Note: Descriptions are shown in the official language in which they were submitted.
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COMPOSITIONS CONTAINING ZINC SALTS FOR
COATING MEDICAL ARTICLES
SPECIFICATION
1. INTRODUCTION
The present invention relates to metl-iods and compositions which
employ low concentrations of combinations of zinc salts and antimicrobial
agents in
coatings for articles such as medical articles. The coatings have an anti-
irritant effect
and inhibit transmission of infectious disease.
2. BACKGROUND OF THE INVENTION
The Center for Disease Control (CDC) estimates that hospital-acquired
infections cost the U.S. healthcare system $4.5 billion a year, and that 80%
of these
infections are transmitted by direct touch. The emollient solvent
octoxyglycerin
("Sensiva") has been found to demonstrate antimicrobial activity, especially
in the
presence of quaternary ammonium compound and an additional antimicrobial
agent,
an activity utilized in hand sanitizer formulations (see United States Patent
No.
6,846,846). In addition to or as an alternative to antimicrobial topical
formulations,
gloves are used by health care practitioners and in other sectors, such as the
food
service industry, as a means of preventing spread of infection. However, many
persons have or develop sensitivities to gloves, including allergic reactions
to latex or
dermatologic reactions to moisture retention.
It has been recognized that zinc salts can inhibit irritation caused by a
variety of agents. See for example, U.S. Patent Nos. 5,708,023, 5,965,610,
6,037,386,
and 5,985,918. These patents teacll the use of relatively high concentrations
of zinc,
which might be detrimental if taken internally.
3. SUMMARY OF THE INVENTION
The present invention relates to articles, especially medical articles,
coated with combinations of two or more water-soluble zinc salts and one or
more
antimicrobial agent. Such coating may further comprise agents such as an
emollient
solvent, an essential oil or coinponent thereof, and/or a silicone powder.
Articles
which may be coated according to the invention include, but are not limited
to,
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gloves, male and female condoms, medical clothing, bandages, footwear, etc..
The
coating of the invention enhances the protective value of the article while
inhibiting
irritation of skin coming in contact with the article.
4. DETAILED DESCRIPTION OF THE INVENTION
The present invention relates, at least in part, to methods and
compositions for coating articles, especially medical articles, which, in the
case of
barrier medical articles and medical articles which come in contact with the
skin or
mucous membranes, respectively, improve the effectiveness of the barriers in
preventing the transmission of infectious disease and decrease skin and/or
mucosal
irritation caused by the article.
In various embodiments, the present invention provides for the use of
low concentrations of water soluble zinc salts and one or more antimicrobial
agent, in
coatings applied to articles that coine in contact with the skin. Such
articles include,
but are not limited to, barrier articles such as gloves, condoms, and
diaphragms, as
well as articles such as eye protection devices, medical drapes, protective
clothing,
footwear, wound dressings, devices applied to stoma (e.g., colostomy bags,
tracheostomy tubes and fittings), surgical masks, etc.. Examples of non-
medical
articles that may be coated according to the invention include, but are not
limited to,
gloves or rubber fingers used in the food service industry, banking industry,
or
gardening, athletic wear including supports and gloves, etc..
When discussing coatings according to the invention, percentages are
in weight percent unless indicated otherwise. Further, such percentages refer
to a
coating solution used to coat the article, rather than the amount present
after the
coating solution has dried, unless indicated otherwise.
The term "low concentration" means that the weight percent of a zinc
salt (including the zinc ion and its binding partner) is less than 2 percent,
for example
between about 0.05 and 2 percent, or between about 0.1 and 2 percent, or
between 0.1
and 0.5 percent, or between 0.5 and 1.5 percent, or between 0.2 and 0.5
percent, or
between about 0.1 and 1 percent or between about 0.5 and 2 percent.
Preferably, the
water-soluble salts of zinc are present in the compositions (formulations and
coatings)
of the present invention in a total amount (weight of all water soluble zinc
salts
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coinbined) of between about 0.1 and 0.5 percent, or less than 0.3 percent, or
less than
or equal to 0.2 percent.
"Water soluble" zinc salts exhibit a molar solubility in water of at least
0.1 moles/liter and preferably at least 0.17 moles/liter, at 25 degrees
Celsius. Water
soluble zinc salts for use in these formulations include zinc acetate (molar
solubility
in water of 1.64 moles/1 at 25 degrees Celsius), zinc butyrate (molar
solubility in
water of 0.4 moles/1), zinc gluconate (molar solubility in water of 0.28
moles/1), zinc
glycerate (moderately water soluble), zinc glycolate (moderately water
soluble), zinc
formate (molar solubility in water of 0.33 moles/1 at 20 degrees Celsius),
zinc lactate
(molar solubility in water of 0.17 moles/1), zinc picolinate (moderately water
soluble),
zinc propionate (molar solubility in water of 1.51 moles/1), zinc salicylate
(low water
solubility), zinc tartrate (moderately water soluble) and zinc undecylenate
(moderately
water soluble). In preferred non-limiting embodiments, the present invention
provides for formulations for coating of articles comprising two or more water
soluble zinc salts each having a molar solubility in water of about 0.17-1.64
moles/liter, wherein the total weight percent of all water soluble zinc salts
is between
about 0.1 and 0.5 percent or less than or equal to about 0.3 percent.
A "water insoluble" zinc salt, as that term is used herein, refers to a
compound having a water solubility of less than 0.1 moles/liter at 25 degrees
Celsius.
Non-limiting examples of water insoluble zinc salts include zinc oxide, zinc
stearate,
zinc citrate, zinc phosphate, zinc carbonate, and zinc borate. In specific,
non-limiting
embodiments, the water insoluble zinc salt is present in a concentration of
between
about 0.05 and 0.5 weight percent or between about 0.1 and 1 weight percent.
In further specific, non-limiting embodiments, the total amount of all
zinc salts, including water soluble and water insoluble salts, is between
about 0.1 and
1.5 weight percent, or between about 0.1 and 1 weight percent.
The terms "prevention" or "reduction" of irritation means a decrease in
objective or subjective signs of irritation in tissues exposed to medical
articles coated
with formulations of the invention comprising low concentrations of two or
more
water-soluble, organic salts of zinc of at least 50%, and more preferably by
greater
than 90% relative to control tissues exposed to the barrier coated with the
same
formulations lacking zinc salts. Irritation in this context may be evidenced
by redness
or other changes in coloration, inflammation or swelling, hypersensitivity,
the
occurrence of burning, itching or other painful stimuli, chapping, wrinkling,
rash,
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hives or other macroscopic or microscopic changes lcnown to those of ordinary
skill in
the art to be associated with irritation.
The forinulations of the invention may be applied as coatings, in an
article having more than one surface, so as to coat at least one surface (the
entire
surface or a portion thereof) of the article. As specific, non-limiting
embodiments, a
coating according to the invention may be applied to the inner surface of a
glove or
condom, or to the outer surface of a glove or condom, or to both inner and
outer
surfaces of a glove or condom. Different coatings may be applied to each
surface. A
coating may be applied over a portion of a surface, for example, but not by
way of
limitation, on the inner surface of one or more fingertip of a glove.
Various embodiments of the invention may comprise an emollient,
such as, but not limited to, PEG 20 almond glycerides, Probutyl DB- 10, Glucam
P-20,
Glucam E-10, Glucam P-10, Glucam E-20, Glucam P-20 distearate, Procetyl-10
(Croda), Incroquat, glycerin, propylene glycol, cetyl acetate, and acetylated
lanolin
alcohol, cetyl ether, myristyril ether, hydroxylated milk glycerides,
polyquaternium
compounds, copolymers of dimethyl dialyl ammonium chloride and acrylic acid,
dipropylene glycol methyl ethers, polypropylene glycol ethers and silicon
polymers.
Other suitable emollients may include hydrocarbon-based emollients such as
petrolatum or mineral oil, fatty ester-based emollients, such as methyl,
isopropyl and
butyl esters of fatty acids such as isopropyl palmitate, isopropyl myristate,
isopropyl
isostearate, isostearyl isostearate, diisopropyl sebacate, and propylene
dipelargonate,
2-ethylhexyl isononoate, 2-ethylhexyl stearate, C12 - C16 fatty alcohol
lactates such as
cetyl lactate and lauryl lactate, isopropyl lanolate, 2-ethylhexyl salicylate,
cetyl
myristate, oleyl myristate, oleyl stearate, oleyl oleate, hexyl laurate, and
isohexyl
laurate. Further emollients include lanolin, olive oil, cocoa butter, and shea
butter.
The present invention provides for the incorporation, into formulations
and coatings, of one or more emollient solvent. Preferred emollient solvents
of the
invention include octoxyglycerin (Sensiva ), pentylene glycol, 1,2 hexanediol
and
caprylyl glycol, for example, and not by way of limitation, at a concentration
of up to
5 percent or up to 3 percent, such as between 0.05 and 5 percent or between
0.1 and 3
percent.
Various embodiments of the invention may comprise a stabilizing
agent, such as, but not limited to, an antioxidant (which may be at a
concentration of
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0.2-1%), such as but not limited to vitamin C (ascorbic acid) or vitamin E
(tocopherol).
The stabilizing agents surprisingly appear to remove the turbidity of
the formulations, resulting in a clear product that imparts a light feel to
the surface to
which it is applied.
Various embodiments of the invention may comprise a thickening
agent, such as but not limited to the following (at a prefeiTed concentration
of 0.6-
2%): stearyl alcohol, cationic hydroxy ethyl cellulose (U Care JR30;
Amerchol),
hydroxy propyl methyl cellulose, hydroxy propyl cellulose (Klucel), Polyox N-
60K,
chitosan pyrrolidone carboxylate (Kytamer), behenyl alcohol, zinc stearate,
Crodamol
STS (Croda) or an emulsifying wax, such as but not limited to, Incroquat and
Polawax. Other thickening and/or gelling agents suitable for incorporation
into the
formulations or ointments described herein include, for exainple, an addition
polymer
of acrylic acid, a resin such as Carbopol ETDT"' 2020, guar gum, acacia,
acrylates/steareth-20 methacrylate copolymer, agar, algin, alginic acid,
ammonium
acrylate co-polyiners, ammonium alginate, ammonium chloride, ammonium sulfate,
amylopectin, attapulgite, bentonite, C9-15 alcohols, calcium acetate, calcium
alginate,
calcium carrageenan, calcium chloride, caprylic alcohol, carbomer 910,
carbomer
934, carbomer 934P, carbomer 940, carbomer 941, carboxymethyl hydroxyethyl
cellulose, carboxymethyl hydroxypropyl guar, carrageenan, cellulose, cellulose
gum,
cetearyl alcohol, cetyl alcohol, corn starch, crodomol, crothix, damar,
dextrin,
dibenzlidine sorbitol, ethylene dihydrogenated tallowamide, ethylene
diolamide,
ethylene distearamide, gelatin, guar gum, guar hydroxypropyltrimonium
chloride,
hectorite, hyaluronic acid, hydrated silica, hydroxybutyl methylcellulose,
hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxyethyl stearamide-
1WIIPA,
isocetyl alcohol, isostearyl alcohol, karaya gum, kelp, lauryl alcohol, locust
bean gum,
magnesium aluminum silicate, magnesium silicate, magnesium trisilicate,
methoxy
PEG-22/dodecyl glycol copolymer, methylcellulose, microcrystalline cellulose,
montmorillonite, myristyl alcohol, oat flour, oleyl alcohol, palm kernel
alcohol,
pectin, PEG-2M, PEG-5M, polyacrylic acid, polyvinyl alcohol, potassium
alginate,
potassium aluminium polyacrylate, potassium carrageenan, potassium chloride,
potassium sulfate, potato starch, propylene glycol, propylene glycol alginate,
sodium
acrylate/vinyl alcohol copolymer, sodium carboxymethyl dextran, sodium
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carrageenan, sodium cellulose sulfate, sodium chloride, sodium
polymethacylate,
sodium silicoaluininate, sodium sulfate, stearalkoniurn bentonite,
stearalkoniuin
hectorite, stearyl alcohol, tallow alcohol, TEA-hydrochloride, tragacanth gum,
tridecyl alcohol, tromethamine magnesium aluminurn silicate, wheat flour,
wheat
starch, xanthan gum, abietyl alcohol, acrylinoleic acid, aluminum behenate,
aluminum
caprylate, aluminum dilinoleate, aluminum salts, such as distearate, and
aluminum
isostearates, beeswax, behenamide, butadiene/acrylonitrile copolymer, C29-70
acid,
calcium behenate, calcium stearate, candelilla wax, carnauba, ceresin,
cholesterol,
cholesterol hydroxystearate, coconut alcohol, copal, diglyceryl stearate
malate,
dihydroabietyl alcohol, dimethyl lauramine oleate, dodecanoic acid/cetearyl
alcohol/glycol copolymer, erucamide, ethylcellulose, glyceryl triacetyl
hydroxystearate, glyceryl tri-acetyl ricinolate, glycol dibehenate, glycol di-
octanoate,
glycol distearate, hexanediol distearate, hydrogenated C6-14 olefin polymers,
hydrogenated castor oil, hydrogenated cottonseed oil, hydrogenated lard,
hydrogenated menhaden oil, hydrogenated palm kernel glycerides, hydrogenated
palm
kernel oil, hydrogenated palm oil, hydrogenated polyisobutene, hydrogenated
soybean
oil, hydrogenated tallow amide, hydrogenated tallow glyceride, hydrogenated
vegetable glyceride, hydrogenated vegetable oil, Japan wax, jojoba wax,
lanolin
alcohol, shea butter, lauramide, methyl dehydroabietate, methyl hydrogenated
rosinate, methyl rosinate, methylstyrene/vinyltoluene copolymer,
microcrystalline
wax, montan acid wax, montan wax, myristyleicosanol, myristyloctadecanol,
octadecene/maleic anhyrdine copolymer, octyldodecyl stearoyl stearate,
oleamide,
oleostearine, ouricury wax, oxidized polyethylene, ozokerite, paraffin,
pentaerythrityl
hydrogenated rosinate, pentaerythrityl tetraoctanoate, pentaerythrityl
rosinate,
pentaerythrityl tetraabietate, pentaerythrityl tetrabehenate, pentaerythrityl
tetraoleate,
pentaerythrityl tetrastearate, ophthalmic anhydride/glycerin/glycidyl
decanoate
copolymer, ophthalmic/trimellitic/glycols copolymer, polybutene, polybutylene
terephthalate, polydipentene, polyethylene, polyisobutene, polyisoprene,
polyvinyl
butyral, polyvinyl laurate, propylene glycol dicaprylate, propylene glycol
dicocoate,
propylene glycol diisononanoate, propylene glycol dilaurate, propylene glycol
dipelargonate, propylene glycol distearate, propylene glycol diundecanoate,
PVP/eiconsene copolymer, PVP/hexadecene copolymer, rice bran wax, stearlkonium
bentonite, stearalkonium hectorite, stearamide, steararnide DEA-distearate,
stearamide
DIBA-stearate, stearamide MEA-stearate, stearone, stearyl erucamide, stearyl
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stearate, stearyl stearoyl stearate, synthetic beeswax, synthetic wax,
trihydroxystearin,
triisononanoin, triisostearin, tri-isostearyl trilinoleate, trilaurin,
trilinoleic acid,
trilinolein, trimyristin, triolein, tripalmitin, tristearin, zinc laurate,
zinc myristate, zinc
neodecanoate, zinc rosinate, and mixtures thereof.
An embodiment of the invention may comprise phenoxyethanol (0.3-
1.0%) as a solubilizing agent.
Various embodiments of the invention may comprise a humectant,
such as but not limited to glycerin, panthenol, Glucam P20, 1-2-propylene
glycol,
dipropylene glycol, polyethylene glycol, 1,3-butylene glycol, or 1,2,6-
hexanetriol.
The concentration of humectant may be between about 0.1 and 5 percent, or
between
about 0.1 and 0.5 percent.
In non-limiting embodiments, coatings of the invention comprise one
or more antimicrobial or preservative agent, preferably at a total
concentration
between 0.05 and 5 weight percent or between 0.05 and 2 weight percent or
between
0.1 and 2 weight percent. Exainples of preferred antimicrobial and/or
preservative
agents include, but are not limited to, chlorhexidine gluconate (CHG),
benzalkonium
chloride (BZK), or iodopropynylbutyl carbamate (IPBC; Germall plus). Further
examples of antimicrobial agents include, but are not limited to, iodophors,
iodine,
benzoic acid, dihydroacetic acid, propionic acid, sorbic acid, methyl paraben,
ethyl
paraben, propyl paraben, butyl paraben, cetrimide, quaternary ammonium
compounds, including but not limited to benzethonium chloride (BZT),
dequalinium
chloride, biguanides such as chlorhexidine (including free base and salts (see
below)),
PHMB (polyhexamethylene biguanide), chloroeresol, chlorxylenol, benzyl
alcohol,
bronopol, chlorbutanol, ethanol, phenoxyethanol, phenylethyl alcohol, 2,4-
dichlorobenzyl alcohol, thiomersal, clindamycin, erythromycin, benzoyl
peroxide,
mupirocin, bacitracin, polymyxin B, neomycin, triclosan, parachlorometaxylene,
foscarnet, miconazole, fluconazole, itriconazole, ketoconazole, and
pharmaceutically
acceptable salts thereof.
Specific, non-limiting embodiments of the invention contain
essentially no quaternary ammonium compound, such as but not limited to
benzalkonium chloride, benzethoniuin chloride (BZT), and dequalinium chloride.
Pharmaceutically acceptable chlorhexidine salts that may be used as
antimicrobial agents according to the invention include, but are not limited
to,
chlorhexidine palmitate, chlorhexidine diphosphanilate, chlorhexidine
digluconate,
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chlorhexidine diacetate, chlorhexidine dihydrochloride, chlorhexidine
dichloride,
chlorhexidine diliydroiodide, chlorhexidine diperchlorate, chlorliexidine
dinitrate,
chlorhexidine sulfate, chlorhexidine sulfite, chlorhexidine thiosulfate,
chlorhexidine
di-acid phosphate, chlorhexidine difluoropllosphate, chlorhexidine diformate,
chlorhexidine dipropionate, chlorhexidine di-iodobutyrate, chlorhexidine di-n-
valerate, chlorhexidine dicaproate, chlorhexidine malonate, chlorliexidine
succinate,
chlorhexidine inalate, chlorhexidine tartrate, chlorhexidine dimonoglycolate,
chlorhexidine monodiglycolate, chlorhexidine dilactate, chlorhexidine di-a-
hydroxyisobutyrate, chlorliexidine diglucoheptonate, chlorhexidine di-
isothionate,
chlorliexidine dibenzoate, chlorhexidine dicinnamate, chlorliexidine
dimandelate,
chlorliexidine di-isophthalate, chlorhexidine di-2-hydroxynapthoate, and
chlorhexidine embonate. Chlorhexidine free base is a further exainple of an
antimicrobial agent.
These and further examples of antimicrobial agents useful in this
invention can be found in such references as Goodman and Gilman's The
Pharmacological Basis of Therapeutics (Goodman Gilman A, Rall TW, Nies AS,
Taylor P, ed. (Pergamon Press; Elmsford, N.Y.: 1990)), the contents of which
are
hereby incorporated by reference.
Various embodiments of the invention may comprise a neutralizing
agent to neutralize carboxyl groups present in one or more other component,
such as
carboxyl groups in a thickening agent. Suitable neutralizing agents include
diisopropylamine and triethanolamine.
Various embodiments of the invention may comprise a surfactant. The
surfactant may be an anionic surfactant, a cationic surfactant, an ampholytic
surfactant, or a nonionic surfactant. Examples of nonionic surfactants include
polyethoxylates, fatty alcohols (e.g., ceteth-20 (a cetyl ether of
polyethylene oxide
having an average of about 20 ethylene oxide units) and other "BRIJ" nonionic
surfactants available from ICI Americas, Inc. (Wilmington, DE)),
cocamidopropyl
betaine, alkyl phenols, fatty acid esters of sorbitol, sorbitan, or
polyoxyetliylene
sorbitan. Suitable anionic surfactants include ammonium lauryl sulfate and
lauryl
ether sulfosuccinate. Preferred surfactants include lauroyl ethylenediamine
triacetic
acid sodium salt at a concentration between about 0.5 - 2.0%, Pluronic F87 at
about
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2.0%, Masil SF-19 (BASF) and incromide. Suitable concentrations of surfactant
are
between about 0.05% and 2%.
Water used in the formulations described herein is preferably deionized water
having
a neutral pH. Alcohols that may be used according to the invention include but
are
not limited to ethanol and isopropyl alcohol.
Non-limiting embodiments of the invention may comprise a silicone
powder, such as, but not limited to, Dow Corning 9701 Cosmetic Powder. In
specific
non-limiting embodiments, the amount of such powder may be between about 0.1
and
5percent, or between 0.2 and 1 percent.
Various embodiments of the invention may comprise additional
additives, including but not limited to a silicone fluid (such as dimethicone
or
cyclomethicone), a silicone emulsion, dyes, fragrances, pH adjusters,
including basic
pH adjusters such as ammonia, mono-, di- and tri- allcyl amines, mono-, di-
and tri-
alkanolamines, alkali metal and alkaline earth metal hydroxides (e.g.,
ammonia,
sodium hydroxide, potassium hydroxide, lithium hydroxide, inonoethanolamine,
triethylamine, isopropylamine, diethanolamine and triethanolamine); acid pH
adjusters such as mineral acids and polycarboxylic acids (e.g., hydrochloric
acid,
nitric acid, phosphoric acid, sulfuric acid, citric acid, glycolic acid, and
lactic acid);
vitamins such as vitamin A, vitamin E and vitamin C; polyamino acids and
salts, such
as ethylenediamine tetraacidic acid (EDTA), preservatives such as Germall plus
and
DMDM hydantoin.
Various embodiments of the invention may comprise an essential oil
("EO"), which is a volatile oil obtained from a plant or an animal source that
comprises one or more active agent (also referred to herein as an Isolated
Component
or "IC") which may be, for example but not by way of limitation, a monoterpene
or
sesquiterpene hydrocarbon, alcohol, ester, ether, aldehyde, ketone, or oxide.
Examples of these EOs include, but are not limited to, almond oil, ylang-ylang
oil,
neroli oil, sandalwood oil, frankincense oil, peppermint oil, lavender oil,
jasmine
absolute, geranium oil bourbon, speannint oil, clove oil, lemongrass oil,
cedarwood
oil, balsam oils, and tangerine oil. Alternatively, the present invention
provides for
the use of active agents found in essential oils (ICs) such as, but not
limited to, 1-
citronellol, a-amylcinnamaldehyde, lyral, geraniol, farnesol,
hydroxycitronellal,
isoeugenol, eugenol, eucalypus oil and eucalyptol, lemon oil, linalool, and
citral.
Apart from their effects as fragrances or flavorants, such compounds also may
be
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useful in the instant invention as antimicrobial agents. The concentrations of
EO or
IC may be between about 0.3 and 1 percent or between about 0.1 and 0.5 percent
or
between 0.5 and 2 percent (all weight percent values).
Ambient temperature is defined herein between 20 a.nd 35 C. Room
temperature is defined herein between 20 and 25 C.
The invention provides for methods of using the foregoing
coinpositions to prevent irritation to an epithelial tissue (e.g. a mucosal
tissue or the
skin) comprising applying an effective amount of the composition to the
surface or
coating an article which is intended to come into contact with the skin or a
mucosal
tissue. Exainples of irritants against which protection may be afforded
include, but
are not limited to, those induced by physical, chemical, mechanical or
biological
irritants. Specific examples of the foregoing irritants include, but are not
limited to,
means for hair removal (e. g. depilatories, waxing and razors), hair relaxants
(e.g.
sodium hydroxide, calcium hydroxide, thioglycolates), antiperspirants (e.g,
aluminum
chlorhydrate and other aluminium salts), dermatological treatments (e.g. alpha
hydroxy acids (AHAs), especially glycolic and trichloroacetic acids),
keratoyltic skin-
irritating conditions (e.g. psoriasis, dandruff, etc.), infectious skin
irritants (e.g.
bacteria and fungi), and agents applied for therapeutic purposes. The
epithelial
surface to be protected from irritation may be dermal or mucosal, including
vaginal,
anorectal, oral or nasal.
Exarnples of infectious agents against which protection may be
afforded include, but are not limited to, infectious agents associated with
sexually
transmitted diseases, including Human Immunodeficiency Virus (HIV), Human
Papilloma Virus (HPV), Herpes Simplex Virus (HSV), Chlamydia trachomatis,
Neisseria gonorrhoea, Trichomonas vaginalis, and Candida albicans, as well as
infectious agents that may be encountered in a health care setting, including
but not
limited to Staphylococcus aui=eus, Pseudomonas aeruginosa, Streptococcus
pneumoniae, Escherichia coli, Salmonella typhimurium, Enterococcus, and
Neisseria
meningitidis, HIV, varicella virus and Hepatitis viruses (e.g., A, B, and C).
In certain alternative non-limiting embodiments, the formulations
and/or coatings of the invention lack an antimicrobial agent selected from the
group
consisting of iodophors, iodine, benzoic acid, dihydroacetic acid, propionic
acid,
sorbic acid, methyl paraben, ethyl paraben, propyl paraben, butyl paraben,
cetrimide,
quaternary ammonium compounds, including but not limited to benzalkonium
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chloride, dequalinium chloride, biguanides such as chlorhexidine (including
free base
and salts (see below)), chloroeresol, chlorxylenol, benzyl alcohol, bronopol,
chlorbutanol, ethanol, phenoxyethanol, phenylethyl alcohol, 2,4-dichlorobenzyl
alcohol, thiomersal, clindamycin, erythromycin, benzoyl peroxide, mupirocin,
bacitracin, polymyxin B, neomycin, triclosan, parachlorometaxylene, foscarnet,
nziconazole, fluconazole, itriconazole, ketoconazole, and pharmaceutically
acceptable
salts thereof.
In still further embodiments, the present invention provides for a zinc
slurry that may be applied to a latex article (such as a condom or glove) to
reduce or
prevent irritation. The zinc slurry may comprise, for example but not by way
of
limitation, at least two water-soluble zinc salts (as set forth above) at a
concentration
of between 0.5-2%, optionally one or more water-insoluble zinc salts (as set
forth
above) at a concentration of 0.1-1 percent, and panthenol at a concentration
of 0.1 -
4%. Such a slurry may be mixed with a liquid, such as a silicone fluid, in a
ratio of
between 1:5 to 1:10, and then applied to the surface of the article which will
be in
contact with the skin. In a specific embodiment nonlimiting embodiment, the
present
invention provides for an emulsion which may be used to coat the interior
surface of a
glove, such as a latex glove.
In one particular set of non-limiting einbodiments, the present
invention provides for a coating for application to or as applied on an
article,
comprising two water soluble zinc salts, each at a concentration of between
0.1 and 1
weight percent, , a derivative of pantothenic acid, such as panthenol, at a
concentration of between about 0.05 and .5 weight percent, and an
antimicrobial agent
as set forth above (e.g., a biguanide such as chlorhexidine), at a
concentration of
between about I and 5 weight percent. Coating solutions may further comprise a
silicone emulsion at a concentration between about 70 and 95 weight percent.
In
certain non-limiting embodiments, said coating further comprises a third water
soluble zinc salt at a concentration of between 0.1 and 1 weight percent. In
certain
non-limiting embodiments, in such coatings, which optionally comprise a third
water
soluble zinc salt, the combined amounts of all water soluble zinc salts is
between
about 0.1 and 2 weight percent. In certain non-limiting embodiments, such
coatings
comprise a silicone powder, as set forth above, at a concentration of between
about
0.2 and 1 percent.
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In particular non-limiting embodiments, the present invention provides
for a coating forinulation comprising:
(i) chlorhexidine gluconate at a concentration of between about 2
and 4 weight percent;
(ii) pantlZenol at a concentration of between about 0.3 and 1 weight
percent;
(iii) zinc acetate at a concentration of between about 0.1 and 0.5
weight percent;
(iv) zinc lactate at a concentration of between about 0.5 and 1.5
percent;
(v) a quaternary ammonium compound at a concentration of
between about 0.05 and 0.2 weight percent; and
(vi) a silicone emulsion at a concentration of between about 1 and 5
weight percent;
wherein the formulation does not comprise a water insoluble zinc salt,
optionally
further comprising between about 0.5 and 2 weight percent farnesol, between
about
0.5 and 3 weight percent octoxyglycerin, and/or between about 0.1 and 0.5
weight
percent silicone powder.
In other non-limiting embodiments, the present invention provides for
a coating formulation comprising:
(i) chlorhexidine gluconate at a concentration of between about 2
and 4 weight percent;
(ii) pantlzenol at a concentration of between about 0.3 and 1 weight
percent;
(iii) zinc acetate at a concentration of between about 0.1 and 0.5
weight percent;
(iv) zinc lactate at a concentration of between about 0.5 and 1.5
percent;
(v) zinc oxide at a concentration of between about 0.1 and 1.0
weight percent; and
(vi) a silicone emulsion at a concentration of between about 1 and 5
weight percent;
wherein the formulation does not comprise a quatemary ammonium compound,
optionally further comprising between about 0.5 and 2 weight percent farnesol,
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between about 0.5 and 3 weight percent octoxyglycerin, and/or between about
0.1 and
0.5 weiglit percent silicone powder.
In yet further non-limiting embodiments, the present invention
provides for a coating formulation comprising:
(i) chlorhexidine gluconate at a concentration of between about 2
and 4 weight percent;
(ii) panthenol at a concentration of between about 0.3 and 1 weight
percent;
(iii) zinc acetate at a concentration of between about 0.1 and 0.5
weight percent;
(iv) zinc lactate at a concentration of between about 0.5 and 1.5
percent;
(v) a quaternary ammonium compound at a concentration of
between about 0.05 and 0.2 weight percent;
(vi) a silicone emulsion at a concentration of between about 1 and 5
weight percent;
(vii) between about 0.5 and 2 weight percent farnesol;
(viii) between about 0.5 and 3 weight percent octoxyglycerin; and
(ix) between about 0.1 andØ5 weight percent silicone powder.
In non-limiting embodiments, the present invention provides for an
article, especially a medical article, prepared by a method which comprises
coating a
surface of an uncoated article with a coating forrnulation as set forth above.
Coating
such articles would render them less irritating if contacted with skin or
mucous
membranes, and would render them more effective in inhibiting transmission of
infectious disease.
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Table 1 sets forth concentration ranges of components which may be
comprised in non-limiting examples of formulations of the invention.
TABLE 1
Constituent Chemical Name
Chlorhexidine Gluconate
20 /o Sol. Soluble or Insoluable Biguanide Salt or free Base 0.05% - 10.0%
Water QS to 100% if needed
D Panthanol D and / or L Panthanol 0 Io - 3.0%
Zinc Acetate, 100% 0% - 2.0%
Zinc Lactate, 100% 0% - 5.0%
Ucare JR30M, 100% Pol uaternium 10 0% - 2.0%
Benzethonium Chloride Quaternary Alkylaryl-Dimethylammonium Chloride
100% Compound 0 l0 - 3.5%
Zinc Gluconate, 100% 0.01 %- 5.0%
Phenoxyethanol, 100% 0% - 3.0%
Teric N-100, 20% Ethoxylated non I phenol with EO from 3 - 150 0% - 10.0 fa
Detex A50, 50% 0% - 3.0%
Silicone
Dow Corning 939, 35% Amenofunctional Siloxane 0% - 7.0%
Farnesol, 100% Ses uiter enoid 0% - 5.0%
1,2-Octanediol, 98+% Aliphatic and / or Aromatic and / or Cyclic glycol 0% -
10.0%
wit of with out double bonds and with carbon
from 2 - 20
Hydrolite 5 Aliphatic and / or Aromatic and / or Cyclic glycol 0% - 10.0%
wit of with out double bonds and with carbon
from 2 - 20
Sensiva Octox I cerin 0 l0 - 5.0%
Silicone - 9701 Amorphous fumed silica 0% - 3.0%
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Table 2 sets forth concentration ranges of components which may be
comprised in non-limiting examples of formulations of the invention, which do
not
comprise insoluble zinc salts:
TABLE 2
CONSTITUENT % wt/wt (Range)
Phase 1
Chlorhexidine Gluconate 2-4
Water - Deionized 40-60
D-L Panthenol 0.3-1.0
Zinc Acetate 0.1-0.5
Zinc Lactate 0.5-1.5
Ucare JR-30M 0.1-0.3
Benzethoniuin Chloride 0-0.2
Zinc Gluconate 0.2-0.5
Phenoxyethanol 0.5-1.0
Phase 2
Water - Deionized 20-30
Silicone - Dow Corning 939 Emulsion 1.0-5.0
Farnesol 0.5-2.0
1,2-Octanediol 1.0-4.0
Sensiva SC-50 0.5-3.0
According to non-limiting methods of the invention, the coating formulation is
prepared by first preparing two solutions (Phase 1 and Phase 2, above), which
are then
mixed together.
CA 02654132 2008-12-02
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Table 3 sets forth concentration ranges of components which may be
comprised in non-limiting examples of formulations of the invention, which
optionally comprise insoluble zinc salts:
TABLE 3
CONSTITUENT % wt/wt (Range)
Phase 1
Chlorhexidine Gluconate 2-4
Water - Deionized 40-60
D-L Panthenol 0.3-1.0
Zinc Acetate 0.1-0.5
Zinc Lactate 0.5-1.5
Ucare JR-30M 0.1-0.3
Benzethonium Chloride 0-0.2
Zinc Gluconate 0.2-0.5
Zinc Oxide 0-1.0
Phenoxyethanol 0.5-1.0
Phase 2
Water - Deionized 20-30
Silicone - Dow Corning 939 Emulsion 1.0-5.0
Farnesol 0.5-2.0
1,2-Octanediol 1.0-4.0
Sensiva SC-50 0.5-3.0
According to non-limiting methods of the invention, the coating formulation is
prepared by first preparing two solutions (Phase 1 and Phase 2, above), which
are then
mixed together.
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One specific, non-limiting embodiment of the invention is the
formulation set forth below in Table 4:
TABLE 4
CONSTITUENT % wt/wt
Phase 1
Chlorhexidine Gluconate 3.00
Water - Deionized 53.90
D' Panthenol 0.36
Zinc Acetate 0.30
Zinc Lactate 1.00
Ucare JR-30M 0.10
Benzethonium Chloride 0.20
Zinc Gluconate 0.30
Phenoxyethanol 0.55
SUBTOTAL: 59.71
Phase 2
Water - Deionized 27.36
Teric N-100 1.90
Cetrimonium Chloride 0.03
Silicone - Dow Corning 939 Emulsion 2.50
Farnesol 1.00
1,2-Octanediol 3.25
Pentylene Glycol 3.00
Sensiva SC-50 1.00
Silicone - Dow Corning 9701 Cosmetic 0.25
Powder
SUBTOTAL: 40.29
TOTAL: 100.00
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Various publications are cited herein, the contents of which are hereby
incorporated by reference in their entireties.
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