Stabilizing alkylglycoside compositions and methods thereof
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Publication Number
US-8772231-B2
Publication Date
2014-07-08
Expiration Date
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.
Core Innovation
The invention relates to pharmaceutical compositions and methods for increasing the stability of human insulin and for reducing aggregation and/or immunogenicity of human insulin. The compositions include human insulin and an alkylglycoside stabilizing agent, where the alkylglycoside consists essentially of dodecyl-b2-D-maltoside, and the compositions are stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius.
The disclosed concept also emphasizes stabilization of therapeutic peptides/proteins by using alkylglycoside/saccharide alkyl ester surfactants, including dodecyl b2-D-maltoside and sucrose fatty-acid esters. The stated stabilization outcomes include reducing aggregation, self-aggregation, fibril formation, and immunogenicity while preserving biological activity.
A further aspect is that the alkylglycoside is described with b1/b2 anomer purity, with b2 anomer and minimal b1 contamination stated to substantially improve stabilization. The document also describes non-aggregated aqueous insulin solutions and manufacturing approaches that admix alkylglycoside in aqueous insulin to produce solutions stable for at least one month at about 25 to 37 degrees Celsius.
Claims Coverage
The provided independent claims cover six distinct aspects of using an alkylglycoside with human insulin: a pharmaceutical composition for stability, aggregation, or immunogenicity reduction; a method of increasing stability by admixing; a method of reducing aggregation or immunogenicity by admixing; manufacturing a non-aggregated aqueous solution stable under storage conditions; and compositions and methods that specify at least 99% dodecyl-b2-D-maltoside. Across the independent claims, the stability requirement is repeatedly defined as at least one month when stored at about 25 to 37 degrees Celsius.
Stabilizing pharmaceutical composition with dodecyl-b2-D-maltoside
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-b2-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius.
Admixing method to increase insulin stability
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-b2-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.
Admixing method to reduce insulin aggregation or immunogenicity
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-b2-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.
Manufacturing non-aggregated aqueous insulin solution with dodecyl-b2-D-maltoside
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-b2-D-maltoside, and wherein the solution is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius.
High-purity dodecyl-b2-D-maltoside composition for insulin stabilization
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-b2-D-maltoside, and wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius.
High-purity dodecyl-b2-D-maltoside method to increase insulin stability
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-b2-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.
Across the independent claims, the central inventive approach is the use of an alkylglycoside whose core species is dodecyl-b2-D-maltoside, either "consists essentially of" that species or "comprises at least 99%" of it, together with human insulin to obtain a formulation or solution that remains stable for at least one month at about 25 to 37 degrees Celsius, while targeting reduced aggregation and/or reduced immunogenicity.
Stated Advantages
Increases the stability of human insulin.
Reduces aggregation of human insulin.
Reduces immunogenicity of human insulin.
Provides compositions stable for at least one month when stored at about 25 to 37 degrees Celsius.
Documented Applications
Pharmaceutical compositions and storage-relevant formulations for human insulin intended to increase stability and reduce aggregation and/or immunogenicity.
Methods for increasing insulin stability by admixing human insulin with an alkylglycoside stabilizing agent.
Methods for reducing insulin aggregation or immunogenicity by admixing human insulin with an alkylglycoside agent.
Manufacturing a non-aggregated aqueous insulin solution by admixing alkylglycoside in aqueous insulin.
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