Compounds and compositions for delivering active agents

Abstract

Modified amino acid compounds useful in the delivery of active agents are provided. The active agents can be peptides. Methods of administration, such as oral, subcutaneous, sublingual, and intranasal administration and methods of preparation of the modified amino acid compounds are also provided.

1 - 29 . (canceled)  
     
     
         30 . A compound comprising:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         31 . The compound of  claim 30  wherein said salt is a sodium salt.  
     
     
         32 . A composition comprising: 
 (A) at least one active agent; and    (B) the compound of  claim 30 .    
     
     
         33 . The compound of  claim 32  wherein said salt is a sodium salt.  
     
     
         34 . The composition of  claim 32 , wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.  
     
     
         35 . The composition of defined in  claim 32 , wherein said biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.  
     
     
         36 . The composition of  claim 35 , wherein said biologically active agent comprises a protein, polypeptide or peptide.  
     
     
         37 . The composition of  claim 35 , wherein said biologically active agent comprises a mucopolysaccharide.  
     
     
         38 . The composition of  claim 34 , wherein said biologically active agent is selected from the group consisting of: growth hormone, growth hormone-releasing hormones, interferons, interleukin-1, interleukin-2, insulin, insulin-like growth factor (IGF), heparin, calcitonin, erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), antimicrobials, anti-fungal agents; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof.  
     
     
         39 . The composition of  claim 38 , wherein said biologically active agent comprises a growth hormone, interferon, insulin, heparin, cromolyn sodium, an antigen, an anti-microbial agent, calcitonin, parathyroid hormone, erythropoietin, and combinations thereof.  
     
     
         40 . The composition of  claim 39 , wherein said growth hormone comprises human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, or a combination thereof.  
     
     
         41 . The composition of  claim 38 , wherein said biologically active agent comprises interferon.  
     
     
         42 . The composition of  claim 38 , wherein said biologically active agent comprises insulin.  
     
     
         43 . The composition of  claim 38 , wherein said insulin comprises porcine insulin, bovine insulin, human insulin, and human recombinant insulin,  
     
     
         44 . The composition of  claim 38 , wherein said biologically active agent comprises heparin.  
     
     
         45 . The composition of  claim 44 , wherein said heparin comprises low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, heparinoids, dermatans, chondroitins, or a combination thereof.  
     
     
         46 . The composition of  claim 45 , wherein said biologically active agent comprises low molecular weight heparin.  
     
     
         47 . The composition of  claim 38 , wherein said biologically active agent comprises cromolyn sodium.  
     
     
         48 . The composition of  claim 47 , wherein said cromolyn sodium comprises sodium chromoglycate, disodium chromoglycate or a combination thereof.  
     
     
         49 . The composition of  claim 38 , wherein said biologically active agent comprises an antigen.  
     
     
         50 . The composition of  claim 38 , wherein said biologically active agent comprises an anti-microbial agent.  
     
     
         51 . The composition of  claim 38 , wherein said biologically active agent comprises calcitonin.  
     
     
         52 . The composition of  claim 51 , wherein said calcitonin comprises salmon calcitonin, eel calcitonin, human calcitonin or a combination thereof  
     
     
         53 . The composition of  claim 38 , wherein said biologically active agent comprises parathyroid hormone.  
     
     
         54 . The composition of  claim 38 , wherein said biologically active agent comprises erythropoietin.  
     
     
         55 . A dosage unit form comprising 
 (A) a composition as defined in  claim 32;  and    (B) 
 (a) an excipient  
 (b) a diluent,  
 (c) a disintegrant,  
 (d) a lubricant,  
 (e) a plasticizer,  
 (f) a colorant,  
 (g) a dosing vehicle, or  
 (h) any combination thereof.  
   
     
     
         56 . The dosage unit of  claim 30  wherein said salt of said compound is a sodium salt.  
     
     
         57 . The dosage unit form of  claim 55 , comprising a powder.  
     
     
         58 . The dosage unit form of  claim 55  comprising a tablet.  
     
     
         59 . The dosage unit form of  claim 55  comprising a capsule.  
     
     
         60 . The dosage unit form of  claim 55  comprising a liquid.  
     
     
         61 . The dosage unit form of  claim 55 , wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.  
     
     
         62 . The dosage unit form of  claim 61 , wherein said biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.  
     
     
         63 . The dosage unit form of  claim 34 , wherein said biologically active agent comprises a protein, polypeptide, peptide.  
     
     
         64 . The dosage unit form of  claim 62 , wherein said biologically active agent comprises a mucopolysaccharide.  
     
     
         65 . The dosage unit form of  claim 55 , wherein said dosing vehicle is selected from the group consisting of water, 1,2-propane diol, ethanol, olive oil or any combination thereof.  
     
     
         66 . The dosage unit form of  claim 55 , wherein said biologically active agent is selected from the group consisting of: growth hormone, growth hormone-releasing hormones, interferons, interleukin-1, interleukin-2, insulin, insulin-like growth factor (IGF), heparin, calcitonin, erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), antimicrobials, anti-fungal agents; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof.  
     
     
         67 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises a growth hormone, interferon, insulin, heparin, cromolyn sodium, an antigen, an anti-microbial agent, calcitonin, parathyroid hormone, erythropoietin, and combinations thereof.  
     
     
         68 . The dosage unit form of  claim 66 , wherein said growth hormone comprises human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, or a combination thereof  
     
     
         69 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises interferon.  
     
     
         70 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises insulin.  
     
     
         71 . The dosage unit form of  claim 70 , wherein said insulin comprises porcine insulin, bovine insulin, human insulin, and human recombinant insulin,  
     
     
         72 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises heparin.  
     
     
         73 . The composition of  claim 72 , wherein said heparin comprises low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, heparinoids, dermatans, chondroitins, or a combination thereof.  
     
     
         74 . The dosage unit form of  claim 73 , wherein said biologically active agent comprises low molecular weight heparin.  
     
     
         75 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises cromolyn sodium.  
     
     
         76 . The composition of  claim 75 , wherein said cromolyn sodium comprises sodium chromoglycate, disodium chromoglycate or a combination thereof.  
     
     
         77 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises an antigen.  
     
     
         78 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises an anti-microbial agent.  
     
     
         79 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises calcitonin.  
     
     
         80 . The dosage unit form of  claim 66 , wherein said calcitonin comprises salmon calcitonin, eel calcitonin, human calcitonin or a combination thereof  
     
     
         81 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises parathyroid hormone.  
     
     
         82 . The dosage unit form of  claim 66 , wherein said biologically active agent comprises erythropoietin.  
     
     
         83 . A method for administering a biologically-active agent to an animal, said method comprising administering to said animal the composition of  claim 32 .  
     
     
         84 . The method of  claim 83  wherein said salt of said compound is a sodium salt.  
     
     
         85 . The method of  claim 83 , wherein said biologically-active agent is administered by a route which is: oral, intranasal, sublingual, intraduodenal, subcutaneous, buccal, intracolonic, rectal, vaginal, mucosal, pulmonary, transdermal, intradermal, parenteral, intravenous, intramuscular and intraocular.  
     
     
         86 . The method of  claim 83 , wherein said biologically-active agent is administered by oral route.  
     
     
         87 . The method of  claim 83 , wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.  
     
     
         88 . The method of  claim 83 , wherein said biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.  
     
     
         89 . The method of  claim 88 , wherein said biologically active agent comprises a protein, polypeptide, peptide.  
     
     
         90 . The method of  claim 60 , wherein said biologically active agent comprises a mucopolysaccharide.  
     
     
         91 . The method of  claim 88 , wherein said biologically active agent is selected from the group consisting of: growth hormone, growth hormone-releasing hormones, interferons, interleukin-1, interleukin-2, insulin, insulin-like growth factor (IGF), heparin, calcitonin, erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), antimicrobials, anti-fungal agents; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof.  
     
     
         92 . The method of  claim 91 , wherein said biologically active agent comprises a growth hormone, interferon, insulin, heparin, cromolyn sodium, an antigen, an anti-microbial agent, calcitonin, parathyroid hormone, erythropoietin, and combinations thereof.  
     
     
         93 . The method of  claim 91 , wherein said growth hormone comprises human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, or a combination thereof  
     
     
         94 . The method of  claim 91 , wherein said biologically active agent comprises interferon.  
     
     
         95 . The method of  claim 91 , wherein said biologically active agent comprises insulin.  
     
     
         96 . The method of  claim 95 , wherein said insulin comprises porcine insulin, bovine insulin, human insulin, and human recombinant insulin,  
     
     
         97 . The method of  claim 91 , wherein said biologically active agent comprises heparin.  
     
     
         98 . The composition of  claim 97 , wherein said heparin comprises low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, heparinoids, dermatans, chondroitins, or a combination thereof.  
     
     
         99 . The method of  claim 98 , wherein said biologically active agent comprises low molecular weight heparin.  
     
     
         100 . The method of  claim 91 , wherein said biologically active agent comprises cromolyn sodium.  
     
     
         101 . The composition of  claim 100 , wherein said cromolyn sodium comprises sodium chromoglycate, disodium chromoglycate or a combination thereof.  
     
     
         102 . The method of  claim 91 , wherein said biologically active agent comprises an antigen.  
     
     
         103 . The method of  claim 74 , wherein said biologically active agent comprises an anti-microbial agent.  
     
     
         104 . The method of  claim 74 , wherein said biologically active agent comprises calcitonin.  
     
     
         105 . The method of  claim 74 , wherein said calcitonin comprises salmon calcitonin, eel calcitonin, human calcitonin or a combination thereof  
     
     
         106 . The method of  claim 74 , wherein said biologically active agent comprises parathyroid hormone.  
     
     
         107 . The method of  claim 74 , wherein said biologically active agent comprises erythropoietin.  
     
     
         108 . A method for preparing a composition, said method comprising mixing: 
 (A) at least one active agent;    (B) at least one compound as defined in  claim 30;     and    and (C) optionally, a dosing vehicle.    
     
     
         109 . The method of  claim 108  wherein said salt of said compound is a sodium salt.  
     
     
         110 . The method of  claim 108 , wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.  
     
     
         111 . The method of  claim 110 , wherein said biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.  
     
     
         112 . The method of  claim 111 , wherein said biologically active agent comprises a protein, polypeptide, peptide.  
     
     
         113 . The method of  claim 111 , wherein said biologically active agent comprises a mucopolysaccharide.  
     
     
         114 . The method of  claim 110 , wherein said biologically active agent is selected from the group consisting of: growth hormone, growth hormone-releasing hormones, interferons, interleukin-1, interleukin-2, insulin, insulin-like growth factor (IGF), heparin, calcitonin, erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), antimicrobials, anti-fungal agents; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof.