U.S. patent application number 15/250802 was filed with the patent office on 2017-05-11 for hydration prevention coating.
This patent application is currently assigned to Bayer HealthCare LLC. The applicant listed for this patent is Bayer HealthCare LLC. Invention is credited to Christopher A. Stout.
Application Number | 20170128257 15/250802 |
Document ID | / |
Family ID | 50346118 |
Filed Date | 2017-05-11 |
United States Patent
Application |
20170128257 |
Kind Code |
A1 |
Stout; Christopher A. |
May 11, 2017 |
HYDRATION PREVENTION COATING
Abstract
Occlusion devices and delivery systems are described in which a
polymerizing oil is used to protect a hydrogel from premature
swelling. In an embodiment, a delivery system includes an occlusion
device releasably coupled within a catheter sheath. The occlusion
device includes an expandable implant and a hydrogel. An at least
partially oxidized polymerizing oil is inside a lumen of the
catheter sheath between the distal end of the catheter sheath and
the hydrogel.
Inventors: |
Stout; Christopher A.; (San
Bruno, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Bayer HealthCare LLC |
Whippany |
NJ |
US |
|
|
Assignee: |
Bayer HealthCare LLC
Whippany
NJ
|
Family ID: |
50346118 |
Appl. No.: |
15/250802 |
Filed: |
August 29, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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13842999 |
Mar 15, 2013 |
9427352 |
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15250802 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 6/22 20130101; A61F
6/005 20130101; A61F 6/20 20130101; A61B 1/00135 20130101; A61F
6/202 20130101; A61L 31/145 20130101; A61L 29/08 20130101; A61L
31/04 20130101; A61L 2420/02 20130101; A61L 31/10 20130101; A61F
6/225 20130101; A61L 31/08 20130101 |
International
Class: |
A61F 6/00 20060101
A61F006/00; A61L 31/10 20060101 A61L031/10; A61L 31/14 20060101
A61L031/14; A61L 29/08 20060101 A61L029/08; A61F 6/20 20060101
A61F006/20; A61F 6/22 20060101 A61F006/22 |
Claims
1. A delivery system comprising: a catheter sheath having a distal
end, a proximal end, and a lumen therebetween; an occlusion device
releasable coupled within the catheter sheath, the collusion device
comprising an expandable implant and a hydrogel on the expandable
implant; a polymerizing oil inside the lumen of the catheter sheath
between the distal end of the catheter sheath and the hydrogel,
wherein the polymerizing oil is at least partially oxidized.
2-16. (canceled)
Description
FIELD
[0001] Embodiments of the present invention relate to the field of
delivery systems for delivering an occlusion device and, in
particular, delivery systems including a hydration prevention
coating.
BACKGROUND
[0002] Contraception and sterilization may be accomplished by
inserting an occlusion device into a reproductive lumen such as
fallopian tube or vas deferens. Devices, systems, and methods for
such contraceptive approaches have been described in various
patents and patent applications assigned to the present assignee.
For example, U.S. Pat. No. 6,526,979 and U.S. Pat. No. 6,634,361
describe devices that are transcervically inserted into an ostium
of a fallopian tube and mechanically anchored within the fallopian
tube. The occlusion devices described in those patents may promote
tissue-ingrowth around and within the occlusion device to achieve
permanent occlusion and contraception. One example of such a device
is known as "Essure" from Conceptus, In. of Mountain View,
California. Tissue in-growth is not immediate, and up to several
months after insertion of the Essure device may be required for
tissue in-growth to completely occlude a fallopian tube and for the
occlusion devices to be permanently effective.
[0003] Other occlusion devices have been described which are
designed to achieve immediate or near immediate occlusion, and
thereby contraception, upon insertion in the reproductive lumen.
For example U.S. Publication No. 2005/0192616 describes an
occlusion device including both permeable and impermeable
components where the permeable components are designed for tissue
in-growth to provide permanent occlusion and effectiveness, and the
impermeable components are impermeable to the passage of sperm or
egg cells to provide immediate effectiveness. Other applications
employ a hydrogel to provide immediate effectiveness. For example,
U.S. Publication No. 2011/0094519, assigned to the present
assignee, and U.S. Publication No. 2007/0056591 describe occlusion
devices including a hydrogel that provides near immediate occlusion
upon insertion in the reproductive lumen. U.S. Publication No.
2011/0094519 additionally describes coating a distal end of a
delivery catheter sheath with a hydrophobic coating to prevent the
hydrogel on the occlusion device from swelling before the occlusion
device is delivered to the target site in the reproductive lumen.
The coating can be bioabsorbable, biodegradable, or pierced by the
occlusion device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] FIG. 1A is a side view illustration of an occlusion device
including a pair of hydrogel sleeves on an expandable implant in
accordance with an embodiment of the invention.
[0005] FIG. 1B is a cross sectional side view taken along line B-B
of FIG. 1A in accordance with an embodiment of the invention.
[0006] FIG. 2 is a schematic side view illustration of a delivery
system in accordance with an embodiment of the invention.
[0007] FIG. 3A is schematic side view illustration of an occlusion
device coated with a polymerizing oil after 24 hours at ambient
conditions in accordance with an embodiment of the invention.
[0008] FIG. 3B is a schematic side view illustration of the coated
occlusion device of FIG. 3A after immersion in water for 7 minutes
in accordance with an embodiment of the invention.
[0009] FIG. 4A is a schematic side-view illustration of the distal
end of the delivery system illustrated in FIG. 2 prior to injecting
the liquid linseed oil into the lumen of the catheter sheath in
accordance with an embodiment of the invention.
[0010] FIG. 4B is a schematic side-view illustration of the distal
end of the delivery system after the linseed oil had been injected
and the delivery system had been hung on the catheter tree proximal
side up, distal side down, for 24 hours at ambient conditions in
accordance with an embodiment of the invention.
[0011] FIG. 4C is a schematic side-view illustration of the
delivery system after immersion in water for 40 minutes and
rollback of the catheter sheath 204 to expose the distal portion of
the occlusion device including the pair of hydrogel sleeves 110 in
accordance with an embodiment of the invention.
[0012] FIG. 5A is a schematic side-view illustration of
polymerizing oil injected into the distal end of a catheter sheath
an allowed to wick around proximally of the proximal hydrogel in
accordance with an embodiment of the invention.
[0013] FIG. 5B is a schematic side-view of the skin of the
polymerizing oil remaining on the inner coil and removed from the
radial surfaces of the hydrogel sleeves after rollback of the
catheter sheath in accordance with an embodiment of the
invention.
[0014] FIG. 5C is a schematic side-view of the skin of the
polymerizing oil remaining on the inner coil and radial surfaces of
the hydrogel sleeves after rollback of the catheter sheath in
accordance with an embodiment of the invention.
[0015] FIGS. 6-10 illustrate a method of delivering an occlusion
device to a fallopian tube and facilitating immediate, or near
immediate, and permanent sterilization in accordance with an
embodiment of the invention.
DETAILED DESCRIPTION
[0016] Embodiments of the invention describe delivery systems and
methods for delivering an occlusion device in which a polymerizing
oil is used to protect a hydrogel from premature swelling. Various
embodiments and aspects will be described with reference to details
discussed below and the accompanying drawings will illustrate the
various embodiments. The following description and drawings are
illustrative of the invention and are not to be construed as
limiting the invention. Numerous specific details are described to
provide a thorough understanding of various embodiments of the
present invention. However, in certain instances, well-known or
conventional details are not described in order to provide a
concise discussion of embodiments of the present invention.
[0017] In one embodiment, a delivery system includes a catheter
sheath and an occlusion device releasably coupled within the
catheter sheath, and the occlusion device includes an expandable
implant and a hydrogel on the expandable implant. In accordance
with embodiments of the invention, the polymerizing oil caps a
portion of the catheter sheath distal to the hydrogel on the
expandable implant within the catheter sheath, or coats the
hydrogel itself. In accordance with embodiments of the invention,
the polymerizing oil is at least partially oxidized and forms a
cross-linked skin that protects the hydrogel from premature
swelling.
[0018] In one aspect, the polymerizing oil and skin create a
hydration barrier that prevents the hydrogel from prematurely
swelling when the portion of the delivery system including the
hydrogel is in contact with a physiological environment.
Specifically, the polymerizing oil and skin thereof may protect the
hydrogel from premature swelling when tracking the occlusion device
to the target deployment site within a body lumen, such as a
reproductive body lumen. In one embodiment, the water repellent
nature of the polymerizing oil confers a liquid barrier property to
the polymerizing oil, while the skin confers a stability to the
polymerizing oil and keeps it in place when tracking the occlusion
device. In one embodiment, the polymerizing oil is linseed oil, and
the water repellent hydrocarbon nature of the C18 fatty acids in
the oil help confer the barrier property, while the auto-oxidized
skin confers the stability to the polymerizing oil.
[0019] In one aspect, embodiments of the invention describe a
system in which a skin can be formed from the polymerizing oil in
ambient conditions. In this manner, while not precluding additional
processing operations, formation of the skin at ambient conditions
allows for a simplified application and curing process that does
not require a separate curing step to effect skin formation. In
other embodiments, cure can be aided by a variety of manners,
including thermal and inclusion of drying agents.
[0020] In one aspect, the cross-linked skin provides a thermally
stable hydration barrier that does not migrate. In this manner, the
solid cross-linked skin keeps the hydration barrier in place and
resists migration over time and due to temperature changes
associated with normal storage and handling of the delivery
system.
[0021] In yet another aspect, the hydration barrier formed by the
polymerizing oil and skin do not substantially affect the
flexibility profile of the delivery system. In this manner, the
hydration barrier can be applied to the delivery system after the
formation and integration of the system components that are
designed for specific flexibilities to track tortuous pathways of
specific body lumens, and without requiring altering of the design
of those system components to maintain a desired flexibility
profile. Thus the hydration barrier may be applied to a variety of
existing systems without substantially requiring redesign of system
flexibility.
[0022] Referring now to FIG. 1A a side view illustration is
provided of an occlusion device including a pair of hydrogel
sleeves on an expandable implant in accordance with an embodiment
of the invention. As shown, the expandable implant 102 can be
formed from one or more metals or polymers and can include fibers
to act as a tissue ingrowth promoting agent to cause tissue to
grown into the implant after it has been implanted into a body
lumen. For example, the fiber may be polyester, polyethylene
terephthalate (PET), or the like, and can be attached to one or
more components of the implant, such as the inner coil 104 or outer
coil 106. The outer coil 106 may be resilient and self-expanding so
that it may be restrained within a catheter sheath and once
deployed can radially expand to resiliently engage the walls of the
body lumen. A delivery shaft or wire in the delivery system can be
removably attached to a proximal end of the inner coil 104. A
connection between the proximal end of the inner coil 104 and a
delivery shaft or wire can be a number of connections including
screw threading or friction fitting that allow the delivery shaft
or wire to be removable coupled to the expandable implant 102. The
inner coil 104 and outer coil 106 can be connected together by a
connection mechanism 108 which can be a solder joint.
Alternatively, a segment of the outer coil is tightly wrapped
around the inner coil 104 to form the connection mechanism.
[0023] In one implementation of manufacture, one or more preformed
hollow cylinders of hydrogel, such as hydrogel cylinders 110 are
applied onto the distal end of the inner coil 104 prior to applying
the distal ball 112. The application of the hydrogel cylinders 110
onto the distal end of the inner coil may be accomplished by
sliding the hydrogel cylinders 110 over the distal end of the inner
coil in a dehydrated state so that they are not swollen. A glue can
be applied between the hydrogel cylinders 110 and the inner coil
104, as well as between the hydrogel cylinders 110 in order to
secure the hydrogel cylinders in place. For example, the glue can
be applied to the inner coil 104, to the hydrogel cylinders 110, or
both. The glue can be applied before or after sliding the hydrogel
cylinders onto the inner coil, or can be applied both before and
after.
[0024] In one embodiment, the glue can be cyanoacrylate such as
LOCTITE (RTM) 4541 or 431 or 3211 or a mixture of cyanoacrylate
glues from Henkel Corporation. The glue can be cured with or
without UV (ultraviolet) light. The glue can be selected to enhance
the structural integrity or strength of the hydrogel after the glue
has been cured. The hydrogels 110 can be applied onto the inner
coil 104 without glue in some embodiments.
[0025] In the particular embodiment illustrated, a region 105 of
the inner coil 104 distal to the outer coil 106 is stretched prior
to applying the hydrogels 110. In this manner the winding density
(number of winds per unit length) is less in the stretch region 105
of the inner coil 104 than for surrounding regions of the inner
coil. In one embodiment, the hydrogels 110 are applied onto the
inner coil so that they each span a portion of the stretched region
105, for example, the proximal and distal portions of the stretched
region 105. Each hydrogel 110 may also span a portion of the inner
coil 104 adjacent the stretched region 105 so that they each span
both stretched and unstretched regions of the inner coil 104. In
one embodiment, applying the hydrogels over the stretched region
allows more area for the glue to penetrate into the inner coil and
ensure the glue wets the inside diameter of the hydrogels 110. In
one embodiment, the application of the deswollen hydrogels 110 may
tend to increase the stiffness of the occlusion device where the
hydrogels are located. By stretching the region 105 of the inner
coil 104 adjacent the hydrogels, this may have the effect of
reducing the stiffness of the inner coil 104 in this region,
thereby resulting in a negligible net stiffness change in the
regions of the hydrogels 110 compared to a similar inner coil 104
region that has not been stretched and does not include
hydrogels.
[0026] After applying the hydrogel cylinders 110 onto the inner
coil 104, distal ball 112 can be attached to the coil 104 (for
example, by soldering or by gluing the ball 112 onto the distal end
of the coil 104). In an alternative embodiment, the ball 112 can be
attached to the coil 104 before the hydrogels 110 are applied onto
the coil (e.g. if the inner diameter of the hydrogels 110 are
larger than the outer diameter of the distal ball 112, or if the
hydrogels are applied by wrapping a hydrogel sheet around the
coil).
[0027] FIG. 1B shows a cross-sectional view of the occlusion device
(shown in FIG. 1A) taken along the line B-B. This cross-sectional
view shows that a hydrogel 110 concentrically surrounds the inner
coil 104. The hydrogels 110 can be formed or cast to fit snugly or
loosely around the inner coil 104, and a layer of glue may exist at
the interface or gap between the inner coil 104 and the inner
diameter of the hydrogels 110.
[0028] The hydrogel can provide immediate or near immediate
sterilization by swelling in a physiological environment once the
occlusion device with hydrogel is deployed, and the tissue
in-growth promoting agent (such as polyester or PET fibers)
promotes in-growth of tissue to permanently occlude the body lumen
into which the occlusion device is implanted. Hydrogels may be
formed from covalently or non-covalently cross-linked materials,
and may be non-degradable ("biostable") in a physiological
environment or broken down (biodegradable) by natural processes
within the body, referred to as biodegradable or bioabsorbable. The
breakdown process may be due to one of many factors in the
physiological environment, such as enzymatic activity, heat,
hydrolysis, or others, including a combination of these
factors.
[0029] Hydrogels that are cross-linked may be cross-linked by any
of a variety of linkages, which may be reversible or irreversible.
Reversible linkages may be due to ionic interaction, hydrogen or
dipole type interactions or the presence of covalent bonds.
Covalent linkages for absorbable or degradable hydrogels may be
chosen from any of a variety of linkages that are known to be
unstable in an animal physiological environment due to the presence
of bonds that break either by hydrolysis (e.g., as found in
synthetic absorbable sutures), enzymatically degraded (e.g., as
found in collagen or glycosamino glycans or carbohydrates), or
those that are thermally labile (e.g., azo or peroxy linkages).
[0030] All of the hydrogel materials appropriate for use in
embodiments of the present invention should be physiologically
acceptable and should be swollen in the presence of water. These
characteristics allow the hydrogels to be introduced into the body
in a "substantially deswollen" state and over a period of time
hydrate to fill a void, a defect in tissue, or create a
hydrogel-filled void within a tissue or organ by mechanically
exerting a gentle force during expansion.
[0031] "Substantially deswollen" is defined as the state of a
hydrogel wherein an increase in volume of the hydrogel of the
article or device formed by such hydrogel is expected on
introduction into the physiological environment. Thus, the hydrogel
may be in a dry state, or less than equilibrium hydrated state, or
may be partially swollen with a pharmaceutically acceptable fluid
that is easily dispersed or is soluble in the physiological
environment. The expansion process also may cause the implanted
hydrogel to become firmly lodged within a hole, an incision, a
puncture, or any defect in tissue which may be congenital,
diseased, or iatrogenic in origin, occlude a tubular or hollow
organ, or support or augment tissue or organs for some therapeutic
purpose.
[0032] FIG. 2 is a schematic side view illustration of a delivery
system in accordance with an embodiment of the invention. As shown,
the delivery system 200 may include a control device, such as a
handle 202, and a catheter sheath 204 extending distally from the
handle 202. In the particular embodiment illustrated, a distal end
of the expandable implant including the distal ball 112 and inner
coil 104 extends distally beyond the distal end of the catheter
sheath 204. As described in further detail below, the distal
portion of the expandable implant protruding from the catheter
sheath 204 may aid in tracking the delivery system 200 through
tortuous body lumens. In accordance with another embodiment, the
expandable implant is entirely countained within the catheter
sheath 204.
[0033] In accordance with embodiments of the invention, at least
two approaches may be used to protect the one or more hydrogels
from hydrating prior to the occlusion device being properly placed
at the target deployment site. In one implementation, the hydrogel
itself can be coated with a polymerizing oil. In another
implementation, the distal end of the catheter sheath can be capped
with a polymerizing oil to prevent liquid from entering through the
distal end of the catheter sheath. In yet another embodiment, a
polymerizing oil can both cap the distal end of the catheter sheath
and partially or fully coat the hydrogel. In accordance with
embodiments of the invention, the polymerizing oil is at least
partially oxidized and forms a cross-linked skin that forms a seal
around the hydrogels or seals the distal end of the catheter sheath
to protect the one or more hydrogels from premature swelling.
Furthermore, the cross-linked skin can keep the polymerizing oil in
place and prevent migration of the seal, while still maintaining
the level of flexibility of the delivery system prior to applying
the polymerizing oil.
[0034] In accordance with embodiments of the invention,
polymerizing oils may be at least partially oxidized when exposed
to ambient environment (room atmosphere, temperature, pressure).
For example, oxidation may result in the formation of a hardened
cross-linked skin on the exterior of the polymerizing oil, or the
portion of the polymerizing oil that is exposed to the ambient
environment due to autoxidation, or the addition of oxygen to an
organic compound and subsequent cross-linking. The cross-linked
skins that form may be elastic, yet not flow or deform readily. In
some embodiments, the interior portion of the polymerizing oil
encapsulated by the hardened elastic skin may remain in a liquid
state. In other embodiments, oxidation and skin formation can be
controlled by exposure to a controlled temperature, pressure, or
oxygen content for a determined period of time.
[0035] In an embodiment, the polymerizing oil is a drying oil.
Drying oils may in general be characterized as being fatty oils
containing glycerin in combination with a fatty acid, and liquid at
room temperature. Fatty oils are insoluble in water, but are
soluble in several organic solvents. Fatty oils occur in many plant
families and are stored in seeds and somewhat in fruits, tubers,
stems and other plant organs. Extraction of fatty oils is generally
performed with solvents, followed by filtering and further
purification.
[0036] In an embodiment, the drying oil is characterized by the
percent of unsaturated fatty acid. Drying oils can be further
characterized as being conjugated oils (i.e. alternating single and
double bonds), non-conjugated oils, or other oils. Non-conjugated
oils, such as linseed oil, are fatty oils that contain
polyunsaturated fatty acids, whose double bonds are separated by at
least two single bonds. Conjugated oils on the other hand, such as
tung oil, are polyunsaturated fatty acids whose double bonds are
partly or fully conjugated.
[0037] Some faster drying non-conjugated polymerizing oils may be
characterized as including alpha-linolenic acid. In an embodiment,
the polymerizing oil is characterized as having at least 20%
alpha-linolenic acid of unsaturated fatty acid content. In terms of
its structure, alpha-linolenic acid is named
all-cis-9,12,15-octadecatrienoic acid. In physiological literature,
it is given the name C18:3 (n-3). Alpha-linolenic acid is a
carboxylic acid with an 18-carbon chain and three cis double bonds.
Other 18-carbon chain fatty acids may also be present in the
polymerizing oil.
[0038] In some embodiments, the initial autoxidation step in
non-conjugated oils (e.g. linseed), is dehydrogenation of the
unsaturated fatty acid by oxygen, which forms a radical. This
starts a radical chain reaction that increases incrementally with
time, leading to the formation of a hydroperoxide. At low levels,
the hydroperoxides produced during autoxidation, decompose to form
free alkoxy and hydroxyl radicals. Higher levels of hydroperoxides
form free radicals through boimolecular disproportionation. The
resultant free radicals react in various ways to accelerate the
autoxidation process. Accordingly, it is expected that a high
degree of unsaturation of the fatty acid content, and particularly,
high content of alpha-linolenic acid may correlate to being more
conducive to skin formation, in accordance with some embodiments of
the invention.
[0039] The drying of tung oil (a conjugated oil) varies
considerably from linseed oil (a non-conjugated oil). Tung oil
typically absorbs approximately 12% oxygen (linseed oil absorbs
approximately 16%) and quickly forms a skin on the surface. Since
less oxygen is absorbed, the viscosity of the oil can increase at a
faster rate. Unlike the hydroperoxide formation during autoxidation
in linseed oil, tung oil forms cyclic peroxides. (The methyl
eleostearate formed has a higher molecular mass than linoleic acid
esters). The direct attack on the double bonds by oxygen forms
cyclic peroxides. The resultant reaction of the peroxides with
allylic methylene groups, leads to the formation of radicals. This
creates a radical chain reaction that forms polymers.
[0040] An iodine value, or iodine adsorption value, may be used to
characterize drying oils, and in particular those including
unsaturated fatty acids. Iodine value is the mass of iodine in
grams that is consumed by 100 grams of a chemical substance, and
may be used to determine the amount of unsaturation in fatty acids.
This unsaturation is in the form of double bonds, which react with
iodine compounds. The higher the iodine number, the more
carbon-carbon double bonds are present in the fat. Oils with an
iodine number of greater than 130 are typically considered drying
oils, and whose with an iodine number of 115-130 are considered
semi-drying, and those with an iodine number of less than 115 are
non-drying.
[0041] However, iodine value is not always a precise indicator of
drying ability. Tung oil and oiticia oil are characterized as
conjugated acid oils, where iodine value is not as significant
measurement of because conjugated acids do not absorb halogens.
Iodine value is not necessarily a measure of drying ability because
drying is based on conjugation of the oil not the amount of
unsaturation of the oil. For example, the fatty acids/triglycerides
of tung and oiticica oils contain three double bonds in conjugated
sequence and which may result in oxidation drying and more robust
skin formation than many drying oils with alpha-linolenic acids
which have three double bonds but are not conjugated.
[0042] Table 1 includes a non-exclusive list of exemplary
polymerizing oils that may be used in accordance with embodiments
of the invention, along with iodine value, and percent
apha-linolenic acid of unsaturated fatty acid content. It is to be
appreciated that the list of exemplary polymerizing oils is a
non-exclusive list of oils that may readily oxidize and form a
skin. However, selection of the appropriate polymerizing oil and
drying conditions may be dependent upon system requirements and
dimensions. For example, it is possible that some polymerizing oils
may form a skin that is too hard for a specific delivery
system.
TABLE-US-00001 TABLE 1 Alpha-linolenic acid Iodine value (C18:3) %
Linseed oil 170-204 35-60 Soybean oil 120-148 5-11 Sunflower oil
125-144 -- Poppy seed oil 133 11 Perilla oil 193-208 62-65 Walnut
oil 143-148 3-8 Hemp seed oil 140-175 24-26 Niger seed oil 125-135
45-66 Rubber seed oil 132-148 21-26 Chia oil 190-199 64 Kiwi seed
oil 170-205 62 Lingonberry oil 49 Camelina oil 127-155 35-45
Purslane oil 35 Sea buckthorn oil 130-200 32 Candlenut oil 135-166
28 Safflower oil 140-150 1 Tall oil 120-155 1-3 Stillingia oil
169-191 40 Tung oil 160-175 * Oiticica oil 150 ** *
alpha-eleostearic acid 80%, alpha-lenolenic acid 3%. ** 73%
conjugated acids, 16% unsaturated acids
[0043] In the following description of Examples 1 and 2, the
results of two tests are described which illustrate the use of a
polymerizing oil to form a seal around a hydrogel or seal the
distal end of a catheter sheath to prevent premature swelling of
the hydrogel in accordance with embodiments of the invention.
EXAMPLE 1
[0044] Boiled liquid linseed oil containing less than 1% cobalt
containing drying agent and less than 1% manganese containing
drying agent (KLEAN-STRIP (RTM) Boiled Linseed Oil, available from
W.M. Barr & Company, Inc. of Memphis, Tenn., USA) was drawn
from the 3.785 liter manufacturer container into a syringe, though
the polymerizing oil could have been drawing into a number of
alternative dispensing containers, such as an engineering fluid
dispenser (EFD). A sufficient amount of liquid linseed oil was
dispensed onto the occlusion device illustrated in FIG. 1A to coat
the hydrogels 110. The occlusion device was then hung proximal side
up, distal side down, for 24 hours at ambient conditions (room
temperature, pressure, atmosphere). During this time the linseed
oil formed an outer skin. The coated occlusion device was then
immersed in a beaker filled with water, and removed after 7 minutes
of immersion in water.
[0045] FIG. 3A is a schematic side-view illustration of the coated
occlusion device after 24 hours at ambient conditions. As shown,
after 24 hours at ambient conditions the linseed oil 300 quantity
formed a cross-linked skin 302 as a result of oxidation. In this
example, the skin 302 additionally encapsulated a liquid portion
304 of the linseed oil. The skin staying in place was observed to
be elastic and deformable to the touch. It was also observed that
the linseed oil 300 did not completely cover the proximal end of
the proximal hydrogel 110.
[0046] FIG. 3B is a schematic side-view illustration of the coated
occlusion device after immersion in water for 7 minutes. As
illustrated, the proximal end of the proximal hydrogel 110 began to
hydrate, while the distal portion of the proximal hydrogel 110, and
the distal hydrogel 110 did not hydrate. Furthermore, upon closer
examination, a split 303 was visible in the coating where the
proximal end of the proximal hydrogel 110 increased in size.
[0047] The results of Example 1 illustrate that a polymerizing oil
can be applied to a hydrogel and allowed to oxidize at ambient
conditions to form a protective skin that protects the hydrgel from
premature swelling. Furthermore, the results of Example 1
illustrate that the protective skin while strong enough to protect
against migration of the drying oil, can be split where the
hydrogel is allowed to absorb water and swell.
EXAMPLE 2
[0048] Boiled liquid linseed oil containing less than 1% cobalt
containing drying agent and less than 1% manganese containing
drying agent (KLEAN-STRIP (RTM) Boiled Linseed Oil, available from
W.M. Barr & Company, Inc. of Memphis, Tenn., USA) was drawn
from the 3.785 liter manufacturer container into a syringe, though
the polymerizing oil could have been drawing into a number of
alternative dispensing containers, such as an EFD. A sufficient
amount of liquid linseed oil was injected into the lumen of the
distal end of the catheter sheath of the delivery system
illustrated in FIG. 2 to form a protective cap distal to the distal
end of the distal hydrogel illustrated in FIG. 1A. The delivery
system was then hung on a catheter tree proximal side up, distal
side down, for 24 hours at ambient conditions (room temperature,
pressure, atmosphere). It is believed that capillary forces
initially retained the linseed oil inside the catheter sheath and
prevented the linseed oil from dripping out of the distal end of
the catheter sheath, which was pointing down. During this time the
linseed oil formed an outer skin. The distal end of the delivery
system including the occlusion device, catheter sheath, and linseed
oil was then immersed in a beaker filled with water, and removed
after 40 minutes of immersion in water. The catheter sheath was
then rolled back to expose the portion of the occlusion device
including the pair of hydrogel sleeves 110.
[0049] FIG. 4A is a schematic side-view illustration of the distal
end of the delivery system illustrated in FIG. 2 prior to injecting
the liquid linseed oil into the lumen of the catheter sheath. As
illustrated, the hydrogel sleeves 110 are located within the lumen
206 of the catheter sheath 204. FIG. 4B is a schematic side-view
illustration of the distal end of the delivery system after the
linseed oil had been injected and the delivery system had been hung
on the catheter tree proximal side up, distal side down, for 24
hours at ambient conditions. As shown, after 24 hours at ambient
conditions the linseed oil quantity 300 formed a cross-linked skin
302 as a result of oxidation. In this example, the skin 302
encapsulated a liquid portion 304 of the linseed oil. The skin
staying in place was observed to be elastic and deformable to the
touch. In the particular embodiment illustrated, the quantity of
linseed oil 300 was located between the distal end of the catheter
sheath 204 and the distal hydrogel 110. In such an embodiment, the
quantity of linseed oil 300 formed a plug distal to the distal
hydrogel 110, and the linseed oil was not substantially formed over
the hydrogels 110. In this manner, it is expected that this
configuration will allow for unobstructed swelling of the hydrogels
after rollback of the catheter sheath 204 in vivo. In other
embodiments, the quantity of linseed oil 300 may be allowed to
partially or completely wick over one or more hydrogels 110.
[0050] FIG. 4C is a schematic side-view illustration of the
delivery system after immersion in water for 40 minutes and
rollback of the catheter sheath 204 to expose the distal portion of
the occlusion device including the pair of hydrogel sleeves 110. As
illustrated, the proximal and distal hydrogels 110 did not hydrate,
and remained in their deswollen shapes. Rollback of the catheter
sheath 204 occurred without issue. In addition, after rollback
portions of the cross-linked skin 302 were observed to remain on
the inner coil 104 of the expandable implant.
[0051] The results of Example 2 illustrate that polymerizing oil
can be injected into a distal end of a catheter sheath to cap or
seal the lumen at the distal end of the catheter in order to
protect against premature swelling of hydrogels within the catheter
sheath. The results of Example 2 additionally illustrate that the
protective skin while strong enough to protect against migration of
the drying oil and liquid penetration into the lumen of the
catheter sheath, the protective skin also does not affect catheter
sheath rollback and can be split or torn upon catheter rollback to
expose the hydrogels. Furthermore, it is expected that this
configuration will allow for unobstructed swelling of the hydrogels
after rollback of the catheter sheath 204 in vivo.
[0052] FIGS. 5A-5C illustrate additional embodiments of the
invention, in which similar to Example 2, a liquid polymerizing oil
can be injected into the distal end of a catheter sheath 204, for
example, by using a syringe or EFD. In an embodiment, the liquid
polymerizing oil is allowed to at least partially wick around the
one or more hydrogels. In the particular embodiment illustrated in
FIG. 5A, the polymerizing oil is allowed to wick around both
hydrogels 110, and proximally of the proximal hydrogel 110. The
polymerizing oil can then be allowed to oxidize to form outer skin
302 as previously described. In the embodiment illustrated in FIG.
5A, the polymerizing oil and skin 302 may encapsulate the one or
more hydrogels 110.
[0053] FIGS. 5B-5C illustrate alternative results upon rolling back
the catheter sheath of FIG. 5A. In the embodiment illustrated in
FIG. 5B, the skin 302 of the polymerizing oil may remain on the
inner coil 104 of the occlusion device but be removed, at least
partially, from the radial surfaces of the hydrogel sleeves 110
that were adjacent the catheter sheath 204. In such an embodiment,
the skin 302 adjacent the catheter sheath 204 may be withdrawn with
the sheath or torn by withdrawal of the sheath to expose the
hydrogel sleeves 110. In the embodiment illustrated in FIG. 5C, the
skin 302 of the polymerizing oil may remain on the inner coil 104
of the occlusion device as well as on the radial surfaces of the
hydrogel sleeves 110.
[0054] In one implementation, the result of FIG. 5B may be
incorporated into a delivery system design in which the skin 302 is
designed to be removed from the expanding surfaces of the hydrogel
sleeves 110 so as to not interfere with the ability of the hydrogel
sleeves 110 to swell and provide immediate or near immediate
occlusion in vivo. In another implementation, the result of FIG. 5C
may be incorporated into a delivery system design in which the skin
302 is designed to remain on the hydrogel sleeves and function as a
timed expansion control element. In an embodiment, the skin 302 may
be bioabsorbable or bioerodable so that it is removed over time. A
bioabsorbable or bioerodable skin may also be beneficial to remove
fragments of the skin that may be inadvertently left behind
adjacent a hydrogel.
[0055] In accordance with embodiments of the invention the
polymerizing oils may be formulated to endure a specific amount of
oxidation or achieve specific skin characteristics such as hardness
(flexibility), thickness, and tear strength. As described above, a
polymerizing oil may be selected based upon its iodine value,
degree of unsaturation, alpha-lenolenic acid content, or amount of
conjugation since these may be used to indicate the propensity for
oxidation and skin formation of the polymerizing oil. Oxidation and
skin formation may also be controlled by exposure time to air, or
controlling the atomosphere or temperature of the atmosphere the
polymerizing oil is exposed to. For example, elevated temperatures
or elevated oxygen levels may increase the amount of oxidation, and
resultantly the amount of skin formation which can correlate to
thickness or hardness of the skin, as well as the amount of liquid
polymerizing oil encapsulated by the skin. In addition, the grade
of drying oil and additives may be selected to achieve the desired
amount of skin formation. In an embodiment, an oil drying agent or
siccative can be added to the polymerizing oil to promote
oxidation. For example, a drying agent may be a metal coordination
complexes with a carboxylic acid derivate. Common drying agents
include carboxylates of zirconium, zinc, calcium, cobalt,
manganese, and iron. Fatty acid metal salts such as cobalt or
manganese naphthenates are also commonly used. Grade of the drying
oil may also affect the resultant skin properties. For example,
linseed oil is available in raw, refined, boiled, cold-pressed,
stand, sun-thickened, and hydrogenated grades.
[0056] FIGS. 6-10 illustrate a method of delivering an occlusion
device to a fallopian tube and facilitating immediate, or near
immediate, and permanent sterilization. Referring now to FIG. 6, a
delivery system S, such as delivery system 200 is introduced
transcervically through uterus U, generally under optical
direction. The physician directs the distal end of the delivery
system toward the ostium O of the fallopian tube F. The uterus U
may be irrigated and/or distended. Once the ostium O is located and
the delivery system S is oriented toward the ostium, the delivery
system S is advanced distally into the ostium.
[0057] In one embodiment, the distal portion of the occlusion
device acts as a guidewire, while the remainder of the occlusion
device remains covered by the sheath 204, as shown in FIG. 7. The
distal ball tip 112 of the distal portion of the occlusion device
aids tracking and navigation through the fallopian tube F, while
the inner coil structure flexes laterally to track the tortuous
bends often found within the fallopian tube. In the exemplary
embodiment, a core wire extends into the distal portion to enhance
column strength of the distal portion beyond sheath, but does not
extend to the ball tip. Hence, the stiffness of distal portion
increases proximally, further enhancing the distal portion's
ability to track the lumen. In another embodiment, the occlusion
device will be entirely within the sheath 204 during delivery and
positioning.
[0058] In the exemplary embodiment, the sheath includes a visual
marker which can be seen from the scope of an hysteroscope. The
marker is preferably positioned partially within the ostium O and
partially within the uterus U, thereby indicating that the
occlusion device is disposed at the target position, as the sheath,
core shaft, and occlusion device are releasably locked together
during advancement and positioning. For example, the marker may
comprise a bumper, or a structure which extends radially from the
sheath to provide a tactile positioning indication.
[0059] Referring now to FIGS. 8-9, the positioned occlusion device
is deployed, in one embodiment, by first withdrawing the catheter
sheath 204 from over the outer coil 106, as shown in FIG. 8. The
outer coil 106 is then separated from the delivery wire 210,
allowing the outer coil 106 to expand affix the occlusion device in
place, as shown in FIG. 9. In one embodiment, withdrawal of the
catheter sheath 204 tears the skin 302 within the lumen of the
catheter sheath 204 exposing the radial, or expanding surfaces of
the one or more hydrogels 110. The one or more hydrogels 110 have,
at this point, begun to swell and will at least temporarily block
the fallopian tube. The occlusion device is then separated from the
remaining components of delivery system, as shown in FIG. 10, where
the catheter sheath 204 and delivery wire 210 are withdrawn into a
hysteroscope sheath. As shown in FIG. 10, the pair of hydrogels 110
may expand to fill in areas of the fallopian tube to block the
fallopian tube. In another embodiment, the skin 302 may remain on
the radial, or expanding surfaces of the one or more hydrogels 110
and function as a time expansion control element that is
bioabsorbable or bioerodable over time.
[0060] In the foregoing specification, various embodiments of the
invention have been described. It will, however, be evident that
various modifications and changes may be made thereto without
departing from the broader spirit and scope of the invention as set
forth in the appended claims. The specification and drawings are,
accordingly, to be regarded in an illustrative sense rather than a
restrictive sense. Hence, the scope of the present invention is
limited solely by the following claims.
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