WO2002047603A2 - Use of levosimendan for treating erictile dysfunction - Google Patents
Use of levosimendan for treating erictile dysfunction Download PDFInfo
- Publication number
- WO2002047603A2 WO2002047603A2 PCT/FI2001/001101 FI0101101W WO0247603A2 WO 2002047603 A2 WO2002047603 A2 WO 2002047603A2 FI 0101101 W FI0101101 W FI 0101101W WO 0247603 A2 WO0247603 A2 WO 0247603A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- levosimendan
- treatment
- dysfunction
- patient
- erectile dysfunction
- 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.)
- Ceased
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- 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
Definitions
- the present invention relates to a method for the treatment of erectile dysfunction by administering levosimendan, or (-)-[[4-(l ,4,5,6-tetrahydro-4-methyl- 6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile (I), or pharmaceutically acceptable salts thereof, to a patient in need of such treatment.
- Levosimendan which is the (-)-enantiomer of [[4-(l,4,5,6-tetrahydro-4- methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, and the method for its preparation is described in EP 565546 Bl.
- Levosimendan is potent in the treatment of heart failure and has significant calcium dependent binding to troponin.
- Levosimendan is represented by the formula:
- Transdermal delivery of levosimendan is described in WO 98/01111.
- Transmucosal delivery of levosimendan is described in WO 99/32081.
- Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients.
- Erectile dysfunction is the inability to obtain and sustain sufficient penile erection and is referred to as impotence. It can result from a variety of underlying causes ranging from purely psychogenic to completely physical dysfunctioning. Both surgical and pharmacological therapies have been used in the treatment of impotence.
- levosimendan is capable of restoring or improving the erectile function in patients suffering from erectile dysfunction.
- the present invention provides the use of levosimendan or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of erectile dysfunction.
- the present invention also provides a method for the treatment of erectile dysfunction in a patient, said method comprising administering to a patient in need thereof an effective amount of levosimendan or a pharmaceutically acceptable salt thereof.
- the method of the invention comprises a step of administering to a subject an amount of levosimendan effective to restore the erectile function of the patient.
- the drug is preferably administered perorally, transmucosally including transurethrally, intravenously, intramuscularly including intracavernosal injection or transdermally.
- the administration may be systemic or local.
- levosimendan is administered orally to man in daily dose from about 0.1 to 15 mg, preferably from about 0.5 to 10 mg, given once a day or divided into several doses a day.
- the daily dose range is from about 0.005 to 0.7 mg/kg, preferably from about 0.01 to 0.5 mg/kg.
- Levosimendan is formulated into dosage forms suitable for the treatment of erectile dysfunction using the principles known in the art. It is given to a patient as such or preferably in combination with suitable pharmaceutical excipients in the form of tablets, dragees, capsules, suppositories, emulsions, suspensions or solutions whereby the contents of the active compound in the formulation is from about 0.5 to 100 % per weight. Choosing suitable ingredients for the composition is a routine for those of ordinary skill in the art. It is evident that suitable carriers, solvents, gel forming ingredients, dispersion forming ingredients, antioxidants, colours, sweeteners, wetting compounds, release controlling components and other ingredients normally used in this field of technology may be also used.
- suitable carriers and excipients include e.g. lactose, corn starch, magnesium stearate, calcium phosphate and talc.
- useful carriers and excipients include e.g. lactose, corn starch, magnesium stearate and talc.
- Disintegrants such as croscarmellose sodium, may be used to accelerate the dissolution of the formulation.
- Tablets can be prepared by mixing the active ingredient with the carriers and excipients and compressing the powdery mixture into tablets.
- Capsules can be prepared by mixing the active ingredient with the carriers and excipients and placing the powdery mixture in capsules, e.g. hard gelatin capsules.
- a tablet or a capsule comprises from about 0.1 to 10 mg, more typically 0.2 to 5 mg, of levosimendan.
- rapidly dissolving peroral tablets or capsules e.g. having a dissintegration time of 1 to 20 minutes, are preferred.
- Formulations suitable for intravenous administration such as injection formulation, comprise sterile isotonic solutions of levosimendan and vehicle, preferably aqueous solutions.
- an intravenous infusion solution comprises from about 0.01 to 0.1 mg/ml of levosimendan.
- Formulations of levosimendan suitable for transmucosal or transdermal administration are disclosed in WO 99/32081 and WO 98/01111, respectively.
- Salts of levosimendan maybe prepared by known methods. Pharmaceutically acceptable salts are useful as active medicaments, however, preferred salts are the salts with alkali or alkaline earth metals.
- Lactose 198 mg The pharmaceutical preparation in the form of a capsule was prepared by mixing levosimendan with lactose and placing the powdery mixture in hard gelatin capsule.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Gynecology & Obstetrics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Levosimendan, or (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, which has been previously suggested for the treatment of congestive heart failure is useful in the treatment of erectile dysfunction.
Description
A METHOD FOR TREATING ERECTILE DYSFUNCTION
Technical field
The present invention relates to a method for the treatment of erectile dysfunction by administering levosimendan, or (-)-[[4-(l ,4,5,6-tetrahydro-4-methyl- 6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile (I), or pharmaceutically acceptable salts thereof, to a patient in need of such treatment.
Background of the invention
Levosimendan, which is the (-)-enantiomer of [[4-(l,4,5,6-tetrahydro-4- methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, and the method for its preparation is described in EP 565546 Bl. Levosimendan is potent in the treatment of heart failure and has significant calcium dependent binding to troponin. Levosimendan is represented by the formula:
The hemodynamic effects of levosimendan in man are described in Sundberg,
S. et al., Am. J. Cardiol., 1995; 75: 1061-1066 and in Lilleberg, J. et al., J. Cardiovasc. Pharmacol., 26(Suppl.l), S63-S69, 1995. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Pharmacol., 26(Suppl.l), S57-S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921. The use of levosimendan in the treatment of pulmonary hypertension is described in WO 99/66912. Transdermal delivery of levosimendan is described in WO 98/01111. Transmucosal delivery of levosimendan is described in WO 99/32081. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients.
Erectile dysfunction is the inability to obtain and sustain sufficient penile erection and is referred to as impotence. It can result from a variety of underlying
causes ranging from purely psychogenic to completely physical dysfunctioning. Both surgical and pharmacological therapies have been used in the treatment of impotence.
Summary of the invention
It has now been found that levosimendan is capable of restoring or improving the erectile function in patients suffering from erectile dysfunction.
Therefore, the present invention provides the use of levosimendan or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of erectile dysfunction.
The present invention also provides a method for the treatment of erectile dysfunction in a patient, said method comprising administering to a patient in need thereof an effective amount of levosimendan or a pharmaceutically acceptable salt thereof.
Detailed description
The method of the invention comprises a step of administering to a subject an amount of levosimendan effective to restore the erectile function of the patient. The drug is preferably administered perorally, transmucosally including transurethrally, intravenously, intramuscularly including intracavernosal injection or transdermally. The administration may be systemic or local.
The effective amount of levosimendan to be administered to a subject depends upon the route of administration. Levosimendan is administered orally to man in daily dose from about 0.1 to 15 mg, preferably from about 0.5 to 10 mg, given once a day or divided into several doses a day. For transmucosal, intravenous, intramuscular or transdeimal delivery the daily dose range is from about 0.005 to 0.7 mg/kg, preferably from about 0.01 to 0.5 mg/kg.
Levosimendan is formulated into dosage forms suitable for the treatment of erectile dysfunction using the principles known in the art. It is given to a patient as such or preferably in combination with suitable pharmaceutical excipients in the form of tablets, dragees, capsules, suppositories, emulsions, suspensions or solutions whereby the contents of the active compound in the formulation is from about 0.5 to 100 % per weight. Choosing suitable ingredients for the composition is a routine for those of ordinary skill in the art. It is evident that suitable carriers, solvents, gel
forming ingredients, dispersion forming ingredients, antioxidants, colours, sweeteners, wetting compounds, release controlling components and other ingredients normally used in this field of technology may be also used.
For oral administration in tablet form, suitable carriers and excipients include e.g. lactose, corn starch, magnesium stearate, calcium phosphate and talc. For oral administration in capsule form, useful carriers and excipients include e.g. lactose, corn starch, magnesium stearate and talc. Disintegrants, such as croscarmellose sodium, may be used to accelerate the dissolution of the formulation.
Tablets can be prepared by mixing the active ingredient with the carriers and excipients and compressing the powdery mixture into tablets. Capsules can be prepared by mixing the active ingredient with the carriers and excipients and placing the powdery mixture in capsules, e.g. hard gelatin capsules. Typically a tablet or a capsule comprises from about 0.1 to 10 mg, more typically 0.2 to 5 mg, of levosimendan. In general, rapidly dissolving peroral tablets or capsules, e.g. having a dissintegration time of 1 to 20 minutes, are preferred.
Formulations suitable for intravenous administration such as injection formulation, comprise sterile isotonic solutions of levosimendan and vehicle, preferably aqueous solutions. Typically an intravenous infusion solution comprises from about 0.01 to 0.1 mg/ml of levosimendan.
Formulations of levosimendan suitable for transmucosal or transdermal administration are disclosed in WO 99/32081 and WO 98/01111, respectively.
Salts of levosimendan maybe prepared by known methods. Pharmaceutically acceptable salts are useful as active medicaments, however, preferred salts are the salts with alkali or alkaline earth metals.
Examples
Pharmaceutical example.
Hard gelatin capsule size 3
Levosimendan 2.0 mg
Lactose 198 mg
The pharmaceutical preparation in the form of a capsule was prepared by mixing levosimendan with lactose and placing the powdery mixture in hard gelatin capsule.
Clinical data
Two NYHA III heart failure patients, who had not had erections for several years were treated with levosimendan. Patient I was exposed to 0.05 μg/kg/min continuous infusion of levosimendan for 7 days. The patient reported erections 1 day after starting the infusion and he had erections in the mornings during the whole study. Patient II reported erections after 0.1 μg/kg/min continuous infusion of levosimendan for 2 days.
Claims
1. Use of levosimendan or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of erectile dysfunction.
2. A method for the treatment of erectile dysfunction in a patient, said method comprising administering to a patient in need thereof an effective amount of levosimendan or a pharmaceutically acceptable salt thereof.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/450,304 US7115604B2 (en) | 2000-12-15 | 2001-12-14 | Method for treating erectile dysfunction |
| CA002431125A CA2431125C (en) | 2000-12-15 | 2001-12-14 | A method for treating erectile dysfunction |
| EP01270296A EP1349551A2 (en) | 2000-12-15 | 2001-12-14 | A method for treating erectile dysfunction |
| AU2002219247A AU2002219247A1 (en) | 2000-12-15 | 2001-12-14 | Use of levosimendan for treating erictile dysfunction |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI20002755 | 2000-12-15 | ||
| FI20002755A FI20002755A0 (en) | 2000-12-15 | 2000-12-15 | Method of therapy for erectile dysfunction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2002047603A2 true WO2002047603A2 (en) | 2002-06-20 |
| WO2002047603A3 WO2002047603A3 (en) | 2003-01-30 |
Family
ID=8559724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FI2001/001101 Ceased WO2002047603A2 (en) | 2000-12-15 | 2001-12-14 | Use of levosimendan for treating erictile dysfunction |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7115604B2 (en) |
| EP (1) | EP1349551A2 (en) |
| AU (1) | AU2002219247A1 (en) |
| CA (1) | CA2431125C (en) |
| FI (1) | FI20002755A0 (en) |
| WO (1) | WO2002047603A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11607412B2 (en) | 2019-12-16 | 2023-03-21 | Tenax Therapeutics Inc. | Levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1252603B (en) * | 1990-04-19 | 1995-06-19 | Giorgio Cavallini | 2,4-DIAMINO-6 PIPERIDINO PIRIMIDINA-3 TOPICAL OXIDE ON THE GLAND IN THE TREATMENT OF ERECTILE IMPOTENCES |
| GB2251615B (en) | 1991-01-03 | 1995-02-08 | Orion Yhtymae Oy | (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]pro panedinitrile |
| GB2266841A (en) | 1992-05-06 | 1993-11-17 | Orion Yhtymae Oy | Compounds for use as anti-ischemic medicaments |
| US5565466A (en) * | 1993-08-13 | 1996-10-15 | Zonagen, Inc. | Methods for modulating the human sexual response |
| DE4338948A1 (en) | 1993-11-15 | 1995-05-18 | Carlen Judith | Treating erectile dysfunction without causing side-effects |
| GB9614098D0 (en) | 1996-07-05 | 1996-09-04 | Orion Yhtymae Oy | Transdermal delivery of levosimendan |
| AU734734B2 (en) * | 1997-10-28 | 2001-06-21 | Vivus, Inc. | Local administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| FI974578L (en) | 1997-12-19 | 1999-06-20 | Orion Yhtymae Oyj | Method of administration of levosimendan |
| FI981473L (en) | 1998-06-25 | 1999-12-26 | Orion Yhtymae Oyj | Method for treating pulmonary hypertension |
-
2000
- 2000-12-15 FI FI20002755A patent/FI20002755A0/en unknown
-
2001
- 2001-12-14 EP EP01270296A patent/EP1349551A2/en not_active Withdrawn
- 2001-12-14 US US10/450,304 patent/US7115604B2/en not_active Expired - Fee Related
- 2001-12-14 WO PCT/FI2001/001101 patent/WO2002047603A2/en not_active Ceased
- 2001-12-14 AU AU2002219247A patent/AU2002219247A1/en not_active Abandoned
- 2001-12-14 CA CA002431125A patent/CA2431125C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11607412B2 (en) | 2019-12-16 | 2023-03-21 | Tenax Therapeutics Inc. | Levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) |
| US11701355B2 (en) | 2019-12-16 | 2023-07-18 | Tenax Therapeutics, Inc. | Levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) |
| US11969424B2 (en) | 2019-12-16 | 2024-04-30 | Tenax Therapeutics, Inc. | Levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) |
Also Published As
| Publication number | Publication date |
|---|---|
| US20040063711A1 (en) | 2004-04-01 |
| CA2431125C (en) | 2009-06-09 |
| CA2431125A1 (en) | 2002-06-20 |
| FI20002755A0 (en) | 2000-12-15 |
| US7115604B2 (en) | 2006-10-03 |
| AU2002219247A1 (en) | 2002-06-24 |
| EP1349551A2 (en) | 2003-10-08 |
| WO2002047603A3 (en) | 2003-01-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1173178B1 (en) | Composition comprising apomorphine and sildenafil and the use thereof for the treatment of erectile dysfunction | |
| JP2904827B2 (en) | Use of trifluoromethylphenyltetrahydropyridine in the preparation of a pharmaceutical composition useful for treating anxiety and anxiety-depressive disorders | |
| JPH08504201A (en) | Use of 2-amino-6-n-propyl-amino-4,5,6,7-tetrahydrobenzothiazole as a pharmaceutical composition having antidepressant activity | |
| EP1202737A2 (en) | Antiviral therapy use of p-glycoprotein modulators | |
| JP2010065060A (en) | Composite treatment for heart failure treatment | |
| JP2006511538A (en) | Use of a combination comprising a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a cytochrome P450 inhibitor such as a protease inhibitor | |
| CA2431125C (en) | A method for treating erectile dysfunction | |
| CA2335280C (en) | Method of treating pulmonary hypertension | |
| JP2001508769A (en) | Pharmaceutical composition comprising alendronate and an agent for promoting gastric emptying | |
| US6593329B1 (en) | Method for the treatment or prevention of coronary graft vasospasm | |
| CA2157671A1 (en) | Medicament for treating or preventing cerebrovascular diseases | |
| JP3272369B2 (en) | Anti-HIV compositions containing imidazole derivatives | |
| EP1401450B1 (en) | Use of a pyridazinone derivative for the treatment of congestive heart failure | |
| JP2522940B2 (en) | Pharmaceuticals containing S-lactoyl glutathione and / or its salt as an active ingredient | |
| JPH04282313A (en) | Hypotensor | |
| JP2621382B2 (en) | Uric acid excretion agent | |
| JPH0753375A (en) | Liver disease treatment agent | |
| JPH10330265A (en) | Liver disease treatment | |
| CN117794544A (en) | Pharmaceutical compositions for solid tumor treatment | |
| JP2002249429A (en) | Therapeutic agent for chronic heptitis c | |
| JP2002128665A (en) | Benign prostatic hypertrophy-treating medicine | |
| JPH0141126B2 (en) | ||
| JPS6148482B2 (en) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 2431125 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2001270296 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 2001270296 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 10450304 Country of ref document: US |
|
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| NENP | Non-entry into the national phase |
Ref country code: JP |
|
| WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 2001270296 Country of ref document: EP |