Methods for Treating Non-Suturable Wounds by the Use of Cyanoacrylate Adhesives
Methods for Treating Non-Suturable Wounds by the Use of Cyanoacrylate Adhesives
US6342213
Company:
Folder:
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Abstract:
A cyanoacrylate adhesive is applied to non-suturable, non-sterile wound surfaces to protect and/or treat such surfaces, to promote wound healing and to retard infection of the wound.
Type of document:
Language:
(12) United States Patent
Barley et al.
US006342213B1
(10) Patent N0.: US 6,342,213 B1
(45) Date of Patent: Jan. 29, 2002
(54) METHODS FOR TREATING NON-
SUTURABLE WOUNDS BY USE OF
CYANOACRYLATE ADHESIVES
(75) Inventors: Leonard V. Barley; Linda M. Barley;
J . Royce Renfrow, all of Colorado
Springs; Patrick J . Tighe, Littleton, all
of CO (US)
(73) Assignee: MedLogic Global Corporation,
Colorado Springs, CO (US)
Subject to any disclaimer, the term of this
patent is extended or adjusted under 35
U.S.C. 154(b) by 0 days.
( * ) Notice:
(21) Appl. N0.: 08/231,638
(22) Filed: Apr. 22, 1994
Related U.S. Application Data
(63) Continuation—in—part of application No. 08/133,190, filed on
Oct. 19, 1993, now abandoned, which is a continuation—in—
part of application No. 07/895,589, filed on May 9, 1992,
now abandoned.
(51) Int. Cl.7 .............................................. .. A61K 31/78
(52) U.S. Cl. .............................. .. 424/78.35; 424/78.02;
424/78.05; 424/78.06; 424/78.07; 424/78.27;
424/407, 523/111
(58) Field of Search ......................... .. 424/78.35, 78.02,
424/78.08, 443, 78.05, 78.06, 78.27, 445,
523/111, 602/42, 43, 52, 54, 904
(56) References Cited
U.S. PATENT DOCUMENTS
2,804,073 A 8/1957 Galliene et al. .. 128/156
3,527,224 A 9/1970 Rabinowitz . . . . . . . . . . . . .. 526/297
3,591,676 A 7/1971 Hawkins et al. .. 424/78.06
3,667,472 A 6/1972 Halpern ................ .. 128/334 R
3,722,599 A 3/1973 Robertson et al.
3,995,641 A 12/1976 Kroenthal et al. ........ .. 558/400
4,035,334 A 7/1977 Davydov et al. ...... .. 424/78.06
4,444,933 A 4/1984 Columbus et al. ........ .. 524/292
4,650,826 A 3/1987 Waniczek et al. 524/730
4,958,748 A 9/1990 Otake ....................... .. 222/108
5,306,490 A * 4/1994 Barley, Jr. ............. .. 424/38.35
5,514,372 A * 5/1996 Leung et al. .......... .. 424/78.35
OTHER PUBLICATIONS
Lehman, Ralph A.W. et al., “Toxicity of Alkyl 2—Cyanoacry-
late: Bacterial Growth”, pp 447-450, Sep. 1966, Archives of
Surgery, vol. 93.
Leonard, Fred et al., “Synthesis and Degradation of Poly-
(alkyl-a-Cyanoacrylate)”, pp 259-272, 1966, Journal of
Applied Polymer Science, vol. 10.
Makady, F.M. et al., “Effect of tissue adhesives and suture
patterns on experimentally induced teat lacerations in lac-
tating dairy cattle”, pp 1932-1934, Jun. 1991, JAVMA,
Reports of Original Studies, vol. 198, No. 11.
Matsumoto, Teruo, “Becteriology and Wound Healing”, pp
106-113, 1972, Chapter 3 in Tissue Adhesives in Surgery.
Vlatsumoto, Teruo, “Clinical Considerations and Appplica-
tions of Bucrylate Tissue Advesive”, pp 226-237, 1972,
Tissue Adhesives in Surgery, Chap. 1, Sec. III.
Vlatsumoto, Teruo, “Reactions of the Organism to Acry-
late-Adhesives”, pp 436-444, 1972, Tissue Adhesives in
Surgery.
Vlatsumoto, Teruo et al., “Tissue Adhesive and Wound
Healing”, pp 266-271, Mar. 1969,Archives of Surgery, vol.
98.
Vlizrahi, S. et al., “Use of Tissue Adhesives in the Repair of
Lacerations in Children”, pp 312-313, Apr. 1988, Journal of
Pediatric Surgery, vol. 23, No. 4.
Vlorton, R.J. et al., “The Use of Histoacryl Tissue Adhesive
for the Primary Closure of Scalp Wounds”, pp 110-112,
1988, Archives of Emergency Medicine, vol. 5.
Ousterhout, D.K. et al., “Cultaneous Absorption of n-Alky-
l-a-Cyanocrylate”, pp 157-163, 1968, Journal of Biomedi-
cal Materials Research, vol. 2.
Pepper, D.C., “Kinetics and Mechanism of Zwitterionic
Polymerization of Alkyl Cyanocrylate”, pp 629-637, 1980,
Polymer Journal, vol. 12, No. 9.
Pepper, David Charles et al., “Kinetics of Polymerization of
Alkyl Cyanoacrylate by Tertiary Amines and Phosphines”,
pp 395-410, 1983, Makromol. Chem., vol. 184.
Ronis, Max L. et al., “Review of Cyanoacylate Tissue Glues
with Emphasis of Their Otorhinolaryngological Applica-
tions”, pp 210-213, Feb. 1984, Laryngoscope., vol. 94.
Saches, Michael Evan., “Enbucrylate as Cartilage Adhesive
in Augmentation Rhinoplasty”, pp 389-393, Jun. 1985,
Archives of Otolaryngology, vol. 111.
Toriumi, Dean M. et al., “Histotoxicity of Cyanoacrylate
Tissue Adhesives: A Comparative Study”, pp 546-550, Jun.
1990, Archives of Otolaryngology Head and Neck Surgery,
vol. 116.
Tseng, Yin-Chao et al., “Modification of Synthesis and
Investigation of Properties for 2-Cyanoacrylate”, pp 73-79,
Jan. 1990, Biomaterials, vol. 11.
Vinters, H.V. et al., “The Histotoxicity of Cyanoacrylate: A
Selective Review”, pp 279-291, 1985, Neuroradiology, vol.
27.
Watson, David P., “Use of Cyanoacrylate Tissue Adhesive
for Closing Facial Lacerations in Children”, p 1014, Oct.
1989, British Medical Journal, vol. 299.
Akers, William A., “Treating Friction Blisters With
Alkyl-ot-Cyanoacrylates”, Arch Dermatol, vol. 107,
544-547, Apr. 1973.
Bhaskar, Surindar N. et al., “Healing of Skin Wounds with
Butyl Cyanoacrylate”, pp 294-297, 1969, Journal of Dental
Research, vol. 48, No. 2.
(List continued on next page.)
Primary Examiner—Neil S. Levy
(74) Attorney, Agent, or Firm—Burns, Doane, Swecker &
Mathis LLP
(57) ABSTRACT
A Cyanoacrylate adhesive is applied to non-suturable, non-
sterile wound surfaces to protect and/or treat such surfaces,
to promote wound healing and to retard infection of the
wound.
5 Claims, No Drawings
US 6,342,213 B1
Page 2
U.S. PATENT DOCUMENTS
Dalvi, A. et al., “Non-suture Closure of Wound Using
Cyanocrylate”, 97-100, 1986, Journal of Postgraduate
Medicine, vol. 32, No. 2.
Eiferman, Richard A. et al., “Antibacterial Effects of
Cyanoacrylate Glue”, pp 958-960, Jun. 1983, Archives of
Ophthalmology, vol. 101.
Ellis, David A.F. et al., “The Ideal Tissue Adhesive in Facial
Plastic and Reconstructive Surgery”, pp 68-72, 1990, The
Journal of Otolaryngology, vol. 19, No. 1.
Fung, Ramona Q. et al., “Use of Butyl-2-Cyanoacrylate in
Rabbit Auricular Cartilage”, pp 459-464, Jul. 1985,
Archives of Otolaryngology, vol. 111.
Galil, K.A. et al., “The Healing of Hamster Skin Ulcers
Treated with N-butyl-2-cyanoacrylate(Histoacryl blue)”,
pp 601-607, 1984, Journal of Biomedical Materials
Research, vol. 18.
Harper, Marion C., “Stabilization of Osteochondral Frag-
ments Using Limited Placement of Cyanoacrylate in Rab-
bits”, pp 272-276, Jun. 1988, Clinical Orthopaedics and
Related Research 231.
Kamer, Frank M. et al., “Histoacryl: Its Use in Aesthetic
Facial Pastic Surgery”, pp 193-197, Feb. 1989, Archives of
Otolaryngology Head and Neck Surgery, vol. 115.
Kosko, Paul I. “Upper Lid Blepharoplasty: Skin Closure
Achieved with Butyl-2-Cyanoacrylate”, pp 424-425, Jun.
1981, Ophthalmic Surgery, vol. 12.
* cited by examiner
US 6,342,213 B1
1
METHODS FOR TREATING NON-
SUTURABLE WOUNDS BY USE OF
CYANOACRYLATE ADHESIVES
CROSS-REFERENCE TO RELATED
APPLICATIONS
This application is a continuation-in-part of U.S. patent
application Ser. No. 08/133,199 filed Oct. 19, 1993 (derived
from International Application Ser. No. PCT/US93/05487),
now abandoned, which is a continuation-in-part of U.S.
patent application Ser. No. 07/895,589, filed Jun. 9, 1992
also now abandoned, both of which applications are incor-
porated herein by reference in their entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention is directed to methods for treating non-
suturable wounds by using cyanoacrylate adhesives. The
cyanoacrylate adhesive to be used can be stored in dispens-
ers for single or repeated/inter-mittent use.
2. State of the Art
Cyanoacrylate adhesives have been suggested for a vari-
ety of adhesive purposes including glues and surgical adhe-
sives. In particular, cyanoacrylates of formula I:
cH2=c—CoR
CN
wherein R is an alkyl or other suitable substituent are
disclosed in U.S. Pat. Nos. 3,527,224; 3,591,676; 3,667,472;
3,995,641; 4,035,334; and 4,650,826. Typically, when used
as an adhesive for living tissues, the R substituent is alkyl of
from 2 to 8 carbon atoms and most often is butyl (e.g.,
n-butyl).
The suggested medical uses for cyanoacrylate adhesives
include surgical environments wherein the cyanoacrylate
adhesive is utilized, e.g., as an alternative to sutures or as a
hemostat and, as such, are necessarily employed in a sterile
environment. See, for example, Halpern, U.S. Pat. No.
3,667,472, and Robertson, et al., U.S. Pat. No. 3,722,599. In
such surgical environments, the cyanoacrylate adhesive is
applied to the soft tissue under sterile conditions and, in the
presence of water or protein found in soft tissue, the adhe-
sive bonds to the tissue as well as polymerizes which, in the
case of adhesive sutures, joins the separated sections of soft
tissue together.
Contrarily, most small wounds are neither treated in a
surgical setting nor in a sterile environment. In a typical
home setting, small wounds are generally cleaned and are
either left exposed (generally if not bleeding) or are covered
with a bandage (generally the case where minor bleeding
occurs or where there is irritation). In either case, the wound
is usually left to heal on its own over time with the
accompanying discomfort during this period.
In any event, the art teaches against the use of alkyl
cyanoacrylates on human skin tissue where it will be
absorbed internally because of the lack of suitable low
toxicity and/or adequate resorption/absorption properties for
these cyanoacrylates. See, for example, Robertson, et al.,
U.S. Pat. No. 3,722,599. Specifically, it has been reported
that, when used as suture supplements or internally, poly-
meric residue of higher homologs of alkyl cyanoacrylate
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(e.g., n-butyl cyanoacrylate) has been observed by histo-
logical examination of the site of application as much as 12
months after application. Apparently, the cyanoacrylate
polymeric residue is encased internally and, due to low
biological absorption/resorption properties, remains at the
site of application for prolonged periods of time. Such poor
absorption/resorption properties are contra-indicative for
their use as tissue adhesives.
SUMMARY OF THE INVENTION
This invention is drawn to methods for treating and/or
protecting small superficial wounds by the application of
alkyl cyanoacrylate adhesive to the surface of such wounds.
Such small superficial wounds are characterized as superfi-
cial cuts or abrasions not penetrating through the dermal
layer of the skin surface to the subcutaneous layer or tissue.
This invention is based, in part, on the discovery that
application of cyanoacrylate adhesive to such small super-
ficial wounds will not result in the undesirable prolonged
internalization of polymeric adhesive. Without being limited
to any theory, Applicants believe that such internalization of
the polymeric residue does not occur because any polymeric
residue entrapped within the epidermal and/or dermal layer
will be shed as part of the normal shedding of these layers.
Moreover, contrary to typical prior art application
methods, Applicants have found that by limiting application
to such superficial cuts and abrasions, the cyanoacrylate
adhesive can be applied under non-sterile conditions typi-
cally employed in consumer usage.
The methods of this invention involve applying a
cyanoacrylate adhesive, particularly, n-butyl cyanoacrylate
adhesive, onto the wound under non-sterile conditions and
allowing the adhesive to polymerize.
In the case of cuts, the cyanoacrylate adhesive is generally
applied between the separated skin defining the cut as well
as over the cut. The cyanoacrylate adhesive is then allowed
to polymerize so as to both bind the separated skin sections
and form a polymer layer over the cut. In addition to serving
as a protective layer, the polymer layer also serves to
promote healing and to retard infection of the cut.
In the case of abrasions, the cyanoacrylate adhesive is
generally applied over the abrasion. The cyanoacrylate
adhesive is allowed to polymerize so as to form a polymer
layer over the abrasion. The polymer layer serves to act as
a protective layer which prevents further aggravation to the
abrasion while also promoting healing and retarding infec-
tion of the abrasion.
Accordingly, in one of its method aspects, this invention
is directed to a method for treating and/or protecting non-
suturable superficial wounds which comprises:
applying to the surface of a non-suturable wound, in a
non-sterile environment, a sufficient amount of a
cyanoacrylate adhesive so as to cover the entire wound
area wherein the wound is characterized as superficial
cuts and/or abrasions which do not penetrate through
the dermal layer of the skin surface to the subcutaneous
layer; and
polymerizing the cyanoacrylate adhesive so as to join
separated skin sections and/or to form an adhesive
coating which adheres to the area where the adhesive
was applied,
wherein the cyanoacrylate, in monomeric form, is repre-
sented by formula I:
US 6,342,213 B1
O
ll
cH2=c—CoR
CN
where R is alkyl of 2 to 10 carbon atoms.
Preferably R is alkyl of from 2 to 8 carbon atoms and
more preferably alkyl of from 4 to 8 carbon atoms. Most
preferably, R is either n-butyl or octyl.
In another of its method aspects, this invention is directed
to a method for treating and/or protecting superficial non-
suturable cuts which method comprises:
applying to the surface of a non-suturable cut in a non-
sterile environment, a sufficient amount of n-butyl
cyanoacrylate adhesive to cover the entire cut area
wherein said cut is characterized as a superficial cut
which does not penetrate through the dermal layer of
the skin surface to the subcutaneous layer; and
polymerizing the cyanoacrylate adhesive so as to join
separated skin sections and to form an adhesive coating
which adheres to the area where the adhesive was
applied
wherein, in monomeric form, the n-butyl cyanoacrylate
adhesive is represented by the formula:
ll
cH2= c— COCHZCHZCHZCH3.
CN
In a preferred embodiment, the cyanoacrylate is applied at
least about 0.02 milliliter (ml), more preferably from about
0.02 to about 0.2 ml, and still more preferably from about
0.02 to about 0.1 ml, of cyanoacrylate adhesive per square
centimeter of skin which is to be covered.
In another preferred embodiment, the cyanoacrylate adhe-
sive to be applied to the skin has a viscosity of from about
2 to about 3000 centipoise at 20° C. More preferably, the
cyanoacrylate adhesive is in monomeric form and has a
viscosity of from about 2 to about 100 centipoise at 20° C.
As used herein, the following terms have the following
meanings:
the term “cyanoacrylate adhesive” refers to adhesive
formulations based on cyanoacrylate monomers of for-
mula I:
O
ll
cH2=c—CoR
CN
where R is selected from the group consisting of alkyl
of 2 to 10 carbon atoms.
Preferably, R is an alkyl group of from 2-8 carbon atoms
including ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,
sec-butyl, n-pentyl, iso-pentyl, n-hexyl, iso-hexyl, 2-ethyl-
hexyl, n-heptyl, and octyl. More preferably, R is butyl or
octyl and most preferably, R is n-butyl.
These cyanoacrylate adhesives are known in the art and
are described in, for example, U.S. Pat. Nos. 3,527,224;
3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826
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the disclosures of each are incorporated herein by reference
in their entirety.
Preferred cyanoacrylate adhesives for use in this inven-
tion are n-butyl-2-cyanoacrylate and octyl-2-cyanoacrylate.
The cyanoacrylate adhesives described herein rapidly
polymerize in the presence of water vapor or tissue protein,
and the n-butyl-cyanoacrylate is capable of bonding human
skin tissue without causing histoxicity or cytotoxicity.
The term “non-suturable or small wounds” means super-
ficial cuts and abrasions characterized as superficial cuts
and/or abrasions which do not penetrate through the dermal
layer of the skin surface to the subcutaneous layer. Such
superficial wounds include cuts where the skin is separated
and can be joined together, as well as abrasions such as
“nicks” or “scrapes” where the skin is removed. However,
non-suturable wounds do not include puncture wounds.
In view of the above, non-suturable wounds as defined
herein include common cuts and scratches which rarely need
medical attention unless located in a sensitive area or unless
secondary infection occurs. As opposed to the edges of
suturable wounds which can be widely separated, the edges
of non-suturable wounds can easily be opposed or brought
together. One particular example of a non-suturable wound
treatable by the methods of this invention is skin tearing
adjacent the site of a catheter implant.
DETAILED DESCRIPTION OF THE
PREFERRED EMBODIMENTS
This invention relates to methods for treating and/or
protecting non-suturable superficial wound surfaces with
cyanoacrylate adhesives in an every day, typical non-sterile
environment.
The cyanoacrylate adhesive to-be-applied to the superfi-
cial wound surface can be monomeric or partially polymeric.
In general, partially polymerized cyanoacrylate adhesives
are liquid polymers having a higher viscosity than that of the
corresponding monomer and, therefore, are better suited for
those applications which are intended to be specific for a
particular skin area. In other words, less viscous materials
are more likely to “run” (i.e., flow) into areas where appli-
cation was not intended.
The cyanoacrylate adhesives used herein preferably have
a viscosity of from about 2 to about 3000 centipoise and
more preferably from about 2 to about 100 centipoise at 20°
C. It is contemplated, however, that pastes and gels having
viscosities of up to 50,000 centipoise at 20° C. can also be
employed and will make for easier skin application.
The specific viscosity of the formulation depends, in part,
on the amount and degree of partially polymerized
cyanoacrylate adhesive employed as well as additives which
are employed in the formulation to enhance or decrease
viscosity. Such factors are readily ascertainable by the
skilled artisan. For example, methods for preparing partially
polymerized cyanoacrylate adhesives are disclosed, for
example, by Rabinowitz, U.S. Pat. No. 3,527,224 which is
incorporated herein by reference in its entirety. Additives
which can be incorporated into the formulation to enhance
its viscosity include polymers such as polymethyl methacry-
late (PMMA) and polymerized cyanoacrylate adhesives as
disclosed in U.S. Pat. Nos. 3,654,239 and 4,038,345 both of
which are incorporated herein by reference in their entirety.
Monomeric forms of cyanoacrylate adhesives are often
preferred where application is to be made to a large surface
area. This preference results from the fact that these forms
are less viscous and, accordingly, will permit more facile
large surface area application. Mixtures of monomeric forms
US 6,342,213 B1
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of cyanoacrylate adhesive and partially polymerized forms
of cyanoacrylate adhesive can also be used to prepare a
formulation having intermediate viscosities.
For purposes of this invention, monomeric or partially
polymerized n-butyl-2-cyanoacrylate is a particularly pre-
ferred adhesive and is capable of effectively bonding human
skin tissue without causing histoxicity or cytotoxicity.
Upon contact with skin moisture and tissue protein, the
cyanoacrylate adhesives will polymerize or, in the case of
partially polymerized cyanoacrylate adhesives, will further
polymerize, at ambient conditions (skin temperature) over
about 10 seconds to 60 seconds to provide a solid layer
which forms over and strongly adheres to the surface of the
skin, thus providing a protective layer to the wound area.
The adhesive is applied to provide an effectively thick
coating over the surface of the superficial wound. Because
the to-be-treated wound is superficial and does not extend
beyond the dermal layer, any polymeric residues diffusing
into or forming in the wound will be naturally extruded from
the skin. Generally, the adhesive provides an adhesive film
coating over the wound area which when set is satisfactorily
flexible and adherent to the tissue without premature peeling
or cracking. Preferably, the adhesive coating has a thickness
of less than about 0.5 millimeter (mm), and more preferably
the coating has a thickness of less than about 0.3 mm. In a
particularly preferred embodiment, the thickness of the
adhesive coating is from about 0.1 millimeter to about 0.5
millimeter and even more preferably from about 0.1 milli-
meter to about 0.3 millimeter.
Adhesive coatings of such thicknesses form a physical
barrier layer over superficial wounds which coatings provide
protection for the wound in the same manner as a conven-
tional bandage, e.g., Band-AidTM brand bandages.
Specifically, the cyanoacrylate adhesive coating provides an
airtight, waterproof seal around the wound which does not
need to be replaced when the wound gets wet. Once applied,
the coating prevents bacterial and contaminant entry into the
wound, thus reducing the rate of secondary infection.
Generally, the adhesive coating does not limit dexterity and
promotes faster wound healing.
Additionally, 11nlike conventional bandages, the adhesive
coating of this invention naturally sloughs off the skin within
2-3 days after application and, accordingly, avoids the
discomfort associated with removal of conventional ban-
dages from the skin. However, if early removal of this
polymeric coating is desired, such can be achieved by use of
solvents such as acetone.
The adhesive coating can be formed by applying at least
about 0.02 ml of cyanoacrylate adhesive per square centi-
meter of skin, more preferably from about 0.02 to about 0.2
ml, and still more preferably from about 0.02 to about 0.1
ml, of cyanoacrylate adhesive per square centimeter of skin
and yet more preferably from about 0.02 to about 0.05 ml of
cyanoacrylate adhesive per square centimeter of skin.
FORMULATIONS
The cyanoacrylate adhesive formulations employed
herein generally comprise monomeric and/or partially poly-
merized compounds of formula I described above and are
sometimes referred to herein as simply cyanoacrylate adhe-
sives. These formulations are liquid in nature and, upon
contact with surface skin proteins and moisture, will poly-
merize to provide a solid film or layer over the skin surface.
The formulations may additionally contain one or more
optional additives such as colorants, plasticizers, perfumes,
anti-diffusion agents, modifying agents and stabilizers. In
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practice, each of these optional additives should be both
miscible and compatible with the cyanoacrylate adhesive.
Compatible additives are those that do not prevent the use of
the cyanoacrylate adhesives in the manner described herein.
In general, colorants are added so that the polymerized
film will contain a discrete and discernable color. Perfumes
are added to provide a pleasant smell to the formulation.
Stabilizers, such as sulfur dioxide, are added to retard in situ
polymerization in containers during storage. Plasticizers,
such as dioctylphthalate or tri (p-cresyl)phosphate, are
added in order to enhance the flexibility of the resulting
polymer layer. Each of these additives is conventional. For
example, suitable stabilizers are disclosed in U.S. Pat. No.
4,650,826 and suitable plasticizers are disclosed in U.S. Pat.
Nos. 2,784,127 and 4,444,933 the disclosures of all of these
patents being incorporated herein by reference in their
entirety.
The amount of each of these optional additives employed
in the cyanoacrylate adhesive is an amount necessary to
achieve the desired effect.
The formulation is generally stored in an applicator for
use in a single dose application or for use in repeated
applications. Single dose applicators include those having
breakable or removable seals that prevent moisture, includ-
ing atmospheric moisture, from contacting the formulation
and causing in situ polymerization.
For repeated and intermittent usage, minimal exposure to
atmospheric moisture is required. This can be achieved by
devices having very narrow outlets and low initial dead
space. One applicator for such repeated intermittent use is
described in U.S. Pat. No. 4,958,748 which is incorporated
herein by reference in its entirety.
Another applicator comprises a conventional spray appli-
cator wherein the cyanoacrylate adhesive is sprayed onto the
surface skin area which includes the superficial wound. The
spray rate of the applicator can be controlled so that appli-
cation of a metered quantity of adhesive per unit area of skin
surface over a set period of time is controlled.
Still another applicator comprises a brush or solid paddle
applicator wherein the cyanoacrylate adhesive is “painted”
onto the surface skin area containing the superficial wound.
Apreferred applicator for repeated and intermittent usage
is an applicator suitable for the non-sterile storage and
metered dispersement of a cyanoacrylate adhesive after
opening of the applicator wherein the applicator is charac-
terized as having a resealable opening of no more than about
0.008 square inches (0.0516 square centimeters) so as to
permit the metered dispersement of the adhesive from the
applicator and which is capable of multiple administrations
of the adhesive and is further characterized as having
resealing means such as a cap which either tightly mates
with the applicator or which screws onto the applicator.
Preferably, the opening of the applicator is about 0.0016
to about 0.003 square inches (about 0.0103 to about 0.0194
square centimeters).
In another preferred embodiment, the walls of the appli-
cator are made of a pliable material, so that upon application
of pressure onto the walls, the walls depress sufficiently to
force the adhesive contained in the applicator through the
opening. Preferably, the applicator is manufactured with its
opening covered by a metal foil or other similar construction
which closes this opening until the device is ready for use.
The opening is then reinstated by use of a pin or similar
device which punctures the covering.
In applicators suitable for repeated intermittent uses, the
cyanoacrylate adhesive is stored at ambient conditions and
US 6,342,213 B1
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is selected to be bacteriostatic. See, for example, Rabinowitz
et al., U.S. Pat. No. 3,527,224. When the selected adhesive
is bacteriostatic, prolonged storage at ambient conditions is
without regard to the sterility of the formulation because
there is no adverse buildup of bacteria during storage.
METHODOLOGY
The above-described formulations are applied to a wound
area under conditions suitable for polymerizing the adhesive
so as to form a protective coating. In general, the wound is
usually first cleaned (soap/water and optionally a
disinfectant), and then sufficient amounts of cyanoacrylate
adhesive are employed to cover or encase the entire scrape,
scratch or nick area and is preferably extended by at least
about 1 centimeter beyond the wound. No other sterilization
methods are required as the methods of this invention are
readily practiced in a non-sterile environment.
For cuts, an amount sufficient to join the opposing skin
edges is applied, and optionally a sufficient amount is
applied to also encase the entire cut area. For scrapes, a
sufficient amount is applied to encase the entire wound area.
In either case, the adhesive polymer coating should pref-
erably be maintained in a unbroken manner over the entire
wound area. This can be assured by careful application of the
adhesive onto the skin/wound. Additionally, the use of a
plasticizer will facilitate the maintenance of the polymer
coating in an unbroken manner. However, to further ensure
that the polymer coating is maintained unbroken, after the
initial layer of adhesive has cured to provide for an adhesive
polymer coating, a second, preferably thinner, layer is
applied over the adhesive polymer coating. Additional
amounts of cyanoacrylate adhesive can be applied as needed
to maintain an unbroken coating covering over the wound
areas.
When the adhesive is applied to cover or encase the
wound area, sufficient cyanoacrylate adhesive is preferably
employed to form a coating of less than about 0.5 mm thick
and more preferably at least about 0.1 mm thick. Such
coatings are formed by applying at least about 0.02 ml of
cyanoacrylate adhesive per square centimeter of skin surface
area.
The amount of cyanoacrylate adhesive applied onto the
skin surface area can be controlled by the amount of
adhesive packaged in a single dose product or by use of a
multiple use dispenser which governs the amount of material
applied onto a unit area of surface skin. In this regard, the
dispenser described by Otake, U.S. Pat. No. 4,958,748,
which is incorporated by reference in its entirety, is particu-
larly advantageous because it dispenses the adhesive in a
controlled drop wise manner. Other methods for the con-
trolled dispersement of the cyanoacrylate adhesive are as
described above including, by way of example, a conven-
tional spray applicator, a brush or solid paddle applicator,
and the like.
Upon application of the cyanoacrylate adhesive, the sur-
face skin moisture, tissue protein, and temperature are
sufficient to initiate polymerization of the adhesive upon
application. Thereafter, the skin surface is maintained under
suitable conditions to allow polymerization to proceed to
formation of an adhesive coating.
In general, the particular length of time required for
polymerization will vary depending on factors such as the
amount of adhesive applied, the temperature of the skin, the
moisture content of the skin, the surface area of the wound,
and the like. However, in a preferred embodiment, polymer-
ization is generally complete within about 10 seconds to
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about 60 seconds while the skin is maintained at ambient
conditions. During this period, the person to whom appli-
cation of the cyanoacrylate adhesive has been made merely
allows the adhesive to form a coating while minimizing any
action to prevent the adhesive from being dislodged from
that portion of the skin where it was applied or to adhere to
unintended objects. Excess adhesive polymer can be
removed with acetone (nail polish remover) which can be
readily conducted except in the case where the adhesive
polymer binds to a sensitive skin part (e.g., eye lids) where
it should be removed by a health care professional. After the
adhesive coating has formed, the coating strongly adheres to
the skin, is flexible and waterproof, thereby protecting the
wound area and promoting healing.
It is important to note that the adhesive coating of the
invention can be applied in a non-sterile environment to a
non-sterile surface. This is directly contrary to the use of
cyanoacrylates as surgical adhesives which requires one-
time use in a sterile environment. The invention provides for
storage of the adhesive in a dispenser for repeated intermit-
tent uses in a non-sterile environment.
In general, the coating will adhere to the skin for a period
of about 2-3 days after which time it sloughs off. Additional
applications can be made if desired.
The coating protects non-suturable wounds because the
adhesive forms a polymer coating which extends over the
entire surface of the wound to protect the wound in much the
way a bandage does while, in the case of cuts, also joins
together the separated skin surfaces. Because the coating is
waterproof, the patient is not prevented from bathing and
other activities involving exposure to water during the
period the adhesive layer protects the wound.
One particular example of a non-suturable wound treat-
able by the methods of this invention is skin tearing adjacent
the site of a catheter implant. Specifically, it is common after
catheter implantation to have the skin adjacent the catheter
to tear, partially due to catheter movement relative to the site
of catheter implantation due to the patient’s muscle
contractions, etc. Such tears are typically non-suturable
wounds and can become the site of infection and are prone
to further tearing. Moreover, as the skin tears adjacent a
catheter implant, it becomes difficult to maintain the catheter
in the implant site. Heretofore, there were no acceptable
methods to treat such tearing and potentially inadvertent
catheter removal other than to reinsert the catheter at another
site.
The methods of this invention now provide for a method
to treat such tearing without removal of the catheter.
Specifically, in this particular aspect of the methods of this
invention, the cyanoacrylate adhesive is applied onto these
tears and then polymerized as described generally above.
This results in joining the separated skin sections of the tear
which protects the tear and retards further tearing thereof.
This method can also be employed prophylactically by
applying the cyanoacrylate adhesive to the skin areas adja-
cent the catheter prior to actual skin tearing. In this regard,
application is generally made in the manner and amounts
described above and is preferably applied to the skin area
approximately 1 centimeter and preferably about 0.5 centi-
meter in diameter around the catheter implant.
Accordingly, this aspect of the present invention is
directed to a method for retarding skin tearing adjacent a
catheter implant which method comprises:
applying a sufficient amount of a cyanoacrylate adhesive
so as to cover an untorn skin area adjacent a catheter
implant; and
US 6,342,213 B1
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polymerizing the cyanoacrylate adhesive so as to form a
polymer film over the skin area which film adheres to
the skin area where the adhesive was applied,
wherein the cyanoacrylate adhesive, in monomeric form,
is represented by formula I as described above.
In the above prophylactic methods, the polymer film or
coating is preferably less than about 0.5 millimeter in
thickness and more preferably from about 0.1 to about 0.5
millimeter in thickness and still more preferably, from about
0.1 to about 0.3 millimeter in thickness.
Whether employed prophylactically or to treat existing
tears, care should be taken during application of the
cyanoacrylate adhesive to the skin areas adjacent catheter
implantation to ensure against penetration of the adhesive
into the skin puncture defined by the catheter so as to avoid
skin irritation. One method for avoiding such penetration of
the adhesive is to employ a viscous cyanoacrylate adhesive
formulation preferably having a viscosity of from about 40
to about 100 centipoise at 20° C. Such viscous formulations
tend to remain at the site of application and not run into the
puncture wound. Moreover, a colorant can be incorporated
into the cyanoacrylate adhesive composition to readily dis-
cern where the adhesive has been applied.
Still another particular example of a non-suturable wound
treatable by the methods of this invention is the superficial
skin tearing remaining after suture removal. Typically, in the
case of suturable wounds (e.g., surgical wounds), the sepa-
rated skin sections are joined by either sutures or by staples
(collectively “sutures”), and the wound typically heals out-
ward. That is to say that the internal sections of the wound
heal first with subsequent healing outward to the skin
surface. Accordingly, when the sutures are removed, the
remaining wound is typically a superficial non-suturable
wound because the non-healed portions of the original
wound typically extend only to the dermal layer of the skin.
In this regard, application of the cyanoacrylate adhesive to
these wounds after suture removal as per the methods
described herein provides an effective method to treat these
wounds. Additionally, when the adhesive is applied to form
an adhesive coating over the wound, the resulting coating is
waterproof and flexible thereby allowing the patient signifi-
cant freedom in bathing, swimming, etc. as compared to
current practice after suture removal where the patient is
instructed to minimize water contact with the wound for
several days.
The following examples illustrates certain embodiments
of the invention but is not meant to limit the scope of the
claims in any way.
EXAMPLES
Example 1
A cyanoacrylate adhesive formulation was prepared in
monomeric form using n-butyl ot-cyano-acrylate. The for-
mulation was placed into the dispensing device described by
Otake, U.S. Pat. No. 4,958,748.
One drop of such a formulation is placed drop wise onto
the skin of a finger having a paper cut of about 0.05
centimeter in depth and about 3 centimeters in length. At this
depth, the cut does not penetrate through the dermal layer.
About 30 seconds is allowed for polymerization of the
adhesive. At which time, the separated skin areas defining
the cut are both joined and encased by a polymer coating.
Example 2
A cyanoacrylate adhesive formulation is prepared in
monomeric form using n-butyl ot-cyano-acrylate and which
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contains a colorant to readily ascertain where the formula-
tion has been applied, 20 weight percent of dioctyl phthalate
which acts as a plasticizer to enhance the flexibility of the
resulting polymer composition, and 200 parts per million
(ppm) of sulfur dioxide which acts as a stabilizer. The
formulation is placed into the dispensing device described
by Otake, U.S. Pat. No. 4,958,748.
One drop of such a formulation is placed drop wise onto
the skin of a finger having a paper cut of about 0.05
centimeter in depth and about 3 centimeters in length. At this
depth, the cut does not penetrate through the dermal layer.
About 30 seconds is allowed for polymerization of the
adhesive. At which time, the separated skin areas defining
the cut are both joined and encased by a polymer coating.
From the foregoing description, various modifications and
changes in the composition and method will occur to those
skilled in the art. All such modifications coming within the
scope of the appended claims are intended to be included
therein.
What is claimed is:
1. A method for treating and/or protecting non-suturable
superficial wounds which comprises:
applying to the surface of a non-suturable wound, in a
non-sterile environment, a sufficient amount of a
cyanoacrylate adhesive so as to cover the entire wound
area wherein the wound is characterized as superficial
cuts and/or abrasions which do not penetrate through
the dermal layer of the skin surface to the subcutaneous
layer; and
polymerizing the cyanoacrylate adhesive so as to join
separated skin sections and/or to form an adhesive
coating which adheres to the area where the adhesive
was applied,
wherein the cyanoacrylate, in monomeric form, is repre-
sented by formula I:
cH2=c—CoR
CN
where R is alkyl of 2 to 10 carbon atoms.
2. A method according to claim 1 wherein R is alkyl of
from 2 to 8 carbon atoms.
3. A method according to claim 2 wherein R is butyl or
octyl.
4. A method according to claim 3 wherein R is n-butyl.
5. A method for treating and/or protecting superficial
non-suturable cuts which method comprises:
applying to the surface of a non-suturable cut in a non-
sterile environment, a sufficient amount of n-butyl
cyanoacrylate adhesive to cover the entire cut area
wherein said cut is characterized as a superficial cut
which does not penetrate through the dermal layer of
the skin to the subcutaneous layer; and
polymerizing the cyanoacrylate adhesive so as to join
separated skin sections and to form an adhesive coating
which adheres to the area where the adhesive was
applied
wherein, in monomeric form, the n-butyl cyanoacrylate
adhesive is represented by the formula:
US 6,342,213 B1
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* * * * *
‘I?
CH2: C: COCHZCHZCHZCH3.
CN 5
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