Compositions and Methods for Treatment of Infections

Abstract

This invention relates to the field of topical treatments for infections such as nail infections, particularly fungal infections of the nail commonly referred to as onychomycosis. Particularly, the invention relates to novel compositions containing peroxide for the treatment of such nail infections and other infections.

Claims

1. An anti-infective composition comprising by weight at least 3% peroxide, at least 40% highly volatile solvent, and optionally water.

2. The composition of claim 1, which is an antifungal composition.

3. The composition of claim 1, wherein the peroxide is selected from the group consisting of hydrogen peroxide, peroxide complexes, and adducts thereof.

4. The composition of claim 3, wherein the peroxide is hydrogen peroxide.

5. The composition of claim 3, wherein the peroxide is carbamide peroxide.

6. The composition of claim 1, wherein the highly volatile solvent is an alcohol.

7. The composition of claim 5, wherein the alcohol is selected from the group consisting of methanol, ethanol, n-propanol, and isopropanol.

8. The composition of claim 7, wherein the alcohol is isopropanol.

9. The composition of claim 1, further comprising a thickening agent.

10. The composition of claim 9, wherein the thickening agent is selected from the group consisting of hydroxypropylcellulose, polyvinylpyrrolidones, polyvinylpyrrolidone/vinyl acetates, and glyceryl polyacrylates.

11. The composition of claim 10, wherein the thickening agent is hydroxpropylcellulose.

12. The composition of claim 1, wherein the peroxide is present from about 3% to 20%.

13. The composition of claim 12, wherein the peroxide is present from about 6% to 15%.

14. The composition of claim 13, wherein the peroxide is present from about 9% to 12%.

15. The composition of claim 1, wherein the highly volatile solvent is present from about 40% to 90%.

16. The composition of claim 1, wherein the thickening agent is present in an amount less than about 10%.

17. The composition of claim 16, wherein the thickening agent is present from about 0.25% to 2.5%.

18. A method of treating infections, comprising the step of applying the composition of claim 1.

19. The method of claim 18, wherein the infection is selected from the group consisting of fungal onychomycosis, ringworm, and canker sores.

20. The method of claim 19, wherein the applying step is performed a plurality of times per day for a plurality of days, whereby the infection is at least partially ameliorated.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0020] This invention provides a method of administering to an infected nail of an animal or human, an effective amount of a peroxide, such as hydrogen peroxide, which yields a thin film of such peroxide at a higher concentration than is possible with typical aqueous solution such as an aqueous solution of 3% H.sub.2O.sub.2. The invention is particularly effective for treatment of a fungus-infected nail. The unique composition of the invention provides for the site of administration being tightly controlled: i.e., only the nail receives the treatment. Peroxide is delivered rapidly into the nail within less than an hour, in contrast to the delivery of conventional antifungal topical treatments which often can be measured in days.

[0021] The composition of the invention is generally a peroxide, a highly volatile solvent, and optionally water. One preferred optional additional component is a thickening agent, which provides for even more tightly controlled site of application. Other optional additional elements may be included, such as fragrances, dyes, surfactants, etc.

[0022] As shown in the Examples below, a variety of embodiments demonstrate penetration into a normal or infected nail of peroxide from such compositions of the invention. In such application, within fifteen minutes a stinging sensation is felt beneath the nail, and the nail turns white. The compositions of this invention penetrate the nail so quickly that within thirty minutes the active peroxide has penetrated the nail and has begun to attack the noxious fungal infection. With other known antifungal composition formulations, nail penetration is normally observed to occur within days or weeks.

The Peroxide Active Agent

[0023] Effective concentrations of peroxide range from 3-20%, 7-15%, 8-12%, or about 9-10%. In one embodiment, the peroxide is hydrogen peroxide at a concentration, by weight, of about 3-6%. In one embodiment, the peroxide is hydrogen peroxide at a concentration, by weight, of about 6-9%. In another embodiment, the hydrogen peroxide is present in a concentration of about 9-12%. In another embodiment, the hydrogen peroxide is present in a concentration of about 12-15%.

[0024] Other peroxides are equally suitable for use in the invention, including adducts of H.sub.2O.sub.2 such as carbamide peroxide. In some embodiments, the peroxide component of the invention comprises at least two different peroxides. For example, hydrogen peroxide may be combined with carbamide peroxide to provide an effective concentration of peroxide active agent in a composition of the invention. The peroxide component of the invention may be combined with the other components as a full strength highly concentrated form, or may be diluted with water prior to combination into the composition of the invention. For example, a 25% peroxide composition may be prepared by combining a 50% aqueous peroxide solution with an equal volume of highly volatile solvent. The thickening agent may be added next, together with any other desirable additional components, such as fragrances, dyes, and/or surfactants. The composition of the invention may also be prepared as a concentrate, requiring only dilution with water or solvent to bring to end-user working strength.

The Highly Volatile Solvent

[0025] Highly volatile solvents are those which generally evaporate at least about twice as fast as water.

[0026] The highly volatile solvent of the composition is generally a low molecular weight alcohol, but other highly volatile solvents may be adapted for use in the invention. Such highly volatile solvents may be selected from those capable of dissolving the peroxide and water components of the invention, and thus includes, but is not limited to, acetone, tetrahydrofuran, and acetonitrile.

[0027] Alkyl alcohols are generally preferred as the highly volatile solvents for use in the invention, preferably lower alkyl alcohols such as methanol, ethanol, and propanol, although other alcohols are amenable to such use. Isopropyl alcohol and ethanol are particularly useful in the invention because they are in common use and are generally regarded as safe.

[0028] The highly volatile solvent is generally present in the composition of the invention at an amount of between about 40% to 95%, by weight.

[0029] In some embodiments, the highly volatile solvent component of the invention comprises at least two or more different solvents. For example, in one embodiment, isopropyl alcohol may be combined with ethanol to produce an effective volatile solvent for use in the composition of the invention.

The Thickening Agent

[0030] The thickening agent of the composition of the invention promotes application of the composition by virtue of its film-forming properties, and retention of the composition on the nail. The thickening agents of the invention may be gelling agents, film-forming agents, and other thickeners. Appropriate thickening agents allow for the composition to be applied by a variety of applicators, including brushes, droppers, patch, and sponges. In one embodiment, the thickening agent is a polymer which, after a certain period of time, ranging from a few minutes to an hour, the user may simply wash off from the nail.

[0031] The thickening agents of the invention include polymers such as hydroxypropyl cellulose. In one embodiment, the thickening agent is hydroxypropyl cellulose, a gelling agent, e.g., Klucel HF, however, other gelling agents may be used so long as they can dissolve in the hydrogen peroxide/highly volatile solvent (and optionally water) composition. Other thickening agent polymers include polyvinylpyrrolidones, polyvinylpyrrolidone/vinyl acetates, and glyceryl polyacrylates. Those of skill in the art will appreciate the wide variety of thickening agents suitable for use in the invention.

[0032] The amount of gelling/thickening agent in the composition generally ranges from 0% to about 10%, or 0.1% to 5%, or 0.2 to 2%, or 0.3 to 1%, or about 0.5%. In one embodiment, the thickening agent is Klucel HF present at about 0.5% by weight.

[0033] The composition of the invention may also contain water as an additional component. Generally, the amount of water is less than about 60%, depending on the concentrations of peroxide, highly volatile solvent, and optional components.

Other Optional Ingredients

[0034] Other optional ingredients include thickening agents, fragrances, dyes, surfactants, excipients, and the like. Additionally, local anesthetics such as lidocaine may be components of the composition such that any mild discomfort associated with higher concentrations of peroxide penetration through the nail is ameliorated.

A Treatment Regimen

[0035] The composition of the invention may be applied as frequently as needed for effective treatment. For example, the composition can be applied once an hour two or three times each day over the course of a week to achieve healthy nail growth. Low concentrations of H.sub.2O.sub.2such as 3% can be applied as frequently as every few minutes. Thus, instead of using a single dose of higher concentration, multiple applications of lower concentrations can be used. The composition may be applied with an applicator, whether a brush, a dropper, or the like. A thin film of liquid or thickened liquid is applied, and allowed to dry.

[0036] Initial penetration of the peroxide through the nail produces the commonly recognized whitening effect, demonstrating such penetration. Lower levels of hydrogen peroxide in the present invention can be used to treat infected skin or mucous membranes such as canker sores. Depending on the concentration of peroxide, penetration through a nail will also elicit sensations in certain subjects ranging from tingling to burning, which may be mildly painful at higher concentrations. Embodiments of the invention comprising an optional local anesthetic may be appropriate when using such higher concentrations. Effectiveness may be measured by a reduction of, or complete eradication of, the nail fungus over the course of treatment, and further evidenced by healthy nail growth.

[0037] Other embodiments, uses, and advantages of the present invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. The specification and examples should be considered exemplary only. The intended scope of the invention is only limited by the claims appended hereto.

EXAMPLES

[0038] The present invention will be further understood by reference to the following non-limiting examples.

Example 1

A Composition of the Invention

[0039] On a weight basis, 9% hydrogen peroxide, 21% water, 69.5% isopropyl alcohol, and 0.5% Klucel HF (a thickening agent, a hydroxypropylcellulose polymer), were mixed in a vessel and allowed to thicken. (The source of the peroxide was a 30% peroxide solution.) The composition could easily be brushed onto a nail surface, which dried in approximately 1 minute, and the residual polymer could subsequently be removed by washing in water. Within a few minutes, a whitening effect of the nail was observed. Within 15 minutes, the subject noted mild pain under the nail.

Example 2a

A Composition of the Invention

[0040] On a weight basis, 6% hydrogen peroxide, 6% water, 87.5% isopropyl alcohol, and 0.5% Klucel HF, were mixed in a vessel and allowed to thicken. (The source of the peroxide was a 50% peroxide solution.) The composition could easily be brushed onto a nail surface, which dried in approximately 1 minute, and the residual polymer could subsequently be removed by washing in water. Within approximately one minute, a significant whitening effect of the nail was observed. Within 15 minutes, one subject noted pain under the nail, while another noted a tingling sensation. In one subject, the composition was applied twice daily to a fungus-infected nail for a period of 2 weeks, at which time new, healthy nail growth was observed. The treatment regimen was terminated.

[0041] Comparative Example 2b

A Composition Lacking a Highly Volatile Solvent

[0042] On a weight basis, 6% hydrogen peroxide, 93.5% water, and 0.5% Klucel HF, were mixed in a vessel and allowed to thicken. The resulting composition differed from that of Example 2a in that there was no isopropyl alcohol or any other highly volatile solvent, the quantity thereof being replaced with water. The composition could easily be brushed onto a nail surface, which dried in approximately 5 minutes, and the residual polymer could subsequently be removed by washing in water. Within 15 minutes of application, no whitening effect of the nail was observed, nor were any sensations of tingling, burning, or pain observed by the patient.

Example 3

A Composition with Insufficient Initial Concentration of Hydrogen Peroxide

[0043] On a weight basis, 3% hydrogen peroxide, 3% water, 93.5% isopropyl alcohol, and 0.5% Klucel HF, were mixed in a vessel and allowed to thicken. (The source of the peroxide was a 50% peroxide solution.) The composition could easily be brushed onto a nail surface, which dried in approximately 1 minute, and the residual polymer could subsequently be removed by washing in water. After even 15 minutes of application no significant whitening effect of the nail was observed. However, if three applications of the 3% H.sub.2O.sub.2are applied about two minutes apart, significant whitening of the nail could be seen, and after 15-30 minutes a slight sensation could be felt beneath the nail.

Example 4

A Composition of the Invention

[0044] On a weight basis, 9% hydrogen peroxide, 9% water, 81.5% isopropyl alcohol, and 0.5% Klucel HF, were mixed in a vessel and allowed to thicken. (The source of the peroxide was a 50% peroxide solution.) The composition could easily be brushed onto a nail surface, which dried in approximately 1 minute, and the residual polymer could subsequently be removed by washing in water. Within a few minutes, a significant whitening effect of the nail was observed.

Example 5

A Composition of the Invention

[0045] On a weight basis, 12% hydrogen peroxide, 12% water, 75.5% isopropyl alcohol, and 0.5% Klucel HF, were mixed in a vessel and allowed to thicken. (The source of the peroxide was a 50% peroxide solution.) The composition could easily be brushed onto a nail surface, which dried in approximately 1 minute, and the residual polymer could subsequently be removed by washing in water. Within one minute, a significant whitening effect of the nail was observed. Within 15 minutes, one subject noted pain (a burning sensation) under the nail.

Example 6

A Composition of the Invention

[0046] On a weight basis, 18.5% carbamide peroxide, 3.0% glycerol, 73.1% ethyl alcohol, 4.5% luviskol VA 64-polyvinylpyrrolidone vinyl alcohol, and 0.9% Klucel HF, were mixed in a vessel and allowed to thicken. The source of peroxide was solid carbamide peroxide, which is only soluble in isopropyl alcohol to about 10% and in ethanol to about 20%, therefore luviskol VA 64-polyvinylpyrrolidone vinyl alcohol is added to supersaturate the carbamide peroxide, and glycerol is added to retain the carbamide peroxide in solution following ethanol evaporation. This composition did show a modest level of precipitation upon overnight rest at 60 F. Subsequent experimentation proved that replacing the ethyl alcohol with methanol successfully retained the carbamide peroxide in solution.

[0047] The composition (with ethanol rather than methanol) could easily be brushed onto a nail surface, which dried in approximately 5 minutes, and the residual polymer could subsequently be removed by washing in water. Within one minute some whitening effect of the nail was observed. After 15 minutes, the subject reported no burning, tingling, or other painful sensation.

Example 7

A Composition of the Invention

[0048] On a weight basis, 6% hydrogen peroxide, 54% water, and 40% isopropyl alcohol were mixed in a vessel and allowed to thicken. (The source of the peroxide was a 50% peroxide solution.) The composition could easily be brushed onto a nail surface, which dried in approximately 1 minute. Within approximately one minute, some whitening effect of the nail was observed.

[0049] The present invention is not to be limited in scope by the specific embodiments described above, which are intended as illustrations of aspects of the invention. Functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those shown and described herein, will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims. All cited references are hereby incorporated by reference.