Drug delivery system involving interaction between protein or polypeptide and hydrophobic biodegradable polymer

Abstract

A drug delivery system for controlled release of a protein or polypeptide comprising a hydrophobic biodegradable polymer and a protein or polypeptide. A physical interaction is present between the polymer and the protein or polypeptide, thus, allowing protection and controlled release of the protein or polypeptide in-vivo. The drug delivery system may be prepared by a polymer precipitation technique or a microsphere technique.

1 . A drug delivery system for controlled release of a protein or polypeptide, said drug delivery system comprising a hydrophobic biodegradable polymer and a protein or polypeptide, wherein a physical interaction is present between said polymer and protein or polypeptide such that protection and controlled release of the protein or polypeptide is achieved in vivo.  
     
     
         2 . The drug delivery system as claimed in  claim 1 , wherein said polymer is selected from the group consisting of polyester, polyorthoester and polyanhydride.  
     
     
         3 . The drug delivery system as claimed in  claim 2 , wherein said polyester is selected from the group consisting of polyglycolic acid, polylactic acid and copolymers of glycolide and L-lactide.  
     
     
         4 . The drug delivery system as claimed in  claim 1 , wherein said protein or polypeptide is selected from the group consisting of calcitonin, insulin, angiotensin, vasopressin, desmopressin, luteinizing hormone-releasing hormone, somatostatin, glucagon, somatomedin, oxytocin, gastrin, secretin, human atrial natriuretic polypeptide, adrenocorticotropic hormone, melanocyte stimulating hormone, beta-endorphin, muramyl dipeptide, enkephalin, neurotensin, bombesin, VIP, CCK-8, parathyroid hormone, calcitonin gene related peptide, endothelin, thyroid releasing hormone, growth hormone and lymphokines.  
     
     
         5 . The drug delivery system as claimed in  claim 4 , wherein said protein or polypeptide is calcitonin.  
     
     
         6 . A drug delivery system for controlled release of protein or polypeptide, said drug delivery system comprising a hydrophobic biodegradable polymer selected from polyglycolic acid, polylactic acid and copolymers of glycolide and L-lactide, and calcitonin, wherein a physical interaction is present between said polymer and calcitonin such that controlled release of the calcitonin is achieved in Vivo.  
     
     
         7 . An oral drug delivery system for controlled release of a protein or polypeptide, said oral drug delivery system comprising a hydrophobic biodegradable polymer and a protein or polypeptide, wherein a physical interaction is present between said polymer and proteins or polypeptide whereby protection and controlled release of the protein or polypeptide is achieved in vivo and the intact drug delivery system is adsorbed from the gastrointestinal tract into the mucosal lining.  
     
     
         8 . The drug delivery system as claimed in  claim 7 , wherein said polymer is selected from the group consisting of polyester, polyorthoester and polyanhydride.  
     
     
         9 . The drug delivery system as claimed in  claim 8 , wherein said polyester is selected from the group consisting of polyglycolic acid, polylactic acid and copolymers of glycolide and L-lactide.  
     
     
         10 . The drug delivery system as claimed in  claim 7 , wherein said protein or polypeptide is selected from the group consisting of calcitonin, insulin, angiotensin, vasopressin, desmopressin, luteinizing hormone-releasing hormone, somatostatin, glucagon, somatomedin, oxytocin, gastrin, secretin, human atrial natriuretic polypeptide, adrenocorticotropic hormone, melanocyte stimulating hormone, beta-endorphin, muramyl dipeptide, enkephalin, neurotensin, bombesin, VIP, CCK-8, parathyroid hormone, calcitonin gene related peptide, endothelin, thyroid releasing hormone, growth hormone and lymphokines.  
     
     
         11 . The drug delivery system as claimed in  claim 10 , wherein said protein or polypeptide is calcitonin.  
     
     
         12 . A process for preparing a drug delivery system for controlled release of a protein or polypeptide, said process comprising: 
 a) dissolving a protein or polypeptide and a hydrophobic biodegradable polymer in a solvent, and    b) forming a precipitate containing the protein or polypeptide and polymer formed as a result of the interaction between the protein or polypeptide and the polymer.    
     
     
         13 . The process as claimed in  claim 12 , wherein the precipitate is formed by cooling the solution comprising the solvent, protein or polypeptide and polymer.  
     
     
         14 . The process as claimed in  claim 12 , wherein the precipitate is reduced in size.  
     
     
         15 . A process for preparing a drug delivery system for controlled release of a protein or polypeptide, said process comprising: 
 a) dissolving a protein or polypeptide and a hydrophobic biodegradable polymer in a first solvent, and    b) adding a second solvent in which the protein or polypeptide is soluble but in which the hydrophobic biodegradable polymer is not soluble in order to form a precipitate containing the protein or polypeptide and polymer formed as a result of the interaction between the protein or polypeptide and the polymer.    
     
     
         16 . The process as claimed in  claim 15 , wherein said polymer is selected from the group consisting of polyester, polyorthoester and polyanhydride.  
     
     
         17 . The process as claimed in  claim 16 , wherein said polyester is selected from the group consisting of polyglycolic acid, polylactic acid and copolymers of glycolide and L-lactide.  
     
     
         18 . The process as claimed in  claim 15 , wherein said protein or polypeptide is selected from the group consisting of calcitonin, insulin, angiotensin, vasopressin, desmopressin, luteinizing hormone-releasing hormone, somatostatin, glucagon, somatomedin, oxytocin, gastrin, secretin, human atrial natriuretic polypeptide, adrenocorticotropic hormone, melanocyte stimulating hormone, beta-endorphin, muramyl dipeptide, enkephalin, neurotensin, bombesin, VIP, CCK-8, parathyroid hormone, calcitonin gene related peptide, endothelin, thyroid releasing hormone, growth hormone and lymphokines.  
     
     
         19 . The process as claimed in  claim 18 , wherein said protein or polypeptide is calcitonin.  
     
     
         20 . The process as claimed in  claim 15 , wherein said first solvent is selected from the group consisting of methylene chloride, hexafluoroacetone, hexafluoroisopropanol, acetonitrile, hexane and cyclohexane.  
     
     
         21 . The process as claimed in  claim 15 , wherein said second solvent is selected from the group consisting of water, aqueous buffer and aqueous-alcoholic mixture.  
     
     
         22 . The process as claimed in  claim 15 , wherein the precipitate is reduced in size.  
     
     
         23 . A process for preparing a drug delivery system for controlled release of a protein or polypeptide, said process comprising forming a microsphere containing the protein or polypeptide and the hydrophobic biodegradable polymer whereby a physical interaction exists between the protein or polypeptide and the hydrophobic biodegradable polymer.  
     
     
         24 . A process for preparing a drug delivery system for controlled release of a protein or polypeptide, said process comprising: 
 a) dissolving a protein or polypeptide and hydrophobic biodegradable polymer in a solvent to form a first phase;    b) dispersing said first phase in a continuous solvent second phase to obtain a suspension, and    c) removing said solvent from said suspension by freeze-drying a solvent extraction to obtain a precipitate containing the protein or polypeptide and polymer formed as a result of the interaction between the protein or polypeptide and the polymer.    
     
     
         25 . The process as claimed in  claim 24 , wherein said polymer is selected from the group consisting of polyester, polyorthoester and polyanhydride.  
     
     
         26 . The process as claimed in  claim 25 , wherein said polyester is selected from the group consisting of polyglycolic acid, polylactic acid and copolymers of glycolide and L-lactide.  
     
     
         27 . The process as claimed in  claim 24 , wherein said protein or polypeptide is selected from the group consisting of calcitonin, insulin, angiotensin, vasopressin, desmopressin, luteinizing hormone-releasing hormone, somatostatin, glucagon, somatomedin, oxytocin, gastrin, secretin, human atrial natriuretic polypeptide, adrenocorticotropic hormone, melanocyte stimulating hormone, beta-endorphin, muramyl dipeptide, enkephalin, neurotensin, bombesin, VIP, CCK-8, parathyroid hormone, calcitonin gene related peptide, endothelin, thyroid releasing hormone, growth hormone and lymphokines.  
     
     
         28 . The process as claimed in  claim 27 , wherein said protein or polypeptide is calcitonin.  
     
     
         29 . The process as claimed in  claim 24 , wherein the precipitate is reduced in size.