WO2000072850A1 - Foot care compositions containing quaternary ammonium organosilanes - Google Patents

Abstract

The present invention describes aqueous formulations containing organosilane quaternary ammonium compounds which when applied to the skin and nails of feet, remain on the skin and nails, are substantive to it and reduce odor and infection through elimination, inactivation or reduction of bacteria and fungi present and prevent reinfection by their presence and substantive character. Antimicrobial foot powder formulations containing quaternary ammonium organosilanes are also described. All formulations may be scented and/or colored and all contain a water-soluble, organosilicon quaternary ammonium compound or mixture thereof; specifically 3-(trimethoxysilyl)propyloctadecyl-dimethyl ammonium chloride or 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride and the trisilanol, polysiloxanol and water-soluble polysiloxane derivatives thereof.

Description

FOOT CARE COMPOSITIONS CONTAINING QUATERNARY AMMONIUM ORGANOSILANES

CROSS-REFERENCE TO RELATED APPLICATION

This application is related to United States Provisional Patent Application No. 60/136,358, filed May 28, 1999, and claims all benefits legally available therefrom.

Provisional Patent Application No. 60/136,358 is hereby incorporated by reference for all purposes capable of being served thereby.

BACKGROUND OF THE INVENTION

1. Field of the Invention This invention relates to the preparation of dry and aqueous formulations containing monomeric, dimeric and oligomeric water-soluble organosilane species having a silicon-bonded quaternary ammonium halide functionality and hydrolyzable alkoxy groups and for their application to skin and nails of the foot, wherein the monomeric and oligomeric species react on the skin to provide an insoluble, polymeric antimicrobial treatment which is substantive to the skin, is not removed by rinsing, retains its microbial activity while present on the skin.

2. Description of the Prior Art

This invention describes a method for odor reduction concurrent with treatment and cure of skin and nail diseases of the feet caused primarily by bacteria and fungi present on and transferred to the skin and nails.

Mycoses are diseases produced by fungi and include superficial and cutaneous mycoses. Cutaneous mycoses, also called dermatophytes or tineas, represent the most common fungal diseases in humans. Tinea corporis is a dermatophytic infection of the smooth or bare parts of the skin. It is caused by the fungi Trichophyton rubrum, Trichophyton mentagrophytes or Microsporum canis. Tinea pedis, also known as athlete's foot is a dermatophytic infection of the feet caused by T. rubrum, T. mentagrophytes or epidermophyton floccosum and sometimes Candida albicans and occurs throughout the world. Tinea unguium is a dermatophytic infection of the nail bed in which the nail plate becomes discolored, thickens and separates from the nail bed. This disease is also caused by the fungi Trichophyton rubrum or Trichophyton mentagrophytes. Treatment is with topical ointments such as clotrimazole (Lotrimin)- miconazole (Monistat-Derm), and tolfinate (Tinactin) for 2 to 4 weeks. Approved topical and oral agents for treating dermatophytoses are griseofulvin (Grifulvin V), intraconaole (Sporanox) and terbafme HC1 (Lamisil). Chemical compounds effective in reducing, eliminating or inhibiting the presence, growth or effects of bacteria, viruses and fungi are antimicrobial materials. Of the large number of available antimicrobial compounds, quaternary ammonium compounds are the largest class of antimicrobials in use today. Quaternary ammonium organosilanes are a more recent development in this area of chemistry. In addition to their reported antimicrobial properties, organosilanes containing quaternary ammonium halides having hydrolyzable alkoxy groups bonded to silicon have been employed in a wide variety of applications. The hydrolyzable groups enable these compounds to form bonds to substrates that contain hydroxy, alkoxy, oxide and similar reactive moieties. Organosilanes have been used to waterproof masonry and brick surfaces, as paint additives, fabric treatments and for surface modification of substrates that enhance miscibility in organic solvents or enable subsequent operations to be conducted on the substrate such as dyeing or painting.

Organosilicon ammonium compounds were first taught by Roth in U.S. Pat. No. 3,560,385. The use of these compounds for algae reduction is taught in U.S. Pat. 3,730,701 to Isquith et al. They teach that neutral to alkaline pH values were more effective in algae control. Algae inhibition and disinfecting of surfaces was also taught by Abbott et al. in U.S. Pat. Nos. 3,794,736 and 3,860,709. The inhibition of algae growth on solid surfaces such as cellulose acetate following treatment with organosilane quaternary ammonium materials was described by Abbott et al. in U.S. Pat. No. 3,817,739. Abbott et al. in U.S. Pat. No. 3,865,728 again describes algicidal reduction on fibrous materials including polyesters as well as cellulose acetate and are used to treat aquarium filters.

Other uses for quaternary ammonium organosilanes not related to their antimicrobial properties are disclosed by Kinstedt in U.S. Pat. No. 4,005,025 in which organosilane quaternaries are useful in imparting soil release properties to hard surfaces in detergent applications such as dishwashing liquids and general hard surface cleaners. U.S. Pat. 4,005,028 to Heckert et al. similarly teaches detergent compositions containing zwitterionic or ampholytic detergents and quaternized organosilanes. Similarly, U.S. Pat. No. 4,005,030 by Heckert and Watt teach detergent formulations useful as oven cleaners, window cleaners or toiler bowl cleaners. No antimicrobial claims are present in the >025, >028 and >030 Patents. Similarly, Burril et al. in U.S. Pat. 4,421,796 teach a method of treating textile fibers with a mixture of quaternized organosilane compositions in an emulsion containing polydimethylsiloxanes to improve removal of oily soil. In U.S. Pat. No. 4,282,366 organosilicon ammonium compounds are taught by

Eudy to render paper substrates resistant to growth of microorganisms and Klein in U.S. Pat. No. 4,394,378 claims 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride as effective against bacteria and fungi on siliceous surfaces, wood, metal, leather, rubber, plastic and textiles. The antimicrobial effect of quaternary ammonium organosilanes for treatment of surgical gowns, bandages and wound dressings are disclosed by Baldwin in U.S. Pats. 4,395,454, 4,408,996, 4,411,928, 4,414,268, 4,425,371 and 4,467,013.

Other applications for these compounds include paint additives and shoe treatments in U.S. Pat. No. 4,394,378. Dentifrice additives are taught in U.S. Pat. No. 4,161,518, and in contact lens disinfectant solution in U.S. Pat. No. 4,615,882. Canadian Patent No. 1,217,004 to Hardy teaches these compounds are antimicrobial when added to bleach such as sodium hypochlorite and can be used as hard surface cleaners.

Eudy in U.S. Pat. No. 4,406,892 describes treatment of cellulosic fabrics to prevent the growth of disease causing organisms. Homan in U.S. Pat. 4,564,456 utilizes organosilicon quaternary ammonium compounds to treat water and inhibit corrosion and metal deposition. Hair conditioning compositions containing 3-(trimethoxysilyl)propyl- dimethyloctadecyl ammonium chloride, when applied at pH 8-10 is taught by Stadnick in U.S. Pat. 4,567,039.

Aqueous emulsions formed by the use of certain organofunctional cationic silanes, including quaternary ammonium organosilanes such as 3-(trimethoxysilyl)- propyldimethyloctadecyl ammonium chloride, are taught by Blehm et al. in U.S. Pat. No. 4,361,273. The disclosed oil-in- water emulsions claimed suitable for personal care products, allow the transfer of water immiscible liquids and the cationic silanes to the surface of substrates with the avoidance of any subsequent rewetting or resolubihzation of the silane or water immiscible liquid and its subsequent loss from the surface. The water immiscible liquid utilized to prevent resolubilizing of the cationic silane into the water phase and away from the substrate may be silicone oils, waxes, hydrocarbons, glycols or aliphatic alcohols. It is noted by the inventors that the quaternary ammonium organosilanes disclosed in this invention retain the alkoxy functionality while in the emulsion so that when applied to a substrate, the alkoxy groups will hydrolyze and bond to the surface. It is also theorized by the inventors that the water immiscible liquid prevents the alkoxysilane from hydrolyzing and polymerizing to an insoluble polymer and is integral to their invention. The preparation of these emulsions utilizes co- surfactants such as nonionic and cationic surfactants and requires a homogenizer using high shear conditions. These emulsions require a water immiscible liquid as described above with which the quaternized organosilane associates, and that a sufficient shear force, requiring specialized mixers, is necessary to form the emulsion they teach. Blehm et al. teaches the prepared emulsion is utilized to transfer the unhydrolyzed quaternized organosilane to the surface where it is protected against resolubihzation by the water immiscible component. The inclusion of antibiotics is also taught.

The prior art disclosed in U.S. Pat. 4,908,355 to Gettings & White for skin applications claims the use of similar oil-in-water emulsion compositions in treating acne vulgaris. This patent teaches a method of treating skin disorders through topical application to the epidermis of an oil-in-water emulsion in which there is a quaternary ammonium organosilane, specifically 3-(trimethoxysilyl)propyl-dimethyloctadecyl ammonium chloride and a highly volatile, low viscosity, water immiscible liquid silicone fluid. These fluids cause the alkoxy substituted quaternized silane to contact the bacteria and penetrate the follicular orifices. The volatile silicone fluid is for the purpose of driving the silane into sebaceous glands and destroying the staphylococcal group of bacteria that may reside there. The formation of these emulsions are essentially the formulations taught in the foregoing '273 patent. This patent teaches the quaternized silane can be used neat, in an organic solvent or in aqueous solvent solutions. It further teaches a water immiscible component such as an oil, wax or grease must be present and included in the compositions applied to the skin. It does not teach homogeneous aqueous solutions of the quaternary ammonium organosilane nor demonstrate substantiveness and efficacy on skin. The ability of the silane to be applied directly to the skin from aqueous solutions and the ability for the silane to remain on the skin and continue to be antimicrobially active even after repeated rinsings or washings is not taught. Glass beads treated with organosilane quaternary compounds are described in U.S.

Pat. No. 4,682,992 to Fuchs as being used in air filters where antimicrobial qualities are desired. U.S. Pat. No. 4,781,974 to Bouchette teaches wet towelettes having as organosilicon quaternary ammonium compound substantive to the fibers, but does not teach it being transferred to surfaces or skin. Bryant in U.S. Pat. 4,797,420 teaches a formulation containing an alkyl dimethyl benzyl ammonium chloride, a nonionic surfactant and a lower alcohol such as isopropanol in water which is used as a disinfectant formulation.

U.S. Pat. 4,847,088 to Blank teaches a quaternary organosilane composition such as 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride when combined with an acid in water will increase the antimicrobial effect. Similar antimicrobial properties are claimed by Gettings et al. in U.S. Pat. No. 5,013,459 for a method and device to dispense ophthalmic fluids, the porous medium of which has been previously treated with an organosilicon quaternary ammonium material. U.S. Pat. 5,41 1,585 to Avery et al. teaches further methods for the production of stable hydrolyzable organosilane quaternary ammonium compounds to render surfaces antimicrobial when applied as ingredients in hard surface cleaners.

Stabilized aqueous organosilane solutions, including quaternary ammonium organosilane compounds are taught by Elfersy et al. in U.S. Pat. 5,954,869. These compositions contain a polyol molecule having at least two hydroxy groups which are separated by no more than three intervening atoms and the organosilane. These compositions may be used to coat a food article, a fluid container or a latex medical article. Sugars are the most common stabilizer taught in this patent.

Methods disclosed in the prior art for treating dermal infections caused by pathogenic dermatophytes and yeasts include broad-spectrum antifungal agents such as clotrimazole, griseofulvin and tolfinate administered in cream, lotion and solution forms. Quaternary ammonium compounds such as benzyldialkyl ammonium halides have also been employed for antibacterial and antifungal purpose in foot care preparations. Such preparations are typically employed in dry powder preparations containing moisture absorbents. These formulations do not contain antimicrobial materials that will bond to the surface of the treated skin. These antifungal and antibacterial compounds may therefore be consumed by the microorganisms or washed from the skin surface by bathing or showering, decreasing or removing the amount of active material required to be effective against the pathogenic microorganism. Skin sensitization and irritation may also result from percutaneous transfer of the active material. Quaternary ammonium organosilanes eliminate microorganisms on contact through cell wall disruption. When bonded to the skin, either as monomer or through a polymeric macromolecular network. The immobilized quaternary silanes retain their antimicrobial character and maintain effective dose concentrations where applied. Commercial quaternary ammonium organosilanes are available as 42% active material in methanol under the trademark Dow Corning5 5700 (3-(trimethoxy- silyl)propyldimethyloctadecyl ammonium chloride) by Aegis Environmental Management, Inc. of Midland, MI and Requat71977 (3-(trimethoxysilyl)- propyldidecylmethyl ammonium chloride) by Sanitized Inc. of New Preston, CT.

Octadecyldimethyl(3-trimethoxysilylpropyl) ammonium chloride (Cat. No. SIO6620.0) as a 60% active solution in methanol, tetradecyldimethyl(3-tri-methoxysilylpropyl) ammonium chloride (Cat. No. SIT7090.0) as a 50% solution in methanol and didecylmethyl(3-trimethoxysilylpropyl) ammonium chloride (Cat. No. SID3392.0) as a 42% solution in methanol are offered by Gelest, Inc. of Tullytown, PA. They are often applied from water or solvent solutions containing lower alcohols.

The prior art and open literature disclose the antimicrobial properties of quaternary ammonium organosilanes against a wide range of pathogens including, but not limited to: Bacteria

Gram Positive Bacteria

Citrobacter freundii

Citrobacter diversus

Corynebacterium diptheriae Diplococcus pneumoniae

Micrococcus sp. (I)

Micrococcus sp. (II)

Micrococcus sp. (Ill)

Mycobacterium spp. Staphylococcus albus

Staphylococcus aureus

Staphylococcus citrens

Staphylococcus epidermidis

Streptococcus faecalis Streptococcus mutans

Streptococcus pyogenes

Gram Negative Bacteria

Acinetobacter calcoaceticus Acromonas hydrophilia

Citrobacter diversus

Citrobacter freundii

Enterobacter aerogenes

Enterobacter aglomerans Enterobacter cloacae Escherichia coli

Klebsiella oxytoca

Klebsiella pneumoniae

Morganella morganii Nisseria gonorrhoeae

Proteus mirabilis

Proteus morganii

Proteus vulgaris

Providencia spp. Pseudomonas aeruginosa

Pseudomonas fluorscens

Pseudomonas fragi

Salmonella choleraesuis

Salmonella enteritidis Salmonella gallinarum

Salmonella paratyphi A

Salmonella schottmuelleri

Salmonella typhimurium

Salmonella typhosa Serratia liquifaciens

Serratia marcescens

Shigella flexnerie Type II

Shigella sonnei

Nirbrio cholerae Xanthomonas campestris

Viruses

Adenovirus Type IV

Feline Pneumonitis

Herpes Simplex Type I & II HIV-1 (AIDS)

Influenza A (Japan)

Influenza A2 (Aichi)

Influenza A2 (Hong Kong)

Parinfluenza (Sendai) Poliovirus

Reovirus

Respiratory Synctia

Fungi

Alternaria alternata Asperigillus flavus

Asperigillus niger

Asperigillus sydowi

Asperigillus terreus

Asperigillus versicolor Aureobasidium pullulans

Candida albicans

Chaetomium globosum Cladosporium cladosporioides

Drechslera australiensis

Gliomastix cerealis

Gloeophyllum trabeum Microsporum audouinii

Monilia grisea

Penicillium chrysogenum

Penicillium funiculosum

Penicillium pinophilium Pencillium variable

Phoma fimeti

Pithomyces chartarum

Poria placenta

Scolecobasidium humicola Trichoderma viride

Trichophyton interdigitale

Trichophyton maidson

Trichophyton mentagrophytes

The open literature and the prior art cited above do not teach topical application of aqueous solutions of organosilicon quaternary ammonium compounds to the skin and nails of the feet. Methods of topical application utilizing these compositions for elimination and reduction of dermatophytes for cure and to prevent foot and nail diseases such as tinea pedis and tinea unguium and to reduce foot odor associated with bacterial elimination are also not taught. The prior art does not disclose methods for the topical application of aqueous solutions of antimicrobial quaternary ammonium organosilanes to the skin and nails of the feet, which are substantive to the skin and resist removal by washing or rinsing.

SUMMARY OF THE INVENTION

This invention describes a method for the cure and prevention of superficial and cutaneous mycoses through topical application to the skin and nails of the feet a solution containing an antimicrobial quaternary ammonium organosilane which is substansitive to the skin and which will also reduce or eliminate foot associated odor by its presence.

A number of formulations containing aqueous solubilized quaternary ammonium organosilanes. suitable as antimicrobial foot care products including solutions, sprays, cleansers, liquid soaps, ointments and lotions have been prepared. The formulations disclosed in this instant invention impart both short-term and long-term antimicrobial functionality to the skin. These functional characteristics remain on the skin throughout normal daily activities and are not removed by bathing. All formulations contain organosilane quaternary ammonium compounds.

The quaternary ammonium organosilanes of the present invention vary widely in structure and include organosilanes having either of the following two formulae:

Y₄-_n Si (R¹ N⁺ R² _aR³ _b Z-)n

Y ₄-_n Si (R¹ N⁺C₅H₅ Z^")_n

wherein:

Y is R or RO where each R is an alkyl radical of 1 to 4 carbon atoms or an alkyl ether radical with 2 to 10 carbon atoms or hydrogen; R¹ denotes a divalent hydrocarbon radical with 1 to 8 carbon atoms;

R² and R³ denote alkyl radicals with 1 to 12 carbon atoms or alkyl ether hydrocarbon radicals of 2 to 12 carbon atoms, preferably -CH₂CH₂ O CH₃ or -CH₂CH₂ O CH₂CH₂CH₃, or hydroxyl containing alkyl radicals of 1 to 10 carbon atoms, preferably -CH₂CH₂OH or -CH₂CH₂CH₂CH(OH)CH₃, or hydrocarbon radicals of 1 to 10 carbons containing nitrogen, preferably

-CH2CH2NH2 or-CH₂CH₂N(CH₃)₂, N⁺C₅H₅ is a pyridonium radical; a is 0, 1 or 2; b is 1, 2 or 3; and the sum of a and b is 3 ;

Z denotes an anion such as chloride, bromide, iodide, tosylate, hydroxide, sulfate or phosphate; and n = 1, 2 or 3.

The terminology used herein is for describing particular embodiments and is not intended to be limiting.

The term "alkyl" as used herein refers to a straight chain or branched saturated hydrocarbon.

The term "alkyl ether" refers to a hydrocarbon moiety containing carbon-oxygen- carbon bonds. "Alkoxy" as used herein refers to alkyl groups defined as above which have a terminal carbon-oxygen linkage. "Lower" as used herein in reference to alkyl, alkoxy and alcohols, indicates groups having 1 to 4 carbons. Prior art has demonstrated that deposition of organosilicon quaternary ammonium compounds onto substrates from aqueous solutions is achievable. It has also been extensively demonstrated that quaternary organosilicon ammonium compounds are effective against a broad spectrum of pathogens including gram positive and gram- negative bacteria, viruses and fungi, including molds and yeast. Prior art has failed to recognize that quaternary ammonium organosilanes containing hydrolyzable groups can form antimicrobially active, clear solutions in aqueous media which are stable over extended periods of time, do not require addition of immiscible materials to form antimicrobially effective emulsions, do not require adjustment of pH and can be applied for therapeutic purpose to the skin and nails of the feet.

The compositions of the present invention can be readily prepared by adding the quaternary ammonium organosilane composition to semiconductor grade water. The addition of lower alcohols in concentrations approaching 80% to lower the freezing point of the solution, to increase evaporation rates of the aqueous media from the skin, to increase the rate of antimicrobial effects, to enhance cleansing properties, or to increase solubility of other additives, does not affect the extended stability or performance of the solution.

The present invention provides methods for treatment and prevention of skin and nail diseases of the feet caused by dermatophytes and bacteria through application of quaternary ammonium organosilane compositions to the skin and nails in which the disclosed compositions are applied to the skin when incorporated as ingredients in aqueous solutions in the amounts of 0.01 to 4.0 percent. All formulations are homogeneous and may be scented and/or colored and may contain water-soluble additives to enhance performance and viscosity. The active quaternary ammonium organosilane ingredients are applied to the skin and nails as liquid, fluid, gel or solid solutions.

Accordingly, in one embodiment, this invention provides a composition for antimicrobially treating skin and nails of feet that is comprised of an effective amount of the water-soluble quaternary ammonium organosilane and an aqueous carrier. In another embodiment, this invention provides a method to prepare a clear water- stable composition comprising the quaternary ammonium organosilane of this invention and water or a water and lower alcohol solution.

In a further embodiment, this invention provides a method of treating skin and nail disorders of the feet by contacting the skin and nails with an aqueous composition containing quaternary ammonium organosilanes for a period of time to sufficiently render the substrate antimicrobially active.

In addition, the present invention provides a method to treat skin and nails with the quaternary ammonium organosilane having adhered thereto. In yet another embodiment of this invention, a method is provided to prepare aqueous compositions containing quaternary ammonium organosilanes which may contain various described additives for color or scent without decreasing the stability of the solution or the antimicrobial character, efficacy or substantiveness when the composition is subsequently applied to the skin and nails of the feet. A further embodiment of the present invention provides a method and compositions for coating skin and nails with a quaternary ammonium organosilane which is antimicrobial, substantive to the skin and which is not removed by rinsing and washing. It is therefore an object of the present invention to provide a treatment method for skin and nails diseases of the feet such as fungi caused tinea pedis and tinea unguium and bacteria produced foot odor by topical application of an aqueous solution of a quaternary ammonium organosilane.

Additional advantages and benefits of the intention are set forth in the description which follows and it is to be understood that the foregoing general description and the following detailed description are explanatory and are not restrictive of the invention as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a graphical representation of the reduction of bacterial concentration on human skin over an 8 hour period.

Figure 2 is a graphical representation of bacterial concentration comparisons on human skin over 64 hours.

Figure 3 is a graphical representation of the effect of pig skin treated with quaternary ammonium organosilane solution on Staphylococcus Aureus.

Figure 4 is a graphical representation of the rinsing effect on pig skin treated with quaternary ammonium organosilane in reducing Staphylococcus Aureus. Figure 5 is a graphical representation of Staphylococcus Aureus reduction with increased surface concentration of quaternary ammonium organosilanes. DETAILED DESCRIPTION OF THE INVENTION AND SPECIFIC EMBODIMENTS

These and other advantages of the present invention are provided by a method of treating the skin and nails of the feet with a stable aqueous solution in which all ingredients are miscible in water and which contains a quaternary ammonium organosilane which on application to the skin causes the quaternary ammonium organosilane to adhere and bond to the skin providing an antimicrobially active coating on the skin which is effective against a broad range of pathogens, remains antimicrobially active on the skin for extended periods. The practice of the disclosed method through application to the skin and nails of the feet is effective for the cure, control and prevention of fungi caused diseases including tinea pedis (athletes foot), tinea corporis and tinea unguium as well as elimination or reduction of odor producing bacteria. The substantive properties of the quaternary ammonium organosilane on the skin promote cure and prevent further infection from transient patho gens .

The term antimicrobial as used herein is used in reference to the ability of the compound composition or article to eliminate, remove, inactivate, kill or reduce microorganisms such as bacteria, viruses, fungi, molds, yeasts and spores. The term antimicrobial as used herein to imply reduction and elimination of the growth and formation of microorganisms such as described above.

Quaternary ammonium organosilanes are generally defined as having a nitrogen atom to which four organic groups are covalently bonded. An exception occurs with nitrogen containing aromatic compounds such as pyridine. The nitrogen atom when so bonded takes on a cationic charge. The associated anion is typically chloride and arises from the starting material in the synthesis process. The multiple uses of these compounds have been described previously in this invention.

Specific quaternary ammonium organosilanes within the scope of the invention are represented by the formulae:

(CH₃O)₃Si(CH₂)₃N⁺(CH₃)₂Cι₈H₃7 Cl^~

(CH₃CH₂O)₃Si(CH₂)₃N⁺(CH₃)₂C₁₈H₃₇ Cl^"

(CH₃O)3Si(CH3)3N⁺(CH3)2C₁₈H37 Br^~ (CH3O)3Si(CH₂)3N⁺(C₁₀H2,)2CH3 Cl^"

(CH3O)3Si(CH₂)₃N⁺⁽CH₃)2C,₄H₂₉ Cl^~

(CH₃O)₃Si(CH₂)₃N⁺(CH₃)₂C,₄H₂₉ Br^"

(CH₃O)3Si(CH2)3N⁺(CH₃)₂C₁₆H33 Cl^~

A requirement of the quaternary ammonium organosilanes used in this present invention is that they be soluble in water at ambient temperature (20-25°C) to be useful. It has been observed that if the organosilanes are not sufficiently soluble in water to form a clear solution at ambient temperature in the quantities in which they are to be incorporated into the aqueous solutions, then the production of clear and stable solutions is precluded.

Another requirement for the practice of this invention is that the aqueous formulations and compositions described herein contain water and water-soluble components. Purified water such as distilled or deionized water which when measured conductively has a minimum resistance of 10 megohm per square centimeter with a purity level of 18 megohm per square centimeter is preferred. The presence of dissolved impurities such as metal ions, metal salt and anionic species, particularly fluoride ions, will greatly decrease the stability and shelf life of the aqueous formulations.

The compositions suitable to practice the present invention contain from 0.01% to 5% by weight of the quaternary ammonium organosilanes described above whether admixed with water singly or jointly as in a mixture of the quaternary ammonium organosilanes. The preferred concentrations of the present invention are 0.1 to 4.0 weight percent. Lower concentrations do not maximize the antimicrobial benefits obtained on application and higher concentrations do not impart additional antimicrobial or moisturizing advantage. While any formulation may be used to cause the quaternary ammonium organosilanes to beneficially adhere to the skin, the most preferred are aqueous solutions containing 0.2 to 0.5 weight percent. Various water-soluble additives and stabilizers as defined in prior art may be incorporated into solutions as practiced in this instant invention which does not change or alter the scope and novelty of this invention. The preferred quaternary ammonium organosilanes of the present invention are the commercially available 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride and 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride. These materials contain hydrolyzable methoxy groups bound to the silicon atom. It is well known from prior art and to those skilled in the art that on addition of these compounds to water, the methoxy groups hydrolyze to form hydroxy substituted silicon atoms termed in the art as silanols with simultaneous liberation of methanol as a by-product of the hydrolysis. The resultant compound formed on addition of quaternary ammonium organosilanes of the above compositions are the respective trisilanol species for 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride (HO)₃Si(CH₂)₃N⁺(CH₃)₂C₁₈H37 CF and 3-(trimethoxysilyl)didecylmethyl ammonium chloride (HO)₃Si(CH₂)₃N⁺(CH₃) (C,oH₂₁)₂ Cl^"

The silanol species prepared on hydrolysis are reactive and may undergo condensation reactions in aqueous solution to form water-soluble silanol containing disiloxane species represented by the following example structure obtained from 3- (trimethoxysilyl)propyldimethyloctadecyl ammonium chloride:

Cι₈H₃₇N⁺Me₂ (CH₂)3Si(OH)₂OSi(OH)₂(CH₂)₃N⁺Me₂Cι₈H₃7 2C1^" where Me = CH₃ These compounds may undergo further condensation reactions with additional trisilanol species present to produce water-soluble polysiloxanol compounds which can be represented as follows for derivatives of the 3-(trimethoxysilyl)dimethyloctadecyl ammonium chloride hydrolysis products:

[C₁₈H₃₇N⁺Me₂ (CH₂)₃Si(OH)₂]₂Si(OH)(CH₂)₃N⁺Me₂C₁₈H₃₇ 3C1^" where Me = CH

Additional water-soluble homologues may be present in the formulations and compositions of this invention. The trisilanol, disiloxanylsilanol and polysiloxanol derivatives are reactive with and bond to the skin and nails on application with liberation of water to form a water insoluble macromolecular network on the skin and nail surface. The resultant polymeric molecular network adhering to and/or bonded to the skin and nail which are obtained on application of the formulations of this invention are derived from 3-(trimethoxysilyl)propyldimethyl-octadecyl ammonium chloride and 3-(trimethoxy- silyl)propyldidecylmethyl ammonium chloride respectively, can be represented by the idealized formulas:

[C₁₈H₃₇N⁺Me₂ (CH₂)₃SiO,.₅]n nCf and [(C₁₀H₂,)2N⁺Me (CH₂)3SiO,_.5]„ nCI^" where n is an integer of 1 to >1000. It is understood by those skilled in the art that these formulations when present on the skin and nail substrate are three dimensional, cross-linked, water-insoluble, polymeric coatings which would be expected to contain some uncondensed silanol moieties. It is also expected that monomeric, dimeric and oligomeric species would be present on the skin following application of the aqueous quaternary ammonium organosilane solution, and these would bond to the skin, whether by covalent, electrostatic or hydrogen-bonding mechanisms and be substansitive to the skin, and not removed by washing or rinsing.

The polysiloxane quaternary ammonium species formed on the skin retain their antimicrobial activity. They are substantive to the skin and nails, insoluble in water and are not removed by rinsing or washing with water. The resultant polymeric coating obtained on application of the formulations of the present invention protect the skin from pathogenic infections, destroys fungi and bacteria which may subsequently come to reside on its surface and through its persistent polymeric nature effects a more rapid cure.

Skin consists of two layers, which include the upper epidermis layer and the lower corium layer. It provides a protective layer for the body and performs a number of important functions including excretory functions such as sweat production to assist in body temperature regulation. Skin is the largest human organ and its anatomy and physiology vary from one part of the body to another.

Normal microbiata which reside on the surface of the skin reflect these variations and can include diptheroids, various species of streptococci, mycobacterium spp., coagulase-negative staphylococci, Candida spp., staphylococcus aureus, bacillus spp. and malassezia furfur. The epidermis is not a favorable environment for microbial colonization, but certain areas of the skin have sufficient sweat generated moisture to support resident microbiota. Enzymes produced from resident gram-positive bacteria can change lipids secreted from the skin to unsaturated fatty acids, which have antimicrobial activity against gram negative bacteria and some fungi. These fatty acids have strong, unpleasant odors that produce the characteristic foot odor. Deodorants may contain antibacterial compounds that selectively reduce or eliminate gram-positive bacteria and associated odors. However, such deodorants can shift the microbial population to predominately gram-negative bacteria and fungi and precipitate subsequent infections. Topical treatment applications should therefore contain a broad spectrum antimicrobial composition to avoid this bacterial shift and provide subsequent reduction of gram- negative bacteria and fungi as disclosed in this invention. Most skin bacteria are found on the epidermis and are closely associated with oil and sweat glands which provide moisture, fatty acids, amino acids and electrolytes that serve as nutrients primarily for Staphylococcus epidermus and aerobic cornebacteria. Moist regions of the skin are preferred by gram-negative bacteria. Fungi also prefer moist areas and can colonize the skin to form superficial and cutaneous mycoses. Superficial mycoses such as tinea versicolor caused by the yeast Malassazia furfur are less common diseases. Cutaneous mycoses are also called dermatophytes, tineas or ringworm are the most common fungal diseases in humans. Common types of dermatophytes involved in these mycoses include Trichophyton and Microsporum. Epidermal fungal infections which produce the disease Tinea pedis, also known as athlete's foot, occurs throughout the world and is most commonly found in adults. Tinea unguium is a dermatophytic infection of the nail bed characterized by a discolored and thickened nail plate, which rises and separates from the nail bed. Trichophyton is the causative fungi. It is well known from prior art and from studies performed within this present invention, quaternary ammonium organosilane species such as derived from 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride and 3-(trimethoxy- silyl)propyldidecylmethyl ammonium chloride are effective when placed on a substrate against a wide range of pathogens, including gram positive bacteria, gram negative bacteria, viruses, fungi, mold, yeast and spores.

In the method of treating skin and nail disorders of the feet in accordance with the present invention there is applied to the nail and epidermis an aqueous solution including an effective amount of quaternary ammonium organosilane. The composition may also include, in addition to the quaternary ammonium organosilane, a water-soluble fragrance or scent, glycols, lower alcohols including methanol, ethanol or isopropanol to increase evaporation rate in addition to lowering the freezing point and a colorant or dye. Such compositions are used for treatment of dermal infections caused by various pathogenic dermatophytes, yeasts, gram-positive and gram- negative bacteria. They are indicated for the treatment of foot odor and dermal infections such as tinea pedis, tinea cruris and tinea corporis. Although many odor and dermal treatments are known as noted herein above, none is known which are antimicrobial on application, adhere and are substantive to the skin wherein it retains antimicrobial character for the duration of its presence on the skin and nails of the feet. In addition to direct application and spray application of aqueous solutions containing quaternized organosilanes, application to the skin by absorbing the antimicrobial solutions of this invention onto polypropylene towelettes was found effective in transferring the quaternary ammonium organosilane to the skin of the feet and nails.

Liquid soaps containing solutions of the quaternary ammonium organosilanes were found effective carriers for transference of the antimicrobial composition to skin and nails of the feet. A number of liquid soap solutions suitable for foot care and prevention of tinea pedis and tinea unguium were formulated. They exhibited excellent lathering, solubility in water, dirt removal and cleansing of skin and were stable for greater than one year. Temperature cycling between 5 and 70°C did not cause precipitation of the quaternary ammonium organosilane dissolved in the formulation. The formulation was determined to be an effective antifungal and foot odor preventing soap.

The following examples are illustrative of the present invention and are not to be considered as limiting the invention. In the examples, the following materials were used:

ODTA: Octadecyldimethyl(3-trimethoxysilyl)propyl ammonium chloride. Obtained from Wright Chemical Corp., Wilmington, NC as a 42% active material in methanol. This material may also be named as 3- (trimethoxysilyl)propyl-dimethyloctadecyl ammonium chloride. Also available as a 42% active material from Aegis Environmental

Management, Inc., Midland, MI marketed as Dow Corning7 5700.

REQUAT: 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride. Obtained from Sanitized Inc., New Preston, CT; Requat 1977 as a 42% active material in methanol.

TDTA: 3-(trimethoxysilyl)propyltetradecyldimethyl ammonium chloride obtained from Gelest, Inc., Tullytown, PA, Cat. No. SIT7090.0 as a 50% solution in methanol.

EXAMPLE 1

A formulation suitable as an antifungal and antibacterial solution useful in treatment for cure and prevention of tinea pedis, tinea unguium and foot odor was prepared by chilling 50 liters of deionized water (18 megohm purity) to 20°C. Ten liters of SDA-3A ethanol was added over 5 minutes to the stirred water producing an exotherm raising the temperature to approximately 50°C. Cooling was maintained on the stirred vessel until the temperature reached 20°C. The stir rate was then increased and 165 g ODTA was added drop-wise over 10 minutes. Stirring and cooling was maintained to keep the temperature at 20°C for 1 hour. The formulation was allowed to return to room temperature over 2 hrs. with stirring. A water-soluble scent (Vanilla; #4510-CBE-WS, Andrea Aromatics, Princeton, NJ) was added to an approximate concentration of 0.008% of the total volume. The solution was passed through a 5 -micron filter and packaged into containers suitable for spray application.

EXAMPLE 2

A formulation suitable for use as an antifungal and antibacterial foot spray was prepared by chilling 50 liters of deionized water (18 megohm purity) to 20°C. The chilled water was stirred with an overhead stirrer and 252 ml. of ODTA was added drop- wise over 30 minutes. After addition was completed, a water-soluble scent (Rain Fresh; #2878-JAB, Andrea Aromatics, Princeton, NJ) was added to a concentration of 0.01%. The clear solution was transferred to an HDPE container and packaged into smaller packages suitable for retail sales. Shelf-life studies demonstrated the product prepared in this manner had a shelf life, when stored at ambient temperature, greater than one year.

EXAMPLE 3

A solution prepared as in Example 1 was tested on human skin to determine the ability of aqueous formulations containing quaternary ammonium organosilanes to reduce bacteria present on skin. The testing and evaluation were performed by Day Break Environmental Corp. (Phoenix, AZ). Bacterial determinations and concentrations reported in colony forming units were performed by Aerotech

Laboratories, Inc. (Phoenix, AZ). The skin of human subjects were used as test surfaces with the skin of the right being treated by spray application with the test solution prepared as in Example 1. The skin of the left hand was washed with a standard soap, but otherwise left untreated. Normal activities were maintained through the duration of the testing. Washing of treated or untreated skin was not performed after initial treatment. Swabs of approximately 100 square centimeters were taken from the skin of the treated right hand, and the untreated skin of the left hand at identical, predetermined intervals, sealed in plastic containers and recorded on Chain of Custody forms. The samples were cultured at 35°C for 48 hours and enumerated for total bacteria. Results are reported in the following Table 1 :

TABLE 1 Skin Bacterial Concentrations in Colony Forming Units

The initial bacterial count ascertained as described above immediately following application of the quaternary ammonium organosilane solution was significantly lower, when compared to the bacterial count obtained from untreated skin on the left hand which was cleansed immediately prior to sampling with standard soap solution. Bacterial counts were approximately one third lower for the treated skin during the first hours of testing. At hour 2 treated skin was inoculated with bacteria from sneeze/cough which caused an average increase in total bacteria to slightly above that of the untreated skin. Bacterial collection and enumeration at hour 4 indicated decreased bacterial counts and emphasized the continuing antimicrobial activity of the treated skin. At 8 hours following initial application, total bacteria on untreated skin were approximately 43 times greater on the untreated skin when compared to the skin treated with the quaternized organosilane. (See Figure 1).

Testing was continued an additional 56 hours. At 16 hours after initial treatment of the skin with the quaternary ammonium organosilane solution, a vigorous, sweat- inducing workout was commenced. Bacterial levels were raised as expected, and were determined to be significantly higher on the untreated skin. Bacterial counts subsequent to the workout indicated lower bacteria levels than prior to the workout on the treated skin, with untreated skin being approximately 200 times greater. Sweat induced by the workout did not remove the substantive quaternary ammonium organosilane treatment as evidenced by the decreasing bacterial counts collected from the treated skin. At the end of the test period, total bacteria present on the untreated skin was approximately 75 times greater than on the skin treated with the quaternary ammonium organosilane. During the course of the testing, sneezing on the treated skin was induced at two hours after initial application to increase bacterial levels. Measurements of bacterial colonies present on the treated skin following inoculation by the sneezing were found to be slightly elevated over the untreated skin. Microbial re-testing of the skin after two hours indicated bacteria to be at the lowest levels counted during the entire test. This result concludes that bacteria and other microbial pathogens introduced to skin previously treated with quaternary ammonium organosilanes are eliminated by the presence thereof. (See Figure 2).

It is believed by the inventors that the antimicrobial activity of the quaternary ammonium organosilane present on the skin is decreased after extended exposure to bacteria by carcasses of dead or deactivated bacteria covering the organosilane surface adherent to the skin. The bacteria and other pathogens present must contact or closely approach the organosilane present on the skin surface to be effected. Contact with the treated skin is hindered or prevented by the presence of bacterial carcasses and detritus. Washing or rinsing of the treated skin to remove materials on the skin and expose the treated skin is expected to restore antimicrobial activity to the treated area.

EXAMPLE 4

A solution suitable for use as an antimicrobial foot care formulation for treating skin and nail disorders and as a base formulation to which other additives, fragrances or dyes could be subsequently added was prepared by charging a 20-liter stainless steel reaction vessel fitted with an overhead stirrer with 10 liters of deionized water. The water was stirred at ambient temperature (22°C) as 72g of ODTA was added drop-wise over 20 minutes. The clear solution was stirred an additional 30 minutes. The material was stable for 18 months when stored in closed HDPE, glass or epoxide coated aluminum containers.

EXAMPLE 5

The antimicrobial effects of quaternary ammonium organosilanes were further demonstrated utilizing pig skin as a test substrate to approximate human skin. Testing was performed by Southern Testing & Research Laboratories, Inc. (Wilson, NC).

Samples of pig skin were obtained and cut to obtain approximately identical surface areas. One pig skin sample was treated with a solution as prepared in Example 1. Treatment of the pig skin sample was accomplished by wetting the surface by spray following which the sample was allowed to air dry. The treated pig skin and an identical sample of untreated pig skin were then tested for efficacy in eliminating and reducing staphylococcus aureus. Determinations were made using the dynamic shake flask method. The number of viable cells per milliliter of staphylococcus aureus for both treated and untreated samples of pig skin were determined at exposure times of 0, 10, 30 and 120 minutes with the following results:

TABLE 2

Numbers reported as viable cells per milliliter

The number of reported viable cells of staphylococcus aureus increased steadily throughout the entire 120-minute exposure to the untreated pig skin, indicating no effect on the pathogen. Conversely, the addition of the treated pig skin to the staphylococcus aureus broth produced a slight rise in the number of viable cells counted per milliliter during the first 10 minutes. This was possibly caused by the replication rate of the staphylococcus aureus being greater than the rate of contact with the treated pig skin surface. After 30 minutes the number of viable cells were greatly reduced through contact with the treated pig skin. At the conclusion of the test and following 120 minutes of contact time with the treated pig skin, the number of viable cells were essentially annihilated as only a single viable cell per milliliter could be detected. This represents a reduction of 5 million viable cells per milliliter to essentially zero cells after 120 minutes contact time with pig skin containing quaternary ammonium organosilanes bonded to its surface. (See Figure 3).

EXAMPLE 6

The novel substantiveness and resistance to removal by rinsing or washing of quaternary ammonium organosilanes applied to skin from an aqueous solution was demonstrated by the following procedure performed by Southern Testing & Research Laboratories, Inc. (Wilson, NC).

Pig skin samples, again chosen for its similar characteristics to human skin, were cut and determined to have approximately identical surface areas. The samples were then treated by spray with an approximately 0.1 % active solution as prepared in Example 1. Following application, the pig skin samples were allowed to air dry and then individually subjected to a number of one second rinses with deionized water in an effort to remove the quaternized organosilane from the surface by dissolution. The minimum number of rinses was one and the maximum number of rinses was nine consecutive rinses on a single pig skin test sample. The amount of quaternary ammonium organosilane remaining on the surface was determined by measuring the reduction in the number of viable cells per milliliter of staphylococcus aureus after a 30 minute contact time utilizing the dynamic shake test method. In the tests, all samples performed identically in reducing the number of viable cells to <10⁴ cells per milliliter over 30 minutes even though the initial test concentrations of staphylococcus aureus varied from 1 to 8 million cells per milliliter. A control sample in the form of an untreated sample of pig skin, when tested under identical conditions, allowed a significant increase of staphylococcus aureus. Results are reported in the following Table 3. as the number of viable cells per milliliter:

TABLE 3

This testing clearly indicates that quaternary ammonium organosilanes bond to skin, are substantive to it, are not removed by rinsing with water and retain antimicrobial activity after rinsing. The coating remaining on the skin after rinsing is as antimicrobially effective as pre-rinse compositions bonded to skin. (See Figure 4).

EXAMPLE 7

Increasing antimicrobial effectiveness and efficiencies in pathogen removal by increasing the surface concentration of the quaternary ammonium organosilane moieties adhering to the skin surface was determined. A sample of pig skin was treated with 0.3 weight percent of the quaternized organosilane prepared as in Example 4. Spray application to thoroughly wet the pig skin surfaces was followed by an air-dry period of 2 hours. A sample of pig skin of approximately identical size was left untreated. The dynamic shake flask test method was employed to test both treated and untreated pig skin samples. Pathogen concentrations were determined at start and at 10, 30 and 120 minute intervals. Testing was performed by Southern Testing & Research Laboratories Inc. (Wilson, NC). Results are reported in Table 4 as the number of viable cells per milliliter follow:

TABLE 4

The treated pig skin depleted the staphylococcus aureus to approximately zero in the test time of 120 minutes. The rise in pathogen levels noted in the preceding Example 6 which tested pig skin samples treated with a 0.1 weight percent active composition as prepared as in Example 1 did not occur when higher concentrations of the active material were employed to treat the pig skin sample. The rate of pathogen decrease was more rapid at the higher treatment concentration. Untreated pig skin permitted the staphylococcus aureus to increase steadily and significantly over the test period. (See Figure 5)

EXAMPLE 8

Test subject A, a 33 year old male suffered a broken left foot in an industrial accident. The subsequent medical procedure included removing toenails from 3 toes on the injured foot. Regrowth over the next 2 years produced replacement nails that were yellow, soft and thickened. The condition was diagnosed as tinea unguium by medical personnel. A corrective procedure involving a daily regimen of foot spray treatment with a formulation prepared as in Example 1 was instituted. Two weeks after start of treatment, examination revealed healthy nail plate growing at the base of the infected yellow nails. Following 3 months of continued spray treatment, 50% of each nail had returned as a normal, healthy nail plate. Following 6 months of treatment, the affected nails had thinned, were no longer discolored and no fungal traces remained.

EXAMPLE 9

A solution prepared as in Example 1 was utilized to prepare towelettes suitable for topical use as antimicrobial skin and nail wipes. Polypropylene towelettes, approximately 5"x7", were moistened with 2 mis. of solution, folded, placed in waterproof packets and sealed. After three months, the pouch was opened. Clean porcelain plates were wiped on one half of one side with the towelettes and allowed to dry. Measurement of the contact angle of water droplets on the surface of the porcelain plates indicated an average contact angle of 65° for the treated side and 43° for the untreated side. The higher contact angles indicate the presence of the quaternary ammonium organosilane on the plate surface. Washing the plate with deionized water following application of the quaternary ammonium organosilane did not change the contact angles as measured previously for the treated and the untreated plate surfaces. Similar experiments utilizing cotton or cellulose towelettes showed a marginal increase in contact angle after treatment of the plate surface with the towelette. This difference was due to the quaternary ammonium organosilane present in the aqueous solution being reduced through reaction with the cotton and cellulose towelettes and, therefore, was not available in solution to be transferred to the substrate. EXAMPLE 10

A liquid antimicrobial spray soap formulation was prepared by adding 120 grams ODTA over a period of 10 minutes to a stirred solution of 15 liters deionized water (18 megohm purity) containing 30 ppm FD&C Yellow #6 while maintaining the reaction temperature at 25°C. To this solution was added over 30 minutes, 5 kg. of Burcoterge LHS (Burlington Chemical, Burlington, NC). The orange mixture was stirred for an additional 2 hrs. The clear liquid solution was stable when stored at ambient temperatures for greater than one year and is suitable for use in liquid spray-soap foot care applications.

EXAMPLE 11

To the formulation prepared as in Example 10 was added 1.5% sodium chloride, with mechanical stirring, over a period of 10 minutes. The formulation thickened immediately and was suitable for use as a clear liquid antimicrobial foot treatment.

EXAMPLE 12

A clear liquid antimicrobial soap suitable for foot care and containing 14.4% actives with a pH of 5.5-6.5, a Gardner color of 1 and a viscosity of 7300 cps at 25°C was prepared utilizing the following materials and procedure obtained from Stepan Company (Northfield, IL). Deionized water (1956 g) was stirred with an overhead stirrer as Biosoft FF-600 (51 g), Amphosol CA (500 g), Ammonyx CDO Special (234 g), Ammonyx CO (99 g), Ninol LMP (60 g), Kessco PEG 6000 DS (30 g), disodiium EDTA (6 g) and ODTA (60 g as a 42 % solution in methanol) were added and stirred for 30 minutes. The mixture was then heated to 60-70°C. Mixing was then continued until all material had dissolved. The clear solution was cooled and the pH adjusted to 5.5-6.5 with citric acid. No salt addition was necessary to adjust viscosity. The material had a shelf life stability greater than one year. Stability and clarity were not effected when citric acid or disodiium EDTA were deleted from the formulation.

EXAMPLE 13

Testing of the soap prepared in Example 12 for antimicrobial efficacy and substantiveness to the skin was performed by comparison tests on the feet of a human, male test subject. Normal washing and rinsing of the right foot with the soap prepared in Example 12 was followed by air-drying. The wash and rinse procedure was then repeated on the left foot with a non-bacterial bar soap and air-dried. Testing for microbial contamination was performed by wiping an area of approximately 25 square centimeters on the bottom of the foot with cotton swabs moistened in deionized water. Sampling was performed at 0, 2, 6 and 24 hours following washing with normal daily activities being maintained. The swabs were then employed to inoculate 15x100mm blood agar plates (tryptic soy agar with 5% sheep's blood) obtained from Hardy Diagnostics of Phoenix, AZ and incubated at 35° for 48 hours. Total bacterial count for both feet at time 0, immediately following washing, was determined to be approximately zero. The bacterial count for the foot washed with regular soap increased steadily over the course of the 24- hour test period. At the conclusion of the test period, bacterial counts for the foot washed with bar soap was on average 125 times higher than bacterial counts obtained from the foot washed with liquid soap containing the quaternary ammonium organosilane component.

EXAMPLE 14

A male test subject was diagnosed as having tinea pedis. A corrective regimen was instituted which included cleansing of the infected area with a spray soap prepared as in Example 10, followed by twice daily application of a foot care spray prepared as in Example 1. Following 1 week of treatment, significant improvement was noted. Following 3 weeks of treatment, tinea pedis was no longer apparent.

EXAMPLE 15

To a vessel having good agitation was added 7.56 kg. of deionized water and 2.0 kg. SD Alcohol 40-B. Stirring was continued until the temperature rise caused by the alcohol addition returned to 25°C. TDTA, 20 g, was added slowly over 15 minutes. To the clear solution and with continued agitation was added 100 g Phospholipid PTC, 20 g PEG-75 (Mona Industries, Paterson, NJ) and 300 g propylene glycol (Aldrich Chemical Co., Milwaukee, WI). The solution was suitable for antimicrobial foot care applications as spray or liquid. EXAMPLE 16

An antimicrobial alcohol gel suitable for foot and nail disinfection was prepared by stirring a solution containing 29.7 weight percent 18 megohm deionized water and 67.0 weight percent ethanol (90%) at room temperature as 0.3 weight percent ODTA was added slowly over 30 minutes. Sepigel 305 in an amount equal to 3.0 weight percent was added with mixing at moderate speed over 20 minutes. Stirring was continued until a clear, transparent gel was obtained.

EXAMPLE 17

A deodorizing, antifungal, antiperspirant foot spray was prepared by stirring a solution containing 46.85 parts 18 megohm deionized water, 10.00 parts propylene glycol and adding 0.1 parts REQUAT over 15 minutes. To the stirred solution at room temperature was added 40.00 parts of a 50% solution of aluminum chlorohydrate, Lexein X250 and Bronopol-Boots (Inolex Chemical Co., Philadelphia, PA) over 20 minutes and stirred until clear. The solution was suitable for packaging into a lined aerosol container with fluorocarbon or carbon dioxide propellant.

It will be apparent to those skilled in the art that various changes, variations and modifications can be made in the present invention without departing from the spirit and scope of the invention. It is intended that the specifications and examples of this patent be considered as exemplary.

Claims

WHAT IS CLAIMED IS:

1. A method for reducing or eliminating the number of viable microorganisms selected from the group consisting of bacteria, viruses, fungi, algae, yeast and spores on the surface of skin and nails of the feet, said method comprising physically contacting the skin and nails with a quaternary ammonium organosilane in an amount effective to eliminate or inhibit the growth of said microorganisms, said quaternary ammonium organosilane being one that is soluble in water and has a formula selected from the group consisting of:

Y₄-_n Si (R¹ N⁺ R² _a R³ _b Z^')_n and Y₄-_n Si (R¹ N⁺C₅H₅ Z^')_n

wherein: Y is a member selected from the group consisting of R and RO in which R is a member selected from the group consisting of alkyl radicals of 1 to 4 carbon atoms, alkyl ether radicals with 2 to 10 carbon atoms, and hydrogen; R¹ denotes a divalent hydrocarbon radical with 1 to 8 carbon atoms; R² and R³ are members independently selected from the group consisting of alkyl radicals of 1 to 12 carbon atoms, alkyl ether hydrocarbon radicals of 2 to 12 carbon atoms, hydroxy-substituted alkyl radicals of 1 to 10 carbon atoms, and nitrogen-containing hydrocarbon radicals of 1 to 10 carbons; N⁺C₅H₅ is a pyridonium radical; a is 0, 1 or 2; b is 1, 2 or 3; and the sum of a and b is 3; Z is an anion selected from the group consisting of chloride, bromide, iodide, tosylate, hydroxide, sulfate and phosphate; and n is 1, 2 or 3.

2. A method in accordance with claim 1 in which Y is a member selected from the group consisting of R and RO, in which R is a member selected from the group consisting of alkyl radicals of 1 to 4 carbon atoms, -CH₂CH₂-O-CH₃, -CH₂CH₂-O-CH₂CH₂CH₃, -CH₃CH₂OH, -CH₂CH₂CH₂CH(OH)CH3, -CH₃CH₂NH₂, and -CH₂CH₂N(CH₃)₂.

3. A method in accordance with claim 1 comprising contacting said skin and nails with an aqueous solution of said quaternary ammonium organosilane, the concentration of said quaternary ammonium organosilane in said aqueous solution being 0.01 to 20% by weight.

4. A method in accordance with claim 1 in which said quaternary ammonium organosilane is formed by combining 3-(trimethoxysilyl)propyldimethyl- octadecyl ammonium chloride with water.

5. A method in accordance with claim 1 in which said quaternary ammonium organosilane is formed by combining 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride with water.

6. A method in accordance with claim 1 in which said quaternary ammonium organosilane is formed by combining 3-(trimethoxysilyl)propyldimethyl- tetradecyl ammonium chloride with water.

7. A method in accordance with claim 1 comprising contacting said skin and nails with an aqueous solution of a mixture of quaternary ammonium organosilanes in accordance with said formulae.

8. A method in accordance with claim 1 in which said microorganisms are a member selected from the group consisting of gram-positive and gram-negative bacteria.

9. A method in accordance with claim 1 in which said microorganisms are viruses.

10. A method in accordance with claim 1 in which said microorganisms are fungi.

11. A method in accordance with claim 1 in which said microorganisms are a member selected from the group consisting of algae and mold.

12. A method in accordance with claim 1 in which said microorganisms are yeasts.

13. A method in accordance with claim 1 in which said microorganisms are spores.

14. A method for reducing or eliminating the number of pathogens on the surface of skin and nails of the feet for an extended period of time, said method comprising contacting the skin and nails with an aqueous solution comprising a quaternary ammonium organosilane at a concentration of 0.01 to 4 weight percent plus water-soluble additives, said quaternary ammonium organosilane having a formula selected from the group consisting of:

Y₄-_n Si (R¹ N⁺ R² _a R³ _b Z-)_n and Y₄-_n Si (R¹ N⁺C₅H₅ Z^")_n

wherein: Y is a member selected from the group consisting of R and RO in which R is a member selected from the group consisting of alkyl radicals of 1 to 4 carbon atoms, alkyl ether radicals with 2 to 10 carbon atoms, and hydrogen; R¹ denotes a divalent hydrocarbon radical with 1 to 8 carbon atoms; R² and R³ are members independently selected from the group consisting of alkyl radicals of 1 to 12 carbon atoms, alkyl ether hydrocarbon radicals of 2 to 12 carbon atoms, hydroxy-substituted alkyl radicals of 1 to 10 carbon atoms, and nitrogen-containing hydrocarbon radicals of 1 to 10 carbons; N⁺C₅H₅ is a pyridonium radical; a is 0, 1 or 2; b is 1, 2 or 3; and the sum of a and b is 3; Z is an anion selected from the group consisting of chloride, bromide, iodide, tosylate, hydroxide, sulfate and phosphate; and n is i, 2 or 3.

15. A method in accordance with claim 14 in which Y is a member selected from the group consisting of R and RO, in which R is a member selected from the group consisting of alkyl radicals of 1 to 4 carbon atoms, -CH₂CH -O-CH₃, -CH₂CH₂-O-CH₂CH₂CH₃, -CH₃CH₂OH, -CH₂CH₂CH₂CH(OH)CH₃, -CH₃CH₂NH₂, and -CH₂CH₂N(CH₃)₂.

16. A method in accordance with claim 14 in which said pathogens are a member selected from the group consisting of gram-positive bacteria, gram-negative bacteria, viruses, and fungi.

17. A method in accordance with claim 14 in which said aqueous solution contains a sufficient amount of said quaternary ammonium organosilane that said extended period of time is 64 hours.

18. A method in accordance with claim 14 in which said quaternary ammonium organosilane is 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride or a mixture of quaternary ammonium organosilanes including 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride.

19. A method in accordance with claim 14 in which said quaternary ammonium organosilane is 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride or a mixture of quaternary ammonium organosilanes including 3-(trimethoxysilyl)propyl- didecylmethyl ammonium chloride.

20. A method in accordance with claim 14 in which said water-soluble additives are from 1 to 80% by weight of a member selected from the group consisting of ethyl, methyl and propyl alcohols, and mixtures thereof.

21. A method in accordance with claim 14 in which said aqueous solution is a soap solution.

22. A method for the preparation of a stable, transparent aqueous solution containing 0.01 to 4 % by weight of a quaternary ammonium organosilane comprising mixing a water-soluble quaternary ammonium organosilane with deionized water having a minimum of 10 megohm purity.

23. A method for the treatment of a dermatophytic infection of the skin and nails comprising applying topically to the skin and nails a solution comprising an antimicrobially effective amount of a quaternary ammonium organosilane having a formula selected from the group consisting of:

Y₄-_n Si (R^I N⁺ R² _a R³ _b Z-)_π and Y₄-_n Si (R¹ N⁺C₅H₅ Z^")„

wherein: Y is a member selected from the group consisting of R and RO in which R is a member selected from the group consisting of alkyl radicals of 1 to 4 carbon atoms, alkyl ether radicals with 2 to 10 carbon atoms, and hydrogen; R¹ denotes a divalent hydrocarbon radical with 1 to 8 carbon atoms; R and R are members independently selected from the group consisting of alkyl radicals of 1 to 12 carbon atoms, alkyl ether hydrocarbon radicals of 2 to 12 carbon atoms, hydroxy-substituted alkyl radicals of 1 to 10 carbon atoms, and nitrogen-containing hydrocarbon radicals of 1 to 10 carbons; N⁺C₅H₅ is a pyridonium radical; a is 0, 1 or 2; b is 1, 2 or 3; and the sum of a and b is 3; Z is an anion selected from the group consisting of chloride, bromide, iodide, tosylate, hydroxide, sulfate and phosphate; and n is 1, 2 or 3.

24. A method in accordance with claim 23 in which said solution is an aqueous solution and said quaternary ammonium organosilane constitutes 0.01 to 20% by weight of said aqueous solution.

25. A method in accordance with claim 23 in which said quaternary ammonium organosilane is formed by combining 3-(trimethoxysilyl)propyldimethyl- octadecyl ammonium chloride with water.

26. A method in accordance with claim 23 in which said quaternary ammonium silane is formed by combining 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride with water.

27. A method in accordance with claim 23 in which said quaternary ammonium silane is formed by combining 3-(trimethoxysilyl)propyldimethyltetradecyl ammonium chloride with water.

28. A method in accordance with claim 23 in which said solution comprises a mixture of said quaternary ammonium organosilanes.

29. A method in accordance with claim 23 in which said dermatophytic infection is tinea pedis.

30. A method in accordance with claim 23 in which said dermatophytic infection is tinea unguium.

31. A method in accordance with claim 23 in which said dermatophytic infection is tinea corporis.

32. A method in accordance with claim 23 in which said quaternary ammonium organosilane is formed by contacting 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride with water.

33. A method in accordance with claim 23 in which said quaternary ammonium organosilane is formed by contacting 3-(trimethoxysilyl)-propyldimethyl- octadecyl ammonium chloride with water.

34. A method in accordance with claim 23 in which said solution comprises a mixture of said quaternary ammonium organosilanes.

35. A method for the preparation of a medicament for the treatment of a dermatophytic infection of the skin and nails of the feet, said method comprising combining water, water-soluble additives and 0.01 to 4 weight percent of a water-soluble quaternary ammonium organosilane having a formula selected from the group consisting of:

Y₄-_n Si (R¹ N⁺ R² _a R³ _b Z^')n and Y₄-_n Si (R¹ N⁺C₅H₅ Z^")„

wherein: Y is a member selected from the group consisting of R and RO in which R is a member selected from the group consisting of alkyl radicals of 1 to 4 carbon atoms, alkyl ether radicals with 2 to 10 carbon atoms, and hydrogen; R¹ denotes a divalent hydrocarbon radical with 1 to 8 carbon atoms;

7 ^ R and R are members independently selected from the group consisting of alkyl radicals of 1 to 12 carbon atoms, alkyl ether hydrocarbon radicals of 2 to 12 carbon atoms, hydroxy-substituted alkyl radicals of 1 to 10 carbon atoms, and nitrogen-containing hydrocarbon radicals of 1 to 10 carbons; N⁺C₅H₅ is a pyridonium radical; a is 0, 1 or 2; b is 1, 2 or 3; and the sum of a and b is 3; Z is an anion selected from the group consisting of chloride, bromide, iodide, tosylate, hydroxide, sulfate and phosphate; and n is 1, 2 or 3.

36. A method in accordance with claim 35 in which said water-soluble additives are soap-forming additives and said medicament is a soap.

37. A method in accordance with claim 35 in which said water-soluble additives are gel-forming additives and said medicament is a gel.

38. A method in accordance with claim 35 in which said medicament is a solid.

39. A method in accordance with claim 35 in which said water-soluble additives comprise dyes at a concentration of 0.001 to 0.2 weight percent.

40. A method in accordance with claim 35 in which said water-soluble additives comprise fragrances at a concentration of 0.001 to 1.0 weight percent.