AU4322200A - Management of pain after joint surgery - Google Patents

Management of pain after joint surgery Download PDF

Info

Publication number
AU4322200A
AU4322200A AU43222/00A AU4322200A AU4322200A AU 4322200 A AU4322200 A AU 4322200A AU 43222/00 A AU43222/00 A AU 43222/00A AU 4322200 A AU4322200 A AU 4322200A AU 4322200 A AU4322200 A AU 4322200A
Authority
AU
Australia
Prior art keywords
joint
composition
effective amount
pharmaceutically acceptable
surgery
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.)
Granted
Application number
AU43222/00A
Other versions
AU778048B2 (en
Inventor
Sveinbjorn Brandsson
Thomas Hedner
Jon Karlsson
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.)
HEL AB
Original Assignee
HEL 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 HEL AB filed Critical HEL AB
Publication of AU4322200A publication Critical patent/AU4322200A/en
Application granted granted Critical
Publication of AU778048B2 publication Critical patent/AU778048B2/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004Monosaccharides having only carbon, hydrogen and oxygen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7012Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00Anaesthetics
    • A61P23/02Local anaesthetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Anesthesiology (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

WO00/61152 PCT/SE00/00620 MANAGEMENT OF PAIN AFTER JOINT SURGERY FIELD OF THE INVENTION 5 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. 10 BACKGROUND OF THE INVENTION Postoperative pain arising after joint surgery, for instance, knee surgery, is often severe and results in long periods of immobilization. The pain is present even at rest 15 and is aggravated during mobilization. It hampers early postoperative mobilization and may prolong hospital care as well as outpatient care. Poor mobilization increases the risk for venous thrombosis and pulmonary embolism. Therefore reduction of pain in patients having undergone joint surgery 20 is of major importance. At present, patients undergoing knee or other types of orthopedic surgery most often are managed by intravenous or intramuscular morphine or other opoid-based treatments. 25 Usually this results in short-lasting and often insufficient analgesia which may be accompanied by side effects such as nausea, vomiting, and respiratory depression. As an alternative, intravenous or intramuscular NSAIDs (non steroid anti-inflammatory drugs), such as diclofenac, 30 ketoprofen or ketorolac may be used. Such therapy, however, 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.
WO00/61152 PCT/SE00/00620 2 When given systemically morphine is transformed mainly in the liver to the 3- and 6-glucuronides. The 6-glucuronide (M6G) also is a potent opoid antagonist. It is substantially 5 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. 10 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 15 respiratory depression cautions against such use of M6G. OBJECTS OF THE INVENTION It is an object of the invention to provide a method for the 20 management of pain and immobilization resulting from joint surgery. It is another object of the invention to provide a means for the management of pain and immobilization resulting from 25 joint surgery. Other objects of the invention will become apparent from the following short description of the invention, the description of preferred embodiments thereof, and the 30 appended claims.
WO 00/61152 PCT/SE00/00620 3 SUMMARY OF THE INVENTION According to the invention is provided a method of the aforementioned kind, comprising the administration of a 5 analgetically effective amount of morphine-6-glucuronide (M6G) into the cavity of the joint on which surgery has been performed. Since local opoid analgesia may have a slow onset of action 10 due to the gradual upregulation of the opoid receptors during the immediate post operative period, administration of M6G is advantageously combined with that of a local anesthetic with a short onset of action, such as lidocaine, bupivacaine, mepivacaine, and ropivacaine, providing 15 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. In combination the local 20 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 25 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 30 fraction of M6G is needed to obtain an analgetic effect (measured at a given point in time post surgery) comparable to that obtained with morphine. In the systemic circulation the concentration of M6G will be very low; it might be even below the detection threshold. This translates to WO00/61152 PCT/SE00/00620 4 substantially reduced central nervous effects - as well as adverse effects - which may not be even noticeable. A preferred dose for obtaining analgesia in a larger joint is from 0.05 to 10 mg. In the context of this application 5 '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. 10 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 15 had been administrated. This retention also translates a substantially reduced risk for adverse central nervous effects. Administration of M6G or of M6G in combination with a short 20 acting local anesthetic will be into the joint capsule, either at the end of surgery before closing the capsule or upon completion of surgery. According to still another advantageous aspect of the 25 invention 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 30 NSAID (COX1/COX2) or COX2 selective drug. According to the invention is also disclosed a pharmaceutical composition for administration to a joint comprising an amount of morphine-6-glucuronide (M6G) WO00/61152 PCT/SE00/00620 5 effective for producing postoperative analgesia in the joint and a pharmaceutically acceptable carrier. In particular the analgesically effective amount of M6G is selected to provide an analgesic effect of at least 24 hrs, more preferred at 5 least 48 hrs. It is 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 10 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 15 synnovial fluid. Thereby an extension of the duration of analgesia may be obtained. In addition to its application in the context of joint surgery the composition of the invention has further uses, 20 such as in treating articular inflammation. In the following the invention will be described in more detail by reference to a preferred but not limiting embodiment. 25 DESCRIPTION OF A PREFERRED EMBODIMENT Example 1 30 Immediately upon meniscectomy (three patients; m, 35 y; m, 18 y; m, 20 y) 0.5 mg M6G and 25 mg of bupivacaine hydrochloride in 2 ml saline were injected into the articular space. The patients were mobilized for the first time already the next day, and could leave the hospital on WO00/61152 PCT/SE00/00620 6 the 2 nd day post surgery. They did not complain of any side effects, and remained substantially free of pain until being dismissed. At the same hospital patients receiving traditional intra-articular analgesia (morphine, 10 mg; 5 bupivacaine, 25 mg) are usually dismissed on the third day after surgery, and often even later. Many of them experience adverse effects caused by morphine, such as nausea and vomiting. 10 Example 2 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 15 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. 20 Example 3 A composition of the invention similar to that of Example 2, but providing extended duration of effect, was prepared by exchanging the saline for an aqueous solution of sodium 25 hyaluronate (Sinvisc T M Roche, containing 8 mg sodium hyaluronate, 8.5 mg sodium chloride, 0.17 mg disodium hydrogen phosphate, and 0.03 mg sodium dihydrogen phosphate per ml).

Claims (21)

1. A method for the management of pain and immobilization resulting from joint surgery, comprising administration of 5 an analgetically effective amount of morphine-6-glucuronide (M6G) into the cavity of the joint on which surgery has been performed.
2. The method of claim 1, comprising administration of an 10 analgetically effective amount of a local anesthetic with a short onset of action.
3. The method of claim 2, wherein the local anesthetic is selected from the group consisting of lidocaine, 15 bupivacaine, mepivacaine, ropivacaine including its pharmaceutically acceptable salts.
4. The method of any of claims 1 to 3, wherein the effective amount of M6G is from 0.05 mg to 10 mg for a 20 larger joint.
5. The method of any of claims 2 or 3, wherein the effective amount of the local anesthetic is from 1 mg to 100 mg. 25
6. The method of any of claims 1-5, comprising the administration of pharmacologically effective amount of a non-steroid anti-inflammatory drug (NSAID) into the cavity of the joint or systemically. 30
7. The method of claim 6, wherein the NSAID is selected from the group consisting of diclofenac, ketorolac, ketoprofen, ibuprofen, naproxen, indometacin, celecoxib including its pharmaceutically acceptable salts. WO00/61152 PCT/SE00/00620 8
8. A pharmaceutical composition for injection into the cavity of a joint on which surgery has been performed, for the management of pain and immobilization resulting from joint surgery, comprising an analgetically effective amount 5 of morphine-6-glucuronide (M6G) and a pharmaceutically acceptable carrier.
9. The composition of claim 8, wherein the amount of M6G is from 0.05 mg to 10 mg. 10
10. The composition of claim 8 or 9, comprising an analgetically effective amount of a local anesthetic with a short onset of action. 15
11. The composition of claim 10, wherein the local anesthetic is selected from the group consisting of lidocaine, bupivacaine, mepivacaine, ropivacaine including its pharmaceutically acceptable salts. 20
12. The composition of any of claims 8 - 11, comprising a non-steroid anti-inflammatory drug (NSAID).
13. The composition of claim 12, wherein the NSAID is selected from the group consisting of diclofenac, ketorolac, 25 ketoprofen, ibuprofen, naproxen, indometacin, celecoxib including its pharmaceutically acceptable salts.
14. The composition of any of claims 8 - 13, comprising means for retention of M6G in the joint cavity. 30
15. The composition of claim 14, wherein said means is hyaluronic acid or a pharmaceutically acceptable salt thereof. WO00/61152 PCT/SE00/00620 9
16. A single dose of a pain-relieving composition for intra-articular administration comprising from 0.05 mg to 10 mg of morphine-6-glucuronide and a pharmaceutically acceptable carrier. 5
17. The single dose of claim 16, comprising from 1 to 100 mg of a member of the group consisting of lidocaine, bupivacaine, mepivacaine, ropivacaine and their pharmaceutically acceptable salts. 10
18. A hypodermic syringe filled with the single dose of claim 16 or 17.
19. The manufacture of a medicament for injection into the 15 cavity of a joint on which surgery has been performed, comprising an analgetically effective amount of morphine-6 glucuronide (M6G)
20. The manufacture of claim 19, wherein the amount of M6G 20 is from 0.1 mg to 10 mg.
21. The manufacture of claim 19 or 20, wherein the medicament comprises an analgetically effective amount of a local anesthetic with a short onset of action. 25
AU43222/00A 1999-04-09 2000-03-30 Management of pain after joint surgery Ceased AU778048B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE9901257 1999-04-09
SE9901257A SE9901257D0 (en) 1999-04-09 1999-04-09 Treatment of pain after joint surgery
PCT/SE2000/000620 WO2000061152A1 (en) 1999-04-09 2000-03-30 Management of pain after joint surgery

Publications (2)

Publication Number Publication Date
AU4322200A true AU4322200A (en) 2000-11-14
AU778048B2 AU778048B2 (en) 2004-11-11

Family

ID=20415151

Family Applications (1)

Application Number Title Priority Date Filing Date
AU43222/00A Ceased AU778048B2 (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)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8403954B2 (en) 2001-05-22 2013-03-26 Sanostec Corp. Nasal congestion, obstruction relief, and drug delivery
CA2493041C (en) * 2002-07-19 2011-08-16 Dominik Meyer Injectable pharmaceutical composition for treating post-operative joint pain comprising an amide local anesthetic
WO2005070333A1 (en) 2004-01-13 2005-08-04 Orthobiologica, Inc. Drug delivery to a joint
EP2300102B1 (en) 2008-05-15 2014-01-08 Dynavax Technologies Corporation Immunostimulatory sequences containing CpG for use in the treatment of allergic rhinitis
WO2010043240A1 (en) * 2008-10-16 2010-04-22 Paion Uk Limited Administration scheme of polar opioid metabolites for post-operative pain management

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9116909D0 (en) * 1991-08-06 1991-09-18 Salford Ultrafine Chem & Res Morphine derivatives
GB2282758A (en) * 1993-08-23 1995-04-19 Euro Celtique Sa Oral morphine-6-glucuronide compositions

Also Published As

Publication number Publication date
JP2002541203A (en) 2002-12-03
AU778048B2 (en) 2004-11-11
SE9901257D0 (en) 1999-04-09
EP1176967A1 (en) 2002-02-06
WO2000061152A1 (en) 2000-10-19
CA2369301A1 (en) 2000-10-19

Similar Documents

Publication Publication Date Title
Kopp et al. Regional anaesthesia in day‐stay and short‐stay surgery
Dahl et al. Relief of postoperative pain by local anaesthetic infiltration: efficacy for major abdominal and orthopedic surgery
CA2592086C (en) Mixture of a vanilloid receptor agonist and a substance inhibiting nerve regeneration, use thereof for producing a painkiller, and method for applying said painkiller
US20100196281A1 (en) Use of resiniferatoxin (rtx) for producing an agent for treating joint pains and method for applying said agent
Brandsson et al. Intraarticular morphine after arthroscopic ACL reconstruction: a double-blind placebo-controlled study of 40 patients
JP5080983B2 (en) Use of vanilloid receptor agonist together with glycolose aminoglycan or proteoglycan for the manufacture of a medicament for the treatment of joint pain and method of applying said medicament
Eisenach Alpha-2 agonists and analgesia
JP2004521112A (en) Use of a neurotoxic substance in manufacturing a therapeutic agent for joint pain
Kulkarni et al. Randomized prospective comparative study of adductor canal block vs periarticular infiltration on early functional outcome after unilateral total knee arthroplasty
CN1859918B (en) Use of hyaluronic acid for treating acute and overuse sprain and strain
JP2008525504A5 (en)
AU778048B2 (en) Management of pain after joint surgery
EP3331509A1 (en) Stable liquid injectable solution of midazolam and pentazocine
JP2005538983A (en) Use of neurotoxic substances for the manufacture of a medicament for the treatment of joint pain and methods of applying the medicament
Kvolik et al. A wound infiltration as a method of postoperative analgesia
US20050176823A1 (en) Intra-operative procedure for post-operative pain control
CA2230648A1 (en) Formulations of haloalkylamines and local anaesthetics and methods for the treatment of reflex sympathetic dystrophy (rsd)
KR20120089444A (en) Treating critically ill patients with intravenous ibuprofen
JP2788340B2 (en) Inflammation treatment
CN1617719A (en) Combination comprising a P-GP inhibitor and an anti-epileptic drug
Bartolek Hamp et al. Femoral nerve block-or intravenous-guided patient control analgesiafor early physical rehabilitation after anterior cruciate ligament reconstruction in" fast-track" orthopedics: what is optimal?
WO2022175973A1 (en) An injectable composition for long term delivery of nalbuphine or nalbuphine ester prodrug or its salts and use thereof
AU719666B2 (en) Formulations of haloalkylamines and local anaesthetics and methods for the treatment of reflex sympathetic dystrophy (RSD)
Memtsoudis et al. Glycopyrrolate as an alternative to vasopressor infusion for hypotension after carotid endarterectomy
CN1492761A (en) Injectable pharmaceutical composition for treatment and reversal of erectile dysfunction