Note: Descriptions are shown in the official language in which they were submitted.
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ORAL CARE ULTRAMULSION BASED PRODUCTS
STJMMARY OF T~ ~VENTION
The present invention is directed to oral care ULTRAMULSIONTM based oral
care products, inr.lll-ling, too~ .Axl~c, treated flosses and dental stim~ tor~, interdental
coating substances, oral rinses, mouth/throat conditioning internal l~e.l.... t products,
and anti-gingivitis products. All of these lJlUdUCI~ are i,.,~,vved when an
5 ULTRAMULSIONTM dispersion cc)~ g silicone and a surf~rt~nt is used as taught
herein. ULTRAMULSIONTM is a l.,.~1,...A.k of WhiteHill Oral Technologies.
The ULTRAMULSIONTM dispersions of the present invention combine certain
rh~r~ct~ristics of ern~ inn~ with certain features of micro~n-ll~inn~ Like
con~ ional emulsions, they are two~phase systems CUlllpli~ g a silicone dispersed in
10 a contimlous, sllrf~rt~nt phase, wherein the silicone is insoluble in the :j... r~ t
Unlike conventional emulsions, but like microemulsions, these dispersions are stable.
Unlike microemulsions, but like conventional emulsions, mrrh~nir~l work is ,c.lui,cd
to form ULTRAMULSIONrM dispersions. Unlike microemulsions, but like
conventional emulsions, these ULTRAMULSION~M dispersions are not formed
15 spontaneously. Like conventional emulsions, the ULTRAMULSIONTM dispersions donot contain a cosolvent commnnly found in micro~mlll~i- n~ Of course, the
ULTRAMULSIONTM dispersions of the present invention can be easily dispersed in
various liquids such as water to obtain stable disp~ion~. These dispersions of
ULTRAMULSION~M dispersions in water have eYrP.llPnt utility in various non-oral
20 care products.
For the purposes of the present invention:
a. "stable" is defined as follows; a dispersion of the ULTRAMULSION~M
dispersion in water when subjected to contrifilging in a 100 G el,vi,.,l.."ent for 5
...;....~, less than about 10% by weight of the ULTRAM[JLSION~M dispersion
25 se~ cs from the cnntimlous water phase and/or a suhst~nti~l portion (i.e., >~0%) of
the dispersed phase resists separation. This latter dPfinition is particularly applicable
CA 02222407 1997-11-26
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--2--
to higher visco~ ilicr~n~ j -
b. "water-free" means that the ULTRAMULSION~ pprsinn of silicone and
snrf~rt~nt is ~ub~ lly free from water.
c. "solvent free" means that the UL~RAMULSION~ dispersion of silicone and
5 ~r,.- l;~ is ~ ."~ y free from co-solvents such as ethanol, isc ~lupdnol, and the
like.
d. '~orient~d~ means that the polar moieties of the "uncoiled"
polydimethylsiloxane in the ULTRAMULSIONTM dispersion are generally aligned in
one plane with the hydrophilic oil seeking moieti~c aligned in a second plane such as
illu~llalcd in Fig. 2.
e. "monolayer" means that the mnnom~lecular film of thc l L1~1~ULSlONTM
rli~p~ion of the present invention when dispersed in watcr i~ .~u ~d to tecth and
mouth ~ulLcc~ by secon-l~ry bonding force to form a su~ n~c c~tng th~eon.
As described above, one ~Icrellcd embodiment of the ~nt tn~entJon relates to
various oral care products co~ .g stable dispersions of cen~n high ~iscosity
on~c in certain ~u,rd~ , wherein:
a. the dispersed silicones, which are insoluble in said surfact~nt, are oriented by
the surfactant such that when dispersed in water they ar~ particulariy adept at forming
oriented co~ting~ on teeth and mouth ~ulrdces with enhanced su~st~- ti~ity, and
b. the particle size of the dispersed silicone is from bctueen about O.l and about
10 microns, with a particle size distribution such that from ~L~e~il about 80 and 95%
of the dispersed silicone is within this particle size range. In certain embo-lim~ontc,
bct~l 80-95% of two ~ p~ed ~ilirnnP~ is less than 1 - 2 microns in particle size.
These stable dispersions are described as ULTRAMULSIONTM disper~ n~, which,
2~ together with their physical properties, when cc ~ d in oral care products, provide
these oral care products with distinctive conditioning, mù~ g~ ~I'uleclillg, etc.
properties where the non contimlou~ silicone phase functions as a reservoir for various
oral care ll'cdLIllell~ b~
The present invention relates to various oral care rinses co~ il.iug, stable,
dispersions of certain high viscosity silicon~ in certain sllrf~.t~ntc; wherein:a. the dispersed silicon~, which are insoluble in said snrf~. f~nt, are oriented by
the ~ulL.,l~lL such that when dispersed in water they are particularly adept at f~rming
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-3 -
ç~l~ co~ g~ on ~ulr~cc~ of the mouth with Pnh~nred ~ ;vi~y, and
b. the particle size of the dispersed silicone is from bcL~. e.. about 0.1 and about
10 microns, with a particle size distribution such that from bcLw~icll about 80 and 95%
of the dispersed silicone is within this particle size range. These stable dispersions
5 are described as ULTRAMULSIONTM dispPr.sion.c, which, together with their physical
~ o~GlLies, when ccn.ti.;..Pd in oral care rinses, provide these rinses with ~nh~nred
s~ ..l;viLy to mouth ~-- r; ~S, where the non c~ ntimlous silicone phase functions as
a reservoir for various active ingredients cc nt~ined therein, inrlu-ling but not limited
to an ~c~nti~l mixture of thymol, eucalyptol, menthol and methyl salicylate.
The present invention relates to unique interdental delivery devices, other thandental floss, which are suitable for cle~ning, ...~ ;..g, and/or treating surfaces of
teeth and gums including illLel~JlU~ lal and ~ul.E;;..~ival areas; whc~ these devices
contain ULTRAMULSIONTM dispersions of high viscosity ciliconrc dispersed in
~u- r; ~ , these dispersions are released into the oral cavity from these devices
15 during use wherein the di~ ed cilic-~n~
a. is insoluble in the ~... r~ l;.u~ and oriented so as to form co~ting.c in the oral
cavity with enh~nred ~u~L~-LiviLy,
b. functions as a reservoir for various lipid soluble and/or liquid dispersible
ingredients to be released onto oral cavity surfaces, and
c. has a particle size from bc;lwt;~ll about 0.1 and about 10 microns with from
between about 80% and about 95% of the particles within this range.
The present invention relates to various oral care products coul,.i..iug stable,dispersions of certain high visco~ily cilircm~c in certain ~ulr~.;kulb for use in treating
mucus co~ .;..g :j... r~ such as in the mouth, throat and stomach and inteStine and
25 the surface of the esophagus which cont~inC no mucus.
a. the dispersed silic~nrc, which are insoluble in said ~ulr~iL~It, are oriented by
the ~... r~ such that when di~l~ed in water they are particularly adept at forming
oriented coatings on mouth, throat and es-.phagus and ~t~ ,ulr~ces with rnh~nre~~ub~L~lLiviLy, and
b. the particle size of the dispersed silicone is from b~Lv~ l about 0.1 and about
10 microns, with a particle size distribution such that from ~llb~li...l;~lly all of the
dispersed silicone is within this particle size range. These stable dispersions are
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d~crribed as ULTRAMULSION~ eper~ci~nc~ which, together with their physical
properties, when cnnt~in~d in mouth, throat, esophagus, stom~rh and illl~l;..r
treatment properties, when c~nt~ined in products, provide these products with
;ve coating protection properties where the rliccQntimlQus silicone phase of
5 said coating functions as a reservoir for various liquid suitable LlcaLI~ suhct~n~P-c,
suitable for release onto the surface being treated.
The present invention relates to various IU~ cQ~ .g, stable, flicper.cjonc
of certain high viscosity silic~ nec in certain s--rf~t~nfc; wherein:
a the rlicp~orced .ciliron~c, which contain triclos~n~ 2~4~4~-trielos~n-2
10 hydroxy/epoxy/ether, are insoluble in said :i... r~ are c riented by the ~ulra ;l~
such that when dispersed in water they are particularly adept at fnrminf~ ~rjent~rl
nonh~lie~l co~tingc on :iulracc:j of the mouth with ~nh~nred ~ .liviLy, and
b. the particle size of the ~icpPrced silicone is from belwccll about 0.1 and about
10 microns, with a particle size distribution such that from bclvv~ about 80 and 95%
15 of the dispersed silicone is within this particle size range. These stable rlicp.orcionc
are described as ULTRAMULSION~ dispersions, which, together with their physical
upcllics, when co~.l;.il.~od in tooll.~ es, provide the tooLh~ c with Pnh~n~ed with
fnh~n-ed :iub~ lLiviLy to mouth :~uLra;c~, where the non cr~ntinllous silicone phase
functions as a lC:~ClVUil for the triclosan cul.t;~ d therein.
The present invention relates to various oral care products cu.. ~il.il.~, stable,
dispersions of certain high viscosity ciliçonec in certain ~ulr~;~lt~; wherein:
a. the dispersed silicones, which are insoluble in said ~u~ ri.. Ii...t, are oriented by
the sllrf~l f~nt such that when dispersed in water they are particularly adept at forming
le~l coatingC on surfaces of the mouth with ~nh~nred ~ul~:~l~ll;viLy, and
2S b. the particle size of dle dispersed silicone is from bcL~v~ l about 0.1 and about
l0 microns, with a particle size distribution such that from bdwccll about 80 and 95%
of the dispersed silicone is within this particle size range. These stable dispersions
are described as UL~RAMULSIONS, which, together with their physical properties,
when c- nt~ined in oral care products, provide these oral care products with ~nh~nred
30 ~ul-~l;l;viLy to mouth surfaces, where the non continllous silicone phase fimctionc as
â reservoir for various active ingredients col.~ .ed therein.
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_ S _
BRIEF DESCRIPIION OF THE DRAWINGS
Fig. 1 i1l~ . ,.1~ the "coiled" m~lf c~ r cnnfi~lr~tion proposed for
polydi"~ ,ylsiloxanes.
Fig. 2 ilh ~ f--~ the proposed molfAc~ r configuration of o. ;- - .t~d
polydi...cill.ylsiloxanes after ULTRAMULSIONTM dispersion pl~
Fig. 3 ill..~l.,.1f ~ srhf~n~t~ lly an ULTRAMULSIONTM ~licpPrcinn process of thepresent invention; and
Figs. 4 and 5 illustrate that the I~LTRAMULSIONTM ~licpfr.cionC of the present
10 invention produced via various high shear di~p~ g means having particle size
distribution of 80+ % under 10 microns.
DETAILED DESCRIPTION OF THE PREE~RRl~D EMBODIMENTS
~eff Ting to the ~awin~ Fig. 1 illu~llal~ the âcc~led "coiled" configuration
advanced for polydimethylsiloxanes, wl,~ l the methyl moieties are oriented
ulw~lly while the oxygen moieties are oriented inwardly toward the axis of the coil
or helix. This configuration does not readily promote, bonding bt;lweel. the oxygen
moietif ~ and comp~tihle surfaces such as tooth enamel.
Fig. 2 illu~LIalt;~ the "uncoiled oriented" configuration proposed for
polydimethylsiloxanes that have been dispersed in the stable, ~LTRAMULSION~M
dispersions of the present invention, wherein the oxygen moieties are generally
oriented in one plane distinct from that of the methyl moieties. This proposed
lln~oiled . ,, ;e~ d configuration appears to support the unique and nnPYrected
stability, bonding and enh~nred :iul~ ;vily properties of the ULTRAMULSION~
dispersions of the present invention, as evidenced by the various coating applications
of these ULTRAMIJLSIONTM dispersions to teeth. See the ~x~ll~lcs provided
below.
Fig. 3 illu~llales the IJLTRAM~SION~M dispersion process of the present
invention wherein a nonionic sllrf~rt~nt and a polydimethyl-~ilox~ne l, ~u~ lly
free from water and co-solvent, are mixed in vessel 2, provided with mixing means 3,
heat source 4, and inert head space 5. The heated and mixed ~ .t-poly-
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--6-
dimethylsiloxane 6, is then subjected to high shear ricp~ion at an elevated
tt~ Cldlulc in di~c~:~ing means 7, to produce the ULTRAMULSIONTM dispersion 8,
of the present invention. The high shear riep~ion device (7) is typically selected
from among devices ...A,...ri.. L~..td by Ross, IKA Works, etc. Other energy sources
5 such as flow-through llltr~conir cells may be used as well.
Fig. 4 is a chart dc~;libi~g the particle size distribution of an
ULI~AMULSIONTM dispersion of the present invention col.l;.i~.;.iF~ from about 50 to
95% by weight nonionic sllrfArtAnt and from about 5 to 50% by weight
pol~di"~cl},ylsiloxane (2.5 million cs) pluduced in a c~...t;....~.us process with an IKA
10 Works di~c ~hlg means, (high shear di:,~cl~i"g) ~,vith an inlet ~tlll~ a~ult of 140~ C
and an outlet ICIII~d~U1C of 210~ C.
Fig. 5 is a chart dP-crrihing the particle size distribution of an I
ULTRAMULSIONTM dispersion of the present invention cnu~ from about 50 to
95% by weight nonionic ~--- r~ Ai~t and from about 5 to 50% by weight
15 polydimethylsiloxane (2.5 million cs) produced in a batch process with a Ross M/E
100 LC ~licp~. ~;..g means fitted with a 20 mesh screen, operated at a temperature
from about 120~ to 160~C.
For purposes of the present invention, the term silicone means a clear, colorless
i;.i.re c~ il.;..g polydialkylcilox~nr polymers with average kinrrn~tic viscosities
ranging from about 100,000 centistokes (cs) to about 50 million cs, preferably from
about 1 million .cs to about 25 million cs, more preferably from about l.5 million cs
to about 10 million cs, and most preferably from about 2 million to about 5 million
cs. This definition intentionally inrhldrc the so-called "gum" ciliçonrc having
viccocitirc of 30 to 50 million cs. Certain high viscosity polydimethylsiloxaneshaving visco~iLies from about 2.5 million cs to about 4 million cs are particularly
p,crc,,cd for the oral care products of the present invention. Other
polydimethylsiloxanes suitable for the present invention include "sub~l;l..ird" water
insoluble silicr,n~-c and Illi~UlCX of polydiorganosiloxanes and ~ul~ .led waterinsoluble silicones. Sperific~lly~ water soluble silicr~nrc are excluded from the
30 ULTRAMULSION~' dispersions of the present invention. See also Tables 1 and 2
below.
The viscosity of some ciliconrc can be measured by means of a glass capillary
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-- 7 -
v;.= ~... ~ . as set forth in Dow Corning Cc~l~<nale Test Method CTM0004, July 20,
1970.
The silicone may be either a high viscosity polyalkyl ~ilox~n--. as described in- detail below, a polyaryl siloxane, a polyalkylaryl .cilnx~n~ or a polyether siloxane
5 copolymer. Mixtures of these 5iliron~o$ may also be used and are plcr~ d in certain
embo.l;.. ..1~ of the present invention.
The polyalkylaryl siloY~nP-~ that may be used indude, for eY~mple,
polymeth~ hcllylsiloxanes having v;.~ic~sil;~c above 1 million ~ '-e~ at 20~C.
Some of these siloxanes are available, for loY~mple, from the General Electric
10 Company, from Dow Corning, and/or from Rhone-Poulenc.
The polyether siloxane copolymer that may be used is, for ~Y~mple, a
polypropylene oxide morlifi~.~l dimethylpolysiloxane although ethylene oxide or
.i~lur~ of ethylene oxide and propylene oxide may also be used.
Rercr~ ces disclosing suitable silicone fluids include U.S. Patent No. 2,826,551 to
Green; U.S. Patent No. 3,964,500 to Drakoff; U.S. Patent No. 4,364,837 to Padnerand British Patent No. 849,433 to Woolston. See also, Silicon Compounds
distributed by Petrarch Systems, Inc., 1984. This reference provides a very goodlisting of suitable silicone mz-t~iz~
Silicone materials found especially useful in the present cc,~ osilions to provide
good dry combing are silicone gums. Silicone gums described by Petrarch and others
in~ ing U.S. Patent No. 4,152,416, May 1, 1979 to Spitzer et al., and Noll, Walter,
''Chc.~ y and Technology of Sili~on~-~," Academic Press, New York (1968). Also
describing silicone gums are various General Electric Silicone Rubber Product Data
Sheets. "Silicone gum" m~tf.ri~lc denote high m-~l.oc~ r weight polydiorgano-
siloxanes having a viscosity up to about 50,000,000 cs. Specific examples include
pol~-]illlcLhylsiloxane; polydimethylsiloxane; methylvinylsiloxane copolymer;
pol~/di,ncLh~l~ilox~n~; diphenylmethvinylsiloxane copolymer and Illi~Lul~ thereof.
As noted above high viscosity polydimethylsiloxanes i.e., those above 100,000 csare p~cr~.lcd in this invention. Particularly plcrcllcd are polydimethylsiloxanes
having v;~cr ~ c ranging from bcLwcen about 2.5 million cs and about 50 million cs.
The safety of polydimethylsiloxanes for use in these various products is well
do~ l See Rowe et al., Journal of Industrial Hygiene, 30(6): 332-352 (1948).
CA 02222407 1997-11-26
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--8-
See also Calandra et al., ACS Polymer Pr,c~,.n~, 17: 1-4 (1976) and K~nn~dy et al.,
J. Toxicol. & Envi/(7n".ental Health, 1: 909-920 (1976).
As noted above, the ~l~,rcll~,d polydimethylsiloxanes useful in the oral care
culll~osiLions of the present invention are described as polymethyl~ x~nt-s with the
rll~rni~l c~ po:,iLion
(CH3)3SiO[SiO(CH3)2]nSi(CH3)3
wherein n is a whole number. These polydimethylsiloxanes have vi~c~iti~ ranging
up to about 50 million cs., and are generally d~e~ibe~l as having high molecularweight.
The particle size of the silicone in the ULI~AMULSION~ rlicp~r~ion~ of the
present invention can range from bclv~ about 0.1 and about 10 microns. In a
~crcllGd embo~limPnt of the present invention the particle size of polydimethyl-~ilox~n~ in the ULTRAMULSIONTM dispersion ranges from below 1 up to about 5
microns. The particle size distribution of the polydimethylsiloxanes in the
ULTRAMULSIONIM dispersions of the present invention generally range from
bclwccll about 80% and about 95% of the particles under 10 microns. See especially
Figs. 4 and 5. In a ~rcrcllcd embodiment of the present invention, from bG~
about 80% and about 95% of the particles are under 5 microns. See also Table 2.
An ~s~P-nti~l component of the llLTRAMULSIONTM dispersion of the present
invention is a surfactant. The surfactant, may be selected from any of a wide variety
of synthetic anionic, amphoteric, zwitterionic and nonionic ~... rf.. L;,...~i The
sulf~rt~nt~ suitable for the pulposes of the present invention must function as the
25 continllous phase and contain the discontinuous silicone phase.
Synthetic anionic ~u. r~. l;...l~ can be ~x~nplified by the alkali metal salts of
organic sulfuric rcaction products having in their moleclll~r structure an alkyl radical
cf~l-t;-il-i--g from 8-22 carbon atoms and a sulfonic acid or sulfuric acid ester radical
(NOTE: in~lllcled in the term alkyl is the alkyl portion of higher açyl radicals).
30 Pll;rcllcd are the sodium, ammonium, pol~iulll or triethanolamine alkyl sulfates,
espe~;~lly those obtained by slllf~*ng the higher ~l~ohol~ (C8-CI8 carbon atoms),
sodium cocon~lt oil fatty acid monoglyceride sulfates and sulfonates; sodium or
pol~ssiulll salts of sulfuric acid esters of the reaction product of 1 mole of a higher
fatty alcohol (e.g., tallow or coconut oil ~ holc) and 1 to 12 moles of ethylene oxide
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_ 9 _
ether sulfate with 1 to 10 units of ethylene oxide per molecule and in which the alkyl
radicals contain from 8 to 12 carbon atoms, sodium alkyl glyceryl ether S~llr~
the reaction product of fatty acids having from 10 to 22 carbon atoms ~ct~rifi~d with
isethionic acid and neutralized with sodium hydroxide; water soluble salts of
5 cnn-lP.n.e~tinn products of fatty acids with ~si,-e; and others known in the ar~
Zwitterionic ~... r~ can be ~Y~mrlifiçd by those which can be broadly
d~c~rihed as d~.ivdLives of ~lirh~tic ~ nl.;....~, phosrhcnil-m, and
s--lfonillm cc",lpuu"ds, in which the alirh~tir radicals can be straight chain or
br~nrh~d, and wl~ one of the ~lirh~ticc sllh.ctitll~ntc cont~inc from about 8 to 18
10 carbon atoms and one cnnt~inc an anionic water-solubilizing group, c.g., carboxyl,
s.llfon~te, sulfate, rhosph~t~?, or phosphnn~t~ A general formub for th~e c~...poL-,.d~
is:
(R3)x
R2 Y(+) - CH2 - R4 Z(~)
wllLI.,;ll R2 co..l~il..c an alkyl, alkenyl, or hydroxyl alk~ c~l of fr~ about 8 to 18
carbon atoms, from 0 to about 10 ethylene oxide moi l . and frorn 0 to I glyceryl
20 moiety; Y is selected from the group consisting of nil.ug..., phosphorouc. and sulfur
atoms; R3 is an alkyl or monohydroxyalkyl group col-t~ ng I to about 3 carbon
atoms; x is 1 when Y is a sulfur atom and 2 when Y is a nitrogen or phosphorous
atom; R4 is an alkylene or hydroxyalkylene of from l to about 4 carbon atoms and Z
is a radical selecte-l from the group col..~;.cl;..g of carboxylate, sulfonate, sulfate,
25 rhnsphon~tç, and rhnsph~te groups. Fx~ c include; 4-[N,N-di(2-hydroxyethyl)-N-
octadecyl:.. l-io]-butane-l-carboxylate; 5-(S-3-hydroxypropyl-S-
h~y~rlecylsulfonio]-3-hydrox~ e-l-sulfate; 3-[P,P-diethyl-P-3,6,9-
trioY~t~ott~lecocylrhosphnnio]-2-hydrox~ e-l-phc~ le~ 3-[N,N-dipropyl-N-3-
dodecoxy-2-hydroxypropylammonio]-propane- 1 -rh. .~ hn l c-~ 3 -[N,N-dimethyl-N-30 h~Y~ cyl~mmonio-p~u~ e-l-sulfnn~t~; 4-[N,N-di(2-hydroxyethyl)-N-(2-
hydroxydodecyl) .. l~io]-butane-l-carboxylate; 3-[S-ethyl-S-(3-dodecoxy-2-
hydroxypropyl)sulfonio]-p, ~.~a"c- l -phospl~ , 3 -[P,P-dimethyl-P-dodecyl-
rhncphonio]-~r~pal,~l-phosrhnn~t~; and 5-(N~N-di(3-hydroxypropyl)-N-h~
~mmnnio]-2-hydroxypentane- 1 -sulfate.
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Other zwitterionics such as betaines are also useful in the present invention.
Examples of betaines useful herein include the higher alkyl b~ .es such as
cocodimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl
dimethyl alpha-carboxyethylene betaine, cetyl dimethyl carboxymethyl betaine, lauryl
5 bis-(2-hydroxyethyl)carboxy methyl betaine, stearyl bis-(20-hydroxy-propyl)-
carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lauryl bis-(2-
hydroxypropyl)alpha-carboxyethyl betaine, etc. The sulfobetaines may be represented
by cocodimethyl sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl
dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxy-ethyl)sulfopropyl betaine and the
10 like; amido betaines and ~mi~ cll1fo betaines, wherein the RCONH(CH~)3 radical is
:~tt~rhed to the nitrogen atom of the betaine are also useful in this invention. The
amido betaines are p,cre.,ed for use in some of the compositions of this invention. A
particularly ~ r~ ;d composition utilizes an arnido betaine, a ~lu~Ltelll~y compound,
a silicone, a suspending agent and has a pH of from about 2 to about 4.
Examples of amphoteric surf~rt~ntc which can be used in the
ULTRAMULSIONTM dispersions of the present invention are those which can be
broadly described as derivatives of aliphatic secon-l~ry and tertiary ;amine in which the
~liph~tic radical can be straight chain or branched and wherein one of the aliph~tic
substituents c~nt~inc from about 8 to about 18 carbon atoms and one cont~inC an
anionic water solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or
ph~sphon~t~ Examples of compounds falling within this definition are sodium 3-
dodecylamino-propionate, sodium 3-dodecylamino-propane sulfonate, N-alkyltaurines
such as the one ~ d by reacting dodecylamine with sodium isethionate according
to the t~ ~rhingc of U.S. Patent No. 2,658,072, N-higher alkyl aspartic acids such as
those produced according to the te~rhinec of U.S. Patent No. 2,438,091, and the
products sold under the trade name "Miranol" and described in U.S. Patent No.
2,528,378.
Nonionic surf~rt~ntc7 which are preferably used in combination with an anionic,
amphoteric or zwitterionic surfactant, can be broadly defined as compounds produced
by the cnnclPnc~tion of alkylene oxide groups (hydrophilic in nature) with an organic
hydrophobic compound, which may be ~liph~tic or alkyl aromatic in nature.
Examples of preferred classes of nonionic ~ ; are:
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1. The polyethylene oxide con~ c of alkyl phenols, e.g., the con(1Pn~tion
products of alkyl phenols having an alkyl group CO~ g from about 6 to 12 carbon
atoms in either a straight chain or branched chain configuration, with ethylene oxide,
the said ethylene oxide being present in amounts equal to 10 to 60 moles of ethylene
5 oxide per mole of alkyl phenol. The alkyl substituent in such co~ uulld~ may be
derived from polymerized propylene, disobutylene, octane, or nonane, for example.
2. Those derived from the cc n-lPn~tion of ethylene oxide with the product
resulting from the reaction of propylene oxide and ethyl~n~d;i....il.r products which
may be varied in composition depending upon the balance belwet;ll the hydrophobic
10 and hydrophilic elements which is desired. For example, colll~oullds c. I.I;~;..;..g from
about 40% to about 80% polyoxyethylene by weight and having a mnlec ll~r weight
of from about S,000 to about lS,000 resulting from the reaction of ethylene oxide
groups with a hydrophobic base cn~ cl of the reaction product of ethylene
n;,~F and excess propylene oxide, said base having a molecular weight of the order
of 2,500 to 3,000 are s~ticf~tory.
3. The cnn~lPn~tion product of ~liph~tic alcohols having from 8 to 18 carbon
atoms, in either straight chain or branched chain configuration, with ethylene oxide,
e.g., a coconut alcohol ethylene oxide contlPn~tP having from 10 to 30 moles of
ethylene oxide per mole of coconut alcohol, the coconut alcohol fraction having from
10 to 14 carbon atoms.
4. Long chain tertiary amine oxides collG~I.onding to the following general
formula:
R,
R3--N ~ O
R2
wheleill R, contains an alkyl, alkenyl or monohydroxy alkyl radical of from about 8
to about 18 carbon atoms from 0 to about 10 ethylene oxide moieties, and from 0 to
1 glyceryl moiety, and R2 and R3 cont~in~ from 1 to about 3 carbon atoms and from 0
to about 1 hydroxy group, e.g., methyl, ethyl, propyl, hydroxy ethyl, or
hydroxypropyl radicals. The arrow in the formula is a cunv~;lltional representation of
a semipolar bond. Example of amine oxides suitable for use in this invention include
dimethyl-dodecylamine oxide, oleyldi(2-hydroxy-ethyl)amine oxide,
CA 02222407 1997-11-26
W O 96~9116 PCTrUS96/08714
- 12 -
dimethyloctylamine oxide, dimethyl-decylamine oxide, dimethyltPtr~ cylamine oxide.
3,6,9-tri~-x~hçpt~-lecyl-diethylamine oxide, di(2-hydroxyethyl)-tetra~cylamine oxide, 2-
dodecoxyethyldimethylamine oxide, 3-dc--lecoxy-2-hydroxypropyldl-(3-hydroxy-
propyl)amine oxide, dimethylh~x~tlecylamine oxide.
5. Long chain tertiary pho~ oxides cu~ ,nding to the following general
fnnm~
R
R'--P ~ O
R"
10 wherein R co~ an alkyl, alkenyl or monohydroxyalkyl radical ranging from 8 to18 carbon atoms in chain length from 0 to about 10 ethylene oxide moieties and from
0 to 1 glyceryl moiety and R' and R" are each alkyl or monohydroxyalkyl groups
co..~ .it.g from 1 to 3 carbon atoms. The arrow in the formula is again the
convt;..tional representation of a semipolar bond. Examples of suitable phosphine
15 oxides are: dodecyldimethylphosphine oxide, tetradecyl-dimethyl-phosphine oxide,
tetradecyl-methylethylphosFhinç oxide. 3,6,9-trioxaocta-decyldimethylphosphine
oxide, cetyldimethylphosphine oxide, 3-dodecoxy-2-hydroxypropyl-di(2-hydroxyl)-
phosphine oxide, stearyldimethylphosphine oxide, cetylethylpropylphosphinç oxide,
cetyldiethylphosphine oxide, dodecyl-diethylphosphine oxide, tetradecyl-
20 diethylphosphine oxide, dodecyldipropylphosphine oxide, dodecyldi(2-
hydroxyethyl)phosphine oxide, tetradecyl-methyl-2-hydroxydodecyldimethylphosphine
oxide.
6. Long chain dialkyl sulfoxides col.t;t;..;l.g one short chain alkyl or hydroxyalkyl radical of 1 to about 3 carbon atoms (usually methyl) and one long
25 hydrophosphinic chain which contain alkyl, alkenyl, hydroxyalkyl, or keto alkyl
radicals c~ ,g from about 8 to about 20 carbon atoms, from 0 to about 10
ethylene oxide moieties and from 0 to 1 glyceryl moiety. Examples include octadecyl
menthyl sulfoxide, 2-ketotridecyl methyl sulfoxide, 3,6,9,-trioxooctadecyl 2-
hydroxyethyl sulfoxide, dodecyl menthyl sulfoxide, oleyl 3-hydroxypropyl sulfoxide,
30 tetradecyl menthyl sulfoxide, 3-methoxytridecyl methyl sulfoxide, 3-hydroxytridecyl
methyl s-llf~-xicl.- 3-hydroxy-4-dodecoxy-butyl methyl sulfoxide.
Many additional nonsoap surfactants are described in McCUTCHEON'S,
CA 02222407 1997-11-26
W O 96/39116 PCT/U~,3G,~714
- 13 -
DETERGENTS AND EMULSIFIERS, 1979 ANNUAL, published by Allured
Puhliqhing Corporation. Particularly plGrc.lcd nonionic s-lrf~rt~ntq are nonionic
polo~m~r ~ulr~c~ of block copolymers of ethylene oxide and propylene oxide
ranging from flowable liquids of varying v;qcos;l;~q, to paste, prills and cast solids
with molecular weights from 1,100 to 150,000. Suitable nonionic ~u~r~ are
m~nnf~t~hlred and m~rket~d by BASF Corporation under the tr~tlrm~rks Pluronic.
Particularly ~rcrcllcd nonionic sl~rf~rt~nte are Pluronic F-68, F-88, F-108 and
Pluronic F-127. These are dP-qrrihed in a BASF brochure entitled "Pluronic and
Tetronic Block Copolymer Sulra~ l." These nonionic surf~rt~ntq suitable for the
present invention can be described by the following structure:
CH
OH-(CH2CH2))X- (CH2CHO)y~ (CH2CH2O)X. - H
where x, y and x' are whole mlmh~rq Su~ gly, the nonionic surfactants of
choice for the ULTRAMULSION~ dispersions of the present invention are reported
in the referenced brochure to have marginal detergency, eml-lqific ~tion and wetting
properties.
As noted above, the ~rcrtllcd nonionic poloxamer surfactants useful in ~e
coating cc",po~ilions of the present invention are described as polyoxyethylene-polyoxypropylene block copolymers such as Pluronic F-68, F-88, F-108 and F-127
(BASF) which have molecular weights of at least about 1000 such as those described
in U.S. Patent Nos. 4,343,785, 4,465,663, 4,511,563 and 4,476,107.
Emulsions of various coating subst~nrrq including polydimethylsiloxanes in
various ~ulr~.;~l~ inr.h~r1ing noninnic sllrf~r$~ntq are disclosed and claimed in U.S.
Patents 4,911,927, 4,942,034; 4,950,479; 5,009,881; 5,032,387; 5,057,306; 5,057,307;
5,057,308, 5,057,309; 5,057,310, 5,098,711, 5,165,913 and 5,284,648. There is
however, no te~ching or ~ugge~lion in these references that these high viscositysilicone emulsions are stable nor that the "coating" s~bst~nrrq are oriented as they are
in the ULTRAMULSIONTM dispersions of the present invention.
The ratio of s~lrf~rt~nt to silicone in the ULTRAMULSIONTM dispersion coating
compositions of the present invention can range from bcl~ l about 400:1 and about
CA 02222407 1997-11-26
W O 96~9116 ' PCTrUS96/08714
-14 -
1:2. In a ~.cr~ d embodiment of the invention the ratio of ~--. r~.J;..~, to silicone is
from bc~lw~el~ about 25:1 and 1:2.
The ULTRAMULSIONTM dispersions of the present invention may be ~ d
as follows; generatly, if not a liquid, the s~rf~rt~nt is first heated to a t~ cldlulc~ at
5 which it becomes a liquid. The silicone is then dispersed in the heated ~... r~. I;.~.t with
various high shear .1;~. .x;~.g means.
In one l~crt;~ed method, the heated ~u.ra.;L~-L is mrrh~nic~lly stirred along with
the cilir,one to form a pre-emlllci-n mixture in which the silicone is ....;ru...~ly
rlicp~rced in the :~U-rd ;~i~lt in droplets of a larger size than desired for the
ULTRAM~SIONTM dispersions but small enough to o~ e the subsequent high
shear dispersions. This mixture is subjected to high-shear dispersions with a means
such as the IKA-WORKS DISPAX-Reactor with at least one ~ul~wrlne generator,
;vely, a Ross Model M.E., 100 LC fitted with a 20 mesh screen or a
ultrasonicator such as MEDSONIC XL2010 fitted with 800-C Flow Cell & 800-21CT
3/4 inch flanged horn can be used.
The ~liecr~ntinllous silicone phase of the ULTRA~IULSIONTM dispersion can also
contain a wide range of lipid soluble and/or lipid dispersible oral care active
ingredients ranging from ~ntimi~robials to des~ ;l.g/s~ c~ to hr~l~ntc such as
aloe to Vi~llLS such as vitamin E, to flavorants, etc. These various ingredients in
the silicone phase of the ULTRAMULSIONTM dispersion perform in various oral careproducts as though they are cont~inrd in a "reservoir" as they contin--~ to be available
at the ULTRAMULSION~f dispersion oral surface interface, as long as the
ULTRAMULSIONTM dispersion coating remains substantive to mouth surfaces.
The various tootl,pa~les of the present invention can be made by mixing the
m~tPri~lc together and heating if n~C.~, .y and following ;~rc~ d m~nllf~rhlringpractices for these various products as drcrrihed in detail below. In addition, other
toolL~a~Les are included in the present invention inrhl-ling whi~ g too~,pa~ s,
tou~ L~ for treating hyposensitivity, tooll,~ les for dry mouth sufferer, toothpastes
for patients undergoing radiation therapy, etc.
The oral care products cont~ining the ULTRAMULSIONTM dispersions of the
present invention will contain a variety of eccPnti~l colll~o~ ranging from
s--rf~rt~ntc and al,.~sives for rle~ning~ to wl.;l~l.~, to gelling aids to fl~vu.d..~ etc.
CA 02222407 1997-11-26
W O 96139116 PCTAJ~,G,'C~714
-15-
These are detailed in various ExAmplec described below.
In addition to the rOlc~goillg, other oral care p-udu~l~, are included in the present
invention, such as chewing gums, prophylactic pastes and denture wearer products to
treat ~ AI;I;C While also in the latter the ULTRAMULSION~5 dispersion provides
5 the base filnrtic)nin~ as a carrier for specific active ingredients such as Candida yeast
- sp. antifungal agents such as stannous fluoride.
In addition the oral care products of this invention can contain a variety of
"on~c~--ntiAl optional co",~ollc.ll~ suitable for rpnr~ ng such cul"l)o~iLions more
acceptable. Such convGI.~ional optional ingredients are well known to those skilled in
10 the art, e.g., prestlvd~ivG~ such as benzyl alcohol, methyl paraben, propyl paraben and
imilliA7oli~1inyl urea; cationic surfactants such as cetyl trimethylAmmnni~lm chloride,
lauryl trimethyl Ammoni~lm chloride, tricetyl methyl Ammonium chloride,
stearyldimethyl benzyl Ammonium chloride, and di(partially hydluge~ (l tallow)-
dimethylammonium chloride; thirl~Pn~r.c and viscosity modifiers such as
15 ~liethAnnlAmi~le of a long chain fatty acid (e.g., PEG 3 lauramide), block polymers of
ethylene oxide and propylene oxide such as Pluronic F88 offered by BASF
Wyandotte, sodium chloride, sodium sulfate, polyvinyl alcohol, and ethyl alcohol; pH
adjusting agents such as citric acid, succinic acid, phosphoric acid, sodium hydroxide,
sodium carbonate, etc., perfumes; dyes; and, sequect~ring agents such as disodium
20 ethylen.-~1iA...il.~ tetrAAretAte Such agents generally are used individually at a level of
from about 0.01% to about 10%, preferably from about 0.5% to about 5.0% by
weight of the composition.
The rliccontimlous silicone phase of the ULTRAM~SIONTM dispersion based
too~p~LG:~ can also contain a wide range of lipid soluble and/or lipid dispersible oral
25 care ingredients ranging from antimicrobials to ~lp-spn~citi7in~/s~ A~ 7 to h~AlAntc
such as aloe to vi~--ins such as vitamin E, to flavorants, etc. These various
ingredients in the silicone phase of the ULTRAMULSION~M dispersion based
too~ Les of the present invention pGlrul... similar to the triclosan, i.e., as though
they are col.tA;..rd in a "reservoir". These various lipid soluble s~lhstAnrPc in the
30 silicone phase continlle to be available at the ULTRAMULSION~ dispersion oralsurface il.l~ ~- e as long as the ULTRAMULSIONTM dispersion coating remains
~ul~s~live to mouth ~u-r~ces. Effects attributed to this "reservoir" are described by
CA 02222407 1997-11-26
W O 96/39116 ~ PCTAJS96/08714
-16-
Rolla et al., supra.
The toolllpa~,~es co,.l;.;..i..g the ULTRAMULSIONTM and triclosan dispersions ofthe present invention will contain a variety of ~s~-nh~l components ranging fromsurfactants and al~ld ,ivcs for ~le~ning, to wl.;l. ..~, to gelling aids to flavuld~ etc.
5 In addition the toolllpa~ products of the invention can contain a variety of
nc,~ l optional components suitable for renrl~ring such compositions more
acceptable. Such c;onvclllional optional ingredients are well known to those skilled in
the art, e.g., preservatives such as ben_yl alcohol, methyl paraben, propyl paraben and
imi~ 7O1idinyl urea; cationic sllrf~rt~nt~ such as cetyl trimethylammonium chloride,
10 lauryl trimethyl ~mmnnillm chloride, tricetyl methyl i~mmonium chloride,
stearyldimethyl benzyl ~mmnnium chloride, and di(partially hydrogenated tallow)-dimethylammonium chloride, thickeners and viscosity modifiers such as
fliPth~nnlamide of a long chain fatty acid (e.g., PEG 3 l~llr~micle), block polymers of
ethylene oxide and propylene oxide such as Pluronic F88 offered by BASF
15 Wyandotte, sodium chloride, sodium sulfate, polyvinyl alcohol, and ethyl alcohol; pH
adjusting agents such as citric acid, succinic acid, phosphoric acid,; sodium hydroxide,
sodium carbonate, etc., p~iùmP~; dyes; and, sequestering agents such as disodiumethylPne~ mine tetr~ et~t~ Such agents generally are used individually at a level of
from about 0.01% to about 10%, preferably from about 0.5% to about 5.0% by
20 weight of the COlllpO ,ilion.
When used for internal (mouth or ingested) treatment products, the discontinllc us
silicone phase of the ULTRAMULSIONIM dispersion can also contain a wide range
of lipid soluble and/or lipid dispersible ingredients suitable for treating various surface
conditions on lips in the mouth, or the throat, .,lc,llla~L and esophagus. These various
25 ingredients in the silicone phase of the ULTRAMULSIONTM dispersion perform their
intPnrlPd function in various treatment products etc. as though they are cont~in~d in a
"reservoir" as they continlle to be available at the ULTRAMULSIONTM dispersion
co~ g surfaces to be treated int~rf~re as long as the ULTRAMULSIONTM
dispersion coating remains substantive to said surface. These ,ub,L~Ilive treatment
30 co~tings are discussed in various examples below.
Such conventional optional ingredients are well known to those skilled in the art,
e.g., preservatives such as ben_yl alcohol, methyl pi~r~h~n, propyl paraben and
CA 02222407 1997-11-26
W O 96/39116 PCTAJS96/08714
-17-
imitl~7cli-1inyl urea; cationic :iu- r~ such as cetyl trimethyl~mmnni--m chloride,
lauryl trimethyl ~mmnnium chloride, tricetyl methyl ~mml~ninm chloride,
stearyldimethyl benzyl ~mmonillm chloride, and di(partially hyd~ .Aled tallow)-
dimethyl~mmcnillm chloride; thic~en~.c and viscosily moflifi~ such as
5 rli~th~nolamide of a long chain fatty acid (e.g., PEG 3 l~nr~mirlP,), block polymers of
ethylene oxide and propylene oxide such as Pluronic F88 offered by BASF
Wyandotte, sodium clllori~l~, sodium sulfate, polyvinyl alcohol, and ethyl alcohol; pH
adju~ling agents such as citric acid, succinic acid, phCsph~ ric acid, sodium hydroxide,
sodium c~l~olldLe, etc., flavors; dyes; and, sequestering agents such as disodium
10 ethylPne~ min~ ç Such agents generally are used individually at a level of
from about 0.01% to about 10%, plGr~ldbly from about 0.5% to about 5.0% by
weight of the composition.
The treating surface conditions of lips and the esophagus as well as various
mucus col.~ .g surfaces such as the mouth, throat, stomach and d~lod~m-m and
15 il,~ These surfaces can be treated with various forms of the
ULTRAMULSIONTM dispersions of the invention ranging from gels and lotions for
the lips, to liquids, for the mouth to liquid and syrups for the throat to liquids for the
esophagus to liquids tablets for the stom~l~h, cluo~l~m-m and i.l~
For internal (e g, the mouth, throat, etc ) tre~tmPnt the rliccnntimlous silicone
20 phase of the ULTRAMULSIONTM dispersion can also contain a wide range of lipidsoluble and/or lipid rlicp~ihle oral care active ingredients ranging from
antimicrobials to des~ ;..g/~ub~lces, to h~ ntc such as aloe to vil~ullills such as
vitamin E, to navOIdllL~, etc These various ingredients in the silicone phase of the
ULTRAMULSIONTM dispersion l clr~lln in various interdental delivery devices once25 they are released from the device as though they are col.~i.;... d in a "reservoir" as they
contimll~ to be available at the ULTRAMULSION~ dispersion oral surface interface,
as long as the ULTRAMULSIONTM dispersion coating remains ~ul,~;...f;ve to mouth
x... I~ C Similar effects attributed to this ~ . V~il effect are described by Rolla et
al., supra.
The illL~ld~,ll~l delivery device of the present invention col.l;1;.. ;.. g the
ULTRAMULSION~ dispersions will contain a variety of ecsPnti~l components
ranging from sllrf~rt~ntc for ~lç~ning, to wl.;~f~u.o~, to flavorants etc These are
CA 02222407 1997-ll-26
W O 96/39116 PCT~US96/08714
-18-
detailed in various F~rnpl~c described below.
The ULTRAMULSION~M dispersions of the invention are particularly useful in
cclllpo~iLions used by professionals to clean teeth. The inrhlcinn of ~ luu~i fluoride
in the ~1iccontinllous phase of the emulsion is particularly allld;live as a means of
5 treating illltl~u~illlal caries. See Segueto et al., Journal of Dental Research, Vol. l0,
No.l,pp.90-96,1961 and Peterson et al., NorthwestDentist~y, 276-278, Sep./Oct.
1963. For oral care, the pH of the present culll~osiLions is preferably from 6 to 8.
The ULTRAMULSIONTM dispersions of the invention are particularly useful in
dellldl devices whose use is under ~u~.vi~ion of a professionaL The inclusion of10 stannous fluoride in the ~liccnntinllouc phase of the emulsion is particularly attractive
as a means of treating i"lc;,~,u~i",al caries. See Segueto et al., Journal of Dental
l~esearch, Vol. l0, No. l, pp. 90-96,1961 and Peterson et al., NorthwestDentistry,
276-278, Sep./Oct. 1963. The pH of the ULTRAMIJLSIONTM dispersions for use
with interdental devices is preferably from about 6 to 8.
Oral care rinses cv~ .g the ULTRAMULSION~ dispersions of the present
invention may contain a variety of eccenti~1 components ranging from other
... r~ ; for cleaning, to other n&vU,cu,~ etc. In addition these oral care rinses may
also contain a variety of non~ssenti~l optional CulllpOll~ suitable for rendering such
cull~po~iLions more acceptable. Such cc,llv~lllional optional ingredients are well
20 known to those skilled in the art, e.g., prese.v~Lives such as benzyl alcohol, methyl
paraben, propyl paraben and imi~ 7nljdinyl urea; cationic surf~rt~ntc such as cetyl
trimethyl~mmnnium chloride, lauryl trimethyl ~mmnnium chloride, tricetyl methyl
~mmonium chloride, stearyldimethyl benzyl ~mmonillm chloride, and di(partially
hydlugellaled tallow)- dimethyl~mmonium chloride; thicl~n~rc and viscosity modifiers
25 such as ~lieth~nolamide of a long chain fatty acid (e.g., PEG 3 l~nr~mide), block
polymers of ethylene oxide and propylene oxide such as Pluronic F88 offered by
BASF Wyandotte, sodium chloride, sodium sulfate, polyvinyl alcohol, and ethyl
alcohol; pH adjusting agents such as citric acid, succinic acid, phnsphoric acid,
sodium hydroxide, sodium carbonate, etc., pPrlilm~c; dyes; and, seq-le-ctering agents
30 such as disodium ethylen~ ...;..c l~ c~ Such agents generally are used
individually at a level of from about 0.01% to about 10%, preferably from about
0.5% to about 5.0% by weight of the cc,lllpo~ilion. The pH of the present
CA 02222407 1997-11-26
W O 96/39116 PCTIU',~'08714
- 19 -
cu~ osiLions for use with oral care rinse products is preferably from about 6 to 8.
Water is an ~ nti~l CO111~011G11~ of most oral care products of the present
invention which contain one or more of the various ULTRAMULSIONTM rli.~p~ion~
- described above. The water in these products is generally present at a level of from
about 20% to about 95%, preferably from bGL~ .l about 60% and about 90%.
The following Tables provide a number of oral care ~oY~mpl~ lltili~ing the
ULI~AMULSION~ p~ion~ of the present invention.
CA 02222407 1997-11-26
W O 96~9116 PCTrUS96/08714
-20-
TABLE 1
ORAL CARE ULTRAMI~LSION DISPERSIONS
% W/W
F. . '~ No. 1 2 3 4 5 6 7 8 9 10 11
DimP.thiconP
viscosit~ (cs)
1 00,000 1 0 - - - - - - - - 33
600,000 - 1 0 - - - - 33 - - , - -
2,500,000 - - 1 0 - - - - 3 3 - : - 1 0
4,000,000 - - - 1 0 - - - - 3 3
30,000,000 - - - - 1 0
50,000,000 - - - 10 , .;
Poloxamer- 1 8 8 - - - - - ~ 67
PoloxamPr-238 - - - - - - - - -; - 90
Poloxamcr-338 90 90 90 90 90 90 - - - . - -
Poloxamer-407 - - - - - - 67 67 67
CA 02222407 1997-11-26
W O 96/39116 PCTAUS96/08714
- 21 -
Z o
~0 o o
O ~ o
~! - . . . .
Z X
''~ ~~ ~
~ E~ o ~D
p ~ ~ ~ o
e
'8
. ~ _ , ~ , ,
C~
O ~C7
O,
O
Z C U ~ o o o o
~3 ~ i~ O ~
CA 02222407 1997-11-26
W O 96/39116 ' PCT~US96/08714
- 22 -
o o o o oo
o o o o 1~0
o o o o oo
_ o o o o ~
o o
o
. 0 0 0 ~ et
o o o o ~o
o o o o C~
U o C ~ - o g - ~ ~
CA 02222407 1997-11-26
W O 96/39116 PCT~US96/08714
- 23 -
/~ o o o
~ V _ ~ oo
.o
! V _. _ ~
~q O
~5 3 v
V~
Y ~ o
V ~t
a -E E E
E ~
1~ Z ~
CA 02222407 1997-11-26
WO 96/39116 PCT/US96/08714
- 24 -
TABLE 4
ORAL CARE
% W/W
Example No. 26 27 28 29 30 31 32 33 34 35
C ,-
D;~... Il~;..~.~r
viscosity (cs)
600,000 - 11.6 - - - 10.0
2,500,000 10.0 - - 11.9 11.9 - - - - 14.0
4,000,000 - 11.6
30,000,000 - - - - - 11.6
50,000,000 - - - - - - 11.6 10.0
Lipid Soluble
(~r....l.~,... ,1
Mixtu;e Of:
Thymol- 24%
Menthol- 16% 1 0.0
Lu~ l- 36% -
Methyl Salicylate
24%
Sta~ous Fluoride - - - - 1.75 - - ~ - - -
Triclosan - 1.16 1.16 - - - 1.16 1.16 - 2.0
M_ ",l,j.1_,l,1,7 _ 1.3 - - - ~ - - ~
RPn7r ~ - - - - - 1.0 - - . -
Sul ' -
Poloxamer 338 80.0 97.24 87.24 86.8 87.25 89.0 87.24 ' 87.24 80.0 84.0
CA 02222407 1997-11-26
W O 96/39116 PCTrUS~ /14
- 25 -
o o ~ o ~ ~_
~ o o 0. 0 oo~, ~
J ~ ~ ~ ~ ~ - o o o o
O O ~D O ~ r-
0. 0 00
o oo o
O O ~D O
_ ~ o~o _ oo ~ ,_
o o ~ o ~ t_
o~ co ~ o ~. Ooo V~
O ~ ~ ~ ~ -- -- O oo o
~ O O ~D O ~D ~
~ ~ ~ ~ ~ ~_~ ~ o oo o
O O ~O O
o ~ ~~ o oo o
, 3 o o ~o o
~ _ o oo
,7 o o ~ o ~
o ~ ~' ~ ~ ~ ~~ ~ o oo o
V~
o o ~ o ~ ~--
00 ~D O ~. ~00
e~ oo o o
O O ~ O ~D
~ oO ~O o. o oO ~, ~
E ~ o o o o
O O ~ O
~o o o. o oo ~, I_
_ _ _. _ _ oo o o
o o ~ o ~ t_
~t ~ ~ ~ ~ _, _o o o o o
D. ~ D ~ ~ ~ o ~ ~ D ~ ~ D ~
CA 02222407 1997-11-26
W O 96/39116 : PCT~US96/08714
- 26 -
o~
~n , . . . . ~ ... . .
X
~ . . . . .
Z
o ~n , , , , o
~ U~ o;
,, , , , o
~ I
o
~5 0 ~ o
U~
_, o
o o
E u~ . , ~ . . . . . . .
o~ o
, ~ , . . . . . .
~
~,~,,oo _
E E
~ ~ E,
CA 02222407 1997-11-26
W O 96~9116 PCT~US9~/C_/14
- 27 -
o o
o~ ~ ~ o
,~ oo o o . ~ . . . .
o
Ga ~
o o o
O~ ~ ~ ~ ~D
~ ~O ~ ~ ~ 00 0 0
O U7
o
o o 'C
~
~ ~ oo o o . . . . ~ . . ,~
O O o ~,c ~
~ t ~ 00 00 ,,, ~,,, c
C
o.O. C~
Z ~ ' ' ~ o
O oo. _
_ ~ ~ ~ ~ ~ . o ~
''~ ~ ~ ' ~ ' ' ' ' ' o
l:~ o o _ ~S: o
O O ~ .. ....
o
,~
o~
O ~ ~
o ~ CQ et ~, ~ ~ ~ ~L~
~ ~ ~ ~ ~ ~~ ~ ¢ ~ ~ ~ & ~
CA 02222407 1997-11-26
W O 96/39116 I PCT~US96/08714
-28-
TABLE 7
ULl~RAl~nJLSION BRU~TEISP~L~Y C O M POSITIONS
% W/W
Esample # 67 68 69 70
C~ oll~,.lt
Water 82.75 82.75 82.75 82.75
Sorbitol - 70% Aq. 8.5 8.5 8.5 8.5
Glycain 3.0 3.0 3.0 3.0
Xanthan Gum 0.4 0.4 0.4 0.4
Sodium ,Sa.~.e.l.,.. ;........ 0 4 0 4 0 4 0 4
Sodium BPn7:0~t~ 0.3 0.3 0.3 0.3
EDTA 0.05 0.05 0.05 0.05
Flavor 0.6 0.6 0.6 0.6
ULTRAMULSIONTM
Example 3 4.0 - - - ;
Example 4 - 4.0
Example 5 - - 4.0
Example 9 - - - 4.0
CA 02222407 l997-ll-26
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TABLE 8
ULTRAMULSION DRY-MOUT~ SPRAY COMPOSITIONS
PîLmp Spray
- % W/W
li. , '- # 71 72 73
C~
Water 93.86 93.86 93.86
Xanthan Gum 0.7 0.7 0.7
Sorbitol - 70% Aq. 3.5 3.5 3.5
po~ ... Chloride 0.1 0.1 0.1
Sodium Chloride 0.06 0.06 0.06
C~ m Chloride 0.02 0.02 0.02
Po~ l Phosphate
Dihydrate 0.04 0.04 0.04
Flavor 0.06 0.06 0.06
Propyl Gallate 0.1 0.1 0.1
UL~l ULSIONTM
Ex~nple 2 1.5 - -
Example 4 - 1.5
Example 6 - 1.5
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TABLE 9
ULTRAMULSION l~ ;l~l~G GEL COMPOSlTIONS
% W/W
F.~r~p'- # 74 7~ -
Cu~
Water 45.7 45.7
Sorbitol - 70% Aq. 34.3 34.3
Glycerine 5.0 5.0
pO~ Sorbate 0.151 0.151
Sodium Sac~L~;........... 0.075 0.075
Citric Acid 0.1 0.1
Methyl Paraben 0.15 0.15
Propylene Glycol 10.0 10.0
SodiurnCarboxyMe~yl
Cellulose 2.52 2.52
UL~AMULSIONTM
Example 4 2.0
Example 6 - 2.0
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. - 31 -
X , , ~ , , O o
z
O X
O ~
~V~
Z ' ' ' ' ' ~ ~ ~
~ ~
X O ~
t-- O I I I I ~ I 1 00
~ O
00 00 ~, O
c, ' E ~ o~ ~' ~- ~~ ~- ~- o K r~ o K
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o o
~ , o
Z
V~ ~ , . , _ , ~ oo
o
O ~ , , , , ~ _
~ C~ , , , _ _
o , , , ~ CO
O o~ _ 0
_
E ~'
X o
X , ~ , o , o
E E E ~ ~ ~ ~~ ~~ ~- ~ ~ E ~
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TABLE 12
F~S '~ No. 97 98 99 100 101
DIMETE~CONE
2,500,000 cs. 10 10 10 10 --
4,000,000 cs. -- -- -- -- 10
LIPID SOLUBLES/DISPERSABLE
Dextromethophenyl
Hyd~ ulllide 1.0 -- -- -- --
D~A~UIIICthOPhenYI
Hyd.ublull.ide -- 2.0 -- -- --
D~All u---e~ophenyl
Hydrobromide -- -- 1.0 -- --
Fr~r~n~e #17.92.3415
(IFF) -- -- -- 1.5 1.0
SURFACTANT
Poloxamer-338 89.0 88.0 89.0 88.5 89.0
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TABLE 13
ULTRAMULSION COMPOSITIONS FOR MOUI~ AND LIPS
% W/W
A. Lip Balm FY~mp'~f: 102 103
Min~l Oil-USP 220 250
Petroleum Jelly-USP 50 50
Ozokerite box 13.0 5.0
Paraffin box 12.0 17.0
ULTRAMULSION
Example #3 3.0
Example #8 - 3.0
TABLE 14
B. Gel for Canker Sore Treatment 104 105
D.I. Water 56.1 46.6
Sorbitol - 70% 32.0 32.0
Propylene Glycol - -
Glycerin - USP 6.0 6.0
P~ ...... Sorbate 0.14 0.14
Sodium Saccharin 0.06 0.06
Sodium CMC 2.50 2.50
Flavor 0.20 0.20
camphor 0.50 0.50
ULTR~IULSION.
lC #10 2.50
Example # 7 - 2.0
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TABLE 15
EXAMPLES 106-108
Cough Drop or Sore Throat C~- r- 'f~ns
% W/W
F.Y~m~ ' ~ 106 (Cough Drop):
Glucose 26.5
Corn Syrup 40.0
Sugar 30.0
Flavor 0.5
ULTRAMULSION:
Example #8 3.0
Esample 107 (Cough Syrup):
Corn Syrup 15.0
Flavoring 0.3
D.I. Water 83.7
ULTRAMULSION:
Example #15 1.0
F. , '- 108 (Sore Throat Spray):
D.I. Water 74.55
Sorbitol-70% Aq. 20.0
Glycerine 3.0
Xan~an Gum 0.05
Flavor 0.40
ULTRAMULSION:
Example #13 2.00
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TABLE 16 - EXAMPLES 109 - 110
Example 109 (Alcohol Free Rinse for Trench Mo!uth)
D.I. Water 83.02
Sorbitol - 70% aq. 10.0
Glycerine - USP 3.0
Sodium .Sacrh~nn 0.06
Sodium Butyrate 0.44
EDTA 0.05
Xanthan Gum 0.03
I~TRAMULSION:
Example #12 3.0
F. ~ 110 (Dual Dispensed Moulh. ~ -L Cc --rtrate):
Phase A
Glycerine-Anhydrous 84.553
SiO-Zeodent 113 15.0
Stannous Fluoride 0.447
Phase B
D.I. Water 70.0
Flavor 4.6
Color Blue #1 0.001
ULTRAMULSION:
Example #14 25.399
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TABLE 17
F. ,~ ntacid Tablets):
Tablet:
A. Min~al Oil 10.0
Flavor 6.0
Sodium Polypho,~,ph, te 2.0
Corn Starch 0.6
Sucrose 41 .9
Talc 0.5
Calcium Carbonate 39.0
B. ULTRAMULSION:
Example #3 5.0
Phase A - Alone 9S 0
C~ ' ~ r~oced~le for F.s~mp~~ 111:
Phase A is dry blended together in a paddle mixcr, c g., Hobart, to form a so-
called wet/dry granulation. Phase A is then heated to 65-70~C while mixing, and the
ULTRAMULSIONTM dispersion is added to the granulation. The
ULTRAMULSIONTM dispersion melts and "plates out" on the surface of each
granulation particle. The resulting gr,m-l~t~d m~t~iAl is cooled to room ~GIllpGldlUlG
and is tableted using 1.3 grams and 40,000 Ibs.
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TABLE 18
F. , '- 112 (Antacid Liquid): :
Phase A
C~lri~m Carbonate 96.0
ULTRAMULSION:
~Y~mple #7 4.0
Phase B
Phase A 4.0
D.I. Water 85.4
Sucrose 6.0
Flavor 1.5
Xanthan Gurn 0.1
Glycerine 3.0
CQ~P -~ g P~uce 1 e for F. - p'~ 112:
Phase A is ~ artd by heating calcium carbonate in an air stream to 65-70%; the
ULTRAMULSIONTM dispersion is introduced at 65-70~C and melts in the hot air
stream and "plates" each individual CaC03 particle. The material is cooled and
~rc~a~ed into a liquid antacid per Phase B.
F.~ 113 ~Ulcer Tr~' Tablet)
~ll.. i.. Hydroxide Powder 55.0
Mineral Oil 14.5
Sodium Polyphnsph~tç22.0
Talc 0.5
ULTRAM~SION:
Example #12 8.0
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TA~BLE 19
INrrEIUDENTAUL DEVICE FORU~nnLATIONS(% WrVV)
T~ # 114 115 116 117 118
Comr- n-ont~-
Sorbitol
- 70% Aq. 7.5 7.5 8.0 9.0 7.0
Sodium
,Sacrh~rin 0.4 0.4 0.4 0.4 0.4
Flavor 5.0 5.0 5.4 5.1 4.8
D.I. Water 75.1 75.1 71.2 74.5 78.8
UL~AMULSION~
Example 1 12
Example 3 - 12
Example 12 - - 15
Example 14 - - - 11
Example 2 - - - - 9
E'-oced ~ for T n~ .g lnterdental Si I-~ ~
1. Material to be i.,.p.c~l.ated (e.g., wooden sticks) with the
ULTRAMULSION~f dispersion (or form~ tion) is placed in suitable C-nt~inPr
capable of holding a vacuum, such as a ~ei~c~t~r, stainless steel covered reactor or
similar device.
2. The liquid fr~rmlll~tion is poured on top of the m~t~i~l and covered
completely by the liquid. A pc r~dLcd disk with ballast is placed on the m~f~ri~l to
keep from floating
3. The cont~in~r is then sealed, and vacuum applied for varying periods of time
ranging from 1 min. to several hours with the plcrcllcd time being between 5-10 min.
4. Vacuum is IllZ.;lllAi~ such that the liquid does not boil, but enough vacuum
to remove e.-L c.~ped air from the device.
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TABLE 19 CONTINI~D
F , '~ of l ~c ~t~ dn ' using ~.oQ ' T ' ~.. 1~1 Si lqtors (IDS)
Collectively, 87.0 grams of wooden hlLGl'dGllldl stim~ tcr~ (IDS) equals about
260 individual stiml-l~trr~ This IDS batch was illl~lc~;lldlGd with the
ULTRAMULSION~M dispersion fcrml-l~tir)n from Fy~mple 22 under vacuum, at 30
rnm of Ill~ for a period of 10 mimlt~ The resulting hll~lG~IldlGd IDS batch was
removed from the r~ e solution and dried at 40~C in collvG-;Lion oven for 1.5
hour. The IDS were dry and the final batch weight was 152.7 grams. This is a
56.9% increase in weight intlir~tine the amount of dry f~rmlll~ti~n i.l.~.G~.lated into
the IDS.
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The present invention has been described in detail, inrlll-lin~ the pl~rt;l~c;d
embo~lim~ntc thereof. However, it will be a~pl~-,idlt;d that those skilled in the art,
upon con~id~ation of the present disclosure, may make mntlifir~tions and/or
hllyl~v~ ~ on this invention and still be within the scope and spirit of this
5 invention as set forth in the following claims.
