CA2344435A1 - Compositions for the treatment of male erectile dysfunction - Google Patents

Compositions for the treatment of male erectile dysfunction Download PDF

Info

Publication number
CA2344435A1
CA2344435A1 CA002344435A CA2344435A CA2344435A1 CA 2344435 A1 CA2344435 A1 CA 2344435A1 CA 002344435 A CA002344435 A CA 002344435A CA 2344435 A CA2344435 A CA 2344435A CA 2344435 A1 CA2344435 A1 CA 2344435A1
Authority
CA
Canada
Prior art keywords
composition
buffer
alprostadil
arginine
range
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002344435A
Other languages
French (fr)
Other versions
CA2344435C (en
Inventor
Joseph S. Podolski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Repros Therapeutics Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2344435A1 publication Critical patent/CA2344435A1/en
Application granted granted Critical
Publication of CA2344435C publication Critical patent/CA2344435C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Improved drug compositions and methods useful in the treatment of male erectile dysfunction. An optimized mixture of the drugs phentolamine mesylat e, papaverine hydrochloride, and alprostadil in a buffer containing L-arginine and glycine is to be injected into the penile tissue to produce an erection in otherwise impotent men.

Claims (107)

1. A composition comprising one or more pharmaceutical agents selected from the group consisting of an .alpha.-adrenergic antagonist, a prostaglandin and optionally, a phosphodiesterase inhibitor.
2. A composition comprising one or more pharmaceutical agents selected from the group consisting of an .alpha.-adrenergic antagonist, a prostaglandin, and optionally, a phosphodiesterase inhibitor in a buffer wherein said buffer comprises a substrate for nitric oxide synthetase.
3. The composition of claim 1 or 2 wherein the .alpha.-adrenergic antagonist is phentolamine mesylate, or a pharmaceutically acceptable salt thereof.
4. The composition of claim 1 or 2 wherein the phosphodiesterase inhibitor is selected from the group consisting of papaverine hydrochloride, Sildenafil, class V phosphodiesterase inhibitors, and pharmaceutically acceptable salts thereof.
5. The composition of claim 3 wherein the phosphodiesterase inhibitor is selected from the group consisting of papaverine hydrochloride, Sildenafil, class V phosphodiesterase inhibitors, and pharmaceutically acceptable salts thereof.
6. The composition of claim 1 or 2 wherein the prostaglandin is alprostadil.
7. The composition of claim 3 wherein the prostaglandin is alprostadil.
8. The composition of claim 5 wherein the prostaglandin is alprostadil.
9. The composition of claim 2, 5, 7 or 8 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
10. The composition of claim 3 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
11. The composition of claim 4 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
12. The composition of claim 6 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
13. The composition of claims 2, 5, 7 or 8 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
14. The composition of claim 3 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
15. The composition of claim 4 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
16. The composition of claim 6 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
17. The composition of claim 1, 2, 5, 7 or 8 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
18. The composition of claim 3 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
19. The composition of claim 15 or 16 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
20. The composition of claim 13 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
21. The composition of claim 17 wherein the buffer comprises glycine and L-arginine in a weight ratio of about 1:20.
22. The composition of claim 18 wherein the buffer comprises a glycine and L-arginine in a weight ratio of about 1:20.
23. The composition of claim 16 or 18 wherein the buffer further comprises benzyl alcohol and mannitol and has a pH range of from about 3 to about 5.
24. The composition of claim 17 wherein the buffer further comprises benzyl alcohol and mannitol and has a pH range of from about 3 to about 5.
25. A composition comprising a combination of phentolamine mesylate, alprostadil and optionally, papaverine hydrochloride in a buffer wherein said buffer comprises a substrate for nitric oxide synthetase.
26. The composition of claim 25 wherein the weight ratio of phentolamine mesylate: papaverine hydrochloride: alprostadil is about 0.5:7.5:0.005 to about 5:30:0.02.
27. The composition of claim 26 wherein the weight ratio of phentolamine mesylate: papaverine hydrochloride: alprostadil is about 5:7.5:0.005.
28. The composition of claim 25 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are from about 0-10 mg/ml phentolamine, about 0-50 mg/ml papaverine, and about 0-40 µg/ml alprostadil.
29. The composition of claim 28 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are from about 1-5 mg/ml phentolamine, about 7.5-30 mg/ml papaverine, and about 5-20 µg/ml alprostadil.
30. The composition of claim 29 wherein the dosages of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 5 mg/ml phentolamine, about 7.5 mg/ml papaverine, and about 0.005 mg/ml alprostadil.
31. The composition of claims 28-30 wherein the vasoactive agents are present in a total volume of 0.5 ml.
32. The composition of claim 25 wherein the dosage of alprostadil is about 5 µg/ml in a total volume of 0.5 ml.
33. The composition of claim 25 wherein the dosage of phentolamine is about 1.25 mg/ml in a total volume of 0.5 ml.
34. The composition of claim 25 wherein the pH range of the composition in buffer is from about 3 to about 9.
35. The composition of claim 34 wherein the pH of the composition in buffer is about 7.
36. A method for the treatment of male erectile dysfunction which comprises administering a pharmacologically effective amount of a composition comprising one or more pharmaceutical agents selected from the group consisting of an a-adrenergic antagonist, a prostaglandin and optionally, a phosphodiesterase inhibitor.
37. A method for the treatment of mate erectile dysfunction which comprises administering a pharmacologically effective amount of a composition comprising one or more pharmaceutical agents selected from the group consisting of an .alpha.-adrenergic antagonist, a prostaglandin and optionally, a phosphodiesterase inhibitor in a buffer wherein said buffer comprises a substrate for nitric oxide synthetase.
38. The method of claim 36 or 37 wherein the .alpha.-adrenergic antagonist is phentolamine mesylate, or pharmaceutically acceptable salt thereof.
39. The method of claim 36 or 37 wherein the phosphodiesterase inhibitor is papaverine hydrochloride or pharmaceutically acceptable salt thereof.
40. The method of claim 38 wherein the phosphodiesterase inhibitor is papaverine hydrochloride or pharmaceutically acceptable salt thereof.
41. The method of claim 36, 37 or 40 wherein the prostaglandin is alprostadil.
42. The method of claim 38 wherein the prostaglandin is alprostadil.
43. The method of claims 36, 37, 40 or 42 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
44. The method of claim 38 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
45. The method of claim 39 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
46. The method of claim 41 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
47. The method of claim 43 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
48. The method of claims 44-46 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
49. The method of claim 47 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
50. The method of claim 48 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
51. The method of claim 49 or 50 wherein the buffer comprises glycine and L-arginine in a weight ratio of about 1:20.
52. The method of claim 49 wherein the buffer further comprises benzyl alcohol and mannitol and has a pH range of from about 3 to about 5.
53. The method of claim 37 wherein the pH of the composition in buffer is about 7.
54. A method for the treatment of male erectile dysfunction which comprises administering a pharmacologically effective amount of a composition comprising one or more of phentolamine mesylate, alprostadil, and optionally, papaverine hydrochloride in a buffer wherein said buffer comprises a substrate for nitric oxide synthetase.
55. The method of claim 50 wherein the weight ratio of phentolamine mesylate: papaverine hydrochloride: alprostadil is about 0.5:7.5:0.005 to about 5:30:0.02.
56. The method of claim 55 wherein the weight ratio of phentolamine mesylate: papaverine hydrochloride: alprostadil is about 5:7.5:0.005.
57. The method of claim 54 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 0-10 mg/ml phentolamine, about 0-50 mg/ml papaverine, and about 0-40 µg/ml alprostadil.
58. The method of claim 57 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 1-5 mg/ml phentolamine, about 7.5-30 mg/ml papaverine, and about 5-20 µg/ml alprostadil.
59. The method of claim 58 wherein the dosages of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 5 mg/ml phentolamine, about 7.5 mg/ml papaverine, and about 0.005 mg/ml alprostadil.
60. The method of claims 57, 58 or 59 wherein the vasoactive agents are present in a total volume of 0.5 ml.
61. The method of claims 54 wherein the dosage of alprostadil is about 5 µg/ml in a total volume of 0.5 ml.
62. The method of claims 54 wherein the dosage of phentolamine is about 1.25 mg/ml in a total volume of 0.5 ml.
63. The method of claim 54 wherein the pH range of the composition in buffer is from about 3 to about 9.
64. The method of claim 63 wherein the pH of the composition in buffer is about 7.
65. A composition comprising an .alpha.-adrenergic antagonist, a prostaglandin and optionally a phosphodiesterase inhibitor in a pharmaceutically acceptable carrier or excipient.
66. The composition of claim 65 wherein the .alpha.-adrenergic antagonist is phentolamine or a pharmaceutically acceptable salt thereof.
67. The composition of claim 65 or 66 wherein the phosphodiesterase inhibitor is selected from the group consisting of papaverine hydrochloride, Sildenafil, class V phosphodiesterase inhibitors, and a pharmaceutically acceptable salt thereof.
68. The composition of claim 65 or 66 wherein the prostaglandin is alprostidil.
69. The composition of claim 67 wherein the prostaglandin is alprostidil.
70. The composition according to claims 65, 66 or 67 further comprising a buffer.
71. The composition of claim 67 further comprises a buffer.
72. The composition of claim 68 further comprises a buffer.
73. The composition according to claim 78 wherein the buffer comprises glycine, arginine, or a mixture thereof.
74. The composition according to claim 71 or 72 wherein the buffer comprises glycine, arginine, or a mixture thereof.
75. The composition according to claim 73 wherein the composition in buffer has a pH range from about 3 to about 9.
76. The composition according to claim 74 wherein the composition in buffer has a pH range from about 3 to about 9.
77. The composition according to claim 75 or 76 wherein the pH of the composition in buffer is about 7.
78. The use of one or more pharmaceutical agents selected from the group consisting of an .alpha.-adrenergic antagonist, a prostaglandin and optionally a phosphodiesterase inhibitor for the manufacture of a medicament for the treatment of erectile dysfunction wherein one or more of said agents are in a buffer comprising a substrate for nitric oxide synthetase.
79. The use of claim 78 wherein the .alpha.-adrenergic antagonist is phentolamine mesylate, or pharmaceutically acceptable salt thereof.
80. The use of claim 78 or 79 wherein the phosphodiesterase inhibitor is selected from the group consisting of papaverine hydrochloride, Sildenafil, class V phosphodiesterase inhibitors, and a pharmaceutically acceptable salt thereof.
81. The use of claim 78 or 79 wherein the prostaglandin is alprostadil.
82. The use of claim 80 wherein the prostaglandin is alprostadil.
83. The use of claims 78, 79 or 82 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
84. The use of claim 80 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
85. The use of claim 81 wherein the buffer comprises L-arginine and, optionally, a pharmaceutically acceptable excipient or carrier.
86. The use of claim 78, 79 or 82 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
87. The use of claim 80 when the buffer comprises glycine having a pH range of from about 3 to about 5.
88. The use of claim 81 wherein the buffer comprises glycine having a pH range of from about 3 to about 5.
89. The use of claim 78, 79 or 82 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
90. The use of claim 80 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
91. The use of claim 81 wherein the buffer comprises a mixture of arginine and glycine having a pH range of from about 3 to about 5.
92. The use of claim 89 wherein the buffer comprises glycine and L-arginine in a weight ratio of about 1:20.
93. The use of claim 90 or 91 wherein the buffer comprises glycine and L-arginine in a weight ratio of about 1:20.
94. The use of claim 89 wherein the buffer further comprises benzyl alcohol and mannitol and has a pH range of from about 3 to about 5.
95. The use of claim 90 wherein the buffer further comprises benzyl alcohol and mannitol and has a pH range of from about 3 to about 5.
96. The use of claim 78 wherein the composition in buffer has a pH of about 7.
97. The use of a composition comprising a combination of phentolamine mesylate, alprostadil and optionally, papaverine hydrochloride in a buffer for the manufacture of a medicament wherein said buffer comprises a substrate for nitric oxide synthetase.
98. The use of claim 97 wherein the weight ratio of phentolamine mesylate: papaverine hydrochloride: alprostadil is about 0.5:7.5:0.005 to about 5:30:02.
99. The use of claim 98 wherein the weight ratio of phentolamine mesylate: papaverine hydrochloride: alprostadil is about 5:7.5:0.005.
100. The use of claim 97 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 0-10 mg/ml phentolamine, about 0-50 mg/ml papaverine, and about 0-40,µg/ml alprostadil.
101. The use of claim 100 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 1-5 mg/ml phentolamine, about 7.5-30 mg/ml papaverine, and about 5-20 µg/ml alprostadil.
102. The use of claim 93 wherein the dosage of phentolamine mesylate, papaverine hydrochloride, and alprostadil are about 5 mg/ml phentolamine mesylate, about 7.5 mg/ml papaverine hydrochloride, and about 0.005 mg/ml alprostadil.
103. The use of claims 100, 101 or 102 wherein the vasoactive agents are present in a total volume of 0.5 ml.
104. The use of claim 97 wherein the dosage of alprostadil is about 5 µg/ml in a total volume of 0.5 ml.
105. The use of claim 97 or 104 wherein the dosage of phentolamine is about 1.25 mg/ml in a total volume of 0.5 ml.
106. The use of claim 97 wherein the pH range of the composition in buffer is from about 3 to about 9.
107. The use of claim 106 wherein the pH of the composition in buffer is about 7.
CA2344435A 1998-09-17 1999-09-17 Compositions for the treatment of male erectile dysfunction Expired - Fee Related CA2344435C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/154,677 1998-09-17
US09/154,677 US6482426B1 (en) 1998-09-17 1998-09-17 Compositions for the treatment of male erectile dysfunction
PCT/US1999/021513 WO2000015233A1 (en) 1998-09-17 1999-09-17 Compositions for the treatment of male erectile dysfunction

Publications (2)

Publication Number Publication Date
CA2344435A1 true CA2344435A1 (en) 2000-03-23
CA2344435C CA2344435C (en) 2010-02-16

Family

ID=22552291

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2344435A Expired - Fee Related CA2344435C (en) 1998-09-17 1999-09-17 Compositions for the treatment of male erectile dysfunction

Country Status (12)

Country Link
US (3) US6482426B1 (en)
EP (1) EP1112075B1 (en)
JP (1) JP4721517B2 (en)
CN (1) CN1338939B (en)
AT (1) ATE338554T1 (en)
AU (1) AU772922B2 (en)
CA (1) CA2344435C (en)
DE (1) DE69933128T2 (en)
DK (1) DK1112075T3 (en)
ES (1) ES2273509T3 (en)
PT (1) PT1112075E (en)
WO (1) WO2000015233A1 (en)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6432401B2 (en) * 2000-05-12 2002-08-13 Novalar Pharmaceuticals, Inc. Local anesthetic methods and kits
US6905707B2 (en) * 1998-05-28 2005-06-14 Medical Research Institute Controlled release arginine alpha ketoglutarate
US6482426B1 (en) * 1998-09-17 2002-11-19 Zonagen, Inc. Compositions for the treatment of male erectile dysfunction
US6476037B1 (en) * 2000-03-23 2002-11-05 The Regents Of The University Of California L-arginine and phosphodiesterase (PDE) inhibitor synergism
CN1315504A (en) * 2000-03-24 2001-10-03 上海博德基因开发有限公司 Polypeptide-human phosphoribosyl glycinamide synthetase 12 and polynucleotide for coding it
GB2375303A (en) * 2001-05-11 2002-11-13 Medical Res Council Method of inducing cervical ripening
DE10142418A1 (en) * 2001-08-31 2003-04-03 Molecular And Clinical Drug Re drug
BRPI0311965B1 (en) * 2002-06-20 2018-04-24 Septodont Holding Sas Stable liquid formulation and its use for enhancing mammalian blood flow, method of preparing stable liquid formulation single dosage form, as well as container and kit
US7037257B1 (en) * 2002-08-22 2006-05-02 Koenig J Frank Erectile dysfuction treatments comprising momentary vacuum therapy alone or with medications
KR20040043996A (en) * 2002-11-20 2004-05-27 조나겐, 아이엔씨. Improved compositions for the treatment of Male Erectile Dysfunction
JP4615929B2 (en) * 2004-08-11 2011-01-19 久光製薬株式会社 Iontophoresis device
AU2006272647A1 (en) * 2005-07-25 2007-02-01 Therimunex Pharmaceuticals, Inc. Peptidyl diacylglycerides
US8642093B2 (en) * 2007-10-30 2014-02-04 The Invention Science Fund I, Llc Methods and systems for use of photolyzable nitric oxide donors
US7862598B2 (en) * 2007-10-30 2011-01-04 The Invention Science Fund I, Llc Devices and systems that deliver nitric oxide
US20090110933A1 (en) * 2007-10-30 2009-04-30 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems and devices related to nitric oxide releasing materials
US20110190604A1 (en) * 2006-12-22 2011-08-04 Hyde Roderick A Nitric oxide sensors and systems
US8221690B2 (en) * 2007-10-30 2012-07-17 The Invention Science Fund I, Llc Systems and devices that utilize photolyzable nitric oxide donors
US20090112197A1 (en) 2007-10-30 2009-04-30 Searete Llc Devices configured to facilitate release of nitric oxide
US9005183B2 (en) * 2007-05-16 2015-04-14 Health Knight, Llc System and method for treating erectile dysfunction
EP2014651A1 (en) * 2007-07-12 2009-01-14 Exonhit Therapeutics SA Compounds and methods for modulating Rho GTPases
US20090112055A1 (en) * 2007-10-30 2009-04-30 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Sleeves configured to facilitate release of nitric oxide
US8980332B2 (en) 2007-10-30 2015-03-17 The Invention Science Fund I, Llc Methods and systems for use of photolyzable nitric oxide donors
US10080823B2 (en) 2007-10-30 2018-09-25 Gearbox Llc Substrates for nitric oxide releasing devices
US7897399B2 (en) 2007-10-30 2011-03-01 The Invention Science Fund I, Llc Nitric oxide sensors and systems
US7846400B2 (en) * 2007-10-30 2010-12-07 The Invention Science Fund I, Llc Substrates for nitric oxide releasing devices
US20090112193A1 (en) * 2007-10-30 2009-04-30 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems and devices that utilize photolyzable nitric oxide donors
US8877508B2 (en) * 2007-10-30 2014-11-04 The Invention Science Fund I, Llc Devices and systems that deliver nitric oxide
US20090259217A1 (en) * 2008-04-09 2009-10-15 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Methods and systems associated with delivery of one or more agents to an individual
US20090259215A1 (en) * 2008-04-09 2009-10-15 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Methods and systems associated with delivery of one or more agents to an individual
US20100184722A1 (en) * 2008-12-19 2010-07-22 Shimoda Biotech (Pty) Ltd Inclusion complexes of alpha-cyclodextrin and sildenafil salt
RU2563990C2 (en) 2010-11-12 2015-09-27 Колгейт-Палмолив Компани Product for oral cavity care and methods of application and obtaining thereof
US8560453B2 (en) 2011-06-30 2013-10-15 Intel Corporation Method and apparatus for dynamic, real-time ad insertion based on meta-data within a hardware based root of trust
US20130303566A1 (en) * 2012-05-09 2013-11-14 David W. Hill Method for treating macular degeneration
WO2017168174A1 (en) 2016-04-02 2017-10-05 N4 Pharma Uk Limited New pharmaceutical forms of sildenafil
WO2018220232A1 (en) * 2017-06-02 2018-12-06 Universite De Versailles-St Quentin En Yvelines Pharmaceutical combination product comprising botulinum toxin for the treatment of erectile dysfunction
CN109820820B (en) * 2019-02-25 2021-12-21 浙江长典药物技术开发有限公司 Alprostadil injection and preparation method thereof
CN110193011B (en) * 2019-06-19 2022-02-11 四川美大康华康药业有限公司 Phentolamine mesylate injection and preparation method thereof
CN111789818B (en) * 2020-08-15 2022-02-22 山东北大高科华泰制药有限公司 Papaverine hydrochloride pharmaceutical composition for injection and preparation method thereof
EP4232002A1 (en) * 2020-10-22 2023-08-30 Standard International Group Holdings, LP Transdermal treatment for erectile dysfunction
CN113143868B (en) * 2021-03-03 2022-04-12 海南久常制药有限公司 Papaverine hydrochloride for injection and preparation method thereof

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3943246A (en) 1972-07-10 1976-03-09 Sandoz Ltd. Organic compounds
US4139617A (en) 1974-05-13 1979-02-13 Richardson-Merrell Inc. 19-Oxygenated-androst-5-enes for the enhancement of libido
US4127118B1 (en) 1977-03-16 1995-12-19 Alvaro Latorre Method of effecting and enhancing an erection
US4746651A (en) * 1983-11-01 1988-05-24 Scripps Clinic And Research Foundation Antimicrobial chemotherapeutic potentiation using substituted nucleoside derivatives
US4530920A (en) 1983-11-07 1985-07-23 Syntex (U.S.A.) Inc. Nonapeptide and decapeptide analogs of LHRH, useful as LHRH agonist
US4885173A (en) 1985-05-01 1989-12-05 University Of Utah Methods and compositions for noninvasive dose-to-effect administration of drugs with cardiovascular or renal vascular activities
US4863911A (en) 1986-08-04 1989-09-05 University Of Florida Method for treating male sexual dysfunction
US4801587A (en) 1987-03-02 1989-01-31 Gene Voss Impotence ointment
US5256652A (en) 1987-11-12 1993-10-26 Pharmedic Co. Topical compositions and methods for treatment of male impotence
SE463851B (en) 1988-09-02 1991-02-04 Amsu Ltd COMPOSITION FOR TREATMENT OF ERECT DYSFUNCTION THROUGH URETRA
US5059603A (en) 1989-06-12 1991-10-22 Centuries Laboratories, Inc. Method and composition for treating impotence
WO1990015583A1 (en) 1989-06-16 1990-12-27 Vsesojuzny Nauchno-Issledovatelsky I Ispytatelny Institut Meditsinskoi Tekhniki Device for treating sexual weakness in men
FR2649613B1 (en) 1989-07-11 1991-09-27 Virag Ronald VASO-ACTIVE MEDICINE
US5079018A (en) 1989-08-14 1992-01-07 Neophore Technologies, Inc. Freeze dry composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs
US5236904A (en) 1989-09-18 1993-08-17 Senetek, Plc Erection-inducing methods and compositions
US5270323A (en) 1990-05-31 1993-12-14 Pfizer Inc. Method of treating impotence
US5399581A (en) 1990-12-26 1995-03-21 Laragh; John H. Method and compositions for treatment of sexual impotence
US5298261A (en) 1992-04-20 1994-03-29 Oregon Freeze Dry, Inc. Rapidly distintegrating tablet
US5646181A (en) * 1992-07-02 1997-07-08 Research Foundation Of State University Of New York Method and compositions for treating impotence
US5565466A (en) 1993-08-13 1996-10-15 Zonagen, Inc. Methods for modulating the human sexual response
US6121276A (en) * 1994-04-22 2000-09-19 Pentech Pharmaceuticals, Inc. Apomorphine-containing dosage forms for ameliorating male erectile dysfunction
US5731339A (en) 1995-04-28 1998-03-24 Zonagen, Inc. Methods and formulations for modulating the human sexual response
DK172203B1 (en) * 1996-03-11 1998-01-05 Gitte Bjeldbak Love forest remedy that acts sexually arousing on the user
ATE333279T1 (en) * 1997-05-19 2006-08-15 Zonagen Inc COMBINATION THERAPY TO MODULATE THE HUMAN SEXUAL RESPONSE
US20020068365A1 (en) * 1998-07-28 2002-06-06 Eric H. Kuhrts Controlled release nitric oxide producing agents
US6482426B1 (en) * 1998-09-17 2002-11-19 Zonagen, Inc. Compositions for the treatment of male erectile dysfunction

Also Published As

Publication number Publication date
CN1338939A (en) 2002-03-06
EP1112075A1 (en) 2001-07-04
DE69933128T2 (en) 2007-08-16
ATE338554T1 (en) 2006-09-15
US20040102475A1 (en) 2004-05-27
US7776899B2 (en) 2010-08-17
DK1112075T3 (en) 2006-12-27
JP2002524520A (en) 2002-08-06
DE69933128D1 (en) 2006-10-19
CA2344435C (en) 2010-02-16
ES2273509T3 (en) 2007-05-01
AU5927099A (en) 2000-04-03
PT1112075E (en) 2006-12-29
EP1112075B1 (en) 2006-09-06
WO2000015233A1 (en) 2000-03-23
US6696072B1 (en) 2004-02-24
AU772922B2 (en) 2004-05-13
US6482426B1 (en) 2002-11-19
JP4721517B2 (en) 2011-07-13
CN1338939B (en) 2012-07-04

Similar Documents

Publication Publication Date Title
CA2344435A1 (en) Compositions for the treatment of male erectile dysfunction
JP2002524520A5 (en)
US8772309B2 (en) Pharmaceutical formulation of apomorphine for buccal administration
WO2001041807A3 (en) Transmucosal composition containing a phosphodiesterase inhibitors for the treatment of erectile dysfunction
RU99117926A (en) MEDICINAL FORMS AND METHOD OF TREATMENT OF DISORDERS OF MEN'S Erectile Function
WO2003000343A3 (en) Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation
EA200400007A1 (en) PHARMACEUTICAL COMPOSITION FOR THE EFFICIENT INTRODUCTION OF APOMORPHIN, 6aR - (-) - N-PROPYL-NORAPOMORPHIN, THEIR DERIVATIVES AND THEIR PROCEDURES
CO5261582A1 (en) VALDECOXIB COMPOSITIONS
HK1054196A1 (en) Pharmaceutical formulation containing tolterodine and its use
NO20043871L (en) Controlled release drug formulations containing a carrier peptide
TR200103613T2 (en) Pharmaceutical formulations and methods containing morphine administered intranasally.
KR20150111918A (en) Transmucosal delivery of glatiramer acetate
TW200416031A (en) Therapeutic treatment
JPH10158169A (en) Pharmaceutical preparation containing trospium chloride, its preparation and use thereof
EP1237538A2 (en) An improved pharmaceutical composition for treating male erectile dysfunction
Hussain et al. Intranasal absorption of oxymorphone
EP1136072A1 (en) Preparations for intraurethral administration
CA2425445A1 (en) Tetrapeptide stimulating functional activity of hepatocytes, pharmacological substance on its basis and the method of its application
WO2001028541A3 (en) Composition comprising sildenafil and l-arginine
WO2002011729A1 (en) Novel compositions and methods for treatment of male erectile dysfunction
RU2003106417A (en) APPLICATION OF A VITAMIN COMBINATION FOR TREATMENT OF PRIMARY HEAD PAIN
JP2005531573A (en) New formulation for parenteral use of clobenetine
CO5410176A1 (en) IMPROVED COMPOSITIONS FOR THE TREATMENT OF MALE ERECTILE DYSFUNCTION
WO2004050019A9 (en) Method and compositions for treating anxiety
CA2422424A1 (en) Pharmaceutical compositions for rectal and vaginal administration

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20190917