is then optionally added to this mixture and the combined product
melt-mixed to form a polymer or radiopaque polymer composition.
[0008] In more particular aspects of the invention, the
biocompatible, radiopaque polymer composition comprises
poly(bisphenol A carbonate), a polyamide, and an inorganic
radiopaque filler. In this or any aspect of the invention, the
polyamide component can be one or more aromatic polyamides and
aliphatic polyamides, such as nylon-6,6, nylon-6, nylon-11,
nylon-12, and nylon 6T. The optional inorganic radiopaque filler
can be one or more of barium sulfate (BaSO.sub.4), bismuth
subcarbonate, bismuth oxychloride, bismuth trioxide, tantalum, and
tungsten, and micropowders of these.
[0009] In particular embodiments, the polymer composition also
includes an organic or aryl phosphite. Phosphites are known as
additives or stabilizers to polymer compositions, and many are
known to be used in biocompatible polymer compositions. Thus, one
or more organic phosphites having the general structure below can
be added to the radiopaque polymer compositions of the
invention.
##STR00001##
[0010] wherein R, R1, and R2 are selected from: a phenyl group;
substituted phenyl groups; phenyl groups substituted by an alkyl
group of 1 to 20 carbon atoms in length.
[0011] A preferred phosphite is
tris(2,4-di-tert-butylphenyl)phosphite (commercially available as,
for example, Albermarle Ethaphos 368, or Cibalrganox B900).
[0012] In addition or in the alternative to the above additives,
the polymer compositions of the invention can include one or more
functionalized polyolefins, thermoplastic olefins, and
thermoplastic olefins having an anhydride reactive group. For
example, the polyolefin or olefin can be selected from one or more
of: methacrylate-butadiene-styrene copolymer (MBS); maleic
anhydride-grafted polyethylene and polypropylene; maleated SBS
(styrene-butadien-styrene copolymer); maleated SIBS
(styrene-isobutylene-styrene); and maleated SIS
(styrene-isoprene-styrene copolymer). Also in addition or in the
alternative to the above additives, the polymer compositions of the
invention can include a functionalized polymer containing an
epoxide group. The functionalized polymer containing an epoxide
group can be one or more of: ethylene-butyl acrylate-acrylic acid
terpolymer with epoxide group; and glycidal methacrylate (GMA).
[0013] Also in addition or in the alternative to the above
additives, the polymer compositions of the invention can include
one or more oxazoline or bis-oxazoline compounds having the
following general formula:
##STR00002##
[0014] wherein R.sub.5 is an alkylene group having 1 to 20 carbon
atoms, or an arylene group having 6 to 12 carbon atoms, or an
alkylene-arylene group having from 7 to 20 carbon atoms;
[0015] R.sub.3 is selected from hydrogen, or alkyl group having 1
to 20 carbons, or aryl group having 6 to 12 carbon atoms, or
alkyl-aryl group having 7 to 20 carbon atoms; and
[0016] R.sub.4 is selected from hydrogen, alkyl group having 1 to
20 carbons, or aryl group having 6 to 12 carbon atoms, or
alkyl-aryl group having 7 to 20 carbon atoms.
[0017] A preferred example of the oxazoline compound is
1,3-phenylene-bisoxazoline or 2,4-phenylene-bisoxazoline.
[0018] Specific ranges of each of the components noted above or
throughout this disclosure can be selected for optimum physical and
mechanical characteristics. For example, a polymer composition
wherein the PC component, such as poly(bisphenol A carbonate), is
present from about 30 to about 90 wt. % can be used in any
combination, and the polyamide component, such as nylon-11 or
nylon-12, can be present from about 10 to about 70 wt. %. The
radiopaque filler can be loaded at or present at about 5 to 60 wt.
%, or preferably about 10 to 40 wt. %. The oxazoline or
bis-oxazoline compound, such as 1,3-phenylbisoxazoline, can be
present at a concentration of about 0.2 to about 5 phr (parts per
hundred resin), or about 0.5 to about 1.0 phr.
[0019] The functionalized polyolefins, thermoplastic olefins, and
thermoplastic olefins having an anhydride reactive group can be
present at about 2 to about 20 wt. %, or about 5 to about 10 wt.
%.
[0020] The functionalized polymer containing an epoxide group can
be present at a concentration of about 2 to 20 wt %, or about 5 to
10 wt %.
[0021] The invention also includes methods of producing a
biocompatible polymer composition. These methods can be used to
produce raw material that can be later used in melt-coating or
melt-extrusion of a medical device or catheter. In general, the
methods comprise using a polycarbonate, such as poly(bisphenol A
carbonate), a polyamide, and optionally an inorganic radiopaque
filler. The polycarbonate and polyamide are mixed and then
processed by melt compounding apparatus, such as batch melt mixer,
or continuous single-screw or twin-screw extruder and the inorganic
radiopaque filler is optionally added during melt mixing.
Generally, melting temperatures from about 220 to about 300.degree.
C. are used, or preferably at about 220 to about 250.degree. C. As
above, a phosphite can be added to the polymer mixture.
[0022] The additive, stabilizer, crosslinking components mentioned
above can all, individually, or any combination, be added in these
melt mixing or compounding methods. In another aspect, the high
performance or radiopaque polymer compositions can be melted onto
an existing layer of a medical device, component of a medical
device, or catheter, for example, so that the device or component
or catheter is coated with a layer of the polymer composition. In a
preferred example, the device or component is part of an inserted
medical device that has an increased opacity to a visualization
method by virtue of the incorporated radiopaque polymer
composition. Furthermore, multilayered structures can also be
produced and used according to the invention, wherein at least one
layer comprises a radiopaque polymer composition. Generally, the
radiopaque layer is the outermost layer of the medical device, but
it is not required to be the outermost layer. In addition, various
lengths of the device can comprise the radiopaque polymer
composition of the invention, anywhere from the entire insertion
length, to less than 10% of the insertion length, to only the
distal tip or inserting end of the insertion device, and even
intermittent or non-contiguous sections covering a desired
percentage of the insertion length can be used. Thus, a
multilayered device can be made and used, and one of skill in the
art is familiar with molding and co-extrusion processes, for
example, for producing these parts of medical devices.
[0023] Accordingly, it is one object of the invention to provide a
medical or surgical device that comprises a radiopaque polymer
composition in part of its length. The parts or elements of the
medical or surgical devices that contain the radiopaque polymer
composition thus exhibit improved mechanical properties with
respect to at least the ability to visualize them, for example
under an X-ray fluoroscope. Other objects, features, details,
utilities, and advantages of the present invention will be apparent
from the following, more particular, written description of various
embodiments and examples of the invention, as further illustrated
in the accompanying examples and defined in the appended
claims.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Throughout this disclosure, applicants refer to texts,
patent documents, and other sources of information. One skilled in
the art can use the entire contents of any of the cited sources of
information to make and use aspects of this invention. Each and
every cited source of information is specifically incorporated
herein by reference in its entirety. Portions of these sources may
be included in this document as allowed or required. However, the
meaning of any term or phrase specifically defined or explained in
this disclosure shall not be modified by the content of any of the
sources.
[0025] The headings (such as "Introduction" and "Brief Summary")
used are intended only for general organization of topics within
the disclosure of the invention and are not intended to limit the
disclosure of the invention or any aspect of it. In particular,
subject matter disclosed in the "Background" includes aspects of
technology within the scope of the invention and thus may not
constitute background art. Subject matter disclosed in the "Brief
Summary" is not an exhaustive or complete disclosure of the entire
scope of the invention or any particular embodiment.
[0026] As used herein, the words "preferred," "preferentially," and
"preferably" refer to embodiments of the invention that afford
certain benefits, under certain circumstances. However, other
embodiments may also be preferred, under the same or other
circumstances. Furthermore, the recitation of one or more preferred
embodiments does not imply that other embodiments are not useful
and is not intended to exclude other embodiments from the scope of
the invention and no disclaimer of other embodiments should be
inferred from the discussion of a preferred embodiment or a figure
showing a preferred embodiment. In fact, the nature of the polymer
compositions of the invention allow one of skill in the art to make
and use the invention on any medical or surgical device available
or contemplated.
[0027] The phrases "radiopaque polymer composition" and "polymer
composition of the invention" all refer to a composition comprising
an inorganic radiopaque filler in a biocompatible polymer or blend
of polymers that is biocompatible. In preferred embodiments, the
composition is composed of polymer compounds and fillers or
additives that have not previously been used together, or
previously used in a particular ratio or ratios, for use in a
medical, surgical, or biomedical device.
[0028] The invention relates to the new, successful development of
various radiopaque compositions, and especially poly(bisphenol A
carbonate) compositions, which can be used to make or melt-coat a
variety of medical and surgical devices. In one aspect, particular
surfaces or elements of devices comprise a radiopaque polymer
composition of the invention. The medical or surgical devices of
preferred interest include, but are not limited to, braided or
non-braided catheter shafts.
[0029] In one general sense and without any intention to limit the
scope to any particular explanation or mechanism for how it works,
the invention provides a high-performance polymer composition. As a
base component, a polycarbonate (PC) polymer is used. PC resins are
widely used and commercially available under tradenames Lexan.RTM.
or Makrolon.RTM.. PC resins are selected primarily due to their
superb material toughness, thermal stability, and excellent
mechanical strength as compared to other polymer materials
currently used for medical devices, such as in the catheter shafts.
Also, PC resins posses an inherent, chemical compatibility or
melt-bondability with the types of polar thermoplastic elastomer
materials that are commonly used for the soft, flexible catheter
tips or other insertion regions of medical devices. These commonly
used thermoplastic elastomers include poly(ether-block-amide),
poly(ether-block-ester), or thermoplastic polyurethanes. There are,
however, limitations in PC resins, such as chemical resistance and
rapid solidification during melt process due to its amorphous
nature. Also, thermal fusion bonding to soft, flexible catheter
tips is conducted at high temperatures where softer thermoplastic
elastomers may be thermally degraded.
[0030] The invention, therefore, improves upon known PC-based
compositions that may have been used in medical devices in order to
improve its chemical resistance, melt processability, and melt
compoundability while maintaining or even enhancing its well-known
mechanical strength and fracture toughness. In addition, the use of
a radiopaque component makes the polymer compositions of the
invention especially useful in medical and surgical procedures.
[0031] There are several technical avenues for modifying a PC resin
and compounding it with the incorporation of radiopaque fillers,
such as barium sulfate. To reduce melt viscosity and improve melt
processability and compoundability of high molecular weight PC, a
small amount of viscosity modifiers, plasticizers, or lubricants
can be added to the PC resin. Also, other polymers or copolymers
with good flow properties, biocompatibility, and chemical
compatibility can be introduced. To increase chemical resistance,
semicrystalline polymer resins are generally blended into the PC
resin, just like commercially marketed PC/PET blends and PC/PBT
blends, where PET refers to poly(ethylene terephthalate) and PBT
refers to poly(butylene terephthalate).
[0032] In one aspect of the methods of making the polymer
compositions of the invention, an in-situ reactive compounding
method is used to prepare various radiopaque PC compounds using at
least three ingredients: a PC homopolymer, a polyamide homopolymer
or copolymer, and an inorganic radiopaque filler or powder. Other
ingredients for enhancing the reactive compounding and stabilizing
the polymer phase or its morphology can be also introduced at one
or more stages. With being bound to or limited by any particular
method of reaction or reaction mechanisms, the present polymer
compositions can be made during reactive compounding process, where
a carbonate-amide exchange reaction (or transamidation) can occur
between the PC and polyamide at temperatures as high as 245.degree.
C., as known in the art. This exchange reaction produces a small
amount of high molecular weight alcohol species, which may act as
highly effective lubricants for reducing melt viscosity of the PC
resin and improving melt compoundability and processability. At the
same time, the transreactions between carbonate ester groups of the
PC resin and the amino or amide groups of polyamide resin generates
high molecular weight poly(carbonate-co-amide), which serves as
chemical compatibilizer and can reduce the interfacial tension
between polyamide and polycarbonate. In certain examples, this
facilitates the dispersion of both nylon melt and barium sulfate
particles, and further enhances the adhesion between the phases in
the solid state. The compatibilizing effects of the in-situ formed
copolymer can improve the mechanical properties of the polymers
produced.
[0033] Polyamide (or nylon) resin is semicrystalline in nature,
thus enhancing the chemical resistance of the polymers and
radiopaque polymers of the invention. In other examples, barium
sulfate has a significant reinforcing effect due to its absorption
by polyamides and polyamide-based thermoplastic elastomers. Thus,
the incorporation of barium sulfate particles, or other inorganic
radiopaque compounds or micropowders, at submicron sizes, could
further improve the mechanical properties of the final polymer
compositions.
[0034] Other ingredients can be added into the compounds containing
PC, polyamide and barium sulfate in order to control the
carbonate-amide exchange reactions or to introduce additional
compatibilizing effects, if needed or desired. Such ingredients can
be phosphites, functionalized polyolefins with anhydride and
epoxide reactive groups, or oxazolines due to their high reactivity
with either carbonate or amide groups, or combinations of these
additives.
[0035] Table 1 outlines several formulations and the relevant
mechanical properties measured from tensile mechanical tests at the
same cross-head speed, 20 in/min (or the same strain rate), on an
Instron tester. The compounds are prepared with the noted
components and mixed/melted using a lab-scale twin screw extruder
equipped with single-screw pellet feeder and twin-screw powder
feeder. The melt-compounding temperatures range from 220 to
250.degree. C. After compounding, standard ASTM mechanical test
specimens are prepared using a micromolding machine.
[0036] Several compositions can be used to manufacture a catheter
shaft, for example. The evaluations in the "Notes" of Table 1
indicate that the compositions listed as "potential" or "high
potential" have characteristics useful for a catheter shaft and
meet stringent clinical needs that surpass existing products made
of some radiopaque polymer materials that do not contain a
polycarbonate component. Other compositions listed in Table 1 can
be useful for other purposes.
[0037] Due to mechanical performance requirements, the sheaths or
shafts of cardiac catheters are generally comprised of at least two
different shaft segments with varying mechanical strength and
flexibility. In one example, these two segments are a proximal
segment or braided shaft segment and a distal segment or a flexible
tip segment. These segments must be integrated or connected via
bonding technology. A polymer material used for the braided shaft
segment must meet the following criteria: 1) high mechanical
strength or performance with synergic balance of rigidity,
toughness, and kink resistance; (2) good thermal bondability with
the flexible tip material such as the resins and compounds of
poly(ether-block-amide) copolymer, or poly(ester-ether) copolymer,
or thermoplastic polyurethane that have durameters of about 20 D to
60 D Shore, preferably 25 to 50 D Shore.
[0038] The braided shaft segment is typically a composite tubular
structure, which generally has an inner and outer polymer layers
made of a relatively rigid polymeric material, and optionally with
a braided layer in between. The forces or torques imposed on the
catheter control devices by an operator or surgeon can be more
effectively transmitted to the catheter tip via the more rigid,
braided shaft, and the catheter can be more easily delivered to the
targeted sites in the body. On the contrary, the distal segment,
for example a catheter tip, is generally made of a soft, flexible
polymer material to ensure atraumatic access to the vessels and
other tissues of the body. The braided shaft segment and flexible
tip segment are integrated via thermal fusion or adhesive bonding
processes.
[0039] In prior methods, the whole shaft of a catheter, including
the braided shaft and flexible tip segments, is made of various
radiopaque compounds of a homologous, thermoplastic elastomer with
varying mechanical properties. This drastically limits the
selection of a high performance polymeric material for making the
catheter shafts. The homologous compounds of polyamide-based
thermoplastic elastomer materials, for example Pebax.RTM., commonly
used for making catheter shafts, in which higher durometers grades,
such as Pebax 7233 and 7033, are used for the braided shaft
segments. Low durometer grade polymers, such as Pebax 4033 and
3533, are used for the flexible tips. Since Pebax materials are
chemically derived from nylon-12 or nylon-6, but with a slightly
higher mechanical strength or rigidity, they are commonly used to
make the braided catheter shaft segments. Similarly, the homologous
compounds of a polyester-based thermoplastic elastomer material,
for example Hytrel.RTM., can be used for the catheter shafts.
However, these shaft materials could not meet some clinical needs
for torque transmission, column strength, or pushability.
Therefore, there is a need for high performance polymer compounds
that can enhance the mechanical performance of the braided shaft
segment, but are still chemically compatible or bondable to a
typical thermoplastic elastomer used for the soft catheter tip
segment.
[0040] Several compositions can be tested by tube extrusion using,
for example, polymer resins including PC, Pebax, nylon-11, and
nylon-12. As expected, the PC tube has the highest mechanical
performance. However, over-coating of PC melt is difficult during
the over-extrusion due to quick melt solidification properties
immediately after exiting the die. Also, the compounding of PC with
radiopaque fillers, such as barium sulfate, at typical loading
concentrations (20 to 30 wt. %) can be difficult due to a high melt
viscosity.
[0041] In order to take advantage of the mechanical performance of
PC resins, we have developed PC-based radiopaque compositions with
improved melt processability through the use of chemical
compatibilization methods, as shown in the numerous examples
below.
[0042] Illustrative Examples
[0043] Together with a mixture comprised of a polycarbonate and a
polyamide, the components of the polymer composition can be varied
to optimize hardness, weight, and thickness, flexibility, and melt
properties, as one skilled in the art is familiar with. In
addition, a stabilizer, such as a phosphite stabilizer, aryl
phosphite, or organic phosphite, can be added. A preferred
phosphite is tris(2,4-di-tert-butylphenyl)phosphite (commercially
available as, for example, Albermarle Ethaphos 368, or Cibalrganox
B900). The potential range of the phosphite in the polymer
compositions is about 0.5 to about 5 phr (part per hundredth
resin), preferably 1 to 2 phr.
[0044] In the Table 1 below, the PC is poly(bisphenol A carbonate)
or polycarbonate resin, such as those commercially available as
Makrolon 3108 (Bayer MaterialSciences), and the polyamide can be
polyamide 12 (PA12), or nylon 12 resin, commercially available as
Grilamid L25 (EMS-Chemie AG). Where used, a
methacrylate-butadiene-styrene copolymer (MBS) can be added,
typically core-shell impact modifier, commercially available as
Clearstrength 950 (Arkema Inc.).
[0045] The optional radiopaque filler can be one or more of those
referred to above, such as an inorganic barium sulfate radiopaque
filler (BaSO.sub.4). Other inorganic radiopaque fillers, such as
tungsten and bismuth subcarbonate, can be also used.
[0046] Additional additives, such as a crosslinking agent like PBO
(1,3-phenylene-bis-oxazoline), commercially available from
Degussa-evonik Industries, can also be added. A poly(ether-block
amide) copolymer, such as Pebax, can also be added, like the
commercially available (PEBA-Pebax 7233) resins from Arkema
Inc.
[0047] Thus, as presented in the Table 1, "85:15 PC:PA12; 1.5 phr
phosphite; 25 % BaSO4" stands for the following composition: the
resin system consists of a dry blend of 85 parts polycarbonate
resin with 15 parts polyamide 12 resin, and 1.5 phr phosphite
added. The resin system, along with the phosphite additive, is
first dry-blended using a tumbling mixer or by manual mixing. The
resin system of the dry blend of the resins is charged into a
twin-screw extruder (i.e. Thermo Eurolab 16 twin-screw compounding
system), and the radiopaque BaSO.sub.4 filler at the loading
concentration of 25 wt. % in the resultant radiopaque polymer
compound is side-fed into the extruder. During melt extrusion, all
ingredients of the composition are mixed at the molten states of
the resin components, extruded, cooled, and then pelletized. The
pellets are dried and molded into specimens of standard geometry
for uniaxial tensile tests. Various mechanical properties [young's
modulus (E (ksi)); yield strength (sigma y (psi)); strain at yield
(epsilon y (%)); ultimate strength at fracture (sigma f (psi));
strain at fracture (epsilon f (%)), and tensile fracture energy
(Jf) (lbf*ft/in.sup.2)] of the polymer compositions and the
reference standards (Ref:) can be measured and are listed in Table
1 below.
TABLE-US-00001 TABLE 1 Exemplary PC Blends and Polymer Compositions
Composition E .sigma..sub.y .epsilon..sub.y .sigma..sub.f
.epsilon..sub.f J.sub.f Notes (ksi) (psi) (%) (psi) (%) (lbf *
ft/in.sup.2) Notes Ref.: PC 142.4 9439 14.9 9.7 190 114 Makrolon
3108 Ref.: PA12 91.2 6751 12.9 7.3 447 195 Grilamid L25 Ref.: Pebax
7233 42.5 3894 28.8 6.2 659 211 or Pebax Ref.: Pebax Filled 90.3
5576 19.4 5.0 438 139 P/N 13268- with 30 wt. % 022 BaSO.sub.4 20:80
PC:Pebax; 75.2 5437.6 21.8 5.2 197 80 potential 0.5 phr PBO 20:80
PC:Pebax; 76.3 5529.2 21.1 5.2 132 60 potential 1.0 phr PBO 20:80
PC:Pebax; 76.2 5607.0 19.7 5.7 369 138 potential 2.0 phr PBO PC; 15
phr MBS. 131.9 8448 14.0 8.3 151 81 -- 50:50 PC:PA12; 125.7 8172
13.1 6.9 236 113 potential 1 phr phosphite. 50:50 PC:PA12; 109.5
7007 12.9 7.1 208 95 No effect 15 phr MBS. by MBS 80:20 PC:PA12;
131.7 9232 15.0 9.2 153 89 potential 1 phr phosphite. 90:10
PC:PA12; 137.7 9519 14.7 9.5 173 102 potential 1 phr phosphite.
85:15 PC:PA12; 164.0 9537 12.5 9.2 129 73 High 1.5 phr phosphite;
potential 25% BaSO.sub.4 91:9 PC:PA12; 169.6 9067 12.1 9.0 150 85
potential 25% BaSO.sub.4 85:15 PC:PA12; 166.4 8939 11.5 9.0 126 71
potential 25+% BaSO.sub.4 85:15 173.3 8549 11.2 8.5 122 64 --
PC:PEBA7233; 25+% BaSO.sub.4 85:15 PC:PA12; 175.5 9177 11.3 9.0 100
53 potential 0.5 phr PBO; 25+% BaSO.sub.4 85:15 165.3 9026 12.3 8.5
100 47 -- PC:PEBA7233; 0.5 phr PBO; 25+% BaSO.sub.4 85:15 PC:PA12;
166.0 9378 11.9 9.2 100 50 potential 1.0 phr PBO; 25% BaSO.sub.4
85:15 156.9 9209 12.9 9.1 100 53 potential PC:PEBA7233; 1.0 phr
PBO; 25% BaSO.sub.4 50:50 PC:PA12; 154.8 8527 11.0 8.5 150 78
potential 25 wt % BaSO.sub.4 (23.6%) 60:40 PC:PA12; 153.1 8682 11.2
8.5 111 60 potential 25 wt % BaSO.sub.4 (21.7%) 70:30 PC:PA12;
150.7 8849 12.2 8.6 124 70 potential 25 wt % BaSO.sub.4 (22.1%)
80:20 PC:PA12; 147.8 9032 13.1 9.0 160 91 High 25 wt % BaSO.sub.4
potential (22.9%) 90:10 PC:PA12; 143.1 9279 13.3 9.3 146 84 High 25
wt % BaSO.sub.4 potential (29.0%) 50:50 PC:PA12; 146.0 9177 12.5
9.0 80 32 -- 1.0 phr phosphite; 25% BaSO.sub.4(21.3) 70:30 PC:PA12;
140.5 9351 12.8 9.0 50 28 1.0 phr phosphite; 25%
BaSO.sub.4(22.0)
[0048] In the Table 1 "Composition Notes," the initial ratio
represents the amount of PC to polyamide (PA) present on wt/wt %; a
preferred PC is Makrolon 3108 (Bayer MaterialScience AG); a
preferred polyamide is nylon-12 (PA12) Grilamid L25 and an
alternative is PEBA7233 and other Pebax polyether block amide; PBO
is a crosslinking additive, such as 1,3-phenylene-bis-oxazoline,
listed as present in phr units; Phosphite is listed as phr also,
and can be commercially available products such as Albermarle
Ethaphos 368; MBS is methacrylate-butadiene-styrene copolymer, such
as Clearstrength 950; and loaded BaSO.sub.4 is listed as wt %, with
the final content as % listed in parenthesis.
[0049] In producing a medical device with any of the polymer or
radiopaque polymer compositions of the invention, melt-processing
of the polymer or radiopaque layer can be used as conventionally
known. For example, a catheter segment or segments can be produced
using a mandrel, such as one designed to form a proximal end and a
distal end, as known in the art. A first or inner polymeric layer
can be placed on the mandrel. The inner polymeric layer may be
knotted at one end (e.g. the distal end) and then fed onto mandrel.
In general, the inner polymeric layer can include a lumen having an
inner surface and an outer surface. Additionally, designs with more
than a single lumen can be used. The inner polymeric layer is
generally an extruded polymer. In one embodiment, the inner
polymeric layer is an extruded thermoplastic elastomer. In other
embodiments, the inner polymer layer can be a
polytetrafluoroethylene (PTFE), such as Teflon.RTM. brand, which is
available commercially. The inner polymeric layer may optionally be
chemically etched to provide better adhesion during melt
processing. In addition or alternatively, the inner polymeric layer
can have a scalloped or ribbed profile to make it more amenable for
use in steerable devices. As a person of skill in the art will
appreciate, the inner polymeric layer may be made of other melt
processable polymers, such as any biocompatible and
melt-processable polymer composition. Various methods of using a
mandrel for the manufacture of devices containing one or more
lumens are known in the art, and any, including those described in
U.S. patent publication no. US 2006/0151923, which is incorporated
herein by reference in its entirety, can be selected.
[0050] A radiopaque or outer polymeric layer can then be placed
directly over the inner polymeric layer. In practice, it may be
desirable to use more than one region of an outer polymer layer,
for example where only the distal end is coated or covered with the
radiopaque polymer compositions of the invention. Thus, the outer
polymeric layer may be made of either single or multiple sections
of tubing that may be either butted together or overlapped with
each other, wherein at least one section is coated or covered with
a polymer or radiopaque composition of the invention. Other outer
polymer layers may be made of melt-processable polymers, such as
poly(ether-block-amide), nylon, polyethylene and other
thermoplastic elastomers. For example, the outer polymeric layer
that is not radiopaque may be made of Pebax.RTM., a polyether block
amide of various durometers, such as Pebax 25 D to Pebax 72 D
(Arkema Inc.). As noted, the outer polymeric layer of a device or
catheter may also comprise more than one layer or segment,
including for example two or more tubes of a melt processing
polymer arranged to abut one another and/or to overlap one another.
Additionally, various durometer materials can also be used in
segments of the device. Thus, a first portion can be made of one
selected Pebax and a second portion can be made of a second
selected Pebax (for its mechanical properties). While the first and
second portions can be different classes of the same material, the
first and second portions can comprise different materials or
compositions as well as be coated or overlaid with the
polycarbonate and/or radiopaque polymer compositions of the
invention. These first and second portions can be fused together by
thermal heating or other means known in the art, as noted in U.S.
patent publication no. 2008/0234660, specifically incorporated
herein by reference in its entirety.
[0051] Optionally, a braided layer or metallic wire braided layer
may be placed between the inner polymeric layer and the outer
polymeric layer. This braided layer may be formed of stainless
steel wire, including, for example, 0.003'' high tensile stainless
steel wire. The braided layer may also be formed of a metal alloy,
for example, a copper alloy. The braided layer may be formed in a
standard braid pattern and density, for example, about 16 wires at
about 45 to about 60 picks per inch ("PPI") density. Alternatively,
a braid may be used that is characterized by a varying braid
density. For example, the braided layer may be characterized by a
first braid density at the proximal end of the catheter and then
transition to one or more different braid densities as the braided
layer approaches the distal end of the device or catheter. The
braid density at the distal end may be greater or less than the
braid density at the proximal end. A catheter assembly having a
braided layer with a varying braid density in described in U.S.
patent publication no. 2007/0299424, which is incorporated herein
by reference in its entirety. Alternatively, the braided layer may
be applied directly about the inner polymer layer.
[0052] The polycarbonate or radiopaque polymer layer can be coated
or melt-processed over the braided layer or the inner polymer layer
using methods know in the art. The mandrel may be removed from the
assembly, leaving behind a device with a lumen.
[0053] Although various embodiments of this invention have been
described above with a certain degree of particularity, or with
reference to one or more individual embodiments, those skilled in
the art could make numerous alterations to the disclosed
embodiments without departing from the spirit or scope of this
invention. It is intended that all matter contained in the above
description and shown in the accompanying drawings shall be
interpreted as illustrative only of particular embodiments and not
limiting. All directional references (e.g., proximal, distal,
upper, lower, upward, downward, left, right, lateral, front, back,
top, bottom, above, below, vertical, horizontal, clockwise, and
counterclockwise) are only used for identification purposes to aid
the reader's understanding of the present invention, and do not
create limitations, particularly as to the position, orientation,
or use of the invention. Connection references (e.g., attached,
coupled, connected, and joined) are to be construed broadly and may
include intermediate members between a collection of elements and
relative movement between elements unless otherwise indicated. As
such, connection references do not necessarily infer that two
elements are directly connected and in fixed relation to each
other. It is intended that all matter contained in the above
description or shown in the accompanying drawings shall be
interpreted as illustrative only and not limiting. Changes in
detail or structure may be made without departing from the basic
elements of the invention as defined in the following claims. The
invention is not limited to any particular embodiment or example
given here. Instead, one of skill in the art can use the
information and concepts described to devise many other embodiments
beyond those given specifically here.
* * * * *