EP1143978A2 - Utilisation d'hormones sexuelles pour l'obtention d'une composition pharmaceutique nasale utile pour le traitement des saignements uterins indesirables - Google Patents

Utilisation d'hormones sexuelles pour l'obtention d'une composition pharmaceutique nasale utile pour le traitement des saignements uterins indesirables

Info

Publication number
EP1143978A2
EP1143978A2 EP00915247A EP00915247A EP1143978A2 EP 1143978 A2 EP1143978 A2 EP 1143978A2 EP 00915247 A EP00915247 A EP 00915247A EP 00915247 A EP00915247 A EP 00915247A EP 1143978 A2 EP1143978 A2 EP 1143978A2
Authority
EP
European Patent Office
Prior art keywords
estradiol
nasal
pharmaceutical composition
use according
cyclodextrin
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.)
Withdrawn
Application number
EP00915247A
Other languages
German (de)
English (en)
French (fr)
Inventor
Yannis Tsouderos
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.)
Laboratoires Servier SAS
Original Assignee
ADIR SARL
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 ADIR SARL filed Critical ADIR SARL
Publication of EP1143978A2 publication Critical patent/EP1143978A2/fr
Withdrawn legal-status Critical Current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
    • A61K31/56—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
    • 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
    • A61K31/565—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
    • A61K31/569—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 substituted in position 17 alpha, e.g. ethisterone
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/724—Cyclodextrins
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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

Definitions

  • the present invention relates to the use of sex hormones for obtaining a pharmaceutical composition suitable for nasal administration useful for the treatment of undesirable uterine bleeding phenomena in women.
  • Sex hormones can be administered in the treatment of diseases due to estrogen deficiencies and to symptoms of estrogen deficiency, notably linked to artificial or natural menopause. These estrogen deficiencies are also implicated in the occurrence of post-menopausal osteoporosis as well as in phenomena of cerebral aging and cardiovascular diseases.
  • sex hormones are also administered, in different doses, for contraceptive purposes or in the treatment of amenorrhea not related to menopause.
  • compositions containing sex hormones currently available to the medical profession are compositions suitable for oral (tablets), transcutaneous (gels, transdermal systems), parenteral (intramuscular injections, implants) or vaginal (creams) administration. , gels, ).
  • the Applicant has now discovered that the use of sex hormones for obtaining a pharmaceutical composition suitable for administration by the nasal route surprisingly makes it possible to treat uterine bleeding observed outside of menstrual periods. This surprising effect obtained via the nasal route has never been observed with the other formulations currently available to the medical profession.
  • sex hormones which can be used in the pharmaceutical compositions according to the invention, mention may be made, without limitation, of natural steroidal estrogens such as 17- ⁇ -estradiol (estradiol), estrone and their derivatives, synthetic steroidal estrogens such as ethinylestradiol, progestins like progesterone, pregnans derived from progesterone or 17- ⁇ -OH-progesterone like dydrogesterone, chlormadinone acetate, medrogesterone, medroxyprogesterone acetate, norpregnanes like demegestone, promegestone, nomegestrol acetate or 19-nortestosterone derivatives, such as norethisterone, ethynodiol diacetate, norgestrel, levonorgestrel, desogestrel, gestodene or norgestimate, or antrogens such as testosterone or dihydrotestosterone.
  • the preferred sex hormones according to the invention are estradiol or estradiol / progestin mixtures. More specifically, the pharmaceutical compositions suitable for the nasal administration of sex hormones are those which contain one or more sex hormones at doses varying according to the needs of the patient and a cyclodextrin.
  • the pharmaceutical compositions according to the invention are characterized in that the cyclodextrin is a partially methylated cyclodextrin.
  • a preferred composition according to the invention is a composition containing estradiol or an estradiol / progestin mixture and a partially and randomly methylated cyclodextrin.
  • the preferred progestin is norethisterone.
  • compositions are preferred for treating undesirable uterine bleeding during menopause.
  • a pharmaceutical composition suitable for nasal administration of estradiol has been prepared and clinically tested with the aim of observing the treatment of phenomena of uterine bleeding in postmenopausal women.
  • This composition is a solution containing 0.21 g of estradiol hemihydrate, 2.10 g of partially randomized methylated cyclodextrin, 0.9 g of sodium chloride and purified water (qs 100 ml) after adjusting the pH of the solution at 6.
  • This solution was packaged in a bottle fitted with a dosing pump to obtain 0.07 ml nasal sprays. Each spray then delivers a dose of 150 ⁇ g of estradiol hemihydrate.
  • estradiol composition of the type described above (estradiol spray) and an oral placebo composition
  • the patients received a progestin, at least for 10 to 14 days per cycle at the doses recommended for each product.
  • the treatments were allocated according to a randomization code, and lasted 3, 6 or 12 months.
  • the daily dose administered for the nasal spray form is 300 ⁇ g of estradiol

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Steroid Compounds (AREA)
EP00915247A 1999-03-31 2000-03-30 Utilisation d'hormones sexuelles pour l'obtention d'une composition pharmaceutique nasale utile pour le traitement des saignements uterins indesirables Withdrawn EP1143978A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9904022A FR2791572A1 (fr) 1999-03-31 1999-03-31 Utilisation d'hormones sexuelles pour l'obtention d'une composition pharmaceutique nasale utile pour le traitement des saignements uterins indesirables
FR9904022 1999-03-31
PCT/FR2000/000790 WO2000059447A2 (fr) 1999-03-31 2000-03-30 Utilisation d'hormones sexuelles pour l'obtention d'une composition pharmaceutique nasale utile pour le traitement des saignements uterins indesirables

Publications (1)

Publication Number Publication Date
EP1143978A2 true EP1143978A2 (fr) 2001-10-17

Family

ID=9543854

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00915247A Withdrawn EP1143978A2 (fr) 1999-03-31 2000-03-30 Utilisation d'hormones sexuelles pour l'obtention d'une composition pharmaceutique nasale utile pour le traitement des saignements uterins indesirables

Country Status (16)

Country Link
EP (1) EP1143978A2 (ko)
JP (1) JP2002541076A (ko)
KR (1) KR20010102464A (ko)
CN (1) CN1346273A (ko)
AU (1) AU3662300A (ko)
BR (1) BR0008577A (ko)
CA (1) CA2361885A1 (ko)
EA (1) EA200100801A1 (ko)
FR (1) FR2791572A1 (ko)
HK (1) HK1044486A1 (ko)
HU (1) HUP0200244A3 (ko)
NO (1) NO20014022D0 (ko)
NZ (1) NZ513672A (ko)
PL (1) PL356767A1 (ko)
WO (1) WO2000059447A2 (ko)
ZA (1) ZA200106689B (ko)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4383993A (en) * 1980-05-30 1983-05-17 University Of Kentucky Research Foundation Nasal dosage forms containing natural female sex hormones
NL8801670A (nl) * 1988-07-01 1990-02-01 Walter Adrianus Josephus Johan Farmaceutisch preparaat.
US5922699A (en) * 1996-06-07 1999-07-13 Pherin Corporation 19-nor-cholane steroids as neurochemical initiators of change in human hypothalamic function
KR20000067970A (ko) * 1996-07-23 2000-11-25 케빈 맥카티 Ｐｍｓ 및 불안증의 증상을 완화시키기 위한 ｖｎｏ의 신경화학

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0059447A2 *

Also Published As

Publication number Publication date
FR2791572A1 (fr) 2000-10-06
NZ513672A (en) 2001-09-28
WO2000059447A2 (fr) 2000-10-12
BR0008577A (pt) 2002-10-01
ZA200106689B (en) 2002-11-14
KR20010102464A (ko) 2001-11-15
AU3662300A (en) 2000-10-23
EA200100801A1 (ru) 2002-04-25
PL356767A1 (en) 2004-07-12
CA2361885A1 (fr) 2000-10-12
HK1044486A1 (zh) 2002-10-25
NO20014022L (no) 2001-08-17
WO2000059447A3 (fr) 2001-04-26
JP2002541076A (ja) 2002-12-03
HUP0200244A2 (hu) 2002-07-29
CN1346273A (zh) 2002-04-24
HUP0200244A3 (en) 2003-05-28
NO20014022D0 (no) 2001-08-17

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