U.S. patent application number 10/637575 was filed with the patent office on 2004-05-20 for distensible dilatation balloon with elastic stress response and manufacture thereof.
Invention is credited to Anderson, Jere R., Barbere, Michael D., Jandris, Louis J., Murphy, Richard T..
Application Number | 20040097878 10/637575 |
Document ID | / |
Family ID | 25495874 |
Filed Date | 2004-05-20 |
United States Patent
Application |
20040097878 |
Kind Code |
A1 |
Anderson, Jere R. ; et
al. |
May 20, 2004 |
Distensible dilatation balloon with elastic stress response and
manufacture thereof
Abstract
Balloons and balloon catheters with a superior overall
combination of distensibility, elastic stress response and
strength. The improved properties of the balloons result from the
method or process used to form the balloons, as well as the
polymeric materials used in said balloon forming process.
Additionally, the enhanced combination of properties of the
balloons will not be adversely affected by the novel sterilization
process contemplated by this invention.
Inventors: |
Anderson, Jere R.;
(Newburyport, MA) ; Jandris, Louis J.;
(Georgetown, MA) ; Barbere, Michael D.;
(Dunstable, MA) ; Murphy, Richard T.; (Dracut,
MA) |
Correspondence
Address: |
MEDTRONIC AVE, INC.
3576 UNOCAL PLACE
SANTA ROSA
CA
95403
US
|
Family ID: |
25495874 |
Appl. No.: |
10/637575 |
Filed: |
August 11, 2003 |
Related U.S. Patent Documents
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Application
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Filing Date |
Patent Number |
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10637575 |
Aug 11, 2003 |
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09942920 |
Aug 31, 2001 |
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6620381 |
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09942920 |
Aug 31, 2001 |
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09192893 |
Nov 16, 1998 |
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6283939 |
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09192893 |
Nov 16, 1998 |
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08883261 |
Jun 26, 1997 |
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6210364 |
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08883261 |
Jun 26, 1997 |
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08440700 |
May 15, 1995 |
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08440700 |
May 15, 1995 |
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07954750 |
Sep 30, 1992 |
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5500180 |
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Current U.S.
Class: |
604/103.11 |
Current CPC
Class: |
A61L 29/06 20130101;
B29L 2022/022 20130101; B29L 2031/7542 20130101; A61L 2202/24
20130101; A61L 2/206 20130101; A61M 25/10 20130101; A61L 29/06
20130101; A61L 29/06 20130101; B29C 2049/4608 20130101; C08L 87/005
20130101; C08L 75/04 20130101; C08L 87/005 20130101; C08L 75/04
20130101; A61L 29/06 20130101; A61M 25/1029 20130101; A61M
2025/0019 20130101; A61L 2/206 20130101 |
Class at
Publication: |
604/103.11 |
International
Class: |
A61M 029/00 |
Claims
1. A balloon characterized by an improved overall combination of
distensibility, elastic stress response and wall tensile strength
made by the process comprising: a. providing a parison of a block
copolymer having regions of inter-molecular chain interaction
separated by regions in which those individual portions of the
polymer chains have the ability to uncoil, said parison having a
predetermined original outer diameter, a predetermined wall
thickness and a predetermined length; b. subjecting said parison to
at least one axial stretch step and at least one radial expansion
step at temperature T.sub.1 which is below the melting temperature
of said block copolymer to increase the diameter and length of said
parison to at least 3 times the original diameter and 2 times the
original length and to decrease the original wall thickness to at
least 20% of the original wall thickness to form an expanded
parison; and c. heating said expanded parison to a temperature of
T.sub.2 which is above T.sub.1 but below the melting temperature of
said block copolymer.
2. The balloon according to claim 1 wherein said radial expansion
step is conducted while said parison is simultaneously subjected to
said axial stretch step.
3. The balloon according to claim 1 wherein said axial stretch and
radial expansion steps are conducted at temperature T.sub.1 which
is greater than the glass transition temperature of said block
copolymer.
4. A balloon according to claim 1 wherein said block copolymer is
selected from the group consisting of polyester block copolymers,
polyamide block copolymers, polyurethane block copolymers, a
mixture of nylon and polyamide block copolymers and a mixture of
polyethylene terephthalate and polyester block copolymers.
5. A balloon according to claim 1 wherein said balloon has a
distensibility of about 5 to about 20%, an elastic stress response
not greater than about 5.00, and a wall tensile strength greater
than about 14,000 psi.
6. A balloon according to claim 1 wherein said balloon has a
distensibility of about 6 to about 17%, an elastic stress response
of about 0.75 to about 4.00 and a wall tensile strength of about
16,000 to about 30,000 psi.
7. A balloon according to claim 1 wherein said block copolymer is a
polyurethane having a Shore Hardness of about 74 D, a specific
gravity of about 1.21, a tensile modulus of about 165,000 psi, a
flexual modulus of about 190,000 psi, an ultimate tensile strength
of about 6,980 psi and an ultimate elongation of about 250%.
8. A balloon according to claim 6 wherein T.sub.1 is about
90-100.degree. C. and T.sub.2 is about 110-120.degree. C.
9. A process of forming a balloon characterized by an improved
overall combination of distensibility, elastic stress response and
wall tensile strength comprising: a. providing a parison of a block
copolymer having regions of inter-molecular chain interaction
separated by regions in which those individual polymer portion of
chains have the ability to uncoil, said parison having a
predetermined original outer diameter, a predetermined wall
thickness and a predetermined length; b. subjecting said parison to
at least one axial stretch step and at least one radial expansion
step at temperature T.sub.1 which is below the melting temperature
of said block copolymer to increase the diameter and length of said
parison to at least 3 times the original diameter and 2 times the
original length and to decrease the original wall thickness to at
least 20% of the original wall thickness to form an expanded
parison; and c. heating said expanded parison to a temperature of
T.sub.2 which is above T.sub.1 but below the melting temperature of
said block copolymer.
10. The process according to claim 9 wherein said radial expansion
step is conducted while said parison is simultaneously subjected to
said axial stretch step.
11. The process according to claim 9 wherein said axial stretch and
radial expansion steps are conducted at temperature T.sub.1 which
is greater than the glass transition temperature of said block
copolymer.
12. A process according to claim 9 wherein said block copolymer is
selected from the group consisting of polyester block copolymers,
polyamide block copolymers, polyurethane block copolymers, a
mixture of nylon and polyamide block copolymers and a mixture of
polyethylene terephthalate and polyester block copolymers.
13. A process according to claim 9 wherein said balloon formed has
a distensibility of about 5 to about 20%, an elastic stress
response of not greater than about 5.00 and a wall tensile strength
greater than about 14,000 psi.
14. A process according to claim 9 wherein the balloon formed has a
distensibility of about 6 to about 17%, an elastic stress response
of about 0.75 to about 4.00 and a wall tensile strength of about
16,000 to about 30,000 psi.
15. A process according to claim 9 wherein said block copolymer is
a polyurethane having a Shore Hardness of about 74 D, a specific
gravity of about 1.21, a tensile modulus of about 165,000 psi, a
flexual modulus of about 190,000 psi, an ultimate tensile strength
of about 6,980 psi and an ultimate elongation of about 250%.
16. A balloon catheter comprising the balloon of claim 1.
17. A process for sterilizing balloons and balloon catheters
comprising: a. subjecting said balloons and balloon catheters to a
temperature of about to about 45.degree. C. and a relative humidity
of about 55% for about 15 hours; b. treating said balloons and
balloon catheters at a temperature of about 35 to about 45.degree.
C. and a relative humidity of about 55% with ethylene oxide for
about 15 hours; and c. discontinuing treatment with ethylene oxide
and subjecting said balloons and balloon catheters to a temperature
of about 35 to about 45.degree. C. for about 22 hours.
Description
BACKGROUND OF INVENTION
[0001] Surgical procedures employing balloons and medical devices
incorporating those balloons (i.e., balloon catheters) are becoming
more common and routine. These procedures, such as angioplasty
procedures, are conducted when it becomes necessary to expand or
open narrow or obstructed openings in blood vessels and other
passageways in the body to increase the flow through the obstructed
areas. For example, in an angioplasty procedure, a dilatation
balloon catheter is used to enlarge or open an occluded blood
vessel which is partially restricted or obstructed due to the
existence of a hardened stenosis or buildup within the vessel. This
procedure requires that a balloon catheter be inserted into the
patient's body and positioned within the vessel so that the
balloon, when inflated, will dilate the site of the obstruction or
stenosis so that the obstruction or stenosis is minimized, thereby
resulting in increased blood flow through the vessel. Often,
however, a stenosis requires treatment with multiple balloon
inflations. Additionally, many times there are multiple stenoses
within the same vessel or artery. Such conditions require that
either the same dilatation balloon must be subjected to repeated
inflations, or that multiple dilatation balloons must be used to
treat an individual stenosis or the multiple stenoses within the
same vessel or artery. Additionally, balloons and medical devices
incorporating those balloons may also be used to administer drugs
to a patient.
[0002] Traditionally, the balloons available to physicians were
classified as either "compliant" or "noncompliant". This
classification is based upon the operating characteristics of the
individual balloon, which in turn depended upon the process used in
forming the balloon, as well as the material used in the balloon
forming process. Both types of balloons provide advantageous
qualities which were not available from the other.
[0003] A balloon which is classified as "noncompliant" is
characterized by the balloon's inability to grow or expand
appreciably beyond its rated or nominal diameter. "Noncompliant"
balloons are referred to as having minimal distensibility. In
balloons currently known in the art (e.g., polyethylene
terephthalate), this minimal distensibility results from the
strength and rigidity of the molecular chains which make up the
base polymer, as well as the orientation and structure of those
chains resulting from the balloon formation process. The strength
resulting from this highly oriented structure is so great that when
the balloon is subjected typical inflation or operating pressures
(i.e., about 70 psi to over 200 psi), it will not be stressed above
the yield point of the polymeric material.
[0004] The yield point of a material is defined as the stress at
which the individual molecular chains move in relation to one
another such that when the pressure or stress is relieved, there is
permanent deformation of the structure. When a material is
subjected to pressure or stress below its yield point, the material
will consistently follow the same stress-strain curve when
subjected to multiple cycles of applying and relieving the stress
or pressure. A material which exhibits the ability to follow the
same stress-strain curve during the repeated application and relief
of stress is defined as being elastic and as having a high degree
of elastic stress response. This elastic behavior is highly
desirable in balloons in order to ensure consistent and predictable
balloon sizing regardless of the balloon's previous inflation
history.
[0005] A balloon which is referred to as being "compliant" is
characterized by the balloon's ability to grow or expand beyond its
nominal or rated diameter. In balloons currently known in the art
(i.e., polyethylene, polyvinylchloride), the balloon's "compliant"
nature or distensibility results from the chemical structure of the
polymeric material used in the formation of the balloon, as well as
the balloon forming process. These polymeric materials have a
relatively low yield point. Thus, the inflation pressures used in
dilation procedures are typically above the yield point of the
materials used to form distensible balloons. A distensible or
"compliant" balloon when inflated to normal operating pressures,
which are greater than the polymeric material's yield point, is
subjected to stress sufficient to permanently realign the
individual molecular chains of the polymeric material. The
realignment of individual polymer chains permits the balloon to
expand beyond its nominal or rated diameter. However, since this
realignment is permanent, the balloon will not follow its original
stress-strain curve on subsequent inflation-deflation cycles.
Therefore, the balloon balloon upon subsequent inflations, will
achieve diameters which are greater than the diameters which were
originally obtained at any given pressure during the course of the
balloon's initial inflation.
[0006] The term "elastic", as it is used in connection with this
invention, refers only to the ability of a material to follow the
same stress-strain curve upon the multiple applications of stress.
See Beer, F. et al., Mechanics of Materials (McGraw-Hill Book
Company 1981), pp. 39-40. Elasticity, however, is not necessarily a
function of how distensible a material is. It is possible to have
an elastic, non-distensible material or a non-elastic, distensible
material. This is best illustrated in FIGS. 1, 2 and 3.
[0007] FIG. 1 represents an elastic, essentially non-distensible
material. If this material was used to form a balloon, the balloon
would be considered non-distensible because there is very little
change in strain (diameter) as the stress applied is increased
(inflation pressure). The balloon would be elastic because it
follows essentially the same stress-strain (pressure-diameter)
curve with the second application of stress (inflation).
[0008] FIG. 2 represents an elastic, distensible material. If this
material was used to form a balloon, the balloon would be
considered distensible because there is significant change in
strain (diameter) as the stress applied is increased (inflation
pressure). The balloon would be considered elastic because it
follows essentially the same stress-strain (pressure-diameter)
curve with the second application of stress (inflation).
[0009] FIG. 3 represents an inelastic, distensible material. Like
FIG. 2, FIG. 3 shows a significant change in strain (diameter) and
would therefore be considered a distensible balloon material.
Unlike FIGS. 1 and 2, however, the same stress-strain
(pressure-diameter) curve is not maintained upon the second
application of stress (inflation).
[0010] It has been found that the optimal size of a dilatation
balloon is about 0.9 to about 1.3 the size of the vessel being
treated. See Nichols et al., Importance of Balloon Size in Coronary
Angioplasty, J. American College of Cardiology, Vol. 13, 1094
(1989). If an undersized balloon is used, there is a high incidence
of significant residual stenosis and a greater need for subsequent
dilatation procedures. However, if an oversized balloon is used,
there is an increased chance of coronary dissection. Therefore,
physicians desire to use a balloon which will closely approximate
the size of the occluded vessel or obstructed cavity being
treated.
[0011] Because physiological vessels such as arteries are generally
tapered, the nominal or rated diameter of balloons commercially
available often do not correspond to the size of the vessel being
treated. Physicians, therefore, are often faced with the prospect
of using an undersized "compliant" balloon which can be expanded
beyond its nominal or rated diameter, or an oversized
"noncompliant" balloon which will follow the same stress-strain
curve during multiple inflations (i.e., is elastic). Thus,
physicians can choose from two general types of balloons depending
upon whether they require a balloon which grows beyond nominal
diameter. They may choose a "noncompliant" balloon if they require
a relatively high strength balloon which will not expand much
beyond its nominal or rated diameter, or a "compliant" balloon if
they require a balloon which is capable of expanding considerably
beyond the normal or rated diameter. As will be shown below, each
of these properties is advantageous. However, it would be desirable
to have to have a "compliant" or distensible balloon which also has
the elastic stress response of a "noncompliant" balloon, as well as
sufficient strength to be used in dilatation procedures.
[0012] Because physicians using a dilatation balloon do not know
prior to the procedure what inflation pressures will be required to
dilate a given obstruction or stenosis, it is desirable that the
balloon being used have strength capable of withstanding the high
inflation pressures typically associated with these procedures
(i.e., about 70 to over 200 psi). A high strength dilatation
balloon, which is capable of withstanding increased inflation
pressure, is safer to use since the chances of the balloon bursting
during the procedure are minimized.
[0013] Strength of a balloon is typically quantified by calculating
the balloon's wall tensile strength. The overall strength of a
balloon can be increased by increasing the balloon's wall
thickness. As the wall thickness is increased, the balloon is
capable of withstanding higher inflation pressures. However, as the
wall thickness of the balloon is increased, the folded profile of
the balloon, as well as the balloon's flexibility, may be adversely
affected.
[0014] The relationship between the ultimate strength of the
balloon, the inflation pressure which the balloon can withstand and
the balloon's wall thickness is determined by the well known
membrane equation: 1 Wall Tensile Strength ( psi ) = ( burst
pressure ( psi ) ) .times. ( nominal balloon diameter ) 2 .times. (
wall thickness )
[0015] Depending upon the material used to form the balloon, the
nominal, or rated diameter is achieved typically when the balloon
is inflated between to about 5 bars to about 8 bars. The burst
pressure is determined at 37.degree. C.
[0016] Since balloons, particularly dilatation balloons, must have
the ability to traverse the confines of the obstructed areas to be
treated, it is desirable to have a balloon which has a narrow
folded profile. This "profile" represents the smallest opening
through which the balloon, in its deflated state, may pass. The
profile of the balloon depends in large part upon the wall
thickness of the finished balloon (i.e., the sterilized dilatation
balloon product). Therefore, it is desirable for a finished balloon
product to have a folded profile which is as narrow as possible,
particularly if the balloon is to be used in an angioplasty
procedure.
[0017] Another important characteristic of balloons in general, and
more specifically dilatation balloons, is the distensibility of the
finished balloon product. Distensibility, also referred to as
percent of radial expansion, is typically determined by comparing
the nominal or rated diameter of the balloon with the diameter at
some arbitrarily selected higher pressure (i.e., 10 bars). The
distensibility or percent radial expansion is calculated using the
following formula with all measurements taking place at about
37.degree. C.: 2 Distensibility = [ Diameter of balloon at 10 bars
Nominal balloon diameter - 1 ] .times. 100 %
[0018] For example, balloons made of polyethylene terephthalate
have a low distensibility (i.e., less than about 5% at 200 psi).
See for example U.S. Pat. Re. Nos. 32,983 and 33,561 to Levy which
discloses balloons formed from polyethylene terephthalate and other
polymeric materials.
[0019] It is also desirable that the balloon be elastic or have a
high degree of elastic stress response. Elasticity, which also can
be referred to as the repeatability of a balloon, is characterized
by the ability of the balloon to consistently follow the same
stress-strain curve after being subjected to multiple inflations to
normal operating or inflation pressures (i.e., about 10 bars or
greater). That is, a balloon which has a high degree of elastic
stress response will retain the same diameter-pressure relationship
and will consistently obtain the same diameter at the same pressure
during repeated inflation-deflation cycles. Balloons which have
poor elasticity or a low degree of elastic stress response have a
tendency to "creep" or "deform" after multiple inflations and fail
to return to their nominal or rated diameters after being subjected
to multiple inflations at increased pressures.
[0020] A dilatation balloon which has a high degree of elastic
stress response is particularly desirable when a physician is
treating multiple stenoses within the same artery. If the balloon
is "inelastic", after the first stenosis is dilated at an increased
pressure, the physician would not know what the balloon's "new"
starting diameter is prior to attempting to dilate subsequent
stenoses. If the physician fails to correctly guess the balloon's
"new" diameter prior to beginning treatment of another stenosis
there is an increased risk of oversizing the balloon which could
result in coronary artery dissection or other damage to the vessel.
Therefore, to ensure the patient's safety, some physicians elect to
remove the balloon catheter from the patient and reintroduce a new
sterile balloon catheter prior to attempting to dilate subsequent
stenosis within the same vessel. However, this is time-consuming
and undesirable for the patient. Additionally, the cost of the
individual balloon catheters prohibits the use of multiple balloon
catheters when treating multiple stenoses within the same vessel.
Thus, to minimize the chance of oversizing the balloon when
treating multiple stenoses within the same vessel, a physician may
attempt to use a dilatation balloon which is noncompliant. However,
as discussed previously, because such a balloon will permit little
expansion beyond the balloon's rated or nominal diameter, the
physician may not have available a balloon of sufficient size to
safely treat the other stenoses within the same vessel.
[0021] Elastic stress response is determined by inflating a balloon
to 5 bars at about 37.degree. C. and measuring the balloon's
diameter. The balloon is then inflated to a pressure of 10 bars in
about 20 seconds and held for an additional 20 seconds at
37.degree. C. The balloon's diameter is then measured. The internal
pressure of the balloon is then decreased to 5 bars and the "new" 5
bar diameter of the balloons is determined. For this invention, the
elastic stress response or repeatability is calculated using the
following equation: 3 Elastic Stress Response = [ Balloon diameter
at 5 bars after inflation to 10 bars Balloon diameter at initial 5
bar inflation - 1 ] .times. 100
[0022] A balloon with maximum or complete elastic stress response
permits the balloon, after being inflated to a pressure of 10 bars,
to return to the same diameter it had at 5 bars prior to the
inflation to the higher pressure. Such a balloon would have maximum
repeatability, or an elastic stress response of 0.00. As the
repeatability of the balloon decreases, the elastic stress response
decreases and, as defined above, numerically becomes greater than
0.00. For example, balloons formed from polyolefin copolymers in
the art have poor repeatability and a relatively low degree of
elastic stress response and have a numerical elastic stress
response of about 9.
[0023] It would be particularly desirable if a "compliant" balloon
was able to possess an adequate degree of distensibility so that
the balloon could be inflated to correspond to the size of the
vessel being treated, while at the same time being highly elastic
to ensure repeatable sizing and a high degree of elastic stress
response so that the physician would know the balloon's "new"
diameter at all inflation pressures prior to attempting to dilate
multiple stenoses within the same vessel. This enhanced combination
of properties would allow physicians to conduct dilation procedures
in a safer manner in arteries where the physician requires balloon
sizing not conveniently provided by "noncompliant" balloon products
currently available in the art.
[0024] Another desirable characteristic of a balloon is
flexibility. Improved flexibility will permit a balloon to
traverse, not only occluded arteries, but also other obstructed or
narrow body cavities and openings resulting in minimal damage to
the vessel or cavity through which the balloon catheter is being
navigated.
[0025] A further desirable property of a dilatation balloon, is the
optical clarity of the finished balloon product. Although the
optical clarity will not adversely affect a balloon's overall
ability to dilate a stenosis or obstruction, most physicians will
not use a balloon which has a cloudy appearance. The optical
characteristics of a balloon or balloon catheter, therefore, must
be taken into account when forming a balloon.
[0026] While the foregoing properties are desirable in balloons,
these attributes are typically adversely affected by the
sterilization process which all balloons and balloon catheters must
be subjected to prior to their use in the human body. For example,
when a balloon in the art is exposed to the increased temperature
and humidity of a traditional sterilization process (e.g., high
humidity, temperature of about 50-60.degree. C., about 12% ethylene
oxide and about 88% Freon.TM. for approximately 12-16 hours) the
balloon tends to shrink which causes a corresponding increase in
wall thickness. Moreover, this increase in wall thickness will
adversely affect the folded profile of the sterilized balloon
product. Furthermore, the distensibility of many balloons is
adversely affected by the sterilization processes currently used in
the art. Therefore, it is also desirable that the sterilization
process used to treat balloons and balloon catheters provide
adequate sterilization while at the same time not adversely
affecting the physical characteristics of the finished balloon or
balloon catheter product.
[0027] It has now been found that novel distensible balloons,
particularly dilatation balloons, can be formed by processing a
polymeric material composed of polymer chains having sufficient
regions of molecular structure with inter-molecular chain
interaction to ensure the integrity and strength of the structure,
as well as sufficient regions which permit sections of the polymer
chains to "uncoil" to permit growth. The balloons contemplated by
this invention (i) are sufficiently distensible (i.e., about 5 to
about 20%) to allow treatment of various sized arteries, (ii) have
a high degree of elastic stress response (i.e., less than about
5.00) which permits the physician to treat multiple stenoses within
the same artery without having to be concerned with increasing
balloon diameter after repeated inflations and (iii) have strength
sufficient to treat hardened stenoses (i.e., greater than about
14,000 psi). The balloons formed using the process of this
invention will have an overall advantageous combination of these
physical properties i.e., distensibility, elastic stress response
and tensile strength, superior to those exhibited by the
"compliant" balloons currently available. It has also been found
that these enhanced properties will not be adversely affected by
subjecting the balloons and balloon catheters formed following the
method or process of this invention to a novel sterilization
process. This novel balloon forming process and novel sterilization
process can be used regardless of whether the balloon is
coated.
SUMMARY OF THE INVENTION
[0028] It is an object of this invention to provide a method or
process for producing a balloon, preferably a dilatation balloon,
which exhibits an improved overall combination of physical
properties, such as distensibility, elastic stress response and
strength, superior to those exhibited by "compliant" balloons
currently known in the art.
[0029] It is further the object of this invention to provide a
novel balloon and a novel balloon catheter in which the balloon
exhibits an advantageous overall combination of distensibility,
elastic stress response and strength which combination of
properties will not be adversely affected by sterilization.
[0030] Still another object of this invention is to provide an
improved sterilization procedure which will not adversely affect
the distensibility, elastic stress response and strength of the
balloons and balloons of the balloon catheters of this
invention.
[0031] It is still a further object of this invention to provide a
process which will ensure that the balloons formed will have
improved optical clarity.
[0032] These objects, as well as others, which will become apparent
from the description which follows, are achieved by forming these
novel balloons and balloon catheters using the novel process of
this invention from certain polymeric materials composed of polymer
chains having regions of inter-molecular chain interaction
separated by regions in which those individual portions of the
polymer chains have the ability to uncoil or stretch. Therefore,
the present invention includes (1) novel balloons and balloon
catheters which have an improved overall combination of
distensibility, elastic stress response and strength, (2) the
process or method of forming balloons and balloon catheters from
polymeric materials which will result in balloons and balloon
catheters exhibiting these improved properties and (3) a novel
sterilization process which will not adversely affect these
enhanced properties.
[0033] The present invention contemplates balloons characterized by
an improved overall combination of distensibility, elastic stress
response and wall tensile strength made by the process comprising
subjecting a parison, made of a block copolymer having polymer
chains with regions of inter-molecular chain interaction separated
by regions in which those individual portions of the polymer chains
have the ability to stretch or uncoil to at least one axial stretch
and at least one radial expansion step. The expanded parison is
then subjected to a heat set step to provide the expanded parison
and resulting balloon with thermal and dimensional stability. The
invention also contemplates a novel sterilization process in which
balloons and balloon catheters, after preconditioning, are exposed
to ethylene oxide at a temperature of about 40.degree. C. and a
relative humidity of about 50-60% for approximately 6 hours. The
balloons and balloon catheters are then subjected to an aeration
step in which the ethylene oxide is allowed to dissipate. The novel
sterilization process does not adversely affect the improved
overall combination of properties exhibited by the balloons of this
invention.
[0034] It should be understood that the foregoing description of
the invention is intended merely to be illustrative and that other
embodiments and modifications may be apparent to those skilled in
the art without departing from the spirit and scope of the
invention.
DETAILED DESCRIPTION OF THE INVENTION
[0035] The present invention provides for the first time
"compliant" balloons, preferably dilatation balloons, which,
because of the method or process used to form the balloons, as well
as the polymeric materials used in the balloon forming process,
produces balloons having a highly desirable combination of
distensibility, elastic stress response and strength (i.e.,
distensibility of about 5 to about 20% and preferably in the range
of about 6 to about 17%, elastic stress response of not greater
than about 5.00 and preferably in the range of about 0.75 to about
4.00 and wall tensile strength of at least about 14,000 psi,
preferably in the range of about 15,000 to about 40,000 psi and
most preferably in the range of about 16,000 to about 30,000 psi).
The invention also provides a unique method or process using a heat
set step in the formation of the balloons of this invention which
ensures that the balloons retain their distensibility and strength,
and provides balloons with improved optical clarity. Moreover, the
invention provides a novel sterilization process which will not
adversely affect, to any significant degree, the enhanced
combination of properties which are obtained using the novel
balloon forming process of this invention.
[0036] The materials which may be used in this novel process or
method include polymeric materials having a molecular structure
which are composed of individual polymer chains having regions or
zones of inter-molecular chain interaction separated by regions or
zones in which those individual portions of the polymer chains have
the ability to stretch or uncoil. The ability of regions or zones
of individual polymer chains to uncoil permits the chains to move
upon the application of stress. However because these zones are
held in place or secured at either end by zones exhibiting
inter-molecular chain interaction, the uncoiled portions return to
their original position once the applied stress is removed.
[0037] These polymers can be considered to be comprised of polymer
chains with individual regions of crystalline and amorphous
material and can be referred to as "hard" and "soft" segments
respectively. The individual polymer chains are able, to a
substantial extent, to coil upon themselves and/or around each
other in such a way that soft segments are associated with soft
segments and hard segments with hard segments, thereby forming
separate "domains" approximating soft and hard bodies of polymer,
each exhibiting its own physical properties in varying degrees. The
hard segments are comprised of regions which have significant
inter-molecular chain interaction. This provides regions with
increased strength and increased elastic stress response. In
addition to providing strength, the hard segments are sufficiently
rigid to permit the soft segments to stretch and uncoil which
provides distensibility.
[0038] The ratio of hard to soft segments and individual chemical
structure of the individual segments define the balloon's
distensibility, elastic stress response and strength. Therefore,
the polymeric material used in accordance with this invention
should have hard segments present in an amount sufficient to
achieve a high degree of elastic stress response (i.e., not greater
than about 5.00) and adequate wall tensile strength (i.e., at least
about 14,000 psi), while at the same time having an adequate amount
of soft segments to ensure that the balloon is also distensible
(i.e., about 5 to about 20%).
[0039] Examples of polymeric materials which have these alternating
zones or regions and which may be used in forming the balloons and
balloon catheters of this invention include block copolymers, and
physical mixtures of different polymers. Examples of block
copolymers which may be used include polyester block copolymers,
polyamide block copolymers and polyurethane block copolymers.
Examples of the mixtures which may be used include mixtures of
nylon and polyamide block copolymers and polyethylene terephthalate
and polyester block copolymers. The preferred block copolymer which
can be used in accordance with the process of this invention is
polyurethane block copolymer. This preferred polymer may be made,
for example, by a reaction between
[0040] a) an organic diisocyanate;
[0041] b) a polyol; and
[0042] c) at least one chain extender.
[0043] The preferred polyurethanes which can be used in this
invention may be varied by using different isocyanates and polyols
which will result in different ratios of hard to soft segments as
well as different chemical interactions within the individual
regions of the polymer.
[0044] An example of the most preferred polyurethane is
manufactured by The Dow Chemical Company and marketed under the
trade name PELLETHANE 2363-75D. This raw material has a Shore
Hardness of about 74 D, a specific gravity of about 1.21, a tensile
modulus of about 165,000 psi, a flexural modulus of about 190,000
psi, an ultimate tensile strength of about 6,980 psi and an
ultimate elongation of about 250%.
[0045] In accordance with this invention, the balloons are formed
from a thin wall parison of a polymeric material, preferably made
of a polyurethane block copolymer, which is treated in accordance
with the process of this invention. The novel process contemplated
by this invention employs a heat set step which will provide a
balloon with temperature and dimensional stability. This stability
results from the fact that the balloon is heated above the
temperature using in the balloon forming process so that the
orientation resulting from the processing conditions is "locked"
into position.
[0046] The balloons and balloon catheters of this invention may be
formed using a mold which can be provided with a heating element.
The mold receives a tubular parison made of a polymeric material of
the type used in accordance with the present invention. The ends of
the parison extend outwardly from the mold and one of the ends is
sealed while the other end is affixed to a source of inflation
fluid, typically nitrogen gas, under pressure. Clamps or "grippers"
are attached to both ends of the parison so that the parison can be
drawn apart axially in order to axially stretch the parison while
at the same time said parison is capable of being expanded radially
or "blown" with the inflation fluid. The radial expansion and axial
stretch step or steps may be conducted simultaneously, or depending
upon the polymeric material of which the parison is made, following
whatever sequence is required to form a balloon. Failure to axial
stretch the parison during the balloon forming process will result
in result in a balloon which will have an uneven wall thickness and
which will exhibit a wall tensile strength lower than the tensile
strength obtained when the parison is both radially expanded and
axially stretched.
[0047] The polymeric parisons used in this invention are preferably
drawn axially and expanded radially simultaneously within the mold.
To improve the overall properties of the balloons formed, it is
desirable that the parison is axially stretched and blown at
temperatures above the glass transition temperature of the
polymeric material used. This expansion usually takes place at a
temperature between about 80 and about 150.degree. C. depending
upon the polymeric material used in the process.
[0048] In accordance with this invention, based upon the polymeric
material used, the parison is dimensioned with respect to the
intended final configuration of the balloon. It is particularly
important that the parison have relatively thin walls. The wall
thickness is considered relative to the inside diameter of the
parison which has wall thickness-to-inside diameter ratios of less
than 0.6 and, preferably between 0.57 and 0.09 or even lower. The
use of a parison with such thin walls enables the parison to be
stretched radially to a greater and more uniform degree because
there is less stress gradient through the wall from the surface of
the inside diameter to the surface of the outside diameter. By
utilizing a parison which has thin walls, there is less difference
in the degree to which the inner and outer surfaces of the tubular
parison are stretched.
[0049] The parison is drawn from a starting length L1 to a drawn
length L2 which preferably is between about 1.10 to about 6 times
the initial length L1. The tubular parison, which has an initial
internal diameter ID1 and an outer diameter OD1 is expanded by the
inflation fluid emitted under pressure to the parison to an
internal diameter ID2 which is preferably about 6 to about 8 times
the initial internal diameter ID1 and an outer diameter OD2 which
is about equal to or preferably greater than about 3 times the
initial outer diameter OD1. The parison is preferably subjected to
between 1 and 5 cycles during which the parison is axially
stretched and radially expanded with an inflation pressure of
between about 100 and about 500 psi. Nitrogen gas is the preferable
inflation fluid for the radial expansion step.
[0050] After the desired number of "blow" cycles have been
completed, the expanded parison is subjected to a heat set or
thermoforming step during which the expanded parison, still
subjected to an inflation pressure of about 100 to about 500 psi,
is held at a temperature above the temperature at which the balloon
was axially stretched and radially expanded, but below the melting
temperature of the polymeric material from which the parison was
formed. This higher temperature induces crystallization and
"freezes" or "locks" the orientation of the polymer chains which
resulted from axially stretching and radially expanding the
parison. The temperatures which can be used in this heat set step
are therefore dependent upon the particular polymeric material used
to form the parison and the ultimate properties desired in the
balloon product (i.e., distensibility, strength and compliancy).
The heat set step ensures that the expanded parison and the
resulting balloon will have temperature and dimensional stability.
After the heat set step is completed, the mold is cooled to about
37.degree. C. The finished balloon will typically obtain its rated
or nominal diameter when inflated to a pressure of about 5 to about
8 bars depending upon the polymeric material used to form the
balloon. The balloon thus formed may be removed from the mold, and
affixed to a catheter.
[0051] For example, if the parison is formed from the polyurethane
marketed by The Dow Chemical Company under the trade name
PELLETHANE 2363-75D and axially stretched and radially expanded at
a temperature of about 90-100.degree. C., the heat set step would
preferably be conducted at about 105-120.degree. C. If this step
was conducted at temperatures much above about 120.degree. C., the
tensile strength of the resulting polyurethane balloon would
decrease significantly. Moreover, if the heat set step was
conducted at temperatures significantly higher than 120.degree. C.,
the distensibility of the resulting polyurethane balloon would also
be adversely affected. However, if the heat set was conducted at
temperatures below about 100.degree. C., the polyurethane balloons
formed would be dimensionally unstable resulting in balloons with
uneven wall thicknesses. Additionally, the lower heat set
temperature would result in balloons exhibiting physical properties
which would more likely be adversely affected during sterilization.
Finally, a balloon having a cloudy appearance, a property which
physicians find particularly undesirable, would be another
consequence of using a low heat set temperature.
[0052] It should be noted that some adjustment in the foregoing
axial stretch and radial expansion ratios, as well as the expansion
and heat set temperatures may be necessary to take into account the
difference in physical properties between the polyurethane block
copolymer exemplified above and any other polymeric materials which
can be used in accordance with this invention.
[0053] In order to preserve a balloon's distensibility, elastic
stress response, wall tensile strength and improved optical
clarity, the balloon formed must also be subjected to the novel
sterilization process contemplated by the invention. For example,
if a sterilization process which is currently available in the art
is used (e.g., high relative humidity at about 50-60.degree. C. in
the presence of about 12% ethylene oxide and about 88% Freon.TM.
for about 9-16 hours), the elastic stress response, distensibility
and the strength of the balloons contemplated by this invention
would be adversely affected. When the novel low temperature, low
humidity, ethylene oxide sterilization process of this invention is
used to sterilize the balloons and balloon catheters of this
invention, the elastic stress response, distensibility and strength
of the balloons are not adversely affected to any significant
degree.
[0054] The novel low temperature, low humidity sterilization
process consists of exposing the balloon or balloon catheter to a
preconditioning step at temperature about 35 to about 45.degree. C.
and a relative humidity of about 55% for about 15 hours. The
balloon or balloon catheter is then treated at a temperature of
about 35 to about 45.degree. C. and a relative humidity of about
55% with ethylene oxide, preferably in a concentration of about
100%. After being exposed to ethylene oxide for about 6 hours, the
products are aerated and kept at a temperature of about 35 to about
45.degree. C. for about 22 hours, in order to permit the ethylene
oxide to dissipate. The sterilized balloon products are now ready
for human use.
[0055] The sterilization process cannot, however, be conducted
above the heat set temperature since this would relieve the
orientation of the polymer chains which was "locked" into place
during heat set process. The sterilization process appears to be an
important factor in determining the final physical characteristics
of the balloons and balloon catheters of this invention. Therefore,
the novel sterilization process is necessary to ensure a clinically
useful and safe finished balloon and balloon catheter with an
overall advantageous combination of physical properties (i.e.,
distensibility, elastic stress response and wall tensile strength)
superior to those exhibited by the "compliant" balloons of the
prior art.
EXAMPLE 1
[0056] A parison was made from the polyurethane manufactured by The
Dow Chemical Company and marketed under the trade name PELLETHANE
2363-75D. This material has a Shore Hardness of about 74 D, a
specific gravity of about 1.21, a tensile strength of about 165,000
psi, a flexural modulus of about 190,000 psi, an ultimate tensile
strength of about 6,980 psi and an ultimate elongation of about
250%. The parison was sealed at one end while the other end was
attached to the source of the pressurized inflation fluid, in this
example nitrogen gas. Clamps were attached to each end of the
parison. The mold was then heated to an operating temperature of
about 90-100.degree. C., while the parison was pressurized with
nitrogen gas at about 290 psi and held for about 70 seconds.
[0057] The pressure was then relieved and the parison was subjected
to a series of radial expansion or "blow" cycles. During each
radial expansion or "blow" cycle, the parison was also axially
stretched while being pressured at about 290 psi for about 5
seconds. The pressure was then relieved, and the parison was
subject to continued axial stretching for about 5 seconds. The
parison was then subjected to another expansion cycle. After three
expansion or blow cycles, the original outer diameter had increased
from 0.035 inches to 0.1181 inches.
[0058] The expanded parison was then pressurized to about 190 psi
and was subjected to a heat set step during which the expanded
parison was held for about 75 seconds at a temperature of about
110.degree. C. The pressurized balloon was then cooled to about
37.degree. C. for about 30 seconds. The pressure was then relieved
and the balloon was held vertically in the mold at about 37.degree.
C. for about 120 seconds to minimize balloon curvature. The balloon
was released from the clamps and removed from the mold. The
balloon, having a nominal or rated diameter of 3.0 mm, displayed an
improved overall combination of distensibility, elastic stress
response and strength when compared to "compliant" balloons of the
art and was ready for attachment to a catheter.
EXAMPLE 2
[0059] The balloons formed following the process set forth in
Example 1 were placed in a sterilization chamber and kept at a
temperature of about 40.degree. C..+-.3.degree. C. and a relative
humidity of about 55% for about 15 hours. The balloons are kept at
a temperature of about 40.degree. C..+-.3.degree. C and were then
treated with 100% ethylene oxide. After being exposed to the
ethylene oxide for about 6 hours, the balloons were removed from
the sterilization chamber and held at a temperature of about
40.degree. C..+-.3.degree. C. and ambient relative humidity for
about 22 hours in order to dissipate the ethylene oxide. At this
point, the balloons were sterilized and ready for human use.
EXAMPLE 3
[0060] The effect which the novel sterilization process of this
invention has on the balloons formed using the balloon forming
process contemplated by this invention are demonstrated below.
Balloons with a nominal diameter of 3.0 mm were formed from
polyurethane following the process described in Example 1. One
group of balloons was subjected to the sterilization process
contemplated by this invention and described previously in Example
2, sterilization process contemplated by this invention and
described previously in Example 2, while the other group of
balloons were subjected to a sterilization process currently used
in the art.
[0061] In that sterilization process (referred to in this Example
as "traditional sterilization process"), the balloons were
preconditioned at a temperature of about 43.degree. C. and a
relative humidity of about 60% for about 24 hours. The balloons
were then treated with about 12% ethylene oxide and 88% Freon.TM.
at a temperature of about 54.degree. C. After being treated with
the ethylene oxide mixture for about 9 hours, the balloons are
removed from the sterilization chamber and kept at a temperature of
about 38.degree. C. for about 22 hours.
[0062] The average wall tensile, burst pressure, elastic stress
response and distensibility (i.e., radial expansion) of both sets
of balloons were compared below.
1 Average Wall Average Tensile Burst Average Sterilization Strength
Pressure Elastic Stress Average Conditions (psi) (atm) Response
Distensibility novel sterilization 16,297 22.0 3.38 9.4% conditions
described in Example 2 traditional 14,497 22.6 10.29* 20.2%
sterilization process *The balloons used to determine elastic
stress response for this comparison with the novel sterilization
conditions were treated with 100% ethylene oxide rather than 12%
ethylene oxide and 88% Freon .TM.. All other temperature and time
conditions were the same.
EXAMPLE 4
[0063] The following example demonstrates the importance of the
heat set step. Three dilatation balloons with a nominal or rated
diameter of 3.0 mm, were formed from polyurethane following the
process described in Example 1. The average burst pressure,
distensibility and wall tensile strength of balloons formed using
different heat set temperatures are compared. The burst pressure
and distensibility were determined at 37.degree. C.
2 Heat Set T Temperature Average Wall Tensile Average Burst Average
(.degree. C.) Strength (psi) Pressure (atm) Distensibility 160
14,712 12.8 10.26% 132 23,364 20.6 5.81% 118 25,346 22.2 5.96%
EXAMPLE 5
[0064] The following example demonstrates the improved elastic
stress response or "repeatability" which can be obtained by the
balloons and balloon catheters formed following the process
contemplated by this invention. In this example, dilatation
balloons with a nominal or rated diameter of 3.0 mm were formed
from polyurethane following the process described in Example 1. A
number of polyurethane balloons were sterilized following the
process previously described in Example 3 (referred to as
"traditional sterilization" in this Example). Another group of
polyurethane balloons were sterilized using the novel sterilization
contemplated by this invention and previously described in Example
2. The elastic stress response of these polyurethanes balloons were
compared with the elastic stress response of other sterilized 3.0
mm balloons known in the art.
3 Average Average Diameter at Diameter at 5 Bars Averag Initial 5
Bar After A Single Elastic Stress Balloon Inflation Inflation to 10
Bars Response Polyurethane 2.96 3.06 3.38 (sterilization described
in Example 2) Polyurethane 2.72 3.00 10.29 (traditional
sterilization) Polyethylene 3.02 3.04 0.66 terephthalate
Cross-linked 2.98 3.11 4.36 polyethylene Cross-linked 2.93 3.19
8.87 polyolefin-ionomer
EXAMPLE 6
[0065] The following example demonstrates the improved overall
combination of distensibility, elastic stress response and wall
tensile strength obtained by forming balloons by using the process
of this invention. Balloons with a nominal or rated diameter of 3.0
mm were formed from polyurethane following the process described in
Example 1. The average elastic stress response, distensibility and
wall tensile strength of those polyurethane balloons are compared
with properties of other 3.0 mm balloons of the art.
4 Average Wall Average Elastic Average Tensile Balloon Stress
Response Distensibility Strength (psi) Polyurethane 3.38 9.4%
16,297 Polyethylene 0.66 3.26% 62,081 terephthalate Cross-linked
4.36 9.67% 8,868 polyethylene Cross-linked 8.87 14.64% 6,793
polyolefin-ionomer
* * * * *