U.S. patent application number 17/678579 was filed with the patent office on 2022-09-01 for preservatives for cosmetic, toiletry and pharmaceutical compositions.
This patent application is currently assigned to Inolex Investment Corporation. The applicant listed for this patent is Inolex Investment Corporation. Invention is credited to Daniel WINN.
Application Number | 20220272973 17/678579 |
Document ID | / |
Family ID | 1000006337102 |
Filed Date | 2022-09-01 |
United States Patent
Application |
20220272973 |
Kind Code |
A1 |
WINN; Daniel |
September 1, 2022 |
Preservatives for Cosmetic, Toiletry and Pharmaceutical
Compositions
Abstract
A composition for and methods of preserving a topical cosmetic,
toiletry or pharmaceutical formulation against microbiological
contamination or growth are described in which the compositions
used herein include at least one hydroxamic acid, salt or complex
thereof, and the methods include addition of an effective amount of
such compounds to a cosmetic, toiletry or pharmaceutical
formulation. Compositions further including alkanediols and/or
solubilizing agents in blends with hydroxamic acid are also
described.
Inventors: |
WINN; Daniel; (Kingston,
NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Inolex Investment Corporation |
Wilmington |
DE |
US |
|
|
Assignee: |
Inolex Investment
Corporation
Wilmington
DE
|
Family ID: |
1000006337102 |
Appl. No.: |
17/678579 |
Filed: |
February 23, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16781636 |
Feb 4, 2020 |
11291204 |
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17678579 |
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15692447 |
Aug 31, 2017 |
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16781636 |
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14614815 |
Feb 5, 2015 |
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15692447 |
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13182292 |
Jul 13, 2011 |
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14614815 |
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12324504 |
Nov 26, 2008 |
8993641 |
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13182292 |
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61004760 |
Nov 29, 2007 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 47/16 20130101;
A01N 31/02 20130101; A61K 8/345 20130101; A61Q 17/04 20130101; A61Q
19/007 20130101; A61K 2800/30 20130101; A61K 8/40 20130101; A61K
2800/592 20130101; A61K 2800/524 20130101; A01N 37/28 20130101;
A61Q 19/10 20130101; A61Q 19/00 20130101 |
International
Class: |
A01N 37/28 20060101
A01N037/28; A61K 8/34 20060101 A61K008/34; A61K 8/40 20060101
A61K008/40; A61Q 17/04 20060101 A61Q017/04; A61Q 19/00 20060101
A61Q019/00; A61K 47/16 20060101 A61K047/16; A01N 31/02 20060101
A01N031/02; A61Q 19/10 20060101 A61Q019/10 |
Claims
1-20. (canceled)
21. A preservative composition comprising: (i) about 4.5% to about
15% of a single alkylhydroxamic acid or a salt thereof selected
from: caprohydroxamic acid or salts thereof, caprylohydroxamic acid
or salts thereof, caprinohydroxamic acid or salts thereof, and
laurohydroxamic acid or salts thereof; (ii) about 7% to about 95.5%
of a diol selected from: a C.sub.3-C.sub.10 1,2-vicinal diol, a
C.sub.5 to C.sub.10 glyceryl monoether, a C.sub.5 to C.sub.10
glyceryl monoester, and combinations thereof; and (iii) about 1% to
about 70% of a solubilizing agent, wherein the preservative
composition is free of parabens.
22. The preservative composition of claim 21, wherein the
solubilizing agent is selected from: a second diol, glycerin, and
combinations thereof.
23. The preservative composition of claim 22, wherein the single
alkylhydroxamic acid or a salt thereof is present in a
concentration of about 5% to about 15%.
24. The preservative composition of claim 23, wherein the diol is
present in a concentration of about 70% to about 95%.
25. The preservative composition of claim 24, wherein the
solubilizing agent is present in a concentration of about 15% to
about 55%.
26. The preservative composition of claim 25, wherein the diol is
selected from: a propanediol, methylpropanediol, a butylene glycol,
1,2-pentanediol, 1,2-hexanediol, caprylyl glycol, 1,2-decanediol,
caprylyl glyceryl ether, ethylhexylglycerin, glyceryl monolaurate,
glyceryl monocaprate, glyceryl monocaprylate, and combinations
thereof.
27. The preservative composition of claim 26, wherein the single
alkylhydroxamic acid or a salt thereof is caprylohydroxamic acid
and salts thereof.
28. A method of preserving a cosmetic, toiletry, or pharmaceutical
formulation against microbiological contamination or growth,
comprising adding an effective amount of the preservative
composition of claim 21 to the cosmetic, toiletry, or
pharmaceutical formulation.
29. The method of claim 28, wherein the cosmetic, toiletry, or
pharmaceutical formulation is free of parabens.
30. The method of claim 29, wherein the effective amount of the
preservative composition prevents the microbiological contamination
or growth of Staphylococcus aureus, Escherichia coli, Pseudomonas
aeruginosa, Candida albicans, Aspergillus niger, or a combination
thereof.
31. The method of claim 29, wherein the effective amount of the
preservative composition maintains the concentration of
Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa,
Candida albicans, or Aspergillus niger present in the cosmetic,
toiletry, or pharmaceutical formulation below 1.00 colony forming
units per gram for a period of at least 28 days.
32. A method for preventing microbiological contamination in a
cosmetic, toiletry, or pharmaceutical formulation against,
comprising adding an effective amount of a preservative composition
to the cosmetic, toiletry, or pharmaceutical formulation, wherein
the preservative composition comprises (i) a single alkylhydroxamic
acid or a salt thereof selected from: hexanohydroxamic acid or
salts thereof, caprylohydroxamic acid or salts thereof,
caprinohydroxamic caprohydroxamic acid or salts thereof, and
laurohydroxamic acid or salts thereof; and (ii) a diol selected
from: a C.sub.3-C.sub.10 1,2-vicinal diol, a C.sub.5 to C.sub.10
glyceryl monoether, a C.sub.5 to C.sub.10 glyceryl monoester, and
combinations thereof, wherein the effective amount of the
preservative composition maintains the concentration of
Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa,
Candida albicans, or Aspergillus niger present in the cosmetic,
toiletry, or pharmaceutical formulation below 1.00 colony forming
units per gram for a period of at least 28 days.
33. The method of claim 32, wherein the cosmetic, toiletry, or
pharmaceutical formulation and preservative composition are free of
parabens.
34. The method of claim 33, wherein the preservative composition
further comprises a solubilizing agent.
35. The method of claim 34, wherein the single alkylhydroxamic acid
is present in a concentration of about 4.5% to about 15%, the diol
is present in a concentration of about 7% to about 95.5%, and the
solubilizing agent is present in a concentration of about 1% to
about 70%.
36. The method of claim 34, wherein the diol is selected from: a
propanediol, methylpropanediol, a butylene glycol, 1,2-pentanediol,
1,2-hexanediol, caprylyl glycol, 1,2-decanediol, caprylyl glyceryl
ether, ethylhexylglycerin, glyceryl monolaurate, glyceryl
monocaprate, glyceryl monocaprylate, and combinations thereof, and
the solubilizing agent is selected from a diol, glycerin, or
combinations thereof.
37. The method of claim 36, wherein the single alkylhydroxamic acid
is present in a concentration of about 5% to about 15%, the diol is
present in a concentration of about 30% to about 95%, and the
solubilizing agent is present in a concentration of about 15% to
about 55%.
38. A cosmetic, toiletry, or pharmaceutical formulation comprising
an effective amount of the preservative composition of claim 21,
wherein the effective amount of the preservative composition
maintains the concentration of Staphylococcus aureus, Escherichia
coli, Pseudomonas aeruginosa, Candida albicans, or Aspergillus
niger present in the cosmetic, toiletry, or pharmaceutical
formulation below 1.00 colony forming units per gram for a period
of at least 28 days.
39. The formulation of claim 38, further comprising one or more
additives selected from the group consisting of water, colorants,
fragrances, humectants, emulsifiers and/or thickeners, chelating
agents, gelling agents, amino acids, emollients, solvents,
sunscreen UVA and/or UVB blocking agents, antioxidants, additional
preservatives, waxes, polymers and copolymers, inorganic and
organic pigments, herbs, natural extracts, oils, pH adjusters, and
combinations thereof.
40. The formulation of claim 38, wherein the effective amount of
the preservative composition of claim 21 is about 1.0% to about
2.0% of the formulation.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of application Ser. No.
15/692,447, filed Aug. 31, 2017, which in turn is a continuation of
Ser. No. 14/614,815, filed Feb. 5, 2015, which in turn is a
continuation of application Ser. No. 13/182,292, filed Jul. 13,
2011, which is itself a divisional of pending application Ser. No.
12/324,504, filed Nov. 26, 2008, now U.S. Pat. No. 8,993,641, which
in turn claims priority under 35 U.S.C. 119(e) to U.S. Provisional
Patent Application 61/004,760, filed Nov. 29, 2007, the entire
contents of each of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] Topical cosmetic, toiletry and pharmaceutical products such
as creams, lotions, pastes, liquids, aerosols, shampoos, gels,
wipes, bats, sticks, powders and granules, are known in the art to
be susceptible to microbial infestation. The raw materials,
packaging, and manufacturing environment for these products are
often not sufficiently sterile, such that small amounts of
microbiological contaminants can enter into final products.
Shipment and storage of packaged cosmetic, toiletry and
pharmaceutical products in some cases are performed under
uncontrolled conditions. Often, a cosmetic, toiletry or
pharmaceutical product may be exposed to higher temperatures than
recommended which can also accelerate the growth rate of microbes
unless a suitably effective antimicrobial component and/or
components are incorporated into the formulation. Once product
packages are opened, they are subject to further contamination from
repeated consumer use. A consumer may notice microbial infestation
by the discoloration and/or unpleasant odor of a product, or they
might see macroscopic quantities of microorganisms such as mold on
the product. Microbial growth can also cause the degradation of
chemical and/or active compounds in the cosmetic, toiletry or
pharmaceutical formulation, which can lead to instability of the
product and/or emulsion. A product that has been contaminated by
microbiological organisms can also lead to user infections once it
is applied to the skin, scalp and/or mucous membranes of a human.
It is therefore important for manufacturers and marketers of such
products to be able to offer products that resist microbial growth
and provide a stable and safe product with a long shelf life.
[0003] Typically, topical cosmetic, toiletry and pharmaceutical
manufacturers add small amounts of one or more preservative
compounds to their formulations to prevent microbial growth. The
preferred preservatives may be water-soluble, since typically it is
the water phase of a product that is most susceptible to microbial
growth. The preferred preservatives are effective at use levels
that lead to cost-effectiveness, and do not cause excessive
irritation, a disadvantage that is associated with many
preservative compounds. The preferred preservatives are those that
do not adversely affect the aesthetic properties of the formulation
such as the odor and the color. Furthermore, it is also desirable
that the preservative does not affect the performance attributes
and/or activity of the product. Finally, such preservatives must
follow the guidelines established by individual national laws and
regulations. In most countries, these regulations limit the type of
and use-level of preservatives that may be included in a product.
In some countries, certain preservatives are permitted only for
rinse-off products (such as shower gels) but not for leave-on
products (such as skin creams.) Therefore, preferred preservatives
would be those that are not wholly prohibited in any country, and
which are not restricted to only certain product types.
[0004] Preservatives used in topical cosmetic, toiletry and
pharmaceutical products must also meet consumer preferences. In
recent years, cosmetic preservatives have been a frequent target of
academics and activist groups who question their toxicological
safety. The resulting media reports have suggested that certain
preservatives can be dangerous. As a result, manufacturers prefer
to use preservatives not tainted by negative publicity and that
will not adversely affect product marketability.
[0005] Preservatives used in cosmetic, toiletry and pharmaceutical
products must enable the products to successfully pass
microbiological testing protocols, known as "challenge tests",
established by government regulations and trade organizations.
Challenge tests are performed by adding known quantities of
microorganisms to a product and measuring the increase or decrease
in microorganism population over time. The organisms include
Gram-positive bacteria, Gram-negative bacteria, yeast and mold. The
Cosmetic, Toiletries, and Fragrance Association (CTFA) has defined
a challenge test that is widely accepted as the standard in the
cosmetic, toiletry and pharmaceutical industry. The test requires
that the quantity of bacteria be reduced by 99% in seven days, and
that the quantity of yeast and fungi (mold) be reduced by 90% in
seven days. In order to pass a challenge test, the product must
contain the appropriate amounts and types of preservative compounds
that will enable antimicrobial efficacy against a broad spectrum of
microorganisms in a short period of time.
[0006] In recent years cosmetic, toiletry and pharmaceutical
manufacturers have been severely limited in their choice of
preservative agents. One class of biocides that has been highly
effective in cosmetic, toiletry and pharmaceutical products
includes formaldehyde donors, such as imidazolidinyl urea,
diazolidinyl urea, and DMDM hydantoin. However, many such compounds
are considered to be skin irritants and the use of formaldehyde
donors is severely restricted by regulations in the EU and
Japan.
[0007] Another class of preservatives includes the
isothiazolinones, such as KATHON.RTM. CG, available commercially
from Rohm & Haas, Philadelphia, Pa., which contains a
chloro-substituted isothiazolinone (methylchloroisothiazolinone).
This chloro-substituted isothiazolinone has demonstrated irritation
potential and it is prohibited from use in leave-on products in
some countries.
[0008] Another class of preservatives is chlorinated aromatic
compounds, such as chlorphenesin. They are not broadly used in
cosmetic, toiletries or pharmaceuticals because they exhibit a very
strong and unpleasant odor. Also chlorinated compounds in general
are used in herbicides and pesticides, and many are known human
toxins, and thus chlorinated compounds may have a negative consumer
perception.
[0009] Yet another class of preservatives is para-hydroxybenzoic
acids, known as parabens. Preservative blends containing parabens,
such as GERMABEN.RTM. and LIQUAPAR.RTM., available commercially
from International Specialty Products, and PHENONIP.RTM., available
commercially from Clariant, are the most widely used preservative
systems and have been used safely and effectively for over 20
years. However, research reports such as the recent Journal of
Applied Toxicology [2004, 24, 5] have suggested that parabens are
possible human carcinogens. The media has suggested that products
containing parabens are dangerous. Consumer groups, such as Breast
Cancer Action, have lobbied cosmetic and toiletry companies to
remove parabens from their products. As a result parabens are now
defacto banned from many segments of the cosmetic and toiletry
industry.
[0010] In U.S. Published Patent Application US-2005-0228032-A1,
International Specialty Products describes a paraben-free,
broad-spectrum preservative blend that includes glycols,
phenoxyethanol and organic acids. In U.S. Pat. No. 6,447,793 B2,
Engelhard Corporation describes paraben-free, broad-spectrum
preservation systems that include phenoxyethanol, chlorphenesin,
and organic acids. Such blends fail to meet all of the
industry-desired needs, because organic acids are only effective as
biocides in products that have an acidic pH. Cosmetic, toiletry and
pharmaceutical products having an acidic pH can be limited to
certain leave-on formulations, such as creams and lotions. Organic
acids are completely ineffective biocides at neutral pH, and thus
these preservative blends are not suitable for pH-neutral cosmetic,
toiletry and toiletry products, such as body washes and
shampoos.
[0011] U.S. Patent Publication No. 2007-0207105-A1 describes an
anti-microbial composition including a vicinal diol, which is a
liquid at room temperature and an isothiazolinone compound to the
composition. The vicinal diol may be a compound such as a
1,2-alkane diol or a glyceryl monoether. The isothiazolinone may be
methylisothiazolinone, such as 2-Methyl-3(2H)isothiazolinone.
[0012] As referred to herein, compounds known as hydroxamic acids
are part of a family of organic acids of general formula
R--C(.dbd.O)--N(R')--OH. The alkenylhydroxamic acid, sorbic
hydroxamic acid, is known in the art to have antifungal properties.
See, e.g., W. F. Dudman, Appl. Microbiol., 11(4), pp. 362-364
(July, 1963). It has been proposed for use as a food preservative.
However, sorbic hydroxamic acid is not used commercially for such
an application because it has proven to be mutagenic.
Alkylhydroxamic acids have excellent metal binding properties and
their commercial use is almost entirely in the mineral processing
industry for enhancing the recovery of valuable ores. See, e.g.,
Pradip and Fuerstenau, "Mineral Flotation with Hydroxamate
Collectors", in "Reagents in the Minerals Industry", Ed. M. J.
Jones and R. Oblatt, Inst. Min. Met., London, pp. 161-168 (1984).
The commercial products AM2.RTM. from Ausmelt Limited of Melbourne,
Australia, and AERO.RTM. S6493 from Cytec Industries, Inc., West
Patterson, N.J., are mineral processing formulations containing
alkylhydroxamic acids.
[0013] Alkylhydroxamic acids are also known to inhibit the
catalytic activity of the enzyme urease, and therefore may be
useful for reducing the odor that results from the decomposition of
urine into ammonia. Esai Corporation Limited of Japan describes the
use of alkylhydroxamic acids as part of deodorizing compositions as
described in U.S. Pat. No. 3,978,208. Esai Corporation has also
demonstrated that alkylhydroxamic acids may be useful for treating
urinary kidney stones in humans as noted in U.S. Pat. No.
4,256,765. More recently, Lion Corporation of Japan demonstrated in
U.S. Pat. No. 4,661,342 that saturated alkylhydroxamic acids, such
as caprylohydroxamic acid, have anti-bacterial effectiveness
against Streptococcus mutans in the human oral cavity. However,
such compounds have not been adopted for topical cosmetic, toiletry
and pharmaceutical formulations.
[0014] There is a need in the art for additional preservatives for
topical cosmetic, toiletry and pharmaceutical purposes that are
free of parabens, formaldehyde donors and chlorinated compounds,
that are globally approved for use in leave-on and rinse-off
products, and that have efficacy against a broad spectrum of
microorganisms at various levels of pH, especially neutral pH.
BRIEF SUMMARY OF THE INVENTION
[0015] The present invention includes use of an effective amount at
least one alkylhydroxamic acid, alone or in combination with at
least one alcohol in topical cosmetic, toiletry and/or
pharmaceutical preparations that are substantially free of
parabens.
[0016] The invention includes a method of preserving a topical
cosmetic, toiletry or pharmaceutical formulation against
microbiological contamination or growth, comprising adding an
effective amount of at least one hydroxamic acid, a salt and/or a
complex thereof.
[0017] A composition is also within the scope of the invention
herein which is useful for the preservation of topical cosmetic,
toiletry and pharmaceutical formulations, wherein the composition
is substantially free of parabens, comprising at least one
hydroxamic acid, a salt and/or a complex thereof, and at least one
alcohol.
[0018] Further included herein is a personal care product
comprising a composition useful for the preservation thereof,
wherein the composition is substantially free of parabens and
comprises at least one hydroxamic acid, a salt and/or a complex
thereof, and at least one alcohol.
[0019] Also within the scope hereof is a pharmaceutical product
comprising a composition useful for the preservation thereof,
wherein the composition is substantially free of parabens and
comprises at least one hydroxamic acid, a salt and/or a complex
thereof, and at least one alcohol.
DETAILED DESCRIPTION OF THE INVENTION
[0020] An alkylhydroxamic or hydroxamic acid as referred to herein
may be present in its free (un-neutralized) or salt (neutralized)
form, and it shall be understood that the terms "hydroxamic acid"
and "alkylhydroxamic acid" include within the scope thereof the
free acid form of the compounds as well as their salts and/or
complexes thereof as well as materials which are precursors to such
compounds, salts and complexes which upon addition react to form
such compounds, salts and complexes, unless otherwise specifically
noted.
[0021] The invention includes a method of preserving a
substantially paraben free, topical, cosmetic, toiletry or
pharmaceutical formulation against microbiological contamination or
growth. As used herein, "topical" means application of the
cosmetic, toiletry or pharmaceutical composition to the hair or
skin and outer surfaces of the body, and does not include oral or
other internal mucous membrane uses. The method includes adding an
effective amount of at least one hydroxamic acid, salt, complex or
precursor(s) thereof alone or in combination with an effective
amount of at least one alcohol to such a formulation. Also within
the invention is a preservative composition, substantially free of
parabens, that includes a blend of at least one hydroxamic acid,
salt, complex or precursor(s) thereof with at least one alcohol, as
well as a personal care product or a pharmaceutical product
including such preservative compositions.
[0022] In the method herein the at least one hydroxamic acid
includes an alkylhydroxamic acid, such as those described further
herein below. An alkylhydroxamic acid may have linear or branched
carbon chain of from about two to about twenty-two carbon atoms,
and preferably from about six to about twelve carbon atoms. The
carbon chains may include double bonds, i.e., areas of unsaturation
and may also have functionality depending on desired end use and
properties. For example hydroxy groups may be beneficial side- or
terminal-substituents on the chain leading to better water
compatibility.
[0023] Other similar functional groups that meet the criteria of
being compatible with and/or suggested for use in cosmetic,
toiletry and/or pharmaceutical formulations are also within the
scope of the invention. Such hydroxamic acids may also be
synthesized from natural oils using lipase catalysis as well as
other hydroxamic synthesis techniques known or to be developed in
the art. Examples of such alkylhydroxamic acids include, but are
not limited to hexanohydroxamic acid, caprylohydroxamic acid,
caprohydroxamic acid, laurohydroxamic acid and mixtures and
combinations thereof, and most preferably is caprylohydroxamic
acid. It should be noted herein that precursors, such as hydroxy
acids in combination with, for example, hydroxylamine hydrochloride
or a similar compounds which can react within solution and/or in
the formulation to form the various hydroxamic and alkylhydroxamic
acids, salts and/or complexes thereof as are known in the art may
also be used instead of a direct additive within the scope of the
invention.
[0024] It is preferred that in the method, the composition further
includes at least one alcohol, preferably a diol, and most
preferably one or more vicinal diols. "Vicinal diols," as used
herein, are materials that have hydroxyl groups which are bonded to
atoms in the molecule which are next to each other, i.e., wherein
two atoms each bearing a hydroxyl group are bonded to each other.
Examples of vicinal diol compounds suitable for use in the
invention, include, but are not limited to, ethylene glycol and
propylene glycol. Such materials are known for use as humectants
and solvents in cosmetic, toiletry and pharmaceutical products.
They are also known to have some modest antimicrobial activity as
described in U.S. Publication No. 2007-0207105-A1, the disclosure
of which in relevant part related to vicinal diols, and
compositions incorporating these compounds are incorporated herein
by reference.
[0025] The most preferred vicinal diols for use in the compositions
described herein when used in cosmetic, toiletry and pharmaceutical
applications are medium-chain length, linear vicinal diols that
demonstrate antimicrobial activity at relatively low use-levels.
Such diols include 1,2-pentanediol, 1,2-hexanediol, caprylyl
glycol, and 1,2-decanediol. Other vicinal diols useful in the
compositions described herein include molecules derived from
glycerin. Glycerin can be reacted with other molecules at its 1- or
3-position, leaving two vicinal hydroxyl groups. For example,
glyceryl monoethers, such as ethylhexylglycerin
[3-(2-ethylhexyloxy)propane-1,2-diol], available commercially as
SENSIVA.RTM. SC50 from Schulke & Mayr, are useful liquid
vicinal diols having antimicrobial properties. Glyceryl monoesters
such as glyceryl monolaurate, glyceryl mono caproate, or glyceryl
monocaprylate, the latter of which is commercially available as
LEXGARD.RTM. GMCY from Inolex Chemical Company, Philadelphia, Pa.,
are also useful antimicrobial vicinal diols. For the preservation
of cosmetics, toiletries and pharmaceuticals, vicinal diols are
known to be effective against bacteria and yeast but weak against
fungi. In the book, D. Steinberg, Preservatives for Cosmetics. 2nd
ed, (2006), pg. 102, the author comments regarding vicinal diols
that "[t]he weakest activity on all of these is fungi." In the
article, D. Smith et al., "The Self-Preserving Challenge," Cosmetic
& Toiletries, No. 1, 115, No. 5 (May 2000), vicinal diols are
described as having activity against bacteria, but to be "limited
against Aspergillus." Since Aspergillus niger is one of the
microorganisms used in the CTFA challenge test, products with
vicinal diols as described herein as the only preservative may not
sufficiently pass the CTFA challenge test.
[0026] The compositions described herein are useful for the
preservation of topical cosmetic, toiletry and pharmaceutical
formulations. In such formulations to achieve the benefits of the
invention it is preferred that the compositions be substantially
free of parabens, and preferably completely free of parabens. The
compositions may be the same as those described above with respect
to the method hereof.
[0027] The compositions preferably include at least one vicinal
diol in amounts of, for example, about 0.001% by weight to about
99.999% by weight of the blend of the hydroxamic acid, salt or
complex thereof with the at least one alcohol. The hydroxamic acid,
salt or complex thereof preferably is present in an amount of about
0.001% to about 99.999% by weight of the noted blend. If precursors
for hydroxamic acids, salts or complexes are used as components
according to one aspect of the invention, the weight percentages
described herein and further below, refer to the amount of formed
compound desired in the blends in the compositions, wherein the
compounds are formed from the precursor reaction or
combination.
[0028] The compositions may further include a solubilizing agent in
amounts of about 1% to about 70% by weight of the hydroxamic
acid/alcohol blends. Examples of solubilizing agents include
diols.
[0029] The invention also includes personal care products and
pharmaceutical products that include compositions useful for the
preservation thereof, wherein the compositions are also preferably
substantially free of parabens and are as described herein
according to the invention.
[0030] In personal care products, the compositions are preferably
present in amounts of about 0.01 to about 10.00% by weight of the
personal care product. In pharmaceutical products, the compositions
are preferably present in an amount of from about 0.01 to about
10.00% by weight of the pharmaceutical product.
[0031] Despite these previous uses of hydroxamic acid in other
industries, the invention describes a method including adding an
effective amount of at least one alkylhydroxamic acid to topical
cosmetic, toiletry and pharmaceutical formulations that result in a
non-toxic, broad pH, and effective preservative method against a
range of gram-positive bacteria, gram-negative bacteria, yeast and
fungi. Formulations provided by the use of this method can pass
regulatory acceptance criteria such as the CTFA challenge.
[0032] Suitable hydroxamic acids include alkylhydroxamic acids that
include at least one alkyl group of a chain length of about two to
about twenty-two carbon atoms, which may be branched or linear in
structure, substituted or unsubstituted, and saturated or
unsaturated as noted hereinabove. Preferred alkylhydroxamic acids
contain alkyl groups of a chain length of about six to about twelve
carbon atoms and most preferably linear chains of that length. Most
preferred alkylhydroxamic acids are caprylohydroxamic acid, having
a linear terminal chain of eight carbon atoms and caprohydroxamic
acid, having a linear chain of ten carbon atoms. Such
alkylhydroxamic acids may be used alone or in combination for
varying effects and properties, and/or may be the result of use of
precursors used as starting components as described above.
[0033] The preferred compounds have a formula as shown in Formula
(I):
##STR00001##
wherein R is a linear or branched, substituted or unsubstituted,
carbon chain of about two to about twenty-two carbon atoms, which
chain may be interrupted by one or more oxygen atoms, and may
include saturated or unsaturated carbon bonds. Accordingly, R
groups may include, for example, alkyl, alkyenyl, alkynyl, alkoxy,
alkenoxy, alkynoxy and similar groups, are branched or linear, and
which groups may be further functionalized using substituted
groups, including hydroxy or other acceptable cosmetic, toiletry
and/or pharmaceutical end groups for use and compatible with such
end applications. R.sup.1 may be hydrogen or R.
[0034] Further effective preservation can be provided to the use of
the hydroxamic acid if an effective amount of at least one alcohol
is used in a blend with the at least one hydroxamic acid. The most
preferred alcohols are vicinal diols.
[0035] In one preferred embodiment, caprylyl glycol is blended with
caprylohydroxamic acid. In another preferred embodiment, caprylyl
glycol is blended with caprylohydroxamic acid and further blended
with one or more glycols or vicinal diols that are liquid at room
temperature, such that the entire blend is liquid and therefore
easy to blend into a cosmetic, toiletry or pharmaceutical emulsion.
Such liquid glycols and vicinal diols include ethylhexylglycerin,
1,2-hexanediol, 1,2-pentanediol, propylene glycol, butylene glycol,
and hexylene glycol.
[0036] It is preferred herein, that in preferred cosmetic, toiletry
or pharmaceutical compositions, that the at least one hydroxamic
acid is present in an amount of about 0.01 to about 10 percent by
weight, and more preferably from about 0.1 to about 5 weight
percent of a blend of the at least one alkylhydroxamic acid with
the at least one vicinal diol and any optional solubilizing agent
and/or water as noted herein. While only one alkylhydroxamic acid
is necessary, such materials as described above may be used alone
or in combinations with each other and with one or more vicinal
diols. The amount of the alkylhydroxamic acid and the vicinal diol
components in the blend should be selected so as to preferably
provide a ratio of alkylhydroxamic acid(s) to vicinal diol(s) in
the blend which is to be provided to the composition of about
99.999:0.001 to about 0.001:99.999 and more preferably about
10.00:0.01 to about 0.01:10.00, and most preferably about 10.0:0.1
to about 0.1:10.0.
[0037] In one preferred embodiment, an additional solvent is also
incorporated into a blend of one vicinal diol and one
alkylhydroxamic acid to make a blend of at least three components
that is then incorporated into a cosmetic, toiletry or toiletry
formulation. In such an embodiment, an additional glycol or vicinal
diol that is liquid at room temperature is included in the blend in
an amount of about 1 percent by weight to about 70 percent by
weight of the blend, based on the total weight of the blend.
[0038] Formulations prepared for topical cosmetic and toiletry
compositions herein referred to as personal care compositions, and
topical pharmaceutical compositions, may include any other
colorants, fragrances, active ingredients or other additives
typically used and/or to be developed in the art for use in
personal care and pharmaceutical formulations, in which additives
will vary depending upon the formulation in which the preferred
compositions are used, i.e., whether the formulations are used in
skin treatments such as moisturizing compositions, skin toners,
skin cleansers, night creams, skin creams, shaving creams, skin
care lotions, or other cosmetic preparations; make-up, such as
foundation, liquid and powder-based make-up, mascara, lipstick,
blush, gloss, eye-liner and the like; or other personal care and/or
pharmaceutical compositions, such as, sunscreens, lip balms,
fragrances, massage oil, shampoos, conditioners, conditioning
shampoos, hair styling gels, hair reparatives, hair tonics, hair
fixatives, hair mousses, bath and shower gels, liquid soaps,
moisturizing sprays, makeup, pressed powder formulations, bath
additives, ophthalmic preparations, foaming soaps and body washes,
sanitizing wipes, hand sanitizers, towelettes and wipes and others.
It should be understood, based on this disclosure that a wide
variety of personal care and pharmaceutical formulations could
benefit from the properties of the methods and compositions of the
present invention, wherein, as used herein, pharmaceutical product
is a product including at least one active pharmaceutical
ingredient (API).
[0039] The personal care and pharmaceutical formulations, if liquid
based (such as gels, hydrogels, lotions, shampoos and the like)
will also preferably include water as part of the liquid base. The
formulations and compositions may include other additives as well,
such as without limitation, at least one humectant, at least one
emulsifier and/or thickener, chelating agent(s), gelling agent(s),
amino acid(s), emollient(s), various solvents, free radicals and
initiators, sunscreen UVA and/or UVB blocking agents, antioxidants,
other preservatives, waxes, polymers and copolymers, inorganic and
organic pigments and/or one more fragrances, coloring agent(s),
herbs, natural extracts, essential oils, pharmaceutical drug
products, and other additives commonly used in such
formulations.
[0040] The personal care and pharmaceutical compositions herein may
be lotion-based, oil-in-water emulsions, water-in-oil emulsions,
water-in-silicone emulsions, silicon-in-water emulsions, gels,
solids, liquids, cream based, oil based, aqueous/alcoholic or
glycolic solution based, dispersions, suspensions or syrups,
microemulsions or a liposome-based formulations.
[0041] In water-based formulations, other than solids and thicker
gels, etc., it is preferred that about 20% by weight to about 95%
by weight (on a wet basis) of water is incorporated therein. The
various additives aside from the water and preferred combination of
preservatives noted herein including hydroxamic acids and alcohols,
would make up the remaining portion of various personal care and
pharmaceutical formulations based on the compositions described
herein. Preferably, each additive is present in an amount of up to
about 75 percent by weight of the entire formulation, and more
preferably up to about 40 percent by weight, with a collective
amount of such additives of preferably no greater than about 50
percent by weight.
Example 1
[0042] A skin care emulsion formulation was developed and then
challenge tested. Table 1 describes two skin care formulations that
are identical with the exception of their preservative system:
Comparative Product A contains no preservative, while Product B
contains 1.05% of a preservative blend according to the invention.
The preservative blend in Product B is a combination of 95.2%
caprylyl glycol and 4.8% caprylohydroxamic acid. The formulations
are shown below in Table 1.
TABLE-US-00001 TABLE 1 Comparative Formulation A Formulation B (%
w/w) (% w/w) Deionized Water Q.S. Q.S. Xanthan Gum 0.40 0.40
Glycerin (96% solution) 1.50 1.50 Butylene Glycol 1.00 1.00
Tetrasodium EDTA 0.10 0.10 Blend (95.2% caprylyl -- 1.05 glycol and
4.8% caprylohydroxamic acid) Octinoxate 7.50 7.50 Oxybenzone 5.25
5.25 Octisalate 5.00 5.00 Avobenzone 2.00 2.00 Homosalate 13.00
13.00 Glyceryl Stearate and 2.50 2.50 PEG-100 Stearate Neopentyl
Glycol 2.25 2.25 Diheptanoate Adipic Acid/Diethylene 3.00 3.00
Glycol/Glycerin Crosspolymer Hydroxyethylacrylate/ 3.50 3.50 Sodium
Acryloyl- dimethyltaurate Copolymer and Squalane and Polysorbate 60
Silica 2.00 2.00 Total 100.00 100.00
[0043] A challenge test complying with USP and CTFA methodologies
was performed. The results are in Table 2. The table indicates the
log value of the number of viable organisms measured after the
expired time interval. The term TNTC is the acronym for "Too
Numerous To Count" and indicates that the number of viable
organisms has increased as compared to the initial inoculum.
Comparative Product A, containing no preservative, fails to meet
the CTFA acceptance criteria of a 99% reduction in bacteria and 90%
reduction in yeast and fungi within seven days. Product B,
containing a preservative blend of a vicinal diol and an
alkylhydroxamic acid according to the invention, meets and far
exceeds the CTFA acceptance criteria.
TABLE-US-00002 TABLE 2 S. aureus E. coli P. aeruginosa C. albicans
A. niger A B A B A B A B A B Inoculum 5.71 5.90 5.95 6.09 5.77 6.16
5.77 5.38 5.3 5.30 Day 7 TNTC <1.0 TNTC <1.0 TNTC <1.0
TNTC <1.0 TNTC <1.0 Day 14 4.41 <1.0 5.17 <1.0 2.53
<1.0 5.03 <1.0 4.9 <1.0 Day 21 Fail <1.0 Fail <1.0
Fail <1.0 Fail <1.0 Fail <1.0 Day 28 Fail <1.0 Fail
<1.0 Fail <1.0 Fail <1.0 Fail <1.0
[0044] As the results show, the compositions according to the
invention hereof may be used to prepare effective preservative for
personal care and pharmaceutical compositions, and contribute to
preservation of topical cosmetic, toiletry and pharmaceutical
compositions.
Example 2
[0045] A body wash formulation was prepared in accordance with the
invention. The ingredients shown in Table 3, below, were combined
to form a body wash base.
TABLE-US-00003 TABLE 3 Ingredient Amount (wt %) Deionized water
Q.S. Na.sub.4 EDTA 0.1 PEG150 distearate 0.75 Sodium lauryl ether
sulfate (30% soln.) 8 Lexaine C 19.3 Lexquat C 2 PEG 80 Sorbitan
laurate 15 NaCl.sub.2 0.8
[0046] Three formulations (A, B, and C) were prepared using the
base body wash. To formulation A was added 0.70 wt. % of a CHA
blend, to formulation B was added 0.80 of a CHA blend, to
formulation C was added 1.0% of a CHA blend. The CHA blend used in
each case was composed of caprylohydroxamic acid, capylyl glycol,
and glycerin in a weight ratio of 15:71:14, respectively.
[0047] LEXAINE C is a proprietary formulation of cocamidylpropyl
betaine. LEXQUAT C is a proprietary formulation of cocamidylpropyl
PG-dimonium chloride. Both are available from Inolex Chemical
Company, Philadelphia, Pa.
[0048] A preservative efficacy test ("PET") was preformed using
each formulation A, B, and C. The results are shown below in Tables
4, 5, and 6.
TABLE-US-00004 TABLE 4 (Formulation A) Log.sub.-10 CFU/g
Staphyloccous Esherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 4.11 3.53 2.52 2.20 4.71 Day 2 3.18 3.21 <1.00
<1.00 4.02 Day 7 <1.00 1.78 <1.00 <1.00 3.78 Day 14
<1.00 <1.00 <1.00 <1.00 3.47 Day 21 <1.00 <1.00
<1.00 <1.00 3.39 Day 28 <1.00 <1.00 <1.00 <1.00
3.40
TABLE-US-00005 TABLE 5 (Formulation B) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 4.56 4.45 2.66 2.16 4.26 Day 2 4.01 3.50 <1.00
<1.00 4.96 Day 7 1.48 2.16 <1.00 <1.00 2.98 Day 14
<1.00 <1.00 <1.00 <1.00 3.48 Day 21 <1.00 <1.00
<1.00 <1.00 3.24 Day 28 <1.00 <1.00 <1.00 <1.00
3.28
TABLE-US-00006 TABLE 6 (Formulation C) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 4.62 4.41 2.51 1.18 4.35 Day 2 3.43 3.72 <1.00
<1.00 4.90 Day 7 1.48 1.79 <1.00 <1.00 3.88 Day 14
<1.00 <1.00 <1.00 <1.00 3.59 Day 21 <1.00 <1.00
<1.00 <1.00 3.24 Day 28 <1.00 <1.00 <1.00 <1.00
3.31
Example 3
[0049] A lotion formulation was prepared in accordance with the
invention. A base lotion formulation was prepared by incorporating
the ingredients and amounts as shown below.
TABLE-US-00007 Ingredient Amount (wt %) Deionized water Q.S.
Keltrol CG 0.3 Glycerine 5 Sodium borate 0.2 Lexol GT-865 15
Stearic acid 4.5 Beeswax 4 Tocopheryl acetate 0.1 Orange wax 0.5
Tegosoft PSE 141G 2.5
[0050] KELTROL CG is a proprietary formulation of xanthan gum,
available from CP Kelco, Atlanta, Ga. LEXOL GT 865 is a proprietary
formulation of propylene glycol dicaprylate/dicaprate, available
from Inolex Chemical Company, Philadelphia, Pa. TEGOSOFT PSE is a
proprietary formulation of sucrose monostearate mixed with tallow
alcohol/coconut alcohol available from Evonik Goldschmidt of
Parsippany, N.J.
[0051] Using this base, three formulations were prepared (D, E and
F). To formulation D was added contained a CHA blend in the amount
of 0.7% by weight; E contained a CHA blend in an amount of 0.8% by
weight, and F contains a blend on an amount of 1.0% by weight. In
each instance the CHA blend consisted of caprylohydroxamic acid,
capylyl glycol, and glycerin in a weight ratio of 15:71:14,
respectively.
[0052] PET evaluations were carried out on each formulation, and
the results are shown below in Tables 7-9.
TABLE-US-00008 TABLE 7 (Formulation D) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 4.78 2.33 <1.00 4.37 4.40 Day 2 4.08 <1.00
<1.00 4.12 4.78 Day 7 <1.00 <1.00 <1.00 <1.00 3.61
Day 14 <1.00 <1.00 <1.00 <1.00 2.65 Day 21 <1.00
<1.00 <1.00 <1.00 2.35 Day 28 <1.00 <1.00 <1.00
<1.00 2.04
TABLE-US-00009 TABLE 8 (Formulation E) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 2.32 <1.00 <1.00 3.45 4.65 Day 2 <1.00
<1.00 <1.00 <1.00 4.73 Day 7 <1.00 <1.00 <1.00
<1.00 3.20 Day 14 <1.00 <1.00 <1.00 <1.00 <1.00
Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00
TABLE-US-00010 TABLE 9 (Formulation F) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 <1.00 <1.00 <1.00 2.49 4.45 Day 2 <1.00
<1.00 <1.00 <1.00 4.41 Day 7 <1.00 <1.00 <1.00
<1.00 2.60 Day 14 <1.00 <1.00 <1.00 <1.00 <1.00
Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00
Example 4
[0053] A sunscreen lotion base formulation having SPF 28 was
prepared by incorporating the ingredients shown below in Table
10:
TABLE-US-00011 TABLE 10 Ingredient Amount (wt. %) Deionized water
Q.S. Keltrol CG 0.4 glycerin (96% solution) 1.5 Na.sub.4 EDTA 0.1
butylene glycol 1 Simugel 3.5 Octinoxate 7.5 Homosalate 13
Octisalate 5 Oxybenzone 5.25 Auobenzone 2 LEXOREZ 100 3 LEXFEEL 7
2.25 LEXEMUL 561 2.5
[0054] SIMUGEL is a proprietary formulation of ammonium
polyacrylate/isohexadane/PEG-40 available from SEPPIC, Countryside,
Ill. LEXOREZ 1 is a proprietary formulation of adipic
acid/diethylene glycol/glycerin, LEXFEEL 7 is a proprietary
formulation of neopentyl glycol diheptanoate, and LEXEMUL 561 is a
proprietary formulation of glyceryl stearate PEG-100 stearate; all
are available from Inolex Chemical Company, Philadelphia, Pa.
[0055] Three formulations (G, H, I) were prepared. To formulation G
was added a CHA blend in an amount of 0.7 wt %. To formulation H,
was added a CHA blend in an amount of 0.8 wt %. To formulation I
was added a CHA blend in an amount of 1.0% by weight. The CHA blend
used in each case was composed of caprylohydroxamic acid, capyrlyl
glycol, and glycerin in a weight ratio of 15:71:14,
respectively.
[0056] A PET evaluation was carried out on each formulation and the
data/results are shown below in Tables 11, 12, and 13.
TABLE-US-00012 TABLE 11 (Formulation G) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 4.52 <1.00 <1.00 4.27 4.64 Day 2 <1.00
<1.00 <1.00 1.60 4.24 Day 7 <1.00 <1.00 <1.00
<1.00 1.90 Day 14 <1.00 <1.00 <1.00 <1.00 <1.00
Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00
TABLE-US-00013 TABLE 12 (Formulation H) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 2.57 <1.00 <1.00 3.19 4.91 Day 2 <1.00
<1.00 <1.00 <1.00 4.00 Day 7 <1.00 <1.00 <1.00
<1.00 <1.00 Day 14 <1.00 <1.00 <1.00 <1.00
<1.00 Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28
<1.00 <1.00 <1.00 <1.00 <1.00
TABLE-US-00014 TABLE 13 (Formulation I) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.94 6.13 5.75 5.56 5.24
level Day 1 <1.00 <1.00 <1.00 <1.00 4.49 Day 2 <1.00
<1.00 <1.00 <1.00 4.08 Day 7 <1.00 <1.00 <1.00
<1.00 <1.00 Day 14 <1.00 <1.00 <1.00 <1.00
<1.00 Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28
<1.00 <1.00 <1.00 <1.00 <1.00
Example 5
[0057] A base SPF 28 sunscreen lotion was prepared using by the
components and amounts shown in Table 10, below. Using this base,
six formulations (J1, J2, J3, K1, K2, and L) were prepared. Each
formulation was prepared by using the CHA blend in the amount noted
below in Table 14:
TABLE-US-00015 TABLE 14 Blend Blend Blend Caprylohydroxamic
Caprylohydroxamic Caprylohydroxamic acid/glyceryl caprylate/
acid/ethylhexylglycerin/ acid/phenoxyethanol// methylpropanediol
methylpropanediol methylpropanediol/water Formulation (10:75:15 wt
ratio) (15:30:55 wt ratio) (15:70:7.5:7.5 wt ratio) J1 1.0 wt % 0 0
J2 1.2 wt % 0 0 J3 1.5 wt % 0 0 K1 0 1.0 wt % 0 K2 0 1.2 wt % 0 L 0
0 1.0 wt %
[0058] A PET evaluation was carried out and the results are shown
in Tables 15-20.
TABLE-US-00016 TABLE 15 (Formulation J1) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.86 6.16 6.03 5.31 5.17
level Day 1 <1.00 <1.00 <1.00 3.74 4.74 Day 2 <1.00
<1.00 <1.00 2.40 4.61 Day 7 <1.00 <1.00 <1.00
<1.00 3.74 Day 14 <1.00 <1.00 <1.00 1.18 2.44 Day 21
<1.00 <1.00 <1.00 <1.00 2.31 Day 28 <1.00 <1.00
<1.00 <1.00 1.00 Validation + + + + +
TABLE-US-00017 TABLE 16 (Formulation J2) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.86 6.16 6.03 5.31 5.17
level Day 1 <1.00 <1.00 <1.00 3.22 4.88 Day 2 <1.00
<1.00 <1.00 <1.00 4.60 Day 7 <1.00 <1.00 <1.00
<1.00 3.55 Day 14 <1.00 <1.00 <1.00 <1.00 2.04 Day
21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00 Validation + + + + +
TABLE-US-00018 TABLE 17 (Formulation J3) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.86 6.16 6.03 5.31 5.17
level Day 1 <1.00 <1.00 <1.00 3.13 4.54 Day 2 <1.00
<1.00 <1.00 <1.00 4.29 Day 7 <1.00 <1.00 <1.00
<1.00 2.52 Day 14 <1.00 <1.00 <1.00 <1.00 <1.00
Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00 Validation + + + + +
TABLE-US-00019 TABLE 18 (Formulation K1) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.86 6.16 6.03 5.31 5.17
level Day 1 2.18 <1.00 <1.00 3.13 4.81 Day 2 <1.00
<1.00 <1.00 <1.00 4.60 Day 7 <1.00 <1.00 <1.00
<1.00 3.11 Day 14 <1.00 <1.00 <1.00 1.70 <1.00 Day
21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00 Validation + + + + +
TABLE-US-00020 TABLE 19 (Formulation K2) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.86 6.16 6.03 5.31 5.17
level Day 1 2.63 <1.00 <1.00 3.29 4.53 Day 2 <1.00
<1.00 <1.00 <1.00 4.23 Day 7 <1.00 <1.00 <1.00
<1.00 2.11 Day 14 <1.00 <1.00 <1.00 1.90 <1.00 Day
21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28 <1.00
<1.00 <1.00 <1.00 <1.00 Validation + + + + +
TABLE-US-00021 TABLE 20 (Formulation L) Log.sub.-10 CFU/g
Staphylococcus Escherichia Pseudomonas Candida Aspergillus aureus
coli aeruginosa albicans niger Inoculum 5.86 6.16 6.03 5.31 5.17
level Day 1 3.37 <1.00 <1.00 3.43 4.45 Day 2 <1.00
<1.00 <1.00 1.65 4.18 Day 7 <1.00 <1.00 <1.00
<1.00 <1.00 Day 14 <1.00 <1.00 <1.00 <1.00
<1.00 Day 21 <1.00 <1.00 <1.00 <1.00 <1.00 Day 28
<1.00 <1.00 <1.00 <1.00 <1.00 Validation + + + +
+
[0059] It will be appreciated by those skilled in the art that
changes could be made to the embodiments described above without
departing from the broad inventive concept thereof. It is
understood, therefore, that this invention is not limited to the
particular embodiments disclosed, but it is intended to cover
modifications within the spirit and scope of the present invention
as defined by the appended claims.
* * * * *