EP0845990A1 - Nouvel emploi de pregnanes-diones comme analgesiques - Google Patents

Nouvel emploi de pregnanes-diones comme analgesiques

Info

Publication number
EP0845990A1
EP0845990A1 EP96927448A EP96927448A EP0845990A1 EP 0845990 A1 EP0845990 A1 EP 0845990A1 EP 96927448 A EP96927448 A EP 96927448A EP 96927448 A EP96927448 A EP 96927448A EP 0845990 A1 EP0845990 A1 EP 0845990A1
Authority
EP
European Patent Office
Prior art keywords
analgesic
compound
formula
composition according
new use
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.)
Withdrawn
Application number
EP96927448A
Other languages
German (de)
English (en)
Other versions
EP0845990A4 (fr
Inventor
Colin Stanley Goodchild
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.)
GOODCHILD, COLIN, STANLEY
NADESON, RAYMOND
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP0845990A1 publication Critical patent/EP0845990A1/fr
Publication of EP0845990A4 publication Critical patent/EP0845990A4/fr
Withdrawn legal-status Critical Current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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Definitions

  • TITLE New Use of Pregnane-diones as analgesic agents
  • This invention relates to compounds and compositions.
  • the present invention provides:-
  • R 1 is H or Me, preferably H; R 2 is OH, preferably in alpha conformation; R 3 is H; or R 2 and R 3 , taken together, are O; R* is H or Me, preferably Me and preferably in alpha conformation; R 5 is H; R 6 is H; or R 5 and R 6 , taken together, are O; R 7 is H or Me, preferably H; R ⁇ is H, Me or -CH 2 0 CO CH 3 .
  • R 1 is H or Me, preferably H
  • R 2 is OH, preferably in alpha conformation
  • R 4 is H or Me, preferably Me and preferably in alpha conformation
  • R 5 is H
  • R 6 is H; or R 5 and R 6 , taken together, are 0;
  • R 7 is H or Me, preferably H
  • R ⁇ is H, Me or -CH 2 0 CO CH 3 .
  • the present invention also provides an analgesic composition
  • an analgesic composition comprising a compound of Formula II wherein
  • R 1 is H or Me, preferably H;
  • R 2 is OH, preferably in alpha conformation;
  • R 3 is H; or R 2 and R 3 , taken together, are 0;
  • R* is H or Me, preferably Me and preferably in alpha conformation;
  • R 5 is H;
  • R 6 is H; or
  • R 5 and R 6 taken together, are 0;
  • R 7 is H or Me, preferably H;
  • R ⁇ is H, Me or -CH 2 0 CO CH 3 together with a pharmaceutically acceptable diluent.
  • German Patent Specification No. 2,162,554 (filed 29th June, 1972, based on British Application No. 60,068/70 filed 17th December, 1970) to GLAXO;
  • a preferred compound for use is
  • the compounds may be used individually or in mixtures with other compounds of Formula II.
  • the compounds for use in this invention may be provided in free acid form or as a salt. It is preferred that the compounds are provided as either sulphate or methane sulphonate salts.
  • the present invention provides a composition in a form suitable for oral administration.
  • That form may include tablet, capsule or lozenge or a liquid form.
  • composition contains a surfactant and/or a solubility improver.
  • a solubility improver is water-soluble polyoxyethylated castor oil.
  • a suitable surfactant is Cremophor EL.
  • a suitable dosage in a 70kg human would be about a maximum of 2.00 grams of the compound of Formula II every 6 hours.
  • Figure 1 is a graph showing results obtained.
  • Figure 2 is a graph showing results obtained
  • figure 2 is a time response curve showing the mean of the responses in all five rats to the drug with vehicle and vehicle (Cremophor) alone. In all cases alphadolone caused rises in ECT pain thresholds in the neck and tail whereas the vehicle alone had no effect.
  • bicuculline 10 pmol was given intrathecally 30 minutes after the intragastric drug or vehicle.
  • Bicuculline is a selective GABA A receptor antagonist. In confining bicuculline to the part of the spinal cord responsible for tail innervation we would expect tail GABA-mediated responses to be reversed but those responsible for neck sensations to be unaffected. That is the result shown in Figure 2.

Landscapes

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

Abstract

L'invention porte sur la nouvelle utilisation d'un composé de formule (II) dans laquelle: R1 est H ou Me, et de préférence H; R2 est OH, de préférence en conformation alpha; R3 est H, ou R2 et R3 pris ensemble représentent O; R4 est H ou Me, et de préférence Me, et de préférence en conformation alpha; R5 est H; R6 est H; ou R5 et R6 pris ensemble représentent O; R7 est H ou Me, de préférence H; R8 est H, Me ou -CH¿2? O CO CH3. L'invention porte également sur une méthode d'analgésie consistant à administrer une dose efficace du composé de formule (II) dans laquelle R?1¿ est H ou Me, et de préférence H; R2 est OH, de préférence en conformation alpha; R3 est H, ou R2 et R3 pris ensemble représentent O; R4 est H ou Me, et de préférence Me, et de préférence en conformation alpha; R5 est H; R6 est H; ou R5 et R6 représentent ensemble O; R7 est H ou Me, de préférence H; R8 est H, Me ou -CH¿2? O CO CH3. L'invention porte en outre sur une composition analgésique comprenant un composé de formule (II) dans laquelle R?1¿ est H ou Me, et de préférence H; R2 est OH, de préférence en conformation alpha; R3 est H, ou R2 et R3 pris ensemble représentent O; R4 est H ou Me, et de préférence Me, et de préférence en conformation alpha; R5 est H; R6 est H; ou R5 et R6 représentent ensemble O; R7 est H ou Me, de préférence H; R8 est H, Me ou -CH¿2? O CO CH3. L'invention concerne également un diluant pharmacocompatible.
EP96927448A 1995-08-23 1996-08-23 Nouvel emploi de pregnanes-diones comme analgesiques Withdrawn EP0845990A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AUPN4980/95 1995-08-23
AUPN4980A AUPN498095A0 (en) 1995-08-23 1995-08-23 Compounds and compositions
PCT/AU1996/000531 WO1997007807A1 (fr) 1995-08-23 1996-08-23 Nouvel emploi de pregnanes-diones comme analgesiques

Publications (2)

Publication Number Publication Date
EP0845990A1 true EP0845990A1 (fr) 1998-06-10
EP0845990A4 EP0845990A4 (fr) 2001-02-14

Family

ID=3789308

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96927448A Withdrawn EP0845990A4 (fr) 1995-08-23 1996-08-23 Nouvel emploi de pregnanes-diones comme analgesiques

Country Status (3)

Country Link
EP (1) EP0845990A4 (fr)
AU (1) AUPN498095A0 (fr)
WO (1) WO1997007807A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPR731901A0 (en) * 2001-08-28 2001-09-20 Goodchild, Colin Stanley Method of treatment
GB0324423D0 (en) * 2003-10-18 2003-11-19 Vernalis Cambridge Ltd Analgesia method

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5439900A (en) * 1993-02-25 1995-08-08 Bukusoglu; Cuneyt Methods and compositions for providing analgesia and enhanced anesthesia

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1317185A (en) * 1969-06-20 1973-05-16 Glaxo Lab Ltd Acyloxy-3alpha-hydroxy-pregnones
US3917830A (en) * 1970-12-17 1975-11-04 Glaxo Lab Ltd Steroidal anaesthetic composition for intraveneous injection
GB1373913A (en) * 1970-12-17 1974-11-13 Glaxo Lab Ltd Pharmaceutical compositions
BE791196A (fr) * 1971-11-11 1973-05-10 Glaxo Lab Ltd Nouveaux steroides, leur procede de preparation et leurs applications
US3959260A (en) * 1972-05-05 1976-05-25 Glaxo Laboratories Limited Anaesthetic steroids of the pregnane and 19-norpregnane series having a sulfur-containing group at the 21-position
FR2318646A1 (fr) * 1975-07-25 1977-02-18 Ile De France Medicament injectable utilisable en anesthesie
US4361558A (en) * 1980-04-29 1982-11-30 Ciba-Geigy Corporation Halogenated steroids
US5212167A (en) * 1991-09-12 1993-05-18 Trustees Of Boston University Modulation of receptor-mediated ion transport
DE69435286D1 (de) * 1993-05-24 2010-05-20 Purdue Pharma Ltd Verfahren und zusammensetzungen zum hervorrufen von schlaf

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5439900A (en) * 1993-02-25 1995-08-08 Bukusoglu; Cuneyt Methods and compositions for providing analgesia and enhanced anesthesia

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CARL...: "pharmacokinetics and pharmacodynamics of..." ACTA ANESTHESIOLOGY SCAND., vol. 38, no. 7, 1994, pages 734-741, XP000965594 *
ERIKSSON H ET AL: "Comparison of eltanolone and thiopental in anaesthesia for termination of pregnancy." ACTA ANAESTHESIOLOGICA SCANDINAVICA, vol. 39, no. 4, 1995, pages 479-484, XP000965595 ISSN: 0001-5172 *
See also references of WO9707807A1 *
SELYE: "correlations between..." ENDOCRINOLOGY, vol. 30, 1942, pages 437-453, XP000974346 *

Also Published As

Publication number Publication date
WO1997007807A1 (fr) 1997-03-06
AUPN498095A0 (en) 1995-09-14
EP0845990A4 (fr) 2001-02-14

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