U.S. patent application number 13/241892 was filed with the patent office on 2012-01-19 for flowable collagen material for dural closure.
This patent application is currently assigned to CODMAN & SHURTLEFF, INC.. Invention is credited to Robert E. Sommerich.
Application Number | 20120015006 13/241892 |
Document ID | / |
Family ID | 40934133 |
Filed Date | 2012-01-19 |
United States Patent
Application |
20120015006 |
Kind Code |
A1 |
Sommerich; Robert E. |
January 19, 2012 |
FLOWABLE COLLAGEN MATERIAL FOR DURAL CLOSURE
Abstract
Flowable graft materials are provided which comprise collagen
powder and a liquid in an amount sufficient to impart a flowable
consistency to the material. The graft materials are sufficiently
formable and pliable so as to provide both superior contact with
and easier access to a surgical site than typical, more rigid
grafts such as collagen sheets. These flowable materials may also
be in a fluidized, paste-like and/or gel-like state and may be
moldable and/or ejectable. The flowable collagen materials reduce
and/or eliminate post implantation problems associated with other
materials, e.g. synthetic dural sealants (hemostasis products),
such as product swelling after application and implantation. The
flowable graft materials are particularly useful as a dural
graft.
Inventors: |
Sommerich; Robert E.;
(Norton, MA) |
Assignee: |
CODMAN & SHURTLEFF,
INC.
Raynham
MA
|
Family ID: |
40934133 |
Appl. No.: |
13/241892 |
Filed: |
September 23, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12427380 |
Apr 21, 2009 |
8039591 |
|
|
13241892 |
|
|
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|
61047149 |
Apr 23, 2008 |
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Current U.S.
Class: |
424/400 ;
514/17.2 |
Current CPC
Class: |
A61P 43/00 20180101;
A61L 27/24 20130101; A61P 41/00 20180101 |
Class at
Publication: |
424/400 ;
514/17.2 |
International
Class: |
A61K 9/00 20060101
A61K009/00; A61P 43/00 20060101 A61P043/00; A61K 38/39 20060101
A61K038/39 |
Claims
1. A graft material comprising collagen powder and a liquid in an
amount effective to impart a flowable consistency, the material
being effective as a dural graft.
2. The graft material of claim 1, wherein collagen is selected from
the group comprising Type 1 bovine collagen, porcine collagen,
porcine small intestine submucosa and fetal bovine skin.
3. The graft material of claim 1, wherein the collagen is present
in an amount of about 25% wt/wt %.
4. The graft material of claim 1, wherein the graft material is
injectable from a syringe.
5. The graft material of claim 1, wherein the graft material is
fluid impermeable.
6. The graft material of claim 1, wherein the collagen powder has a
particle size in the range of about 0.1 to 10,000 microns.
7. The graft material of claim 6, wherein the collagen powder has
an average particle size in the range of about 100 to 400
microns.
8. A graft material comprising collagen powder and a liquid, the
collagen powder present in an amount of about 20% wt/wt %, the
graft material being flowable and extrudable.
9. The graft material of claim 8, wherein the collagen powder is
present in an amount of about 11% wt/wt %.
10. The graft material of claim 8, wherein the liquid is
saline.
11. The graft material of claim 8, wherein the graft material is
effective for use a dural graft.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a divisional of U.S. application
Ser. No. 12/427,380 filed on Apr. 21, 2009 and entitled "Flowable
Collagen Material For Dural Closure," which claims priority to U.S.
Application No. 61/047,149 filed on Apr. 23, 2008 and entitled
"Flowable Collagen Material For Dural Closure," both of which are
hereby incorporated by reference in their entireties.
FIELD
[0002] The present application relates to flowable collagen dural
graft materials for repairing, replacing, reinforcing or
strengthening bodily tissue, as an adhesion barrier, or for use as
a short-term body contact for moisture retention, hemostasis or
tissue protection.
BACKGROUND
[0003] The human brain and spinal cord are protected, preserved and
enveloped by a meningeal system comprising meningeal membranes. A
meningeal membrane is composed of an intricate network of three
overlapping tissue layers: the dura mater (or dura) outermost
layer, the arachnoid middle layer, and the pia mater innermost
layer. The outermost layer is tough and waterproof. The innermost
layer follows along and contacts the entire surface of the brain
and spinal cord, carrying blood vessels to service them. The middle
layer acts as a gliding system between the inner and outer
surfaces. Any damage to this network causes acute problems to the
central nervous system.
[0004] Repairing damaged meningeal membranes has largely focused on
implantable and/or resorbable constructs known as dural
substitutes. These dural substitutes are grafted to the damaged
dura mater and are designed to replace and/or regenerate the
damaged tissue. A number of synthetic and animal based dural repair
products are currently available. However, most of these are
categorized into either suturable or onlay (sutureless) grafts,
typically available in sponges, sheets, nonwoven matrixes or
combinations thereof In some instances, these products can be
difficult to apply, and in some cases limited pliability, or
moldability, may not enable them to adequately reach the entire
damaged area.
[0005] Synthetic gelatin and polymeric dural sealants have also
been disclosed. However, with these synthetic sealants, certain
problems persist as well. Some are porous, therefore not creating a
tight seal. They may also be nonelastic and/or insoluble, thus
leading to time consuming application. Furthermore, most are
subject to swelling once applied and/or implanted because they must
be hydrated or mixed at the surgical site rather than being
prepared in advance of the procedure. Swelling of the material,
post implantation, can be detrimental to the patient, for example,
where such swelling causes compression of brain tissue, a nerve
root or the spinal cord.
[0006] Thus, there is a need for a dural graft material that is
especially adapted for use in those areas or locations where it is
difficult to apply conventional dural grafts. Furthermore, there is
a need for a dural graft material which minimizes or eliminates
post implantation swelling as well as reduces the quantity of
implant material necessary to repair the damage. Finally, a dural
graft material is needed which simplifies the procedure in terms of
mateability, risks and time duration as compared with conventional
dural graft products.
SUMMARY
[0007] The present invention provides a flowable collagen graft
materials useful, for example, as a dural graft. These graft
materials comprise a collagen powder and a liquid in an amount
effective to impart a flowable consistency for application to an
area of concern. The collagen graft materials, when used as a dural
graft, are sufficiently flowable so as to provide both superior
contact with and easier access to a surgical site than typical,
more rigid dural grafts such as collagen sheets or synthetic
gelatin or polymeric dural sealants. The flowable graft materials
are moldable and/or extrudable and have particular application in
areas where other materials simply cannot access a site because
they lack adequate pliability or moldability.
[0008] The flowable collagen graft materials can also be used in
applications to reduce and/or eliminate post implantation problems
associated with other materials (synthetic dural sealants
(hemostasis products)), such as product swelling after application
and implantation.
[0009] In another aspect, there is provided a method for repairing
damaged dura utilizing the flowable collagen graft materials
described herein. In one aspect the method involves applying a
flowable dural graft material comprising a mixture of collagen and
a liquid to a desired site, and conforming the dural graft material
to a curvature of the site. The flowable graft material can be
applied through a variety of techniques, including by ejections
from a syringe and by manual spreading.
DETAILED DESCRIPTION
[0010] Certain exemplary embodiments will now be described to
provide an overall understanding of the principles of the
structure, function, manufacture, and use of the devices and
methods disclosed herein. Those skilled in the art will understand
that the devices and methods specifically described herein and
illustrated in the accompanying drawings are non-limiting exemplary
embodiments and that the scope is defined solely by the claims. The
features illustrated or described in connection with one exemplary
embodiment may be combined with the features of other embodiments.
Such modifications and variations are intended to be included
within the scope of the present application.
[0011] One aspect of the invention provides a dural graft material
that can be dispensed in a flowable, fluidized, gel-like and/or
paste-like form and, during application, shaped to conform to and
remain in place in a desired location. In use as a dural substitute
or adhesion barrier, or for short-term body contact for moisture
retention, hemostasis, or tissue protection, the flowable dural
graft material may be placed in contact with the desired bodily
tissue. Once implanted at the desired site, contact between the
flowable collagen material and the bodily tissues is maintained as
a result of the paste-like consistency of the material. Over time,
usually about 3 to 6 months, the flowable collagen material will be
fully resorbed.
[0012] A flowable collagen material in accordance with the present
application can be formed from a collagen powder and a liquid in an
amount effective to impart a flowable consistency to the resulting
product. This flowable product, which is gel-like and/or paste-like
in consistency, can be applied to the desired location by a number
of techniques, as described below. Further, as a result of being a
flowable material, the dural graft material described herein can be
molded such that it is able to substantially conform to the
geometery of the anatomical site at which it is implanted, e.g.,
the curvature of the site of dura damage.
[0013] The collagen source for the flowable dural substitute
described herein can be obtained from a variety of sources as known
to those skilled in the art. By way of example, such collagen
sources may include, bovine collagen, such as Type 1 bovine
collagen, as well as porcine collagen, porcine small intestine
submucosa, and fetal bovine skin.
[0014] Generally, the collagen material is in a powdered form,
however the powder can be derived from sheets of a collagen
material that are ground to a powder having the desired particle
size distribution. Exemplary collagen materials can be crosslinked,
either before or after grinding the collagen to a powder form, but
before combining with a liquid to form a flowable material.
Alternatively, the flowable collagen graft material may be
crosslinked by a variety of known techniques, including vapor
crosslinking or solution crosslinking. Exemplary crosslinking
agents include formaldehyde, glutaraldehyde, carbodiimides, and
difunctional succinimides. The flowable collagen graft material may
also be crosslinked by dehydrothermal crosslinking or UV
radiation.
[0015] The particle size of the collagen material can vary
depending on factors such as the desired use of the material as
well as the properties desired of the flowable material. In one
embodiment, the particle size of the collagen powder of the
flowable dural graft material is in the range of about 0.1 to
10,000 microns. In another embodiment, collagen powder has a
particle size in the range of about 10 to 1,000 microns. In yet
another embodiment, the collagen powder has a particle size in the
range of about 50 to 800 microns. In further embodiment, collagen
powder has a particle size in the range of about 100 to 400
microns.
[0016] One skilled in the art will appreciate that a variety of
biocompatible liquids can be mixed with the collagen material to
form the flowable graft material. Exemplary liquids include water
(e.g., purified water), saline, blood, plasma, collagen gels, and
any other biocompatible solvents commonly used in the art.
[0017] The relative amounts of collagen and liquid used to form the
flowable dural graft material can vary depending on the desired
applications and properties. One skilled in the art can readily
determine the appropriate ratios of these components to achieve a
flowable graft material that is suitable for a desired use and
application technique. For example, flowable materials that are to
be injectable, such as through a conventional syringe, should
generally be less viscous than a flowable dural graft material that
is to be applied by other techniques, such as by manual
application. One skilled in the art will appreciate that
conventional syringes have a standard luer lock at the distal end.
However, a custom syringe with a different size opening can be
designed to allow a thicker, more viscous material to be delivered.
Consistent with these qualifications, the collagen powder component
can generally be present in an amount of about 25% wt/wt %. In
another embodiment, the collagen powder component can be present in
an amount of about 20% wt/wt %. In a further embodiment, the
collagen powder component can be present in an amount of about 11%
wt/wt %. In yet another embodiment, the collagen powder component
can be present in an amount of about 6% wt/wt %.
[0018] One skilled in the art will appreciate that a variety of
additives can be incorporated into the flowable graft material.
Examples of such additives include, in effective amounts,
antimicrobial agents, bioactive compounds, growth factors,
immunosuppressive agents, permeation enhancers, antiviral agents,
antitumor agents, and gelling agents. The flowable graft material
may also include effective amounts of meningeal tissue growth
factors.
[0019] The flowable graft material described herein can be used as
dural graft, or it can be used in a variety of other applications,
including as an adhesion barrier, for short-term body contact for
moisture retention, hemostasis, and tissue protection. Although the
flowable graft and its method of use is primarily described in the
context of a dural graft, one skilled in the art will understand
the additional uses and applications of such a material.
Independent of the intended use, the flowable collagen material can
be deliverable in a fluidized, paste or gel state. One exemplary
method for applying the material is by ejection from a delivery
device such as a syringe. The material can be applied by ejection
from a delivery device in the desired pattern or it can be applied
by other techniques (e.g., manually or by other handling tools) and
subsequently shaped to the desired pattern. For example, for
thicker pastes, the material may be ejected with a caulking gun or
similar type system
[0020] In one embodiment, the dural graft material is prepared
before it is applied to a surgical site. However, the material may
also be prepared simultaneously with application to the surgical
site.
[0021] One use of the flowable collagen graft is in a surgical
procedure as a dural graft material to repair or protect damaged
meningeal membranes. The graft material can be implanted by
applying an effective amount of the flowable collagen graft by the
desired application technique (e.g., by ejection from a delivery
device) through an opening of the cranium and is placed in contact
with the meningeal membrane at the area of concern. An effective
amount of the flowable collagen dural graft material may comprise a
volume sufficient to slightly overlap with and contact a portion of
non-damaged meningeal membrane. The flowable nature of the graft
material enables it to substantially conform to the curvature of
the meningeal membrane. In addition, the flowable graft material
provides a superior seal and advantageously effectively avoids gaps
between the graft material and the meningeal membrane. Further
advantages of this material as a dural graft include its fluid
impermeable nature and its abilty to be implanted in a sutureless
manner.
EXAMPLE
[0022] A non-limiting example illustrating the preparation of a
flowable dural graft material in accordance with the present
invention is provided below. Bovine collagen (Type I Tendon sheet)
is ground into powder having an average particle size of 100-500
microns. The collagen powder is then added to saline in the
following four ratios to determine the weight percent lower limit
for applying the material to the site of dural damage in a
conventional 60 ml syringe:
[0023] (A) 25% wt/wt % collagen powder (0.511 g bovine collagen
powder to 2.0 ml saline);
[0024] (B) 20% wt/wt % collagen powder (0.511 g bovine collagen
powder to 2.5 ml saline);
[0025] (C) 11% wt/wt % collagen powder (0.511 g bovine collagen
powder to 4.5 ml saline);
[0026] (D) 6% wt/wt % collagen powder (0.511 g bovine collagen
powder to 8.5 ml saline).
The product resulting from sample (A) is a thick paste that is too
thick to be suitable for ejection from a conventional 60 ml syringe
and it is not moldable. The product resulting from sample (B) is a
balled thick paste that is moldable and it likewise is not
ejectable from a conventional 60 ml syringe. However, this material
may be applied to the site of dura damage by other application
techniques such as using a custom syringe with a larger opening,
delivering the material as a log shape and then spreading over the
defect, or using a delivery system with mechanical advantage such
as a caulking gun. The product resulting from sample (C) is not
tacky, resists "wash away" when some additional saline is added to
the material, and is both moldable and ejectable from a
conventional 60 ml syringe. The product resulting from sample (D)
is also moldable and ejectable from a conventional 60 ml
syringe.
[0027] One skilled in the art will appreciate further features and
advantages based on the above-described embodiments. Accordingly,
the disclosure is not to be limited by what has been particularly
shown and described, except as indicated by the appended claims.
All publications and references cited herein are expressly
incorporated herein by reference in their entirety.
* * * * *