U.S. patent application number 10/887884 was filed with the patent office on 2006-01-12 for adhesive-containing wound closure device and method.
This patent application is currently assigned to CLOSURE MEDICAL CORPORATION. Invention is credited to Glenn Hoskin, Jerry Jonn, Julian Quintero, Susan L. Roweton.
Application Number | 20060009099 10/887884 |
Document ID | / |
Family ID | 35541967 |
Filed Date | 2006-01-12 |
United States Patent
Application |
20060009099 |
Kind Code |
A1 |
Jonn; Jerry ; et
al. |
January 12, 2006 |
Adhesive-containing wound closure device and method
Abstract
An article, such as a tissue bonding article, includes a
flexible material, a polymerization initiator or rate modifier
disposed in or on the flexible material, and a polymerizable
adhesive composition permeated throughout at least a portion of the
flexible material, where the polymerization initiator or rate
modifier is a polymerization initiator or rate modifier for the
polymerizable adhesive composition.
Inventors: |
Jonn; Jerry; (Raleigh,
NC) ; Quintero; Julian; (Raleigh, NC) ;
Hoskin; Glenn; (Apex, NC) ; Roweton; Susan L.;
(Raleigh, NC) |
Correspondence
Address: |
HUTCHISON & MASON PLLC
PO BOX 31686
RALEIGH
NC
27612
US
|
Assignee: |
CLOSURE MEDICAL CORPORATION
Raleigh
NC
27616
|
Family ID: |
35541967 |
Appl. No.: |
10/887884 |
Filed: |
July 12, 2004 |
Current U.S.
Class: |
442/43 ; 442/1;
442/49; 442/59 |
Current CPC
Class: |
A61L 15/58 20130101;
A61L 15/425 20130101; Y10T 442/10 20150401; Y10T 442/172 20150401;
A61L 15/24 20130101; A61L 15/44 20130101; Y10T 442/183 20150401;
Y10T 442/20 20150401 |
Class at
Publication: |
442/043 ;
442/001; 442/049; 442/059 |
International
Class: |
D03D 19/00 20060101
D03D019/00; B32B 27/04 20060101 B32B027/04; D03D 15/00 20060101
D03D015/00; B32B 3/00 20060101 B32B003/00 |
Claims
1. A composite article, comprising: a flexible material; a
polymerization initiator or rate modifier disposed in or on said
flexible material; and a polymerizable adhesive composition
permeated throughout at least a portion of said flexible material,
wherein said polymerization initiator or rate modifier is a
polymerization initiator or rate modifier for said polymerizable
adhesive composition.
2. The article of claim 1, wherein said flexible material is a
mesh.
3. The article of claim 1, wherein said flexible material is
flexible and porous.
4. The article of claim 1, wherein said flexible material is
substantially free of elastin.
5. The article of claim 1, wherein said flexible material is
elastic.
6. The article of claim 1, further comprising a pressure sensitive
adhesive located on at least a portion of said flexible
material.
7. The article of claim 1, wherein said polymerizable adhesive
composition is a monomeric composition.
8. The article of claim 1, wherein said polymerizable adhesive
composition is polymerized.
9. The article of claim 1, wherein said polymerizable adhesive
composition comprises a 1,1-disubstituted monomer.
10. The article of claim 1, wherein said polymerizable adhesive
composition comprises a cyanoacrylate monomer.
11. The article of claim 1, wherein said polymerizable adhesive
composition, after polymerization, substantially covers surfaces on
at least a bottom side and a top side of said flexible
material.
12. The article of claim 1, wherein said polymerization initiator
or rate modifier is immobilized on said flexible material.
13. The article of claim 1, wherein said polymerization initiator
or rate modifier is adsorbed or absorbed on said flexible
material.
14. The article of claim 1, wherein said polymerization initiator
or rate modifier is chemically bonded to said flexible
material.
15. The article of claim 1, wherein said polymerization initiator
or rate modifier is soluble or dispersible in said polymerizable
adhesive composition
16. The article of claim 1, further comprising a bioactive material
disposed in or on said flexible material.
17. The article of claim 16, wherein said bioactive material is
chemically bonded to said flexible material.
18. The article of claim 16, wherein said bioactive material is not
immobilized on said flexible material, but is soluble or
dispersible in said polymerizable adhesive composition.
19. The article of claim 1, further comprising a non-bioactive
material disposed in or on said flexible material.
20. The article of claim 19, wherein said non-bioactive material is
selected from the group consisting of colorants, scents, protective
coatings that do not chemically detach, and temperature sensitive
agents.
21. The article of claim 1, wherein the flexible material is
biodegradable.
22. The article of claim 1, wherein the flexible material is not
biodegradable.
23. The article of claim 1, wherein the flexible material and the
polymerizable adhesive composition are together biodegradable.
24. The article of claim 1, wherein the flexible material and the
polymerizable adhesive composition are together not
biodegradable.
25. The article of claim 1, wherein the article is opaque.
26. The article of claim 1, wherein the article is translucent.
27. The article of claim 1, wherein said flexible substrate does
not include features that penetrate an underlying substrate during
use.
28. The article of claim 1, wherein said article is a tissue
bonding article.
29. A composite article, comprising: a flexible material; a
polymerization initiator or rate modifier disposed in or on said
flexible material; and a polymerized adhesive composition permeated
throughout at least a portion of said flexible material, wherein
said polymerization initiator or rate modifier is a polymerization
initiator or rate modifier for said polymerizable adhesive
composition.
30. A method of bonding, comprising: placing a flexible material
over a substrate, wherein a polymerization initiator or rate
modifier disposed in or on said flexible material; applying a
polymerizable adhesive composition over and substantially covering
at least a portion of the flexible material; and allowing the
polymerizable adhesive composition to permeate into and under the
flexible material and polymerize to form a composite structure
bonded to said substrate.
31. The method of claim 30, wherein said polymerization initiator
or rate modifier is a polymerization initiator or rate modifier for
said polymerizable adhesive composition.
32. The method of claim 30, wherein said substrate is tissue.
33. The method of claim 30, wherein said tissue is selected from
the group consisting of bone, organ surfaces, skin, and mucous
membranes.
34. The method of claim 30, wherein said substrate is tissue is
internal tissue.
35. The method of claim 30, wherein said substrate is tissue is
external tissue.
36. The method of claim 30, wherein said substrate is a section of
tissue that includes a wound to be closed.
37. The method of claim 36, wherein said flexible material fully
covers said wound.
38. The method of claim 30, wherein said applying comprises:
placing a quantity of said polymerizable adhesive composition on an
exposed side of the flexible material; and spreading the quantity
of polymerizable adhesive composition to substantially cover the
flexible material.
39. The method of claim 30, further comprising applying a
polymerizable adhesive composition to said substrate prior to
placing said flexible material over said substrate.
40. The article of claim 1, wherein the flexible material is
sterilized.
41. The article of claim 1, wherein the polymerizable adhesive
composition is sterilized.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of Invention
[0002] The present invention relates to medical and surgical wound
closure and management, and methods for making and using such
devices. In particular, the present invention relates to medical
and surgical wound closure and management, and related methods,
where the tissue bonding article or wound closure device
incorporates a polymerizable adhesive material applied to an
initiator-loaded textile material. The materials and methods of the
present invention provide an improvement over, and a substitute
for, conventional bandages, sutures and staples, and provide
improved methods for both approximating and covering and/or closing
wounds, thus providing improved wound management.
[0003] 2. Description of Related Art
[0004] There are currently in primary use at least four basic ways
for closing wounds resulting from surgical incisions or accidental
lacerations. These are sutures, surgical staples, surgical skin
tapes, and adhesive compositions. Sutures are generally recognized
as providing adequate wound support for the duration of wound
healing. However, suturing involves additional trauma to the wound,
as the needle and suture material must be passed through the tissue
at the margins of the wound. In addition, suturing can cause
cosmetically unattractive wound closure marks, can be time
consuming, and, depending on techniques and types of sutures used,
may require removal. Such removal entails further medical attention
and can involve additional pain and trauma to the patient
particularly if the sutures become embedded in the wound. In some
cases, suture removal can require anesthetic, and can result in a
railroad track appearance at the wound site.
[0005] Surgical staples have disadvantages similar to sutures in
terms of cosmetic result. However, staples are generally believed
to be even worse then sutures, at least in terms of the pain and
trauma inflicted on the patient, and the resultant cosmetic
appearance of the staple and wound marks. Further, removal of the
staples can be painful and, depending on location and patient pain
threshold, may require topical anesthetics.
[0006] Skin closure strips, such as conventional adhesive bandages,
are utilized for closure of relatively superficial skin wounds, but
their use is limited to only certain types and degrees of wounds.
However, the contact adhesives that are used with such strips
typically retain holding power for no more than a day or two and
can lose holding power quickly in the presence of moisture, for
example, perspiration.
[0007] Direct application of adhesives has also been proposed and
used for wound closure purposes, especially involving cyanoacrylate
adhesives. Such materials are achieving more widespread use for
wound closure.
[0008] For example, monomer and polymer adhesives are used in both
industrial (including household) and medical applications. Included
among these adhesives are the 1,1-disubstituted ethylene monomers
and polymers, such as the .alpha.-cyanoacrylates. Since the
discovery of the adhesive properties of such monomers and polymers,
they have found wide use due to the speed with which they cure, the
strength of the resulting bond formed, and their relative ease of
use. These characteristics have made .alpha.-cyanoacrylate
adhesives the primary choice for numerous applications such as
bonding plastics, rubbers, glass, metals, wood, and, more recently,
biological tissues.
[0009] It is known that monomeric forms of .alpha.-cyanoacrylates
are extremely reactive, polymerizing rapidly in the presence of
even minute amounts of an initiator, including moisture present in
the air or on moist surfaces such as animal tissue. Monomers of
.alpha.-cyanoacrylates are anionically polymerizable or free
radical polymerizable, or polymerizable by zwitterions or ion pairs
to form polymers. Once polymerization has been initiated, the cure
rate can be very rapid.
[0010] Medical applications of 1,1-disubstituted ethylene adhesive
compositions include use as an alternate or an adjunct to surgical
sutures and staples in wound closure as well as for covering and
protecting surface wounds such as lacerations, abrasions, burns,
stomatitis, sores, and other surface wounds. When an adhesive is
applied, it is usually applied in its monomeric form, and the
resultant polymerization gives rise to the desired adhesive
bond.
[0011] For example, polymerizable 1,1-disubstituted ethylene
monomers, and adhesive compositions comprising such monomers, are
disclosed in U.S. Pat. No. 5,328,687 to Leung et al. Suitable
methods for applying such compositions to substrates, and
particularly in medical applications, are described in, for
example, U.S. Pat. Nos. 5,582,834, 5,575,997, and 5,624,669, all to
Leung et al.
[0012] Combinations of the above approaches have also been used in
the art. For example, attempts have been made to combine the use of
sutures or staples and adhesive compositions. See, for example,
U.S. Pat. No. 5,254,132. Likewise, attempts have been made to
combine the use of conventional bandages or tapes and adhesive
compositions. See, for example, U.S. Pat. Nos. 5,259,835 and
5,445,597. However, these approaches have typically met the same
issues as described above for the individual approaches, namely
difficulties arising from the use of the sutures, staples and/or
bandages or tapes.
[0013] Current approaches for combining the above wound closure
approaches also include combining the use of adhesive compositions
and bandage-like dressings. For example, U.S. Patent Publications
Nos. 2002-0049503 and 2004-0106888 each disclose the combined use
of adhesive compositions and mesh bandage-like materials. In each
case, a mesh-like structure is applied to a wound, and an adhesive
composition is applied to the mesh-like structure. When the
adhesive composition sets, it bonds the mesh-like structure to the
wound. In U.S. Patent Publication No. 2004-0106888, the wound
dressing includes removable ends that adhere the mesh-like
structure to the wound, but which can be removed after the adhesive
composition sets, leaving the adherent dressing in place.
[0014] Commonly assigned U.S. patent application Ser. No.
10/779,721, filed Feb. 18, 2004, also discloses a combined adhesive
composition and bandage-like dressing. The application discloses a
tissue bonding article, comprising: a flexible material; an
adhesive substance applied over at least a portion of a bottom side
of said flexible material, for at least temporarily adhering the
flexible material to a wound surface; and a polymerizable adhesive
composition permeated throughout at least a portion of said
flexible material. When the polymerizable adhesive polymerizes, the
flexible material is adhered to the wound surface to provide an
adherent composite dressing. The entire disclosure of this
application is incorporated herein by reference.
[0015] A difficulty with these combined adhesive/flexible substrate
approaches is in the application and polymerization of the adhesive
composition. For example, where a polymerizable adhesive
composition is applied to the substrate, the adhesive is either
applied from an applicator device that includes a polymerization
initiator, or the adhesive composition (which contains no
initiator) is applied to the flexible substrate and wound site
where polymerization is initiated by moisture or other fluids
present at the wound site. In the first instance, polymerization of
the adhesive composition is rapid, but the presence of the
polymerization initiator in the applicator device creates a short
working time, requiring that the adhesive composition be applied
rather quickly. In the second instance, the working time of the
adhesive composition is longer because the applicator device does
not include a polymerization initiator. However, polymerization of
the adhesive composition on the wound site is typically much longer
and less consistent because polymerization relies upon weaker
species (such as moisture or other natural substances present on
the skin and not added specifically for polymerization initiation)
that may be present in differing amounts.
[0016] Accordingly, a need continues to exist for improved
materials and methods for wound approximation. A need also
continues to exist for improved materials and methods that have a
wider range of applications, from external to internal use, and
from essentially non-biodegradable (where the materials are removed
from the application site) to biodegradable (where the materials
are not directly removed from the application site, but instead
degrade over time).
SUMMARY OF THE INVENTION
[0017] The present invention addresses the above needs in the art,
and others, by providing improved materials and methods for wound
management, bonding, and approximation.
[0018] In embodiments, the materials and methods of the present
invention provide significant advantages over the current materials
and methods for wound closure. The materials and methods of the
present invention can fully replace the use of bandages, sutures,
and/or staples on a variety of wounds and tissue surfaces. These
advantages include, among others, improved wound closure, improved
wound approximation, provision of an improved durable microbial
barrier, reduced procedure time, improved working time, improved
cosmesis, less pain (during staple/suture removal) resulting in
increased patient satisfaction, and improved financial/economic
outcomes by eliminating follow-up visits for staple/suture
removal.
[0019] In embodiments, the materials and methods of the present
invention also provide significant advantages in terms of
application of the wound closure device. In particular, because the
flexible material is loaded with initiator for the subsequently
applied polymerizable adhesive material, the polymerizable adhesive
material rapidly and uniformly polymerizes on and in the flexible
material to form an adherent device, but without unacceptably high
heat generation. This faster set time (the time between application
and substantial polymerization of the polymerizable adhesive
material) means that wound closure can be quickly effected.
Furthermore, because the flexible material is loaded with initiator
for the subsequently applied polymerizable adhesive material, the
polymerizable adhesive material does not need to be applied in a
mixed state including initiator or through an applicator device
that provides an initiator. As such, the working time (the time
during which the polymerizable adhesive material can be applied
before becoming polymerized in the applicator) is unlimited.
[0020] In an embodiment, the present invention provides an article,
comprising: a flexible material; a polymerization initiator or rate
modifier disposed in or on said flexible material; and a
polymerizable adhesive composition permeated throughout at least a
portion of said flexible material, wherein said polymerization
initiator or rate modifier is a polymerization initiator or rate
modifier for said polymerizable adhesive composition. The article
can be a tissue bonding article for bonding tissue surfaces, or can
be used in other applications.
[0021] In another embodiment, the present invention provides a
method of bonding tissue, comprising: placing a flexible material
over a substrate, wherein a polymerization initiator or rate
modifier disposed in or on said flexible material; applying a
polymerizable adhesive composition over and substantially covering
at least a portion of the flexible material; and allowing the
polymerizable adhesive composition to permeate into and under the
flexible material and polymerize to form a composite structure
bonded to said substrate.
[0022] The composite structures of the present invention, when used
as tissue bonding articles, can be used to bond a variety of tissue
ranging from hard tissue (such as bone) to soft tissue (such as
skin, organs, mucous membranes, and the like). The tissue can be
either internal or external.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0023] In embodiments, the present invention provides wound closure
devices and methods, that provide some or all of the above
advantages. The present invention provides such benefits by
providing, as a wound closure device, a flexible material that can
be applied to a surface, and impregnated with a polymerizable
monomeric adhesive composition, which upon setting or curing
provides an adherent structure over the surface. Polymerization
(setting or curing) of the polymerizable monomeric adhesive
composition is assisted by the flexible material being loaded,
coated, or the like with a polymerization initiator or rate
modifier for the polymerizable monomeric adhesive composition.
[0024] In embodiments, the flexible or compliant material can be
formed of any suitable flexible or compliant material, providing
that the aims of the present invention are obtained. Preferably,
the flexible or compliant material is a material that is flexible,
porous, and non-toxic. As used herein, the term "flexible" is used
to refer to the flexible or compliant material. However, unless
stated differently in context, the term "flexible" is meant to
cover a range of materials, which exhibit one or more properties
such as being flexible, compliant, elastic, or memory retentive.
For example, "flexible" is also meant to refer to materials that
exhibit elastic or memory properties, i.e., the ability for the
material to return to its original shape when stresses applied
thereto are reduced or eliminated.
[0025] The flexible material is preferably flexible or compliant,
to allow the flexible substrate to be placed on the desired surface
(such as skin, organ, tissue, or the like) in a manner that allows
the flexible substrate to conform to the topology of the desired
surface. Likewise, the flexible material is preferably porous, to
allow the subsequently applied polymerizable adhesive material to
pass through or permeate through the flexible material and to
polymerize as a layer beneath the flexible material, while adhering
the flexible material to the desired substrate. By "porous" is
meant herein either that the bulk of the flexible material has
pores, such that the subsequently applied polymerizable adhesive
material is soaked up or absorbed by the bulk material, or that the
bulk of the flexible material has voids (like a net or screen),
such that the subsequently applied polymerizable adhesive material
passes directly through the bulk material, with or without being
soaked up or absorbed by the bulk material. For example, in the
case of textile materials, "porous" is generally used to mean that
the applied adhesive composition permeates and passes through
interstices between the fibers, but does not necessarily pass into
and through the fibers themselves.
[0026] Such porosity (or other properties such as hydrophobicity or
hydrophilicity) will also allow a polymerization initiator or rate
modifier to be loaded on the flexible material prior to use, to
initiate the subsequently applied polymerizable adhesive material.
Such porosity will also preferably allow air and water to pass
through the flexible material (either through pores per se, or
through voids in the bulk material). Depending upon the degree of
porosity (and/or the size of the openings in the textile), such
porosity of the flexible material or ability of air and water to
permeate through the flexible material may be tailored to either
remain after the final composite material is formed, or to be
absent therefrom. The flexible material is also preferably
non-toxic, as it is intended to be used as a wound covering, such
as on biological tissues. As such, the flexible material should be
biologically compatible with the desired substrate (such as tissue,
skin, organ, or the like), and is preferably a material that is
governmentally approved or generally regarded as safe for the
desired purpose.
[0027] In other embodiments, the flexible material may be selected
to be elastic or have some memory effect. In such embodiments, the
elastic properties of the flexible material may desirably provide a
degree of pressure or stress at the application site, for example,
to maintain wound edge approximation. Likewise, in embodiments
where such additional degree of pressure or stress at the
application site is not desired, the flexible material may be
selected to have less or no elasticity.
[0028] In embodiments of the present invention, the flexible
material can be either biodegradable, or not biodegradable.
"Biodegradable" in this invention is meant that the flexible
substrate biodegrades over time in vivo, such that it does not
require physical removal (such as by peeling) of the composite
structure after a set period of time. Thus, for example, a
biodegradable flexible material is one that, in the in vivo
environment, will biodegrade over a period of from about one week
to about five years. A non biodegradable material is one that does
not biodegrade in an in vivo environment within about five years.
Such a non biodegradable material thus would require physical
removal of the composite structure at a desired time, rather than
slowly deteriorating over time. Likewise, in some embodiments, it
is preferred that the combination of materials forming the
composite structure (i.e., the flexible material and the
polymerizable adhesive composition) together be biodegradable,
while in other embodiments, it is preferred that the combination of
materials forming the composite structure (i.e., the flexible
material and the polymerizable adhesive composition) together be
not biodegradable. Biodegradable and non-biodegradable
polymerizable adhesive compositions are known in the art and are
described below. Alternatively, combination of two or more
biodegradable and/or non-biodegradable materials can be used, to
provide tailored results in terms of properties such as
biodegradation and the like.
[0029] For biodegradable materials, a range of materials can be
selected as the flexible material, preferably to provide a desired
target biodegradation time. Thus, for example, suitable materials
can be selected to provide either a short biodegradation period
(such as between about one week and about two months) or a longer
biodegradation period (such as between about two months and about
five years). Suitable selection of the flexible material will thus
allow tailoring of the flexible substrate to the particular
application. For example, in embodiments where the flexible
substrate is used to form a composite structure on the surface of a
patient's skin (such as in the conventional context of a bandage),
it is desirable that the flexible substrate is not biodegradable.
Rather, after a set period of time, the composite structure is
physically removed (such as by peeling, by the use of a chemical
removal substance to break the adhesive bond, or by natural
sloughing off of the composite structure with the surface skin),
either to permit completion of healing or to reapply a new
composite structure. Such removal of the composite structure from
the tissue surface is easier than removal of a layer of
polymerizable adhesive composition alone. In other embodiments,
however, it may be desirable that the composite structure
biodegrade over a set period of time, for example when the
composite structure is used internally where subsequent removal
would otherwise require further trauma to the tissue.
[0030] In embodiments, it is preferred that the flexible material
is a textile or mesh/web material. Suitable textile materials can
be formed of either synthetic or natural materials. Such textile
material can be formed of either woven or non-woven fabrics or
materials. The flexible material may be, for example, any suitable
polymeric film, plastic foam (including open celled foam), a woven
fabric, knitted fabric, a non-woven fabric, mixture thereof, or the
like. In particular, suitable flexible materials may thus be
prepared, for example, from nylon, a polyolefin film, such as
polyethylene, polypropylene, ethylene propylene copolymers, and
ethylene butylene copolymers, polyurethanes, polyurethane foams,
polystyrenes, plasticized polyvinylchlorides, polyesters,
polyamides, and cotton. Suitable specific examples include, for
example, nylon, polyethylene, polypropylene, ethylene propylene
copolymers, ethylene butylene copolymers, polyurethane,
polystyrene, plasticized polyvinylchloride, polyester, polyamide,
cotton, polytetrafluoroethylene (PTFE), biovascular material,
collagen, Gore-Tex.RTM., DACRON.RTM., etc.
[0031] In some embodiments, it is preferred that the textile
material not be formed of elastin, or elastin-based materials.
Although elastin may be suitable for some uses, synthetic materials
are preferred in embodiments in view of their availability, ease of
manufacture, physical properties such as strength and durability,
and biological compatibility. Thus, in such embodiments, it is
preferred that the textile material is substantially or completely
free of elastin or elastin-based materials. Further, in such
embodiments, it is preferred that the entire flexible substrate
(i.e., the combination of the flexible material and the adhesive
substance) is substantially or completely free of elastin or
elastin-based materials.
[0032] In other embodiments, it is preferred that the flexible
material be formed of a synthetic, semi-synthetic, or natural
organic material. Thus, for example, it is preferred that the
flexible material be formed of a synthetic or natural polymer
material, but not from a material such as metal (such as silver,
steel or the like) or glass or ceramic.
[0033] The flexible material is preferably flexible, as described
above, yet resistant to tearing. In one embodiment, the thickness
of the flexible material of the present invention is from about 0.1
mil to about 50 mils. In another embodiment, the thickness of the
flexible material is from about 0.5 mil to about 20 mils,
preferably from about 0.7 mil to about 10 mils, or from about 1 mil
to about 5 mils.
[0034] The flexible material may be opaque or translucent. In some
embodiments of the present invention, the flexible material is
provided to have a skin color, such that the flexible material
masks the appearance of the underlying surface (such as a wound).
However, in other embodiments, the flexible material can be
provided with "designer" colors and/or patterns, or even cartoon
character designs. In other embodiments, the flexible material may
be clear, thus not masking the underlying surface.
[0035] In some embodiments, the flexible material can include a
pressure sensitive adhesive on at least one face, to assist in
initial placement of the flexible material on the desired surface.
However, in other embodiments, the flexible material preferably
does not include such pressure sensitive adhesive on one or both
sides, as such pressure sensitive adhesive can hinder subsequent
attachment of the flexible material to the surface by the
polymerizable adhesive composition.
[0036] In embodiments where the flexible material includes a
pressure sensitive adhesive applied to portions of the flexible
material, the pressure sensitive adhesive can be applied to an
entire surface of the flexible material, or only to portions (such
as peripheral edges) of the surface of the flexible material. The
exposed pressure sensitive adhesive can be covered by a suitable
release layer or liner, if desired, to preserve the adhesiveness of
the flexible material until time of use. The pressure sensitive
adhesive, if present, can be applied in the various manners shown
in U.S. patent application Ser. No. 10/779,721, the entire
disclosure of which is incorporated herein by reference.
[0037] The size of the flexible material can be tailored for
specific intended uses, or it can be provided in a sheet or roll
form. Thus, for example, when forming a rectangular composite for
use in the present invention, any suitable dimensions of the
flexible material can be provided. For example, in the conventional
bandage configuration, the flexible material can range in width
from about 1/4 inch to about 2 or 3 inches or more, although
preferred widths in embodiments may be from about 1/2 to about 1 or
11/2 inches, and can range in length from about 1/2 inch to about 4
or 5 inches or more, although preferred lengths in embodiments may
be from about 1 to about 2 or 3 inches. Likewise, in the
configuration of being a lengthwise bandage or rolled tape, such as
to be used to cover lengthwise wounds or surfaces, the flexible
material can range in width from about 1/2 inch to about 4 or 5
inches or more, although preferred widths in embodiments may be
from about 1 to about 2 or 3 inches, and can range in length from
about 1 inch to about 6 or 8 inches or more, although preferred
lengths in embodiments may be from about 2 to about 4 or 5 inches.
However, a particular advantage of this embodiment is that the
flexible material may be used to form a composite structure over a
longer wound, such as a long laceration on incision. As such,
embodiments of the present invention can provide a flexible
material having a length exceeding 8 or even 12 inches, such as
ranging in lengths up to 18 inches, 24 inches, 30 inches, or more.
When provided in the configuration of a roll, the flexible material
can have virtually any practical length, such as 5, 6, 8, 10, or 12
feet or more, which can be cut to desired length at the time of
use. Of course, it will be apparent that the materials of the
present invention are not limited to any particular dimensions, and
that the dimensions (length, width, thickness, etc.) of the
flexible material can be varied and tailored, as desired.
[0038] As such, various sized flexible materials can be prepared
and packaged for use. For example, shorter length materials (for
example, in lengths up to about 2, 3 or 4 inches) can be prepared
and packaged for use in "short laceration" applications, while
longer length materials (for example, in lengths up to about 10,
15, 20 or 30 inches) can be prepared and packaged for use in "long
laceration" applications. In other embodiments, a variety of length
materials can be provided, with the intention that the materials
are single use materials, where any leftover length of the flexible
material is discarded. Such single-use embodiments are particularly
desirable where the flexible material is sterilized, and sterility
is desired to be maintained until the time of use. In other
embodiments, such as where sterility is not a requirement, a longer
length of flexible material can be provided where any unused
portion can be saved for later use.
[0039] Still other configurations for the flexible material will be
apparent to those skilled in the art. For example, although
described above as being in rectangular or square configurations,
the flexible substrate can take any number of other shapes, which
can be designed for particular applications. For example, circular
or round (disc-shaped) flexible materials can be used, such as to
cover blister bases, sores, or the like; arc-shaped (curved
rectangular shaped) flexible materials can be used, such as to
cover curved lacerations or incisions; and the like. Other shapes,
such as oval, triangular, polygonal, semi-circular, and the like,
can also be used, in embodiments.
[0040] Preferably, the flexible material does not include
additional structures for attaching the flexible material to the
desired application or treatment site. Thus, for example, the
flexible material does not further include other physical
attachment means such as hooks, barbs, pins, projections, or the
like, which operate to physically latch or otherwise attach the
flexible substrate to the desired application or treatment site.
Such attachment means are not desired, for example, because they
introduce additional trauma to the underlying surface. Thus, it is
preferred that the flexible material not include features that
penetrate even surface layers of the underlying substrate, such as
dermal layers of the skin.
[0041] According to the present invention, the flexible material
includes one or more chemical materials located within the flexible
material. For example, one or more chemical substances can be
dispersed in the flexible material, such as being chemically bound,
physically bound, absorbed, or adsorbed to the flexible material.
Thus, for example, the flexible material includes at least a
polymerization initiator or rate modifier, and can optionally
include one or more bioactive materials. As desired, the one or
more chemical substances can be either immobilized on the flexible
material, for example so that it has a desired effect but is not
detached from the flexible material during use, or it can be
attached to the flexible material in a manner such that it becomes
detached during use.
[0042] For example, according to the present invention, a
polymerization initiator or rate modifier is loaded on the flexible
material, so that the initiator or rate modifier provides the
desired initiation or rate modification effect to a subsequently
applied polymerizable adhesive composition. The polymerization
initiator or rate modifier can be immobilized on the flexible
material, so that the initiator or rate modifier does not become
detached from the flexible material and its residues dispersed in
the resultant polymeric material. Alternatively, for example, the
polymerization initiator or rate modifier may be initially attached
to the flexible material, but only in such a manner that it becomes
mobilized or solubilized by a subsequently applied polymerizable
adhesive composition and dispersed in the resultant polymeric
material.
[0043] If desired, a combination of chemical substances can also be
provided on the flexible material, to provide multiple effects. For
example, as described above, a first chemical species (such as a
polymerization initiator or rate modifier) can be immobilized on
the flexible material, while a second, different chemical species
(such as a bioactive material) can be detachably attached to the
flexible material. Other combinations of chemical species and
resultant effects are also envisioned by the present invention.
[0044] When present in or on the flexible material, the chemical
substances (i.e., polymerization initiator, rate modifier, and/or
bioactive materials, or other additives), can be incorporated in or
on the flexible material in any suitable manner. For example, the
chemical substance can be added to the flexible material by
contacting the flexible material with a solution, mixture, or the
like including the chemical substances. The chemical substance can
be added to the flexible material, for example, by dipping,
spraying, roll coating, gravure coating, brushing, vapor
deposition, or the like. Alternatively, the chemical substance can
be incorporated into or onto the flexible material during
manufacture of the flexible material, such as during molding or the
like of the flexible material.
[0045] The chemical substance can be present in or on the flexible
material in any suitable concentration and manner. For example, the
chemical substance can be applied in a uniform manner to the
flexible material, such that there is a substantially uniform
concentration of the chemical substance across the flexible
material. Alternatively, the chemical substance can be applied such
that a concentration gradient exists across or through the flexible
material. For example, a greater or smaller concentration of the
chemical substance could exist at the center or edges of the
flexible material, or a greater or smaller concentration of the
chemical substance could be applied on one side of the flexible
material as compared to an opposite side. Further, the chemical
substance can be applied in a uniform manner to the flexible
substrate, or it can be applied in a non-uniform random or
patterned manner (such as lines, dots, concentric circles, or the
like).
[0046] Other chemical substances that can be present in or on the
flexible material include, but are not limited to, any suitable and
preferably compatible additive that enhances performance of the
composite structure. Such additional chemical substances can be
bioactive or non-bioactive. Suitable other chemical substances thus
include, but are not limited to, colorants (such as inks, dyes and
pigments), scents, protective coatings that do not chemically
detach, temperature sensitive agents, drugs, and the like.
[0047] The present invention, by virtue of the polymerization
initiator or rate modifier being loaded on the flexible material,
provides a number of advantages over the prior art. For example,
the structure of the present invention, in embodiments, allows for
tailoring of the setting or polymerization time of the applied
polymerizable adhesive composition. For example, as is well known
in the art, the type and/or concentration of initiator that is
applied to the flexible material can be selected so as to provide
faster or slower polymerization time. For example, the
concentration of polymerization initiator or rate modifier can be
increased to provide a faster polymerization time, or can be
decreased to provide a slower polymerization time.
[0048] Other properties of the polymerization can also be adjusted,
in embodiments. For example, the polymerization can be made more
uniform than previously possible, at least because the
polymerization initiator or rate modifier is generally more
uniformly applied to the flexible material. The cure temperature of
the polymerizable adhesive composition can also be more easily
tailored. For example, the initiator type and/or concentration can
be selected to provide a desired polymerization or set time, while
not generating excessive heat that could damage the underlying
application surface.
[0049] These embodiments are preferred over at least some
embodiments of the prior art. In the prior art, one method of
applying a polymerizable adhesive composition was to apply the
polymerizable adhesive composition to a substrate, and allow
polymerization to be initiated by moisture of other species that
may naturally be present. This often created long polymerization or
set times, and led to undesirable results. For example, if tissue
surfaces were being joined, the tissue surfaces would need to be
physically held in place longer while the slow polymerization
progressed, to avoid the wound from being opened. In such methods,
polymerization time often varied from use to use, and thus was less
reliable.
[0050] The present invention also provides, in embodiments, a
longer working time for the polymerizable adhesive composition that
is being used. Because the polymerization initiator or rate
modifier is loaded directly on the flexible material, it is not
necessary to mix the polymerizable adhesive composition with a
polymerization initiator or rate modifier in an applicator prior to
application. Thus, the applicator of the polymerizable adhesive
composition does not suffer from the drawback of becoming plugged
and unuseable as polymerizable adhesive composition polymerizes in
an applicator tip. This can allow a longer working time, where the
polymerizable monomer composition can be more precisely and
carefully applied over a longer period of time.
[0051] These embodiments are thus likewise preferred over at least
some other embodiments of the prior art. In the prior art, another
method of applying a polymerizable adhesive composition was to
apply the polymerizable adhesive composition through a porous
applicator tip. The porous applicator tip is loaded with
polymerization initiator or rate modifier, such that the
polymerizable adhesive composition and polymerization initiator or
rate modifier mix in the applicator tip. A drawback is that because
the materials mix in the applicator tip, polymerization starts in
the applicator tip. Accordingly, material within the applicator tip
begins to polymerize, and can rapidly plug or clog the applicator
tip, rendering the applicator and any further polymerizable
adhesive composition contained therein unuseable. Such embodiments
accordingly required faster use of the adhesive composition, and
higher waste of adhesive composition.
[0052] In other embodiments, the present invention also provides
still further operational advantages. For example, because the
textile material tends to trap or act as a barrier to flow of the
polymerizable adhesive composition, there is less running of the
adhesive composition away from the application site. In addition,
where one or more chemical substances are present in or on the
textile, such chemical substances can be more specifically or
precisely applied to the textile. For example, the chemical
substances can be applied to the textile material only at specific
locations, or in a gradient pattern, if desired. In these and other
embodiments, the present invention provides a stronger composite
structure than is provided by a polymerizable adhesive composition
alone.
[0053] The above advantages, alone or in combination, can be
provided by various embodiments of the present invention.
[0054] A method for using the flexible substrate and resultant
composite structure will now be described.
[0055] The materials of the present invention are advantageously
used as wound dressings. For example, the materials of the present
invention are advantageously used as replacements for conventional
bandages, or as replacements for conventional use of sutures and
staples for closing wounds. As compared to conventional bandages,
the flexible material of the present invention generally provides
the same wound approximation and pressure benefits. However,
because the flexible material is used to provide a composite
structure by the addition of a polymerizable adhesive composition,
the resultant composite structure provides significant benefits
over the conventional bandage in terms of improved wound
management, stronger adhesion to the underlying application site,
microbial barrier properties, improved patient satisfaction, and
the like. According to embodiments of the present invention, a
polymerizable adhesive material is applied to the upper surface of
the flexible material, which subsequently permeates through the
flexible material (or at least through openings such as voids or
pores in the flexible material) as the adhesive polymerizes, to
form a flexible, adherent wound dressing. If desired, a first
amount of a polymerizable adhesive material can be applied to the
application site prior to applying the flexible material. The
result is a unitary composite structure over the wound.
Furthermore, as compared to conventional sutures and staples, the
composite structure of the present invention also generally
provides the same wound approximation and pressure benefits.
However, because the composite structure uses a polymerizable
adhesive composition rather than punctures for adhesion to the
underlying application site, the resultant composite structure
provides significant benefits over the conventional sutures and
staples in terms of improved wound management, stronger adhesion to
the underlying application site, microbial barrier properties,
improved patient satisfaction, less tissue trauma (since additional
punctures are not made), lessened scarring, and the like.
[0056] The materials of the present invention can also be
advantageously used in non-medical or non-healthcare settings. For
example, the materials of the present invention can also
advantageously be used in commercial or household settings, where
the flexible material/polymerizable adhesive composition composite
structure can be used to provide stronger adhesion.
[0057] One method according to the present invention is described
below. The method is described with reference to closing and
covering a wound on a tissue surface. However, the invention is not
limited to this embodiment.
[0058] In a first step, the application site, such as a wound or
the like, is preferably cleaned by removing excess exudates (blood
or the like) to provide as dry a wound as possible to assist in
wound closure.
[0059] In a second step, a portion of flexible material is
provided. Preferably, the length and width of the flexible material
is longer and wider than the wound to be closed, and extend beyond
opposite ends of the wound a sufficient distance to permit
sufficient bonding. Thus, for example, the length of flexible
material is preferably sufficient to extend at least 1/4 inch, more
preferably at least 1/2 inch or at least 3/4 inch, and even more
preferably at least one inch beyond each end of the wound.
Furthermore, the flexible material is preferably wide enough to
extend beyond each lateral edge of the wound throughout the length
of the wound. The width of the flexible material is preferably wide
enough that the entire wound is covered, with excess coverage, by
the flexible material. That is, the flexible material preferably
covers the full width of the wound, and extends beyond opposite
lateral edges of the wound a sufficient distance to permit
sufficient bonding. Thus, for example, the width of flexible
material is preferably sufficient to extend at least 1/4 inch, more
preferably at least 1/2 inch or at least 3/4 inch, and even more
preferably at least one inch beyond each lateral edge of the
wound.
[0060] In the second step, the flexible material is applied over
the wound or desired surface. For ease of application, the surface
is preferably horizontal, to help avoid slipping of the flexible
material from the application site prior to complete polymerization
of the subsequently applied polymerizable adhesive composition.
However, where horizontal application is not possible or practical,
the flexible material can be held in place by any suitable means
including, but not limited to, by hand, forceps, tape, pressure
sensitive adhesive, pressure, vacuum, or the like.
[0061] In a modification of this application method, a portion of a
polymerizable adhesive material is applied to the application site
prior to applying the flexible material. When so applied, the
polymerizable adhesive material is preferably not allowed to fully
polymerize prior to application of the flexible material and
subsequent application of further amounts of polymerizable adhesive
material. The polymerizable adhesive material applied prior to
application of the flexible material can be the same as or
different from the polymerizable adhesive material subsequently
applied to the flexible material.
[0062] In a third step, a polymerizable adhesive composition, such
as a polymerizable monomeric adhesive composition, is applied over
at least a portion of the surface of the flexible material.
Preferably, the polymerizable adhesive composition is applied to
fully cover the surface of the flexible material. However, if
desired, a lesser amount of the polymerizable adhesive composition
can be used to conserve materials and assist in subsequent removal.
For example, if a portion of the flexible material is not covered
by the polymerizable adhesive composition, that portion can be used
either to maintain control over the flexible material during
placement and polymerization, and then subsequently trimmed off, or
it can be maintained and used as a tab to assist in subsequent
removal (such as by sloughing off or peeling off of the composite
structure, or by the use of a remover substance). In this instance,
the polymerizable adhesive composition is preferably applied to the
flexible material at least in an area sufficient to cover the
underlying wound or substrate.
[0063] In this step of applying the polymerizable adhesive
composition, a sufficient amount of polymerizable adhesive
composition should be applied to form the desired composite
structure once the polymerizable adhesive composition has
polymerized (or cured). Thus, for example, the amount of
polymerizable adhesive composition should be sufficient to
preferably allow the composition to penetrate through the flexible
material to form a continuous coating between the flexible material
and substrate, which continuous coating subsequently polymerizes or
cures to form a continuous polymeric coating between the flexible
substrate and the underlying surface. The quantity of polymerizable
adhesive composition should preferably further allow for a quantity
of the composition to remain in, and preferably over, the flexible
material. This further amount of polymerizable adhesive composition
polymerizes or cures with the remaining polymerizable adhesive
composition to provide a unitary composite structure that is bonded
to the underlying surface.
[0064] If necessary or desired, the step of applying polymerizable
adhesive composition to the flexible material can be repeated one
or more times. Thus, for example, a second or subsequent coating of
the polymerizable adhesive composition can be applied, either prior
or subsequent to complete curing of the underlying layer of
polymerizable adhesive composition. Preferably, where multiple
layers are to be applied, it is preferred that subsequent layers be
applied after curing of the underlying layer has begun, but before
curing is complete. If desired or necessary, subsequent layers of
polymerizable adhesive material can be applied with an added
polymerization initiator or rate modifier, to assist in
polymerization of the adhesive composition.
[0065] As appropriate, the polymerizable adhesive composition can
be applied to the flexible material either in the form of a
continuous coating, or as discrete dots or dabs. For example, the
discrete dots or dabs can be used either where the polymerizable
adhesive composition is of high viscosity, and it is desired that
the composite structure retain such discrete areas of adhesion, or
where the polymerizable adhesive composition is of low viscosity
such that the discrete dots or dabs will readily flow to form a
continuous coating. A continuous coating can be assisted, for
example, by spreading the applied polymerizable adhesive
composition to any extent necessary.
[0066] However, if a continuous coating is desired when applying
the polymerizable adhesive composition to the flexible material,
the polymerizable adhesive composition is preferably applied over
an entire surface of the flexible material. That is, while the
flexible material may provide some wicking, flowing, or capillary
movement of the polymerizable adhesive composition within the bulk
material of the flexible substrate, such wicking or capillary
movement is minimal, and is not intended to provide complete
coverage of the polymerizable adhesive composition over the
flexible material. Thus, for example, it will generally not be
possible to apply one or two drops of the polymerizable adhesive
composition to the flexible material, and expect the polymerizable
adhesive composition to completely cover the flexible material
(unless, of course, the flexible material is such a small size that
the drops substantially cover the surface). Rather, in embodiments
of the present invention, the polymerizable adhesive composition is
applied by dabbing, brushing, rolling, painting, swabbing or the
like, the polymerizable adhesive composition onto the flexible
material. If necessary, the applied polymerizable adhesive
composition can be spread around on the surface of the flexible
material to provide improved coverage.
[0067] Once the polymerizable adhesive composition is cured, it
forms a composite structure with the flexible material, covering
the desired surface. The composite structure is adherent to the
underlying surface, and provides the benefits described above.
[0068] Of course, although the invention is described with respect
to the above application method, other methods will be readily
apparent to those skilled in the art. The application methods are
in no way limited to the methods described above.
[0069] As described above, one or more additives may be applied to
the flexible substrate, which can subsequently chemically or
physically interact with an applied polymerizable adhesive
composition. Such chemical substances can include, for example, one
or more polymerization initiators or rate modifiers, one or more
additive materials, combinations thereof, and the like. According
to the present invention, in embodiments, the flexible material is
at least loaded or impregnated with one or more polymerization
initiators or rate modifiers, as described above, to provide
polymerization initiation to the subsequently applied polymerizable
adhesive composition.
[0070] Suitable polymerization and/or cross-linking initiators and
rate modifiers, and methods for applying them to substrates, are
described in, for example, U.S. Pat. Nos. 5,928,611, 6,352,704,
6,455,064, 6,579,469 and 6,595,940 and U.S. Patent Applications No.
09/430,177, filed Oct. 29, 1999, Ser. No. 09/430,289; 09/385,030
filed Aug. 30, 1999; and Ser. No. 09/176,889 filed Oct. 22, 1998,
the entire disclosures of which are incorporated herein by
reference. Preferred initiators for some medical uses include
benzalkonium chloride, benzyldimethylhexa-decylammonium chloride,
and for some industrial uses include dimethyl toluidine.
[0071] Particular initiators and rate modifiers for particular
monomers may be readily selected by one of skill in the art without
undue experimentation. Control of the molecular weight distribution
of the applied adhesive can be enhanced by selection of the
concentration and functionality of the initiator or rate modifier
vis-a-vis the selected monomer. Suitable polymerization initiators
and rate modifiers for cyanoacrylate compositions include, but are
not limited to, detergent compositions; surfactants, including
nonionic surfactants such as polysorbate 20 product (e.g., Tween
20.TM. product; ICI Americas), polysorbate 80 product (e.g., Tween
80.TM. product; ICI Americas), and poloxamers; cationic surfactants
such as tetrabutylammonium bromide; anionic surfactants, including
quaternary ammonium halides such as benzalkonium chloride or its
pure components, and benzethonium chloride; stannous octoate (tin
(II) 2-ethylhexanoate), and sodium tetradecyl sulfate; and
amphoteric or zwitterionic surfactants such as
dodecyldimethyl(3-sulfopropyl) ammonium hydroxide, inner salt;
amines, imines, and amides, such as imidazole, tryptamine, urea,
arginine and povidine; phosphines, phosphites and phosphonium
salts, such as triphenylphosphine and triethyl phosphite; alcohols
such as ethylene glycol; methyl gallate; ascorbic acid; tannins and
tannic acid; inorganic bases and salts, such as sodium bisulfite,
magnesium hydroxide, calcium sulfate and sodium silicate; sulfur
compounds such as thiourea and polysulfides; polymeric cyclic
ethers such as monensin, nonactin, crown ethers, calixarenes and
polymeric epoxides; cyclic and acyclic carbonates, such as diethyl
carbonate; phase transfer catalysts such as Aliquat.TM. 336
(General Mills, Inc., Minneapolis, Minn.); organometallics;
manganese acetylacetonate; radical initiators and radicals, such as
di-t-butyl peroxide and azobisisobutyronitrile; and bioactive
compounds or agents.
[0072] In preferred embodiments, the initiator may be a bioactive
material (i.e., a material that affects a surrounding biological
environment in addition to acting as a polymerization initiator),
including quaternary ammonium halides such as
alkylbenzyldimethylammonium chloride (benzalkonium chloride; BAC)
its pure components, or mixtures thereof, especially those with an
alkyl containing 6-18 carbon atoms; benzethonium chloride; and
salts of sulfadiazine. Cobalt napthenate can be used as an
accelerator for peroxide.
[0073] In preferred embodiments, the initiator may also be a
bioactive material that possesses antiviral, antimicrobial,
antifungal and/or wound healing properties. An example of such a
material that possesses polymerization initiation and antiviral,
antimicrobial, and/or antifungal properties is Gentian Violet, also
known as crystal violet or methylrosaniline chloride. Examples of
materials that possess polymerization initiation and wound healing
properties also include various zinc complexes and zinc salts,
antioxidants such as vitamin E and other vitamins and the like, and
copper compounds such as copper chloride, copper sulfate and copper
peptides. Such materials are particularly preferred because they
can serve not only as the polymerization initiator or rate modifier
for the cyanoacrylate monomer, they can also provide additional
benefits to the wound site, such as antiviral effects,
antimicrobial effects and/or antifungal effects or help to promote
wound healing.
[0074] When zinc compounds are present, the zinc compound can be
present in various forms, such as zinc salts. For example, suitable
zinc compounds include, but are not limited to, zinc salts of
cyanoacrylic acid, zinc salts of cyanoacetic acid, zinc salts of
dicyanoglutaric acid, zinc salts of rosin, zinc oxide, zinc salts
of polycyanoacrylic acid, zinc salts of polyacrylic acid, zinc
bacitracin, zinc salicylate, zinc stearate, zinc citrate, zinc
lactate, mixtures thereof, and the like. Preferably, the zinc
compounds are of Zn.sup.2+. Incorporation of such zinc compounds
into the polymerizable adhesive composition is particularly
effective in promoting wound healing of leg ulcers, thermal burns,
and the like.
[0075] The polymerizable adhesive composition and/or the flexible
material may also contain an initiator and/or a rate modifier which
is inactive until activated by a catalyst or accelerator (included
within the scope of the term "initiator" as used herein).
Initiators activated by stimulation such as heat and/or light
(e.g., ultraviolet or visible light) are also suitable if the
flexible material is appropriately subjected to such
stimulation.
[0076] In addition to the polymerization and/or cross-linking
initiator and/or rate modifier, the flexible material can also
include various other materials that may or may not act as a
polymerization initiator and/or rate modifier. For example, the
flexible material can include a bioactive material, which may or
may not also be a polymerization and/or cross-linking initiator
and/or rate modifier. Thus, in embodiments, the initiator and/or
the rate modifier can be, but does not have to be, bioactive. In
embodiments where the initiator and/or the rate modifier is
bioactive, the method of the invention can be used to close, cover,
or protect tissue and wounds while simultaneously providing a
bioactive material to the tissue or wound.
[0077] Suitable bioactive materials include, but are not limited
to, medicaments such as antibiotics, antimicrobials, antiseptics,
bacteriocins, bacteriostats, disinfectants, steroids, anesthetics,
antifungal agents, anti-inflammatory agents, antibacterial agents,
antiviral agents, antitumor agents, growth promoting substances,
antioxidants, or mixtures thereof. Such compounds include, but are
not limited to, acetic acid, aluminum acetate, bacitracin,
bacitracin zinc, benzalkonium chloride, benzethonium chloride,
betadine, calcium chloroplatinate, certrimide, cloramine T,
chlorhexidine phosphanilate, chlorhexidine, chlorhexidine sulfate,
chloropenidine, chloroplatinatic acid, ciprofloxacin, clindamycin,
clioquinol, cysostaphin, gentamicin sulfate, hydrogen peroxide,
iodinated polyvinylidone, iodine, iodophor, minocycline, mupirocin,
neomycin, neomycin sulfate, nitrofurazone, non-onynol 9, potassium
permanganate, penicillin, polymycin, polymycin B, polymyxin,
polymyxin B sulfate, polyvinylpyrrolidone iodine, povidone iodine,
8-hydroxyquinoline, quinolone thioureas, rifampin, rifamycin,
copper chloride, copper sulfate, copper peptides, silver acetate,
silver benzoate, silver carbonate, silver chloride, silver citrate,
silver iodide, silver nitrate, silver oxide, silver sulfate, sodium
chloroplatinate, sodium hypochlorite, sphingolipids, tetracycline,
zinc oxide, salts of sulfadiazine (such as silver, sodium, and
zinc), antioxidants such as vitamins such as vitamin E, other
agents mentioned above, and mixtures thereof. Preferable bioactive
materials are USP approved, more preferably USP monographed.
[0078] As described above, the polymerization and/or cross-linking
initiator and/or rate modifier, and/or the bioactive material, may
be applied to the flexible material by any suitable means,
including, but not limited to, spraying, dipping, injecting, or
brushing the flexible material with a liquid medium containing the
material to be applied.
[0079] As also described above, the composite structure is formed
by applying a polymerizable adhesive composition to the flexible
material, and allowing the polymerizable adhesive composition to
polymerize. Polymerization of the polymerizable adhesive
composition is initiated, or assisted, by the polymerization
initiator or rate modifier that was previously loaded on the
flexible material.
[0080] The polymerizable (i.e., monomer and/or prepolymeric)
adhesive composition may include one or more polymerizable
monomers, which preferably are synthetic or semi-synthetic
monomers. Preferred monomers that may be used in this invention are
readily polymerizable, e.g. anionically polymerizable or free
radical polymerizable, or polymerizable by zwitterions or ion pairs
to form polymers. Such monomers include those that form polymers,
that may, but do not need to, biodegrade. Such monomers are
disclosed in, for example, U.S. Pat. Nos. 5,328,687, 5,928,611 and
6,183,593, U.S. patent application Ser. No. 09/430,177, filed on
Oct. 29, 1999, and U.S. Pat. No. 6,183,593, which are hereby
incorporated in their entirety by reference herein.
[0081] Preferred monomers include 1,1-disubstituted ethylene
monomers, such as .alpha.-cyanoacrylates including, but not limited
to, alkyl .alpha.-cyanoacrylates having an alkyl chain length of
from about 1 to about 20 carbon atoms or more, preferably from
about 3 to about 8 carbon atoms.
[0082] The .alpha.-cyanoacrylates of the present invention can be
prepared according to several methods known in the art. U.S. Pat.
Nos. 2,721,858, 3,254,111, 3,995,641, and 4,364,876, each of which
is hereby incorporated in its entirety by reference herein,
disclose methods for preparing .alpha.-cyanoacrylates.
[0083] Preferred .alpha.-cyanoacrylate monomers used in this
invention include methyl cyanoacrylate, ethyl cyanoacrylate,
n-butyl cyanoacrylate, 2-octyl cyanoacrylate, methoxyethyl
cyanoacrylate, ethoxyethyl cyanoacrylate, dodecyl cyanoacrylate,
2-ethylhexyl cyanoacrylate, butyl cyanoacrylate, 3-methoxybutyl
cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl
cyanoacrylate, 1-methoxy-2-propyl cyanoacrylate, hexyl
cyanoacrylate, or dodecylcyanoacrylate.
[0084] Other suitable cyanoacrylates for use in the present
invention also include, but are not limited to, alkyl ester
cyanoacrylate monomers such as those having the formula ##STR1##
wherein R.sub.1 and R.sub.2 are, independently H, a straight,
branched or cyclic alkyl, or are combined together in a cyclic
alkyl group, and R.sub.3 is a straight, branched or cyclic alkyl
group. Preferably, R.sub.1 is H or a C.sub.1, C.sub.2 or C.sub.3
alkyl group, such as methyl or ethyl; R.sub.2 is H or a C.sub.1,
C.sub.2 or C.sub.3 alkyl group, such as methyl or ethyl; and
R.sub.3 is a C.sub.1-C.sub.16 alkyl group, more preferably a
C.sub.1-C.sub.10 alkyl group, such as methyl, ethyl, propyl, butyl,
pentyl, hexyl, heptyl, octyl, nonyl or decyl, and even more
preferably a C.sub.2, C.sub.3 or C.sub.4 alkyl group. Such alkyl
ester cyanoacrylates and other suitable monomers are disclosed in,
for example, U.S. patent application Ser. No. 09/919,877, filed
Aug. 2, 2001, and U.S. Pat. No. 6,620,846, the entire disclosures
of which are incorporated herein by reference.
[0085] Examples of preferred alkyl ester cyanoacrylates include,
but are not limited to, butyl lactoyl cyanoacrylate (BLCA), butyl
glycoloyl cyanoacrylate (BGCA), ethyl lactoyl cyanoacrylate (ELCA),
and ethyl glycoloyl cyanoacrylate (EGCA). BLCA may be represented
by the above formula, wherein R.sub.1 is H, R.sub.2 is methyl and
R.sub.3 is butyl. BGCA may be represented by the above formula,
wherein R.sub.1 is H, R.sub.2 is H and R.sub.3 is butyl. ELCA may
be represented by the above formula, wherein R.sub.1 is H, R.sub.2
is methyl and R.sub.3 is ethyl. EGCA may be represented by the
above formula, wherein R.sub.1 is H, R.sub.2 is H and R.sub.3 is
ethyl.
[0086] The composition may optionally also include at least one
other plasticizing agent that assists in imparting flexibility to
the polymer formed from the monomer. The plasticizing agent
preferably contains little or no moisture and should not
significantly affect the stability or polymerization of the
monomer. Examples of suitable plasticizers include but are not
limited to tributyl citrate, acetyl tri-n-butyl citrate (ATBC),
polymethylmethacrylate, polydimethylsiloxane, hexadimethylsilazane
and others as listed in U.S. Pat. No. 6,183,593, the disclosure of
which is incorporated in its entirety by reference herein.
[0087] The composition may also optionally include at least one
thixotropic agent. Suitable thixotropic agents are known to the
skilled artisan and include, but are not limited to, silica gels
such as those treated with a silyl isocyanate, and optionally
surface treated titanium dioxide. Examples of suitable thixotropic
agents and thickeners are disclosed in, for example, U.S. Pat. No.
4,720,513, and U.S. Pat. No. 6,310,166, the disclosures of which
are hereby incorporated in their entireties by reference
herein.
[0088] The composition may optionally also include thickeners.
Suitable thickeners may include poly (2-ethylhexy methacrylate),
poly(2-ethylhexyl acrylate) and others as listed in U.S. Pat. No.
6,183,593, the disclosure of which is incorporated by reference
herein in its entirety.
[0089] The composition may also optionally include at least one
natural or synthetic rubber to impart impact resistance. Suitable
rubbers are known to the skilled artisan. Such rubbers include, but
are not limited to, dienes, styrenes, acrylonitriles, and mixtures
thereof. Examples of suitable rubbers are disclosed in, for
example, U.S. Pat. Nos. 4,313,865 and 4,560,723, the disclosures of
which are hereby incorporated in their entireties by reference
herein.
[0090] The composition may optionally also include one or more
stabilizers, preferably both at least one anionic vapor phase
stabilizer and at least one anionic liquid phase stabilizer. These
stabilizing agents may inhibit premature polymerization. Suitable
stabilizers may include those listed in U.S. Pat. No. 6,183,593,
the disclosure of which is incorporated by reference herein in its
entirety. Furthermore, certain stabilizers may also function as
anti-microbial agents, such as, for example, various acidic
anti-microbials, as identified above.
[0091] The compositions may also include pH modifiers to control
the rate of degradation of the resulting polymer, as disclosed in
U.S. Pat. No. 6,143,352, the entire disclosure of which is hereby
incorporated by reference herein in its entirety.
[0092] To improve the cohesive strength of adhesives formed from
the compositions of this invention, difunctional monomeric
cross-linking agents may be added to the monomer compositions of
this invention. Such crosslinking agents are known. U.S. Pat. No.
3,940,362 to Overhults, which is hereby incorporated herein in its
entirety by reference, discloses exemplary cross-linking
agents.
[0093] The compositions of this invention may further contain
colorants such as dyes, pigments, and pigment dyes.
[0094] The polymerizable compositions useful in the present
invention may also further contain one or more preservatives, for
prolonging the storage life of the composition. Suitable
preservatives, and methods for selecting them and incorporating
them into adhesive compositions, are disclosed in U.S. patent
application Ser. No. 09/430,180, the entire disclosure of which is
incorporated herein by reference. Such preservatives can be in
addition to any anti-microbial agent that may or may not be added
to the composition. Such preservatives can be included irrespective
of whether the composition and containers are sterilized.
[0095] In embodiments, the materials and processes of the present
invention provide significant advantages over the current materials
and methods for wound closure. These advantages include, among
others, improved wound closure, improved wound approximation,
improved strength, ability to use on longer wounds, less run-off of
adhesive, longer working time, provision of an improved durable
microbial barrier, reduced procedure time, improved cosmesis, less
pain (during staple/suture removal) resulting in increased patient
satisfaction, and improved financial/economic outcomes by
eliminating follow-up visits for staple/suture removal.
[0096] The materials and processes of the present invention provide
improved wound closure. Because the composite structure provides a
flexible polymeric covering over the wound site, it provides a
degree of tension to assist in closing the wound and maintain the
wound closed. By a combination of the flexible material within the
composite structure, and the rigidity and adhesion provided by
polymerization of the polymerizable adhesive composition, the
composite structure provides improved strength, decreases wound
dehiscence, and assists healing.
[0097] The materials and processes of the present invention also
provide an improved microbial barrier. Because the composite
structure fully covers the wound, microbial transport into and out
of the wound are decreased. This in turn helps battle or prevent
infection, in turn resulting in faster wound healing.
[0098] The materials and processes of the present invention also
provide improved cosmesis. Such cosmesis benefits includes improved
cosmetic appearances both during and after the wound healing
process. For example, during wound healing, the composite
structures of the present invention provide decreased dressing bulk
and thickness and improved appearance. Furthermore, because the
composite structures permit more precise and sustained wound
approximation, the composite structures can provide decreased scar
appearance, such as in terms of scar width, scar tissue height,
scar coloration, and the like.
[0099] Related to the above advantages, the materials and processes
of the present invention provide increased patient satisfaction.
Increased satisfaction is provided, for example, due to the
improved cosmetic results, and improved assurance of wound closure
and dressing strength, and the like. In addition, because of the
strong bond provided, the composite structure of the present
invention is expected to remain in place over an external wound for
about 10 to 14 days, although shorter or longer times may be
provided. During that time, the patient can bathe without worrying
about water and contaminants entering the wound through the
dressing. Furthermore, because staple or suture removal is not
required, the patient experiences less pain and anticipation,
improving the healing experience.
[0100] The present invention is thus applicable to a wide range of
treatments, including wound treatment and other medical procedures.
For example, the present invention can be used as a replacement
for, or in addition to, sutures or staples to join together two
surfaces. The invention can also be used to coat, protect, or
otherwise cover surface, superficial, internal, or topical wounds
including, but not limited to, minor cuts, scrapes, irritations,
compromised skin, superficial lacerations, abrasions, burns, sores,
and stomatitis. The methods of the invention can also be used on
tissues that do not show any signs of tissue damage. For example,
the methods can be used to deliver medicaments to a patient through
healthy tissue. They can also be used, for example, to locally
deliver medicaments to tissues such as tumors or organs.
[0101] Specific embodiments of the invention will now be described
in detail. These Examples are intended to be illustrative, and the
invention is not limited to the materials, conditions, or process
parameters set forth in these embodiments. All parts and
percentages are by weight unless otherwise indicated.
EXAMPLES
Example 1
[0102] The working and setting times of the inventive composite
device, using a flexible textile material and a cyanoacrylate
polymerizable adhesive formulation, are compared to the working and
setting times of conventional available cyanoacrylate devices. The
conventional available cyanoacrylate devices used are the
DERMABOND.RTM. topical skin adhesive products comprising a
polymerizable monomer dispersed from an applicator having a porous
tip containing polymerization initiator. Two DERMABOND.RTM.
adhesive formulations are tested namely, a low viscosity adhesive
formulation, referred to here as DERMABOND LV and a high viscosity
adhesive formulation, referred to here as DERMABOND HV (both
manufactured by Closure Medical Corporation and available from
Ethicon). The composite devices of the present invention are also
prepared using the cyanoacrylate polymerizable adhesive
compositions of the DERMABOND LV and DERMABOND HV formulations,
with the cyanoacrylate polymerizable adhesive compositions being
extracted from the commercial applicators so that the composition
does not contact polymerization initiator that is present in the
applicator tips. These extracted cyanoacrylate polymerizable
adhesive compositions are referred to here as "composite adhesive
formulations".
[0103] Working time is a measurement of the time during which the
polymerizable adhesive composition can be expressed as a liquid
from the application device. Once the working time has expired, the
adhesive has polymerized within the applicator, clogging or
plugging the applicator tip. Setting time is the time required for
the adhesive to polymerize on a substrate once it has been
applied.
[0104] Synthetic SPECTRA MESH.RTM. filtration material (available
from Spectrum Laboratories, Inc.), a textile with 70 .mu.m pores
(openings) and an open area of 36%, is cut into strips 1.0
cm.times.3.75 cm. Benzyldimethylhexa-decylammonium chloride (BHC)
initiator is immobilized within the textile by dipping the strips
of textile in either 0.1 M or 0.15 M solutions of BHC in methanol.
Each strip is fully saturated with initiator solution by dipping
for 2 to 3 seconds. Following dipping, the textile strips are
placed onto a polyethylene board and allowed to air-dry for at
least 24 hours at 25.degree. C.
[0105] The DERMABOND LV and DERMABOND HV adhesive formulations and
the composite adhesive formulations are tested by applying them to
poly(vinyl chloride) (PVC) slides heated to 31.5.degree.
C..+-.1.5.degree. C. The slides are used in concert with a
thermocouple data acquisition apparatus, which is used to monitor
setting time and temperature of the samples.
[0106] For evaluation of setting times, DERMABOND LV adhesive
formulation is applied to the PVC slides in a thin layer using the
commercially-available DERMABOND.RTM. applicator that includes a
porous tip loaded with initiator for initiation of the adhesive
polymerization. Setting times and temperatures are determined for
10 samples. Working times are determined by inspection. Similarly,
DERMABOND HV adhesive formulation setting time is tested and data
is acquired for 10 samples. The results are shown in Table 2
below.
[0107] The setting and working times of adhesive formulations of
four composite devices are also investigated: (1) DERMABOND LV
adhesive formulation and SPECTRA MESH.RTM. filtration material
dipped in 0.1 M BHC solution (Composite A); (2) DERMABOND LV
adhesive formulation and SPECTRA MESH.RTM. filtration material
dipped in 0.15 M BHC solution (Composite B); (3) DERMABOND HV
adhesive formulation and SPECTRA MESH.RTM. filtration material
dipped in 0.15 M BHC solution (Composite C); and, (4) DERMABOND LV
adhesive formulation and SPECTRA MESH.RTM. filtration material used
as-received, without the addition of BHC initiator (Composite
Control). In the composite formulations, the DERMABOND LV and
DERMABOND HV adhesive formulations used are the same as those
formulations found in the commercial DERMABOND LV adhesive
applicator and the DERMABOND HV applicator; however, when testing
the composite adhesive formulations, these adhesives are used
without initiation by an applicator device including an initiated
porous tip. Instead, a pipetter is used to dispense the adhesives,
and initiation of the adhesive polymerization is accomplished by
the BHC initiator immobilized within the nylon mesh. The components
of the composite devices are summarized in the following Table 1.
TABLE-US-00001 TABLE 1 Composite Devices Initiator Solution Applied
to Flexible Adhesive Sample Flexible Material Material Composition
DERMABOND LV None None DERMABOND LV (applicator initiated)
DERMABOND LV None None DERMABOND HV (applicator initiated)
Composite A SPECTRA MESH .RTM. 0.1 M BHC DERMABOND LV Composite B
SPECTRA MESH .RTM. 0.15 M BHC DERMABOND LV Composite C SPECTRA MESH
.RTM. 0.15 M BHC DERMABOND HV Composite Control SPECTRA MESH .RTM.
None DERMABOND LV
[0108] During composite formulation testing, 75 .mu.L of adhesive
is pipetted onto the center of each mesh test strip. Nineteen (19)
samples are tested for Composite A, 20 samples for Composite B, 10
samples for Composite C, and 20 samples for the composite control.
The thermocouple data acquisition apparatus is used to monitor
setting time and temperature as with the DERMABOND LV and DERMABOND
HV samples. Working times are determined by inspection.
TABLE-US-00002 TABLE 2 Testing Results Setting Working Setting Time
Temperature Formulation Time (sec) (.degree. C.) DERMABOND LV <3
min 74.9 .+-. 20.8 44.2 .+-. 4.0 DERMABOND HV <3 min 110.1 .+-.
18.9 50.0 .+-. 6.3 Composite A >8 hours 32.7 .+-. 6.3 47.1 .+-.
5.5 Composite B >8 hours 30.9 .+-. 4.8 49.2 .+-. 5.7 Composite C
>8 hours 49.6 .+-. 10.2 50.1 .+-. 5.9 Composite >8 hours
>5400 ND (non- Control detectable)
[0109] Evaluation of the data presented in the table reveals the
effects of the initiation method used in the cyanoacrylate textile
(mesh) composite on both working and setting times, and the
resulting composite structure. Initiation of the adhesive
polymerization using initiator immobilized within the mesh, instead
of initiator contained within a porous applicator tip, dramatically
increases the working time of the adhesive. Commercially-available
DERMABOND.RTM. adhesive applicators have a working time that is
determined by the polymerization time of the adhesive within the
initiated applicator. The inventive composite formulation does not
require an initiated application tip. The initiator is present
within the mesh, and initiation of the adhesive occurs only on the
substrate when adhesive is applied to the mesh. Adhesive can be
applied to the mesh at any desired rate, and it will remain liquid
in the applicator for a much longer period of time than it would in
an adhesive applicator that includes initiator in an applicator
tip.
[0110] Setting time is also dramatically affected by the initiation
method of the inventive adhesive mesh composite. The setting times
of Composite A and Composite B are approximately 50% the setting
time of DERMABOND LV adhesive and approximately 30% the setting
time of DERMABOND HV adhesive. Composite C shows similarly dramatic
results. Setting times are lowered in the composites without
increasing setting temperatures, something that would not be
possible using conventional application devices that include
initiator in the applicator tip. To decrease setting time using
current applicator technology, the amount of initiator in the
porous applicator tip would have to be significantly increased,
which would be accompanied by a concomitant increase in the
associated setting temperature. Having initiator evenly distributed
throughout the textile alters initiation and polymerization
kinetics, facilitating more efficient initiator-adhesive mixing.
This improved mixing configuration serves to lower setting times
while maintaining low setting temperatures. In addition, this
mixing configuration enables improved control of setting time and
temperature through controlled distribution of initiator within the
composite. As a result, the composite structure can be formed as a
wound covering and closure device in a manner that is quick (i.e.,
that has a fast setting time) and easier to apply (longer working
time), but which remain comfortable to the patient (i.e., as not
having a significantly high setting temperature).
[0111] The above improvements provided by the present invention
also provide valuable benefits to medical professionals or other
using the methods and devices of the invention. For example, the
faster setting time enables medical professionals to apply the
composite structure as a wound closure device much faster than
previously possible, freeing up the medical professional to proceed
to other tasks and to speed the treatment process, providing faster
and more efficient procedures. This in turn could result in lower
operating room and treatment costs, and reduced patient and
insurance charges.
Example 2
[0112] The tensile strength of film samples of DERMABOND LV
adhesive are compared to the tensile strength of Composite A,
described in Example 1 above.
[0113] Thin films of DERMABOND LV adhesive are prepared by
expressing the adhesive from a DERMABOND LV applicator onto a glass
plate. Subsequently, a second glass plate of the same size is
placed on top of the adhesive such that the adhesive is pressed
between the two plates. Once the adhesive polymerizes, the glass
plates are separated and the film of adhesive is removed. This film
was then cut into strips with dimensions 4.0 inch.times.0.5 inch.
Ten DERMABOND LV film strips are thus prepared.
[0114] Strips of Composite A are prepared using SPECTRA MESH.RTM.
filtration material loaded with initiator by dip coating in an 0.1
M solution of BHC in methanol, as described above. Dip coated
strips are allowed to dry for 24 hours prior to their use. Mesh
strips, measuring 4.0 inch.times.0.5 inches, are saturated with
DERMABOND LV adhesive by expressing the adhesive from a pipetter
onto the strips in the same manner as in Example 1. By this method,
10 strips of Composite A are prepared.
[0115] An MTS Sintech 2/G apparatus is used for tensile testing.
Prior to testing, all film samples are stored at 25.degree. C. for
at least 4 hours. The dimensions of each sample are measured 3
times before testing, and the average values are determined. The
average width of the DERMABOND LV adhesive films is 0.513 inch and
the average thickness is 0.009 inch. The average width of the
Composite A strips is 0.494 inch and the average thickness is 0.014
inch. The tensile strengths of the DERMABOND LV adhesive strips and
the Composite A strips are tested by pulling the strips to failure
by breakage using a gauge length of 1.0 inch and a crosshead speed
of 3.0 inch per minute. The tensile strength data is shown in Table
3 below: TABLE-US-00003 TABLE 3 Tensile Strength Results Stress
Elongation Strain at Break at Break at Break Sample (PSI) (in) (%)
DERMABOND LV 615.3 .+-. 123.3 3.07 .+-. 1.03 301.8 .+-. 101.3
Composite A 1932.6 .+-. 298.2 0.38 .+-. 0.05 37.2 .+-. 5.2
[0116] Review of the tensile strength data reveals the dramatically
higher tensile strength of Composite A in comparison to DERMABOND
LV adhesive film. Formation of a composite adhesive by the method
used for Composite A results in a stress at break (i.e., the amount
of stress applied immediately before sample breaks) for that
composite that is more than 300% that of the DERMABOND LV adhesive
film. The strain at break for Composite A is also dramatically
different than that of DERMABOND LV adhesive film, its value being
approximately 12% of that of the strain at break value for
DERMABOND LV. This data demonstrates that composite structures of
the present invention have distinctively different mechanical
properties than films of commercially-available DERMABOND LV
adhesive.
[0117] While the invention has been described with reference to
preferred embodiments, the invention is not limited to the specific
examples given, and other embodiments and modifications can be made
by those skilled in the art without departing from the spirit and
scope of the invention.
* * * * *