Antimicrobial composition

A rapidly acting antimicrobial alcohol-containing composition and method of using the composition to disinfect surfaces, such as the hands is disclosed.

The present invention relates antimicrobial compositions which are 
topically applied to a substrate, such as the hands. 
BACKGROUND OF THE INVENTION 
Alcohol-containing antimicrobial compositions have been used in the 
healthcare industry for many years. More recently, alcohol and 
chlorhexidine gluconate compositions have been developed due to their long 
lasting efficacy and rapid kill of microorganisms. However, recent 
emergence of resistant microorganisms to antibiotic drugs and multi-drug 
resistance to a number of other antibiotics restricted the use of topical 
products containing antibiotics. Hospital staffs are seeking 
multifunctional products which meet their needs in terms of safety and 
performance against these emerging organisms. It would also be highly 
desirable to be able to provide this antimicrobial composition in a 
convenient dosage form for the hospital environment. 
One attempt at solving this problem is the use of multiple antimicrobial 
compositions as disclosed in U.S. Pat. No. 5,403,864. This patent 
discloses an alcohol based solution which contains antimicrobial 
compounds, triclosan and chloroxylenol. 
In addition to hospital and healthcare environments, awareness among 
consumers regarding antimicrobial compounds are increasing, and the desire 
for safe, mild and effective compositions for the home are also necessary. 
Preferably the antimicrobial compositions will solve these problems while 
remaining non-drying or preferably providing moisture that reduces the 
irritation levels associated with present antimicrobial compositions. 
Accordingly, there is a continuing desire for an antimicrobial composition 
that is effective while also being non-irritating to users. 
SUMMARY OF THE INVENTION 
One embodiment of the present invention provides an antimicrobial 
composition comprising of a) an antimicrobial selected from the group 
consisting of more than 30% by volume alcohol and an effective amount of 
triclosan; and b) an effective amount of phenoxy ethanol, an effective 
amount of benzalkonium chloride or benzethonium chloride; and an effective 
amount of PHOSPOLIPID CDM. 
In a second embodiment of the invention the antimicrobials are provided 
with an effective amount of triclosan, GERMALL PLUS and GERMABEN II. 
Additionally, the antimicrobial composition optionally also contains an 
effective amount of PHOSPOLIPID PTC. 
In yet another embodiment of the present invention, the antimicrobial 
compositions also demonstrated surprising bactericidal activity against 
Staphyloccus aureaus (MRSA). The present invention also demonstrated 
excellent bactericidal activity against Serratia marcescens ATCC 14756 
which has demonstrated weak susceptibility to triclosan-based 
formulations. 
DETAILED DESCRIPTION OF THE INVENTION 
The alcohol content of the present invention is greater than about 30 
percent by volume, typically from about 55 to about 90 percent by volume, 
preferably from 60 to about 85 and most preferably from 60 to about 70% by 
volume of the composition. The alcohols useful in the present invention 
include, ethyl alcohol, iso-propyl alcohol, n-propyl alcohol and 
combinations thereof. Ethyl alcohol may be used as the only alcohol in the 
invention or in another embodiment the alcohol content in the invention 
provides ethyl alcohol from about 40 to about 70% by volume, iso-propyl 
alcohol from about 5 to about 25% by volume and n-propyl alcohol from 
about 5 to about 25% by volume. 
Triclosan is employed from about 0.1 to about 0.5, preferably from about 
0.2 to about 0.4 by weight. 
The present invention contains a mixture of an effective amount of 
antimicrobials phenoxy ethyl alcohol, PHOSPHOLIPID CDM, benzalkonium 
chloride, and preferably GERMALL PLUS and GERMABEN II. Phenoxy ethanol is 
used from about 0.25 to about 5.0 percent by weight, preferably from about 
0.3 to about 0.7, most preferably at about 0.05 percent by weight. 
PHOSPHOLIPID CDM is used from about 0.01 to about 1.0, preferably from 
about 0.03 to about 0.7, most preferably 0.5 percent by weight. 
Benzethonium chloride or preferably benzalkonium chloride is used from 
about 0.02 to about 1.0, preferably from about 0.08 to about 0.5, most 
preferably about 0.1 to about 0.2 percent by weight. 
Other antimicrobial compositions have been found to particularly effective 
in improving the efficacy of the invention. These compositions include 
triclosan, PHOSPHOLIPID PTC, GERMALL PLUS and GERMABEN II. 
The amount of GERMALL PLUS and GERMABEN II, independently provided in the 
invention varies from about 0.05 to about 0.5 with 0.1 percent by weight 
preferred. In the present invention the use of GERMALL PLUS and GERMABEN 
II together has been found to be highly effective. The ratio of the two 
materials when employed together is from about 0.1:1 to 1:0.1 and most 
preferably 1:1 weight ratio. 
In addition to the antimicrobial compositions recited above, other 
antimicrobials may be employed with the present invention including nisin, 
bis-guanides, chlorhexidine gluconate, chlorohexidine digluconate, 
chlorhexidine diacetate, chlorhexidine dihydrochlorider tricloban, sodium 
hydroxy methyl glycinate, octanoyl collagenic acid, cetyl pyridium 
chloride, phenol, iodine, parachlorometaxylenol (PCMX), polymeric 
quaternary ammonium compounds, their combinations and the like. The 
antimicrobial compositions are typically added at a level of from 0.1 to 
about 4.0 percent by weight. 
Other preferred ingredients employed in the invention include PHOSPOLIPID 
PTC, which is employed from about 0.01 to about 1.0, preferably from about 
0.02 to about 0.08, and most preferably about 0.05 percent by weight. 
Australian tea tree oil and lemon grass oil are used in 1:1 ratio from 
about 0.5 to about 10.0, preferably from about 1.0 to about 7.0, and most 
preferably 5.0 weight percent. 
One highly preferred embodiment of the invention provides more than 40% by 
weight alcohol, an effective amount of phenoxy ethanol, an effective 
amount of benzalkonium chloride, an effective amount of GERMALL PLUS, an 
effective amount of GERMABEN-II, and an effective amount of PHOSPOLIPID 
CDM. Additionally, the antimicrobial composition optionally also contains 
an effective amount of PHOSPOLIPID PTC. 
In another preferred embodiment the antimicrobial mixture comprises greater 
than about 40% by weight alcohol, an effective amount of phenoxy ethanol, 
an effective amount of benzalkonium chloride, an effective amount of 
triclosan, an effective amount of GERMALL Plus, an effective amount of 
GERMABEN-II, and an effective amount of PHOSPOLIPID CDM. 
In yet another preferred embodiment of the invention the antimicrobial 
mixture contains greater than about 40% by weight alcohol, an effective 
amount of phenoxy ethanol, an effective amount of benzalkonium chloride, 
an effective amount of benzethonium chloride, an effective amount of 
triclosan, an effective amount of GERMALL Plus, an effective amount of 
GERMABEN-II, and an effective amount of PHOSPOLIPID CDM. 
In another highly preferred embodiment of the invention the antimicrobial 
mixture is greater than 40% by weight a mixture of alcohols such as ethyl 
alcohol, iso-propyl alcohol, and n-propyl alcohol, a mixture of two 
essential oils such as Australian tea tree oil, and lemon grass oil, an 
effective amount of phenoxy ethanol, an effective amount of benzalkonium 
chloride, an effective amount of triclosan, an effective amount of GERMALL 
plus, an effective amount of GERMABEN-II, and an effective amount of 
PHOSPOLIPID CDM. Additionally, the antimicrobial composition optionally 
also contains an effective amount of Vitamin E linoleate. 
The antimicrobial compositions of the present invention are found to 
possess immediate and persistent activity over time. The compositions of 
the present invention also compare favorably with antimicrobial 
compositions which contain high levels of chlorhexidine gluconate or 
commercial products such as HIBISTAT and HIBICLENS, available from ZENECA 
Pharmaceuticals, which are commonly being used for disinfecting surgical 
scrubs, hand disinfectants and in preoperative preparation of patients. 
It is known in the art that chlorohexidine gluconate formulations exhibit a 
great build-up in activity between washes 1 and 7. This increase in 
activity is believed to be caused by its polar structure and its ability 
to attach to skin. After ten washes and neutralization with suitable 
inactivator, the activity of chlorohexidine gluconate falls significantly 
(approximately 30-50%) at wash 10, when testing is performed in accordance 
with a Health Care personel hand wash protocol. Surprisingly, the 
compositions of the present invention provide more persistent 
antimicrobial activity than these other well-known antimicrobial agents. 
Another advantage of the present invention is the residual activity 
provided by the antimicrobial product. The present invention provides 
effective protection against a broad spectrum of organisms, including gram 
positive, gram negative, yeast and fungi both at the initial application 
time, but also after an extended period of time. We have found that unike 
other antimicrobial compositions which are initially effective in killing 
microbes but which quickly lose their efficacy in about one hour. 
Surprisingly, the present invention is effective in preventing the 
appearance of microbes for an extended periods of time, such as greater 
than two hours, preferably for about three or four hours or more. 
It is preferable to include other ingredients in the formulation to enhance 
the efficacy of the antimicrobial composition. Included in this are 
essential oils to improve the rate at which the antimicrobial composition 
works as well as its residual activity. Suitable essential oils include 
Australian tea tree oil, lemongrass oil, thyme oil, lavender oil and clove 
oil and combinations thereof. Essential oils are used to increase the 
emolliency, moisturization, emollient and penetration properties of the 
present invention. Typically these oils are incorporated at the level of 
from about 1 to about 10 weighgt percent, and most preferably at about 5 
weight percent based upon the total composition. 
The present invention also employs thickening agents of acrylic acid which 
are crosslinked with an unsaturated polyfunctional agent such as polyallyl 
ether of sucrose. These acrylic acid functionalized polymers, commonly 
known as carbomers, are disclosed in U.S. Pat. Nos. 2,798,053 and 
3,133,865 herein incorporated by reference. 
The selection of the proper carbomer provides the antimicrobial formulation 
with the desired viscosity values. In order to have the desired feel the 
viscosity of the formulation must have a value of greater than about 5,000 
centipoise. More preferably the formulations will have a viscosity of from 
about 9,000 to about 22,000 and most preferably from about 11,000 to about 
20,000 centipoise as measured at 25.degree. C. 
A thickening agent, which is an addition agent comprised of an acrylic acid 
polymer crosslinked with an unsaturated polyallyl ether of sucrose is 
employed. The polymers are used in an amount sufficient to obtain a gelled 
composition of viscosity in the desired range. 
A number of these polymers, known in the art as carbomers are commercially 
marketed by B.F. Goodrich, (Cleveland, Ohio) such as CARBOPOL.RTM. 934, 
940 and 941; and by R.I.T.A. (Crystal Lake, Ill.) as ACRITAMER.RTM. 
934,940 and 941, respectively. Typically the carbomer compounds are used 
from about 0.2 to about 2.0 percent by weight, and are preferably employed 
at a level of from about 0.4 to about 0.7 by weight of the total 
antimicrobial composition. 
A preferred carbomer polymer, among several preferred carbomers is R.I.T.A. 
ACRITAMER.RTM. 505E, a polyvinyl carboxy polymer crosslinked with ethers 
of pentaerythritol. ACRITAMER.RTM. 505E is preferred as a gelling agent or 
viscosity enhancer because it provides a transparent or translucent gel in 
the present invention. 
The most preferred carbomer is ULTREZ.RTM. 10 (available from BF Goodrich) 
a modified copolymer having a major portion of a monoolefinically 
unsaturated carboxylic acid monomer or its anhydride of 3 to 6 carbon 
atoms and a minor portion of a long chain acrylate or methacrylte ester 
monomer. The polymer is predominately acrylic acid and a smaller amount of 
a long chain acrylate monomer. The polymer is described in U.S. Pat. No. 
5,004,598, hereby incorporated by reference in its entirety. 
Another particularly preferred group of ingredients in the present 
invention are tack modifiers such as silicone waxes, stearoxy trimethyl 
silane, cyclomethicone, cetyl lactate, and alkyl lactates, (typically 
lengths C.sub.12 -C.sub.15). Moisturizers such as glycerin, water, lipids, 
waxes and the like are also helpful when employed in the present 
invention. Other solvents are also employed, such as propylene glycol, in 
order to provide for a more stable formulation. 
Other ingredients which may be added to the compositions include 
fragrances, emollients, pH adjusters, viscosity modifiers such as acrylic 
polymers, gums, xanthan gums and the like; transdermal enhancers, 
surfactants, dyes, colors and the like. These ingredients are well known 
in the art and are disclosed for example in U.S. Pat. No. 5,403,864 and 
5,403,587. The remainder of the present formulation is made up of water, 
preferably deionized water. Water typically makes up from 10 to about 40% 
by weight of the antimicrobial composition. 
The following formulation possesses highly effective antimicrobial 
properties. 
1. Ethyl alcohol (40-70%), Isopropyl alcohol (20-25%),n-Propyl alcohol 
(5-10%) 
2. Diisobutyl Phenoxy Ethoxy Ethyl Dimethyl Benzyl Ammonium chloride 
(0.05-0.5%), commonly known as benzethonium chloride 
3. triclosan, commonly known as, 2, 4, 4'-trichloro-2-hydoxydiphenyl ether 
(0.2-0.5%) 
4. N, N-Bis (Hydroxymethyl) urea (0.08-0.5%), Methyl p-Hydroxybenzoate 
(0.009-0.5%), Propyl p-Hydroxy benzoate (0.0025-0.5%), 1, 2-Propane diol 
(0.050-0.056%), 
5. Coco Phosphotidyl PG-Dimonium chloride (0.05-0.5%) 
6. DL- and L-Ofloxacin (0.01-0.5%) 
7. Australian Tea Tree oil (1.0-5.0%) 
8. Lemongrass oil (1.0-5.0%) 
9. Thyme oil (1.0-5.0%) 
10. Lavender oil (1.0-5.0%) 
11. Clove oil (1.0-5.0%) 
The antimicrobial compositions of the present invention are effective in 
controlling microorganisms when an effective amount of the composition is 
topically applied to a substrate or location, such as the hands, acne 
sites, or injection site for catheters, etc. The amount applied to be 
effective depends upon such environmental factors as the length of 
application, the amount of contact of the antimicrobial composition and 
the substrate, as well temperature and evaporation rates. Those with skill 
in the art will readily be able to determine the effective level necessary 
to control the microorganisms. Typically, from about 0.5 to about 10 
milliliters, preferably from about 1.0 to about 8, and most preferably 
from about 2.5 to about 5 milliliters of the antimicrobial composition is 
applied. This amount of the antimicrobial composition is found to be 
effective, to provide a log.sub.10 reduction of 2 or more in the microbe 
population. 
The present invention can also be prepared as an emulsion using techniques 
well known in the art, see for example U.S. Pat. No. 5,308,890. The active 
ingredients, excipients, ect., may be emulsified with an anionic, 
cationic, or nonionic surfactant or dispersing agent, or compatible 
mixtures thereof such as a mixture of an anionic or a nonionic surfactant, 
using, for example, from about 0.05% to about 5% by weight of a surfactant 
or dispersing agent based on the weight of the ingredients to be 
emulsified. Suitable cationic dispersion agents include lauryl pyridinium 
chloride, cetyldimethyl amine acetate, and alkyldimethylbenzylammonium 
chloride, in which the alkyl group has from 8 to 18 carbon atoms. Suitable 
anionic dispersing agents include, for example, alkali fatty alcohol 
sulfates, such as sodium lauryl sulfate, and the like; arylalkyl 
sulfonates, and the like; alkali alkyl sulfosuccinates, such as sodium 
octyl sulfosuccinate, and the like; and alkali arylalkylpolyethoxyethanol 
sulfates or sulfonates, such as sodium octylphenoxypolyethoxyethyl 
sulfate, having 1 to 5 oxyethylene units, and the like. Suitable non-ionic 
dispersing agents include, for example, alkyl phenoxypolyethoxy ethanols 
having alkyl groups from about 7 to 18 carbon atoms and from about 6 to 
about 60 oxyethylene units such as, for example, heptyl 
phenoxypolyethoxyethanols, ethylene oxide derivatives of long chained 
carboxylic acids such as lauric acid, myristic acid, palmitic acid, oleic 
acid, and the like, or mixtures of acids such as those found in tall oil 
containing from about 6 to 60 oxyethylene units; ethylene oxide 
condensates of long chained alcohols such as octyl, decyl, lauryl, or 
cetyl alcohols containing from 6 to 60 oxyethylene units; ethylene oxide 
condensates of long-chain or branched chain amines such as dodecyl amine, 
hexadecyl amine, and octadecyl amine, containing from about 6 to 60 
oxyethylene units; and block copolymers of ethylene oxide sections 
combined with one or more hydrophobic propylene oxide sections. High 
molecular weight polymers such as hydroxyethyl cellulose, methyl 
cellulose, polyacrylic acid, polyvinyl alcohol, and the like, may be used 
as emulsion stabilizers and protective colloids. 
The following examples are illustrative of the present invention and are 
not intended to limit the invention to the following compositions. Unless 
noted to the contrary, all percentages presented in this application are 
understood to be weight percent. 
The following compositions were used in this application: 
AMP 95 is a mixture of 2-amino-2-methyl-1-propanol, 
2-(methylamino)-2-methyl-1-propanol and water in a ratio of from about 
90:5:5, commercially available from Angus Chemical Company. 
ACRITAMER.RTM. 505E, a polyvinyl carboxy polymer crosslinked with ethers of 
pentaerythritol, R.I.T.A.available from Crystal Lake, Ill. 
ESS 9090IC is a fragrance, available from Givudan-Roure Corporation 
CERAPHYL 28 is primarily cetyl lactate, a waxy solid commmercially 
available from ISP Van Dyk Inc. 
CERAPHYL 41 is a mixture of C.sub.12 -C.sub.15 alcohol lactates, available 
from ISP Van Dyk Inc. 
DOW CORNING.RTM. 580 wax is a mixture of stearoxy trimethoxy silane and 
stearyl alcohol. 
GERMABEN II is a mixture comprised of diazolindinyl urea (about 30%); 
methyl paraben (about 11%); propyl paraben (about 3%) and propylene glycol 
(about 56%), available from Sutton Laboratories. 
GERMALL PLUS is a mixture of diazolidinyl urea (about 99%), 
3-Iodo-propynylbutylcarbamate available from Sutton Laboratories. 
LEXOREZ 100 is a saturated crosslinked hydroxy functional; polyester, 
comprised of glycerin, diethylene glycol, adipate crosslinked polymer, 
which is a viscous, hydrophobic liquid at room temperature and is 
dispersible in many lipids and emollients. 
PHOSPOLIPID CDM is cocophosphatidyl (PG)-dimonium chloride,a co-synthetic, 
phospholipid available from Mona Industries, Inc. 
PHOSPOLIPID PTC is cocamidopropyl phosphatidyl PG-dimonium chloride, 
available from Mona Industries. 
SILSOFT PEDM phenylethyl dimethicone, available from Witco Corporation, Osi 
Specialties, Inc. 
TRICLOSAN--2, 4, 4'-trichloro-2-hydoxydiphenyl ether. 
ULTREZ.RTM. 10 a carbomer polymer, available from BF Goodrich, Cleveland 
Ohio, and disclosed in U.S. Pat. No. 5,004,598, the contents of which are 
incorporated by reference in its entirety.