Note: Descriptions are shown in the official language in which they were submitted.
1~35~82
This invention relates to a wound dressing or
skin coating material suitable for household and
veterinary use for application to minor cuts, burns,
abrasions, lesions and the like and for application to
healthy skin. More particularly, the invention relates
to hydrogel-forming wound dressing materials which can
be self-applied or applied by an untrained person and
similarly removed.
In order to allow the healing of lesions to
take place at an appropriate rate and without undue
pain, an appropriate coverage is placed over the
affected area.
It is desirable that this coverage or dressing
material constitute ingredients that are all compatible
with human or animal skin, and provide, between the
environment and the wound, an effective transmission of
moisture, while specifically excluding microorganisms
from the wound site.
It would be advantageous for such a
preparation to be very quick drying, otherwise the home-
user or clinician will not have the patience to use it,
nor in many cases the opportunity, especially where
children or animals are involved.
Another advantageous property of this dressing
would be transparency, not only for cosmetic reasons but
also to permit inspection of the healing process.
Ideally, it should also be capable of being applied as
1~3~8~
very thin layers so that the resulting dressing would
not be cumbersome.
It is also desired that such a dressing be
easy to apply and remove, aesthetically pleasing, and
non-odourous.
. Although such a preparation encompassing all
of the above advantages is not presently available,
there is a gen~l~ne ~e~An~ for it in many areas including
the health care delivery area.
A wide variety of products are currently
available on the market in the field of wound dressings.
For example, sterile gauze-type dressings that are
arranged in strips of various shapes and can be applied
directly to the wound, are widely employed in the home
for minor injuries. These dressings are mounted on
plastic or fabric strips, with an adhesive coating for
attachment to skin. Gauze pads are frequently covered
with a perforated plastic strip to prevent adhesion of
gauze to the wound surface.
U.S. Patent No. 4,616,644, which issued to
Johnson and Johnson Products, discloses a hemostatic
adhesive bandage which comprises a pressure-sensitive
adhesive-coated backing attached to an absorbent pad
covered with a perforated plastic film wound release
cover, the wound release cover having a thin coating of
polyethylene oxide.
Despite their wide acceptance, the gauze-type
dressings are not without their disadvantages. For
instance, frequent and sometimes painful change~ of such
dressings are necessary in order to observe that the
healing process is proceeding as desired, and to renew
1339682
medication. These traditional dressings include two
disposable strips called "release sheets" to protect the
adhesive, which when removed, present a litter disposal
problem. They are usually in strips which are difficult
to scale to the size and shape of the individual wounds,
especially between fingers and on ~oints. When applying
these preparations to the fingers, it is often necessary
to wrap the dressing around several times, so that
despite the fact that they are semi-permeable, moisture
may not be able to escape adequately leaving the wound
site and healthy skin around the wound site swollen and
lighter in colour. Moreover, wetting of these gauze-
type dressings results in a retained water layer which
favours microbial growth. Some manufacturers, such as
Johnson and Johnson, have addressed this problem by
incorporating an anti-microbial agent, such as
benzalkonium chloride, into the gauze pad.
Hydrogels are apparently solid materials,
which have some characteristics of animal skin and
presumably would provide a good basis for wound
dressings. According to Joseph D. Andrade in Hydrogels
for Medical and Related Applications, A.C.S. Symposium
Series 31, American Chemical Society, 1976, page xi,
hydrogels "are three-dimensional networks of hydrophilic
polymers, generally covalently or ionically cross-
linked, which interact with aqueous solutions by
swelling to some equilibrium value". It is known, in
some instances, that complexing or interaction between
polymer chains occurs by way of hydrogen bonding to form
a hydrogel.
It is known to use hydrogel preparations for
the clinical treatment of wounds, in particular severe
burns. U.S. Patent No. 4,572,906 discloses a self-
supporting film for use as a surgical dressing in the
13~9~82
treatment of severe burns, comprising the hydrogel (15%
water) blend o~ gelatin, chitosan and a compatible
plasticizer. The dressing may be removed from the wound
by soaking in physiological saline or water.
Canadian Patent No. 1,176,932 also relates to
a hydrogel-based wound adherent film for surgical
application consisting of gelatin and a water soluble
resin such as polyethylene oxide or polyethylene imine.
Canadian Patent No. 1,180 622 discloses a
hydrogel slmilar to Canadian Patent No. 1,176,932,
however, the combination of gelatin and water soluble
resin is in a liquid preparation to be poured by a
skilled surgeon directly onto the wound as opposed to
existing as a preformed film.
Although these hydrogel preparations provide
good protection for wounds, allowing transmission of
water vapour from the wound, generally cause less trauma
of the skin surrounding the wound after removal
(lightness of colour, swelling) compared to conventional
dressings, and are transparent allowing the surgeon to
monitor the progress of the healing, they do not lend
themselves to household use. These hydrogel wound
dressings contain, in some instances (Canadian Patents
Nos. 1,180,622 and 1,176,932) ingredients having
systemic toxicity such as polyethylene imine. These
dressings are therefore suitable for human use only when
applied by or under the supervision of a professional
for application to large areas of human tissue. For
application to smaller areas, self-application may, in
some instances, be possible. These preparations are
also insufficiently quick-drying for household use.
13~b82
Other dressings useful in surgical application
include those of U.S. Patent No. 4,524,064 and U.S.
Patent No. 4,243,656.
U.S. patent 4,524,064 to Nambu discloses a
wound covering comprising polyvinyl alcohol, a water-
soluble polyhydric alcohol and a high-viscosity water-
soluble macromolecular substance. This latter
ingredient provides high viscosity for the covering
which interferes with migration of the covering
components. It is recited in the disclosure of this
patent that only high-viscosity macromolecular
substances may be used, with the exception of polyvinyl
alcohol and a list is given which includes polyacrylic
acid. In this instance, polyacrylic acid is employed in
a very small amount, and does not provide adhesion to
the coating. It is merely added as a viscosity builder.
U.S. patent 4,243,656 to Walliczek discloses a
paint-on liquid dressing for first and second degree
burns consisting of acrylic polymer, gelatin, glycerol
and water. The acrylic polymer is in the form of an
emulsion and is not hydrogel-forming. Accordingly,
although gelatin is hydrogel-forming, it merely acts to
dilute the emulsion which, when applied to the skin,
collapses due to evaporation of water. The emulsion,
once collapsed, is not entirely hydrophobic, that is it
will absorb some water although it is to such a small
extent that it is outside the conventional recognized
definition of a hydrogel.
It is known to utilize hydrogel wound
dressings for the household treatment of wounds. Two
alleged household wound dressings are disclosed in U.S.
Patent No. 3,419,006. These preparations, composed of
hydrophilic, polymeric gels are almost entirely water
13~82
(i.e. approximately 96% water), which leads to poor
adhesion to the wound site. They must be reinforced
with nylon mesh to prevent breakage. These preparations
are primarily intended for use as shoe inserts to
prevent chaffing against the skin.
It is an ob~ect of this invention to provide
an inexpensive wound dressing material that contains
only wound compatible ingredients to allow household and
clinical use of such a preparation, allows effective
transmission of water vapour from the wound site, and
provides an effective barrier for the wound against
exogenous microorganisms.
It is another ob~ect of this invention to
provide an aesthetically pleasing, wound dressing
material that is relatively quick-drying and
transparent, although capable of being made opaque, and
is easy to apply to allow self-application or
application by an untrained person and similar easy
removal.
It is another ob~ect of the present invention
to provide a skin coating material.
According to the present invention, there is
provided a hydrogel-forming wound dressing or skin
coating material consisting substantially entirely of
wound-compatible and skin-compatible ingredients and
comprising a first hydrophilic polymer selected from
polymers or copolymers of acrylic acid, polymers or
copolymers of methacrylic acid, polymers or copolymers
of itaconic acid, polymers or copolymers of maleic acid,
and polymers or copolymers of 3-butene-1,2,3-
133~82
tricarboxylic acid, or combinations thereof; a second
hyd~o~hilic polymer which is capable of interacting with
the first polymer to produce, upon drying, a hydrogel of
improved water resistance and film-forming properties
relative to the first hyd~o~hilic polymer alone; and
water; the material being film-forming and substantially
transparent or translucent although capable of being
made opaque.
This non-toxic wound dressing material allows,
between the wound and the environment, transmission of
water vapour to facilitate wound healing. It also
provides a suitable barrier for the wound against
microorganisms including some viruses, which may lead to
infection and therefore delay the healing process.
The term "wound-compatible" referred to
herein, describes materials which can be applied to a
flesh wound site of a human or other animal and will be
compatible with the wound site and surrounding flesh,
and will not deleteriously interfere with the normal
healthy biological processes encountered at the wound
site. In the instances where this dressing is used as a
skin coating, in such applications as an insect
repellent, a sunscreen or a fragrance vehicle, the term
"skin compatible" means not deleterious to normal,
healthy skin on which it is applied.
The wound dressing or skin coating material
described herein is relatively quick-drying to provide
the con~enience necessary for household use, and may be
substantially transparent which makes the material not
only aesthetically appealing but also permits the
inspection of the healing process without dressing
removal.
13~9 i~82
Although transparency in most instances, is a
desirable feature in a wound dressing preparation, an
additional embodiment of this invention, described
hereinbelow, discloses an opaque wound dressing or skin
coating material for use on occasions when opacity or
non-transparency is desirèd.
After removal of the material according to the
invention from the wound site, the skin surrounding the
wound area is relatively free from the swelling and
lightness of colour which results from use of
traditional dressings. The elimination of these
problems is due, in part, to the enhanced water vapour
transmission of the dressing of the present invention.
Moreover, this dressing may be applied from a tube, so
as to avoid immediate litter disposal problems.
This preparation, since it forms a hydrogel,
may, while maintaining a water concentration equilibrium
with the air, swell and absorb many times its weight in
water. It is compatible with normal human and animal
skin and is capable of conforming to skin contours and
folds to allow application to finger and elbow joints.
The wound dressing material described herein
may effectively be applied to minor cuts, burns,
abrasions, dermatological disorders such as eczema and
acne, and may be used in the treatment of warts.
It is also contemplated within the scope of
the present invention that the skin-coating materials
described herein may be used as insect repellents,
sunscreens and vehicles for the controlled release of
fragrances such as perfume and cologne.
-- 8
In a preferred form of this invention, a
hydrogel-forming wound dressing or skin-coating for
application directly to the wound, or to areas of
healthy skin, consistlng substantially entirely of
wound-compatible ingredients, is prepared comprising a
first hydrophilic polymer selected from polymers or
copolymers of acrylic acid (PAA), polymers or copolymers
of methacrylic acid (PMA), polymers or copolymers of
itaconic acid (PIA), polymers or copolymers of maleic
acid (PLA) and polymers or copolymers of 3-butene-1,2,3-
tricarboxylic acid (PBA), or combinations thereof, a
lS second hydrophilic polymer selected from polyvinyl
alcohol (PVA), polyvinyl pyrrolidone (PVP), polyethylene
oxide (PEO), copolymer combinations of propylene oxide
and ethylene oxide [P(EO/PO)], and gelatin; and water.
This material, when applied as a liquid, dries in situ
on the wound and adjacent healthy skin to a continuous
film that will withstand immersion in sea or tap water
or normal wAsh~ng, as well as overcoatings with hand
creams and waterless hand cleaners. This material will
allow relatively free movement of the area containing
2S the wound, and will permit a generous transmission of
water vapour from the wound site while providing a
barrier to microorganisms including some viruses.
It is preferred although not strictly
necessary in all embodiments, that at least one suitable
plasticizer be added to the hydrogel-forming material.
One preferred embodiment of this invention is
a wound dressing or skin-coating material for
application to minor cuts, burns, abrasions, lesions and
the like, comprising effective amounts of polymers or
g
133~2
copolymers of acrylic acid, polymers or copolymers of
methacrylic acid, polymers or copolymers of itaconic
acid, polymers or copolymers of maleic acid or polymers
or copolymers of 3-butene-1,2,3-tricarboxylic acid, or
combinations thereof as first hydrophilic polymer,
polyvinyl alcohol as second hydrophilic polymer,
suitable plasticizer(s) and water.
Polyvinyl alcohol (PVA), prepared by
hydrolysis of polyvinyl acetate, falls into two main,
useful commercial grades: "fully hydrolyzed" (98 +
mole% hydrolyzed) or "partially hydrolyzed" (87-89 mole~
hydrolyzed). Both fully and partially hydrolyzed grades
- are water soluble but the fully hydrolyzed grade should
normally be heated to 80~C or higher before it will
dissolve. Fully hydrolyzed grades of PVA are present in
the composition to enhance water resistance. When
immersed in water, fully hydrolyzed grades of PVA swell
in length and width substantially more than partially
hydrolyzed grades. The increase in length and width
creates a shear force which promotes dislodgement of the
swollen dressing. A mixture of fully and partially
hydrolyzed grades is therefore preferred. Low molecular
weight PVA is used to maximize the solids level in the
composition and therefore to reduce the drying time.
Preferably, a ratio of partially hydrolyzed
PVA to fully hydrolyzed PVA of 0.5:1 to 2.5:1, most
preferably 1.7:1 is used. It is considered that a ratio
of 0:1 and 1:0 would give useful dressing or skin-
coating materials.
Films of the second hydrophilic polymer alone,
such as polyvinyl alcohol alone, formed by evaporation
of solutions on the skin, generally have poor adhesion
to the skin. This problem is greatly alleviated by
-- 10 --
1~96~2
mixing the second hydrophilic polymer with polymers of
acrylic acid as first hydrophilic polymer eg:
polyacrylic acid (PAA). If the molecular weight (MW) of
the PAA is too low, optimum physical properties and
water resistance of the wound dressing will be adversely
affected. On the other hànd, low MW grades of PAA make
possible higher solids levels in the liquid dressing
because of their low viscosity. If the molecular weight
of the PAA grade is too high (i.e., 300,000 - 500,000 or
higher), the PAA may be strongly gelled by the addition
of certain compounds. It may be advantageous to combine
PAA grades of low and intermediate molecular weight. A
wide range of combinations are possible within the scope
of this invention. Suitable combinations are readily
determinable by those skilled in the art, based upon
exemplified values given in the specific examples below.
The combination of heat vulcanized PVA and PAA
is known in medical research to produce an artificial
muscle capable of dilating and contracting with changes
in pH (Nature, v.189, 381 (1961)).
Preferred plasticizers for use in this
invention are propylene glycol, polyhydroxy compounds of
low molecular weight including glycerol, sorbitol,
gluconolactone, and gluconic acid and urea. A wide
range of amounts of plasticizers may be added to the
wound dressing or skin coating material, the amounts
being evident to those skilled in the art.
In a further embodiment of this invention, the
wound dressing or skin coating material comprising the
first hydrophilic polymer and the second hydrophilic
polymer is mixed with suitable preservatives to improve
the shelf life of the product and reduce microbial
growth. Many frequently used preservatives known in the
1~39g~82
art are suitable for use in this invention, however,
most preferably sodium benzoate, a common component of
fruit juices, and sorbic acid, a common component of
cheeses and products thereof, are added.
If it is desired that the water resistance of
the wound dressing or skin coating material be further
increased, (i.e. a reduction in the loss of polymer and
in the development of tackiness ~following immersion in
water) an agent may be added to the material to cross-
link the first h~dlo~hilic polymer. An agent that may
be used comprises aluminum ion, added in the form of a
substantially water-soluble aluminum salt. Aluminum
salts which are compatible with humans and animals are
widely used such as aluminum chlorhydroxide in underarm
deodorants, and ammonium alum as flocculant for
clarification of drinking water and in styptic pencils
for the treatment of shaving cuts, and may be considered
appropriate for use in the present invention. Most
preferably, where the first polymer in the material is
PAA and the second polymer is PVA, suitable agents to
cross-link PAA are ammonium alum Al(NH4)(SO4 )2 .12H20,
potassium alum AlK( S~4 )2 .12H2 O, sodium alum
AlNa(SO4 )2 .12H2O, and all~m;nllr sulfate Al2(SO4 )3 .16H20.
Polyvalent cations, including the tetravalent ion
zirconium (Zr~4) and the divalent ion zinc (Zn' 2 ) may
effectively cross-link PAA. In addition, iron salts
such as ferric sulfate and elements such as magnesium
may be used as cross-linking agents.
In a further embodiment of this invention, the
wound dressing or skin coating material comprises a
drying aid.
In one aspect, the drying aid is an aqueous
acid insoluble biocompatible powder which increases the
- 12 -
~ 3~9S8~
solids level of the composition and may be selected from
the group comprising chitin, cross-linked starch, cross-
linked gelatin and fully hydrolyzed PVA. This list is
not considered exhaustive as other biocompatible
materials may be envisaged by one skilled in the art.
Chitin is a polysaccharidè which forms the cell walls of
fungi and the hard shell of insects and crustaceans, and
possesses the ability to promote the healing of wounds.
To ensure the necessary degree of histocompatibility,
the chitin when used should be substantially protein
free. The biocompatible powder may also reduce the
gloss of the composition, in situ.
In another aspect, the drying aid is a
suitable organic solvent. Non-limiting examples of
appropriate solvents include ethanol, methanol and
isopropanol. The organic solvent increases the fluidity
of the dressing material and thereby permits a higher
solids level which accordingly reduces the drying time
of the composition. Generally, sufficient organic
solvent, e.g. ethanol, may be added to give a 0.5 - 1:1
ratio with water. This ratio may be varied depending on
consistency of the dressing material desired and the
mode of application of the dressing, as discussed
hereinbelow. The addition of too much solvent, e.g.
ethanol, may cause precipitation of some of the polymers
and settling of dispersed powder during storage of the
dressing material. However, within the preferred
concentration range, it has been found that ethanol
actually prevents aggregation of the biocompatible
powder, e.g. starch powder.
In a preferred aspect, the process for
producing the hydrogel-forming wound dressing or skin
coating material wherein the first polymer is PAA and
the second polymer is PVA comprises preparing a
- 13 -
133~2
homogenous aqueous solution of the first h~dlo~hilic
polymer with the second hydrophilic polymer at an
elevated temperature and adding, to the resultant
solution, at least one plasticizer. The solution is
then diluted with alcohol and water and the resultant
mixture deaerated.
Accordingly, a preferred process comprises
preparing a homogeneous 25% aqueous solution of a
mixture of two grades of PAA, 2-6 parts by weight, most
preferably 4.1 parts by weight. Subsequently, fully
hydrolyzed PVA powder is dissolved in the above
solution, and then partially hydrolyzed PVA, together
comprising 2-6 parts by weight, most preferably 3.8
parts by weight, in the homogeneous mixture, by heating
at 90~C in a covered vessel to reduce the evaporation of
water. While still hot, liquid glycerol 1.7 parts by
weight, powdered sorbitol 1.8 parts by weight and 1,5-
gluconolactone, 1.8 parts by weight are added.
Alternatively, the solids may be added directly. The
total plasticizer content may be between 13 - 31% on the
total solids level. Most preferably plasticizers
comprise 26.5% of the total solids. Optionally, 0.033
parts by weight of granulated sodium benzoate may be
added. Ideally, the amount of sodium benzoate may be
between 0.001% - 0.1%. After the mixture has cooled to
between 50 - 80~C, most preferably 75~C, sorbic acid,
0.03 parts by weight may optionally be added. Once the
solution temperature reaches between 45 - 75~C, most
preferably 70~C, appropriate amounts of cross-linked
starch powder, 3 - 7 parts by weight and then ammonium
alum powder, 1.7 parts by weight may optionally be
included. Alternatively, ammonium alum may be added as
a hot glycerol solution (1 part by weight in 1.7 parts
by weight glycerol) or as a water solution. In order to
attain satisfactory flow properties, portions of water
- 14 -
1~3~
and ethanol or mixtures thereof may be added at room
temperature. Bubbles present in the ensuing mixture are
then separated by any appropriate means, such as
centrifugation.
The PAA, PMA, P'IA, PLA or PBA/PVA, PAA, PMA,
PIA, PLA or PBA/PVP, PAA, PMA, PIA, PLA or PBA/PEO, and
PAA, PMA, PIA, PLA or PBA/P(EO/P0) wound dressing or
skin coating materials contemplated as preferred aspects
of this invention may be applied as liquid formulations
to the wound which will dry on the skin in situ. The
lngredients in these dressings and relative amounts of
the ingredients are as described herein.
In a preferred aspect, the process for
producing the hydrogel-forming wound dressing or skin
coating materials comprises mixing an aqueous solution
of the first hydrophlilic polymer with an aqueous
solution of the second hydrophilic polymer under
agitation. The viscous liquid or gum which forms is
separated from the aqueous phase, which is discarded.
Water occluded (as opposed to dissolved or emulsified)
in a viscous liquid can be removed by centrifugation.
Water occluded in a gum can be removed by kneading. A
suitable organic solvent such as ethanol or isopropanol
is mixed with the viscous liquid or gum to convert it to
a fluid state. If necessary, heat may be used to
dissolve the organic solvent in the viscous liquid or
gum. The resultant liquids generally do not gel at room
temperature, and in this case gelation controlling
agents are not necessary.
It is preferred, in any embodiment in which
post-water-immersion-tackiness is a problem, e.g. in a
liquid formulation, that a suitable cross-linking agent
be added to the polymers. Cross-linking enhances the
- 15 -
1~3~82
water resistance and reduces the aforementioned
tackiness.
It is also preferred, in any embodiment in
which reduced drying time and low viscosity are desired
in the wound dressing or skin coating material, e.g. in
a liquid formulation, that a drying aid, as described
hereinabove, be added. Most preferably, ethanol is
added.
It is also preferred in a liquid wound
dressing or skin coating material that a suitable gloss-
reducing powder, such as cross-linked starch powder, may
be added for aesthetic purposes.
Another preferred embodiment of this invention
is a wound dressing or skin coating material for
application to minor cuts, burns, abrasions, lesions and
the like or for application to healthy skin, comprising
effective amounts of polymers or copolymers of acrylic
acid, polymers or copolymers of methacrylic acid,
polymers or copolymers of itaconic acid, polymers or
copolymers of maleic acid or polymers or copolymers of
3-butene-1,2,3-tricarboxylic acid, or combinations
thereof, gelatin, suitable plasticizer(s), and water.
Gelatin is a protein material produced by
hydrolysis of collagen from animal bones and connective
tissues. Gelatin has served as an encapsulating
material, a coating for pills, an emulsifying agent, a
coating for photographic materials, a bacterial culture
medium, a major ingredient of popular desserts, and for
many other widely varied uses. Gelatin is completely
soluble in water at elevated temperatures and
essentially insoluble at ordinary temperatures.
- 16 -
1~3~82
In the embodiment where gelatin is the second
hydrophilic polymer and PAA is the first hydrophilic
polymer, a range of PAA grades and molecular weights may
be used as in the embodiments described. Having the
examples herein which recite non-limiting grades and
molecular weight ranges of PAA, a skilled worker could
readily determine other appropriate grades and molecular
weight ranges of PAA that would be suitable for use
within the materials of the present invention.
Likewise, the determination of suitable grades and
molecular weight ranges of the other first hydrophilic
polymers is readily within the skill of an artisan in
this area.
If gelatin is the second hydrophilic polymer
and PAA is the first hydrophilic polymer, cross-linking
agents as described above may optionally be added.
Preferred plasticizers are as described
hereinabove.
In this embodiment, an organic solvent should
be added to dissolve the precipitate which separates
when gelatin and PAA are mixed. Ethanol is preferred,
but other solvents such as isopropanol are acceptable.
Optionally, preservative(s) and a gloss
reducing powder, as described above, may be added to
this wound dressing or skin coating material.
In a preferred aspect, the process for
producing the hydrogel-forming wound dressing or skin
coating comprises mixing an aqueous solution of the
first h~dLophilic polymer with an agueous solution of
the second hydrophilic polymer under agitation. The
resultant gum is separated from the aqueous phase and
- 17 -
~ 3 ~ ~ ~ 2
kneaded to remove occluded water. A sui le organic
solvent such as ethanol or isopropanol is mixed with the
gum and the resultant mixture heated to convert the gum
to a liquid. This liquid may tend to gel at room
temperature, in which case a gel retarding agent may be
added. Examples of su'itable gel retarding agents
include calcium chloride and urea.
Accordingly, a preferred process for producing
the hydrogel-forming wound dressing or skin coating
material wherein the first polymer is PAA and the second
polymer is gelatin, comprises mixing a warm aqueous
solution of low molecular weight PAA (5-15 parts by
weight, most preferably, 10 parts by weight) with a warm
aqueous gelatin solution (5-15 parts by weight, most
preferably, 10 parts by weight) with continuous
stirring. Once the mixture consolidates, the aqueous
phase is then decanted by conventional methods, and
excess water is removed by kneading the resultant gum,
for about 30 minutes. The gum is then mixed with
glycerol (2-8 parts by weight, most preferably 5 parts
by weight), and optionally with a modest amount of
ethanol (2-7 parts by weight, most preferably, 5.0 parts
by weight) and heated. In order to control gelation of
the material at room temperature, calcium chloride
dihydrate (2-6 parts by weight, most preferably 4 parts
by weight) may be dissolved in the heated material.
Bubbles introduced during mixing may be removed by a
suitable process, such as centrifugation.
The PAA, PMA, PIA, PLA or PBA/gelatin wound
dressing or skin coating materials contemplated in this
invention may be applied as a liquid formulation to the
wound or healthy skin which will dry on the skin in
situ. The ingredients and their relative amounts are as
described herein.
1339~.3~2
It is preferred, in any embodiment in which
reduced drying time is desired in the material, that a
drying aid, as described above, be added.
If the material'is to be manufactured and used
only as a liquid, it is desirable to add a gloss-
reducing powder, as described above.
It is to be understood that certain wound
dressing or skin coating embodiments of the present
invention may result in "emulsion" materials as opposed
to "liquid" materials. In particular, it has been found
that the PAA/PVP and PMA/PEO embodiments may form water-
in-oil emulsions after mixing the two polymer
constituents.
The liquid formulation of the wound dressing
or skin coating materials of the present invention may
be adapted to be applied in other forms. For example,
the liquid formulation may be delivered with a suitable
inert gas and propellant under pressure in an
appropriate vessel to produce an aerosol spray of the
material. In some instances, it is not necessary in the
aerosol preparation to add a cross-linking agent, drying
aid or gloss-reducing powder. Whether these optional
ingredients are incorporated into the material depends
on the particular properties desired in the aerosol
formulation. It is necessary, however, that the
preparation to be used in the aerosol vessel be of a
sufficiently low viscosity to be propelled effectively
through the spray mechanism of the aerosol vessel and
that the particle size and dispersion of the optional
powder be such that the orifice does not become clogged.
-- 19 --
13~9~82
Alternatively, the liquid or emulsion
formulation of the wound dressing or skin coating
materials may be delivered, optionally under pressure,
from a pump or bottle, preferably from a hand-operated
5spray pump. Other delivery or packaging embodiments for
this novel material will become apparent to the skilled
artisan and include, but are not limited to, plastic
tubes, squeeze bottles or droppers, and pre-coated swabs
or tissue.
Due to the permeability and biological
inertness of the hydrogel-forming material, the novel
materials of this invention are particularly suited for
the incorporation therein of a wide variety of
15chemotherapeutic agents, medicinal agents and additives.
For instance, the dressing can contain topical
keratolytics such as salicylic acid and the like, or
agents which accelerate healing, or agents with anti-
microbial or hemostatic activity.
The quantity of medicinal agents,
chemotherapeutic agents or additives which can be
incorporated into the material will of course depend on
the particular agent, its solubility properties and the
25presence of other additives. In general, however, the
agents will be employed in a therapeutic amount.
In a further embodiment of this invention, the
hydrogel-forming material may serve as a viral barrier
30coating. Optionally, anti-viral agents may be included.
When it is desired that the hydrogel-forming
materials described herein be used as skin coatings for
insect repulsion, sun protection or fragrance delivery,
35various other ingredients may be associated with the
material. In the case of an insect repellent
- 20 -
6 ~ 2
formulation, an approprlate repellent component, such as
N,N-diethyl-meta-toluamide may be included. In the case
of a sunscreen formulation, a wide variety of sunblocks
such as octyldimethyl-Para-aminobenzoic acid,
ethylhydro~y~Lopyl-para-aminobenzoic acid, benzophenone
and menthyl salicylate may be incorporated. In the case
of a fragrance vehicle, the desired fragrance in an oil,
liquid or powder form is dissolved or suspended in the
formulation.
It is a recognized problem with many
fragrances for personal use that the odour does not
persist long enough after application to the body. In
some instances, there is a change in the quality of the
perceived odour. This is often manifested by the odour
being less desirable. It is contemplated within the
scope of this invention that the fragrance be
incorporated into the hydrogel-forming material, and
that the latter material be applied to various parts of
the body. The rate of diffusion of the fragrance to the
atmosphere is accordingly reduced, thus providing the
advantage that the fragrance can be detected for a much
longer period. In addition, in some instances, the
quality of the fragrance is maintained or even enhanced.
In a further embodiment of this invention, the
novel materials described hereinabove are made opaque,
optionally with added medicinal agents, for application
onto diseased or discoloured skin. There are numerous
opacifying means known to those skilled in the art. For
example, the bubbles present in the dressing
composition, which are removed by an appropriate method
for preparation of the transparent material, may be left
in to create an opaque material. Optionally, agents
such as cosmetic grades of talc, titanium dioxide or
ferric oxide may be added. Wound dressing or skin
- 21 -
33~87
coating materials containing opacifying agents would be
suitable for the coverage of discoloured burn wounds,
bruises, surgical scars, varicose veins, birthmarks such
as Nevus flammeus, as well as unwanted tattoos.
The following examples set out hereinbelow are
not intended to be limiting in any way and merely
represent a selection of the hydrogel-forming wound
dressing and skin coating materials of the present
inventlon.
By way of background, many of the following
examples include performance results of the hydrogel-
forming material under selected testing conditions.
There are two basic sets of tests that were used to
evaluate the coatings on healthy skin:
1) General Application Testing
2) Water Resistance Testing
a) 5 Second Immersion Test
b) 4 Minute Immersion Test
c) Occlusive Glove Test.
For the General Application Testing, a coating
of the hydrogel-forming test material was placed on
either the back of the right or left hand, on the inside
of the right or left forearm, or on the outside of the
right or left lower leg. The characteristics of the
material were assessed at 2-minute time intervals and
then 1 to 12 hours post-application.
For all three of the water resistance tests, a
coating of the hydrogel-forming test material was placed
on healthy skin on the backs of the fingers of the test
subjects and allowed to dry for at least one hour before
the actual test. The same coating may be used for all
three tests, but the 4-minute immersion test must be
performed last.
5-Second Immersion Test
The adherent coating is immersed in tap water
at 35~ C for 5 seconds, removed, shaken once to remove
excess water, exposed to the ambient atmosphere for 60
seconds, and then tested for tackiness. The tack test
consists of bringing the end of a clean, dry finger in
contact with the surface of the coating using very light
pressure, and then breaking contact. The surface is
then described as either not tacky, very slightly tacky,
slightly tacky, moderately tacky, or very tacky. In
some cases in which the surface is not tacky, it is very
slippery due to a thin layer of polymer solution. Other
observations may include a change in the transparency.
The tack level is generally re-assessed at 2 minutes
after removing the finger from the bath.
4-Minute Immersion Test
The finger bearing the adherent coating is
immersed in a bath containing a minimum of l litre,
preferably at least 3 litres, of tap water at 35~ C.
The temperature loss of the water bath is generally so
small over the 4-minute test period that external
heating to maintain the temperature is not generally
necessary. During the 4-minute immersion, the finger is
constantly moved. Upon withdrawal from the bath, the
finger is shaken once to remove the excess water, and
then the tack level of the coating is determined
immediately using the procedure as described above for
the 5-second immersion test. Other observations may be
made at this time, including a change in transparency,
decrease in thickness or increase in thickness
(swelling). In some of the examples, the finger is
exposed to the ambient atmosphere and the tack level is
- 23 -
13'.~8~
re-assessed at 2 minutes, 4 minutes, and 6 minutes
following withdrawal. The coating is allowed to dry
completely by continued exposure to the ambient
atmosphere for at least 1 hour. Qualitative changes in
flexibility as a result of immersion are noted. The
changes may be more readily apparent after a further
(optional in many examples) 6 - 24 hour period if
cracking of the film occurs at certain stress points
such as over a knuckle.
Occlusive Glove Test
A disposable examination glove is placed on
the hand bearing the test coating and an elastic band is
placed around the glove at the wrist to loosely seal the
atmosphere inside the glove. Normal activities are
resumed in the ambient atmosphere until tiny water
droplets are visible inside the glove (10 - 15 minutes).
The glove is lightly pressed against the dressing and
the presence or absence of adhesion is noted. The glove
is then removed and the tackiness of the coating surface
toward healthy skin is determined using the parameters
as described above for the 5-minute immersion test.
The occlusive glove test is very important for
establishing the suitability of coatings for use under
rubber gloves or in any other circumstance involving a
high relative humidity. Both "vinyl" (Beckton,
Dickinson, Product #2203) and polyethylene gloves were
used.
In the following examples, two grades of
polyvinyl alcohol, partially hydrolyzed and fully
hydrolyzed, are indicated as constituents of the
hydrogel-forming materials. Th~ fully hydrolyzed
35 ~; polyvinyl alcohol (PVA) is Vinol 107~(98.0 - 98.8 mole %
hydrolyzed); the partially hydrolyzed polyvinyl alcohol
- 24 -
1:339~82
(PVA) is Vinol 203 (87.0 - 89.0 mole % hydrolyzed).
Both products are low viscosity grades from Air Products
,~.,~.
& Chemicals, Inc.
In many of the example~, the polyacrylic acid
is described only as Acrysol~ A-l or Acrysol A-3.
Acrysol A-1 is a 25~ aqueous solution of PAA having a
molecular weight of less than 50,000. Acrysol A-3 is a
25~ aqueous solution of PAA having a molecular weight of
less than 150,000. Both are products of Rohm & Haas.
Throughout the examples, it is to be
appreciated that the particular type of gluconolactone
that was used was delta-gluconolactone powder. The
starch powder was highly cross-linked.
During the preparation of the hydrogel-forming
materials described hereinbelow, samplés of the test
material were, in some instances, centrifuged. The
purpose of the centrifuging step was either to remove
the bubbles introduced by stirring or to separate the
suspended matter where desired. This suspended matter
excludes deliberately suspended matter such as
opacifying powders, gloss reducing powders or drying aid
powders.
Over centrifuging a particular hydrogel-
forming material may lead to settling of the
deliberately suspended matter; however, the
determination of an appropriate centrifuging time and
speed, given the particular centrifuge apparatus being
used, is well within the purview of a skilled artisan.
~ f~
- 25 -
339b8:~
Example 1 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Water, Glycerol and Gelatin Powder"
In a glass vessel of 400 ml, 100 g of Vinol
107 (Lot #0809242) were dissolved in a mixture of 50 g
of glycerol in 200 ml of distilled water by heating with
occasional stirring in a hot water bath (80 - 90~) for
approximately 3 hours. Trapped bubbles caused by the
occasional stirring were allowed to rise during the
final hour and at the end of this time, the foam on the
top of the solution, which was quite thick, was removed.
The resultant solutlon formed a strong gel on cooling.
3.1% of this gel was heated with 12.4 g of a 25~ aqueous
solution of PAA (Polysciences, Inc., cat #0627; Lot
#55107; molecular weight ~50,000) and stirred until
homogeneous.
Thirteen packages of size 12 (20 X 60 mm)
20 ~ Gelfoam~(sponge of cross-linked gelatin from Upjohn Co.)
were opened and the foam sponges were torn into sections
20 X 20 mm and placed in a consumer appliance for
grinding coffee beans (Krups 5 ~ type 202). Grinding of
the sponges was carried out for approximately 5 minutes.
The product was a slightly off-white, fine powder. All
of this powder, 0.6 g, was added to the hot, homogeneous
liquid. The lumps in this mixture were crushed against
the sides and the bottom of the container to ensure
complete dispersion. The resultant mixture was white,
translucent, and very viscous.
The dressing was slightly difficult to spread,
but had good levelling properties. A small amount was
spread over healthy skin on the back of a finger.
Approximately 7 minutes after application, the material
was still tacky. At 15 minutes after application, the
- 26 -
~-d4~-~d~
1339682
material was tacky only in thick areas. At approximately 27
minutes after application, the material was completely dry,
very supple and unobtrusive.
The finger on which this material was applied was
immersed in water at 35~C for 5 seconds, shaken to remove the
excess, and observed 60 seconds later. It was found to be
very tacky. There was some loss of material from the surface
when the tack probe was removed. The finger was agitated in
water at 35~C for 4 minutes. The material was found to be not
tacky.
Example 2 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Water, Sodium Benzoate,
Sorbic Acid, Alum and Chitin Powder".
One hundred and six grams of a 25% aqueous solution
of PAA (Polysciences, Inc.; Product #0627, Lot #55107; MW ~
50,000) were placed in a 250 ml glass vessel. 37 g of Vinol
107 (Lot #0809242) were added and the mixture was stirred
manually to disperse the PVA granules. Dispersion was very
rapid. The mixture was covered with a watch glass to minimize
the loss of water vapour from the mixture. The mixture was
then placed in a water bath in which the temperature was
raised to 95~C and held at between 95-98~C for 2 hours. During
this time, the mixture was not stirred. At the end of this
heating, the hot mixture was stirred manually with a rod for
several minutes. Heating, without stirring, was continued for
a further 1.2 hours. The mixture was removed from the water
bath, and the following ingredients were added in the order
given below before the liquid mixture had cooled
significantly:
1) a solution of 11 grams of glycerol in 11 ml of distilled
water.
1~3968~
2) a solution of 0.18 g of sodium benzoate in 3
ml of distilled water.
3) 0.18 g of sorbic acid added in powder form.
The mixture was stirred manually with a rod
after each ingredient addition and for about 5 minutes
after the final addition. At the end of this time the
temperature of the liquid was 55~ C. 30 ml of ethanol
were added with constant stirring.
In order to decrease the viscosity of this
mixture, 10 ml of distilled water and then 5 ml of
ethanol, and finally a mixture of 20 ml of distilled
water and 10 ml of ethanol were added. The resulting
solution had much better flow properties.
Ammonium alum (N.F., Product #220913 from Drug
Trading Company) in an amount of 1.0 g was dissolved in
14 ml of distilled water. This ammonium alum solution
was added to the hydrogel-forming mixture. The mixture
was stirred with a stiff rod to homogenize it. The
final mixture was clear and flowed easily. It was
allowed to stand for 35 minutes at room temperature. To
27.4 g of this mixture were added 2.5 g of chitin powder
(protein-free, finely powdered chitin obtained from
Bentech Laboratories, Pleasanton, California) and an
additional 5ml of distilled water were mixed in. The
material was centrifuged.
On application to a subject's finger, the
material was thick but spreading was not difficult.
Thirteen minutes after application the material was
moderately tacky. Fifteen minutes after application the
material was neither tacky nor soft. The gloss of the
material was equivalent to skin itself and, in fact, it
was difficult to detect on the skin from a distance.
- 28 -
13f.~682
5-second immersion test: the material had a slight
tack.
4-minute immersion test: the material was moderately
opaque, not tacky, adhesion was fair to good, had lost
adhesion by swelling and buckling only in a relatively
small area and had very good water resistance.
Occlusive glove test: a loose fitting polyethylene
glove was used. The material showed no adhesion to the
polyethylene, nor was it tacky when touched with a
finger immediately after removal of the glove.
Example 3 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Water, Sorbic Acid, Sodium
8enzoate, Starch Powder, Alum, Glycerol
and Ethanol".
To 100 g of a 25% aqueous solution of PAA
(Polysciences, Cat #0627, Lot #55107; MW ~ 50,000) were
added 22 g of Vinol 203, (Lot #01081424). The liquid
and solid were mixed by brief stirring with a rod and
then 13 g of Vinol 107 (Lot #0809242) were added. The
resultant mixture was heated in bath at 85 - 98~ C and
intermittently stirred. When the mixture was not being
stirred, the container was covered with a watch glass.
14 ml of distilled water were added and the mixture was
stirred and heated in a hot water bath (90 - 98~ C) for
approximately 1 hour. The liquid was stirred with a rod
for approximately 5 minutes as it cooled in the
laboratory atmosphere. Upon cooling, a quasi-gel
resulted.
55.7 g of this gel were heated to 75~ and the
following additions were made:
- 29 -
1~39~82
1) 0.075 g sorbic acid.
2) A solution in 2ml distilled water of 0.075 g
sodium benzoate (BDH Chemicals, Product
#B30112, Lot #93224/9185).
5 ~ 3) 15~g of cross-linked starch powder ("Amistar
B", St. Lawrencè Starch Co., Lot #08275-B).
4) 10 ml of distilled water.
After each addition, the polymer mixture was
stirred.
A solution of 1.0 g ammonium alum N.F. (Drug
Trading Co.; Product #220913) in 1.7 g of glycerol was
- prepared by heating the mixture to approximately 70 C.
The hot solution was then added to 23.6 g of the polymer
mixture in which the internal temperature had previously
been raised to 70~ C. The resultant mixture was stirred
and 7.5 ml of ethanol were added. The resultant mixture
was then centrifuged.
The resultant hydrogel-forming liquid was
applied to the finger of a test sub~ect. Seven minutes
after application the material was slightly tacky.
Four-minute immersion test:
Immediately after removal - no tack;
slippery, whitish.
Five minutes after removal - slight tack;
Fifteen minutes after removal - no tack; white
haze almost disappeared.
- 30 -
Example 4 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Sorbitol, Glycerol, Sodium
Benzoate, Sorbic Acid, Starch Powde~, 3 3 ~ ~ 8
Gluconolactone, ~mmon;um Alum, Water,
Ethanol and Polysorbate".
50 g of a 25~ aqueous solution of PAA (Polysciences
Inc., cat #0627, Lot #55107 MW ~ 50,000) and 50 g of Acrysol
A-3 were stirred manually with a rod until homogeneous. 6.6 g
of Vinol 107 were added and dissolved by heating in a bath at
95-98~C and 11.2 g of Vinol 203 were dissolved in the mixture.
While the solution was stilled in the bath, the following
materials were added in order.
1) 11.0 g of sorbitol.
2) 10.9 g of glycerol.
3) 0.2 g of sodium benzoate.
The mixture was stirred after each addition and was
subsequently cooled to 71~C. 0.2 g of sorbic acid were added
with manual stirring. When the internal temperature of the
mixture was 62~C, 24 g of starch powder were added with
constant stirring.
43.5 g of the resultant polymer mixture were heated
to 70~C internally and a warm solution of 2.9 g gluconolactone
in 5 ml of distilled water was added. The polymer mixture was
stirred manually.
The temperature of the polymer mixture was raised to
70~C once again, and 3.2 g of crushed ammonium alum N.F. (Drug
Trading Co., DT #220913) were added. The mixture was diluted
with 15 ml of ethanol and 2 ml of distilled water. 10 ml of
the resultant mixture were removed and centrifuged for 1 hour.
The hydrogel-forming material was labeled 55-A.
~3~2
31.8 g of 55-A were transferred to a clean
glass vessel and mixed with 1.4 g of polyo~yethylene
~ sorbitan mono-oleate ("Polysorbate 8C~"; from
5 ~ Polysciences, cat #3300, Lot #K-475). The mixture was
covered, stirred and heatèd to approximately 60~ C. It
was further diluted with 5 ml distilled water and 12 ml
95% ethanol. The resultant mixture was centrifuged to
remove the tiny air bubbles and labelled 76-A.
The hydrogel-forming materials designated 55-A
and 76-A were applied to areas of healthy human skin and
the following observations made:
Table I
General Application Testing
2 min. post- 4 min. post- 1 hour po~t-
Sample application application application
55-A slight tack at slight tack at not tacky
light ~L~_u-e moderate p-~ re
76-A very tacky moderate tack not tacky:
at moderate very supple
p~SSu~ Pr~ -e
It should be noted that with both 55-A and 76-
A, 100~ of the original area remained adherent for 8
hours post-application.
- 32 -
133~2
Table II
~ater Resistance
' 5 second 4 min.
Sample Immersion Test Immersion Test
1 min. 2 min. ~ O min. 2 min. 4 min.
post- post- post- post- post-
immersion immersion immersion immersion immersion
55-A very very very very very
slight slight slight slight slight
tack tack tack tack tack
76-A slight slight not very not
tack tack tacky slight tacky
tack
Example 5 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Water, Dextran, Glycerol,
Sorbitol, Starch, Ammonium Alum and Ethanol".
100 g of a 25% aqueous solution of PAA
(Polysciences Inc., cat #0627, Lot #55107; MW <50,000)
were mixed with 11.6 g of Vinol 107 (Lot #0809242) by
heating in a bath at 95 - 98~ C with occasional
stirring.
The polymer mixture was heated to 70~ C and
1.0 g of dextran, which had been dissolved by agitation
in 4 ml of distilled water at 40~ C, was added. The
following ingredients were then added:
1) 2.5 g glycerol,
2) 2.5 g sorbitol;
3) 1.3 g Vinol 203;
4) 4 ml of distilled water.
1 3 3 ~ b 8 2
The internal temperature of the mixture was
raised to 68~ C and 6 g of cross-linked starch powder
(Amistar B from St. Lawrence Starch, Lot #08275/B) were
added. After further heating, the mixture was diluted
with 4 ml of distilled water and 2.3 g of crushed
ammonium alum N.F. (Drug Trading Co., D.T. #220913) were
stirred into the mixture. After removal from the heat,
the mixture was diluted with a total of 9 ml of ethanol
and 2 ml of distilled water and then centrifuged.
The resultant hydrogel-forming material was
applied to an area of healthy, human skin and the
following observations were made:
- 34
1~3~b82
Table III
General Application Testing
2 min. 4 min. 5 hours
post-appln. post-appln. post-appln.
tacky slight tack at >99.5% Or area
moderate p..- _ e alh-..nt
Table IV
Water ~esistance
.
5 Second Immersion Test 4 Min. Immersion Test
1 min. 2 min. O min. 2 min. 4 min.
post- post- post- post- post-
immersion immersion immersion immersion immersion
slight tack slight tack neither no tack no tack
hO~
tacky 30t
slippery
This example illustrates that, in some
instances, a polymer in addition to the first and second
hydrophilic polymers may be incorporated into the
hydrogel-forming material.
Example 6 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbic Acid, Sodium
Benzoate, Starch, Water, Alum and Ethanol"
72 g of Acrysol A-3 (Lot #9-71784) were
diluted with 20 ml of distilled water. 9.4 g of Vinol
1~39~82
107 (Lot #0809242) was added at room temperature. The
mixture was stirred to disperse the powder and was then
covered and placed in a water bath at 95 - 98~ C for 25
minutes with occasional stirring. 15.8 g of Vinol 203
(Lot #01081424) were added in a similar fashion.
The following ingredients were mixed together
in a separate vessel:
1) 11.0 g of glycerol:
2) 0.2 g of sorbic acid;
3) 0.2 g of sodium benzoate;
4) 2 ml of distilled water.
After the PAA/PVA polymer mixture had cooled
to approximately 74~ C, the previously mixed ingredients
were added with occasional stirring.
When the internal temperature of the mixture
was approximately 60~ C, 25 g of starch powder ("Amistar
B", St. Lawrence Starch Co., Lot #08275-B) were added.
42.4 g of this resultant mixture were heated
to 70~ C and 0.6 g of crushed ammonium alum N.F. (Drug
Trading Co., #220913) were added. The mixture was
quickly stirred. Mobility was attained by the addition
of 33 ml of ethanol and 12 ml of distilled water. The
mixture was then centrifuged for 40 minutes.
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
- 36 -
13~6~3L~
Table V
General Application Testing
3 min. - 8 min. 5 hours
poLt-application post-application post-application
tacky moderate tack; 1% o~ original area
detached;
no cracks; t~ a~el.t
Table VI
Water Resistance
4 minute
Immersion Test
0 min. 3 min. 5 min. 15 min.
post- po~t- post- post-
immersion immersion immersion immersion
not tacky; slight high no tack;
very tack tack haze gone;
aL~ ,; no detached
haze edges
It should be noted that 7.5 hours after
removal of the subject's finger from the 4 minute
immersion test, 96~ of the original area of the
hydrogel-forming material on the finger remained
adherent. No cracks were found at this time. The hand
on which the test material had been placed was then
washed with soap and warm water. Subsequent to the
wash, the test material cracked at some of the major
skin creases; however, it was still adherent to most of
' ~39~2
the original area. It was found that despite the
washing, adhesion was still very good.
Example 7 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbitol, Gluconolactone,
Sodium Benzoate, Sorbic Acid, Water, Alum,
Ethanol and Salicylic Acid"
50 g of a 25% aqueous solution of PAA
(Polysciences, #0627, Lot #55107; MW 50,000) were
combined in a glass vessel with 50 g of Acrysol A-3.
8.6 g of Vinol 107 (Lot #0809242) were rapidly stirred
into the PAA mixture until dispersed. The entire
mixture was then heated to dissolve the PVA in a bath at
95 - 98~C with occasional stirring, and then 14.6 g of
Vinol 203 (Lot #01081424) were dissolved in the
solution.
The following ingredients were combined with
the PAA/PVA mixture with manual stirring:
1) 10.4 g of glycerol USP.
2) 11.0 g of sorbitol.
3) 11.0 g of 1, 5-gluconolactone were dissolved
in 24 ml of distilled water. After
approximately 30 minutes the gluconolactone
solution was added to the hot solution of
PAA/PVA subsequent to the glycerol and
sorbitol additions.
4) 0.2 g of sodium benzoate.
5) 0.20 g of sorbic acid was added to the
solution resulting from step 4) after the
solution had been cooled to 75~ C.
2.9 g of ammonium alum N.F. (Drug Trading Co.;
#D.T. 220913, crushed with a spatula) were added to 49.1
g of the mixture resulting from the above additions,
-- 38 --
1339~82
when this mixture reached a temperature of 71~ C. The
mixture was immediately stirred outside of the heating
bath with a rod. The mixture was then re-heated to a
temperature of 60~ C and a solution of 10.0 g of
salicylic acid B.P. (Drug Trading Co., #D.T. 225193; Lot
#680480) in 35 ml of 95% èthanol was added. The mixture
was stirred manually after cooling for several minutes
and was then reheated to approximately 60 C. The
resulting product was then centrifuged.
Example 8 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbic Acid, Sodium
Benzoate, Starch, Water, Alum, Ethanol and
Polyvinyl Pyrrolidone-Iodine Complex (PVP I2)"
72 g of Acrysol A-3 (Lot #9-71784) were
diluted with 20 ml of distilled water in a glass vessel.
9.4 g of Vinol 107 (Lot #0809242) were added to the PAA
at room temperature. The mixture was stirred to
disperse the powder and was then covered and placed in a
bath at 95 - 98~ C for 25 minutes. 15.8 g of Vinol 203
(Lot #01081424) were ~ dissolved in the hot solution.
The following ingredients were mixed together
in a separate vessel:
1) 11.0 g of glycerol.
2) 0.2 g of sorbic acid.
3) 0.2 g of sodium benzoate.
4) 2 ml of distilled water.
This mixture was then added to the PAA/PVA
solution after the latter solution had cooled to 74~ C.
When the internal temperature of the solution was 60~ C,
5 g of starch powder ("Amistar B", St. Lawrence Starch
Co., Lot #08275-B) were added.
- 39 -
1~39~82
To 41.8 g of this mixture were added 12 ml of
distilled water with constant stirring for several
minutes. Part of this resultant mixture was
centrifuged. Both parts of the mixture, that is both
the centrifuged and uncentrifuged parts, were heated in
a hot water bath until the internal temperature was 70~
C. 0.77 g of crushed ammonium alum N.F. (Drug Trading
Co., #DT220913) were added and the mixture was stirred.
Consistency was improved by the addition of 21 ml of
ethanol. The material resulting from the ethanol
dilution was then centrifuged and labelled 25-A.
.. ~jr ~
~ 8.5 g of Plasdon~ K29-32 from GAF Corp. (PVP,
also labelled Povidone NF; Lot #G30121B) were dissolved
in 50ml of distilled water. 1.5 g of iodine crystals
(Aldrich Chemical Co., Product #20,777-2; Lot #5030JL)
were added. When shaken, the iodine dissolved very
slowly.
1.0 g of the PVP-I2 solution described above,
was added to the PAA/PVA solution designated 25-A. The
mixture was stirred with a stiff rod for about 3 minutes
and then centrifuged.
A coating of this hydrog~l-forming material
was placed on a sheet of Handi-Wrap~(Dow). The colour
was noted as brownish-purple. Approximately 3 days
later, this colour had not disappeared during exposure
to the laboratory atmosphere. There was no odour of I2
and the material was relatively supple.
d~d~
- 40 -
1~3~682~xample 9 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbic Acid, Sodium
Benzoate, Starch, Ammonium Alum, Water,
Ethanol, and Iodine".
72 g of a 25~ aqueous solution of PAA (Polysciences,
#0627, Lot #55107) and 20 ml of distilled water were placed in
a glass vessel and stirred briefly. 9.4 g of Vinol 107 (Lot
#0809242) were added to the PAA mixture at room temperature
with rapid stirring. The mixture was then covered and heated
in a bath at 95-98~C for 40 minutes. 15.8 g of Vinol 203 (Lot
#01081424) were then dissolved in the hot solution in a
similar fashion to the addition of Vinol 107.
The following components were then added as
described hereinbelow:
1) 11 g of glycerol
2) 0.20 of sorbic acid
3) a solution of 0.20 g of sodium benzoate in 2 ml of
distilled water
4) 5.0 g of starch powder ("amistar B", Lot #08275-B, from
St. Lawrence Starch Co.)
5) 6.2 g of ammonium alum N.F. (Drug Trading Co., Product
#220913 which was crushed with a spatula), were added to
the mixture resulting from step 4) when this latter
mixture was at a temperature of 65~C
6) a total of 48 ml (37.5 g) of ethanol.
The resultant mixture was centrifuged for 45
minutes.
A solution of 2.4 g of glycerol in 2 ml of distilled
water was added to the mixture with continual stirring for
approximately 40 minutes. The hydrogel-
41
1 3 ~ 2
forming material was centrifuged and then applied to an
area of healthy human skin and the following
observations were made:
Table VII
General Application Testing
5 min. 12 min. 3 1/2 hrs.
post-appln. post-appln. post-appln.
tacky not tacky no crack~
maintained over 99.5%
of original area
Table VIII
Water Resistance
4 minute Immersion Test
0 min. 2 min. 4 min. 15 min. 2.5 hrs.
post- post- post- post- post-
immersion immersion immersion immersion immersion
whitish: slight slight haze some crack~
not tacky: tack tack ~ L~e~red: at knuckle
not no tack: creases
slippery
A portion of the hydrogel-forming material
which was not used for the skin tests was transferred to
another container.
0.24 g of A.C.S. grade iodine crystals
(Aldrich Chemicals, Product #20,777-2) were dissolved
in 5 ml of ethanol. This solution was added all at once
- 42 -
lX39b82
to 23.8 g of the hydrogel-forming material described
above and the resulting mixture was stirred vigorously.
In order to increase further the mobility of the
mixture, 3 ml of ethanol were stirred in and the
material was centrifuged for 30 minutes. A dry coating
of this iodine-cont~ining'hydrogel-forming material had
a dark brown colour.
Example lO - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbitol,
Gluconolactone, Sodium Benzoate, Sorbic
Acid, Starch, Distilled Water, Ethanol and
Ammonium Alum or Potassium Alum"
30 g of Acrysol A-1 were added to 30 g of
Acrysol A-3. 5.2 g of Vinol 107 (Lot #0809242) were
then added to the PAA mixture. The mixture was covered
and heated in a water bath at 95~ C with intermittent
stirring until the PVA had dissolved. 8.8 g of Vinol
203 (Lot #01081424) were dissolved in the hot solution.
The following ingredients were then added to
the PAA/PVA mixture:
1) 6.6 g of glycerol USP
2) 6.6 g of crushed sorbitol
3) 6.6 g of 1,5-gluconolactone dissolved in 11 ml
of distilled water
4) 0.12 g of sodium benzoate.
All these additions were made while the
PAA/PVA mixture was still in the hot water bath at 95
C.
The internal temperature of the mixture was
then lowered to 71~ C and 0.12 g of sorbic acid were
stirred in. With the internal temperature lowered to
- 43 -
8 2
67 C, 18.3 g of starch powder ("Amlstar B" St. Lawrence
Starch Co.: Lot #08275-B) were added to the polymer
mixture. The hydrogel-forming material thus formed was
divided into two 58.9 g portions.
The internal temperature of the first portion
was raised to 69 C. 3.5 g of ammonium alum USP (Drug
Trading Co. D.T. #003251 ground to a fine powder) were
added. The alum was stirred into the mixture as quickly
as possible. The mixture was then diluted with 6 ml of
ethanol and 5 ml of distilled water. This hydrogel-
forming material was labelled 89-A.
The internal temperature of the second portion
was raised to 69~ C. 3.7 g of potassium alum (BDH
Chemicals, Code #B10009, Lot #99529/5592 ground to a
fine powder) were added and the mixture was stirred.
The mixture was then diluted with 6 ml of ethanol and 5
ml of distilled water. The resultant hydrogel-forming
material was labelled 90-A.
Each of the hydrogel-forming materials 89-A
and 90-A were applied to healthy normal skin and the
following observations were made:
Table IX
General Application ~esting
2 min. 4 min. 6 min.
Sample post-appln post-appln. post-appln
89-A tacky slight tack slight tack
90-A tacky still tacky slight tack
~ - 44 -
13~82
Table X
Water Resistance
5 second 4 min.
Immersion Test Immersion Test
Sample 1 min. 2 min. 0 min. 2 min. 4 min. 3 hrs.
post- post- post- post- post- post-
imm'n imm'n imm'n imm'n imm'n imm'n
89-A slight no no no no slight
tack; . tack tack tack tack det- ' t:
some
cracks
90-A slight no no no no some
tack: tack tack: tack tack cracking:
some
detachment
Example 11 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbitol, Gluconolactone,
Sodium Benzoate Sorbic Acid, Distilled Water,
Starch, Ammonium Alum and optionally
Isopropanol or Ethanol"
60 g of Acrysol A-1 and 60 g of Acrysol A-3
were mixed together. 10.4 g of Vinol 107 (Lot #0809242)
were added to the PAA solution. The resultant mixture
was covered and heated in a water bath at 95~ C with
intermittent stirring until the PVA had dissolved. 17.6
g of Vinol 203 (Lot #01081424) were dissolved in the hot
solution.
1339~82
The following ingredients were then added to
the PAA/PVA mixture as described hereinbelow:
1) 13.2 g of glycerol USP
2) 13.2 g of crushed sorbitol
3) 13.2 g of 1,5-gluconolactone dissolved in 22ml
of distilled water
4) 0.24 g of sodium benzoate.
All of these additions were made to the
mixture while it was still in the hot water bath at 95~
C. The internal temperature was then lowered to 71~ C
and 0.24 g of sorbic acid was stirred in. The resultant
hydrogel-forming mixture was divided into four 49.5 g
portions.
6 ml of distilled water were added to the
first portion and the internal temperature was raised to
68 C. 9.1 g of starch powder ("Amistar B" St. Lawrence
Starch Co., Lot #08275-B) were added with constant
stirring. 3.5 g of ammonium alum U.S.P. (Drug Trading
Co. D.T. #003251 ground to a fine powder) were added.
The alum was stirred into the mixture as ~uickly as
possible, the mixture was diluted with 20 ml of water
and the resultant mixture was labelled 75-A. A sample
of 75-A was centrifuged to remove the bubbles.
To the second 49.5 g portion of the original
PAA/PVA mixture were added 6 ml of isopropanol (BDH
Chemicals Analar; water 0.2~, Lot #39721). The internal
temperature of the mixture was raised to 68~ C and 9.1 g
of starch powder ("Amistar B" St. Lawrence Co., Lot
#08275-B) were added all at once with constant stirring.
3.5 g of ammonium alum USP (Drug Trading Co. D.T.
#003251 ground to a fine powder) were added. The
mixture was stirred and then diluted with 8 ml of
- 46 -
133~682
isopropanol. The resultant mixture was centrifuged and
labelled 76-A.
The internal temperature of the third 49.5 g
portion of the original PAA/PVA mixture was raised to
68~ C. 9.1 g of starch powder (as above) were added
with constant stirring. 3.5 g of ammonium alum USP (as
a~ove) were added. The mixture was stirred, diluted
with 5 ml of isopropanol and 7 ml of distilled water,
centrifuged and labelled 77-A.
The internal temperature of the fourth 49.5 g
portion of the original PAA/PVA mixture was raised to
68~ C. Starch powder and ammonium alum were added to
this portion as described hereinabove. The resultant
mixture was then diluted with 4 ml of ethanol and 3 ml
of water, centrifuged and labelled 78-A.
Each of the hydrogel-forming materials 75-A,
76-A, 77-A and 78-A were applied to healthy skin and the
following observations were made:
- 47 -
1;33~R2
Table XI
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 10 min. 1 hr.
post post post post post post post
Sample imm'n imm'n imm'n imm'n imm'n imm'n imm'n
75-A slight not not not not some
tack tacky tacky tacky tacky crack-
ing:
76-A slight slight not slippery tacky very crack-
tack tack tacky: tacky ing:
smooth some
surface peeling
77-A slight least not slippery tacky tacky no
tack tack tacky: crack~:
no
peeling
78-A slight least not no slight no cracked:
tack tack tacky: tack tack tack peeling
(with rough
77-A) surface
'~ ~ 48 ~
1~9~82
~xample 12 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Gluconolactone, Sodium 8enzoate,
Sorbitol, Sorbic Acid, Distilled Water,
Glycerol, Starch, and Ammonium Alum"
120 g of the two grades of 25% aqueous PAA
and 28 g of PVA were prepared and mixed in the manner
described above for Example 11. Unless otherwise
indicated, the specific product quality and information
is the same as in Example 11. Subsequent additions of
1) 13.2 g 1,5-gluconolactone
2) 0.24 g sodium benzoate
3) 13.2 g sorbitol
4) 0.24 g sorbic acid
5) 107 ml distilled water
were then made in accordance with the directions of
Example 11. The resultant mixture was divided into four
46.0 g portions.
The internal temperature of the first portion
was raised to 75 C. The following additions were made:
1) 3.3 g of glycerol U.S.P.
2) 9.1 g of starch powder ("Amistar B", St.
Lawrence Starch Co., Lot #08275-B)
3) 3.5 g of ammonium alum U.S.P. (Drug Trading
Co., D.T. #003251 ground to a fine powder)
dissolved in 10 ml of hot water.
The mixture was then diluted with 5 ml of
ethanol and 5 ml of water. The hydrogel-forming
material resulting from the first portion was labelled
67-A.
The internal temperature of the second portion
was raised to 68~ C. The following additions were made:
- 49 -
13-~9~82
1) 9.1 g of starch powder ("Amistar B", St.
Lawrence Starch Co., Lot #08275-B)
2) 3.5 g of ammonium alum USP (Drug Trading Co.
DT #003251 ground to a fine powder) dissolved
in 3.3 g of glycerol USP. The ammonium alum
was partially dissolved at room temperature
and almost completely dissolved in a hot water
bath at 80~ C.
The mixture was then diluted with 6 ml of
ethanol and 6 ml of water. The hydrogel-forming
material resulting from the second portion was labelled
68-A.
The third portion was diluted with 3 ml of
ethanol and 2 ml of water and then the internal
temperature of the mixture was raised to 68~ C. The
following additions were made:
l) 3.3 g of glycerol USP
2) 9.1 g of starch powder ("Amistar B", St.
Lawrence Starch Co., Lot #08275-B)
3) 3.5 g of ammonium alum USP (Drug Trading Co.,
DT #003251 ground to a fine powder) dissolved
in 6 ml of water in a hot water bath at 80~ C.
This material was diluted with 8 ml of ethanol
and 7 ml of water. The hydrogel-forming material
resulting from the third portion was labelled 69-A.
The fourth portion was diluted with 3 ml of
ethanol and 3 ml of water and the internal temperature
of the mixture was raised to 68~ C. The following
additions were made:
1) 9.1 g of starch powder (as above)
2) 3.5 g of ammonium alum USP (as above)
dissolved in 3.3 g of glycerol and 1 ml of
- 50 -
13~b82
distilled water. This alum mixture was heated
to 80~ C prior to adding to the fourth
portion.
The resulting mixture was diluted with 8 ml of
ethanol and 7 ml of water and was labelled 70-A.
Each of the samples was centrifuged.
Each of the four samples was then applied to
an area of healthy skin and the following observations
were made:
Table XII
General Application Testing
2 min. ' 4 min. 6 min. 1 hr.
Sample post-appln. post-appln. post-appln. post-appln.
67-A very tacky very tacky tacky least
9108sy
68-A very tacky very tacky tacky some gloss
69-A very tacky very tacky tacky some gloss
.
70-A very tacky very tacky slight tack most glossy
1~39~2
Table XIII
Water Resistance
5 Second 4 Minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 4 min. 4 min. 1 hr.
. post post post post post post
Sample imm'n imm'n imm'n imm'n imm'n imm'n
67-A slight less not no tack no tack slight
tack tack tacky: crack;
rough slight
surface peeling
68-A slight little not no tack very no
tack less tacky: slight cracks:
tack rough tack no
surface peeling;
69-A slight little not no tack slight no
tack less tacky: tack cracks:
tack rough no
surface peeling:
70-A slight little not no tack slight no
tack less tacky: tack cracks:
tack rough no
surface peeling
1~3~82
Example 13 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Potassium Hydroxide, Glycerol,
Sorbitol, Gluconolactone, Sodium Benzoate,
Sorbic Acid, Starch, Ammonium Alum,
Distilled Water and Ethanol"
30 g of Acrysol A-1 and 30 g of Acrysol A-3
were placed together in a glass vessel with constant
stirring. 4 ml of a 10% solution of potassium hydroxide
(BDH Chemicals Product #Bl0210, Lot #84277/5804) were
added to this mixture and stirred in to reduce the
acidity. The initial pH value of the mixture was 1.5.
After the potassium hydroxide addition, the pH was 3Ø
5.2 g of Vinol 107 (Lot #0809242) were added
and the mixture was covered and heated in a water bath
at 95~ C with intermittent stirring until the PVA had
dissolved. 8.8 g of Vinol 203 (Lot #01081424) were
added to the hot polymer mixture and dissolved by
continued heating in the hot bath at 95~ C with
intermittent stirring. The following ingredients were
then added in order:
1) 6.6 g of glycerol USP
2) 6.6 g of crushed sorbitol
3) 6.6 g of 1,5-gluconolactone dissolved in 10 ml
of distilled water
4) 0.12 g of sodium benzoate.
The internal temperature of the mixture was
lowered to 69~ C. 0.12 g of sorbic acid were stirred
in. With the internal temperature at 68~ C, 18.3 g of
starch powder ("Amistar B", St. Lawrence Starch Co., Lot
#08275-B) were added. The internal temperature was then
maintained at 66~ C and 7.0 g of ammonium alum (as in
Example 12) were added. Lastly, the mixture was
diluted with 30 ml of ethanol and centrifuged.
- 53 -
1339~82
The hydrogel-forming material was then applied
to an area of healthy skin and the following
observations were made:
Tablè XIV
General Application Testing
2 min. 4 min. 6 min. 12 min.
post-appln. post-appln. post-appln. post-appln.
slightly slightly slightly no
tacky tacky tacky tack
Table XV
Water ~esistance
4 min. Immersion Test
0 min. 2 min. 4 min. 6 min. 1 hr.
post- post- ; post- post- post-
imm'n imm'n imm'n imm'n imm'n
some no tack no tack no tack: tough;
swelling: dry: dry:
no gloss slight
cracking
~ 54 -
133~82
Example 14 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Potassium Hydroxide, Glycerol,
Sorbitol, Gluconolactone, Sodium Benzoate,
Sorbic Acid, Starch, Distilled Water,
Ethanol and Aluminum Sulfate"
Where the specific product quality and
information is not indicated in this example, it is to
be assumed that it is the same as in Example 13.
60 g of Acrysol A-1 and 60 g of Acrysol A-3
were placed together in a glass vessel with constant
stirring. 9 ml of a 10% potassium hydroxide solution
were added to this mixture and stirred in. While the
mixture was heated in a water bath at 95~ C, 10.4 g of
Vinol 107 and 17.6 g of Vinol 203 were added with
intermittent stirring until the PVA had dissolved. The
following ingredients were added in sequence:
1) 13.2 g of glycerol B.P.
2) 13.2 g of crushed sorbitol
3) 13.2 g of 1,5-gluconolactone dissolved in 22ml
of distilled water at 80~ C
4) 0.24 g of sodium benzoate.
Each of these additions was made while the
mixture was in a hot water bath at 95~ C.
The internal temperature was lowered to 72 C
and 0.24 g of sorbic acid were stirred in. With the
internal temperature at 68~ C, 36.6 g of starch powder
were stirred in.
59.0 g of this mixture were added to 6 ml of
-~ 40% v/v ethanol in water. 2.4 g of al~uminum sulfate
i~ hexadecahydrate (BDH Chemicals; "Anala~ Lot #44368)
dissolved in 6 ml of distilled water were added to the
- 55 -
1~39 b82
mixture at room temperature. Dilution of the mixture
was made with 4 ml of 40~ v/v ethanol in water and the
material was centrifuged.
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
Table XVI
General Application Testing
2 min. 4 min. 6 min. 2 hours
post- po-t- post- post-
application application application application
tacky tacky moderate no cracks:
tack in low gloss
thin area~
Table XVII
Water Re~istance
5 second ~ 4 minute
Immersion Te~t Immerqion Test
-
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 5 hr.
post- po~t- post- post- post- poqt- post-
imm'n imm'n imm'n imm'n imm'n imm'n imm'n
very very opaque; no very very e~ten~ive
qlight ~light no tack qlight slight crackq:
tack tack tack tack tack a~h~
good to
very good
- 56 -
1:~39~82
Example 15 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Gluconolactone,
Sorbitol, Sodium Benzoate, Sorbic Acid,
Starch Powder, Distilled Water,
Ammonium Alum and Ethanol"
Two grades of PAA and two grades of PVA were mixed
together as indicated in Example 11. The subsequent additions
of glycerol, sorbitol, 1,5-gluconolactone, sodium benzoate and
sorbic acid were also made in accordance with the amounts and
directions of Example 11. Unless otherwise indicated, the
specific product quality and information is the same as in
Example 11.
With the internal temperature of the resultant
mixture at 68~C, 36.6 g of starch powder were added and
stirred in.
7.0 g of ammonium alum N.F. (Drug Trading Co.,
#DT220913, crushed) were stirred into 116.6 g of the polymeric
mixture as quickly as possible. The flow properties of the
resultant mixture were improved by the addition of 10 ml of
distilled water and 12 ml of 95~ ethyl alcohol.
Example 16 - "Hydrogel-Forming Material Comprising:
PAA/PVA, Glycerol, Sorbitol,
Gluconolactone, Sodium Benzoate, Sorbic Acid,
Starch Powder, Ammonium Alum, Ethanol and
Water - Viral Barrier Testing"
Two grades of PAA and two grades of PVA were mixed
together as indicated in Example 11. The subsequent additions
of glycerol, 1,5-gluconolactone, sorbitol, sodium benzoate,
sorbic acid and starch powder were also made in accordance
with the amounts and
1339~82
directions of Example 11. Unless otherwise indicated,
the specific product information and quality is the same
as in Example 11.
The resultant mixture was heated to an
internal temperature of 68~ C and 10.0 g of ammonium
alum USP (Drug Trading Co., DT #003251, ground) were
added. The mixture was diluted with, in total, 32.5 ml
of ethanol and 27.5 ml of water. The material was then
centrifuged.
Five circles~ (11 cm diameter, thickness 0.18-
O.20 mm) of Whatman~#40 filter paper (W.& R. Balston
Limited) were arranged in a row on a levelled surface
and secured with tape at the edges. Two spacer bars 1.0
mm thick were placed on either side of, and parallel to,
the row of circles. About 25 ml of the hydrogel-forming
material were spread over the circles to form a
substantially uniform coating using a sheet of stainless
steel with a straight edge drawn over the spacer bars.
After the coating had dried for 1 day in the ambient
atmosphere, test squares 1.5 X 1.5 cm were cut from the
coated filter paper circles and included the attached
filter paper. The thickness of these coated test
squares was 0.40 - 0.46 mm. Control squares 1.5 X 1.5
cm with no coating were cut from circles of Whatman #40
paper from the same box.
Barrier tests were carried out using a
cylinder 16 mm deep and 60 mm I.D. having a closed end.
The open end was placed on top of a circle of filter
paper 60 mm in diameter which had been soaked in cell
growth medium and dried. The test squares and control
squares were placed on this impregnated paper and
treated with a viral suspension as described below.
- 58 -
-~r~
- 1339~82
The impregnated paper was supported by a circular,
open mesh of polyethylene, and the mesh was maintained about
l0 mm above a bench surface by a metal ring with 4 "legs" to
allow free access of air to the underside of the paper.
The virus suspension was of ECHO ll, TDID50 = 106.
This pico RNA virus was chosen for its small size and
hardiness. For the test, 0.l ml of the suspension was placed
on the test or control square. In test Group A, the
suspension was left on the-square for l0 seconds and then
wiped off with a cotton swab. In test Group B, the suspension
was not wiped off. Typically, a test run for a single time
period consisted of two coated test squares and two control
test squares on a circle of paper impregnated with medium.
One test and one control square were in Group A and the other
test and control squares were in Group B. At the end of the
time period, measured from application of the viral
suspension, sections (approximately l.5 X l.5 cm) of the
impregnated paper beneath the test squares were cut out and
tested for the presence of the virus by culturing for 2 days
with MRC-5 cells in a suitable medium (MEM).
59
~33~82
Detection of Vlral Penetr~tion o~
Hydrogel ~rrier; "~ ~ detected~ not detected
Group A Oroup ~
(9~re~Qi-- wiped O~r (_ ,!r-io~ not
a~ter 10 ~econd~) wiped o~)
Test N~ Control Nydrogel Control
period -coated ~quare -coated square
O ~qyare squ~re
30 sec. not ~ not
det~--ni r-' det~ r -a
2 min,
5 min. - ~ ~
10 min. - ~ ~
30 min. -
1 hr. - ~ not
determined
Example 17 - "Hydrogel-Forming Material Comprising:
PAA/PE0, Water, Ethanol and Ammonium Alum"
~ 80 g of Polyox WSRN-750 (Union Carbide, Lot
#J-856 PE0 of MW 300,000) were dlssolved ln 800 g of
distilled water.
This solution was diluted with 600 g of
distilled water. To 3J4 or 1,110 g of the resultant
solution were added, with vigorous manual stirring, a
- 60 -
d~Y
1339~82
solution of 240 g of Acrysol A-1 in 250 g of distilled
water over a period of 5 minutes.
After standing overnight, a cream coloured
semi-opaque gum had formed at the bottom of a semi-
opaque white liquid. The liquid was decanted and the
gum was kneaded with a rod for about 15 minutes to
express any water.
To 55.3 g of this gum were added 29.9 g of
ethanol. After standing overnight, liquid and gum
portions had once again separated. The material was
loosely covered and stirred occasionally in a bath at 50
- 60~ C for 1 hour. The material was diluted with a
total of 69.2 g of ethanol and 9.6 g of water.
The mixture was then heated in a water bath at
approximately 60~ C until the internal temperature was
approximately 57 C. A total of 7 g of powdered
ammonium alum (BDH Chemicals "Analar" grade, Product
#Bl0007, Lot #10085/4784) were added and the mixture was
stirred and heated.
The resultant mixture was diluted in a final
stage with 10.6 g of ethanol and 5.6 g of distilled
water and then centrifuged. The liquid phase was
separated and the sediment discarded.
The resultant hydrogel-forming material was
applied to an area of healthy human skin and the
following observations were made:
- 61 -
1~39f~82
Table XVIII
General Application Testing
2 min. 4 min. 6 min. 1 hr.
post- post- post- post-
appl'n. appl'n. appl'n. appl'n.
very very slightly medium
tacky tacky tacky gloss: one
small crack
Table XIX
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 3 hrs.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
no no no no slight slight no
tack tack tack tack tack tack gloss:
invisible
Example 18 - "Hydrogel-Forming Emulsion Material
Comprising: PAA/copolymer of PE0, Water,
Ethanol, Propylene Glycol and Aluminum
Sulfate"
~
100.2 g of Pluronic F108-(BASF copolymer of
ethylene oxide/propylene oxide; 14,000; E0/P0 = 256/54)
were dissolved in 552 g of distilled water (unless
otherwise indicated, the specific product quality and
information is the same as in Example 17).
~ T~ 62 -
1~3~82
400.1 g of Acrysol A-1 were added with
vigorous stirring to the PE0 mixture at room
temperature. The resultant mixture after stirring and
settling at room temperature consisted of a mobile,
5clear liquid phase and a translucent, viscous lower
layer. The upper liquid'layer, which also comprises a
foam, was decanted and the lower layer was centrifuged
to separate any remaining mobile liquid.
1060.9 g of this viscous liquid were placed in a
250ml glass vessel and 9.8 g of ethanol were added. 4.0
g of aluminum sulfate hexadecahydrate BDH Chemicals,
"Analar" grade, Lot #44368) were dissolved in 10.1 g of
distilled water and the solution was diluted with 4.1 g
15of ethanol. The aluminum sulfate solution was then
mixed with the polymer solution at room temperature with
constant stirring. 1.9 g of propylene glycol U.S.P.
were added along with 10.3 g of ethanol. 3.7 g of this
material was labelled 13-D. 31.4 g of this material was
20centrifuged. The sediment and the clear, lower layer
were discarded and the top layer was labelled 14-B.
The hydrogel-forming emulsion materials 13-D
and 14-B were applied to areas of healthy human skin and
25the following observations were made:
- 63 -
13 3 9 b 82
Table XX
Water Resistance
~ 5 second 4 minute
Sample Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 8 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n
13-D slight slight moder- moder- slight very no
tack tack ate ate tack slight cracks:
tack tack tack adhesion
good:
very
supple
14-B moder- moder- moder- very slight very no
ate ate ate tacky tack slight detach-
tack tack tack tack ment:
adhesion
good:
very
supple
This example shows a hydrogel-forming material
comprising a PEO co-polymer which is complexed with PAA.
The addition of aluminum sulfate as a cross-linking
agent is also exemplified. The material resulting from
this example is in the form of a water-in-oil emulsion
which was applied to the skin in a similar fashion to
the liquid materials.
- 64 -
1 ~ 3 ~ 2
Example 19 - "Hydrogel-Forming Emulsion Material
Comprising: PAA/PE0, Water, Glycerol,
Ethanol, Ammonium Alum and Starch Powder"
40.2 g of Polyox WSR-N-10 (Union Carbide; PE0
MW 100,000; Lot #H-155) were dissolved in 200 g of
distilled water (unless otherwise indicated, the
specific product quality and information is the same as
in Example 17) and the solution was further diluted with
50 g of distilled water.
The solution was stirred while 160.1 g of
Acrysol A-l were added over 30 seconds. Stirring was
continued for 5 minutes after the completion of the
addition. The clear aqueous phase was decanted and
discarded. The viscous phase was centrifuged and the
aqueous phase was again discarded.
9.1 g of glycerol were stirred into the
mixture at room temperature, followed by 33.1 g of
ethanol.
49.5 g of the resultant mixture were
transferred to a 250ml glass vessel and the liquid was
heated to 62~ C. 4.5 g of powdered ammonium alum were
added. While the mixture was still warm, 4.6 g of
starch powder were stirred in. A total of 9.4 g of
ethanol was added to dilute the mixture.
Part of the resultant mixture was centrifuged
and labelled 25-B. Another part of this mixture (34.3
g) was mixed with 4.2 g of starch powder with manual
stirring. The material was then diluted with 3.9 g of
ethanol, centrifuged and labelled 25-D.
- 65 -
1~3~82
Each of the hydrogel-forming emulsion
materials 25-B and 25-D were applied to healthy areas of
human skin and the following observations were made:
Table XXI
General Application Testing
2 min. 4 min. 6 min. 8 hr.
post- post- post- post-
Sample appl'n. appl'n. appl'n. appl'n.
25-D tacky slight very low gloss:
tack slight good
tack -- - ~ nn
good
transparency
25-B tacky tacky slight gloss high:
tack transparency
good: good
adhesion
' ~ 66 -
133~8~
Table XXII
Water Resistance
5 second 4 second
Immersion Test Immersion Test
Samples 1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 10 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
25-D no no no no no no cracked;
tack tack tack tack: tack; tack; A~hPcinn
~light slight slight haze good
haze haze haze gone
25-8 very very no no no no overall
slight slight tack tack tack tack appear-
tack tack ance very
good;
some
large
cracks:
no gloss,
adhesion
good
Example 20 - "Hydrogel-Forming Material Comprising:
PAA/PE0, Water, Glycerol, Ethanol, Ferric
Sulfate and Starch Powder"
The material of the present example was
prepared in accordance with Example 19 up to and
including the addition of 9.1 g of glycerol and 33.1 g
of ethanol to the bottom layer of the viscous liquid of
the PAA/PE0 complex. Unless otherwise indicated, the
1~3~2
specific product quality and information is the same as
in Example 19.
49.4 g of the material thus formed were placed
in a 250 ml glass vessel and heated to 62~ C. 2.2 g of
ferric sulfate powder (Fisher Scientific Co., Product
#I-142, Lot #793709, Fe2[so4 ]3 .nH20) were stirred into
the liquid with constant stirring. While the mixture
was still warm, 7.0 g of starch powder along with 37.9 g
of ethanol and 0.9 g of water were added.
The material was left to stand overnight at
room temperature. It was then stirred intermittently in
a bath at 50 - 60~ C for 30 minutes, appropriately
cooled and then centrifuged.
The hydrogel-forming material was then applied
to an area of healthy human skin and the following
observations were made:
Table XNII
General Application Testing
2 min. 4 min. 6 min. 1 hr.
post- post- post- post-
appl'n. appl'n. appl'n. appl'n.
tacky very slight no tack no cracks:
tack substantially
transparent:
not tacky
- 68 ~
13~9~82
Table XXIV
Water Re~istance
5 second 4 minute
Immersion Test Immersion Te~t
1 min. 2 min. O min. 2 min. 4 min. 6 min. 9 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
no no no no no no L ~ h~ y
tack tack tack tack tack tack t~ ~ ~nt:
extensively
cracked
Example 21 - "Hydrogel-Forming Emulsion Material
Comprising: PAA/PVP, Water, Ethanol,
Propylene Glycol and Urea"
100 g of Plasdone K29-32 (PVP, also labelled
Plasdone NF from GAF Corporation, Lot #G-90504B-54) were
dissolved in 400 ml of distilled water. 400 g of
Acrysol A-l were diluted with 400 g of distilled water.
~ The PVP solution, in a 2-litre Pyrex~glass measuring
vessel was stirred manually as the PAA solution was
slowly added. With continued stirring for approximately
5 minutes, a pale yellow liquid separated from the
fibrous mass. The liquid was decanted and the fibrous
mass was compressed with a stirring rod in a kneading
motion as further liquid was expressed. Kneading was
continued at intervals over the next 2 hours until the
precipitate was a stiff, non-tacky, cream- coloured gum.
Stirring and manipulation of the decanted liquid was
continued until it yielded a similar gummy material.
~ 69 -
133~b82
The two portions of gummy material were
combined and cut into small pieces with a pair of
scissors and placed in a 500 ml vessel with 65 g of
ethanol. The mixture was loosely covered and kept in a
water bath at 75~ C for 1.4 hours and then heated at
between 65 - 75~ C for an additional hour. The material
was left to stand overnight.
The next day the material was covered and
heated in a bath at 75~ C for 2 hours with constant
stirring. The mixture was then diluted with 156 g of
ethanol and 19.5 g of distilled water and the mixture
was heated in a bath at 70 - 75~ C for 2 hours without
stirring.
170.2 g of this mixture were placed in a 500
ml glass vessel and 25.0 g of propylene glycol USP were
added. 18.0 g of urea (BDH Chemicals, "Analar" grade,
Product #B10290, Lot #99795/4060) were stirred into the
mixture. Further dilutions with 16.8 g of ethanol and
2.7 g of distilled water were made after the mixture had
been warmed. A further 18.0 g of urea were added and
the mixture was stirred at room temperature. A further
9.1 g of propylene glycol USP were added with constant
stirring at room temperature.
The material resulting from these additions
was centrifuged and the top layer of clear mobile liquid
was discarded. The bottom layer was the hydrogel-
forming emulsion material.
This emulsion material was applied to areas of
healthy human skin and the following observations were
made:
-- 70 --
13~82
Tsble XXV
General Application Te-ting
2 min 4 min 6 min 2 hr 7 hr
post- post- post- po~t- po~t-
appl'n appl'n appl'n appl'n appl'n
tacky slight to slioht no lo-- oi no lo~- or
moderate tack ~ ad ~ .c ;
tack no crack- no crack~
very very
81i~ht 811ght
tack tack
Table XXVI
Water Re~i~tance
5 second 4 minute
Immer~ion Te-t Immer~ion Te~t
1 min 2 min 0 min 2 min 4 min 6 min 3 hr
po~t- po-t- po-t- po-t- po-t- po-t- po~t-
imm'n imm'n imm'n imm'n imm'n imm'n imm'n
moder- very opaque slight slight very clear;
ate slight white tack tack slight ~ew
tack tack no tack partially tack mcdium
cle-r crack-
no
detached
areaa
jl~ ~h ~ 'n
very
good
- 71 -
1~3~82
The hydrogel-forming emulsion material of this
example shows that a cross-linking agent need not be
added in all of the embodiments of this invention to
obtain reasonably good water resistance.
Example 22 - "Hydrogel-Forming Emulsion Material
Comprising: PAA/PVP, Water, Ethanol and
Glycerol"
The material of the present example was
prepared in accordance with Example 21 described
hereinabove up to and including the addition of 163 g of
ethanol and 19.5 g of water to the PAA/PVA gummy
complex. Unless otherwise indicated, the specific
product information and quality is the same as in
Example 21.
170.4 g of the material thus formed were
placed in a 500 ml glass vessel and heated at
approximately 85 C with frequent stirring. The
material was cooled and 53.6 g were transferred to a 300
ml glass vessel. A solution of 8.0 g of glycerol in
13.5 g of ethanol was added at room temperature. The
mixture was stirred in a bath at approximately 70~ C,
cooled, and centrifuged.
The hydrogel-forming emulsion material was
then applied to an area of healthy human skin and the
following observations were made:
7 2 --
~3~82
Table XVII
General Application Testing
2 min. 4 min. ' 6 min. 2 hr. 7 hr.
S post- post- post- post- post-
appl'n. appl'n. appl'n. appl'n. appl'n.
slight very very no loss of 2% of area
tack slight slight A~h~Qi~- detached:
tack: tack no cracks: medium
soft no tack crack:
no tack
Table XXVIII
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 3 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
slight no tack opaque slight very no tack: clear:
tackwhite: tack slight partially 1 crack:
clear 5% of
area
detached:
poor flexi-
bility
This example illustrates a hydrogel-forming
material with good water resistance having no cross-
linking agent.
- 73 -
1 3 ~ 2
Example 23 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol and Ethanol"
~ 60 g of gelatin, USP)Bloom 275 (Canada Packers
"Gelrite" Type A porcine hide gelatin, Lot #B647) were
dissolved in 400 g of distilled water. 240 g of Acrysol
A-.3, were diluted with 200 g of distilled water and the
internal temperature was raised to 60~ C.
The internal temperature of the gelatin
mixture was raised to 45 C. The diluted PAA at 45~ C
was added quickly to the gelatin solution at 45~ C with
constant electric mixing.
152.4 g of the resultant mixture were stored
at room temperature. After storage, 2.0 g of rejected
water were discarded. There was no evidence of
microbial growth. 16.3 g of glycerol BP and 20.2 g of
ethanol were added. The mixture was kept in a water
bath at 60 - 65~ C for 25 minutes and then stirred with
a rod. A further 5.7 g of ethanol were added.
Example 24 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol, Ethanol,
Calcium Chloride ~ Optionally
Ammonium Alum"
The material of the present example was
prepared in accordance with Example 23 up to and
including the addition of the glycerol and ethanol to
the PAA/gelatin complex. Unless otherwise indicated,
the specific product quality and information is the same
as in Example 23.
~ f ~ 74 -
1~39~82
The material thus formed was divided into
three portions.
To 179.4 g of the complex prepared as in
Example 23 were added 13.3 g of calcium chloride
dihydrate as a granular solid (BDH Chemicals; Analar
grade; Product #B10070; Lot #96660/9711).
.
A first portion, 29.1 g of this complex, was
not treated any further and was labelled 64-D.
A second portion, 29.9 g of this complex was
placed in a small glass vessel, covered with a watch
glass and heated in a water bath at 65~ C for 30
minutes. 2.5 g of powdered ammonium alum (Drug Trading
Co., BP grade; #003251; Lot #270486) were stirred into
the mixture as rapidly as possible with a stiff rod.
The mixture was then diluted with a total of 38.2 g of
ethanol and 22.6 g of distilled water and labelled 68-A.
13.3 g of this mixture were centrifuged and labelled 66-
B.
A third portion, 29.1 g of this complex, was
covered and heated in a bath at 60 - 70~ C for
approximately 30 minutes, after which the internal
temperature was approximately 56~ C. 1.0 g of powdered
ammonium alum (as above) was stirred in as quickly as
possible. The mixture was diluted with a total of 27.8
g of ethanol and 24.7 g of water. The material was
allowed to stand at room temperature overnight and then
a further 8.7 g of ethanol and 3.3 g of distilled water
were added. 11.9 g of this mixture were centrifuged and
labelled 68-B.
Samples of the hydrogel-forming materials
labelled 64-D, 66-B and 68-B were applied to areas of
- 75 -
13 ~ 9 b 8 ~
healthy human skin and the following observations were
made:
Table XXIX
General Application Testing
2 min. 4 min. 6 min. 1 hr. 2 hr. 10 hr.
post- post- post- post- poct- post-
Sample appl'n. appl'n. appl'n. appl'n. appl'n. appl'n.
64-D still very very - tran8-
viscous tacky tacky parent:
liquid glossy:
no loss of
adhesion
66-B set but slight no - no los_
tacky tack tack of l~h~c;
no cracks
68-B tacky tacky slight trans- - no
stronger tack parent: detached
gel no areas:
than at cracks: no cracks
2 min. no tack:
completely
adherent ¦
- 76 -
Table XXX
Water Resistance 13 3 ~ ~ 8 2
5 second 4 minute
Immersion Test Immersion Test
see see
Sample 1 min. 2 min. 0 min. 2 min. 4 min. 6 min. below below
64-D tacky slight very very very tacky 1 hr:
tack tacky tacky tacky l small
crack:
no 1088
of
adhe8ion
66-B not not not very no no 7 hr.: 13 hr:
tacky tacky tacky slight tack tack no 1088
tack of ad- adhe-
hesion sion
llent
68-B slight slight very very no no l.5 hr:
tack tack slight slight tack: tack no loss
tack: tack trans- of
whitish parent adhesion:
good to
very
good
adhesio~
1339~82
~xample 25 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Ethanol, Glycerol,
Calcium Chloride, Ammonium
Alum and Starch Powder"
s
The material of the present example was
prepared in accordance with Example 24. Unless
otherwise indicated, the specific product information
and quality is the same as in Example 24.
To the material labelled 68-A in Example 24
were added 4.5 g of cross-linked starch powder (Amistar
"B", St. Lawrence Starch Co.), and the mixture was
stirred for about 7 minutes. The material was diluted
with 2.1 g of ethanol and 2.9 g of water and 14.0 g of
the resultant mixture were centrifuged.
The hydrogel-forming material was then applied
to an area of healthy human skin and the following
observations were made:
Table XXXI
General Application Testing
2 min. post- 4 min. post- 6 min. post- 2 hr. post-
Application Application Application Application
tacky slight tack very slight transparent;
but set tack slight gloss:
no detachment
~ - 78 -
Table XXXII 13 3 9 ~ 8 2
Water Resistance
5 second 4 minute
S Immersion Test Immersion Test
1 min. 2 min. O min. 2 min. 4 min. 6 min. 1 hr.
po~.t- post- post- post- post- po~t- post-
imm'n. im~'n. imm'n. imm'n. imm'n. imm'n. imm'n.
slight slight no tack; very al~st no tack AAh~.i,
tack to very some slia,ht trans gcod
sli~ht capacitv tack ~arent
tack sllqht
tack
In the occlusive glove test, this hydrogel-
forming material performed quite well and it was not
damaged on removal of the glove. Finger tack was
slight.
Example 26 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Ethanol, Glycerol
and Polyethylene Glycol"
Unless otherwise indicated in this example,
the specific product quality and information is the same
as in Example 25.
60 g of gelatin were dissolved in 400 g of
distilled water. 240 g of a 25~ aqueous PAA solution
were diluted with 200 g of distilled water and the
internal temperature was raised to 60~ C. With the
internal temperature of the gelatin solution at 45~ C,
the diluted PAA at 55~ C was added quickly to the
- 79 -
1339~82
gelatin with continual mechanical mixing. Upon cooling
the material separated into a liquid and a gel. The
liquid layer was decanted and as much water as possible
was squeezed out of the gel to form a gum.
64 g of this complex were heated and the
following components were mixed together and added to
the PAA/gelatin complex:
1) 10 g of polyethylene glycol PEG-300
2) 10 g of 100% ethanol
3) 4 g of glycerol B.P.
The resultant mixture was then diluted with 10
ml of distilled water and 10 ml of 100% ethanol.
Example 27 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Ethanol, Glycerol,
Propylene Glycol, PVP, Calcium
Chloride, Sodium Benzoate, Sorbic Acid &
Chitin Powder"
30 g of gelatin (retail grade; Davis Gelatine
Co., Bloom #150; Lot #B22451) were dissolved in 240 ml
of distilled water in a 1 litre glass vessel. The
mixture was heated to approximately 60 C.
120 g of a 25% a~ueous solution of PAA
(Polysciences Inc.; Product #0627, Lot #55107) were
diluted with 150 ml of distilled water giving a solution
of 30 g of PAA in 240 ml of distilled water. The PAA
solution was warmed to 42~ C and added to the gelatin
solution with manual stirring. A precipitate formed.
The aqueous phase was decanted and discarded. The gummy
precipitate was kneaded for 1 hour and expressed water
was discarded.
- 80 -
133g682
To 42.3 g of the gumm~ precipitate were added
1.2 g of glycerol and 2.3 g of propylene glycol. The
resulting mixture was heated at 70 - 80~ C and stirred
until homogeneous. While still warm, a solution of 3.0
g of PVP (GAF Corp., Plasdone K-29-32, Lot #G-30121B) in
7 ml of ethanol was added.
23.4 g of this mixture were heated in a bath
at 70 - 80~ C until it became mobile and 2.0 g of
calcium chloride dihydrate (BDH Chemicals, Product
#B10070, Lot #96660/9711) were added with manual
stirring. After this mixture had cooled, 26.5 mg of
sodium benzoate and 24.5 mg of sorbic acid were added as
dry powders.
The resulting mixture was heated once again in
a bath at 70 - 80~ C and 1.3 g of protein-free, finely
powdered chitin (Bentech Laboratories) were added. The
chitin powder dispersed very quickly when the mixture
was stir~ed.
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
Table XXXIII
General Application Testing
2 min. 4 min. 6 min. 12 min. 1 hr.
post- post- post- post- post-
appl'n. appl'n. appl'n. appl'n. appl'n.
very tacky very tacky slight tack not tacky: soft but
very soft much
il, uv~d
~ 81 -
1 33~b82
It was found that this material had good
adhesion 7 hours after application; however, it was
extensively cracked at knuckle joint creases.
Example 28 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Propylene Glycol,
Ethanol, Calcium Chloride and Chitin
Powder"
A PA~ /gelatin complex comprising 20 g of
gelatin (Bloom~150) in 140 ml of water and 20 g of PAA
in 140 ml of water was prepared in accordance with
Example 27. Unless otherwise indicated, the specific
product quality and information is the same as in
Example 27.
21.8 g of the PAA/gelatin complex thus formed
was mixed with 2 g of propylene glycol USP. The mixture
was heated in a bath at approximately 80~ C and stirred
until homogeneous. 2 ml of ethanol were then added to
the clear solution with brief stirring. While still
warm, 2 g of calcium chloride dihydrate were added.
The hydrogel-forming material was applied to
an area of healthy human skin. The water resistance of
the dry coating was quite good. Even after about 10
hand washings with Ivory bar soap, traces of the
material still remained on the skin.
Example 29 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin and Water"
To a solution, at 43~, of 10.5 g of gelatin
(retail grade; Davis Gelatine Co., Bloom #150; Lot
#B22451) in 50 ml of distilled water was added a
solution of 10 g of PAA (MW 5,000) in 96 ml of distilled
- 82 -
~ r~
1 ~ 3 9 b 8 2
water at 42~ over 15 seconds. A viscous amber liquid
separated. The top layer was decanted and discarded.
The PAA/gelatin complex thus formed was
applied to an area of healthy human skin and the
following observations were made:
Table XXXIV
General Application Testing
15 min. 18 min. 24 min. ~ 2 hrs.
post-appl'n. post-appl'n. post-appl'n. post-appl'n.
moderate slight tack not tacky: film
tack soft in inflexible;
thick areas cracked in
some areas:
transparent
Approximately 6 hours after application, the
coating was immersed in lukewarm water for 2 minutes.
At the end of this time, it was tacky but still retained
excellent adhesion to the area of skin originally
covered and showed no sign of dissolution. It was
removed without difficulty by "rolling" it off the
coated area.
Example 30 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol,
Isopropanol and Calcium Chloride"
A PAA/gelatin complex comprising 10 g of
gelatin (Bloom #150) in 50 ml of water and 10 g of PAA
(MW S50,000) in 60 ml of water was prepared in
accordance with Example 27. Unless otherwise indicated,
- 83 -
1~3~82
the specific product quality and information is the same
as in Example 27.
To the PAA/gelatin complex thus formed, were
added 10 g of glycerol and 20ml of isopropanol (BDH
Chemicals: "Analar" grade: Lot #39721). The mixture was
stirred in a water bath at approximately 50~ C until it
was homogeneous. It was then allowed to stand until the
bubbles had risen.
Half of this mixture was heated in a hot water
bath until it became very fluid. 17 ml of isopropanol
were added wlth constant stirrlng for several minutes.
The material was left overnight and it set to a gel with
significant strength. Upon heating at 75 - 80~ C, the
material melted to a translucent liquid. 2.6 g of
calcium chloride dihydrate were added and the mixture
was stirred manually for 5 minutes.
The hydrogel-forming material, which did not
gel at room temperature, was applied to an area of
healthy human skin and the following observations were
made:
Table XXXV
General Application Testing
7 min. 15 min. 25 min. 4 hr. ~9 hr.
post-appln. post-appln. post-appln. post-appln. post-appln.
glight to ~light ~light very no tack;
moderate tack: - tack S~ hle: no detac~nent
tack tL ~ ~.. t very at edqes
sliqht
tack
~ 84 -
133~82
Table XXXVI
Water Resistance
5 minute 4 minute
Immersion Test Immersion Test
1 min. O min.
post-imm'n. post-imm'n.
tL~ A~: tL~.. O~aLC.. t
vory twky oO~t gum
The hydrogel-forming material was stored for 2
years at room temperature. After this storage, the
material appeared unchanged except for a small, opaque
lower layer which was easily re-dispersed by agitation.
Example 31 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol, Calcium
Chloride, and Ethanol"
A PAA/gelatin complex comprising 30 g of
gelatin (Bloom 150) in 200 ml of water and 30 g of PAA
(MW <50,000) in 210 ml of water was prepared in
accordance with Example 27. Unless otherwise indicated,
the specific product quality and information is the same
as in Example 27.
To 22.3 g of the PAA/gelatin complex thus
formed were added 2.5 g of glycerol. The mixture was
homogenized with heating and stirring. 2.0 g of calcium
hloride dihydrate were then added and the mixture became
an opaque soft gum on cooling. It was warmed in a bath
- 85 -
~33~82
at 55~ C and then 4 ml of ethanol were added. The
material did not gel at room temperature.
Example 32 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol and Ethanol"
40 g of a 25~ of solution of PAA
(Polysciences; Category #0627; Lot #55107; MW <50,000)
were diluted with 30 ml of distilled water.
10 g of Polypro 15,000 (George A. Hormel &
~o.; Lot #294-5; gelatin hydrolysate, MW ~ 15,000) were
dissolved in 50ml of distilled water. When the solution
was at a temperature of 23~ C the PAA solution was added
with vigorous stirring. A viscous liquid separated.
The mobile aqueous phase was decanted and the viscous
liquid was kneaded while additional water was decanted.
10 g of glycerol were mixed into the liquid by stirring
and heating.
15 ml of ethanol were added and the resultant
mixture was heated in a bath at approximately 50 C
until the bubbles had risen to the surface. The mixture
was then allowed to cool at room temperature.
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
P~
i - 86 -
~3~82
Table XXXVII
General Application Testing
4 min. 9 min. 18 min. ~ 11 hr.
post-appl'n. po~t-appl'n. po~t-appl'n. post-appl'n.
tacky thick area~ slight tack adherent to 100~
liquid ~till tacky of original area:
transparent: supple
Example 33 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol and
Isopropanol"
A PAA/gelatin complex comprising 10 g of
gelatin hydrolysate (Polypro 15,000) in 130 ml of water
and 10 g of a PAA solution (MW -300,000 Polysciences,
Lot #36668, Cat. #4551) in 50 ml of water was prepared
in accordance with Example 32. Unless otherwise
indicated, the specific product quality and information
is the same as in Example 32.
To the PAA/gelatin complex thus formed were
added 10 g of glycerol. The mixture was heated until
homogeneous and then cooled to room temperature. 15 ml
of isopropanol (BDH Chemical Co., Analar, Lot #39721)
were added with additional stirring and heating.
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
- 87 -
1~39 i~2
Table XXXVIII
General Application Testing
4 min. 10 min. 24 min. 49 min. 10 hr.
post-appln. post-appln. post-appln. post-appln. po~t-appln.
thin areas tack in coating so~t: adherent to
not tacky: thick areas soft supple: 100% o~
thick area~ ~imin~h~d ~ nt original
~light tack area
Table XXXIX
Water Re~i~tance
5 second 4 minute
Immer~ion Test Immersion Test
1 min. 0 min. 23 min.
post-imm'n. post-imm'n. post-imm'n.
clear: whitish: clear:
moderate tack tran~lucent transparent:
but intact slight tack
and adherent:
tacky
Example 34 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin and Water"
240 g of Acrysol A-1 were diluted with 200 g
of distilled water and the mixture was heated to 47~ C.
60 g of gelatin USP (Gelrite 150, Canada Packers, Lot
#0175) were dissolved in 404 g of distilled water by
stirring and heating. The temperature of the liquid did
not exceed 55~ C during the dissolving process. The
gelatin solution was stirred and maintained at 48~ C.
1~3~'S82
The PAA solution at 47~ C was added to the gelatin
solution over a period of approximately 1 minute.
Stirring of the resulting precipitate was continued for
approximately 16 minutes. The material was then left to
stand overnight at room temperature. The resulting
material consisted of a gùmmy solid on top of an almost
clear liquid which was decanted and discarded.
Example 35 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol, Ethanol,
Urea, Ammonium Alum and Optionally Starch
Powder"
A PAA/gelatin complex was prepared in
accordance with Example 34. Unless otherwise indicated,
the specific product quality and information is the same
as in Example 34.
44 g of the gummy PAA/gelatin complex thus
formed was mixed with 4.7 g of glycerol B.P. and 6.9 g
of ethanol. The mixture was loosely covered and heated
to approximately 50~ C with intermittent stirring until
the mixture became homogeneous. 12.0 g of urea (BDH
Chemicals, Product #B10290, Lot #99795/4060) were added.
46.8 g of this mixture were maintained at
approximately 60~ C and then 1.4 g of powdered ammonium
alum (BDH Chemicals "Analar" grade, Product #B10007, Lot
#100085/4784) were added with stirring. The mixture was
then diluted with a total of 15.8 g of ethanol and 6.9 g
of water and was left to stand at room temperature for 3
hours.
A 21.5 g sample of this material was labelled
62-A. The remainder of the material, 47.6 g, was mixed
- 89 -
1~39~82
with 4.3 g of Amistar "B" starch powder (St. Lawrence
Starch Co.). A further dilution with 3.6 g of ethanol
and 1.3 g of distilled water was made with continual
stirring.
23.8 g of this material were transferred to a
clean vessel and stirred for approximately 5 minutes
with 3.5 g of Amistar "B" starch powder. A further
dilution with 2.5 g of ethanol and 0.9 g of distilled
water was made. The material was centrifuged and
labelled 63-C.
Samples of the hydrogel-forming materials 62-A
and 63-C were applied to areas of healthy human skin and
the following observations were made:
Table XL
General Application Testing
2 min. ~ 4 min. 6 min. 6 hr.
Sample post-appln. post-appln. post-appln. post-appln.
62-A very tacky very tacky very tacky very slight to
slight tack: no
loss of adhesion:
no cracks:
trsnsparent
63-C moderate slight very no tack: no areas
tack tack slight of lost ~
tack no crack~:
t.~ arent
-- 90 --
1~3~2
Table XLI
Water Resistance
~ 5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 1.5 hr.
post- po~t- post- post- post- post- post-
Sample imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
62-A slight slight very very very no 1 large
tack tack slight slight slight tack crack:
tack: tack tack 3% of
~ thick original
areas area
hazy detached
63-C no no noslight very no many
tack tack tack: tack slight tack cracks:
thick tack 8% of
areas original
whitish area
detached
Example 36 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol, Ethanol,
Calcium Chloride, Ammonium Alum and
Starch Powder"
A PAA/gelatin complex was prepared as in
Example 34. Unless otherwise indicated, the specific
product quality and information is the same as in
Examples 34 and 35.
To 208 g of the gummy complex resulting from
- 91 -
133~b82
Example 34 were added 22.5 g of glycerol and 21.1 g of
ethanol. The material was labelled 33-0.
53.1 g of this material were heated in a water
bath until the internal temperature of the solution was
53 C. 4.1 g of calcium chloride dihydrate (BDH
Chemicals, "Analar" grade Product #B10070, Lot
#96660/9711) were added with brief stirring. 2.0 g of
powdered aluminum ammonium sulfate (BDH Chemicals,
"Anaiar" grade Product #Bl0007, Lot #100085/4784) were
added to the warm mixture and stirred in as quickly as
possible. The mixture was cooled and diluted with a
mixture of 17.0 g of ethanol and 4.9 g of dlstilled
water.
The resulting material was centrifuged and the
beige, translucent liquid which formed was decanted from
the white sediment. 5.4 g of crosslinked starch powder
(Amistar "B"; St. Lawrence Starch Co.) were added to the
liquid at room temperature with manual stirring for
approximately 4 minutes. The mixture was then diluted
with a total of 4.2 g of ethanol and 2.2 g of water.
Once again, the material was centrifuged.
Example 37 - "Hydrogel-Forming Material Suitable for
Aerosol Use Comprising: PAA/Gelatin,
Water, Ethanol, Calcium Chloride and
Ammonium Alum"
Unless otherwise indicated, the specific
product quality and information in this example is the
same as in Example 36.
29.7 g of the complex designated 33-0 in
Example 36 were loosely covered and heated in a water
bath at 60 C for 30 minutes. 2.3 g of calcium chloride
- 92 -
1339~2
dihydrate were added and the mixture was stirred until
the solid disappeared. 1.1 g of powdered ammonium alum
were stirred into the warm mixture. Dilution with 23.9
g of water and 50.8 g of ethanol was then effected. The
material was centrifuged for 20 minutes and the liquid
was decanted from the white sediment.
Some of the liquid was p~ ced in a Drixoral
~ ~ pump spray (container from Drixoral decongestant nasal
spray sold by Shering Canada Inc.). When the pump was
activated, this particular liquid materlal was ~udged
too viscous for use in this device.
Accordingly, 84.9 g of the liquid were further
diluted with a mixture of 12.1 g of water and 25.6 g of
ethanol (ratio 32:68). The material thus formed was
loaded into the Drixoral pump spray and the aerosol
effluent was ~udged to be acceptable.
The underside of the wrist of the left hand
was held 6 inches above the pump spray and maintained
horizontal. Six sprays about 1.5 seconds apart were
directed at the skin of the wrist which formed a wet
area about 5 centimeters in diameter. The following
observations were made:
Table XLII
General Application Testing
2 min. 4 min. 6 min. 8 min.
post-appl'n. post-appl'n. post-appl'n. post-appl'n.
tacky substantially slight tack slight tack
dry: tacky
~ g3 -
~f~d4~h~
1~3~82
Table XLIII
Water Resistance
4 Minute Immersion Te~t
O min. 2 min. 4 min. 6 min. 10 min.
post-imm'n. po~t-imm'n. post-imm'n. post-imm'n. po~t-imm'n.
not tacky not tacky ~light tack ~light tack no tack
Example 38 - "Hydrogel-Forming Material Comprising:
PAA/Gelatin, Water, Glycerol, Ethanol,
Calcium Chloride, Ammonium Alum, and
PVA Powder"
Unless otherwise indicated, the specific
product quality and information is the same as in
Example 36.
29.4 g of the complex designated 33-0 in
Example 36 were loosely covered and heated in a water
bath at approximately 60 C. 2.3 g of calcium chloride
dihydrate and 1.1 g of powdered ammonium alum were added
and the mixture was stirred, cooled and stirred again.
The mixture was diluted at room temperature with 9.5 g
of ethanol and 3.8 g of distilled water and was
centrifuged to remove the sediment. The liquid was
~ decanted into a clean vessel and 8.0 g of PVA (Elvanol~
75-15, Lot #L6K024, a fully hydrolyzed medium molecular
weight grade of PVA manufactured by DuPont), which had
been seived using an 8" #170 mesh (US Standard, aperture
88 microns), were added. A total of 14.4 g of ethanol
and 9.9 g of water was then added and the material was
centrifuged.
- 94 -
1333b8.~
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
Table XLIV
General Application Testing
2 min. 4 min. 6 min. 2 hr.
post-appl'n. post-appl'n. post-appl'n. post-appl'n.
moderate very slight no tack: no tack:
tack tack soft 1% original
- area detached:
transparent:
no gloss
Table XLV
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 1.5 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
no tack no tack no tack no tack no tack no tack many cracks:
50% o$
original
area
detached
3 5
- 9 5 -
1339~2
Example 39 - "Hydrogel-Forming Emulsion Material
Comprising:
PMA/PE0, Water and Ethanol"
10.0 g of poly(methacrylic acid) powder (PMA,
Polysciences Inc., cat. #578, Lot #213-11) were
dissolved in 200 g of distilled water. The PMA solution
was added to a solution of 10 g of Polyox WSRN-750
(Union Carbide; Lot #J-856 - PE0 of MW 300,000) in 350 g
of distilled water with vigorous stirring. A fibrous
white precipitate formed during the addition.
After standing overnight, the precipitate had
formed a solid gel which was subsequently kneaded to
remove the occluded water. This produced 28.3 g of a
friable solid.
To 13.9 g of this solid were added 15.3 g of
ethanol. The mixture was loosely covered and heated in a
bath at 50 - 60~ C for 1 hour with occasional stirring.
The material was diluted with 11.3 g of ethanol.
After standing overnight, the mixture was
heated briefly in a bath at 50 - 60~ C and diluted with
6.0 g of ethanol and 2.3 g of distilled water.
The hydrogel-forming emulsion material was
applied to an area of healthy human skin and the
following observations were made:
"' ' -- 96 --
133~2
Table XLVI
General Application Testing
2 min. 4 min. 6 min. 1 hr.
post-appl'n. post-appl'n. post-appln. post-appl'n.
moderately not tacky: not tacky: medium gloss:
tacky transparent 2 large
cracks
Table XLVII
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
l min. 2 min. 0 min. 2 min. 4 min. 6 min. 3 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
no tack no tack no tack: very no tack no tack glossy:
trans- slight no detached
parent tack area
Example 40 - "Hydrogel-Forming Material Comprising:
PMA/Gelatin, Water, Ethanol, Glycerol
and Calcium Chloride"
30 g of poly(methacrylic acid) (Polysciences
Inc., Cat. #0578, Lot #74687) were dissolved in 300 g of
distilled water.
- 97 -
13~682
The temperature of a solution of 30 g of
gelatin (Gelrite 150 USP, Lot #0175, Canada Packers,
Bloom #150), in 200 g of distilled water was adjusted to
46~ C. To it was added the warmed (48~ C) PMA solution
with vigorous manual stirring. The resultant gel was
kneaded with a stiff rod'to express as much water as
possible; this resulted in a strong, non-tacky cream
coloured gum.
61 g of this gum were left to stand overnight
and the water which had separated was decanted. 21.2 g
of the resultant gum was cut with scissors into small
pieces. 3.6 g of glycerol BP and 6.6 g of ethanol were
added. The material was loosely covered and placed in a
bath at approximately 60~ C and stirred occasionally.
27.1 g of ethanol were added over a period of
approximately 3 hours with intermittent stirring. The
vessel was uncovered and heated in a bath at 60 - 70~ C
until 7.7 g had evaporated. To 28.5 g of the resulting
mixture were added 1.6 g of calcium chloride dihydrate
(BDH Chemicals, Product #B10070, Lot #96660-9711).
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
- 98 -
1~39~82
Table XLVIII
General Application Testing
2 min. 4 min. 1 hr.
post-appl'n. post-appl'n. post-appl'n.
slight tack: very slight high gloss:
soft tack: soft no tack:
no cracks:
no dets ' t
Table XLIX
lS Water ~esistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 8 hr.
post- po~t- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
very no tack opaque no tack no tack no tack 4% of area
slight white: detached:
tack no tack some cracks
Example 41 - "Hydrogel-Forming Material Comprising:
PMA/PVA, Water, Glycerol and Ethanol"
15.0 g of polymethacrylic acid powder
(Polysciences Inc., Cat #0578, Lot #74687) were
dissolved in 110 g of distilled water. To the solution,
while heated in a bath at 87~ C, were added 15 g of
Vinol 203 (Lot #08050377) as the solid with manual
_ 99 _
133~82
stirring. The solid dissolved quickly and as it did so
a gum separated. The resultant gum was maintained in a
bath at approximately 87~ C and kneaded with a stirrer
for approximately 15 minutes. Upon cooling, the gum was
again kneaded and the liquid phase was decanted. 12.6 g
of glycerol BP were added to the gum followed by 15.8 g
of ethanol and the material was loosely covered and
placed in a bath at approximnately 60~ C. The gum was
kneaded from time-to-time over a period of 30 minutes
until no gel particles could be detected. The clear,
viscous liquid was then diluted-with 11.0 g of ethanol.
The hydrogel-forming material was applied to
- an area of healthy human skin and the following
observations were made:
Table L
General Application Testing
\
2 min. 4 min. 6min. 1 hr.
post-appl'n. post-appl'n. post-appl'n. post-appl'n.
moderate slight tack slight high gloss:
tack tack no tack:
no cracks:
no detachment
- 100 -
1:~3~82
Table LI
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. O min. 2 min. 4 min. 6 min. 8 hr.
post- post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
slight slight hazy: very moderate very no tack;
tack tack slippery: slight tack tacky very
no tack tack strong:
supple,
1% o~ area
detached
Example 42 - "Hydrogel-Forming Material Comprising:
PMA/PVP, Water, Glycerol, Ethanol, and
Ammonium Alum"
20.0 g of poly(methacrylic acid) (Polysciences
Inc., Cat #0578, Lot #74687) were dissolved in 150 g of
distilled water.
20.0 g of PVP (Povidone USP; Plasdone K-2932;
GAF Corp.; Lot #G-90504-B-54) were dissolved in 150 g of
distilled water.
The PMA solution was added to the PVP solution
with vigorous manual stirring at room temperature over a
period of 30 seconds. The material was left to stand at
room temperature which resulted in a separation of a top
layer and a lower layer containing settled gel
particles. The top layer was decanted and discarded.
-- 101 --
d~lc
133~2
The bottom layer was centrifuged to remove some of the
occluded water.
To this centrifuged bottom layer (105.7 g)
were added 7.9 g of glycerol BP and the mixture was
heated in an open vessel in a bath at 78~ C with
intermittent stirring for approximately 6.5 hours during
which time the weight loss was 49.3 g.
While the mixture was still warm, 21.1 g of
ethanol were stirred in. After cooling, a small portion
of the mixture was centrifuged to remove small bubbles
and labelled 33-B.
The remainder of the mixture, 59.2 g, was
heated to an internal temperature of 69~ C, and 5.0 g of
powdered ammonium alum (BDH Chemicals, Analar grade,
product #B10007; Lot 100085/4784) were added with manual
stirring. The mixture rapidly thickened to a very
coherent, near gum. When it had cooled to near room
temperature, it was stirred with 6.2 g of ethanol. The
resulting mixture, which flowed easily, was centrifuged
to remove suspended solid. A top layer of foam was
skimmed from the centrifuged liquid, which was decanted
from the sediment and labelled 34-A.
The hydrogel-forming materials 33-B and 34-A
were applied to areas of healthy human skin and the
following observations were made:
- 102 -
1~3968~
Table LII
General Application Testing
2 min. 4 min. 6 min. 2 hr.
post- post- post- post-
Sample appl'n. appl'n. appl'n. appl'n.
33-B tacky, slight very tr~r.S~al.. t:
but set tack slight low gloss:
tack 2% of area
detached
34-A tacky, slight very 3% of area
but set tack slight to detached:
slight many large
tack cracks:
transparent:
medium to
high gloss
ZO
-- ] 03 --
1339~82
Table LIII
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
Sample 1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 1 hr.
post- post- post- post- post- po~t- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
33-B slight slight no tack: very very slight no
to tack slippery: tacky tacky tack tack:
moderate hazy trans-
tack parent:
good
s~h~e; on
34-B very very no tack: no tack slight very no tack:
slight slight very tack slight exten-
tack tack slight tack eively
haze cracked:
10% of
good
adhesion
Example 43 - "Hydrogel-Forming Material Comprising:
PMA/PVP, Water, Glycerol, Ethanol,
Ammonium Alum, and Titanium Dioxide"
The specific product quality and information
in this example is the same as in Example 42.
14.8 g of the hydrogel-forming material
designated 34-A in Example 42 was manually stirred at
- 104 -
133~682
room temperature with 2.0 g of titanium dioxide powder
(J.T. Baker; product #4162; Lot #41177) until the powder
was well dispersed. The mixture was diluted by stirring
in 1.0 g of ethanol.
This opaque, white hydrogel-forming material
was applied to an area of healthy human skin, and the
following observations were made:
Table LIV
General Application Tegting
2 min. 4 min. 6 min. 21 hr.
post- post- post- post-
appl'n. appl'n. appl'n. appl'n.
slight very very good
tack slight slight adhegion:
tack tack many large
cracks at
stress points:
50% of ori-
ginal area
detached
- 105 ~
13;39682
Table LV
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. O min. 2 min. 4 min. 6 min.
post- post- post- post- post- post-
imm'n. imm'n. imm'n. imm'n. imm'n. imm'n.
~0
no tack no tack no tack slight no tack no tack
tack
Example 44 - "Hydrogel-Forming Material Comprising: PAA
Copolymer/ PE0, Water, Ethanol, Ammonium
Alum."
A solution of 100.1 g of Sokalan CP5 powder
(sodium salt of a copolymer of acrylic acid and maleic
acid, MW 70,000, from BASF, Lot #78-0695) in 140 g of
distilled water had a pH of 7.5. Concentrated aqueous
hydrochloric acid (~ 37~ w/w HCl) was added in portions
of 2-10 ml with stirring until the pH had fallen to
about 1.7. The solution was diluted with 258 g of
ethanol and allowed to stand for 30 minutes in order to
allow the precipitated white solid to settle. The hazy
liquid was decanted from the white sediment, which was
centrifuged in order to recover more liquid from it.
The liquid obtained by centrifiguation and the original
decanted liquid were combined and diluted with 410 g of
acetone. This produced an opacity due to the formation
of a relatively small amount of suspended white solid.
The suspension was allowed to stand at room temperature
for two weeks, after which it was decanted from a small
amount of white sediment. The suspension was then
- 106 -
133968~
placed in an open dish and gently warmed as a current of air
was passed over it until the total amount of evaporated
solvent was 663 g. The resulting solution, which was hazy but
no longer opaque, was diluted with 200 g of distilled water.
One half (244 g) of the above solution was added
with manual stirring over 30 seconds to a solution of 40.0 g
of Polyox WSRN-80 (PEO of MW 200,000, narrow MW distribution;
from Union Carbide; lot I-273) in 400 g of distilled water.
The mixture became opaque during the addition. It was stirred
for a further two minutes and allowed to stand for 20 hours,
after which it consisted of a hazy, mobile top layer, which
was discarded, and a translucent, viscous lower liquid layer.
After the lower layer had been centrifuged to remove some of
the occluded water, it weighed 130.6 g.
65.2 g of the viscous liquid were placed in an open
vessel and keep in a bath at 75-80~C with intermittent
stirring until the evaporative weight loss had reached 26.0 g
(2 hours). While still warm, the mixture was diluted with a
total of 16.5 g of ethanol, added in portions with stirring.
The resulting clear, mobile solution was allowed to stand at
room temperature for 13 days. While loosely covered, it was
then heated in a bath at about 75~C until the internal
temperature reached 67~C, and 6.1 g of powdered ammonium alum
(BDH Chemicals; Analar grade; product B10007; Lot 100085/4784)
were added. The mixture was stirred manually for three
minutes while in the bath and three minutes while out of the
bath. The alum addition caused an increase in viscosity. A
viscosity suitable for spreading on skin was produced by
dilution, in stages, with a total of 21.6 g of ethanol. After
centrifuging
107
1339~82
to settle suspended solid, the translucent liquid was
decanted and labelled 43-A.
The hydrogel-forming material was applied to
an area of healthy human skin and the following
observations were made:
Table LVI
General Application Testing
2 min. 4 min. 6 min. 16 min. 2 hr.
post-appl'n post-appl'n post-appl'n post-appl'n post-appl'n
tacky. slight slight to very slight no tack:
but set tack very slight tack: no cracks:
tack transparent: no detached
medium gloss areas
Table LVII
Water Resistance
5 second 4 minute
Immersion Test Immersion Test
1 min. 2 min. 0 min. 2 min. 4 min. 6 min. 8 hr.
post- post- post- post- post- post- post-
imm'n imm'n imm'n imm'n imm'n imm'n imm'n
very slight no tack: slight tacky slight no tack:
slight tack slippery: tack tack no cracks:
tack some loss low to y~lV~
by gloss:
dissolution very good
A~'- ~~i~'m
- 108 -
133~82
Example 45 - "Hydrogel - Forming Material Comprising:
PAA Copolymer/PEO, Water, Ethanol, Ammonium
Alum, and a Fragrance"
The specific product quality and information
in this example is the same as in Example 44.
To 15.6 g of the hydrogel-forming material 43- 1
~ A of Example 44 were added 0.5 g of Cachet Spray Cologne~
(Prince Matchabelli, Markham, Ontario, Canada). The
mixture was stirred manually for one minute, and its
viscosity was reduced by stirring in a total of 2.7 g of
ethanol. The mixture was centrifuged to remove tiny
bubbles and was labelled 44-A.
The fragrance delivery capability of the
hydrogel-forming skin coating material was compared
directly with that of a coating of Cachet Spray Cologne
as follows: Two sites 2 x 3 cm were delineated on the
insides of the left and right forearms of a volunteer.
To the site on the left arm were spread approximately
0.3 ml of 44-A, and to the site on the right arm were
spread 2 drops (approx. 0.1 g) of Cachet Spray Cologne.
The results of subjective sniff tests of both sites
carried out in an identical manner by the same person at
various times following application are given in Table
LVIII below. The test sites were kept from contact with
water during the total test period.
- 109 -
1~3~82
Table LVIII
Fragrance Delivery Characteristics
Time Perceived Odour Level C , ative
post- Coating Pure Cachet Odour
appl'n of 44-A Spray Cologne Quality
10 min. strong moderate to strong
30 min. moderate moderate to strong
60 min. moderate moderate to strong 44-A more
pleasant (less
sharp")
2 hr. weak to moderate 44-A more
moderate pleasant (less
"sharp")
3 hr. weak to moderate 44-A more
moderate pleasant (less
"sharp )
5 hr. weak weak 44-A much more
pleasant
15 hr. weak weak 44-A much more
pleasant
-- 110 --
1~3~2
20 hr. weak very weak detection of
differences
difficult
because of
~ r ~ss of
odour from
pure Cachet
site
27 hr. weak extremely weak detection of
differences
difficult
because of
~le r of
odour from
pure Cachet
site
41 hr. weak extremely weak detection of
differences
difficult
because of
weakness of
odour from
pure Cachet
site
67 hr. very weak not detectable
114 hr. extremely - -
weak
- 111 --
133~2
Example 46 - "Hydrogel-Forming Material Comprising:
PAA Copolymer/PE0, Water, Ethanol,
Ammonium Alum, and a Fragrance"
The specific product quality and information
in this example is the same as in Example 44.
To 15.6 g of the hydrogel-forming material 43-
A of E~ample 44 were added 0.3 g of Chantilly Purse
~ Perfume~ #1404, Houbigant Ltee, Montreal, P.Q., Canada).
~ The mixture was stirred for two minutes using a stiff
rod, centrifuged to remove tiny bubbles, and labelled
45-A.
The fragrance delivery capability of the
hydrogel-forming skin coating material was compared
directly with that of a coating of Chantilly Purse
Perfume as follows: two sites 2 X 3 were delineated on
the insides of the calves of the left and right legs of
a volunteer. To the site on the left leg were spread
approximately 0.3 ml of 45-A, and to the site on the
right leg were spread two drops (approximately 0.1 g) of
Chantilly Purse Perfume. The results of subjective
sniff tests of both sites carried out in an identical
manner by the same person at various times following
application are given in Table LIX below. The test
sites were kept from contact with water during the total
test period.
- 112 -
Table LIX 133~2
Fragrance Delivery Characteristics
Time post- Perceived Level Pure Comparative
S appl'n Odour Coating Chantilly Odour
of 45-A Purse Perfume Quality
l0 min. strong strong
30 min. strong moderate to 45-A
strong marginally
more pleasant
than Chantilly
60 min. moderate to moderate to 45-A
strong strong marginally
more pleasant
than Chantilly
3 hr. weak to moderate 45-A
moderate marginally
more pleasant
than
Chantilly;
45-A "sweeter"
and less
"harsh"
5 hr. weak to weak 45-A
moderate marginally
more pleasant
than Chantilly
12 hr. weak weak 45-A
marginally
more pleasant
than Chantilly
20 hr. weak weak; a little 45-A
weaker than marginally
45-A more pleasant
than Chantilly
32 hr. weak weak
113
1339b82
41 hr. weak extremely weak
67 hr. weak not detectable 45-A still pleasant
114 hr. weak - 45-A still pleasant
- 114 -
