Claims for Patent: 6,638,917

Summary for Patent: 6,638,917

Title:	Reducing adhesion
Abstract:	A method of reducing adhesion at a site of trauma includes forming a film from an alginate solution, contacting the film with a cross-linking solution to form a cross-linked mechanically stable sheet, and placing at least a portion of the sheet at the site of trauma. An anti-adhesion barrier includes a sheet of ionically cross-linked alginate having a thickness in a range of 0.25 mm to 10 mm. The sheet has a tear strength sufficient for suturing and repositioning. A drug delivery device includes a cross-linked alginate container that can be filled with a drug.
Inventor(s):	Li; Jianmin (Lexington, MA), Bucay-Couto; Weenna (Bedford, MA), Harrah; Timothy P. (Newton, MA)
Assignee:	SciMed Life Systems, Inc. (Maple Grove, MN)
Application Number:	09/791,490
Patent Claims:	1. A device for insertion into a body to reduce adhesion, comprising: a sheet comprising ionically cross-linked alginate and having sufficient mechanical stability to allow suturing of the sheet to a body tissue, the sheet providing a barrier to reduce adhesion between the body tissue and a neighboring body tissue. 2. The device of claim 1 wherein the sheet has a thickness in a range of 0.25 mm to 10 mm. 3. The device of claim 1 wherein the sheet has a tear strength in a range of 5 psi to 500 psi. 4. The device of claim 1 wherein the sheet further comprises more than 25% water by weight. 5. The device of claim 1 wherein the sheet has a geometrical shape selected from the group consisting of a polygon, a disk and an oval. 6. The device of claim 1 wherein an outer portion of the sheet has a lower density of cross-linking relative to an inner portion of the sheet. 7. The device of claim 1 wherein the tonically cross-linked alginate comprises alginate having an active ester or aldehyde at a carboxylate site that is cross-linked by a bifunctional cross-linker. 8. The device of claim 7 wherein the bifunctional cross-linker consists of carbodiimide or dihydrazide. 9. The device of claim 1 wherein the sheet further comprises a surfactant. 10. The device of claim 1 wherein the sheet further comprises a filler. 11. The device of claim 10 wherein the filler comprises an agent for extending a lifetime of the sheet in the body. 12. The device of claim 11 wherein the agent comprises a sulfate of calcium, barium, strontium, copper, zinc or iron. 13. The device of claim 10 wherein the filler comprises non-dissolvable polymer or biodegradable suture material to strengthen the sheet. 14. The device of claim 1 wherein the cross-linked alginate comprises alginate and one or more polymers selected from the group consisting of a biodegradable polymer, a polysaccharide, a polylactide and a polymer with covalent cross-linking, the one or more polymers selected to modify an elastic modulus and hydrophobicity of the sheet. 15. The device of claim 10 wherein the filler comprises radiopaque particles. 16. The device of claim 1 wherein the sheet further comprises polyester selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone, copolymers of lactic acid, glycolic acid, and .epsilon.-caprolactone. 17. The device of claim 1 wherein the sheet further comprises a biocompatible dye. 18. The device of claim 17 wherein the biocompatible dye is selected from the group consisting of FD&C blue No. 1, FD&C blue No. 2, FD&C green No. 3, FD&C green No. 5, FD&C yellow No. 5, FD&C yellow No. 6, FD&C yellow No. 10, .beta. carotene, ginseng violet and food blue. 19. The device of claim 1 wherein the sheet further comprises a divalent or trivalent metal. 20. The device of claim 19 wherein the divalent or trivalent metal is selected from the group consisting of barium, calcium, copper, cobalt, aluminum, iron, boron, beryllium, lead and silver. 21. The device of claim 1 wherein the ionically cross-linked alginate is formed from alginic acid having an active ester or aldehyde at a carboxylate site and a bifunctional cross-linker. 22. The device of claim 21 wherein the bifunctional cross-linker consists of carbodiimide or dihydrazide. 23. The device of claim 1 wherein the sheet further comprises a surfactant. 24. The device of claim 1 further comprising a suture for tying the sheet to a tissue. 25. A drug delivery device for insertion in a body, comprising: a container comprising mechanically stable ionically cross-linked alginate, wherein the container can be inserted into a body after being filled with one or more drugs. 26. The device of claim 25 further comprising a drug enclosed by the container. 27. The device of claim 26 wherein the drug is selected from the group consisting of an antiseptic, an antibiotic, an anticoagulant, a contraceptive, a nucleic acid molecule, a protein and a medicine. 28. A method of forming a sheet for use as an adhesion barrier, comprising: forming a film from an alginate solution; and contacting the film with a cross-linking solution to form a cross-linked mechanically stable sheet for placement of at least a portion of the sheet at a site of trauma to create the adhesion barrier. 29. The method of claim 28, further comprising placing at least the portion of the sheet at the site of trauma. 30. The method of claim 28 wherein the alginate solution comprises water and a water soluble alginate selected from the group consisting of sodium alginate, potassium alginate, magnesium alginate or propylene glycol alginate. 31. The method of claim 30 wherein the alginate solution comprises less than 40% sodium alginate by weight. 32. The method of claim 28 wherein the alginate solution comprises a filler. 33. The method of claim 32 wherein the filler comprises an agent for extending a lifetime of the sheet in the body. 34. The method of claim 33 wherein the agent comprises a sulfate of calcium, barium, strontium, copper, zinc or iron. 35. The method of claim 32 wherein the filler comprises non-dissolvable polymer or biodegradable suture material to strengthen the sheet. 36. The method of claim 28 wherein the alginate solution comprises alginate and one or more polymers selected from the group consisting of a biodegradable polymer, a polysaccharide, a polyester and a polymer with covalent cross-linking, the one or more polymers selected to modify an elastic modulus and hydrophobicity of the sheet. 37. The method of claim 32 wherein the filler comprises radiopaque particles. 38. The method of claim 28 wherein the alginate solution comprises a biocompatible dye. 39. The method of claim 38 wherein the biocompatible dye is selected from the group consisting of FD&C blue No. 1, FD&C blue No. 2, FD&C green No. 3, FD&C green No. 5, FD&C yellow No. 5, FD&C yellow No. 6, FD&C yellow No. 10, .beta. carotene, ginseng violet and food blue. 40. The method of claim 28 wherein the cross-linking solution comprises a divalent or trivalent metal salt. 41. The method of claim 40 wherein the divalent or trivalent metal salt is a salt of a metal selected from a group consisting of barium, calcium, copper, cobalt, aluminum, iron, boron, beryllium, lead and silver. 42. The method of claim 41 wherein the cross-linking solution comprises less than 40% calcium chloride by weight. 43. The method of claim 28 wherein the alginate solution comprises alginic acid having an active ester or aldehyde at a carboxylate site, and the cross-linking solution comprises a bifunctional cross-linker. 44. The method of claim 43 wherein the bifunctional cross-linker consists of carbodiimide or dihydrazide. 45. The method of claim 28 wherein forming a film from alginate solution comprises depositing the alginate solution on a substrate selected from the group consisting of glass, polymer, aluminum and steel. 46. The method of claim 28 wherein the alginate solution comprises a surfactant. 47. The method of claim 28 further comprising suturing the portion of the sheet to secure it to the site of trauma. 48. The method of claim 28 wherein forming a film from alginate solution comprises selecting a quantity of solution to yield the sheet having a thickness in a range of 025 mm to 10 mm. 49. The method of claim 48 wherein the thickness range of the sheet is 0.5 mm to 5 mm. 50. The method of claim 28 wherein contacting comprises waiting a preselected period of time to obtain a preselected density of cross-linking. 51. The method of claim 28 further comprising storing at least the portion of the sheet. 52. The method of claim 51 wherein the portion of the sheet is stored in saline solution or sterile water. 53. The method of claim 51 further comprising drying the portion of the sheet. 54. The method of claim 28 further comprising drying the film formed from the alginate solution. 55. The method of claim 54 wherein drying comprises freeze-drying or air-drying. 56. The method of claim 54 wherein the alginate solution comprises a surfactant. 57. The method of claim 28 wherein contacting comprises extruding the film formed from the alginate solution into the cross-linking solution. 58. The method of claim 28 wherein contacting comprises pouring the cross-linking solution onto the film formed from the alginate solution. 59. The method of claim 28 wherein contacting comprises spraying the cross-linking solution onto the film formed from the alginate solution. 60. The method of claim 28 wherein contacting comprises pouring the alginate solution onto the cross-linking solution. 61. The method of claim 28 wherein forming the film from alginate solution comprises dipping a substrate in a bath of the alginate solution. 62. The method of claim 28 wherein contacting the film with the cross-linking solution comprises dipping a substrate in a bath of the cross-linking solution. 63. The method of claim 28 further comprising contacting the cross-linked mechanically stable sheet with an ion stripping agent to reduce a density of cross-linking in an outer portion of the sheet relative to an inner portion of the sheet. 64. The method of claim 28 wherein the alginate solution comprises alginate and one or more hemostatic compounds. 65. The method of claim 28 wherein the alginate solution comprises alginate and one or more drugs. 66. The method of claim 29 further comprising sterilizing the portion of the sheet. 67. A method of making a drug delivery device for insertion in a body, comprising: forming a film from an alginate solution; contacting the film with a cross-linking solution to cross-link an exterior portion of the film; and draining a substantially non-cross-linked interior portion of the film through an opening in the exterior portion to leave the exterior portion defining an interior space for filling with one or more drugs and insertion in the body. 68. The method of claim 67 further comprising filling the interior space at least partially with cross-linking solution to further cross-link an inside wall of the exterior portion. 69. A method of reducing adhesion at a site of trauma, comprising: disposing a film of alginate solution at the site of trauma; and contacting the film disposed at the site of trauma with a cross-linking solution to form a cross-linked alginate barrier layer. 70. A method for reduction of adhesion at a site of trauma, comprising: disposing a film of cross-linking solution at the site of trauma; and contacting the film disposed at the site of trauma with an alginate solution to form a cross-linked alginate barrier layer.

Details for Patent 6,638,917

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2020-02-25