AU2003259464A1 - Use of a quinazoline derivative for treating lower urinary tract symptoms - Google Patents
Use of a quinazoline derivative for treating lower urinary tract symptoms Download PDFInfo
- Publication number
- AU2003259464A1 AU2003259464A1 AU2003259464A AU2003259464A AU2003259464A1 AU 2003259464 A1 AU2003259464 A1 AU 2003259464A1 AU 2003259464 A AU2003259464 A AU 2003259464A AU 2003259464 A AU2003259464 A AU 2003259464A AU 2003259464 A1 AU2003259464 A1 AU 2003259464A1
- Authority
- AU
- Australia
- Prior art keywords
- quinazoline
- dimethoxy
- pyridyl
- luts
- amino
- 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.)
- Abandoned
Links
- 206010071289 Lower urinary tract symptoms Diseases 0.000 title description 16
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- 210000003903 pelvic floor Anatomy 0.000 claims description 13
- 230000004064 dysfunction Effects 0.000 claims description 12
- 201000007094 prostatitis Diseases 0.000 claims description 12
- 208000013507 chronic prostatitis Diseases 0.000 claims description 11
- OLYXPBZBZBVRGD-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=NC(N)=C2C=1C1=CC=CC=N1 OLYXPBZBZBVRGD-UHFFFAOYSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 206010037211 Psychomotor hyperactivity Diseases 0.000 claims 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 10
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 10
- 230000000622 irritating effect Effects 0.000 description 10
- 208000020629 overactive bladder Diseases 0.000 description 10
- 239000000203 mixture Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 206010029446 nocturia Diseases 0.000 description 4
- 235000011037 adipic acid Nutrition 0.000 description 3
- 239000001361 adipic acid Substances 0.000 description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000000414 obstructive effect Effects 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- VNMIUZVHPVIQNW-UHFFFAOYSA-N 5-pyridin-2-ylquinazoline Chemical compound N1=CC=CC=C1C1=CC=CC2=NC=NC=C12 VNMIUZVHPVIQNW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- -1 Calcium Hydrogen Chemical class 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 229920003094 Methocel™ K4M Polymers 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010036018 Pollakiuria Diseases 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- OHXYXVCPAYXMBR-UHFFFAOYSA-N methanesulfonic acid;n-[2-(5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound CS(O)(=O)=O.C1CC=2C(NS(=O)(=O)C)=CC=CC=2CN1C(N=C1C=CC=2)=NC=C1C=2C1=CC=CC=N1 OHXYXVCPAYXMBR-UHFFFAOYSA-N 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- PELLFYXDXSYSSE-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=NC(N)=C2C=1C1=CC=CC=N1 PELLFYXDXSYSSE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 208000026455 prostate symptom Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 206010046494 urge incontinence Diseases 0.000 description 1
- 230000003202 urodynamic effect Effects 0.000 description 1
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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
WO 2004/026312 PCT/IB2003/003905 -1 USE OF A QUINAZOLINE DERIVATIVE FOR TREATING LOWER URINARY TRACT SYMPTOMS This invention relates to a new use of 4-amino-6,7-dimethoxy-2-(5 methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline 5 (disclosed as example 19 in International Patent Application Publication No. WO 98/30560), and its pharmaceutically acceptable derivatives. The mesylate salt is disclosed in International Patent Application Publication No. WO 01/64672 (e.g. Example 2). Both WO 98/30560 and WO 01/64672 are incorporated herein by reference. It is indicated in the treatment of Benign Prostatic Hyperplasia (BPH) 10 and has the following structure: HN o N N
NH
2 N NH Lower urinary tract symptoms (LUTS) comprise three groups of symptoms, which 15 are irritative, obstructive and post micturition symptoms. Irritative symptoms comprise urgency, frequency and nocturia, which can be associated with: overactive bladder (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis. 20 Over Active Bladder (OAB) is defined as urgency, with or without urge incontinence, usually with frequency and nocturia [Abrams et al., Neurourology and Urodynamics 21:167-178 (2002)]. Prevalence of OAB in men and women is similar, with approximately 16% of the population of the USA suffering from the WO 2004/026312 PCT/IB2003/003905 -2 condition [Stewart et al, Prevalence of Overactive Bladder in the United States: Results from the NOBLE Program; Abstract Presented at the 2 nd International Consultation on Incontinence, July 2001, Paris, France]. 5 Pelvic floor dysfunction (PFD) occurs when the muscles of the pelvic floor no longer relax properly during urination while the bladder contracts. The muscles may become irritated and often contract abnormally. PFD may result in irritative LUTS. 10 Chronic prostatitis is an inflammatory condition of the prostate, which may or may not be associated with uropathogenic bacteria detected by standard microbiological methodology. It is characterized by the presence of genitourinary pain or discomfort, often associated with irritative LUTS. 15 Overactive bladder may be suffered by individuals of any age, while pelvic floor dysfunction and prostatitis are conditions typically suffered by middle-aged men. Patients with any of these conditions are likely to experience irritative lower urinary tract symptoms, and often the eventual diagnosis is empirical. 20 Surprisingly it has been found that 4-amino-6,7-dimethoxy-2-(5 methanesulfonamido-1 ,2,3,4-tetrahydroisoqu inol-2-yl)-5-(2-pyridyl)quinazoline is useful in the treatment of LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis. 25 Thus, in accordance with the present invention, there is provided the use of 4 amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquino-2-y) 5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, for the manufacture of a medicament for the treatment of LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or 30 chronic prostatitis.
WO 2004/026312 PCT/IB2003/003905 -3 Preferably the LUTS is associated with pelvic floor dysfunction. Alternatively, the LUTS is preferably associated with chronic prostatitis. Preferably the 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4 5 tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline is in the form of its mesylate salt. The compound, or a pharmaceutically acceptable derivative thereof, can be administered alone or in any convenient pharmaceutical presentation. Oral administration is preferred. In the present indication, a suitable dosage of the 10 compound, or of the active moiety in a pharmaceutically acceptable derivative thereof, is from about 0.01 to 10.0 mg/kg of body weight, and preferably about 0.05 to 1.0 mg/kg is suitable. Administration may be in single does of from 1 to 4 times daily or preferably it may be in a controlled release formulation such as is disclosed in International Application Publication No. WO 03/032956 (see in 15 particular examples 1 to 5). Administration may be p.r.n. for occasions when the patient may have limited access to toilet facilities, e.g. during a long journey. The invention further provides 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido 1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically 20 acceptable derivative thereof, for use in the treatment of LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis. The invention further provides a method of treating LUTS associated with: OAB 25 (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis, which comprises administering 4-amino-6,7-dimethoxy-2-(5 methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, to a patient in need of such treatment.
WO 2004/026312 PCT/IB2003/003905 -4 Examples 1-5 Tablet formulations of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido 1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline mesylate containing Methocel TM K4M 5 The following table shows the ingredients for preparing five tablet formulations containing, respectively, 1, 3, 6, 9 and 12 mg of active ingredient, expressed as free base, according to International Application Publication No. WO 03/032956. Ingredient (mg) Ex 1 Ex 2 Ex 3 Ex 4 Ex 5 (reference to standard) 4-amino-6,7-dimethoxy-2- 1.1890) 3.567 7.134 10.701 14.268 (5-methanesulfonamido 1,2,3,4-tetrahydroisoquinol 2-yl)-5-(2 pyridyl)quinazoline mesylate (Pfizer) HPMC 30.000 30.000 30.000 22.500 22.500 (Methocel K4M, Ph.Eur) Lactose Monohydrate 13.203 10.108 9.216 10.200 9.308 (Ph.Eur) Calcium Hydrogen 39.608 30.325 27.650 30.599 27.924 Phosphate, Anhydrous (Ph.Eur) Adipic Acid 15.000 25.000 25.000 25.000 25.000 [DAB (2] Magnesium Stearate 1.000 1.000 1.000 1.000 1.000 (Ph.Eur) Tablet weight (mg) 100.000 100.000 100.000 100.000 100.000 10 Equivalent to 1.0 mg 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4 tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, in the form of its free base DAB is the Deutsches Arzneibuch (German Pharmacopoeia) WO 2004/026312 PCT/IB2003/003905 -5 Method The adipic acid was first screened through a suitable screen (e.g. 500 micron). The lactose monohydrate, hydroxypropylmethyl cellulose, 4-amino-6,7-dimethoxy 2-(5-methanesufonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline 5 mesylate, the screened adipic acid and calcium hydrogen phosphate, anhydrous were then added to a suitable blender (e.g. a tumble mixer) and blended. The blend was screened through a suitable screen (e.g. 500 micron) and reblended. About 50% of the lubricant (magnesium stearate) was screened, added to the blend and blended briefly. 10 The blend was roller compacted through a suitable roller compactor. The ribbon blend was then granulated, by screening through a suitable screen (e.g. 500 micron) and reblended. The remaining lubricant was screened, added to the blend and blended briefly. 15 The granules were then tabletted using appropriate 6 mm tooling to give 6 mm standard round convex white tablets with no engraving, which were then de dusted. 20 Example 6: In vivo study A 12-Week Study in men with lower urinary tract symptoms was undertaken in which the IPSS (International Prostate Symptom Score) was recorded at baseline during, and at the end of, double-blind treatment. The IPSS is composed of seven 25 questions, each with potential responses of 0-5 on a Likert scale. These questions are grouped into two validated domains: the irritative domain (urgency, frequency and nocturia) and the obstructive domain (incomplete emptying, intermittency, weak stream and straining to begin). In addition, a bladder diary was completed by each subject to provide baseline incidence of individual 30 symptoms, and subsequently to demonstrate change in incidence of these symptoms following double blind treatment. The average daily incidence of urgency, daytime micturition frequency and nocturia (the irritative symptoms) for WO 2004/026312 PCT/IB2003/003905 -6 each subject were derived from this diary. In this study, there were five treatment groups: 6mg fixed dose of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido 1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, 6mg escalated to 12mg at Week 4 of the compound, and placebo. Controlled release formulations 5 according to International Application Publication No. WO 03/032956 were used in each case. For those subjects with irritative LUTS at baseline, improvement in these symptoms was confirmed in the compound 6mg fixed dose group and the 12mg 10 dose escalation group, compared with the placebo treated group. In subjects with baseline IPSS irritative domain score a8 at baseline, improvement in this domain of the IPSS was similarly confirmed in both the compound 6mg fixed dose group and the 12mg dose escalation group. 15 The results of the study are illustrated in figures 1 to 4 which show 4-amino-6,7 dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquino-2-yl)-5-(2 pyridyl)quinazoline produced a clinically significant attenuation of irritative LUTS.
Claims (6)
1. Use of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4 tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically 5 acceptable derivative thereof, for the manufacture of a medicament for the treatment of LUTS associated with: OAB (with or without concomitant detrusor overactivity); pelvic floor dysfunction; or chronic prostatitis.
2. 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4 10 tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, for use in the treatment of LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis. 15
3. A method of treating LUTS associated with: OAB (with or without concomitant detrusor over activity); pelvic floor dysfunction; or chronic prostatitis, comprising administering 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido 1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, or a pharmaceutically acceptable derivative thereof, to a patient in need of such treatment. 20
4. A use or method as claimed in any of claims 1 to 3, wherein the 4-amino-6,7 dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2 pyridyl)quinazoline is in the form of its mesylate salt. 25
5. A use or method as claimed in any of claims 1 to 4, wherein the LUTS is associated with pelvic floor dysfunction.
6. A use or method as claimed in any of claims 1 to 4, wherein the LUTS is associated with chronic prostatitis.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0221582.0A GB0221582D0 (en) | 2002-09-17 | 2002-09-17 | Method of treatment |
| GB0221582.0 | 2002-09-17 | ||
| PCT/IB2003/003905 WO2004026312A1 (en) | 2002-09-17 | 2003-09-04 | Use of a quinazoline derivative for treating lower urinary tract symptoms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2003259464A1 true AU2003259464A1 (en) | 2004-04-08 |
Family
ID=9944253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003259464A Abandoned AU2003259464A1 (en) | 2002-09-17 | 2003-09-04 | Use of a quinazoline derivative for treating lower urinary tract symptoms |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1545541A1 (en) |
| JP (1) | JP2006501276A (en) |
| KR (1) | KR20050057349A (en) |
| CN (1) | CN1681506A (en) |
| AU (1) | AU2003259464A1 (en) |
| BR (1) | BR0314381A (en) |
| CA (1) | CA2495311A1 (en) |
| GB (1) | GB0221582D0 (en) |
| MX (1) | MXPA05002912A (en) |
| PL (1) | PL374730A1 (en) |
| TW (1) | TW200409770A (en) |
| WO (1) | WO2004026312A1 (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9700504D0 (en) * | 1997-01-11 | 1997-02-26 | Pfizer Ltd | Pharmaceutical compounds |
| IL141235A (en) * | 2000-02-09 | 2012-04-30 | Novartis Int Pharm Ltd | Combined use of an alpha-adrenoceptor antagonist and a muscarinic antagonist in the manufacture of a medicament for the treatment of benign prostatic hyperplasia |
| TR200302130T4 (en) * | 2000-03-03 | 2004-01-21 | Pfizer Inc. | 4-Amino-6,7-Demethoxy-2- (5-Methanesulfonamido-1,2,3,4-Tetrahydroisoquinol-2-yl) -5- (2-Pyridyl) Quinazoline Mesylate and Polymorphs |
-
2002
- 2002-09-17 GB GBGB0221582.0A patent/GB0221582D0/en not_active Ceased
-
2003
- 2003-09-04 PL PL03374730A patent/PL374730A1/en not_active Application Discontinuation
- 2003-09-04 KR KR1020057004463A patent/KR20050057349A/en not_active Ceased
- 2003-09-04 JP JP2004537394A patent/JP2006501276A/en active Pending
- 2003-09-04 MX MXPA05002912A patent/MXPA05002912A/en unknown
- 2003-09-04 WO PCT/IB2003/003905 patent/WO2004026312A1/en not_active Ceased
- 2003-09-04 AU AU2003259464A patent/AU2003259464A1/en not_active Abandoned
- 2003-09-04 CA CA002495311A patent/CA2495311A1/en not_active Abandoned
- 2003-09-04 BR BR0314381-3A patent/BR0314381A/en not_active IP Right Cessation
- 2003-09-04 CN CNA038219786A patent/CN1681506A/en active Pending
- 2003-09-04 EP EP03797435A patent/EP1545541A1/en not_active Withdrawn
- 2003-09-15 TW TW092125390A patent/TW200409770A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1681506A (en) | 2005-10-12 |
| WO2004026312A1 (en) | 2004-04-01 |
| CA2495311A1 (en) | 2004-04-01 |
| KR20050057349A (en) | 2005-06-16 |
| JP2006501276A (en) | 2006-01-12 |
| PL374730A1 (en) | 2005-10-31 |
| EP1545541A1 (en) | 2005-06-29 |
| GB0221582D0 (en) | 2002-10-23 |
| TW200409770A (en) | 2004-06-16 |
| BR0314381A (en) | 2005-07-19 |
| MXPA05002912A (en) | 2005-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1552825A1 (en) | Therapeutic agent for overactive bladder | |
| US20060293309A1 (en) | Method of treating disorders and conditions using peripherally-restricted antagonists and inhibitors | |
| RU2261098C2 (en) | Mirtazapine-containing orally decomposing composition | |
| AU2015326392B2 (en) | Pharmaceutical compositions comprising alpelisib | |
| JP2013199506A (en) | Method of treatment | |
| Lee | Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia | |
| CN109862895A (en) | Treatment of prurigo nodularis | |
| Vanmolkot et al. | Impact of antihypertensive treatment on quality of life: comparison between bisoprolol and bendrofluazide | |
| US20040116451A1 (en) | Method of treatment | |
| AU2003259464A1 (en) | Use of a quinazoline derivative for treating lower urinary tract symptoms | |
| US5876751A (en) | Antispasmodic and antinflammatory composition and a process for the manufacture thereof | |
| JP5106809B2 (en) | Pharmaceutical composition and processed food containing lactoferrin | |
| HK1078465A (en) | Use of a quinazoline derivative for treating lower urinary tract symptoms | |
| EP4665333A1 (en) | Regimens and compositions useful for alleviating pain | |
| EP4633628A1 (en) | Regimens and compositions useful for alleviating pain | |
| WO2024129782A1 (en) | Regimens and compositions useful for alleviating pain | |
| WO2024173714A1 (en) | Regimens and compositions useful for alleviating pain | |
| UA146868U (en) | PHARMACEUTICAL COMPOSITION FOR TREATMENT OF PAIN | |
| HK40003409A (en) | Treatment of prurigo nodularis | |
| UA146303U (en) | METHOD OF SYMPTOMATIC TREATMENT OF PAIN | |
| HK1073779B (en) | The use of darifenacin and the salt thereof | |
| JP2002138052A (en) | Antipruritic drug | |
| Ruscin | Update on the Role of Anticholinergic Drug Therapy in the Management of Overactive Bladder | |
| HK1078012A (en) | Therapeutic agent for overactive bladder | |
| WO2017142442A1 (en) | Pharmaceutical composition for preventing and treating sleep disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |