SK9592002A3 - A method for reduction or elimination of the incidence of menopausal symptoms, method of treatment or decreasing the risk of an acquiring disease, a pharmaceutical composition and a kit - Google Patents

A method for reduction or elimination of the incidence of menopausal symptoms, method of treatment or decreasing the risk of an acquiring disease, a pharmaceutical composition and a kit Download PDF

Info

Publication number: SK9592002A3
Authority: SK; Slovakia
Prior art keywords: group; pharmaceutical composition; estrogen; acid; effective amount
Prior art date: 2000-01-28

Application number

SK959-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Fernand Labrie

Original Assignee

Endorech Inc

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.)

2000-01-28

Filing date

2001-01-26

Publication date

2003-12-02

2001-01-26 Application filed by Endorech Inc filed Critical Endorech Inc

2003-12-02 Publication of SK9592002A3 publication Critical patent/SK9592002A3/sk

Links

238000011282 treatment Methods 0.000 title claims abstract description 144
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 52
230000009467 reduction Effects 0.000 title claims abstract description 9
206010027304 Menopausal symptoms Diseases 0.000 title claims abstract description 6
238000000034 method Methods 0.000 title abstract description 81
201000010099 disease Diseases 0.000 title abstract description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 22
230000003247 decreasing effect Effects 0.000 title abstract description 14
230000008030 elimination Effects 0.000 title abstract 2
238000003379 elimination reaction Methods 0.000 title abstract 2
239000000262 estrogen Substances 0.000 claims abstract description 146
229940011871 estrogen Drugs 0.000 claims abstract description 146
239000000333 selective estrogen receptor modulator Substances 0.000 claims abstract description 133
229940095743 selective estrogen receptor modulator Drugs 0.000 claims abstract description 111
150000001875 compounds Chemical class 0.000 claims abstract description 83
208000026310 Breast neoplasm Diseases 0.000 claims abstract description 43
206010006187 Breast cancer Diseases 0.000 claims abstract description 40
210000000481 breast Anatomy 0.000 claims abstract description 24
230000001076 estrogenic effect Effects 0.000 claims abstract description 21
208000001132 Osteoporosis Diseases 0.000 claims abstract description 19
206010060800 Hot flush Diseases 0.000 claims abstract description 17
208000033830 Hot Flashes Diseases 0.000 claims abstract description 15
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 11
208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 11
208000008589 Obesity Diseases 0.000 claims abstract description 11
235000020824 obesity Nutrition 0.000 claims abstract description 11
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 10
206010020772 Hypertension Diseases 0.000 claims abstract description 10
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
206010022489 Insulin Resistance Diseases 0.000 claims abstract description 9
210000003205 muscle Anatomy 0.000 claims abstract description 9
208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 9
229940122361 Bisphosphonate Drugs 0.000 claims abstract description 8
150000004663 bisphosphonates Chemical class 0.000 claims abstract description 7
206010014733 Endometrial cancer Diseases 0.000 claims abstract description 6
206010014759 Endometrial neoplasm Diseases 0.000 claims abstract description 6
206010047791 Vulvovaginal dryness Diseases 0.000 claims abstract description 4
208000037093 Menstruation Disturbances Diseases 0.000 claims abstract description 3
206010027339 Menstruation irregular Diseases 0.000 claims abstract description 3
FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 claims description 119
FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 claims description 116
229960002847 prasterone Drugs 0.000 claims description 116
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 claims description 99
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims description 73
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 73
229960003399 estrone Drugs 0.000 claims description 52
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 51
DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 claims description 48
239000000203 mixture Substances 0.000 claims description 37
GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 33
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229940002612 prodrug Drugs 0.000 claims description 30
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-1 SH 646 Chemical compound 0.000 claims description 29
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UCJGJABZCDBEDK-UHFFFAOYSA-N bazedoxifene Chemical group C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UCJGJABZCDBEDK-UHFFFAOYSA-N 0.000 claims description 27
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 25
229960001603 tamoxifen Drugs 0.000 claims description 25
229960005309 estradiol Drugs 0.000 claims description 24
HJQQVNIORAQATK-DDJBQNAASA-N (e)-3-[4-[(z)-1,2-diphenylbut-1-enyl]phenyl]prop-2-enoic acid Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(\C=C\C(O)=O)=CC=1)/C1=CC=CC=C1 HJQQVNIORAQATK-DDJBQNAASA-N 0.000 claims description 22
239000003098 androgen Substances 0.000 claims description 22
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
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230000002357 endometrial effect Effects 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
230000009245 menopause Effects 0.000 claims description 15
208000024891 symptom Diseases 0.000 claims description 14
XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 14
ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 13
229950004203 droloxifene Drugs 0.000 claims description 13
238000002657 hormone replacement therapy Methods 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 12
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 claims description 11
238000001727 in vivo Methods 0.000 claims description 11
BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 claims description 10
CZWCKYRVOZZJNM-UHFFFAOYSA-N Prasterone sodium sulfate Natural products C1C(OS(O)(=O)=O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 CZWCKYRVOZZJNM-UHFFFAOYSA-N 0.000 claims description 10
CZWCKYRVOZZJNM-USOAJAOKSA-N dehydroepiandrosterone sulfate Chemical compound C1[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 CZWCKYRVOZZJNM-USOAJAOKSA-N 0.000 claims description 10
150000002148 esters Chemical class 0.000 claims description 10
229950009829 prasterone sulfate Drugs 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 claims description 8
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
239000000654 additive Substances 0.000 claims description 7
229960005471 androstenedione Drugs 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
IMSSROKUHAOUJS-MJCUULBUSA-N mestranol Chemical compound C1C[C@]2(C)[C@@](C#C)(O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 IMSSROKUHAOUJS-MJCUULBUSA-N 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
206010046788 Uterine haemorrhage Diseases 0.000 claims description 6
206010046910 Vaginal haemorrhage Diseases 0.000 claims description 6
AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 claims description 6
AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 claims description 6
229940035811 conjugated estrogen Drugs 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 claims description 5
206010006298 Breast pain Diseases 0.000 claims description 5
208000006662 Mastodynia Diseases 0.000 claims description 5
230000000996 additive effect Effects 0.000 claims description 5
150000001562 benzopyrans Chemical class 0.000 claims description 5
WKRLQDKEXYKHJB-HFTRVMKXSA-N equilin Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 WKRLQDKEXYKHJB-HFTRVMKXSA-N 0.000 claims description 5
PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 claims description 5
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WZDGZWOAQTVYBX-XOINTXKNSA-N tibolone Chemical compound C([C@@H]12)C[C@]3(C)[C@@](C#C)(O)CC[C@H]3[C@@H]1[C@H](C)CC1=C2CCC(=O)C1 WZDGZWOAQTVYBX-XOINTXKNSA-N 0.000 claims description 5
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229960001023 tibolone Drugs 0.000 claims description 4
230000001457 vasomotor Effects 0.000 claims description 4
JICOGKJOQXTAIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 JICOGKJOQXTAIP-UHFFFAOYSA-N 0.000 claims description 3
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MCGDSOGUHLTADD-UHFFFAOYSA-N arzoxifene Chemical compound C1=CC(OC)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 MCGDSOGUHLTADD-UHFFFAOYSA-N 0.000 claims description 2
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MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims 8
HQALDKFFRYFTKP-UHFFFAOYSA-N 2-[4-[4-(2-benzyl-1-benzothiophen-3-yl)phenyl]-2-bromo-6-(3-methoxyphenyl)phenoxy]acetic acid Chemical compound COC1=CC=CC(C=2C(=C(Br)C=C(C=2)C=2C=CC(=CC=2)C=2C3=CC=CC=C3SC=2CC=2C=CC=CC=2)OCC(O)=O)=C1 HQALDKFFRYFTKP-UHFFFAOYSA-N 0.000 claims 7
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229910052736 halogen Chemical group 0.000 claims 3
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Classifications

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- 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
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic 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
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (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)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Physical Education & Sports Medicine (AREA)
Obesity (AREA)
Hematology (AREA)
Endocrinology (AREA)
Orthopedic Medicine & Surgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
Psychiatry (AREA)
Vascular Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Reproductive Health (AREA)
Hospice & Palliative Care (AREA)
Child & Adolescent Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK959-2002A 2000-01-28 2001-01-26 A method for reduction or elimination of the incidence of menopausal symptoms, method of treatment or decreasing the risk of an acquiring disease, a pharmaceutical composition and a kit SK9592002A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17860100P	2000-01-28	2000-01-28
PCT/CA2001/000086 WO2001054699A1 (en)	2000-01-28	2001-01-26	Selective estrogen receptor modulators in combination with estrogens

Publications (1)

Publication Number	Publication Date
SK9592002A3 true SK9592002A3 (en)	2003-12-02

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ID=22653187

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SK959-2002A SK9592002A3 (en)	2000-01-28	2001-01-26	A method for reduction or elimination of the incidence of menopausal symptoms, method of treatment or decreasing the risk of an acquiring disease, a pharmaceutical composition and a kit

Country Status (21)

Country	Link
US (3)	US20020198179A1 (cs)
EP (1)	EP1251855A1 (cs)
JP (1)	JP2003520817A (cs)
KR (1)	KR20020073566A (cs)
CN (1)	CN1400904A (cs)
AR (1)	AR035564A1 (cs)
AU (1)	AU2991301A (cs)
BR (1)	BR0108107A (cs)
CA (1)	CA2395730A1 (cs)
CZ (1)	CZ20022401A3 (cs)
HK (1)	HK1048761A1 (cs)
HU (1)	HUP0204211A3 (cs)
IL (1)	IL149990A0 (cs)
MX (1)	MXPA02007165A (cs)
NO (1)	NO20023484D0 (cs)
NZ (1)	NZ534348A (cs)
PL (1)	PL357163A1 (cs)
RU (1)	RU2342145C2 (cs)
SK (1)	SK9592002A3 (cs)
WO (1)	WO2001054699A1 (cs)
ZA (1)	ZA200205926B (cs)

Families Citing this family (74)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0862445B2 (en) *	1995-10-06	2017-03-22	Arch Development Corporation	Combination of herpes simplex virus and chemotherapy for treating cancer
WO2002003988A2 (en) *	2000-07-06	2002-01-17	Wyeth	Use of substituted indole compounds for treating neuropeptide y-related conditions
EP1296674A2 (en) *	2000-07-06	2003-04-02	Wyeth	Use of substituted indole compounds for increasing nitric oxide synthase activity
US6245819B1 (en)	2000-07-21	2001-06-12	Hormos Medical Oy, Ltd.	Method for the treatment of vaginal dryness and sexual dysfunction in women during or after the menopause
US6503894B1 (en)	2000-08-30	2003-01-07	Unimed Pharmaceuticals, Inc.	Pharmaceutical composition and method for treating hypogonadism
IL145838A (en) *	2000-10-16	2008-11-03	Pfizer Prod Inc	Use of an estrogen agonist/antagonist for the manufacture of a medicament for treating vaginitis
DK1404331T3 (da) *	2001-07-06	2008-01-28	Penwest Pharmaceuticals Co	Sustained release-formuleringer af oxymorphon
CN1599606A (zh)	2001-07-31	2005-03-23	辉瑞产品公司	包含雌激素激动剂/拮抗剂、雌激素与孕激素组合的药物组合物、试剂盒和方法
US20080249183A1 (en) *	2001-11-29	2008-10-09	Steiner Mitchell S	Treatment of androgen-deprivation induced osteoporosis
US20050080143A1 (en) *	2001-11-29	2005-04-14	Steiner Mitchell S.	Treatment of androgen-deprivation induced osteoporosis
US20070197664A1 (en) *	2001-11-29	2007-08-23	Steiner Mitchell S	Prevention and treatment of androgen-deprivation induced osteoporosis
US20060269611A1 (en) *	2001-11-29	2006-11-30	Steiner Mitchell S	Prevention and treatment of androgen-deprivation induced osteoporosis
US20040214898A1 (en) *	2001-11-29	2004-10-28	Steiner Mitchell S.	Methods for treating hot flashes
TW200307553A (en) *	2002-05-24	2003-12-16	Akzo Nobel Nv	Treatment of post-menopausal complaints in breast cancer patients
NZ536118A (en) *	2002-06-06	2007-08-31	Hormos Medical Ltd	Method for the inhibition of urogenital atrophy or for treatment or prevention of urogenital atrophy-related symptoms in women
ES2243919T3 (es) *	2003-05-23	2005-12-01	Akzo Nobel N.V.	Formulacion solida farmaceutica que contiene tibolona.
WO2005073190A1 (en) *	2004-01-29	2005-08-11	Eli Lilly And Company	Selective estrogen receptor modulators
DE102004026669A1 (de) *	2004-05-28	2005-12-15	Grünenthal GmbH	Verwendung einer Kombination aus Ethinylestradiol und Chlormadinonacetat zur Herstellung eines Arzneimittels
US8080675B2 (en)	2004-09-21	2011-12-20	Marshall Edwards, Inc.	Chroman derivatives, medicaments and use in therapy
CN101056868B (zh)	2004-09-21	2012-05-02	马休爱德华兹股份有限公司	取代的苯并二氢吡喃衍生物、药物及其在治疗中的应用
CN106038572A (zh) *	2004-10-20	2016-10-26	恩多研究公司	性甾体前体单独或与选择性雌激素受体调节剂联合用于预防和治疗绝经后女性的性功能障碍
AU2006214515A1 (en) *	2005-02-16	2006-08-24	Wyeth	Use of estrogen receptor-b selective agonists for radiation-or chemotherapy-induced mucosistis and radiation cystitis
KR20090029237A (ko)	2006-06-02	2009-03-20	피어 트리 파머슈티칼스 인코포레이티드	위축성 질염을 치료하는 방법
CA2656067C (en) *	2006-06-23	2014-08-12	Radius Health, Inc.	Treatment of vasomotor symptoms with selective estrogen receptor modulators
WO2008101030A1 (en) *	2007-02-13	2008-08-21	The Regents Of The University Of California	Methods for amplifying steroid hormone effects
ES2590262T3 (es)	2007-02-14	2016-11-21	Hormos Medical Ltd.	Método para la preparación de derivados de trifenilbuteno con valor terapéutico
WO2008099060A2 (en)	2007-02-14	2008-08-21	Hormos Medical Ltd	Methods for the preparation of fispemifene from ospemifene
US8268806B2 (en)	2007-08-10	2012-09-18	Endorecherche, Inc.	Pharmaceutical compositions
US20140040862A1 (en) *	2008-04-03	2014-02-06	Adobe Systems Incorporated	Copying Reusable Components from a Remote Source
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
AU2016235019B2 (en) *	2009-06-16	2018-06-28	Endorecherche, Inc.	Treatment of alzheimer's disease, loss of cognition, memory loss, and dementia with sex steroid precursors in combination with selective estrogen receptor modulators
AU2014201406B2 (en) *	2009-06-16	2016-08-11	Endorecherche, Inc.	Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators
PL2568806T3 (pl)	2010-05-12	2017-03-31	Radius Health, Inc.	Schematy lecznicze
EP3205648A1 (en) *	2010-06-10	2017-08-16	Seragon Pharmaceuticals, Inc.	Estrogen receptor modulators and uses thereof
US8853423B2 (en)	2010-06-17	2014-10-07	Seragon Pharmaceuticals, Inc.	Indane estrogen receptor modulators and uses thereof
WO2012061409A1 (en)	2010-11-01	2012-05-10	Marshall Edwards, Inc.	Isoflavonoid compounds and methods for the treatment of cancer
UA113291C2 (xx)	2011-08-04	2017-01-10		Метаболіти транскломіфену і їх застосування
EP2782584B1 (en)	2011-11-23	2021-06-09	TherapeuticsMD, Inc.	Natural combination hormone replacement formulations and therapies
US9301920B2 (en)	2012-06-18	2016-04-05	Therapeuticsmd, Inc.	Natural combination hormone replacement formulations and therapies
EP2791132A4 (en)	2011-12-14	2015-08-05	Seragon Pharmaceuticals Inc	ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
BR112014014767A2 (pt)	2011-12-16	2017-06-13	Olema Pharmaceuticals Inc	novos compostos de benzopirano, composições e usos dos mesmos
CN102584687A (zh) *	2011-12-30	2012-07-18	北京赛林泰医药技术有限公司	作为选择性雌激素受体调节剂的乙烯衍生物
AU2013221478B2 (en) *	2012-02-14	2017-06-01	Repros Therapeutics Inc.	Selective estrogen receptor modulators with short half-lives and uses thereof
CN102631677A (zh) *	2012-04-19	2012-08-15	中国农业大学	一种预防和/或治疗动脉粥样硬化的药物组合物
US10806697B2 (en)	2012-12-21	2020-10-20	Therapeuticsmd, Inc.	Vaginal inserted estradiol pharmaceutical compositions and methods
US20150196640A1 (en)	2012-06-18	2015-07-16	Therapeuticsmd, Inc.	Progesterone formulations having a desirable pk profile
US10806740B2 (en)	2012-06-18	2020-10-20	Therapeuticsmd, Inc.	Natural combination hormone replacement formulations and therapies
US20130338122A1 (en)	2012-06-18	2013-12-19	Therapeuticsmd, Inc.	Transdermal hormone replacement therapies
US9321712B2 (en)	2012-10-19	2016-04-26	Fermion Oy	Process for the preparation of ospemifene
CN104994877A (zh)	2012-11-02	2015-10-21	利普生物药剂公司	用于癌症治疗的反式-克罗米芬
US11246875B2 (en)	2012-12-21	2022-02-15	Therapeuticsmd, Inc.	Vaginal inserted estradiol pharmaceutical compositions and methods
US11266661B2 (en)	2012-12-21	2022-03-08	Therapeuticsmd, Inc.	Vaginal inserted estradiol pharmaceutical compositions and methods
US10568891B2 (en)	2012-12-21	2020-02-25	Therapeuticsmd, Inc.	Vaginal inserted estradiol pharmaceutical compositions and methods
US10471072B2 (en)	2012-12-21	2019-11-12	Therapeuticsmd, Inc.	Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en)	2012-12-21	2015-11-10	Therapeuticsmd, Inc.	Soluble estradiol capsule for vaginal insertion
US10537581B2 (en)	2012-12-21	2020-01-21	Therapeuticsmd, Inc.	Vaginal inserted estradiol pharmaceutical compositions and methods
WO2014203132A1 (en)	2013-06-19	2014-12-24	Olema Pharmaceuticals, Inc.	Substituted benzopyran compounds, compositions and uses thereof
WO2014203129A1 (en)	2013-06-19	2014-12-24	Olema Pharmaceuticals, Inc.	Combinations of benzopyran compounds, compositions and uses 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
US9421264B2 (en)	2014-03-28	2016-08-23	Duke University	Method of treating cancer using selective estrogen receptor modulators
ES2939940T3 (es)	2014-03-28	2023-04-28	Univ Duke	Tratamiento del cáncer de mama utilizando moduladores selectivos de los receptores de estrógenos
AR100562A1 (es)	2014-05-22	2016-10-12	Therapeuticsmd Inc	Composición farmacéutica de estradiol y progesterona para terapia de reemplazo hormonal
KR20170040209A (ko)	2014-07-29	2017-04-12	쎄러퓨틱스엠디, 인코퍼레이티드	경피 크림
PT3253208T (pt)	2015-02-02	2021-06-17	The Spanish National Cancer Res Centre	Terapêuticas de combinação para utilização no tratamento do cancro da mama
JP2018512450A (ja) *	2015-03-19	2018-05-17	ウェンディアンエプスタインＥＰＳＴＥＩＮ，ＷｅｎｄｙＡｎｎｅ	女性の性的障害を治療するための化合物及び剤型
US10328087B2 (en)	2015-07-23	2019-06-25	Therapeuticsmd, Inc.	Formulations for solubilizing hormones
WO2017173044A1 (en)	2016-04-01	2017-10-05	Therapeuticsmd Inc.	Steroid hormone compositions in medium chain oils
KR20180126582A (ko)	2016-04-01	2018-11-27	쎄러퓨틱스엠디, 인코퍼레이티드	스테로이드 호르몬 약제학적 조성물
CN110099680B (zh)	2016-10-11	2021-02-05	杜克大学	Er+乳腺癌的拉索昔芬治疗
EP3565542B1 (en)	2017-01-05	2024-04-10	Radius Pharmaceuticals, Inc.	Polymorphic forms of rad1901-2hcl
US20180207264A1 (en) *	2017-01-23	2018-07-26	Government Of The United States As Represented By The Secretary Of The Air Force	Porcine immune modulation model
CN117771239A (zh)	2018-04-10	2024-03-29	杜克大学	乳腺癌的拉索昔芬治疗
GB202116903D0 (en)	2021-11-18	2022-01-05	Sermonix Pharmaceuticals Inc	Lasofoxifene treatment of aromatase-resistant er+ cancer
CN116508778B (zh) *	2023-03-02	2024-12-27	广西师范大学	一种新性信息素美雌醇的应用

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5776923A (en) *	1993-01-19	1998-07-07	Endorecherche, Inc.	Method of treating or preventing osteoporosis by adminstering dehydropiandrosterone
US5468736A (en) *	1993-02-25	1995-11-21	The Medical College Of Hampton Road	Hormone replacement therapy
US5446061A (en) *	1993-11-05	1995-08-29	Eli Lilly And Company	Methods for lowering serum cholesterol
DE4405898A1 (de) *	1994-02-18	1995-08-24	Schering Ag	Transdermale therapeutische Systeme enthaltend Sexualsteroide
US5446071A (en) *	1994-11-18	1995-08-29	Eli Lilly And Company	Methods for lowering serum cholesterol
US5922349A (en) *	1995-09-28	1999-07-13	Schering Aktiengesellschaft	Hormone replacement therapy method and hormone dispenser
SK281737B6 (sk) *	1996-04-19	2001-07-10	American Home Products Corporation	2-fenylindolové zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie
AR017256A1 (es) *	1997-08-21	2001-09-05	American Home Prod	Compuestos de indol sustituidos, metodo para la sintesis en fase solida de los mismos, conjuntos de combinacion para ser empleados en dicho metodo, uso delos compuestos para preparar un medicamento y composiciones farmaceuticas que los comprenden
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
DE19916419B4 (de) *	1999-04-08	2005-06-16	Schering Ag	Kombinationspräparat aus Vitamin-D-Metaboliten oder Vitamin-D-Analoga und einem Östrogenpartialagonisten zur Behandlung von Osteoporose
JP4790178B2 (ja) *	1999-07-06	2011-10-12	アンドルシェルシュ・インコーポレイテッド	体重増加の処置方法および／または抑制方法

2001
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- 2001-01-26 IL IL14999001A patent/IL149990A0/xx unknown
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- 2001-01-26 JP JP2001554683A patent/JP2003520817A/ja active Pending
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- 2001-01-26 NZ NZ534348A patent/NZ534348A/en active IP Right Revival
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2002
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PL357163A1 (en)	2004-07-26
CZ20022401A3 (cs)	2003-10-15
HUP0204211A3 (en)	2005-06-28
RU2002123047A (ru)	2004-03-10
HK1048761A1 (zh)	2003-04-17
AR035564A1 (es)	2004-06-16
WO2001054699A1 (en)	2001-08-02
EP1251855A1 (en)	2002-10-30
NO20023484L (no)	2002-07-22
IL149990A0 (en)	2002-12-01
BR0108107A (pt)	2003-03-11
US20030065008A1 (en)	2003-04-03
RU2342145C2 (ru)	2008-12-27
AU2991301A (en)	2001-08-07
MXPA02007165A (es)	2003-09-22
NZ534348A (en)	2006-06-30
NO20023484D0 (no)	2002-07-22
HUP0204211A2 (hu)	2003-04-28
US20020198179A1 (en)	2002-12-26
US20030040510A1 (en)	2003-02-27
CN1400904A (zh)	2003-03-05
JP2003520817A (ja)	2003-07-08
KR20020073566A (ko)	2002-09-27
ZA200205926B (en)	2003-07-24
CA2395730A1 (en)	2001-08-02

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Publication	Publication Date	Title
CZ20022401A3 (cs)	2003-10-15	Farmaceutický prostředek a souprava pro snížení nebo eliminaci výskytu symptomů menopauzy
US8188066B2 (en)	2012-05-29	Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
TWI612044B (zh)	2018-01-21	以性類固醇前驅物組合選擇性雌激素受體調節物治療熱潮紅、血管舒縮症狀及夜汗之技術
TWI293251B (en)	2008-02-11	Selective estrogen receptor modulators incombination with estrogens
AU2006201900A1 (en)	2006-06-01	Selective estrogen receptor modulators in combination with estrogens
PL203438B1 (pl)	2009-10-30	Kompozycja farmaceutyczna zawieraj aca dehydroepiandrosteron, pochodn a trifenyloetylenu i farmaceutycznie dopuszczaln a zaróbk e, zestaw i zastosowanie dehydroepiandrosteronu
PL203439B1 (pl)	2009-10-30	Kompozycja farmaceutyczna zawieraj aca dehydroepiandrosteron, pochodn a indolu i farmaceutycznie dopuszczaln a zaróbk e, zestaw i zastosowanie dehydroepiandrosteronu