US2004038948A1PendingUtilityA1

Therapeutic compositions and methods

Priority: Dec 7, 1999Filed: Feb 18, 2003Published: Feb 26, 2004
Est. expiryDec 7, 2019(expired)· nominal 20-yr term from priority
A61L 27/18A61L 2300/434A61K 9/0063A61L 26/0066A61L 27/54A61K 31/365A61K 31/00A61L 2300/604A61K 47/34A61L 2300/41A61K 47/59A61K 31/415A61K 9/0024
52
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Claims

Abstract

Methods of promoting healing through enhanced regeneration of tissue (e.g. hard tissue or soft tissue) by contacting the tissue or the surrounding tissue with an anti-inflammatory agent. These methods are useful in a variety of dental and orthopedic applications.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . The use of an anti-inflammatory agent to prepare a medicament useful for treating periodontal disease by administration at the site of the periodontal disease.  
     
     
         2 . The use of  claim 1  wherein the agent is a salicylate.  
     
     
         3 . The use of  claim 1  wherein the agent is a non-steroidal anti-inflammatory compound.  
     
     
         4 . The use of  claim 1  wherein the agent is an aromatic anti-inflammatory compound.  
     
     
         5 . The use of  claim 1  wherein the agent is a cyclooxygenase inhibitor.  
     
     
         6 . The use of  claim 1  wherein the agent is a cyclooxygenase-1 inhibitor.  
     
     
         7 . The use of  claim 1  wherein the agent is a cyclooxygenase-2 inhibitor.  
     
     
         8 . The use of  claim 1  wherein the agent is etodolac, celebrex, meloxicam, piroxicam, nimesulide, nabumetone, or rofecoxib.  
     
     
         9 . The use of  claim 1  wherein the agent is formulated for controlled release at the site of the periodontal disease.  
     
     
         10 . The use of  claim 9  wherein the agent is incorporated in the matrix of a biodegradable polymer.  
     
     
         11 . The use of  claim 10  wherein the agent is Isonixin, Amtolmetin Guacil, Proglumetacin, Piketoprofen, Difenamizole, Epirizole, Apazone, Feprazone, Morazone, Phenylbutazone, Pipebuzone, Propyphenazone, Ramifenazone, Thiazolinobutazone, Aspirin, Benorylate, Calcium Acetylsalicylate, Etersalate, Imidazole Salicylate, Lysine Acetylsalicylate, Morpholine Salicylate, 1-Naphthyl Salicylate, Phenyl Acetylsalicylate, Ampiroxicam, Droxicam, S-Adenosylmethionine, Amixetrine, Benzydamine, Bucolome, Difenpiramide, Emorfazone, Guaiazulene, Nabumetone, Nimesulide, Proquazone, Superoxide Dismutase, or Tenidap.  
     
     
         12 . The use of  claim 10  wherein the polymer comprises anhydride bonds in the polymer backbone.  
     
     
         13 . The use of  claim 10  wherein the polymer is a polyanhydride comprising a repeating unit having the structure:  
       
         
           
           
               
               
           
         
       
       wherein Ar is a substituted or unsubstituted aromatic ring and R is —Z 1 —R 1 — substituted on each Ar ortho to the anhydride group, wherein R 1  is a difunctional organic moiety and Z 1  is a difunctional moiety selected from the group consisting of esters, amides, urethanes, carbamates and carbonates.  
     
     
         14 . The use of  claim 9  wherein the agent is appended to a biodegradable polymer.  
     
     
         15 . The use of  claim 14  wherein the agent is Etofenamate, Talniflumate Terofenamate, Acemetacin, Alclofenac, Bufexamac, Cinmetacin, Clopirac, Felbinac, Fenclozic Acid, Fentiazac, Ibufenac, Indomethacin, Isofezolac, Isoxepac, Lonazolac, Metiazinic Acid, Mofezolac, Oxametacine, Pirazolac, Sulindac, Tiaramide, Tolmetin, Tropesin, Zomepirac, Bumadizon, Butibufen, Fenbufen, Xenbucin, Clidanac, Ketorolac, Tinoridine, Benoxaprofen, Bermoprofen, Bucloxic Acid, Fenoprofen, Flunoxaprofen, Flurbiprofen, Ibuprofen, Ibuproxam, Indoprofen, Ketoprofen, Loxoprofen, Naproxen, Oxaprozin, Pirprofen, Pranoprofen, Protizinic Acid, Suprofen, Tiaprofenic Acid, Zaltoprofen, Benzpiperylon, Mofebutazone, Oxyphenbutazone, Suxibuzone, Acetaminosalol, Parsalmide, Phenyl Salicylate, Salacetamide, Salicylsulfuric Acid, Isoxicam, Lomoxicam, Piroxicam, Tenoxicam, ε-Acetamidocaproic Acid, Bendazac, α-Bisabolol, Paranyline, Perisoxal, or Zileuton.  
     
     
         16 . The use of  claim 1  wherein the agent is administered after periodontal surgery.  
     
     
         17 . The use of  claim 14  wherein the polymer comprises anhydride bonds in the polymer backbone.  
     
     
         18 . The use of  claim 14  wherein the polymer is a polyanhydride comprising a repeating unit having the structure:  
       
         
           
           
               
               
           
         
       
       wherein Ar is a substituted or unsubstituted aromatic ring and R is —Z 1 —R 1 —Z 1 — substituted on each Ar ortho to the anhydride group, wherein R 1  is a difunctional organic moiety and Z 1  is a difunctional moiety selected from the group consisting of esters, amides, urethanes, carbamates and carbonates.  
     
     
         19 . The use of  claim 9  wherein the agent is incorporated into the backbone of a biodegradable polymer.  
     
     
         20 . The use of  claim 19  wherein the agent is Enfenamic Acid, Aceclofenac, Glucametacin, Alminoprofen, Carprofen, Ximoprofen, Salsalate, 3-Amino-4-hydroxybutyric Acid, Ditazol, Fepradinol, or Oxaceprol.  
     
     
         21 . The use of  claim 19  wherein the polymer comprises anhydride bonds in the polymer backbone.  
     
     
         22 . The use of  claim 19  wherein the polymer is an aromatic polyanhydride.  
     
     
         23 . The use of  claim 19  wherein the polymer is a polyanhydride comprising a repeating unit having the structure:  
       
         
           
           
               
               
           
         
       
       where Ar is a substituted or unsubstituted aromatic ring and R is —Z 1 —R 1 —Z 1 — substituted on each Ar ortho to the anhydride group, wherein R 1  is a difunctional organic moiety and Z 1  is a difunctional moiety selected from the group consisting of esters, amides, urethanes, carbamates and carbonates.  
     
     
         24 . The use of  claim 19  wherein Ar is Flufenamic Acid, Meclofenamic Acid, Mefenamic Acid, Niflumic Acid, Tolfenamic Acid, Amfenac, Bromfenac, Diclofenac Sodium, Etodolac, Bromosaligenin, Diflunisal, Fendosal, Gentisic Acid, Glycol Salicylate, Mesalamine, Olsalazine, Salicylamide O-Acetic Acid, Salicilic Acid, Sulfasalazine,  
     
     
         25 . The use of  claim 19  wherein the polymer is incorporated into a film, paste, gel, fiber, chip, microsphere or scaffolding for cell ingrowth.  
     
     
         26 . The use of  claim 23  wherein each Z 1  is an ester.  
     
     
         27 . An orthopedic device comprising an anti-inflammatory agent that is formulated for controlled release.  
     
     
         28 . The device of  claim 27  wherein the agent is incorporated in the matrix of a biodegradable polymer.  
     
     
         29 . The device of  claim 28  wherein the agent is Isonixin, Amtolmetin Guacil, Proglumetacin, Piketoprofen, Difenamizole, Epirizole, Apazone, Feprazone, Morazone, Phenylbutazone, Pipebuzone, Propyphenazone, Ramifenazone, Thiazolinobutazone, Aspirin, Benorylate, Calcium Acetylsalicylate, Etersalate, Imidazole Salicylate, Lysine Acetylsalicylate, Morpholine Salicylate, 1-Naphthyl Salicylate, Phenyl Acetylsalicylate, Ampiroxicam, Droxicam, S-Adenosylmethionine, Amixetrine, Benzydamine, Bucolome, Difenpiramide, Emorfazone, Guaiazulene, Nabumetone, Nimesulide, Proquazone, Superoxide Dismutase, or Tenidap.  
     
     
         30 . The use of  claim 28  wherein the polymer comprises anhydride bonds in the polymer backbone.  
     
     
         31 . The device of  claim 28  wherein the polymer is a polyanhydride comprising a repeating unit having the structure:  
       
         
           
           
               
               
           
         
       
       where Ar is a substituted or unsubstituted aromatic ring and R is —Z 1 —R 1 —Z 1 — substituted on each Ar ortho to the anhydride group, wherein R 1  is a difunctional organic moiety and Z 1  is a difunctional moiety selected from the group consisting of esters, amides, urethanes, carbamates and carbonates.  
     
     
         32 . The device use of  claim 28  wherein the agent is appended to a biodegradable polymer.  
     
     
         33 . The use of  claim 32  wherein the agent is Etofenamate, Talniflumate Terofenamate, Acemetacin, Alclofenac, Bufexamac, Cinmetacin, Clopirac, Felbinac, Fenclozic Acid, Fentiazac, Ibufenac, Indomethacin, Isofezolac, Isoxepac, Lonazolac, Metiazinic Acid, Mofezolac, Oxametacine, Pirazolac, Sulindac, Tiaramide, Tolmetin, Tropesin, Zomepirac, Bumadizon, Butibufen, Fenbufen, Xenbucin, Clidanac, Ketorolac, Tinoridine, Benoxaprofen, Bermoprofen, Bucloxic Acid, Fenoprofen, Flunoxaprofen, Flurbiprofen, Ibuprofen, Ibuproxam, Indoprofen, Ketoprofen, Loxoprofen, Naproxen, Oxaprozin, Pirprofen, Pranoprofen, Protizinic Acid, Suprofen, Tiaprofenic Acid, Zaltoprofen, Benzpiperylon, Mofebutazone, Oxyphenbutazone, Suxibuzone, Acetaminosalol, Parsalmide, Phenyl Salicylate, Salacetamide, Salicylsulfuric Acid, Isoxicam, Lomoxicam, Piroxicam, Tenoxicam, ε-Acetamidocaproic Acid, Bendazac, α-Bisabolol, Paranyline, Perisoxal, or Zileuton.  
     
     
         34 . The device of  claim 32  wherein the polymer comprises anhydride bonds in the polymer backbone.  
     
     
         35 . The device of  claim 32  wherein the polymer is a polyanhydride comprising a repeating unit having the structure:  
       
         
           
           
               
               
           
         
       
       wherein Ar is a substituted or unsubstituted aromatic ring and R is —Z 1 —R 1 —Z 1 — substituted on each Ar ortho to the anhydride group, wherein R 1  is a difunctional organic moiety and Z 1  is a difunctional moiety selected from the group consisting of esters, amides, urethanes, carbamates and carbonates.  
     
     
         36 . The device of  claim 28  wherein the agent is incorporated into the backbone of a biodegradable polymer.  
     
     
         37 . The device of  claim 36  wherein the agent is Enfenamic Acid, Aceclofenac, Glucametacin, Alminoprofen, Carprofen, Ximoprofen, Salsalate, 3-Amino4-hydroxybutyric Acid, Ditazol, Fepradinol, or Oxaceprol.  
     
     
         38 . The device of  claim 36  wherein the polymer comprises anhydride bonds in the polymer backbone.  
     
     
         39 . The device of  claim 36  wherein the polymer is an aromatic polyanhydride.  
     
     
         40 . The device of  claim 36  wherein the polymer is a polyanhydride comprising a repeating unit having the structure:  
       
         
           
           
               
               
           
         
       
       wherein Ar is a substituted or unsubstituted aromatic ring and R is —Z 1 —R 1 —Z 1 — substituted on each Ar orthio to the anhydride group, wherein R 1  is a difunctional organic moiety and Z 1  is a difunctional moiety selected from the group consisting of esters, amides, urethanes, carbamates and carbonates.  
     
     
         41 . The device of  claim 40  wherein Ar is Flufenamic Acid, Meclofenamic Acid, Mefenamic Acid, Niflumic Acid, Tolfenamic Acid, Amfenac, Bromfenac, Diclofenac Sodium, Etodolac, Bromosaligenin, Diflunisal, Fendosal, Gentisic Acid, Glycol Salicylate, Mesalamine, Olsalazine, Salicylamide O-Acetic Acid, Salicilic Acid, Sulfasalazine,  
     
     
         42 . The device of  claim 36  wherein the polymer is incorporated into a film, paste, gel, fiber, chip, microsphere or scaffolding for cell ingrowth.  
     
     
         43 . The device of  claim 40  wherein each Z 1  is an ester.  
     
     
         44 . The device of  claim 27  wherein the agent enhances bone growth.  
     
     
         45 . A bioactive implant comprising: 
 a polymer film configured to be received in or near the gingival cleft, the film including an anti-inflammatory agent.    
     
     
         46 . The bioactive implant of  claim 45 , wherein the film has a thickness of about 0.1-2.0 mm, a width of about 1-5 mm, and a height of about 1-2 mm.  
     
     
         47 . The bioactive implant of  claim 45 , wherein the film is configured to be disposed adjacent to a bone.

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