ARYLSULFANYL COMPOUNDS AND COMPOSITIONS FOR DELIVERING ACTIVE AGENTS
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.