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
  • A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
  • A61K31/5685—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
• • 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
  • A61K31/566—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 having an oxo group in position 17, e.g. estrone
• • 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
  • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P5/00—Drugs for disorders of the endocrine system
  • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones

Definitions

• the present invention relates to a method for treating infertility in a female host in need thereof comprising the administration of an ovarian follicular stimulating effective amount of exemestane to the female host.
• infertility is defined as the inability to conceive after 12 months of unprotected sexual intercourse.
• infertility can be attributed primarily to male factors in 25%, female factors in 58%, and is unexplained in about 17% of couples.
• Ovulation is the process where an ovum or ova are released from the ovaries. The timing of ovulation within the menstrual cycle is of foremost importance for fertilization. It is well known that follicles acquire the ability to ovulate following growth and maturation stimulated by the pituitary gonadotropins.
• Ovulation induction is a therapeutic procedure commonly used to manage infertile patients. Ovulation induction is employed in particular for the following two purposes: 1 ) to treat anovulation in patients with hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders and 2) to stimulate multiple folliculogenesis in patients (mostly with normal menstrual cycles) who are candidates for assisted reproduction techniques. These procedures are also termed controlled ovarian stimulation or hyperstimulation. However there are several complications caused by ovulation induction, including for instance multiple gestations and ovarian hyperstimulation syndrome. The complications mostly occur in polycystic ovary syndrome patients and/or full-dose gonadotropin regimens are employed. The inventor of the present invention has found that exemestane can be safely used in ovarian follicular stimulation for treating infertility in a host in need thereof, namely without causing the above side effects.
• Exemestane was first taught by US patent 4,808,616 and it is currently administered orally at the dosage of 25 mg/day in treating breast cancer in postmenopausal women. Exemestane is endowed with a peculiar mechanism of aromatase inhibition.
• the aromatase enzyme (450 arO m) is a specific form of cytochrome P450 hemoprotein composed of a P450 (heme) moiety and a peptidic moiety. The enzyme catalyzes a multistep reaction leading to aromatization of the A ring of the androgen substrate (mainly androstenedione) to estrone, requiring the presence of the cofactor NADPH.
• exemestane The newly found therapeutic utility of exemestane is actually surprising. From the pharmacological point of view, the ovarian follicular stimulating activity of exemestane may be found in several concurrent factors, including its peculiar mechanism of aromatase inactivation, the dosage and the treatment schedule.
• a first object of the present invention is to provide a method for treating infertility in a female host in need thereof comprising the administration of a therapeutically effective follicular stimulating amount of exemestane to said host.
• a method is provided for inducing ovarian follicular stimulation in a female host in need thereof comprising the administration and subsequent removal of a therapeutically effective follicular stimulating and/or inhibiting amount of exemestane to said host.
• a female host is for instance a mammalian female, in particular a woman.
• Preferred examples of such hosts are patients with hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders, and patients who otherwise are candidate for assisted reproduction techniques.
• the clinical terms as used herein have their plain meanings, well known in the art.
• anovulation refers to lack of ovulation, of course.
• Ovarian follicular stimulation refers to the process wherein exemestane is used to bring about ovulation in female hosts, who are otherwise anovulatory, resulting in induction of follicular rupture and ovulation of fertilizable oocytes.
• a therapeutically effective follicular stimulating amount refers to an amount which is effective, upon single or multiple dose administration to the patient, in treating infertility e.g. by inducing ovarian follicular stimulation either when being taken or after its stoppage causing a rebound hyperstimulation of the ovaries.
• a method for inducing ovarian follicular stimulation in a female host suffering from hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders, or who is candidates for assisted reproduction techniques comprising the administration of a therapeutically effective follicular stimulating amount of exemestane to said host.
• a further object of the invention is the use of exemestane in the manufacture of a medicament for use in treating infertility in a female host.
• the invention also provides the use of exemestane in the manufacture of a medicament for use in inducing ovarian follicular stimulation in a female host.
• the effect of exemestane on ovarian follicular stimulation can for instance be seen in animal models once its administration is stopped with a resultant increase in follicle development and rupture.
• exemestane can be administered in any form or mode, which makes the compound bioavailable in therapeutically effective amounts.
• routes of administration include oral, sublingual, intranasal, subcutaneous, intradermal, intraperitoneal, intramuscularly, intravenous, transdermal, vaginal, rectal and the like.
• Oral or intramuscular administration is generally preferred.
• suitable oral forms are tablets, capsules, sugar and film coated tablets.
• the dosage of exemestane to be used is, of course, dependent on various factors such as the host to be treated (e.g.
• Exemestane can be administered to a woman, for instance orally, at a dosage range varying from about 5 mg/day to about 200 mg/day, possibly in divided doses, e.g. from 2 to 3 or 4.
• exemestane is administered in the early part of the menstrual cycle (day 5 to day 7) and then stopped or it is administered throughout the entire cycle and then discontinued, in order to achieve the desired effective hematic follicular stimulating hormone level.

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• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Endocrinology (AREA)
• Reproductive Health (AREA)
• Organic Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Pregnancy & Childbirth (AREA)
• Gynecology & Obstetrics (AREA)
• Diabetes (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Steroid Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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• 2003
  • 2003-07-02 PL PL03373219A patent/PL373219A1/xx not_active Application Discontinuation
  • 2003-07-02 MX MXPA05000251A patent/MXPA05000251A/es unknown
  • 2003-07-02 JP JP2004519563A patent/JP2005536490A/ja active Pending
  • 2003-07-02 EP EP03762980A patent/EP1531829A2/en not_active Withdrawn
  • 2003-07-02 BR BR0312393-6A patent/BR0312393A/pt not_active IP Right Cessation
  • 2003-07-02 KR KR1020057000051A patent/KR20050077045A/ko not_active Application Discontinuation
  • 2003-07-02 WO PCT/US2003/016252 patent/WO2004004634A2/en active Application Filing
  • 2003-07-02 CN CN038157306A patent/CN1665516A/zh active Pending
  • 2003-07-02 CA CA002491372A patent/CA2491372A1/en not_active Abandoned
  • 2003-07-02 AU AU2003247404A patent/AU2003247404A1/en not_active Abandoned
• 2004
  • 2004-12-16 IL IL16581304A patent/IL165813A0/xx unknown
• 2005
  • 2005-12-15 ZA ZA200410135A patent/ZA200410135B/en unknown

Non-Patent Citations (1)

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