Drug-oligomer conjugates with polyethylene glycol components
View Patent ↗The present invention relates generally to hydrolyzable drug-oligomer conjugates, pharmaceutical compositions comprising such conjugates, and to methods for making and using such conjugates and pharmaceutical compositions. For example, a conjugate of insulin, PEG, and oleic acid can be orally administered.
1. A drug-oligomer conjugate having the formula:
D—H p
wherein D is a therapeutic drug moiety selected from the group consisting of insulin, insulin lispro, and a functional equivalent of insulin;
H is a PEG polymer having from 1 to 7 PEG units; and
p is a number from 1 to the maximum number of covalent bonding sites at which —H can form a bond with D.
2. The drug-oligomer conjugate of claim 1 , wherein the D—H bonds are non-hydrolyzable.
3. The drug-oligomer conjugate of claim 1 , wherein the D—H bonds are selected from the group consisting of carbamate, amide and secondary amine.
4. The drug-oligomer conjugate of claim 1 , wherein H is a PEG polymer having 2, 3, 4 or 5 PEG units.
5. The drug-oligomer conjugate of claim 1 , wherein H is a PEG polymer having 3 PEG units.
6. A drug-PEG conjugate having the formula:
D—H p
wherein D is selected from the group consisting of insulin, insulin lispro, and a functional equivalent of insulin;
H is a PEG polymer having from 1 to 7 PEG units; and
p is a number from 1 to the maximum number of covalent bonding sites at which
—H can form a bond with D,
wherein the drug-PEG conjugate has enhanced activity in comparison with a corresponding unconjugated insulin molecule, unconjugated insulin lispro molecule or unconjugated functional equivalent thereof.
7. A method of treating an insulin deficiency comprising causing the drug-oligomer conjugate of claim 1 to circulate in the bloodstream of a subject.
8. A method of treating an insulin deficiency comprising causing the drug-oligomer conjugate of claim 2 to circulate in the bloodstream of a subject.
9. A method of treating an insulin deficiency comprising causing the drug-oligomer conjugate of claim 3 to circulate in the bloodstream of a subject.
10. A method of treating an insulin deficiency comprising causing the drug-oligomer conjugate of claim 4 to circulate in the bloodstream of a subject.
11. A method of treating an insulin deficiency comprising causing the drug-oligomer conjugate of claim 5 to circulate in the bloodstream of a subject.
12. A method of treating an insulin deficiency comprising causing the drug-PEG conjugate of claim 6 to circulate in the bloodstream of a subject.