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 peptide, polypeptide, or variant thereof, for example insulin and Peptide T or analog thereof.
1. A pharmaceutical composition for reducing aggregation or reducing immunogenicity of growth hormone comprising:
growth hormone;
a buffering agent; and
an alkylglycoside;
wherein the alkylglycoside is selected from the group consisting of dodecyl maltoside, tridecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate.
2. The composition of claim 1 , wherein the alkylglycoside has a critical micelle concentration (CMC) of less than about 1 mM.
3. 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.
4. The composition of claim 3 , further comprising benzalkonium chloride or chloroethanol.
5. 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.
6. The composition of claim 1 , further comprising a modulatory agent of epithelial junction physiology, a vasodilator agent or a selective transport-enhancing agent.
7. The composition of claim 1 , wherein the composition is in a lyophilized form.
8. The composition of claim 7 , wherein the lyophilized composition retains greater than 50% biological activity upon reconstitution.
9. The composition of claim 1 , wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius.
10. The composition of claim 1 , wherein the composition is stable for at least one year when stored at about 4 degrees Celsius.
11. The composition of claim 1 , wherein the growth hormone bioactivity is measured in an in vivo or in vitro assay.
12. The composition of claim 7 , wherein the lyophilized composition further comprises a bulking agent selected from the group consisting of albumin, collagen, alginate, and mannitol.
13. The composition of claim 7 , wherein the lyophilized composition is reconstituted prior to administering to a mammalian subject.
14. The composition of claim 1 , which is stable to denaturation as determined by lack of increased light scatter for at least 2 weeks upon agitation at 150 RPM at 37 degrees Celsius.
15. A pharmaceutical composition comprising:
growth hormone;
a buffering agent; and
an alkylglycoside, wherein the composition is formulated to be stable to denaturation as determined by lack of increased light scatter for at least 2 weeks upon agitation at 150 RPM at 37 degrees Celsius, and wherein the alkylglycoside is selected from the group consisting of dodecyl maltoside, tridecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate.