CA2116037C - Method of producing polysaccharide foams - Google Patents
Method of producing polysaccharide foams Download PDFInfo
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- CA2116037C CA2116037C CA002116037A CA2116037A CA2116037C CA 2116037 C CA2116037 C CA 2116037C CA 002116037 A CA002116037 A CA 002116037A CA 2116037 A CA2116037 A CA 2116037A CA 2116037 C CA2116037 C CA 2116037C
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- foam
- polysaccharide
- aqueous solution
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- wet
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/30—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by mixing gases into liquid compositions or plastisols, e.g. frothing with air
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/04—Alginic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
Abstract
A method of producing a polysaccharide foam is provided. The method comprises mechanically foaming an aqueous solution of a soluble polysaccharide and thereafter reacting the foam to produce stable foam. Typically, the soluble polysaccharide is an alginate, hyaluronate, carrageenans, chitosan or starch.
Description
2 ~ 3 '~ PCT/US93/05993 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 -~ 2 -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.
WO 94/00512 ~ ~ ~ ~ ~ ~ ~ PCT/US93/05993 -~ 3 -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.
211603' 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 -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 21160~'~
-~ 6 -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
WO 94/00512 . ~ 11 ~ 0 3 '~ PCT/US93/05993 g _ 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 ~
2116fl3'~
_ 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 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 ~116~~'~ _.
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 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 211~~~'~
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 ~- 15 -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.
WO 94/00512 ~ PCT/US93/05993 211~03'~
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 WO 94/00512 ~ ~ ~ ~ ~ PCT/US93/05993 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 .
211~~3'~ _v _ 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 WO 94/00512 ~ ~ ~ ~ ~ PCT/US93/05993 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.
211~~37 .- 2d -~'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;
~~~,~~3~
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 2116~3"~
.. 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.
WO 94/00512 ~ ~ ~ ~ ~ ~ PCT/US93/05993 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.
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 %
211~03'~
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 2~~.6~3'~
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.
2~.16~3'~
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.
_ 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.
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 -~ 2 -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.
WO 94/00512 ~ ~ ~ ~ ~ ~ ~ PCT/US93/05993 -~ 3 -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.
211603' 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 -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 21160~'~
-~ 6 -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
WO 94/00512 . ~ 11 ~ 0 3 '~ PCT/US93/05993 g _ 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 ~
2116fl3'~
_ 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 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 ~116~~'~ _.
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 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 211~~~'~
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 ~- 15 -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.
WO 94/00512 ~ PCT/US93/05993 211~03'~
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 WO 94/00512 ~ ~ ~ ~ ~ PCT/US93/05993 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 .
211~~3'~ _v _ 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 WO 94/00512 ~ ~ ~ ~ ~ PCT/US93/05993 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.
211~~37 .- 2d -~'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;
~~~,~~3~
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 2116~3"~
.. 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.
WO 94/00512 ~ ~ ~ ~ ~ ~ PCT/US93/05993 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.
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 %
211~03'~
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 2~~.6~3'~
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.
2~.16~3'~
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.
_ 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.
Claims (52)
1. A method of forming a dry polysaccharide form from an aqueous polysaccharide solution, comprising the steps of:
a) forming an aqueous solution of a polysaccharide selected from the group consisting of alginic acid, a soluble alginate salt, and other soluble polysaccharides containing exchangeable counter-rations;
b) introducing a gas into the aqueous solution to form a wet foam by agitating the solution;
c) homogeneously dispersing an insoluble carbonate or hydrogen carbonate salt having one or more di- or tri-valent rations in the wet foam and subsequently treating the wet foam with an acid having a concentration not in excess of 1 N thereby liberating carbon dioxide as a gas and the rations to produce a cross-linked polysaccharide foam; and d) drying tree wet foam to form a dry polysaccharide foam;
wherein the dry foam is predominantly comprised of polysaccharide.
a) forming an aqueous solution of a polysaccharide selected from the group consisting of alginic acid, a soluble alginate salt, and other soluble polysaccharides containing exchangeable counter-rations;
b) introducing a gas into the aqueous solution to form a wet foam by agitating the solution;
c) homogeneously dispersing an insoluble carbonate or hydrogen carbonate salt having one or more di- or tri-valent rations in the wet foam and subsequently treating the wet foam with an acid having a concentration not in excess of 1 N thereby liberating carbon dioxide as a gas and the rations to produce a cross-linked polysaccharide foam; and d) drying tree wet foam to form a dry polysaccharide foam;
wherein the dry foam is predominantly comprised of polysaccharide.
2. The method as claimed in claim 1, wherein the forming of the wet foam is facilitated by beating or by mechanical agitation.
3. A method as claimed in claim 1, wherein the polysaccharide is selected from the group consisting of a soluble polysaccharide salt, a soluble alginate, a soluble hyaluronate, alginic acid, hyaluronic acid, carrageenans, chitosan, starch, amylose, guar gum, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and amylopectin.
4. A method as claimed in claim 1, wherein the polysaccharide is chitosan foamed in an acidic solution.
5. A method as claimed in claim 1, wherein the polysaccharide is selected from the group consisting of starch, amylose and amylopectin foamed in a basic solution.
6. A method as claimed in claim 1, wherein the aqueous solution of polysaccharide contains at least one agent selected from the group consisting of foam stabilizers and foaming agents.
7. A method as claimed in claim 1, wherein the aqueous solution includes a foaming agent selected from the group consisting of sodium stearate, sodium dodecyl sulfate, alpha olefin sulfonates, sulfoalkyl amide, monocarboxyl coca imidazoline compounds, dicarboxyl coco imidazoline compounds, sulfated fatty polyoxyethylene quaternary nitrogen compounds, octylphenol ethoxylate, modified linear aliphatic polyethers and sorbitan esters.
8. A method as claimed in claim 1, further including the step of introducing a plasticizer in the aqueous solution selected from the group consisting of glycerol, glucose, polyhydric alcohols, triethanolamine and stearates.
9. A method as claimed in claim 1, further including the step of introducing an oligomeric or polymeric foam modifier in the aqueous solution selected from the group consisting of polyethylene glycol, guar gum, albumin, gelatin, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyacrylamide, polyacrylic acid, polyvinyl alcohol, polyvinyl pyrollidone, polyoxazoline and polyethyleneimine.
10. A method as claimed in claim 9, wherein polyethylene glycol functionalized with vinyl groups is introduced as the foam modifier and the foam is irradiated to effect polymerization of the functionalized polyethylene glycol forming a polymer network in the foam.
11. A method as claimed in claim 2, further including the step of introducing an oligomeric or polymeric foam modifier in the aqueous solution selected from the group consisting of polyethylene glycol, guar gum, albumin, gelatin, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyacrylamide, polyacrylic acid, polyvinyl alcohol, polyvinyl pyrrolidone, polyoxazoline and polyethyleneimine.
12. A method as claimed in claim 11, wherein polyethylene glycol functionalized with vinyl groups is introduced as t=he foam modifier and the foam is irradiated to effect polymerization of the functionalized polyethylene glycol forming a polymer network in the foam.
13. A method as claimed in claim 1, further including the step of introducing a foam stabilizer into the aqueous solution selected from the group consisting of ammonium stearate, dodecyl alcohol, tetradecanol, hexadecanol, tridecyloxypolyethanol and polyoxyethylated oleylamine.
14. A method as claimed in claim 1, wherein the polysaccharide foam is coagulated to form a water insoluble foam.
15. A method as claimed in claim 1, wherein the polysaccharide foam is cross-linked to form a water insoluble foam.
16. A method as claimed in claim 14, wherein the polysaccharide foam is chitosan coagulated by treatment with a base.
17. A method as claimed in claim 15, wherein the polysaccharide is chitosan, and the chitosan foam is cross-linked by ionic bonding by treatment with an aqueous solution of polyvalent anions selected from the group consisting of sodium sulfate, octyl sulfate, lauryl sulfate, hexadecylsulfate, tripolyphosphate, pyrophosphate, octapolyphosphate and mixtures thereof.
18. A method as claimed in claim 15, wherein the polysaccharide :is chitosan, and the chitosan foam is cross-linked by covalent bonding by treatment with a dialdehyde selected from the group consisting of glyoxal, glutaraldehyde and dialdehyde starch.
19. A method as claimed in claim 14, wherein the polysaccharide is starch, and the starch foam is coagulated by treatment with aqueous ammonium sulfate.
20. A method as claimed in claim 15, wherein the polysaccharide is starch, and the starch foam is cross-linked by treatment with formaldehyde in an alcohol solvent.
21. A method as claimed in claim 14, wherein the coagulated foam is washed and then redried.
22. A method as claimed in claim 1, further including the step of cross-linking or coagulating the wet foam to form a cross-linked or coagulated wet foam.
23. A method a.s claimed in claim 22, wherein the polysaccharide is selected from the group consisting of alginic acid, a soluble aginate salt, gelatin, and other soluble polysaccharides containing exchangeable counter-cations, and wherein the cross-linking is effected by reacting the wet foam with di- or tri-valent rations.
24. A method as claimed in claim 23, further including the step of homogeneously dispersing an insoluble carbonate or hydrogen carbonate salt having one or more di- or tri-valent rations in the wet foam and subsequently treating the wet foam with an acid having a concentration no-t in excess of 1 N thereby liberating carbon dioxide as a gas and the rations which then produce cross-linked polysaccharide foam.
25. A method as claimed in claim 22, further including the step of washing and drying the cross-linked or coagulated wet foam to form a dried continuous polysaccharide foam.
26. A method as claimed in claim 23, wherein the cross-linked wet foam is converted by treating the foam with an aqueous solution containing solubilizing mono-valent rations so that at least a portion of the cross-linking di- or tri-valent rations in the foam are replaced by the mono-valent rations thereby imparting a degree of solubility in the wet foam.
27. A method as claimed in claim 26, further including the step of washing and drying the converted and cross-linked wet foam to form a dried continuous polysaccharide foam.
28. A method as claimed in claim 1, wherein at least one ingredient selected from the group consisting of particulate fillers, barium sulfate, pulp-like fibres of cellulose or other fibrous materials, moisture retaining materials, and reinforcing filler materials are introduced into the aqueous solution.
29. A method as claimed in claim 1, wherein the wet foam is cast as a layer and dried to form a dried continuous sheet of polysaccharide foam.
30. A method as claimed in claim 1, wherein the wet foam is cast in the form of buttons, beads, balls, cylinders or hemispheres or in the shape of a part of a human body or animal body and dried.
31. A method as claimed in claim 1, wherein the wet foam is cast as a layer on a substrate and dried.
32. A method as claimed in claim 31, wherein the substrate is a woven, non-woven fibrous article, a film, or a foam.
33. A method as claimed in claim 32, wherein the substrate is a layer of polysaccharide foam having a different mean pore size or pore size distribution relative to the east foam layer.
34. A method as claimed in claim 1, wherein a beneficial agent is introduced into the aqueous solution.
35. A method as claimed in claim 1, wherein a beneficial agent is introduced into the polysaccharide foam.
36. A dried continuous polysaccharide foam produced in accordance with a method as defined in claim 1.
37. A wound dressing, cell culture replicating medium, barrier medium or delivery device consisting essentially of polysaccharide foam produced in accordance with a method as defined in claim 1.
38. A wound dressing, cell culture replicating medium, barrier medium or delivery device consisting essentially of polysaccharide foam produced in accordance with a method as defined in claim 14.
39. A wound dressing, cell culture replicating medium, barrier medium or delivery device consisting essentially of polysaccharide foam produced in accordance with a method as defined in claim 22.
40. A method of forming a wet polysaccharide foam stored under pressure from a method as defined in claim 1 further including the step of storing the wet foam under pressure.
41. A method as claimed in claim 40, wherein the forming of the wet foam is facilitated by beating or by mechanical agitation.
42. A method as claimed in claim 40, wherein the polysaccharide is selected from the group consisting of a soluble polysaccharide salt, a soluble alginate, a soluble hyaluronate, alginic acid, hyaluronic acid, carrageenans, chitosan, starch, amylose, guar gum, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and amylopectin.
43. A method as claimed in claim 40, wherein the aqueous solution includes a foaming agent which facilitates the formation of the foam and is selected from the group consisting of sodium stearate, sodium dodecyl sulfate, alpha olefin sulfonates, sulfoalkyl amide, monocarboxyl coco imidazoline compounds, dicarboxyl coco imidazoline compounds, sulfated fatty polyoxyethylene quaternary nitrogen compounds, octylphenol ethoxylate, modified linear aliphatic polyethers and sorbitan esters.
44. A method as claimed in claim 40, further including the step of introducing a plasticizer in the aqueous solution selected from the group consisting of glycerol, glucose, polyhydric alcohols, triethanolamine and stearates.
45. A method as claimed in claim 40, further including the step of introducing a foam stabilizer into the aqueous solution selected from the group consisting of ammonium stearate, dodecyl alcohol, tetradecanol, hexadecanol, tri.decyloxypolyethanol and polyoxyethylated oleylamine.
46. A method as claimed in claim 40, wherein at least one ingredient selected from the group consisting of particulate fillers, barium sulfate, pulp-like fibres of cellulose or other fibrous materials, moisture retaining materials, and reinforcing filler materials are introduced into the aqueous solution.
47. The method as claimed in claim 40, wherein a beneficial agent is introduced into the aqueous solution.
48. A method as claimed in claim 40, wherein the wet foam is stored in a pressurized spray can.
49. A method as claimed in claim 40, further including the step of introducing polyethylene glycol functionalized with vinyl groups as an oligomeric or polymeric foam modifier in the aqueous solution and wherein after the wet foam is released from storage it is irradiated to effect polymerization of the functionalized polyethylene glycol forming a polymer network in the foam.
50. A wound dressing, cell culture replicating medium, barrier medium or delivery device consisting essentially of polysaccharide foam produced in accordance with the method of claim 40, wherein the wet foam is stored in a pressurized dispenser.
51. A wound dressing as claimed in claim 50, wherein the wet foam is incorporated with a propellant selected from the group consisting of a gaseous lower alkane, nitrogen and carbon dioxide.
52. A wound dressing, cell culture replicating medium barrier medium or delivery device consisting essentially of polysaccharide foam produced in accordance with the method of claim 40.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9212976.6 | 1992-06-19 | ||
| GB929212976A GB9212976D0 (en) | 1992-06-19 | 1992-06-19 | Wound dressings |
| GB9224255.1 | 1992-11-19 | ||
| GB929224255A GB9224255D0 (en) | 1992-11-19 | 1992-11-19 | Alginate wound dressings |
| PCT/US1993/005993 WO1994000512A1 (en) | 1992-06-19 | 1993-06-18 | Method of producing polysaccharide foams |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2116037A1 CA2116037A1 (en) | 1994-01-06 |
| CA2116037C true CA2116037C (en) | 2000-01-04 |
Family
ID=26301095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002116037A Expired - Fee Related CA2116037C (en) | 1992-06-19 | 1993-06-18 | Method of producing polysaccharide foams |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0612331A4 (en) |
| JP (1) | JP2644626B2 (en) |
| AU (1) | AU672214B2 (en) |
| BR (1) | BR9305552A (en) |
| CA (1) | CA2116037C (en) |
| FI (1) | FI940735A (en) |
| WO (1) | WO1994000512A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110433321A (en) * | 2019-07-06 | 2019-11-12 | 张明 | A kind of preparation method of the medical foam dressing with sustained-release antibacterial |
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| IL104441A (en) * | 1993-01-19 | 2001-01-28 | Yossi Res Dev Company Of The H | Sponges from hydrocolloids and method for their production |
| GB9424562D0 (en) | 1994-12-06 | 1995-01-25 | Giltech Ltd | Product |
| NO953115L (en) * | 1995-06-07 | 1996-12-09 | Albany Int Research | Process for the preparation of polysaccharide foam |
| DE19729273C2 (en) * | 1997-07-09 | 2000-08-17 | Aventis Res & Tech Gmbh & Co | Thermoplastic mixture based on 1,4-alpha-D-polyglucan, process for its production and use |
| AU6216299A (en) * | 1998-10-07 | 2000-04-26 | Giltech Limited | Foamable formulation and foam |
| ATE499953T1 (en) * | 1999-03-02 | 2011-03-15 | Convatec Technologies Inc | HYDROCOLLOID GLUE |
| CA2364570A1 (en) * | 1999-04-09 | 2000-10-19 | The Regents Of The University Of Michigan | Preparing porous hydrogel products |
| GB2357765B (en) * | 1999-04-29 | 2004-04-21 | George H Scherr | Alginate foam compositions |
| DE19935231A1 (en) * | 1999-07-28 | 2001-02-01 | Ulrich Zimmermann | Crosslinking of ionotropic gels |
| SE518736C2 (en) | 1999-08-30 | 2002-11-12 | Sca Hygiene Prod Ab | Absorbent, open-celled foam material with good liquid storage capacity and absorbent structure in an absorbent article |
| SE514898C2 (en) | 1999-08-30 | 2001-05-14 | Sca Hygiene Prod Ab | Absorbent structure comprising a compressed regenerated cellulose foam material, method for its preparation, and absorbent articles such as a diaper comprising the structure |
| US7408057B2 (en) | 2000-07-03 | 2008-08-05 | Marine Bioproducts Intenational | Clarified hydrocolloids of undiminished properties and method of producing same |
| IL160685A0 (en) * | 2001-09-04 | 2004-08-31 | Dow Global Technologies Inc | Aqueous air foam |
| EP1620076A4 (en) * | 2003-04-25 | 2010-08-25 | Kos Life Sciences Inc | Formation of strong superporous hydrogels |
| DK1663326T3 (en) * | 2003-09-08 | 2010-06-21 | Fmc Biopolymer As | Gel foam based on biopolymer |
| DE102004025495A1 (en) | 2004-05-21 | 2005-12-15 | Dr. Suwelack Skin & Health Care Ag | Process for the production of alginate-containing porous moldings |
| BRPI0708422A2 (en) * | 2006-03-01 | 2011-05-31 | Fmc Biopolymer As E Fmc Corp | METHOD FOR FORMING A COMPOSITE, COMPOSITE, METHODS FOR PROMOTING CELLULAR PROLIFERATION IN THE COMPOSITE, FOR INHIBITING CELLULAR PROLIFERATION AND FOR RECOVERING COMPOSITE CELLS, USING A COMPOSITE, AND, METHODS FOR FIXING A COMPOSITE, A COMPOSITE. , TO INDUCE IN SITU GELEIFICATION INSIDE THE PORES OF AN ALGINATE FOAM, TO PREVENT FABRIC ADHESION TO ADJACENE TISSUE AND TO FORM A DRY ABSORBENT FOAM |
| WO2009038783A1 (en) * | 2007-09-19 | 2009-03-26 | Surmodics, Inc. | Biocompatible foams, systems, and methods |
| FR2925315B1 (en) * | 2007-12-21 | 2010-02-12 | Oreal | KIT COMPRISING AN ALGINATE AND A COMPLEXING AGENT IN THE FORM OF WATER-SOLUBLE SALT |
| FR2925316B1 (en) * | 2007-12-21 | 2010-02-12 | Oreal | KIT COMPRISING AN ALGINATE AND A COMPRISING AGENT IN THE FORM OF WATER-INSOLUBLE SALT |
| CA2741415A1 (en) * | 2008-10-22 | 2010-04-29 | Surmodics, Inc. | Swellable biodegradable polymeric matrices and methods |
| JP4358895B1 (en) * | 2009-01-06 | 2009-11-04 | 昭和高分子株式会社 | Foamable resin composition and foam |
| MX347272B (en) * | 2011-04-07 | 2017-04-20 | Procter & Gamble | Continuous process of making an article of dissolution upon use to deliver surfactants. |
| JP6206089B2 (en) * | 2013-04-23 | 2017-10-04 | Jnc株式会社 | Polysaccharide monolith structure and production method thereof |
| CN106536606B (en) | 2014-05-19 | 2019-11-08 | 巴斯夫欧洲公司 | The method for preparing the porous aerogel based on alginate |
| FR3025203B1 (en) | 2014-08-26 | 2016-12-09 | Renfortech | EPOXY FOAMS DERIVED FROM REACTIVE FORMULATIONS BIOSOURCEES |
| FR3068039B1 (en) | 2017-06-22 | 2020-07-10 | Jellynov | SELF-FOAMING COMPOSITION IN ACID MEDIUM AND PREPARATION METHOD |
| JP2019037608A (en) * | 2017-08-28 | 2019-03-14 | 大日精化工業株式会社 | Method of manufacturing flexible molded body, and flexible molded body |
| FR3089224B1 (en) | 2018-12-04 | 2020-12-11 | Jellynov | Self-foaming composition in an acid medium and method of preparation |
| FR3102364B1 (en) | 2019-10-28 | 2022-08-12 | Urgo Rech Innovation Et Developpement | Polysaccharide gel foam |
| EP3848409A1 (en) | 2020-01-13 | 2021-07-14 | Basf Se | Polyurea/polyurethane-crosslinked alginate aerogels |
| WO2022070845A1 (en) | 2020-09-29 | 2022-04-07 | 日東電工株式会社 | Foam and production method therefor |
| WO2023170134A1 (en) | 2022-03-08 | 2023-09-14 | Aerogel-It Gmbh | Process for producing porous materials |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868355A (en) * | 1972-12-26 | 1975-02-25 | Pillsbury Co | Foam separation of gluten and starch |
| US4002178A (en) * | 1973-12-27 | 1977-01-11 | Amf Incorporated | Foams and sponge sheet for cigar manufacture |
| CA1079016A (en) * | 1976-03-25 | 1980-06-10 | Donald S. Greif | Water insensitive starch fibers and a process for the production thereof |
| CA2080035A1 (en) * | 1991-10-15 | 1993-04-16 | George Colegrove | Gelled foams |
-
1993
- 1993-06-18 CA CA002116037A patent/CA2116037C/en not_active Expired - Fee Related
- 1993-06-18 EP EP19930915464 patent/EP0612331A4/en not_active Withdrawn
- 1993-06-18 WO PCT/US1993/005993 patent/WO1994000512A1/en not_active Application Discontinuation
- 1993-06-18 AU AU45437/93A patent/AU672214B2/en not_active Ceased
- 1993-06-18 JP JP50254994A patent/JP2644626B2/en not_active Expired - Lifetime
- 1993-06-18 BR BR9305552A patent/BR9305552A/en not_active Application Discontinuation
-
1994
- 1994-02-16 FI FI940735A patent/FI940735A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110433321A (en) * | 2019-07-06 | 2019-11-12 | 张明 | A kind of preparation method of the medical foam dressing with sustained-release antibacterial |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0612331A1 (en) | 1994-08-31 |
| BR9305552A (en) | 1994-12-20 |
| JPH06510330A (en) | 1994-11-17 |
| JP2644626B2 (en) | 1997-08-25 |
| FI940735A0 (en) | 1994-02-16 |
| WO1994000512A1 (en) | 1994-01-06 |
| EP0612331A4 (en) | 1994-11-23 |
| CA2116037A1 (en) | 1994-01-06 |
| AU672214B2 (en) | 1996-09-26 |
| FI940735A (en) | 1994-02-16 |
| AU4543793A (en) | 1994-01-24 |
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