CA2224798A1 - Stable hydroalcoholic compositions - Google Patents

Abstract

Disclosed is a composition including a lower alcohol and water in a weight ratio of about 35:65 to 100:0, between at least 0.5 % and 8.0 % by weight thickener system comprised of at least two emulsifiers, each emulsifier present in at least 0.05 % by weight wherein the composition free of auxiliary thickeners has a viscosity of at least 4,000 centipoise at 23 degrees C and wherein each emulsifier is comprised of at least one hydrophobic group and at least one hydrophilic group. The composition is useful as a presurgical scrub replacement, a lotion or other hand preparation.

Description

STABLE ~IYDROALCO~OLIC COMPOSmONS

Field of the Invention The present invention relates to compositions useful as skin 5 ~l;c;"l~ "c surgical hand plepa.alions~ patient skin plc;~ alions and antimicrobial hand lotions. More speçific~lly the invention relates to stable hydroalcoholic compositions which are thicl~ened using mixed emllleifiçr systems.

Backgro~nd of the Invention Control of nosocomial infection and exposure to infectious disease is of pal~-lo~mt concelll to doctors, nurses, and clinici~ns who work in hospitals and surgery centers. One of the most effective methods for controlling infection is re~...ç.~ed hand dish~,lion before and possibly after each patient contact and particularly before and after each surgical procedure. Hand dicinfection is generally n~co.~.pli~hed using antimicrobial soaps with water. These soaps are usually form~ ted to include either povidone-iodine (usually 7. 5% by weight) or chlorhPYidine gluconate (CHG) (usually 2 or 4% by weight) as the active ~ntim;crobial agent. In addition, these formul~ted soaps may contain surfactants and possibly low levels of hl l~llec~ s such as glycerin.
Hand disinfection is also accomplished using presurgical scrub rep!~c~...f..ls These are used instead ofthe soap and water scrub. Presurgical scrub replacç..~ ideally achieve bacterial kill equal to or better than a traditional soap and water scrub and in a shorter period of time. Additionally, they .~ or improve the skin's natural barrier to microbial and chemical co.~ ion while 25 providing acceptable tactile prope.Lies. E~aln~Jles of presurgical scrub repl~ ..en~
include hydroalcoholic gels which generally include high levels of either ethanol or isopropanol as the di~ fe~ g agent and also include a thickener and optionally include a humect~nt (e.g. glycerin). To date, thickeners used in hydroalcoholic gels have been based on anionic polymers such as polyacrylic acid (sold under the 30 tr~dçn~me Carbopol by BF Goodrich Specialty Polymers and Chemicals Division of Cleveland, Ohio). US Patent 4,915,934 to Tomlinson discloses the use of CHG-co~1Aini~ anl;sc~,lic foams based on hydroalcoholic solvents, a fatty alcohol, and a surfactant. The surfactant is selected from the group of ethoxylated SGIbi~all alkylates, ethoxylated fatty alcohols, and ethoxylated nonyl phenolc Form.-l~ting stable viscous hydroalcoholic emulsions is difficlllt for two reasons. First, addition of short chain alcohols (such as ethanol) to an Mlueo~ls system de~-~ases the surface tension dr~m~tir~lly. For e~ ,le, 40% by weight ethanol in water has a surface tension of approximately 31 dyne~cm colllpa ed topure water which has a surface tension of about 72 dyne/cm at 20~C. A
hydro~lcoholic solution at 60% by weight ethanol has a dr~m~tic~lly dec-l,ased surface tension as con.pared to water. Such a composition has a surface tension of appr~ .Ately 27 dyne/cm at 20~C. Second, many surf~ct~ntc typically used in cosmetic emulsions become completely or partially soluble in hydroalcoholic systems.
In bulletin 51-0001-259 regarding skin care, Specialty Chemicals of ICI America of Wilmin~on, DE stated that although ethanol can provide several benefits to skin care emulsions, formulators often avoid ethanol as it is difficult to prepare stable emulsions in its presence. In fact, the bulletin continlled that ethanol is often used to break emulsions.
US Patent Number 4,956,170 to Lee discloses a hydroalcoholic skin moisturizing/conditioning ~ntimicrobial gel. The gel comprises 60-75% ethanol and 0.4-2% of a polymeric thirlr~nine agent. The formulations also comprise polyethoxylated non-ionic surf~ct~nt~/emulsifiers to stabilize the added emollient oils in addition to a fatty alcohol.
US Patent Number 5,167,950 to Lins discloses an antimicrobial aerosol mousse having a high alcohol content. The mousse comprises alcohol, water, a polymeric gelling agent and a surfactant system co~ Jlis;ng a C 16-C22 alcohol, aerosol propellant and a non-ionic polyethoxylated surfactant.

Summary of the Invention This invention provides compositions useful as products for skin disi.~_lion such as presurgical hand preps, patient preps, and lotions. The pr~rel~ed WO 97/00667 PCTrUS96/08924 formulations of this invention, in general, have a very nice feel after both single and mult:ple applications. Additionally, prert;r,ed formulations ...~ or improve theskin conditiQn after multiple applications and no slimy or abnol"lal feeling is noticed during post application hand washing. When used as a presurgical scrub 5 rep1acPmçnt this invention achieves bacterial, fungal, and viral kill equal to or better than a traditional soap and water scrub in a shorter period oftime while ~ ini or improving the skin's natural barrier to microbial and çhemic~l CG~ Theinvention o~erco",es the shortcomings of past compositions by providing a vis,cous composition which inc~lldçs a high concen~lalion of a lower alcohol but does not10 require a polymeric tki~L çnPr to make the composition viscous. Further, the composition has a cosmPtically elegant feel and may be dispensed as a lotion or as a foam.
This invention provides a composition comprising a lower alcohol and water in a weight ratio of about 35:65 to 100:0, beL~een at least 0.5% and 8.0%
15 by weight thickener system comprised of at least two Pmlllcifiers, each çmllleifiçr present in at least 0.05% by weight wherein the emul~ifip~rs are selec,ted such that the co~..pos;l;on free of auxiliary thickeners has a viscosity of at least 4,000 ccrlt;poise at 23 degrees C and wherein each emulsifier is con,~,ised of at least one hydrophobic group and at least one hydrophilic group, wherein: (i) the hydrophobic group is 20 cGIllpl;sed of an alkyl group of at least 16 carbon atoms; an alkenyl group of at least 16 carbon atoms; or an aralkyl or an aralkenyl group of at least 20 carbon atoms; and (ii) the L~d, ophilic group is comprised of an amide having the structure - NHR"' where R"' is cGIl~p~;sed of hydrogen or an alkyl group of 1-10 carbon atoms optionally substituted in available positions by N, O and S; esters of short chain 25 alcohols or acids (e.g., -C(O)OR' or -OC(O)R') where R' is Cl-C4 ~,~,.,I.ed or straight chain alkyl optionally substituted in available positions by hydroxyl groups;
polyglucosides having 1-10 glucose units; polyglycerol esters having 1-15 glycerol units; second~ y amines; tertiary amines; quaternary amines; anionic groups in~lu~ling sulfate (-OS020-M), sulfonate (-S020-M), phosphate ((-O) 2P(O)O or ~ 30 -OP(0)(0-)2M), phosphonate WO97/00667 PCT/U~'0~924 (-PO(O-)2M), and carboxylate (-CO2-M); zwitterionic compounds co.~-. ing to the structure: -N+(R")2(CHQ) xL' or O
S -opo(cHRl)xN+(Rl )3 o where R" is hydrogen or an alkyl or alkylene group optionally substituted with nitrogen, oxygen, or sulfur atoms, or an alkylene carboxyl group, which alkyl or10 alkylene carboxyl group comprises I to 6 carbon atoms; each Q is indepçnd~ntly hydrogen or hydroxyl; x=l to 4; and L' is -C02-M; -OP(0)(0-)2M, (-0)2P(O)O-M, -SO2O-M or -OSO2 O-M; M is a positively charged counter ion present in a molar ratio necess~ry to achieve a net neutral charge on the emulsifier and is selected from the group coni,;sling of hydrogen, sodium, pot~cci-~m, lithium, ammonium, c~lci~lm 15 ma~esi~lm or N+R'3 where each R' is independently an alkyl group of 1 to 4 carbon atoms optionally substituted with N, O, or S; and optionally alcohol; and/or polyethylene glycol bonded to said hydrophobic group through an ether or ester bond having 2-150 moles of ethylene oxide units per mole of hydrophobe, polyethylene glycol/polypropylene glycol polymers having 2-150 moles of ethylene20 oxide units per mole of hydrophobe and optionally terrnin~ted by C 1 -C36 alkyl or alkaryl ester; and/or esters of polyhydric alcohols and their polyethoxylated derivatives; and so-l,ilan and polyethoxylated sorbilan; as well as con.bi~ ionc of these groups.
This invention further provides a method of p. e~,~ing a stabl 25 hydroalcoholic composition comprising the steps of p-epa~ing a thickener system comprised of at least two emulsifiers, each emulsifier present in at least 0.05% by weight in the composition wherein said emulsifiers are selected such that the composition free of auxiliary thickeners has a viscosity of at least 4,000 celllipoise at 23 degrees C and wherein each emulsifier is comprised of at least one l~dlophobic 30 group and at least one hydrophilic group, wherein: (i) the hydrophobic group is comprised of an alkyl group of at least 16 carbon atoms; an alkenyl group of at least W 097/00667 PCTrUS96/08924 16 carbon atoms; or an aralkyl or an aralkenyl group of at least 20 carbon atoms; and (ii) the hydrophilic group is co,l,~,ised of an amide having the structure -NHR"' wht~ R"' is cG~ ised of hydrogen or an alkyl group of 1-10 carbon atoms optionally sllbstituted in available positions by N, O and S; esters of short chain S ~Icohnls or acids (e.g., -C(O)OR' or -OC(O)R') where R' is Cl-C4 b.~,.,hed or straight chain alkyl optionally s~bstit lted in available positions by l."dl u~yl groups;
polyglucosides having 1-10 glucose units; polyglycerol esters having 1-15 glycerol units; secon~i...y amines; tertiary amines; quaternary amines; anionic groups including sulfate ~OS020-M), sulfonate (-S020 M), phosphate ((-O) 2P(O)O-M) or (-OP(O)(O-M)2)3, phosphonate (-PO(O-)2M, and carboxylate (-CO2-M);
zwitterionic compounds conro~l,llng to the structure:
-N~''2(CHQ)XL' or O
Il opo(cHRl)xN~(R )3 o where R" is hydrogen or an alkyl or alkylene group optionally substituted with nitrogen, oxygen, or sulfur atoms; or an alkylene carboxyl group, which alkyl or and L' is -CO2-M, -OP(O)(O-)2M, (-O) 2P(O)O-M, -SO2O-M or -OSO2O-M; where M
is a positively charged counter ion present in a molar ratio necess-~ y to achieve a net neutral charge on the em~llsifier and is s~lected from the group cohslsling of hydrogen, sodium, pot~csillm~ lithium, ~ ol~iulll, c~l~ium, m~gJ-ç~;.. or N~R'3where each R' is independently an alkyl group of 1 to 4 carbon atoms optionally 25 substituted with N, O, or S; Q is hydrogen or hydroxyl; x=1 to 4; and optionally alcohol; and/or polyethylene glycol bonded to said hydrophobic group through an ether or ester bond having 2-lS0 moles of ethylene oxide units per mole of h~dlophobe, polyethylene glycol/polypropylene glycol copolymers having 2-150 moles of ethylene oxide plus propylene oxide units per mole of hydrophobe and 30 optionally tel~ ed by C1-C36 alkyl or alkaryl ester; and/or esters and ethers of polyhydric alcohols and their polyethoxylated derivatives; and soll,i~an and W O 97/00667 PC~rAUS96/08924 polyethoxylated so.l,ilan, as well as co,.,binalions ofthese groups, and co",bi,..ng a hydroalcoholic solvent with the thirkçn~r system at a telll~Je~alllre s~fficient to melt said thic~nlor system and in an amount that provides a composition having bel~. ~n at least about 0.5% and 8 0% by weight thif~ner system This invention also provides a method of p, ~pa,il-g a stable hydroqlc~holic con.l)os;lion comprising the steps of: (a) heating a thi~ener system to a telllpelal~lre sl-fficient to melt said thic~ener system, wht~eill the th;c~ener system is cGn.~,.;sed of at least two emulsifiers, each ~mllleifi~r present in the co..")os:lion in at least 0.5% by weight wl,ere;n said ~mllleifiers are s~ ed such 10 that the composition free of auxiliary thickeners has a viscosity of at least 4,000 cenlipoise at 23 degrees C and wL~,reh~ each emulsifier is co...~u~ ;3ed of at least one h~drophobic group and at least one hydrophilic group, wLe,ein: (i) the l.~drophobic group is comprised of an alkyl group of at least 16 carbon atoms; an alkenyl group of at least 16 carbon atoms; or an aralkyl or an aralkenyl group of at least 20 carbon 15 atoms; and (ii) the hydrophilic group is comprised of an amide having the structure -NHRN' where R"' is co..,~,ised of hydrogen or an alkyl group of 1-10 carbon atoms optionally substituted in available positions by N, O and S; esters of short chain alcohols or acids (e.g., -C(O)OR' or -OC(O)R') where R' is Cl-C4 branched or straight chain alkyl optionally substituted in available positions by hydroxyl groups;
polyglucosides having 1-10 glucose units; polyglycerol esters having 1-15 glycerol units; secondary amines; tertiary amines; quaternary amines; anionic groups inclll-ling sulfate (-O-SO2O-M), sulfonate (-SO2O-M), phosphate ((-O) 2P(O)O-M) or (-OP(0)(0-)2M), phosphonate (-PO(0-)2M), and carboxylate (-CO-2M);
zwitterionic compounds col~"---ng to the structure:-N+R''2(CHQxL')or O
Il -O P O(c~nRl)x N + ~ )3 I

O-where R" is hydrogen or an alkyl or alkylene group optionally substituted with nitrogen, oxygen, or sulfur atoms, or an alkylene carboxyl group, which alkyl or W O 97/00667 PCT~US96/08924 alkylene carboxyl group comprises 1 to 6 carbon atoms; Q is hydrogen or hydroxyl;
x--l to 4; and L' is -CO2-M, -OP(O)(O-)2M, (-0)2P(O)O-M, -S~2O-M or -OS020-M where M is a positively charged counter ion present in a molar ratio necess~y to achieve a net neutral charge on the eml-lsifier and is sPIected from the S group consisting of hydrogen, so~illnn~ pot~c~ium~ lithium, ~-.. oni~m c~lci~lm ma~esi..m or N~'3 where each R' is independently an alkyl group of 1 to 4 carbon atoms optionally su'Qstituted with N, O. or S; and optionally alcohol; and/or polyethylene glycol bonded to said hydrophobic group through an ether or ester bond having 2-150 moles of ethylene oxide units per mole of l,~drophobe, 10 polyethylene glycol/polypropylene glycol copolymers having 2-150 moles of ethylene oxide plus propylene oxide units per mole of hydrophobe and optionally tel .. .;..~ed by Cl-C36 alkyl or alkaryl ester; and/or esters of polyhydric alcohols and theirpolyethoxylated derivatives; and so-bilan and polyethoxylated sorbitan, as well as co,..bil,dlions of these groups, (b) co,nbining the thickener system and an aqueous 15 phase, and (c) adding a lower chain alcohol to the aqueous/thickener system co",billalion wherein the alcohol to water weight ratio in the composition is bcl~,en about 35:65 to 100:0 and the thickener system is present in the composition between at least about 0.5% and 8.0% by weight.

Definitions "Ambient te,npe~ lre" as used herein refers to the tellll)elalule range between about 21 and 25 degrees C.
"Auxiliary thickeners" as used herein refers to additives (other than the elnlltcifip~rs which comprise the thickener system described below) which increa~c.e the viscosity of the solvent phase even in the ~bs~- ~ce of the thi~ L f ,cr system.
Certain auxiliary th -keners may act synergistically with the thiCL f ner system to increase the viscosity of the resultant forinula. Auxiliary thickeners include but are not limited to soluble and swellable polymers and associative colloidal thicL-Pners such as silica, m~gn~P~ivm ~ mimlm silicate, and the like.

~ F.molli~nt~ as used herein refers broadly to materials which are capable of ...~ A;n;~ or improving the moisture level compli~nce7 or appe~ance of the skin when used repeatedly.
~ F.m--l$ifier" as used herein is synonymous with "surfactant" and 5 refers to mole~lles comprising hydrophilic (polar) and hydrophobic (non-polar) regions on the same molecule.
"Fm~ ;on" as used herein refers to a stable dispersion of one liquid in a second i.. iCriblc liquid.
"Lotion" means liquid or cream free of any propellant.
"Melt te"",e,al-lre" (Tm ) as used herein refers to the te",pe,al~lre at which compositions or emulsions of the present invention dramatically lose viscosity.
"Polymer" as used herein refers to a natural or synthetic molecule having repetitive units and a number average molecular weight of at least 20,000.
"Solvent", "solvent system" or "hydroalcoholic solvent" as used 15 herein refer to the alcohol and water cor,.bh~ation in the present invention."Stable" as used herein refers to a composition that displays less than or equal to 10% by volume separation after centrifuging at 2275 x g for 30 mimltes at &".bie.-l te---pc~ re.
"Surfactant" as used herein is synonymous with "emllleifier," the 20 definition of which is given above.
"Thickener system" as used herein refers to a co",bh~alion of at least two emllleifiers each present in a concenll~lion of at least 0.05% by weight capable of providing a viscosity of at least 4,000 cenlipoise at 23~C to the compositions of the present invention without auxiliary thickeners.
Detailed Description of the Invention The invention provides a composition comprised of a lower chain alcohol water, and thickening system. Alcohols used in the present invention arefirst tliecus5ed followed by a discussion of thickening systems. Ingredients which are 30 optionally added to the composition such as antimicrobial agents and emollients are W O 97/00667 PCT~US96/08924 then rliscussed followed by a discussion of how to prepare colnposllions of the present invention.

- Alcohol The alcohol used in the present invention is a lower hydrocarbon chain alcohol such as a C l-C4 alcohol. In pl crel l ~d embo~ 1 e the alcohol ischosen from ethanol, 2-propanol, or n-propanol, and most preferably ethanol.
Ethanol is a prere-led alcohol since it provides broad spectrum and quick killing of microbes and has an odor acceptable to consumers such as doctors, nurses and 10 clinicians. The invention anticipates that a single alcohol may be used or that a blend of two or more alcohols may coll.~ -ise the alcohol content of the composition.
The alcohol to water ratio in the present invention is between about 35:65 and 100:0 by weight. Compositions having alcohol to water ratios within the range 40:60 and 95:5 range ensure an efficacious i.. e~;~le bacterial kill. In aplerell~d embodiment the alcohol:water ratio is between about 50:50 and 85:15, more preferably between about 60:40 and about 75:25, and most preferably the alcohol:water ratio is between about 64:36 and 72:28 by weight. ~igher alcohol to water ratios are used in a p.~rel.ed embodiment for optimum antim;crobial activity and to ensure the composition is fast drying.
Thic1~ç.ner System The thi~.L .onçr system useful in this invention affects the cosmetic attributes of the final composition. Preferably, hand preps and lotions of the invention have the following desirable cosmetic attributes. The composition should 25 not result in excessive clumping of glove powder beneath powdered surgical gloves and should not affect the integrity of the glove material. The composition should n an acceptable viscosity at 25~C and p,t:re,~bly up to 35~C. Finally, in most the prere- -~:d embodiments formulations are stable to heat and cool cycles (heating up to 50~C or higher and cooling to ambient temperature) as well as freeze/thaw 30 cycles (cooling to -30~C and warming to ambient te...pe-~ re). All of these co~emetic attributes are affected by the types and amounts of em~lleifiçrs chosen ~CA O 2 2 2 4 7 9 8 P9 9 7 - 12 ~ ~ o(e~c~ L~ ~S
~ ~ h~ ~C5Q~ 6 ~ 7 ~ ~ hy~p~

which comprise the thickener system of ~he present invention and are ~ c~cse below.
The thickener system of tne invention must be conl~aLi~le with the hydroalcoholic solvent system described above in order to provide acceptable 5 cosmetic ?roperties and appropriate viscosity. Compositions of this invention have a viscosity of at least 4,000cps at 23~C, pre~erably at least 20,000cps, more preferably at least 50,000cps and most preferably about 80,Q00 to 500,000cps measured using a very low shear viScometçr such as Broo3cfield LVDV-I+ viscometer and T spindles with a heliopath adapter. Since th~ ~ntollient system and other optional ingredients 10 may affect the viscosity (either positively or negatively), the measured viscosity is that of the final composition without any added auxiliary th cl;encrs.
The viscosity of the present invention is irnparted by a thickener system comprised of at least two emulsifiers. In a pre~., ed embodiment at least one ofthe emlJlsifiers is a solid at room temperature comprising at least one long chain 15 hydrocarbon of at least 16 carbon atoms,~erably at least 18 carbon atoms, andmore preferably at least 22 carbon atoms.fFmlllsifiers ofthis invention are comprised of molecules ha~ ing hydrophilic (polar) and hydrophobic (non-polar) regions on the same molecule and conform to the general structu,e:

(R)a(~ )b Where "R" represents a hydrophobic group and L reprcsents a hydrophilic group. In this invention "~" cGlnl,.ises an all~ ~u~) of at le~st 16 carl;vn at;)ms, pr~ferably a~ ~6 18 carbon atoms and morc preferably(~l~rbon atoms and most preferably~a~ t about 22 carb~n~ms; alkenyl group of 2~ Ic"st 16 carbcrl atoms, preferably~and most preferably(~arbon atoms; or aralkyl or aralkenyl group Ot ;1~ least 20 carbon atoms, p.eferably at least ~4 carbon atoms and most prefcrably at least 26 carbon atoms. In a plefe-led embodiment R is unbranched. Where "L" is co~n~.ised of an ~ ' ~ amide having the structured~'~ where R"' is hydrogen or an alkyi group of 1-_ c ,-, 30 10 carbon atoms optionally substituted in available positions by N, O and S; esters of - c ~ short chain alcohols or acidsR~L = -C(O)OR' or -OC(O)R' where ~' is Cl-C4 ~ ~ Z~ L ~ c(o~ 1~ "' c~ _ c t~ o-, .
PCT/Us96/08924 A~4ENDED SHE~T

branched or straight chain alkyl optionally substituted in available positions by hydroxyl groups); polyglucoside~ ha~ing 1-10 glucose units and more preferably 1-3 glucose units; poiygtycerol esters having l-lS glycerol ~mits, more preferably 2-12, and most pre~erably ~-10 glycerol units; seco~dary amille; tertialy amine; quaternary 5 amine; anionic groups inclu~in~ sulfate, sulfonate, phosphate, phosphonate, and carboxy!ate. "~" is further comprised of zwitterionic ~omgpound/s havir,g the ,~
structure -N~(R")2~CHQ)XL' or O
!l -OPO(CHR~ (R")3 where R" is hydrogen or sn alkYI or alk~a group optionally substituted with nitrogen or oxygen or sulfi~r atoms, or an al!~e carboxyl gro~lp. which alkvi orall~ carboxyl group comprises I to 6 carbon atoms; Q is hydrogen or hydroxyl;
x is 1 to 4; and L' s compr;ised of -~021~or -OP(O)(O-)2M or (-0)2P(O)O~or -SO2O~or -OSO2O~ where M is a positively cnarged counter ion p.esent in a molar ratio necessaly to aehieve a net neutral charge on the e T:lllcifie~ and is selected from the group consisting of hydrogen, sodium, potassium, lithium, ammonium, calcium, m~gn~si~lm or ~R~4where each R' is independently an a'l~l group of 1 to ,~
20 4 carbon atoms optionally substituted ~.vith N, O, or S ~d further where L is ~ R~d ~ F~opy4~c 0Y/dt - C t~ u~ q~4ur ~ cc~sJ
optionally ~tcoho!; and/or yolysthyl~ne ~tyco~6Onded tO ~ hydropho~ t~rough an ether or ester bond l~?vin~ 2 t 50 molos of ~t}l~lGn~ oXi~G ur,itQ p~r r~sle of hy~tr~phobe, p~ly~l~ Ae g~ol/polyp~opyt~nc gly~ol Gopolymors havin~ ~ 150 ~d ~,~ ,h ~S~t g~Ou~, p~ e~O~6~y moles Ol ethyle~e oxldc plus ~p~p~e G,~,de u...L~ ~c. .~I~)lc Ol k~,~nc~ an~
(; c., c~ y~q~uph~ ou~J
25 ~.omlly t~.l..;..A~od b~Cl-C36 all;yl or alkaryi es~ an~ester,g ~ether~f ~ , 4~ ~OUp ~ polyhydric alcohol~ m~t po yethoxylated derivative~n~orbitan 2~ o~
~ v~ ~o-, a~d, polyethoxylated~o~ ;,rv/el ~ lbina~ionsofthesegroups,c.g.a poly~thox~late~ poly~}c6~;d~. Where "a" and "bl' are independently 1 to 4. The hydrophobic and l~dlophilic groups on non-ionic emulsifiers are generally selected 3~ to have a hydrophile/lipophile balance (HLB) of 2 to 20 and more preferably 4 to 16. Furthermore, the weight average HLB of th thisker~er system is ple~rably 4 to 16 and more plefe.~ly 8 ~o 12. ~For example, a thickener system co-.-~-ised of 40%
-Il- ~eS~o~~~>

A~llEh~D~ 'n~~T

~'~yft~t ~ ~c~CCA 0222-4fi98 1997_i2 16~ ~
0~ aho~ ~ 5~ 3h~ ~ o~

by wcight of an em~lcifier with an ~B of 10 and ~0% by weight oî an e~lcifier with an HLB of 15 has a weight avcrage HLB o~ l3.) The em~ fiers which comprise thicker.er systems may be chosen from a single cl~ss of surf~ct~nts (e.g., a r.~~xture of ,,}l.~ir~. length alkylS polyglucosides) but is preferably a mixture of emulsifier classes. Many co~ l,ereially available emulsifiers are actually comprised of a mixturc of chain lengths. Fcr exarnple, some behenyl alcohol as commercially supplied is actual'y a rrfixture of alcohols consisting of primarily C22 and C20 fractions but contain detect~lble levels of C24, Cl 8 and ~16 fractions. For this reason, the chair. Iengths specined herein 10 refer to the number average chain length. Furthermore, in multiple em~-lcifier thicliener systems of the present invention, each emulsifier must be present in a concen~lation of at least O.OS"~o and more prcfera~ly at least 0.1% by weight to be considered a component of ~ thickener system. Thickener systems of the present invention are capable of achieving high viscosities at relatively low total em~lsifier 15 concenh ~Lions. The total concentration of emulsifiers p; esent as a thickener system is generally less than about 8% by weight, prefèrably less than about 5% by weight, more preferably less than 4% by weight, ~nd most preferably less than 3% by weight of the total composition of the present inventior~s used herein 2n ennllcifier is considered part ofthe thickener system if its p,esel~ce in the formula results in an 20 increase in the viscosity of the composition. If a certain emulsifier does not result in increasing the viscosity of the composition, it is considered an emcllient or stabilizer as defined below.
~ ref~ d compositions ofthe present invention which are s~b,l~ y free of polymeric thickening agents have a "melt tel-lpe~ re" (Tm). If 25 conlpo~;lions are heated abo ~e this melt te.npe, dL~Ire, they dramatically lose visco~ . The compositions of the present invention preferably have melt temperatures greater than 25~C in order to ~ t~in a high viscosity at room te.."~e.al~lre. More prefer~bly the melt te,-ll;e.~ re is greater than 3~~C in order to n~ ;n visco~ily once applied to the slcin. The most prefe,.ed formulations have a 30 melt te,npe, dlure greater than 40~C in order to allow shipping and h~nrl~ wiehout refrigeration. Thiel~en~r systems affect the mell tempera.ure cf a given evll.po~ilion.

,4~fi~ti;~ t~ T

W O 97t00667 PCTAUS96/08924 In order to obtain a prefe,l~;d melt te."pe.~l~lre a prere"t;d thic~ner system inr.l~ldes at least one emulsifier which is solid at ~llbie.ll te",pe. aLLlre. Preferably, all eml~leifiers of a thiclr.o.ner system are solid at ambient te.llp~,.alulc to incr~e the melt te,llpe.~ re ofthe result~nt co""~os;~ion.
The structure of eml~lcifiers in a thi~n~r system affects the melt - tem~e~al~lre ofthe result~nt composition. In a pleft"ed embodiment at least one çmul~ifier in a th;r1~n~r system is capable of promoting a crystalline structure.
Crystallinity is promoted by long straight chain alkyl groups, the.erure, at least one emlllcifier prefe. ably comprises a saturated straight chain hydrocarbon of at least 16, ple~lably at least 18 and most p, efe,~bly at least 20 carbon atoms. Certain hydrophilic head groups have been found to particularly prolllote association and crystA~ tion. Suitable crystalline emulsifiers include alkyl alcohols, alkyl polyglllcosides polyglycerol alkyl esters, C1-C4 esters of alkyl alcohols, Cl-C4esters of alkyl carboxylates, optionally substituted alkyl amides, alkyl belaines and alkyl phosphates or phospholipids, alkyl quaternary amines, alkyl amine oxides polyethoxylated alkyl alcohols and alkyl esters of polyethylene glycol.
In addition to ~ff~cting the melt te.l",e.al~lre of a composition, the em~llcifi~r chain length also helps to determine the maximum level of ethanol which can be used in the composition and the concentration of emlllsifiers required in the thickener system. At higher levels of alcohol, longer chain en~ cifiers are required to produce viscous stable emulsions. It is believed that higher levels of alcohol tend to swell or solubilize the emlllcifiers to a greater degree than lower levels of alcohol.
Therefore, as the conce--l,~lion of ethanol increases the chain length ofthe hydrocarbon chains in a thickening system must also increase in order to ll~A;~ a melt tel"~,e,~ re over 35~C. For example, systems based on a C16/C18 alkyl polygll~coside (Montanov 68 available from Seppic, Inc. of Fairfield, New Jersey) in co".binalion with a C18 polyethoxylate (Brij 76 available from ICI of Wilmin~tQn, Delaware) in 68:32 ethanol:water have a melt te-npe-al~re of approxi--lately 35~C.
Similar systems having C22 hydrocarbon chains have melt temperatures of 45~C or higher. In a~ition, as the chain length ofthe hydrophobic co",ponent in the thicl~ner system increases, the amount of emulsifier required to achieve a certain viscosity decreases. For example, the Montanov 68 (C16/C18 alkyl poly~ll)Gosicle)/Brij 76 (polyethoxylated C18 alcohol) thic~n~r system requires appro~ çly 5% total emlllcifier to achieve a suitable viscosity. A similar system based on C22 hydrophobes achieves a suitable viscosity at only 2% total çmlllcifirr The nature and size of hydrophilic head groups of emlllcifi~rs are illlpOl l~ll and help to determine which thick~ning systems produce viscous stable systems. Certain co..l~inalions of emulsifiers will produce viscous stable çmlllcionc Without being bound by theory, it is believed that the size, charge, and degree of hydrogen bonding are important palalll~lel~ to determine how emlllcifiers interact.
Many prer~.~ed thirlr~nçr systems are capable of prodllr.i~
elaslic co-.-~,osilions which are very stable. By varying the ratio of çmlllcifiçrs, the degree of elasticity can be adjusted from almost a purely viscous co.--posi~ion to a highly elastic and even stringy composition. If emollients are added, increasing the elasticity of the system imparts added stability to prevent separation of i....~.;c~ le 15 emollients. Excessive elasticity, however, is not pr~rel.ed since an elastic composition usually does not provide a cosrllçtic~lly appealing product. Addition of certain emlllcifi~rs with at least two hydrophobic components has been shown to limit the viscoel~cticity while ~ls~llh~g viscous stable compositions. A favored class of multiple hydrophobic component emlllcifiçrs are quaternary ~.~nlo~ m salts 20 co-~lllling substantially to the following structure:

R"' +
I

R'- N - R" X~

R""

where: R' and R" are long chain alkyl or alkenyl hydrocarbon chains of at least 16 carbon atoms;
R"' is a short chain alkyl group of 1 to 4 carbon atoms, pi~rel~bly methyl or ethyl;
R"" is equivalent to either R' or R"' and is preferably equivalent to R"';
and W O 97/00667 PCTrUS96/08924 X is a halogen, R"'SO3-, R"'SO4-, or R"'CO2-Some p,er~"ed structures include distearyldimethylammonium chloride, eh~.yldimethyl~mmoninm chloride, and dibehenyldimethyl~,~ nium .s~ f~te while ~I;be~c .yldimethyl~.. on; ~m methosulfate is a more p,efe,l~d 5 structure. Other suitable multiple hydrophobic em~leifiers include dialkylglycerol esters, trialkylglycerol esters, polyglycerol alkyl esters, ethylene glycol dialkylesters, polyethylene glycol dialkylesters, dialkylamides of di~..;nes such as ethylene ~ minç, polyalkylesters of penlaelytl"i~ol and dialkyl (optionally ethoxylated) phosph~ee and alkyl esters of polyethyoxylated alkyl alcohols.
The following emulsifier classes are offered as nonl;n.;~ , e,, r")!es of suitable çm~lleifiers for use in the present invention. Examples of some prefell~,d .omuleifiçrs are provided for each emulsifier class. For the present invention an em.~leifier must be present with at least one coemulsifier to provide a thickener system to produce stable viscous compositions.
1. Alkyloralkenylpolyg~ o~

O~

HO\l 1/ ~ CH2 OH _ n ~1 ~\
~OH 1/
OH
where R is a straight chain alkyl or alkenyl group of at least 16 carbon atoms prerel~bly at least 18 and most preferably at least 20 carbon atoms; or an aralkyl or 20 aralkenyl group of at least 22 carbon atoms, preferably at least 24 carbon atoms and most preferably at least 26 carbon atoms; and n = 1-10, pre~,ably 1-5 and more preferably 1-3.
Nonl;...;~ g eY~mples of prefelled alkyl or alkenyl polyglucoside çml)leifi~rs include cetearyl glucosidè sold as Montanov 68 by Seppic, Inc. of W O 97/00667 PCT~US~53~4 Fairfield, New Jersey; Behenyl ~lucoside produced ~ e. ;..~ lly as Essai 624 MP,an alkyl polyglucoside p, epar~d with 92% C-22 alcohol and corn-derived glucoside by Seppic, Inc.; and oleyl glucoside.

5 2. Short Chain Esters of long chain ~4~coJIQl~ orAcids:

RC(O)OR' or ROC(O)R' where R is as defined above and 10 R' is Cl-C4 bl~ncl,ed or straight chain alkyl optionally substituted in available positions by hydroxyl groups.
Some pleÇe.,ed short chain esters of long chain ~lcohols or acids include but are not limited to methyl behenate sold as Ke.l,e~er 9022 by Witco, Humko Chemical Division of Memphis, Tennecsee; methyl stearate sold as K~rn~stçr4516 by Witco; methyl oleate sold as Kçmester 205 by Witco; arachidyl proprionate available as Waxenol 801 from Alzo of Sayreville, New Jersey; behenyl lactate, stearyl acetate; and glycerol monoerucate available from Croda, Inc. of Pals;ppal"r, New Jersey.

20 3. Alkyl and Alkenyl Alcohols:

where R6 is a straight or branched chain alkyl or alkenyl hydrocarbon chain of at least 16 carbon atoms, p,~;rel~bly at least 18 and most preferably at least 20 carbon 25 atoms; or an aralkyl or alkenyl group of at least 22 carbon atoms, prere~bly at least 24 carbon atoms and most plere,~bly at least 26 carbon atoms optionally substituted in available positions by N, O, and S.
Nonl;...;l;ng examples of p~erelled alkyl and alkenyl alcohol çrn~ ifiers useful in a thickener system of the invention include stearyl alcohol 30 available as Lanette 18 from Henkel's Emery Division of Cincinnati, Ohio; Behenyl Alcohol available as Lanette 22 from Henkel; Oleyl alcohol available as Novol from WO 97/00667 PCr/US96/08924 Croda; C-24 alcohol available as Unilin 350 from Petrolite of Tulsa, Okl~hom~, C3 1 alcohol available as Unilin 425 from Petrolite; and arachidyl alcohol available as AR-20 from M. Michel and Co~ of New York, New York.

5 4. r~ cc~ ~l Ester ORl OR

RlO-CH2-CH-CH2-(O-CH2-CH-CH2)n-ORl 10 where each Rl is indepentlently hydrogen or a straight chain alkyl group of at least 16 carbon atoms, preferably at least 18 and more preferably at least 20 carbon atoms; or an aralkyl or aralkenyl group of at least 22 carbon atoms, preferably at least 24 carbon atoms, and most prerel~bly at least 26 carbon atoms; and n = 0 to 15, preferably 1 to 12, and most pic:r~ably 2 to 10.
Some examples of p, ere" t;d polyglycerol ester em~ ifiers useful in a ner system of the present invention include but are not limited to decaglycerol monostearate available as Polyaldo 10-1-S from Lonza Inc. of Fairlawn, New Jersey;
tetraglycerol monoslealale available as Tetraglyn 1-S from Barnet Products CollJolalion of Pdtcl~on, New Jersey; and decaglycerolt~ hehe~ e 5. Quaternary Anune I

R-N+-R2 X-where R is as defined above; R2 is the same as R3 or a long chain alkyl or alkenyl hydrocarbon chain of at least 16 carbon atoms, preferably at least 18 and more 30 p,ere,~bly at least 20 carbon atoms optionally substituted in available positions by N, O, and S; or an aralkyl or aralkenyl group of at least 22 carbon atoms, p-ere,~bly at least 24 carbon atoms, and most preferably at least 26 carbon atoms;

WO 97/00667 PCT~US96/08924 R3 is a short chain alkyl group of 1 to 4 carbon atoms, preferably methyl or ethyl;
R4 is equivalent to either R2 or R3 and is preferably equivalent to R3; and X is a hqloeen, R3S03-, R3SOi, R3C02, (R3) 2P~4 . or (R3) 2P~4 Nonl;~ g c ,~, ples of quaternary amine emlJlsifi~rs include 5 dil,ehe.~ldimethyl~ .o~ m methosulfate available as Incroquat DBM-90 from Croda; behenyll.i",.,ll,y'~ m chloride available as Nikkol CA-2580 ~om Barnet; and tallourl,i~"~Ll,yl~.. ol-i~lm chloride available as Arquad T-27W from Akzo ChPmic~ls~ Inc. of Chicago, Illinois.

0 6. TerharyAmineanditsProtonatedsalts R-N -R2 or R-N+-R2 Y-l l where R, R2, and R3 are as defined above and R2 and R3 may also be selected frompolyethoxylated or polyproxylated alkyl or alkenyl alcohol chains having 1-50 moles 20 of ethylene oxide or propylene oxide groups per mole of emulcifiP,r and Y is a halogen, RsS03-, RsS04-, RsC02-, (Rs)P~4~, or (R5) 2P~4=, where R5 is an alkyl or alkenyl group of 1-22 carbon atoms optionally substituted in available positions by N, 0, and S.
Some examples of emlllcifiPrs from the class of tertiary amines and their 25 protonated salts useful in a thic~Pner system of the invention include but are not limited to tPhP ~~.. 10propyldimethylamine available as Incror"ine BB from Croda;
behP-~ dopropyldimethylamine gluconate; tallowdhllclllylamine hydrochloride;
dihydrogenated tallow methyl amine; stearyl diethanolamine hydrochloride;
polyethoxylated stearyl diethanolamine hydrochloride.

7. Amine Oxides Rq I

R6 - N ~ Q

where R2, R3 and ~ are ~s ~efined above.
Nonlimiting exarnples of emulsiliers fircnl the class of arnine oxides suitable in 10 a thickener system of the invention include b~hen~ ne o~ade (bPhenyldimethylamine oxide) available as IncrGmine B-30P from Croda; stearamine oxide available as Incramin~ Oxide S from Crod2; behen2r.lidoFrcsp~ldilnethyl aminc oxide; and bis(2-hydroxyethyl)tallov/ ar.inc oxide avail..ble as 14romox T112 from ~kzo.
a~ ~c r ~0~
15 8. Polyethoxyl~tedfAIccJIols and ~.cte~. a.2d Derivatil~es t~iereof C~I;
R6(C(0~ 0(CI~2CH~O)rr{CH~C~O)rR~, where R6 is as defined above; m = ~-200 p eferably 2-50, most preferabiy ~-20;
p = 0 or I ;
o ll R8 = H or ~--~12, where R12 is an alkyl ~roup of 1-36 carbon atoms optionally substituted by N, O or S or an ~rallyl br ~Ik~ 3 ~ of 6 to 36 carbon atoms; and r= ~50.
Some C ~ ~ es cf l~,efe, l~d emulsifiers from the class of polyetho~ylated ~c~hols and esters include but are not limi~ed to Steareth-2 ~vailakle as Brij 72 from ICI Americas Inc. of ~llmington, DE; Cteareth-lO ~vailabte as E~rij 7~; from ICI;
behe~ h 5 available as N~kkol B~-5 fir3m Barret Products Inc.; behe~elh-10 avaiiable as Nkkol BB-10 from Barnet; C3 1 alkyl-10EO availakle as Unithox 450 from Petrolite ~orp. of Tulsa, OK; C:3 1 alkyl-40 EO avzilablP as Unithox 480n fr~m Petrolite, and the lauric ester of Unithox 480 available from Petrolite as X-S171.

. Zwitterionics o RN+(R7)2(CT-IQ)XL' or ROPO(CHR7)~R7)3 I

O_ where R is as defined above; each R7 is independently hydrogen or an alkyl ~-oup of I to 4 carbon atoms optionally substituted by N, O, and S or an a!!~!ene carboxyl '5 O~o dQ~ Ld p~ J
group; L' is -C02-, -OP(O)~O-~2~ (-0)2P(O)O-. -S020-, or -OS020-; each Q is independently ~ or OH; and x = I to 4.
Nonlimiting examp!es of emulsifiers from the class of zwitterions usefill in a thickener system of the invention include StearamidopropylPG-1~ dim~onium chlonde phosphate availa~le as Phospholipid SV ~om .~Iona Industries of Paterson, New Jersey; and behenyi betaine available as Incronarn B40 from Croda.

l a Alkyl and Alkenyl Ami~les:

I

R6-C(~)N (R7)2 ând R6-NC(O) R~

where I~6 and R7 are as de~ned above.
Examples of some ~refelled çmllk:ifiers îrom the clâss of alkyl and alkenyl amides usefiul in a thic3cener system of the invention include but are not limited to bçhen~ de available as Kem~rride B from Witco; steararnide available as Uniwax 1750 from Petrolite; Beh~n~ ~idopropyldimethyl amine availabie as Incr~,llul1e BB from Croaa; steary~ eth~r!ol~snide ~vailable as T.ir~ e S from Lipo Cherniç~ls Inc. of Paterson, NJ; ar,d Erucamide available as Arsnid E ~om Akzo.

Il. Esters and Ethers of Poiyhydnc ,4lcohols Rg Rg O

HO(CH2C)(cH~Sto(c)s~l2 Ro, o~JJ
where t = 0~; where each ~9 is ind~penclently chosen from H;rH2 ORlo; or a 10 hydrocarbon chain of 1 to 4 carbon atoms, preferably Cl; S= 0 or 1; Rlo =~ or where R12 is as defined above'~Lnd X - II or ORIo.~

Examples of esters and ethers incl~lde glycerol monol:)ehenate, pentae~hritol distearate and glycerol tribehenate.
Esters and ethers cfpolycthoxylated polyhydric alcohols are also usefiul. For example, these include but are not limited to polycthoxylated glycerol monostearate, polyethoxylated penta erythritol behen~e, polyethoxylated propylene glycol monostearate.

20 12. Anioni~s [(RI2)aL-cd~ +b~e Where P~,~ is an alkyl or allcenyl group of a~ ;eact 16 csrbQn atoms, preferably25 at least 18 carbon atoms and most preferably at least 20 carbon ~toms optionally comprissng oxygen, nitrogen, or sulfur atoms within or substituted upon the alkyl or alkenyl chain or a polyethoxylated and/or pol~ opo~-~lated alkyl or alkenyl group which alkyl or alkenvl group coll,p,.ses at le~; 16 carbon atoms, preferably at least 18 carbon ato-ns and most p[efe,~bly at 30 least 20 carbon atoms optionally com~ ing oxygen, nitrogen, or sulfur atoms within or substinlted upon the alkyl or all;enyl chain and R12 is a polyethoxylated or polypropoxylated substituent or a copolymer of ethylene oxide and propylene oxide, these polymeric subunits are present in mounts of 1 to 100 moles, preferably 1 to 20 moles per mole of hydrophobe; L is sulfate (~SO2O-), sulfonate (--SO2O ), phosphate ((~)2P(O)O or ~P(O)(O-)2), or carboxylzt~ ~-~~2~, M is hydrogen (~), sodium 5 (Na+), potassium (K+), lithium ~Li+), ammonium (NH4+), calcium (Ca+2), n.osium (Mg+2), or R"A+, wherein R" is R, wherein R is hydrogen or an alkyl or cycloalkyl group OI about 1 to 10 carbon atoms, and A+ is selected from the group consisting of N~3, ~e.g., ~(CH3R)4, HN~(CH2CH2OH)3, H2N(CH2CH20H)2); or a heterocyclic ~B wherein B compr;,ses 3 to 7 10 atoms selected from the group consisting of carbon, nitrogen, sulfur and oxygen atoms which complete the ~itrog~n-cont~ining l1cterocyclic ring: and wherein R may be substituted in availabic positions with oxy~en, nitrogen or sulfur atoms;
a and c are independently 1 or 2;
15 b and d are independently 1, 2 or 3; and e is equal to (c times d)/b.
Nolllimiting examples of preferred emulsifiers ~om the anion~c class of emulsifiers suitable for use in a thickener system of the invention include behenic acid available as Croacid B from Croda, Inc.; steary! phosphate available as 20 Sippostat 0018 from Specialty Industrial Products, Jnc. of Spartanburg, SC; and sodium stearate avai!able from Witco.

13. So~bitan FattyAc~Esfers Rl IocH2cH2)vo O(CH2CH20)VRI 3 O ~{)(cH2cH20)vRl3 CH20(CH2CH2},~lCI ~RI3 O

W O 97/00667 PCTrUS96/08924 where R6 is as defined above R13 is H or CR12 and each v is in~epend.ontly 0 30.
Fatty acid esters of so~ an and its polyethoxylated derivatives, polyoAyelh~lene derivatives of mono and poly-fatty esters are also exarnples of ~d~ition~l ~m~llcifiers useful in the present invention.
Certain colllbinalions of the above-listed em--lcifi~rs are useful in some prefel l ed embodim~nts to form viscous stable th -l ~n~r systems of the present invention. These p.tr~ ,d systems are listed below.

WO 97/00667 PCT~US96/08924 ~ .8 L ~ ~o ~, ~ ~ ~ ~ ~- v, ~ ~ ~ ~ ~ ~ ~
c ~ ~ --O --O ~
' o 8 ~ ~ ~ E
~ ~ ~ ~ E

~ ~ ~ _ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
~ ~ s8 8 8 ~ 8 8 8 8 8 8 ~ - - - - - - - - - -c ~ ~
.~ ,~
o x~ ~ -~ o~ ~' ~' c~ ~X " X~ ~ X' ~3 X~ 8 i~ ~ x~

.#
;~

~ o o ~8 ~ ~ ~ c ~
~8 8~ G~ C~ c, c~ ~ ~ ~ -- ~--_ ~ ~

2 ~ 2 ~ i ~ ~ o x ~~
~ _ _ _ - o~ ~ ~ _ _ - - - 2 ~ ~~ -#
E ~
C, U~ ~
o _ ~ ~ ~ ~ ~o t' X ~ o o WO 97/00667 PCTrUS96/08924 It is a simple matter to test certain cG,l,bi"alions of eml~lcifiers to detc;, llfillc if they provide a suitable thickener system. Screening methodology is set forth in the Examples. The e . !es illustrate the i",po, l~nce of the head group5 size with respect to the ratio ofthe mixed çmul~ifiers required to produce a stable Pmulsion For çy~mrle~ systems based on a C16/C18 alkyl polyglucoside co"lbilled with C18 polyethoxylates of varying level of ethoxylation (Brij) produce stable emlll~;om at widely varying ratios.
Without intton~ling to be bound by theory, the physical structure of 10 the co"")osilion ofthe invention is believed to be that of an emulsion. A classic definition of an ~mlll~jon is a stable dispersion of one liquid in a second i.. ;~rible liquid. However as stated earlier the present co",posilion is preferably formed using at least one emlll~ifier which is a wax at room te"")e~ re. Although compositions of the present invention are not well characterized they are believed 15 to be a viscous stable mixture of a solid semisolid or liquid phase in a second liquid phase. It is believed that if certain hydrophobic emollients are added to the present invention I,~d,ophobic çmlllcifiçrs and immi~cible emollients form an "oil" or l,~dlophobic phase which is dispersed in the hydroalcoholic liquid phase to form an "oil" in "water" emulsion. The hydroalcoholic phase is refe"ed to herein as the 20 "water" phase. Since many pl ere" ed emulsions are somewhat viscoelastic, these emulsions are believed to be liquid crystalline emulsions which have been cooledbelow the cryst~ tion telllpel ~L~Ires of the chosen emulsifiers to form a semi-crystalline gel-like network. Certain formulations may be simply swollen crystalline p~e~ tes rO,.""~g a strongly interacting network in the hydroalcoholic phase (so25 called coagel phase). The compositions of the present invention may also exist as combinalions of these structures. Liquid crystalline and coagel phases in aqueous systems are described in "Application of Emulsion Stability Theories to Mobile and Semi~oli~ O/W Emulsions," Cosmetics and Toiletries~ Vol. 101, pp 73-92 (1986), and "Tnfll~çnce of Long Chain Alcohols (or Acids) and Surf~ct~nt~ on the Stability 30 and Conci~tçncies of Cosmetic Lotions and Creams " Cosmetics and Toiletries. Vol.
92, pp. 21-28 (1977). The exact type of molecular association that occurs depends WO 97t00667 PCTAUS96/08924 on many factors in~hldin~ the nature, size, and physical and çhemic~l states of the polar and hydrocarbon portions ofthe emulsifiers which co,..~lise the thickener system at a specified te.,Jp~ re.
F.mlllcifisrs other than those required in the co.~ros;l;on to provide a S 1' ~~.ner system may also be added as emollients or stabilizers. These ~ml~leifi~rs are ~t;r~ d to herein as auxiliary emulsifiers. For ~ ,lc, certain emolliPnts are also co.,.p.ised of hydrophobic and hydrophilic regions and are useful in the present invention since they are believed to become incol~ora~ed into the liquid crystalline network. These emollients tend to el~h~l-ce the stability ofthe composition as is 10 tlicc~ssed more fully below. Furthermore, certain dimethicone copolyol surf~ct~ntc can actually improve the stability of formulations incorporating emollients. This is also ~liccl~csed in more detail below.

Optional Ingredients In addition to alcohol, water and thickener system, the compositions of the present invention may optionally include ingredients such as salts, emollients, stabilizers, antimicrobials, fragrances, therapeutic agents, propellants and additional emulcifi~rs. Each ofthese optional ingredients along with the effect each has upon the p~upellies ofthe final composition is diccussed below.
Salts The melt te...pt;l ~L~re of the compositions of the present invention may be increased by adding salts. As the concentration of salt is illCI eased, the ratio of emulsifiers will often need to change in order to .~ i" a stable composition. It 25 is i",po, 1~,1 to choose salts which do not create an unstable system and are compalil)le with any antimicrobials present in the system. For example, chlorh~Yisline digluconate (CHG) will precipilate rapidly in the p, ecence of halide salts above a concen~-~lion of about 0. lM. Therefore, if a system includes CHG,prel~,~bly gluconate salts such as triethanolamine gluconate or sodium gluconate, 30 are used.

Stabilizers A stable composition is one which does not separate more than 10%
by volume after centrifuging at 2275 x g for 30 mim~tes as measured at the lon~tudin~l midpoint of the sample tube. It is also recognized that stability may be 5 time ~e--~lenl due to cryct~lli7~tion of em~lcifiPrs and/or emt~llipntc present in the system, CQ~l~SC~ ncc of PmolliPnts~ emlllsifiPrs and the like and, Ih~"~rore, pl~ftlled comrocitionC do not exhibit separation of more than 10% after st~n-lin~ for 6 months at r~ nt con~itionc Two types of st~bili7~prs are useful in the present invention. These include (1) those stabilizers that cOl ~ x with çmlllcifiPr 10 L~dlophilic head groups, and (2) those that associate with the çmlllcifier hydrophobic tails. Certain stabilizers may pe-ro-ll. both fimctions For CA~IIPIC~
PmllicifiPrs comprising 1,2 diol-co. ~ ing head groups such as alkylpoly~l..cosi~Ps, mono~l~ylglycerides, and polyglycerol alkyl esters, may be "stabilized" by adding borate ion. Without intçnding to be bound by theory, it is believed that borate ions 15 complex with adj~cent head groups which may increase the association of L~dro?hobic tails by holding them in close proAill,-ly. Natural or synthetic polymers comprised of pendent long chain alkyl groups (greater than 12 and preferably greater than 16 carbon atoms) such as stearyl modified celll~lose derivatives, stearyl modified proteins such as wheat protein, stearyl modified collagen and the like are 20 capable of stabilizing compositions of the present invention. Such added colll?ontllls may also increase the melt temperature of compositions of the present invention. It is believed that the pendent alkyl groups in these polymers associate by Van der Waals interactions with the hydrophobes of a thickening system, thereby enh~n~ g the stability ofthe crystalline structure. Polymeric thickeners which do 25 not have acsoc~ e pendent alkyl chains may also increase the melt telllpelalule presumably by increasing the viscosity of the continuous phase. A nonlimiting e~ le of such thickeners are quaternary celluloses such as CelquatTM 230M as available from National Starch of Bridgewater, New Jersey. In a prerelled ~ embodiment stearyl~imoni-~m hydroxypropyl cellulose co,l""e-cially available as 30 Crodacel QS from Croda Inc., Pa- ~ippa"y, NJ is added as a stabilizer.

WO 97100667 PCTAJS9~'0~24 Emollients Emollients are typically added to hand lotions or hand preps because they act to increase the moisture content of the stratum corneum. Emollients aregenerally sep~aled into two broad classes based on their fi~nr-tion The first class of emollients fi~nction by r~,lll.,l,~ an occlusive barrier to prevent water evaporation from the stratum CGIll~ lll. The second class of emollients pen~,llale into the stratum corneum and physically bind water to prevent evaporation. The first class of çmo~ nt~ is subdivided into compounds which are waxes at room telll~ alul e and compounds which are liquid oils. The second class of emollients inrludes those 10 which are water soluble and are often refel.ed to as hulllecl~
For the purposes of this invention the thickener system is considered separate and distinct from any emollients which may be added even though it is recognized that the emnleifiers may function as occlusive emollients and aid in n.,.;..l~.ning or improving the skin condition. Emollients are inclllded in a pr~;relled 15 embodiment of the invention and preferably comprise between about 3 and 30%, more plefelably between about 4 and 20% and most preferably between about 5 and 12% by weight of the formulation.
The ratio of wax to liquid emollients (oils and h- . ~ e) in a prefer,ed embodiment of the invention is between about 5 :1 to 1:5 and pr~;fe,~bly 20 between about 1:3 to 3:1. Emollients may be selected from any ofthe classes known in the art. A general list of useful emollients appears in US patent 4,478,853 and EPO patent application 0 522 624 A1 and in the CTFA Cosmetic Ingredient Handbook published by The Cosmetic, Toiletry, and Fragrance Association, Wash.
D.C. (1992) under the listings "Skin Conditioning agents," "emollients,"
25 'lh~ ;t~ s~ "miec~ n~ous" and "occlusive."
In prerel.ed embo-1iments, emollients are chosen from the following nonl;.,.;l;n~ list of general emollients, occlusive emollients and hllmect~nts Examples of general emollients include short chain alkyl or aryl esters (C1 -C6) of long chain straight or branched chain alkyl or alkenyl alcohols or acids (C8-C36) 30 and their polyethoxylated derivatives; short chain alkyl or aryl esters (C 1 -C6) of C4-C12 diacids or diols optionally substituted in available positions by -OH; alkyl or aryl C I -C9 esters of glycerol, pentaerythritol, ethylene glycol, propylene glycol, as well as polyethoxylated derivatives of these and polyethylene glycol; C 12-C22 alkyl esters or ethers of polypropylene glycol; C12-C22 alkyl esters or ethers of polypropylene glycoVpolyethylene glycol copolymer; and polyether polysiloY~n~o 5 copolymers. In aA~litiQn to many of the ~mlllcifi~rs ofprere.red 1l~ cL çl-çr systems, ~ a~litionA~ 'es of occlusive emolli~ntc include cyclic dimethicones, polydialkylcilox~n~c, polyaryl/alkylsiloxanes, long chain (C8 - C36) alkyl and alkenyl esters of long straight or branched chain alkyl or alkenyl alcohols or acids; long chain (C8 - C36) alkyl and alkenyl amides of long straight or bl~nclled chain (C8-10 C36) alkyl or alkenyl amines or acids; hydrocallons including straight and bl~ched chain alkanes and alkenes such as sq-l~lene, squalane, and mineral oil; polysiloxane polyalkylene copolymers, dialkoxy dimethyl polysiloxanes, short chain alkyl or aryl esters (C1-C6) of C12-C22 diacids or diols optionally substituted in available positions by OH; and C12-C22 alkyl and alkenyl alcohols. Nonlimiting examples of15 prere,led hl-...ec~ type emollients include glycerol, propylene glycol, dip,o~ylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, pantothenol, gluconic acid salts and the like.
Although a thic~çnçr system is responsible for the stability and overall concictency ofcon")osilionsof the present invention, emo~ ntc may also 20 affect the viscosity, stability, and melt temperature of a composition. It is~nticirated that a single emollient may be added to the present invention or two or more emollients may be added to the composition. A wide range of emollients may be added to the formulations of the present invention. Preferably wax and oil type emollients along with water soluble emo~ ntc are used. In a prere.led embodiment, 25 ~mc~lliçnt systems are comprised of hllm~ct~ntc in addition to occlusive wax and oil emn~ ntc in conce,~ lions which achieve a moisturizing but not greasy composition which n.~.nlA;nc and improves the condition of the skin upon repeated use. Ideally, çmolliçnts are non-comedogenic and are chosen to ensure no skin irritation or sçnc;~ l;on reaction occurs. This is particularly critical since the 30 composition ofthe present invention will likely be worn in an occluded con~lition under surgical gloves. Furth~lll,ore, emo!li~nts should be chosen which do not affect the inleg,ily ofthe glove material. For example, since hydrocarbon ems71liçntc such as mineral oil and petrolatum can dcl~;...~nl~lly affect the tear ~l~c~ of surgical gloves, these emolli~ntc may need to be avoided for compositions employed as p~ ~C~ ~;sillré~l~llS.
Without being bound or limited by theory, it is believed that if Pmolli~P.nts are added to the present compositions, they may be present in four distinct regions. The emollients could occur (1) as a soluble species in the solvent phase, (2) dispel~ed as emulsified droplets within the rnixed emlllcifip~r micelle or crystalline gel network, (3) incor~,o,aled into the mixed eml~lcifier micelle orcrystalline gel nelwo~k, or (4) as a separate and distinct emulsion. As earlier stated, PmnlliPntS can affect the melt ttnlpel al,lre of a composition. Those emollients that are soluble or dispersible in the solvent phase tend to have little or no affect on the melt te~"pe~ re and are therefo, e p, ere" ed. These emollients include the h~....ec~ and general emollients. The most prere"cd general emolliPrlts are those 15 which are essçnti~lly insoluble in water but soluble in the hydroalcoholic solvent.
These emollipntc are also prefelled since they remain soluble and uniformly disp~ ed even above the melt te~pcl ~ re so that upon cooling to room tempclal~lre a uniform composition results. In addition, they are also believed to have little effect on surgical gloves. Such general emollients typically do not have 20 alkyl or alkenyl chains greater than about 14, preferably not greater than 12 and most preferably not greater than about 9 carbon atoms.
Those emollients which are insoluble in the hydroalcoholic solvent may associate with the emulsifiers of the thic~Pner system and/or become inco",o, aled into the micelle or crystalline gel network. Pl cfcl .cd emollients within 25 this class are those emollients that are very hydrophobic since they tend to ~ ;nl~;n a high melt temperature. For example, hPY~ec~ne was found to increase the vi.ccoPl~cti--.ity of certain thickener systems. Those emollients which are capable of associating with and disrupting the emulsifiers of the thickener system tend to decrease the melt te",pe,all~re and may influence the stability ofthe composition.
30 Certain branch alkyl esters of greater than about 12 carbon atoms per hydrophobe have been found to be particularly effective at decreasing the melt temperature. For c.~..ple, trioctyldodecyl citrate has been found to si~ifiç~ntly decrease the melt temperature of some systems.
Emollients which become inco.l,ol~led into the thickener system tend to decrease the melt temperature. For . ~ ple, laureth- 1 (Brij 30) appears to S illcotyo~ale into the thicl~rnçr system since it does not phase out when heated above - the melt te.l,p~" alur e at concenl, ~lions below about 1% by weight. Laureth4 also tends to decrease the melt te~l~pelal~re of the composition.
Certain emollients which are insoluble in the hydro~lcoh- lic solvent can be em~lcified in what is believed to be a sepa~a~e and distinct Pml~lQ;on These 10 Pmolli~nts have little affect on the melt telni)elal~lre of a composition. For CA-__ rlC, certain cyclic silicones, polysiloxanes, and dialkoxypolysiloxanes can be ~mlll~ified in hydroalcoholic solvents using polyether/polysiloxane copolymers surf~ct~ntc Cyclic silicones such as DC344 (available from Dow Corning of Midland, l~lir.higPn) in the presel ce of certain polyether/polysiloxane copolymers such as Abil B88 183 15 available from Go~dsçhmidt Chemical Corp. of Hopewell, VA., can form a thermally stable emulsion such that the compositions remain uniform both above and below the melt temperature. In fact, the cGl..binalion of a long chain dialkoxypolycilox~ne and polyether/polysiloxane copolymer has been found to actually promote the stability of certain thickener systems. The dialkoxypolysiloxane is believed to 20 interact with the thir~çner system as well as the polyether/polysiloxane copolymer.
These compounds have the following structures:

Dialkaxy di~ hi~

R-o-si(cH3)2-o[si(cH3)2-o]z-si(cH3)2-oR

where R is a straight chain alkyl group of 14-50, preferably 16-24 carbon atoms, and z= 5-300 r~ J.~oly~ . e Copo~ymers (Dil rthi~one Col)olyols):

(CH3)3-Si-O-[Si(CH3)Rl l-~]z[si(CH3)R8~~]y~si(CH3)3 where R8 is a polyether substituted alkyl group with the structure:
-Rg-O(C2H40)P(C3H60)9Rlo;
where Rg is an alkyl group of 1 to 6 carbon atoms;
Rlo is hydrogen or an alky group of 1-22 carbon atoms; and R1 1 is an alkyl group of 1 to 22 carbon atoms or phenyl.
Note that b~l cl1ed chain polysiloxanes modified as shown in the two stluctures above are also possible.
The following are nonlimitinE çy~mrles of emllleifi~orlemollient co"")onents which improve thic~çning/stability of compositions of the present 15 invention.

a. Certain wax çmlllcifiers/emollients have been found to be particularly usefuland include solid waxy esters such as: Myristyl Myristate, Cetyl p~lmit~t~ Myristyl Stearate, Stearyl Behçn~tç, Behenyl Isostearate, Isostearyl Beh~n~te, Behenyl 20 Beh~n~te, Lauryl Bçhçn~te, Behenyl Erucate. These have the following formula:
Rl-cO2-R2 where: R1 is at least C14 carbon atoms; and R2 is an alkyl or alkenyl of at least 4 carbon atoms.
b. Long chain hydrocarbon di-esters, tri-esters, of polyhydric alcohols with melting point greater than 23~C include solid esters such as glycerol tribehenate and sorbitan tristearate.

c. Pure lanolins and lanolin derivatives (e.g. hydrog~n~ted lanolin) provide eYcçll~nt çmolliency but can also improve the stability of the emulsion when used in co~ ;on with oil emollients.
.

5 d. Petrol~hlmc provide ~Ycçll~nt emolliency and can also improve the stabilityofthe emlllciQn when used in co-llb;nalion with oil emollients. Petrolatums are mixtures of oily and waxy long chain hydrocarbons.

e. Microcrystalline waxes and branched hydrocarbon waxes with a melting point greater than 50~C and a molecular weight greater than 400. An ~ ,~le of this incl~des but is not limited to Vybar 103 which is a branched hydrocarbon with a number average molecular weight of 2800 and is available from Petrolite Corp. ofTulsa, Oklahoma and UltraflexTM which is a microcrystalline wax also available from Petrolite Corp.
~ Oxidized waxes and modified hydrocarbon waxes may find application in the present invention. These are prepared from waxes modified by oxidation, salts ofoxi~i7.ed waxes, maleic anhydride ~dducts of polyolefins and urethane derivatives of oxidized synthetic or petroleum waxes. Applicable waxes could include Petrolite's Cardis or Pelrond~lba microcrystalline and polyethylene-based oxidized products,Polymekon (salts) and Ceramer (anhydride adducts).

g. Fully saturated homopolymers of polyethylene or copolymers of various alkene monomers may be used to form polymers with a molecular weight at or below 3,000 with a melting point below 130~C and low melt viscosities. Applicable waxes could include Polywax~ available from Petrolite Corp.

Fragrances The formulations may also comprise a fragrance. If fragrances are included the fragrances must be chosen carefully since some fragrances are knownto cause skin irritation and/or sçnC;l;~Alion reactions.

Antimicrobials In addition to the lower a;cohols present in the composition of the present invention, other anti~r.icrobials may be added to enh~nce the antimicrobial action of the compositions of the present invention. This m~y be particularly desirable in critical uses such as presurgica! hand scrubs or presurgical patient skin scrub replacements. Suitable additional antimic~obials in~lude iodine and its complexed forms such as povidone/iodine, chlorhexidine salts such as chlorhexidine digluconate (CHG), parachlo. ol;let~xylenol (PC~, hexachlorophene, phenols, 10 surfAcPntc ccmprising a long ehain hydropl1obe (C12-C2q) and a quaternary group, triclosan, Lauricidin, ~uaternary silanes, h~drogen peroxide, ~.c.~G!~ silver, silver k' salts such as silver chloride, sil ier oxide and s lver sulradia7.ine and the iike. In order to reduce chances for irritation &nd ~;et m~int,.in efficacy, the antimicrobial level should be adjusted to the n;inimum le~el which r~int~ins ~ low bacteriological 15 count for 6 and most preferably for 12 hours ~er application~
The most preferred additional antimicrobial is chlorhexidine since it is capable of ensuring long term antimicrobial efficacy. If chlorhexidine is added to the present invention it is preferably present as a soluble salt. The di~cetate and digluconate salts are ~ re,l~d. The most preferred antimicrobial is chlorhexidine 20 digluconate (CHG). CHG is prefer~bly present at a concentration of 0.05-5.0%,more preferably rrom 0.1 - 3% and most preferably from O.q5-2% by weight.
Chlorhexidine is a bis~diguanide) and therefore is very basic and is capable of ing mllltiple ionic bonds with ;mionic materials. For this reason, chlorhexidine-co.~1~inin~ thicl~ener system are preferably based on non-ionic and/or cationic 25 emulsifiers. Certain zwitterionic, very insoluble, or non-precipit~tin~ anionic em~lcifiers may also be useful.

Foams The conlpos;lions of the present invention may also be formul~ted 30 into an aerosol foam or mousse by addition of an approp, ;a~e propellant. Thepropellant must be chosen to ensure proper delivery from the container to ?revent clo~ng of the valve. The propellant can be chosen from chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), hydrofluorocarbons (HFCs), perfluorinated ~Ik~nPc and lower alkanes (C l-C5) as well as nitrous oxide dimethyl ether and other solvent-soluble propellants. F~relled propellants are lower alkanes 5 such as propanc, butane, and isobutane since these result in a drarnatic loss in ~iscosily making the formulation easy to dispense. A 70/30 mi~lure of p-opa~ sobulane is a particularly plef~"cd embodiment. In order to produce an aerosol comrosition the ~ntimicrobial lotion is first form~ ted and ch~,ed into an &ppropliale pressure rated co~lahle[ If convenient, the form.~lation may be heated 10 above the melt temperature in order to fAr.ilitAte filling. The propellant is then added under pressure at applo~i",dtely 2-30% preferably 3-20% by volume. The propellant may form a separate layer or may remain ~m~ ified in the composition.
Alternate aPPlications for h~dro-alcoholic liauid cr~stalline solutions:
The compositions of this invention may be compounded with W
abso,l,e.~ and oils to deliver fast-drying sunscreells. Antimicrobials such as benzoyl peroxide may also be added to the formulations and the forrnulations may be useful as an acne medication. The systems of this invention may also be forn .-l~ted with barrier compounds to form barrier creams and lotions. Materials which may be 20 added to provide barrier protection for use as skin barriers to protect against diaper rash include but are not limited to 0.1 to 60% aldioxa, allantoin, Al~-minl~m acetate, Al~lminllm hydroxide, bismuth subnitrate, boric acid, calamine, cellulose (microporous), cholecalciferol, cocoa butter, cod liver oil (in col"bil,alion), colloidal o~tme.~l, cysteine hydrochloride, dc,~l,AI.lh~nol, di",~tl,icone, glycerin kaolin, lanolin 25 (in co...bil,alion), live yeast cell derivative, mineral oil, peruvian balsam, peruvian balsam oil, petrolatum, protein hydrolysate (l-leucine, l-isoleucine, l-methionine, 1-phenylAIAnine, and l-tyrosine), racçmethionine, shark liver oil, sodium bicarbonate, sulfur, talc, tannic acid, topical starch, vitamin A, white petrolatum, zinc acetate, zinc ca,l,onale and zinc oxide. Formulations are also contçmp!Ated cGr.lAi~ g 30 ~ntifimgAI agents for treating fungal infections of the skin such as athlete's foot and the like.

A rel~ted patent application ~ntitled~ "Stable Hydroalcohol c "U.s. s~. c /~9~ s~~
Compositions," attorney docl~et number 51800 USA 7~ filed Oll June 2', 1995 by inventors Asmus, Scholz and Ch~,e.~Lier.
MET~ODS OF PREPARATION
The compositions of the present invention may be prepared by a variety of techniques. For example, the process can often be as simple as adding the thickener system to the hydroalcoholic solvent at a te~ el ~t~lre above the melting point of the em~lcifiers, mixing briefly and cooling. Nevertheless, to ensurc a composition of m~l~imllm stabilitv the colllponents are preferably subjected to high 10 shear (e.g. homogenized) for a limited time period while above the melting point of the thickener system followed by low shear mixing while cooling. The system should be mixed under high shear long enough to ensure a very small "droplet" size, however, excessive high shear mixing may result in decreased viscosity and s~ability.
The cooling rate may be inlpol Lant depending on the particular 15 thic~-ençr system. Certain thickener systems can bc homogenized and tnen allowed to cool slowly, however, rapid coolin~ appears beneficial for most systems.
The order of adding the components may also affect the stability and viscosity ofthe system. In generzl it wvr~s well to melt the rnixed emlllsifiers with aqueous-insoluble emollients together in one vessel. The hydroalcoholic solvent and 20 any aqueous rniscible emollients are mi.Yed in a second vessel. Both components are heated above the melting tenlpel aLure of the thickener system. T'ne hct liquid co~lponents are mixed together rapidly followed by 3?pro~imately 1 to 5 min~tes of homog~ni7~tion for typic&l batches under 5î;0 grarns. While still !ow in viscosity the system is stirred using moderate agitation and cooled. It is also ?ossible to add the 25 molten 11~; L F ~er system along with any solvent insoluble emolliellts to hot water (i.e., water at a te."~.aL~lre above the melting te."~ LLIre) followed by high she~r n~ixing and subsequent dilution with alcohol. The processing vasiables in~lu~in~amount and i~ nsiL~ of high shear mixing, rate of cooling, and order of ad~iitio~ are easily det~l,l;l,ed by one skilled in the art.

TEST MET~ODS
Viscosity In the following Examples (except where inflic~ted) viscosity was l.leasul~;d at 23~C at ambient pressure using a Brookfield LVDV-I+ vi~col~et~
5 equipped with a model D Brookfield heliopath and T spindles B-F. The spindle and speed was chosen for each particular sample such that the Visco~ te- was Opc-aling in the middle of its range All samples were allowed to equilibrate at 23~C for 24 hours prior to llleas~re...enl Preferably the viscosity is taken at the lowest speed possible while staying within 20-80% of the viscol..eler range and more prertl, bly 10 bet~.cel 30-70% ofthe range In all cases the sample size and conlainer geGlllelly was chosen to ensure that there were no wall effects By "wall effects" it is meant the viscosity value is not affected by the co~.lai"e- and is essenti~lly equivalent to the viscosity taken in an infinitely large con~ainer For this reason lower viscositysamples required a larger sample size to accommodate the larger spin~lles The 15 following table outlines p. efe..ed spindles for various sample viscosities Sample Viscosity T Spindle to Use The viscosity of each sample was taken as the highest relatively stable reading achieved oh the first path the spindle traversed using the heliopath 20 adapter Stability The stability of samples was measured 24 hours after conditioning at ~l.bi~n~ conditions by placing 12ml of a formulation that formed a lotion/cream in a 25 15ml gr~du~ted centrifuge tube The tube was then centrifuged in a Labofuge B

WO 97/00667 PCT~US96/08924 (Heraeus Sepateçh GmbH, Model 2650, rotor 2150 and buckets #2101) at 3000 rpm (2275 x g when measured at the longitudin~l midpoint of the sarnple tube) for 30 mimltes at 23~C. Stability is recorded as a volume percent separation in the Examples below.
s Melt T~ )e.alllre (Tm) The melt telllpel a~lre was measured by placing appro~i.l.ately 15 grams sample in a 25cc sealed glass vial and placing the vial in a water bath. The t~ p~-alult of the bath was increased periodically in discrete illCl~.lle-ltS and the 10 contents cher~ed after approx;~atrly 1 hour at a given telllpela~ e. The melttoml)elalure was taken as the tempelalule at which the mixture becarne very low in VlSCOSity.

Mi~ u.~ Inhibitory Conce,.l,~lion (MIC) An overnight culture of E. coli ATCC 8739 (lab strain 223) and/or S.
Aureus ATCC 14154 (lab strain 502) grown on trypticase soy agar plates was çnded in Mueller-Hinton Broth to a cell density of 0.6- 1.2xl o6 colony fo..."ng units per milliliter. Chlorhexidine samples were prepa,ed by adjusting CHG
to 512 llg/ml in Mueller-Hinton Broth and serially diluting in two-fold steps in20 Mueller-Hinton Broth. The CHG-co~ ini~-g Mueller-Hinton Broth was placed in 96-well sterile microliter plates and each well was inoculated with the bacteria. The plates were then inr,ubated for 24-48 hrs at 37~C. Bacterial growth was determined visually by CGIllludl h~g the plates. The MIC was determined as the lowest conce--l-alion of CHG that resulted in complete kill of the test organism.
Cosmetic PropertiestTactile Testin~
For use in presurgical disinfection the compositions of this invention are preferably fornn-lated with emollients to achieve a moisturized but relatively dry feel. Lotions with excessive emollients tend to be perceived as greasy and can result 30 in excessive clumping of the powder under surgical gloves. The formulations of this invention do not provide a tacky or sticky feel even in high humidity envil ol~ne..ls throu~hollt the application process. The invention formulations prerelably yield a smooth, soft, non-tacky, and moisturized feeling. Testing of the cosmP,tic or tactile prope. Iies of the compositions was conducted with preferably greater than ten evaluators who applied a ple...eA~.lred amount of product, approx;...~ly 2ml.
S Since hand WdSI~ g can affect the feel of the compositions, evaluators washed thoroughly with Ivory Skin CI~AI~ Liquid Gel hand soap available from Procter and Gamble, Ci~ l-n-l; OH before applying the sample. After drying, the composition was rubbed uniformly over the surfaces of both hands until the cGll,po ;lion was dry. The feel of the composition on the skin during subsequent10 washing with soap and water was also important. Appro~u,.,alely 30-60 min. after application of the composition the feel during subsequent washing was ev~ ted.
"ed formulations did not result in an abnormal feeling such as slimy, slippery, or sticky characteristics.

The following Exa",ples are provided to illustrate the invention and are not intended to limit the scope of the invention.

E~ample 1: Alkvl PolyPlucoside Thickener Svstems An alkyl polyglucoside emulsifier having an alkyl chain of 16 to 18 carbons was obtained as Montanov 68 from Seppic Inc. of Fairfield, NJ. This highly crystalline Pmulsifier was combined with other emulsifiers to form thickener systems in a hydroalcoholic solvent. The solvent was either 60:40 or 68:32 ethanol:water by weight. 200 proof ethanol and distilled water were used. The Montanov 68/co-2S emulsifier ratio was varied keeping the total emulsifier concentration fixed at 5% by weight accordil g to the following table:

WO 97/00667 PCT~US96/08924 Formulation (grams) Emulsifier A B C D
Montanov 68 2 1.5 1 0.5 Co-çm--lcifier 0.5 l.0 1.5 2.0 60:40 ethanol:water 47.5 47.5 47.5 47.5 Each co-~m~lcifierlMontanov 68 composition was plep~ed using the following procedure:
1. The emulsifiers were heated above their melting te..,l)c,alure to 75~C
2. The hydroalcoholic solvent was heated to 75~C in a sealed jar.
3. The hot hydroalcoholic solvent was rapidly added to the molten çml 1l cifiçrs.

4. The mixture was homogenized at maximum speed for 4 min~tes using a Silverson L4R homogenizer available from Silverson ~r.hin~c Waterside F.ngl~n~l 5. The vessel was then immersed in 1 5-20~C water with moderate agitation using an overhead paddle impeller for 20 mimltes ~o-WO 97/00667 PCTrUS96/08924 F~
Viscosity (c~s) ~nd/or % 5-r~ n by Vol~me F ' '7.r Solvent A B C D
Niklcol BB-5 (b-' ' 5) 60:40 240,000cps 2200 cps 29300cps 26600 t~ r t ~ ~O ~ /O
~ .~ cco BB- (b h~ ' 5; 6~ n ~ '0~10 : ---00 ~r~oo clco BB-~(b~l~ ' 0) 6'~ 0 '~ ~0 BB- ~ e ~eneth-~O) ~ O
Br (oetet~ 1 a~ .. 0 '~O0 41~0 Br' (cetetl- u) 6~ 00 ~-~ i. .1 < ~
Br(stearet~ 000 h~ o 4~10 Br~ (stearetl-'~' 6':-" ~S~ 0 1~ 0 Br; ~(stearetl- ~) 6':~_ -5C~00 ~ 0 ~ < i-~
Br ~~ (stearetl-' i~) 6~ 0 ~ 000 ~ o r~
Br ~' (s~re l-' ' 6n:. 2 ';~0 ~ 0 ~-~Jnthox~ (C:lalcy1-2EO) 6~: 2 :(~ "() 6~t Jnthox~ (C: 1 akyl-9.80) 6'::2 6~)0 '~ ~-i;oo ~S
ncromine BB 60:~0 NS : 600 . ~00 630 (tl '- ~~-, U~ 0% <2% 24%
~nine) - BB 68:32 6000 420 520 NS
- ~ - BB ~h. 60:40 75 23000 1200 2000 5~% ~O ~~/O 5~~-Annid 18(o ~e~ ~ -) 60:~0 < ~0 ,anette 1" 'Steargl alconol) 60:~0 Jniwax l~50(~t~.~,.;ce) 60:~0 TritonX- ~ 68:~2 ,h~.~ol ethoxylate) Triton X-35 68:32 NS NS NS NS
(oc~yl~,h~lol et~- y~
* NS = not stable The results show that certain thickener systems form stable viscous compositions. Those thickener systems that form stable compositions have widely 5 varying viscosities depending on the emulsifiers and the ratio of the alkylpolyglucoside to co-çm--lsifier. For example, rnixtures of Montanov 68 and Brij 52 had viscosities which varied from 950 to 240,000 cps. This example also illustrates the effect alcohol:water ratio has on rçs~-lting stability and viscosity. For e.~.,ple, at an eth~nol water ratio of 60:40, the Montanov 68:Brij 72 system had a m~iml~m viscosity of 470,000 cps at a weight ratio of 4: l (formulation A). Whenthe ethanol:water ratio was increased to 68:32 the 4: l ratio was no longer stable and the m~iml-m viscosity was only 34,000 cps at a weight ratio of 2:3 (formulation C).
Similar shifts appear for the Montanov 68:Nikkol BB5 and Montanov 68:Brij 78. Itappears that higher viscosities are achievable at lower alcohol levels presumably due ~1-to lower solubility ofthe em..lcifiers and that peak viscosities appear at higher concenllalions of Montanov 68 presumably due to the highly crystalline nature ofalkyl polyglucoside eml~lcifiers.
The results also indic~te that the size of the hydrophilic group 5 inflllenr.es the stability and viscosity even within the group of mixed eml~lcifi~rs which produce stable systems. For example, as the degree of ethoxylation inc,oases, the hydrophilic group size increases and, in general, the peak viscosity decl~ases.
For example, within the ceteth series (Brij 52-58) the ~ ;n~ n- viscosity is 240,000cps for Ceteth-2 whereas Ceteth-20 had only a .. ~;... viscosity of 60,000cps. Similar results were found for the steareth series (Brij 72-78) and the behenelh series (Nikkol BB series).

E~amPle 2: Alk~l Pol~,rl~.coside/ Brii 72 OPtimization A series of 15 formulations were prepared using a three CGIllpon.,lll 15 mixture design based on the results of Example 1. The following concel,l, ~lion ranges were investig~tçd using a solvent ratio of 68:32 ethanol:water.

Component Percent by wei~ht Montanov 68 0.26 - 3 Brij72 1.0-5.2 Solvent 94 - 98 Each formulation was prepared and subsequently tested for stability 20 and viscosity. The viscosities of the resulting formulations ranged from less than 50 cps to 93,600 cps. Stability results ranged from 0 - 83%. E~...ples of several opli"li~ed formulations appear below:

~2-WO 97/00667 PCTrUS96/08924 Formula Montanov68 Brij Solvent Viscosity Stability 72 (cps) (~/Ovolume separation) Percent by weigh.
A 0.26 5.20 94.54 65,000 3 B 3.00 3.00 94 93,600 0 C 2.20 2.92 94.88 72,000 0 2.20 1.92 95.88 30,000 0 1.80 2.70 95.5 30,000 0 3.20 2.30 94.5 50,000 0 These results together with those of FyAmple 1 in~iG~te that the viscosity of the formula for this thickener system is dependent upon the ratio of the çml~lcifi~rs The results also indic~te that even when varying the ratio ofthe S çmllleifi~rs in thickener systems, high viscosities are still obtained while ~ Ail-;--~acceptable stability values. Furthermore, the total conce~ lion of thickener system l-ecçc.cA. y to achieve a certain viscosity varies considerably depçn-ling on the ratio of em.llcifiers. For example, Formula D had a viscosity of 30,000 cps with a total em..lcifier concenll~lion of only 4.12% by weight.
Esample 3: AlkvlPolv~lucoside Ternary Thickener SYstems:
Based on the results obtained in Example 2, formulae E and F were chosen for use as base systems to which a third emulsifier was added to further inclease the viscosity. The third em.llcifier was added at concenll~lions of 0.3, 0.8, 1.3 and 1.8% by weight keeping the ratio of Montanov 68 and Brij 72 at the ratios found effective in formulations E and F of Example 2 accol dillg to the following table:

~3-Formula Cs .-- ¦ A ¦ B¦ C ¦ D ¦ E ¦ F ¦ G ¦ H
Amount (~rams) M(,l~ 68 0.92 0.920.92 0.92 1.11 1.11 1.11 1.11 Brij 72 1.37 1.371.37 1.37 1.55 1.55 1.55 1.55 Coem~.lcifi~r 0.15 0.400.65 0.90 0.15 0.40 0.65 0.90 So1vent 47.57 47.3247.07 46.82 47.19 46.94 46.69 46.44 The solvent used was 68:32 ethanol:water. The form~ tion~ were pl~a.ed and subsequ~ntly tested for stability and viscosity. The third co-çm~ ifi~rs 5 used were behenyl alcohol (Lanette 22, Henkel Corp.) and stearamide tiieth~nolamine (Liparnide S, Lipo Chemical of Paterson, New Jersey). The following viscosity results were found:

VISCOSITY (cps) C~ A B C D E F G H

1 . ~I S 42,500 70,500 82,800 111,000 75,500 120,000 91,100 90,000 LaN~R22 59,100 88,800 93,600 92,300 14,500 62,000 86,800 81,600 All formulations had stability values of 0% separation except formula A/Lanette 22 which showed a trace (C5%) amount of separation. The results in~ic~te that addition of a third emulsifier into the thickener system can i"cr~,ase the viscosity. The results also indicate that the length of the hydrocarbon on the third emulsifier does not necessarily predict viscosity. In this example, Lipamide S, although it has a significantly shorter hydrocarbon chain than Lanette 22, generally, produced higher viscosity compositions.

E~ample 4: Effect of Shear on Viscosity and Stabilit~
Formulation C from Example 2 was used as a base system to test the effect of varying levels of shear on the resulting viscosity and stability of the compositions. The thickener and the solvent were heated to 75~C in separate CO~ . The solvent was added to the çmlllcifiers rapidly and the composition mixed as des~;libed below:

A hand shaken for less than 1 minute B hand shaken for less than 1 n~inute, sealed and placed on a roller for 4 hours at 50 rpm C stirred 20 minutes at low speed with an overhead stirrer D 1~ 6~ ~ for 4 minutes, sealed and allowed to sit E ~ ~ ' for 2 minutes, stirred 10 minutes at low speed with an ~._,h~d stirrer F ~ for I minute, stirred 10 minutes at low speed with an u.~ ' - ' stiner G ~ ~t, i for 4 minutes, stirred 20 minutes at low speed with an o.~ ~ - - ' stirrer H ~ for 4 minutes, placed on a roller for 3.2S hours at 50 rpm homo~ for 4 minutes, placed on a roller for 50 minutes at 50 rpm A wide variety of concictencies resulted as indicated below:

Viscosity Stability Formul Appearance (cps) (% separation) A white, peal escelll, crystallineregions 7,400 64 B opaque wh te cream 1,290 0 C opaque, pearlescent, cohesive 60,700 0 D bluish, ll~ls~ enl, pearlescent, 27,600 0 cohesive E opaque, pearescent, cohesve 81,200 0 F op~que, pear escent, cohes ve 85,500 0 G whte, opaque, pearlescent, cohesive 61,700 0 H blushopaque, not cohesive 995 0 * 27,000 0 * App~ce not recorded The results in~iic~te that for this thickener system the intensity and 10 degree of mixing have an affect on the resultant product. Both too little mixing (Pormula A) and too much mixing (Formula H) had deleterious affects on the viscosity. A prerelled method of mixing is a coll-binaLion of brief (1-2 minutes) high shear homog-oni7~ion followed by overhead stirring for 10 minutes (Formulae E
and F).

ExamPle 5: Effect of Added Polymers This eY~mrle investig~ted the effects of adding various polymers ((1) polymers cG~ ;ng pendant alkyl groups and (2) linear and soluble in the solvent 5 and (3) c-~,s~ ed and swellable in the solvent) to a thir~ner system. The polymers used were: -(1) Crodacel QS (Croda, Inc. of Pa~;ppa,ly, New Jersey)- Stearyl~iimoniun hydroxypropyloxyethyl cç~ ose 10 (2) Quatrisoft LM-200 (Amerchol Corp. Edison, New Jersey) Lauryldi.. onium modified hydroxyethylcellulose (CTFA
Polyquaternium 24) (3) Salcare 96 (Allied Colloids of Sufolk, New Jersey), polymethacryloyloxyethyl trimethyla-,..,-olul~m chloride (CTFA
Polyquaternium 37) The polymers were added to the formlll~tion~ at levels of 0.1, 0.25, 0.37, 0.5 and 0.75% by weight accord;l-g to the following table:

Formula 0.11 0.25 1 0.37 1 0.50 1 0.75 Component Formu a Number Anount (~ram~ ) Montanov 68 2.0 2.0 2.0 2.0 2.0 Brij 76 0.5 0.5 0.5 0.5 0.5 Polymer 0.05 0.125 0.185 0.25 0.37 Solvent 47.45 47.37 47.32 47.25 47.12 68:32 The formulations were prepared as in Example 1 except the polymers were added to the solvent (68:32 ethanol:water by weight) prior to mixing. Note that formula number refers to weight percent polymer. If the polymer was supplied 25 in water, the water in the solvent system was corrected to reflect the exact formulation shown above. The results are shown below:

~6-Polymer Concentration Vi wiily(cps) (weight %) Polymer Polymeradded added Before high Post high shear shear Initial time 48 hours None ~ 3700 3700 Crodacel QS (1) 0.1 <500 ------- ---- -0.25 22000 --- -- - ----0.50 292000 178000 231000 0.75 152000 42500 93000 Quatrisoft LM-200 (2) 0.1 <500 ------- -------0.25 62000 32900 14700 0.37 31000 -------0.50 <500 Salcare (3) 0.1 1550 ------- -------0.25 1500 ---------- ----------0.37 155000 -----0.50 296000 ------- --- --The results indicate that Crodacel QS with pendant stearyl groups has a synergistic effect on the viscosity of the composition. This is evident since the 5 polymer itself contributes little thic~ening Crodacel QS is supplied as a 20%
aqueous solution and at concentrations under 1% by weight the viscosity ofthis polymer in 68:32 ethanol:water is less than 50cps. It is believed that this polymer ~csoci~tes with the thickener system in the formulation. The Quatrisoft polymer also contributed to thic~ning the forrnulations. The Crodacel QS and Quatrisoft 10 polymer forrnulations with the peak viscosity were prepared again except that the polymer was added to the thickener system after the composition was p~ epared and cooled to room te,l,pe.~tllre. Even under these conditions the polymer cQnl~;ni~g formulation had a higher viscosity than the formulation without the polymer. A
pre~"ed method of pl ep~h-g the formulations is adding the polymer to the hot 15 solvent before adding the thickener system so that the polymer and çmllicifiers can interact while above the melt temperature. The Crodacel formulations were also found to be stable, showing no separation.

~7-EsamPle 6: Effect of Added Emollients A series of wax, oil occlusive emollients and hllmect~nt type çmolli.ont~ were added to a thickener system to evaluate the effect on viscosity.
Each emollient was added to two formulations shown below:

Formula Component A ¦ B
Amount (~rams) Montanov 68 4 1.8 Brij 76 2 0.45 Croadcel QS (20% solution in water) 0 1.13 Ethanol:water 68:32 by weight 90.3 40 Emollient 3.7 1.7 The procedure of Example 1 was used to prepare the form.ll~tiom except emQlli~nts were either added to the hot solvent or the thiç1~ner system prior to mixing. Glycerine and Qu~mect~nt were added to the solvent. Other emollients 10 were added to the thickener system. The viscosity results are shown below:

~8-EmollientName ChemicalDescription Vi ccsit~(cps) A B
Bemel Ester 20141 octyldodecyl myristate 12,900 39,000 Bernel Citmol 3201 troctyldodecyl citrate 15,600 168,000 LipovolMOS 1302 trdecylstearateand 28,000 39,000 tridecyltrim~llit~te and ~irç
hPx~c~ ate Fitoderm3 Squalane 39,200 93,750 DC3444 cyclomethicone <100 2,700 Jarcol I-165 2-hexyldecanol <50* 59,100(0.5 wt%) 2,900 (1 wt%) Lexol PG 8656 propyleneglycol <50 dicaprylate/dicaprate Glycerin glycerol 28,600 274,000 Qus.. e.,1s.. ~1 AM50' 6-(N-acetylamino)~- 61,000 141,000 oxahexyll.i~,~elhyl~ ,ol~ium chloride Astorwax OK 2368 paraffin wax 39,000 I Bernel Chemical Co., Inc., Englewood, N.J.
2 Lipo Ch~m - -l Paterson, NJ.
3 Hispano Quimica S.A. - Quimica Organica, Barcelona, Spain.
4 Dow Corning, Midland, MI.
5 5 Vista Chemical Co., Lisle, IL.

6 Inolex Chemical Co., Phil~delphi~ PA
~ Brooks Industries Inc., South Plainfield, NJ.
8 AstorWax, Doravilla, GA.
10 ~ Formula A was completely solubilized. Therefore, this emollient was added to formula B at the reduced levels in~ic~ted This example shows that some emollients affect final viscosity of the composition. ~m..ec~ which are soluble in the system appear to have much less 15 effect, such as glycerin. The greatest viscosity reduction appears due to adding emollients with bl~ ched chain hydrocarbons (e.g., Jarcol I-16).

E~ample 7: Effect of sddition of Borate ~on In this example sodium borate was added to a premade 20 alkylpolyglucoside thickener composition. It is believed that the borate ion ~ associates with ~di~cçnt polyglucose hydrophilic head groups to hold them in the "micelle" structure thus elevating the melt telllpe,~ re.

7 PCTrUS96/08924 A solution of sodium borate in water was added to a concentration of 0.7% by weight to the formulation of Example 6A co..l~ining Fitoderm squ~l~n~The resultin~ formulation with sodium borate was visibly thicker with a higher melt te~llpc~alllre. The sample without borate melted rapidly when diclJen~ed into the 5 palm of a hand. The sample with borate did not melt when di~ nced into the hand.
To evaluate the effect of borate ion at dillere.ll pH values, 10.21 grams boric acid was added to 160 grams distilled water. Using a pH meter sodiumborate was added while stirring until a pH of S was reached (0.33 grams sodium borate). A 57 gram sample was removed. To the re ..~il.;.~g solvtion was added sodium borate to a pH of 6.0 (1.6 grams sodium borate). Again a 57 gram sample was removed and to the r .~ inp solution was added 1.94 grams sodium borate to reach a pH of 7Ø These three solutions were added to the following form.ll~tion Component Concentration (wei~ht percent) Montanov 68 4 Brij 76 Crodacel QS (20% solution in water) 2.5 Ethanol/water 68:32 92.5 The base formulation was pl epa, ed accol-dh~g to Example 1 with the Crodacel QS added to the solvent system prior to mixing. The borate solutions were added to yield the weight percent borate shown in the table below after thethir~enrr system had cooled to room temperature. The following observations and melt te",l)e,al~lres were recorded:

Borate Soln pH wt % C c~ Tm (~C) Boron None-CONTROL 0 Stable <31 0.02 st~ble and thicl~.er th~l con-rol 31 0.~ t I c cer than p~-~ 5 w t 1 0.0~% Borate 3~
O.i~ tlccerthanp- 5wtl0.0~Borate 3~.5 O. 2 slnlar-opHSwtl(~.08E-~rate ~ ~.S,c39 6 0.0'~ ;,y.~ ;, s, not as tl cc as p - ' aoaog <:
6 0.0~ syneres s, not as th c ~ as p = ' ana og 31 -: 4 6 0.0 syneres s, not as t 1 c c as p~-~ S ana og : -34 6 0.1 S~ ,S ~, not as tl c c as pH 5 ana og ~ '.' 7 0.014 more phase s~ iol~ than pH 6 <: 1 analog, no thi~L~
7 0.04 more phase separation than pH 6 <31 analog, no thirL tonin~
7 0.07 more phase separation than pH 6 31 analog, no thi~n~
7 0.10 more phase separation than pH 6 31 analog, no ~ rL~

The results show that adding borate ion to the composition increases the melt telllpel~ re. This is more pronounced at lower pH values.
s E~ample 8: Effect of ~tl~ ol Concentration on Melt Temperature;
Formulations co..~ ,;"g 7% Montanov 68, 1.76% Brij 76, 0.5%
Crodacel QS polymer (on a solids basis)were plepared in accordance with Example 5. For each formulation the percent solvent was held constant at 90.74% but the ratio of ethanol:water was varied from 50:50 to 68:32. The melt temperature was measured as described above.

Solvent ratio Melt Temp Ethanol:water (~C) 50:50 40 55:45 38.5 60:40 36 64:36 36 68:32 33 The results illustrate that as the alcohol:water ratio is increased, the melt te",l)e, alLlre decreases for this thickener system.

E~smple 9: Antimicrobial Efficacy of Compositions Containing Chlorhexidine Gluconate The following th~ ener systems were produced with and without chlorh~xi~ine gluconate (CHG) to determine if the CHG is effectively delivered in a thiclrçner system. The borate pH S solution from Example 7 was used.

o ~ -- ~ o~
-- o o o _ _ o ~ ~ ~, o~ ~ o _ U~

X o X V~
t' -- ~ -- ~ ,_ oo o o o o o _ V~ ~
~: ~ ~ ~ -- o '~
,&
o, ~o o o o o _ o U~
V'~
V~ ~ o _ t ~ X ~
~r o o o --o o ~

t~ oo o ~o U') o o 3 .~ _ x ~o ct m ~~ ~

E E F? o c,c ~ ,3 c c The ~inimnm Inhibitory Conce.,ll alion (~C) for both E Coli and S
Aureus was dete..~ ed accordi..g to the test methods outlined above and is reported in the table below MIC (,l~/ml) Sample E. coli S. aureus >256 >25611g/ml 3 >256 >256 >256 >256 7 >256 >256 9 >256 >256 0 5%CHGstd 4 4 Hibiclens* 4 4 *4% w/v CHG antimicrobial soap sold by Stuart Pha,~ ce~ltic~le The results show that none of the components of this forrnulation of the invention inactivate the CHG
~0 Example 11: A Presurgical Antimicrobial ~Iand Lotion Using an Alk~ l~,ol~gl~.coside Containing Thickener System The following formulation was prepared using the procedure of Example 6:

Component Wt. %
Montanov 68 4.0 Brij 76 1.0 ~en~mi~e B o.5 LipovolMOS 130 1.5 Fitoderm 2.3 350ctk po ydi,l,~ l ,yl siloxane (Carbide L45/350) 0.50 Cro'-acel Q~ (20% solution in water) 2.5 NaCI (2% in water)* 2.5 Ethanol 59.3 Water 25.9 *Sodium chloride was added at a level of 0.05% to mimic the ionic S~ glh of 0.5% CHG.

The resl-ltin~ formulation had an ethanol:water ratio of 68:32. This 5 formulation was applied to hands repeatedly throughout the day by several volunteers. Hands were washed with Ivory soap between applications. The feel of the lotion was well received and skin condition was ~ h~ed E~ample 12: Alh~lpol~ lucoside/Polyethoxylated alkyl alcohoVEster of Short Chain AlcohoVAmine Oxide/Quaternary Amine Thickener Systems The following compositions were p, e~ d by heating separately the solvent (alcohol and water) and the thickener system to 70~C. The solvent was rapidly added to the thiclren~r system and homogenized on a Silverson L4R
15 homogenizer. This was followed by 10 minutes of stirring with an overhead inverted "T" paddle stirrer with the glass container immersed in a 10-15~C water bath.
Co",posilions A-C were mixed for 10 minutes while C and D were mixed for 4 and 5min~tes respectively. The compositions were then cooled to allow the çm~ ifiers to solidify.

WO 97/00667 PCl'tUS96/08924 Co.. -~)ollenl A ¦ B ¦ C ¦ D ¦ E ¦ F ¦ G
Amount (~r ms) ~nt~nov 68 1.2 1.2 1.2 3.2 3.2 1 80¦ 1 80 Brij 76 0.3 0.3 0.3 0.8 0.8 0.45 0.45 Il~c.o~ e oxide 0.5 0.75 1.0 B30P*(30% solution in water) Nikkol CA-2580~* 0.18 0.35 Incroquat DMB- 0.50 0.50 90*~**(90% in 10%
ethano1) Lanette 22 0.65 1.3 . 9022*** 0.6 0.6 0.6 1.6 1.6 0.23 68:32Ethanol/water 27.40 27.15 26.90 73.57 72.57 40.4540.23 * In.;,u,...ne oxide B-30P = behçn~mine oxide available from Croda Inc., P~u~ippal.y, NJ
** Nikkol CA-2580 = Behenyltrimethylammonium Chloride, Barnet Products Corp., Paterson, NJ
*** Kemester 9022 = methyl behenate, Witco, Humko Chemical Div. Memphis TN
**** Incroquat DBM-90 = Dibehenyldimethylammonium methosl-lf~te available from Croda Inc., Pa. sipl)any, NJ
Compositions A, B, and C were viscûus creams with little elasticity.
Visually, sample C was more viscous than B which was more viscous than A. This shows that the amine oxide contributed to the viscosity of the compositions.
Compositions D and E were very viscous and quite elastic in nature. Composition E
15 was significantly thicker. This shows that this quaternary amine contributed to a more elastic composition. Samples F and G were opaque white creams of good con~i~tenCy. Sample G was more viscous than Sample F. Sample F had some s~neresis.
The melting temperature (Tm) of the compositions was measured 20 according to the protocol outlined above. The results are shown below:

-s6-Composition A B C D E F G
Tm(~C) 37-39 39 39 39 42 38 38 Heat cycle * HS HS HS HS HS HS HS

~ Once the s~ ples were melted, they were allowed to very slowly cool to room tel"pc~al~lre by simply turning offthe water bath. The time to cool was several hours. The samples were judged as heat stable (HS) if macroscopically they appe~ed 5 the same as the original sample.

Example 13: Long Chain Alk~l~ol~lucoside/Polyetho~l&t~d allyl alcohoUQuaternary Amine Thickener System A series of 10 formulations were prepared using a three component 10 mixture design with the total emulsifier level fixed at 2% by weight. The following conce"l,~lion ranges were investigated using a solvent ratio of 68:32 ethanol:water further co~ 0.5% by weight CHG.

F.m~ ifier Percent by weight Eassi 624MP 0.25 - 1.5% by weight Nikkol BB5 0.25 - 1.5 Incroquat DBM-90 0.25 - 1.5 Eassi 624MP is an alkylpolyglucoside prepared from an alcohol feed stock of 92% by weight behenyl alcohol and was obtained from Seppic Inc., Fairfield, NJ. The product had a melting point of 83~C and a 5% aqueous solution had a pH of 6.4. Each formulation was prepaled by adding 49 grams solvent at 80~C to 2 gramsth:-~Pnf~r system at 80~C followed by 45 seconds of homogenization followed by 320 minlltes of overhead mixing while immersed in a 15~C water bath. The samples were subsequ~ntly diluted to 2% solids by adding 49 grams solvent mixture. Each composition was subsequently tested for viscosity and Tm. The viscosities of theres.ll~ing formulations ranged from less than 165,000 cps to 309,000 cps. Examples of several pl~r~lled formulations appear below:

wo 97/00667 Pcr/uss6/08924 S~mple Component A ¦ B¦ C ¦ D ¦ E ¦ F
Amount (~r~.ns) Eassi 624MP 1.' 1.08 0.25 0.6;. 0. '5 0 7 NiklcolBB5 0.25 0.46 1.5 0.6 0. ~ 0."~
I.. wu.~t DBM 90(90~/O) 0. '5 0.46 0.25 0.66 0."~ 0. '-Viscosity (cps) 309,000 192 000 175,000 227 000 252 000 220 000 Tm (~C) >57~C 52-57 52 52-57 44 52-57 The results show that the behenylpolyglucoside ;ncf ases the melt t~ lpc~alllre~ Co"~a,ing the melt te"~pe~ res ofthis eY~mrle with those of Fx~mple 12F shows that h~cl ~as;ng the chain length of the hydrophobes in the 5 thirlrener system i"c~ t;ases the Tm. The thickener system of the formulations in this p'e produce homogenous viscous creams with varying ratios ofthe em~.l.cifi~rs.

E~ample 14: Disinfectant Hand Lotion based on Alk~ Ipol~ .coside /Polyetho~ylated alkyl alcohoUQuaternary Amine Thickener System Dish~;lalll hand creams/lotions were prepaled based on the thi~L f~ner system of Example 13F. The compositions are shown below:

Co .- A ¦ B
Amount (~rarns) .~assi 624MP 0.88 0."~
~iklcol BBS 0.8~ 0."~
,~"~ DBM 90(90% solution in ethanol) -~.2~ 0.~.
ilwet 7001~ (75% solution in water) .3 DC3441 '.00 2.
Proce~l 10~ 2.0 Macol 30 "" 1.00 Arcol PPC--725~*~ 2.00 2.00 Bemel Ester ''014 2.00 P uronic P~*~ 0.50 6~:32 e~ano :water 91 89 *Silwet 7001 = a methyl termin~ted polyether pendant silicone copolyol having a polyethylene oxide/polypropylene oxide ratio of 40/60 and a molecular weight of 20,000 available from OSI Speci~lties Inc.
5 **Procetyl S0 = PPG-50 cetyl ether, Croda Inc.
***Arcol PPa725 = polypropylene glycol having a molecular weight of appro~ lalely 750, Arco Chemical Co.
****Pluronic P-65 = polyethylene oxide capped polypropylene oxide having a EO/PO mole ratio of 1 and a molecular weight of appro~"~ately 3400 available from 10 BASF Wyandotte Corp. P~ippa"y, NJ.
"'Macol 30P = PPG-30 cetyl ether, PPG Industries Inc., Mazer Ch~mic~l, Gurnee, m.
'DC344 = D4, D5, cyclodimethicone available from Dow Corning, Midland, MI.

The compositions were prepal ed by heating the solvent and Silwet to 75~C in one conlainer and heating the le...~ components to 75~C in a second co"lainer. The solvent was rapidly added to the emulsifiers/emollients followed by 45 seconds of homogenization with no subsequent mixing. Both formulae had a nice feel when 2ml was applied to the hands and rubbed in the skin. Formula B was a little20 more appealing due to a better hand feel. Tm was measured as 48~C for A and 45.5~C for B.

Example 15: Polyglycerol Ester Containing Thickener Systems The formulations for Example 15 (as described in the table below) 25 were prepared by heating the thirl~ener system and the solvent in separate jars to 75~C, rapidly adding the solvent to the thickeners, shaking vigorously, and stirring with an overhead stirrer for 10 mim~tes while immersed in a 10-1 5~C water bath. The Tm was ~lleasuled as described above.

Sample Component Ch ~~'ne~ lion A ¦ B ¦ C
Amount(~runs) Decaglyn l-S decagl~ P~rate, 1.3S
Barnet of Paterson, NJ
Hexaglyn l-S hexaglyc~.vl~... o~o,~.a~, 1.35 Barnet of Paterson, NJ
Tetraglyn l-S tetragl~c~.u~.. o ~c"~~-.ate, 1.35 Barnet of Pdte.~n, NJ
Brij 76 Steareth-10 0.23 0.23 0.23 Lanette 22 3ehenyl alcohol Ethanol:water 42.98 42.98 42.98 68:32 Tm(~C) ¦ ¦44 ¦38.5 ¦38.5 The samples were tested for stability. Samples A, B and C produced stable compositions of varying viscosity. Visual observation showed that sample A
had a higher viscosity than B which was higher than C. A longer polyglycerol chain length is plere.led in this thickener system and even though the longer chain polyglycerol çm~ ifier is expected to be more soluble in the solvent system, it increased the Tm ofthe formulation.

Esample 16: More Polyglycerol Ester Containing Thickener Systems The following compositions were prepared as described in Example 15.

W O 97/00667 PCTrUS96/08924 Sample Cl .~ I A ¦ B
Aunount(~ms) rXxa~lynl-S
Poly~dolO-l-S~ 1.5 1.5 Bnj76 0.5 0.5 ~~nene22 _anenc18 ~ nc,., DBM90 0.56 0.38 C~ ~ 9022 .~u...,li~l~lPM3~
A~IP'G~25~* ~.0 Fr~ 50 '.0 E~no/water68:32 47.44 ~3.63 Tm(~C) ¦39~1 ¦4014 *Polyaldo 10-1-S = decaglycerolmonostearate, Lonza of Fairlawn, NJ.
**Plu~ islyl PM-3 = PPG-3 myristyl ether, Crûda of P~ip~ r, NJ.
***Arcol PPG~25 = polypropylene glycol, MW = approximalely 450, Arcol S Ch~n-:csl Co.

Samples A and B were homogenous viscous tr~n~ cent almost gel-like compositions. Sample B had a fairly nice feel but was a little tacky.

10 E~ample 17: Polyglycerol ester/Amine Oxide/Quaternary Amine Thickener Systems The following compositions were prepart;d as described in Example 15. The viscosity (Tm) was measured for each sample.

WO 97t00667 PCTrUS96/08924 Sample Component A ¦ B ¦ C ¦ D
Amour t (~rams) Polyaldo 10-1-S 1.2 0.9 0.6 0.3 Incron~ine Oxide 1330P(30% 1.0 2 0 3.0 4.0 solution in water) Incroquat DBM-90 (90% solution 0.28 0.28 0.28 0.28 in ethanol) Ethanol:water 68:32 47.5 46.8 46.1 45.4 Viscosity (cps) 530,000 105,000 146,000 75,000 Tm (~C) 40 40 40 37 The samples were allowed to cool after melting All samples produced tr~ns!ucent gel-like compositions of acceptable viscosity and melt temperature Samples C and D returned to a uniform appearance after heating aboveS the melt tel.lpe.~ re and allowing to slowly cool F~srlpl~ 18: Decaglyceroltetrabehenate Containing Thickener System The following compositions were prepared by heating the thickener system and solvent in separate jars to 80~C, rapidly adding the solvent to the thicl~en~r~ homogçni7ing for 20 seconds, and stirring with an overhead stirrer for 10 m;m~tçs while i----n~ ed in a 10-15~C water bath The Tm and viscosity were ~--eas.ll-ed for some of the samples Sam le C . A ¦ B ¦ C ¦ D fE ¦ F ¦ G ¦ H Amount 'grams) Kemester 9022 0.8 0.60 0.40 0.20 ~ Oxide B30P 2.67 2.0 1.33 0.67 (30% solution in w ter) Dcca~ r~ t~ 0.20 0.40 0.60 0.80 0.20 0.40 0.60 0.80 Ethanol:water 68:3~ 48.72 48.72 48.72 48.7246.86 47.32 47.79 48.26 Tm(~C) ¦ 49 1 ~ 39 ¦ 39 ¦--Viscosity(cps) 1 135,000 1 ----- I ----- I ------ I 8.500 1 6,500 1 6,700 1 10~00 W O 97/00667 PCT~US96/08924 Samples B-D produced homogenous compositions of low viscosity.
Sarnple A was an opaque viscous cream with a fairly high melt telllp~lalLlre. S~mp'~s E-H were lower in viscosity and melt temperature than Sample A.

5 E~ample 19: Ester/Amine Oxide/ Quaternary Amine Thickener Systems:
The following compositions were prepared using the procedure outlined in Example 15.
Sam le C~ . A¦ B fc I D
Amount ~rams) - Oxide B30P(30% solution in w ater) 2.0 2.0 2.0 2.0 ol CA-258~ (85% solution in water) 0.29 0.17 ulllnCBB;g---- (36.5%solution in water) 0.68 1.37 ELlano :water6r:32 46.81 46.93 ELlano 31.4230.82 water 15.014.91 Tm(~C) ~ 49 1 _ Samples A and B did not produce stable homogenous compositions.
10 Composition C and D produced viscous compositions but composition D appeared non-uniform. The melt temperature of Composition C was quite high.

E~ample 20: Amine Oxide/Ester/ Quaternary Amine Thickener System A series of 18 formulations were prepared using a three component mixture design. The total thickener level varied from 2.45 to 4.55% by weight. The following conce"L~alion ranges were investigated using a solvent ratio of 68:32 ethanol:water.

Component Percent by weight Inclo",;ne Oxide B30P 0.80 - 1.87 K~mester 9022 1.40 - 2.47 IncroquatDBM-90 0.05- 0.92 The compositions were prepal ed by heating the thickener system and the solvent in separate jars to 75~C, rapidly adding the solvent to the eml~lcifi~
shaking vigorously, and stirring with an overhead stirrer for 5 mimltes while il""le.~ed in a 10-15~C water bath. The melt tel~pe~lure (Tm), viscosity and S stability were measured as described above. All ratios produced stable compositions having a viscosity range of 10 000-270 000cps and a Tm of 45~7~C. Fl~cticity wasmeasured by gently stirring the sample and was judged on a scale of 1-5 where 5 was a very stringy composition and I was viscous but not elastic. A few of the compositions prepal ed are shown below:

Cl -'- --C~ ~ A ¦ B ¦ C ¦ D ¦ E
Amoun. (gran.s' ~-'.' 9022 1.17 1.43 1.1- .17 1.17 L.~ Oxide B30P(30% solution in 2.6 3.47 4.06 .14 2.60water) 1 ~t DBM90 (90% solution in ethanol) 0.60 0.33 0.30 0.33 0.05Ethanol:water 68:32 60.63 59.45 59.45 62.36 61.18 T~(~C) 47 45 45 46 45 ~ SCosty(cps) 280,000 270,000 270,000 250,000 30,000 E astic ty (1-5) 2 4.5 4 1 5 The results in~ic~te that this thickener system produces stable compositions with varying ratios of emulsifiers but that the physical p,ope, lies of the compositions vary widely. Composition D is a p,efelled formulation since it is high 15 in viscosity at low total solids content (2.83%), has very little elasticity and a high melt tt",pt~ure.
The following disinfectant hand lotion was produced using the thickener system and the procedure of Example 14:

Component Amount (grams) ~mestçr 9022 0.72 Incro.,.. ne Oxide B30P (30% solution in water) 1.48 Incroquat DBM90 (90% solution in ethanol) 0.10 ~ Pluroric P65 0.25 Berne Ester2014 1.00 Maco CA30P 0.50 PPG725 1.00 DC344 1.10 Silwet 7001 0.70 68:32 eth~nol water 43.28 This composition was stable with a nice viscosity and a Tm of 41 ~C.

E~ample 21: Allyl AlcohoVQuaternary Amine Thickener System The following formulations were prepared using Lanette 22 (Henkel Corp of Ambler, PA), Behenyl Alcohol Nikkol CA-2580 (Barnet Products Corp., Paterson, NJ), Behenyltrimethyl~...~.onium Chloride Composition Component A ¦ B ¦ C
Amount (~rams) Nikkol CA-2580 0.59 0.59 0.44 Lanette 22 1.5 2.00 1.63 68:32 Ethanol:water 47.91 47.41 47.93 The compositions were p.epaled by separately heating the solvent and the thickener system to 65-70~C. The solvent was rapidly added to the thi~ onçr system followed by stirring with an overhead paddle stirrer with the glass conlail1er immersed in a 10~C water bath. Each composition was mixed for 4.5 minutes after which the compositions cooled sufficiently for the emulsifiers to solidify.
All three compositions were viscoelastic. The samples appeared ~ pearlescent with macroscopically obvious crystalline regions. The crystals appealed macroscopically lamellar in nature. A small amount of syneresis was seen on st~ntiing -6s-WO 97/00667 PCTrUS96/08924 at 23~C overnight. The Tm of sarnple C was appro~ul,lately 47~C. (The sample didnot melt uni~llllly and even at 47~C still had some solid regions.) E~ample 22: Alkyl AlcoholtEstertQuaternary Amine Thickener Systems S A series of 10 formulations were prepared using a three cGlllpone mixture design. The total thickener system level was held cohalanl at 2.00% by weight. The following concentration ranges were investig~ted using a solvent ratio of 68:32 eth~nol water cont~ining 0.5% by weight CHG:

Coll.l)one.. l Percent by weight Lanette 22 0.25 - 1.25 ICçmester 9022 0.50 - 1.50 Incroquat DBM-90 0.25 - 1.25 The compositions were pl cpared by heating the thir~nçr system and the solvent in separate jars to 75~C, rapidly adding the solvent to the thir~ner, homogenizing for 40 seconds on a Silverson L4R homogenizer at maximum speed, and stirring with an overhead stirrer for 5 minutes while immersed in a 10-15~C water 15 bath. The Tm, viscosity and stability were measured. Only select ratios produced high viscosity stable compositions having a viscosity range of 76,000-274,000 cps and a Tm of 47-53~C. Stability was measured according to Example 1. Several of the formulations are shown below:

W O 97/00667 PCTrUS96/08924 Sample Component A ¦ B ¦ C ¦ D ¦ E
Per.ent by w~i~ht ~--.. P,I~r 9022 1.50 0.50 1.00 0.50 1~.67 - T ~nette 22 0.25 0.25 0.75 1.25 0.92 Il~woqudt DBM90 0.25 1.25 0.25 0.25 0.42 Ethanol:water 68:32 (0.5%CHG) 98 98 98 98 98 Tm (~C) 47 49 51 52 53 Viscosity (cps) 76000 76000 250000 274000 125000 Stability (% Volume separation) <2 2 2 10 5 The results indicate that this thickener system produces stable compositions with varying ratios of emulsifiers but that the physical plopellies ofthe compositions differ considerably. Composition C is a particularly p.~re .ed 5 form~ tiQn since it has a high viscosity, high melt telnpe- ~ re, and little separation.
After 51~n~ing for 1-2 days at 23~C, all ofthe above formulae showed a small amount of s~ ;res,s, i.e. a small amount of clear low viscosity solvent phase separated on the top of the sample.

10 Example 23: Addition of an Allylene Alcohol Oleyl alcohol was incorporated into the formulation shown in Example 22C by adding it to the molten thickeners prior to mixing with the solvent. The composition is shown below:

Component: Amount (~rams) Lanette 22 0.38 Kemester 9022 0.50 Incroquat DBM90 0.14 Novol (oleyl alcohol, Croda) 0.20 Ethanol:water 68:32 48.78 A stable quite viscous gel-like composition resulted. The Tm was measured as 50~C. The stability was measured as 5%.

E~ample 24: Addition of Dialkoxy Dimethicone and Polyether-Polysilo~ane Col~ol~-..er~ for Enhanced Stability The compositions of Example 22 had very good viscosity, Tm, . nd stability propc~l;es but showed a slight arnount of syneresis on st~nrli~ Su".,is;..gl~, 5 adding a co...l-;nAl;on of dialkoxy dimethicone and polyether-polysiloxane copolymers ensured no syneresis and also provided a smooth non-waxy feel. The following system was prep~ed using the thickener ratios identified in Example 22C and the procedure of Example 22. The Abil wax2440 was heated with the em~.lcifiers while the Abil B88183 was heated in the solvent:
Base Systems Component Amount (~rams) Kçmestçr 9022 0.50 Lanette 22 0.38 Irc-oquat DBM90 (90% solution in ethanol) 0.14 Ab wax2440' 0.25 A~ B881832 (35% solution in water) 0.71 Ethanol:water 72:28 48.03 Tm (~C) l 47 ' Abil wax2440 = dibehenoxypolydiemthyl siloxane available from Goldsr.hmidt Chemical Corp., Hopewell, VA.
2 Abil B88183 = dimethicone copolyol having a EO/PO ratio of 77/23 and a viscosity in water at 35% solids at 25C of 95mm2/sec available from Goldsçhmidt Chemical 15 Corp., Hopewell, VA.

The system was stable and showed no signs of syneresis even after 13 days of room temperature storage. The melt temperature of the base formulation is reduced col..pared to that of Example 22C most likely due to the increase in the level 20 of ethanol in the solvent.
This formulation was evaluated for activity of CHG at O.S% by weight and was also used to prepare a hand lotion cont~ining numerous emollients by p-epa~i..g the following formulations:

W O 97/00667 PCT~US96/08924 Sample C- . ' I 1 2 1 3 1 4 1 5 1 6 17 18 ~ ~unt (~ram~) 9022 ~ .s~ " .
,anette 22 .~ ~ DBM90 (90% . ~ o. ~ ,. h sc I . ti ~ 1 ethanol) A~ 4i~ 0.75 0.38 0.75 0.3B
A~ '1 '3 (35% solution in 1.43 0.72 1.43 0.72 ~ ter) P wonic P65 yoeri ~
~ermo DIPS~ .1 .. .
~lacol CA30P .~
A~ PPG725 DC3~ ~ .- ~1 ~ .i .~
CHG scln (20% in water) 0.25 1.39 1.26 .~l~
Ethano :water68:32 97.97 51.21 95.79 48.1S 88.29 L' .''9 Ethano 6.8 6.77 Water 3.2 2.98 E. coli223MIC(Ilg/ml) >256 4 >256 2~ >256 2~ >256 4 S aureus 502 MIC (~Ig/ml >256 4 >256 2 >256 4 >256 4 Derrnol DIPS = diisopropyl seb~c~te available from Alzo Inc. Sayerville, NJ

A 0.5% CHG standard was also run and found to have an MIC of 4 5 for both bacterial strains. These results indicate that the thickener system does not interfere with the CHG activity and that the compositions have no inherent ~ntimiGrobial activity except due to the ethanol:water solvent system. Sample 7 had nice cosmetic properties.

10 E~ample 25: Repeat Application of a Preferred Eland Lotion Composition The following hand lotion composition was p.~pared as described in Exarnple 23.

Component Weight %
KeTnester 9022 1.0 Lanette 22 0.75 Ir c-oquat DBM90 (90% solution in ethanol) 0.28 A~ 2440 0.75 A -I 88183 (35% solution in water) 1.43 ~lyc~ 2.50 Dermo DIPS 1.00 Derrno 4892 1.00 Arcol PPG 725 2.00 Derrno G-7DI' 0.5 Ethano :water 68:32 88.29 Dermol G-7DI = glycereth-7-diisonon~no~te available from Alzo Inc.
Sayerville, NJ
2 Derrnol 489 = diethyleneglycol dioctanoate/diisonon~noate available from Alzo Inc. Sayerville, NJ

The formulation was first evaluated in tactile testing by applying 2rnl in the palm of one hand and rubbing the lotion thoroughly into both hands. This composition had good cosmetic properties. A panel of five volunteers then applied 10 the lotion as described eight times a day in appro~imately 1 hour intervals after first washing with water and Ivory liquid soap (Procter and Garnble, C;nçinn~ Ohio) and drying the hands thoroughly before each application. This was repeated for a total of 5 days and was conducted during the winter to exaggerate any potential drying effect.
The lotion was rated positively in all cosmetic categories surveyed inçludin~ overall 15 feel, lack of oiliness, moisturization, smoothness during application, and feel while washing. Expert grading was used to judge the condition ofthe skin. Using a 5 point scale: l=Very slightly scaly -occasional scale not necessarily uniformly distributed 2=Slightly Scaly -Scale in sulci and on plateaus. More visible scale that is more uniformly distributed 20 3= Scaly - Visible scale giving the overall appearance of the skin surface a whitish appearance. Definite upliP~ing of edges or scale-sections. Hand is rough to the touch.

W O 97/00667 PCTrUS96i'CB924 4=Scaly to very scaly- More scale and pronounced separation of scale edges from skin, although they may still be Iying flat on the skin surface. Some evidence of cracking in sulci and on plateaus. Some reddçning may appear.
5=Very scaly- excessive cracking of skin surface. Skin appears very irritated with S wide;"~ d reddçning The skin condition was evaluated initially and at the end of days 3 and 5 and results are shown in the table below.

Time Me~n Skin Ratin~* Standard Deviation Initial 2.6 0 93 Day 3 1.80 1.53 Day 5 1.60 0.77 10 *five subjects two hands each (n=10) The results intlicate that overall the skin condition significantly improved.

E~ample 26: Polyetlloxylated Alcohol/Ester/Quaternary Amine Thickener System The following thickener system compositions were prepared by heating the solvent and the thickener system separately to 75~C. The solvent wasadded to the thickener system and homogenized on a Silverson L4R at maximum speed for 45 seconds followed by stirring with an overhead paddle stirrer in a glass co~ er immersed in a 20~C water bath. Each composition was mixed for 3 minl-tes 20 and the compositions were cooled sufficiently to allow the thickeners to solidify.

WO 97/00667 PCT~US96/08924 C~ ;lion CL .~ A ¦B ¦C ¦D
Amount (~rams) -J~thox 4~01 0.18 0.35 0.53 0.70 ~nP,~Pr 9022 0.70 0.53 0.3~ 0.18 ~ uqua~ DBM-90(90% solution in eh~nol) 0.13 0.13 0.13 0.13 _thanol:water 70:30 49 00 49.00 49.00 49.00 Tm (~C) ¦ 47 ¦ 47-50 147-50 142 I Unithox 450 is a p~ hv~ ~ yl alcohol having an a~yl chain length of d~l~ 36 car~ons and nine units of ethylene oxide having a -- ~ weight of 2125 available from Petrolite Special~ Polymers Group, Tulsa, OK.

All four formulations formed viscous compositions. Formula B was more tr~ncl-lc~nt and gel-like than A. Formulation D appeared less viscous. The melt te",pe,~lures were higher at ratios of Unithox 450:~emeSter9022 Of 0.66 to 1.5 but were fairly high for all formulations.
Example 27: Polyethoxylated Alcohol/Ester/Quaternary Amine Thickener System The following thickener systems were prepared according to the procedure of Example 26:

Composition Component A ¦ B ¦ C ¦ D
Amount (~rams) Abil 2440 0.18 0.350.53 0.70 Kemester 9022 0.70 0.530.34 0.18 Incroquat DBM-90 0.13 0.130.13 0.13 Ethanol:water 68:32 49.00 49.00 49.00 49.00 Formulation A produced a stable thick creamy composition having a Tm Of4445OC Formulations B and C were quite low in viscosity and Formulation D showed almost no increase in viscosity.

Example 28: Alkylene Alcohol/Ester/Quaternary Amine Tl~icl~Pner System The following thir~ener systems were prep~red according to the procedure of Example 26 except that the composition was homogenized for or.ly 15 secontlc .
Formulation Component A ¦ B ¦ C ¦ D
Amount (grams) Novol 1.08 0.81 0.54 0.27 IC~mPst~r 9022 0.27 0.54 0.81 1.08 Incroquat DBM-90 0.25 0.25 0.25 0.25 Ethanol:water 60:40 43.40 43.40 43.40 43.40 Viscosity(cps) ¦ unstable ¦ low ¦ 125,000 ¦ 340,000 Formulation A was unstable and showed significant phase separation.
Formulation B was homogenous and had very low viscosity. Formulation C was a viscous cream but showed some syneresis on st~n~ing Formulation D was opaque 10 and gel-like with a high viscosity and showed only a slight amount of syneresis.

Example 29: Alkylene Alcohol/Ester/Amine Oxide Thickener System The following thickener systems were prepared according to the procedure of Example 28.

Formulation Component A ¦ B ¦ C ¦ D
Amount (grams) Novol 1.08 0.81 0.54 0.27 Kemester 9022 0.27 0.54 0.81 1.08 Incrom. ne Oxide B30P 1.80 1.80 1.80 1.80 Ethano :water 60:40 41.85 41.85 41.85 41.85 Viscosity(cps) 1 1,7501 15,700 1 40,800 1 65,400 Composition A was tr~nclucent fairly elastic and low in viscosity.
Composition B was tr~ncluc~nt, pearlescent, and fairly elastic but significantly more W O 97/00667 PC~rrUS96/08924 viscous then composition A. Compositions C and D were pearlescent, slightly opaque, and fairly elastic with higher viscosities.

Esample 30: Alkyl Phospholipid/Polyetho~ylated Alkyl Alcohol Thickener System The following thickener systems were prepared according to the procedure of Example 28.

F~
C~ A ¦ B ¦ C ¦ D ¦ E ¦ F ¦ G ¦ H
Amount (~rams) 1 SVI (35% 1.0~ 0.81 0.54 0.27 solution in water) Bch~ o~h~ 2.7 2.03 1.35 0.68 (4l~% solution in water) N~ ckol BB-5 0.27 0.54 0.81 1.08 0.27 0.54 0.81 1.08 Et lanol:water 60:40 43.65 43.65 43.65 43.65 Et lanol 25.72 25.84 25.96 26.07 Water 16.31 16.60 16.88 17.17 Viscosity (cps) <100 <100 6.170 4,590 <100 <100 6,300 29,400 Viscosity (cps) post CHG 9,000 12,400 6,400 37,200 Addition 10 l Phospholipid SV is a zwitterionic surfactant that is stearamidopropyl PG-dimmonium chloride phosphate (a stearyl derived phospholipid) also conS~ininP cetyl alcohol available from Mona Industries Inc. of Paterson, NJ.
2 Behenylphospholipid is a behenyl derived phospholipid similar in composition to Phospholipid SV.
Samples A ,B, E and F were uniform and stable but had low viscosity.
Samples C, D, G, and H were opaque and pearlescent with higher viscosity values.CHG was added as a 20% solution in water to a final concentration of 0.5% by weight to formulations C, D, G, and H. The viscosity was measured one day after 20 adding CHG. The results indicate that the thickener systems are tolerant to CHG
- addition and that addition of CHG may actually increase the viscosity for these systems. It should be noted that Phospholipid SV, like many single long chain quaternary amine-cont~ining surf~ct~nt~, is reported to have significant antimicrobial activity.

WO 97/00667 PCTrUS96/08924 Example 31: Alkyl BetainetPolyethoxylated Alkyl Alcohol Thickener System The following formulations systems were prepared according to the procedure of Example 28. After measuring the viscosity, CHG was added as a 20%
5 solution to a final concentration of 0.5% by weight. The viscosity was measured again one day later.

Formulation Component A ¦ B ¦ C ¦ D
Amount (~rams) Incrona.,. B40' (40% solution in water) 2.70 2.03 1.35 0.68 Nikkol BB-5 0.27 0.54 0.81 1.08 Ethanol:water 60:40 42.03 42.44 42.82 43.25 Viscosity (cps) 40,700 52,600 52,500 35,300 Viscosity (cps) post-CHG Addition 52,000 54,500 54,000 38,000 Incronam B-40 = behenyl betaine available from Croda Inc. of Parsippeny, NJ.
Formulation A and B were opaque with some elasticity.
Formulations C and D were similar but were more elastic. All formulations were homogenous after adding CHG and the CHG actually increased the viscosity of the formulations.

Example 32: Hydroxyfunctional Ester Containing Thickener Systems Behenyl Lactate was prepared by reacting methyl lactate (Aldrich Chemical Company, Inc. of Milwaukee, WI) with Lanette 22 (behenyl alcohol, 90%, Henkel Corp. of Ambler, PA) in a transesterification reaction according to the following method: 0.2 g sodium hydride (60% in mineral oil) was added to 32.6 grams Lanette 22 at 70~C in a 3-neck 250ml glass flask purged with nitrogen and inserted with overhead stirrer, Dean Stark trap, therrnometer, and condenser. To this was slowly added 9.4g of methyl lactate and the contents were slowly heated to 160~C and held at that temperature for one hour. At this temperature over 2ml ofmeth~nol was collected. The contents were heated to 200~C with a nitrogen sweep WO 97t00667 PCTAUS96/08924 to remove any volatile components. After appro~il,lately 15 minutes at 200~C thecorltent~ were cooled. Upon cooling the product cryst~lli7~d and had a melting point of approxim~tely 57~C.
The following th;~ on~r systems were prepared incl~lAine sllbseq~çnt 5 addition of CHG as described in Example 31.

W O 97/00667 PCTrUS96/08924 ~_ o ~ ~~ ~
_~ o -- e~ _ ~

O O ~t X ~ g~ O
O O 't ~ ~

~O O
-- O'-t -- ~
O O
et, O -- O

~ Y o o o ~t ~ ~

X ~ ~ ~0O~ O~
O O O ~t~ --X r~ t~ X~
~- ~ V X
-- O O ~

~ X ~ o ~
.~ o ~ ~~ _~
o _ ~ o~ .--v~ 8 o .~ X ~ ô ~ô
o o o o X
o o ~ _ o~

~ o o ~ ~ ~~ X

O --o' CL

~ m ~
~ Y~ .'' C

The results show that behenyl lactate is a useful çm~ ifier for the purposes of the present invention. Behenyl lactate forms homogenous high viscosity emulsions in a variety of systems over a broad range of thickener ratios. Although sample A was low in viscosity, Samples B-D formed very pearlescent viscoelastic 5 composition~ .c~mpl~- E-L formed very viscous gel-like compositions. The compositions are also stable to CHG addition.

Example 33: Alkylene MonoglyceridelEster/Amine O~ide thickener System The following thickener systems were prepared by heating separately 10 the solvent and the thickener system to 75~C. The solvent was added to the thickener system rapidly followed by homogenization on a Silverson L4R at maximum speed for 15 seconds followed by stirring with an overhead paddle stirrer in a glass container i~ ed in a 5-10~C water bath. Each composition was mixed for 3 minntes after which the composition cooled sufficiently for the emulsifiers to solidify.
15 The viscosity was measured as described above. To each sample was then added CHG as a 20% solution in water to a final concentration of 0.5% by weight. The CHG was mixed in well using a spatula and the sample was allowed to equilibrate for 24 hours. The viscosity was then measured again.
Composition Component A ¦ B ¦ C ¦ D
Amount (.~rams) Glycerol monoeurucate' 1.20 0.90 0.60 0.30 Kemester 9022 0.27 0.54 0.81 1.08 Incroquat DBM-90 0.25 0.25 0.25 0.25 Ethanol:water 60:40 43:28 43:31 43:34 43:37 Viscosity (cps) 630 10~,000 149,000 173,000 Viscosity (cps) post CHG 9,200 110,000 205,000 202,000 addition 20 ' sample obtained from Croda Inc. of Parsippeny, New Jersey and consisted of 90%
monoeurucate, 8% dieurucate and 2% trierucate by weight.

Composition A was bluish translucent but had a low viscosity.
Composition B was similar to A but much more viscous than Composition A.

Composition C was semi-opaque and even more viscous than Composition B.
Sample D was opaque white with a fairly high viscosity.

Example 34: V;SCG~ as a Function of Shear Rate The following eY~mrle illustrates the pseudoplastic rheology and shear sensitivity of the compositions of the present invention. The viscosity was measured as a function of shear rate using a Rheometrics Dyanamic Analyzer (RDA-II) with a 25mm cone/plate fixture with a cone angle of 0.1 rad at a temperature of 25~C.
Entrapped air was removed from the samples prior to testing by centrifugation. The viscosity was measured in steady shear by keeping the rate of rotation conslalll. This was done over a shear rate range of 0.06 - 40 per second. The samples used for this testing were p,epared according to Example 1, Sample A (Brij 78) and Example 32,Sample B. The following results were obtained:

Viscosity (cps) Shear Rate Ex. 1, Sample A Ex. 32, Sample B
Brookfield LVDV-I+ 294000 92500 0.06 Rheometrics 42000 7200 0.10 Rheome.rics 37000 5700 1.0 Rleometr cs 14000 2300 3.0 Rheometr .-s 3800 680 10.0 Rleometr cs 2100 420 40.0 Rleometr cs 720 140 The results in-iic~te that the viscosity is very shear sensitive. This allows the compositions to dispense well into the hand without running and yet allows the compositions to spread easily across the skin surface.

20 Example 35: Foam Formulation 90g of the formulation of Example 25 was charged to a glass pressure vessel at room temperature. To this was added 7g propane and 3g isobutane. The addition of the propellant resulted in a dramatic drop in viscosity. The viscosity appeared to be about the viscosity of water. The formulation appeared as a single çmulcified opaque white liquid. A~er sitting for several days the propellant formed a separate phase but was easily reem-llcified by .ch~king The formulation produced a white foam.

S Esample 36 This example demonstrates that monovalent salts of acids are useful as co-emlllcifi~rs in the present invention.
The samples were plepared accordh-g to the formulae outlined in the table below by placing all components in a 4-oz. jar. The jar was capped and heated 10 to 65~C until all components were dissolved. The jar was then swirled to mix the components, removed from the heat and allowed to cool to ambient te",pe~ re.
Viscosity measurements were taken as identified in the table. Separation tests were done as outlined in Example 3.

Sample A ¦ B
Component Amourt (grams) BB-5 0.96 0.96 Sodium Stearate 0.36 0.96 190 Ethanol 42.00 41.60 Deionized Water 16.70 16.50 Viscosity (cps) 5,9041 320,0002 % Separation (by Volume) 0 0 15 lMeasurements taken at ambient temperature using a Brookfield LVDV-I+
viscometer with a TC Heliopath Spindle at 0.3 rpm.
2Measure",e"ls taken at ambient temperature using a Brookfield LVDV-I+
viscometer with a TD Heliopath Spindle at 0.3 rpm.

While in accordance with the patent st~tutec description of the prere" ed weight fractions, processing conditions, and product usages have been provided, the scope of the invention is not intended to be limited thereto or thereby.
Various modifications and alterations ofthe present invention will be appalen~ to those skilled in the art without departing from the scope and spirit of the present invention. The Examples described in this application are illustrative of the ~ossi~ ties of varying the type, quantity and ratio of composition as well as the methods for making formulations of the present invention.

Claims (16)

What is claimed is:

1. A composition comprising:
a) a lower alcohol and water in a weight ratio of about 35:65 to about 100:0;and b) a thickener system present in an amount of about 0.5% by weight to about 8% by weight, based on the total weight of the composition; wherein the thickener system comprises at least two solid emulsifiers, each in all amount of at least about 0.05% by weight, based on the total weight of the composition; wherein at least one emulsifier comprises:
(i) at least one hydrophobic group selected from the group of:
(A) an alkyl group of at least 16 carbon atoms; and (B) an alkenyl group of at least 16 carbon atoms; and (C) an aralkyl or an aralkenyl group of at least 20 carbon atoms; and (ii) at least one hydrophilic group selected from the group of:
(A) an amide group;
(B) a short chain ester of a long chain alcohol or acid, optionally substituted in available positions by hydroxyl groups;
(C) a polyglucoside group having 1- 10 glucose units;
(D) a polyglycerol ester group having 1-15 glycerol units;
(E) a secondary amine group;
(F) a tertiary amine group;
(G) a quaternary group;
(H) an anionic group;
(I) a zwitterionic group; and (J) combinations of these groups;
wherein the composition has a viscosity of at least about 4,000 centipoise at 23 °C in the absence of polymeric thickeners.

2. The composition of claim 1 wherein the second emulsifier comprises at least one emulsifier having:
(i) at least one hydrophobic group selected from the group of:
(A) an alkyl group of at least 16 carbon atoms;
(B) an alkenyl group of at least 16 carbon atoms; and (C) an aralkyl or an aralkenyl group of at least 20 carbon atoms;
and (ii) at least one hydrophilic group selected from the group of:
(A) an ethylene oxide- and/or propylene oxide-containing group, which is bonded to the hydrophobic group through an ether or ester bond and optionally terminated with an ester group;
(B) an alcohol group;
(C) an ester or ether group of a polyhydric alcohol or polyethoxylated derivative thereof;
(D) an ester group of sorbitan or polyethoxylated derivative thereof; and (E) combination of these groups.

3. The composition of claim 1 wherein the zwitterionic group has the formula:
-N+ (R")2(CHQ)xL' or o wherein:
each R" is independently hydrogen, an alkyl group, an alkenyl group, an alkyl carboxyl group, or an alkenyl carboxyl group, which alkyl or alkenyl groups are optionally substituted with N, O, or S atoms;
Q is hydrogen or hydroxyl;
x is 1 to 4; and L' is -CO2-, -OP(O)(O-)(O-M+), SO2O-, or -OSO2O- wherein:

M+ is a positively charged counterion present in a molar ratio necessary to achieve a net neutral charge on the emulsifier and is selected from the group of hydrogen, sodium, potassium, lithium, ammonium, calcium, magnesium, and N+R'4, where each R' is independently an alkyl group of 1 to 4 carbon atoms optionally substituted with N, O or S.

4. The composition of claims 1-3 which does not separate by more than about 10% by volume when centrifuged for 30 minutes at 2275 x g.

5. The composition of claims 1-4 wherein the hydrophobic and hydrophilic groups are selected to provide a thickener system having a weight average hydrophile/lipophile balance of 8 to 12.

6. The composition of claims 1-5 further comprising at least one emollient distinct from the thickener system.

7. The composition of claim 6 wherein the at least one emollient is in the form of a wax or a liquid.

8. The composition of claims 1-7 further comprising an antimicrobial agent distinct from the lower alcohol.

9. The composition of claim 8 wherein the antimicrobial agent is selected from the group of a chlorhexidine salt. iodine, a complexed form of iodine, parachlorometaxylenol, triclosan, ant mixtures thereof.

10. The composition of claim 1 wherein at least one emulsifier is selected from the group of an alkyl polyglucoside, an alkenyl polyglucoside, a short chain ester of a long chain alcohol, a short chain ester of a long chain acid, a polyglycerol ester, a quaternary amine, a tertiary amine and protonated salts thereof, an amine oxide, a zwitterionic compound, an alkyl amide, an alkenyl amide, an anionic compound, and mixtures thereof.

11. The composition of claim 2 wherein at least one emulsifier selected from the group of a poly(ethoxylated and/or propoxylated)alcohol, a poly(ethoxylated and/or propoxylated)ester. a derivative of a poly(ethoxylated and/or propoxylated)alcohol. a derivative of a poly(ethoxylated and/or propoxylated)ester, an alkyl alcohol, an alkenyl alcohol, an ester of a polyhydric alcohol, an ether of a polyhydric alcohol, an ester of a polyethoxylated terivative of a polyhytric alcohol, an ether of a polyethoxylated derivative of a polyhydric alcohol, a sorbitan fatty acid ester, a polyethoxylated derivative of a sorbitan fatty acid ester, and mixtures thereof.

12. The composition of claim 1 wherein the thickener system comprises a polycthoxylated alcohol, an alkyl or alkenyl alcohol, and a quaternary amine.

13. The composition of claim 1 wherein the thickener system comprises an alkyl polyglucoside, a polyethoxylated alcohol, and a quatemary amine.

14. A composition comprising:
a) a lower alcohol ant water in a weight ratio of about 35:65 to about 100:0;

/t l q i ~ ' s ' ! .~ t b) a thickener system present in an amount of about 0.5% by weight to about 8% by weight, based on the total weight of the composition; wherein the thickener system comprises at least two emulsifiers: each in an amount of at least about 0.05% by weight, based on the total weight of the composition;
wherein at least one emulsifier comprises:
(i) at least one hydrophobic group selected from the group of:
(A) an alkenyl group of at least 16 carbon atoms;
(B) an alkenyl group of at least 16 carbon atoms; and (C) an aralkyl or an aralkenyl group of at least 20 carbon atoms; and (ii) at least one hydrophilic group selected from the group of:
(A) an amide group;
(B) a short chain ester of a long chain alcohol or acid, optionally substituted in available positions by ~ groups;
(C) a polyglucoside group having 1-10 glucose units;
(D) a polyglycerol ester group having 1-15 glycerol units;
(E) a secondary amine group;
(F) a tertiary amine group;
(G) a quatemary amine group;
(II) an anionic group;
(I) a zwitterionic group; and (J) combinations of these groups; and wherein at least one emulsifier comprises:
(i) at least one hydrophobic group selected from the group of:
(A) an alkyl group of at least 16 carbon atoms;
(B) an alkenyl group of at least 16 carbon atoms; and (C) an aralkyl or an aralkenyl group oral least 20 carbon atoms; and (ii) at least one hydrophilic group selected from the group of:
(A) an ethylene oxide- and/or propylene oxide-containing group, which is bonded to the hydrophobic group through an ether or ester bond and optionally terminated with an ester group;
(B) an alcohol group;
(C) an ester or ether group of a polyhydric alcohol or polyethoxylated derivative thereof;
(D) an ester group of sorbitan or polyethoxylated derivative thereof; and (E) combinations of these groups; and c) an antimicrobial agent distinct from the lower alcohol.
wherein the composition has a melt temperature of greater than about 35°C and a viscosity of at least about 4.000 centipoise at 23°C.

15. A method of preparing a stable composition of claims 1, 2, or 14, the method comprising:
a) preparing the thickener system of claims 1, 2, or 14; and b) combining the thickener system with a solvent system at a temperature sufficient to melt the thickener system and form the composition.

16. The method of claim 15 wherein:
a) the step of preparing comprises heating the thickener system of claims 1, 2, or 14 to a temperature sufficient to melt it; and b) the step of combining comprises;
i) heating water to a temperature above the melt temperature of the the thickener system;

ii) combining the thickener system and the water; and iii) adding a lower alcohol to the thickener system and water to form the composition.

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