Title:  Composition and method for topically treating Peyronie's Disease, Dupuytren's hand contracture, Ledderhose Fibrosis, erectile dysfunction arising from plaque accumulations, and scarring

United States Patent:  6,353,028

Appl. No.:  411175

The invention is of a topical medicament and associated methodology for use thereof, through the use of which fibrotic or connective tissue disorders involving scarring, sub-dermal plaque accumulations or fibrosis of muscle tissue may be effectively, cost effectively, and painlessly treated. One or more calcium channel blocker agents serve as the primary active ingredient of the present compositions, with carrier agents facilitating non-invasive transdermal delivery of the calcium channel blocker(s) to subdermal disease sites.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a novel medicament useful in the treatment of connective tissue disorders, exemplified by sub-dermal plaque formation and accumulation, such as Peyronie's disease, Dupuytren's contracture, Ledderhose Fibrosis and fibrosis of muscle tissue such as underlies erectile dysfunction.

It is another object of the present invention to provide a novel and unobvious medicament useful in the treatment of conditions characterized by hyperprolipheration of connective tissue such as Peyronie's disease, Dupuytren's contracture, Ledderhose Fibrosis, and scarring.

It is another object of the present invention to provide a novel and unobvious medicament useful in the treatment of fibrotic tissue disorders, which medicament is more effective than existing means for treatment.

It is another object of the present invention to provide a novel and unobvious medicament useful in the treatment of connective tissue disorders through the non-invasive, topical application thereof.

It is another object of the present invention to provide a novel and unobvious medicament useful in the treatment of connective tissue disorders through the non-invasive, topical application thereof, which topical application is of at least equal efficacy than invasive and/or less convenient treatment regimens.

In satisfaction of these and related objectives, Applicant's present invention provides a topical medicament and associated methodology for use thereof, through the use of which Peyronie's disease, Dupuytren's contracture, Ledderhose Fibrosis, and related fibrotic tissues disorders (including scarring and fibrosis-based erectile dysfunction) may be effectively, cost effectively, and painlessly treated.

The invention, although exemplified by specific embodiments which are based upon, or rely on the use of specific calcium channel blockers, is not limited to such species. Rather, observations by the present inventor indicate that when coupled with a suitable carrier for transdennal delivery, all thus-far-evaluated calcium channel blockers effect reduction of fibrotic tissue disorder symptoms. Therefore, the true scope of the invention encompasses preparations and methods of use facilitating or involving the use of transdermal application of calcium channel blockers in the treatment of fibrotic tissue disorders which exhibit subdennal plaque accumulations (Peyronie's disease, Dupuytren's contracture, and Ledderhose Fibrosis, for example) or scarring.

The medicament of the present invention is a topical gel which has repeatably effected, in many cases, a complete reversal of perceptible Peyronie's disease symptoms, and in all cases, a substantial reduction of such symptoms to a substantially greater degree and substantially higher incidence than previously experienced by patient populations over-all, and in individual instances wherein patients had previously attempted alternative treatment regimens.

All observations of efficacy of the present compositions and methods arise from physician-supervised and prescribed treatment regimens involving use of the medicaments of the present invention. In most cases to date, use of the present medicaments and prescribed treatment regimens followed prior, wholly or substantially unsuccessful attempts to treat patients' fibrotic tissue disorders, most such cases to date involving Peyronie's disease. Recent studies (as discussed below) involve the treatment of erectile dysfunction though use of the medicaments taught herein. These later studies indicate that use of topical calcium channel blocker medicaments taught herein are highly effective in treating erectile dysfunction which appear to relate to fibrosis of cavernosal smooth muscle tissue.

In a experimental study, 142 patients reporting decreased quality erections were treated with topical Verapamil (80 mg/mL). One hundred thirty four (94.3%) experienced improvement of erectile rigidity and/or improvement of penile girth upon erection. These patients applied 0.5 mL of the Verapamil topical compound to the entire shaft of the penis twice a day. The length of treatment varied from one to several months, with the mean treatment period being 3.5 months. Patients were either examined or interviewed and counseled at least every thirty days in order to evaluate progress and monitor side effects. The only side effect reported was contact dermatitis in less than one percent of the patient population. This side effect was easily controlled with topical corticosteroids.

Similar results have been observed in patients treated with a topical Nifedipine compound (40-60 mg/ml) or a combination of Verapamil and Nifedipine.

Formulations for the topical Verapamil, Nifedipine, and combination Verapamil-Nifedipine are identical to those provided herein with respect to Peyronie's Disease and the other discussed connective tissue disorders.

Upon initial suggestion of the present compositions and methods for use in treating fibrotic or connective tissue disorders, the present inventor experienced, at the hands of experienced practitioners in the field, expressions of serious doubt as to efficacy, and, in some cases, outright ridicule. The stated basis for such initial doubts and criticisms related to the fact that intralessional injections of precisely the same substances (calcium channel blockers) in the attempted treatment of Peyronie's disease and similar fibrotic tissue disorders had yielded very sporadic and limited results. The present inventor was told repeatedly by those experienced in the treatment of fibrotic tissue disorders (Peyronie's disease, in particular) that a topical preparation based on calcium channel blockers could "never" have efficacy in view of the failure of injections of the same substances directly into the plaques of these conditions. As mentioned previously, actual experience teaches that the strikingly counter-intuitive effect of the compositions and methods of the present invention in the treatment of fibrotic tissue disorders is very much real--a fact born out by the substantial commercial success of the present medicaments in a very short time (less than a year at the time of preparation of this application) and with no commercial marketing whatsoever, as well as the immediate replacement of existing treatment regimens by the medicaments and methods of the present invention by numerous medical practitioners.

Another remarkable use of the medicaments of the present invention (all based on topically applied calcium channel blocker preparations) relates to the treatment of existing scars, such as arise from injury and surgical procedures. Preliminary studies indicate that the topical channel blocker preparations of the present invention, when applied to existing scars (as opposed to sites of injury in any attempt to prevent scar formation ab initio) substantially reduces the dimensions and color aberrations of scars.

Claim 1 of 1 Claim

I claim:

1. A method for treating a connective tissue disorder selected from the group consisting of Peyronie's disease, Dupuytren's hand contracture and Ledederhose Fibrosis, each disorder manifesting sub-dermal plaque accumulations or scar tissue, wherein the method consists of non-invasive transdermal application of a topical gel composition to a portion of dermis which overlies the sub-dermal plaque or scar tissue, said composition consisting essentially of (i) a calcium channel blocker selected from the group consisting of verapamil, nifedipine, diltiazem, amalodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine, bepridil and mixtures thereof; and (ii) a non-invasive transdermal carrier agent.

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