WO1998033504A1 - Treatment of urinary incontinence - Google Patents
Treatment of urinary incontinence Download PDFInfo
- Publication number
- WO1998033504A1 WO1998033504A1 PCT/EP1998/000576 EP9800576W WO9833504A1 WO 1998033504 A1 WO1998033504 A1 WO 1998033504A1 EP 9800576 W EP9800576 W EP 9800576W WO 9833504 A1 WO9833504 A1 WO 9833504A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- urinary incontinence
- pharmaceutically acceptable
- pyridinyl
- piperazine
- trifluoromethyl
- Prior art date
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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
- A61K31/495—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
Definitions
- the present invention relates to a new medical use of 1-[6-chloro-5- (trifluoromethyl)-2-pyridinyl]piperazine, or a pharmaceutically acceptable acid addition salt thereof.
- a new method of treating urinary incontinence to a new medical use of 1-[6-chloro-5- (trifluoromethyl)-2-pyridinyl]piperazine, or a pharmaceutically acceptable acid addition salt thereof.
- Urinary incontinence is a common problem. It is estimated that the incidence of urinary incontinence ranges from between 1.6-42% in the elderly, with an incidence of between 15-30% in the community dwelling elderly. Whilst the prevalence of urinary incontinence is twice as high in women compared to men, it afflicts significant numbers of both sexes.
- Urge urinary incontinence is the involuntary loss of urine during activities that increase the abdominal pressure, such as sneezing, coughing and laughing. Urge incontinence is due to the involuntary contraction of the bladder or to irritability and urge voiding even if the bladder is not full. Mixed incontinence is a combination of the previous two. In addition, there is also overflow incontinence which refers to a condition where there is constant dribbling, hesitancy, poor stream and impaired bladder sensation. Urinary incontinence can be attributed to a number of different causes, including infections of the bladder, urethral hypermobility, intrinsic urethral sphincter incompetence, urethral or detrusor instability.
- the present invention further includes the use of a compound according to the present invention for the manufacture of a medicament for the treatment or prophylaxis of urinary incontinence in an animal, for example, mammal including a human.
- the present invention provides a method of treating urinary incontinence in an animal, including a human, which comprises treating said animal with a therapeutically effective amount of 1-[6- I*
- the compounds according to the present invention have utility in treating any of the aforementioned types of urinary incontinence. These compounds are particularly useful in treating urinary incontinence in the elderly.
- Suitable acid addition salts include hydrochloric, fumahc, maleic, citric or succinic acid, these acids being mentioned only by way of illustration and without implied limitation.
- Preferred salts include the hydrochloric and fumahc acid salt.
- the amount of a compound of formula (A) or a pharmaceutically acceptable acid addition salt, also referred to herein as the active ingredient, which is required to achieve a therapeutic effect will, of course, vary with the particular compound, the route of administration, the age and condition of the recipient, and the particular disorder being treated.
- a suitable daily dose for any of the above mentioned disorders will be in the range of 0.01 to 5 mg per kilogram body weight of the recipient (e.g. a human) per day, preferably in the range of 0.1 to 2 mg per kilogram body weight per day and most preferably in the range 0.3 to 1.0 mg per kilogram body weight per day.
- treatments can be further optimalised by increasing the dose upto 2-10 times in the course of a chronic treatment in humans.
- the desired dose may be presented as one, two, three, four, five or more sub-doses administered at appropriate intervals throughout the day. While it is possible for the active ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation.
- the present invention further provides a pharmaceutical formulation for use in the treatment of urinary incontinence comprising a compound of formula (A) or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier thereof and optionally other therapeutic agents.
- the carrier must be "acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipients thereof.
- the invention further includes a pharmaceutical formulation, as hereinbefore described, in combination with packaging material suitable for the pharmaceutical formulation, said packaging material including instructions for the use of the pharmaceutical formulation in the treatment of urinary incontinence.
- Formulations include those adapted for oral, rectal, nasal, topical (including transdermal, buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal and epidural) administration.
- the formulations may be prepared by any methods well known in the art of pharmacy, for example, using methods such as those described in Gennaro et a!., Remington's Pharmaceutical Sciences ( 18th ed., Mack Publishing company, 1990, see especially Part 8 : Pharmaceutical Preparations and their Manufacture).
- Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients.
- Such accessory ingredients include those conventional in the art, such as, fillers, binders, diluents, disintegrants, lubricants, colorants, flavoring agents and wetting agents.
- Formulations adapted for oral administration may be presented as discrete units such as tablets or capsules each containing a predetermined amount of active ingredient; as a powder or granulates; as a solution or suspension.
- the active ingredient may also be presented as a bolus or paste, or may be contained within liposomes or microparticles.
- Formulations for rectal administration may be presented as a suppository or enema.
- Formulations adapted for parenteral administration include aqueous and non- aqueous sterile injection.
- the formulations may be presented in unit-dose or multi-dose containers, for example, sealed vials and ampoules, and may be stored in a freeze dried (lyophiiised) condition requiring only the addition of the sterile liquid carrier, for example, water prior to use.
- Formulations adapted for administration by nasal inhalation include fine dusts or mists which may be generated by means of metered dose pressurised aerosols, nebulisers or insufflators.
- Formulations may, for example, be presented in a suitable sustained release form, for example, in a device such as the MinipumpTM.
- the compounds according to the invention may be presented for use in the form of a veterinary formulation, such formulations may be prepared by methods conventional in the art.
- the compounds according to the present invention are non-toxic.
- the compound of formula (A) and its pharmaceutically acceptable acid addition salts may be prepared by any method known in the art for the preparation of a compound of similar structure. Typically the compounds are prepared by the methods described in US patent No.4,971 ,969 the contents of which are incorporated herein by reference.
- mice Female mice (Swiss CD-1 , Charles River, Paderhorn), weighing 24-31 grams were housed in groups of 8 or 10 per cage of 40 x 24 x 14 cm (Marcrolon®, type III).
- mice On the day of the experiment the mice were injected subcutaneously with either saline or test compound in different concentrations. The volume of injection was 0.2 ml/10 grams body weight. This is a two times larger injection volume than the usual 0.1 ml/10 grams in order to stimulate urine production. After injection there was no food and water available. Immediately or 15 min. after injection (experiment with Compound A) the mice were placed individually without food and water in clean cages of 40 x 24 x 14 cm (Marcrolon®, type III) with filter paper on the floor. Separate bouts of urination were quantified after allowing 5 minutes of spreading on the filter paper and measuring the diameter of the wet spot on the filter paper. The size of the urine-spots was calculated by the formula ⁇ D 2 , where D is the diameter of the spot in cm. assuming that the spots were circular in shape.
- the filter paper was renewed when several urine spots were made. Also, faecal droppings were counted. Cumulative measures of urine and faecal pellet production were obtained by observing continuously for 2 or 5 hours after injection. For the experiments with single treatment with Compound A we report here only the urine production results during the first hour after injection.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a new medical use of 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine, or a pharmaceutically acceptable acid addition salt thereof, in particular, to a new method of treating urinary incontinence.
Description
Treatment of Urinary Incontinence
The present invention relates to a new medical use of 1-[6-chloro-5- (trifluoromethyl)-2-pyridinyl]piperazine, or a pharmaceutically acceptable acid addition salt thereof. In particular, to a new method of treating urinary incontinence.
Urinary incontinence is a common problem. It is estimated that the incidence of urinary incontinence ranges from between 1.6-42% in the elderly, with an incidence of between 15-30% in the community dwelling elderly. Whilst the prevalence of urinary incontinence is twice as high in women compared to men, it afflicts significant numbers of both sexes.
Besides the elderly, children frequently have nocturnal incontinence and some studies have shown incontinence in as many as 17% of young women who show no other signs of ill health.
There are three main types of urinary incontinence: 1 ) Stress, 2) Urge and 3) Mixed urinary incontinence. Stress urinary incontinence is the involuntary loss of urine during activities that increase the abdominal pressure, such as sneezing, coughing and laughing. Urge incontinence is due to the involuntary contraction of the bladder or to irritability and urge voiding even if the bladder is not full. Mixed incontinence is a combination of the previous two. In addition, there is also overflow incontinence which refers to a condition where there is constant dribbling, hesitancy, poor stream and impaired bladder sensation.
Urinary incontinence can be attributed to a number of different causes, including infections of the bladder, urethral hypermobility, intrinsic urethral sphincter incompetence, urethral or detrusor instability.
There are a number of different approaches to treating incontinence. These include physiotherapy, pelvic floor electrical stimulation, different surgical techniques, treatment with papaverine, the use of antichoiinergics, for example propantheline, antispasmolitics such as oxybutynin, flavoxate and dicyclomine, and alpha-adrenergic agonists, for example, pseudoephedrine, ephedrine and phenylpropanolamine. However, these treatments have met with only limited success and many of the treatments are invasive or result in unwanted side effects. For example, ephedrine and phenylpropanolamine can increase blood pressure, anxiety, insomnia, headaches and cardiac arrhythmias. Papaverine treated patients reported anticholinergic symptoms including dry mouth, constipation and blurred vision.
There is, therefore, a continuing need for new agents which are effective in the treatment or prophylaxis of urinary incontinence.
As described in Steers and De Groat (Am. J Physiol Vol 257 pp R1441- R1449 ) meta-chiorophenyl-piperazine was investigated on bladder function in experiments with male anaesthetized rats. Results revealed a reciprocal action of this drug on penile and bladder activity. US patent No.4,971 ,969 and European patent No. 0 370 560 describe certain 1-[mono- or bis- (trifluoromethyl) 2-pyridinyl]piperazines and their pharmaceutically acceptable acid addition salts for use in the treatment of disorders of the central nervous system. It has now been found that one of these compounds, namely 1-[6- chloro-5-(trifluoromethyl)-2-pyridinyl]-piperazine and its pharmaceutically
acceptable acid addition salts is useful for the treatment of urinary incontinence in both sexes.
Accordingly, the present invention provides the use of a compound of formula (A):
(A)
which is 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]-piperazine and its pharmaceutically acceptable acid addition salts, for the manufacture of a medicament for the treatment or prophylaxis of urinary incontinence.
The compound of formula (A) and its pharmaceutically acceptable acid addition salts will be referred to collectively as compounds according to the present invention.
The present invention further includes the use of a compound according to the present invention for the manufacture of a medicament for the treatment or prophylaxis of urinary incontinence in an animal, for example, mammal including a human.
According to a further aspect, the present invention provides a method of treating urinary incontinence in an animal, including a human, which comprises treating said animal with a therapeutically effective amount of 1-[6-
I*
chioro-5-(trifluoromethyl)-2-pyridinyl]-piperazine, or a pharmaceutically acceptable acid addition salt thereof.
The compounds according to the present invention have utility in treating any of the aforementioned types of urinary incontinence. These compounds are particularly useful in treating urinary incontinence in the elderly.
Suitable acid addition salts include hydrochloric, fumahc, maleic, citric or succinic acid, these acids being mentioned only by way of illustration and without implied limitation. Preferred salts include the hydrochloric and fumahc acid salt.
The amount of a compound of formula (A) or a pharmaceutically acceptable acid addition salt, also referred to herein as the active ingredient, which is required to achieve a therapeutic effect will, of course, vary with the particular compound, the route of administration, the age and condition of the recipient, and the particular disorder being treated.
A suitable daily dose for any of the above mentioned disorders will be in the range of 0.01 to 5 mg per kilogram body weight of the recipient (e.g. a human) per day, preferably in the range of 0.1 to 2 mg per kilogram body weight per day and most preferably in the range 0.3 to 1.0 mg per kilogram body weight per day. In the case of tolerance development, treatments can be further optimalised by increasing the dose upto 2-10 times in the course of a chronic treatment in humans. The desired dose may be presented as one, two, three, four, five or more sub-doses administered at appropriate intervals throughout the day.
While it is possible for the active ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation. Accordingly, the present invention further provides a pharmaceutical formulation for use in the treatment of urinary incontinence comprising a compound of formula (A) or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier thereof and optionally other therapeutic agents. The carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipients thereof. The invention further includes a pharmaceutical formulation, as hereinbefore described, in combination with packaging material suitable for the pharmaceutical formulation, said packaging material including instructions for the use of the pharmaceutical formulation in the treatment of urinary incontinence.
Formulations include those adapted for oral, rectal, nasal, topical (including transdermal, buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal and epidural) administration. The formulations may be prepared by any methods well known in the art of pharmacy, for example, using methods such as those described in Gennaro et a!., Remington's Pharmaceutical Sciences ( 18th ed., Mack Publishing company, 1990, see especially Part 8 : Pharmaceutical Preparations and their Manufacture). Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients. Such accessory ingredients include those conventional in the art, such as, fillers, binders, diluents, disintegrants, lubricants, colorants, flavoring agents and wetting agents.
Formulations adapted for oral administration may be presented as discrete units such as tablets or capsules each containing a predetermined amount of active ingredient; as a powder or granulates; as a solution or suspension. The
active ingredient may also be presented as a bolus or paste, or may be contained within liposomes or microparticles.
Formulations for rectal administration may be presented as a suppository or enema.
Formulations adapted for parenteral administration include aqueous and non- aqueous sterile injection. The formulations may be presented in unit-dose or multi-dose containers, for example, sealed vials and ampoules, and may be stored in a freeze dried (lyophiiised) condition requiring only the addition of the sterile liquid carrier, for example, water prior to use.
Formulations adapted for administration by nasal inhalation include fine dusts or mists which may be generated by means of metered dose pressurised aerosols, nebulisers or insufflators.
Formulations may, for example, be presented in a suitable sustained release form, for example, in a device such as the Minipump™.
The compounds according to the invention may be presented for use in the form of a veterinary formulation, such formulations may be prepared by methods conventional in the art.
The compounds according to the present invention are non-toxic.
The compound of formula (A) and its pharmaceutically acceptable acid addition salts may be prepared by any method known in the art for the preparation of a compound of similar structure. Typically the compounds are
prepared by the methods described in US patent No.4,971 ,969 the contents of which are incorporated herein by reference.
The following examples are for illustration and should not be considered to be limiting in anyway:-
Exgmple 1 1-[6- hloro-5-ιtrifluoromethvn-2-pyridinyl]piperazine
The title compound was prepared in accordance with the procedure described in US patent No.4,971 ,969.
Example 2
Urination Assay
Method
Female mice (Swiss CD-1 , Charles River, Paderhorn), weighing 24-31 grams were housed in groups of 8 or 10 per cage of 40 x 24 x 14 cm (Marcrolon®, type III).
On the day of the experiment the mice were injected subcutaneously with either saline or test compound in different concentrations. The volume of injection was 0.2 ml/10 grams body weight. This is a two times larger injection volume than the usual 0.1 ml/10 grams in order to stimulate urine production. After injection there was no food and water available. Immediately or 15 min. after injection (experiment with Compound A) the mice were placed individually without food and water in clean cages of 40 x 24 x 14 cm (Marcrolon®, type III) with filter paper on the floor.
Separate bouts of urination were quantified after allowing 5 minutes of spreading on the filter paper and measuring the diameter of the wet spot on the filter paper. The size of the urine-spots was calculated by the formula π D2, where D is the diameter of the spot in cm. assuming that the spots were circular in shape.
The filter paper was renewed when several urine spots were made. Also, faecal droppings were counted. Cumulative measures of urine and faecal pellet production were obtained by observing continuously for 2 or 5 hours after injection. For the experiments with single treatment with Compound A we report here only the urine production results during the first hour after injection.
Route of administration: subcutaneously (s.c.) Vehicle: 0.9% (m/v) NaCi in water for all compounds.
Results
Compound A
P < 0.05 with Mann-Whitney U-test
Claims
I .Use of 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]-piperazine, or a pharmaceutically acceptable acid addition salt thereof for the manufacture of a medicament in the treatment or prophylaxis of urinary incontinence.
2. Use according to claim 1 , wherein the compound is 1-[6-chloro-5- (trifluoromethyl)-2-pyridinyl]-piperazine.
3. Use according to claim 1 , wherein the incontinence is stress or urge incontinence.
4. Use according to any of claims 1 to 3, wherein the medicament is adapted for oral administration.
5. Use according to any of claims 1 to 4, wherein the medicament is in a unit dosage form.
6. Use according to any of claims 1 to 5, wherein the incontinence is in the elderly.
7.A method of treating urinary incontinence in an animal which comprises treating said animal with a therapeutically effective amount of 1 -[6-chloro-5- (trifluoromethyl)-2-pyridinyl]-piperazine, or a pharmaceutically acceptable acid addition salt thereof.
8. A method according to claim 7 wherein the animal is a human.
9.A pharmaceutical formulation adapted for the treatment of urinary incontinence comprising 1 -[6-chloro-5-(trifluoromethyl)-2-pyridinyl]- piperazine, or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable derivative therefor.
10.An anti-urinary incontinence formulation comprising 1 -[6-chloro-5- (trifluoromethyl)-2-pyridinyl]-piperazine, or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable derivative therefor.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU66193/98A AU6619398A (en) | 1997-02-03 | 1998-01-30 | Treatment of urinary incontinence |
| PCT/EP1998/000576 WO1998033504A1 (en) | 1997-02-03 | 1998-01-30 | Treatment of urinary incontinence |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97200285.1 | 1997-02-03 | ||
| PCT/EP1998/000576 WO1998033504A1 (en) | 1997-02-03 | 1998-01-30 | Treatment of urinary incontinence |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998033504A1 true WO1998033504A1 (en) | 1998-08-06 |
Family
ID=8166857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1998/000576 WO1998033504A1 (en) | 1997-02-03 | 1998-01-30 | Treatment of urinary incontinence |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1998033504A1 (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002030902A1 (en) * | 2000-10-13 | 2002-04-18 | Akzo Nobel N.V. | Crystal forms of 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine.hydrochloride |
| WO2003097636A1 (en) * | 2002-05-17 | 2003-11-27 | Biovitrum Ab | Novel compounds and their use |
| WO2004000830A1 (en) | 2002-06-19 | 2003-12-31 | Biovitrum Ab | Novel compounds, their use and preparation |
| WO2004096196A3 (en) * | 2003-04-25 | 2005-03-10 | Pfizer Ltd | Treatment of incontinence with 5htc2 agonists |
| WO2006022420A1 (en) * | 2004-08-25 | 2006-03-02 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| WO2007132841A1 (en) | 2006-05-16 | 2007-11-22 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound and use thereof |
| WO2009063992A1 (en) | 2007-11-15 | 2009-05-22 | Takeda Pharmaceutical Company Limited | Condensed pyridine derivative and use thereof |
| US7923426B2 (en) | 2008-06-04 | 2011-04-12 | The Procter & Gamble Company | Detergent composition |
| US7947643B2 (en) | 2008-06-20 | 2011-05-24 | The Procter & Gamble Company | Laundry composition comprising a substituted polysaccharide |
| WO2011071136A1 (en) | 2009-12-11 | 2011-06-16 | アステラス製薬株式会社 | Therapeutic agent for fibromyalgia |
| WO2019131902A1 (en) | 2017-12-27 | 2019-07-04 | 武田薬品工業株式会社 | Therapeutic agent for stress urinary incontinence and fecal incontinence |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0370560A1 (en) * | 1988-11-24 | 1990-05-30 | Akzo Nobel N.V. | Pharmaceutical composition containing 1-[mono- or bis (trifluoromethyl)-2-pyridinyl] piperazines |
-
1998
- 1998-01-30 WO PCT/EP1998/000576 patent/WO1998033504A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0370560A1 (en) * | 1988-11-24 | 1990-05-30 | Akzo Nobel N.V. | Pharmaceutical composition containing 1-[mono- or bis (trifluoromethyl)-2-pyridinyl] piperazines |
Non-Patent Citations (1)
| Title |
|---|
| W.D. STEERS ET AL.: "Effects of m-chlorophenylpiperazine on penile and bladder function in rats", AMERICAN JOURNAL OF PHYSIOLOGY, vol. 257, no. 6 pt 2, December 1989 (1989-12-01), pages r1441 - R1449, XP000654934 * |
Cited By (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002030902A1 (en) * | 2000-10-13 | 2002-04-18 | Akzo Nobel N.V. | Crystal forms of 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine.hydrochloride |
| CN1329389C (en) * | 2002-05-17 | 2007-08-01 | 比奥维特罗姆股份公司 | Novel compounds and their use |
| JP2005529926A (en) * | 2002-05-17 | 2005-10-06 | ビオヴィトルム・アクチボラゲット | New compounds and their use |
| JP4865221B2 (en) * | 2002-05-17 | 2012-02-01 | プロキシマゲン・リミテッド | New compounds and their use |
| EA007543B1 (en) * | 2002-05-17 | 2006-10-27 | Биовитрум Аб | 4-3(trifluoromethyl-pyridine-5-yl)piperazine derivatives, pharmaceutical composition, methods of their preparing and use |
| US7229997B2 (en) | 2002-05-17 | 2007-06-12 | Biovitrum Ab | Compounds and their use |
| AU2003228196B2 (en) * | 2002-05-17 | 2009-12-17 | Biovitrum Ab (Publ) | Novel compounds and their use |
| WO2003097636A1 (en) * | 2002-05-17 | 2003-11-27 | Biovitrum Ab | Novel compounds and their use |
| WO2004000830A1 (en) | 2002-06-19 | 2003-12-31 | Biovitrum Ab | Novel compounds, their use and preparation |
| WO2004096196A3 (en) * | 2003-04-25 | 2005-03-10 | Pfizer Ltd | Treatment of incontinence with 5htc2 agonists |
| JP2006524679A (en) * | 2003-04-25 | 2006-11-02 | ファイザー・インク | Incontinence treatment |
| EP2277513A3 (en) * | 2003-04-25 | 2011-09-07 | Pfizer Inc. | Treatment of incontinence with 5htc2 agonists |
| EP2277513A2 (en) | 2003-04-25 | 2011-01-26 | Pfizer Inc. | Treatment of incontinence with 5htc2 agonists |
| EP2248524A2 (en) | 2004-08-25 | 2010-11-10 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| EP2400300A1 (en) | 2004-08-25 | 2011-12-28 | Takeda Pharmaceutical Company Limited | Method of screening preventives/remedies for stress urinary incontinence |
| JPWO2006022420A1 (en) * | 2004-08-25 | 2008-05-08 | 武田薬品工業株式会社 | Preventive and therapeutic agent for stress urinary incontinence and screening method thereof |
| EP2248524A3 (en) * | 2004-08-25 | 2011-03-09 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| US8685924B2 (en) | 2004-08-25 | 2014-04-01 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| JP5173190B2 (en) * | 2004-08-25 | 2013-03-27 | 武田薬品工業株式会社 | Preventive and therapeutic agent for stress urinary incontinence and screening method thereof |
| WO2006022420A1 (en) * | 2004-08-25 | 2006-03-02 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| WO2007132841A1 (en) | 2006-05-16 | 2007-11-22 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound and use thereof |
| EP2727585A1 (en) | 2006-05-16 | 2014-05-07 | Takeda Pharmaceutical Company Limited | In-vivo screening method |
| EP2742936A1 (en) | 2006-05-16 | 2014-06-18 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound and use thereof |
| WO2009063992A1 (en) | 2007-11-15 | 2009-05-22 | Takeda Pharmaceutical Company Limited | Condensed pyridine derivative and use thereof |
| EP2789338A2 (en) | 2007-11-15 | 2014-10-15 | Takeda Pharmaceutical Company Limited | Condensed pyridine derivate and use thereof |
| US7923426B2 (en) | 2008-06-04 | 2011-04-12 | The Procter & Gamble Company | Detergent composition |
| US7947643B2 (en) | 2008-06-20 | 2011-05-24 | The Procter & Gamble Company | Laundry composition comprising a substituted polysaccharide |
| WO2011071136A1 (en) | 2009-12-11 | 2011-06-16 | アステラス製薬株式会社 | Therapeutic agent for fibromyalgia |
| WO2019131902A1 (en) | 2017-12-27 | 2019-07-04 | 武田薬品工業株式会社 | Therapeutic agent for stress urinary incontinence and fecal incontinence |
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