CA2049055C - Biodegradable superabsorbing sponge - Google Patents

Abstract

Abstract of the Invention new superabsorber which gels and cross-links as hydrated has been developed. The superabsorber contains a branched-chain polyanionic carbohydrate such as carboxymethylcellulose,a cross-linking agent, and a hydrophobic carboxylic acid. The superabsorber is biodegradable and non-toxic.

Description

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~IODEeRA12AE~LE~ SQRE~INQ~Q~ ~ ' :'-. ~. ;', ' Ba~rQuna Qf~e Inven~Qa The present ~nvent~or~ r~l~te~ to bi~egra~abl~ gel~ wh~ch ~ct ~ sup~absorblng 5 spon~e~. Moro particularly, ~ha 9~l o~E th~ ~nYention has ~s h~gh, or hl~her, ligul~ an~ ~aline uptake t~n the p~lyacryl~ts superabsorber~ now being use~ wh~
~aving the advant~ge o~ be~ng comple~ely biodegra~a~

Biodegradabil~ty ha~ become a necessity ~n . ~;:
society in the la~t few years. As ~ore and more .
pro~uct~ are maae aisposable, the waste problems associatea with these ~isposables have become increasingly important. One example o thi~ I~ the ;
15 disposable ~iaper ~iel~. Unti~ a few y~3r~ ago, .
disposable aiapers, though convenient, ha~ not received widesprea~ use beeause the amou~t o~ l~qu~
whi~h cou~ be a~sorbe~ was limit~q Thi~ limi~t~on ;~-lea~ to use of the ~i~per~ ~or eactraor~in~ry 20 circumstarlces but they wer~ not feas~ble for most people on ~ day-to-~2y ba~i~ because o~ the le~k~ge ~:
and result~ng diaper ra~h pro~lem. In or~e~ to ~olQ~re these problems, tho l~aper manuf~turer fir~t uEe~
~ery thicl~ pers, placlng l~rge amou~lts of i~er ;
25 such as eellulo~ in the ~i3per to ~ICt ~ a liqu~
pr~ma~ly ~ n~ an~ ur~ne, absorber. The~e bulky diapers ~t~ll h~d ï~mlt~t~on~ on :tbe amount o . .

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l~qu~s they coul~ retaln whlle tb~ ~ulk m~ the~ ;
uncomfortable ~or the ~nfant~ to wear.

The ir~t ma~o~ ~mprovemen~ ~n t~o di~posable ~iaper f~el~ wa~ the ad~ition o th~
~o-calle~ ~uperabsorbers~ a8 l~u~ trap8. The8 superabsorbe~ ar~ primarlly polyacryl~te part~cle~
which ar~ plaee~ he ~aper in loo~ or~ or ~r~
entrappe~ amonq celluloso ~ber~. Theso polyacrylat~
particles absor~ larg~ quan~t~e~ of wa~er ~q I 10 swelling ~n~ act~ng a~ in~ ual pseuao-spo~e~
¦ ,Since t~e amount of ~allne and ur~ne which c~n be absorbe~ by these superabsorber~ ~ so much greater than cellulo~e or other natural fiber~, ~ery thi~
diaper~ coul~ be use~, minimizlng the problems to 15~ infants and ma~ing di~posables the ~iaper of choice.
. The polyacrylate gel beads move freely relative to ~ .
each other ana ~orm large ~paces between each other.
~owever, once fully hydrate~, these polyacryl~to .~
~uper~bsorber~ ten~ to clump, causing a lumpy ~i~per ~. .p ~.
20 an~ discomfort to the inf ant. ~ f In aadition to the use ~n ~apers, the super~bsorbers ha~e other uses. ~ny other items wh~ch are usea for absorptlon ~ liqu~ are ~ gertile .
groun~ for use o the superabsorber~. Howe~er, the polyacrylate super~b~or~er~ have on~ ma~or ~sa~ant~ge; th~y are not b~o~e~ra~abl~. ~h~ m~ns .
th~ the ~oper~ all other ~ro~ucts ma~e u~ln~
th~se ~uperabsorber~ ara not te~r3~e~ ~o~ ~e~a~es; ~n :~
f~et, th~y nee~ hun~re~s o~ yeaEs to bre~down. This 3Q lsad~ to the ~forement~sne~ ~ste pro~lem. ~o her d~adv~ntag2 of the poly~cryl~te~ i5 th~t they a~sorb '.'~.,.~ ' . ,. '~.
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- 20g~05~ -ma~mally at 0% ~ ne while u~n~ ~nd most ~o~y ~lu~ ar~ ~bout 0.~5 ~ ~alino. ~ ~
....
Mater~als wh~ch ~bsorb ligul~ ~n~ a~o bio~egradable such ~ ~hose o~ th@ present ~nventio~
5 have other possible uses as well. ~he~ entrapment o part~cles, ~nclu~lng macromoleeule~ ~uc~
hemoglobln and c~ uch a~ orythroc~te~
parti~ul~rly ~mportank ~o~ ~eminine ~pkin~ ~nd -~
c~m~lar psoducts. ~uperabsoxbe~ ba~o not ma~e ~
lO 9reat ~ent ~n this f~el~ even th~ugh tbey have the hecessary liqui~ absorpt~on because they cannot entrap lsrge p3rticulates.

Another possible use for a biodeqradable ~;~
material which will entrDp ligui~ an~/or particles is as a sustaine~ release vehicle. In certDin instances, the molecule~ to be ~elivered c~n be part '~
of the structural materi~l of the sp~nge itself. .
Nost mater~als which are presently ~e~ng teste~ as :~
sustained release vehicles, e.g., microcapsules, liposomes an~ relate~ cap~ular type ~ro~u~t~, have substanti~l costs an~ tlme ~5~0ci~te~ with their manuacture. The ~bil~ty to make ~ pro~u~t in fi~
npply ~t to ~ given area, ~n~ then let ~t ~egr~e under or~inary conditions to release entrapped m~terial, woul~ solve many problems.

A ~urthe~ u~e o~ a gel wh~eh entraps l~qui~s ~n~ part~cles ~s as ~ ~ologic~l protectiY~ h~rrier.
For esample, a gel wh~c~ ~ntr3ps bacter~a ~s ~t ~s hy~rate~, or provents the~r pass~ge o~c~ ~or~ea, c~n 3~ be use~ ns a wouna ~ressing, protect~ng the woun~

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~rom bDcteria while ollowin~ ~r flo~ ~n~or fre~
10w o~ liquid to th~ ~n~u~y. A fu~ther U8e ~ ~n a ~iaper wher~ coli~orm ~acteria can ~reakdown urea in -~
ur~ne to ammon~, chang~ng tha pH ~n~ promotinq s ~i~per ra~

Accor~n~ly, 8~ ob~e~t o~ ~hle ~nvent~on to provid2 ~ biodegra~ble mater~l that has high uptak~ fo~ wator ~n~ ~AllnQ. .

~ r~other ob~t of t~e inverlt~o~ to lo,prov~e ~ b~o~egradable carr~er or ~ust~rJe~ rele~se ~el~very system for ~rugs ana other moleculeE. . -:

A further ob~ect of the invent~o~ is to:
provi~e a material and metho~ for entrapment of part~culates such as erythrocytes an~ proteln 15 molecules ~uch as hemoglobin.

A st~ll further object o~ the ~nvention i~
to provide ~ proteetive barrier wh~ch prevent~ the passage o p~rticles ~uch as b~cter~a or ~-macromolecules, eOg., for use as ~ woun~ bandage. r,~

These tn~ other object~ ~n~ feature~ o~ the in~ention w~ll be apparent ~rom the ~ollow~ng ~escription.

~umm3rY o~ the In~n~Qn The present ~n~ention ~e2~ure6 a ~o~po8ition 25 of matter which ~Ct~ ~ a ~ynthetic ~ponge a~ well ~s metho~s ~f ~b~or~ing ~gueou~ or 5alin~ ~olut~ons.

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The ~nvent~on ~urth~r featur~ metho~ o gntr~pp~ngparticle~ ~n a 9~1~ Th~ gel-l~ke compo~tion of matter ~an ba u~e~ a~ a protect~ve barrier an~ ~ a susta~ned release ~eh~cle which release~ entrappe~
5 particles or molecul~ ~uch ~ ugs o~er t~

~ n br~e, ~ sompos~tlo~ of m~ltter h~ bee~
aevelope~ wh~eh DCt~l 19S a 6ynthetlG spon~e wher~
allowe~ to hy~rato. ~ h~gh molecul~r w~ght, e~mplos carbo~ydrate w~th mult~ple anion-terminat~ branche~
lo an~ a ~ross-l~n~g agent are blen~ed ~n~er ~substant~ally anhy~rous conait~ons, preferably w1th a carbo~ylic ac~d with a substantial hy~rophobi~
region. Preferre~ carboxyl~c acids with su~s~antial hy~rophobic regio~ Are ~atty Dcids ~electea rom a :~
group consist~ng of lauric ac~d, palmitic 3cid, oleic acia, stear~c acid, benzoic ac~, or mi~tures thereof. A substant~al hydrophobic region me~n~ ana -~
implies a region with ~ substantial hy~rocarbon cha~n or ring ~tructure. Preferre~ br~nch comple~
carbohy~r~tes inclu~e carbosymethylcellulose, ~n~
chemical ~nalogues thereofO ~inear comple~
carbohydrates such as Gellulose, gum santhan~ ~um -~
kar~ya, or algln~c ~ci~ m~y ~l~o be inclu~e~

Once the component~ ~re intimately blen~e~, :
e.g., m~lle~ to~ethe~, the component~ o the mi~ture can be hy~rate~ ~n~ ~ro~-linke~ su~t~nt~lly ~multaneously when ~n the pres2nc~ o~ tha hy~r~tin~
: ~olution. Any o the component~ m~y be premise~
together or impregn~te~ wlth one another. In .
~it~on, the other re~Gtant~ m~y ~e ~erivatl~e~ W~t~
~he comples or l~near c~rbohydr~t-s us~ng an :

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~ ~-isopropo~e or other ~imilar reac~on. ~,ome or all :7 o~ t~e ~atty aci~ can be repl~ced wit~ a ~~nction~
~atty aci~ or a long-ch2in car~o~yli~ ac~. A~
use~ herein, the ter~ ~func~lonal ~atty ~c~ m~an~
S ~nclu~es and ~efines a mo~ecule having a term~n~l carbo~yli~ ac~, a substant~al al~phat$c portlon, ~n~
5 b~olog~cal funct~on other than ~ ~ break~own pro~uct or precur~or in ~h~ ~oOa ~ha~a. Funot~on~
fatty ac~ nclu~e ~Ci~8 such as undecylen~c ~c~
10 arachi~onic a~i~, p~ostaglana~ns, pros~cycl~ns, thrombo~anes, an~ their ~er~ati~e~, chemic~
analogue~ ana precursor~

As noted, the composit~on of matter of the invention ~ncludes ~ cross-linking ~gent as ~n : :
15 essent~al component. The preferred ~ross-link~ng agents ore~metallo-organic compoun~s o mult~valent metal~, Organ~c cross-l~nk~ng agent~ ~uch as .:. -~ .
ch~tosan, ~oly-Cup* cbymene, an~ ~eff~mlne m~y be us,ed, bu~ are les~ eff~cient than the metal~o-or~ni~
20 comple~e~. O~ytetracyl~n~ ~ a h~ghly efect~ve ~ -~
cros~-lin~ing 2gent but ~as l~mite~ ~pplic~t~on because of ~ts biological ~CtiY~ty. Althou~h .
bivalent molecules ~uch ~s cdlcium might be use~ in certain ~ir~umst~nce~, the multivalent metal~
25 ~valence 3 an~ o~er) sUch ~s Dluminum or chrom~um are ~:.
preerre~. For m~ny appllcations aluminum ~n the form ~f hydroxy-~lumlnum d~et~te, borate-stabll~zed dihy~ro~y-~luminum ~cet~t~ ~n~or ~lum~nu~
6ulfate~cit~te, m~y be ~at~5factory~ A mo~t ~ ~-30 preferre~ ~oss-linking ~gent pro~id~ng superior performance ~ ~n ~luminum metallo-~rgan~c comple~ of the hy~ro~y-aluminum/hy~rophob~c earbosylate form *Trade Mark : ~'`'`

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., ~uch as hy~ro~y-~umlnum ben~osto. Th~ ~yent ean a~t as both the hyarophoblc car~o~yl~c aci~ ~n~ the cross-linkin~ agent ~n ~ ~in~le moleclulo. O~her hydrophobic c~rbo~yli~ ~ci~ ~uch a~ ~ur~o, ~ 5 ~tearat~, oleate or benzo~te can ~l~o b~ use~ ~ the ,Yj metallo-orsanie eompl~

i The in~ent~on ~urther feature~ ~ metho~ o~
; absor~ing agueou~ or ~al~ne solut~on~ uslng tho ~ b~o~eyr~ble ~ynthetl~ ~ponge compo~it~on of th~
`~ 10 invent~on. ~he synthe~lc ~ponge compos~t~on 1~
pro~ed ~n a ~ubst~ntially unhyBr~te~ o~m, or .~ esample, by blen~ing the components togetber to obtAin particles of the ~esired size, an~ then the -~
solution i8 absorbe~ by contacting the solution w~th 15 the synthetic sponse composition. ~he ~ynthetic sponge composition hydrates to ~bsorb t~e solution an~ substantially simult~neously cross-llnks into a gel which bin~s tbe ~olution.

The same basic materi~l m~y be u~e~ to 20 encapsul~te part~cle~ ~n ~ 9el. The synthetic ~ponqe eomposition i8 prov~e~ ~n a ~ubstantially unby~rate~
form ~na a solut~on cont~ining ~he particles to be entrappe~ within the gel i~ mi2ed with the composition, The gel form~ by Gross-linking, 25 absorbing the ligui~ ~n~ entrapp~ng the part~cles ~: :
wit~n the qel. P~rt~cl~s ~h~ch can be 2ntrappe~ ~n th~s way ~nclu~e ma~rom~lecule~ os prot~ns ~uch hemoglo~in, bicter~a, os Gell6 ~ueh ~s erythrocyte~
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3 ~ub~t~nti~lly the ~me ~ntrapment ~roce~ure 30 ~an be used to creato a ~u~t~ined rele~se vehlcl~
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For esample, ~el~ cros~ n~e~ by oxytetr~cycl~n~ c~ p;
b~ use~ a~ ~ ~u~t~ne~ rele~ ehicle ~or thl~
~rug. Many po~tl~tely ch~rge~ ~rugs can ~o hell~ ~n polydnioll~c gel8 ~or ~ust~ine~ releAse. By mo~i~ying 5 the r~t~o~ o~ the ~ferent ~omponent~, an~ ~elect~0 the ~pec~f~ materi~ls wh~ch mak~ up thle 9~1, th~
~tabillty, zbsorp~cion 9.~rel~, ~n~ irmnle~ o~ t~ g~
can be mo~ e~. ~o~ e~ mpl~, chanç~ th~ atty ~c~carbohy~rAt~ r~t~Lo can ~ramdtically c2 ~ng~ th0 10 absorption, ar~l~ ths ~ubsequent relea~o ~at~, o l~gu~ rom the gel. Further, ~he a~tion o~ ot~er materi~ls to the gel, ~.9., surfactant~ ~u~h ~8 -~
polyosyethylene fatty a~ ether~ or spacer~ such as `~
5ilic3 or clays, c~n ch~nge the properties of the 15 9el. This chdnse of properties ~s mor0 ~learly e~plaine~ ~n the de~cription ~n~ the E~amples. ;
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.,-~ ~ . , -, ,, petailed Description o~ ~he I~ventiQn The hydrate~ gel descr~be~ here~n ~8 ~ormea by the ~multaneou~ hyar~t~on an~ cross-l~n~ng by 20 cross-linkin~ a~ent of polyan~onic c~rbohydr~te~
pre~erably together with hydrophobis car~o~yl~t~
In contrast to the polyacrylste ~uperabsorber~, whi~h necessarily form ~i~crete particles ~s ~o ~ov~lently c~oss-linked moleeules ~uch a~ cro~s-l~nke~
25 carbosymethylcellulose, gel~t~ns, an~ ~lgin~te~), the materi~l of the present ~nvent~on ~ ts ln uncro~-llnked form pr~or to hy~r~tlon. Upon '~
hy~r~tion, the m~terial gorms e~tena, w~ter-binB~ng network~ of b~o~e~r~fl~ble ~arbohy~rate ~olymer, 30 prefer~bly ~urther cro~ nked w~th est~n~
multll~mell~r ~hee~ o~ ~egr~bl~, an~onic llpl~

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Macroscoplcally, th~ 9~1~ ar~ ~t~le ~nd ~an e~ten~ -~
se~er~l ~ent~me~er~ ~n ~ever~ re~t~ons upon hy~rat~on. Thes~ gel~ ~an al~o be ~orme~ ln o a - ~ariety o~ geome~rle~ 6uch ~ ro~5, ~i~;kst on~
5 ~la~s. The consist~ncy o~ the gel, ~n~ th~ ~mount of li~ui~ ab~srbe~, ~an be ~hanged by mo~fy~g tho in~t~al compos~tlon. ~n ~dit1on, a ~rt~ally hy~rate~ 9~1 ~an bg further ~y~r~tg~ at ~ l~ter t~m~
~y absorpt~on of more l~qu~

~he c~p~city for upt~ke o~ l~qu~ o the composft~ons of the prese~t ~n~ention ~urthermore depen~s on the ratio of ~ctiv~ ac~, e.g., lipi~s, to a~tive carbohydrate. At low l~pia/carbohyarate .: :~
ratios ton a weight ~as~s), e.~., a 0.1 - 0.2 rat~o, 15 h~gh flui~ absorptlon ~s observe~. ~n fact, ~s m~y be seen frDm the follow~ng E~amples, the uptake of ~ .
0.15 N saline ~s considerably greater than that of ~, the polya~ry~ate ~upera~sorberL. When the rat~o of fatty aci~ to carbohy~rate ~ much higher, ~.9., 20 appros~mately 1, the ~els ~o not a~sorb ~s much liqui~, give up ths l~qu~ easier, ~n~ ~ct a~ better del~very systems.

Funct~onal ~tty ~ci~ c~n be use~ to repla~e ~ome or ~11 o~ the fatty Doi~. Tho mD~or a~ant~ge o~ us1ng the~e ~unct~onal gatty ~c~
that a~ the gel~ ~ro ~egrD~e~, the unct~onal atty ac~ rele~se~. Th~ ~ct~ as a typ~ o Aeli~eIy ~ystem wh~ch c~n have ~ much hi~her ~oncentr~t~on o the materi~l to be ~ell~erea than ~oul~ b~ po~ le 3~ in another type o~ enc~psulat~on or entr~pment .
~y~tem. In fact, ~ cert~n proport~on of the ~atty ;~
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ac~ ean ba replacs~ by any carbo~yl term~nat~
molecula.

Althoug~ ~r~nohe~ ~omple~ carbohy~rates ~ro nece~sary ~o~ p~ctic~ o~ ~he ~n~ent~on, ~om~ o~ ~ -5 ~hese branchea carhohy~rate ~ractions ~an be repl~ce~
by l~near ca~bohy~rate~ 8uch a~ ~llulo~. Th~
a~d~t~on of the~s l~ne~r c~rbohy~r~tes sppe~r~ to improYe tha ~bsorçt~on eap~bll~ty of the ~y~te~
~ct~n~ syner~st~c~lly with the other component~O ~: ;
10 Other l~ea~ c~rbohy~r~tes wh~ch ha~ bee~ shown to ~-~
be e~fect~e inclu~e ~arbohyarate~ w~th terminal glucoron~c aci~ ~uch a~ algin~ aci~, gum santhan ~n~
gum karaya. Non-cross-linkable ~oluble c~rbo~yli~ :
acida do not Dppear to work. . . ~
;,.. ' ''"'' . .'' ffrhe following E~amples will m~re clearly esplain the proceBures sn~ processes of the present invention.

E~amPle 1, ..?~
Th~'s Esample ~hows the flui~ uptake of .
20 saline for ~ compos~tion o~ the ~nvention w~th low --l~pin~carbohydrate rat~o un~er pressur~ eon~ition~
~esigne~ for testing polyacryl~te ~uperabsorber~
Approsim~tely 0.05 9 (0.2 mmol) o p~lmitic ac~ W~8 blende~ w~th 0.5 9 carbo~ymethyl~ellulo~e an~ 0.02 9 (0.14 mmol) bor~te-~t~b~ ze~ ~ihydro~y ~lu~lnum~
~cetate an~ 1.5 g og cellulose f~ber,. U en~ing too~
pl~ce ~t roo,m temper~ture by mi~ing the materi~
togetber until they were uniformlr blen~e~. Th~
material~,~, wer~ then ~ille~ into 500 micron p~rtioles.

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Sn a paralleI e~per~me~t9 s ~igh lip~L~/carbohy~rate materi~ m~ n~l te~ted un~or ths ~ame con~t~on2. Th~s hlgh r~t~o mat~ri~
made by blen~ing 1 g of ~s~m~tic aci~ with 1 9 o ~:
5 carbo~ymethylcellulo~e ~nd 0~04 g o the borate-sta~ Lze~ ~ihydro~y ~lumiLnu~ ac~t~t~
comple~. ~mall portiLon~ o~ th~ sampl~ ~ppro~ma~ly 0.1 9) were ~lende~ wlth 0.5 9 o~ cellulo~e ib~r.

~he two ~ample~ WBr9 te6te~ un~er t~e ~em~
10 procedure, ~ ~a~ polyacrylate i~upera~or~er. ~he ~est proceaure hy~ra~e~ the mater~al~ by eap~lla~y action with 0.15 M NaCl un~er ~ppl~ea loa~ of 0.22 lbs.~n2 for s~s~y m~nutes a~ room tempera~ure. The . : .
amount o ~lui~ ta~e up was then determlne~
15 gravimetrically. ~he tat~ shown ln all the lrDbl2s of ;~
E~ample~ ~how the amount o ~lula uptake for the :
synthet~c 6ponge, determine~ ~y corre~t~ng ~or the amount of flu~fl taken up ~y the cellulose ~o~e which was determine~ ~eparately. ;~

TABLE~
SYStem FlYid UDt ak~ ~mL~Q~ *

L~w ~ipi~Carbohydrate 37~3 ;
~igh Lipia~C~rbohy~r~te 21.1 .~
8up~r~b~orb~ 30O4 .. s ~able 1 ~hows that the ~lu~a upt~ke for the low l~pi~/csrbohyarate r~tio, ~n ml of l~qu~g of ~.~.
~b~orber, 1~ he~ th-- the uDer~bsorber ~hile ~

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, . ., -lower ~mount, but ~tlll ~ni~unt~ 18 ~bsorbe~ by the hi~h lipid~carbohydrat~ rat~o ma~er~alO ~h~
shows that ~ ~lmpl~ mo~if~cat~on of riDt~o~, ~slng ' e~actly the same mater~31~, ~an le~ ~to ~ control ~n -~
s the amount of llqui~ tJ~en up ~y the l~el. .. ~ -E~ampXe ~ thi~ Esampls, ~ ~ere~t te~ w~ u~
to ~etesmin~ ~lui~ ~etention by two diferent ~els o~
the in~ention ~na a poly~cryl~t~ ~uperabsorberO ~he 10 ,fi~st ~ low lipi~carbohy~r~te rat~o gel, w~
maae by blen~ing 0.05 9 palmit~ ac~ w~th 0.5 g carbo~ymethylcellulose dnd 0.02 9 of the borate-stabilized ~ihy~rosy aluminum acetate .
comple2. Appro~imat~ly 0.3 g of th~s misture W25 then blended with 1.5 ~ of cellulose ~iber.
..'.: ':.' ~, ' ;
The second gel o~ the ~n~ention w~s made by blending ~.0 9 of palm~tic aei~ w~th 1.0 9 of carbo~ymethylcellulose ~n~ 0.04 9 of the ;~
borate-~tabilize~ dihydrosy aluminum hcetate comple~. Again, 0.3 9 of ~h~ mi~ure ~A~ blen~
with 0.5 0 o~ cellulo~ flber.

Samples o~ each of the two ~ompos~tio~s ~f the lnventlon ~n~ a superabsQrber ~0.3 ~ e~ch) were ~ n, ~eale~ ~n tea b~g~ ~n~ lmmer~ ln 0.1~ ~ ~ali~Q for.'.
thirty m~nute at room temper~ture. Aft~r remov~
from the ~sl~ne, th~ tea ~gs wer~ centr~fuge~ at'',.,t~.,~'."~,,''',.',''~, 300 X q for thirty minute8 ~n~ th~ amou~t of saline ret~ine~ w~th~n th~ m~t~r~al wa~ ~eter~ned grav~metrically- A~ain, th~re wa~ a corre~tion ~ade.,,,",~,,"!,, ,''''~''.','.','',"~"'"".''''`'~
':' ';.

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for th~ e~ces~ cellulo~. Tabl0 2 ~how~ the re~ult~
of this test~n~

5 ~o~ ~pl~Carbohy~r~o 43.0 High ~ipi~Carbohy~r~t~ 21.1 :
Superabsorber 36 . 5 As is clear, the low l~p~carbohy~r~
ratio mater~al ha~ a greater flui~ retent~on than ~he 10 superabsorber while the h~h l~pi~carbohy~rate ratio material ha~ a lower retention.
.,: ~ ,. , E~ample 3.

In th~ ser~es of esperiments~ the retention of particulate materi~l by the gels of the ~nvent~on ~.-15 were teste~. In each esperiment, 1.0 g of palmitic .. ~
aci~ was uniformly ~len~e~ w~th 1.0 9 o~ m -., carbosymethylcellulo~e an~ 0.04 9 of the .-.
borate-~tabili~e~ dihydro~y ~lumi~um acet~te comples, making ~ high r~t~o ~el. About 0.5 9 o the m~ture .
20 was hydr~te~ w~th 25 ml of the te~t ~u~pensio~. In the ~r~t ts~t, the hy~ration mater~al w~
~u~pen~o~ of huma~ ~e~ cells ~n 0.15 ~ ~line. Tbe .. -~
gelat~on occurre~ with~n t~rty m~nuto~O Ater two hou~, the re~ult~ng ~el W98 ~ent~ifuqally w~she~
~th ~e volumes ~ 20% ~e~tran (140,000 ~ol. Wt.) ~issol~e~ ~n 0.15 ~ sal~ne. Each wash ha~ the ~mple .. .
cent~ifuge~ for th~rty m~nutes at 3,000 ~pm in ~

- lq - 2 0 4 ~ 0 5 5 , . " ,; ~ . . ~ . -Be~kman centrlfuge. The re~ cell-containing gel :~
contracte~ an~ 10ate~ t9 the top hDlf o~ th~
centrifuge tube while there wa8 ~ubstantially no ' ~`
release o~ red cells. If the cell~ ha~ been free, 5 they would pellet ~t the bottom of the centrifuq~
tu~ h~ s~ows the ~etent~on ~4 the partlculag~
matter, in part~uldr erythrocytes, by the 9~1 of the ~nven~on. O~r 99~ o ~he cell~ wero cont~e~
within the gel, as ~eterm~ne~
10 6pectrophot~metr~cally. Th~ was true ~or re~ cell ., suspension o~ 2.5-12.5 t~me~ the misture ~mount ,u~e~. In a ~im~l~r e~per~men~ with heparin-tre~tea whole blood, the gel was ~ble to absor~ 20 times it~
weight with ~im~lar retention characterist~cs. -~

Similar experiments were carrie~ out i.
replacing the re~ cell suspension with a solution of human hemoglobin ~n normal ~al~ne. Gelation lea~ to complete incorporation o~ the hemoglobin ~olution. ~ ~'`''"'`?''`'''''`'' After standing for two days, the ~el wa~ r~
centrifugally washed ~i~e t~mes at the 3,000 rpm for thirty minutes in the ~ec~man centrifuge ~n a de~tran -~
gradient. Only traces of hemo~lobin were obser~e~
released into the de~tran barrier while substantially all of the rest of the hemoglobin was retaine~ within ~ - :
the gel. By spectrophoto~raphic~ measurement, about 88~ o the hemoglQbin wa~ retaine~

A further experiment wa~ cdrr~ed out u~ng ;~
the ~me ~roce~ure but repl~cin9 the re~ ~ell .~
~uspenslon with a ~uspension of p~uc~lamellar lipi~ ~t ~esicles, ma~e using the mater~al~ ~n~ proce~ures descri~zed in co pendi~ C~adian Patent Applicaticsn Serial -, -~. . . ~ . .

,' ~, .

204~055 ~o.56l,290, with an ~ver3g2 ~ameter o ~bout 0.5 ~. These Yesi~les ha~ an oil-bas~ center with the liposoluble ~e~ ~ye ~Oil Re~ O~ ~ncorporated ~n : :
- the oil ~s ~ marke~. ~elat~on ~n the presence of the 5 vesi~le~ lea~ to eompl~e ~ncorpsrat~on of th~
ves~cles. Over ~wo ~ay3, five cen~riu~al wash~n~
of th~ qel~ showea a gr~u~l r~l~a~ of th~
~ye-containing ~esicles without fr~ct~on~t~n os ~reakao~n of the ~eslcl~ hls ~how~ tbat th~ typ@
0 of gel coul~ be use~ susta~ne~ relea~e ~ehicl~
or th~t ~t can ~ct ~ ~ protecti~e b~rrier to large .
part~cle~. Other paucildmellar l~pl~ ves~cl~s h~vo also been encapsulatea. ~ ~-E~amPle 4.

In thls e~perlment, the same blgh '',',''.,'!' lipl~carbohy~ra~e ratio ~el ~s used ~n E~ample 3 was use~ to ~how the effect~ of i~otonic changes and .
permeab~llty o ~mall particle~. The gel wa~
. manufactured as ~escribed above an~ wa~ hydr~te~ with ~ m~ ~.
20 25 ml of plain water. The 9¢l was then ~oake~
alternately ~n sever~l çhanges o~ 0.5 ml o 1 ~ucrose then water~ ..

The s~fts from the hypertonic to hypotonic me~ium an~ back cau~ed only tr2nsient ch~nge~ in gel ~ i ~s ~ol~me ~t the t~me of the change o~ the medium, in~icat~ng ~ree permea~ ty o~ the gel~ to ~ucro~e. ..
~herefore, it i~ e~pecte~ that the ~el~ woul~ al~o be ;~
permeable to molecule~ of ~pproYirn~tely the s~me ~ze ~s ~ucro~e~nclu~ing many ~rug6. Accor~ngly, the gel~ ~oul~ be u~e~ as a woun~ ban~age which ~llow~

x:

2 ~ ~L 9 pa~age o~ a arug throug~ ~h~ ~1 to wher~ ~t l~
necessary but prot~ct~on 3g~in~t l~r~
partlculste-typ~ matto~ 6uch a~ b~cteri~l cell~. ln contrast, esQo~ure o gel~ ~o a 20~ ~olution o h~gh ;~
5 molecular weigh~ De~tran (1~0,000 Mol. Wt.~ eau~e~
revers~ble 6hrinkln~, ~ugge~t~ng t~at thes~ molecul~
~o not penetr3t~ the gel~ an~ c~us~ o~rnoti~ 108~ 0 water f~om the gel~

Ex~mPle 5 10 , In ~hi~ Esampl~, ~ functional atty a~
undecylenic aci~, ~5 usea ~n place of a ~tanaar~
fatty AC~ in form~ng the gel of the invent~on. Th~s functional fatty aci~ i8 a pot~nt fungi~l~e.
, :, . i,. ,,.,., ,.i "~ ,~
To make thi~ gel, 1~0 g o undecylenic aci~
15 was un~formly blen~e~ with 1.0 g of ..
carbo~ymethylcellulose ana 0~036 9 o~ th~
borate~tabilize~ ~luminum ~cetate comples. The `~
~ample wa~ ~ydrated by mi~ing 25 ~1 of water wlth 0.5 .
g of the misture. Hy~r~t~on w~ ~ompl~te with~n 20 thirty minute~, ~orm~ng ~ sot gal. The gel ~lowly . .
release~ the undecylen~c a~i~ over t~me. A mo~e .~`
rig~d qel can be ~orme~ by us~n~ blen~ of th~
unct~onal fatty ~cia w~th p~lmitic or tearlc ~c~d~

~he ~o~t ~el ~ slightly turb~ pre~a~
e~ly, nd ~tick~ to the ~k~n. Bec~u~e o~ th~4, a ban~ge or wouna coverin~ o the un~ecyle~ic aci~ gel ~oul~ be 3ppli~ to th~ n, ~ro~ ng ~un~ l ~ r~i benef~t~ a~ ~ell a~ prote~t~on ~a~nst part~ul2te bacter~a ~n~ ~n~eet~on. .

' '`,'' "`.' `:

. ~ . . -...

- 17 - 2 ~ ~ ~ V~ 3 ~ n thi~ Esampl~, two ~ffero~t me'csllo-org~nic complea:e~ useul ~ cro~-linl~
agentæ with~ln ~he BCOpl~ O~ the ~nv~nt~on w~r~ m0~0.
5 The f~r~t, a palm~tatQ-~age~ alum~num metallo-org~n~C
GOmple~ (~?X-I.), ~8 maa~ ~ m~inSJ 0.6A g palm~t~
aci~ ~0.25 mmol~ olve~ a 5 lol o~ ~t~anol w~h 1.4 9 ~10 nunol) ~lum~num morloacetn~e ~t~b~ e~ wlth borlc ac~ ln S ml o wat~r. ~n op~leæoeslt Isolut~
10 resulte~, Th~ opalesc:ent ~uspens~on c:an be m~e with carbo:~ymethylc:ellulo~e (C~C~, with or w~thQut : ;~
cellulose ~ber, to prl~vi~e a cross-linkinq agent - . ~ `
impregnate~ ~n the CMC. Th~ æame procedure may be use~ w~th equ~l molar amounts o~ laur~c or ~eari~ :
15 aci~ to form ~im~lar comple~es.
. .~,. .: ;." ,", ~o fo.m ~n benzoate~baseD aluminum .
metallo-~rganic comple~ ~BX-~), a more ~llute ~olution i~ use~. Spe~l~ically, O.Cl g of benzo~c acid (0.50 mmo}) was dissolvea in 7.5 ml of ethanol.
20 The benzoi~ ~ia ~olu~on was ~i~ed with a solution ~ontain~ng 1.4 9 ~10 mmol) ~luminum monoacet~te .
stabilized with boric aci~ ln 7.5 ~1 o water.
Again, ~n op~lescent ~u~pens~on resulte~. ~his cros~-linking agent c~n ~l~o be impregnate~ ~nto or 25 der~v~t~zed with CM~ or cellulo~e f~ber. ::

~. ., .. ~..~ ., In th~s E-~mple, the or~no-~et~ e -cro~sl~n~in~ ag2nt6 orme~ ~n E~mple C w~r~ u~e~ to form the sponge-like ~ater~al o~ the ~nvention. In . ' ' . ' .' ~' '' ~, , ~....

', '`~', ' ~`.

- 18 - 20~0~

the irst ~uch test, o.a 9 0~ c~rbo~ymeth~lcelluloise (CMC), 0.04 9 of palmit~ ~ci~ ~P~?, 0.2 ml of the benzoate-based alumi~num metallo-orqanic cross-linking agent (BX-~ ma~e in E~ampla 6, an~ 50 ml of 0.15 W
5 salSne wer~ b~ende~. ~8 one o~ the two variat~orls of th~ e~periment, 0~6 g of cellulo~e w~ ~lso use~O
, ~, ." ",',', ~5""'~
The mi~ture wa~ hy~rate~ by th~ty ~econ~s o~ ma~net~ irring ~n~ the st~ll liQui~ m xture wa~
transferre~ to 50 ~1 cen~r~uge tubes ~n~ centriugea 10 at 300 X ~ fos thirty minutes. ~t the en~ o~ th~
thirty minute centrifuge per~o~, any free flu~ wa~
collecte~ by filtration throuQh a 150 ~ pore s~ze : : .
nylon mesh. ~iqhly cohes~ve, firm gets form within the thirty minute centrifuqation. .,.

Retention of ligui~ was me~sured at least :.
twenty-four hours ~ter formation. Gel piece aliquots were cut out, weighed, ~n~ place~ in a centrifuge tube: insert, close~ its bottom by perforated ~creen ~upporting D piece o non-woYen -~
20 tea-ba~ paper. After centrifuyat~o~ at 300 X ~ for .
thirty minute~, the am~unt o l~Qui~ release~ from `
the qel was determined grav~metr~cally. TabIe 3 ~hows the results of this testing ~or the material of . ~
the ~n~ent~ on (CMC~PA~BX-L), with or w~thout .`:
25 cell~lo6e. ~he ~ame test was carrle~ out usinq a ~imil~r amount o~ ~anwet*~MlS~0 U.S.~ ~ p~ly~cryl~c super~bsor~er, ~s ~ control. ~11 v~lue~ w~th ~ellulose ars correctea to non-cellulo~ ~cti~tie~
~n thi~ an~ the ~ollow~ E~ample6. ;
*Trade Mark -: - . .-:. . .
''' `''''~''~''.`'.

2 ~ ~ 9 ~

CMC~Palmitate~Ben~sa~e X~ 162 ~ 10 .. `~
~llulo~ 201 ~
5 Polyacryli~ ~uper~bso~bor C0 *
~Ce~lulos~ 70 ~
.... " .
A~ ca~ een ~rom the re~ult~ of ~abl~ 3, .
~he compos,~t~on o~ ~hs l~vention, eithe~ ~ith o~
,without cellulose, clearly:~s ~uper~or to the : ,".. ,.. ,,:!j",~.,',",.,", 10 polyacryli~ superab~orber~ in ~erms of retention of ..
0.15 N saline. ~`
.,,. ~ .,.~ ,....

The i~entic~l esperiment WDS performe~ us~ng .
a compositlon o the ~nvention which had the palmitate-base~ cross-linking agent ~PX-~) in plwe ?:
of the benzoate-ba~e~ cros~-llnking 2gent (~X~
Table ~ shows the result~, of this esperiment, nqain .`~
~ompare~ to the ~uper~bsorber re~ult~
!, ~

i' .; '~,. !, 20 CMC~Palmit~te~Palm~t~ X-lin~ 207 ICellulo~ 205 : . Poly~r~lic ~uper~b~or~er 60 ~ ~Cellulo~e 70 ,," . ~j,, "

- 20 - 2 a ~ 9 ~

In ~his E~ampl~, ~ 20~ whoie ~loo~ colut~on was teste~ fnr absgrpt~on by a compo~ition of th0 ~nY~nt~on made w~th th~ benzoate-base~ crosg~ ing : -sagent (BX-~) of ~sampl~ 6. Th~ compo~tion wa m~e by mising 0.2 g o~ carbo~ymethylcellulo~o, 0.04 9 o~
palm~t~ , 50 ml o~20~ whol~ bloo~ .15 ~
sallne ~n~ 1 ml of the crg~ nkin~ ~entO hg~n, tbe mater~al w~ ~este~ ~th An~ withou~ 0.6 ~ ~ ; W -c~llulo~2. After hy~r~tion, the ~tlll-ligu~ ml~
~ivide~ ~nto to ~wo 25 ml port~on~, these were -~ - r.
tran~ferre~ to 50 ml centri~uge tu~e~, and ~elation ` .
was allowe~ to proceed under ~entr~fugat~on at 300 X
g ~aver2ge 4800 lbs.~in2) ~or thirty m~nute3. At the 15 end of the centriugation, any free 1u~d was collecte~ by filtr~t~on though 150 ~ pore ~i~e nylon .~
mesh. Ta~le 5 ~hows the result~ o~ th~ te~t. The . `-:.. `
value without the cellulose ~s equ~valent to ~n .:
absorption of 3~ ml of whole blooa, while the .,~
20 cellulose aaded value i5 even higher.

' ~ :'.' '.
CMC~Palmit~te~enzoate X-l~nk 175 ~ 1 ~Cellulo~ 223 ~
. ; - ~
25 E~amPle 9.

In thlE E~ample, un~ecylen~c acl~
~ncorporated ~nto ~ gel ~ontain~ng the benzo~te-ba~e~

. ,-; ~.:
.~ .

- 21 2 ~ ll 9 ~ ~ 3 ~

æluminu~ metallo-org~n~ c~mple~ of E~amplQ 6.
~ppros~mately 0.5 ml o the cross-link~ng compl~ was combine~ with 0.5 ml c~rboxymethylcellulo~e an~ 0.5 g of undecy~enic ~ci~. The mater~al was ~ydrate~ w~th S 70 ~1 wlth ~elon~ze~ w~ter. A high cohe~ve ~ut ~:~
mobile gel forme~ with~n thir~y m~nute~. There W8~
no relea~e of ~at~r o~er a perio~ of mc,~ th~n thr@~ ~ -hour~ an~ ther~ wa~ no separat~on o ree un~e~ylen~
~c~

lo The 6~me ~pproach ~oul~ b~ u~ea to .
~corporate a ~ar~e~y o~ carboYyl termin~l ~unct~onal molecules such as prostaglana~ns, prsstacycl~ns, . ;~
thrombosanes ~n~ thei~ precursors such as arach~onic .
acid. In addition, certain antibiotics ~uch as 15 oYytetracyline can be use~ in place of some or all oE ... ~.
the cross-linking agents.
.: . ,,. :-.. ..
Other materials which coul~ be use~ to replace part the fatty ~ci~ inclu~e carbosyl~ acids, carbo~ylic pepti~es, nonionic surfactants, an~
20 ~teroifls such as cholesterol or hydrocortisone. :~ ~
Selection o~ proper ~ci~ic const~tuents can mod1y ~.:;~ ` .
gel propert~es. ~he Eiteroi~ can ~e present ~n the system up to at le~st 10~ o the atty ac~ w~thout d~turb~ng the gel. ~herefore, these gels coula be 25 u~ed a~ a ~el~ry 5y8tem5 ~or a va~ety o molecul~
u~h as i~tero~
'"~` ''' '" ' In a~it~on, ~ hown pre~iously, lipi~
vesicles can be lncorp~rate~ ~nto the gels a~
p~rt~cul~e ~att~. 8~nc~ these l~p~ veslcl~ c~n 30 ~l~o be ~es~ne~ to carry ~ v~r~ety of materl~li6i . . ~. .

: ~

- 22 - 2 ~ 4 9 ~

wh~ch ~oul~ not othe~w~se bQ c~rr~ n the woun~ patc:h c~ other ~:overlng mad6~ o~ th0 g~l w~th ..
the ~res~cles diispersed. there~n coul~ be used to ~pply ~rugs on a t~me-releasea basi~i to a i~;electel~ ~1t~. -Those 6k~ d ~n ~che art wl~l bo ~ to ~eterm~ne other mod~f~ca~cio~i of t~e ~a~empla~y proceâures an~ mater~al~. ~u~h ot~e~ mo~~t~on~
~re w~t~ tbe scope of the o~10w~n~ cl~m~

Wh~t ~s ~ me~

.`.,~ . ,,' ~' ,.
,~ .. ., ~ .

., ~, :: ,'',' ,'' ~: .

:

~ ~' -"`. .''

Claims (33)

1. A composition of matter which acts as a synthetic sponge when allowed to hydrate comprising a non-hydrated mixture of:

a carboxylic acid with a substantial hydrophobic region; and a branched complex carbohydrate; and a separate cross-linking agent;

whereby said composition can be hydrated and cross-linked simultaneously in the presence of a hydrating solution.

2. The composition of claim 1 wherein said carboxylic acid comprises a fatty acid.

3. The composition of claim 2 wherein said fatty acid is selected from the group consisting of lauric acid, palmitic acid, stearic acid, oleic acid, and mixtures thereof.

4. The composition of claim 1 wherein said carboxylic acid comprises a functional fatty acid.

The composition of claim 4 wherein said functional fatty acid is selected from the group consisting of arachidonic acid, prostaglandins, prostacyclins and thromboxanes.

6. The composition of claim 1 wherein said branched complex carbohydrate is selected from the group consisting of carboxymethylcellulose and chitosan.

7. The composition of claim 1 further comprising a linear carbohydrate.

8. The composition of claim 1 wherein said cross-linking agent is a metallo-organic cross-linking agent which includes a multivalent metal ion.

9. The composition of claim 8 wherein said multivalent metal ion is selected from the group consisting of aluminum ions, chromium ions, and other metal ions with a valence greater than 2.

10. The composition of claim 8 wherein said metallo-organic cross-linking agent also acts as said cross-linking agent.

11. The composition of claim 1 wherein said cross-linking agent is an organic cross-linking agent contains a metal having an effective valence of at least 3.

12. The composition of claim 2 wherein said fatty acid is selected from the group consisting of lauric, palmitic, oleic, and stearic acids, said branched complex carbohydrate is selected from the group consisting of carboxymethylcellulose, chitosan, and mixtures thereof, and said cross-linking agent is selected from the group consisting of aluminum acetate, aluminum borate, benzoate-based aluminum metallo-organic complex, palmitate-based aluminum metallo-organic complex, and mixtures thereof.

13. A method of absorbing aqueous or saline solution using a biodegradable synthetic sponge composition comprising the steps of:

providing said synthetic sponge composition in a substantially unhydrated form, said synthetic sponge composition containing a carboxylic acid with a substantial hydrophobic region, a separate cross-linking agent, and a branched complex carbohydrate;

contacting said solution to be absorbed with said synthetic sponge composition;

whereby said synthetic sponge composition hydrates to absorb said solution and cross-links into a gel substantially simultaneously.

14. The method of claim 13 wherein said carboxylic acid comprises a fatty acid.

15. The method of claim 14 wherein said fatty acid is selected from the group consisting of lauric, palmitic, and stearic acids, and mixtures thereof.

16. The method of claim 13 wherein said branched complex carbohydrate is selected from the group consisting of carboxymethylcellulose and chitosan.

17. The method of claim 13. wherein said composition further comprises a linear carbohydrate.

18. The method of claim 13 wherein said cross linking agent is selected from a group consisting of metallo-organic complexes containing aluminum ions, chromium ions, and other metal ions with a valence of at least 3.

19. The method of claim 13 wherein said carboxylic acid and said cross-linking agent comprise the same molecule.

20.. The method of entrapping particles in a gel comprising the steps of:

providing a synthetic sponge composition in a substantially unhydrated form, said synthetic sponge composition containing a carboxylic acid with a substantial hydrophobic region, a branched complex carbohydrate and a separate cross-linking agent;

contacting a solution containing said particles to be entrapped with said synthetic sponge composition;

whereby said gel is formed by the combined hydration and cross-linking of said synthetic sponge composition, thereby entrapping the particles.

21. The method of claim 20 wherein said carboxylic acid comprises a fatty acid.

22. The method of claim 20 wherein said particles to be entrapped are selected from the group consisting of cells, bacteria, and macromolecules.

23. The method of claim 21 wherein said fatty acid is selected from the group consisting of lauric, palmitic, and stearic acids, and mixtures thereof.

24. The method of claim 20 wherein said branched complex carbohydrate is selected from the group consisting of carboxymethylcellulose and chitosan.

25. The method of claim 20 wherein said composition further comprises a linear carbohydrate.

26. The method of claim 20 wherein said cross-linking agent is selected from the group consisting of metallo-organic complexes containing aluminum ions, chromium ions, and other metal ions with a valence of at least 3.

27. The method of claim 20 wherein said entrapment acts as a barrier to the passage of said entrapped particles.

28. The method of claim 20 wherein said entrapped particles are released over time from said gel, whereby said gel acts as a sustained release vehicle.

29. The method of claim 20 wherein said carboxylic acid and said cross-linking agent comprise the same molecule.

30. A composition of matter which acts a synthetic sponge when allowed to hydrate and releases undecylenic acid upon degradation comprising a non-hydrated mixture of:
undecylenic acid; and carboxymethylcellulose;
whereby said composition can be hydrated and cross-linked simultaneously in the presence of a hydrating solution.

31. The composition of claim 1 wherein said carboxylic acid comprises benzoic acid.

32. The method of claim 13 wherein said carboxylic acid comprises benzoic acid.

33. The method of claim 20 wherein said carboxylic acid comprises benzoic acid.