Treatment of erectile dysfunction and other indications
Inventors
Assignees
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Publication Number
US-9833456-B2
Publication Date
2017-12-05
Expiration Date
Abstract
The present invention generally relates to the transdermal delivery of various compounds. In some aspects, transdermal delivery may be facilitated by the use of a hostile biophysical environment. One set of embodiments provides a composition for topical delivery comprising a phosphodiesterase type 5 inhibitor and/or a salt thereof, and optionally, a hostile biophysical environment and/or a nitric oxide donor. In some cases, the composition may be stabilized using a combination of a stabilization polymer (such as xanthan gum, KELTROL® BT and/or KELTROL® RD), propylene glycol, and a polysorbate surfactant such as Polysorbate 20, which combination unexpectedly provides temperature stability to the composition, e.g., at elevated temperatures such as at least 40° C. (at least about 104° F.), as compared to compositions lacking one or more of these.
Core Innovation
The disclosure relates to transdermal and topical compositions and methods for treating sexual dysfunction, including erectile dysfunction. A composition comprising a cream, gel, or lotion is applied to a genital region to produce an erection in less than 15 minutes after application. The composition includes a phosphodiesterase type 5 (PDE5) inhibitor, with examples including sildenafil and related agents such as avanafil, lodenafil, mirodenafil, tadalafil, vardenafil, udenafil, acetildenafil, and thiomethisosildenafil, and it optionally includes a nitric oxide donor.
The compositions are formulated to remain effective in a hostile biophysical environment, including an environment characterized by high chloride and ionic strength. In this context, the composition can include nitric oxide donor components comprising L-arginine and/or L-arginine hydrochloride together with an ionic salt at at least about 0.25 M. The formulation further includes xanthan gum at no more than about 1 wt %, propylene glycol at at least about 6% by weight, and Polysorbate 20 at no more than about 3 wt %.
A stabilization strategy combines a stabilization polymer such as xanthan gum and stabilization polymers of the KELTROL® types, together with propylene glycol and a Polysorbate such as Polysorbate 20, to achieve temperature stability and improved transdermal delivery/local effects. The stabilization approach is described as enabling unexpected temperature stability, including stability at least 40°C, and reducing systemic exposure while maintaining delivery performance. The disclosure also describes formulation approaches involving oil/water and water-in-oil emulsions for topical or transdermal delivery concepts.
Claims Coverage
The independent claims are clm-00001 and clm-00012. The claims each center on applying a cream, gel, or lotion to a genital region with a nitric oxide donor and specified excipient concentration limits, together with a pharmaceutical agent for treating sexual dysfunction.
Rapid erection after genital application with specified formulation limits
Applying a composition comprising a cream, gel, or lotion to the genital region, including in one independent claim to a male subject, such that the composition produces an erection in less than 15 minutes after application, while the composition includes a nitric oxide donor, an ionic salt, xanthan gum, propylene glycol, Polysorbate 20, and a pharmaceutical agent for treating sexual dysfunction.
Nitric oxide donor with high ionic salt plus excipient concentration constraints
Providing a nitric oxide donor comprising L-arginine and/or L-arginine hydrochloride at about 2.5% to about 15% by weight, an ionic salt at at least about 0.25 M, xanthan gum at no more than about 1 wt %, propylene glycol at at least about 6% by weight, and Polysorbate 20 at no more than about 3 wt %, together with a pharmaceutical agent and/or salt thereof at at least about 0.1% by weight.
Across clm-00001 and clm-00012, the core claim coverage is directed to topical/transdermal genital application using a cream, gel, or lotion containing a nitric oxide donor within a specified concentration range, combined with an ionic salt above a minimum level and constrained amounts of xanthan gum, propylene glycol, and Polysorbate 20, while including a pharmaceutical agent for treating sexual dysfunction.
Stated Advantages
Improved transdermal delivery/local effects with reduced systemic exposure.
Unexpected temperature stability, including stability at least 40°C.
Erection produced in less than 15 minutes after application.
Documented Applications
Topical or transdermal application of a cream, gel, or lotion to the genital region for treating sexual dysfunction, including erectile dysfunction.
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