Claims for Patent: 6,599,516

Summary for Patent: 6,599,516

Title:	Malleable implant containing solid element that resorbs or fractures to provide access channels
Abstract:	A malleable implant for implantation into living tissue is prepared having access means for cells into the interior of the implant. The implant is capable of being deformed under pressure required to insert the implant into an implant site. The access means can be hollow or solid. The solid comprises a material that more rapidly resorbs in vivo than the malleable implant to provide channels, or comprises a mechanically weak material that fractures under force at an implant site to produce channels or cracks. The access means may be inserted in the malleable implant at an implant site. A multilaminar structure may be formed having layers of malleable implant and layers of access means, or the access means may be heterogeneously distributed throughout the malleable implant. A kit can contain a powder such as calcium phosphate for making a paste implant material, and an access means insertable into the paste.
Inventor(s):	Knaack; David (Somerville, MA)
Assignee:	Etex Corporation (Cambridge, MA)
Application Number:	09/661,828
Patent Claims:	1. An implant for implantation into an implant site of living tissue, comprising: a malleable implant material, capable of being deformed under pressure required to insert the malleable implant material into the implant site; and a non-particulate, bioresorbable solid element having a greater resorption rate in vivo than the implanted malleable implant material, or the element comprising a mechanically weak material susceptible to fracturing under force at the implant site resulting in channels or cracks, at least a portion of the element being contained in the interior of the malleable implant material, for providing macroscopic access into the interior of the implant to cells of the living tissue by the element more rapidly resorbing in vivo than the implanted malleable implant material, or the element fracturing under force at the implant site to produce channels or cracks. 2. The implant of claim 1, wherein the implant has at least one cross-sectional dimension of greater than 3 mm. 3. The implant of claim 1, wherein the implant has at least one cross-sectional dimension of greater than 1 cm. 4. The implant of claim 1, wherein the malleable implant material is comprised of a bioresorbable material and a physiologically acceptable fluid. 5. The implant of claim 1, wherein the malleable implant material is selected from the group consisting of calcium phosphates, collagens, and fibrins. 6. The implant of claim 1, wherein the malleable implant material is hardenable. 7. The implant of claim 1, wherein the malleable implant material comprises an osteoconductive material. 8. The implant of claim 5, wherein the calcium phosphate is selected from the group consisting of amorphous calcium phosphate, tricalcium phosphate, hydroxyapatite, calcium deficient hydroxyapatite, poorly crystalline hydroxyapatite (PCHA), dicalcium phosphate dihydrate (DCPD), tetracalcium phosphate, and dahlite (Ca.sub.5 (PO.sub.4,CO.sub.3).sub.3 F). 9. The implant of claim 1, wherein the element is selected from the group consisting of rods, fibers, sheets, fibrous mats, star-shapes and jack-shapes. 10. The implant of claim 1, wherein the element has an outer diameter greater than that of cells of the living tissue. 11. The implant of claim 1, wherein the element is selected from the group consisting of poly(lactide), poly(lactide-co-glycolide), gelatins, collagen, alginate, tissue culture medium, calcium phosphates, calcium sulfate, sugars, carbohydrates, and salts. 12. The implant of claim 1, wherein the element is comprised of a material resorbable by dissolution, enzymatic action or cellular action to provide cellular access to the interior of the implant. 13. The implant of claim 1, wherein the element is comprised of a nutrient of a cell of the living tissue. 14. The implant of claim 1, wherein the element comprises a polymer capable of acting as a substrate for cell attachment. 15. The implant of claim 1, further comprising a material for promoting cell adhesion. 16. The implant of claim 1, wherein the element has a dimension greater than 0.5 mm. 17. The implant of claim 1, wherein the element has a dimension greater than 1 mm. 18. The implant of claim 1, wherein the element has a dimension greater than 5.0 mm. 19. The implant of claim 1, wherein the element is insertable into the malleable implant material at an implant site. 20. The implant of claim 1, wherein the implant is a multilaminar structure having layers of malleable implant material and element. 21. The implant of claim 1, wherein the element is heterogeneously distributed throughout the implant. 22. The implant of claim 1, further comprising additives capable of controlling the resorption rate of the implant material. 23. The implant of claim 22, wherein the additives are selected from the group consisting of bone morphogenic protein, OP-1 parathyroid hormone, parathyroid-hormone-related peptide, 1,25-dihydroxyvitamin D, interleukin-1, tumor necrosis factor, thyroid hormones, vitamin A, transforming growth factor/epidermal growth factor, fibroblast growth factor, heparin, bacterial endotoxin, thrombin, bradykinin, prostaglandin E.sub.2, transforming growth factor .beta., lymphocyte inhibitory factor/differentiation inducing factor, calcitonin, interferon-.gamma., glucocortinoids, estrogens, and androgens. 24. The implant of claim 1, further comprising reinforcing additives. 25. An implant for implantation into an implant site of living tissue comprising: a biocompatible, hardened implant material; and a non-particulate, bioresorbable, solid element having a greater resorption rate in vivo than the hardened implant material, or the element comprising a mechanically weak material susceptible to fracturing under force at the implant site resulting in channels or cracks, at least a portion of the element being contained in the interior of the hardened implant material, for providing macroscopic access into the interior of the hardened implant material to cells of the living tissue by the element more rapidly resorbing in vivo than the hardened implant material, or the element fracturing under force at the implant site to produce channels or cracks. 26. The implant of claim 25, wherein the biocompatible, hardened implant material comprises an osteoconductive material. 27. The implant of claim 25, wherein the biocompatible, hardened implant material is selected from the group consisting of calcium phosphates, collagens, and fibrins. 28. The implant of claim 27, wherein the calcium phosphate is selected from the group consisting of amorphous calcium phosphate, tricalcium phosphate, hydroxyapatite, calcium deficient hydroxyapatite, poorly crystalline hydroxyapatite (PCHA), dicalcium phosphate dihydrate (DCPD), tetracalcium phosphate, and dahlite (Ca.sub.5 (PO.sub.4,CO.sub.3).sub.3 F). 29. The implant of claim 25, wherein the element is selected from the group consisting of rods, fibers, sheets, fibrous mats, star-shapes and jack-shapes. 30. The implant of claim 25, wherein the element has an outer diameter greater than that of cells of the living tissue. 31. The implant of claim 25, wherein the element has a dimension greater than 0.5 mm. 32. The implant of claim 25, further comprising a material for promoting cell adhesion. 33. A kit for applying an implant into an implant site of living tissue comprising: a powder for use in preparing a paste implant material; and a non-particulate, bioresorbable solid element insertable into the paste implant material, said element having a greater resorption rate in vivo than the implanted paste implant material, or the element comprising a mechanically weak material susceptible to fracturing under force at the implant site resulting in channels or cracks, and said element providing macroscopic access into the interior of the implant to cells of the living tissue by the element more rapidly resorbing in vivo than the implanted paste implant material, or the element fracturing under force at the implant site to produce channels or cracks. 34. The kit of claim 33, further comprising a mixing pouch. 35. The kit of claim 33, further comprising a physiologically acceptable fluid. 36. The kit of claim 33, wherein the powder comprises a calcium phosphate. 37. A method of making an implant and implanting the implant into an implant site of a host, comprising: implanting a malleable implant material into an implant site of a host, wherein said malleable implant material is capable of being deformed under pressure required to insert the malleable implant material into the implant site; and, before or after implanting said malleable implant material, introducing a non-particulate, bioresorbable solid element into the malleable implant material for providing macroscopic access into the interior of the implant to cells of the host, wherein said macroscopic access results from said element more rapidly resorbing in vivo than the implanted malleable implant material, or the element comprising a mechanically weak material and fracturing under force at the implant site to produce channels or cracks. 38. The method of claim 37, wherein the implant has at least one cross-sectional dimension of greater than 3 mm. 39. The method of claim 37, wherein the implant has at least one cross-sectional dimension of greater than 1 cm. 40. The method of claim 37, wherein the malleable implant material is comprised of a bioresorbable material and a physiologically acceptable fluid. 41. The method of claim 37, wherein the malleable implant material is hardenable. 42. The method of claim 37, wherein the malleable implant material comprises an osteoconductive material. 43. The method of claim 42, wherein the osteoconductive material is selected from the group consisting of calcium phosphates, collagens, and fibrins. 44. The method of claim 43, wherein the calcium phosphate is selected from the group consisting of amorphous calcium phosphate, tricalcium phosphate, hydroxyapatite, calcium deficient hydroxyapatite, poorly crystalline hydroxyapatite (PCHA), dicalcium phosphate dihydrate (DCPD), tetracalcium phosphate, and dahlite (Ca.sub.5 (PO.sub.4,CO.sub.3).sub.3 F). 45. The method of claim 37, wherein the element is selected from the group consisting of rods, fibers, sheets, fibrous mats, star-shapes and jack-shapes. 46. The method of claim 37, wherein the element has an outer diameter greater than that of cells of the living tissue. 47. The method of claim 37, wherein the element is selected from the group consisting of poly(lactide), poly(lactide-co-glycolide), gelatins, collagen, alginate, tissue culture medium, calcium phosphates, calcium sulfate, sugars, carbohydrates, and salts. 48. The method of claim 37, wherein the element is comprised of a material resorbable by dissolution, enzymatic action or cellular action to provide access to the interior of the implant. 49. The method of claim 37, wherein the element is comprised of a nutrient of a cell of the living tissue. 50. The method of claim 37, wherein the element comprises a polymer capable of acting as a substrate for cell attachment. 51. The method of claim 37, wherein the implant further comprises a material for promoting cell adhesion. 52. The method of claim 37, wherein the element has a dimension greater than 0.5 mm. 53. The method of claim 37, wherein the element has a dimension greater than 1 mm. 54. The method of claim 37, wherein the element has a dimension greater than 5.0 mm. 55. The method of claim 37, wherein the element is insertable into the malleable implant material at an implant site. 56. The method of claim 37, wherein the implant is a multilaminar structure having layers of malleable implant material and element. 57. The method of claim 37, wherein the element is heterogeneously distributed throughout the implant. 58. The method of claim 37, wherein the implant further comprises additives capable of controlling the resorption rate of the implant material. 59. The method of claim 37, wherein the implant further comprises reinforcing additives. 60. A method of making an implant and implanting the implant into an implant site of a host, comprising: providing a paste implant material capable of hardening; before said paste implant material hardens, introducing a non-particulate, bioresorbable, solid element into the paste implant material for providing macroscopic access into the interior of the hardened implant material to cells of the host, allowing said paste implant material to harden; and implanting said hardened implant material into an implant site of a host, wherein said macroscopic access results from said element more rapidly resorbing in vivo than the hardened implant material, or the element containing a mechanically weak material and fracturing under force at the implant site to produce channels or cracks. 61. The method of claim 60, wherein the hardened implant material comprises an osteoconductive material. 62. The method of claim 60, wherein the hardened implant material is selected from the group consisting of calcium phosphates, collagens, and fibrins. 63. The method of claim 62, wherein the calcium phosphate is selected from the group consisting of amorphous calcium phosphate, tricalcium phosphate, hydroxyapatite, calcium deficient hydroxyapatite, poorly crystalline hydroxyapatite (PCHA), dicalcium phosphate dihydrate (DCPD), tetracalcium phosphate, and dahlite (Ca.sub.5 (PO.sub.4,CO.sub.3).sub.3 F). 64. The method of claim 60, wherein the element is selected from the group consisting of rods, fibers, sheets, fibrous mats, star-shapes and jack-shapes. 65. The method of claim 60, wherein the element has an outer diameter greater than that of cells of the living tissue. 66. The method of claim 60, wherein the element has a dimension greater than 0.5 mm. 67. The method of claim 60, wherein the hardened implant material further comprises a material for promoting cell adhesion.

Details for Patent 6,599,516

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2039-03-29