U.S. patent application number 13/282344 was filed with the patent office on 2013-05-02 for bioabsorbable co-filler for cerebrovascular aneurysms.
This patent application is currently assigned to Abbott Cardiovasculr Systems, Inc.. The applicant listed for this patent is Michael Huy Ngo, Mikael Trollsas. Invention is credited to Michael Huy Ngo, Mikael Trollsas.
Application Number | 20130108550 13/282344 |
Document ID | / |
Family ID | 48172667 |
Filed Date | 2013-05-02 |
United States Patent
Application |
20130108550 |
Kind Code |
A1 |
Trollsas; Mikael ; et
al. |
May 2, 2013 |
Bioabsorbable Co-Filler for Cerebrovascular Aneurysms
Abstract
Materials and Methods for delivering materials for filling
aneurysms in which the materials comprise a glycosaminoglycan and
optionally, contrast media and physiological buffers and in which
delivery methods include percutaneous delivery with a balloon
catheter or a needle catheter.
Inventors: |
Trollsas; Mikael; (San Jose,
CA) ; Ngo; Michael Huy; (San Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Trollsas; Mikael
Ngo; Michael Huy |
San Jose
San Jose |
CA
CA |
US
US |
|
|
Assignee: |
Abbott Cardiovasculr Systems,
Inc.
Santa Clara
CA
|
Family ID: |
48172667 |
Appl. No.: |
13/282344 |
Filed: |
October 26, 2011 |
Current U.S.
Class: |
424/9.1 |
Current CPC
Class: |
A61B 17/12145 20130101;
A61P 9/00 20180101; A61K 49/0054 20130101; A61P 9/14 20180101; A61K
49/0457 20130101; A61K 49/0409 20130101; A61K 49/0438 20130101 |
Class at
Publication: |
424/9.1 |
International
Class: |
A61K 49/00 20060101
A61K049/00; A61P 9/14 20060101 A61P009/14; A61P 9/00 20060101
A61P009/00 |
Claims
1. A composition comprising a mixture of a non-particulate,
flowable, non-fibrotic glycosaminoglycan or mucopolysaccharide, and
a sufficient amount of a material comprising contrast media such
that the mixture is medically imageable.
2. The composition of claim 1 further comprising a physiological
buffer.
3. The composition of claim 2 further comprising avian protein.
4. The composition of claim 2 wherein the glycosaminoglycan or
mucopolysaccharide is selected from hyaluronic acid, sodium
hyaluronate, chondroitin sulfate, dermatan sulfate, keratan
sulfate, or heparin sulfate.
5. The composition of claim 2 further comprising blood protein
components, blood protein decomposition products, blood cells,
blood cell decomposition products, other endogenous compounds,
aneurytic tissue components, aneurytic tissue decomposition
products, or coil decomposition products.
6. The composition of claim 5 wherein the glycosaminoglycan or
mucopolysaccharide has a hydrogel nature, has a high viscosity, and
is non-thrombogenic.
7. The composition of claim 1 wherein the glycosaminoglycan or
mucopolysaccharide is selected from hyaluronic acid, sodium
hyaluronate, chondroitin sulfate, dermatan sulfate, keratan
sulfate, or heparin sulfate.
8. The composition of claim 7 wherein the contrast media is
selected from metrizamide, iodecimol, ioglucol, ioglucamide,
ioglunide, iogulamide, iomeprol, iopentol, iopromide, iosarcol,
iosimide, iotasul, ioxilan, iohexyl, ioversol, iopamidol, iotrolan,
ioxaglate, iodixanol, iothalamate, ioxithalamate, iodamide,
metrizoate, copper-zinc ferrite, nickel-zinc ferrite,
manganese-zinc ferrite, zinc ferrite, magnesium ferrite,
.alpha.-ferric oxide, ferrosoferric oxide, diatrizoate, barium
sulfate, diatrizoic acid, metrizoic acid, iotalamic acid,
ioxitalamic acid, ioglicic acid, acetrizoic acid, iocarmic acid,
methiodal, diodone, ioxaglic acid, iobitridol, iodoxamic acid,
iotroxic acid, ioglycamic acid, adipiodone, iobenzamic acid,
iopanoic acid, iocetamic acid, sodium iopodate, tyropanoic acid,
calcium iopodate, ethyl esters of iodized fatty acids, iopydol,
propyliodone, iofendylate, or lipiodol.
9. The composition of claim 8 wherein the molecular ratio of
glycosaminoglycan or mucopolysaccharide to contrast media ranges
from 1.2:1 to 1,000,000:1.
10. A composition comprising a mixture of a non-particulate,
flowable, non-fibrotic glycosaminoglycan and a sufficient amount of
a material comprising contrast media such that the mixture is
medically imageable and wherein the contrast media is selected from
metrizamide, iodecimol, ioglucol, ioglucamide, ioglunide,
iogulamide, iomeprol, iopentol, iopromide, iosarcol, iosimide,
iotasul, ioxilan, iohexyl, ioversol, iopamidol, iotrolan,
ioxaglate, iodixanol, iothalamate, ioxithalamate, iodamide,
metrizoate, copper-zinc ferrite, nickel-zinc ferrite,
manganese-zinc ferrite, zinc ferrite, magnesium ferrite,
.alpha.-ferric oxide, ferrosoferric oxide, diatrizoate, barium
sulfate, diatrizoic acid, metrizoic acid, iotalamic acid,
ioxitalamic acid, ioglicic acid, acetrizoic acid, iocarmic acid,
methiodal, diodone, ioxaglic acid, iobitridol, iodoxamic acid,
iotroxic acid, ioglycamic acid, adipiodone, iobenzamic acid,
iopanoic acid, iocetamic acid, sodium iopodate, tyropanoic acid,
calcium iopodate, ethyl esters of iodized fatty acids, iopydol,
propyliodone, iofendylate, or lipiodol.
11. The composition of claim 10 wherein the glycosaminoglycan is
hyaluronic acid.
12. The composition of claim 11 wherein the composition is adapted
to migrate out of the aneurysm or break down within the aneurysm
and be replaced with endogenous compounds over 7-90 days.
13. The composition of claim 12 wherein the hyaluronic acid has a
hydrogel nature, has a high viscosity, and is non-thrombogenic.
14. The composition of claim 13 wherein the molecular ratio of
glycosaminoglycan to contrast media ranges from 1.2:1 to
1,000,000:1.
15. The composition of claim 10 wherein the composition is adapted
to migrate out of the aneurysm or break down within the aneurysm
and be replaced with endogenous compounds over 7-90 days.
16. The composition of claim 15 wherein the molecular ratio of
glycosaminoglycan to contrast media ranges from 1.2:1 to
1,000,000:1.
17. A method comprising supplying a mixture of a non-particulate,
flowable, non-fibrotic glycosaminoglycan or mucopolysaccharide, and
a sufficient amount of a material comprising contrast media such
that the mixture is medically imageable, and delivering the mixture
to an aneurytic site in mammalian vasculature.
18. The method of claim 17 wherein the glycosaminoglycan or
mucopolysaccharide is selected from hyaluronic acid, sodium
hyaluronate, chondroitin sulfate, dermatan sulfate, keratan
sulfate, or heparin sulfate.
19. The method of claim 17 wherein the contrast media is selected
from metrizamide, iodecimol, ioglucol, ioglucamide, ioglunide,
iogulamide, iomeprol, iopentol, iopromide, iosarcol, iosimide,
iotasul, ioxilan, iohexyl, ioversol, iopamidol, iotrolan,
ioxaglate, iodixanol, iothalamate, ioxithalamate, iodamide,
metrizoate, copper-zinc ferrite, nickel-zinc ferrite,
manganese-zinc ferrite, zinc ferrite, magnesium ferrite,
.alpha.-ferric oxide, ferrosoferric oxide, diatrizoate, barium
sulfate, diatrizoic acid, metrizoic acid, iotalamic acid,
ioxitalamic acid, ioglicic acid, acetrizoic acid, iocarmic acid,
methiodal, diodone, ioxaglic acid, iobitridol, iodoxamic acid,
iotroxic acid, ioglycamic acid, adipiodone, iobenzamic acid,
iopanoic acid, iocetamic acid, sodium iopodate, tyropanoic acid,
calcium iopodate, ethyl esters of iodized fatty acids, iopydol,
propyliodone, iofendylate, or lipiodol; and the glycosaminoglycan
or mucopolysaccharide is selected from hyaluronic acid, sodium
hyaluronate, chondroitin sulfate, dermatan sulfate, keratan
sulfate, or heparin sulfate.
20. The method of claim 19 wherein delivering the mixture comprises
inserting a needle into the aneurysm or delivering a catheter or
needle catheter delivery system device to the aneurytic site and
depositing the composition into the aneurysm.
21. The method of claim 20 further comprising delivering a coil to
the aneurysm before, during, or after delivering the mixture.
22. The method of claim 18 wherein delivering the composition
comprises inserting a needle into the aneurysm or delivering a
catheter or needle catheter delivery system device to the aneurytic
site and depositing the composition into the aneurysm.
23. The method of claim 22 further comprising delivering a coil to
the aneurysm before, during, or after delivering the mixture.
24. The method of claim 19 wherein delivering the mixture comprises
inserting a needle into the aneurysm or delivering a catheter or
needle catheter delivery system device to the aneurytic site and
depositing the composition into the aneurysm.
25. The method of claim 24 further comprising delivering a coil to
the aneurysm before, during, or after delivering the mixture.
Description
BACKGROUND
[0001] In many cases, aneurysms form in the vessel walls of an
organism. If such an aneurysm were to rupture, the organism would
be in danger of severely bleeding from the rupture site. Depending
on the location of the aneurysm, its rupture could lead to stroke.
And if large enough, the aneurysm's rupture could even lead to
exsanguination.
[0002] The extreme risks associated with aneurysms call for their
treatment. Typical treatments of un-ruptured aneurysms include
surgically removing them in situations where such removal is
possible. Another treatment centers on filling an aneurysm sack
with coils of various materials, which may decrease the pressure in
the sack. In some cases, the danger from the aneurysm decreases
when the pressure in the sack falls. To reduce the pressure in the
sack, it is important to fill the sack well, and then slowly allow
the sack to fill up with scarring or other extracellular matrix
material. A practitioner could orchestrate slow filling followed by
scarring or the migration of other matrix material using coils with
bioabsorbable, pro-inflammatory coatings. Alternatively, changes in
the hemodynamics cause by filling the aneurysm promote the
formation of thrombus inside the aneurysm sack, which also lowers
aneurysm pressure.
[0003] In many cases, filling treatment results in an aneurysm
permanently filled with foreign material. This treatment may lower
the pressure and restore normal hemodynamics near the aneurysm. But
it also interferes with the aneurysm's complete healing.
[0004] What is needed is a way to temporarily fill the aneurysm in
a controllable manner such that endogenous compounds could later
gradually replace the filling material.
SUMMARY
[0005] As in one inventive embodiment, one useful filling material
is a composition that comprises a glycosaminoglycan or a
mucopolysaccharide. In some embodiments, this composition is
augmented with a physiological buffer, with a contrast media or
with both.
[0006] Additionally, some embodiments are formed in-situ, inside of
the aneurysm sack and may additionally comprise avian protein,
blood protein components, blood protein decomposition products,
blood cells, blood cell decomposition products, other endogenous
compounds, or coil decomposition products.
[0007] In some embodiments, the filling material is prepared as a
hydrogel.
[0008] In some embodiments, the filling material is prepared so
that it slowly migrates out of the aneurysm or is broken down
within the aneurysm and replaced by endogenous compounds over a
7-90 day period; 14-70 day period; or 21-60 day period.
[0009] Some embodiments are directed at methods for treating
aneurysms. For example, in one embodiment the method of treating an
aneurysm comprises delivering a glycosaminoglycan or a
mucopolysaccharide to the aneurysm or into an aneurysm. Moreover,
various embodiments in which an aneurysm is treated by delivering a
filling material as described in this document, to the aneurysm or
into the aneurysm. A variation of these embodiments includes
delivering a metallic or polymeric coil to the aneurysm before,
during, or after delivery of the filling material or delivery of a
glycosaminoglycan or a mucopolysaccharide.
[0010] Some embodiments use direct surgery or hypodermic needle
delivery directly to the aneurysm. Other embodiments use balloon or
needle catheters to deliver the filling material to the aneurysm
percutaneously.
DETAILED DESCRIPTION
[0011] The following description of several embodiments describes
non-limiting examples that further illustrate the invention. All
titles of sections contained herein, including those appearing
above, are not to be construed as limitations on the invention, but
rather they are provided to structure the illustrative description
of the invention that is provided by the specification.
[0012] Unless defined otherwise, all technical and scientific terms
used in this document mean what one skilled in the art to which the
disclosed invention pertains commonly understands them to mean.
Singular forms--a, an, and the--include plural referents unless the
context clearly indicates otherwise. Thus, for example, reference
to "fluid" refers to one or more fluids, such as two or more
fluids, three or more fluids, etc. When an aspect is said to
include a list of components, the list is representative. If the
component choice is specifically limited to the list, the
disclosure will say so. Moreover, listing components acknowledges
that embodiments exist for each of the components and any
combination of the components--including combinations that
specifically exclude any one or any combination of the listed
components. For example, "component A is chosen from A, B, or C"
discloses embodiments with A, B, C, AB, AC, BC, and ABC. It also
discloses (AB but not C), (AC but not B), and (BC but not A) as
embodiments, for example. Combinations that one of ordinary skill
in the art knows to be incompatible with each other or with the
components' function in the invention are excluded from the
invention, in some embodiments.
[0013] In some embodiments, treatment methods include delivering a
material to the aneurysm. So that the physician can monitor the
degree of filling of the aneurysm, the material mixture may contain
a contrast medium, which, for example fluoroscopy, could reveal
during the treatment. The exact mechanics of delivering a material
to the aneurysm depends on which type of aneurysm afflicts the
patient.
[0014] Some aneurysms consist of larger regions of weakened vessel
wall that may bulge from the normal vessel walls, pushed out by the
blood pressure within the vessel. Other aneurysms consist of a
weakening of a smaller region of the vessel wall that then balloons
out from the vessel wall again pushed out by blood pressure within
the vessel. These aneurysm types serve as the ends of a continuum
that encompasses most aneurysms.
[0015] A difference between these two types of aneurysms is in
their ability to contain a treatment agent. For example, an
aneurysm with more of a balloon-like structure may be able to
accept and hold a material that blood flow would wash away from a
less balloon-like aneurysm or an aneurysm that simply bulges from a
larger region of vessel wall. Thus, sometimes a practitioner treats
aneurysm with a coil of polymeric or metallic wire such as a coil
of platinum wire before introducing a "filling" material. In some
embodiments, treatment comprises delivering the material to the
aneurysm before, after, or during the delivery of the coil.
[0016] Regardless of the type of aneurysm and regardless of whether
using a coil promotes retaining a filling material at the aneurysm
site, practitioners may choose to treat the aneurysm with a filling
material and either use or omit a coil at their discretion. All
instances of treating an aneurysm with the filling material
described in this document (with or without a coil) are within the
scope of the invention.
[0017] In some embodiments, the filling material comprises a
glycosaminoglycan or a mucopolysaccharide. One advantage of using a
glycosaminoglycan or a mucopolysaccharide is that, over time, these
materials can be replaced by compounds that are endogenous to the
body. Thus, over time, the filling material disappears along with
the contrast medium. As one of ordinary skill in the art will
recognize, examination of the treatment site days to months after
treatment will reveal less and less of an image as endogenous
compounds replace the filing material (and the contrast medium). By
analyzing the intensity changes at the treatment site, a physician
can monitor the degree of healing of the aneurysm.
[0018] Another advantage of using glycosaminoglycans or
mucopolysaccharides is that these large molecules show extremely
little variation species to species. Therefore, human
glycosaminoglycans are almost identical to avian glycosaminoglycans
allowing the use of the avian glycosaminoglycan or
mucopolysaccharide in treating a human patient without substantial
risk of a foreign body reaction in the human patient. In fact, most
medical grade glycosaminoglycans or mucopolysaccharides are
produced from sources other than human sources and may contain
residual proteins or other materials from those sources.
[0019] Once the aneurysm is filled, the hydrodynamics of the blood
near the aneurysm become less abnormal. Subsequently, the filling
material begins to break down and thrombin, blood cell
decomposition products, blood protein components, other endogenous
materials, and, in the case of aneurysms also treated with a coil,
the decomposition products of the coil or any coil coating all
begin to take the place of the filling material. For purposes of
this disclosure, coil decomposition products are materials that
were once part of a medical device that was inserted into an
aneurysm. In some cases, the device was a wire coil, hence the term
coil decomposition products. Coil composition products need not
come from wire coils, but are the decomposition products from any
medical device, as discussed above.
[0020] For purposes of this disclosure, an aneurytic site is a
region in mammalian vasculature near an aneurysm or near aneurytic
tissue. And for purposes of this disclosure, aneurytic tissue is
any type of tissue associated with or created by the formation of
an aneurysm or any tissue composing an aneurysm or the vascular
tissue near an aneurysm.
Filling Material
[0021] Various compositions are suitable for applying or supplying
to or into an aneurysm to treat it. The filling material of the
current invention comprises a base (Component I) and optionally a
contrast agent or medium (Component II) and optionally a drug or
bioactive agent (component III). Of course, other materials and
formulations for use on mammalian patients may also compose the
filling material. One such material is a physiological buffer.
[0022] In some embodiments, an invention composition comprises a
mixture of the Component I and Component II compositions. For
purposes of this disclosure, an invention mixture is a combination
of two or more components in which the components substantially
retain their chemical identity upon combination. The components
substantially retain the chemical nature that they had before
combination into the mixture.
Component I
[0023] In some embodiments, the base comprises a glycosaminoglycan
or a mucopolysaccharide. Useful glycosaminoglycans or
mucopolysaccharides include hyaluronic acid, sodium hyaluronate,
chondroitin sulfate, dermatan sulfate, keratan sulfate, or heparin
sulfate, in some embodiments. Also, useful polyanionic
polysaccharides include carboxymethylcellulose,
carboxymethylamylose and their derivatives. These are described
more fully below. In some embodiments, the base comprises
hyaluronic acid. In these or other embodiments, hyaluronic acid
comprises HEALON (a product of Abbott Medical Optics). A variety of
embodiments use such HEALON bases, which are described below in the
discussion of U.S. Pat. Nos. 5,681,825; 6,086,597; and
6,271,216.
[0024] U.S. Pat. No. 5,681,825, issued October 1997, discloses
examples of useful hyaluronic acid base materials. In some
embodiments, the base is an aqueous solution of hyaluronic acid
with an average molecular weight of 4 million to 12 million. In
some of these embodiments, the zero shear viscosity of the base
hyaluronic acid ranges from 1 thousand to 80 thousand Pas. Other
embodiments include hyaluronic acid bases with an average molecular
weight of 4.5 million to 8 million. In some of these embodiments,
the zero shear viscosity of the material is 1 thousand to 9
thousand Pas.
[0025] U.S. Pat. No. 6,086,597, issued in July 2000, also discloses
examples of useful hyaluronic acid base materials. In some
embodiments, the base is an aqueous solution of 18-40 mg sodium
hyaluronate per milliliter of water in which the sodium hyaluronate
has a <M>.sub.r,M=1.times.10.sup.6 to 10.times.10.sup.6. In
some embodiments, the base is an aqueous solution of 20 mg of
<M>.sub.r,M=3.times.10.sup.6 sodium hyaluronate; 8.5
milligrams of sodium chloride, and one milliliter of water. In some
embodiments, the base is an aqueous solution of 25 mg of
<M>.sub.r,M=3.times.10.sup.6 sodium hyaluronate; 8.5
milligrams of sodium chloride, and one milliliter of water.
[0026] U.S. Pat. No. 6,271,216, issued in August 2001, also
discloses examples of useful hyaluronic acid base materials. In
some embodiments, the base is an aqueous solution of about 0.1 to
five percent by weight or one to three percent by weight sodium
hyaluronate having an average molecular weight of
0.2.times.10.sup.6 to 10.0.times.10.sup.6 or 0.25.times.10.sup.6 to
4.times.10.sup.6. These solutions have sodium ions present from
about 80 to 185 millimolar or 90 to 110 millimolar exclusive of the
sodium contributed by the sodium hyaluronate. In some embodiments,
the solution is prepared with 30 milligrams of sodium hyaluronate;
3-3.4 milligrams sodium chloride; and one milliliter of water. In
some embodiments, the solution is prepared with 30 milligrams
sodium hyaluronate, 4.3-4.7 milligrams sodium chloride, and one
milliliter of water. In some embodiments, solutions prepared with
30 milligrams sodium hyaluronate, 3.2 milligrams sodium chloride,
and one milliliter of water are useful. In some of these
embodiments, the sodium hyaluronate has an average molecular weight
of 400 thousand. Finally, as disclosed in the '216 patent,
solutions prepared with 30 milligrams of sodium hyaluronate with a
molecular weight of 400 thousand; 4.58 milligrams of sodium
chloride, and one milliliter of water are useful in some
embodiments as part of Component I. Some embodiments employ
cross-linked hyaluronic acid as part of the base, as well. One type
of cross-linked hyaluronic acid has disulfide cross-links.
[0027] In addition to polyanionic polysaccharides and
hyaluronic-acid-based polymers, modified polymers may be used in
the present invention. These are disclosed in U.S. Pat. No.
7,829,118. Such polymers include polyanionic polysaccharides that
have been modified in a number of ways. In some embodiments, the
unmodified polyanionic polysaccharides are any one or any
combination of hyaluronic acid, carboxymethylcellulose,
carboxymethylamylose, chondroitin-4-sulfate, chondroitin-6-sulfate,
dermatan sulfate, dermatin-6-sulfate, heparin sulfate, heparin,
keratin sulfate and their derivatives.
[0028] Similar other useful polymers are known in the art, and
described, for example, in U.S. Pat. No. 6,056,970. Other
biodegradable polymers include fibrin, fibrinogen, starch,
poly(amino acids); peptides, proteins, gelatin and collagen.
[0029] Hyaluronic acid may be derivatized by reacting its hydroxyl
groups with divinyl sulfone. The hyaluronic acid will typically
have a degree of modification of reactive hydroxyl groups ranging
from 1 to 80%; 1 to 50%; or 1 to 25%. That is to say, a 1% degree
of modification or substitution means that an average of 1% of the
hyaluronic acid disaccharide units contain a vinyl sulfone
group.
[0030] Alternatively, the polymer may be thiol-derivatized, such as
a thiol-derivatized hyaluronic acid. Exemplary thiol-derivatized
hyaluronic acid polymers include those described in U.S. Pat. Nos.
6,884,788; 6,620,927; 6,548,081, 6,537,979; 606,013,679; U.S. Pat.
Nos. 5,502,081; and 5,356,883, relevant portions of which related
to such thiol-derivatized polymers being incorporated herein by
reference in their entireties.
[0031] Additional examples of hyaluronic acid polymers include
cysteine-derivatized hyaluronic acid, including those polymers
disclosed in "Controlled Release from Glycosaminoglycan Drug
Complexes" R. V. Sparer et al.
[0032] Some embodiments use a gel comprised of the reaction product
of two components. In those embodiments that employ such a filling
material base, the gel's components must be chosen so that the
material sets up relatively quickly--less than 60, 45, 30, 15, 5,
or 1 seconds. Within that time, the material should exceed 80, 85,
90, or 95% of its final viscosity or modulus. For example, a gel
based on silk elastin materials may be used as a component of the
filling material.
[0033] Various embodiments use a Component I that has one or more
of the following features: a non-particulate nature; a flowable
nature; or a non-fibrotic nature. For purposes of this disclosure,
having a non-particulate nature means that neither the
glycosaminoglycan nor the mucopolysaccharide of Component I has
been subjected to any physical or chemical treatment designed to
make it take the form of a particle. For purposes of this
disclosure, having a flowable nature means that the
glycosaminoglycan or mucopolysaccharide of Component I can flow
within a delivery device. For purposes of this disclosure, having a
non-fibrotic nature means that the glycosaminoglycan or
mucopolysaccharide of Component I does not produce enough fibrotic
tissue to produce a permanent or obstructive scar in the
vasculature.
[0034] A non-thrombogenic material is any material that, when
inserted into mammalian vasculature, does not have a tendency to
produce a blood clot substantially higher than the tendency of
vascular tissue to produce a blood clot, when measured over a
1-hour, 2-hour, 1-day, 2-day, 1-week, or 2-week time.
[0035] For purposes of this disclosure, a high viscosity material
is a material with a viscosity greater than or equal to that of
mammalian blood, with a viscosity sufficiently high to prevent
substantial mixing between the material and blood for 1-1000;
2-100; 2-50; 2-25; or 2-10 minutes, with a viscosity sufficiently
high to allow the material to remain on aneurytic tissue or within
an aneurysm for 1-1000; 2-100; 2-50; 2-25; or 2-10 minutes, or with
a viscosity sufficiently high to allow the material to remain on
aneurytic tissue or within an aneurysm long enough for the material
to gel, harden, or solidify.
Component II
[0036] The base material may comprise any of the Component I
materials described above, or the base material may comprise any
combination of the Component I materials described above. Moreover,
the base material may contain any other material that does not
interfere with the function or operation of the base material so
much that one of ordinary skill in the art would reject adding that
other material. Some of those other materials are described below
under the Component II and Component III headings.
[0037] Another optional component is a contrast medium for reasons
described above or for other reasons. Useful contrast media include
materials comprising metrizamide, iodecimol, ioglucol, ioglucamide,
ioglunide, iogulamide, iomeprol, iopentol, iopromide, iosarcol,
iosimide, iotasul, ioxilan, iohexyl, ioversol, iopamidol, iotrolan,
ioxaglate, iodixanol, iothalamate, ioxithalamate, iodamide,
metrizoate, copper-zinc ferrite, nickel-zinc ferrite,
manganese-zinc ferrite, zinc ferrite, magnesium ferrite,
.alpha.-ferric oxide, ferrosoferric oxide, diatrizoate, barium
sulfate, diatrizoic acid, metrizoic acid, iotalamic acid,
ioxitalamic acid, ioglicic acid, acetrizoic acid, iocarmic acid,
methiodal, diodone, ioxaglic acid, iobitridol, iodoxamic acid,
iotroxic acid, ioglycamic acid, adipiodone, iobenzamic acid,
iopanoic acid, iocetamic acid, sodium iopodate, tyropanoic acid,
calcium iopodate, ethyl esters of iodized fatty acids, iopydol,
propyliodone, iofendylate, or lipiodol.
[0038] For purposes of this disclosure, a sufficient amount of a
material comprising contrast media means that the material
comprises enough contrast media to make the mixture medically
imageable. For purposes of this disclosure, medically imageable
means that the material is visible enough when imaged with a
radiological device that the person treating the patient is able to
detect that the mixture is entering the vasculature and to what
extent the mixture is entering the vasculature in substantially
real time. For purposes of this disclosure, a radiological device
is any device capable of viewing inside a patient's body
non-invasively, irrespective of whether or not the device employs
electromagnetic radiation as part of the viewing process.
[0039] Other optional components in the filling material are drugs
such as pro-healing drugs or growth factors. In some embodiments,
an optional drug component is any pro-healing drug or growth factor
or any combination of pro-healing drugs or growth factors.
[0040] As used herein, "pro-healing" refers to a moiety that aids
in the healing process at the aneurysm or within the aneurysm.
Pro-healing drugs are useful as drugs and are optionally added to
the filling material. In some embodiments, pro-healing drugs are
materials that promote the controlled proliferation of muscle cells
with a normal and physiologically benign composition, useful
pro-healing drugs include enzymes, anti-inflammatory agents,
antivirals, anticancer drugs, anticoagulant agents, free radical
scavengers, steroidal anti-inflammatory agents, non-steroidal
anti-inflammatory agents, antibiotics, estradiol, VEGF, an EPC
antibody, biorest, nitric oxide donors, super oxide dismutases,
endothelial progenitor cells, super oxide dismutases mimics, nitric
oxide, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl
(4-amino-TEMPO), dexamethasone, clobetasol, aspirin, pro-drugs of
these drugs, co-drugs of these drugs. Any compatible combination of
pro-healing drug is also suitable for use in this invention.
[0041] The polypeptide Arg-Gly-Asp (RGD) has been demonstrated to
be a bioactive factor for human endothelial cell attachment and
therefore is expected to exhibit prohealing characteristics. In
addition to RGD itself, cyclic RGD (cRGD) and RGD mimetics and
small molecules capable of binding as does RGD to other adhesion
receptors are within the scope of optional filling material
components. RGD mimetics can be prepared by modification of RGD or
cRGD. Peptide synthesis, including the synthesis of peptide
mimetics, is well documented and can be readily achieved using, for
example, combinatorial chemistry. Some examples of cRGD or RGD
mimetics include V3 antagonists such as IIb/IIIb antagonists, one
example of which is Abciximax; XJ 735; anti-3-integrin antibody
F11; cRGD; and other sequences such as laminin-derived SIKVAV;
laminin-derived YIGSR; KQAGDV; and VAPG.
[0042] Useful drugs also include any substance or combination of
substances capable of exerting a therapeutic or prophylactic effect
in the practice of the present invention as well as having positive
pharmacological effects on the expression of the extracellular
matrix. The active ingredient can also enhance wound healing in a
vascular site or improve the structural and elastic properties of
the vascular site.
[0043] Growth factors are also useful drugs in this invention.
Growth factors include any one or any combination of
vasoendothelial growth factor, fibroblast growth factor, hypoxia
inducing factor, monocyte chemoattractant protein, lipid factors,
vascular endothelial growth factors, fibroblast growth factors,
nicotine, platelet derived growth factor, insulin-like growth
factor 1, transforming growth factor, hepatocyte growth factor,
estrogens, follistatin, proliferin, prostaglandin E1, prostaglandin
E2, tumor necrosis factor, interleukin-8, hematopoietic growth
factors, erythropoietin, granulocyte-colony stimulating factors,
and platelet-derived endothelial growth factor.
[0044] Angiogenic substances are growth factors and may be any one
or any combination of the following substances, and hormones and
genes that encode any one of the following substances: vascular
endothelial growth factor, fibroblast growth factors, monocyte
chemoattractant proteins, transforming growth factor beta,
transforming growth factor alpha, lipid factors, hypoxia-inducible
factor 1-alpha, PR39, nicotine, insulin-like growth factors,
placental growth factor, hepatocyte growth factor, estrogen,
follistatin, proliferin, cytokines, tumor necrosis factor,
erythropoietin, granulocyte colony-stimulating factor, granulocyte
macrophage colony-stimulating factor, and angiogenin.
[0045] Also, endogenous compounds may be added to these compounds
as drugs, see below.
[0046] Anti-inflammatory agents may be added to the filling
material mixture. Suitable anti-inflammatory agents include,
without limitation, steroidal anti-inflammatory agents, a
nonsteroidal anti-inflammatory agent, or a combination thereof. In
some embodiments, anti-inflammatory agents include clobetasol,
alclofenac, alclometasone dipropionate, algestone acetonide, alpha
amylase, amcinafal, amcinafide, amfenac sodium, amiprilose
hydrochloride, anakinra, anirolac, anitrazafen, apazone,
balsalazide disodium, bendazac, benoxaprofen, benzydamine
hydrochloride, bromelains, broperamole, budesonide, carprofen,
cicloprofen, cintazone, cliprofen, clobetasol propionate,
clobetasone butyrate, clopirac, cloticasone propionate,
cormethasone acetate, cortodoxone, deflazacort, desonide,
desoximetasone, dexamethasone dipropionate, diclofenac potassium,
diclofenac sodium, diflorasone diacetate, diflumidone sodium,
diflunisal, difluprednate, diftalone, dimethyl sulfoxide,
drocinonide, endrysone, enlimomab, enolicam sodium, epirizole,
etodolac, etofenamate, felbinac, fenamole, fenbufen, fenclofenac,
fenclorac, fendosal, fenpipalone, fentiazac, flazalone, fluazacort,
flufenamic acid, flumizole, flunisolide acetate, flunixin, flunixin
meglumine, fluocortin butyl, fluorometholone acetate, fluquazone,
flurbiprofen, fluretofen, fluticasone propionate, furaprofen,
furobufen, halcinonide, halobetasol propionate, halopredone
acetate, ibufenac, ibuprofen, ibuprofen aluminum, ibuprofen
piconol, ilonidap, indomethacin, indomethacin sodium, indoprofen,
indoxole, intrazole, isoflupredone acetate, isoxepac, isoxicam,
ketoprofen, lofemizole hydrochloride, lomoxicam, loteprednol
etabonate, meclofenamate sodium, meclofenamic acid, meclorisone
dibutyrate, mefenamic acid, mesalamine, meseclazone,
methylprednisolone suleptanate, morniflumate, nabumetone, naproxen,
naproxen sodium, naproxol, nimazone, olsalazine sodium, orgotein,
orpanoxin, oxaprozin, oxyphenbutazone, paranyline hydrochloride,
pentosan polysulfate sodium, phenbutazone sodium glycerate,
pirfenidone, piroxicam, piroxicam cinnamate, piroxicam olamine,
pirprofen, prednazate, prifelone, prodolic acid, proquazone,
proxazole, proxazole citrate, rimexolone, romazarit, salcolex,
salnacedin, salsalate, sanguinarium chloride, seclazone,
sermetacin, sudoxicam, sulindac, suprofen, talmetacin,
talniflumate, talosalate, tebufelone, tenidap, tenidap sodium,
tenoxicam, tesicam, tesimide, tetrydamine, tiopinac, tixocortol
pivalate, tolmetin, tolmetin sodium, triclonide, triflumidate,
zidometacin, zomepirac sodium, aspirin (acetylsalicylic acid),
salicylic acid, corticosteroids, glucocorticoids, tacrolimus,
pimecorlimus, prodrugs thereof, co-drugs thereof, and combinations
thereof. The anti-inflammatory agent may also be a biological
inhibitor of pro-inflammatory signaling molecules including
antibodies to such biological inflammatory signaling molecules.
[0047] Depending on their source, the components may contain trace
amounts of extraneous, but supposedly benign materials. Thus, the
compositions of this invention may comprise one or more of these
trace materials. For example, an avian-sourced glycosaminoglycan or
mucopolysaccharide may contain trace amounts of avian protein,
which in turn leads to inventive embodiments that may comprise
avian protein.
[0048] In some embodiments, the filling materials or components of
the filling materials are prepared to be hydrogels.
[0049] For purposes of this document, filling materials assembled
or produced outside of the patient are referred to as stage I
materials. After a stage I material is delivered to the aneurysm,
the patient's body begins to break the material down. Moreover,
during this time, blood cells and proteins migrate into the stage I
material creating a new material within the aneurysm--called a
stage II material. The stage II material, formed in situ, is
suitable for filling aneurysms. Thus, a stage II material may
comprise any of the components of the stage I material, may
comprise blood cells or blood proteins, may comprise
glycosaminoglycan or mucopolysaccharide decomposition products, may
comprise blood cell or blood protein decomposition products, may
comprise other endogenous materials or may comprise, for those
embodiments employing some type of coil, materials arising from the
coil's decomposition.
[0050] Endogenous materials include those materials created by the
patient's body that one of ordinary skill in the art would expect
the patient's body to create or deposit near the aneurysm treatment
site. Specifically, endogenous compounds include among other
compounds, extracellular matrix. The extracellular matrix is the
extracellular part of animal tissue that usually provides
structural support to the animal cells in addition to performing
various other important functions. The extracellular matrix is the
defining feature of connective tissue in animals. Extracellular
matrix includes the interstitial matrix and the basement membrane.
Interstitial matrix is present between various animal cells (i.e.,
in the intercellular spaces). Gels of polysaccharides and fibrous
proteins fill the interstitial space and act as a compression
buffer against the stress placed on the matrix. The extracellular
matrix is composed of an interlocking mesh of fibrous proteins and
glycosaminoglycans (GAGs). GAGs are carbohydrate polymers and are
usually attached to extracellular matrix proteins to form
proteoglycans. Heparan sulfate is a linear polysaccharide found in
all animal tissues. Chondroitin sulfate is a sulfated
glycosaminoglycan composed of a chain of alternating sugars.
Keratan sulfate, also called keratosulfate, is any of several
sulfated glycosaminoglycans that have been found especially in the
cornea, cartilage, and bone. Collagen is a group of naturally
occurring proteins. In nature, it is found exclusively in animals,
especially in the flesh and connective tissues of mammals. It is
the main component of connective tissue, and is the most abundant
protein in mammals, making up about 25% to 35% of the whole-body
protein content. Collagen, in the form of elongated fibrils, is
mostly found in fibrous tissues such as tendon, ligament and skin,
and is also abundant in cornea, cartilage, bone, blood vessels, the
gut, and intervertebral disc. Elastin is a protein in connective
tissue that is elastic and allows many tissues in the body to
resume their shape after stretching or contracting. Elastin helps
skin to return to its original position when it is poked or
pinched. Fibronectins are proteins that connect cells with collagen
fibers in the extracellular matrix. Laminins are major proteins in
the basal lamina, a protein network foundation for most cells and
organs. Generally see Extracellular Matrix article on
Wikipedia.org.
[0051] The difference between the extracellular matrix materials
described here as endogenous compounds and those described above as
Component I constituents is that the endogenous compounds are
prepared by the patient's body and become involved with the
aneurysm because of the treatment of the aneurysm. The ones
described above, although of similar or perhaps nearly identical
structure are typically produced synthetically or by another
organism. But this need not be the case.
[0052] In some embodiments, the stage I material decomposes and
eventually substantially completely decomposes. In some of these
embodiments, the stage I material substantially completely
decomposes after 7-90 days.
Delivery
[0053] The practitioner can deliver the filling material
percutaneously using a catheter system, a balloon catheter system,
or a needle catheter system. Alternatively, the practitioner can
deliver the material directly to the aneurysm by hypodermic needle
injection or by some surgical techniques such as open surgery or
laparoscopic surgery.
[0054] Some embodiments comprise a treatment method wherein an
aneurysm is visualized such as by fluoroscopy. A catheter or other
delivery devices is inserted into the patient percutaneously and
tracked along the vasculature until the delivery device is
positioned near the aneurysm. One way of doing this is tracking a
catheter over a guidewire. Once the delivery device is correctly
positioned near the aneurysm, a filling material is delivered to
the aneurysm. Some embodiments of the filling material comprise a
glycosaminoglycan and, optionally, a contrast media, a
physiological buffer or both. In these or other embodiments, the
filling material comprises a glycosaminoglycan selected from
hyaluronic acid, sodium hyaluronate, chondroitin sulfate, dermatan
sulfate, keratan sulfate, or heparin sulfate; and optionally a
contrast media, a physiological buffer, or both. In these or other
embodiments, the contrast media is selected from material
comprising metrizamide, iodecimol, ioglucol, ioglucamide,
ioglunide, iogulamide, iomeprol, iopentol, iopromide, iosarcol,
iosimide, iotasul, ioxilan, iohexyl, ioversol, iopamidol, iotrolan,
ioxaglate, iodixanol, iothalamate, ioxithalamate, iodamide,
metrizoate, copper-zinc ferrite, nickel-zinc ferrite,
manganese-zinc ferrite, zinc ferrite, magnesium ferrite,
.alpha.-ferric oxide, ferrosoferric oxide, diatrizoate, barium
sulfate, diatrizoic acid, metrizoic acid, iotalamic acid,
ioxitalamic acid, ioglicic acid, acetrizoic acid, iocarmic acid,
methiodal, diodone, ioxaglic acid, iobitridol, iodoxamic acid,
iotroxic acid, ioglycamic acid, adipiodone, iobenzamic acid,
iopanoic acid, iocetamic acid, sodium iopodate, tyropanoic acid,
calcium iopodate, ethyl esters of iodized fatty acids, iopydol,
propyliodone, iofendylate, or lipiodol.
[0055] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from the embodiments of this invention in its broader
aspects and, therefore, the appended claims are to encompass within
their scope all such changes and modifications as fall within the
true spirit and scope of the embodiments of this invention.
Additionally, various embodiments have been described above. For
convenience's sake, combinations of aspects composing invention
embodiments have been listed in such a way that one of ordinary
skill in the art may read them exclusive of each other when they
are not necessarily intended to be exclusive. But a recitation of
an aspect for one embodiment is meant to disclose its use in all
embodiments in which that aspect can be incorporated without undue
experimentation. In like manner, a recitation of an aspect as
composing part of an embodiment is a tacit recognition that a
supplementary embodiment exists that specifically excludes that
aspect. All patents, test procedures, and other documents cited in
this specification are fully incorporated by reference to the
extent that this material is consistent with this specification and
for all jurisdictions in which such incorporation is permitted.
[0056] Moreover, some embodiments recite ranges. When this is done,
it is meant to disclose the ranges as a range, and to disclose each
and every point within the range, including end points. For those
embodiments that disclose a specific value or condition for an
aspect, supplementary embodiments exist that are otherwise
identical, but that specifically exclude the value or the
conditions for the aspect.
[0057] Finally, headings are for the convenience of the reader and
do not alter the meaning or content of the disclosure or the scope
of the claims.
* * * * *