WO2000061152A1 - Management of pain after joint surgery - Google Patents
Management of pain after joint surgery Download PDFInfo
- Publication number
- WO2000061152A1 WO2000061152A1 PCT/SE2000/000620 SE0000620W WO0061152A1 WO 2000061152 A1 WO2000061152 A1 WO 2000061152A1 SE 0000620 W SE0000620 W SE 0000620W WO 0061152 A1 WO0061152 A1 WO 0061152A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- joint
- composition
- effective amount
- surgery
- pharmaceutically acceptable
- Prior art date
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
- A61K31/70—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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7012—Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a method for the management of pain and immobilization resulting from joint surgery, to composition for use in the method, and to the manufacture of the composition.
- intravenous or intramuscular morphine or other opoid-based treatments patients undergoing knee or other types of orthopedic surgery most often are managed by intravenous or intramuscular morphine or other opoid-based treatments. Usually this results in short-lasting and often insufficient analgesia which may be accompanied by side effects such as nausea, vomiting, and respiratory depression.
- intravenous or intramuscular NSAIDs non- steroid anti-inflammatory drugs
- diclofenac non- steroid anti-inflammatory drugs
- ketoprofen or ketorolac may be used.
- Such therapy is not more efficient than administration of opoids while entailing the risk of other side effects such as gastric ulcer, asthma, and severe skin reactions. A better management of postoperative pain thus is desirable.
- the 6-glucuronide also is a potent opoid antagonist. It is substantially more hydrophilic than most opoids in clinical use. Therefore M6G has less tendency to penetrate the blood/brain barrier, thus decreasing the risk for adverse central nervous effects .
- Morphine 6-glucuronide has been used as a preoperatively intrathecally administered analgesic to reduce postoperative pain in total hip replacement (D Grace et al., Anest. Analg. 83 (1996) 1055-9) and in knee surgery (Brit. J. Anaest. 69 (1992) 2) . In both studies the observation of delayed respiratory depression cautions against such use of M6G.
- a method of the aforementioned kind comprising the administration of a analgetically effective amount of morphine-6-glucuronide
- M6G is advantageously combined with that of a local anesthetic with a short onset of action, such as lidocaine, bupivacaine, mepivacaine, and ropivacaine, providing anesthesia of medium or long duration, such as up to 3 h and longer. While the local anesthetic will exert an immediate but shorter lasting effect, the onset of action of M6G will be slower but its effect will be substantially longer than that of the local anesthetic.
- a local anesthetic with a short onset of action, such as lidocaine, bupivacaine, mepivacaine, and ropivacaine
- the local anesthetic and M6G thus will exert a beneficial analgesic effect covering an extended period of time from administration and up to 48 hour or more.
- This long lasting analgesic effect will let the patient be mobilized earlier, and thus reduce the risk of adverse effects related to postoperative immobilization, such as venous thrombosis and pulmonary embolism. Early mobilization also translates to reduced health care costs.
- An advantageous aspect of the invention is that only a fraction of M6G is needed to obtain an analgetic effect
- a preferred dose for obtaining analgesia in a larger joint is from 0.05 to 10 mg.
- larger joint' refers to such as the knee joint, the hip joint, the shoulder joint, the elbow joint, and the ankle joint.
- Preferred doses for the local anesthetic with short onset vary according to its nature. For bupivacain and mepivacaine a dose of 5 mg to 100 mg is preferred.
- Another advantageous aspect of the invention is the longer duration of analgesic effect obtained with M6G. This may be due to the hydrophilicity of M6G by which it is retained for a longer time in the synovial fluid of the joint to which it had been administrated. This retention also translates a substantially reduced risk for adverse central nervous effects.
- M6G or of M6G in combination with a short acting local anesthetic will be into the joint capsule, either at the end of surgery before closing the capsule or upon completion of surgery.
- the method according to the invention comprises the administration of a non-steroid anti-inflammatory drug (NSAID) , such as diclofenac, ketorolac, ketoprofen, ibuprofen, naproxen, indometacin, celecoxib and their pharmacutically acceptable salts or another nonselective NSAID (COX1/COX2) or COX2 selective drug.
- NSAID non-steroid anti-inflammatory drug
- a pharmaceutical composition for administration to a joint comprising an amount of morphine-6-glucuronide (M6G) effective for producing postoperative analgesia in the joint and a pharmaceutically acceptable carrier.
- M6G morphine-6-glucuronide
- the analgesically effective amount of M6G is selected to provide an analgesic effect of at least 24 hrs, more preferred at least 48 hrs.
- the composition also preferred for the composition to comprise a short-acting local anesthetic with a short onset of action, such as lidocaine, bupivacaine, mepivacaine, and ropivacaine and their pharmaceutically acceptable salts, but of comparatively short duration, such as a duration of up to one hour or up to three hours.
- the pharmaceutically acceptable carrier may be simply saline but also other carriers are conceivable, such as an aqueous solution of hyaluronic acid which is a substitute for synnovial fluid. Thereby an extension of the duration of analgesia may be obtained.
- composition of the invention has further uses, such as in treating articular inflammation.
- a composition of the invention for in form of a single dose intra-articular administration in connection with surgery of a larger joint was prepared by dissolving a multiple of 0.5 mg of morphine-6-glucuronide (Pharmacopeia Nordica) and 25 mg of bupivacaine hydrochloride in 2 ml of saline and filling hypodermic syringes under sterile conditions therewith.
- the composition is ready for use.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002369301A CA2369301A1 (en) | 1999-04-09 | 2000-03-30 | Management of pain after joint surgery |
JP2000610485A JP2002541203A (en) | 1999-04-09 | 2000-03-30 | Pain management after joint surgery |
EP00923038A EP1176967A1 (en) | 1999-04-09 | 2000-03-30 | Management of pain after joint surgery |
AU43222/00A AU778048B2 (en) | 1999-04-09 | 2000-03-30 | Management of pain after joint surgery |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9901257-7 | 1999-04-09 | ||
SE9901257A SE9901257D0 (en) | 1999-04-09 | 1999-04-09 | Treatment of pain after joint surgery |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000061152A1 true WO2000061152A1 (en) | 2000-10-19 |
Family
ID=20415151
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE2000/000620 WO2000061152A1 (en) | 1999-04-09 | 2000-03-30 | Management of pain after joint surgery |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1176967A1 (en) |
JP (1) | JP2002541203A (en) |
AU (1) | AU778048B2 (en) |
CA (1) | CA2369301A1 (en) |
SE (1) | SE9901257D0 (en) |
WO (1) | WO2000061152A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004009064A1 (en) * | 2002-07-19 | 2004-01-29 | Mestex Ag | Use of neurotoxic substances for the production of a means for the treatment of joint pain and method for application of said means |
WO2007065083A2 (en) | 2005-11-30 | 2007-06-07 | Sanostec Corporation | Nasal congestion, obstruction relief, and drug delivery |
WO2010043240A1 (en) * | 2008-10-16 | 2010-04-22 | Paion Uk Limited | Administration scheme of polar opioid metabolites for post-operative pain management |
US7976858B2 (en) | 2004-01-13 | 2011-07-12 | The Hospital For Special Surgery | Drug delivery to a joint |
US8815817B2 (en) | 2008-05-15 | 2014-08-26 | Dynavax Technologies Corporation | Long term disease modification using immunostimulatory oligonucleotides |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993003051A1 (en) * | 1991-08-06 | 1993-02-18 | Salford Ultrafine Chemicals And Research Limited | A process for making morphine-6-glucuronide or substituted morphine-6-glucuronide |
GB2282758A (en) * | 1993-08-23 | 1995-04-19 | Euro Celtique Sa | Oral morphine-6-glucuronide compositions |
-
1999
- 1999-04-09 SE SE9901257A patent/SE9901257D0/en unknown
-
2000
- 2000-03-30 JP JP2000610485A patent/JP2002541203A/en active Pending
- 2000-03-30 WO PCT/SE2000/000620 patent/WO2000061152A1/en not_active Application Discontinuation
- 2000-03-30 AU AU43222/00A patent/AU778048B2/en not_active Ceased
- 2000-03-30 EP EP00923038A patent/EP1176967A1/en not_active Withdrawn
- 2000-03-30 CA CA002369301A patent/CA2369301A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993003051A1 (en) * | 1991-08-06 | 1993-02-18 | Salford Ultrafine Chemicals And Research Limited | A process for making morphine-6-glucuronide or substituted morphine-6-glucuronide |
GB2282758A (en) * | 1993-08-23 | 1995-04-19 | Euro Celtique Sa | Oral morphine-6-glucuronide compositions |
Non-Patent Citations (3)
Title |
---|
A.J. COE ET AL.: "Intrathecal morphine-6-glucuronide and bupivacaine for postoperative pain", BRITISH JOURNAL OF ANAESTHESIA, vol. 69, no. 2, 1992, pages 221P, XP002933617 * |
GRACE D. ET AL.: "A comparison of intrathecal morphine-6-glucuronide and intrathecal morphine sulfate as analgesics for total hip replacement", ANESTH. ANALG., vol. 83, 1996, pages 1055 - 1059, XP002933615 * |
THOMPSON DENNIS F. ET AL.: "Local analgesia with opioid drugs", THE ANNALS OF PHARMACOTHERAPY, vol. 29, February 1995 (1995-02-01), pages 189 - 190, XP002933616 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004009064A1 (en) * | 2002-07-19 | 2004-01-29 | Mestex Ag | Use of neurotoxic substances for the production of a means for the treatment of joint pain and method for application of said means |
US7976858B2 (en) | 2004-01-13 | 2011-07-12 | The Hospital For Special Surgery | Drug delivery to a joint |
WO2007065083A2 (en) | 2005-11-30 | 2007-06-07 | Sanostec Corporation | Nasal congestion, obstruction relief, and drug delivery |
US8815817B2 (en) | 2008-05-15 | 2014-08-26 | Dynavax Technologies Corporation | Long term disease modification using immunostimulatory oligonucleotides |
WO2010043240A1 (en) * | 2008-10-16 | 2010-04-22 | Paion Uk Limited | Administration scheme of polar opioid metabolites for post-operative pain management |
Also Published As
Publication number | Publication date |
---|---|
AU778048B2 (en) | 2004-11-11 |
JP2002541203A (en) | 2002-12-03 |
CA2369301A1 (en) | 2000-10-19 |
EP1176967A1 (en) | 2002-02-06 |
AU4322200A (en) | 2000-11-14 |
SE9901257D0 (en) | 1999-04-09 |
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