Electrically assisted transdermal method and apparatus for the treatment of erectile dysfunction

• US 6,266,560 B1
• Filed: 06/18/1999
• Issued: 07/24/2001
• Est. Priority Date: 06/19/1998
• Status: Expired due to Fees

• Current Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Zhang, Lei, Hofmann, Gunter A., Rabussay, Dietmar
• Primary Examiner(s): Kamm, William E.
• Application Number:
  US09/336,400
• Time in Patent Office: 767 Days
• Field of Search: 607/39, 607/43, 607/20
• US Class Current: 604/20
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: Y10S 977/906 Drug delivery

Abstract

A non-invasive method is provided for treating erectile dysfunction using electroporation enhanced with delivery of a vasoactive or androgenic composition applied to the penis which affords an alternative treatment for patients afflicted with erectile dysfunction (ED). Sufficient electric pulses temporarily create new pathways in the penile skin thereby driving a composition, such as a vasoactive or androgenic medication, into the corporal cavernosum.

Claims

1. A method for enhancing erectile function in a subject, said method comprising applying an electric pulse to the penis and substantially contemporaneously applying a vasoactive or androgenic composition thereto, said electric pulse having sufficient strength and duration for transdermally introducing an effective amount of the composition into the penis, thereby enhancing erectile function in the subject.

2. The method of claim 1, wherein the electric pulse is applied to the penile glans.

3. The method of claim 1, wherein the electric pulse is applied to the penile shaft.

4. The method of claim 1, wherein the electric pulse has a voltage from about 50 to 80 volts.

5. The method of claim 1, wherein multiple electric pulses are applied.

6. The method of claim 1, further comprising restricting venous flow from the penis.

7. The method of claim 1, further comprising iontophoresis.

8. The method of claim 1, further comprising vibration.

9. The method of claim 1, further comprising administering a vasoactive or androgenic composition to the subject orally, by injection or transurethrally.

10. The method of claim 1, wherein said composition is a vasoactive composition selected from the group consisting of prazosin, PGE₁, PGE₂, PGE₁, papeverine, PGA₁, PGB₁, PGF₁, 19-hydroxy-PGA₁, 19-hydroxy-PGB₁, PGE₂, PGA₂, PGB₂, 19-hydroxy-PGA₂, 19-hydroxy-PGB₂, PGE₃, PGF₃, PGI₁, PGI₂, carboprost tromethamine, dinoprost tromethamine, dinoprostone, lipoprost, gemeprost, metenoprost, sulprostone, tiaprost, nitroglycerin, isosorbide dinitrate, erythrityl tetranitrate, amyl nitrate, sodium nitroprusside, molsidomine, (Z)-1-{N-methyl-N-[6-(N-methyl-ammoniohexyl)amino]}diazen-1-ium-1,2-diolate (MAHMA/NO), (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA/NO), (Z)-1-{N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino}diazen-1-ium-1,2-diolate (SPER/NO), sodium (Z)-1-(N,N-diethylamino)diazenium-1,2-diolate (DEA/NO), linsidomine (SIN-1), S-nitrosothiols, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), S-nitroso-N-cysteine and S-nitroso-N-glutathione (SNO-GLU), smooth muscle relaxants, leukotriene inhibitors, calcium channel blockers, α

1-adrenergic antagonists, α

2-adrenergic agonists, phosphodiesterase inhibitors, antihypertensive agents, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, phenoxybenzamine, dibenamine, doxazosin, terazosin, phentolamine, tolazoline, prazosin, trimazosin, alfuzosin, indoramin, ergotamine analogs, ergotamine analogs, acetergamine, brazergoline, bromerguride, cianergoline, delorgotrile, disulergine, ergonovine maleate, ergotamine tartrate, etisulergine, lergotrile, lysergide, mesulergine, metergoline, metergotamine, nicergoline, pergolide, propisergide, proterguride, terguride, diazoxide, hydralazine and minoxidil, nimodepine, pinacidil, cyclandelate, dipyridamole, isoxsuprine, chlorpromazine, haloperidol, yohimbine, trazodone, apomorphine, bromocriptine, naltrexone and vasoactive intestinal peptide.

11. The method of claim 1, wherein said composition is an androgenic composition selected from the group consisting of:

androsterone, testosterone, dihydrotestosterone, dehydroepiandrosterone (DHEA), DHEA sulfate, enanthate, propionate, cypionate esters of testosterone, phenylacetate esters of testosterone, testosterone alkyls, methyltestosterone, testolactone, oxymetholone and fluoxymesterone.

12. A method for treating impotence in a subject comprising applying an electric pulse to the penis of the subject and substantially contemporaneously applying a vasoactive or androgenic composition thereto, said electric pulse having sufficient strength and duration for transdermally introducing an effective amount of the composition into the penis thereby enhancing erectile function in the subject.

13. The method of claim 12, wherein the electric pulse is applied to the penile glans.

14. The method of claim 12, wherein the electric pulse is applied to the penile shaft.

15. The method of claim 12, wherein the electric pulse has a voltage from about 50 to 80 volts.

16. The method of claim 12, wherein multiple electric pulses are applied.

17. The method of claim 12, further comprising restricting venous flow from the penis.

18. The method of claim 12, further comprising iontophoresis.

19. The method of claim 12, further comprising vibration.

20. The method of claim 12, further comprising administering a vasoactive or androgenic composition to the subject orally, by injection or transurethrally.

21. The method of claim 12, wherein said composition is a vasoactive composition selected from the group consisting of prazosin, PGE₁, PGE₂, PGE₁, papeverine, PGA₁, PGB₁, PGF₁, 19-hydroxy-PGA₁, 19-hydroxy-PGB₁, PGE₂, PGA₂, PGB₂, 19-hydroxy-PGA₂, 19-hydroxy-PGB₂, PGE₃, PGF₃, PGI₁, PGI₂, carboprost tromethamine, dinoprost tromethamine, dinoprostone, lipoprost, gemeprost, metenoprost, sulprostone, tiaprost, nitroglycerin, isosorbide dinitrate, erythirityl tetranitrate, amyl nitrate, sodium nitroprusside, molsidomine, (Z)-1-{N-methyl-N-[6-(N-methyl-ammoniohexyl)amino]}diazen-1-ium-1,2-diolate (MAHMA/NO), (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA/NO), (Z)-1-{N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]amino}-diazen-1-ium-1,2-diolate (SPER/NO), sodium (Z)-1-(N,N-diethylamino)diazenium-1,2-diolate (DEA/NO), linsidomine (SIN-1), S-nitrosothiols, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), S-nitroso-N-cysteine and S-nitroso-N-glutathione (SNO-GLU), smooth muscle relaxants, leukotriene inhibitors, calcium channel blockers, α

1-adrenergic antagonists, α

2-adrenergic agonists, phosphodiesterase inhibitors, antihypertensive agents, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, phenoxybenzamine, dibenamine, doxazosin, terazosin, phentolamine, tolazoline, prazosin, trimazosin, alfuzosin, indoramin, ergotamine analogs, ergotamine analogs, acetergamine, brazergoline, bromerguride, cianergoline, delorgotrile, disulergine, ergonovine maleate, ergotamine tartrate, etisulergine, lergotrile, lysergide, mesulergine, metergoline, metergotamine, nicergoline, pergolide, propisergide, proterguride, terguride, diazoxide, hydralazine and minoxidil, nimodepine, pinacidil, cyclandelate, dipyridamole, isoxsuprine, chlorpromazine, haloperidol, yohimbine, trazodone, apomorphine, bromocriptine, naltrexone and vasoactive intestinal peptide.

22. The method of claim 12, wherein said composition is an androgenic composition selected from the group consisting of:

androsterone, testosterone, dihydrotestosterone, dehydroepiandrosterone (DHEA), DHEA sulfate, enanthate, propionate, cypionate esters of testosterone, phenylacetate esters of testosterone, testosterone alkyls, methyltestosterone, testolactone, oxymetholone and fluoxymesterone.

23. A method for delivering a composition into the penis of a subject comprising applying an electric pulse to the penis and substantially contemporaneously applying the composition to the penis, said electric pulse having sufficient strength and duration for transdermally introducing the composition into the penis in an amount greater than provided by passive diffusion of the composition into the penis when applied thereto.