[go: up one dir, main page]

WO2003080066A1 - Utilisation de devazepide pour le traitement de la constipation - Google Patents

Utilisation de devazepide pour le traitement de la constipation Download PDF

Info

Publication number
WO2003080066A1
WO2003080066A1 PCT/GB2003/001285 GB0301285W WO03080066A1 WO 2003080066 A1 WO2003080066 A1 WO 2003080066A1 GB 0301285 W GB0301285 W GB 0301285W WO 03080066 A1 WO03080066 A1 WO 03080066A1
Authority
WO
WIPO (PCT)
Prior art keywords
devazepide
opioid
administration
analgesic
day
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.)
Ceased
Application number
PCT/GB2003/001285
Other languages
English (en)
Inventor
Karen Jackson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Innovata Ltd
Original Assignee
ML Laboratories PLC
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 ML Laboratories PLC filed Critical ML Laboratories PLC
Priority to AU2003226509A priority Critical patent/AU2003226509A1/en
Publication of WO2003080066A1 publication Critical patent/WO2003080066A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives

Definitions

  • This invention relates to a novel method of treatment related thereto and a novel use related thereto.
  • WO 99/18967 describes pharmaceutical compositions for treating chronic and neuropathic pain which comprises an analgesic amount of an opioid and an opioid potentiating amount of a CCK antagonist.
  • WO '967 describes the use of both CCK- A (CCK-1) antagonists and CCK-B (CCK-2) antagonists, although it is described that, generally, CCK-B (CCK-2) antagonists are preferred.
  • page 2, lines 6 to 8 of WO '967 describes that CCK-A (CCK- 1) antagonists may be suitable, but only at relatively higher dosages.
  • CCK-A antagonist which is mentioned in WO 99/18967 is devazepide (Devacade®), which is 3s-(-)-l,3-dihydro-3-(2-indolecarbonylamino)-l-methyl-5- phenyl-2H- 1 ,4-benzodiazepin-2-one.
  • Devacade® devazepide
  • Devazepide is usually administered alongside an opioid analgesic, e.g. such as morphine.
  • an opioid analgesic e.g. such as morphine.
  • morphine e.g. a opioid analgesic
  • tolerance generally develops with long-term use, but not to constipation which is the most common undesirable side effect of morphine treatment.
  • the method comprises the administration of a effective amount of devazepide.
  • the method of the invention is especially suited to the treatment of constipation experienced due to the administration of an analgesic, such as an opioid analgesic.
  • analgesic such as an opioid analgesic
  • the method comprises the administration of a effective amount of devazepide.
  • the amount of devazepide used may be a therapeutically effective amount of devazepide.
  • a therapeutically effective amount of devazepide By this we mean an amount which is therapeutically effective as a laxative and/or stool softener. However, in a most preferred embodiment this is an amount of devazepide which is also effective in the enhancement of opioid analgesia.
  • the method of the invention may comprise the administration of an analgesic with devazepide, e.g. a laxative and/or stool softening .amount of devazepide.
  • an analgesic with devazepide e.g. a laxative and/or stool softening .amount of devazepide.
  • a method of treatment of a patient requiring analgesia which comprises the separate, simultaneous or sequential administration of a therapeutically effective .amount of an analgesic and a laxative and/or stool softening amount of devazepide.
  • the amount of devazepide administered is sufficient so that the devazepide exhibits a laxative and/or stool softening effect and an analgesic potentiating effect.
  • the analgesic is preferably an opioid.
  • opioids may be used.
  • the opioid may be selected from those which are effective analgesics and particularly those which need to be administered at relatively high or increasing doses. Examples include morphine, or a salt thereof such as the sulphate, chloride or hydrochloride, or the other 1,4-hydroxymorphinan opioid analgesics such as meperidine, buto ⁇ hanol or pentazocine, or morphine-6- glucuronide, codeine, dihydrocodeine, diamorphine, dextropropoxyphene, pethidine, fentanyl, alfentanil, alphaprodine, buprenorphine, dextromoramide, diphenoxylate, dipipanone, heroin (diacetylmorphine), hydrocodone (dihydrocodeinone), hydromorphone (dihydromo ⁇ hinone), levo ⁇ hanol, meptazinol, methad
  • nihydrohydroxycodeinone oxymo ⁇ hone (dihydrohydroxymo ⁇ hinone), phenadoxone, phenazocine, remifentanil, tramadol, or a salt of any of these.
  • Naloxone is also included within the definition of an opioid.
  • analgesics which may be mentioned are hydromo ⁇ hone, oxycodone, mo ⁇ hine, e.g. mo ⁇ hine sulphate and fentanyl.
  • the analgesic is mo ⁇ hine or mo ⁇ hine sulphate.
  • the opioid is fentanyl, or a salt thereof.
  • the devazepide and/or the opioid may be administered using any methods conventionally known er se.
  • such methods would include, but shall not be limited to, administration intravenously, intra-arterially, orally, intrathecally, intranasally, intrarectally, intramuscularly/subcutaneously, by inhalation and by transdermal patch.
  • the devazepide and/or opioid When the devazepide and/or opioid is administered intravenously, it may, for example, be as an intravenous bolus or a continuous intravenous infusion.
  • the devazepide and/or the opioid is administered subcutaneously, it may, for example, be by subcutaneous infusion.
  • the opioid and/or devazepide are administered orally.
  • the opioid and the devazepide will be administered using the same mode of administration.
  • the opioid when the opioid is administered orally then the devazepide may be administered orally also.
  • the opioid it is within the scope of the invention for the opioid to be administered intravenously and the devazepide to be administered orally.
  • the opioid may be administered by a transdermal patch.
  • the preferred opioid is fentanyl or a salt thereof.
  • the daily dosage of devazepide may vary depending upon, mter alia, the weight of the patient, the method of administration, etc. In patients that are suffering serious disorders, such as cancer patients, the weight of the patient may be very low and therefore the dosage of devazepide consequentially may be low.
  • the daily dosage of devazepide may be up to 0.7 mg/kg/day.
  • the daily dosage of devazepide may be from 25 ⁇ g/kg/day to 0.7 mg/Tcg/day, more preferably from 50 ⁇ g/kg/day to 0.5 mg/kg/day.
  • the daily dosage of devazepide may be from 0.07 mg/kg/day to 0.7 mg/kg/day, preferably 0.07 mg/kg/day to 0.29 mg/kg/day.
  • the dosage of devazepide is preferably 50 ⁇ g/kg/day to 0.5 mg/kg/day.
  • the dosage of the opioid analgesic administered may vary depending upon, inter alia, the nature of the opioid analgesic, the weight of the patient, the method of administration, etc.
  • the dosage of, e.g. an opioid, such as mo ⁇ hine may be from 5 to 2000mg daily.
  • a particular dosage which may be mentioned is from 10 to 240mg daily.
  • a daily dosage of mo ⁇ hine maybe from 5 to lOOmg or occasionally up to 500mg.
  • devazepide may be provided as a composition inco ⁇ orating, for example, a filler, and or other excipients.
  • the composition may be made up into a capsule formulation, e.g. with a fill weight of 150 mg ⁇ 5% by weight or 300 mg ⁇ 5% by weight.
  • the capsule formulation may comprise 1.25mg devazepide, and 148.75 mg of a filler and/or other excipient, e.g. corn starch.
  • the capsule formulation may comprise 2.5mg devazepide, and 297.5 mg of a filler and/or other excipient, e.g. corn starch.
  • fillers may be selected from the group lactose, mannitol, talc, magnesium stearate, sodium chloride, potassium chloride, citric acid, spray-dried lactose, hydrolysed starches, directly compressible starch, microcrystalline cellulose, cellulosics, sorbitol, sucrose, sucrose-based materials, icodextrin, calcium sulphate, dibasic calcium phosphate and dextrose.
  • a preferred filler is starch, e.g. corn starch.
  • the size of the devazepide and filler particles may be the same or different. However, in a preferred embodiment the sizes of the devazepide and filler particles will differ. Preferentially, the devazepide .and/or the filler may be of reduced particle size, e.g. by milling.
  • a preferred embodiment of the invention comprises a composition as hereinbefore described filled into a capsule. Any conventionally known materials may be used for the capsule, however a preferred material is gelatin.
  • devazepide in the manufacture of medicament suitable for use in a method as hereinbefore described.
  • the devazepide used in the method of the invention is the S enantiomer, preferentially, the S enantiomer wherein the level of R enantiomer, which may be present as an impurity, is not greater than 1.5% w/w.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de traitement d'un patient souffrant de constipation. Ce procédé se caractérise en ce qu'il consiste à administrer une quantité efficace de dévazépide. L'invention traite aussi d'un procédé de traitement d'un patient nécessitant une analgésie. Ce procédé consiste à administrer de manière séparée, simultanée ou séquentielle une quantité thérapeutiquement efficace d'un analgésique et d'un laxatif et/ou d'une quantité ramolissant les fèces de dévazépide. L'invention a aussi pour objet l'utilisation de dévazépide pour la fabrication d'un médicament.
PCT/GB2003/001285 2002-03-26 2003-03-26 Utilisation de devazepide pour le traitement de la constipation Ceased WO2003080066A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003226509A AU2003226509A1 (en) 2002-03-26 2003-03-26 Use of devazepide for the treatment of constipation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0207091.0A GB0207091D0 (en) 2002-03-26 2002-03-26 Method of treatment
GB0207091.0 2002-03-26

Publications (1)

Publication Number Publication Date
WO2003080066A1 true WO2003080066A1 (fr) 2003-10-02

Family

ID=9933725

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2003/001285 Ceased WO2003080066A1 (fr) 2002-03-26 2003-03-26 Utilisation de devazepide pour le traitement de la constipation

Country Status (3)

Country Link
AU (1) AU2003226509A1 (fr)
GB (1) GB0207091D0 (fr)
WO (1) WO2003080066A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006094434A1 (fr) * 2005-03-10 2006-09-14 Maoji Zheng Type non invasif de dispositif d'aide a la defecation a l'aide d'une aspiration provoquee par une purge d'air et une reduction de pression

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0685233A2 (fr) * 1994-06-03 1995-12-06 Eli Lilly And Company Thieno 1,5 benzodiazepine pour le traitement des troubles gastrointestinaux
US5760032A (en) * 1994-06-01 1998-06-02 Yoshitomi Pharmaceutical Industries, Ltd. Thienylazole compound and thienotriazolodiazepine compound
WO1999018967A1 (fr) * 1997-10-15 1999-04-22 Panos Therapeutics Limited Compositions analgesiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5760032A (en) * 1994-06-01 1998-06-02 Yoshitomi Pharmaceutical Industries, Ltd. Thienylazole compound and thienotriazolodiazepine compound
EP0685233A2 (fr) * 1994-06-03 1995-12-06 Eli Lilly And Company Thieno 1,5 benzodiazepine pour le traitement des troubles gastrointestinaux
WO1999018967A1 (fr) * 1997-10-15 1999-04-22 Panos Therapeutics Limited Compositions analgesiques

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GOULD R J ET AL: "A MODEL OF GASTRIC EMPTYING IN CATS SHOWS SOLID EMPTYING IS PROMOTED BY MK-329: A CCK ANTAGONIST", JOURNAL OF NUCLEAR MEDICINE, SOCIETY OF NUCLEAR MEDICINE. NEW YORK, US, vol. 31, no. 9, September 1990 (1990-09-01), pages 1494 - 1500, XP000985568, ISSN: 0161-5505 *
SINGH L ET AL: "MODULATION OF THE IN VIVO ACTIONS OF MORPHINE BY THE MIXED CCKA/B RECEPTOR ANTAGONIST PD 142898", EUROPEAN JOURNAL OF PHARMACOLOGY, AMSTERDAM, NL, vol. 307, no. 3, 1996, pages 283 - 289, XP000607452, ISSN: 0014-2999 *
WILLIAMS CYNTHIA L ET AL: "Cholecystokinin-induced antinociception is not blocked by CCK-A or CCK-B receptor antagonists.", PEPTIDES (TARRYTOWN), vol. 18, no. 3, 1997, pages 409 - 414, XP002245814, ISSN: 0196-9781 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006094434A1 (fr) * 2005-03-10 2006-09-14 Maoji Zheng Type non invasif de dispositif d'aide a la defecation a l'aide d'une aspiration provoquee par une purge d'air et une reduction de pression

Also Published As

Publication number Publication date
GB0207091D0 (en) 2002-05-08
AU2003226509A1 (en) 2003-10-08

Similar Documents

Publication Publication Date Title
US6713470B2 (en) Method of treatment
EP1467718B1 (fr) Methode de traitement d'un patient necessitant une analgesie
CA2302754A1 (fr) Noribogaine utilisee pour le traitement de la douleur et de la toxicomanie
JP2001527554A (ja) 抗うつ薬とｎｍｄａレセプター拮抗薬とを組み合わせる神経障害痛の治療用組成物及び治療方法
JP2000508341A (ja) 片頭痛の治療法及び薬効の強化組成物
SK14282000A3 (sk) Farmaceutický prostriedok na liečenie závislosti od alkoholu a drog obsahujúci opiátového antagonistu a modulátor súhrnu nmda receptorov
AU782523B2 (en) Salts and bases of 17-(cyclopropylmethyl)-4,5 alpha-epoxy-6-methylenemorphinan-3,14 diol for optimizing dopamine homeostasis during administration of opioid analgesics
US20030139396A1 (en) Method of treatment
JP2005521655A5 (fr)
WO2003080066A1 (fr) Utilisation de devazepide pour le traitement de la constipation
US20040043990A1 (en) Method of treatment
JPH0653683B2 (ja) 慢性痛あるいは慢性咳を治療する経口用組成物
EP1492540B1 (fr) Utilisation du devazepide comme analgesique
RU2003135201A (ru) Применение антагониста опиоидов налтрексона для предупреждения и контроля побочных воздействий, вызванных опиоидами
EP1569654A1 (fr) Utilisation du devazepide en combinaison avec un analgesique opioide pour potentialiser l'activite de cet analgesique
US20040167146A1 (en) Method of treatment
US20040198723A1 (en) Method of treatment
AU2003212486A1 (en) Method of treatment of a patient requiring analgesia
JP2005533046A5 (fr)
US20080125414A1 (en) Method of Treatment
Sinatra Opioids and opioid receptors
Silverman Buprenorphine for pain and opioid dependence
Mohsin et al. The safety and efficacy of remifentanil and alfentanil in patients undergoing major abdominal surgery.
Mercadante Is morphine the drug of choice in cancer pain?
US20110046173A1 (en) Combination analgesic opioid pain therapy

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP