Note: Descriptions are shown in the official language in which they were submitted.
WO 94/00512 ~ 3 '~ PCT/US93/05993
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METHOD OF PRaDUCII!1G PC)LYSACCHARID>~ FOAMS
DES~3tIPTION
The present inv~tio:n relai-.as tv n method of psroducing
polysaccharide foams; in particular alginate, chitosan,
starch and hyaluranate foams. The invention also
embraces polysaccharide foamed materials produced in
accordance with the method of the invention and wr~ur~d
dressings, foamed cell culture replicating media,
barrier media for preventing tissue adherents and ether
absorbent materials cauprising such foams.
Alginates, particularly calci~n alginates and converted
calciian alginates, have long bean lasvwn for their
ability to farm fibres and yarns which can be knittod
into fabrics or formed into no~nwvven materials
primarily for use as swabs or dressings for medical,
surgical yr other purposes.
PCf/US93/05993
WO 94/00512
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For instau~~ Britl~;h patent Specification No. 1283399
describes and claims; a method of preparing a solublized
calcium-containing alginate n~terial which comprises
acidifying calcilan alginate with a calculated quantity
of acid sufficient to r~nwe a desired amount of
calcium, reacting the acidified calcium alginate with
an excess of base selected Iran a~swnis. amines and
substituted amin~a~s and washing the solubilized
calcium-containing alginate to rove the excess of
base.
This material may be formed into a number of pieces of
gauze which can thean be further treated as described in
the specification.
British Patent S~~ecificatian No. 3.394742 relates to a
surgical dressing material comprising a layer of
lrnitted gauze adl;iered to a layQr of fibrous backing
material, the gauz~a coenpriBing alginate material and
the dressing material being of lower flexibility and
stretchability than the gauze itself.
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British Patent Spec9.ficatioa tro. 1570485 relates to an
absorbent materis~l for aqueous fluids which comprises
an open cell fosra containing within the cells a
hydrophilic gel hav:~ng specific properties. Typical of
the hydrophilic gel: is alginates. The specification
describes the incc~rporatien of these materials is a
reticulated foara; ithe gel being contained within the
cells of the :foam thus providing an absorbent
material.
United States Pat~ant Specification Ho. 4,421,583
relates to a non~-woven alginate fabric useful as a
wound dressing made by spreading a tow of calcium
alginarx filaments into a flocs of water, over-feeding
the spread filaments onto a water pervious support so
that the filaments cross over each ether, and drying
the filaments so that they became bonded to oath other
at their points of contact where they cross over. The
filaments used have preferably been pre-stretched in an
atrmsphere of ste~un and wash water and not dried and
are preferably subsequently dried by suction on the
water pervious support.
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United States Patent Specification No. 4,793,337
discloses an improved adhesive structure for adhesion
of an article to a fhiid emitting wound. the structure
having an absorbent. region comprising an absorbent
fibrous fabric or foam material intermediate first and
second contact ~rec~ions, whereby enhanced cohesion
between the first and second re~io~ns and between the
second regioru end tt~e article under conditions of haavy
fluid anission 5_a provided. This specification
discloses the use of: sodium alginate in combination
with a calciiun powdESr by wav of absorbent material.
United States pat:~nt Specification No. 4,948,575
discloses a dicxi~ally stable alginate hydrogel foam
wound dressing thmt absorbs wound e'nydate without any
appreciable swellir~g. The wound dressing includes
alkaline metal W (except magnecium).salts and Group
zII metal-salts of eilginic acid. ~e hydrogel foam may
be formed by m; _: rig together a first liquid component
ccamprising ( a ) an ac(ueous suspension of particles of a
_ water insoluble di-~ or trivalent metal salt and (b) an
effervescent cc~mpo~aud which effezvesces upon reaction
with an acid; and e~ second liquid component canprising
an aqueous .solution of biocaopatible, water-soluble
WO 94/00512 '~ ~ ~ ~ Q ~ "~ PCT/US93/05993
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acid wherein at leapt vne of the components further
comprises a water-soll~ble alginate dissolved therein.
Upon mixing, the v~~ater-insoluble metal salt reacts
with the water soluble: acid to form a water soluble
metal salt that is sur~seq~uently ionized. The polyvalent
cations released from the water-soluble metal salt
complex with the carboxylate groups of the
water-soluble alginate cauaimg the formation and
precipitation of a crater insoluble alginate hydrogel.
At the same time the e:fferveacent compound is reacting
with the water solux~le aci3; the resultant evolution
of gases e:E*ecta the l:oreaation of a stable hydmgel
foam.
Commercially available alginate products are marketed
inter alia as haeQioatatic wound dressings using
non-woven fibre technc~loqy. However non-.woven alginate
materials, while performing their function
satisfactorily, are difficult to handle. Several
attempts have been made to improve handling, for
example S~.~edish Patent Application published under
No. 424956 describes an alginate hydrogel wound
dressing farmed on ~~ wound in cc~abi,nation with an
elnatiC rubber_like ca~osition. In another attempt at
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providing a more rE3adily usable material, it has been
proposed to use a foeeze-dried foam as disclosed in
United States Pate:~t Specification No. 4.fi42,903. The
disndventage of all these prier art foam metswds is
that there is lititle or no control aver the foam size
and that the resosltant products are relatively
difficult to handle.
According to one .aspect of the present invention,
therefore, there is provided a method of foaaing a
polysaccharide foam which ~isQS preparing an
aqueous solution including a soluble polysaccharide and
thereafter mechanically foaming the solution.
The foam may be produced by boating or otherwise
mechanically agitating the material to cause the
polysaccharide to foam. The mechanical foaming may
involve the introduction of gas into the solution, and
shearing of the solution to create a mixing effect which
may result in a very fine dispersion of gas bubbles in
the solution. In the early stages of mechanical
foaming, when the total amount of gas entrained in the
solution is small, thp gas bubbles may be substantially
spherical in shape. As the total volume of gas
WO 94/00512 ~ ~ ~ ~ ~ ~ ~ PCT/US93/05993
._
entrained in the ;solution i.ncrQases, the gas bubbles
may undergo a transition frown the spherical shape to a
substantially pohyhedral shape, with the solution
distributed in thin membranes between adjacent gas
bubbles and in ribs or spokes where several gas bubbles
come into very close proximity to each other; the
result is a foamod polymer having gas dispersed
throughout the solution in a cellular structure. It
will be appreciated by a person skilled in the art
that, in sane embodiments of the pre~t invention, the
relative violence and/or period of agitation of
mechanical action may be used to provide control over
the foam pore wine. The foam pore wise may be
controlled in the range 5 - 500 ~; typically 50 -
500 ~.
said soluble polyraa~acharide may be alginic acid or
hyaluronic acid. In same embodiinanis, said soluble
polysaccharide may toe a soluble polysaccharide salt
such, for exa,~pl~s, as an alginate or hyaluronate;
typically, sodium alginate or sodium hyaluronate may be
used. Alternativelst, the soluble polysaccharide may be
cazrageenans~ chitosan, starch, or separately,
amylose or amylopect:in. A person skilled in the art
~1 18037
_ __
will appreciate that chitosan is soluble in acid, but
is insoluble in neutral and basic solutions; on the
other hand starch is soluble in basic solutions. Thus,
where chitosan i~~ used in accordance with the present
invention, the mechanical foaming step should be
conducted in an ~~cidic aqueous solution; where starch
is used, foaming should be conducted in aqueous base.
In one aspect of the invention, a foaming agent may be
included in the aqueous solution to assist in foaming
the solution. Th~~ foaming agent may be a surfactant,
typically an ionic or non-ionic surfactant. The ionic
surfactant may be selected from sodium stearate, sodium
dodecyl sulfate, alpha olefin sulfonates (commercially
available under the trade name "Siponate 301-10"),
sulfoalkyl amide, monocarboxyl coco imidazoline
compounds, dicar:boxyl coco imidazoline compounds and
sulfated fatty polyoxyethylene quaternary nitrogen
compounds.
Said non-ionic surfactant may be selected from
octylphenol ethc>xylate (commercially available from
Rohm & Haas under the trade mark TRITON X-100),
B
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modified linear alLphatic polyethers and sorbitan
esters.
1n another aspect of the invention, a plasticizer may
be included in the ac~eous solutian_ Said plaaticizer
may be selected frcaa glycerol, glucose, polyhydric
alcohols, triethanole~mine and stearates.
In aama esnbodimants, an oligomQ.ric or polymeric foam
modifier may be inclvd~ed in the aquoous solution; said
foam modifier may be selected fraan polyethylene Qlycol,
g118r qum, albumin, gelatin, carboxymethyl cellulose,
hy~troxyethyl cellulose, hydmxypropyl cellulose,
polyacrylamide, polyacrylic acid, polyvinyl alcohol,
polY"~Yl pyrzcLidone, polyoxazoline and
PolYeeimtne. These foam modifiers may be used to
improve the flexibility and toughn,eaa of the
polysaccharide foam.
In a particular aagect of fine invention the foam
modifier may tie polye~thyieae glycoz functionalised with
vinyl groups such, far example, as aczylates. After
f~ing, the functionalised polyethylene glyvol may be
polymerised by irraclia~tion ( e. g. a . v. or electron ~
WO 94/00512 PCT/US93/05993
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_ lp _
form a polymer metraork writhin the foam; said network
may imprrnre the flexibility and toughness of the
foam.
In a different aspect of the invention, the aqueous
solution of po7.ysacehatide may include a foam
stabiliser. Said foam stabliser may be selected from
ammonium stearate, dodecyl alcohol, tetradecanol,
hexadecanol, tridecylaxypolyethanol and
polyoxyethylated o7.eylamine.
in some esabodiment;, the resultant polysaccharide foam,
including foam stst~iliser, may be air dried after
formation. On dlzying, the foam material in an
interior region of the foam may »collapse~ giving the
appearance' of crushod foam: the cells
constituting the foam may distort such that in ono
dimension each cell may becoas: smaller than in another
dimension substantially noaaal to the one din~enSion;
this change in shape can be described as a sphere
distorting to an ellipsoid. When the cells distort in
this gay, the foam is referred to herein as a
"collapsec'.~ foam. The foam material juxtaposed the
surface of the foam may maintain its integrity
WO 94/00512 ? ~ ~ ~ ~ PCT/US93/05993
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prese=vin~g its mean pore size and pore size
distribution.
Where the polysacclmride is chitoaan which is foamed in
an acidic aqueous solution it may be desirable, in
some e~nbodimenta, t.a remove the acid after foaming
while the foam is. still wet since, on drying, any
acid present may heave an injurious effect on the
chitosan foam. Said acid may be removed after feasting
by volatilisation or' neutralisation. ~rpically, the
acid may be aqueous acetic acid which may be rennved
by volatilisation.
In another aspect of the invention, the foam may
stabilized by cross-linking or coagulation thereby to
provide a dimensionally stable foam. ~rpi~ly~ ~e
foam may be cross-ainkod or coagulated while wet;
where a foam stabilizer is used the foam may be
cross-linked or coag~ilated after initial dr~,ing, ~e
foam may then be re-dried.
When the polysaccharide,is selected from alginic acid,
hyaluroni.c acid, hyaluonate, and other
soluble polysaccharide materials containing
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exchangeable counter-caticns, the cross-linking may be
effected by reacting the foamed polysaccharide with di-
or tri- valent cat.ions. Said polysaccharide foam may,
in some embodiments;, be im~wraed in or sprayed with a
solution of they di- or tri- valent cations.
Typically, the canons rosy be selected fram
Ca2+(aq), Fe2+(aq) and Fe3+(aq).
Alternatively, in some eaabodiments, an insoluble
carbonate yr hydrogen carbonate salt having one or more
di- or tri- val.ent canons may be hoanogeneously
dispersed in the foamed polysaccharide, and the foam
may be subsequently treated with a st=ung acid to
liberate carbon dicudde as gns and said rations which
then cross-link with the polysaccharide to form a
dimensionally stable foam structur~. Zhe strong acid
may have a concentration of up to 1N, typically 0.1 -
0.2N. Typically, calcium carbonate may be used as an
insoluble carbonate salt. This latter method of
cross-linking has the advantage that a relatively thick
foam may be, stabilized uniformly through its thickness;
typically a foam thickness of up to about 5 mn may ~ .
hanbgeneoualy stabilized using this method to provide a
stable foam structure.
WO 94/00512 ~ ~ ~ ~ ~ rf PCT/US93/05993
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In a different aspect of the invention, the
cross-linked alginente ar hyaluronate foam may be
~ronv~erted" by tre~stment with an aqueous solution of a
z~eagent having soluhilising mono-valent rations so that
a proportion of »he cross-linking di- or tri-valent
rations in the foam may be replaced by the mono-valent
rations, thereby :i.mparting a degree of solubility in
the foam; when caa~t.~ncted with water, the c~onv~erted f oam
may form a gel. In same e~nbodia~nts, the degree of
conversion may be controlled; typically a small
proportion of the cross linking cationa may be replaced
to provide a lightl~r 9olling foam (wham contacted with
water). AlternatjLvely, in same embodiments,
substantially all i:he cross-linking rations may be
replaced to provide a substantially water soluble foam.
The reagent may be E~elected from sodium acetate and
dilute hydrochloric: acid. Typically, the treatment
may be performed at a phi in the range 4 - 7.
Where the soluble yolysaccharide is chitosan, the foam
may be coagulated by treatment with base. Typically,
said base may be sodiuan hydroude solution.
Alternatively, the chitosan foam may be cross-linked
by ionic or covalent bonding, Ionic cross-linking may
WO 94/00512 PCT/US93/05993
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be obtained by treatment with an aqueous solution of
polyvalent anions; typically one or more of sodium
sulfate, octyl sulfate, lauzyl sulfate,
hexndecylsulfate, tri.polyphosphate, pyraphospate and
octapolyphosphate may be used as a source o!
polyvalent anions. In other embodiments, covalent
cross-linking may be obtained by treating the chitosan
foam With one or more dialdehydes e.g. glyoxal,
glutareldehye and dialdehyde starch.
Where the polysaccharide is starch, the starch foam may
be coagulated by treatment with aqueous amc~nium
sulfate. Alternatively starch foam u~ay be crass-linked
by treatment With formaldehyde; this treatment may be
perfozmed in the gaseous or liquid state. If the
treatment is perfozmed in the liguid state a solution
in alcohol may typically be flayed.
The cross-linked or-coagulated polysaccharide foam may
be dried in air. ,i~fter drying, the dry, cross-linked
or coagulated foam may be wrashed with water and then
redried. Washing may be used to revive e.g. any .
foaming agent or fa3m stabiliser residual in the foa~a,
WO 94/00512 ~ ~ ~ ~ ~ ~ ~ PGT/US93/05993
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Said aqueous solution of polysaccharide may further
ccxnprise one or more ingredients selected from
particulate fillers" barium sulfate, pulp-like fibres
of cellulose or other fibrous material and moisture
retaining or reini:orcing filler matQrials. where
barium sulfate is used, it will be appreciated that
the resultant foam may be substantially opaque to
X-rays; the foam racy therefore be useful as a medical
implant in radiography.
In some e~obodi~ents~, .the foam mey be bleached. Bleach
may be included in the aqueous solution of
polysaccharide; tyyically, the. bleach may be selected
from hydrogen perox~.de and sodium hypochlorite.
The present invention also irrciudes a polysaccharade
foam produced in acc~orc3ancQ with the method of the
invention; the foam can be controlled at various
thicianesses, pore sizes and pore size distributions.
The foam may be cross-linked or coagulat~d; the foam
may be a soluble foam, an insoluble foam or a
"converGed~ .foam having a desired degree of solubility
in at least part of 'the foam. Typically the foam may
be an alginate, hyal»tonatra, chitosaa or starch foaut.
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In another aspect of the invention, the foam, when wet,
may be cant as rs layer or as a shaped article. Said
foam may be cast inter alia in the form of buttons,
beads, balls, cylinders yr heroispherea. In
sane e~nbodimente, the foam may be cast in the shape of
a part of s human or animal body a.g. in the shape of
J
an ear or nose.
In a particular as~aect of the insrentioal, the foam may
be cast as a layer on a substrate. Said substrate may
be a woven or non-wven fibrou3 article, a film or a
foam. In sane ecN~odiments, the substrate ioay comprise
an assemblage of polysaccharide fibres or yarns. In a
particular aspect of the invention the substrate may
cartprise another layer of polysaccharide foam in
accordance with l:he invention. Said other layer foam
may have.a different mean pore sine . and/or pore size
distribution frown l:he first mentioned foam.
The foam may be ca.~t as a thin foam layer having a
thicJaiesa up to about 1 mn. Alternatively, the foam in
accordance with ttie present invention rosy be cast as a
thick foam layer having a thiclaiess of up to about
SQmm. Said thick foam layer may have an interior
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layer of "collapsed" foam; the foam juxtaposed the
surface of the foam may be not significantly collapsed,
being similar in appearance and having a pare size and
pore size distribution about equal tv the foam when
freshly formed.
The present invention also includes a wound drer~sing
comprising a polysaccharide foam produced by the method
in accordance with the present invention. Typically the
wpund dressing may ccxnpriae a layer of said
polysaccharide foam. In some embodiments the foam may
be disposed on a substrate, the substrate may be a
polysaccharide fab=ic or cvarpoaed of polysaccharide
yarn .
The present invention .al$o includes a cell culture
replicating medium ca~rising n polysaccharide foam
produced in accordance with the presort invQntion; the
cells to be replicated can be disposed in the pores in
the foam to locate the cells.
In some e~nbodi~en~ts, the cell culture replicating .
medium may constivtute an implant, typically a
bio-absorbable i~l~int .
WO 94/00512 PCT/US93/05993
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_ 18 -
Cultured cells, e.g. mamnalizing cello, may be
disposed in the poz~ea of the implant which may then be
implanted surgically in a human or animal body. The
implant containing cultured cells may encourage tissue
growth in and arour~d the implant in vivo .
The present invention also includes n barrier medium
for preventing tissue adherence, said barrier medium
comprising d pOlyS~tCCharlde foam in accordance with the
invention.
In another aspects of the present invention, the
polysaccharide fo~s~n mny constitute a carrier for a
beneficial agent formulation. Said beneficial agent
foanulation may be accaranodated within the cells of thQ
foam. Typically the fo~ul.stivn may ca~nprise a
beneficial agent and a phaanaceutically acceptable
excipient therefor. In some m~bodiments, the
beneficial agent may be a drug which can be
administered to a patient transdermally. Typically,
the beneficial agent fozmulation may be included in the
aqueous solution oi: polysaccharide prior to foaming..
Alternatively, however, the beneficial agent
formulation rosy bEa incorporated in the foam after
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formation; in Nome embodiments the foam may be
immersed in or spr~~yed with the fomrulatian (which may
itself be in so;lutionj; in other esrbodiments the
formulation may be dispersed in a solid particulate
fosim in the cellular structure of the foam, or produced
by living cells (e. g. microbes) in'the foam structure.
In yet another aspe=ct of the present invention, a foam
in accordance with the present invention, when wet, may
be stored under pressure; typically the wet foam may
be stored in a pressurised dispenser such, fvr example,
as a conveantional, pressurised spray can. In some
embodiments, the wet foam may be incorporated with a
propellant to assie~t in subsequent delivery of the foeum
from the disperu~r; said propellant may be any
suitable propellant, known to a person skilled in the
art e.g. a gaseous lower alkane (Prc~e. butane,
pentane and the like), nitrogen and carbon dioxide. It
will be appreciated that storage under pressure
constitues a convenient method of storing a ~t f~
prior to use; when required, the foam may simply be
~BPensed directly ~to the environment of use.
WO 94/00512 PCT/US93/05993
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~'or example, a wet :Foamed w~ouru3 dr~sinQ in accordance
with the inventio~a nay be Stored under pressure in a
dispenser and dispensed directly onto a patient s skin
to treat e.g. ab:raded skin, burns and open wounds.
A wet foam carrying a beneficial agent in accordance
with the present invention may be stored and dispensed
in the same way to provide rapid therapeutic treatment
of a wound or other injury when required. It will be
appreciated by a person skilled in the art that a
foamed wound dressing or beneficial agent formulation
carrier which is stored in a pressurised dispenser may
be particularly suitable far the purposes of applying
first aid to a patient in an emergency.
Following is a description by way of exile only and
with reference to the accompanying drawings of methods
of carrying the invention into effect.
In the drawings:
Figure 1 is a scanning electron microscope ("SEli")
photograph showings a surface of a single layer foam
produced in accordance with the present invention;
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Figure 2 is an SEhi photograph of another surface of the
single layer foam .of Figure 1;
Figure 3 is an SEM photograph of a cross section
through the thic)aZ~esa of the single layer foam of
Figures 1 and 2 ;
Figure 4 is an SEM photograph of a surface of a tvao
layer foam prodm"ad in accordance with the present
invention;
Figure 5 is an SF~i photograph of another surface of the
two layer foam of l:'igure 4 ;
Figure 6 is an SEls photogoraph of a cross section
through the thiclaiess of the two layer foam of Figures
4 and 5.
f~CAi~LE 1
A solution containing 3 wt % of sodium alginate having
a viscosity of 1500 oentipoise was prepared and to 100.
grams of this solution was added 0.1 grams of sodium
dodecyl sulfate as a foaming agent. The resultant
solution was beaten with a Kitchenaid mixer to foam a
WO 94/00512 PCT/US93/05993
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.. 22 -
foam. The foam vJaa spread on a metal tray and
cross-linked with a~n aqueous solution containing 5% by
weight calcium chlo~:ide. The foam was then dried and
after drying was frn~rbd to be 0.05 mm thick and weighing
7 grams per square meter. A acaru~.iug electron
microscope photogra~~h of the croaa-linked foam revealed
an open pore structure which was found to have an air
permeability of 110 m/min measured at 12.7 men H20
pressure.
A portion of the foam produc~ad in the manner described
above was converted by placing it in an aqueous
solution of hydrog~ chloride with a pH of 5 for 30
minutes. The conversion did not affect the gauge
weight or pore size, but did change the solubility
characteristics. Contact of the non-converted foam
with a 1% sodi~ citrate solution did not affect the
stzucture, whereas the contact of the converted foam
with the same 1% sodium citrate solution resulted in a
gelation of the foam. This latter action suggested the
solubility characteristics were modified by the
conversion process.
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F~ 2
A 3"x 3" gauze pad comprising a 12-ply 20 x 12 mesh
fabric was used af~ a substrate for a layer of alginate
foam as deacri_bed 3n Example 1. The foam was spread on
the fabric and cross-linked with a 5% aqueous solution
of calcium chlaridE:. The material was then dried and
it was found that the cross-linked foam had adhered to
the gauze pad to fc:rm a coating. A photomicrograph of
the resultant structure reveals a thin, 0.05 uan thick
foam coating on the gauze pad which had a similar
structure as the fc~a without the aubatrate described
in ~xampie 1.
When the coated pad was placed in an aqueous solution
of hydrogen chloride at a pH of 5 for 30 minutes, the
calcium structure was converted to a soluble form.
Contact of the converted material with sodium citrate
once again resulted in gelation of the alginate
coating.
ALE 3
An agueoua solution containing 2 wt ~ sodium alginate
was prepared. To this solution was added 0.2 wt %
ammonium stearate a:~ a foam stabiliser and 2 wt %
WO 94/00512 PGT/US93/05993
211~03'~
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calcium carbonate. The mixture was them well mixed in
a kitchenaid mixer to produce a foam having the calcium
carbonate dispersed therethrough. The foam was drawn
in a plastic tray, a~ad 200m1 of O.1N hydrochloric acid
was then added in the tray. As a result of the
addition of strong acid, the foam cross-linked. After
drying, the foam was found to have a final thickness of
2.lmtn, a density of 0.22g/cm3 and an air permeability
of 6m/min at a pressure of 12.7 mm 820.
The foam vas found to be coagulated uniformly through
its thicla~ess _
EXAI~LE 4
A 3% wt aqueous solution of sodium alginate was
prepared. To the solution was added 0.85 grams of
sodium dodecyl sulF~hate per 100 grams of alginate
solution as a foaming agent. In addition, 2.3 grams of
ammonium stearate pEx 100 grams of alginate solution
was added as a foam stabilizer. The resultant solution
was beaten with a Ki.tchenaid mixer to tone a foam. The
foam was spread vn a~ polyester sheet and allowed to air.
dry. The surface of the dried foam maintained a
similar appearancs~ to the wet foam and did not
WO 94/00512 PCT/US93/05993
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- 25 -
collapse; the foa:a material in the interior of the foam
was found to have "collapsed" and had the appearance of
crushed foam. The dried foam was immersed in a 5% wt
calcium chloride so~.ution and then allowed to air dry.
Once again the dried foam maintained the appearance of
the original drawn material. Inspection under an
optical microscope rEwealed the foam was an open-cell
structure with fairly unifoan pore sizes. The foam had
a final thickness of 2.8 ma, a density of 0.05 g/ctn,
and a pezmeability of 90 m/min at 12.7 mm Fi20.
I~~LE 5
To a solution of s~i~ailar composition to Fxample 1 was
added 1 gram of anhydrous glycerol per gram of alginate
material. The solution was foamed mechanically, drawn
into a desired thiekiieas and allomed to air dry. The
dried foam was cross-linked using a 5% wt calcium
chloride solution and air dried. The resultant foam
had a final thiciaiess of 0.25 mm, a density of 0.14
g/csn3 and an air ~.~eability of 100 m/min at 12.7 mm
H20 pressure. AftE3r 3 months under ambient conditions,
the foam had a simile~r handling ability as a newly
farmed foam.
WO 94/00512 PCT/US93/05993
2~.16~3'~
- 26
Ex;~2~'LE 6
A single layer alginate foam was produced by a method
similar to the metha3 described in Example 4 above.
Figures 1 to 3 are Scanning Electron Microscope
photographs of the resultant dried foam (10). It will
be noted that an interior region (12) of the foam is
"collapsed giving the appearance of "crushed° foam,
while the surfaces (14, 16) of the foam substantially
maintain their pore size and pore size distributions.
EXR1~LE 7
Another alginate foam layer was made by a method
similar to the method of Exaa~rle 4 above; this foam
layer wras foamed mechanically in accordance with the
invention to have a relatively large mean pore size and
dried. A second foam layer controll~d to have a
relatively smaller moan pore size was then cast on one
surface of the first n~ntivned layer and dried. Figures
4 to 6 are Scanning Electron Microscope photographs of
the resultant two-layer foam (20). It will be noted
that an interior (22) of the foam is ~collapsed°, while
the surfaces (24, 26) substantially maintain their
controlled pore sizes and pore size distributions.
WO 94/00512 ~ 116 c~ ~ "~ P~/US93/05993
,_
~xa~le B
An aqueous solution containing 5 wt~ sodium hyaluronate
was prepared. To this solution was added 2.7 grams of
sodium dodecyl sulphate and 5.3 grams of ammonium
stearate per 100 gr~sms of solution. 2~e mi.xture was
well beaten with a KitchenAid mixer to fog a foam.
The foam was aprend onto a polyester sheet and air
dried. Inspection sunder an optical microscope revealed
the foam was an opera-cell structure with fairly uniform
pore Size.
WO 94/00512 PCT/US93/05993
2116037
_ 2g
Example 9
A solution was prepared with 10 grams of 37.5 w/w HC1
and X90 grams water. Fifteen grams of chitosan were
added and dissolved in the acid. To thQ solution were
added l.S grams of sodium dodecyl sulfate and 15 grams
of ammoniian stearate. The mixture was beaten in a
KitchenAid mixer to fog a foam which ~s subsequently
drawn to 25 arils thickness and air dried. Inspection
under an optical unicrosccpe revealed the foam was
open-celled and fairly uniform in pore size.
