CA1051776A - Poloxamer-iodine gel - Google Patents
Poloxamer-iodine gelInfo
- Publication number
- CA1051776A CA1051776A CA232,731A CA232731A CA1051776A CA 1051776 A CA1051776 A CA 1051776A CA 232731 A CA232731 A CA 232731A CA 1051776 A CA1051776 A CA 1051776A
- Authority
- CA
- Canada
- Prior art keywords
- iodine
- gel
- poloxamer
- weight
- amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
- A01N59/12—Iodine, e.g. iodophors; Compounds thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
- A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
Abstract
POLOXAMER-IODINE GEL
Abstract of the Disclosure A poloxamer-iodine gel composition adapted for use as a topical germicide is provided by combining with an aqueous iodide-iodine solution, preferably containing a compatible buffering agent, a polyoxyethylene-polyoxypropylene block polymer in which the polyoxypropylene hydrophobic block has a molecular weight of about 3500 to 4500, and the molecular weight of the polymer is about 11,000-12,000, in an amount to comprise about 20 to 30% by weight of the gel composition.
The gel composition may contain 0.25 to 2% of elemental iodine, and 0.25 to 2% of iodide (I-), with the I-:I2 ratio being in excess of 0.25:1;
and a compatible buffering agent, such as a citrate, preferably comprising about 0.2 to 1.0%, of the gel composition.
S P E C I F I C A T I O N
Abstract of the Disclosure A poloxamer-iodine gel composition adapted for use as a topical germicide is provided by combining with an aqueous iodide-iodine solution, preferably containing a compatible buffering agent, a polyoxyethylene-polyoxypropylene block polymer in which the polyoxypropylene hydrophobic block has a molecular weight of about 3500 to 4500, and the molecular weight of the polymer is about 11,000-12,000, in an amount to comprise about 20 to 30% by weight of the gel composition.
The gel composition may contain 0.25 to 2% of elemental iodine, and 0.25 to 2% of iodide (I-), with the I-:I2 ratio being in excess of 0.25:1;
and a compatible buffering agent, such as a citrate, preferably comprising about 0.2 to 1.0%, of the gel composition.
S P E C I F I C A T I O N
Description
7~i~
'I`hi s :invenl,lo~l relates to lodine cont,aining polox~lmer-gel composltlc)rls ur-lique1y adapted for use as topiccll germ-icides, by virtue Or their ar-omalous liquef`ying when chilled arld gelling when warmed. Ihe gels are prepared by co~bining with an aqueous iodide-iodine solutiorl, preferably contain-ing a comp~tible buff`ering agen-t, a polyoxyet;hylene-polyoxy-propylene block polymer in which the polyoxypropylene hydro-phobic block has a molecular weight of about 3500 to ~500, and the molecular weight of -the polymer is abou-t 11,000-12,000, in an amount to comprise about 20 to 30~ by weight of the gel composition.
The gel composition may contain 0.25 to 2% of` elemental iodine, and 0.25 -to 2% of iodide (I ), wi-th the I :I2 ratio being in excess o~ 0.25:1; and a compa-tible bu~f`ering agent such as sodium citrate, preferably comprising about 0.2 -to 1.0% of said composition.
_ ckground of the Invention It has long been known that polyoxyethylene-polyoxy-propylene block polymers of the general formula H0(C2H40)X (C3H6o)y (C2H4 )x' where y equals at leas-t 15 and (C2H40)x+x, equals 20 to 90%
of the total weigh-t of -the compound, show excellent iodine complexing proper-ties, as disclosed in U.S. Patent 2,759,869 assigned to app]icant's assignee. In such pa-tent, however the emphasis was on formulations in which the molecular weigh-t of the polymers was relatively low, i.e., generally within range of about 2500 to 8000. Polymers of -the general -type are available commercially, being distributed under the trademark "Pluronic".
'I`hi s :invenl,lo~l relates to lodine cont,aining polox~lmer-gel composltlc)rls ur-lique1y adapted for use as topiccll germ-icides, by virtue Or their ar-omalous liquef`ying when chilled arld gelling when warmed. Ihe gels are prepared by co~bining with an aqueous iodide-iodine solutiorl, preferably contain-ing a comp~tible buff`ering agen-t, a polyoxyet;hylene-polyoxy-propylene block polymer in which the polyoxypropylene hydro-phobic block has a molecular weight of about 3500 to ~500, and the molecular weight of -the polymer is abou-t 11,000-12,000, in an amount to comprise about 20 to 30~ by weight of the gel composition.
The gel composition may contain 0.25 to 2% of` elemental iodine, and 0.25 -to 2% of iodide (I ), wi-th the I :I2 ratio being in excess o~ 0.25:1; and a compa-tible bu~f`ering agent such as sodium citrate, preferably comprising about 0.2 -to 1.0% of said composition.
_ ckground of the Invention It has long been known that polyoxyethylene-polyoxy-propylene block polymers of the general formula H0(C2H40)X (C3H6o)y (C2H4 )x' where y equals at leas-t 15 and (C2H40)x+x, equals 20 to 90%
of the total weigh-t of -the compound, show excellent iodine complexing proper-ties, as disclosed in U.S. Patent 2,759,869 assigned to app]icant's assignee. In such pa-tent, however the emphasis was on formulations in which the molecular weigh-t of the polymers was relatively low, i.e., generally within range of about 2500 to 8000. Polymers of -the general -type are available commercially, being distributed under the trademark "Pluronic".
- 2 I t has al~o ~)een kr~<>wn ~`or s(>rne time, as dis(l~ d ir .S. I~ltent 3,028,29'~, assigrled to t;he app]iclntls ~Issigrlee~
thclt -the complexil-lg o~ .iodirle in aqueolls sollltion by vari-OUS surfa(tarlts, e.g. polymeri(- materi~l1 inc1ud-ing "~'luro-ni(sll, is grea-tly enhanced by inchldirlg in the composition a source of iodide ion (I ) such as to provide arl I :I2 ratio in excess Or 0.25:1. Such en}-l~nced iodine complex-ing is readily measured in terms of di.stribution coeffi-cient, D.C., which depends on the equilibrium oi iodine between an aqueous solution containing a complexing agent and a norl-miscible solvent, heptane.
More recently in ~.S. Patent 3,740,421 assigned to BASF
Wyandotte Corporation, it has been disclosed -that polyoxy-ethylene-polyoxypropylene block polymers of -the general formula above mentioned, and having average molecular weights in the range of about 4600 to 20,000 can bind water as gel composi-tions useful in -the formulation of topically-applicable cosme-tic and pharmaceutical compositions. The amount of water bound in these gels varies with the molec-- ular weight of the block polymer, and the proportion of the polyoxypropylene (hydrophobic) and polyoxye-thylene (hydrophilic)blocks therein. In general -the a.mount of water will be in the range of lO~o to 60 or 70% of the gel, although when the block polymer is of ver-y high molecular weight, 16,000 to 20,000 -the amow~-t of bound water may be as h:igh as about 80% of the gel composition. While the patent lists a number of cosme-tic and pharmaceu-tical com-ponents as compa-tible additions to -the gels, there is a noticeable absence of any men-tioned prior art showing re-lated block polymers of lower molecular weiglrt to be ex-cellent iodine complexing agents.
~ ' .
'7~
I ~ ha~i r~oW ~ er~ cli sc c)vc~r ~ rl ~Ic~cc)rdanc ( Wi 1,1) t,~le pr c sel~t inver-~tion, ~hat by prc)pcr selection oI` b]ocl< polymer~;
oL` thl~ t,ype bro(ldly disclosed in U.S. I'aterlt 3,7~0,42] it is possible to prcp.lre 1odine containing gel composit,i,ons which are extremel,y stab1e and uniquely suited for use as olntmen-ts f`or topical germicidal purposes. Many oL the gel systems disclosed in said patent are unsuited for this purpose because of the limi,ted amount of wa-ter which is bound, the inappropria-te consistency of the gel or -the dif-ficulty in formulation due -to viscosity ol` the system in the low temperature, non-gelled state.
The block polymers useful for our purpose are those of intermediate molecular weight, about ll,000 to 12,000 in which the polyoxypropylene hydrophobic has an average molecular weigh-t of about 3500-4500 and the e-thylene oxide blocks comprise about 60 to 80% of the weight of the poly-mers. A block polymer fit-ting this description is commer-cially available as "Pluronic F-l27".
Satisfactory iodine containing gels can be prepared us~
ing aslittle as 20 to 30 percent by weight of "Pluronic F-127" wi-th 25% b~ing the preferred amoun-t. Ihis means tha-t the gel is a predominantly aqueous system in which the iodine, al-though strongly complexed by -the block polymer, is available in the aqueous phase -to exer-t i-ts germicidal action much as is the case with the known liquid "Pluronic"
-iodine compositions.
Furthermore, the "Pluronic F-127" a-t 25% by weigh-t con-centration provides an ideal combination of fluid and gel properties wi-th very low viscosity a-t reduced formulating temperatures and a form retaining but easily spreadable consis-tency at room -tempera-ture.
. a~ _ :~051.77~:i A~ ointment~ for variouq topleal applic~t~on3D the new gel compositLon will cont~ln ~bout OD25 to 2% by weigh~ of eleme~tal lod~nel and the iodine ¦comple~ing by the blook polymer i9 preferably enhanced by including in the com-¦position a water soluble iod~de ln an amount to proYide about 0025 to 2% by ¦weight of iodide ion ~I), wlth the amo~nt of iodide ln a particul~r composl~
¦tion belng such 85 to assure ~n I-:I2 ratio in exce~s of 0.25:1.
¦ As the new gel ~ompositions sre ~rimarlly intended for application to ¦the skln ~t is preferable to include a small amount of compatible buffering lagent to maintain an essentially ne~tral pH during periods of extended stora~e ¦by rounteracting the acidifylng effect of posslble form~tion of acid dur~ng ¦storage. While various buffering agents can be employed we prefer ~o use .
¦sodium citrate in ~he amount of about 002 to 1.07., ~nd suitably about 0,6% by ¦w~lght of the gel composition.
¦ In preparing the new gel composition it is preferable to first combine ¦the iodine~ iodlde~ and buffer lf present, with ~bout half the to$al amount of ¦block polymer and the bulk o~ the total waterO After this mlxing has been completed the mlxture is cooled to about 40~50F and maintalned at thls temperature durln~ the final mixing with the balance o the blvck polymer This fin~l mixlng establishes the critioal gel-forming proportion of the block polymer so that the composition gels as the temperature is allowed to rlse to soom ~emperature. Care sho~ld be ~aken to hold the temperature irl the reduced 40-50F range until mixing ~s complete.aq an elevatlon, even to 60F, can so ¦ increase the vi.scosity a~ ~o interfere with proper mixing.
The resulting gel f 5 a re~ersible gel capable of belng repeatedly l~quef~ed by co~llng ~nd retur~ed to gel form by heati~ s actcr 3i~nlflcant ~ 77~
ln b~lk h~ndl~ng~ p3ckaging an~ use~ The gel i9 ~table ~t temperatures sub-_ st~tislly ~bove ro~m te~perature ~l~d the c~p~sle~n ~3 not ~d~ersely ~ffected by free~lngc The ne~ gel compo~i~ions of the presen~ ention ~nd their method of preparati~n will be ~ore fully understood fro~ a consideration ~f the followl~
e~mplesl but it is to be under~ool~ that these e~a~ples are ~ven b~ way of illustration and not of limitatlon~
Example An iodine gel Dint~nent is prepared conta~ning, by wei~ht . "Pluronic F 127"2500~.
Iodine 1.25 Svdium Iodide (U.S~P.) 0.60 cieric Acid ~U.S~PI~ 0.35 Sodium Hydroxide (4$~Be~ 0~43 Wa ter 7 2 . 37 . 1~OJ 0~.
The s~d~um iodide ls first dîssolved ln approxim~tely an equivalent amount of water and the~ the elemental iodine is added and mixed until homo-~eneous. In a separate vessel the citric acid is dissolved in the bulk of the water and to this solution ls added approximately half the "Pluronic F^127"
with stirring until completely dissolved. To this is added the iodine concentrate above mentioned and thP ~ixture is stirred until homoge~eous, Then the ~odiam hydroxide ~46~Be) ls added and ~horoughly blended.
~ 7~
¦ At thi3 point the batch :15 cooled to 40~50F, the ~lanee of the ¦"Pluron$o P-127~' and ~-ater ~re added~ and the mi~ture stlrred ur~til ~11 the ¦"Pl~r~nic F 127" has dl3~01ve~ thereby complet~ the formulatlo~ The product, poured intD suitable con~alners5 and all~wed to rise to room temper^
a~ureD ~et~ to 2 firm "rlng1ng" gelO The gel has a form retaining conJis~ency penmlttin~ a container to be ln~erted and even shaken without any displaceme~t, yet quantl~ies of gel can e~sily be removed by the flngers ~r implement, and spread t~ a film ~f any deslred ~hickne-ss.
Testlng of this product for tltratable iodlne and pH stzbllity gives the following resultsO . .
Available Iodi~e I ~ ~
Initial 1.14 6~50 Overnight at 50C 1~09 5.90 1 week at 50C 1~02 S~35 2 weeks* a~ 50C 0,95 5.25 ~equates to about ~o-years at ~oom ~empera~ureO
. The vlscosity chara~teristios of ~he gel are as foll~ws.
Tem~erature V1scosity ~ c~
10C 350 ~llquid) 15C 460 ~llquld) 18.5C ' 1,240 (liquid) 20C ~ery viscous (paste3 2305C 800,000 ~el3 26C 970~000 (gel) ..~..
1 ~5~7~ l l Th~,d1~tribut1O~ ~oe~f1c1en~ ~.C~) or ~hi~ ~el at-15C (to fl~ldize ¦
¦the ~mp~sitlon) i~ ~ppr~ ately 600, whlch i.~ fln indic~Lion of ~e~y effectiYe ¦l~dine eomplexin~ by the blGck po1yaler~
¦ Example II
¦ ~ol1cwiDg ~h~ pr~cedure described tn E~ample I ~with the .sod1um ¦citrate bein~ formed in sltu)~ se~er~l~el compositions were prepared containing ¦d~fferi~g a~ounts of the block polymer and observed for physiea1 character1s ¦tics at 10C and 22C w1th results as 1ndicated in t~e fol1Owing t~b~la~ionO
~ sition I ~
I ~e~ 1 2 ~ 4 5 6 ~ _ ~, ¦Pluronic F-127 15.00% 18.007.2O~00/D~5~0~ 25~0070 30~00L
¦~lemental Iod~ne1.25% 1025% 1~10701~25% 1025%1~25%
¦W~I 0.607~ 0~6~k 0~6~7000607o 0063Z0960%
Na3Citraee (anhydrous~0.137O Do23% none 0~60% 0~20% 0~40%
Water to 10~L~/W 100%W~W 100% W~W 100% W~ 100%~/W 10Q%W/~
¦ Observation I ~
Physica1 state @ 10C 1iquid liquidliqu1d llquid very . liquld Physlcal state @ 22C1iq~id liquid Y1iiSqCOUdS gel gel gel On the basis of gelling tende.lcy i~ will be appsrent that compositions 1 ~nd 2 in ~he above tabulation are en~irely unsatiafactory, compositiorls 4 and 5 are satisfa~eory9 and composik1ons 3 ~nd S ~re borderline9 Composi~ion 3 which provides a v~scous liquid r~ther than n gel ~e 22DG, cou1d atill pr~vlde 8 desirnb1e praduct for top~c~l app1ieatio~l. Composition 6~ on-the other hand~
. ' o8, ~L~5~'77~i ~
prov~de~ an excellent gel ~t 22C bl.t i5 ~ery dlffic~lt t~ prepS~re due to the high ~lSCD9~ty I~ the 1~ te~pe~ture, llquld st~te~
~a~ed on these result~ the optlm~m rdnge in the ~:oune of "PltJronlc F~1?7" to gi~ good gel without formulating difflel3~tie~ is con-sidered to be about ~2% to 2~7. by weight of the gel composltion~ .
Whlle compositlons 4 and 5 both provlde excellent gels, compo.sitio~ 5 ¦ shows ~ pH drop to about pH 4 on ~ ~eeks stvra~e at 50C. Thus at the parv .
tlcular iodlne and iodlde leYels ~t is preferable to employ the slightly higher b~ffer concentration as i~ compositio~ 4 Example IXI
Followin~ the procedure described ln E~a~ple I~ a number of iodine ~gels are prep~red having differi~g iodI~e and iodide c~ntent, as follo~s~
Composition I Com~onent 1 Z 3 I . _ __ __ __ "Pluronic F- 121~' 25 o 00% 25~00~ 25~00%
~o~ 00~57~ 1~30% 2~07o Sodiu~ Iodide 0030Z0 2~5% 2.35%
Sodium Citratc (anhydrous) 0 40~ 0 8C7o l~OO
Water to10070 lOQZ 100/.
These oompositions, which are typical of the variation in iodine con~
tent whlch may be deslred for Ysri~us tGplcal applic3t.ions~ all provide excell~nt ~el~ with ~e l~dine stron~ly complexedA and exhibl~ing good pll ~ab~l~ty on storal~e~
Va~lous changes ~nd modific~ltions in the poloxamer-iodlne gel composl-tls~ns hereln disclosQd may occur to those skllled in the ~rt~ and to the extent that such changes and modific~tions are embrflced by the ~pp~nded cla~m~ it is to be unde~stood that th2y constitute pa~t of the present invent~on.
ll -10-
thclt -the complexil-lg o~ .iodirle in aqueolls sollltion by vari-OUS surfa(tarlts, e.g. polymeri(- materi~l1 inc1ud-ing "~'luro-ni(sll, is grea-tly enhanced by inchldirlg in the composition a source of iodide ion (I ) such as to provide arl I :I2 ratio in excess Or 0.25:1. Such en}-l~nced iodine complex-ing is readily measured in terms of di.stribution coeffi-cient, D.C., which depends on the equilibrium oi iodine between an aqueous solution containing a complexing agent and a norl-miscible solvent, heptane.
More recently in ~.S. Patent 3,740,421 assigned to BASF
Wyandotte Corporation, it has been disclosed -that polyoxy-ethylene-polyoxypropylene block polymers of -the general formula above mentioned, and having average molecular weights in the range of about 4600 to 20,000 can bind water as gel composi-tions useful in -the formulation of topically-applicable cosme-tic and pharmaceutical compositions. The amount of water bound in these gels varies with the molec-- ular weight of the block polymer, and the proportion of the polyoxypropylene (hydrophobic) and polyoxye-thylene (hydrophilic)blocks therein. In general -the a.mount of water will be in the range of lO~o to 60 or 70% of the gel, although when the block polymer is of ver-y high molecular weight, 16,000 to 20,000 -the amow~-t of bound water may be as h:igh as about 80% of the gel composition. While the patent lists a number of cosme-tic and pharmaceu-tical com-ponents as compa-tible additions to -the gels, there is a noticeable absence of any men-tioned prior art showing re-lated block polymers of lower molecular weiglrt to be ex-cellent iodine complexing agents.
~ ' .
'7~
I ~ ha~i r~oW ~ er~ cli sc c)vc~r ~ rl ~Ic~cc)rdanc ( Wi 1,1) t,~le pr c sel~t inver-~tion, ~hat by prc)pcr selection oI` b]ocl< polymer~;
oL` thl~ t,ype bro(ldly disclosed in U.S. I'aterlt 3,7~0,42] it is possible to prcp.lre 1odine containing gel composit,i,ons which are extremel,y stab1e and uniquely suited for use as olntmen-ts f`or topical germicidal purposes. Many oL the gel systems disclosed in said patent are unsuited for this purpose because of the limi,ted amount of wa-ter which is bound, the inappropria-te consistency of the gel or -the dif-ficulty in formulation due -to viscosity ol` the system in the low temperature, non-gelled state.
The block polymers useful for our purpose are those of intermediate molecular weight, about ll,000 to 12,000 in which the polyoxypropylene hydrophobic has an average molecular weigh-t of about 3500-4500 and the e-thylene oxide blocks comprise about 60 to 80% of the weight of the poly-mers. A block polymer fit-ting this description is commer-cially available as "Pluronic F-l27".
Satisfactory iodine containing gels can be prepared us~
ing aslittle as 20 to 30 percent by weight of "Pluronic F-127" wi-th 25% b~ing the preferred amoun-t. Ihis means tha-t the gel is a predominantly aqueous system in which the iodine, al-though strongly complexed by -the block polymer, is available in the aqueous phase -to exer-t i-ts germicidal action much as is the case with the known liquid "Pluronic"
-iodine compositions.
Furthermore, the "Pluronic F-127" a-t 25% by weigh-t con-centration provides an ideal combination of fluid and gel properties wi-th very low viscosity a-t reduced formulating temperatures and a form retaining but easily spreadable consis-tency at room -tempera-ture.
. a~ _ :~051.77~:i A~ ointment~ for variouq topleal applic~t~on3D the new gel compositLon will cont~ln ~bout OD25 to 2% by weigh~ of eleme~tal lod~nel and the iodine ¦comple~ing by the blook polymer i9 preferably enhanced by including in the com-¦position a water soluble iod~de ln an amount to proYide about 0025 to 2% by ¦weight of iodide ion ~I), wlth the amo~nt of iodide ln a particul~r composl~
¦tion belng such 85 to assure ~n I-:I2 ratio in exce~s of 0.25:1.
¦ As the new gel ~ompositions sre ~rimarlly intended for application to ¦the skln ~t is preferable to include a small amount of compatible buffering lagent to maintain an essentially ne~tral pH during periods of extended stora~e ¦by rounteracting the acidifylng effect of posslble form~tion of acid dur~ng ¦storage. While various buffering agents can be employed we prefer ~o use .
¦sodium citrate in ~he amount of about 002 to 1.07., ~nd suitably about 0,6% by ¦w~lght of the gel composition.
¦ In preparing the new gel composition it is preferable to first combine ¦the iodine~ iodlde~ and buffer lf present, with ~bout half the to$al amount of ¦block polymer and the bulk o~ the total waterO After this mlxing has been completed the mlxture is cooled to about 40~50F and maintalned at thls temperature durln~ the final mixing with the balance o the blvck polymer This fin~l mixlng establishes the critioal gel-forming proportion of the block polymer so that the composition gels as the temperature is allowed to rlse to soom ~emperature. Care sho~ld be ~aken to hold the temperature irl the reduced 40-50F range until mixing ~s complete.aq an elevatlon, even to 60F, can so ¦ increase the vi.scosity a~ ~o interfere with proper mixing.
The resulting gel f 5 a re~ersible gel capable of belng repeatedly l~quef~ed by co~llng ~nd retur~ed to gel form by heati~ s actcr 3i~nlflcant ~ 77~
ln b~lk h~ndl~ng~ p3ckaging an~ use~ The gel i9 ~table ~t temperatures sub-_ st~tislly ~bove ro~m te~perature ~l~d the c~p~sle~n ~3 not ~d~ersely ~ffected by free~lngc The ne~ gel compo~i~ions of the presen~ ention ~nd their method of preparati~n will be ~ore fully understood fro~ a consideration ~f the followl~
e~mplesl but it is to be under~ool~ that these e~a~ples are ~ven b~ way of illustration and not of limitatlon~
Example An iodine gel Dint~nent is prepared conta~ning, by wei~ht . "Pluronic F 127"2500~.
Iodine 1.25 Svdium Iodide (U.S~P.) 0.60 cieric Acid ~U.S~PI~ 0.35 Sodium Hydroxide (4$~Be~ 0~43 Wa ter 7 2 . 37 . 1~OJ 0~.
The s~d~um iodide ls first dîssolved ln approxim~tely an equivalent amount of water and the~ the elemental iodine is added and mixed until homo-~eneous. In a separate vessel the citric acid is dissolved in the bulk of the water and to this solution ls added approximately half the "Pluronic F^127"
with stirring until completely dissolved. To this is added the iodine concentrate above mentioned and thP ~ixture is stirred until homoge~eous, Then the ~odiam hydroxide ~46~Be) ls added and ~horoughly blended.
~ 7~
¦ At thi3 point the batch :15 cooled to 40~50F, the ~lanee of the ¦"Pluron$o P-127~' and ~-ater ~re added~ and the mi~ture stlrred ur~til ~11 the ¦"Pl~r~nic F 127" has dl3~01ve~ thereby complet~ the formulatlo~ The product, poured intD suitable con~alners5 and all~wed to rise to room temper^
a~ureD ~et~ to 2 firm "rlng1ng" gelO The gel has a form retaining conJis~ency penmlttin~ a container to be ln~erted and even shaken without any displaceme~t, yet quantl~ies of gel can e~sily be removed by the flngers ~r implement, and spread t~ a film ~f any deslred ~hickne-ss.
Testlng of this product for tltratable iodlne and pH stzbllity gives the following resultsO . .
Available Iodi~e I ~ ~
Initial 1.14 6~50 Overnight at 50C 1~09 5.90 1 week at 50C 1~02 S~35 2 weeks* a~ 50C 0,95 5.25 ~equates to about ~o-years at ~oom ~empera~ureO
. The vlscosity chara~teristios of ~he gel are as foll~ws.
Tem~erature V1scosity ~ c~
10C 350 ~llquid) 15C 460 ~llquld) 18.5C ' 1,240 (liquid) 20C ~ery viscous (paste3 2305C 800,000 ~el3 26C 970~000 (gel) ..~..
1 ~5~7~ l l Th~,d1~tribut1O~ ~oe~f1c1en~ ~.C~) or ~hi~ ~el at-15C (to fl~ldize ¦
¦the ~mp~sitlon) i~ ~ppr~ ately 600, whlch i.~ fln indic~Lion of ~e~y effectiYe ¦l~dine eomplexin~ by the blGck po1yaler~
¦ Example II
¦ ~ol1cwiDg ~h~ pr~cedure described tn E~ample I ~with the .sod1um ¦citrate bein~ formed in sltu)~ se~er~l~el compositions were prepared containing ¦d~fferi~g a~ounts of the block polymer and observed for physiea1 character1s ¦tics at 10C and 22C w1th results as 1ndicated in t~e fol1Owing t~b~la~ionO
~ sition I ~
I ~e~ 1 2 ~ 4 5 6 ~ _ ~, ¦Pluronic F-127 15.00% 18.007.2O~00/D~5~0~ 25~0070 30~00L
¦~lemental Iod~ne1.25% 1025% 1~10701~25% 1025%1~25%
¦W~I 0.607~ 0~6~k 0~6~7000607o 0063Z0960%
Na3Citraee (anhydrous~0.137O Do23% none 0~60% 0~20% 0~40%
Water to 10~L~/W 100%W~W 100% W~W 100% W~ 100%~/W 10Q%W/~
¦ Observation I ~
Physica1 state @ 10C 1iquid liquidliqu1d llquid very . liquld Physlcal state @ 22C1iq~id liquid Y1iiSqCOUdS gel gel gel On the basis of gelling tende.lcy i~ will be appsrent that compositions 1 ~nd 2 in ~he above tabulation are en~irely unsatiafactory, compositiorls 4 and 5 are satisfa~eory9 and composik1ons 3 ~nd S ~re borderline9 Composi~ion 3 which provides a v~scous liquid r~ther than n gel ~e 22DG, cou1d atill pr~vlde 8 desirnb1e praduct for top~c~l app1ieatio~l. Composition 6~ on-the other hand~
. ' o8, ~L~5~'77~i ~
prov~de~ an excellent gel ~t 22C bl.t i5 ~ery dlffic~lt t~ prepS~re due to the high ~lSCD9~ty I~ the 1~ te~pe~ture, llquld st~te~
~a~ed on these result~ the optlm~m rdnge in the ~:oune of "PltJronlc F~1?7" to gi~ good gel without formulating difflel3~tie~ is con-sidered to be about ~2% to 2~7. by weight of the gel composltion~ .
Whlle compositlons 4 and 5 both provlde excellent gels, compo.sitio~ 5 ¦ shows ~ pH drop to about pH 4 on ~ ~eeks stvra~e at 50C. Thus at the parv .
tlcular iodlne and iodlde leYels ~t is preferable to employ the slightly higher b~ffer concentration as i~ compositio~ 4 Example IXI
Followin~ the procedure described ln E~a~ple I~ a number of iodine ~gels are prep~red having differi~g iodI~e and iodide c~ntent, as follo~s~
Composition I Com~onent 1 Z 3 I . _ __ __ __ "Pluronic F- 121~' 25 o 00% 25~00~ 25~00%
~o~ 00~57~ 1~30% 2~07o Sodiu~ Iodide 0030Z0 2~5% 2.35%
Sodium Citratc (anhydrous) 0 40~ 0 8C7o l~OO
Water to10070 lOQZ 100/.
These oompositions, which are typical of the variation in iodine con~
tent whlch may be deslred for Ysri~us tGplcal applic3t.ions~ all provide excell~nt ~el~ with ~e l~dine stron~ly complexedA and exhibl~ing good pll ~ab~l~ty on storal~e~
Va~lous changes ~nd modific~ltions in the poloxamer-iodlne gel composl-tls~ns hereln disclosQd may occur to those skllled in the ~rt~ and to the extent that such changes and modific~tions are embrflced by the ~pp~nded cla~m~ it is to be unde~stood that th2y constitute pa~t of the present invent~on.
ll -10-
Claims (6)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A poloxamer-iodine gel composition comprising an aqueous medium containing a germicidally effective amount of iodine, an amount of water soluble iodide to provide an I:I-ratio in excess of 0.25:1, about 20 to 30%, based on the total weight of said composition, of a block polymer of the formula:
HO(C2H4O)X (C3H6O)y (C2H4O)x,H
wherein the molecular weight of the hydrophobic (C3H6O)y is about 3500 to 4500 and the overall molecular weight is about 11,000 to 12,000 and about 0.2 to 1.0% by weight of a buffering agent compatible with the skin.
HO(C2H4O)X (C3H6O)y (C2H4O)x,H
wherein the molecular weight of the hydrophobic (C3H6O)y is about 3500 to 4500 and the overall molecular weight is about 11,000 to 12,000 and about 0.2 to 1.0% by weight of a buffering agent compatible with the skin.
2. A poloxamer-iodine gel composition as defined in claim 1, wherein the amount of said block polymer is about 22 to 28% by weight of said composition.
3. A poloxamer-iodine gel as defined in claim 1, wherein the amount of said block polymer is about 25% by weight of said composition.
4. A poloxamer-iodine gel composition as defined in claim 1, 2 or 3 wherein the buffering agent is sodium citrate.
5. A poloxamer-iodine gel composition as defined in claim 1, 2 or 3 wherein iodine is present in the amount of about 0.25 to 2% by weight.
6. A poloxamer-iodine gel composition as defined in claim 1, 2 or 3 wherein iodine is present in the amount of about 0.25 to 2% by weight, and a water soluble iodide is present in an amount to provide about 0.25 to 2% by weight of iodide ion (I-).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49603574A | 1974-08-09 | 1974-08-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1051776A true CA1051776A (en) | 1979-04-03 |
Family
ID=23970988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA232,731A Expired CA1051776A (en) | 1974-08-09 | 1975-08-01 | Poloxamer-iodine gel |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA1051776A (en) |
| GB (1) | GB1516653A (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4215116A (en) * | 1978-06-30 | 1980-07-29 | Block Drug Company Inc. | Propoxylate toxicants |
| WO1981000207A1 (en) * | 1979-07-11 | 1981-02-05 | P Harrigan | Pharmaceutical preparation |
| DE3131112A1 (en) * | 1981-08-06 | 1983-02-24 | Braun Melsungen Ag | ANTIMICROBIAL PREPARATIONS FOR TREATING WET OPEN Wounds |
| DE3428264A1 (en) * | 1984-07-27 | 1986-03-06 | Schering Ag | VALID PHARMACEUTICAL PREPARATIONS |
| US4851217A (en) * | 1987-05-05 | 1989-07-25 | Basf Corporation | All aqueous formulations of organo-phosphorous pesticides |
| MX9305535A (en) * | 1992-09-18 | 1994-03-31 | West Agro Inc | COMPOSITIONS AND CONCENTRATES GERMICIDES BASED ON IODINE-DETERGENT, WATER AND STABLE. |
| GB2281697A (en) * | 1993-09-14 | 1995-03-15 | Euro Celtique Sa | Laxative compositions in capsules |
| AU2018452571A1 (en) | 2018-12-14 | 2021-07-29 | Ecolab Usa Inc. | Stable iodine-containing antimicrobial teat dip compositions |
-
1975
- 1975-08-01 CA CA232,731A patent/CA1051776A/en not_active Expired
- 1975-08-07 GB GB32983/75A patent/GB1516653A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB1516653A (en) | 1978-07-05 |
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