WO2002002113A1 - Combinaison pharmaceutique d'anti-androgene et de letrozole a effet anti-androgenique avec inhibition d'aromatase - Google Patents
Combinaison pharmaceutique d'anti-androgene et de letrozole a effet anti-androgenique avec inhibition d'aromatase Download PDFInfo
- Publication number
- WO2002002113A1 WO2002002113A1 PCT/SE2001/001547 SE0101547W WO0202113A1 WO 2002002113 A1 WO2002002113 A1 WO 2002002113A1 SE 0101547 W SE0101547 W SE 0101547W WO 0202113 A1 WO0202113 A1 WO 0202113A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- androgen
- patient
- solvate
- pharmaceutically acceptable
- acceptable salt
- Prior art date
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- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960004824 triptorelin Drugs 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P5/28—Antiandrogens
Definitions
- the present invention relates to a pharmaceutical product, daily dose or dose regimen comprising an anti-androgen and letrozole, wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone.
- the invention also relates to a method of providing an anti-androgenic effect and aromatase inhibition in a patient, wherein the aromatase inhibition is provided substantially without causing an additional increase in the levels of circulating androgens.
- the invention relates to the use of an anti-androgen and letrozole in the manufacture of a pharmaceutical product for this purpose, wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone.
- Letrozole an aromatase inhibitor, is known by the trade name FEMARA .
- Letrozole is known by the alternative names 4,4'-(lH-l,2,4-triazol-l-ylmethylene)-bisbenzonitrile; 1- [bis(4-cyanophenyl)methyl]- 1 ,2,4-triazole; and 4-[ 1 -(4-cyanophenyl)- 1 -(1 ,2,4-triazol- 1 - yl)methyl]benzonitrile.
- Letrozole is disclosed in US 4,978,672. The corresponding structure is shown in formula I:-
- Flutamide an anti-androgen, is known by the trade name EULEXIN . Flutamide is also known by the alternative names 2-methyl-N-[4-nitro-3- (trifluoromethyl)phenyl]propanamide; ⁇ , ⁇ , ⁇ -trifluoro-2-methyl-4 ' -nitro- - propionotoluidide; and 4'-nitro-3'-trifluoromethylisobutyranilide. Flutamide is disclosed in US 3,847,988. The corresponding structure is shown in formula II:-
- Nilutamide an anti-androgen, is known by the trade name NILANDRON . Nilutamide is also known by the alternative names 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]- 2,4-imidazolidinedione; and l-(3'-trifluoromethyl-4'-nitrophenyl)-4,4- dimethylimidazoline-2,5-dione. Nilutamide is disclosed in US 4,097,578. The corresponding structure is shown in formula III:-
- Chlormadinone in its acetate form, is an anti-androgen.
- the acetate form is known by the alternative names 17-(acetyloxy)-6-chloropregna-4,6-diene-3,20-dione; 6-chloro-17- hydroxypregna-4,6-diene-3,20-dione acetate; 6-chloro-6-dehydro-17 ⁇ - hydroxyprogesterone acetate; 6-chloro-6-dehydro-17 ⁇ -acetoxyprogesterone; and 17 ⁇ - acetoxy-6-choro-6,7-dehydroprogesterone.
- Chormadinone is disclosed in US 3,485,852.
- Cyproterone is known by the alternative names (l ⁇ ,2 ⁇ )-6-chloro-l,2-dihydro-17-hydroxy- 3'H-cyclopropa[l,2]pregna-l,4,6-triene-3,20 dione; 6-chloro-17-hydroxy-l ⁇ ,2 ⁇ - methylenepregna-4,6-diene-3,20-dione; 6-chloro-6-dehydro-17 -hydroxy-l,2 - methyleneprogesterone; and 6-chloro-l,2 ⁇ -methylene-4,6-pregnadien-17 -ol-3,20-dione. Cyproterone is disclosed in US 3,234,093. Cyproterone in its free alcohol and acetate forms is an anti-androgen.
- Anti-androgens such as flutamide and nilutamide are used in the treatment of prostate cancer. This is also the case for another anti-androgen, bicalutamide.
- Such compounds are generally used in combination with an inhibitor of gonadotrophin secretion, for example a luteinising hormone releasing hormone (L ⁇ R ⁇ ) agonist such as goserelin, buserelin, leuprorelin or triptorelin.
- L ⁇ R ⁇ luteinising hormone releasing hormone
- the properties and usefulness of these anti-androgens have been reviewed, for example in the following documents which are incorporated herein by way of reference :- flutamide R O Neri, J. Drug Develop., 1987, 1 (Suppl.), 5-9 and Urology. 1989,
- nilutamide causes an increase in the basal level of circulating testosterone (A U Decensi et al., J. Urology, 1991, 146, 377-381). It is believed that such increases in the level of testosterone occur when sufficient of the anti-androgen gains access to the CNS and blocks androgen receptors in the hypothalamus. The consequential lack of feedback of androgen causes additional release of LHRH by the hypothalamus which in turn causes release of luteinising hormone (LH) and follicle stimulating hormone (FSH) by the pituitary gland and production of testosterone in the testes.
- LH luteinising hormone
- FSH follicle stimulating hormone
- Aromatase enzyme in fat and other tissues converts some of the increased concentration of testosterone to oestradiol, which results in increased concentrations of oestrogen in the blood. Further discussion of this is provided by C Mahler et al, Clinical Pharmacokinetics, 1998, 34(5), pp 405-417.
- a disadvantageous effect is produced. Namely, the increase in the levels of circulating oestrogen may cause one or more of the side effects of gynaecomastia, breast tenderness, hot flushes, impotence and reduction in libido.
- a discussion on gynaecomastia can be found in C J Tyrrell, Prostate Cancer and Prostatic Diseases, 1999, 2(4): pp 167-171.
- the present invention fulfils this need by providing a pharmaceutical product for administration to a patient for providing an anti-androgenic effect and aromatase inhibition in the patient, the product comprising an anti-androgen and letrozole or a pharmaceutically acceptable salt or solvate thereof, wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone or a pharmaceutically acceptable salt or solvate thereof.
- the cyproterone is in its free alcohol or acetate form.
- the anti-androgen and letrozole are provided in a ratio of 25 to 1000 : 0.005 to 100 respectively.
- the aromatase inhibition is provided substantially without causing an additional increase in the levels of circulating androgens.
- the present invention also provides a daily pharmaceutical dose for administration to a patient for providing an anti-androgenic effect and aromatase inhibition in the patient, the dose comprising an anti-androgen and from 0.005 to 100 mg of letrozole or a pharmaceutically acceptable salt or solvate thereof, wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone or a pharmaceutically acceptable salt or solvate thereof.
- the present invention provides a dose regimen for such purpose comprising an anti-androgen and from 0.005 to 100 mg of letrozole or a pharmaceutically acceptable salt or solvate thereof for simultaneous or sequential administration to the patient, wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone or a pharmaceutically acceptable salt or solvate thereof.
- aspects of the invention relate to the use in the manufacture of a pharmaceutical product of an anti-androgen and letrozole or a pharmaceutically acceptable salt or solvate thereof that are simultaneously or sequentially administrable to a patient, for:-
- anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone or a pharmaceutically acceptable salt or solvate thereof.
- suppressing increase in the incidence or severity of a side effect we mean providing a lower incidence or severity compared with the side effect produced when the anti- androgen is administered alone, or eliminating the side effect.
- the present invention further provides a method of providing an anti-androgenic effect in a patient comprising simultaneously or sequentially administering an anti-androgen and letrozole or a pharmaceutically acceptable salt or solvate thereof to the patient, wherein the method further provides aromatase inhibition in the patient substantially without causing an additional increase in the levels of circulating androgens, and wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone or a pharmaceutically acceptable salt or solvate thereof.
- the present invention provides both an anti-androgenic effect and aromatase inhibition in a patient, wherein the aromatase inhibition is produced substantially without causing an additional increase in the levels of circulating androgens. This is achieved by administering to the patient a product comprising an anti-androgen and letrozole or a pharmaceutically acceptable salt or solvate thereof, wherein the anti-androgen is selected from flutamide, nilutamide, chlormadinone acetate and cyproterone or a pharmaceutically acceptable salt or solvate thereof.
- the anti-androgen and letrozole are provided in a ratio respectively of 25 to 1000 (preferably the lower end of the range being 50 or 100; preferably the upper end of the range being 500, 350, 300, 150 or 50; suitable values in the ranges being 750, 375, 150, 125 or 50) : 0.005 to 100 (preferably the lower end of the range being 0.05 or 0.5; preferably the upper end of the range being 50, 10 or 1; the most preferred range being 0.5 to 1 ; a suitable value in the range being 1).
- flutamide a preferred range is 100 to 1000, and a preferred value is 750 or 375.
- chlormadinone acetate a preferred value is 50.
- a preferred range is 200 to 300.
- a preferred range is 50 to 500, and a preferred value is 150 or 300.
- the term "product" is intended to mean either a mixture of the anti-androgen and letrozole (eg, provided as a capsule or tablet containing both compounds) or a kit comprising separate amounts of the compounds (eg, a set of letrozole tablets and a separate set of tablets of the anti-androgen). The latter product can be used for simultaneous or sequential (ie, temporally spaced) administration of the compounds to the patient, while the pre-mixed compounds are for simultaneous administration.
- Factors such as the rate of absorption, metabolism and the rate of excretion of each agent will affect their presence at the tumour site. Such factors are routinely considered by, and are well within the ordinary skill of, the clinician when he contemplates the treatment of a medical condition which requires the conjoint administration of two agents in order to obtain a beneficial effect.
- the invention contemplates the use of pharmaceutically acceptable salts and solvates of the anti-androgen (for flutamide and nilutamide) and/or letrozole.
- Suitable salts are, for example acid addition salts, such as hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartarate, citrate, oxalate, methanesulphonate or -toluenesulphonate, or alkali metal salts such as sodium or potassium salts.
- the letrozole is included to provide aromatase inhibition, in that this compound inhibits conversion of testosterone to oestradiol by aromatase enzyme.
- the anti-androgenic effect is useful for treating cancer, for example prostate cancer.
- cancer for example prostate cancer.
- Particular examples are advanced prostate cancer and early prostate cancer.
- the anti- androgenic effect may be useful for prophylaxis, in order to reduce the risk of prostate cancer occurrence in patients. This could be especially useful in men genetically pre- disposed to prostate cancer.
- Conventional methods are available to classify patients according to their risk of contracting prostate cancer, for example by assessment of family history and measurements over time of particular blood proteins such as prostate specific antigen (PSA).
- PSA prostate specific antigen
- Other uses for the anti-androgenic effect are the treatment of a non- malignant disease of the prostate gland (eg, benign prostatic hyperplasia or hypertrophy) and acne.
- the aromatase inhibition is useful for suppressing increase in the incidence or severity of a side effect selected from gynaecomastia, breast tenderness, hot flushes, impotence, reduction in libido, nausea, vomiting, fatigue and diarrhoea.
- a side effect selected from gynaecomastia, breast tenderness, hot flushes, impotence, reduction in libido, nausea, vomiting, fatigue and diarrhoea.
- a side effect selected from gynaecomastia, breast tenderness, hot flushes, impotence, reduction in libido, nausea, vomiting, fatigue and diarrhoea.
- the side effect is one or both of gynaecomastia and breast tenderness.
- a suitable dose regimen or daily pharmaceutical dose comprises the anti-androgen and from 0.005 to 100 mg of letrozole or a pharmaceutically acceptable salt or solvate thereof.
- the lower end of the range is 0.05 or 0.5 mg; preferably the upper end of the range is 50, 10 or 1 mg; the most preferred range is 0.5 to 1 mg; a suitable value in the range being 1 mg.
- the dose or the regimen preferably comprises from 25 to 1000 mg of the anti-androgen or a pharmaceutically acceptable salt or solvate thereof.
- the lower end of the range is 50 or 100 mg; preferably the upper end of the range is 350, 300, 150 or 50 mg; suitable values in the ranges are 750, 375, 150, 125 or 50 mg.
- a preferred range is 100 to 1000 mg, and a preferred value is 750 or 375 mg.
- a preferred value is 50 mg.
- cyproterone a preferred range is 200 to 300 mg.
- nilutamide a preferred range is 50 to 500 mg, and a preferred value is 150 or 300 mg.
- each compound is preferably administered daily.
- Another possible regime would be dosing of the anti-androgen on alternate days and dosing of the letrozole also on (the same or different) alternate days.
- the regimen may include administration instructions.
- a dose of the anti-androgen is administered every 3, 4, 5, 6 or 7 days and the letrozole is administered every 3, 4, 5, 6 or 7 days (eg, on the same day as the anti-androgen).
- the regimen or daily dose comprises 3 times 250 mg of flutamide (eg, 250 mg administered every 8 hours) or 3 times 125 mg of flutamide (eg, 125 mg administered every 8 hours).
- the patient can be a human male, eg an adult, but the treatment of other mammals (except rats) is also contemplated.
- the products, doses and regimens of the invention may be in a form suitable for oral use (for example as tablets, capsules, aqueous or oily suspensions, emulsions or dispersible powders or granules), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions; for example for use within a transdermal patch), for parenteral administration (for example as a sterile aqueous or oily solution or suspension for intravenous, subcutaneous, intramuscular or intravascular dosing), or as a suppository for rectal dosing.
- the compositions of the invention are in a form suitable for oral use, for example as tablets or capsules.
- the products, doses and regimens of the invention may be obtained by conventional procedures using conventional pharmaceutically-acceptable diluents or carriers that are well known in the art.
- Suitable pharmaceutically-acceptable diluents or carriers for a tablet formulation include, for example, inert diluents such as lactose, sodium carbonate, calcium phosphate or calcium carbonate, granulating and disintegrating agents such as corn starch or alginic acid; binding agents such as gelatin or starch; lubricating agents such as magnesium stearate, stearic acid or talc; preservative agents such as ethyl or propyl -hydroxybenzoate, and anti-oxidants, such as ascorbic acid.
- inert diluents such as lactose, sodium carbonate, calcium phosphate or calcium carbonate
- granulating and disintegrating agents such as corn starch or alginic acid
- binding agents such as gelatin or starch
- lubricating agents such as magnesium stearate, stearic acid or talc
- preservative agents such as ethyl or propyl -hydroxybenzoate, and anti
- Tablet formulations may be uncoated or coated either to modify their disintegration and the subsequent absorption of the active ingredient within the gastrointestinal tract, or to improve their stability and/or appearance, in either case using conventional coating agents and procedures well known in the art.
- Compositions for oral use may be in the form of hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin or olive oil.
- ARJMIDEX anastrozole, which is an aromatase inhibitor
- CASODEX TM was administered daily at a dose of 150 mg and the ARIMIDEXTM was administered daily at a dose of 1 mg. All treatments were in tablet form and taken once daily. Daily treatment with CASODEX TM was for 6 weeks, and with ARIMIDEX TM for the final 2 weeks of this period. The treatment periods were selected as the minimum time to attain steady-state plasma concentrations for the drugs.
- CASODEX TM beyond the 4 th week, this figure would be expected to rise (corresponding to an approximate doubling of the mean total testosterone concentration).
- Verhelst, J et al Enddocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer
- Verhelst, J et al Clin. Endocrinol. (Oxf) 1994, Oct., 41(4), pp 525-30
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- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
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Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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AU2001271162A AU2001271162A1 (en) | 2000-07-05 | 2001-07-04 | Pharmaceutical combination of an anti-androgen and letrozole for providing an anit-androgenic effect and aromatase inhibition |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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GB0016429A GB0016429D0 (en) | 2000-07-05 | 2000-07-05 | Pharmaceutical combination |
GB0016429.3 | 2000-07-05 | ||
GB0020768A GB0020768D0 (en) | 2000-08-24 | 2000-08-24 | Pharmaceutical combination |
GB0020768.8 | 2000-08-24 |
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WO2002002113A1 true WO2002002113A1 (fr) | 2002-01-10 |
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ID=26244592
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PCT/SE2001/001547 WO2002002113A1 (fr) | 2000-07-05 | 2001-07-04 | Combinaison pharmaceutique d'anti-androgene et de letrozole a effet anti-androgenique avec inhibition d'aromatase |
Country Status (2)
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AU (1) | AU2001271162A1 (fr) |
WO (1) | WO2002002113A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6960474B2 (en) | 2000-06-28 | 2005-11-01 | Bristol-Myers Squibb Company | Method for the treatment of a condition remediable by administration of a selective androgen receptor modulator |
CN103796644A (zh) * | 2011-09-08 | 2014-05-14 | 诺华股份有限公司 | 芳香酶抑制剂用于治疗性腺功能减退和相关疾病的用途 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2102287A (en) * | 1981-05-22 | 1983-02-02 | Schering Ag | Use of aromatase-inhibitors with antiandrogens for treatment of prostatic hyperplasia. |
US4895715A (en) * | 1988-04-14 | 1990-01-23 | Schering Corporation | Method of treating gynecomastia |
WO1998003180A2 (fr) * | 1996-07-22 | 1998-01-29 | The Victoria University Of Manchester | Utilisation de modulateurs de l'activite de steroides sexuels pour le traitement de plaies et d'etats pathologiques de type 'fibreux' |
WO2001049294A1 (fr) * | 1999-12-30 | 2001-07-12 | Pharmacia Italia S.P.A. | Produit pour le traitement de la gynecomastie |
-
2001
- 2001-07-04 AU AU2001271162A patent/AU2001271162A1/en not_active Abandoned
- 2001-07-04 WO PCT/SE2001/001547 patent/WO2002002113A1/fr active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2102287A (en) * | 1981-05-22 | 1983-02-02 | Schering Ag | Use of aromatase-inhibitors with antiandrogens for treatment of prostatic hyperplasia. |
US4895715A (en) * | 1988-04-14 | 1990-01-23 | Schering Corporation | Method of treating gynecomastia |
WO1998003180A2 (fr) * | 1996-07-22 | 1998-01-29 | The Victoria University Of Manchester | Utilisation de modulateurs de l'activite de steroides sexuels pour le traitement de plaies et d'etats pathologiques de type 'fibreux' |
WO2001049294A1 (fr) * | 1999-12-30 | 2001-07-12 | Pharmacia Italia S.P.A. | Produit pour le traitement de la gynecomastie |
Non-Patent Citations (2)
Title |
---|
JEROME P. RICHIE: "Anti-androgens and other hormonal therapies for prostate cancer", UROLOGY, vol. 54, no. 6A, 1999, pages 15 - 18, XP002948822 * |
R.C. COOMBES ET AL.: "Aromatase inhibitors and their use in the sequential setting", ENDOCRINE-RELATED CANCER, vol. 6, 1999, pages 259 - 263, XP002948821 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6960474B2 (en) | 2000-06-28 | 2005-11-01 | Bristol-Myers Squibb Company | Method for the treatment of a condition remediable by administration of a selective androgen receptor modulator |
CN103796644A (zh) * | 2011-09-08 | 2014-05-14 | 诺华股份有限公司 | 芳香酶抑制剂用于治疗性腺功能减退和相关疾病的用途 |
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