SG175658A1 - USE OF ESTRADIOL VALERATE OR 17β-ESTRADIOL IN COMBINATION WITH DIENOGEST FOR ORAL THERAPY FOR MAINTAINING AND/OR INCREASING THE FEMALE LIBIDO - Google Patents
USE OF ESTRADIOL VALERATE OR 17β-ESTRADIOL IN COMBINATION WITH DIENOGEST FOR ORAL THERAPY FOR MAINTAINING AND/OR INCREASING THE FEMALE LIBIDO Download PDFInfo
- Publication number
- SG175658A1 SG175658A1 SG2011076619A SG2011076619A SG175658A1 SG 175658 A1 SG175658 A1 SG 175658A1 SG 2011076619 A SG2011076619 A SG 2011076619A SG 2011076619 A SG2011076619 A SG 2011076619A SG 175658 A1 SG175658 A1 SG 175658A1
- Authority
- SG
- Singapore
- Prior art keywords
- estradiol
- combination
- daily dose
- dienogest
- dose units
- Prior art date
Links
- RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 title claims abstract description 38
- 229960004766 estradiol valerate Drugs 0.000 title claims abstract description 37
- 229960005309 estradiol Drugs 0.000 title claims abstract description 30
- AZFLJNIPTRTECV-FUMNGEBKSA-N dienogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC#N)CC3)C3=C21 AZFLJNIPTRTECV-FUMNGEBKSA-N 0.000 title claims abstract description 28
- 229960003309 dienogest Drugs 0.000 title claims abstract description 28
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 title claims abstract description 27
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 12
- 229930182833 estradiol Natural products 0.000 claims abstract description 25
- 229940068196 placebo Drugs 0.000 claims abstract description 11
- 239000000902 placebo Substances 0.000 claims abstract description 11
- 239000013066 combination product Substances 0.000 claims description 9
- 229940127555 combination product Drugs 0.000 claims description 9
- 229940083544 estradiol 2 mg Drugs 0.000 claims 1
- 238000011282 treatment Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 3
- 229940008227 dienogest and estradiol Drugs 0.000 description 2
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 206010024419 Libido decreased Diseases 0.000 description 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 208000017020 hypoactive sexual desire disease Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003217 oral combined contraceptive Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000009933 reproductive health Effects 0.000 description 1
- 230000035946 sexual desire Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
USE OF ESTRADIOL VALERATE OR 1713-ESTRADIOL IN COMBINATION WITH DIENOGEST FOR ORAL THERAPY FOR MAINTAINING AND/OR INCREASING THE FEMALE LIBIDO The invention relates to the use of estradiol valerate or estradiol in combination with 17a cyanomethy1-17-ß-hydroxyestra-4,9-dien-3-one (dienogest) in a multiphase or single-phase combination preparation for oral therapy for maintaining and/or increasing the female libido, optionally also in unity with oral contraception. The total daily dose units of the multiphase combination and of the pharmaceutically acceptable placebo or of the single-phase combination and the active-ingredient-free and placebo-free daily dose units correspond to 28 days.FIGURES NONE
Description
-|-
Use of estradiol valerate or 175-estradiol in combination with dienogest for oral therapy for maintaining and/or increasing the female libido
The invention relates to the use of estradiol valerate or 178-estradiol (estradiol) in combination with 170- cyanomethyl-17-B-hydroxyestra-4,8-dien-3one (dienogest) { in a multiphase or single-phase combination product for _ oral therapy for maintaining and/or increasing female libido, where appropriate also united with oral contraception.
The total number of daily dose units of the multiphase combination and of one of the pharmaceutically acceptable placebo or of the single-phase combination and, where appropriate, the pharmaceutically acceptable placebo-containing or the placebo- and hormone-free daily dose units correspond to 28 daily dose units, ( Prior art
Female libido is a very complex event which is influenced by numerous hormonal and psychosocial factors. It has long been known that the onset of the . menopause may be accompanied by a decrease in sexual desire in women. Reasons being discussed in this context are the decreasing level of endogenous estradiol and the reduced androgen level. Less known is the fact that intake of conventional combined oral contraceptives and progestin-only pills (POPs) way lead to an acquired loss of/decrease in libido. Disorders of this kind are subsumed under the term “acquired OC- associated hypoactive sexual desire disorder (HSDD}”. (Blitzer: Kontrazeption und Sexualitét, Therapeutische
Umschau, Vol. 51, 19%4, edition 2, 110-114). The cause of this is not clear, various theses are being discussed. It has to date not been possible to prevent this observed phenomenon sufficiently. (Sex steroids and libido, The European Journal of Contraception and reproductive Health care (1997 - 253-258).
The invention is based on the object of finding a means ( for maintaining and/or increasing female libido.
The object is achieved according to the invention through the use of estradiol valerate or estradiol in combination with 170-cyanomethyl-17-B-hydroxyestra-4,9- dien-3one (dienogest) for producing a multiphase combination product or single-phase combination product for oral therapy for maintaining and/or increasing female libido.
It has been found, surprisingly, that oral contraception occurs concomitantly with the maintenance ( of and/or the increase in female libido.
Advantageously, estradiol valerate or estradiol is employed in combination with 17c-cyanomethyl-17-3- hydroxyestra-4,9-dien-3one (dienogest), comprising a first phase of 2 daily dose units of 3 mg of estradiol valerate or of an equivalent dose of estradiol (less than 3 mg), a second phase of 2 groups of daily dose units, where the first group comprises 5 daily dose units of a combination of 2 mg of estradiol valerate or of an equivalent dose of estradiol (less than 2 mg) and 2 mg of dienogest, and the second group comprises 17 daily dose units of a combination of 2 mg of estradiol valerate or of an equivalent dose of estradiol (less than 2 mg) and 3 mg of dienogest, a third phase of 2 daily dose units with 1 mg of estradiol valerate or an equivalent dose of estradiol {less than 1 mg) and a further phase of 2 daily dose units of pharmaceutically acceptable placebo for producing a multiphase combination product having a total number of 28, for oral therapy for maintaining and/or increasing female libido, where appropriate united with oral contraception.
Advantageously, also estradiol valerate or estradiol is ( employed in combination with 17a-cyanomethyl-17-0- hydroxyestra-4, 9-dien-3one, (dienogest), comprising a first phase of 2 daily dose units of 3 mg of estradiol valerate or of an equivalent dose of estradicl (less than 3 mg), a second phase of 2 groups of daily dose units, where the first group comprises 5 daily dose units of a combination of 2 mg of estradiol valerate or of an equivalent dose of estradiol (less than 2 mg) and 3 mg of dienogest, and the second group comprises 17 daily dose units of a combination of 2 mg of estradiol valerate or of an equivalent dose of estradiol (less than 2 mg) and 4 mg of dienogest, a ; third phase of 2 daily dose units with 1 mg of \ estradiol valerate or an equivalent dose of estradiol (less than 1 mg) and a further phase of 2 daily dose units of pharmaceutically acceptable placebo for producing a multiphase combination product having a total number of 28, for oral therapy for maintaining and/or increasing female libido, where appropriate united with oral contraception.
Also, advantageously, estradiol valerate or estradiol is employed in combination with 17a-cyanomethyl-17-(- hydroxyestra-4,9-dien-3one (dienogest), comprising a first phase of 2 daily dose units of 3 mg of estradiol valerate or of an equivalent dose of estradiol (less than 3 mg), a second phase of 2 groups of daily dose
- 4 = units, where the first group comprises 5 daily dose units of a combination of 2 mg of estradiol valerate ox of an equivalent dose of estradiol (less than 2 mg) and 1 mg of dienogest, and the second group comprises 17 daily dose units of a combination of 2 mg of estradiol valerate or of an equivalent dose of estradiol (less than 2 mg) and 2 mg of dienogest, a third phase of 2 daily dose units with 1 mg of estradiol valerate or an equivalent dose of estradiol (less than 1 mg) and a further phase of 2 daily dose ( units of pharmaceutically acceptable placebo for producing a multiphase ” combination product having a total number of 28, for oral therapy for maintaining and/or increasing female libido, where appropriate united with oral contraception.
Advantageously, also, estradiol valerate or estradiol is employed in combination with 170-cyanomethyl-17-p- hydroxyestra-4,9-dien-3one (dienogest), comprising a first phase of 3 daily dose units of 3 mg of estradiol valerate or of an equivalent dose of estradiol (less than 3 mg), a second phase of 2 groups of daily dose units, where the first group comprises 4 daily dose ( units of a combination of 2 mg of estradiol valerate ox of an equivalent dose of estradiol (less than 2 mg) and 1 mg of dienogest, and the second group comprises 16 daily dose units of a combination of 2 mg of estradiol valerate or of an equivalent dose of estradicl (less than 2 mg} and 2 mg of dienogest, a third phase of 2 daily dose units with 1 mg of estradiol valerate or an equivalent dose of estradiol {less than 1 mg) and a further phase of 3 daily dose units of pharmaceutically acceptable placebo for producing a multiphase combination product having =a total number of 28, for oral therapy for maintaining and/or increasing female libido, where appropriate united with oral contraception.
Also, advantageously, less than or equal to 3 mg of estradiol valerate or estradiol are employed in combination with less than or egual to 2.00 mg of 170- cyanomethyl-17-p8-hydroxyestra-4, 9-dien-3one (dienogest) in a single-phase product for oral therapy for maintaining and/or increasing female libido, where appropriate united with oral contraception. The single- phase combination comprises 21, 22, 23, 24, 25, 26, 27 . daily dose units with constant amount of dienogest and estradiol valerate or dienogest and estradiol, and 7, ( 6, 5, 4, 3, 2, 1 pharmaceutically acceptable placebo- containing or placebo- and hormone-£free daily dose units, to give a total number of daily dose units corresponding to 28.
Tt is likewise advantageous to administer the single- phase product in an extended cycle comprising - a first phase of a single-phase preparation of 1.0-2.0 mg of dienogest and 10-30 ug of ethinyl estradiol of n x 21 daily dose units with n = 2 to 5 and with constant amount of dienogest and egtradiol ( - a second phase following n = 2 to 5 of 7 pill-£free ° daily dose units.
It proves particularly advantageous to use the single- phase product with 21-27 daily dose units of dienogest, estradiol valerate or estradiol and 1 to 7 placebo- or hormone-free or consists of 1 to 7 placebo-containing daily dose units, so as to give a total number of daily dose units corresponding to 28, and thereafter in the above extended cycle.
’ WO 2008/046559 PCT/EP2007/008866 - 5 =
Investigations of the efficacy of the claimed formulation
Clinical trials with an orally administered multiphase combination of ‘estradiol valerate and dienogest, in which the first phase consists of 2 daily dose units of 3 mg of estradiol valerate, the second phase of 2 groupe of daily dose units. The first group of this second phase consists of 5 daily dose units of a combination of 2 mg of estradiol valerate and 2 wg of ( dienogest and the second group of 17 daily dose units of a combination of 2 mg of estradiol valerate and 3 mg cf dienogest. The third phase comprises 2 daily dose units with 1 mg of estradiol valerate and a further phase consists of 2 daily dose units of pharmaceutically acceptable placebo. The total of days of an administration cycle of the multiphase combination and of the pharmaceutically acceptable placebo corresponds to 28 days. . 20
In a randomized, double-blind clinical trial, 800 women aged between 18 and 50 years (400 in the 18 to 35 years age group and 400 in the 36 to 50 years age group} and ( having given written informed consent to their participation in the trial were treated with 2 different treatments.
Treatment (A) corresponded to the combination mentioned. The second treatment (B) corresponded to
Miranova (standard OC).
The study comprised a pre-treatment cycle, 7 treatment cycles and one after~treatment cycle (follow-up phase).
Claims (1)
1. Use of estradiol valerate or 17fR-estradiol in combination with 17a-cyanomethyl-17-f- hydroxyestra-4,9-dien-3-one (dienogest) , for producing a multiphase combination product for oral therapy for increasing female libido, where appropriate united with oral contraception, wherein the multiphase combination product comprises a first phase of 2 daily dose units of 3 mg of estradiol, a second phase of 2 groups of daily dose units, where the first group comprises 5 daily dose units of a combination of 2 mg of estradiol valerate and 2 mg of Dienogest and the second group comprises 17 daily dose units of a combination of 2 mg of estradiol valerate and 3 mg of dienogest, a third phase of 2 daily dose units with 1 mg of estradiol valerate and a further phase of 2 daily dose units of pharmaceutically acceptable placebo.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06022091 | 2006-10-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SG175658A1 true SG175658A1 (en) | 2011-11-28 |
Family
ID=37491810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG2011076619A SG175658A1 (en) | 2006-10-20 | 2007-10-12 | USE OF ESTRADIOL VALERATE OR 17β-ESTRADIOL IN COMBINATION WITH DIENOGEST FOR ORAL THERAPY FOR MAINTAINING AND/OR INCREASING THE FEMALE LIBIDO |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN101553234A (en) |
| SG (1) | SG175658A1 (en) |
| UA (1) | UA97960C2 (en) |
-
2007
- 2007-10-12 SG SG2011076619A patent/SG175658A1/en unknown
- 2007-10-12 UA UAA200904273A patent/UA97960C2/en unknown
- 2007-10-12 CN CNA2007800389446A patent/CN101553234A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| UA97960C2 (en) | 2012-04-10 |
| CN101553234A (en) | 2009-10-07 |
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