Compositions for intranasal delivery of human insulin and uses thereof

Abstract

What is described is a pharmaceutical formulation for intranasal delivery of insulin to a patient, comprising an aqueous mixture of human insulin, a solubilizing agent, a surface active agent, and a thickening agent, wherein said formulation provides a ultra-rapid acting profile to regular human insulin.

1 .- 88 . (canceled) 
     
     
         89 . An aqueous pharmaceutical formulation comprising an aqueous mixture of an insulin molecule, a solubilizing agent, a surface active agent, and a thickening agent, wherein the pharmaceutical formulation confers an ultra-rapid acting insulin profile to a non-ultra-rapid acting insulin. 
     
     
         90 . The pharmaceutical formulation of  claim 89 , wherein the pharmaceutical formulation is able to provide peak serum levels of the administered human insulin within at least about 40 minutes and glucose troughs within at least 60 minutes post-administration of the pharmaceutical formulation to the patient. 
     
     
         91 . The pharmaceutical formulation of  claim 89 , wherein the insulin molecule is selected from group consisting of a natural human insulin; LysB3, GluB29-human insulin; LysB3, IleB28 human insulin; GlyA21, HisB31, HisB32-human insulin; AspB10-human insulin, LysB28, and ProB29-human insulin. 
     
     
         92 . The pharmaceutical formulation of  claim 89 , wherein the solubilizing agent is selected from the group consisting of a cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutylether β-cyclodextrin, methyl-β-cyclodextrin, and mixtures thereof. 
     
     
         93 . The pharmaceutical formulation of  claim 89 , wherein the surface-active agent is selected from the group consisting of nonionic polyoxyethylene ether, fusidic acid and derivatives thereof, sodium taurodihydrofusidate, L-α-phosphatidylcholine didecanoyl, polysorbate 80, polysorbate 20, polyethylene glycol, cetyl alcohol, polyvinylpyrolidone, polyvinyl alcohol, lanolin alcohol, sorbitan monooleate, and mixtures thereof. 
     
     
         94 . The pharmaceutical formulation of  claim 89 , wherein the thickening agent is selected from a group consisting of gelatin, hydroxypropyl methylcellulose, methylcellulose, a carbomer, carboxymethylcellulose, and mixtures thereof. 
     
     
         95 . An aqueous pharmaceutical formulation comprising an aqueous mixture of an insulin molecule, a solubilizing agent, a surface active agent, and a thickening agent, wherein the insulin molecule is selected from the group consisting of a natural human insulin; LysB3, GluB29-human insulin; LysB3, IleB28 human insulin; GlyA21, HisB31, HisB32-human insulin; AspB10-human insulin, LysB28, and ProB29-human insulin. 
     
     
         96 . The pharmaceutical formulation of  claim 95 , wherein the solubilizing agent is selected from the group consisting of a cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, methyl-β-cyclodextrin, and mixtures thereof. 
     
     
         97 . The pharmaceutical formulation of  claim 95 , wherein the surface-active agent is selected from the group consisting of nonionic polyoxyethylene ether, fusidic acid and its derivatives, sodium taurodihydrofusidate, L-α-phosphatidylcholine didecanoyl, polysorbate 80, polysorbate 20, polyethylene glycol, cetyl alcohol, polyvinylpyrolidone, polyvinyl alcohol, lanolin alcohol, sorbitan monooleate, and mixtures thereof. 
     
     
         98 . The pharmaceutical formulation of  claim 95 , where the thickening agent is selected from a group consisting of gelatin, hydroxypropyl methylcellulose, methylcellulose, a carbomer, carboxymethylcellulose, and mixtures thereof. 
     
     
         99 . The pharmaceutical formulation of  claim 95 , wherein the formulation has a pH of about 7. 
     
     
         100 . The pharmaceutical formulation of  claim 95 , wherein the formulation after administration to a subject provides a bioavailability of insulin in the patient of greater than about 15%. 
     
     
         101 . A method of treating a metabolic syndrome in a human by administration of the pharmaceutical formulation of  claim 89  to the human, wherein the metabolic syndrome is selected from the group consisting of Type 2 diabetes, Type 1 diabetes, impaired glucose tolerance, hyperglycemia, metabolic syndrome (syndrome X and/or insulin resistance syndrome), glucosuria, metabolic acidosis, arthritis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, short stature due to growth hormone deficiency, infertility due to polycystic ovary syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome; short bowel syndrome; and the prevention of disease progression in Type 2 diabetes. 
     
     
         102 . A method of treating a metabolic syndrome in a human by administration of the pharmaceutical formulation of  claim 95  to the human, wherein the metabolic syndrome is selected from the group consisting of Type 2 diabetes, Type 1 diabetes, impaired glucose tolerance, hyperglycemia, metabolic syndrome (syndrome X and/or insulin resistance syndrome), glucosuria, metabolic acidosis, arthritis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, short stature due to growth hormone deficiency, infertility due to polycystic ovary syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome; short bowel syndrome; and the prevention of disease progression in Type 2 diabetes.