Arylsulfanyl compounds and compositions for delivering active agents

Abstract

Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are also provided.

1 . A compound represented by the formula: 
       
         
           
           
               
               
           
         
         wherein 
         A is a branched or unbranched C 1 -C 13  alkylene, C 3 -C 13  arylene group, or a C 3 -C 13  alkyl(arylene) group, 
         R 1 -R 5  are independently a hydrogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, C 2 -C 4  alkenyl, halogen or hydroxy group with the proviso that when A is an unsubstituted C 1  group, R 2  and R 3 , or R 3  and R 4  are not both chlorine, or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof. 
     
     
         3 . A composition comprising:
 (A) an active agent; and   (B) at least one compound selected from the group consisting of   
       
         
           
           
               
               
           
         
       
       wherein 
       A is a branched or unbranched C 1 -C 13  alkylene, C 3 -C 13  arylene group, or a C 3 -C 13  alkyl(arylene) group, 
       R 1 -R 5  are independently a hydrogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, C 2 -C 4  alkenyl, halogen or hydroxy group, or pharmaceutically acceptable salts thereof. 
     
     
         4 . A composition comprising:
 (A) at least one active agent; and   (B) at least one compound selected from the group consisting of   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof. 
     
     
         5 . The composition of  claim 3 , wherein the active agent is selected from the group consisting of a biologically active agent, a chemically active agent, and a combination thereof. 
     
     
         6 . The composition of  claim 5 , wherein the biologically active agent is a protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid. 
     
     
         7 . The composition of  claim 6 , wherein the biologically active agent is selected from the group consisting of: BIBN-4096BS, growth hormones, human growth hormones recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone releasing hormones, growth hormone releasing factor, glucagon, interferons, α-interferon, β-interferon, γ-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor (IGF), IGF-1, heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human 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, thrombopoeitin, filgrastim. postaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, glucagon-like peptide 1 (GLP-1), antimicrobials, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; gallium or gallium salts; glucagons; zanamivir, sumatriptan, almotriptan, naratriptan, rizatriptan, frovatriptan, eletriptan, caspofungin acetate, CPHPC, RNAi and any combination thereof. 
     
     
         8 . The composition of  claim 7 , wherein the biologically active agent is selected from insulin, leutenizing-hormone releasing hormone, heparin, recombinant human growth hormone, glucagon, caspofungin acetate, calcitonin, PTH, zanamivir, erythropoietin, analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof. 
     
     
         9 . The composition of  claim 7 , wherein the biologically active agent comprises insulin. 
     
     
         10 . A dosage unit form comprising:
 (A) a delivery agent of  claim 3 ; and   (B) an active agent; and   (C) (a) an excipient,
 (b) a diluents, 
 (c) a disintegrant, 
 (d) a lubricant, 
 (e) a plasticizer, 
 (f) a colorant, 
 (g) a dosing vehicle, or 
 (h) any combination thereof. 
   
     
     
         11 . The dosage unit form of  claim 10 , wherein the active agent is selected from the group consisting of a biologically active agent, a chemically active agent, and a combination thereof. 
     
     
         12 . The dosage unit form of  claim 11 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid. 
     
     
         13 . The dosage unit form of  claim 12 , wherein the biologically active agent is selected from the group consisting of: argatroban, BIBN-4096BS, growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone releasing hormones, growth hormone releasing factor, interferons, glucagon, α-interferon, β-interferon, γ-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor, insulin-like growth factor-1, heparin, un fractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin; erythropoietin, atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoeitin, filgrastim. postaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine, parathyroid hormone, fragments of PTH, glucagon-like peptide 1 (GLP-1), antimicrobials, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds; gallium or gallium salts; glucagons, zanamivir, sumatriptan, almotriptan, naratriptan, rizatriptan, frovatriptan, eletriptan, capsofungin acetate, CPHPC, RNAi and any combination thereof. 
     
     
         14 . The dosage unit form of  claim 13 , wherein the biologically active agent comprises insulin, insulin, Leutenizing-hormone releasing hormone, heparin, Recombinant Human Growth Hormone, glucagon, caspofungin acetate, calcitonin, PTH, zanamivir, erythropoietin or combinations thereof. 
     
     
         15 . The dosage unit form of  claim 12 , wherein the active agent comprises insulin. 
     
     
         16 . The dosage unit form of  claim 12 , wherein the active agent comprises glucagon. 
     
     
         17 . The dosage unit form of  claim 12 , wherein the dosage unit form comprises a dosing vehicle comprising a tablet, a capsule, a powder, or a liquid. 
     
     
         18 . The dosage unit form of  claim 19 , wherein the dosing vehicle is a liquid selected from the group consisting of water, 1,2-propane diol, ethanol, and any combination thereof. 
     
     
         19 . A method for administering a biologically-active agent to an animal in need of the agent, the method comprising administering orally to the animal the composition of  claim 3 . 
     
     
         20 . A method for preparing a composition comprising mixing:
 (A) at least one active agent;   (B) at least one compound of  claim 1 ; and   (C) optionally, a dosing vehicle.