EP0873120A1 - Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of menopausal symptoms - Google Patents

Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of menopausal symptoms

Info

Publication number
EP0873120A1
EP0873120A1 EP97900200A EP97900200A EP0873120A1 EP 0873120 A1 EP0873120 A1 EP 0873120A1 EP 97900200 A EP97900200 A EP 97900200A EP 97900200 A EP97900200 A EP 97900200A EP 0873120 A1 EP0873120 A1 EP 0873120A1
Authority
EP
European Patent Office
Prior art keywords
use according
com
phenyl
compound
treatment
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Withdrawn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
EP97900200A
Other languages
German (de)
English (en)
French (fr)
Inventor
Michael Shalmi
Niels Korsgaard
Birgitte Hjort Guldhammer
James Robertson Piggott
Virender Mohan Labroo
Steven Bain
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.)
Novo Nordisk AS
Original Assignee
Novo Nordisk AS
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 Novo Nordisk AS filed Critical Novo Nordisk AS
Publication of EP0873120A1 publication Critical patent/EP0873120A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12Drugs for genital or sexual disorders; Contraceptives for climacteric disorders

Definitions

  • the present invention relates to the use of compounds of the general formula I for the prevention and treatment of menopausal symptoms.
  • the present inventi ⁇ on also embraces pharmaceutical compositions comprising these compounds and methods of using the compounds and their pharmaceutical compositions.
  • the menopause is defined as the final episode of menstrual bleeding in women. However, the term is used commonly to refer to the period of the female climac- teric that encompasses the transitional period between the reproductive years up to and beyond the last episode of menstrual bleeding. This period is also referred to as the peri-menopause or the climacterium. During this period there is a gra ⁇ dual but progressive loss of ovarian function and a variety of endocrine, somatic and psycological changes. The median age of the women at the time of cessati- on of menstrual bleeding is 50 to 51 years. Since the life expectancy of women in developed countries is now close to 80 years, approximately one-third of a woman's life-span occurs after cessation of reproductive function.
  • the symptoms associated with declining estrogen levels in the perimenopause include hot flashes and sweats, atrophic vaginitis, headache, dizziness, joint pain, sleeplessness, apathy, lassitude, muscular weakness, palpitations and psy ⁇ chological symptoms such as changes in mood, depression, memory and concen ⁇ tration deficits, irritability and problems related to sexual functioning. All of these symptoms are a direct consequence of the declining estrogen production.
  • the treatment of these disorders involves different regimens of estro ⁇ gen administration with or without concomitant progestin administration. Estro ⁇ gen alone and in different combinations is often associated with unacceptable side effects.
  • progestin are often poorly tolerated causing depressi- on and may even in some tissues negate the positive results of estrogen.
  • the hormone replacement theraphy often causes unpleasant effects such as water retention, frequently weight gain and prolonged therapy is associated with an in ⁇ creased risk of endometrial cancer.
  • a new compound which ameliorates the symptoms of the menopause, but which is safe and cau- ses less side effects, and preferably brings the woman into a stable post- menopausal state in a reduced period of time than known compounds.
  • Centchroman is a non-steroidal compound known to have antiestrogenic activity. It is in use in India as an oral contraceptive (see, for example, Salman et al., U.S. Patent Specification No. 4,447,622; Singh et al., Acta Endocrinal ( Copenh ) 123 (1992), 444 - 450; Grubb, £un £ ⁇ i ⁇ £bsl ⁇ l Gyo ⁇ cfii 3. ( 1 991 ), 491 - 495; San- karan et al., Contraception 9 ( 1 974), 279 - 289; Indian Patent Specification No. 1 29187).
  • Centchroman has also been investigated as an anti-cancer agent for treatment of advanced breast cancer (Misra et al., Int J Cancer 43 (1 989), 781 - 783. Recently, centchroman as a racemate has been found as a potent choleste ⁇ rol lowering pharmaceutical expressed by a significant decrease of the serum concentrations (S.D. Bain et al., J Min Eon fi£S 2 ( 1 994), S 394).
  • U.S. patent 5,453,442 describes methods of lowering serum cholesterol and in- hibiting smoother muscle cell proliferation in humans and inhibiting uterine fibroid disease and endometriosis in women by administering compounds of formula I as shown therein.
  • US patent 5,280,040 describes methods and phar ⁇ maceutical compositions for reducing bone loss using 3,4-diaryl chromans and their pharmaceutically acceptable salts. There is no disclosure in the patents of using the compounds to treat or prevent menopausal symptoms.
  • One object of the present invention is to provide compounds which can effecti ⁇ vely be used in the treatment or prophylaxis of menopausal symptoms.
  • the present invention is based in part on the discovery that a representative 3,4- diarylchroman, centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-[p-(beta- pyrrolidinoethox ⁇ )phenyl]-7-methoxychroman) is a partial estrogen antago- nist/agonist and elicits similar actions as estrogen in a range of animal models and is useful in the treatment of climacteric symptoms and complaints without having the adverse effects associated with estrogen treatment.
  • compounds of formula I or their pharmaceutically acceptable salts are used for prevention and treatment of menopausal symptoms in a patient.
  • R 1 , R 4 and R 5 are individually hydrogen, hydroxy, halogen, trifluoromethyl, C, .6 alkyl, C ⁇ alkoxy or (tertiary amino)(C 1 . 6 alkoxy); and R 2 and
  • R 3 are individually hydrogen or a C 1 -6 alkyl.
  • C ⁇ alkyl includes straight and branched chain alkyl radicals containing from 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-amyl, sec- amyl, n-hexyl, 2-ethylbutyl, 2,3-dimethylbutyl and the like.
  • C, ⁇ al ⁇ koxy includes straight and branched chain alkoxy radicals containing from 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-amyloxy, sec-amyloxy, n-hexyloxy, 2-ethylbutoxy, 2,3- dimethylbutoxy and the like.
  • Hydrogen includes chloro, fluoro, bromo and iodo.
  • (tertiary amino)(C,. 6 alkoxy) is a C,. 6 alkoxy group which is substituted by a tertiary amino radical.
  • the tertiary amino radical may be a N,N- dialkylamine such as a N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino and N,N-dibutylamino or a polymethyleneimine, e.g., piperidine, pyrrolidine, N- methylpiperazine or morpholine.
  • Preferred compounds include those in which R ' is C,. 6 alkoxy; R 2 and R 3 are C,. 6 alkyl, especially methyl; R 4 is hydrogen; and R 5 is (tertiary amino)(C 1 . 6 alkoxy) of the polymethyleneimine type.
  • R 1 is in the 7-position and is C ⁇ alkoxy, particu ⁇ larly methoxy; each of R 2 and R 3 is methyl, R 4 is hydrogen, and R 5 is in the 4- position and is a (tertiary amino)(C,. 6 alkoxy) radical such as 2-(pyrrolidin-1 - yDethoxy with formula II
  • a particularly preferred compound for use within the present invention is cen ⁇ tchroman having the formula IV
  • 3,4-diarylchromans are prepared according to known methods, such as those di ⁇ sclosed in U.S. Patent Specification No. 3,340,276 to Carney et al., U.S. Patent Specification No. 3,822,287 to Bolger, and Ray et al., Med Chem 12 (1 976), 276 - 279, the contents of which are incorporated herein by reference.
  • Conver ⁇ sion of the cis isomer to the trans configuration by means of an organometallic base-catalyzed rearrangement is disclosed in U.S. Patent Specification No. 3,822,287.
  • the optically active d- and l-enantiomers may be prepared as disclo ⁇ sed by Salman et al.
  • 3,4-diarylchromans of formula I may be prepared in the form of pharmaceutically acceptable salts, especially acid-addition salts, in- eluding salts of organic acids and mineral acids.
  • salts include salts of organic acids such as formic acid, fumaric acid, acetic acid, propionic a- cid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, succinic acid, malic acid, tartaric acid, citric acid, benzoic acid, salicylic acid and the like.
  • Suitable inorga ⁇ nic acid-addition salts include salts of hydrochloric, hydrobromic, sulphuric and phosphoric acids and the like.
  • the acid addition salts may be obtained as the di ⁇ rect products of compound synthesis.
  • the free base may be dissolved in a suitable solvent containing the appropriate acid, and the salt isola ⁇ ted by evaporating the solvent or otherwise separating the salt and solvent.
  • 3,4-diarylchromans of formula I and their salts are useful within human and vete ⁇ rinary medicine, for example, in the treatment of patients suffering from meno ⁇ pausal symptoms.
  • 3,4-diarylchromans of formula I and their pharmaceutically acceptable salts are formulated with a phar ⁇ maceutically acceptable carrier to provide a medicament for parenteral, oral, na- sal, rectal, subdermal or intradermal or transdermal administration according to conventional methods.
  • Formulations may further include one or more diluents, fillers, emulsifiers, preservatives, buffers, excipients, etc.
  • the active compound of formula I is prepa- red in a form suitable for oral administration, such as a tablet or capsule.
  • a pharmaceutically acceptable salt of the compound of formula I is com ⁇ bined with a carrier and moulded into a tablet.
  • Suitable carriers in this regard in ⁇ clude starch, sugars, dicalcium phosphate, calcium stearate, magnesium stearate and the like.
  • Such compositions may further include one or more auxiliary sub- stances, such as wetting agents, emulsifiers, preservatives, stabilizers, colouring additives, etc.
  • compositions containing a compound of formula I may be admini ⁇ stered one or more times per day or week.
  • An effective amount of such a phar- maceutical composition is the amount that provides a clinically significant effect against menopausal symptoms. Such amounts will depend, in part, on the parti ⁇ cular condition to be treated, age, weight, and general health of the patient, and other factors evident to those skilled in the art.
  • a typical daily dose will contain a nontoxic dosage range of from about 0.001 to about 75 mg/kg patient per day of a compound of the present invention.
  • compositions containing a compound of formula I may be administered in unit dosage form one or more times per day or week.
  • they may be provided as controlled release formulations suitable for dermal implantation.
  • Implants are formulated to provide release of active com ⁇ pound over the desired period of time, which can be up to several years.
  • Con ⁇ trolled-release formulations are disclosed by, for example, Sanders et al., J Pharm Sci 73 ( 1 964), 1 294 - 1 297, 1 984; U.S: Patent Specification No. 4,489,056; and U.S. Patent Specification No. 4,210,644, which are incorpora- ted herein by reference.
  • the following examples are offered by way of illustration, not limitation.
  • Examples of preferred compounds of formula I are centchroman as a racemic mixture and as isolated l-centchroman and d-centchroman enantiomers. Further- more, 3,4-trans-2,2-dimethyl-3-phenyl-4- ⁇ 4-(2-(pyrrolidin-1 -yl)ethoxy)phenyl]-7- hydroxychroman is a preferred compound. The more preferred compound is isola ⁇ ted l-centchroman (l-3,4-trans-2,2-dimethyl-3-phenyl-4-[4-(2-(pyrrolidin-1 - yl)ethoxy)phenyl]-7-methoxychroman).
  • Examples of pharmaceutically acceptable acid addition salts are salts with non- toxic acids, either inorganic acids such as hydrochloric acid, sulphuric acid and phosphoric acid, or organic acids such as formic acid, fumaric acid, acetic acid, propionic acid, succinic acid, gluconic acid, lactic acid, citric acid, ascorbic acid, benzoic acid, embonic acid, methanesulphonic acid and malonic acid.
  • inorganic acids such as hydrochloric acid, sulphuric acid and phosphoric acid
  • organic acids such as formic acid, fumaric acid, acetic acid, propionic acid, succinic acid, gluconic acid, lactic acid, citric acid, ascorbic acid, benzoic acid, embonic acid, methanesulphonic acid and malonic acid.
  • a compound of the invention is given in the amount of 0,001 to 75 mg/kg pa ⁇ tient per day and the frequency of vasomotor symptoms are closely monitored together with the variables laid down in the Green Scale or Kupperman Indeks monitoring systems. The dosing of the compound of the invention continues for a period of 4 weeks.
  • This test is ran as Test 1 , except the dosing period is for a period of 6 months.
  • Activity defined as either total cessation of one or more sequellae of the patient, or reduced severity or occurrence thereof, or a more rapid advancement to men ⁇ opausal state, in any of the above assays indicates that the compounds of the invention are useful in the treatment of menopausal symptoms.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Reproductive Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrane Compounds (AREA)
EP97900200A 1996-01-11 1997-01-09 Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of menopausal symptoms Withdrawn EP0873120A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US678261 1984-12-05
US983496P 1996-01-11 1996-01-11
US9834P 1996-01-11
US67826196A 1996-07-11 1996-07-11
PCT/DK1997/000008 WO1997025035A1 (en) 1996-01-11 1997-01-09 Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of menopausal symptoms

Publications (1)

Publication Number Publication Date
EP0873120A1 true EP0873120A1 (en) 1998-10-28

Family

ID=26679921

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97900200A Withdrawn EP0873120A1 (en) 1996-01-11 1997-01-09 Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of menopausal symptoms

Country Status (12)

Country Link
EP (1) EP0873120A1 (ko)
JP (1) JP2000506505A (ko)
KR (1) KR19990077156A (ko)
AU (1) AU1367297A (ko)
BR (1) BR9706967A (ko)
CA (1) CA2241623A1 (ko)
CZ (1) CZ217298A3 (ko)
HU (1) HUP9902683A3 (ko)
IL (1) IL124882A0 (ko)
NO (1) NO983178L (ko)
PL (1) PL327831A1 (ko)
WO (1) WO1997025035A1 (ko)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6465445B1 (en) 1998-06-11 2002-10-15 Endorecherche, Inc. Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
US7005428B1 (en) 1998-06-11 2006-02-28 Endorecherche, Inc. Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
DK1246814T3 (da) * 1999-12-30 2005-05-30 Signal Pharm Llc Forbindelser og fremgangsmåder til modulation af östrogenreceptorer
US8080675B2 (en) 2004-09-21 2011-12-20 Marshall Edwards, Inc. Chroman derivatives, medicaments and use in therapy
ATE532777T1 (de) 2004-09-21 2011-11-15 Marshall Edwards Inc Substituierte chromanderivate, medikamente und anwendungen in der therapie
WO2006042409A1 (en) 2004-10-20 2006-04-27 Endorecherche, Inc. Sex steroid precursors alone or in combination with a selective estrogen receptor modulator and/or with estrogens and/or a type 5 cgmp phosphodiesterase inhibitor for the prevention and treatment of vaginal dryness and sexual dysfunction in postmenopausal women
US8268806B2 (en) 2007-08-10 2012-09-18 Endorecherche, Inc. Pharmaceutical compositions
JP5558358B2 (ja) 2007-10-16 2014-07-23 レプロス セラピューティクス インコーポレイティド メタボリック症候群用のtrans−クロミフェン
US20100317635A1 (en) 2009-06-16 2010-12-16 Endorecherche, Inc. Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators
KR20130031339A (ko) 2010-06-16 2013-03-28 앙도르쉐르슈 인코포레이티드 에스트로겐-관련 질병의 치료 또는 예방 방법
JP6013349B2 (ja) 2010-11-01 2016-10-25 メイ ファーマ, インク.Mei Pharma, Inc. 癌の処置のためのイソフラボノイド化合物および方法
CA2865234A1 (en) 2012-02-29 2013-09-06 Repros Therapeutics Inc. Combination therapy for treating androgen deficiency
AU2015213484B2 (en) 2014-02-07 2015-11-05 Kazia Therapeutics Limited Functionalised benzopyran compounds and use thereof
US9744177B2 (en) 2014-03-10 2017-08-29 Endorecherche, Inc. Treatment of male androgen deficiency symptoms or diseases with sex steroid precursor combined with SERM
ES2877712T3 (es) 2015-02-02 2021-11-17 Mei Pharma Inc Terapias combinadas para su uso en el tratamiento del cáncer de mama
AU2016352592B2 (en) 2015-11-10 2023-04-27 Paracrine Therapeutics Ab Treatment of ER-negative breast cancer with an PDGF-CC inhibitor and an anti estrogen

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4729999A (en) * 1984-10-12 1988-03-08 Bcm Technologies Antiestrogen therapy for symptoms of estrogen deficiency

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9725035A1 *

Also Published As

Publication number Publication date
PL327831A1 (en) 1999-01-04
NO983178L (no) 1998-07-10
HUP9902683A3 (en) 2001-08-28
CZ217298A3 (cs) 1999-01-13
KR19990077156A (ko) 1999-10-25
HUP9902683A2 (hu) 2001-04-28
CA2241623A1 (en) 1997-07-17
WO1997025035A1 (en) 1997-07-17
IL124882A0 (en) 1999-01-26
JP2000506505A (ja) 2000-05-30
AU1367297A (en) 1997-08-01
BR9706967A (pt) 1999-05-04

Similar Documents

Publication Publication Date Title
US5726202A (en) Benign prostatic hypertrophy
AU693628B2 (en) Use of 3,4-diphenylchromans
EP0873120A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of menopausal symptoms
EP0873122B1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of prostatic carcinoma
EP0873121A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of atrophy of skin and/or mucous membranes
US6008242A (en) Use of 1-centchroman for the manufacture of a pharmaceutical composition for the treatment of obesity
WO1998033499A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for increasing libido in post-menopausal women
US5886021A (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for vasodilatory treatment or prophylaxis
AU702407B2 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment of prophylaxis of idiopathic or physiologic gynaecomastia
US5780502A (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for inhibiting one or more symptoms of premenstrual syndrome
EP0921797A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for lowering intraocular pressure
WO1998002154A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for inhibiting one or more symptoms of premenstrual syndrome
WO1998033500A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for inhibiting senescence-associated motor impairment
WO1998032437A1 (en) Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for inhibiting one or more psychiatric disorders
MXPA97005219A (en) Use of 3,4-difenil-chromanos for the manufacture of a pharmaceutical composition for the treatment of profilaxis of disorders ginecologi
KR19980701383A (ko) 부인병 질환의 치료 또는 예방용 약학적 조성물의 제조를 위한 3,4-디페닐크로만의 사용(use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment of prophylaxis of idiopathic or physiologic gynaecomastia)
MXPA97005379A (en) Use of the 3,4-difenil-chromians for the manufacture of a pharmaceutical composition for treatment or profilaxis vasodilatad
MXPA97005218A (es) Uso de los 3,4-difenil-cromanos para la fabricacion de una composicion farmaceutica para el tratamiento o profilaxis de ginecomastia idiopatica o fisiologica
KR19980701384A (ko) 측발성 또는 생리적 여성형유방의 치료 또는 예방용 약학적 조성물의 제조를 위한 3,4-디페닐크로만의 사용

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19980811

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

RIN1 Information on inventor provided before grant (corrected)

Inventor name: BAIN, STEVEN

Inventor name: LABROO, VIRENDER, MOHAN

Inventor name: PIGGOTT, JAMES, ROBERTSON

Inventor name: GULDHAMMER, BIRGITTE, HJORT

Inventor name: KORSGAARD, NIELS

Inventor name: SHALMI, MICHAEL

RIN1 Information on inventor provided before grant (corrected)

Inventor name: BAIN, STEVEN

Inventor name: LABROO, VIRENDER, MOHAN

Inventor name: PIGGOTT, JAMES, ROBERTSON

Inventor name: GULDHAMMER, BIRGITTE, HJORT

Inventor name: KORSGAARD, NIELS

Inventor name: SHALMI, MICHAEL

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Withdrawal date: 19991203