Abstract:
The impregnation of a foam rubber, or similar polymeric material, insole with an effective antibacterial and antifungal agent along with a deodorant provides a simple, clean source of active ingredients for curative and prophylactic treatment of infections of the feet and reduces odors during the course of the treatment. The agent of choice in such a product must be stable to the conditions of use and be sufficiently non-volatile to be retained in the insole over a period of days or weeks.

Description:
BACKGROUND OF THE INVENTION 
     The present invention is related to foam rubber insoles which contain an antimicrobial agent to inhibit the growth of bacteria and fungi so as to aid in the prevention and treatment of microbial infections such as athlete&#39;s foot. The insoles typically further contain a deodorizing agent. 
     When feet are enclosed in shoes, sneakers, etc., they have a tendency to perspire. This warm, moist condition is ideal in promoting the prolific growth of bacteria and fungi. The organisms can produce an unpleasant, undesirable odor during proliferation and also can cause infections of the foot leading to the common condition known as athlete&#39;s foot. The regular application of an antimicrobial and antifungal agent to the infected area will cure or alleviate the infection, but compliance with a regimen of topical applications is difficult and, furthermore, the use of powders, creams and/or lotions causes soiling of footwear such as socks and shoes. A clean, dry, and long-acting source of the antimicrobial agent in contact with the source of infection is very desirable. 
     Initial attempts to use an antimicrobial agent such as parachlorometaxylenol (PCMX) were unsuccessful due to the volatility of the compound, which resulted in its loss during manufacture of the insole as a result of the heat treatment required for curing of the preparation. A solution to this problem is achieved by the present invention by using Ottacide-P (trademark of Ottawa Chemical Division of Ferro Corporation), a stable, non-volatile borate ester of PCMX having the formula: ##STR1## Ottacide-P is only partially lost during the manufacture of the insole and as such it retains its antimicrobial activity. 
     It has been reported that Ottacide-P is useful fungicide when incorporated in plastics. Ritzinger, Rubber &amp; Plastics Age 40, 1067 (1959), indicates that Ottacide-P is a useful fungicide when compounded with neoprene. The product brochure of Ottawa Chemical Division of Ferro Corporation for Ottacide-P and Chemical Engineering News, Jan. 26, 1959, p. 49, indicate that Ottacide-P inhibits fungus growth on polyvinylchloride and its copolymers when incorporated therein. None of these references describes the concept of the present invention wherein the impregnated foam rubber acts as a source of antifungal agent to protect the user from infection and to aid in treatment of infection if contacted before use of the impregnated insoles. 
     SUMMARY OF THE INVENTION 
     The present invention provides for foam rubber insoles impregnated with Ottacide-P. Examples of polymeric materials useful for preparing the foam rubber include rubber latex, polyurethane/latex combinations, polypropylene/latex combinations, and butyl foam/latex combinations. It is preferred that the final content of Ottacide-P in the impregnated insole be from about 0.5% to about 5%. In a preferred embodiment, the impregnated insole also contains about 1% to about 10% of a deodorizer, e.g., sodium bicarbonate. The impregnated insole is prepared by mixing a slurry of the uncured latex with the additives, then casting the slurry into suitable support fabric and drying and curing the foam pad. The impregnated insoles are useful in shoes to inhibit the growth of bacteria and fungi and to act as a treatment of microbial infections such as athlete&#39;s foot. 
     DETAILED DESCRIPTION OF THE INVENTION 
     Foam rubber insoles can be formed from numerous polymeric materials. The following polymeric materials are suitable for preparing foam rubber insoles: rubber latex, polyurethane/latex combinations, polypropylene/latex combinations, and butyl foam/latex combinations. According to the present invention, the impregnated foam rubber insolve, i.e., the final cured product, contains from about 85% to about 99.5% of the polymeric materials. 
     The foam rubber insoles are prepared so that they contain the antibacterial, antifungal agent Ottacide-P. The finished, cured foam rubber insoles contain from about 0.5% to about 5.0% Ottacide-P, although higher or lower amounts may be used. It was discovered that about 70% of the Ottacide-P which was added to the latex mixture was volatilized during the curing process. As a result, it is necessary to add about 31/3 times the desired final concentration of Ottacide-P to the latex formulation in order to obtain the desired concentration in the cured insole. 
     A further aspect of the invention is to prepare the foam rubber insoles so that the cured product contains a deodorizing agent, e.g., sodium bicarbonate, in addition to Ottacide-P. This optional ingredient is utilized to control odor. If the cured foam rubber insole contains a deodorizing agent, it is present in a concentration from about 1% to about 10%. Consequently, the impregnated, cured foam rubber insole has the following composition: 
     
         ______________________________________             Generally                     Preferred______________________________________Polymeric material (foam rubber)                85-99.5%  85-98.5%Ottacide-P          0.5-5%    0.5-5%Deodorizing Agent     0-10%   1.0-10%______________________________________ 
    
     The foam rubber insoles are prepared by mixing a slurry of the uncured latex with the Ottacide-P and deodorizing agent, if desired, in appropriate concentrations to provide the concentrations described above in the cured product. The slurry is then cast onto a suitable support fabric such as bleached white drill material. The support fabric may be any of those conventionally used in preparing foam rubber insoles. The coated fabric is then dried and the latex cured at temperatures well known to workers in the art to yield the finished foam rubber insole pad. The pad can then be cut and shaped to the desired dimensions as is again well known in the art. 
     The impregnated foam rubber insoles are inserted in shoes. The deodorizing agent helps reduce or eliminate foot odor. The Ottacide-P functions to inhibit the growth of bacteria and fungi. The foam rubber insoles of the present invention have been found to act as a treatment for microbial infections, such as athlete&#39;s foot, upon use of the insole. 
    
    
     The invention will be further described by the following examples: 
     EXAMPLE 1 
     Ottacide-P and sodium bicarbonate were added to a latex mixture comprising rubber latex. The foam rubber insoles were prepared from this mixture according to established methods in the art of manufacturing foam rubber insoles. Three foam rubber insoles were prepared which had the following composition before curing and after curing: 
     
         ______________________________________        uncured mixture                   insole______________________________________(A)    Ottacide-P  1.50%        0.43%  NaHCO.sub.3 1.10%        1.10%  latex       97.4%        98.47%(B)    Ottacide-P  3.00%        1.22%  NaHCO.sub.3 1.10%        1.10%  latex       95.9%        97.68%(C)    Ottacide-P  3.00%        0.80%  NaHCO.sub.3 1.10%        1.10%  latex       95.9%        98.10%______________________________________ 
    
     EXAMPLE 2 
     Foam rubber insoles were prepared as in Example 1 and were packaged in foil. The stability of the packaged foam rubber insoles to moisture and heat was examined over a period of six months. No significant loss of the Ottacide-P and sodium bicarbonate was noted over this time period. The results of this test are shown in Table 1. 
     
                                           TABLE 1__________________________________________________________________________Stability Data for Ottacide-P Impregnated Foam Padsin Three Different Foil Laminate Packagesat 37° C. and at 70% RH at 23° C.#      1             2             3Time (mos.)  % Ottacide-P         % NAHCO.sub.3                % Ottacide-P                       % NaHCO.sub.3                              % Ottacide-P                                     % NaHCO.sub.3__________________________________________________________________________at 37° C.0      0.82   1.14   0.82   1.14   0.82   1.141      0.89   1.39   0.97   1.67   0.77   1.443      0.49   1.27   0.87   1.47   0.93   1.476      0.88   1.42   0.78   1.41   0.71   1.28at 70% Relative Humidity at 23° C.0      0.82   1.14   0.82   1.14   0.82   1.141      0.71   1.38   0.83   1.55   0.71   1.473      0.54   1.29   0.87   1.45   0.96   1.536      0.79   1.36   0.64   1.41   0.77   1.37__________________________________________________________________________ #1 as packaged in IL141 laminate (Polyethylene/foil/Polyethylene). #2 was packaged in L161 laminate (Polyethylene/foil/Polyethylene). #3 was packaged in M079 laminate (Polyethylene/foil/Polyethylene). 
    
     EXAMPLE 3 
     The foam rubber insoles A and B were tested for antifungal activity against a number of organisms according to the following procedures: 
     SEEDED AGAR PLATE METHOD FOR TESTING FUNGISTATIC ACTIVITY 
     A. Stock cultures of test fungi are maintained on Dextrose Neopeptone Agar at room temperature under sterile mineral oil. All strains are pathogenic isolates recovered from patient&#39;s lesions. 
     B. Preparation of Conidial Suspensions. Test fungi were grown on Brain-Heart Infusion agar plates for approximately two weeks to allow for luxurious conidial production. The aerial mycelia were harvested in physiologic saline with 0.05% Tween-80. The resulting suspensions were filtered through gauze and sterile absorbent cotton to remove hyphal elements but to allow the conidia to filter through. The density of the conidial suspensions was determined by counting on a hemacytometer. Suspensions were standardized to a final use concentration of approximately 5 million conidia/ml. 
     C. The Agar Plate Technique. Tubes containing 30 ml of Mycosel agar were melted and cooled at 45° C. and then inoculated with 0.2 ml of the fungal conidial suspensions. The inoculated agar was then poured aseptically into sterile disposable 9 mm petri dishes and allowed to solidify. Discs of foam rubber samples, 18 mm in diameter, were implanted in the center of the plate. Plates were incubated at 30° C. for seven to 10 days, at which time there were sharply defined zones of confluent growth surrounding the clear zones of growth inhibition around the disc. The diameters of the clear zones were measured and recorded. 
     The results are shown in Table 2, in which it can be seen that the foam rubber insoles were effective in inhibiting the growth of the various fungi. 
     
                       TABLE 2______________________________________Inhibition of Fungal Growthby Foam Rubber Insoles             Diameter of Zones of             Inhibition (mm) 1Test Organism       A         B______________________________________Trichophyton mentagrophytex #1               43        60Trichophyton mentagrophytes #2               41        54Trichophyton rubrum #1               51        63Trichophyton rubrum #2               45        58Epidermophyton flocossum #1               50        61Epidermophyton flocossum #2               52        64Candida albicans #1 24        38Candida albicans #2 25        36______________________________________ 1 Diameter of rubber foam disc = 18 mm. 
    
     While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications. This application is intended to cover any variations, uses or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known and customary practice within the art to which the invention pertains.