# US 8,772,231 B2 · Stabilizing alkylglycoside compositions and methods thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,772,231 B2 - Document ID: US8772231B2 - Status: Granted - Kind: B2 - Application number: 12/896,640 - Filed: 2010-10-01 - Published: 2011-01-27 - Granted: 2014-07-08 - Earliest claimed: 2006-06-23 - Assignees: Aegis Therapeutics, LLC - Applicants: Edward T. Maggio - Inventors: Edward T. Maggio - Web page: https://patentgrep.com/patent/US8772231B2 ## CPC - A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) - A61K 9/0043: {Nose} - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 38/162: {from virus} - A61K 38/1816: {Erythropoietin [EPO]} - A61K 38/21: Interferons {[IFN]} - A61K 38/27: Growth hormone [GH], i.e. somatotropin - A61K 38/28: Insulins - A61K 38/29: Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of insulin or an analog thereof. ## Claims ### Claim 1 A pharmaceutical composition for increasing the stability, reducing aggregation or reducing immunogenicity of human insulin comprising: human insulin; and an alkylglycoside, wherein the alkylglycoside stabilizes, reduces aggregation, or reduces immunogenicity of the human insulin, wherein the alkylglycoside consists essentially of dodecyl-β-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius. ### Claim 2 (depends on 1) The composition of claim 1, further comprising a buffering agent. ### Claim 3 (depends on 1) The composition of claim 1, further comprising a mucosal delivery-enhancing agent selected from the group consisting of an aggregation inhibitory agent, a charge-modifying agent, a pH control agent, a degradative enzyme inhibitory agent, a mucolytic or mucus clearing agent, a chitosan, and a ciliostatic agent. ### Claim 4 (depends on 1) The composition of claim 1, further comprising a membrane penetration-enhancing agent selected from the group consisting of a surfactant, a bile salt, a phospholipid additive, a mixed micelle, a liposome, a carrier, an alcohol, an enamine, a nitric oxide donor compound, a long-chain amphipathic molecule, a small hydrophobic penetration enhancer, a sodium or a salicylic acid derivative, a glycerol ester of acetoacetic acid, a cyclodextrin or beta-cyclodextrin derivative, a medium-chain fatty acid, a chelating agent, an amino acid or salt thereof, an N-acetylamino acid or salt thereof, an enzyme degradative to a selected membrane component and any combination thereof. ### Claim 5 (depends on 1) The composition of claim 1, wherein the composition is in a lyophilized form. ### Claim 6 (depends on 5) The composition of claim 5, wherein the lyophilized composition retains greater than 50% biological activity upon reconstitution. ### Claim 7 (depends on 1) The composition of claim 1, wherein the composition is stable for at least two months. ### Claim 8 (depends on 1) The composition of claim 1, wherein the composition is stable for at least one year when stored at about 4 degrees Celsius. ### Claim 9 (depends on 1) The composition of claim 1, wherein the stability of the composition is determined by determining the bioactivity in an in vivo or in vitro assay. ### Claim 10 (depends on 1) The composition of claim 1, wherein the composition is formulated for intransal, pulmonary, or buccal delivery. ### Claim 11 (depends on 1) The composition of claim 1, with the proviso that the composition does not include a preservative. ### Claim 12 (depends on 1) The composition of claim 1, wherein the composition is stable at room temperature for at least 60 days. ### Claim 13 A method for increasing the stability of human insulin comprising: admixing human insulin and a stabilizing agent to form a composition, wherein the stabilizing agent is an alkylglycoside, wherein the alkylglycoside consists essentially of dodecyl-β-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius, thereby increasing the stability of human insulin. ### Claim 14 (depends on 13) The method of claim 13, wherein the composition further comprises a buffer. ### Claim 15 (depends on 13) The method of claim 13, wherein the composition further comprises a mucosal delivery-enhancing agent selected from the group consisting of an aggregation inhibitory agent, a charge-modifying agent, a pH control agent, a degradative enzyme inhibitory agent, a mucolytic or mucus clearing agent, a chitosan, and a ciliostatic agent. ### Claim 16 (depends on 13) The method of claim 13, wherein the composition further comprises a membrane penetration-enhancing agent selected from the group consisting of a surfactant, a bile salt, a phospholipid additive, a mixed micelle, a liposome, a carrier, an alcohol, an enamine, a nitric oxide donor compound, a long-chain amphipathic molecule, a small hydrophobic penetration enhancer, a sodium or a salicylic acid derivative, a glycerol ester of acetoacetic acid, a cyclodextrin or beta-cyclodextrin derivative, a medium-chain fatty acid, a chelating agent, an amino acid or salt thereof, an N-acetylamino acid or salt thereof, an enzyme degradative to a selected membrane component and any combination thereof. ### Claim 17 (depends on 13) The method of claim 13, wherein the composition is in a lyophilized form. ### Claim 18 (depends on 13) The method of claim 13, with the proviso that the composition does not include a preservative. ### Claim 19 (depends on 13) The method of claim 13, wherein the composition is stable at room temperature for at least 60 days. ### Claim 20 A method for reducing aggregation or immunogenicity of human insulin comprising: admixing human insulin, and an agent to form a composition, wherein the agent is an alkylglycoside, wherein the alkylglycoside consists essentially of dodecyl-β-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius, thereby reducing aggregation or immunogenicity of human insulin. ### Claim 21 (depends on 20) The method of claim 20, wherein the composition further comprises a buffering agent. ### Claim 22 (depends on 20) The method of claim 20, wherein the composition further comprises EDTA. ### Claim 23 (depends on 20) The method of claim 20, wherein the composition further comprises a mucosal delivery-enhancing agent selected from the group consisting of an aggregation inhibitory agent, a charge-modifying agent, a pH control agent, a degradative enzyme inhibitory agent, a mucolytic or mucus clearing agent, a chitosan, and a ciliostatic agent. ### Claim 24 (depends on 20) The method of claim 20, wherein the composition further comprises a membrane penetration-enhancing agent selected from the group consisting of a surfactant, a bile salt, a phospholipid additive, a mixed micelle, a liposome, a carrier, an alcohol, an enamine, a nitric oxide donor compound, a long-chain amphipathic molecule, a small hydrophobic penetration enhancer, a sodium or a salicylic acid derivative, a glycerol ester of acetoacetic acid, a cyclodextrin or beta-cyclodextrin derivative, a medium-chain fatty acid, a chelating agent, an amino acid or salt thereof, an N-acetylamino acid or salt thereof, an enzyme degradative to a selected membrane component and any combination thereof. ### Claim 25 (depends on 20) The method of claim 20, wherein the composition is in a lyophilized form. ### Claim 26 (depends on 25) The method of claim 25, wherein the composition retains greater than 50% biological activity upon reconstitution. ### Claim 27 (depends on 20) The method of claim 20, with the proviso that the composition does not include a preservative. ### Claim 28 (depends on 20) The method of claim 20, wherein the composition is stable at room temperature for at least 60 days. ### Claim 29 A method of manufacturing a non-aggregated aqueous solution of human insulin comprising admixing an alkylglycoside in an aqueous solution of human insulin, wherein the alkylglycoside consists essentially of dodecyl-β-D-maltoside, and wherein the solution is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius. ### Claim 30 (depends on 29) The method of claim 29, wherein the solution is concentrated by ultrafiltration, affinity chromatography, selective absorption chromatography, ion exchange chromatography, lyophilization, dialysis, precipitation or salting-out. ### Claim 31 A pharmaceutical composition for increasing the stability, reducing aggregation or reducing immunogenicity of human insulin comprising: human insulin; and an agent comprising at least one alkylglycoside, wherein the alkylglycoside stabilizes, reduces aggregation, or reduces immunogenicity of the human insulin, wherein the alkylglycoside comprises at least 99% dodecyl-β-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius. ### Claim 32 (depends on 31) The composition of claim 31, wherein the composition is stable for at least 60 days. ### Claim 33 A method for increasing the stability of human insulin comprising: admixing human insulin and a stabilizing agent to form a composition, wherein the stabilizing agent comprises an alkylglycoside, wherein the alkylglycoside comprises at least 99% dodecyl-β-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius, thereby increasing the stability of human insulin. ### Claim 34 (depends on 33) The method of claim 33, wherein the composition is stable for at least 60 days.