U.S. patent application number 13/006583 was filed with the patent office on 2011-05-12 for stable hydroalcoholic compositions.
This patent application is currently assigned to 3M Innovative Properties Company. Invention is credited to Robert A. Asmus, Jill R. Charpentier, Matthew T. Scholz.
Application Number | 20110110869 13/006583 |
Document ID | / |
Family ID | 23961400 |
Filed Date | 2011-05-12 |
United States Patent
Application |
20110110869 |
Kind Code |
A1 |
Scholz; Matthew T. ; et
al. |
May 12, 2011 |
STABLE HYDROALCOHOLIC COMPOSITIONS
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
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.
Inventors: |
Scholz; Matthew T.;
(Woodbury, MN) ; Asmus; Robert A.; (Hudson,
WI) ; Charpentier; Jill R.; (Minnetonka, MN) |
Assignee: |
3M Innovative Properties
Company
|
Family ID: |
23961400 |
Appl. No.: |
13/006583 |
Filed: |
January 14, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10400597 |
Mar 27, 2003 |
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13006583 |
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10016264 |
Dec 10, 2001 |
6562360 |
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10400597 |
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09320590 |
May 27, 1999 |
6352701 |
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10016264 |
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08781090 |
Jan 9, 1997 |
5951993 |
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09320590 |
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08493714 |
Jun 22, 1995 |
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08781090 |
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Current U.S.
Class: |
424/45 |
Current CPC
Class: |
A61K 8/342 20130101;
A61K 8/39 20130101; A61K 8/37 20130101; A61K 8/416 20130101; Y10S
514/873 20130101; Y10S 514/846 20130101; Y10S 514/975 20130101;
A61Q 19/00 20130101; Y10S 514/944 20130101; A61P 31/02 20180101;
A61P 31/00 20180101; A61K 8/604 20130101; A61K 8/86 20130101; A61Q
17/005 20130101; A61K 8/34 20130101; Y10S 514/946 20130101; Y10S
514/945 20130101 |
Class at
Publication: |
424/45 |
International
Class: |
A61K 9/12 20060101
A61K009/12 |
Claims
1. A hydroalcoholic foam comprising: a hydroalcoholic solvent
comprising a lower alcohol and water in a weight ratio of about
60:40 to about 95:5; wherein the lower alcohol is present in the
hydroalcoholic foam in an amount of at least 60 wt-%; a
polyether/polysiloxane copolymer; and a surfactant or emulsifier
other than a polyether/polysiloxane copolymer; wherein the total
amount of surfactant or emulsifier other than
polyether/polysiloxane copolymer is present in the hydroalcoholic
foam in an amount of less than 5% by weight of the total foam.
2. The foam of claim 1 further comprising at least one emollient
that is a wax at room temperature and at least one emollient that
is a liquid at room temperature, wherein the weight ratio of wax to
liquid emollients is from 5:1 to 1:5.
3. The foam of claim 1 further comprising a mixture of emollients,
wherein the mixture comprises an occlusive emollient and a
humectant.
4. The foam of claim 1 wherein the total amount of surfactant or
emulsifier other than polyether/polysiloxane copolymer is less than
4% by weight of the total foam.
5. The foam of claim 4 wherein the total amount of surfactant or
emulsifier other than polyether/polysiloxane copolymer is less than
3% by weight of the total foam.
6. The foam of claim 1 wherein the hydroalcoholic solvent comprises
a lower alcohol and water in a weight ratio of about 60:40 to about
85:15.
7. The foam of claim 1 wherein the polyether/polysiloxane copolymer
surfactant has the following chemical structure:
(CH.sub.3).sub.3--Si--O--[Si(CH.sub.3)R.sub.11--O].sub.x[Si(CH.sub.3)R.su-
b.8--O].sub.y--Si(CH.sub.3).sub.3 where x+y=5-400, and R.sub.8 is a
polyether substituted alkyl group with the structure:
--R.sub.9--O(C.sub.2H.sub.4O).sub.p(C.sub.3H.sub.6O).sub.qR.sub.10;
where R.sub.9 is an alkyl group of 1 to 6 carbon atoms; R.sub.10 is
hydrogen or an alky group of 1-22 carbon atoms; R.sub.11 is an
alkyl group of 1 to 22 carbon atoms or phenyl; p=2-300; and
q=0-100.
8. The foam of claim 1 wherein the polyether/polysiloxane copolymer
is present in an amount of at least 0.8%.
9. The foam of claim 1 further comprising an antimicrobial agent
distinct from the lower alcohol.
10. A hydroalcoholic foam comprising: a hydroalcoholic solvent
comprising a lower alcohol and water in a weight ratio of about
60:40 to about 95:5; wherein the lower alcohol is present in the
hydroalcoholic foam in an amount of at least 60 wt-%; a
polyether/polysiloxane copolymer; an antimicrobial agent distinct
from the lower alcohol; and optionally, a surfactant or emulsifier
other than a polyether/polysiloxane copolymer; wherein the total
amount of surfactant or emulsifier other than
polyether/polysiloxane copolymer, if present, is less than 5% by
weight of the total foam.
11. The foam of claim 10 further comprising at least one emollient
that is a wax at room temperature and at least one emollient that
is a liquid at room temperature, wherein the weight ratio of wax to
liquid emollients is from 5:1 to 1:5.
12. The foam of claim 10 further comprising a mixture of
emollients, wherein the mixture comprises an occlusive emollient
and a humectant.
13. The foam of claim 10 wherein the total amount of surfactant or
emulsifier other than polyether/polysiloxane copolymer, if present,
is less than 4% by weight of the total foam.
14. The foam of claim 13 wherein the total amount of surfactant or
emulsifier other than polyether/polysiloxane copolymer, if present,
is less than 3% by weight of the total foam.
15. The foam of claim 10 wherein the hydroalcoholic solvent
comprises a lower alcohol and water in a weight ratio of about
60:40 to about 85:15.
16. The foam of claim 10 wherein the polyether/polysiloxane
copolymer surfactant has the following chemical structure:
(CH.sub.3).sub.3--Si--O--[Si(CH.sub.3)R.sub.11--O].sub.x[Si(CH.sub.3)R.su-
b.8--O].sub.y--Si(CH.sub.3).sub.3 where x+y=5-400, and R.sub.8 is a
polyether substituted alkyl group with the structure:
--R.sub.9--O(C.sub.2H.sub.4O).sub.p(C.sub.3H.sub.6O).sub.qR.sub.10;
where R.sub.9 is an alkyl group of 1 to 6 carbon atoms; R.sub.10 is
hydrogen or an alky group of 1-22 carbon atoms; R.sub.11 is an
alkyl group of 1 to 22 carbon atoms or phenyl; p=2-300; and
q=0-100.
17. The foam of claim 10 wherein the polyether/polysiloxane
copolymer is present in an amount of at least 0.8%.
18. The foam of claim 10 further comprising at least one additional
emollient other than the polyether/polysiloxane copolymer.
19. The foam of claim 10 wherein the antimicrobial agent is a
chlorhexidene salt.
20. A hydroalcoholic foam comprising: a hydroalcoholic solvent
comprising a lower alcohol and water in a weight ratio of about
60:40 to about 95:5; wherein the lower alcohol is present in the
hydroalcoholic foam in an amount of at least 60 wt-%; a
polyether/polysiloxane copolymer; and a mixture of emollients,
wherein the mixture comprises an occlusive emollient and a
humectant.
21. The foam of claim 20 wherein the mixture of emollients
comprises two or more selected from the group consisting of a
poly(ethylene oxide) homopolymer, a poly(alkylene oxide)
homopolymer, a poly(alkylene oxide) copolymer, a
polyoxyethylene/polyoxypropylene glycol, an alkyl phenol with 6 to
12 carbon atoms in the alkyl chain condensed with 2 to 20 moles of
ethylene oxide, a mono- or di-fatty acid ester of ethylene glycol
wherein the fatty acid moiety contains from 10 to 20 carbon atoms,
a fatty acid monoglyceride wherein the fatty acid moiety contains
from 10 to 20 carbon atoms, a polyethylene glycols of molecular
weight 200 to 6000, a polyoxyethylene sorbitol, a hydrophilic wax
ester, an ethoxylated glyceride, a polyoxyethylene polyol fatty
acid ester, and mixtures thereof.
22. The foam of claim 20 wherein at least one emollient is a wax at
room temperature and at least one emollient is a liquid at room
temperature, wherein the weight ratio of wax to liquid emollients
is from 5:1 to 1:5.
23. The foam of claim 22 wherein at least one emollient is a wax at
room temperature and at least one emollient is a liquid at room
temperature, wherein the weight ratio of wax to liquid emollients
is from 3:1 to 1:3.
24. The foam of claim 20 further comprising an antimicrobial agent
distinct from the lower alcohol.
25. The foam of claim 20 further comprising a surfactant or
emulsifier other than a polyether/polysiloxane copolymer.
26. The foam of claim 25 wherein the surfactant or emulsifier
comprises at least one long chain hydrocarbon of at least 18 carbon
atoms.
27. A hydroalcoholic foam comprising: a hydroalcoholic solvent
comprising a lower alcohol and water in a weight ratio of about
60:40 to about 95:5; a polyether/polysiloxane copolymer; at least
one emulsifier or surfactant other than a polyether/polysiloxane
copolymer; at least one emollient other than the
polyether/polysiloxane copolymer; wherein the total amount of
surfactant or emulsifier other than polyether/polysiloxane
copolymer is present in an amount of less than 5% by weight of the
total foam; wherein the emulsifier or surfactant is selected from
the group consisting 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
polyalkoxylated derivative of a polyhydric alcohol, an ether of a
polyalkoxylated derivative of a polyhydric alcohol, a sorbitan
fatty acid ester, a polyalkoxylated derivative of a sorbitan fatty
acid ester, and mixture thereof; and wherein the emollient is
selected from the group consisting of a poly(ethylene oxide)
homopolymer, a poly(alkylene oxide) homopolymer, a poly(alkylene
oxide) copolymer, a polyoxyethylene/polyoxypropylene glycol, an
alkyl phenol with 6 to 12 carbon atoms in the alkyl chain condensed
with 2 to 20 moles of ethylene oxide, a mono- or di-fatty acid
ester of ethylene glycol wherein the fatty acid moiety contains
from 10 to 20 carbon atoms, a fatty acid monoglyceride wherein the
fatty acid moiety contains from 10 to 20 carbon atoms, a
polyethylene glycols of molecular weight 200 to 6000, a
polyoxyethylene sorbitol, a hydrophilic wax ester, an ethoxylated
glyceride, a polyoxyethylene polyol fatty acid ester, and mixtures
thereof.
28. A method of controlling infection comprising disinfecting hands
using a hydroalcoholic foam comprising: a hydroalcoholic solvent
comprising a lower alcohol and water in a weight ratio of about
60:40 to about 95:5; wherein the lower alcohol is present in the
hydroalcoholic foam in an amount of at least 60 wt-%; and a
polyether/polysiloxane copolymer; wherein the foam does not
detrimentally affect the tear strength of surgical gloves.
29. The method of claim 28 wherein the foam further comprises an
antimicrobial agent distinct from the lower alcohol.
30. The method of claim 28 wherein the foam further comprises an
emollient other than the polyether/polysiloxane copolymer.
31. The method of claim 28 wherein the foam further comprises a
surfactant or emulsifier other than polyether/polysiloxane
copolymer.
32. The method of claim 31 wherein the total amount of surfactant
or emulsifier other than polyether/polysiloxane copolymer, if
present, is less than 5% by weight of the total foam.
33. The method of claim 31 wherein the surfactant or emulsifier
comprises at least one long chain hydrocarbon of at least 18 carbon
atoms.
Description
[0001] This application is a divisional of application Ser. No.
10/400,597, filed Mar. 27, 2003, which is a continuation of
application Ser. No. 10/016,264 filed on 10 Dec. 2001 (U.S. Pat.
No. 6,562,360), which is a divisional of application Ser. No.
09/320,590 filed on May 27, 1999 (U.S. Pat. No. 6,352,701), which
is a continuation of application Ser. No. 08/781,090, filed on Jan.
9, 1997 (U.S. Pat. No. 5,951,993), which is a continuation-in-part
of application Ser. No. 08/493,714, filed Jun. 22, 1995
(abandoned), all of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions useful as skin
disinfectants, surgical hand preparations, patient skin
preparations and antimicrobial hand lotions. More specifically the
invention relates to stable hydroalcoholic compositions which are
thickened using mixed emulsifier systems.
BACKGROUND OF THE INVENTION
[0003] Control of nosocomial infection and exposure to infectious
disease is of paramount concern to doctors, nurses, and clinicians
who work in hospitals and surgery centers. One of the most
effective methods for controlling infection is regimented hand
disinfection before and possibly after each patient contact and
particularly before and after each surgical procedure. Hand
disinfection is generally accomplished using antimicrobial soaps
with water. These soaps are usually formulated to include either
povidone-iodine (usually 7.5% by weight) or chlorhexidine gluconate
(CHG) (usually 2 or 4% by weight) as the active antimicrobial
agent. In addition, these formulated soaps may contain surfactants
and possibly low levels of humectants such as glycerin.
[0004] Hand disinfection is also accomplished using presurgical
scrub replacements. These are used instead of the soap and water
scrub. Presurgical scrub replacements ideally achieve bacterial
kill equal to or better than a traditional soap and water scrub and
in a shorter period of time. Additionally, they maintain or improve
the skin's natural barrier to microbial and chemical contamination
while providing acceptable tactile properties. Examples of
presurgical scrub replacements include hydroalcoholic gels which
generally include high levels of either ethanol or isopropanol as
the disinfecting agent and also include a thickener and optionally
include a humectant (e.g. glycerin). To date, thickeners used in
hydroalcoholic gels have been based on anionic polymers such as
polyacrylic acid (sold under the tradename Carbopol by BF Goodrich
Specialty Polymers and Chemicals Division of Cleveland, Ohio). U.S.
Pat. No. 4,915,934 to Tomlinson discloses the use of CHG-containing
antiseptic foams based on hydroalcoholic solvents, a fatty alcohol,
and a surfactant. The surfactant is selected from the group of
ethoxylated sorbitan alkylates, ethoxylated fatty alcohols, and
ethoxylated nonyl phenols.
[0005] Formulating stable viscous hydroalcoholic emulsions is
difficult for two reasons. First, addition of short chain alcohols
(such as ethanol) to an aqueous system decreases the surface
tension dramatically. For example, 40% by weight ethanol in water
has a surface tension of approximately 31 dyne/cm compared to pure
water which has a surface tension of about 72 dyne/cm at 20.degree.
C. A hydroalcoholic solution at 60% by weight ethanol has a
dramatically decreased surface tension as compared to water. Such a
composition has a surface tension of approximately 27 dyne/cm at
20.degree. C. Second, many surfactants typically used in cosmetic
emulsions become completely or partially soluble in hydroalcoholic
systems.
[0006] In bulletin 51-0001-259 regarding skin care, Specialty
Chemicals of ICI America of Wilmington, Del. 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 continued
that ethanol is often used to break emulsions.
[0007] U.S. Pat. No. 4,956,170 to Lee discloses a hydroalcoholic
skin moisturizing/conditioning antimicrobial gel. The gel comprises
60-75% ethanol and 0.4-2% of a polymeric thickening agent. The
formulations also comprise polyethoxylated non-ionic
surfactants/emulsifiers to stabilize the added emollient oils in
addition to a fatty alcohol.
[0008] U.S. Pat. No. 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
comprising a C16-C22 alcohol, aerosol propellant and a non-ionic
polyethoxylated surfactant.
SUMMARY OF THE INVENTION
[0009] This invention provides compositions useful as products for
skin disinfection such as presurgical hand preps, patient preps,
and lotions. The preferred formulations of this invention, in
general, have a very nice feel after both single and multiple
applications. Additionally, preferred formulations maintain or
improve the skin condition after multiple applications and no slimy
or abnormal feeling is noticed during post application hand
washing. When used as a presurgical scrub replacement, this
invention achieves bacterial, fungal, and viral kill equal to or
better than a traditional soap and water scrub in a shorter period
of time while maintaining or improving the skin's natural barrier
to microbial and chemical contaminants. The invention overcomes the
shortcomings of past compositions by providing a viscous
composition which includes a high concentration of a lower alcohol
but does not require a polymeric thickener to make the composition
viscous. Further, the composition has a cosmetically elegant feel
and may be dispensed as a lotion or as a foam.
[0010] This invention provides a composition comprising 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 emulsifiers are selected such that 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, wherein: (i) the hydrophobic 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 atoms; and (ii) the hydrophilic group of at least
one emulsifier is comprised of an amide group having the structure
--NHC(O)R''' or --C(O)NHR''' where R''' is hydrogen or an alkyl
group of 1-10 carbon atoms optionally substituted in available
positions by N, O, and S atoms; an ester group of short chain
alcohols or acids (e.g., L=--C(O)OR' or --OC(O)R' where R' is C1-C4
branched or straight chain alkyl optionally substituted in
available positions by hydroxyl groups); a polyglucoside group
having 1-10 glucose units; a polyglycerol ester group having 1-15
glycerol units, a secondary amine group; a tertiary amine group; a
quaternary amine group; an anionic group such as a sulfate,
sulfonate, phosphate, phosphonate, or carboxylate group; or a
zwitterionic group having the formula:
##STR00001##
wherein each R'' is independently hydrogen or an alkyl group
(having 1-5 carbon atoms) or alkenyl group (having 2-4 carbon
atoms), which alkyl or alkenyl groups are optionally substituted
with nitrogen, oxygen, or sulfur atoms, including alkyl or alkenyl
carboxyl groups; Q is hydrogen or hydroxyl; x is 1 to 4; and L' is
--CO.sub.2.sup.-, --OP(O)(O.sup.-)(O.sup.-M.sup.+),
--(O)P(OR''')(O)(O.sup.-) (where R''' is hydrogen or an alkyl group
of 1-10 carbon atoms optionally substituted in available positions
by N, O, or S atoms), --SO.sub.2O.sup.-, or --OSO.sub.2O.sup.-,
where M.sup.+ 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, or N.sup.+R''.sub.4; as well
as combinations of these groups; and (iii) the hydrophilic group of
at least one emulsifier is comprised of an alcohol group; an
ethylene oxide/propylene oxide copolymer group having 2-150 moles
of ethylene oxide plus propylene oxide per mole of hydrophobe ("R")
and bonded to the hydrophobe through an ether or ester linkage, and
optionally terminated by C1-C36 alkyl or C6 to C36 alkaryl ester;
an ester or ether group of a polyhydric alcohol and their
polyalkoxylated derivatives; an ester or ether of sorbitan or
polyalkoxylated sorbitan group, as well as combinations of these
groups. Thus, it will be understood by one of skill in the art that
the emulsifiers can include combinations of all "L" hydrophilic
groups described herein (e.g., ester groups and amide groups in one
molecule).
[0011] This invention further provides a method of preparing a
stable hydroalcoholic composition comprising the steps of preparing
a thickener system comprised of at least two emulsifiers as
described above; and combining a hydroalcoholic solvent with the
thickener system at a temperature sufficient to melt said thickener
system and in an amount that provides a composition having between
at least about 0.5% and 8.0% by weight thickener system.
[0012] This invention also provides a method of preparing a stable
hydroalcoholic composition comprising the steps of: (a) heating a
thickener system to a temperature sufficient to melt said thickener
system, wherein the thickener system is comprised of at least two
emulsifiers as described above; (b) combining the thickener system
and an aqueous phase, and (c) adding a lower chain alcohol to the
aqueous/thickener system combination wherein the alcohol to water
weight ratio in the composition is between 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. Methods of applying such
compositions to skin are also provided.
DEFINITIONS
[0013] "Ambient temperature" as used herein refers to the
temperature range between about 21 and 25 degrees C.
[0014] "Auxiliary thickeners" as used herein refers to additives
(other than the emulsifiers which comprise the thickener system
described below) which increase the viscosity of the solvent phase
even in the absence of the thickener system. Certain auxiliary
thickeners may act synergistically with the thickener system to
increase the viscosity of the resultant formula. Auxiliary
thickeners include but are not limited to soluble and swellable
polymers and associative colloidal thickeners such as silica,
magnesium aluminum silicate, and the like.
[0015] "Emollient" as used herein refers broadly to materials which
are capable of maintaining or improving the moisture level,
compliance, or appearance of the skin when used repeatedly.
[0016] "Emulsifier" as used herein is synonymous with "surfactant"
and refers to molecules comprising hydrophilic (polar) and
hydrophobic (non-polar) regions on the same molecule.
[0017] "Emulsion" as used herein refers to a stable dispersion of
one liquid in a second immiscible liquid.
[0018] "Lotion" means liquid or cream, free of any propellant.
[0019] "Melt temperature" (Tm) as used herein refers to the
temperature at which compositions or emulsions of the present
invention dramatically lose viscosity.
[0020] "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.
[0021] "Solvent", "solvent system" or "hydroalcoholic solvent" as
used herein refer to the alcohol and water combination in the
present invention.
[0022] "Stable" as used herein refers to a composition that
displays less than or equal to 10% by volume separation after
centrifuging at 2275.times.g for 30 minutes at ambient
temperature.
[0023] "Surfactant" as used herein is synonymous with "emulsifier,"
the definition of which is given above.
[0024] "Thickener system" as used herein refers to a combination of
at least two emulsifiers each present in a concentration of at
least 0.05% by weight capable of providing a viscosity of at least
4,000 centipoise at 23.degree. C. to the compositions of the
present invention without auxiliary thickeners.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The invention provides a composition comprised of a lower
chain alcohol, water, and thickening system. Alcohols used in the
present invention are first discussed followed by a discussion of
thickening systems. Ingredients which are optionally added to the
composition such as antimicrobial agents and emollients are then
discussed followed by a discussion of how to prepare compositions
of the present invention.
Alcohol
[0026] The alcohol used in the present invention is a lower
hydrocarbon chain alcohol such as a C1-C4 alcohol. In preferred
embodiments the alcohol is chosen from ethanol, 2-propanol, or
n-propanol, and most preferably ethanol. Ethanol is a preferred
alcohol since it provides broad spectrum and quick killing of
microbes and has an odor acceptable to consumers such as doctors,
nurses and clinicians. The invention anticipates that a single
alcohol may be used or that a blend of two or more alcohols may
comprise the alcohol content of the composition.
[0027] 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 immediate bacterial kill. In a preferred
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. Higher alcohol to water ratios are used in a
preferred embodiment for optimum antimicrobial activity and to
ensure the composition is fast drying.
Thickener System
[0028] The thickener 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 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 maintain an acceptable viscosity at 25.degree.
C. and preferably up to 35.degree. C. Finally, in most the
preferred embodiments formulations are stable to heat and cool
cycles (heating up to 50.degree. C. or higher and cooling to
ambient temperature) as well as freeze/thaw cycles (cooling to
-30.degree. C. and warming to ambient temperature). All of these
cosmetic attributes are affected by the types and amounts of
emulsifiers chosen which comprise the thickener system of the
present invention and are discussed below.
[0029] The thickener system of the invention must be compatible
with the hydroalcoholic solvent system described above in order to
provide acceptable cosmetic properties and appropriate viscosity.
Compositions of this invention have a viscosity of at least about
4,000 cps at 23.degree. C., preferably at least about 10,000 cps,
more preferably at least about 20,000, even more preferably at
least about 50,000 cps, even more preferably at least about 100,000
cps, and most preferably about 80,000 to about 500,000 cps measured
using a very low shear viscometer such as Brookfield LVDV-I.sup.+
viscometer and T spindles with a heliopath adapter. Since the
emollient system and other optional ingredients may affect the
viscosity (either positively or negatively), the measured viscosity
is that of the final composition without any added auxiliary
thickeners.
[0030] The viscosity of the present invention is imparted by a
thickener system comprised of at least two emulsifiers, and
preferably at least two emulsifiers from different classes. In a
preferred embodiment at least one of the emulsifiers is a solid at
room temperature comprising at least one long chain hydrocarbon of
at least 16 carbon atoms, preferably at least 18 carbon atoms, and
more preferably at least 22 carbon atoms. At lower alcohol:water
ratios of greater than 6:40 the long chain hydrocarbon preferably
has greater than 22 carbon atoms. The thickener system of the
present invention can be described in terms of the number average
chain length of greater than about 22 carbon atoms.
[0031] Emulsifiers of this invention are comprised of molecules
having hydrophilic (polar) and hydrophobic (non-polar) regions on
the same molecule and conform to the general structure:
(R).sub.a(L).sub.b
P Where "R" represents a hydrophobic group, "L" represents a
hydrophilic group, and "a" and "b" are independently 1 to 4.
[0032] In this invention "R" comprises an alkyl group of at least
16 carbon atoms, preferably at least 18 carbon atoms and more
preferably at least 20 carbon atoms and most preferably at least
about 22 carbon atoms; alkenyl group of at least 16 carbon atoms,
preferably at least 18 and most preferably at least 20 carbon
atoms; or aralkyl or aralkenyl group of at least 20 carbon atoms,
preferably at least 24 carbon atoms and most preferably at least 26
carbon atoms. In a preferred embodiment R is unbranched.
[0033] In the above formula, "L" represents a hydrophilic group.
For example, L can include an amide group having the structure
--NHC(O)R''' or --C(O)NHR''' where R''' is hydrogen or an alkyl
group of 1-10 carbon atoms optionally substituted in available
positions by N, O, and S atoms; an ester group of short chain
alcohols or acids (e.g., L=--C(O)OR' or --OC(O)R' where R' is C1-C4
branched or straight chain alkyl optionally substituted in
available positions by hydroxyl groups); a polyglucoside group
having 1-10 glucose units and more preferably 1-3 glucose units; a
polyglycerol ester group having 1-15 glycerol units, preferably
2-12 glycerol units, and more preferably 3-10 glycerol units; a
secondary amine group; a tertiary amine group; and a quaternary
amine group.
[0034] "L" can also include an anionic group such as a sulfate,
sulfonate, phosphate, phosphonate, or carboxylate group, or a
zwitterionic group having the formula:
##STR00002##
wherein each R'' is independently hydrogen or an alkyl group
(having 1-5 carbon atoms) or alkenyl group (having 2-4 carbon
atoms), which alkyl or alkenyl groups are optionally substituted
with nitrogen, oxygen, or sulfur atoms, including alkyl or alkenyl
carboxyl groups; Q is hydrogen or hydroxyl; x is 1 to 4; and L' is
--CO.sub.2.sup.-, --OP(O)(O.sup.-)(O.sup.-M.sup.+),
--(O)P(OR''')(O)(O.sup.-) (where R''' is hydrogen or an alkyl group
of 1-10 carbon atoms optionally substituted in available positions
by N, O, or S atoms), --SO.sub.2O.sup.-, or --OSO.sub.2O.sup.-,
where M.sup.+ 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, or N.sup.+R''.sub.4.
[0035] "L" can also include an alcohol group; a polyhydric alcohol
group such as, but not limited to, ethylene glycol, propylene
glycol, butylene glycol, pentaerythrytol, glycerol, and sorbitol;
an ethylene oxide and/or propylene oxide group, preferably having
2-150 moles of ethylene oxide plus propylene oxide per mole of
hydrophobe ("R"), which is bonded to the hydrophobe through an
ether or ester linkage, and optionally terminated by C1-C36 alkyl
ester, C2-C36 alkenyl ester, or C6 to C36 alkaryl ester (i.e.,
aralkyl ester); an ester or ether group of a polyhydric alcohol and
their polyalkoxylated derivatives; an ester or ether of sorbitan or
polyalkoxylated (i.e., polyalkyleneoxide) sorbitan group,
preferably having 2-150 moles of alkylene oxide per mole of
hydrophobic group; as well as combinations of these groups, e.g., a
polyethoxylated polyglucoside group. Thus, it will be understood by
one of skill in the art that the emulsifiers can include
combinations of all "L" hydrophilic groups described herein (e.g.,
ester groups and amide groups in one molecule).
[0036] The hydrophobic and hydrophilic groups on non-ionic
emulsifiers are generally selected to have a hydrophile/lipophile
balance (HLB) of 2 to 20 and more preferably 4 to 16. Furthermore,
the weight average HLB of the thickener system is preferably 4 to
16 and more preferably 8 to 12. (For example, a thickener system
comprised of 40% by weight of an emulsifier with an HLB of 10 and
60% by weight of an emulsifier with an HLB of 15 has a weight
average HLB of 13.)
[0037] The emulsifiers which comprise thickener systems may be
chosen from a single class of surfactants (e.g., a mixture of chain
length alkyl polyglucosides) but is preferably a mixture of
emulsifier classes. Many commercially available emulsifiers are
actually comprised of a mixture of chain lengths. For example, some
behenyl alcohol as commercially supplied is actually a mixture of
alcohols consisting of primarily C22 and C20 fractions but contain
detectable levels of C24, C18 and C16 fractions. For this reason,
the chain lengths specified herein refer to the number average
chain length. Furthermore, in multiple emulsifier thickener systems
of the present invention, each emulsifier must be present in a
concentration of at least about 0.05% and more preferably at least
about 0.1% by weight to be considered a component of a thickener
system. Thickener systems of the present invention are capable of
achieving high viscosities at relatively low total emulsifier
concentrations. The total concentration of emulsifiers present as a
thickener system is generally less than about 8% by weight,
preferably less than about 5% by weight, more preferably less than
about 4% by weight, and most preferably less than about 3% by
weight of the total composition of the present invention.
Typically, the thickener system is present in the composition in an
amount of at least about 0.5% by weight, based on the total weight
of the composition. In the most preferred compositions of this
invention, the thickener system comprises between about 0.75% by
weight to about 5% by weight, more preferably between about 1.0% by
weight to about 3.5% by weight and most preferably between about
1.5% by weight to about 3% by weight of the composition. As used
herein an emulsifier is considered part of the thickener system if
its presence in the formula results in an 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
emollient or stabilizer as defined below.
[0038] Preferred compositions of the present invention which are
substantially free of polymeric thickening agents have a "melt
temperature" (Tm). If compositions are heated above this melt
temperature, they dramatically lose viscosity. The compositions of
the present invention preferably have melt temperatures greater
than 25.degree. C. in order to maintain a high viscosity at room
temperature. More preferably the melt temperature is greater than
35.degree. C. in order to maintain viscosity once applied to the
skin. The most preferred formulations have a melt temperature
greater than 40.degree. C. in order to allow shipping and handling
without refrigeration. Thickener systems affect the melt
temperature of a given composition. In order to obtain a preferred
melt temperature a preferred thickener system includes at least one
emulsifier which is solid at ambient temperature. Preferably, all
emulsifiers of a thickener system are solid at ambient temperature
to increase the melt temperature of the resultant composition.
[0039] The structure of emulsifiers in a thickener system affects
the melt temperature of the resultant composition. In a preferred
embodiment at least one emulsifier in a thickener system is capable
of promoting a crystalline structure. Crystallinity is promoted by
long straight chain alkyl groups, therefore, at least one
emulsifier preferably comprises a saturated straight chain
hydrocarbon of at least 16, preferably at least 18 and most
preferably at least 20 carbon atoms. Certain hydrophilic head
groups have been found to particularly promote association and
crystallization. Suitable crystalline emulsifiers include alkyl
alcohols, alkyl polyglucosides, polyglycerol alkyl esters, C1-C4
esters of alkyl alcohols, C1-C4 esters of alkyl carboxylates,
optionally substituted alkyl amides, alkyl betaines and alkyl
phosphates or phospholipids, alkyl quaternary amines, alkyl amine
oxides polyethoxylated alkyl alcohols and alkyl esters of
polyethylene glycol.
[0040] In addition to affecting the melt temperature of a
composition, the emulsifier chain length also helps to determine
the maximum level of ethanol which can be used in the composition
and the concentration of emulsifiers required in the thickener
system. At higher levels of alcohol, longer chain emulsifiers are
required to produce viscous stable emulsions. It is believed that
higher levels of alcohol tend to swell or solubilize the
emulsifiers to a greater degree than lower levels of alcohol.
Therefore, as the concentration of ethanol increases the chain
length of the hydrocarbon chains in a thickening system must also
increase in order to maintain a melt temperature over 35.degree. C.
That is, the amount of lower alcohol in the hydroalcoholic system
can affect the choice of surfactant (i.e., emulsifier), and vice
versa. For example, if the composition includes a lower alcohol to
water ratio in excess of about 50:50, the thickener system should
include at least one surfactant having a number average chain
length of at least 16 carbon atoms. If the composition includes a
lower alcohol to water ratio in excess of about 60:40, the
thickener system should include at least one surfactant having a
number average chain length of at least 18 carbon atoms. If the
composition includes a lower alcohol to water ratio in excess of
about 64:36, the thickener system should include at least one
surfactant having a number average chain length of at least 20
carbon atoms.
[0041] For example, systems based on a C16/C18 alkyl polyglucoside
(Montanov 68 available from Seppic, Inc. of Fairfield, N.J.) in
combination with a C18 polyethoxylate (Brij 76 available from ICI
of Wilmington, Del.) in 68:32 ethanol:water have a melt temperature
of approximately 35.degree. C. Similar systems having C22
hydrocarbon chains have melt temperatures of 45.degree. C. or
higher. In addition, as the chain length of the hydrophobic
component in the thickener system increases, the amount of
emulsifier required to achieve a certain viscosity decreases. For
example, the Montanov 68 (C16/C18 alkyl polyglucoside)/Brij 76
(polyethoxylated C.sub.1-8 alcohol) thickener system requires
approximately 5% total emulsifier to achieve a suitable viscosity.
A similar system based on C22 hydrophobes achieves a suitable
viscosity at only 2% total emulsifier.
[0042] The nature and size of hydrophilic head groups of
emulsifiers are important and help to determine which thickening
systems produce viscous stable systems. Certain combinations of
emulsifiers will produce viscous stable emulsions. Without being
bound by theory, it is believed that the size, charge, and degree
of hydrogen bonding are important parameters to determine how
emulsifiers interact.
[0043] Many preferred thickener systems are capable of producing
viscoelastic compositions which are very stable. By varying the
ratio of emulsifiers, the degree of elasticity can be adjusted from
almost a purely viscous composition 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 immiscible emollients. Excessive elasticity, however,
is not preferred since an elastic composition usually does not
provide a cosmetically appealing product. Addition of certain
emulsifiers with at least two hydrophobic components has been shown
to limit the viscoelasticity while ensuring viscous stable
compositions. A favored class of multiple hydrophobic component
emulsifiers are quaternary ammonium salts conforming substantially
to the following structure:
##STR00003##
where: R' and R'' are long chain alkyl or alkenyl hydrocarbon
chains of at least 16 carbon atoms;
[0044] R''' is a short chain alkyl group of 1 to 4 carbon atoms,
preferably methyl or ethyl;
[0045] R'''' is equivalent to either R' or R''' and is preferably
equivalent to R''; and
[0046] X is a halogen, R'''SO.sub.3--, R'''SO.sub.4--, or
R'''CO.sub.2
Some preferred structures include distearyldimethylammonium
chloride, dibehenyldimethylammonium chloride, and
dibehenyldimethylammonium methosulfate, while
dibehenyldimethylammonium methosulfate is a more preferred
structure. Other suitable multiple hydrophobic emulsifiers include
dialkylglycerol esters, trialkylglycerol esters, polyglycerol alkyl
esters, ethylene glycol dialkylesters, polyethylene glycol
dialkylesters, dialkylamides of diamines such as ethylene diamine,
polyalkylesters of pentaerythritol and dialkyl (optionally
ethoxylated) phosphates, and alkyl esters of polyethyoxylated alkyl
alcohols.
[0047] The following emulsifier classes are offered as nonlimiting
examples of suitable emulsifiers for use in the present invention.
Examples of some preferred emulsifiers are provided for each
emulsifier class. For the present invention an emulsifier must be
present with at least one coemulsifier to provide a thickener
system to produce stable viscous compositions.
Class 1. Alkyl or Alkenyl Polyglucosides:
##STR00004##
[0048] where R is a straight chain alkyl or alkenyl group of at
least 16 carbon atoms, preferably at least 18 carbon atoms, and
most 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 preferably at least 26 carbon atoms; and
n=0-10 (when n=0, the valence of the oxygen atom is completed by
H), preferably 1-5 and more preferably 1-3.
[0049] Nonlimiting examples of preferred alkyl or alkenyl
polyglucoside emulsifiers include cetearyl glucoside sold as
"MONTANOV" 68 by Seppic, Inc. of Fairfield, N.J.; behenyl
glucoside, produced experimentally as "ESSAI 624" MP, an alkyl
polyglucoside prepared with 92% C-22 alcohol and corn-derived
glucoside by Seppic, Inc.; and oleyl glucoside.
Class 2. Short Chain Esters of long chain Alcohols or Acids:
RC(O)OR' or ROC(O)R'
where R is as defined immediately above for Emulsifier Class 1; and
R' is C1-C4 branched or straight chain alkyl group, optionally
substituted in available positions by hydroxyl groups.
[0050] Some preferred short chain esters of long chain alcohols or
acids include but are not limited to methyl behenate sold as
"KEMESTER 9022" by Witco, Humko Chemical Division of Memphis,
Tenn.; methyl stearate sold as "KEMESTER 4516" by Witco; methyl
oleate sold as "KEMESTER 205" by Witco; arachidyl proprionate
available as "WAXENOL 801" from Alzo of Sayreville, N.J.; behenyl
lactate, stearyl acetate; and glycerol monoerucate available from
Croda, Inc. of Parsippany, N.J.
Class 3. Alkyl and Alkenyl Alcohols:
[0051] R.sub.6--OH
where R.sub.6 is a straight or branched chain alkyl or alkenyl
hydrocarbon chain of at least 16 carbon atoms, preferably at least
18, more preferably at least 20 carbon atoms, and most preferably
at least 22 carbon atoms, optionally substituted in available
positions by N, O, or S atoms; or an aralkyl or aralkenyl group of
at least 22 carbon atoms, preferably at least 24 carbon atoms and
most preferably at least 26 carbon atoms optionally substituted in
available positions by N, O, and S atoms.
[0052] Nonlimiting examples of preferred alkyl and alkenyl alcohol
emulsifiers useful in a thickener system of the invention include
stearyl alcohol 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 Croda;
C-24 alcohol available as "UNILIN 350" from Petrolite of Tulsa,
Okla.; C31 alcohol available as "UNILIN 425" from Petrolite; and
arachidyl alcohol available as "AR-20" from M. Michel and Co. of
New York, N.Y.
Class 4. Polyglycerol Ester
##STR00005##
[0053] where each R.sub.1 is independently 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 preferably at least 26 carbon atoms; and n=0
to 15, preferably 1 to 12, and most preferably 2 to 10.
[0054] Some examples of preferred polyglycerol ester emulsifiers
useful in a thickener system of the present invention include but
are not limited to decaglycerol monostearate available as "POLYALDO
10.sup.-1-S" from Lonza Inc. of Fairlawn, N.J.; tetraglycerol
monostearate available as "TETRAGLYN 1-S" from Barnet Products
Corporation of Englewood Cliffs, N.J.; and
decaglyceroltetrabehenate.
Class 5. Quaternary Amine
##STR00006##
[0055] where R is as defined above in Emulsifier Class 1; R.sub.2
is the same as R.sub.3 or a long chain alkyl or alkenyl hydrocarbon
chain of at least 16 carbon atoms, preferably at least 18 and more
preferably 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, preferably at least 24 carbon
atoms, and most preferably at least 26 carbon atoms; R.sub.3 is a
short chain alkyl group of 1 to 4 carbon atoms, preferably methyl
or ethyl; R.sub.4 is equivalent to either R.sub.2 or R.sub.3 and is
preferably equivalent to R.sub.3; and X is a halogen,
R.sub.5SO.sub.3.sup.-, R.sub.5SO.sub.4.sup.-,
R.sub.5CO.sub.2.sup.-, (R.sub.5).sub.2PO.sub.4.sup.-, or
(R.sub.5)PO.sub.4.sup.=; where R.sub.5 is defined in Class 6
below.
[0056] Nonlimiting examples of quaternary amine emulsifiers include
dibehenyldimethylammonium methosulfate available as "INCORQUAT
DBM-90" from Croda; behenyltrimethylammonium chloride available as
"NIKKOL CA-2580" from Barnet; and tallowtrimethylammonium chloride
available as "ARQUAD T-27W" from Akzo Chemicals, Inc. of Chicago,
Ill.
Class 6. Tertiary Amine and its Protonated salts
##STR00007##
where R, R.sub.2, and R.sub.3 are as defined above in Class 5 and
R.sub.2 and R.sub.3 may also be selected from polyethoxylated or
polyproxylated alkyl or alkenyl alcohol chains having 1-50 moles of
ethylene oxide or propylene oxide groups per mole of emulsifier and
Y is a halogen, R.sub.5SO.sub.3--, R.sub.5SO.sub.4--,
R.sub.5CO.sub.2--, (R.sub.5)PO.sub.4.sup.-, or
(R.sub.5)PO.sub.4.sup.=, where R.sub.5 is an alkyl or alkenyl group
of 1-22 carbon atoms optionally substituted in available positions
by N, O, and S.
[0057] Some examples of emulsifiers from the class of tertiary
amines and their protonated salts useful in a thickener system of
the invention include but are not limited to
behenamidopropyldimethylamine available as "INCROMINE BB" from
Croda; behenamidopropyldimethylamine gluconate;
tallowedimethylamine hydrochloride; dihydrogenated tallow methyl
amine; stearyl diethanolamine hydrochloride; polyethoxylated
stearyl diethanolamine hydrochloride.
Class 7. Amine Oxides
##STR00008##
[0058] where R.sub.2 and R.sub.3 are as defined above for Class 6
and R.sub.6 is as defined above for Class 3.
[0059] Nonlimiting examples of emulsifiers from the class of amine
oxides suitable in a thickener system of the invention include
behenamine oxide (behenyldimethylamine oxide) available as
"INCROMINE B-30P" from Croda; stearamine oxide available as
"INCROMINE Oxide S" from Croda; behenamidopropyldimethyl amine
oxide; and bis(2-hydroxyethyl)tallow amine oxide available as
"AROMOX T/12" from Akzo.
Class 8. Polyethoxylated and/or Polypropoxylated Alcohols and
Esters and Derivatives thereof
##STR00009##
where R.sub.6 is as defined above for Emulsifier Class 3; m=0-200,
preferably 2-50, most preferably 4-20; p=0 or 1; R.sub.8.dbd.H or
--C(O)--R.sub.12, where R.sub.12 is an alkyl or alkenyl group of
1-36 carbon atoms optionally substituted by N, O or S, or an
aralkyl group of 6 to 36 carbon atoms; and r=0-50.
[0060] Some examples of preferred emulsifiers from the class of
polyethoxylated alcohols and esters include but are not limited to
steareth-2 available as "BRIJ 72" from ICI Americas Inc. of
Wilmington, Del.; steareth-10 available as "BRIJ 76" from ICI;
beheneth-5 available as "NIKKOL BB-5" from Barnet Products Inc.;
beheneth-10 available as "NIKKOL BB-10" from Barnet; C31 alkyl-10EO
available as "UNITHOX 450" from Petrolite Corp. of Tulsa, Okla.;
C31 alkyl-40 EO available as "UNITHOX 480" from Petrolite, and the
lauric ester of "UNITHOX 480" available from Petrolite as
X-5171.
Class 9. Zwitterionics:
##STR00010##
[0061] wherein R is as defined above for Emulsifier Class 1; each
R.sub.7 is independently hydrogen or an alkyl group (having 1-5
carbon atoms) or alkenyl group (having 2-4 carbon atoms), which
alkyl or alkenyl groups are optionally substituted with nitrogen,
oxygen, or sulfur atoms, including alkyl or alkenyl carboxyl
groups; Q is hydrogen or hydroxyl; x is 1 to 4; and L' is
--CO.sub.2.sup.-, --OP(O)(O.sup.-)(O.sup.-M.sup.+),
--(O)P(OR''')(O)(O.sup.-M.sup.+) (where R''' is hydrogen or an
alkyl group of 1-10 carbon atoms optionally substituted in
available positions by N, O, or S atoms) --SO.sub.2O.sup.-, or
-OSO.sub.2O.sup.-, where M.sup.+ 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, or
N.sup.+R'.sub.4 where each R' is independently an alkyl group of 1
to 4 carbon atoms optionally substituted with N, O, or S atoms.
[0062] Nonlimiting examples of emulsifiers from the class of
zwitterions useful in the emulsifier system of the invention
include stearamidopropylPG-dimmonium chloride phosphate available
as "PHOSPHOLIPID SV" from Mona Industries of Paterson, N.J.; and
behenyl betaine available as "INCRONAM B-40" from Croda.
Class 10. Alkyl and Alkenyl Amides:
##STR00011##
[0063] where R.sub.6, R.sub.7, and R.sub.12 are as defined above in
Classes 3, 9, and 8 respectively.
[0064] Examples of some preferred emulsifiers from the class of
alkyl and alkenyl amides useful in a thickener system of the
invention include but are not limited to behenamide available as
"KEMAMIDE B" from Witco; stearamide available as "UNIWAX 1750" from
Petrolite; Behenamidopropyldimethyl amine available as "INCROMINE
BB" from Croda; stearyldiethanolamide available as "LIPAMIDE S"
from Lipo Chemicals Inc. of Paterson, N.J.; and Erucamide available
as "ARMID E" from Akzo.
Class 11. Esters and Ethers of Polyhydric Alcohols
##STR00012##
[0065] wherein t=0-4; each R.sub.9 is independently chosen from H,
--CH.sub.2OR.sub.10, --OH, or a hydrocarbon chain of 1 to 4 carbon
atoms, preferably containing 1 carbon atom; s=0 or 1; wherein
R.sub.10=H or R.sub.12 wherein R.sub.12 is as defined above for
Emulsifier Class 8.
[0066] Examples of esters and ethers include glycerol monobehenate,
pentaerythritol distearate and glycerol tribehenate.
[0067] Esters and ethers of polyethoxylated polyhydric alcohols are
also useful. For example, these include but are not limited to
polyethoxylated glycerol monostearate, polyethoxylated penta
erythritol behenate, polyethoxylated propylene glycol
monostearate.
Class 12. Anionics
[0068] [(R.sub.14).sub.aL.sup.-c.sub.d](M.sup.+b).sub.e
Where R.sub.14 is an alkyl, alkenyl, or aralky group of at least 16
carbon atoms, preferably at least 18 carbon atoms and most
preferably at least 20 carbon atoms optionally comprising oxygen,
nitrogen, or sulfur atoms within or substituted upon the alkyl or
alkenyl chain; or a polyethoxylated and/or polypropoxylated alkyl,
alkenyl or aralkyl group, which alkyl, alkenyl, or aralkyl group
comprises at least 16 carbon atoms, preferably at least 18 carbon
atoms and most preferably at least 20 carbon atoms optionally
comprising oxygen, nitrogen, or sulfur atoms within or substituted
upon the alkyl, alkenyl, or aralkyl chain. When R.sub.14 comprises
a polyethoxylated or polypropoxylated substituent or a copolymeric
substituent of ethylene oxide and propylene oxide, these subunits
are present in amounts of 1 to 100 moles, preferably 1 to 20 moles
per mole of hydrophobe; L is sulfate (--OSO.sub.2O.sup.-),
sulfonate (--SO.sub.2O.sup.-), phosphate ((--O).sub.2P(O)O.sup.- or
--OP(O)(O.sup.-).sub.2), or carboxylate (--CO.sub.2.sup.-); M is
hydrogen (H.sup.+), sodium (Na.sup.+), potassium (K.sup.+), lithium
(Li.sup.+), ammonium (NH.sub.4.sup.+), calcium (Ca.sup.+2),
magnesium (Mg.sup.+2), or R''A.sup.+, wherein R'' is hydrogen or an
alkyl or cycloalkyl group of about 1 to 10 carbon atoms, and
A.sup.+ is selected from the group consisting of N.sup.+(R).sub.3
(e.g., R''A.sup.+ can be N.sup.+(CH.sub.3R).sub.4,
HN.sup.+(CH.sub.2CH.sub.2OH).sub.3,
H.sub.2N(CH.sub.2CH.sub.2OH).sub.2) or a heterocyclic --N.sup.+B
wherein B comprises 3 to 7 atoms selected from the group consisting
of carbon, nitrogen, sulfur and oxygen atoms which complete the
nitrogen-containing heterocyclic ring and satisfy the valence on
the nitrogen atom; and wherein R is the same as R'' and may also be
substituted in available positions with oxygen, nitrogen or sulfur
atoms; a and c are independently 1 or 2; b and d are independently
1, 2 or 3; and e is equal to (c times d)/b.
[0069] Nonlimiting examples of preferred emulsifiers from the
anionic class of emulsifiers suitable for use in a thickener system
of the invention include behenic acid available as Croacid B from
Croda, Inc.; stearyl phosphate available as Sippostat 0018 from
Specialty Industrial Products, Inc. of Spartanburg, S.C.; and
sodium stearate available from Witco.
Class 13. Sorbitan Fatty Acid Esters
##STR00013##
[0070] where R.sub.6 is as defined above in Emulsifier Class 3,
R.sub.13 is H or --C(O)R.sub.6 and each v is independently
0-30.
[0071] Fatty acid esters of sorbitan and its polyethoxylated
derivatives, polyoxyethylene derivatives of mono and poly-fatty
esters are also examples of additional emulsifiers useful in the
present invention.
[0072] Certain combinations of the above-listed emulsifiers are
useful in some preferred embodiments to form viscous stable
thickener systems of the present invention. These preferred systems
are listed below.
TABLE-US-00001 Nonlimiting Examples of Suitable Thickener Systems:
System # Emulsifier 1/(Class)* Emulsifier 2/(Class)* Emulsifier
3/(Class)* Emulsifier 4(Class)* 1 alkyl polyglucoside (1)
polyethoxylated alkyl alcohol (8) quaternary amine (5) 2 alkyl
polyglucoside (1) polyethoxylated alkyl alcohol (8) amine Oxide (7)
3 alkyl polyglucoside (1) tertiary amine (6) 4 alkyl polyglucoside
(1) quaternary amine (5) 5 polyglycerol ester (4) polyethoxylated
alkyl alcohol (8) alkyl alcohol (3) 6 polyglycerol ester (4)
polyethoxylated alkyl alcohol (8) alkyl alcohol (3) alkyl ester (2)
7 polyglycerol ester (4) polyethoxylated alkyl alcohol (8)
quaternary amine (5) 8 polyglycerol ester (4) alkyl ester (2)
quaternary amine (5) 9 polyglycerol ester (4) amine oxide (7)
quaternary amine (5) 10 alkyl/alkenyl alcohol (3) alkyl ester (2)
quaternary amine (5) 11 alkyl/alkenyl alcohol (3) alkyl ester (2)
amine oxide (7) 12 alkyl ester (2) polyethoxylated alkyl alcohol
(8) quaternary amine (5) 13 alkyl betaine (7) polyethoxylated alkyl
alcohol (8) 14 alkyl phospholipid (9) polyethoxylated alkyl alcohol
(8) 15 alkyl ester (2) alkyl alcohol (3) dialkoxydimethicone 16
hydroxyfunctional ester (2) polyethoxylated alcohol (8) 17
hydroxyfunctional ester (2) alkyl alcohol (3) quaternary amine (5)
18 hydroxyfunctional ester (2) quaternary amine (5) 19 polyglycerol
ester (4) polyethoxylated alkyl alcohol (8) 20 alkyl carboxylate
(12) polyethoxylated alkyl alcohol (8) *Refers to Emulsifier
Classes identified above.
[0073] It is a simple matter to test certain combinations of
emulsifiers to determine if they provide a suitable thickener
system. Screening methodology is set forth in the Examples. The
examples illustrate the importance of the head group size with
respect to the ratio of the mixed emulsifiers required to produce a
stable emulsion. For example, systems based on a C16/C18 alkyl
polyglucoside combined with C18 polyethoxylates of varying level of
ethoxylation (Brij) produce stable emulsions at widely varying
ratios.
[0074] Without intending to be bound by theory, the physical
structure of the composition of the invention is believed to be
that of an emulsion. A classic definition of an emulsion is a
stable dispersion of one liquid in a second immiscible liquid.
However, as stated earlier, the present composition is preferably
formed using at least one emulsifier which is a wax at room
temperature. Although compositions of the present invention are not
well characterized, they are believed 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, hydrophobic emulsifiers and
immiscible emollients form an "oil" or hydrophobic phase which is
dispersed in the hydroalcoholic liquid phase to form an "oil" in
"water" emulsion. The hydroalcoholic phase is referred to herein as
the "water" phase. Since many preferred emulsions are somewhat
viscoelastic, these emulsions are believed to be liquid crystalline
emulsions which have been cooled below the crystallization
temperatures of the chosen emulsifiers to form a semi-crystalline
gel-like network. Certain formulations may be simply swollen
crystalline precipitates forming a strongly interacting network in
the hydroalcoholic phase (so called coagel phase). The compositions
of the present invention may also exist as combinations of these
structures. Liquid crystalline and coagel phases in aqueous systems
are described in "Application of Emulsion Stability Theories to
Mobile and Semisolid O/W Emulsions," Cosmetics and Toiletries, Vol.
101, pp 73-92 (1986), and "Influence of Long Chain Alcohols (or
Acids) and Surfactants on the Stability and Consistencies of
Cosmetic Lotions and Creams," Cosmetics and Toiletries, Vol. 92,
pp. 21-28 (1977) both of which are hereby incorporated by
reference. The exact type of molecular association that occurs
depends on many factors including the nature, size, and physical
and chemical states of the polar and hydrocarbon portions of the
emulsifiers which comprise the thickener system at a specified
temperature.
[0075] Emulsifiers other than those required in the composition to
provide a thickener system may also be added as emollients or
stabilizers. These emulsifiers are referred to herein as auxiliary
emulsifiers. For example, certain emollients are also comprised of
hydrophobic and hydrophilic regions and are useful in the present
invention since they are believed to become incorporated into the
liquid crystalline network. These emollients tend to enhance the
stability of the composition as is discussed more fully below.
Furthermore, certain dimethicone copolyol surfactants can actually
improve the stability of formulations incorporating emollients.
This is also discussed in more detail below.
Optional Ingredients
[0076] 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
emulsifiers. Each of these optional ingredients along with the
effect each has upon the properties of the final composition is
discussed below.
Salts
[0077] The melt temperature of the compositions of the present
invention may be increased by adding salts. As the concentration of
salt is increased, the ratio of emulsifiers will often need to
change in order to maintain a stable composition. It is important
to choose salts which do not create an unstable system and are
compatible with any antimicrobials present in the system. For
example, chlorhexidine digluconate (CHG) will precipitate rapidly
in the presence of halide salts above a concentration of about
0.1M. Therefore, if a system includes CHG, preferably gluconate
salts such as triethanolamine gluconate or sodium gluconate, are
used.
Stabilizers
[0078] A stable composition is one which does not separate more
than 10% by volume after centrifuging at 2275.times.g for 30
minutes as measured at the longitudinal midpoint of the sample
tube. It is also recognized that stability may be time dependent
due to crystallization of emulsifiers and/or emollients present in
the system, coalescence of emollients, emulsifiers and the like
and, therefore, preferred compositions do not exhibit separation of
more than 10% after standing for 6 months at ambient conditions.
Two types of stabilizers are useful in the present invention. These
include (1) those stabilizers that complex with emulsifier
hydrophilic head groups, and (2) those that associate with the
emulsifier hydrophobic tails. Certain stabilizers may perform both
functions. For example, emulsifiers comprising 1,2 diol-containing
head groups such as alkylpolyglucosides, monoalkylglycerides, and
polyglycerol alkyl esters, may be "stabilized" by adding borate
ion. Without intending to be bound by theory, it is believed that
borate ions complex with adjacent head groups which may increase
the association of hydrophobic tails by holding them in close
proximity. 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 cellulose derivatives,
stearyl modified proteins such as wheat protein, stearyl modified
collagen and the like are capable of stabilizing compositions of
the present invention. Such added components 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 enhancing the stability of the crystalline
structure. Polymeric thickeners which do not have associative
pendent alkyl chains may also increase the melt temperature
presumably by increasing the viscosity of the continuous phase. A
nonlimiting example of such thickeners are quaternary celluloses
such as Celquat.TM. 230M as available from National Starch of
Bridgewater, N.J. In a preferred embodiment stearyldimonium
hydroxypropyl cellulose commercially available as Crodacel QS from
Croda Inc., Parsippany, N.J. is added as a stabilizer.
Emollients
[0079] Emollients are typically added to hand lotions or hand preps
because they act to increase the moisture content of the stratum
corneum. Emollients are generally separated into two broad classes
based on their function. The first class of emollients function by
forming an occlusive barrier to prevent water evaporation from the
stratum corneum. The second class of emollients penetrate into the
stratum corneum and physically bind water to prevent evaporation.
The first class of emollients is subdivided into compounds which
are waxes at room temperature and compounds which are liquid oils.
The second class of emollients includes those which are water
soluble and are often referred to as humectants.
[0080] 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 emulsifiers may
function as occlusive emollients and aid in maintaining or
improving the skin condition. Emollients are included in a
preferred embodiment of the invention and preferably comprise
between about 3 and 30%, more preferably between about 4 and 20%
and most preferably between about 5 and 12% by weight of the
formulation.
[0081] The ratio of wax to liquid emollients (oils and humectants)
in a preferred embodiment of the invention is between about 5:1 to
1:5 and preferably between about 1:3 to 3:1. Also, the ratio of wax
emollients and wax emulsifiers to liquid emollients and liquid
emulsifiers in a preferred embodiment of this invention is from
about 1:5 to about 5:1, and more preferably, from about 1:3 to
about 3:1. Emollients may be selected from any of the classes known
in the art. A general list of useful emollients appears in U.S.
Pat. No. 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," "humectants,"
"miscellaneous" and "occlusive," each of these references is hereby
incorporated by reference.
[0082] U.S. Pat. No. 4,478,853 (Chausee) discloses examples of
emollients, many of which are waxes at room temperature. These
include, for example a poly(ethylene oxide) homopolymer, a
poly(alkylene oxide) homopolymer, a poly(alkylene oxide) copolymer,
a polyoxyethylene/polyoxypropylene glycol, an alkyl phenol with 6
to 12 carbon atoms in the alkyl chain condensed with 2 to 20 moles
of ethylene oxide, a mono- or di-fatty acid ester of ethylene
glycol wherein the fatty acid moiety contains from 10 to 20 carbon
atoms, a fatty acid monoglyceride wherein the fatty acid moiety
contains from 10 to 20 carbon atoms, a polyethylene glycols of
molecular weight 200 to 6000, a polyoxyethylene sorbitol, a
polyoxyethylene sorbitan, a hydrophilic wax ester, an ethoxylated
glyceride, such as ethoxylated glyceryl monostearate, a
polyoxyethylene polyol fatty acid ester, and mixtures thereof. U.S.
Pat. No. 4,478,853 (Chausee) also discloses polyether derivatives
that act to increase emollience. Such polyether derivatives include
poly(ethylene oxide) homopolymers (molecular weight
100,000-5,000,000), poly(propylene oxide) homopolymers,
polyoxypropylene derivatives of trimethylolpropane and other
suitable poly(alkylene oxide) homo- and copolymers.
[0083] In preferred embodiments, emollients are chosen from the
following nonlimiting list of general emollients, occlusive
emollients and humectants. 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) and
their polyethoxylated derivatives; short chain alkyl or aryl esters
(C1-C6) of C4-C12 diacids or diols optionally substituted in
available positions by --OH; alkyl or aryl C1-C9 esters of
glycerol, pentaerythritol, ethylene glycol, propylene glycol, as
well as polyethoxylated derivatives of these and polyethylene
glycol; C12-C22 alkyl esters or ethers of polypropylene glycol;
C12-C22 alkyl esters or ethers of polypropylene glycol/polyethylene
glycol copolymer; and polyether polysiloxane copolymers. In
addition to many of the emulsifiers of preferred thickener systems,
additional examples of occlusive emollients include cyclic
dimethicones, polydialkylsiloxanes, 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 branched
chain (C8-C36) alkyl or alkenyl amines or acids; hydrocarbons
including straight and branched chain alkanes and alkenes such as
squalene, 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 of preferred humectant type
emollients include glycerol, propylene glycol, dipropylene glycol,
polypropylene glycol, polyethylene glycol, sorbitol, pantothenol,
gluconic acid salts and the like.
[0084] Although a thickener system is responsible for the stability
and overall consistency of compositions of the present invention,
emollients may also affect the viscosity, stability, and melt
temperature of a composition. It is anticipated 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 emollients are used. In a preferred embodiment, emollient
systems are comprised of humectants in addition to occlusive wax
and oil emollients in concentrations which achieve a moisturizing
but not greasy composition which maintains and improves the
condition of the skin upon repeated use. Ideally, emollients are
non-comedogenic and are chosen to ensure no skin irritation or
sensitization reaction occurs. This is particularly critical since
the composition of the present invention will likely be worn in an
occluded condition under surgical gloves.
[0085] Furthermore, emollients should be chosen which do not affect
the integrity of the glove material. For example, since hydrocarbon
emollients such as mineral oil and petrolatum can detrimentally
affect the tear strength of surgical gloves, these emollients may
need to be avoided for compositions employed as presurgical
disinfectants. Without being bound or limited by theory, it is
believed that if emollients 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) dispersed
as emulsified droplets within the mixed emulsifier micelle or
crystalline gel network, (3) incorporated into the mixed emulsifier
micelle or crystalline gel network, or (4) as a separate and
distinct emulsion. As earlier stated, emollients can affect the
melt temperature of a composition. Those emollients that are
soluble or dispersible in the solvent phase tend to have little or
no affect on the melt temperature and are therefore preferred.
These emollients include the humectant and general emollients. The
most preferred general emollients are those which are essentially
insoluble in water but soluble in the hydroalcoholic solvent. These
emollients are also preferred since they remain soluble and
uniformly dispersed even above the melt temperature so that upon
cooling to room temperature a uniform composition results. In
addition, they are also believed to have little effect on surgical
gloves. Such general emollients typically do not have alkyl or
alkenyl chains greater than about 14, preferably not greater than
12 and most preferably not greater than about 9 carbon atoms.
[0086] Those emollients which are insoluble in the hydroalcoholic
solvent may associate with the emulsifiers of the thickener system
and/or become incorporated into the micelle or crystalline gel
network. Preferred emollients within this class are those
emollients that are very hydrophobic since they tend to maintain a
high melt temperature. For example, hexadecane was found to
increase the viscoelasticity 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
temperature and may influence the stability of the composition.
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 example, trioctyldodecyl
citrate has been found to significantly decrease the melt
temperature of some systems.
[0087] Emollients which become incorporated into the thickener
system tend to decrease the melt temperature. For example,
laureth-4 (Brij 30) appears to incorporate into the thickener
system since it does not phase out when heated above the melt
temperature at concentrations below about 1% by weight. Laureth-4
also tends to decrease the melt temperature of the composition.
[0088] Certain emollients which are insoluble in the hydroalcoholic
solvent can be emulsified in what is believed to be a separate and
distinct emulsion. These emollients have little affect on the melt
temperature of a composition. For example, certain cyclic
silicones, polysiloxanes, and dialkoxypolysiloxanes can be
emulsified in hydroalcoholic solvents using polyether/polysiloxane
copolymers surfactants. Cyclic silicones such as DC344 (available
from Dow Corning of Midland, Mich.) in the presence of certain
polyether/polysiloxane copolymers such as Abil B88183 available
from Goldschmidt 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 combination
of a long chain dialkoxypolysiloxane and polyether/polysiloxane
copolymer has been found to actually promote the stability of
certain thickener systems. The dialkoxypolysiloxane is believed to
interact with the thickener system as well as the
polyether/polysiloxane copolymer. These compounds have the
following structures:
Dialkoxy Dimethicones
[0089]
R--O--Si(CH.sub.3).sub.2--O[Si(CH.sub.3).sub.2--O].sub.z--Si(CH.su-
b.3).sub.2--OR
where R is a straight chain alkyl group of 14-50, preferably 16-24
carbon atoms, and
[0090] z=5-300
Polyether/Polysiloxane Copolymers (Dimethicone Copolyols):
[0091]
(CH.sub.3).sub.3--Si--O--[Si(CH.sub.3)R.sub.11--O].sub.x[Si(CH.sub-
.3)R.sub.8--O].sub.y--Si(CH.sub.3).sub.3
where
[0092] x+y=5-400, preferably 15-200, and
[0093] R.sub.8 is a polyether substituted alkyl group with the
structure:
--R.sub.9--O(C.sub.2H.sub.4O).sub.p(C.sub.3H.sub.6O).sub.qR.sub.10;
where
[0094] R.sub.9 is an alkyl group of 1 to 6 carbon atoms;
[0095] R.sub.10 is hydrogen or an alky group of 1-22 carbon
atoms;
[0096] R.sub.11 is an alkyl group of 1 to 22 carbon atoms or
phenyl;
[0097] p=2-300, preferably 8-100; and
[0098] q=0-100.
[0099] Note that branched chain polysiloxanes modified as shown in
the two structures above are also possible.
[0100] The following are nonlimiting examples of
emulsifier/emollient components which improve thickening/stability
of compositions of the present invention.
[0101] a. Certain wax emulsifiers/emollients have been found to be
particularly useful and include solid waxy esters such as: Myristyl
Myristate, Cetyl Palmitate, Myristyl Stearate, Stearyl Behenate,
Behenyl Isostearate, Isostearyl Behenate, Behenyl Behenate, Lauryl
Behenate, Behenyl Erucate. These have the following formula:
R.sub.1--CO.sub.2--R.sub.2
where: [0102] R.sub.1 is at least 14 carbon atoms; and [0103]
R.sub.2 is an alkyl or alkenyl of at least 4 carbon atoms.
[0104] b. Long chain hydrocarbon di-esters, tri-esters, of
polyhydric alcohols with melting point greater than 23.degree. C.
include solid esters such as glycerol tribehenate and sorbitan
tristearate.
[0105] c. Pure lanolins and lanolin derivatives (e.g. hydrogenated
lanolin) provide excellent emolliency but can also improve the
stability of the emulsion when used in combination with oil
emollients.
[0106] d. Petrolatums provide excellent emolliency and can also
improve the stability of the emulsion when used in combination with
oil emollients. Petrolatums are mixtures of oily and waxy long
chain hydrocarbons.
[0107] e. Microcrystalline waxes and branched hydrocarbon waxes
with a melting point greater than 50.degree. C. and a molecular
weight greater than 400. An example of this includes 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. of Tulsa, Okla. and "ULTRAFLEX" which is a microcrystalline
wax also available from Petrolite Corp.
[0108] f. Oxidized waxes and modified hydrocarbon waxes may find
application in the present invention. These are prepared from waxes
modified by oxidation, salts of oxidized waxes, maleic anhydride
adducts of polyolefins and urethane derivatives of oxidized
synthetic or petroleum waxes. Applicable waxes could include
Petrolite's Cardis or Petronauba microcrystalline and
polyethylene-based oxidized products, Polymekon (salts) and Ceramer
(anhydride adducts).
[0109] 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.degree. C. and low melt viscosities. Applicable waxes
could include "POLYWAX" available from Petrolite Corp.
Fragrances
[0110] The formulations may also comprise a fragrance. If
fragrances are included the fragrances must be chosen carefully
since some fragrances are known to cause skin irritation and/or
sensitization reactions.
Antimicrobials
[0111] In addition to the lower alcohols present in the composition
of the present invention, other antimicrobials may be added to
enhance the antimicrobial action of the compositions of the present
invention. This may be particularly desirable in critical uses such
as presurgical hand scrubs or presurgical patient skin scrub
replacements. Suitable additional antimicrobials include iodine and
its complexed forms such as povidone/iodine, chlorhexidine salts
such as chlorhexidine digluconate (CHG), parachlorometaxylenol
(PCMX), hexachlorophene, phenols, surfactants comprising a long
chain hydrophobe (C12-C22) and a quaternary group, triclosan,
Lauricidin, quaternary silanes, hydrogen peroxide, silver, silver
salts such as silver chloride, silver oxide and silver sulfadiazine
and the like. In order to reduce chances for irritation and yet
maintain efficacy, the antimicrobial level should be adjusted to
the minimum level which maintains a low bacteriological count for 6
and most preferably for 12 hours after application.
[0112] 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 diacetate and digluconate salts are
preferred. The most preferred antimicrobial is chlorhexidine
digluconate (CHG). CHG is preferably present at a concentration of
0.05-5.0%, more preferably from 0.1-3% and most preferably from
0.25-2% by weight. Chlorhexidine is a bis(diguanide) and therefore
is very basic and is capable of forming multiple ionic bonds with
anionic materials. For this reason, chlorhexidine-containing
thickener system are preferably based on non-ionic and/or cationic
emulsifiers. Certain zwitterionic, very insoluble, or
non-precipitating anionic emulsifiers may also be useful.
Foams
[0113] The compositions of the present invention may also be
formulated into an aerosol foam or mousse by addition of an
appropriate propellant. The propellant must be chosen to ensure
proper delivery from the container to prevent clogging of the
valve. The propellant can be chosen from chlorofluorocarbons
(CFCs), hydrochlorofluorocarbons (HCFCs), hydrofluorocarbons
(HFCs), perfluorinated alkanes, and lower alkanes (C1-C5) as well
as nitrous oxide dimethyl ether and other solvent-soluble
propellants. Preferred propellants are lower alkanes such as
propane, butane, and isobutane since these result in a dramatic
loss in viscosity making the formulation easy to dispense. A 70/30
mixture of propane/isobutane is a particularly preferred
embodiment. In order to produce an aerosol composition the
antimicrobial lotion is first formulated and charged into an
appropriate pressure rated container. If convenient, the
formulation may be heated above the melt temperature in order to
facilitate filling. The propellant is then added under pressure at
approximately 2-30% preferably 3-20% by volume. The propellant may
form a separate layer or may remain emulsified in the
composition.
Alternate Applications for Hydro-Alcoholic Liquid Crystalline
Solutions:
[0114] The compositions of this invention may be compounded with UV
absorbers and oils to deliver fast-drying sunscreens.
Antimicrobials such as benzoyl peroxide may also be added to the
formulations and the formulations may be useful as an acne
medication. The systems of this invention may also be formulated
with barrier compounds to form barrier creams and lotions.
Materials which may be 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, aluminum acetate,
aluminum hydroxide, bismuth subnitrate, boric acid, calamine,
cellulose (microporous), cholecalciferol, cocoa butter, cod liver
oil (in combination), colloidal oatmeal, cysteine hydrochloride,
dexpanthenol, dimethicone, glycerin kaolin, lanolin (in
combination), live yeast cell derivative, mineral oil, peruvian
balsam, peruvian balsam oil, petrolatum, protein hydrolysate
(1-leucine, 1-isoleucine, 1-methionine, 1-phenylalanine, and
1-tyrosine), racemethionine, shark liver oil, sodium bicarbonate,
sulfur, talc, tannic acid, topical starch, vitamin A, white
petrolatum, zinc acetate, zinc carbonate and zinc oxide.
Formulations are also contemplated containing antifungal agents for
treating fungal infections of the skin such as athlete's foot and
the like.
[0115] A related patent application entitled, "Stable
Hydroalcoholic Compositions," U.S. patent application Ser. No.
08/493,695, filed on Jun. 22, 1995 by inventors Asmus, Scholz and
Charpentier is hereby incorporated by reference.
[0116] Since many of the compositions of the present invention
contain antimicrobials, it is important that they be dispensed in
an efficacious and precise amount. The compositions of the present
invention can be dispensed in a discreet, substantially uniform
amount using the dispensers disclosed in Applicants' Assignee's
Copending U.S. patent application Ser. No. 08/668,198, filed Jun.
21, 1996, entitled "Dispenser for Antimicrobial Liquids," issued as
U.S. Pat. No. 5,897,031, and Ser. No. 08/668,270, filed Jun. 21,
1996, entitled "Drip Resistant Nozzle for a Dispenser," issued as
U.S. Pat. No. 5,799,841.
Methods of Preparation
[0117] 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 temperature above the melting point of the emulsifiers, mixing
briefly and cooling. Nevertheless, to ensure a composition of
maximum stability the components are preferably subjected to high
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
stability.
[0118] The cooling rate may be important depending on the
particular thickener system. Certain thickener systems can be
homogenized and then allowed to cool slowly, however, rapid cooling
appears beneficial for most systems.
[0119] The order of adding the components may also affect the
stability and viscosity of the system. In general it works well to
melt the mixed emulsifiers with aqueous-insoluble emollients
together in one vessel. The hydroalcoholic solvent and any aqueous
miscible emollients are mixed in a second vessel. Both components
are heated above the melting temperature of the thickener system.
The hot liquid components are mixed together rapidly followed by
approximately 1 to 5 minutes of homogenization for typical batches
under 500 grams. While still low in viscosity the system is stirred
using moderate agitation and cooled. It is also possible to add the
molten thickener system along with any solvent insoluble emollients
to hot water (i.e., water at a temperature above the melting
temperature) followed by high shear mixing and subsequent dilution
with alcohol. The processing variables including amount and
intensity of high shear mixing, rate of cooling, and order of
addition are easily determined by one skilled in the art.
Test Methods
Viscosity
[0120] In the following Examples (except where indicated) viscosity
was measured at 23.degree. C. at ambient pressure using a
Brookfield LVDV-I.sup.+ viscometer 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 viscometer was
operating in the middle of its range. All samples were allowed to
equilibrate at 23.degree. C. for 24 hours prior to measurement.
Preferably the viscosity is taken at the lowest speed possible
while staying within 20-80% of the viscometer range and more
preferably between 30-70% of the range. In all cases the sample
size and container geometry was chosen to ensure that there were no
wall effects. By "wall effects" it is meant the viscosity value is
not affected by the container and is essentially equivalent to the
viscosity taken in an infinitely large container. For this reason
lower viscosity samples required a larger sample size to
accommodate the larger spindles. The following table outlines
preferred spindles for various sample viscosities.
TABLE-US-00002 Sample Viscosity T Spindle to Use 1,000-100,000 B
10,000-200,000 C 50,000-500,000 D 100,000-1,250,000 E
500,000-3,000,000 F
[0121] The viscosity of each sample was taken as the highest
relatively stable reading achieved on the first path the spindle
traversed using the heliopath adapter.
Stability
[0122] The stability of samples was measured 24 hours after
conditioning at ambient conditions by placing 12 ml of a
formulation that formed a lotion/cream in a 15 ml graduated
centrifuge tube. The tube was then centrifuged in a Labofuge B
(Heraeus Sepatech GmbH, Model 2650, rotor 2150 and buckets #2101)
at 3000 rpm (2275.times.g when measured at the longitudinal
midpoint of the sample tube) for 30 minutes at 23.degree. C.
Stability is recorded as a volume percent separation in the
Examples below.
Melt Temperature (Tm)
[0123] The melt temperature was measured by placing approximately
15 grams sample in a 25 cc sealed glass vial and placing the vial
in a water bath. The temperature of the bath was increased
periodically in discrete increments and the contents checked after
approximately 1 hour at a given temperature. The melt temperature
was taken as the temperature at which the mixture became very low
in viscosity.
Minimum Inhibitory Concentration (MIC)
[0124] 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 resuspended in Mueller-Hinton Broth to a cell
density of 0.6-1.2.times.10.sup.6 colony forming units per
milliliter. Chlorhexidine samples were prepared by adjusting CHG to
512 .mu.g/ml in Mueller-Hinton Broth and serially diluting in
two-fold steps in Mueller-Hinton Broth. The CHG-containing
Mueller-Hinton Broth was placed in 96-well sterile microliter
plates and each well was inoculated with the bacteria. The plates
were then incubated for 24-48 hrs at 37.degree. C. Bacterial growth
was determined visually by comparing the plates. The MIC was
determined as the lowest concentration of CHG that resulted in
complete kill of the test organism.
Cosmetic Properties/Tactile Testing
[0125] For use in presurgical disinfection the compositions of this
invention are preferably formulated with emollients to achieve a
moisturized but relatively dry feel. Lotions with excessive
emollients tend to be perceived as greasy and can result 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 environments throughout the application
process. The invention formulations preferably yield a smooth,
soft, non-tacky, and moisturized feeling. Testing of the cosmetic
or tactile properties of the compositions was conducted with
preferably greater than ten evaluators who applied a premeasured
amount of product, approximately 2 ml. Since hand washing can
affect the feel of the compositions, evaluators washed thoroughly
with Ivory Skin Cleansing Liquid Gel hand soap available from
Procter and Gamble, Cincinnati, Ohio before applying the sample.
After drying, the composition was rubbed uniformly over the
surfaces of both hands until the composition was dry. The feel of
the composition on the skin during subsequent washing with soap and
water was also important. Approximately 30-60 min. after
application of the composition the feel during subsequent washing
was evaluated. Preferred formulations did not result in an abnormal
feeling such as slimy, slippery, or sticky characteristics.
EXAMPLES
[0126] The following Examples are provided to illustrate the
invention and are not intended to limit the scope of the
invention.
Example 1
Alkyl Polyglucoside Thickener Systems
[0127] An alkyl polyglucoside emulsifier having an alkyl chain of
16 to 18 carbons was obtained as Montanov 68 from Seppic Inc. of
Fairfield, N.J. This highly crystalline emulsifier 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-emulsifier ratio was varied keeping the
total emulsifier concentration fixed at 5% by weight according to
the following table:
TABLE-US-00003 Formulation (grams) Emulsifier A B C D Montanov 68 2
1.5 1 0.5 Co-emulsifier 0.5 1.0 1.5 2.0 60:40 ethanol:water 47.5
47.5 47.5 47.5
[0128] Each co-emulsifier/Montanov 68 composition was prepared
using the following procedure: [0129] 1. The emulsifiers were
heated above their melting temperature to 75.degree. C. [0130] 2.
The hydroalcoholic solvent was heated to 75.degree. C. in a sealed
jar. [0131] 3. The hot hydroalcoholic solvent was rapidly added to
the molten emulsifiers. [0132] 4. The mixture was homogenized at
maximum speed for 4 minutes using a Silverson L4R homogenizer
available from Silverson Machines, Waterside England. [0133] 5. The
vessel was then immersed in 15-20.degree. C. water with moderate
agitation using an overhead paddle impeller for 20 minutes.
TABLE-US-00004 [0133] Formulation Viscosity (cps) and/or %
Separation by Volume Emulsifier Solvent A B C D Nikkol BB-5
(beheneth-5) 60:40 240,000 cps 2200 cps 29300 cps 26600 0%
separation 0% 0% 0% Nikkol BB-5 (beheneth-5) 68:32 1500 48000 57000
25000 Nikkol BB-10 (beheneth-10) 68:32 3400 17000 9300 NS Nikkol
BB-10 (beheneth-20) 68:32 32000 6800 450 NS Brij 52 (ceteth-2)
60:40 950 240000 36000 43000 Brij 58 (ceteth-20) 60:40 56000 60000
770 <100 Brij 72 (steareth-2) 60:40 470000 66000 48000 49000
Brij 72 (steareth-2) 68:32 NS* 1500 34000 14000 Brij 76
(steareth-10) 68:32 35000 14600 3100 <100 Brij 78 (steareth-20)
60:40 294000 54000 6200 270 Brij 78 (steareth-20) 68:32 2700 1300
200 NS Unithox 420 (C31 alkyl-2EO) 68:32 730 850 600 NS Unithox 450
(C31 alkyl-9.8O) 68:32 600 770 17600 NS Incromine BB 60:40 NS 3600
70000 630 (behenmidopropyldimethyl 0% <2% 24% amine) Incromine
BB 68:32 6000 420 520 NS Incromine BB gluconate 60:40 75 23000 1200
2000 50% 0% 0% 5% Armid 18 (octadecenamine) 60:40 <100 NS NS NS
Lanette 18 (Stearyl alcohol) 60:40 NS NS NS NS Uniwax 1750
(stearamide) 60:40 NS NS NS NS Triton X-15 68:32 NS NS NS NS
(octylphenol ethoxylate) Triton X-35 68:32 NS NS NS NS (octylphenol
ethoxylate) *NS = not stable
[0134] The results show that certain thickener systems form stable
viscous compositions. Those thickener systems that form stable
compositions have widely varying viscosities depending on the
emulsifiers and the ratio of the alkylpolyglucoside to
co-emulsifier. For example, mixtures 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 resulting
stability and viscosity. For example, at an ethanol:water ratio of
60:40, the Montanov 68:Brij 72 system had a maximum viscosity of
470,000 cps at a weight ratio of 4:1 (formulation A). When the
ethanol:water ratio was increased to 68:32 the 4:1 ratio was no
longer stable and the maximum 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. It appears that
higher viscosities are achievable at lower alcohol levels
presumably due to lower solubility of the emulsifiers and that peak
viscosities appear at higher concentrations of Montanov 68
presumably due to the highly crystalline nature of alkyl
polyglucoside emulsifiers.
[0135] The results also indicate that the size of the hydrophilic
group influences the stability and viscosity even within the group
of mixed emulsifiers which produce stable systems. For example, as
the degree of ethoxylation increases, the hydrophilic group size
increases and, in general, the peak viscosity decreases. For
example, within the ceteth series (Brij 52-58) the maximum
viscosity is 240,000 cps for Ceteth-2 whereas Ceteth-20 had only a
maximum viscosity of 60,000 cps. Similar results were found for the
steareth series (Brij 72-78) and the beheneth series (Nikkol BB
series).
Example 2
Alkyl Polyglucoside/Brij 72 Optimization
[0136] A series of 15 formulations were prepared using a three
component mixture design based on the results of Example 1. The
following concentration ranges were investigated using a solvent
ratio of 68:32 ethanol:water.
TABLE-US-00005 Component Percent by weight Montanov 68 0.26-3 Brij
72 1.0-5.2 Solvent 94-98
[0137] Each formulation was prepared and subsequently tested for
stability and viscosity. The viscosities of the resulting
formulations ranged from less than 50 cps to 93,600 cps. Stability
results ranged from 0-83%. Examples of several optimized
formulations appear below:
TABLE-US-00006 Montanov Stability 68 Brij 72 Solvent Viscosity (%
volume Formula Percent by weight (cps) separation) 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 D
2.20 1.92 95.88 30,000 0 E 1.80 2.70 95.5 30,000 0 F 3.20 2.30 94.5
50,000 0
[0138] These results together with those of Example 1 indicate that
the viscosity of the formula for this thickener system is dependent
upon the ratio of the emulsifiers. The results also indicate that
even when varying the ratio of the emulsifiers in thickener
systems, high viscosities are still obtained while maintaining
acceptable stability values. Furthermore, the total concentration
of thickener system necessary to achieve a certain viscosity varies
considerably depending on the ratio of emulsifiers. For example,
Formula D had a viscosity of 30,000 cps with a total emulsifier
concentration of only 4.12% by weight.
Example 3
Alkylpolyglucoside Ternary Thickener Systems
[0139] 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 increase the viscosity. The third emulsifier was
added at concentrations 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 according to the following
table:
TABLE-US-00007 Formula Component A B C D E F G H Amount (grams)
Montanov 68 0.92 0.92 0.92 0.92 1.11 1.11 1.11 1.11 Brij 72 1.37
1.37 1.37 1.37 1.55 1.55 1.55 1.55 Coemulsifier 0.15 0.40 0.65 0.90
0.15 0.40 0.65 0.90 Solvent 47.57 47.32 47.07 46.82 47.19 46.94
46.69 46.44
[0140] The solvent used was 68:32 ethanol:water. The formulations
were prepared and subsequently tested for stability and viscosity.
The third co-emulsifiers used were behenyl alcohol (Lanette 22,
Henkel Corp.) and stearamide diethanolamine (Lipamide S, Lipo
Chemical of Paterson, N.J.). The following viscosity results were
found:
TABLE-US-00008 VISCOSITY (cps) Coemulsifier A B C D E F G H
Lipamide S 42,500 70,500 82,800 111,000 75,500 120,000 91,100
90,000 Lanette 22 59,100 88,800 93,600 92,300 14,500 62,000 86,800
81,600
[0141] All formulations had stability values of 0% separation
except formula A/Lanette 22 which showed a trace (<5%) amount of
separation. The results indicate that addition of a third
emulsifier into the thickener system can increase 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.
Example 4
Effect of Shear on Viscosity and Stability
[0142] 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.degree. C. in separate containers. The
solvent was added to the emulsifiers rapidly and the composition
mixed as described below:
TABLE-US-00009 A hand shaken for less than 1 minute B hand shaken
for less than 1 minute, sealed and placed on a roller for 4 hours
at 50 rpm C stirred 20 minutes at low speed with an overhead
stirrer D homogenized for 4 minutes, sealed and allowed to sit E
homogenized for 2 minutes, stirred 10 minutes at low speed with an
overhead stirrer F homogenized for 1 minute, stirred 10 minutes at
low speed with an overhead stirrer G homogenized for 4 minutes,
stirred 20 minutes at low speed with an overhead stirrer H
homogenized for 4 minutes, placed on a roller for 3.25 hours at 50
rpm I homogenized for 4 minutes, placed on a roller for 50 minutes
at 50 rpm
[0143] A wide variety of consistencies resulted as indicated
below:
TABLE-US-00010 Viscosity Stability Formula Appearance (cps) (%
separation) A white, pearlescent, crystalline 7,400 64 regions B
opaque white cream 1,290 0 C opaque, pearlescent, cohesive 60,700 0
D bluish, transparent, 27,600 0 pearlescent, cohesive E opaque,
pearlescent, cohesive 81,200 0 F opaque, pearlescent, cohesive
85,500 0 G white, opaque, pearlescent, 61,700 0 cohesive H bluish
opaque, not cohesive 995 0 I * 27,000 0 * Appearance not
recorded
[0144] The results indicate that for this thickener system the
intensity and degree of mixing have an affect on the resultant
product. Both too little mixing (Formula A) and too much mixing
(Formula H) had deleterious affects on the viscosity. A preferred
method of mixing is a combination of brief (1-2 minutes) high shear
homogenization followed by overhead stirring for 10 minutes
(Formulae E and F).
Example 5
Effect of Added Polymers
[0145] This example investigated the effects of adding various
polymers ((1) polymers containing pendant alkyl groups and (2)
linear and soluble in the solvent and (3) crosslinked and swellable
in the solvent) to a thickener system. The polymers used were:
[0146] (1) Crodacel QS (Croda, Inc. of Parsippany,
N.J.)--Stearyldimonium hydroxypropyloxyethyl cellulose [0147] (2)
Quatrisoft LM-200 (Amerchol Corp. Edison, N.J.) Lauryldimmonium
modified hydroxyethylcellulose (CTFA Polyquaternium 24) [0148] (3)
Salcare 96 (Allied Colloids of Sufolk, N.J.),
polymethacryloyloxyethyl trimethylammonium chloride (CTFA
Polyquaternium 37)
[0149] The polymers were added to the formulations at levels of
0.1, 0.25, 0.37, 0.5 and 0.75% by weight according to the following
table:
TABLE-US-00011 Formula 0.1 0.25 0.37 0.50 0.75 Component Formula
Number Amount (grams) 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
[0150] 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 in water, the water in the
solvent system was corrected to reflect the exact formulation shown
above. The results are shown below:
TABLE-US-00012 Viscosity (cps) Polymer added Polymer added
Concentration Before high Post high shear Polymer (weight %) shear
Initial time 48 hours None 0 3700 3700 Crodacel 0.1 <500 -- --
QS (1) 0.25 22000 -- -- 0.50 292000 178000 231000 0.75 152000 42500
93000 Quatrisoft 0.1 <500 -- -- LM-200 (2) 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 -- --
[0151] 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 polymer itself contributes
little thickening. Crodacel QS is supplied as a 20% aqueous
solution and at concentrations under 1% by weight the viscosity of
this polymer in 68:32 ethanol:water is less than 50 cps. It is
believed that this polymer associates with the thickener system in
the formulation. The Quatrisoft polymer also contributed to
thickening the formulations. The Crodacel QS and Quatrisoft polymer
formulations with the peak viscosity were prepared again except
that the polymer was added to the thickener system after the
composition was prepared and cooled to room temperature. Even under
these conditions the polymer containing formulation had a higher
viscosity than the formulation without the polymer. A preferred
method of preparing the formulations is adding the polymer to the
hot solvent before adding the thickener system so that the polymer
and emulsifiers can interact while above the melt temperature. The
Crodacel formulations were also found to be stable, showing no
separation.
Example 6
Effect of Added Emollients
[0152] A series of wax, oil occlusive emollients and humectant type
emollients were added to a thickener system to evaluate the effect
on viscosity. Each emollient was added to two formulations shown
below:
TABLE-US-00013 Formula A B Component Amount (grams) 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
[0153] The procedure of Example 1 was used to prepare the
formulations except emollients were either added to the hot solvent
or the thickener system prior to mixing. Glycerine and Quamectant
were added to the solvent. Other emollients were added to the
thickener system. The viscosity results are shown below:
TABLE-US-00014 Viscosity (cps) Emollient Name Chemical Description
A B Bernel Ester 2014.sup.1 octyldodecyl myristate 12,900 39,000
Bernel Citmol 320.sup.1 trioctyldodecyl citrate 15,600 168,000
Lipovol MOS 130.sup.2 tridecyl stearate and 28,000 39,000
tridecyltrimellitate and dipentaerythritol hexacaprate
Fitoderm.sup.3 Squalane 39,200 93,750 DC344.sup.4 cyclomethicone
<100 2,700 Jarcol I-16.sup.5 2-hexyldecanol <50* 59,100 (0.5
wt %) 2,900 (1 wt %) Lexol PG 865.sup.6 propyleneglycol <50
dicaprylate/dicaprate Glycerin glycerol 28,600 274,000 Quamectant
AM50.sup.7 6-(N-acetylamino)-4- 61,000 141,000
oxahexyltrimethylammonium chloride Astorwax OK 236.sup.8 paraffin
wax 39,000 .sup.1Bernel Chemical Co., Inc., Englewood, N.J.
.sup.2Lipo Chemical, Paterson, NJ. .sup.3Hispano Quimica S.A. -
Quimica Organica, Barcelona, Spain. .sup.4Dow Corning, Midland, MI.
.sup.5Vista Chemical Co., Lisle, IL. .sup.6Inolex Chemical Co.,
Philadelphia, PA .sup.7Brooks Industries Inc., South Plainfield,
NJ. .sup.8AstorWax, Doravilla, GA. *Formula A was completely
solubilized. Therefore, this emollient was added to formula B at
the reduced levels indicated.
[0154] This example shows that some emollients affect final
viscosity of the composition. Humectants which are soluble in the
system appear to have much less effect, such as glycerin. The
greatest viscosity reduction appears due to adding emollients with
branched chain hydrocarbons (e.g., Jarcol I-16).
Example 7
Effect of addition of Borate Ion
[0155] In this example sodium borate was added to a premade
alkylpolyglucoside thickener composition. It is believed that the
borate ion associates with adjacent polyglucose hydrophilic head
groups to hold them in the "micelle" structure thus elevating the
melt temperature.
[0156] A solution of sodium borate in water was added to a
concentration of 0.7% by weight to the formulation of Example 6A
containing Fitoderm squalane. The resulting formulation with sodium
borate was visibly thicker with a higher melt temperature. The
sample without borate melted rapidly when dispensed into the palm
of a hand. The sample with borate did not melt when dispensed into
the hand.
[0157] To evaluate the effect of borate ion at different pH values,
10.21 grams boric acid was added to 160 grams distilled water.
Using a pH meter sodium borate was added while stirring until a pH
of 5 was reached (0.33 grams sodium borate). A 57 gram sample was
removed. To the remaining solution 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 remaining solution was added 1.94 grams sodium
borate to reach a pH of 7.0. These three solutions were added to
the following formulation:
TABLE-US-00015 Concentration Component (weight percent) Montanov 68
4 Brij 76 1 Crodacel QS 2.5 (20% solution in water) Ethanol/water
68:32 92.5
[0158] The base formulation was prepared according 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 the thickener system had cooled to
room temperature. The following observations and melt temperatures
were recorded:
TABLE-US-00016 Borate wt % Soln pH Boron Consistency Tm (.degree.
C.) None- 0 Stable <31 CONTROL 5 0.02 stable and thicker than
control 31 5 0.04 thicker than pH 5 with 0.02% Borate 34 5 0.08
thicker than pH 5 with 0.04 Borate 35.5 5 0.12 similar to pH 5 with
0.08 Borate >35.5, <39 6 0.02 syneresis, not as thick as pH 5
analog <31 6 0.04 syneresis, not as thick as pH 5 analog 31-34 6
0.08 syneresis, not as thick as pH 5 analog 31-34 6 0.11 syneresis,
not as thick as pH 5 analog 35.5 7 0.014 more phase separation than
pH 6 <31 analog, no thickening 7 0.04 more phase separation than
pH 6 <31 analog, no thickening 7 0.07 more phase separation than
pH 6 31 analog, no thickening 7 0.10 more phase separation than pH
6 31 analog, no thickening
[0159] The results show that adding borate ion to the composition
increases the melt temperature. This is more pronounced at lower pH
values.
Example 8
Effect of Ethanol Concentration on Melt Temperature
[0160] Formulations containing 7% Montanov 68, 1.76% Brij 76, 0.5%
Crodacel QS polymer (on a solids basis) were prepared 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.
TABLE-US-00017 Solvent ratio Melt Temp Ethanol:water (.degree. C.)
50:50 40 55:45 38.5 60:40 36 64:36 36 68:32 33
[0161] The results illustrate that as the alcohol:water ratio is
increased, the melt temperature decreases for this thickener
system.
Example 9
Antimicrobial Efficacy of Compositions Containing Chlorhexidine
Gluconate
[0162] The following thickener systems were produced with and
without chlorhexidine gluconate (CHG) to determine if the CHG is
effectively delivered in a thickener system. The borate pH 5
solution from Example 7 was used.
TABLE-US-00018 Formula Amount (grams) Component 1 2 3 4 5 6 7 8 9
10 Montanov 68 2.0 0.77 2 0.76 2 0.76 2.0 0.69 Brij 76 0.5 0.19 0.5
0.19 0.5 0.19 0.5 0.17 Crodacel QS (20%) 1.25 0.48 1.25 0.48 1.25
0.43 Kenamide B 0.25 0.10 (behenamide, Witco) Borate ion solution,
pH 5 5.61 1.93 CHG (20% soln) 0.25 0.48 0.48 0.48 Ethanol:water
68:32 47.5 18.2 46.25 17.6 46 17.5 46.25 15.9 Ethanol 6.8 6.77
Water 3.2 2.98
[0163] The Minimum Inhibitory Concentration (MIC) for both E. Coli
and S. Aureus was determined according to the test methods outlined
above and is reported in the table below:
TABLE-US-00019 MIC (.mu.g/ml) Sample E. coli S. aureus 1 >256
>256 .mu.g/ml 2 4-8 4 3 >256 >256 4 2-4 2 5 >256
>256 6 4 4 7 >256 >256 8 4 4 9 >256 >256 10 4-8 4
0.5% CHG std. 4 4 Hibiclens* 4 4 *4% w/v CHG antimicrobial soap
sold by Stuart Pharmaceuticals
[0164] The results show that none of the components of this
formulation of the invention inactivate the CHG.
Example 11
A Presurgical Antimicrobial Hand Lotion Using an Alkylpolyglucoside
Containing Thickener System
[0165] The following formulation was prepared using the procedure
of Example 6:
TABLE-US-00020 Component Wt. % Montanov 68 4.0 Brij 76 1.0 Kenamide
B 0.5 Lipovol MOS 130 1.5 Fitoderm 2.3 350 ctk polydimethyl
siloxane (Carbide L45/350) 0.50 Crodacel QS (20% solution in water)
2.5 NaCl (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 strength
of 0.5% CHG.
[0166] The resulting formulation had an ethanol:water ratio of
68:32. This 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 maintained.
Example 12
Alkylpolyglucoside/Polyethoxylated alkyl alcohol/Ester of Short
Chain Alcohol/Amine Oxide/Quaternary Amine Thickener Systems
[0167] The following compositions were prepared by heating
separately the solvent (alcohol and water) and the thickener system
to 70.degree. C. The solvent was rapidly added to the thickener
system and homogenized on a Silverson L4R 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.degree.
C. water bath. Compositions A-C were mixed for 10 minutes while C
and D were mixed for 4 and 5 minutes respectively. The compositions
were then cooled to allow the emulsifiers to solidify.
TABLE-US-00021 A B C D E F G Component Amount (grams) Montanov 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
Incromine oxide 0.5 0.75 1.0 B30P*(30% solution in water) Nikkol
CA- 0.18 0.35 2580** Incroquat DMB- 0.50 0.50 90****(90% in 10%
ethanol) Lanette 22 0.65 1.3 Kemester 0.6 0.6 0.6 1.6 1.6 0.23
9022*** 68:32 27.40 27.15 26.90 73.57 72.57 40.45 40.23
Ethanol/water *Incromine oxide B-30P = behenamine oxide available
from Croda Inc., Parsippany, 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
methosulfate available from Croda Inc., Parsippany, NJ
[0168] Compositions A, B, and C were viscous 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 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 consistency. Sample G was more viscous
than Sample F. Sample F had some syneresis.
[0169] The melting temperature (Tm) of the compositions was
measured according to the protocol outlined above. The results are
shown below:
TABLE-US-00022 Composition A B C D E F G Tm(.degree. C.) 37-39 39
39 39 42 38 38 Heat cycle * HS HS HS HS HS HS HS * Once the samples
were melted, they were allowed to very slowly cool to room
temperature by simply turning off the water bath. The time to cool
was several hours. The samples were judged as heat stable (HS) if
macroscopically they appeared the same as the original sample.
Example 13
Long Chain Alkylpolyglucoside/Polyethoxylated alkyl
alcohol/Quaternary Amine Thickener System
[0170] A series of 10 formulations were prepared using a three
component mixture design with the total emulsifier level fixed at
2% by weight. The following concentration ranges were investigated
using a solvent ratio of 68:32 ethanol:water further containing
0.5% by weight CHG.
TABLE-US-00023 Emulsifier Percent by weight Eassi 624MP 0.25-1.5%
by weight Nikkol BB5 0.25-1.5 Incroquat DBM-90 0.25-1.5
[0171] Eassi 624 MP is an alkylpolyglucoside prepared from an
alcohol feed stock of 92% by weight behenyl alcohol and was
obtained from Seppic Inc., Fairfield, N.J. The product had a
melting point of 83.degree. C. and a 5% aqueous solution had a pH
of 6.4. Each formulation was prepared by adding 49 grams solvent at
80.degree. C. to 2 grams thickener system at 80.degree. C. followed
by 45 seconds of homogenization followed by 3 minutes of overhead
mixing while immersed in a 15.degree. C. water bath. The samples
were subsequently diluted to 2% solids by adding 49 grams solvent
mixture. Each composition was subsequently tested for viscosity and
Tm. The viscosities of the resulting formulations ranged from less
than 165,000 cps to 309,000 cps. Examples of several preferred
formulations appear below:
TABLE-US-00024 Sample A B C D E F Component Amount (grams) Eassi
624MP 1.5 1.08 0.25 0.66 0.25 0.87 Nikkol BB5 0.25 0.46 1.5 0.67
0.88 0.88 Incroquat DBM 0.25 0.46 0.25 0.66 0.87 0.25 90(90%)
Viscosity (cps) 309,000 192,000 175,000 227,000 252,000 220,000 Tm
(.degree. C.) >57.degree. C. 52-57 52 52-57 44 52-57
[0172] The results show that the behenylpolyglucoside increases the
melt temperature. Comparing the melt temperatures of this example
with those of Example 12F shows that increasing the chain length of
the hydrophobes in the thickener system increases the Tm. The
thickener system of the formulations in this example produce
homogenous viscous creams with varying ratios of the
emulsifiers.
Example 14
Disinfectant Hand Lotion based on
Alkylpolyglucoside/Polyethoxylated Alkyl Alcohol/Quaternary Amine
Thickener System
[0173] Disinfectant hand creams/lotions were prepared based on the
thickener system of Example 13F. The compositions are shown
below:
TABLE-US-00025 A B Component Amount (grams) Eassi 624MP 0.88 0.88
Nikkol BB5 0.87 0.87 Incroquat DBM 90 0.25 0.25 (90% solution in
ethanol) Silwet 7001* 1.33 1.33 (75% solution in water) DC344.sup.1
2.00 2.00 Procetyl 50** 2.0 Macol 30P''' 1.00 Arcol PPG-725*** 2.00
2.00 Bernel Ester 2014 2.00 Pluronic P-65**** 0.50 68:32
ethanol:water 91 89 *Silwet 7001 = a methyl terminated polyether
pendant silicone copolyol having a polyethylene oxide/polypropylene
oxide ratio of 40/60 and a molecular weight of 20,000 available
from OSI Specialties Inc. **Procetyl 50 = PPG-50 cetyl ether, Croda
Inc. ***Arcol PPG-725 = polypropylene glycol having a molecular
weight of approximately 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 approximately 3400 available
from BASF Wyandotte Corp. Parsippany, NJ. '''Macol 30P = PPG-30
cetyl ether, PPG Industries Inc., Mazer Chemical, Gurnee, Ill.
.sup.1DC344 = D4, D5, cyclodimethicone available from Dow Corning,
Midland, MI.
[0174] The compositions were prepared by heating the solvent and
Silwet to 75.degree. C. in one container and heating the remaining
components to 75.degree. C. in a second container. 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 2 ml was applied to the hands and rubbed in the
skin. Formula B was a little more appealing due to a better hand
feel. Tm was measured as 48.degree. C. for A and 45.5.degree. C.
for B.
Example 15
Polyglycerol Ester Containing Thickener Systems
[0175] The formulations for Example 15 (as described in the table
below) were prepared by heating the thickener system and the
solvent in separate jars to 75.degree. C., rapidly adding the
solvent to the thickeners, shaking vigorously, and stirring with an
overhead stirrer for 10 minutes while immersed in a 10-15.degree.
C. water bath. The Tm was measured as described above.
TABLE-US-00026 Sample A B C Component Chemical Description Amount
(grams) Decaglyn 1-S decaglycerolmonostearate, 1.35 Barnet of
Paterson, NJ Hexaglyn 1-S hexaglycerolmonostearate, 1.35 Barnet of
Paterson, NJ Tetraglyn 1-S tetraglycerolmonostearate, 1.35 Barnet
of Paterson, NJ Brij 76 Steareth-10 0.23 0.23 0.23 Ethanol:water
42.98 42.98 42.98 68:32 Tm(.degree. C.) 44 38.5 38.5
[0176] 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
preferred in this thickener system and even though the longer chain
polyglycerol emulsifier is expected to be more soluble in the
solvent system, it increased the Tm of the formulation.
Example 16
More Polyglycerol Ester Containing Thickener Systems
[0177] The following compositions were prepared as described in
Example 15.
TABLE-US-00027 Sample A B Component Amount (grams) Decaglyn 1-S
Polyaldo 10-1-S* 1.5 1.5 Brij 76 0.5 0.5 Incroquat DBM90 0.56 0.38
Arcol PPG-425*** 2.0 Procetyl 50 2.0 Ethanol/water 68:32 47.44
43.63 Tm(.degree. C.) 39-41 40-44 *Polyaldo 10-1-S =
decaglycerolmonostearate, Lonza of Fairlawn, NJ. **Promyristyl PM-3
= PPG-3 myristyl ether, Croda of Parsippany, NJ. ***Arcol PPG-425 =
polypropylene glycol, MW = approximately 450, Arcol Chemical
Co.
[0178] Samples A and B were homogenous viscous translucent almost
gel-like compositions. Sample B had a fairly nice feel but was a
little tacky.
Example 17
Polyglycerol ester/Amine Oxide/Quaternary Amine Thickener
Systems
[0179] The following compositions were prepared as described in
Example 15. The viscosity (Tm) was measured for each sample.
TABLE-US-00028 Sample A B C D Component Amount (grams) Polyaldo
10-1-S 1.2 0.9 0.6 0.3 Incromine Oxide B30P 1.0 2.0 3.0 4.0 (30%
solution in water) Incroquat DBM-90 0.28 0.28 0.28 0.28 (90%
solution 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 (.degree. C.) 40
40 40 37
[0180] The samples were allowed to cool after melting. All samples
produced translucent gel-like compositions of acceptable viscosity
and melt temperature. Samples C and D returned to a uniform
appearance after heating above the melt temperature and allowing to
slowly cool.
Example 18
Decaglyceroltetrabehenate Containing Thickener System
[0181] The following compositions were prepared by heating the
thickener system and solvent in separate jars to 80.degree. C.,
rapidly adding the solvent to the thickener, homogenizing for 20
seconds, and stirring with an overhead stirrer for 10 minutes while
immersed in a 10-15.degree. C. water bath. The Tm and viscosity
were measured for some of the samples.
TABLE-US-00029 Sample A B C D E F G H Component Amount (grams)
Kemester 9022 0.8 0.60 0.40 0.20 Incromine Oxide 2.67 2.0 1.33 0.67
B30P (30% solution in water) Decaglyceroltetra- 0.20 0.40 0.60 0.80
0.20 0.40 0.60 0.80 behenate Ethanol:water 68:32 48.72 48.72 48.72
48.72 46.86 47.32 47.79 48.26 Tm (.degree. C.) 49 -- -- -- -- 39 39
-- Viscosity (cps) 135,000 -- -- -- 8,500 6,500 6,700 10,500
[0182] Samples B-D produced homogenous compositions of low
viscosity. Sample A was an opaque viscous cream with a fairly high
melt temperature. Samples E-H were lower in viscosity and melt
temperature than Sample A.
Example 19
Ester/Amine Oxide/Quaternary Amine Thickener Systems
[0183] The following compositions were prepared using the procedure
outlined in Example 15.
TABLE-US-00030 Sample A B C D Component Amount (grams) Kemester
9022 0.9 0.9 0.9 0.9 Incromine Oxide B30P 2.0 2.0 2.0 2.0 (30%
solution in water) Nikkol CA-2580 0.29 0.17 (85% solution in water)
Incromine BB gluconate 0.68 1.37 (36.5% solution in water)
Ethanol:water 68:32 46.81 46.93 Ethanol 31.42 30.82 water 15.0
14.91 Tm (.degree. C.) -- -- 49 --
[0184] Samples A and B did not produce stable homogenous
compositions. Composition C and D produced viscous compositions but
composition D appeared non-uniform. The melt temperature of
Composition C was quite high.
Example 20
Amine Oxide/Ester/Quaternary Amine Thickener System
[0185] 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 concentration ranges were
investigated using a solvent ratio of 68:32 ethanol:water.
TABLE-US-00031 Component Percent by weight Incromine Oxide B30P
0.80-1.87 Kemester 9022 1.40-2.47 Incroquat DBM-90 0.05-0.92
[0186] The compositions were prepared by heating the thickener
system and the solvent in separate jars to 75.degree. C., rapidly
adding the solvent to the emulsifiers, shaking vigorously, and
stirring with an overhead stirrer for 5 minutes while immersed in a
10-15.degree. C. water bath. The melt temperature (Tm), viscosity
and stability were measured as described above. All ratios produced
stable compositions having a viscosity range of 10,000-270,000 cps
and a Tm of 45-47.degree. C. Elasticity was measured by gently
stirring the sample and was judged on a scale of 1-5 where 5 was a
very stringy composition and 1 was viscous but not elastic. A few
of the compositions prepared are shown below:
TABLE-US-00032 Composition A B C D E Component Amount (grams)
Kemester 9022 1.17 1.43 1.17 1.17 1.17 Incromine Oxide B30P 2.6
3.47 4.06 1.14 2.60 (30% solution in water) Incroquat DBM90 0.60
0.33 0.30 0.33 0.05 (90% solution in ethanol) Ethanol:water 68:32
60.63 59.45 59.45 62.36 61.18 Tm (.degree. C.) 47 45 45 46 45
Viscosity (cps) 280,000 270,000 270,000 250,000 30,000 Elasticity
(1-5) 2 4.5 4 1 5
[0187] The results indicate that this thickener system produces
stable compositions with varying ratios of emulsifiers but that the
physical properties of the compositions vary widely. Composition D
is a preferred formulation since it is high in viscosity at low
total solids content (2.83%), has very little elasticity and a high
melt temperature.
[0188] The following disinfectant hand lotion was produced using
the thickener system and the procedure of Example 14:
TABLE-US-00033 Component Amount (grams) Kemester 9022 0.72
Incromine Oxide B30P 1.48 (30% solution in water) Incroquat DBM90
0.10 (90% solution in ethanol) Pluronic P65 0.25 Bernel Ester 2014
1.00 Macol CA30P 0.50 PPG725 1.00 DC344 1.10 Silwet 7001 0.70 68:32
ethanol:water 43.28
[0189] This composition was stable with a nice viscosity and a Tm
of 41.degree. C.
Example 21
Alkyl Alcohol/Quaternary Amine Thickener System
[0190] The following formulations were prepared using Lanette 22
(Henkel Corp of Ambler, Pa.), Behenyl Alcohol Nikkol CA-2580
(Barnet Products Corp., Paterson, N.J.), Behenyltrimethylammonium
Chloride
TABLE-US-00034 Composition A B C Component Amount (grams) 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
[0191] The compositions were prepared by separately heating the
solvent and the thickener system to 65-70.degree. C. The solvent
was rapidly added to the thickener system followed by stirring with
an overhead paddle stirrer with the glass container immersed in a
10.degree. C. water bath. Each composition was mixed for 4.5
minutes after which the compositions cooled sufficiently for the
emulsifiers to solidify.
[0192] All three compositions were viscoelastic. The samples
appeared pearlescent with macroscopically obvious crystalline
regions. The crystals appeared macroscopically lamellar in nature.
A small amount of syneresis was seen on standing at 23.degree. C.
overnight. The Tm of sample C was approximately 47.degree. C. (The
sample did not melt uniformly and even at 47.degree. C. still had
some solid regions.)
Example 22
Alkyl Alcohol/Ester/Quaternary Amine Thickener Systems
[0193] A series of 10 formulations were prepared using a three
component mixture design. The total thickener system level was held
constant at 2.00% by weight. The following concentration ranges
were investigated using a solvent ratio of 68:32 ethanol:water
containing 0.5% by weight CHG:
TABLE-US-00035 Component Percent by weight Lanette 22 0.25-1.25
Kemester 9022 0.50-1.50 Incroquat DBM-90 0.25-1.25
[0194] The compositions were prepared by heating the thickener
system and the solvent in separate jars to 75.degree. C., rapidly
adding the solvent to the thickener, 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.degree. C.
water 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.degree. C.
Stability was measured according to Example 1. Several of the
formulations are shown below:
TABLE-US-00036 Sample A B C D E Component Percent by weight
Kemester 9022 1.50 0.50 1.00 0.50 0.67 Lanette 22 0.25 0.25 0.75
1.25 0.92 Incroquat DBM90 0.25 1.25 0.25 0.25 0.42 Ethanol:water
68:32 (0.5% 98 98 98 98 98 CHG) Tm (.degree. C.) 47 49 51 52 53
Viscosity (cps) 76000 76000 250000 274000 125000 Stability <2 2
2 10 5 (% Volume separation)
[0195] The results indicate that this thickener system produces
stable compositions with varying ratios of emulsifiers but that the
physical properties of the compositions differ considerably.
Composition C is a particularly preferred formulation since it has
a high viscosity, high melt temperature, and little separation.
After standing for 1-2 days at 23.degree. C., all of the above
formulae showed a small amount of syneresis, i.e. a small amount of
clear low viscosity solvent phase separated on the top of the
sample.
Example 23
Addition of an Alkenyl Alcohol
[0196] 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:
TABLE-US-00037 Component: Amount (grams) Lanette 22 0.38 Kemester
9022 0.50 Incroquat DBM90 0.14 Novol (oleyl alcohol, Croda) 0.20
Ethanol:water 68:32 48.78
[0197] A stable quite viscous gel-like composition resulted. The Tm
was measured as 50.degree. C. The stability was measured as 5%.
Example 24
Addition of Dialkoxy Dimethicone and Polyether-Polysiloxane
Copolymers for Enhanced Stability
[0198] The compositions of Example 22 had very good viscosity, Tm,
and stability properties but showed a slight amount of syneresis on
standing. Surprisingly, adding a combination of dialkoxy
dimethicone and polyether-polysiloxane copolymers ensured no
syneresis and also provided a smooth non-waxy feel. The following
system was prepared using the thickener ratios identified in
Example 22C and the procedure of Example 22. The Abil wax2440 was
heated with the emulsifiers while the Abil B88183 was heated in the
solvent:
TABLE-US-00038 Base Systems Component Amount (grams) Kemester 9022
0.50 Lanette 22 0.38 Incroquat DBM90 (90% solution in ethanol) 0.14
Abil wax2440.sup.1 0.25 Abil B88183.sup.2 (35% solution in water)
0.71 Ethanol:water 72:28 48.03 Tm (.degree. C.) 47 .sup.1Abil
wax2440 = dibehenoxypolydiemthyl siloxane available from
Goldschmidt Chemical Corp., Hopewell, VA. .sup.2Abil B88183 =
dimethicone copolyol having a EO/PO ratio of 77/23 and a viscosity
in water at 35% solids at 25 C of 95 mm.sup.2/sec available from
Goldschmidt Chemical Corp., Hopewell, VA.
[0199] 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 compared to that of Example 22C
most likely due to the increase in the level of ethanol in the
solvent.
[0200] This formulation was evaluated for activity of CHG at 0.5%
by weight and was also used to prepare a hand lotion containing
numerous emollients by preparing the following formulations:
TABLE-US-00039 Sample 1 2 3 4 5 6 8 Component Amount (grams)
Kemester 9022 1.00 0.52 1.00 0.50 1.00 0.51 Lanette 22 0.75 0.39
0.75 0.38 0.75 0.38 Incroquat DBM90 0.28 0.15 0.28 0.14 0.28 0.14
(90% solution in ethanol) Abil 2440 0.75 0.38 0.75 0.38 Abil 88183
(35% 1.43 0.72 1.43 0.72 solution in water) Pluronic P65 0.50 0.26
glycerin 1.00 0.51 Dermol DIPS.sup.1 1.00 0.51 Macol CA30P 1.00
0.51 Arcol PPG 725 2.00 1.03 DC344 2.00 1.03 CHG soln (20% in 0.25
1.39 1.26 1.28 water) Ethanol:water 68:32 97.97 51.21 95.79 48.15
88.29 45.29 Ethanol 6.8 6.77 Water 3.2 2.98 E. coli 223 MIC >256
4 >256 2-4 >256 2-4 >256 4 (.mu.g/ml) S. aureus 502 MIC
>256 4 >256 2 >256 4 >256 4 (.mu.g/ml .sup.1Dermol DIPS
= diisopropyl sebacate available from Alzo Inc. Sayerville, NJ
[0201] A 0.5% CHG standard was also run and found to have an MIC of
4 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 antimicrobial activity except due
to the ethanol:water solvent system. Sample 7 had nice cosmetic
properties.
Example 25
Repeat Application of a Preferred Hand Lotion Composition
[0202] The following hand lotion composition was prepared as
described in Example 23.
TABLE-US-00040 Component Weight % Kemester 9022 1.0 Lanette 22 0.75
Incroquat DBM90 (90% solution in ethanol) 0.28 Abil 2440 0.75 Abil
88183 (35% solution in water) 1.43 Glycerin 2.50 Dermol DIPS 1.00
Dermol 489.sup.2 1.00 Arcol PPG 725 2.00 DC344 0.50 Dermol
G-7DI.sup.1 0.5 Ethanol:water 68:32 88.29 .sup.1Dermol G-7DI =
glycereth-7-diisononanoate available from Alzo Inc. Sayerville, NJ
.sup.2Dermol 489 = diethyleneglycol dioctanoate/diisononanoate
available from Alzo Inc. Sayerville, NJ
[0203] The formulation was first evaluated in tactile testing by
applying 2 ml 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 the lotion as
described eight times a day in approximately 1 hour intervals after
first washing with water and Ivory liquid soap (Procter and Gamble,
Cincinnati, 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 including overall feel, lack of oiliness, moisturization,
smoothness during application, and feel while washing. Expert
grading was used to judge the condition of the skin. Using a 5
point scale:
1=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 3=Scaly--Visible
scale giving the overall appearance of the skin surface a whitish
appearance. Definite uplifting of edges or scale-sections. Hand is
rough to the touch. 4=Scaly to very scaly--More scale and
pronounced separation of scale edges from skin, although they may
still be lying flat on the skin surface. Some evidence of cracking
in sulci and on plateaus. Some reddening may appear. 5=Very
scaly--excessive cracking of skin surface. Skin appears very
irritated with widespread reddening
[0204] The skin condition was evaluated initially and at the end of
days 3 and 5 and results are shown in the table below.
TABLE-US-00041 Time Mean Skin Rating* Standard Deviation Initial
2.6 0.93 Day 3 1.80 1.53 Day 5 1.60 0.77 *five subjects two hands
each (n = 10)
The results indicate that overall the skin condition significantly
improved.
Example 26
Polyethoxylated Alcohol/Ester/Quaternary Amine Thickener System
[0205] The following thickener system compositions were prepared by
heating the solvent and the thickener system separately to
75.degree. C. The solvent was added 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
container immersed in a 20.degree. C. water bath. Each composition
was mixed for 3 minutes and the compositions were cooled
sufficiently to allow the thickeners to solidify.
TABLE-US-00042 Composition A B C D Component Amount (grams) Unithox
450.sup.1 0.18 0.35 0.53 0.70 Kemester 9022 0.70 0.53 0.35 0.18
Incroquat DBM- 0.13 0.13 0.13 0.13 90 (90% solution in ethanol)
Ethanol:water 49.00 49.00 49.00 49.00 70:30 Tm (.degree. C.) 47
47-50 47-50 42 .sup.1Unithox 450 is a polyethoxylated alkyl alcohol
having an alkyl chain length of approximately 36 carbons and nine
units of ethylene oxide having a molecular weight of 2125 available
from Petrolite Specialty Polymers Group, Tulsa, OK.
[0206] All four formulations formed viscous compositions. Formula B
was more translucent and gel-like than A. Formulation D appeared
less viscous. The melt temperatures were higher at ratios of
Unithox 450:Kemester 9022 of 0.66 to 1.5 but were fairly high for
all formulations.
Example 27
Polyethoxylated Alcohol/Ester/Quaternary Amine Thickener System
[0207] The following thickener systems were prepared according to
the procedure of Example 26:
TABLE-US-00043 Composition A B C D Component Amount (grams) Abil
2440 0.18 0.35 0.53 0.70 Kemester 9022 0.70 0.53 0.34 0.18
Incroquat DBM- 0.13 0.13 0.13 0.13 90 Ethanol:water 49.00 49.00
49.00 49.00 68:32
[0208] Formulation A produced a stable thick creamy composition
having a Tm of 44-45.degree. C. Formulations B and C were quite low
in viscosity and Formulation D showed almost no increase in
viscosity.
Example 28
Alkenyl Alcohol/Ester/Quaternary Amine Thickener System
[0209] The following thickener systems were prepared according to
the procedure of Example 26 except that the composition was
homogenized for only 15 seconds.
TABLE-US-00044 Formulation A B C D Component Amount (grams) Novol
1.08 0.81 0.54 0.27 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 43.40 43.40 43.40
43.40 Viscosity (cps) unstable low 125,000 340,000
[0210] 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 standing. Formulation D was opaque and gel-like with a
high viscosity and showed only a slight amount of syneresis.
Example 29
Alkenyl Alcohol/Ester/Amine Oxide Thickener System
[0211] The following thickener systems were prepared according to
the procedure of Example 28.
TABLE-US-00045 Formulation A B C D Component Amount (grams) Novol
1.08 0.81 0.54 0.27 Kemester 9022 0.27 0.54 0.81 1.08 Incromine
Oxide B30P 1.80 1.80 1.80 1.80 Ethanol:water 60:40 41.85 41.85
41.85 41.85 Viscosity (cps) 1,750 15,700 40,800 65,400
[0212] Composition A was translucent, fairly elastic and low in
viscosity. Composition B was translucent, pearlescent, and fairly
elastic but significantly more viscous then composition A.
Compositions C and D were pearlescent, slightly opaque, and fairly
elastic with higher viscosities.
Example 30
Alkyl Phospholipid/Polyethoxylated Alkyl Alcohol Thickener
System
[0213] The following thickener systems were prepared according to
the procedure of Example 28.
TABLE-US-00046 Formulation A B C D E F G H Component Amount (grams)
Phospholipid SV.sup.1 (35% 1.08 0.81 0.54 0.27 solution in water)
Behenylphospholipid.sup.2 2.7 2.03 1.35 0.68 (40% solution in
water) Nikkol BB-5 0.27 0.54 0.81 1.08 0.27 0.54 0.81 1.08
Ethanol:water 60:40 43.65 43.65 43.65 43.65 Ethanol 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 9,000 12,400 6,400 37,200 CHG Addition .sup.1Phospholipid SV
is a zwitterionic surfactant that is stearamidopropyl PG-dimmonium
chloride phosphate (a stearyl derived phospholipid) also containing
cetyl alcohol available from Mona Industries Inc. of Paterson, NJ.
.sup.2Behenylphospholipid is a behenyl derived phospholipid similar
in composition to Phospholipid SV.
[0214] 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 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-containing
surfactants, is reported to have significant antimicrobial
activity.
Example 31
Alkyl Betaine/Polyethoxylated Alkyl Alcohol Thickener System
[0215] The following formulations systems were prepared according
to the procedure of Example 28. After measuring the viscosity, CHG
was added as a 20% solution to a final concentration of 0.5% by
weight. The viscosity was measured again one day later.
TABLE-US-00047 Formulation A B C D Component Amount (grams)
Incronam B-40.sup.1 2.70 2.03 1.35 0.68 (40% solution in water)
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) 52,000 54,500 54,000 38,000 post-CHG Addition .sup.1Incronam
B-40 = behenyl betaine available from Croda Inc. of Parsippeny,
NJ
[0216] 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
[0217] Behenyl Lactate was prepared by reacting methyl lactate
(Aldrich Chemical Company, Inc. of Milwaukee, Wis.) 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.degree. C. in a 3-neck 250 ml glass flask purged
with nitrogen and inserted with overhead stirrer, Dean Stark trap,
thermometer, and condenser. To this was slowly added 9.4 g of
methyl lactate and the contents were slowly heated to 160.degree.
C. and held at that temperature for one hour. At this temperature
over 2 ml of methanol was collected. The contents were heated to
200.degree. C. with a nitrogen sweep to remove any volatile
components. After approximately 15 minutes at 200.degree. C. the
contents were cooled. Upon cooling the product crystallized and had
a melting point of approximately 57.degree. C.
[0218] The following thickener systems were prepared including
subsequent addition of CHG as described in Example 31.
TABLE-US-00048 Formulation A B C D E F G Component Amount (grams)
Behenyl lactate 1.08 0.81 0.54 0.27 1.08 0.81 0.54 Nikkol BB-5 0.27
0.54 0.81 1.08 Lanette 22 0.27 0.54 0.81 Incroquat DBM90 0.25 0.25
0.25 (90% in isopropyl alcohol) Ethanol:water 60:40 43.65 43.65
43.65 43.65 43.40 43.40 43.40 Viscosity (cps) 3,300 122,000 90,700
96,000 164,000 206,000 205,000 Viscosity (cps) 875 92,500 76,300
71,500 188,000 193,000 207,000 post CHG addition Formulation H I J
K L Component Amount (grams) Behenyl lactate 0.27 1.08 0.81 0.54
0.27 Nikkol BB-5 Lanette 22 1.08 Incroquat DBM90 0.25 0.30 0.60
0.90 1.20 (90% in isopropyl alcohol) Ethanol:water 60:40 43.40
43.62 43.59 43.56 43.53 Viscosity (cps) 306,000 190,000 255,000
306,000 128,000 Viscosity (cps) 214,000 207,000 256,000 266,000
233,000 post CHG addition
[0219] The results show that behenyl lactate is a useful emulsifier
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
compositions. Samples E-L formed very viscous gel-like
compositions. The compositions are also stable to CHG addition.
Example 33
Alkenyl Monoglyceride/Ester/Amine Oxide thickener System
[0220] The following thickener systems were prepared by heating
separately the solvent and the thickener system to 75.degree. 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 immersed in a 5-10.degree. C. water bath. Each
composition was mixed for 3 minutes after which the composition
cooled sufficiently for the emulsifiers to solidify. 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.
TABLE-US-00049 Composition A B C D Component Amount (grams)
Glycerol monoeurucate.sup.1 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) 630 105,000 149,000
173,000 Viscosity (cps) post CHG addition 9,200 110,000 205,000
202,000 .sup.1sample obtained from Croda Inc. of Parsippeny, New
Jersey and consisted of 90% monoeurucate, 8% dieurucate and 2%
trierucate by weight.
[0221] 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
Viscosity as a Function of Shear Rate
[0222] The following example 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 25 mm cone/plate
fixture with a cone angle of 0.1 rad at a temperature of 25.degree.
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 constant. This was done over a shear
rate range of 0.06-40 per second. The samples used for this testing
were prepared according to Example 1, Sample A (Brij 78) and
Example 32, Sample B. The following results were obtained:
TABLE-US-00050 Viscosity (cps) Shear Rate Ex. 1, Sample A Ex. 32,
Sample B Brookfield LVDV-I+ 294000 92500 0.06 Rheometrics 42000
7200 0.10 Rheometrics 37000 5700 1.0 Rheometrics 14000 2300 3.0
Rheometrics 3800 680 10.0 Rheometrics 2100 420 40.0 Rheometrics 720
140
The results indicate 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.
Example 35
Foam Formulation
[0223] 90 g of the formulation of Example 25 was charged to a glass
pressure vessel at room temperature. To this was added 7 g propane
and 3 g 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 emulsified
opaque white liquid. After sitting for several days the propellant
formed a separate phase but was easily reemulsified by shaking. The
formulation produced a white foam.
Example 36
[0224] This example demonstrates that monovalent salts of acids are
useful as co-emulsifiers in the present invention.
[0225] The samples were prepared according to the formulae outlined
in the table below by placing all components in a 4-oz. jar. The
jar was capped and heated to 65.degree. 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 temperature.
Viscosity measurements were taken as identified in the table.
Separation tests were done as outlined in Example 3.
TABLE-US-00051 Sample A B Component Amount (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) 5,904.sup.1 320,000.sup.2 % Separation
(by Volume) 0 0 .sup.1Measurements taken at ambient temperature
using a Brookfield LVDV-I+ viscometer with a TC Heliopath Spindle
at 0.3 rpm. .sup.2Measurements taken at ambient temperature using a
Brookfield LVDV-I+ viscometer with a TD Heliopath Spindle at 0.3
rpm.
Example 37
Alkyl Alcohol/Long Chain Polyethoxylate/Quaternary Amine Thickener
System
[0226] The following formulation was prepared using the compounds
listed below in the percentages indicated.
TABLE-US-00052 Ingredient Number Ingredient wt. Percent Part A 1
Beheneth Ether (BB-10).sup.1 1.08 2 Dibehenyldimethylammonium 0.25
methosulfate.sup.2 3 Behenyl Alcohol.sup.3 (BE-22) 0.67 Part B 4
Diisopropyl Dimerate.sup.4 1.50 5 Squalane.sup.5 1.50 6 Dimethicone
L45/350.sup.6 0.50 Part C 7 Polyethylene Glycol 900.sup.7 1.26 8
Polyethylene Glycol 600.sup.8 0.54 9 Glycerol.sup.9 0.72 10 Water
25.11 11 Ethyl Alcohol 61.86 12 Chlorhexidine.sup.10 Gluconate
solution 5.00 .sup.1Beheneth-10 available from Barnet Products
Corporation, Englewood Cliffs, NJ .sup.2Dibehenyldimethylammonium
methosulfate as Incroquat DBM-90 from Croda, Inc. Parsippany, NY
.sup.3Behenyl alcohol as Cachelot BE-22 available from M. Michel
& Company, Inc, New York, NY .sup.4Diisopropylpalmitate as
Pripure from Unichema North America, Chicago, Ill. .sup.5Squalane
from Barnet Products Corporation, Englewood Cliffs, NJ
.sup.6Diemthicone L45/350 from OSI Spoecialties, Inc. Danbury, CT
.sup.7Polyethylene glycol 900 from Dow Chemical, Midland, MI
.sup.8Polyethylene glycol 600 as Carbowax 600 from Union Carbide
.sup.9Glycerol as Optim from Dow Chemical, Midland, MI
.sup.10Chlorhexidine, Medichem, Barcelona, Spain 20.1% wt/vol. in
water Ethanol used was 200 proof
[0227] A total batch size of 500 g of the composition was prepared
by placing the ingredients of Parts A and B into a sealed one quart
glass jar followed by heating to 90.degree. C. until all components
were melted (about 75 min.). The ingredients of Part C along with
the water were placed into a one 200 ml glass jar and heated to
90.degree. C. (also about 75 min.) Part C was added to the Part A/B
molten mixture and homogenized using the Silverson homogenizer at
full speed for 60 seconds. This was sealed and heated at 56.degree.
C. for approximately 1 hour and then allowed to cool on a roller.
Once cooled the ethanol was added followed by sealing and shaking
the contents vigorously for 60 seconds until the sample was
homogenous. The contents were once again sheared on the homogenizer
at full speed for 60 seconds followed by vigorous shaking for 20
seconds and repeat homogenization for 60 seconds.
[0228] This formula was applied by numerous volunteers and found to
have very nice cosmetic properties.
[0229] While in accordance with the patent statutes, description of
the preferred 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 of the present invention will be apparent 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 possibilities of varying the type, quantity
and ratio of composition as well as the methods for making
formulations of the present invention. The complete disclosures of
all patents, patent applications, and publications recited herein
are incorporated by reference, as if individually incorporated by
reference.
* * * * *