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WO1990000390A1 - Nouvelle preparation synergique renfermant de la dezocine et un anesthesiant local, ainsi que nouveau procede pour soulager la douleur - Google Patents

Nouvelle preparation synergique renfermant de la dezocine et un anesthesiant local, ainsi que nouveau procede pour soulager la douleur Download PDF

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Publication number
WO1990000390A1
WO1990000390A1 PCT/SE1989/000348 SE8900348W WO9000390A1 WO 1990000390 A1 WO1990000390 A1 WO 1990000390A1 SE 8900348 W SE8900348 W SE 8900348W WO 9000390 A1 WO9000390 A1 WO 9000390A1
Authority
WO
WIPO (PCT)
Prior art keywords
dezocine
pharmaceutical preparation
local anaesthetic
physiologically acceptable
acceptable salt
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/SE1989/000348
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English (en)
Inventor
Claes Tomas Post
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.)
AstraZeneca AB
Original Assignee
Astra AB
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 Astra AB filed Critical Astra AB
Publication of WO1990000390A1 publication Critical patent/WO1990000390A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine

Definitions

  • the present invention is related to new synergistic pharmaceutical preparations, a method for their preparation and to a new method of alleviation of postoperative pain and pain related to pathophysiological changes in man, such as severe chronic pain, wherein the new pharmaceutical preparations are used.
  • the suffering from pain after operations, and that related to diseases as cancer and neurological diseases, has been the subject to treatment with e.g. conventional opiate analgesics.
  • opiate analgesics have several severe draw-backs, as e.g. development of tolerance, addiction and sedation with risk for respiratory depression.
  • analgesic agents intended for pain relief post-operatively and for relief of severe pain of other origins, which do not have the mentioned draw-backs.
  • the opiate agonist/antagonist analgesics have been shown to have several advantages in this respect.
  • Another type of drug that has been used ⁇ pinally to treat pain, is the local anaesthetic compounds.
  • the known compound dezocine when administered together with a known local anaesthetic compound, e.g. bupivacaine, lidocaine, tetracaine or ropivacaine, gives an unexpected synergistic antinociceptive effect when administered intrathecally.
  • a known local anaesthetic compound e.g. bupivacaine, lidocaine, tetracaine or ropivacaine.
  • physiologically acceptable salts which are used according to this invention are hydrochloride, hydrobromide, lactate, acetate or sulphamate.
  • physiologically acceptable salts are the hydrochlorides of dezocine and bupivacaine.
  • the present invention thus provides new pharmaceutical preparations containing dezocine and a local anaesthetic agent, methods for preparing such preparations and methods for alleviating pain sensation wherein said pharmaceutical preparation is used in the post-operative period for the treatment of severe chronic pain.
  • the pharmaceutical preparations are for spinal analgesia. They are preferably administered by intrathecal or epidural injection.
  • dezocine and bupivacaine are incorporated in a pharmaceutical preparation suitable for intrathecal or epidural injection.
  • dezocine HC1 is incorporated in a pharmaceutical preparation suitable for intrathecal injection together with bupivacaine HCl.
  • a convenient route of administration of the new preparations is spinally i.e. intrathecally or epidurally, which will allow repeated administration over a long period of time.
  • intrathecally a convenient way of restricting spread to segments more ro ⁇ trally than intended, would be to make the solution hyperbaric by adding i.e. glucose to the desired density.
  • a vasoconstrictor such as adrenaline may be added to the solution.
  • the dosage of administration of dezocine and the local anaesthetic depend i.a. on the route of administration and the pharmaceutical formulation.
  • a suitable dosage for obtaining analgesia by intrathecal or epidural administration is between 3 and 500 ⁇ g/kg of dezocine and between 0.1 and 1.5 mg/kg of bupivacaine.
  • the preparations will normally be injected intrathecally or epidurally.
  • the preparations used are solutions which contain between 0.01 and 0.1 % by weight of dezocine between 0.1 and 1 % by weight of the local anaesthetic, and between 5-10 % by weight of glucose in order to increase the baricity of the solution. It is also possible to add a small amount of the vasoconstrictor adrenaline to the solution in order to restrict spreading.
  • the preparations are made by dissolving the active ingredient or ingredients in a physiologically acceptable solvent.
  • Example 1 is considered to represent the best mode of carrying out the invention known at present.
  • the antinociceptive effect of the new preparations may be established by the hot plate and tail-flick test.
  • Analgesiameter was set at a temperature of 58+0.2°C.
  • the criteria for a pain response was licking or kicking of either of the hindpaws.
  • the cut-off time in the hot plate test was 30 sec. and in the tail-flick test 10 sec.
  • the pain responsiveness was examined in male NMRI mice in a weight range of 22-25 g. They were housed in groups of 10 in each cage for at least 4 days after delivery.
  • the animals were tested for hot plate and tail-flick tests.
  • the drugs were administered in a volume of 5 ⁇ l, and testing of hot plate and tail-flick reaction latencies took place at the intervals given in the tables.
  • the animals were not tested until the local anaesthetic effect of bupivacaine had disappeared, which normally took between 10 and 15 minutes.
  • the cut-off time in the tail-flick test was 10 sec and in the hot plate test 30 sec.
  • the values are reaction times (seconds) expressed as means + S.E.M. and represent the results from experiments performed in 10 mice. Note that the reaction time at 0 min represents the basal value for the animals, and that an increase from this value represents antinociception.
  • the synergistic antinociceptive effects in animals injected with the combination of dezocine and bupivacaine is therefore, obvious at 60 and 120 min. in the tail-flick test and at 30 and 60 min. in the hot plate test (Mann-Whitney U-test) . ** P ⁇ 0.01 when the difference between dezocine injected alone or together with bupivacaine is calculated.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Sont décrits une préparation pharmaceutique pour analgésie spinale, laquelle soulage les douleurs post-opératoires ou chroniques et renferme de la dézocine ou son sel physiologiquement acceptable conjointement avec un anesthésiant local tel que la bupivacaïne ou son sel physiologiquement acceptable, un procédé pour obtenir ladite préparation ainsi qu'un procédé pour parvenir à l'analgésie d'un patient en lui administrant ladite préparation.
PCT/SE1989/000348 1988-07-08 1989-06-19 Nouvelle preparation synergique renfermant de la dezocine et un anesthesiant local, ainsi que nouveau procede pour soulager la douleur Ceased WO1990000390A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8802564-8 1988-07-08
SE8802564A SE8802564D0 (sv) 1988-07-08 1988-07-08 New synergistic preparations and a new method of alleviation of pain

Publications (1)

Publication Number Publication Date
WO1990000390A1 true WO1990000390A1 (fr) 1990-01-25

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Family Applications (1)

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PCT/SE1989/000348 Ceased WO1990000390A1 (fr) 1988-07-08 1989-06-19 Nouvelle preparation synergique renfermant de la dezocine et un anesthesiant local, ainsi que nouveau procede pour soulager la douleur

Country Status (3)

Country Link
AU (1) AU3856489A (fr)
SE (1) SE8802564D0 (fr)
WO (1) WO1990000390A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995008661A1 (fr) * 1993-09-21 1995-03-30 W.L. Gore & Associates, Inc. Materiau isolant gonfle et ses procedes de fabrication
WO1999025349A1 (fr) * 1997-11-19 1999-05-27 Darwin Discovery Limited Formulation anesthesique
WO2010017996A1 (fr) 2008-08-14 2010-02-18 Klaus Strackharn Utilisation à faible dose d'anesthésiques locaux ou de leurs dérivés pour la thérapie de douleurs chroniques, en particulier la migraine
US20100247671A1 (en) * 2009-03-26 2010-09-30 Thomas Jeffrey E Method and composition for alleviating or preventing ischemic tissue damage
WO2017009862A1 (fr) * 2015-07-13 2017-01-19 Neon Laboratories Limited Injection de solution hyperbare de chlorhydrate de lévobupivacaïne comprenant du chlorhydrate de lévobupivacaïne
CN110483315A (zh) * 2018-05-15 2019-11-22 扬子江药业集团有限公司 一种地佐辛杂质c的制备方法
JP2020525401A (ja) * 2017-07-03 2020-08-27 山東丹紅制薬有限公司Ｓｈａｎｄｏｎｇ Ｄａｎｈｏｎｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏ．， Ｌｔｄ． デゾシン類似体塩酸塩の結晶形及び非晶質
CN116763931A (zh) * 2018-07-06 2023-09-19 华创合成制药股份有限公司 盐酸在制备提高地佐辛稳定性和溶解度的制剂中的应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2382546A (en) * 1941-11-03 1945-08-14 Curtis David Anesthetic solutions
EP0164320A1 (fr) * 1984-03-14 1985-12-11 Astra Läkemedel Aktiebolag Préparations pharmaceutiques pour l'analgésie spinale contenant de la guanfacine et leur procédé de préparation
EP0180303A1 (fr) * 1984-09-28 1986-05-07 American Home Products Corporation Composition parentérale

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2382546A (en) * 1941-11-03 1945-08-14 Curtis David Anesthetic solutions
EP0164320A1 (fr) * 1984-03-14 1985-12-11 Astra Läkemedel Aktiebolag Préparations pharmaceutiques pour l'analgésie spinale contenant de la guanfacine et leur procédé de préparation
EP0180303A1 (fr) * 1984-09-28 1986-05-07 American Home Products Corporation Composition parentérale

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANESTHESIA AND ANALGESIA, Volume 57, issued 1978 (Cleveland), R.J. FRAGEN & N. CALDWELL, "Comparison of dezocine (WY 16, 225) and meperidine as postoperative analgesics", see pages 563-566, especially p. 563, first paragraph. *
ANESTHESIA AND ANALGESIA, Volume 62, No. 10, issued 1983 (New York), J.C. ROWLINGSON et al.: "Anesthetic potency of dezocine and its interaction with morphine in rats", see pages 899-902, especially p. 900, richt column, second paragraph. *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995008661A1 (fr) * 1993-09-21 1995-03-30 W.L. Gore & Associates, Inc. Materiau isolant gonfle et ses procedes de fabrication
WO1999025349A1 (fr) * 1997-11-19 1999-05-27 Darwin Discovery Limited Formulation anesthesique
US5932597A (en) * 1997-11-19 1999-08-03 Darwin Discovery Limited Anaesthetic formulation
AU740914B2 (en) * 1997-11-19 2001-11-15 Darwin Discovery Limited Anaesthetic formulation
CN1131033C (zh) * 1997-11-19 2003-12-17 达尔文发现有限公司 麻醉制剂
KR100695588B1 (ko) * 1997-11-19 2007-03-14 다윈 디스커버리 리미티드 마취용 제형물
WO2010017996A1 (fr) 2008-08-14 2010-02-18 Klaus Strackharn Utilisation à faible dose d'anesthésiques locaux ou de leurs dérivés pour la thérapie de douleurs chroniques, en particulier la migraine
DE102008037682A1 (de) 2008-08-14 2010-04-08 Strackharn, Klaus, Dr.med. Verwendung äquipotenter Dosierungen von Lokalanästetika oder Derivaten davon zur Therapie chronischer Schmerzen
US20100247671A1 (en) * 2009-03-26 2010-09-30 Thomas Jeffrey E Method and composition for alleviating or preventing ischemic tissue damage
US10369228B2 (en) 2009-03-26 2019-08-06 Jeffrey E. Thomas Method and composition for alleviating or preventing ischemic tissue damage
WO2017009862A1 (fr) * 2015-07-13 2017-01-19 Neon Laboratories Limited Injection de solution hyperbare de chlorhydrate de lévobupivacaïne comprenant du chlorhydrate de lévobupivacaïne
EP3331508B1 (fr) * 2015-07-13 2024-08-14 Neon Laboratories Ltd. Injection de solution hyperbare de chlorhydrate de lévobupivacaïne comprenant du chlorhydrate de lévobupivacaïne
JP2020525401A (ja) * 2017-07-03 2020-08-27 山東丹紅制薬有限公司Ｓｈａｎｄｏｎｇ Ｄａｎｈｏｎｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏ．， Ｌｔｄ． デゾシン類似体塩酸塩の結晶形及び非晶質
CN110483315A (zh) * 2018-05-15 2019-11-22 扬子江药业集团有限公司 一种地佐辛杂质c的制备方法
CN110483315B (zh) * 2018-05-15 2021-11-09 扬子江药业集团有限公司 一种地佐辛杂质c的制备方法
CN116763931A (zh) * 2018-07-06 2023-09-19 华创合成制药股份有限公司 盐酸在制备提高地佐辛稳定性和溶解度的制剂中的应用

Also Published As

Publication number Publication date
AU3856489A (en) 1990-02-05
SE8802564D0 (sv) 1988-07-08

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