Claims for Patent: 9,956,172

Summary for Patent: 9,956,172

Title:	Implant compositions for the unidirectional delivery of therapeutic compounds to the brain
Abstract:	The present invention provides, in some aspects, bilayered and trilayered pharmaceutical implant compositions for the unidirectional delivery of anti-cancer compounds to the brain over a period of time (e.g., several weeks, 1, 2, 3, 4, 5, 6, 7 days, or 1, 2, 3, weeks, or any range derivable therein) following the removal of glioblastoma multiforme or other malignant tumors in the brain.
Inventor(s):	McGinity; Michael J. (San Antonio, TX), Zhang; Feng (Pflugerville, TX), Floyd; John R. (San Antonio, TX), McGinity; James W. (Austin, TX)
Assignee:	BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (Austin, TX)
Application Number:	15/221,827
Patent Claims:	1. A biocompatible drug delivery implant for positioning adjacent to a biological tissue for delivering one or more drugs thereto, the implant comprising at least two layers, a drug-containing layer having a drug elution surface to be positioned proximal to the tissue, and, a further layer or layers comprising a lipophilic backing layer and/or a hydrophobic coating, said further layer or layers being positioned distal to the drug elution surface, wherein: a) the drug-containing layer comprises one or more drugs, a hydrophilic polymer or pore forming agent, and glyceryl behenate; b) the lipophilic backing layer comprises glyceryl behenate; and c) the hydrophobic coating comprises glyceryl behenate and coats surfaces of the implant that are not to be positioned proximal to the tissue and; and further, when each of layers a), b) and c) are present, the lipophilic backing layer is positioned between the drug-containing layer and the hydrophobic coating. 2. The implant of claim 1, wherein the implant further comprises a drug-permeable, hydrophilic layer d) positioned between the drug elution surface of the drug-containing layer and to be positioned proximal to the tissue. 3. The implant of claim 2, wherein the layer d) contains a steroid and the drug. 4. The implant of claim 3, wherein the steroid is dexamethasone. 5. The implant of claim 1, wherein the hydrophilic polymer present in layer a) and/or d) is a polyether or a polysaccharide. 6. The implant of claim 5, wherein the hydrophilic polymer is a polyethylene oxide, polypropylene oxide, or a polyethylene glycol. 7. The implant of claim 5, wherein the polysaccharide is chitosan or polyanhydroglucuronic acid. 8. The implant of claim 1, wherein the drug is an anti-cancer compound or a chemotherapeutic. 9. The implant of claim 8, wherein the chemotherapeutic is temozolomide, paclitaxel, cetuximab, irinotecan, everolimus, carboplatin, or docetaxel. 10. The implant of claim 1, wherein the implant is substantially circular or elliptical in shape or is further defined as a wafer. 11. The implant of claim 1, wherein the drug-containing layer comprises glyceryl behenate, stearic acid, polyanhydroglucuronic acid, or polyethylene oxide. 12. The implant of claim 1, wherein the hydrophobic coating further comprises stearic acid, palmitic acid, cholesterol, or chitosan. 13. The implant of claim 1, wherein the drug-containing layer further comprises stearic acid, lipase, cholesterol, glyceryl tristearate, poloxamer F-68, and/or polyanhydroglucuronic acid. 14. The implant of claim 1, wherein the implant comprises: 0.1-50% of the drug, 5-95% of glyceryl behenate, and about 3-50% of the hydrophilic polymer or pore forming agent. 15. The implant of claim 1, comprising layers a) and b). 16. The implant of claim 1, comprising layers a) and c). 17. The implant of claim 1, comprising layers a), b) and c). 18. The implant of claim 2, wherein the layer d) does not contain the drug. 19. The implant of claim 2, wherein the layer d) contains a steroid. 20. The implant of claim 2, wherein the layer d) contains the drug. 21. The implant of claim 6, wherein the hydrophilic polymer is a polyethylene oxide. 22. The implant of claim 5, wherein the hydrophilic polymer is a polysaccharide. 23. The implant of claim 5, wherein the hydrophilic polymer comprises a mixture of a polyether and a polysaccharide. 24. The implant of claim 23, wherein the hydrophilic polymer is a mixture comprising polyethylene oxide and chitosan. 25. The implant of claim 5, wherein the hydrophilic polymer is polyethylene oxide or polyanhydroglucuronic acid. 26. The implant of claim 5, wherein the hydrophilic polymer is polyethylene oxide, chitosan, povidone (PVP or polyvinylpyrrolidone), or polyanhydroglucuronic acid. 27. The implant of claim 8, wherein the anti-cancer compound is a chemotherapy or a chemotherapeutic agent. 28. The implant of claim 1, wherein the drug is cisplatin, topotecan, bevacizumab, doxorubicin, everolimus, paclitaxel, irinotecan, carboplatin, D-actinomycin, docetaxel, pitavastatin, methotrexate, temozolomide, epirubicin, cetuximab, a copper chelating agent, carmustine, a synthetic alkyl lysophospholipid, a bioactive sulfated saponin, steroid, or a statin. 29. The implant of any one of claim 1, wherein the drug is a steroid. 30. The implant of any one of claim 1, wherein layer a) comprises both a chemotherapeutic agent and a steroid. 31. The implant of claim 2, wherein layer a) comprises a chemotherapeutic agent, and wherein the implant further comprises the layer d), wherein layer d) comprises a steroid. 32. The implant of claim 31, wherein layer a) further comprises a steroid. 33. The implant of any one of claim 29, wherein the steroid is dexamethasone or dexamethasone sodium phosphate. 34. The implant of claim 30, wherein chemotherapeutic agent is temozolomide or paclitaxel; and wherein the steroid is dexamethasone. 35. The implant of any one of claim 1, wherein the implant is further defined as a wafer. 36. The implant of claim 35, wherein the wafer or tablet is configured for insertion into a resection cavity. 37. The implant of claim 1, wherein the implant or wafer further comprises an additional therapeutic agent. 38. The implant of claim 37, wherein the additional therapeutic agent is an antibiotic, an antimicrobial agent, a statin, an anti-fungal agent, an anti-viral agent, a steroid, an anesthetic, a local anesthetic, or a NSAID. 39. The implant of claim 38, wherein the additional therapeutic agent is an antibiotic or an antimicrobial agent. 40. The implant of claim 1, wherein the implant does not contain an organic solvent. 41. The implant of claim 1, wherein the implant contains an organic solvent. 42. The implant of claim 41, wherein the implant contains no more than a trace amount or a residual amount of the organic solvent. 43. The implant of claim 41, wherein the organic solvent is ethanol, dichloromethane, acetone, tetrahydrofuran, or ethyl acetate. 44. The implant of claim 1, wherein the lipophilic backing layer and the hydrophobic coating are made of the same or essentially the same compounds or mixture of compounds. 45. The implant of claim 44, wherein the lipophilic backing layer and the hydrophobic coating together form a substantially homogenous hydrophobic layer. 46. The implant of claim 1, wherein the lipophilic backing layer and the hydrophobic coating comprise different compounds. 47. The implant of claim 1, wherein the hydrophobic coating consists of or consists essentially of glyceryl behenate. 48. The implant of claim 1, where the drug-containing layer comprises glyceryl behenate and stearic acid, in combination with polyanhydroglucuronic acid and/or polyethylene oxide. 49. The implant of claim 48, wherein the drug-containing layer comprises glyceryl behenate, stearic acid, and polyethylene oxide. 50. The implant of claim 48, wherein the drug-containing layer further comprises lipase, cholesterol, glyceryl tristearate, and/or poloxamer F-68. 51. The implant of claim 50, wherein layer c) and/or layer b) contain lipase. 52. The implant of claim 1, wherein the drug-containing layer comprises polyethylene oxide or polyanhydroglucoronic acid. 53. The implant of claim 52, wherein the drug-containing layer comprises polyethylene oxide, glycerol behenate, and/or cholesterol. 54. The implant of claim 1, wherein the hydrophilic polymer is a polyethylene oxide, a polysaccharide, a protein, an oxidized cellulose polymer, polyanhydroglucuronic acid, a poloxomer, chitosan, or providone (PVP). 55. The implant of claim 1, wherein the implant further comprises lipase. 56. The implant of claim 1, wherein the implant is configured for insertion into a resection cavity. 57. The implant of claim 1, wherein the implant has been cured at temperatures of at least about 40.degree. C., 45.degree. C., 50.degree. C., 55.degree. C., 60.degree. C., 65.degree. C., 70.degree. C., 75.degree. C., 80.degree. C., 85.degree. C., 90.degree. C., 95.degree. C., 100.degree. C., or up to 200.degree. C. 58. The implant of claim 1, wherein the implant has been sterilized by gamma radiation, ethylene oxide, or electron beam radiation. 59. The implant of claim 1, wherein the implant or wafer has been processed by compression, hot-melt extrusion, injection molding, dry powder coating, dipping, coating, spraying, hot-melt granulation, casting, an evaporation technology, or any combination thereof. 60. The implant of claim 1, wherein the implant is further defined as a bilayered implant or wafer. 61. The implant of claim 1, wherein the implant is further defined as a trilayered implant or wafer. 62. The implant of claim 1, wherein the implant allows for release of the drug over a period of at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 or more days, or at least 1, 2, 3, 4, 5, or 6 weeks, or any range derivable therein. 63. The implant of claim 1, wherein the implant further comprises a surfactant, a carbohydrate, a polyol, a protein, a peptide, and/or an excipient. 64. A method of treating a disease or traumatic injury in a mammalian subject, comprising administering into a resection cavity in the subject the implant of claim 1, wherein the drug elution surface is positioned proximal to the resection cavity, and, the further layer or layers comprising the lipophilic backing layer and/or the hydrophobic coating are positioned distal and/or lateral to the drug elution surface.

Details for Patent 9,956,172

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2035-07-28
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2035-07-28
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2035-07-28