Polymeric Paste Compositions for Drug Delivery

Abstract

This invention provides compositions for controlled localized release of one or more drugs within a subject. More particularly, described herein are compositions comprising a hydrophobic water-insoluble polymer, a low molecular weight biocompatible glycol, and one or more drugs. The compositions described herein may also optionally include a di-block copolymer and/or a swelling agent.

1 .- 29 . (canceled) 
     
     
         30 . A composition, the composition comprising a mixture of the following components:
 (a) a hydrophobic water-insoluble polymer having an inherent viscosity (IV) of about 0.15 to about 0.5 dL/g;   (b) a low molecular weight biocompatible glycol; with a molecular weight at or below 1,450 Daltons; and   (c) one or more drug compounds or pharmaceutically acceptable salt, solvate or solvate of the salt thereof,   wherein the components (a) and (b) do not form covalent bonds with each other,   wherein the ratio of the low molecular weight biocompatible glycol to the hydrophobic water-insoluble polymer is between about 70%:30% and about 40%:60%, and   wherein the composition forms a soft implant in an aqueous environment at about 37° C. and that remains soft.   
     
     
         31 . The composition of  claim 30 , further comprising a di-block copolymer. 
     
     
         32 . The composition of  claim 30 , wherein the hydrophobic water-insoluble polymer having an inherent viscosity (IV) of about 0.15 to about 0.5 dL/g is polylactic-co-glycolic acid (PLGA). 
     
     
         33 . The composition of  claim 32 , wherein the PLGA has a ratio of lactic acid (LA):glycolic acid (GA) at or below 75:25. 
     
     
         34 . The composition of  claim 30 , wherein the hydrophobic water-insoluble polymer has an inherent viscosity (IV) of about 0.15 to about 0.3 dL/g. 
     
     
         35 . The composition of  claim 30 , wherein the hydrophobic water-insoluble polymer has an inherent viscosity (IV) of about 0.15 to about 0.25 dL/g. 
     
     
         36 . The composition of  claim 30 , wherein the low molecular weight biocompatible glycol has a molecular weight between about 76 Daltons and about 1,450 Daltons. 
     
     
         37 . The composition of  claim 30 , wherein the low molecular weight biocompatible glycol is selected from Polyethylene glycol (PEG), methoxypolyethylene glycol (mePEG) and propylene glycol. 
     
     
         38 . The composition of  claim 30 , wherein the low molecular weight biocompatible glycol is selected from PEG and mePEG. 
     
     
         39 . The composition of  claim 38 , wherein the PEG or mePEG has an average molecular weight of between 300 Daltons and 1,450 Daltons. 
     
     
         40 . The composition of  claim 30 , wherein the hydrophobic water-insoluble polymer having an inherent viscosity (IV) of about 0.15 to about 0.5 dL/g is PLGA having an LA:GA ratio of 50:50 and the low molecular weight biocompatible glycol is PEG or mePEG with a molecular weight of about 300 Daltons to about 1,450 Daltons. 
     
     
         41 . The composition of  claim 40 , wherein the ratio of PEG or mePEG to PLGA is between about 60%:40% and about 40%:60%. 
     
     
         42 . The composition of  claim 41 , wherein the ratio of PEG or mePEG to PLGA is between about 60%:40% and about 50%:50%. 
     
     
         43 . The composition of  claim 30 , wherein the low molecular weight biocompatible glycol is PEG 300. 
     
     
         44 . The composition of  claim 30 , wherein the di-block copolymer is between 13% and 26% of the total. 
     
     
         45 . The composition of  claim 44 , wherein the di-block copolymer has one hydrophobic monomer and one hydrophilic monomer. 
     
     
         46 . The composition of  claim 45 , wherein the hydrophilic monomer is selected from: PEG; and MePEG; and the hydrophobic monomer is selected from: PLGA; polylactic acid (PLA); Poly-L-lactic Acid (PLLA); and Polycaprolactone (PCL). 
     
     
         47 . The composition of  claim 44 , wherein the di-block copolymer is amphiphilic. 
     
     
         48 . The composition of  claim 45 , wherein di-block copolymer is PLLAmePEG. 
     
     
         49 . The composition of  claim 30 , wherein the one or more drug compounds or pharmaceutically acceptable salt, solvate or solvate of the salt thereof is selected from one or more of the following categories: anti-cancer drugs; anti-inflammatory agents; antibacterial; anti-fibrotic; anesthetic; and analgesic. 
     
     
         50 . The composition of  claim 30 , wherein the one or more drug compounds or pharmaceutically acceptable salt, solvate or solvate of the salt thereof is hydrophobic. 
     
     
         51 . The composition of  claim 30 , wherein the one or more drug compounds or pharmaceutically acceptable salt, solvate or solvate of the salt thereof is hydrophilic. 
     
     
         52 . The composition of  claim 49 , wherein the anti-cancer drug is selected from one or more of the following: Actinomycin; All-trans retinoic acid; Azacitidine; Azathioprine; Bleomycin; Bortezomib; Carboplatin; Capecitabine; Cisplatin; Chlorambucil; Cyclophosphamide; Cytarabine; Daunorubicin; Docetaxel; Doxifluridine; Doxorubicin; Epirubicin; Epothilone; Etoposide; Fluorouracil; Gemcitabine; Hydroxyurea; Idarubicin; Imatinib; Irinotecan; Mechlorethamine; Mercaptopurine; Methotrexate; Mitoxantrone; Oxaliplatin; Paclitaxel; Pemetrexed; Teniposide; Tioguanine; Topotecan; Valrubicin; Vemurafenib; Vinblastine; Vincristine; Vindesine; and Vinorelbine. 
     
     
         53 . The composition of  claim 49 , wherein the anesthetic drug is a local anesthetic selected from one or more of the following: Procaine; Benzocaine; Chloroprocaine; Cocaine; Cyclomethycaine; Dimethocaine/Larocaine; Piperocaine; Propoxycaine; Procaine/Novocaine; Proparacaine; Tetracaine/Amethocaine; Articaine; Bupivacaine; Cinchocaine/Dibucaine; Etidocaine; Levobupivacaine; Lidocaine/Lignocaine/Xylocaine; Mepivacaine; Prilocaine; Ropivacaine; and Trimecaine. 
     
     
         54 . A pharmaceutical composition comprising a composition of  claim 30 , together with a pharmaceutically acceptable diluent or carrier.