Stabilizing alkylglycoside compositions and methods thereof
View Patent ↗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 a cyclic polypeptide.
1. A pharmaceutical composition comprising:
a) a therapeutically effective amount of a cyclic polypeptide; and
b) at least one alkylglycoside, wherein the at least one alkylglycoside comprises dodecyl-β-D-maltoside,
with the proviso that the composition is free of calcitonin.
2. The composition of claim 1 , wherein the composition is stable for at least one month when stored at temperatures from about 25° to 37° Celsius.
3. The composition of claim 2 , wherein the composition is stable for at least two months.
4. The composition of claim 1 , wherein the composition is stable for at least one year when stored at about 4° Celsius.
5. The composition of claim 1 , further comprising a vasodilator agent.
6. The composition of claim 1 , further comprising ethylenediaminetetraacetic acid (EDTA).
7. The composition of claim 1 , further comprising benzalkonium chloride or chloroethanol.
8. The composition of claim 1 , further comprising a buffering agent.
9. 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.
10. 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.
11. The composition of claim 1 , further comprising a modulatory agent of epithelial junction physiology.
12. The composition of claim 1 , wherein the composition further comprises a bulking agent selected from the group consisting of albumin, collagen, alginate, and mannitol.
13. The composition of claim 1 , wherein the composition is formulated for intranasal, pulmonary, or buccal delivery.
14. The composition of claim 1 , wherein the composition is an aqueous liquid.
15. A method for increasing stability of a cyclic polypeptide comprising admixing the cyclic polypeptide and at least one alkylglycoside to form a composition, wherein the alkylglycoside comprises dodecyl-β-D-maltoside, and with the proviso that the composition is free of calcitonin, thereby increasing the stability of the cyclic polypeptide.
16. A method for decreasing immunogenicity of a cyclic polypeptide upon administration to a subject comprising:
a) admixing the cyclic polypeptide, and at least one alkylglycoside to form a composition, wherein the alkylglycoside comprises dodecyl-β-D-maltoside, and with the proviso that the composition is free of calcitonin; and
b) administering the composition to the subject, thereby decreasing immunogenicity of the cyclic polypeptide upon administration to the subject.
17. The method of claim 16 , wherein the subject is a mammal.
18. The method of claim 17 , wherein the mammal is a human.