WO1998033504A1 - Traitement de l'incontinence urinaire - Google Patents

Traitement de l'incontinence urinaire Download PDF

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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
Application number
PCT/EP1998/000576
Other languages
English (en)
Inventor
Christophorus Louis Eduard Broekkamp
Original Assignee
Akzo Nobel N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Akzo Nobel N.V. filed Critical Akzo Nobel N.V.
Priority to PCT/EP1998/000576 priority Critical patent/WO1998033504A1/fr
Priority to AU66193/98A priority patent/AU6619398A/en
Publication of WO1998033504A1 publication Critical patent/WO1998033504A1/fr

Links

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.

Abstract

La présente invention concerne une nouvelle utilisation médicale de la 1-[6-chloro-5-(trifluorométhyl)-2-pyridinyl]pipérazine ou d'un sel d'addition de celle-ci avec un acide acceptable sur le plan pharmaceutique. Cette nouvelle utilisation concerne, plus particulièrement, le traitement de l'incontinence urinaire.
PCT/EP1998/000576 1997-02-03 1998-01-30 Traitement de l'incontinence urinaire WO1998033504A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/EP1998/000576 WO1998033504A1 (fr) 1997-02-03 1998-01-30 Traitement de l'incontinence urinaire
AU66193/98A AU6619398A (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 (fr) 1997-02-03 1998-01-30 Traitement de l'incontinence urinaire

Publications (1)

Publication Number Publication Date
WO1998033504A1 true WO1998033504A1 (fr) 1998-08-06

Family

ID=8166857

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/000576 WO1998033504A1 (fr) 1997-02-03 1998-01-30 Traitement de l'incontinence urinaire

Country Status (1)

Country Link
WO (1) WO1998033504A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030902A1 (fr) * 2000-10-13 2002-04-18 Akzo Nobel N.V. Formes cristallines d'hydrochlorure de 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine
WO2003097636A1 (fr) * 2002-05-17 2003-11-27 Biovitrum Ab Nouveaux composes et leur utilisation
WO2004000830A1 (fr) 2002-06-19 2003-12-31 Biovitrum Ab Nouveaux composes, leur utilisation et leur preparation
WO2004096196A2 (fr) * 2003-04-25 2004-11-11 Pfizer Limited Traitement de l'incontinence
WO2006022420A1 (fr) * 2004-08-25 2006-03-02 Takeda Pharmaceutical Company Limited Agents préventifs/remèdes pour l’incontinence de stress et procédé de sélection de ceux-ci
WO2007132841A1 (fr) 2006-05-16 2007-11-22 Takeda Pharmaceutical Company Limited Composé hétérocyclique fusionné et utilisation
WO2009063992A1 (fr) 2007-11-15 2009-05-22 Takeda Pharmaceutical Company Limited Dérivé de pyridine condensé et son utilisation
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 (fr) 2009-12-11 2011-06-16 アステラス製薬株式会社 Agent thérapeutique pour la fibromyalgie
WO2019131902A1 (fr) 2017-12-27 2019-07-04 武田薬品工業株式会社 Agent thérapeutique pour incontinence urinaire de stress et incontinence fécale

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0370560A1 (fr) * 1988-11-24 1990-05-30 Akzo Nobel N.V. Compositions pharmaceutiques contenant des 1-[mono ou bis(trifluorométhyl)-2-pyridinyl]pipérazines

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0370560A1 (fr) * 1988-11-24 1990-05-30 Akzo Nobel N.V. Compositions pharmaceutiques contenant des 1-[mono ou bis(trifluorométhyl)-2-pyridinyl]pipérazines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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 (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030902A1 (fr) * 2000-10-13 2002-04-18 Akzo Nobel N.V. Formes cristallines d'hydrochlorure de 1-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine
AU2003228196B2 (en) * 2002-05-17 2009-12-17 Biovitrum Ab (Publ) Novel compounds and their use
JP2005529926A (ja) * 2002-05-17 2005-10-06 ビオヴィトルム・アクチボラゲット 新規化合物とそれらの使用
JP4865221B2 (ja) * 2002-05-17 2012-02-01 プロキシマゲン・リミテッド 新規化合物とそれらの使用
WO2003097636A1 (fr) * 2002-05-17 2003-11-27 Biovitrum Ab Nouveaux composes et leur utilisation
CN1329389C (zh) * 2002-05-17 2007-08-01 比奥维特罗姆股份公司 化合物和它们的用途
US7229997B2 (en) 2002-05-17 2007-06-12 Biovitrum Ab Compounds and their use
EA007543B1 (ru) * 2002-05-17 2006-10-27 Биовитрум Аб Производные 4-(3-трифторметилпиридин-5-ил)пиперазина, фармацевтическая композиция, способы их получения и применение
WO2004000830A1 (fr) 2002-06-19 2003-12-31 Biovitrum Ab Nouveaux composes, leur utilisation et leur preparation
WO2004096196A3 (fr) * 2003-04-25 2005-03-10 Pfizer Ltd Traitement de l'incontinence
EP2277513A3 (fr) * 2003-04-25 2011-09-07 Pfizer Inc. Traitement de l'incontinence avec des 5ht2c agonistes
EP2277513A2 (fr) 2003-04-25 2011-01-26 Pfizer Inc. Traitement de l'incontinence avec des 5ht2c agonistes
WO2004096196A2 (fr) * 2003-04-25 2004-11-11 Pfizer Limited Traitement de l'incontinence
JP2006524679A (ja) * 2003-04-25 2006-11-02 ファイザー・インク 失禁の治療
US8685924B2 (en) 2004-08-25 2014-04-01 Takeda Pharmaceutical Company Limited Preventives/remedies for stress urinary incontinence and method of screening the same
EP2248524A3 (fr) * 2004-08-25 2011-03-09 Takeda Pharmaceutical Company Limited Agents preventifs/remedes pour l'incontinence de stress et procede de selecetion de ceux-ci
WO2006022420A1 (fr) * 2004-08-25 2006-03-02 Takeda Pharmaceutical Company Limited Agents préventifs/remèdes pour l’incontinence de stress et procédé de sélection de ceux-ci
JP5173190B2 (ja) * 2004-08-25 2013-03-27 武田薬品工業株式会社 腹圧性尿失禁の予防・治療剤及びそのスクリーニング方法
JPWO2006022420A1 (ja) * 2004-08-25 2008-05-08 武田薬品工業株式会社 腹圧性尿失禁の予防・治療剤及びそのスクリーニング方法
EP2400300A1 (fr) 2004-08-25 2011-12-28 Takeda Pharmaceutical Company Limited Procédé de sélection d'agents préventifs/remèdes pour l'incontinence de stress
EP2248524A2 (fr) 2004-08-25 2010-11-10 Takeda Pharmaceutical Company Limited Agents préventifs/remèdes pour l'incontinence de stress et procédé de séléction de ceux-ci
EP2742936A1 (fr) 2006-05-16 2014-06-18 Takeda Pharmaceutical Company Limited Composé hétérocyclique condensé et son utilisation
EP2727585A1 (fr) 2006-05-16 2014-05-07 Takeda Pharmaceutical Company Limited Méthode de dépistage in-vivo
WO2007132841A1 (fr) 2006-05-16 2007-11-22 Takeda Pharmaceutical Company Limited Composé hétérocyclique fusionné et utilisation
WO2009063992A1 (fr) 2007-11-15 2009-05-22 Takeda Pharmaceutical Company Limited Dérivé de pyridine condensé et son utilisation
EP2789338A2 (fr) 2007-11-15 2014-10-15 Takeda Pharmaceutical Company Limited Dérivé de pyridine condensé et son utilisation
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 (fr) 2009-12-11 2011-06-16 アステラス製薬株式会社 Agent thérapeutique pour la fibromyalgie
WO2019131902A1 (fr) 2017-12-27 2019-07-04 武田薬品工業株式会社 Agent thérapeutique pour incontinence urinaire de stress et incontinence fécale

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