Formulations and Methods of Treatment for Treating Nail Fungal Infections

Abstract

The present invention relates to methods and compositions for the treatment of infections of the nails, in particular the treatment of onychomycosis.

Claims

1. A composition for the treatment of onychomycosis comprising at least one antibiotic, at least one antifungal agent in a tissue penetrating agent.

2. The composition of claim 1 further comprising a non-steroidal anti-inflammatory agent.

3. The composition of claim 2 wherein the antifungal agents are itraconazole and fluconazole and the antibiotics are vancomycin, levofloxacin and mupirocin.

4. The composition of claim 3 wherein the antifungal agents are itraconazole and fluconazole and the antibiotics are vancomycin, levofloxacin and mupirocin and the non-steroidal anti-inflammatory agent is ibuprofen.

5. The composition of claim 6 wherein the itraconazole is at about 0.5 wt % to about 1.5 wt %, the fluconazole is about 0.5 wt % to about 1.5 wt %, the vancomycin is about 4 wt %to about 5 wt %, the levofloxacin is about 1 wt % to about 3 wt %, the mupirocin is about 3 wt % to about 5 wt % and the ibuprofen is about 1 wt % to about 3 wt % and the tissue penetrating agent is DMSO.

6. The composition of claim 5 wherein the itraconazole is at about 1 wt %, the fluconazole is about 1 wt %, the vancomycin is about 5 wt %, the levofloxacin is about 2 wt %, the mupirocin is about 4 wt % and the ibuprofen is about 2 wt % and the tissue penetrating agent is DMSO.

7. A method treating onychomycosis comprising administering to the nail(s) of a patient having onychomycosis the composition of claim 5.

8. The method of claim 7 wherein the administration is daily

9. The method of claim 8 wherein the duration of the treatment is at least a week.

10. A method of determining an optimal formulation for treating onychomycosis in an individual patient comprising: a) testing a nail sample that is infected; b) determining the pathogen species present in the infection; and c) formulating a composition for treating onychomycosis based on the types of fungal and/or bacterial species present in the sample.

11. The method of claim 10 wherein the sample is tested by real time PCR or multiplex PCR assay.

12. The method of claim 10 wherein the sample is tested by DNA sequencing.

13. The method of claim 12 wherein the sample tested by DNA sequencing can determine the relative percentage of pathogens in the sample.

14. A composition for the treatment of onychomycosis comprising hydrogen peroxide and an antibiotic.

15. The composition of claim 14 wherein the antibiotic is either vancomycin or clindamycin.

16. The composition of claim 15 wherein the vancomycin is present in an amount from 1-5 wt %.

17. The composition of claim 15 wherein the clindamycin is present in an amount from 1-5 wt %.

18. The composition of claim 14 wherein the hydrogen peroxide is present in an amount of about 20 to about 30%.

19. The composition of claim 18 wherein the vancomycin is present in an amount from 1-5 wt %.

20. The composition of claim 18 wherein the clindamycin is present in an amount from 1-5 wt %.

Description

EXAMPLES

Example 1

DNA Sequencing of OMB infection

[0028] DNA sequencing methods were used to identify pathogens and estimate the percentage population of those pathogens present in specimens of OMB. Seven patients with OMB were tested to determine the pathogens present in the OMB sample. Table 1 indicates the frequency of pathogens present in the samples.

TABLE-US-00001 TABLE 1 Detected Not Detected Pathogen Acinetobacter baumannii 0 7 Escherichia coli 0 7 Enterobacter aerogenes 0 7 Enterobacter cloacae 0 7 Enterococci faecalis 1 6 Enterococci faecium 0 7 Klebsiella pneumoniae 0 7 Proteus mirabilis 1 6 Pseudomonas aeruginosa 0 7 Serratia marcescens 0 7 Stenotrophonmonas maltophilia 0 7 Methicillin resistant staph aureus 2 5 Staphylococcus aureus 0 7 Panton-Vallentine leucocidin (PVL) gene 0 7 Coagulase negative Staphylococcus 3 4 Methicillin resistant Coagulase negative Staphylococcus 3 4 Staphylococcus epidermidis 2 5 Antibiotic resistant Aminoglycosides resistance 1 6 Cephalosporin resistance 4 3 Erythromycin-Clindamycin resistance 5 2 Methicillin resistant (staphylococcus) 4 3 Tetracycline resistance 6 1 Vancomycin resistance 0 7

[0029] In another study the following pathogens were found in specimen at the given percentage:

TABLE-US-00002 TABLE 2 Pathogen Percentage Staphylococcus epidermis 82% Cornebacterium kroppenstedii  8% Propionibacterium granulosum  3% Staphylococcus pasteuri  2%

[0030] Within this disclosure, any indication that a feature is optional is intended provide adequate support (e.g., under 35 U.S.C. 112 or Art. 83 and 84 of EPC) for claims that include closed or exclusive or negative language with reference to the optional feature. Exclusive language specifically excludes the particular recited feature from including any additional subject matter. For example, if it is indicated that A can be drug X, such language is intended to provide support for a claim that explicitly specifies that A consists of X alone, or that A does not include any other drugs besides X. “Negative” language explicitly excludes the optional feature itself from the scope of the claims. For example, if it is indicated that element A can include X, such language is intended to provide support for a claim that explicitly specifies that A does not include X. Non-limiting examples of exclusive or negative terms include “only,” “solely,” “consisting of,” “consisting essentially of,” “alone,” “without”, “in the absence of (e.g., other items of the same type, structure and/or function)” “excluding,” “not including”, “not”, “cannot,” or any combination and/or variation of such language.

[0031] Similarly, referents such as “a,” “an,” “said,” or “the,” are intended to support both single and/or plural occurrences unless the context indicates otherwise. For example “a dog” is intended to include support for one dog, no more than one dog, at least one dog, a plurality of dogs, etc. Non-limiting examples of qualifying terms that indicate singularity include “a single”, “one,” “alone”, “only one,” “not more than one”, etc. Non-limiting examples of qualifying terms that indicate (potential or actual) plurality include “at least one,” “one or more,” “more than one,” “two or more,” “a multiplicity,” “a plurality,” “any combination of,” “any permutation of,” “any one or more of,” etc. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context.

[0032] Where ranges are given herein, the endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[0033] All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

[0034] While this invention has been particularly shown and described with references to example embodiments thereof, it will be understood by those skilled in the art that the various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.