U.S. patent number RE32,300 [Application Number 06/752,332] was granted by the patent office on 1986-12-02 for basic amino or ammonium antimicrobial agent-polyethylene glycol ester surfactant-betaine and/or amine oxide surfactant compositions and method of use thereof.
This patent grant is currently assigned to Sterling Drug Inc.. Invention is credited to William G. Gorman, Karl F. Popp.
United States Patent |
RE32,300 |
Gorman , et al. |
December 2, 1986 |
Basic amino or ammonium antimicrobial agent-polyethylene glycol
ester surfactant-betaine and/or amine oxide surfactant compositions
and method of use thereof
Abstract
Basic amino or ammonium antimicrobial agent (especially
bisbiguanide, quarternary ammonium salt and
bispyridine)-polyethylene glycol ester surfactant-betaine and/or
amine oxide surfactant antimicrobial skin cleansing compositions
and method of use thereof are disclosed.
Inventors: |
Gorman; William G. (East
Greenbush, NY), Popp; Karl F. (Schodack Landing, NY) |
Assignee: |
Sterling Drug Inc. (New York,
NY)
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Family
ID: |
26746132 |
Appl.
No.: |
06/752,332 |
Filed: |
July 3, 1985 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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245089 |
Mar 18, 1981 |
|
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158737 |
Jun 12, 1980 |
|
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65885 |
Aug 13, 1979 |
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Reissue of: |
320754 |
Nov 12, 1981 |
04420484 |
Dec 13, 1983 |
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Current U.S.
Class: |
514/635 |
Current CPC
Class: |
A61K
8/39 (20130101); A61K 8/40 (20130101); A61K
8/416 (20130101); A61K 8/43 (20130101); A61K
8/44 (20130101); C11D 3/48 (20130101); A61Q
17/005 (20130101); A61Q 19/10 (20130101); C11D
1/74 (20130101); C11D 1/75 (20130101); C11D
1/90 (20130101); A61K 8/4926 (20130101) |
Current International
Class: |
A61K
8/40 (20060101); A61K 8/30 (20060101); C11D
1/74 (20060101); C11D 1/75 (20060101); C11D
1/90 (20060101); C11D 1/88 (20060101); C11D
3/48 (20060101); A61K 031/155 () |
Field of
Search: |
;514/635 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Other References
The Merck Index, Ninth Edition, Merck & Co., Inc., 1976:
Monographs 224, 1059, 1078, 1987, 2060 and 2874. .
Disinfection, Sterilization and Preservation (Block), 2nd Edition,
Lea & Febiger, 1977, pp. 325-360. .
Nonionic Surfactants (Schick), Marcel Dekker Inc., 1967, pp.
142-174. .
AROMOX Amine Oxides, Armak Co. Bulletin No. 74-21, 1974. .
CTFA Cosmetic Ingredient Dictionary, Second Edition, The Cosmetic,
Toiletry and Fragrance Association, Inc., 1977, pp. 1, 24, 65-68,
95, 110, 152, 179, 203, 211, 212, 219, 255, 311. .
CTFA Cosmetic Ingredient Dictionary, Third Edition, The Cosmetic,
Toiletry and Fragrance Association, Inc., 1982, p. 55..
|
Primary Examiner: Schenkman; Leonard
Attorney, Agent or Firm: Miller; Theodore C. Dupont; Paul E.
Wyatt; B. Woodrow
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
.[.This application.]. .Iadd.This is an application for reissue of
U.S. Pat. No. 4,420,484, which issued Dec. 13, 1983 from
application Ser. No. 320,754 filed Nov. 12, 1981, which .Iaddend.is
a continuation-in-part of our copending application Ser. No.
245,089 filed Mar. 18, 1981 .Iadd.and .Iaddend.now abandoned, which
is a continuation-in-part of our copending application Ser. No.
158,737 filed June 12, 1980 and now abandoned, which is a
continuation-in-part of our copending application Ser. No. 65,885
filed Aug. 13, 1979 and now abandoned.
Claims
We claim:
1. An antimicrobial skin cleansing composition consisting
essentially of
an antimicrobially effective amount of one or more antimicrobial
agents selected from the group consisting of
(a) a compound having the structural formula ##STR14## wherein R
taken alone is phenyl substituted by alkyl, alkoxy, nitro or halo,
p-(2,2-dichlorocyclopropyl)phenyl, alkyl having from 6 to 16 carbon
atoms, cycloalkyl or polycyclic alkyl having more than 6 carbon
atoms or lower-alkyl-cycloalkyl or cycloalkyl-lower-alkyl having
from 1 to 4 carbons in lower alkyl; R' taken alone is hydrogen; R
and R' taken together are 3-azabicyclo(3,2,2)nonyl; and n is an
integer from 3 to 9; or a pharmaceutically acceptable salt
thereof;
(b) a compound having the structural formula ##STR15## wherein
R.sup.1 is long-chain alkyl or aralkyl; R.sup.2 is short-chain
alkyl, long-chain alkyl or aralkyl, benzyl or part of an aromatic
system or non-aromatic system; R.sup.3 and R.sup.4 are short-chain
alkyl or part of an aromatic ring system or non-aromatic ring
system; Z is a carbon-hydrogen chain; and X is a pharmaceutically
acceptable anion; and
(c) a compound having the structural formula ##STR16## wherein R is
an alkyl group containing from 6 to 18 carbon atoms, a cycloalkyl
group containing from 5 to 7 carbon atoms, benzyl, benzyl
substituted by one or two substituents selected from the group
consisting of halogen, hydroxy, lower-alkyl, lower-alkoxy, nitro,
cyano and trifluoromethyl or phenyl substituted by methylenedioxy
or one or two substituents selected from the group consisting of
halogen, lower-alkyl, lower-alkoxy, nitro, cyano and
trifluoromethyl;
Y is an alkylene group containing from 4 to 18 carbon atoms and
separating the two 4-(R-NH)-1-pyridinyl groups by from 4 to 18
carbon atoms;
A is a pharmaceutically acceptable anion;
m is 1 or 3;
n is 1 or 2;
x is 1, 2 or 3; and
(m)(2)=(n)(x);
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants having the structural
formulas ##STR17## wherein R is alkyl or alkenyl having from about
8 to about 20 carbon atoms or lanolin and n is an integer from
about 8 to about 200;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from the group consisting of
(a) betaines having the structural formulas ##STR18## wherein
R.sup.1 is alkyl or alkenyl having from about 8 to about 18 carbon
atoms; R.sup.2 is methyl, ethyl or 2-hydroxyethyl; R.sup.3 is
2-hydroxyethyl .[.or CH.sub.2 COO.sup.- .].; R.sup.4 is .[.CH.sub.2
COO.sup.- or CH.sub.2 CH.sub.2 --O--CH.sub.2 COO.sup.- ; an.].
.Iadd.CH.sub.2 CH.sub.2 COONa; and .Iaddend.n is 2 or 3; and
(b) amine oxides having the structural formula ##STR19## wherein
R.sup.1 taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.2
taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.1 and R.sup.2
taken together are morpholino; R.sup.3 is alkyl having from about 8
to about 18 carbon atoms or R.sup.4 CONH(CH.sub.2).sub.3 wherein
R.sup.4 is alkyl having from about 8 to about 18 carbon atoms; and
wherein 2-hydroxyethyl can be condensed with from 1 to about 200
units of ethylene oxide; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
2. A composition according to claim 1 wherein the amount of
antimicrobial agent is from about 0.01% to about 10% by weight of
the composition.
3. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 2.
4. An antimicrobial skin cleansing composition consisting
essentially of
(A) an antimicrobially effective amount of one or more
antimicrobial agents selected from the group consisting of a
compound having the structural formula ##STR20## wherein R taken
alone is phenyl substituted by alkyl, alkoxy, nitro or halo,
p-(2,2-dichlorocyclopropyl)phenyl, alkyl having from 6 to 16 carbon
atoms, cycloalkyl or polycyclic alkyl having more than 6 carbon
atoms or lower-alkyl-cycloalkyl or cycloalkyl-lower-alkyl having
from 1 to 4 carbons in lower alkyl; R' taken alone is hydrogen; R
and R' taken together are 3-azabicyclo(3,2,2)nonyl; and n is an
integer from 3 to 9; or a pharmaceutically acceptable salt
thereof;
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants having the structural
formulas ##STR21## wherein R is alkyl or alkenyl having from about
8 to about 20 carbon atoms or lanolin and n is an integer from
about 8 to about 200;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from the group consisting of
(a) betaines having the structural formulas ##STR22## wherein
R.sup.1 is alkyl or alkenyl having from about 8 to about 18 carbon
atoms; R.sup.2 is methyl, ethyl or 2-hydroxyethyl; R.sup.3 is
2-hydroxyethyl .[.or CH.sub.2 COO.sup.- .].; R.sup.4 is .[.CH.sub.2
COO.sup.- or CH.sub.2 CH.sub.2 --O--CH.sub.2 COO.sup.- ;.].
.Iadd.CH.sub.2 CH.sub.2 COONa; .Iaddend.and n is 2 or 3; and
(b) amine oxides having the structural formula ##STR23## wherein
R.sup.1 taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.2
taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.1 and R.sup.2
taken together are morpholino; R.sup.3 is alkyl having from about 8
to about 18 carbon atoms or R.sup.4 CONH(CH.sub.2).sub.3 wherein
R.sup.4 is alkyl having from about 8 to about 18 carbon atoms, and
wherein 2-hydroxyethyl can be condensed with from 1 to about 200
units of ethylene oxide; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
5. A composition according to claim 4 wherein the amount of
antimicrobial agent is from about 0.01% to about 10% by weight of
the composition.
6. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 5.
7. A composition according to claim 5 wherein the antimicrobial
agent is chlorhexidine or a pharmaceutically acceptable salt
thereof.
8. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 7.
9. A composition according to claim 7 wherein the salt is the
digluconate salt.
10. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 9.
11. A composition according to claim 9 wherein the surfactant of
part (C) is a betaine.
12. A composition according to claim 11 wherein the betaine has the
structural formula ##STR24## wherein R.sup.1 represents the coconut
radical, R.sup.3 is 2-hydroxyethyl and R.sup.4 is .[.CH.sub.2
COO.sup.-..]. .Iadd.CH.sub.2 CH.sub.2 COONa..Iaddend.
13. A composition according to claim 12 which contains two
polyethylene glycol ester surfactants of part (B), both having the
structural formula ##STR25## wherein ##STR26## represents the
coconut acid radical, one wherein n has an average value of 78 and
the other wherein n has an average value of 30.
14. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 11.
15. An antimicrobial skin cleansing composition consisting
essentially of
(A) an antimicrobially effective amount of one or more
antimicrobial agents selected from the group consisting of a
compound having the structural formula ##STR27## wherein R.sup.1 is
long-chain alkyl or aralkyl; R.sup.2 is short-chain alkyl,
long-chain alkyl or aralkyl, benzyl or part of an aromatic system
or non-aromatic system; R.sup.3 and R.sup.4 are short-chain alkyl
or part of an aromatic ring system or non-aromatic ring system; Z
is a carbon-hydrogen chain; and X is a pharmaceutically acceptable
anion;
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants having the structural
formulas ##STR28## wherein R is alkyl or alkenyl having from about
8 to about 20 carbon atoms or lanolin and n is an integer from
about 8 to about 200;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from the group consisting of
(a) betaines having the structural formulas ##STR29## wherein
R.sup.1 is alkyl or alkenyl having from about 8 to about 18 carbon
atoms; R.sup.2 is methyl, ethyl or 2-hydroxyethyl; R.sup.3 is
3-hydroxyethyl .[.or CH.sub.2 COO.sup.- .].; R.sup.4 is .[.CH.sub.2
COO.sup.- or CH.sub.2 CH.sub.2 --O--CH.sub.2 COO.sup.- ;.].
.Iadd.CH.sub.2 CH.sub.2 COONa; .Iaddend.and n is 2 or 3; and
(b) amine oxides having the structural formula ##STR30## wherein
R.sup.1 taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.2
taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.1 and R.sup.2
taken together are morpholino; R.sup.3 is alkyl having from about 8
to about 18 carbon atoms or R.sup.4 CONH(CH.sub.2).sub.3 wherein
R.sup.4 is alkyl having from about 8 to about 18 carbon atoms, and
wherein 2-hydroxyethyl can be condensed with from 1 to about 200
units of ethylene oxide; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
16. A composition according to claim 15 wherein the amount of
antimicrobial agent is from about 0.01% to about 10% by weight of
the composition.
17. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 16.
18. A composition according to claim 16 wherein the antimicrobial
agent is benzalkonium chloride.
19. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 18.
20. An antimicrobial skin cleansing composition consisting
essentially of
(A) an antimicrobially effective amount of one or more
antimicrobial agents selected from the group consisting of a
compound having the structural formula ##STR31## wherein R is an
alkyl group containing from 6 to 18 carbon atoms, a cycloalkyl
group containing from 5 to 7 carbon atoms, benzyl, benzyl
substituted by one or two substituents selected from the group
consisting of halogen, hydroxy, lower-alkyl, lower-alkoxy, nitro,
cyano and trifluoromethyl or phenyl substituted by methylenedioxy
or one or two substituents selected from the group consisting of
halogen, lower-alkyl, lower-alkoxy, nitro, cyano and
trifluoromethyl;
Y is an alkylene group containing from 4 to 18 carbon atoms and
separating the two 4-(R--NH)-1-pyridinyl groups by from 4 to 18
carbon atoms;
A is a pharmaceutically acceptable anion;
m is 1 or 3;
n is 1 or 2;
x is 1, 2 or 3; and
(m)(2)=(n)(x);
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants having the structural
formulas ##STR32## wherein R is alkyl or alkenyl having from about
8 to about 20 carbon atoms or lanolin and n is an integer from
about 8 to about 200;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from the group consisting of
(a) betaines having the structural formulas ##STR33## wherein
R.sup.1 is alkyl or alkenyl having from about 8 to about 18 carbon
atoms; R.sup.2 is methyl, ethyl or 2-hydroxyethyl; R.sup.3 is
2-hydroxyethyl .[.or CH.sub.2 COO.sup.- .].; R.sup.4 is .[.CH.sub.2
COO.sup.- or CH.sub.2 CH.sub.2 --O--CH.sub.2 COO.sup.- ; and.].
.Iadd.CH.sub.2 CH.sub.2 COONa; and .Iaddend.n is 2 or 3; and
(b) amine oxides having the structural formula ##STR34## wherein
R.sup.1 taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.2
taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.1 and R.sup.2
taken together are morpholino; R.sup.3 is alkyl having from about 8
to about 18 carbon atoms or R.sup.4 CONH(CH.sub.2).sub.3 wherein
R.sup.4 is alkyl having from about 8 to about 18 carbon atoms, and
wherein 2-hydroxyethyl can be condensed with from 1 to about 200
units of ethylene oxide; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
21. A composition according to claim 20 wherein the amount of
antimicrobial agent is from about 0.01% to about 10% by weight of
the composition.
22. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 21.
23. A composition according to claim 21 wherein in the structural
formula of the antimicrobial agent R is CH.sub.3 (CH.sub.2).sub.7,
Y is (CH.sub.2).sub.10, A is Cl or Br, m is 1, n is 2 and x is
1.
24. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 23.
25. A composition according to claim 23 wherein the surfactant of
part (C) is a betaine.
26. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 25.
27. A composition according to claim 23 wherein the surfactant of
part (C) is an amine oxide.
28. A composition according to claim 27 wherein in the amine oxide
having the structural formula ##STR35## R.sup.1 is hydroxyethyl,
R.sup.2 is hydroxyethyl and R.sup.3 is the coconut radical.
29. A composition according to claim 27 wherein the polyethylene
glycol surfactant of part (B) has the structural formula ##STR36##
wherein ##STR37## represents the coconut acid radical and n has an
average value of 78.
30. The process of reducing the number of microbes on living skin
which comprises applying to the skin an antimicrobially effective
amount of a composition according to claim 27.
31. An antimicrobial skin cleansing composition consisting
essentially of
(A) an antimicrobially effective amount of chlorhexidine
gluconate;
(B) from about 0.75% to about 30% by weight of two polyethylene
glycol ester surfactants having the structural formula ##STR38##
wherein ##STR39## represents the coconut acid radical, one wherein
n has an average value of 78 and the other wherein n has an average
value of 30;
(C) from about 0.5% to about 30% by weight of a betaine surfactant
having the structural formula ##STR40## wherein R.sup.1 represents
the coconut radical, R.sup.3 is 2-hydroxyethyl and R.sup.4 is
.[.CH.sub.2 COO.sup.- ; and.]. .Iadd.CH.sub.2 CH.sub.2 COONa; and
.Iaddend.
(D) water.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to basic amino or ammonium antimicrobial
agent (especially bisbiguanide, quaternary ammonium salt and
bispyridine)-polyethylene glycol ester surfactantbetaine and/or
amine oxide surfactants antimicrobial skin cleansing compositions
and method of use thereof.
2. Description of the Prior Art
Antimicrobial aryl bisbiguanides (U.S. Pat. No. 2,684,924; U.S.
Pat. No. 4,053,636) including chlorhexidine (The Merck Index, Ninth
Edition, 1976, monograph 2060) and chlorhexidine digluconate salt
(U.S. Pat. No. 2,990,425) are known. U.S. Pat. No. 3,855,140
describes polyoxyethylene-polyoxypropylene block copolymer
cleansing compositions of certain chlorhexidine salts including
chlorhexidine digluconate salt. Antimicrobial alkyl bisbiguanides
(U.S. Pat. No. 3,468,898) including alexidine (The Merck Index,
ibid., monograph 224) and aqueous compositions thereof with "a
compatible surfactant or surfactant mixture selected from the
cationic, non-ionic and amphoteric surfactants" (Belgian Pat. No.
862,808) and cycloalkyl bisbiguanides (U.S. Pat. No. 4,022,834) are
also known.
The quaternary ammonium disinfectants (A. N. Petrocci,
Disinfection, Sterilization, and Preservation, 2nd Edition, Seymour
S. Block, Editor, Lea & Febiger, Philadelphia, 1977, pp.
325-347) are a well-known class of antimicrobial agents.
Particularly well-known examples are benzalkonium chloride (The
Merck Index, ibid., monograph 1059), benzethonium chloride (ibid.,
monograph 1078), cetylpyridinium chloride (ibid., monograph 1987),
dequalinium chloride (ibid., monograph 2874) and
N-myristyl-N-methylmorpholinium methyl sulfate.
Antimicrobial bispyridines and compositions thereof "with any
compatible pharmaceutically acceptable surfactant, preferably a
non-ionic surfactant, such as the polyoxyethylene polyoxypropylene
copolymers . . . amine oxides, such as stearyl dimethyl amine oxide
. . . or with mixtures of these" are described by British Pat. No.
1,533,952.
Numerous other basic amino and ammonium antimicrobial agents are
described by the prior art, as illustrated by the following
examples. Amidinoureas are described by U.S. Pat. No. 4,045,483.
U.S. Pat. No. 3,940,441 describes bisphenoxybenzyldiamines. U.S.
Pat. No. 3,775,477, U.S. Pat. No. 3,867,454 and U.S. Pat. No.
4,140,860 describe dioldiamines.
The polyethylene glycol or polyoxyethylene esters of fatty acids
are a known class of surfactants (W. B. Satkowski, S. K. Huang and
R. L. Liss in Nonionic Surfactants, Martin J. Schick, Editor,
Marcel Dekker, Inc., New York, 1967, pp. 142-174) of the nonionic
type, members of which are listed by trade name (McCutcheon's
Detergents & Emulsifiers, North American Edition, McCutcheon
Division, MC Publishing Co., 175 Rock Road, Glen Rock, N.J. 07452,
1977) and generic name (CTFA Cosmetic Ingredient Dictionary, Second
Edition, The Cosmetic, Toiletry and Fragrance Association, Inc.,
1133 Fifteenth Street, N.W., Washington, D.C. 20005, 1977).
The betaine surfactants are also known and are of the amphoteric
type (McCutcheon's Detergents & Emulsifiers, ibid.; CTFA
Cosmetic Ingredient Dictionary, ibid.). Members of the class have
antimicrobial properties as well as surfactant properties (Seymour
S. Block, Disinfection, Sterilization, and Preservation, ibid., pp.
348-360).
The amine oxide detergents are also known and are of the nonionic
type (AROMOX Amine Oxides, Product Data Bulletin No. 74-21 of Armak
Company, Box 1805, Chicago, Ill., 60690, 1974; McCutcheon's
Detergents and Emulsifiers, ibid., CTFA Cosmetic Ingredient
Dictionary, ibid.).
There is a need for antimicrobial skin cleansing compositions
having better sudsing ability than the compositions of the prior
art, especially those of above-cited U.S. Pat. No. 3,855,140. The
presently described and claimed invention is designed to meet this
need.
SUMMARY OF THE INVENTION
In a composition of matter aspect the invention is an antimicrobial
skin cleansing composition consisting essentially of
(A) an antimicrobially effective amount of one or more
antimicrobial agents selected from the group consisting of
(a) a compound having the structural formula ##STR1## wherein R
taken alone is phenyl substituted by alkyl, alkoxy, nitro or halo,
p-(2,2-dichlorocyclopropyl)phenyl, alkyl having from 6 to 16 carbon
atoms, cycloalkyl or polycyclic alkyl having more than 6 carbon
atoms or lower-alkyl-cycloalkyl or cycloalkyl-lower-alkyl having
from 1 to 4 carbons in lower alkyl; R' taken alone is hydrogen; R
and R' taken together are 3-azabicyclo(3,2,2)nonyl; and n is an
integer from 3 to 9; or a pharmaceutically acceptable salt
thereof;
(b) a compound having the structural formula ##STR2## wherein
R.sup.1 is long-chain alkyl or aralkyl; R.sup.2 is short-chain
alkyl, long-chain alkyl or aralkyl, benzyl or part of an aromatic
system or non-aromatic system; R.sup.3 and R.sup.4 are short-chain
alkyl or part of an aromatic ring system or non-aromatic ring
system; Z is a carbonhydrogen chain; and X is a pharmaceutically
acceptable anion; and
(c) a compound having the structural formula ##STR3## wherein R is
an alkyl group containing from 6 to 18 carbon atoms, a cycloalkyl
group containing from 5 to 7 carbon atoms, benzyl, benzyl
substituted by one or two substituents selected from the group
consisting of halogen, hydroxy, lower-alkyl lower-alkoxy, nitro,
cyano and trifluoromethyl or phenyl substituted by methylenedioxy
or one or two substituents selected from the group consisting of
halogen, lower-alkyl, lower-alkoxy, nitro, cyano and
trifluoromethyl;
Y is an alkylene group containing from 4 to 18 carbon atoms and
separating the two 4-(R,NH)-1-pyridinyl groups by from 4 to 18
carbon atoms;
A is a pharmaceutically acceptable anion;
m is 1 or 3;
n is 1 or 2;
x is 1, 2 or 3; and
(m)(2)=(n)(x);
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants having the structural
formulas ##STR4## wherein R is alkyl or alkenyl having from about 8
to about 20 carbon atoms or lanolin and n is an integer from about
8 to about 200;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from
(a) betaines having the structural formulas ##STR5## wherein
R.sup.1 is alkyl or alkenyl having from about 8 to about 18 carbon
atoms; R.sup.2 is methyl, ethyl or 2-hydroxyethyl; R.sup.3 is
2-hydroxyethyl .[.or CH.sub.2 COO.sup.- .].; R.sup.4 is .[.CH.sub.2
COO.sup.- or CH.sub.2 CH.sub.2 --O--CH.sub.2 COO.sup.- ;.].
.Iadd.CH.sub.2 CH.sub.2 COONa; .Iaddend.and n is 2 or 3; and
(b) amine oxides having the structural formula ##STR6## wherein
R.sup.1 taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.2
taken alone is methyl, ethyl or 2-hydroxyethyl; R.sup.1 and R.sup.2
taken together are morpholino; R.sup.3 is alkyl having from about 8
to about 18 carbon atoms or R.sup.4 CONH(CH.sub.2).sub.3 wherein
R.sup.4 is alkyl having from about 8 to about 18 carbon atoms, and
wherein 2-hydroxyethyl can be condensed with from 1 to about 200
units of ethylene oxide; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
The preferred amount of antimicrobial agent in the composition is
from about 0.01% to about 10% by weight of the composition.
In a process aspect the invention is the process of reducing the
number of microbes on living skin which comprises applying to the
skin an antimicrobially effective amount of a composition
consisting essentially of
(A) from about 0.01% to about 10% by weight of one or more
antimicrobial agents selected from the group consisting of
(a) a compound of Formula I,
(b) a compound of Formula II or Formula III,
(c) a compound of Formula IV;
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants of Formula V, Formula VI and
Formula VII;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from
(a) betaines of Formula VIII, Formula IX, Formula X, Formula XI and
Formula XII; and
(b) amine oxides of Formula XIII; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
In a broader composition of matter aspect the invention is an
antimicrobial skin cleansing composition consisting essentially
of
(A) an antimicrobially effective amount of a basic amino or
ammonium antimicrobial agent;
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants of Formula V, Formula VI and
Formula VIII;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from
(a) betaines of Formula VIII, Formula IX, Formula X, Formula XI and
Formula XII; and
(b) amine oxides of formula XIII; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
The preferred amount of antimicrobial agent in the composition is
from about 0.01% to about 10% by weight of the composition.
In a broader process aspect the invention is the method of reducing
the number of microbes on living skin which comprises applying to
the skin an antimicrobially effective amount of a composition
consisting essentially of
(A) from about 0.01% to about 10% by weight of a basic amino or
ammonium antimicrobial agent;
(B) from about 0.75% to about 30% by weight of one or more
polyethylene glycol ester surfactants of Formula V, Formula VI and
Formula VII;
(C) from about 0.5% to about 30% by weight of one or more
surfactants selected from
(a) betaines of Formula VIII, Formula IX, Formula X, Formula XI and
Formula XII; and
(b) amine oxides of Formula XIII; and
(D) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an
aqueous ethyl alcohol-isopropyl alcohol mixture.
DETAILED DESCRIPTION OF THE INVENTION INCLUSIVE OF THE PREFERRED
EMBODIMENTS
Compositions
The essential ingredients of the compositions are generally and, in
most instances, particularly described by the prior art cited
above. The compositions are prepared by conventional pharmaceutical
methods and in addition to the essential ingredients may also
include pharmaceutical adjuncts, for example, emollients,
lubricants, stabilizers, dyes, perfumes and preservatives. It spite
of the presence of the antimicrobial agent, a preservative may be
necessary to prevent growth of microorganisms in the compositions.
A pharmaceutically acceptable acid or base may also be added for pH
adjustment.
Particularly preferred bisbiguanides are the following compounds of
Formula I.
______________________________________ Compound of Formula R R' n
______________________________________ Ia p-ClC.sub.6 H.sub.5 H 6
Ib ##STR7## H 6 Ic CH.sub.3 (CH.sub.2).sub.3 CH(CH.sub.2
CH.sub.3)CH.sub.2 H 6 Id CH.sub.3 (CH.sub.2).sub.6 H 6
______________________________________
The compound of Formula Ia is chlorhexidine (The Merck Index,
ibid., monograph 2060). The compound of Formula Ic is alexidine
(ibid., monograph 224). The digluconate salt (chlorhexidine
gluconate) is a particularly preferred bisbiguanide salt.
A particularly preferred quaternary ammonium salt is benzalkonium
chloride (ibid., monograph 1059; R is tetradecyl) (Roccal MC-14
Dihydrate:McCutcheon's Detergents and Emulsifiers, ibid., p. 214),
which has the structural formula ##STR8##
The following bispyridines of Formula IV are particularly
preferred.
______________________________________ Com- pound of Formula R Y A
m n % ______________________________________ IVa CH.sub.3
(CH.sub.2).sub.6 (CH.sub.2).sub.12 Cl or Br 1 2 1 IVb CH.sub.3
(CH.sub.2).sub.7 (CH.sub.2).sub.10 Cl or Br 1 2 1 IVc ##STR9##
(CH.sub.2).sub.12 Cl or Br 1 2 1
______________________________________
Although any polyethylene glycol ester surfactant of Formula V,
Formula VI or Formula VII and any betaine surfactant of Formula
VIII, Formula IX, Formula X or Formula XI and any amine oxide
surfactant of Formula XII can be used in carrying out this
invention, specific members of each class may show advantages in
specific application areas. Some that have been commercialized only
recently are not listed in the current editions of CTFA Cosmetic
Ingredient Dictionary (ibid.) or McCutcheon's Detergents &
Emulsifiers (ibid.).
Particularly preferred polyethylene glycol ester surfactants are
tabulated below.
______________________________________ CTFA Cosmetic Ingredient
Generic Name Dictionary Page ______________________________________
PEG-150 Laurate 219 PEG-150 Distearate 211 PEG-78 Glyceryl Cocoate
212 (Cf. PEG-7 Glyceryl Cocoate) PEG-30 Glyceryl Cocoate 212 (Cf.
PEG-7 Glyceryl Cocoate) ______________________________________
PEG-150 Laurate is the compound of Formula V wherein R is undecyl
and n has an average value of 150. PEG-150 Distearate is the
compound of Formula VI wherein R is heptadecyl and n has an average
value of 150. PEG-78 Glyceryl Cocoate is the compound of Formula
VII wherein ##STR10## represents the coconut acid radical and n has
an average value of 78. PEG-30 Glyceryl Cocoate is the compound of
Formula VII wherein ##STR11## represents the coconut acid radical
and n has an average value of 30.
Particularly preferred betaine surfactants are tabulated below.
______________________________________ CTFA Cosmetic Ingredient
Generic Name Type Dictionary Page
______________________________________ Coco-betaine Formula VIII 67
Coco-sultaine Formula IX 68 Cocamidopropyl Formula X 65 Betaine
Cocamidopropyl Formula XI 66 Sultaine .[.Amphoteric-l Formula XII
24.]. .[.Cocoamphoglycinate Formula XII 55*.].
.Iadd.Cocoamphopropionate Formula XII 55*
______________________________________ *CTFA Cosmetic Ingredient
Dictionary, Third Edition, The Cosmetic, Toiletry and Fragrance
Association, Inc., 1110 Vermont Avenue, N.W., Washington, D.C.
20005, 1982 .Iaddend.
Coco-betaine is the compound of Formula VIII wherein R.sup.1
represents the coconut radical. Coco-sultaine is the compound of
Formula IX wherein R.sup.1 represents the coconut radical.
Cocamidopropyl Betaine is the compound of Formula X wherein n is 3,
##STR12## represents the coconut acid radical and R.sup.2 is
methyl. Cocamidopropyl Sultaine is the compound of Formula XI
wherein is 3, ##STR13## represents the coconut acid radical and
R.sup.2 is methyl. .[.Amphoteric-1.]. .Iadd.Cocoamphopropionate
.Iaddend.is the compound of Formula XII wherein R.sup.1 represents
the coconut radical, R.sup.3 is 2-hydroxyethyl and R.sup.4 is
.[.CH.sub.2 COO.sup.-..]. .Iadd.CH.sub.2 CH.sub.2
COONa..Iaddend.
Particularly preferred amine oxide surfactants are tabulated
below.
______________________________________ CTFA Cosmetic Ingredient
Generic Name Dictionary Page ______________________________________
Myristamine Oxide 179 Coco-morpholine Oxide 67 Cocamidopropylamine
Oxide 65 Dihydroxyethyl Cocamine Oxide 95
______________________________________
Myristamine Oxide is the compound of Formula XIII wherein R.sup.1
is methyl, R.sup.2 is methyl and R.sup.3 is tetradecyl.
Coco-morpholine Oxide is the compound of Formula XIII wherein
R.sup.1 and R.sup.2 taken together are morpholino and R.sup.3
represents the coconut radical. Cocamidopropylamine Oxide is the
compound of Formula I wherein R.sup.1 is methyl, R.sup.2 is methyl
and R.sup.3 is R.sup.4 CONH(CH.sub.2).sub.3 wherein R.sup.4 CO
represents the coconut acid radical. Dihydroxyethyl Cocamine Oxide
is the compound of Formula XIII wherein R.sup.1 is 2-hydroxyethyl,
R.sup.2 is 2-hydroxyethyl and R.sup.3 is the coconut radical.
Compatibility
Compatability of the antimicrobial agents of Formula Id, Formula
IIa, Formula IVa (A=Br), Formula IVb (A=Br) and Formula IVc (A=Br)
with a prototype vehicle of the invention was tested by a serial
dilution test against Staphylococcus aureus ATCC 6538. Volumes of
two milliliters were used. Dilutions were in tryptosephosphate
broth. Incubation was for 16-18 hours at 37.degree. C. Growth was
verified with 2,3,5-triphenyltetrazolium chloride. The inoculum was
1.8.times.10.sup.5 viable cells per tube. There follows the formula
of the prototype vehicle.
______________________________________ Ingredient Percent by Weight
______________________________________ PEG-150 Laurate 12.0
Isopropyl Alcohol* 3.22 Cocamidopropyl Betaine 3.00 Laneth-16 1.00
Edetate Disodium 0.500 PEG-150 Distearate 0.500 PEG-2M 0.100
Perfume 0.100 FD&C Blue No. 1 0.000800 FD&C Yellow No. 5
0.000320 Gluconic Acid or Sodium pH about 5.5 Hydroxide to make
Purified Water to make 100.0 ______________________________________
Laneth-16 is the polyethylene glycol ether of Lanolin Alcohol with
an average ethoxylation value of 16. PEG2M is the polymer of
ethylene oxide having the structural formula H(OCH.sub.2
CH.sub.2).sub.n OH wherein n ha an average value of 2000. *To make
4% by volume
The following results were obtained.
______________________________________ Added Minimum Inhibitory
Concentration (MIC) (.mu.g/ml) Vehicle of Compound of Formula
(.mu.g/ml) Id.sup.+ IIa IVa.degree. IVb.degree. IVc.degree.
______________________________________ 0 0.25 0.5 0.39 0.5 0.25
15.6 0.25 0.5 0.195 0.5 0.25 31.2 0.25 0.5 0.39 0.5 0.25 62.5 0.25
0.5 0.39 0.5 0.25 125.0 0.25 0.5 0.10 0.5 0.125 250.0 0.25 0.5 0.10
0.25 0.0625 500.0 0.25 0.5 0.10 0.125 0.125 1000.0 0.25 1.0 0.195
0.125 0.125 2000.0 0.50 1.0 0.10 0.125 0.125 4000.0 0.50 1.95 0.195
0.25 0.25 8000.0 0.50 1.95 0.10 0.25 0.25 16000.0 * * * * * 32000.0
** ** ** ** ** 64000.0 ** ** ** ** **
______________________________________ .sup.+ Expressed as free
base .degree.Expressed as cation *MIC of vehicle alone **No growth
at this concentration of vehicle
It was concluded that each of the five antimicrobial agents tested
was compatible with the prototype vehicle.
EXAMPLES
The following examples still more particularly describe the
compositions of the invention.
EXAMPLE 1
______________________________________ Ingredient Percent by Weight
______________________________________ Chlorhexidine Gluconate 4.00
PEG-78 Glyceryl Cocoate 10.0 .[.Amphoteric-l 5.00.].
.Iadd.Cocoamphopropionate 5.00.Iaddend. Laneth-16 1.00 Benzyl
Alcohol 1.00 Acetamide MEA 0.750 PEG-30 Glyceryl Cocoate 0.500
Color 0.00100 Perfume 0.0500 Gluconic Acid to make pH 2.19 about
5.5, about Purified Water to make 100.0
______________________________________ Acetamide MEA is
N--(2hydroxyethyl)acetamide.
EXAMPLE 2
______________________________________ Ingredient Percent by Weight
______________________________________ Compound of Formula IVb (A =
Cl) 2.00 PEG-150 Laurate 12.0 Isopropyl Alcohol 3.22 Cocamidopropyl
Betaine 5.00 Laneth-16 1.00 Edetate Disodium 0.500 PEG-150
Distearate 0.500 PEG-2M 0.100 Perfume 0.100 Color 0.00100 Sodium
Hydroxide to make 0.023 pH about 5.5 Purified Water to make 100.00
______________________________________
EXAMPLE 3
______________________________________ Ingredient Percent by Weight
______________________________________ Compound of Formula IVb 2.00
(A = Cl) PEG-78 Glyceryl Cocoate 10.0 Dihydroxyethyl Cocoamine
Oxide 5.00 Citric Acid 0.384 Sodium Hydroxide to make -- pH about
5.5 Purified Water to make 100.00
______________________________________
EXAMPLE 4
______________________________________ Ingredient Percent by Weight
______________________________________ Chlorhexidine Gluconate 4.00
.[.Amphoteric-l 2.50.]. .Iadd.Cocoamphopropionate 2.50.Iaddend.
Cocamidopropylamine Oxide 2.00 PEG-78 Glyceryl Cocoate 10.0 PEG-30
Glyceryl Cocoate 0.500 Laneth-16 1.00 Acetamide MEA 0.750 Color
0.00100 Perfume 0.0500 Gluconic Acid or Sodium Hy- -- droxide to
make pH about 5.5 Acetic Acid 0.500 Benzyl Alcohol 1.00 Purified
Water to make 100.00 ______________________________________
EXAMPLE 5
______________________________________ Ingredient Percent by Weight
______________________________________ Chlorhexidine Gluconate 4.00
Dihydroxyethyl Cocamine Oxide 3.00 PEG-150 Distearate 0.750
Laneth-16 1.00 Benzyl Alcohol 2.00 Perfume 0.100 Color 0.00100
Gluconic Acid or Sodium Hydroxide -- to make pH about 5.5 Purified
Water to make 100.00 ______________________________________
Method of Use
The composition of Example 2 was tested for antimicrobial effect on
human hands using a gloved-hand model (R. N. Michaud, M. B. McGrath
and W. A. Goss, Journal of Clinical Microbiology, vol. 3, 1976, pp.
406-413). Twelve hands were randomly assigned for washes with the
composition of Example 2, and twelve hands were randomly assigned
for washes with a corresponding composition differing only by
absence of the antimicrobial agent (control). Each hand was washed
four times within six hours with a minimum of one hour between
washes using five milliliters of each composition for each wash.
During each wash the opposite hand of each person was protected
with a surgical glove.
Microbiological samples for quantitative determination of aerobic
resident bacteria were obtained from each hand immediately prior to
the first wash (Wash 1 Pre), after a glove-wearing period of one
hour subsequent to the first (Wash 1 T.sub.1), second (Wash 2
T.sub.1) and fourth (Wash 4 T.sub.1) washes, and after a
non-glove-wearing period of twenty hours after the fourth wash
(Wash 4 T.sub.20). Total bacterial counts per hand were expressed
as logarithms to the base 10. The hand-degerming effect after one
wash was evaluated as the bacterial reduction (Wash 1 Pre-Wash 1
T.sub.1), abbreviated (W.sub.1 Pre-W.sub.1 T.sub.1). Cumulative
effects after two washes and four washes were evaluated as the
bacterial reductions (Wash 1 Pre-Wash 2 T.sub.1), abbreviated
(W.sub.1 Pre-W.sub.2 T.sub.1), and (Wash1 Pre-Wash 4 T.sub.1),
abbreviated (W.sub.1 Pre-W.sub.4 T.sub.1). Persistent effect was
evaluated as the bacterial reduction (Wash 1 Pre-Wash 4 T.sub.20),
abbreviated (W.sub. 1 Pre-W.sub.4 T.sub.20).
Microbiological samples were taken by extracting each gloved hand
with sampling fluid (100 ml. of 0.1% Triton X-100 in 0.074 M
phosphate buffer at pH 7.8.+-.0.1). An aliquot (10 ml.) of each
extract was mixed with chilled neutralizer (10 ml. of 0.0003 M
potassium dihydrogen phosphate buffer of pH 7.2 containing 2% Tamol
N Micro brand of sodium salt of condensed naphthalene sulfonic acid
anionic dispersant). Decimal dilutions (10.sup.-1, 10.sup.-2,
10.sup.-3) of the neuturalized aliquot were prepared in 0.0003 M
KH.sub.2 PO.sub.4 buffer, pH 7.2, and were plated in triplicate
with trypticase soy agar using the pour-plate technique. Plates
were incubated aerobically at 30.degree..+-.2.degree. C. for 48-72
hours. A total colony count for each plate was determined using an
automated colony counter. Average colony counts were used to
estimate the total number of bacteria recovered per hand.
The following results were obtained
______________________________________ Number of Bacteria Mean (n =
12) Log.sub.10 Recovered Per Hand Sample Control Example 2
______________________________________ Wash 1 Pre 6.372 6.165 Wash
1 T.sub.1 6.537 5.770 Wash 2 T.sub.1 6.316 5.030 Wash 4 T.sub.1
5.978 4.296 Wash 4 T.sub.20 5.846 4.867
______________________________________ Bacterial Reductions Mean (n
= 12) Log.sub.10 Per Hand Difference Control Example 2
______________________________________ W.sub.1 Pre - W.sub.1
T.sub.1 -0.166 0.394 W.sub.1 Pre - W.sub.2 T.sub.1 0.055 1.135
W.sub.1 Pre - W.sub.4 T.sub.1 0.393 1.869 W.sub.1 Pre - W.sub.4
T.sub.20 0.525 1.297 ______________________________________
The foregoing mean log.sub.10 bacterial reductions were
significantly greater (P.ltoreq.0.01) for the hands treated with
the composition of Example 2 than for the hands treated with the
control composition.
Opacified Compositions
The foregoing examples of the compositions aspect of the invention
are clear as contrasted with opaque. By addition of appropriate
ingredients compositions according to the invention can be
opacified and emulsified as illustrated by the following
examples.
EXAMPLE 6
______________________________________ Ingredient Percent by Weight
______________________________________ Chlorhexidine Gluconate 1.00
PEG-78 Glyceryl Cocoate 10.0 EMPIGEN OB (Tertiary Alkylamine 10.0
Oxide 30%) White Soft Paraffin 6.0 Dihydroxyethyl Cocamine Oxide
5.26 Acetamide MEA (75%) 1.0 Benzyl Alcohol 1.0 Polysorbate 60 1.0
Sorbitan Stearate 1.00 Gluconic Acid to make pH 5.8 -- Purified
Water to make 100.0 ______________________________________
Polysorbate 60 is a mixture of stearate esters of sorbitol and
sorbitol anhydrides, consisting predominantly of the monoester,
condensed with approximately 20 moles of ethylene oxide. Sorbitan
Stearate is the monoester of stearic and hexitol anhydrides derived
from sorbitol.
EXAMPLE 7
is the same as Example 6 except tht the percent by weight of
chlorhexidine gluconate is increased to 4.00.
Comparative Sudsing Test and Sudsing Attribute Evaluation
In order to show that the presently described and claimed invention
achieves its above-stated objective to provide antimicrobial skin
cleansing compositions having better sudsing ability than the
compositions of the prior art, the following comparative in vitro
sudsing test and in vivo sudsing attribute evaluation were
conducted.
In Vitro Sudsing Test
The compositions compared in this test were the composition of
Example 1 of the present specification, the composition of Example
1 of the present specification excluding chlorhexidine gluconate,
and Hibiclens, which is a commercial
polyoxyethylene-polyoxypropylene block copolymer antimicrobial skin
cleansing composition containing chlorhexidine gluconate and which
is considered to be the composition described by EXAMPLE 1 of
above-cited U.S. Pat. No. 3,855,140. The composition of Example 1
of the present specification excluding chlorhexidine gluconate was
tested in this test in order to show that the absence of the
chlorhexidine gluconate does not significantly affect sudsability.
This was necessary because, without approval by the United States
Food and Drug Administration and due to the presence of the
chlorhexidine gluconate, the composition of Example 1 of the
present specification could not be evaluated in the in vivo sudsing
attribute evaluation described below, which was conducted in
humans.
The test composition (0.25 g.) was diluted to 100 ml. with
artificially hardened water (0.3 g. calcium chloride in 1 l. of
distilled water) in a 250 ml. stoppered graduate cylinder. Lanolin
oil (0.05 g.) was added to simulate the natural oil of human hands.
The cylinder was rotated end over end at a constant rate and the
foam volume was read after 25, 50, 75 and 100 rotations. Five
cylinders were used for each composition. The mean foam volumes and
standard deviations for each composition were calculated, affording
the following results:
______________________________________ Number of Foam Volume (ml.)
Rotations 25 50 75 100 ______________________________________
Example 1 132 .+-. 4.5 142 .+-. 7.7 164 .+-. 10.5 173 .+-. 6.6
Example 1 127 .+-. 6.0 135 .+-. 10.9 149 .+-. 13.7 162 .+-. 22.3
without Chlorhexidine Gluconate Hibiclens 107 .+-. 2.3 111 .+-. 2.6
115 .+-. 2.6 120 .+-. 3.8
______________________________________
The means for Example 1 with or without chlorhexidine gluconate are
significantly different from the means for Hibiclens (P<0.01).
The means for Example 1 with chlorhexidine gluconate are not
significantly different from the means for Example 1 without
chlorhexidine gluconate (P<0.1).
In Vivo Sudsing Attribute Evaluation
Since Hibiclens is red in color and the preferred color of the
composition of Example 1 of the present specification is green,
both a red formulation and a green formulation according to Example
1 (Both lacking chlorhexidine gluconate) were tested. The results
were not significantly affected by the difference in color.
Ten persons participated in the evaluation. Each person was
instructed to: (1) wash his or her hands with soap and water, (2)
rinse the hands and leave them wet, (3) apply one teaspoonful of
the skin cleansing compositions to the hands, (4) wash the hands
with the skin cleanser for one full minute, adding water as
desired, (5) rinse the hands, (6) dry the hands with a towel and
(7) repeat steps (1) through (6) three times allowing at least one
hour between repetitions.
Each person was instructed to evaluate the skin cleansing
composition with regard to four criteria relating to sudsing and to
assign one of five values to each criterion as follows: Criteria:
initial or flash foam, foam quantity, foam texture, foam stability.
Criterion values: poor, fair, mediocre, good, excellent.
The five criterion values were assigned the following numerical
values: poor, 0; fair, 25; mediocre, 50; good, 75; excellent, 100.
The criterion values for each criterion were averaged and gave the
following results:
______________________________________ Criterion Value Example 1
Example 1 Without Without Chlorhexidine Chlorhexidine Gluconate
Gluconate Hibiclens Criterion (Green) (Red) (Red)
______________________________________ Initial or 78 .+-. 8 78 .+-.
8 23 .+-. 28 Flash Foam Foam Quantity 85 .+-. 13 78 .+-. 8 35 .+-.
32 Foam Texture 83 .+-. 17 80 .+-. 11 35 .+-. 32 Foam Stability 83
.+-. 17 78 .+-. 8 38 .+-. 34
______________________________________
All of the criterion values for Example 1 without chlorhexidine
gluconate are significantly different from those of Hibiclens
(P<0.01).
* * * * *