Claims for Patent: RE45877

Summary for Patent: RE45877

Title:	Method of doping surfaces
Abstract:	Disclosed herein are methods of treating an article surface. The method comprises removing a metal oxide surface from the metal substrate to expose a metal surface; and delivering particles comprising a dopant from at least one fluid jet to the metal surface to impregnate the surface of the article with the dopant. The method also comprises delivering substantially simultaneously a first set of particles comprising a dopant and a second set of particles comprising an abrasive from at least one fluid jet to a surface of an article to impregnate the surface of the article with the dopant.
Inventor(s):	O\'Donoghue; John Gerard (Dungarvan, IE), Haverty; Donncha (Co. Limerick, IE)
Assignee:	EnBio Limited (Dublin, IE)
Application Number:	14/587,200
Patent Claims:	1. A method of treating a metal substrate, comprising: removing, by abrasively blasting, a metal oxide from a surface of the metal substrate to expose a metal surface; and delivering particles comprising a dopant from at least one fluid jet to the metal surface to impregnate the surface of the substrate with the dopant.[.,.]..Iadd.; wherein the step of abrasively blasting is performed simultaneously with the step of delivering the particles comprising the dopant; and .Iaddend. wherein the metal substrate forms at least part of an implantable medical device. 2. A method as claimed in claim 1, wherein the removing is performed under an inert atmosphere. 3. A method as claimed in claim 1, wherein the removing is performed substantially simultaneously with the delivering such that the metal surface is not .[.substantially.]. oxidized prior to the delivering. 4. A method as claimed in claim 1, wherein the step of abrasively blasting is selected from grit blasting, micro blasting, water jet blasting, and shot peening. .[.5. A method as claimed in claim 1, wherein the step of abrasively blasting is performed simultaneously with the step of delivering the particles comprising the dopant..]. 6. A method as claimed in claim 1, wherein the substrate is selected from titanium, stainless steel, aluminium, and nitinol. 7. A method as claimed in claim 1, wherein the at least one fluid jet is from wet blasters. 8. A method as claimed in claim 7, wherein the at least one fluid jet operates at a pressure ranging from 0.5 to 100 bar. 9. A method as claimed in claim 7, wherein the at least one fluid jet operates at a pressure ranging from 1 to 30 bar. 10. A method as claimed in claim 7, wherein the at least one fluid jet operates at a pressure ranging from 1 to 10 bar. 11. A method as claimed in claim 1, wherein the at least one fluid jet is selected from dry blasters, grit blasters, sand blasters(s), and micro-blasters. 12. A method as claimed in claim 11, wherein the at least one fluid jet operates at a pressure ranging from 0.5 to 100 bar. 13. A method as claimed in claim 11, wherein the at least one fluid jet operates at a pressure ranging from 1 to 30 bar. 14. A method as claimed in claim 11, wherein the at least one fluid jet operates at a pressure ranging from 3 to 10 bar. 15. A method as claimed in claim 1, wherein the metal substrate is chosen from pure metals, metal alloys, intermetals comprising single or multiple phases, intermetals comprising amorphous phases, intermetals comprising single crystal phases, and intermetals comprising polycrystalline phases. 16. A method as claimed in claim 1, wherein the metal substrate is selected from titanium, titanium alloys, ferrous alloys, stainless steel, stainless steel alloys, carbon steel, carbon steel alloys, aluminum, aluminum alloys, nickel, nickel alloys, nickel titanium alloys, tantalum, tantalum alloys, niobium, niobium alloys, chromium, chromium alloys, cobalt, cobalt alloys, precious metals, and precious metal alloys. 17. A method as claimed in claim 1, wherein the metal substrate is selected from titanium, aluminum, stainless steel, and nitinol. 18. A method as claimed in claim 1, wherein the implantable medical device is selected from a catheter, guide wires, and baskets used in the removal of pathological calcifications. 19. A method as claimed in claim 1, wherein the particles are delivered in a gaseous carrier fluid. 20. A method as claimed in claim 19, wherein the carrier fluid is selected from nitrogen, hydrogen, argon, helium, air, ethylene oxide, and combinations thereof. 21. A method as claimed in claim 1, wherein the particles are delivered in a liquid carrier fluid. 22. A method as claimed in claim 21, wherein the liquid is also an etching liquid. 23. A method as claimed in claim 22, wherein the etching liquid is basic. 24. A method as claimed in claim 22, wherein the etching liquid is acidic. 25. A method as claimed in claim 1, wherein the delivering is carried out in an inert environment. 26. A method as claimed in claim 1, wherein the abrasively blasting is performed with an abrasive selected from silica, alumina, zirconia, barium titanate, calcium titanate, sodium titanate, titanium oxide, glass, biocompatible glass, diamond, silicon carbide, calcium phosphate, calcium carbonate, metallic powders, metallic wires, carbon fiber composites, polymers, polymeric composites, titanium, stainless steel, hardened steel, chromium alloys. 27. A method as claimed in claim 1, wherein the abrasively blasting is performed with an abrasive having a mohs hardness ranging from 0.1 to 10. 28. A method as claimed in claim 27, wherein the abrasive has a mohs hardness ranging from 1 to 10. 29. A method as claimed in claim 27, wherein the abrasive has a mohs hardness ranging from 5 to 10. 30. A method as claimed in claim 1, wherein the abrasively blasting is performed with an abrasive having a particle size ranging from 0.1 .mu.m to 10000 .mu.m. 31. A method as claimed in claim 30, wherein the abrasive has a particle size ranging from 1 .mu.m to 5000 .mu.m. 32. A method as claimed in claim 30, wherein the abrasive has a particle size ranging from 10 .mu.m to 1000 .mu.m. 33. A method as claimed in claim 1, wherein the dopant is selected from polymers, metals, ceramics and combinations thereof. 34. A method as claimed in claim 1, wherein the dopant comprises two or more different materials. 35. A method as claimed in claim 1, wherein the dopant is a metal oxide. 36. A method as claimed in claim 1, wherein the dopant is selected from barium titanate, calcium titanate, sodium titanate, zeolite, silaceous zeolite, zeolites containing phosphorous, silica, alumina, zirconia, calcium carbonate, biocompatible glass, calcium phosphate glass, and titanium dioxide. 37. A method as claimed in claim 1, wherein the dopant is an osteoconductive or osteointegrative agent. 38. A method as claimed in claim 37, wherein the osteoconductive or osteointegrative agent is a modified calcium phosphate. 39. A method as claimed in claim 37, wherein the osteoconductive or osteointegrative agent is selected from Ca.sub.5(PO.sub.4).sub.3OH, CaHPO.sub.42H.sub.2O, CaHPO.sub.4, Ca.sub.8H.sub.2(PO.sub.4).sub.65H.sub.2O, .alpha.-Ca.sub.3(PO.sub.4).sub.2, and combinations thereof. 40. A method as claimed in claim 38, wherein the modified calcium phosphate contains at least one anion selected from carbonate, chloride, fluoride, silicate and aluminate. 41. A method as claimed in claim 38, wherein the modified calcium phosphate contains at least one cation selected from protons, potassium, sodium, magnesium, barium and strontium. 42. A method as claimed in claim 1, wherein the dopant is a therapeutic agent. 43. A method as claimed in claim 42, wherein the therapeutic agent is immobilized on or in a carrier material. 44. A method as claimed in claim 43, wherein the carrier material is selected from polymers, calcium phosphate, titanium dioxide, silica, biopolymers, biocompatible glasses, zeolite, demineralised bone, de-proteinated bone, allograft bone, and composite combinations thereof. 45. A method as claimed in claim 44, wherein the polymers are selected from polyurethanes, polyethylene terephthalate, PLLA-poly-glycolic acid (PGA) copolymer (PLGA), poly-caprolactone, poly-(hydroxybutyrate/hydroxyvalerate) copolymer, poly(vinylpyrrolidone), polytetrafluoroethylene, poly(2-hydroxyethylmethacrylate), poly(etherurethane urea), silicones, acrylics, epoxides, polyesters, urethanes, parlenes, polyphosphazene polymers, fluoropolymers, polyamides, polyolefins, and blends and copolymers thereof. 46. A method as claimed in claim 44, wherein the biopolymers are selected from polysaccharides, gelatin, collagen, alginate, hyaluronic acid, alginic acid, carrageenan, chondroitin, pectin, chitosan, and derivatives, blends and copolymers thereof. 47. A method as claimed in claim 42, wherein the therapeutic agent is selected from anti-cancer drugs, anti-inflammatory drugs, immunosuppressants, antibiotics, heparin, functional proteins, a regulatory protein, structural proteins, oligo-peptides, antigenic peptides, nucleic acids, immunogens, and combinations thereof. 48. A method as claimed in claim 47, wherein the anticancer drugs are selected from acivicin, aclarubicin, acodazole, acronycine, adozelesin, alanosine, aldesleukin, allopurinol sodium, altretamine, aminoglutethimide, amonafide, ampligen, amsacrine, androgens, anguidine, aphidicolin glycinate, asaley, asparaginase, 5-azacitidine, azathioprine, Bacillus calmette-guerin (BCG), Baker's Antifol (soluble), beta-2'-deoxythioguanosine, bisantrene HCl, bleomycin sulfate, busulfan, buthionine sulfoximine, BWA 773U82, BW 502U83.HCl, BW 7U85 mesylate, ceracemide, carbetimer, carboplatin, carmustine, chlorambucil, chloroquinoxaline-sulfonamide, chlorozotocin, chromomycin A3, cisplatin, cladribine, corticosteroids, Corynebacterium parvum, CPT-11, crisnatol, cyclocytidine, cyclophosphamide, cytarabine, cytembena, dabis maleate, dacarbazine, dactinomycin, daunorubicin HCl, deazauridine, dexrazoxane, dianhydrogalactitol, diaziquone, dibromodulcitol, didemnin B, diethyldithiocarbamate, diglycoaldehyde, dihydro-5-azacytidine, doxorubicin, echinomycin, edatrexate, edelfosine, eflornithine, Elliott's solution, elsamitrucin, epirubicin, esorubicin, estramustine phosphate, estrogens, etanidazole, ethiofos, etoposide, fadrazole, fazarabine, fenretinide, filgrastim, finasteride, flavone acetic acid, floxuridine, fludarabine phosphate, 5-fluorouracil, Fluosol., flutamide, gallium nitrate, gemcitabine, goserelin acetate, hepsulfam, hexamethylene bisacetamide, homoharringtonine, hydrazine sulfate, 4-hydroxyandrostenedione, hydrozyurea, idarubicin HCl, ifosfamide, interferon alfa, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, 4-ipomeanol, iproplatin, isotretinoin, leucovorin calcium, leuprolide acetate, levamisole, liposomal daunorubicin, liposome encapsulated doxorubicin, lomustine, lonidamine, maytansine, mechlorethamine hydrochloride, melphalan, menogaril, merbarone, 6-mercaptopurine, mesna, methanol extraction residue of Bacillus calmetteguerin, methotrexate, N-methylformamide, mifepristone, mitoguazone, mitomycin-C, mitotane, mitoxantrone hydrochloride, monocyte/macrophage colony-stimulating factor, nabilone, nafoxidine, neocarzinostatin, octreotide acetate, ormaplatin, oxaliplatin, paclitaxel, pala, pentostatin, piperazinedione, pipobroman, pirarubicin, piritrexim, piroxantrone hydrochloride, PIXY-321, plicamycin, porfimer sodium, prednimustine, procarbazine, progestins, pyrazofurin, razoxane, sargramostim, semustine, spirogermanium, spiromustine, streptonigrin, streptozocin, sulofenur, suramin sodium, tamoxifen, taxotere, tegafur, teniposide, terephthalamidine, teroxirone, thioguanine, thiotepa, thymidine injection, tiazofurin, topotecan, toremifene, tretinoin, trifluoperazine hydrochloride, trifluridine, trimetrexate, tumor necrosis factor, uracil mustard, vinblastine sulfate, vincristine sulfate, vindesine, vinorelbine, vinzolidine, Yoshi 864, zorubicin, and mixtures thereof. 49. A method as claimed in claim 47, wherein the anti-inflammatory drugs are selected from non-steroidal anti-inflammatory drugs, COX-2 inhibitors, glucocorticoids, and mixtures thereof. 50. A method as claimed in claim 49, wherein the non-steroidal anti-inflammatory drugs are selected from aspirin, diclofenac, indomethacin, sulindac, ketoprofen, flurbiprofen, ibuprofen, naproxen, piroxicam, tenoxicam, tolmetin, ketorolac, oxaprosin, mefenamic acid, fenoprofen, nambumetone, acetaminophen, and mixtures thereof. 51. A method as claimed in claim 49, wherein the COX-2 inhibitors are selected from nimesulide, NS-398, flosulid, L-745337, celecoxib, rofecoxib, SC-57666, DuP-697, parecoxib sodium, JTE-522, valdecoxib, SC-58125, etoricoxib, RS-57067, L-748780, L-761066, APHS, etodolac, meloxicam, S-2474, and mixtures thereof. 52. A method as claimed in claim 49, wherein the glucocorticoids are selected from such as hydrocortisone, cortisone, prednisone, prednisolone, methylprednisolone, meprednisone, triamcinolone, paramethasone, fluprednisolone, betamethasone, dexamethasone, fludrocortisone, desoxycorticosterone, and mixtures thereof. 53. A method as claimed in claim 47, wherein the antibiotics are chosen from tobramycin, vancomycin, gentamicin, ampicillin, penicillin, cephalosporin C, cephalexin, cefaclor, cefamandole and ciprofloxacin, and mixtures thereof. 54. A method according to claim 47, wherein the proteins are chosen from albumin, casein, gelatin, lysosime, fibronectin, fibrin, chitosan, polylysine, polyalanine, polycysteine, Bone Morphogenetic Protein (BMP), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (bFGF), Nerve Growth Factor (NGF), Bone Derived Growth Factor (BDGF), Transforming Growth Factor-.beta.1 (TGF-.beta.1), Transforming Growth Factor-.beta. (TGF-.beta.), the tri-peptide arginine-glycine-aspartic acid (RGD), vitamin D3, dexamethasone, and human Growth Hormone (hGH), epidermal growth factors, transforming growth factor .alpha., transforming growth factor .beta., vaccinia growth factors, fibroblast growth factors, insulin-like growth factors, platelet derived growth factors, cartilage derived growth factors, interlukin-2, nerve cell growth factors, hemopoietic cell growth factors, lymphocyte growth factors, bone morphogenic proteins, osteogenic factors, chondrogenic factors, or and mixtures thereof. 55. A method as claimed in claim 47, wherein the heparin is selected from recombinant heparin, heparin derivatives, and heparin analogues or combinations thereof. 56. A method as claimed in claim 47, wherein the oligopeptide is a bactericidal oligo-peptide. 57. A method as claimed in claim 47, wherein the immunogen is a viral antigen, a bacterial antigen, a fungal antigen, a parasitic antigen, tumor antigens, a peptide fragment of a tumor antigen, meta static specific antigens, a passive or active vaccine, a synthetic vaccine or a subunit vaccine. 58. A method as claimed in claim 1, wherein the dopant is a radio opaque material. 59. A method as claimed in claim 58, wherein the radio opaque material is chosen from alkalis earth metals, transition metals, rare earth metals, and oxides, sulphates, phosphates and combinations thereof. 60. A method as claimed in claim 58, wherein the radio-opaque material is a polymer. 61. A method of treating a metal substrate surface, the method comprising: removing, by abrasively blasting, a metal oxide from the surface of the metal substrate to expose a metal surface; and delivering substantially simultaneously a first set of particles comprising a dopant and a second set of particles comprising an abrasive from at least one fluid jet to the surface of the metal substrate to impregnate the surface of the metal with the dopant, wherein the metal substrate forms at least part of an implantable medical device. 62. A method as claimed in claim 61, wherein the at least one fluid jet is from wet blasters. 63. A method as claimed in claim 61, wherein the at least one fluid jet is selected from dry blasters, grit blasters, sand blasters(s), and micro-blasters. 64. A method as claimed in claim 62, wherein the at least one fluid jet operates at a pressure ranging from 0.5 to 100 bar. 65. A method as claimed in claim 62 wherein the at least one fluid jet operates at a pressure ranging from 1 to 30 bar. 66. A method as claimed in claim 62, wherein the at least one fluid jet operates at a pressure ranging from 1 to 10 bar. 67. A method as claimed in claim 63, wherein the at least one fluid jet operates at a pressure ranging from 0.5 to 100 bar. 68. A method as claimed in claim 63, wherein the at least one fluid jet operates at a pressure ranging from 1 to 30 bar. 69. A method as claimed in claim 63, wherein the at least one fluid jet operates at a pressure ranging from 3 to 10 bar. 70. A method as claimed in claim 61, wherein the metal substrate is chosen from pure metals, metal alloys, intermetals comprising single or multiple phases, intermetals comprising amorphous phases, intermetals comprising singe crystal phases, and intermetals comprising polycrystalline phases. 71. A method as claimed in claim 61, wherein the metal substrate is selected from titanium, titanium alloys, ferrous alloys, stainless steel, stainless steel alloys, carbon steel, carbon steel alloys, aluminum, aluminum alloys, nickel, nickel alloys, nickel titanium alloys, tantalum, tantalum alloys, niobium, niobium alloys, chromium, chromium alloys, cobalt, cobalt alloys, precious metals, and precious metal alloys. 72. A method as claimed in claim 61, wherein the metal substrate is selected from titanium, aluminum, stainless steel, and nitinol. 73. A method as claimed in claim 61, wherein the implantable medical device is selected from a catheter, guide wires, and baskets used in the removal of pathological calcifications. 74. A method as claimed in claim 61, wherein the first and second particles are delivered in a gaseous carrier fluid. 75. A method as claimed in claim 74, wherein the carrier fluid is selected from nitrogen, hydrogen, argon, helium, air, ethylene oxide, and combinations thereof. 76. A method as claimed in claim 61, wherein the first and second particles are delivered in a liquid carrier fluid. 77. A method as claimed in claim 76, wherein the liquid is also an etching liquid. 78. A method as claimed in claim 77, wherein the etching liquid is basic. 79. A method as claimed in claim 77, wherein the etching liquid is acidic. 80. A method as claimed in claim 61, wherein the delivering is carried out in an inert environment. 81. A method as claimed in claim 61, wherein the abrasive is selected from silica, alumina, zirconia, barium titanate, calcium titanate, sodium titanate, titanium oxide, glass, biocompatible glass, diamond, silicon carbide, calcium phosphate, calcium carbonate, metallic powders, metallic wires, carbon fiber composites, polymers, polymeric composites, titanium, stainless steel, hardened steel, chromium alloys. 82. A method as claimed in claim 61, wherein the abrasive has a mohs hardness ranging from 0.1 to 10. 83. A method as claimed in claim 61, wherein the abrasive has a mohs hardness ranging from 1 to 10. 84. A method as claimed in claim 61, wherein the abrasive has a mohs hardness ranging from 5 to 10. 85. A method as claimed in claim 61, wherein the abrasive has a particle size ranging from 0.1 .mu.m to 10000 .mu.m. 86. A method as claimed in claim 61, wherein the abrasive has a particle size ranging from 1 .mu.m to 5000 .mu.m. 87. A method as claimed in claim 61, wherein the abrasive has a particle size ranging from 10 .mu.m to 1000 .mu.m. 88. A method as claimed in claim 61, wherein the dopant is selected from polymers, metals, ceramics and combinations thereof. 89. A method as claimed in claim 61, wherein the dopant comprises two or more different materials. 90. A method as claimed in claim 61, wherein the dopant is a metal oxide. 91. A method as claimed in claim 61, wherein the dopant is selected from barium titanate, calcium titanate, sodium titanate, zeolite, silaceous zeolite, zeolites containing phosphorous, silica, alumina, zirconia, calcium carbonate, biocompatible glass, calcium phosphate glass, and titanium dioxide. 92. A method as claimed in claim 61, wherein the dopant is an osteoconductive or osteointegrative agent. 93. A method as claimed in claim 92, wherein the osteoconductive or osteointegrative agent is a modified calcium phosphate. 94. A method as claimed in claim 92, wherein the osteoconductive or osteointegrative agent is selected from Ca.sub.5(PO.sub.4).sub.3OH, CaHPO.sub.4.2H.sub.2O, CaHPO.sub.4, Ca.sub.8H.sub.2(PO.sub.4).sub.6.5H.sub.2O, .alpha.-Ca.sub.3(PO.sub.4).sub.2, .beta.-Ca.sub.3(PO.sub.4).sub.2, and combinations thereof. 95. A method as claimed in claim 93, wherein the modified calcium phosphate contains at least one anion selected from carbonate, chloride, fluoride, silicate and aluminate. 96. A method as claimed in claim 93, wherein the modified calcium phosphate contains at least one cation selected from protons, potassium, sodium, magnesium, barium and strontium. 97. A method as claimed in claim 61, wherein the dopant is a therapeutic agent. 98. A method as claimed in claim 97, wherein the therapeutic agent is immobilized on or in a carrier material. 99. A method as claimed in claim 98, wherein the carrier material is selected from polymers, calcium phosphate, titanium dioxide, silica, biopolymers, biocompatible glasses, zeolite, demineralised bone, de-proteinated bone, allograft bone, and composite combinations thereof. 100. A method as claimed in claim 99, wherein the polymers are selected from polyurethanes, polyethylene terephthalate, PLLA-poly-glycolic acid (PGA) copolymer (PLGA), polycaprolactone, poly-(hydroxybutyrate/hydroxyvalerate) copolymer, poly(vinylpyrrolidone), polytetrafluoroethylene, poly(2-hydroxyethylmethacrylate), poly(etherurethane urea), silicones, acrylics, epoxides, polyesters, urethanes, parlenes, polyphosphazene polymers, fluoropolymers, polyamides, polyolefins, and blends and copolymers thereof. 101. The method as claimed in claim 99 wherein the biopolymers are selected from polysaccharides, gelatin, collagen, alginate, hyaluronic acid, alginic acid, carrageenan, chondroitin, pectin, chitosan, and derivatives, blends and copolymers thereof. 102. A method as claimed in claim 98, wherein the therapeutic agent is selected from anti-cancer drugs, anti-inflammatory drugs, immunosuppressants, an antibiotic, heparin, a functional protein, a regulatory protein, structural proteins, oligo-peptides, antigenic peptides, nucleic acids, immunogens, and combinations there of. 103. A method as claimed in claim 102, wherein the anti-cancer drugs are selected from acivicin, aclarubicin, acodazole, acronycine, adozelesin, alanosine, aldesleukin, allopurinol sodium, altretamine, aminoglutethimide, amonafide, ampligen, amsacrine, androgens, anguidine, aphidicolin glycinate, asaley, asparaginase, 5-azacitidine, azathioprine, Bacillus calmette-guerin (BCG), Baker's Antifol (soluble), beta-2'-deoxythioguanosine, bisantrene HCl, bleomycin sulfate, busulfan, buthionine sulfoximine, BWA 773U82, BW 502U83.HCl, BW 7U85 mesylate, ceracemide, carbetimer, carboplatin, carmustine, chlorambucil, chloroquinoxalinesulfonamide, chlorozotocin, chromomycin A3, cisplatin, cladribine, corticosteroids, Corynebacterium parvum, CPT-11, crisnatol, cyclocytidine, cyclophosphamide, cytarabine, cytembena, dabis maleate, dacarbazine, dactinomycin, daunorubicin HCl, deazauridine, dexrazoxane, dianhydrogalactitol, diaziquone, dibromodulcitol, didemnin B, diethyldithiocarbamate, diglycoaldehyde, dihydro-5-azacytidine, doxorubicin, echinomycin, edatrexate, edelfosine, eflornithine, Elliott's solution, elsamitrucin, epirubicin, esorubicin, estramustine phosphate, estrogens, etanidazole, ethiofos, etoposide, fadrazole, fazarabine, fenretinide, filgrastim, finasteride, flavone acetic acid, floxuridine, fludarabine phosphate, 5-fluorouracil, Fluosol, flutamide, gallium nitrate, gemcitabine, goserelin acetate, hepsulfam, hexamethylene bisacetamide, homoharringtonine, hydrazine sulfate, 4-hydroxyandrostenedione, hydrozyurea, idarubicin HCl, ifosfamide, interferon alfa, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, 4-ipomeanol, iproplatin, isotretinoin, leucovorin calcium, leuprolide acetate, levamisole, liposomal daunorubicin, liposome encapsulated doxorubicin, lomustine, lonidamine, maytansine, mechlorethamine hydrochloride, melphalan, menogaril, merbarone, 6-mercaptopurine, mesna, methanol extraction residue of Bacillus calmetteguerin, methotrexate, N-methylformamide, mifepristone, mitoguazone, mitomycin-C, mitotane, mitoxantrone hydrochloride, monocyte/macrophage colony-stimulating factor nabilone, nafoxidine, neocarzinostatin, octreotide acetate, ormaplatin, oxaliplatin, paclitaxel, pala, pentostatin, piperazinedione, pipobroman, pirarubicin, piritrexim, piroxantrone hydrochloride, PIXY-321, plicamycin, porfimer sodium, prednimustine, procarbazine, progestins, pyrazofurin, razoxane, sargramostim, semustine, spirogermanium, spiromustine, streptonigrin, streptozocin, sulofenur, suramin sodium, tamoxifen, taxotere, tegafur, teniposide, terephthalamidine, teroxirone, thioguanine, thiotepa, thymidine injection, tiazofuran, topotecan, toremifene, tretinoin, trifluoperazine hydrochloride, trifluridine, trimetrexate, tumor necrosis factor, uracil mustard, vinblastine sulfate, vincristine sulfate, vindesine, vinorelbine, vinzolidine, Yoshi 864, zorubicin, and mixtures thereof. 104. A method as claimed in claim 102, wherein the anti-inflammatory drugs are selected from non-steroidal anti-inflammatory drugs, COX-2 inhibitors, glucocorticoids, and mixtures thereof. 105. A method as claimed in claim 104, wherein the non-steroidal anti-inflammatory drugs are selected from aspirin, diclofenac, indomethacin, sulindac, ketoprofen, flurbiprofen, ibuprofen, naproxen, piroxicam, tenoxicam, tolmetin, ketorolac, oxaprosin, mefenamic acid, fenoprofen, nambumetone, acetaminophen, and mixtures thereof. 106. A method as claimed in claim 104, wherein the COX-2 inhibitors are selected from nimesulide, NS-398, flosulid, L-745337, celecoxib, rofecoxib, SC-57666, DuP-697, parecoxib sodium, JTE-522, valdecoxib, SC-58125, etoricoxib, RS-57067, L-748780, L-761066, APHS, etodolac, meloxicam, S-2474, and mixtures thereof. 107. A method as claimed in claim 104, wherein the glucocorticoids are selected from such as hydrocortisone, cortisone, prednisone, prednisolone, methylprednisolone, meprednisone, triamcinolone, paramethasone, fluprednisolone, betamethasone, dexamethasone, fludrocortisone, desoxycorticosterone, and mixtures thereof. 108. A method as claimed in claim 102, wherein the antibiotics are chosen from tobramycin, vancomycin, gentamicin, ampicillin, penicillin, cephalosporin C, cephalexin, cefaclor, cefamandole and ciprofloxacin, and mixtures thereof. 109. A method according to claim 102, wherein the proteins are chosen from albumin, casein, gelatin, lysosime, fibronectin, fibrin, chitosan, polylysine, polyalanine, polycysteine, Bone Morphogenetic Protein (BMP), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (bFGF), Nerve Growth Factor (NGF), Bone Derived Growth Factor (BDGF), Transforming Growth Factor-.beta.1 (TGF-.beta.1), Transforming Growth Factor-.beta. (TGF-.beta.), the tri-peptide arginine-glycine-aspartic acid (RGD), vitamin D3, dexamethasone and human Growth Hormone (hGH), epidermal growth factors, transforming growth factor .alpha., transforming growth factor .beta., vaccinia growth factors, fibroblast growth factors, insulin-like growth factors, platelet derived growth factors, cartilage derived growth factors, interlukin-2, nerve cell growth factors, hemopoietic cell growth factors, lymphocyte growth factors, bone morphogenic proteins, osteogenic factors, chondrogenic factors, or and mixtures thereof. 110. A method as claimed in claim 102, wherein the heparin is selected from recombinant heparin, heparin derivatives, and heparin analogues or combinations thereof. 111. A method as claimed in claim 102, wherein the oligopeptide is a bactericidal oligo-peptide. 112. A method as claimed in claim 102, wherein the immunogen is a viral antigen, a bacterial antigen, a fungal antigen, a parasitic antigen, tumor antigens, a peptide fragment of a tumor antigen, meta static specific antigens, a passive or active vaccine, a synthetic vaccine or a subunit vaccine. 113. A method as claimed in claim 61, wherein the dopant is a radio opaque material. 114. A method as claimed in claim 113, wherein the radio opaque material is chosen from alkalis earth metals, transition metals, rare earth metals, and oxides, sulphates, phosphates and combinations thereof. 115. A method as claimed in claim 113, wherein the radio-opaque material is a polymer. 116. A method as claimed in claim 61, wherein the first and second set of particles are delivered to the surface from the same fluid jet. 117. A method as claimed in claim 61, wherein the first and second set of particles are delivered to the surface from separate fluid jets.

Details for Patent RE45877

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2026-09-11
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	06/21/1989		2026-09-11
Clinigen, Inc.	PROLEUKIN	aldesleukin	For Injection	103293	05/05/1992		2026-09-11
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2026-09-11
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2026-09-11