Methods and kits for treating joints and soft tissues

• US 20090324678A1
• Filed: 06/23/2009
• Published: 12/31/2009
• Est. Priority Date: 07/16/2004
• Status: Abandoned Application

• Current Assignee: Spinal Restoration, Inc.
• Original Assignee: Spinal Restoration, Inc.
• Inventors: Thorne, Kevin, Burkinshaw, Brian
• Application Number:
  US12/457,841
• Publication Number:
  US 20090324678A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 35/58 Reptiles antigens from snakes A61K39/38
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 24/106 Fibrin; Fibrinogen
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/24 : for joint reconstruction
• CPC Class Codes: A61L 27/18 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/225 : Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 23/02 : Local anaesthetics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 5/44 : Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
• CPC Class Codes: C08L 73/02 : Polyanhydrides

Abstract

Methods to treat and provide pain relief for damaged and degenerated tissues of a musculoskeletal joint are disclosed. These methods include introducing into, around and/or on the musculoskeletal joint an effective amount of a pharmaceutical composition containing a biocompatible matrix or biocompatible polymeric compound, a pain reliever, and a corticosteroid formulated for extended-release, wherein at least a portion of the biocompatible matrix or biocompatible polymeric compound is activated and polymerized in situ. Also disclosed is a composition for treating a damaged or degenerated joint or soft tissue. The composition contains a polymerizable material capable of forming a biocompatible and biodegradable matrix in situ at a treatment site, a pain reliever; and a corticosteroid formulated for extended-release.

Claims

1. A method for treating a damaged or degenerated joint or a portion thereof, comprising:

introducing into, around or on the degenerated or damaged joint an effective amount of a pharmaceutical composition comprising;

a biocompatible matrix or biocompatible polymeric compound;

a pain reliever; and

a corticosteroid formulated for extended release,

wherein at least a portion of the biocompatible matrix or biocompatible polymeric compound is activated and polymerized in situ.

2. The method of claim 1, wherein the biocompatible matrix or biocompatible polymeric compound comprises fibrin.

3. The method of claim 1, wherein the biocompatible matrix or biocompatible polymeric compound comprises polyanhydrides.

4. The method of claim 1, wherein the pain reliever is selected from the group consisting of lidocaine, soluble salts and bases from Sarraceniaceae, bupivacaine, procaine, ropivacaine, paracetamol, benzodiazepine, enflurane, etomidate, halothane, isoflurane, ketamine, methohexital, methoxyflurane, nitrous oxide, opioids, propofol, thiopental and combinations thereof.

5. The method of claim 1, wherein the corticosteroid is selected from the group consisting of cortisone, hydrocortisone, prednisone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, fluocinolone and combinations thereof.

6. The method of claim 1, wherein the corticosteroid is dispersed in biodegradable micro-particles.

7. The method of claim 1, wherein the pain reliever comprises a short acting anesthetic and is delivered temporally and consistently into, around or on the degenerated or damaged joint to reach a local concentration of 1.5% w/v to about 4% w/v.

8. The method of claim 1, wherein the pain reliever comprises a long acting anesthetic and is delivered temporally and consistently into, around or on the degenerated or damaged joint to reach a local concentration of 0.5% w/v to about 0.75% w/v.

9. The method of claim 1, wherein the pharmaceutical composition further comprises an additive.

10. The method of claim 9, wherein the additive comprises glucose and wherein the glucose is delivered into, around or on the degenerated or damaged joint in a consistent and temporal manner to reach a local concentration of 0.5-1.5 g/L.

11. The method of claim 10, wherein the glucose is delivered into, around or on the degenerated or damaged joint in a consistent and temporal manner to reach a local concentration of 0.8-1.2 g/L.

12. The method of claim 1, wherein the introducing step comprises injecting the pharmaceutical composition into, around or on the degenerated or damaged joint with a multi-chambered syringe injection device.

13. The method of claim 12, wherein said injecting is performed under fluoroscopic or endoscopic visualization or under direct visualization.

14. The method of claim 1, wherein said damaged or degenerated joint or a portion thereof comprises a soft tissue selected from the group consisting of muscles, tendons, ligaments, cartilage and associated subchondral interface surfaces, meniscus and labrum.

15. A method for treating soft tissue damage associated with a damaged or degenerated joint, comprising:

introducing into, around or on the degenerated or damaged joint an effective amount of a pharmaceutical composition comprising;

a biocompatible matrix or biocompatible polymeric compound;

a pain reliever; and

a corticosteroid formulated for extended release,

wherein at least a portion of the biocompatible matrix or biocompatible polymeric compound is activated and polymerized in situ.

16. The method of claim 15, wherein the biocompatible matrix or biocompatible polymeric compound comprises fibrin.

17. The method of claim 15, wherein the biocompatible matrix or biocompatible polymeric compound comprises polyanhydrides.

18. The method of claim 15, wherein the pain reliever is selected from the group consisting of lidocaine, soluble salts and bases from Sarraceniaceae, bupivacaine, procaine, ropivacaine, paracetamol, benzodiazepine, enflurane, etomidate, halothane, isoflurane, ketamine, methohexital, methoxyflurane, nitrous oxide, opioids, propofol, thiopental and combinations thereof.

19. The method of claim 15, wherein the corticosteroid is selected from the group consisting of cortisone, hydrocortisone, prednisone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, fluocinolone and combinations thereof.

20. The method of claim 15, wherein the corticosteroid is dispersed in biodegradable micro-particles.

21. The method of claim 15, wherein the pain reliever comprises a short acting anesthetic and is delivered temporally and consistently into, around or on the degenerated or damaged joint to reach a local concentration of 1.5% w/v to about 4% w/v.

22. The method of claim 15, wherein the pain reliever comprises a long acting anesthetic and is delivered temporally and consistently into, around or on the degenerated or damaged joint to reach a local concentration of 0.5% w/v to about 0.75% w/v.

23. The method of claim 15, wherein the pharmaceutical composition further comprises an additive.

24. The method of claim 23, wherein the additive comprises glucose and wherein the glucose is delivered into, around or on the degenerated or damaged joint in a-consistent and temporal manner to reach a local concentration of 0.5-1.5 g/L.

25. The method of claim 24, wherein the glucose is delivered into, around or on the degenerated or damaged joint in a consistent and temporal manner to reach a local concentration of 0.8-1.2 g/L.

26. The method of claim 15, wherein the introducing step comprises injecting the pharmaceutical composition into, around or on the degenerated or damaged joint with a multi-chambered syringe injection device.

27. The method of claim 26, wherein said injecting is performed under fluoroscopic or endoscopic visualization or under direct visualization.

28. The method of claim 15, wherein said soft tissue is selected from the group consisting of muscles, tendons, ligaments, cartilage and associated subchondral interface surfaces, meniscus and labrum.

29. A method for treating pain associated with a damaged or degenerated joint or a portion thereof, comprising:

introducing into, around or on the degenerated or damaged joint an effective amount of a pharmaceutical composition comprising;

a biocompatible matrix or biocompatible polymeric compound;

a pain reliever; and

a corticosteroid formulated for extended release,

wherein at least a portion of the biocompatible matrix or biocompatible polymeric compound is activated and polymerized in situ.

30. The method of claim 29, wherein the biocompatible matrix or biocompatible polymeric compound comprises fibrin.

31. The method of claim 29, wherein the biocompatible matrix or biocompatible polymeric compound comprises polyanhydrides.

32. The method of claim 29, wherein the pain reliever is selected from the group consisting of lidocaine, soluble salts and bases from Sarraceniaceae, bupivacaine, procaine, ropivacaine, paracetamol, benzodiazepine, enflurane, etomidate, halothane, isoflurane, ketamine, methohexital, methoxyflurane, nitrous oxide, opioids, propofol, thiopental and combinations thereof.

33. The method of claim 29, wherein the corticosteroid is selected from the group consisting of cortisone, hydrocortisone, prednisone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, fluocinolone and combinations thereof.

34. The method of claim 29, wherein the corticosteroid is dispersed in biodegradable micro-particles.

35. The method of claim 29, wherein the pain reliever comprises a short acting anesthetic and is delivered temporally and consistently into, around or on the degenerated or damaged joint to reach a local concentration of 1.5% w/v to about 4% w/v.

36. The method of claim 29, wherein the pain reliever comprises a long acting anesthetic and is delivered temporally and consistently into, around or on the degenerated or damaged joint to reach a local concentration of 0.5% w/v to about 0.75% w/v.

37. The method of claim 29, wherein the pharmaceutical composition further comprises an additive.

38. The method of claim 37, wherein the additive comprises glucose and wherein the glucose is delivered into, around or on the degenerated or damaged joint in a consistent and temporal manner to reach a local concentration of 0.5-1.5 g/L.

39. The method of claim 38, wherein the glucose is delivered into, around or on the degenerated or damaged joint in a consistent and temporal manner to reach a local concentration of 0.8-1.2 g/L.

40. The method of claim 29, wherein the introducing step comprises injecting the pharmaceutical composition into, around or on the degenerated or damaged joint with a multi-chambered syringe injection device.

41. The method of claim 40, wherein said injecting is performed under fluoroscopic or endoscopic visualization or under direct visualization.

42. The method of claim 29, wherein said damaged or degenerated joint or a portion thereof comprises a soft tissue selected from the group consisting of muscles, tendons, ligaments, cartilage and associated subchondral interface surfaces, meniscus and labrum.

43. A composition for treating a damaged or degenerated joint soft tissue, comprising:

a polymerizable material formulated to form a biocompatible and biodegradable matrix in situ at a treatment site;

a pain reliever; and

a corticosteroid formulated for extended-release.

44. The composition of claim 43, wherein the biocompatible matrix or biocompatible polymeric compound comprises fibrin.

45. The composition of claim 43, wherein the pain reliever is selected from the group consisting of lidocaine, soluble salts and bases from Sarraceniaceae, bupivacaine, procaine, ropivacaine, paracetamol, benzodiazepine, enflurane, etomidate, halothane, isoflurane, ketamine, methohexital, methoxyflurane, nitrous oxide, opioids, propofol, thiopental and combinations thereof.

46. The composition of claim 43, wherein the corticosteroid is selected from the group consisting of cortisone, hydrocortisone, prednisone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, fluocinolone and combinations thereof.

47. The composition of claim 43, wherein the corticosteroid is dispersed in biodegradable micro-particles.

48. The composition of claim 47, wherein the biodegradable micro-particles are in a size range from about 0.5 microns to about 200 microns in diameter.

49. The composition of claim 48, wherein the biodegradable micro-particles are in a size range from about 5 microns to about 100 microns in diameter.

50. The composition of claim 47, wherein the biodegradable micro-particles are constructed to degrade in vivo over a period of less than about six months.

51. The composition of claim 47 wherein the biodegradable micro-particles have an average corticosteroid loading from about 1% (w/w) to about 80% (w/w).

52. The composition of claim 47, wherein the biodegradable micro-particles comprise one or more biocompatible, biodegradable polymers selected from the group consisting of albumin, collagen, gelatin, synthetic poly(amino acids), prolamines, glycosaminoglycans, polysaccharides, poly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PG), polyhydroxybutyric acid, poly(trimethylene carbonate), polycaprolactone (PCL), polyvalerolactone, poly(alpha-hydroxy acids), poly(lactones), poly(amino-acids), poly(anhydrides), polyketals poly(arylates), poly(orthoesters), poly(orthocarbonates), poly(phosphoesters), poly(ester-co-amide), poly(lactide-co-urethane, polyethylene glycol (PEG), polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer(polyactive), methacrylates, poly(N-isopropylacrylamide), PEO-PPO-PEO copolymers, PEO-PPO-PAA copolymers, PLGA-PEO-PLGA copolymers, and combinations thereof.

53. The composition of claim 43, further comprising an additive.

54. The additive of claim 53 wherein the additive comprising glucose.

55. The composition of claim 43, wherein said damaged or degenerated joint or a portion thereof comprises a soft tissue selected from the group consisting of muscles, tendons, ligaments, cartilage and associated subchondral interface surfaces, meniscus and labrum.