Methods and compositions for improved articular surgery using collagen

• US 7,119,062 B1
• Filed: 02/22/2002
• Issued: 10/10/2006
• Est. Priority Date: 02/23/2001
• Status: Expired due to Fees

• Current Assignee: Surgical Specialties Corporation Limited (Ssc Holdco Ltd)
• Original Assignee: NeuColl, Inc. (Angiotech Pharmaceuticals Incorporated)
• Inventors: Alvis, Mark Ray, Brown, Melissa K. C., Fiebiger, Roy C.
• Primary Examiner(s): Weber, Jon
• Assistant Examiner(s): Mohamed, Abdel A.
• Application Number:
  US10/082,443
• Time in Patent Office: 1,691 Days
• Field of Search: 514/2, 514/21, 514/963, 530/356, 604/96.01
• US Class Current: 514/17.2
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• 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: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

The invention provides methods for treating post-surgical articular or incisional pain and/or discomfort in a patient. The invention further provides improved surgical methods and controlled release formulations for treating an articular injury of a joint in a patient, in which a collagen formulation is used in conjunction with a surgical procedure to treat the articular injury or the side effects of the surgical procedure. Collagen formulations of the invention and their use, in addition to the surgical procedure, may provide at least one or more of the following benefits: reduced patient pain, shortened recovery time and/or improved joint condition (including treatment of the underlying articular injury). Moreover, the methods and compositions of the invention can be used in conjunction with essentially any surgical procedure used to treat an articular injury. The invention further provides compositions and methods for treating post-surgical articular or incisional pain in a patient as well as a catheter for use in the methods of the invention.

Claims

1. A composition for the treatment of post-surgical articular or incisional pain or discomfort consisting essentially of an aqueous dispersion of insoluble non-crosslinked type I fibrillar atelopeptide collagen and an anesthetic;

wherein the composition is formulated to release an effective amount of the anesthetic from the collagen for at least 48 hours, wherein the collagen and the anesthetic are in a ratio of from about 0.5;

1 to about 10;

1, and wherein the melting temperature of the composition is from about 42°

C. to about 46°

C.

2. The composition of claim 1, wherein the anesthetic is soluble in the dispersion.

3. The composition of claim 1, wherein the composition is formulated to release an effective amount of the anesthetic from the collagen for at least 72 hours.

4. The composition of claim 1, wherein the collagen consists essentially of at least 95% Type I non-crosslinked fibrillar atelopeptide collagen.

5. The composition of claim 1, wherein the collagen is less than 5% Type III collagen.

6. The composition of claim 1, wherein the anesthetic is bupivacaine, lidocaine, procaine, procainamide, tetracaine, mepivacaine, or etidocaine.

7. The composition of claim 1, wherein the collagen is human collagen or bovine dermal collagen.

8. The composition of claim 1, wherein a total amount of anesthetic released is from about 5 mg to 1 g.

9. The composition of claim 1, further comprising one or more pharmaceutically acceptable excipient(s).

10. The composition of claim 1, wherein the melting temperature of the composition is about 45°

C.

11. The composition of claim 1, wherein the collagen and the anesthetic are in a ratio of from about 1:

1 to about 5;

1.

12. The composition of claim 11, wherein the collagen and the anesthetic are in a ratio of from about 1:

1.

13. The composition of claim 1, wherein the anesthetic concentration is about 4–

30 mg/ml.

14. The composition of claim 13, wherein the anesthetic concentration is from about 4 mg/ml to about 10 mg/ml.

15. The composition of claim 1, wherein the effective amount of anesthetic released is from about 2–

15 mg per day.

16. The composition of claim 15, wherein the effective amount of anesthetic released is about 10 mg per day.

17. The composition of claim 1, wherein the collagen concentration is from about 3 mg/ml to about 100 mg/ml.

18. The composition of claim 17, wherein the collagen concentration is from about 65 mg/ml.

19. The composition of claim 17, wherein the collagen concentration is from about 16 mg/ml to about 28 mg/ml.

20. A composition for the treatment of post-surgical articular or incisional pain or discomfort consisting essentially of an aqueous dispersion of insoluble non-crosslinked type I fibrillar atelopeptide collagen and bupivacaine;

wherein the composition is formulated to release an effective amount of the bupivacaine from the collagen for at least 48 hours, wherein the collagen and bupivacaine are in a ratio of from about 0.5;

1 to about 10;

1, and wherein the melting temperature of the composition is from about 42°

C. to about 46°

C.

21. The composition of claim 20, wherein the bupivacaine is soluble in the dispersion.

22. The composition of claim 20, wherein the composition is formulated to release an effective amount of bupivacaine from the collagen for at least 72 hours.

23. The composition of claim 20, wherein the collagen consists essentially of at least 95% Type I non-crosslinked fibrillar atelopeptide collagen.

24. The composition of claim 20, wherein the collagen is less than 5% Type III collagen.

25. The composition of claim 20, wherein a total amount of bupivacaine released is from 5 mg to 1 g.

26. The composition of claim 20, wherein the effective amount of bupivacaine released is about 2–

15 mg per day.

27. The composition of claim 20, further comprising one or more pharmaceutically acceptable excipients.

28. The composition of claim 20, wherein the melting temperature of the composition is about 45°

C.

29. The composition of claim 20, wherein the collagen and bupivacaine are in a ratio of from about 1:

1 to about 5;

1.

30. The composition of claim 29, wherein the collagen and bupivacaine are in a ratio of from about 3.1 to about 4.7:

1.

31. The composition of claim 20, wherein the bupivacaine concentration of is about 4–

30 mg/ml.

32. The composition of claim 31, wherein the bupivacaine concentration is from about 4 mg/ml to about 10 mg/ml.

33. The composition of claim 20, wherein the collagen concentration is from about 10 mg/ml to about 100 mg/ml.

34. The composition of claim 33, wherein the collagen concentration is about 65 mg/ml.

35. The composition of claim 33, wherein the collagen concentration is from about 16 mg/ml to about 28 mg/ml.

36. A method for the treatment of post-surgical pain or discomfort in a joint(s) comprising the step of intra-articularly administering to a joint(s) in a patient a composition consisting essentially of an aqueous dispersion of insoluble non-crosslinked Type I fibrillar atelopeptide collagen and an anesthetic;

wherein the composition is formulated to release an effective amount of the anesthetic from the collagen for at least 48 hours, wherein the collagen and the anesthetic are in a ratio of from about 0.5;

1 to about 10;

1, wherein the melting temperature of the composition is from about 42°

C. to about 46°

C., and wherein the composition is administered before, during or after a surgical procedure.

37. The method of claim 36, wherein the composition is administered during the surgical procedure.

38. The method of claim 36, wherein the composition is administered after the surgical procedure.

39. The method of claim 36, wherein the composition is administered via a catheter.

40. The method of claim 36, wherein the surgical procedure is arthroscopy, arthrotomy, implantation of chondrocytes, implantation of cartilage, partial joint arthroplasty or total joint arthroplasty.

41. The method of claim 36, wherein the composition is formulated to release an effective amount of the anesthetic from the collagen for at least 72 hours.

42. The method of claim 36, wherein the collagen and the anesthetic are in a ratio of from about 1:

1 to about 5;

1.

43. The method of claim 36, wherein the collagen consists essentially of at least 95% Type I non-crosslinked fibrillar atelopeptide collagen.

44. The method of claim 36, wherein the collagen is less than 5% Type III collagen.

45. The method of claim 36, wherein the anesthetic is bupivacaine, lidocaine, procaine, procainamide, tetracaine, mepivacaine, or etidocaine.

46. The method of claim 36, wherein the collagen concentration is from about 3 mg/ml to about 100 mg/ml.

47. The method of claim 36, wherein a total amount of anesthetic released is from about 5 mg to 1 g.

48. The method of claim 36, wherein the amount of composition administered is greater than 2 mL.

49. The method of claim 36, wherein the composition further includes one or more pharmaceutically acceptable excipient(s).

50. The method of claim 36, wherein the joint is a knee, shoulder, ankle, hip, wrist, elbow or temporomandibular joint.

51. The method of claim 50, wherein the joint is a knee.

52. The method of claim 36, wherein the patient is a human or veterinary patient.

53. The method of claim 52, wherein the patient is a human.

54. The method of claim 36, wherein the composition is administered before the surgical procedure.

55. The method of claim 54, wherein the method further comprises the step of at least one additional administration of the composition during or after the surgical procedure.

56. The method of claim 36, wherein the surgical procedure is used in the treatment of a condition selected from the group consisting of meniscal injury, anterior cruciate ligament injury, rotator cuff injury, carpal tunnel syndrome, synovitis, chondromalacia, patellar tendon rupture, tibial tubercle fracture, loose bodies of bone or cartilage, osteochondritis dissecans, adhesive capsulitis, impingement syndrome, shoulder dislocation, Dupuytren'"'"'s syndrome, scaphoid fracture, stenosing tenosynovitis, lateral facet syndrome, anterior patello-femoral pain syndrome, lateral pressure syndrome, malalignment syndrome, and maltracking syndrome.

57. The method of claim 56, wherein the condition is not a degenerative articular process.

58. The method of claim 36, wherein the anesthetic concentration is about 4–

30 mg/ml.

59. The method of claim 58, wherein the anesthetic concentration is from about 4 mg/ml to about 10 mg/ml.

60. The method of claim 36, wherein the effective amount of anesthetic released is from about 2–

15 mg per day.

61. The method of claim 60, wherein the effective amount of anesthetic released is about 10 mg per day.

62. A method for the treatment of post-surgical pain or discomfort associated with one or more incisions comprising the step administering to a patient'"'"'s incision(s) a composition consisting essentially of an aqueous dispersion of insoluble non-crosslinked type I fibrillar atelopeptide collagen and an anesthetic;

wherein the composition is formulated to release an effective amount of the anesthetic from the collagen for at least 48 hours, wherein the collagen and the anesthetic are in a ratio of from about 0.5;

1 to about 10;

1, wherein the melting temperature of the composition is from about 42°

C. to about 46°

C., and wherein the composition is administered before, during or after a surgical procedure.

63. The method of claim 62, wherein the composition is administered via injection.

64. The method of claim 62, wherein the composition is administered during the surgical procedure.

65. The method of claim 62, wherein the composition is administered after the surgical procedure.

66. The method of claim 62, wherein the composition is administered via a catheter.

67. The method of claim 62, wherein the anesthetic is bupivacaine.

68. The method of claim 62, wherein the surgical procedure is an abdominal, spinal or breast operation.

69. The method of claim 68, wherein the abdominal operation is a cesarean birth, hernia repair, or hysterectomy.

70. The method of claim 62, wherein the patient is a human or veterinary patient.

71. The method of claim 70, wherein the patient is a human.

72. The method of claim 62, wherein the composition is administered before the surgical procedure.

73. The method of claim 72, wherein the method further comprises the step of at least one additional administration of the composition during or after the surgical procedure.

74. A method for the treatment of post-surgical pain or discomfort in a joint(s) comprising the step of intra-articularly administering to a joint(s) in a patient a composition consisting essentially of an aqueous dispersion of insoluble non-crosslinked type I fibrillar atelopeptide collagen and bupivacaine, wherein the composition is formulated to release an effective amount of the bupivacaine from the collagen for at least 48 hours, wherein the collagen and bupivacaine are in a ratio of from about 0.5:

1 to about 10;

1, wherein the melting temperature of the composition is from about 42°

C. to about 46°

C., and wherein the composition is administered before, during or after a surgical procedure.

75. The method of claim 74, wherein the composition is administered during the surgical procedure.

76. The method of claim 74, wherein the composition is administered after the surgical procedure.

77. The method of claim 74, wherein the composition is administered via a catheter.

78. The method of claim 74, wherein the surgical procedure is arthroscopy, arthrotomy, implantation of chondrocytes, implantation of cartilage, partial joint arthroplasty or total joint arthroplasty.

79. The method of claim 74, wherein the surgical procedure is used in the treatment of a condition selected from the group consisting of meniscal injury, anterior cruciate ligament injury, rotator cuff injury, carpal tunnel syndrome, synovitis, chondromalacia, patellar tendon rupture, tibial tubercle fracture, loose bodies of bone or cartilage, osteochondritis dissecans, adhesive capsulitis, impingement syndrome, shoulder dislocation, Dupuytren'"'"'s syndrome, scaphoid fracture, stenosing tenosynovitis, lateral facet syndrome, anterior patello-femoral pain syndrome, lateral pressure syndrome, malalignment syndrome, and maltracking syndrome.

80. The method of claim 74, wherein the composition is formulated to release an effective amount of bupivacaine from the collagen for at least 72 hours.

81. The method of claim 74, wherein the collagen and bupivacaine are in a ratio of from about 1:

1 to about 5;

1.

82. The method of claim 74, wherein the collagen consists essentially of at least 95% Type I non-crosslinked fibrillar atelopeptide collagen.

83. The method of claim 74, wherein the collagen is less than 5% Type III collagen.

84. The method of claim 74, wherein the collagen is human collagen or bovine dermal collagen.

85. The method of claim 74, wherein the collagen concentration is from about 3 mg/ml to about 100 mg/ml.

86. The method of claim 74, wherein a total amount of bupivacaine released is from about 5 mg to 1 g.

87. The method of claim 74, wherein the amount of composition administered is greater than 2 mL.

88. The method of claim 74, wherein the composition further includes one or more pharmaceutically acceptable excipient(s).

89. The method of claim 74, wherein the joint is a knee, shoulder, ankle, hip, wrist, elbow or temporomandibular joint.

90. The method of claim 89, wherein the joint is a knee.

91. The method of claim 74, wherein the patient is a human or veterinary patient.

92. The method of claim 91, wherein the patient is a human.

93. The method of claim 74, wherein the composition is administered before the surgical procedure.

94. The method of claim 93, wherein the method further comprises the step of at least one additional administration of the composition during or after the surgical procedure.

95. The method of claim 74, wherein the bupivacaine concentration is about 4–

30 mg/ml.

96. The method of claim 95, wherein the bupivacaine concentration is from about 4 mg/ml to about 10 mg/ml.

97. The method of claim 74, wherein the effective amount of bupivacaine released is from about 2–

15 mg per day.

98. The method of claim 74, wherein the effective amount of bupivacaine released is about 10 mg per day.