Note: Descriptions are shown in the official language in which they were submitted.
W092/049~3 PCT/CA91/00327
~ 9 2 7 0 ~
This invention relates to wound coverings, of the
type commonly applied adhesively to minor cuts, burns,
post-operative incision sites and wounds. ~ore particular-
ly, the invention relates to adhesive bandages or patches
which ar~ applied domestically to cover and protect such
wounds, by adhesion to the wound itself or to its periph-
ery~ The best known examples of such adhesive patches are
those sold under the names BAND-AID (trade-mar~ of Johnson
& Johnson, Inc.), ELASTOPLAST (trade-mark of Smith & Nephew
Limited) and HANSAPLAST (txade-mark of Beiersdorf A.G.).
These familiar s~rip bandages commonly comprise
a patch of sterile gauze mounted on a plastic or fabric
strip, with an adhesive coating for attachment to the skin.
The gauze may be covered with a perforated plastic strip,
to prevent adhesion of the gauze to the wound surface. It
is known also to incorporate medicaments such as antisep-
tics in the gauze patches thereof.
'~,,
Although simple, convenient and generally effec-
tive in their use on the household or domestic scale, the
commonly available strip bandages have certain disadvan-
tages. For example, frequent and sometimes painful changes
of such bandages are necessary in order to check the
healing process and apply medications. In many cases
moisture cannot adequately escape through them, so that the
tissue swells and healing is retarded. When the wound site
is washed, the bandage may be removed or loosened. When it
is wetted, a retained water layer in the fibrous material
favours microbial growth and swelling of the tissue.
Application to highly contoured parts of the body is
difficult.
~ ' ~
An important factor in the wound healing process
;~ is the maintenance of an appropriately moist environment
around the wound site. Wound coverings~which may protect
` the wound site from contamination, or which promote drying
,~
.;
,:
wo92/n4923 PCT/CA91/003V
2~927 ~ 2 -
and scab formation, are not totally satisfactory. The
healing process is ~etter promoted by contact of the wound
with an appropriately moisture controlled atmosphere, as
well as protection of the wound from contamination.
U,S. Patent 4,750.482 (SieverdingL discloses a
water-insoluble, hydrophilic, pressure-sensitive adhesive
useful for attaching electrodes and wound dressings and the
like to mammalian tissue. The adhesiYe composition
; includPs an irradiation crosslinked synthetia organic
polymer formed from a solution or dispersion of at least
one gel-forming, uncrosslinked synthetic organic polymer,
in the solubilizing plasticizer. On irradiation crosslink-
ing, a gel is ~ormed which retains a solubilizing
plasticizer within the three dimensional network. Poly-
acrylic acid admixed with polyethylene oxidet in the weight
ratio of 14:1, is given as one example of an uncrosslinked
synthetic organic polymer suitable for subsequent irradi-
~ ation crosslinking. The solubilizing plasticizer includes
a non-volatile elasticizer, which is generally a liquid at
room temperature.
! C~a~ian ~ent 1 180,244 ~Muchin) discloses a
medical covering for adhesive fixing to a subject, and
comprising a stretchable film sheet of polyurethane or
other copolymer material carrying an adhesive on one
surface, and an unstretchable, rigid film sheet carrier on
the oppo~ed surface, removable from the stretcha~le sheet
after adhesive application of the assemblv to a patient.
The adhesive is of conventional form.
.
U.S. Patent 3 419.006 (Kin~) discloses a
polyethylene oxide polymer complex dressing. The polymer
complexes disclosed have a very high water content.
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W092tO4923 PCT/CA91/00327
_ 3 ~ 27~ :
An object o~ the present invention is to provide
novel skin and wound coverings employing polymer complexes
as skin and wound contacting material.
.
The present invPntion provides a novel adhesive
covering for application to skin lesions (this term being
understood to cover cuts, burns, abrasions, lesions due to
skin infection or skin disorder, post-operative incision
sites and other skin damaged or skin punctured locations~
as well as bruised areas and skin locations overlying
damaged or inflamed tissues, bruised bones or muscles which
can when appropriate be applied at the domestic or housa-
hold level. The adhesive covering according to this
invention has a water vapour permeable self-supporting
outer backing layer and a wound contacting layer of biocom-
patib~e high water content polymer complex capable of
adhering to the wound site, and supported by the backing
layer. It has been found according to the present inven-
tion that biocompatible, wound and skin adhesive polymer
complexes as described herein, in combination with an
appropriate backing layer, provide a highly satisfactory,
controlled-moisture environment for the promotion of
healing of skin lesions.
The polymer complexes used as the skin lesion-
contacting layer in the products of the present invention
are tack~, solid or semi-solid materials. In order for
them to be skin adherent, they typically have a water
content of from about 20 - 70% by weight. The complexes
are swellable in water but essentially water-insoluble.
They are prepared by coprecipitation from mixed solutions,
preferably aqueous solutions, of a~ least two hydrophillic
polymers, followed by removal of the coprecipitate from the
medium, op~ionally followed by adjustment of the residual
water content of the coprecipitate. The polymer complexes
lose substantial amounts of water when exposed to a normal
,
: .
W092~0~923 PCT/CA91/003~7
'~09'~7~4 - 4 - ;
room environment, but this is essentially rev~rsible upon
immersion in wa~er or exposure to very high humidity. The
polymer complexes are inter-reacted products of the indi-
vidual polymers in the sense that they are not physically
separable into ~heir individual polymeric constituents, but
are essentially chemically non-crosslinked. Tac~iness of
them is increased by moistening.
Thus according to one aspect of the present
invention, there is provided an adhesive covering suitable
for adhesive attachment to mammalian tissue for contacting
treatment areas thereof, and comprising:
an outer layer of self-supporting, water vapour
permeable film;
an inner, treatment-area contacting layer of high
water content, tacky polymer complex supported by the outer
layer;
the polymer complex layer composition being
substantially wound- and skin-compatible, having a water
content sufficient to render it skin-adhesive, and compris-
ing the tacky, polymer complex product produced by copreci-
pitation as a result of mixing solutions of first and
second coprecipitatable hydrophilic polymers, and optional-
ly ad;usting the water content thereof.
According to another aspect of the invention,
there is provided a process for making an adhesive covering
material suitable for adhesive attachment to mammalian
tissue for contacting treatment areas thereof, which
comprises: :
mixing together solutions of coprecipitatable,
hydrophilic polymers and forming a solid or semi-solid
. ~.
.' .
,
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W092/04923 PCT/CA91/00327
~ 5 ~ 2~9270~ ;
:
coprecipitated wound-compatible polymer complex thereof;
forming a laminate of said polymer complex with
a self-supporting water vapour-permeable film by applica-
tion of the polymer complex to a surface of said film;
and, before or after its application to the film
surface, if necessary, adjusting the water content o~ said
polymer complex as necessary to render it skin adhesive.
The coverings of the presant invention are thus
produced bv a simple procedure easily adapted to an.econ- ~
omically large scale, in order to produce materials of the :
desired structure and composition. .
In the accompanying drawings~
FIGURE 1~ is a diagrammatic cross-section of a
basic structure o~ a packaged bilayer adhesive wound :~
dressing of the invention;
; FIGURE 1~3 and FIGURE lC are similar views of
modifications of the embodiment of FIGURE lA; ~:
FIGURE 2 is a similar diagrammatic cross-section :
of an alternative embodiment of the invention;
FIGURE 3A is a similar diagrammatic cross-section
of a further embodiment of the invention; ` -.
FIGURE 3B is a similar view of a modified form of .:~
the FIGURE 3A embodiment; ::.~ ` ;
FIGURE 3C is an underneath plan view o~ the
embodiment of FIGURE 3A and FIGURE 3B with the bottom
: release sheet removed fcr application; .
FIGURE 4 is.a similar diagrammatic cross-section
of a further embodiment of the invention;. - :.
FIGU~E 5 and 6 are similar diagrammatic cross- . :
` sections of further and most preferred embodiments of the
invention, in packaged form. -
i
,
W092/04923 PCT/CA91/00321
20927~4 - 6 -
In the drawings, like reference numerals indicats
like parts.
" .
With reference to FIGURE 1 of the accompanying
drawings, this basic embodiment includes an outer package
13 with ~ood water vapour barrier properties to enclose an
atmosphere 20 of high humidity around the packaged wound
covering. The wound covering itself comprises a sel~-
supporting layer 22 o~ ~ilm ~optionally perforated)l foam
or fabric of high water vapour transmission, a polymer
complex layer 24 supported by layer 22 and release sheet 30
protecting the undersurface of the polymer complex layer
24. Release sheet 30 is provided with an end-projecting
tab 32 to facilitate its removal prior to application~ In
the modification shown in FIGURE lB, the tab is replaced by
an integral lateral extension 32b. In the modification
shown in FIGUR~ lC, the release sheet 30 is provided in two
parts, each with a projection 32c to facilitate removal.
The high humidity atmosphere 20 within the package 13
prevents drying out of the polymer complex layer 24.
Release sheet 30 preven~s adhesion of the assembly to the
package. `~
~ ith reference to FIGURE 2, the embodiment shown
thereon (omitting the package) is essentially similar to
that of FIGURE 1 with the dif~erence that an adhesive layer
26 i5 interposed between the top, self-supporting layer 22
and the polymer complex 24, to improve the adhesion of the
polymer complex to the supporting carrier layer. The - ~`
combination of adhesive layer 26 and self-supporting layer
22 must have ade~uate water vapour transmission.
,
; With reference to FIGURE 3A, this embodiment
(also omitting the package) include~ a rim 36 of adhesive
material surrounding the polymer complex layer 24. The
~ .
W092tO4923 PCr/CA91/00327
- 7 - 2~9270'1
adhesive rim 36 is provided on the underside of the lat-
erally extending periphery o~ the self-supporting layer 22.
In FIGURE 3A, this rim 36 cons~itutes ~he only portion of
adhesive, other ~han polymer complex 24, in the structure.
In FIGURE 3B, this rim 36 is formed by the peripheral
extension of the adhesive layer 26, which bonds the self-
supporting layer 22 to the polymer complex layer 24, beyond
the layer 24. In either case the adhesive rim 36 is dis-
posed between the top layer and the release sheet 30, to
become exposed for skin adhesion when the release sheet 30
is removed. Then the underneath of the assembly has the
appearance shown in FIGURE 3C in either embodiment. The
adhesive 26 in this embodiment is skin compatible.
.
With reference to FIGURE 4, this embodiment
includes a covering for the top layer 22, in the form of a
self-supporting film 34 and a weak adhesive layer 46 to
attach Xilm 34 to top layer 22. Tabs 42 and 32 are pro-
vided to facilitate the removal of the release sheets 34
and 30 respectively. With this embodiment, the top layer
22 is protected until application. The weak adhesive layer
46 should be strong enough to hold the film 34 in position
while release sheet 30 is removed. Adhesive 46 remains
attached to film 34 a~ter removal of film 34 from the
structure.
The embodiments shown in FIGURES 5 and 6, which
are the most preferred embodiments, have a release sheet 34
attached over the top layer 22, as in the embodiment shown
in FIGURE 4. In the FIGURE S embodiment, the upper release
sheet 34 has a lateral extension 43 forming a tab to
facilitate its removal, and is attached to the top layer 22
by means of an adhesive layer 46. The portion of the
adhesive layer 46 underlying the extension 43 is provided
with a protective patch 44 of suitable mzterial. The
release sheet 30 covering the polymer complex layer 24 has
J '
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W092/04923 PCT/CA91/00327
2~ r~4 - 8 -
a tab 32 to facilitate its removal. An adhesive layer 26
is pxovided, as in FIGU~E 3B, to protrude peripherally
beyond the layer 24 for adhesion to the skin. The whole is
packaged in a sealed outer package 13, preferably contain-
ing an atmosphere of high humidity, to keep the polymer
complex 24 in moist condition prior to application. The
package 13 is suitably of aluminum Poil/thermoplastic
laminate or metallized thermoplastic film, so as to be heat
sealahle. The hea~ seal should allow convenient package
opening by peeling apart of the pac~age edges. Alterna-
tively, the package may be suitably marginally notched for
ease of opening. In the FIGURE 6 embodiment, the release
sheet 34 is non-adhesively attached to the top layer 22,
e.g. by solution casting o~ the top layer 22 onto the
release sheet surface. Otherwise it is the same as the
FIGURE 5 embodiment.
It will be appreciated that the illustrated
embodiments are exemplary only, and do not limit the scope
of the invention.
In use, the sealed outer package is opened and
the assembly removed fxom its package. The release sheet
30 covering the polymer complex layer 24 is removed and the
patch is applied to the wound site with the layer 24
contactirg the wound. Adhesion of the patch to the wound
is effe~ted by the inherently adhesive nature of the
polymer complex layer 24 and, in the embodiments of FIGURES
3, 5 and 6, by the adhesion of the peripheral adhesive
layer 36 to the skin surrounding of the wound site.
Substantially immediately after the patch has been applied
to the wound site, pressure can be applied on or through
the top layer 22, to retard bleeding from the wound site.
Thereafter, the patch provides an appropriately moist
environment to the wound site.
W092/04923 PCr/CA91/00327
209270~
The polymer complex compositions used as the
wound-contacting layer in the coverings of the present
invention are substantially wound compatible and skin
compatibïe. The term "wound compatible" used herein
- describes materials which can be applied to a flesh wound
site of a human or other animal and will not deleteriously
interfere with the normal healthy biological processes
encounte.ed at the wound si~e. The term "skin compatible"
means not deleterious to normal healthy skin on which it is
applied. ~he adhesive coverings of the present invention
provide appropriate wa~er vapour transmission between the
wound site and the environment, and act as suitable bar-
riers for the wound against microorganisms including
viruses, and agatnst harmful contaminations and physical ~
contact damage, which would otherwise impede the healing ~ -
process. After removal of these adhesive coverings, the
skin surrounding the wound area is relatively free from
swelling and discoloration, largely due to the appropriate
water vapour transmission properties of the assembly. ~
' ' ':
~ oth the polymer complex layer and the outer
layer and, i~ present, the adhesive layer between them,
remain overlying the wound after application, and can if
desired be made transparent, so that the wound can be
inspected and process in its healing can be monitored
visually. Moreover, such an adhesive covering can be made
~; cosmetically appealing, e.g. by coloration, opacity or
gloss reduction, and can carry medication to treat the
wound site. These layers are all suitably permeable to
; water vapour, for best healing properties. Preferably,
'~ they are also oxygen permeable.
` The polymer complexes used in the present inven-
tion are wound compatible, tacky products produced by -~
coprecipitation from solution of at least two water-sol-
uble, hydrophilic polymers. Preferably, the polymers are
',`; ~ ''
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W092/04923 PCT/CA91/00327_
20927~ - 10 - '"
coprecipitated fo~m aqueous solution. The two polymers are
chosen, in relationship to one another so that, when
solution~; o~ the two pol~mers are mixed together, a copre-
cipitate of the two polymers forms, either on mixing, after
standing, or on subsequen~ concentration of, p~ adjustment
of or addition of a suitable solu~e to, the resultant
solution.
The coprecipitate is usually of a semi-solid
"gummy" consistency, and may be separated by decantation
and dissolved in an appropriate solvent such as aqueous
ethanol, aqueous acetone or aqueous isoprapanol, at room or
slightly elevated temperatures. Then this solution can be
applied to the self-supporting, outer layer and allowed to
dry. Alternatively, the polymer solution may be cast on a
suitable transfer surface, allowed to dry, applied to the
self-supporting outer layer as a transfer coating and, if
deemed necessary subsequently rehydrated to some extent to
increase tack, before the final assembly of the product,
with release`sheets etc. Preferred polymer complexes used
in the present invention are those which can be dried to a
non-tacky, self supporting film, and subsequently remoist-
ened to a taaky condition. Such materials are convenient
to handle in their dry film form, e.g. in manufacturing and
cutting machines.
If the gummy coprecipitate is sufficiently mobile
at room cr elevated temperatures, dissolution in a solvent
may not be necessary, and the coprecipitate may be case
directly onto the outer layer or onto a suitable transfer -
surface. After formation and application to the self-
supporting layer, the polymer complexes are preferably
maintained in a moist condition until use, e.g. by packag-
ing in a sealed, water vapour containing envelope as previ- , -
ously described. ~
':
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: - . . . . ..
W092/0~923 PCT/CA91/00327
When it is desired to a~d additional ingredient~
such as plasticizers, colourants, medicaments, etc. for
in¢orporation in th~ polymer complex layer, these are
suitably mixed with the coprecipitate or ~he coprecipitate
solution.
Thus it is necessary, in accordance with the
present invention, to choose polymers which are hydrophi-
lic, water-soluble, coprecipitatable together from sol-
utions, preferably aqueous solutions, to form a wound
compatible polymer complex coprecipitate. The choice oP
first polymer may be made from polymers and copolymers of
acxylic acid (PAA), polymers and copolymers of methacrylic
acid (PMA), polymers and copolymers of itaconic acid (PIA),
polymers and copolymers of maleic acid (PMLA), and combina-
tions thereof. The second hydrophilic polymer may be
selected from polymers or copolymers o~ vinyl pyrrolidone,
polymers or copolymers of ethylene oxide, including
copolymer combina~ions of propylene oxide and ethylene
oxide [P(E0/P0)], chitosan, derivatives of chitosan such as
N,O-carbomethoxy chitosan, gelatin, and combinations ; -
thereof. -
At the time of application to the self-supporting
layer and when packaged in the envelope, the polymer
complex layer has a very substantial water content, i.e. 20
- 70% by weight of the total, the corresponding 80 - 30% by
weight being solid polymer. After application to the wound
site, the water content of the polymer complex comes to an ;~
equilibrium, dependent upon the rate of water vapour loss
through the wound dressing as a whole, and the rate of
water vapour production by the wound and skin beneath the
dressing. The contac~ of the wound site with the assembly ~1
of the polymer complex of Z0 - 70% water content and the
self sup~orting layer has a beneficial effect on wound
healing, by avoiding dehydration of the wound site. ~;~
' ~
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... ;'.'.. . ,' ',: .''~ , . .. : : '. : . ' :: , . . . .
WOg2/04923 PCT/CA91/00327
- 12 -
2~9270~
Additional benefits may be obtained, on occasion, by
inclusion of appropriate medicaments such as antibiotics,
anti-infectives, analgesics, antipruritics, growth factors
and the like, in the polymer complex layer. Such materials
are particularly easy to incorporate in the polymer com-
plexes of the present invention, since the polymer com-
plexes, after formation by coprecipitation, are
subsequently redissolved in organic solvents, generally a
particularly good medium in which to add the medicaments to
the polymer complex.
Accordingly, the adhesive coverings of the
present invention can serve as an especially useful trans-
dermal drug delivery system, for example, for delivery of
medicaments to alleviate the discomfort of muscle pains,
bruises and the like. In addition, these adhesive
coverings are particularly valuable ~or delivery oP those
drugs which penetrate the skin with difficulty and
consequently are unsuitable for membrane rate controlling
or membrane based transdermal drug delivery devices.
When adherent to a treatment site, the assembly
of the polymer complex layer and the self-supporting
backing film provides an effective barrier to microorgan-
isms and other healing-inhibiting foreign substances. The
adherent assembly will withstand immersion in sea water or
tap water, or normal washing, and will withstand applica-
tions of common skin creams and lotions.
,.
The tacky polymer complex layer may also incl~de
a reinforcing mesh disposed within the thicXness of the
polymer complex layer, to strengthen it and to increase its
cohesiveness. Such a reinforcing mesh may be a non-woven,
fibrous sheet, consisting essentially of cellulose fibres
and of high porosity, resembling tea-bag tissue. Such
..
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W092/04923 PCT/CA91/00327
.
- 13 - 2ag27 ~
materials are known for use in connection with hydrogel
wound dressing materials.
Examples of suitable commercially available such
material are high strength, ligh~weight, high porosity
tissues comprised of a special blend of hemp and other
selected cellulose fibres, marketed by The Nonwoven Di~i-
sion of lhe Dexter Corporation, Windsor Locks, Connecticut,
as Dexter Grades 785D and 198T.
Alternatively, the reinforcing mesh may be a
thermoplastically welded fibrous web, of thermoplastic
fi~res such a polypropylene, high density polyethylene or
polyester. An example of a suitable, commercially avail- ~ ;
able such web is that sold under the trade name DELNE~, by
Applied Extrusion Technology, Middleton, Delaware. ~`
. .: .
Such reinforcing meshes may be incorporated into
the polymer layer during or after the application of the
polymer in liquid form to the self-supporting outer layer.
,~
Particularly preferred for use as `the second
hydrophilic polymer is a polymer or copolymer of ethylene
ox$de, or a polymer or copolymer of vinyl pyrrolidone,
especially polyethylene oxide or polyvinyl pyrrolidone. ~ ~ -
,
Acrylic acid polymers or copolymers, especially
polyacrylic acid, are particularly preferred choices of
first hydrophilic polymer for forming the polymer complex
adhesive layer in the adhesive patches of the present
invention. A wide range of grades and molecular weights of
P~A may be used, choioe of which is within the skill of the
art. Suitable PAA has a molecular weight of at least 2,500
and preferably 5,000 - 4S0,000.
:: :
., .
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W092/04923 PCT/CA91/0032~
:~ '2~3~27~ - 14 -
Especially preferred for use in the present
invention are polymer complexes derived from PAA as first
polymer and PE0 as second polymer. PE0 of widely varying
molecular weights, from about 2,500 up, can be used, with
those of molecular weight 6,000 to 600,000 being especially
suitable.
As noted, plasticizers can be incorporated in the
polymer complex layers of this invention, to adjust the
final consistency of the layer. Suitable such plasticizers
include urea, propylene glycol, polyhydroxy compounds of
low molecular weight including glycerol, sorbitol, glucono-
lactone, triethanolamine and gluconic acid. Alkaline
plasticizers such as triethanolamine can be used to reduce
the level of complexation in the polymer complex, by
neutralization of some of the carboxylic acid groups of the
first hydrophilic polymer, to increase the tackiness on
rehydration. Conventional alXalies e.g. caustic soda or
ammonia may also be advantageous for the same purpose in
some instances. Additionally, the wound contacting polymer
complex material may include suitable preservatives to
control microbial growth. Many frequently used preserv-
atives known in the art are suitable for this use, includ-
ing sodium benzoate and sorbic acid.
.... . .
In another embodime~t of the present invention,
the polymer complex layer is subjected, after application
to the outer film layer, to a crosslinking process, to
effect a limited degree of crosslin~ing of the polymers for
strength improvement and sterilization purposes. This is
conveniently effected by subjecting the polymer layer to a
controll~d dose of suitable radiation, e.g. gamma radiation
of 3 - 4 Mrad, arter application to the film layer. In
practice, it is found that the irradiated products tend to
give better bleeding control when applied to wound sites,
as compared with non-irradiated products.
'
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W092/04923 PCT/CA91/00327
- 15 -
2~27~ll
The outer layer of the assembly according to the
invention is self-supporting and has a high water vapour
transmission, which may result from high inherent permea- I
bility,~from microporosity or from perforations. Preferab- j
ly, it also has high oxygen transmission, good drape
properties so as to be conformable to wound sites, and good
extensibility and elasticity.
.~ . '
-The combination of the outer layer and the
polymer complex acts as a barrier to ~he dehydration of the
wound site, but must permit adequate water vapour trans-
mission away from the wound site such that the wound site
and adj~cent skin do not become edematous (swollen),
thereby having a deleterious effect on wound healing, or - -
resulting in fluid build-up at the patc~-wound interface ~ -
such that the adhesion is lost. For this purpose the
backing layer suitably has a water vapour permeability o~
at least l~O gm/m2/24 hours. When necessarv, the water `~
vapaur permeability can be increased by introduction of
perforations or microporosity. The degree of perforation
is not critical, and is determined by the requirement for
~ the backing layer to protect and hold the polymer complex.
`;~Thus the size and nature of any such perforation should not
be such as to interfere with the function of the bac~ing
sheet to protect the polymer complex. It must of course
hold the polymer complex in position, and not allow diffu-
sion of the polymer through the backing sheet. For a
discussion of water vapour permeability of wound dressings
and their methods of measurement, reference may be made to ;i
an article by Marcel F. Jonkman et al., "New Method to
Assess the Water Vapour Permeance of Wound Dressings",
~iomaterials, 1988, Volume 9, May, pages 263 - 267. ~-~
`Perforations provided in the outer layer also
serve the additional purpose of enhancing the bonding of
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W092/04923 PCT/CA91/003
- 16 -
2~9270~
the polymer complex layer to the outer layer, and counter-
acting the tendency towards delamination. In effect, the
perforations form a ~ype of physical interlock between the
outer layer and the polymer complex. Advantageously, the
per~orations are in the form of lacerations, i.e. a series
of slits. The physical interlock can also be provided by
embossing, pin pointing or roughening the surface of the
outer film layer which is to receive the polymer complex or
adhesive
The outer layer can be made of substantially any
skin compatible material exhibiting suita~le properties of
permeability. It may be a self-supporting film, foam or
fabric. Suitable such materials are known in the prior
art, and those useful in prior art adhesive wound covering
patchas are generally use~ul in the present invention.
Examples include polyester polyure~hanes, polyether
polyurethanes, silicones, polyethylene, polypropylene,
ethylene-vinyl acetate copolymers, polyvinyl chloride, etc.
It may be opaque, semi-opaque, coloured or transparent, or
printed with designs or character.
; . .:
Ultra-thin polyurethane films which are semi-
permeable to water vapour, as exemplified by the commer-
cially available wound dressing OP-SITE, which consists of
a polyurethane film coated with a medical grade adhesive,
are particularly preferred. These often have appropriate
permeability without perforation. Elastic silicone mem-
branes constitute another preferred film outer layer. They
need to be perforated to provide appropriate permeability.
Foam sheets, preferably of open cell foam or
perforated closed cell foam, non-woven or woven fabric
bandages of natural, synthetic of mixed fibres, may also be
used as the outer layer for the assembly of the invention.
,~ :
.''~""''' .: '. :' ' ' ' .'.: . '. , .' :
W092/04923 PCr/CA91/00327
- 17 ~ 2~927 04
Similarly, non-polymer complex adhesives used for
skin contacting layers in the assembly of embodiments of
the present inven~ion are suitably those known from the
prior art for use with conventional wound dressing patches.
Pressure sensitive, skin-compatible adhesives are commonly
used. Porous adhesive coatings are especially preferred.
These adhesives may comprise acrylic polymers or silicones
(e.g. Dow Corning Medical adhesive); these are merely
exemplary of suitable, available materials.
~ , .
With reference again to the accompanying draw-
ings, and specifically to FIGURES 4 and 5, the adhesion of
upper release sheet 34 to the outer self-supporting layer
22 ef~ected by adhesive layer 46, should be strong enough
to withstand the removal of lowermost release sheet 30 but
:. ~
significantly weaker than the adhesion of the polymer
complex layer 24 to the wound site (augmented, in the
embodiment shown in FIGURE 5, by the adhesion of adhesive
26 to the wound surrounds). This will permit the removal
of release sheet 34 after application of the dressing to
the wound area. The adhesive 46 should have sufficiently
stronger adhesive bonding to the upper release sheet 34
than to the outex, self-supporting layer 22. Thus the
choice o~ material of adhesive 46 will be determined to
some extent by the nature of the top surface of layer 22.
For polyurethane films, the adhesive 46 would be
much weaker than the adhesive 26. Such weak adhesives are
often referred to in the art as ~repositionable adhesives".
If still weaker adhesion is required, the adhesive may be
applied to a part only of the surface of ~heet 34, or a
backside coating may be applied to the top surface of top
layer 22.
Another preferred embodiment of the invention is
as illustrated in FIGURE 6. As compared with that shown in
.
. : :
W092/04923 PCT/CA91/00327
20 92rl Oll - 18 -
FIGURE 5, it omits the adhesive layer 46 so that the top
release sheet 34 is in direct adhesive contact with the top
surface of backing s~ee~ 22. This can be accomplished by
solution casting of a solution of the backing sheet 22 onto
the appropriate isur~aca of the top release sheet, and
allowing it to dry and if neces5ary, curing. Alternatively
it may be applied to the release sheet by a hot melt
process. The end result is adhesion of the backing sheet to
the release sheet, by direct contact, without the inter-
mediary of a layer of adhesive~
~ he invention is further described in the follow-
ing illustrative but non-limiting examples.
-
,~ . ,` '.
.'
.
.` - .
., ., ~ ., , ", . .. .. . . . .
WO 92/04923 PCI'/CA91/00327
19 209270~ ~
EXAMPLE 1 -- PREPARATION OF }: OLYMEE~< COMPLEX LAYER--
PAA/PEO WITH PLASTICIZERS
" ~
A solutlon of 30 g of poly~thylene oxide
(Polyox WSR-205 from Union Carbide) in 600 ml of
distilled water wa~ stirre~ rapidly at room temperature
as 120 g of Acrysol A-3 (a 25~ aqueous solution of
polyacrylic acid from Rohm and Haas) were added. After
completion of the addition, tha mixture was stirred for
25 minutes. It was the~ covered and allowed to stand at
room temperature for 6 weeks. At the end of this time,
the mixture consisted of a turbid, non-viscous liquid
and a translucent, rubbery solid. The liquid phase was
discarded. The rubbery solid waighed 143 g. A total of
91 g of ethanol was worked into the rubbery solid by
gentle warming (bath at 35-60C) and by
kneading/stirring with a stiff rod having a rlng at the
bottom. The following materials, in order, were then
worked into the mixture by stirring at room temperature:
a solution o~ 6 g of urea in a mixture of 7 g
o~ distilled water and 20 g of ethanol,
a solution of 5 g of triethanolamine and 2.3 g
of tartaric acid B.P. in 24 g of distilled water and 8 g
~thanol:
and a total of 80 g of distilled water and 267
g of ethanol added in portions individually and as
mixtures. The mixture was allowed to stand for 2 days,
and finally was diluted with a total of 58 g of
distilled water and 1~5 g of ethanol. The hazy, viscous
solution was cast on a sheet of low dens1ty polyethylene
attached to a levelled glass plate. The cast liquid was
left exposed to the laboratory atmosphere (about 40%
relative humidity) for 17 days, after which it was a
_ transparent and somewhat elastic film. The top of the
film was covered with #1361 release liner (3M Co.).
;
W092/04g23 PCT/CA91/00327
2~9~7~20
Sectlons of film about 0.17 mm thlck were used as the
polymer complex layer of bilayer wound coverings~ The
requlred shape was cut while the polyethylene and #1361
release liner were stlll attached.
'
EXAMP~E 2 -- PREPARATION OF POLYMER COMPLEX LAYER--
PAA/PEO WIT~OUT PLASTICIZERS
A solution of 60 g of polyethylene oxide(Polyox WSRN-750 from Union Carbide) in 1050 g of
distilled water was rapidly stirred at room temperature
as 240 g of Acrysol A-1 (a 25% aqueous solu~ion of PAA
from Rohm & ~aas) diluted with 250g of distilled water
were added over a period of 5 minutes. The mixture was
stlrred for a further 5 minutes after completion of the
additlon, and was then allowed to stand for 22 hours.
At the end of this time, it consisted of a translucent
gum and a semi-opaque, mobile liquid. The liquid was
decanted, and the gum was kneaded to express occluded
liquid. The resulting gum weighed 282 y. Of this, 56.2
g were separated and allowed to stand at room
tempera~ure in a covered vessel for 4 months. The gum
was then diæsolved to form a solution suitable for
castln~ by the addition, in portions, o ethanol/water
ml~tures ollowed by stirring at room temperature. In
total, 154.8 g o ethanol and 82.3 g of distilled water
were used. The solution was cast on sheets of 7 mil
high density polyethylene secured to levelled glass
plates. The cast liquid was exposed to the laboratory
atmosphere (relatlve humidity 30-37%) for 4 days, after
which the resulting film was transparent and elastic.
It was cooled to 4C to facilitate removal from the
polyethylene. The film was----stored with` #W-89-SPiP
release liners (Mead Release Products) on either side.
Sections of film about 0.11 mm thick were used for the
polymer complex layer of bilayer wound coverings. The
., ~ .
.
, ' ', ', ,
, . . ,~. .
W0~2/04923 PCT/CA91/00327
- 21 ~ 2~927 0~
required shape was cut while the release liners were
still attached.
EXAMPLE 3 ~- ASSEMBLY AND PERFORM~NCE OF_A 8ILAYER
POLYMER COMPLEX WOUND COVERING
The bilayer wound covering for this example
was produced in accordance with the preferred embodimen~
of the invention, FIGURE 5. The adhesive layer 46,
which was supplied as a weak film between two release
sheets, was placed on the self-supporting top film 34.
One release sheet was removed to leave a sandwich of
adhesive between a release sheet and film 34. Then the
assembly was cut to an appropriate rectangular shape and
size, and the release sheet was removed. Tha
rectangular tab 44 was next applied over adhesive 46.
An o~al shape of top layer 22 with adhesive 26 thereon,
and having a release sheet protecting the adhesive 26,
was placed over the adhesive 46 on top film 34 and
pressed firmly into place. The release sheet was
removed. Cast polymer complex film was cut to the
appropriate size and shape, and after removal of one of :
the release sheets, was applled over top layer 22 with
the exposed face of the polymer complex against the top
layer. It was pressed firmly in place, and the
remaining release sheet was removed. The assembly was
malntained under conditions of high humidity to hydrate
the polymer complex untll it became tacky. The bottom
release sheet 30, wlth removal tab 32, was then applied,
to complete the assembly. It was then heat sealed into
a laminated aluminum foil package 13.
The above-described procedure was used to
assemble a bilayer wound covering from the following
specific components, reference numbered to accord with
the drawlngs, especially FIGURE 5: ;
.
.. .. ..
W092/04923 PCT/CA9l/00327
'~a927~1~
- 22 -
top layer rslease sheet 34 and adhesive layer
46 -- 2 mil polyester backing coated wi~h strips of a
re-positionable adhesive 2 mm wide placed 2 mm apart.
The adhesive strlps were parallel to the long direction
of the patch:
. ,
tab 44 covering part of adhesiYe 46 -- 5 mil
high density polyethylene;
top layer 22 and adhesive coating 26 -- 1.5
mil polyester polyurethane coa~ed with a porous pressure
sensitive adhesive (PSA) (#KM1393-OO from Semex
Medical~;
polymer complex layer 24 -- film from Example
2;
; polymer complex release sheet 30 -- 3 mil high
density polyethylene with a silicone coating cured with
an electron beam (#3-H~D-S233~-WHITE from Mead ~elease
Products).
TEST ON HEALTHY SKIN
,
The complete, assembled wound covering was
-removed from its hermetically sealed pouch and applied
to a forearm test site of a human volunteer. A~ter 11 -~
days, 95~ of the area o~ the wound covering was still ;
adherent to the skin. During the entire test period,
there was no discomfort, an~ no evidence of skin
;irritation. At lS days, when the wound covering was
removod, there was no noticeable edema.
,
:, .
'~-
. ~ ., ... , , , - ,
.. ~.. . . .. - - : . :: . - . : ,: . . :: - : .. . - . : , :~
", ",, ,, ,, ~ ,, .,, ,.,, ....... .. ~ :` ' ` "' ' ' " ' ' ' ~' ' ''
WO 92/M923 PCltCA91/00327
2~27~
- 23 - :
TEST ON FINGER CUT
A male, q7, in good health, suffered a paper '
cut on the end of the ring finger, perpendicular to the
plane of the hand. The cut wa~ 5 mm long and had an
estimated dep~h of 2 mm. Bleedlng was substantlal.
Blood wa~ absar~ed wi~h a facial tissue for about 60
seconds, and the~ a complete, assembled wound covering
prepared aæ described above wa~ removed from its
hermetically sealed pouch and applied. The patch was
left on the injury for ~ive continuous days. During
this time, ~he hand was involved in all narmal
activities, except that it was kept from immersion in
water. ;
The patch remained transparent during the five
day period. Inflammatlon at the edges of the cut
disappeared over the first few days, leaving a thin
raddish brown line as the only evidence of in~ury. At -~
no tlme was there any fluid buildup beneath the
dressing. On the fith day, the patch was st~ll
adherent to the skin surrounding the in~ury, although by
this time there had been peripheral detachment
correspondlng to about half of the area of the patch.
The patch was pulled off. The inJury appeared
completely healed, and the ad~acent skin which had been
covered continuously for five days appeared quite
healthy.
TEST ON AN ABRASION INJURY UNDER ADVERSE CONDITIONS
. . .
A male, 37, in good health sustained an
abrasion injury to the ring finger of the right hand in
a routine domestic accident. The injury was located on
the top of the finger a~out 1 cm from the central
s knuckle toward the end of the finger. The zbrasion was
:' .
;: '
. ~ , . .
wo 92/M9t3 Pcr/cA91/oo32l
209270~
- 24
, .
.
about 6 mm in diamg~er and extended well into the
dermis~
., .
Bleeding was stopped by absorption with facial
tissue. The wound was left exposed for about four
hours, and then a complete, assembled wound covering was
removed from its henmetically sealed pouch and applied~
There was no sensation on application. Af~er
application, the volunteer was involved in vigorous
outdoor activities including swimming, water skiing and
chopping wood. During these activities, the patch
remained adherent to the wound and to immediately
ad~acent healthy skin for about 36 hours, after which i~
; there was some peripheral detachment. The patch was
removed at thls tlme. The wound appeared hea~thy and -
was left exposed. Subsequent healing was highly
satisfactory.
,~ .
EXAMPLE 4 -- ASSEMBLY AND PERFORMANCE OF A BILAYER
POLYMER COMPLEX WOUND_COVERING `
The procedure outlined in Example 3 was used i,,
to assemble a bilayer covering from the following
ccmponents, referring to the drawings as regards the ~
speaiflc componentsl ;
top layer release sheet 34 and adhesive 46-
~as in Example 3;
tab 44 coverlng part of adhesive 46 -- as in
` Example 3; -
top layer 22 and adhesive coating 26 -- 0.7
mil polyether polyurethane coated with a porous pressure ! `~
~i s~nsitive adheslve ~#KM1391-02 from Semex Medical);
polymer complex layer 24 -- film from Example
2;
.,, :"
' " ' ,. '' .'` ' ' . ' .' .,. .. . .: : . , . ,:, ,`,.,:`' ,"' :. ::.: ;:, ' :' :,` . ~' .'` ,,` ' ,~' ' ' ' : ' . :
W092/04923 PCTICA91/00327
- 25 - 20927
,
polymer complex layer release sheet 30 -- as I -
in Example 3.
The polymer complex layer was moisturized by
exposure to an atmosphere of lOO~ relative humidity for
- 3.5 hours. The complete, assei~bled wound covering was
kept in a hermetically sealed pouch for 1 day before
application to a forearm test site of a human pa~ient.
After 5 days, 88~ of the area of the covering was still
adherent to the skin. During the 5-day period, there
was no discomfort and no evidence of skin irritation. ;
When the wound covering was removed, there was no
noticeable edema.
EXAMPLE 5 -- ASSEM~LY AND TEST OF BILAYER POLYMER -~
COMPLEX WOUND COVERING
. ~
The procedure outllned in Example 3 was used
to assemble a bilayer covering from the followlng
components, referring to the drawings:
` top layer release sheet 34 -- laminate of an
outer layer o 2.8 mil low density polyethylene bonded
to a film of 0.5 mil polyester bonded by a layer of
polyacrylate adhesive;
adhesive 46 - repositionable adhesive on the
0.5 mil polyegter component of the laminate formin~ top
` layer release sheet 34 described above; ~-
tab 44 covering part of adhesive on 46 -- as
, in Example 3;
top layer 22 and adhesive c~ating 26 -- 1.5 ~
mil polyether polyurethane coated with a porous pressure ~ -
sensitive adhesive (#KM-1393-02 from Semex Medical);
polymer complex layer 24 -- film from Example
;:
`,!
~ W092/04923 PCT/CA91/003~
20~270~
- 26 -
polymer complex layer release sheet 30 -- as
in Example 3~
The polymer oomplex layer was moisturi~ed by
exposure to an atmosphere of 100% relative humidity for
16.5 hours. The complete, assembled wound covering was
kept in a hermetically sealed pouch one day. The pouch
was opened and the covering was applied to a forearm
test site o~ a human patient. Af~er 18 days, 96~ of the
area of the wound covering was still adherent to the
skin. During the 18 day period, the test si~e was
exposed to five warm showers. At the end of the 18 day
period, the covering was still transparent. There was
never any dlscomfort or evidence of skin irritation.
EXAMPLE 6 -- ASSEM~LY AND TEST OF BILAYER POLYMER ~ `
COMPLEX WOUND COVERING ~" ~
' ' ~`" .,
A complete, assembled wound covering identical
with the one described in Example 5 was kept in a
hermetically sealed pouch for a total of 25 days. On
the 13th day, while still sealed in the pouch, it was
given a dose of 1.92 Mrad of gamma radiation, for
sterilizatlon purpogeg. ~he pouch was opened at 25 days
and the covering was applied to a forearm test site of a
human patient. After six days, 94% of the area of the
wound covering was still adherent to the skin. During
the six-day period, there was no discomfort, and no
evidence of skin irritation.
,: , .:
EXAMPLE 7
:........... , I
The procedure outlined in Example 3 was used
to assemble a bilayer covering from the following ;
components, referring to the drawings:
, . ~ .
", I '`',
WO92J04923 PCT/CA91/00327
~270'1
- 27 -
top layer release sheet 34 and adhesive layer
46 -- as in Example 3;
tab 4~ covering part of adhesive 46 -- as in
~xample 3;
- top layer 22 and adhesive coating 26 -- 3 mil
polyvinyl chloride, yellowish tan ("flesh colour"),
partially transparent, coated with a pressure sensitive
adhesive (No. 1103-5 from Betham Corporation);
polymer complex layer 24 -- fllm from Example
~; 2;
polymer complex release sheet 30 -- as in
Example 3. -
The polymer complex layer was moisturized by
exposure to an atmosphere of 100~ relative humidity for
18 hours. The complete, assembled wound covering was
kept in a hermetlcally se~led pouch for 40 days before
application to a forearm test site of a human patient.
After six days, 93% o~ the area of the wound coverlng
was still adherent to` the skin. Hairs and veins were
visible through the dressing. At 11 days, when the
wound covering was removed, the skin whlch had been
adherent to the covaring was much whiter than the
surrounding skin. Th~s whiteness had disappeared after
exposure to ambient air or 30 minutes. During the
entire test period, there was no discomfort, and no
evidence of skin irritation.
.` ' ''
EXAMPLE 8
- The procedure outlined in Example 3 was used
to assemble a bilayer covering from the following
components, referring to the drawings:
top layer release sheet 3~ and adhesive layer
W092/04923 PCT/CA91/0032
~8
20927~
46 -- 1 mil polyester backing coated with a
repositionable adhesi~e;
tab 44 covering part of adhesive 46 -- as in
~xample 3;
top layer 22 and adhesive coating 26--
porous, spunlaced polyes~er non-wo~en fabric, fabric
weight 1.2 oz/s~.yd., coated with a porous pressure
sensitive adhesi~e ~No. PA 1251-01 from Semex Medical);
polymer complex layer 2~ -- film from Example
2;
polymer complex release shee~ 30 -- as in
Example 3.
The polymer complex layer was moisturized by
~ exposure to an atmosphere of 100~ relative humidity for
; 22 hours. ~he complete, assembled wound covering was
kept in a hermetically sealed pouch for one day before
application to a test site on the back of a finger of a
human patient between the first (closest to the
fingernail) and second ~oints. After 3.5 days, 80~ of
the area o~ the wound covering was still adherent to the
skln. The wound covering was removed at this time;
there was no noticeable edema or evidence of skin 'r
irritation. All normal activitieg were carried out ~ -
during the test period, including approximately 16
washings of the hands with soap and warm water.
EXAMPLE 9
:' . ' ,:
The procedure outlined in Example 3 was used
to assemble a bilayer covering from the following
components, referring to the drawings:
,~
top layer release sheet 34 and adhesive layer
46 -- as in Example 3;
. 1
.. . .:, ...
::'i,:., : . . :. : :. . ';. : :: : ' ' : . ''' ~ :~.. : . '
W0~2/04923 PCT/CA91/00327
~927~
tab 44 covering part of adhesive 46 -- as in
Example 3;
top layer 22 -- 1 mil microporous
polypropylene (45% porosity, oblong pores about O.04 x
0.2 micrometers), Celyard 2500 from Celanese
Corporation;
adhesive 26 -- approximately 0.6 mil coating
of polydimethylsiloxane applied to one side of the top
layer as follows: the spray from an aerosol can of
Hollister Medical Adhesive (No. 7730 from Hollister
Incorporated) was directed onto a small jar until about
15 ml had been collected. A portion of thls liquid was
spread on one side of the top layer material, which had
been secured to a levelled surface by taping the edges.
The solvent in the coating was allowed to evaporate by
exposure to the laboratory a~mosphere. The tacky
residue was then protected by application of a release `
sheet of 3 mil polyester; "
polymer complex layer 24 -- film from Example
2:
polymer complex ralease sheet 30 -- as in
Example 3.
The polymer complex layer was moisturized by
exposure to an atmosphere of 100% relative humidity for
68 hours. The complete, assembled wound covering was
~ept in a hermetically gealed pouch for one day before
application to a forearm test site of a human patient.
After four days, 85~ of the area of the wound covering
was still adherent to the skin. About 8~ of this
adherent area had become transparent, possibly because
of migration of low molecular weight silicone polymers
into the top layer. One day later, after five days, 65%
of the area of the wound covering was still adherent to
the skin, and 85~ of this adherent area was transparent.
W092/04923 PCr/CA91/003~7
Q~ :
- 30 -
When the wound covering wa removad at six days, there
was no edema and no evidence of skin irritation.
EXAMPLE 10
This example shows that, under favourable ~:
conditions, a polymer complex layer 24 which displays
little or no adhesion to skin becausa it has not been
moisturized, can become adherent a~ter application of a
bilayer wound covering if the wound covering has a
peripherally protrud~ng adhesive layer 26 as shown in
FIGURES 3-6.
::
The procedure outlined in Example 3 was used
to assemble a bilayer coverlng, except that the polymer
complex layer was never moisturized, the assem~ly was
never completed by the additlon of a polymer complex
release sheet and was never placed in a hermeticallY :
sealed package.
The components used were as follows, with
reference to FIGURE 5:
: .
top layer release sheet 34 -- laminate of an ~'
outer layer of 2.8 mil low density polyethylene bonded
to a film of 1 mil polyester with an adhesive layer;
adhesive 46 -- repositionable adhesive on the
0.5 mil polyester component of the laminate forming top
layer release sheet 34 described above;
. tab 44 covering part of adhesive 46 -- as in ;~
Example 3; ~
top layer 22 and adhesive coating 26 -- as in . ::
Example 3;
2 polymer complex layer 24 -- film from Example
. .
, '
`: :
: . . . . .
WO9~/04923 PCT/CA91/OU327
- 31 ~ 7 ~ ~
The assembly, complete except for the addition
of polymer comple~ release s~aet 30, was kept at ambient
temperature and relative humidity (23%) for no more than
30 minutes and was then applied to a test site on the
back of a finger of a human patient between the first
and second ~oints. During the next 33 hours, the hand
was never in contact wl~h water, but otherwise all
normal hand activlties were carried ou~. At the end of
the 33-hour period, the entire area covered by the
peripherally protruding part of the bllayer wound
covering was stlll adherent. The polymer complex layer
had very good adhesion to the skin of the test site.
EXAMPLE 11
The procedure outlined in Example 3 was used
to assemble a bilayer covering from the following
components, referring to the drawings:
top layer release sheet 34 -- as in Example 9;
. tab 44 covering part o adhesive ~6 -- as in
. Example 3:
top layer 22 and adhesive coating 26--
polyethylene foam, 1/16th inch thick (4 lbs.), coated
with an acrylic pressure~sensitive adhesive (No. 1117-W
from ~tham Corporation);
. polymer complex layer 24 -- film from Example
; 2;
polymer complex release sheet 30 -- as in
Example 3.
,. . .
The polymer complex layer was moisturized by
' exposure to an atmosphere of 100~ relative ~umidity for
21 hours. The complete, assembled wound covering was
. kept in a hermetically sealed pouch for one day before
: application to a test site on the back of a finger of a
,
W092/04923 PCT/CA91/00327
92~'~ - 32 -
human patient between the first and second joints.
After one day, only 50% of the bllayer wound covering
was still adherent to the skin. This exceptionally
rapid loss of adhesion can be attributed to a
combination of the s~iffness of the foam and the high
curvature of the finger. The covering was removed at
this time. The area under that part of the wound
covering which had maintained adhesion was whitish.
EXAMPLE 12
The bilayer wound covering for this example
was produced in accordance with the embodiment shown in
FIGURE 4, except ~or the presence of layer 26 between
the top layer 22 and the polymer complex layer 24 as
shown in FIGURE 2. Tab 42 in FIGURE 4 was present as an
extension of top layar release sheet 34 and adhesive
layer 46. The protruding adhesive portion of layer 46
was covered wlth a tab of 5 mil high density
polyethylene. Tab 32 on polymer complex release sheet
30 was present as a ~olded back extenslon of sheet 30.
The general method of assembly is as described
for Example 3, using the following speci~ic components: ~
; ;-
top layer release sheet 34 and adhesive layer
46 -- 2 mil polyester backing coated with strips of a
repositionable adhesive 2 mm wide placed l.5 mm apart;
top layer 22 and adhesive coating 26 -- as in
Example 3;
polymer complex layer 24 -- film from Example
2;
polymer complex release sheet 30 - as in
Example 3.
W092/04923 PCTICA91/00327
.
- 33 - 2~92 ~0~
The polymer complex layer, which was an oval
with maximum dimensions 27 x 16 mm, was moisturized by
exposure to an atmosphere of 100% relative humidity for
four hours, application of approximately 25 mg of
distllled watèr to the surface in the form of 2 drops
from a syrlnge followed by spreading over the surface,
and continued exposure to an atmosphere of 100~ relative
humidlty for 2.5 hours. The complete, assembled wound
coverlng was kept in a hermetically sealed pouch for two
days before application to a test site on the back of a
finger of a human patient between the first and second
~oints. After three hours, the test area with the
attached wound covering was immersed in a 5~ solution of
soap at 39C for one minute and then towelled dry.
Thereafter, contact with water was avoided, but all
normal hand activities were undertaken. During days two
and three, prolonged operation of a power tool with a
two-handed overlapping grip caused a significant creep
of the wound covering. After four days, 75% of the area
of the wound covering was still adherent to the s~in,
and the adhesion was ~ound to be very good. There was
no evldence of skin irritation.
'' ~
The performance of an identical bilayer wound
coverlng, which had been placed on a similar test site
on an ad~acent finger and which had been immersed for
one minute in distilled water at 39C instead of a soap
solution, was indistinguishable.
EXAMPLE 13 -- PREPARATION AND EVALUATION OF POLYMER
COMPLEX LAYER - PAA/PVP WITH PLASTICIZERS ~;
100 grams of polyvinylpyrrolidone tPVP)
(Plasdone ~-29/32 from GAF Corporation) were dissolved
in 100 grams of distilled water. 400 grams of AcrySol
A-l (a 25% aqueous solution of PAA from Rohm and Haas)
.
~,
W092/04923 PCT/CA91/003~7
Z~27 ~
- 34 -
were stlrred as the PVP solution was added to lt. A gum
separated during the addit~on. The liquid phase was
decanted and discarded. The gum was kneaded to express
occluded liquid, which was discarded. The gum was
dlssolved in 32 grams of ethanol by heating and
stirring, and the solu~ion was diluted with 8 grams of
ethanol. ~he resulting solution was labelled 81-B. To
50.2 grams of 81-~, while kept warm in a hot water bath,
were added, in order, with stirring, 12.0 grams of
propylene glycol USP (Daminco Inc.) 9.0 grams of urea
(BDH Chemicals), 8 grams of ethanol, and finally a
mixture of 8.4 grams of distilled water and 7 grams of
ethanol. The warm solution, labelled 97-C, was cast on
a polyethylene surface kept at 53 C. After one day,
the dry film was transparent and flexible.
. .
To 0.70 grams of the dry film in a small pouch
of 3 ml polyethylene were added 0.4 grams of distilled
water, and the pouch was sealed. After 2.5 days at room
temperature, the pouch was cut open and the tack of the
film was assessed by pressing clean, dry skin on the end
of a finger against it for three seconds. Its tack
level was ~udged "very good".
EXAMP~E 14 -- PREPARATION AND EVALUATION OF POLYMER
COMP EX - PAA/PVP WITH PLASTICIZERS
50.9 grams of 81-B from EXAMPLE 13 were warmed
in a hot water bath, and the following additions were
made in order with stirring 5.5 grams of propylene
glycol: a solution of 4.0 grams of triethanolamine
(Fisher Scienti~iC) in 7 grams of ethanol; 16 grams of 1 ~`
ethanol. ~
, I , .
,
The resulting solution, while still warm, was
cast on a level glass surface kept at room temperature-
WO 92/04923 PCr/CA91/00327
2 ~ s3 ~
-- 35 --
To 0 .70 gram~ of the dr~ fllm in a small pouchof 3 ml polyethylene wer2 added 0.14 yrams of distilled
water, znd the pouch was sealed. Af~er 2.5 days at room
temperature, the pouch was cut open and the tack o ~he
film was assessed by pressing clean, dry skin on the Pnd
of a finger against it for three seconds. The tack was
judged "good".
