Pentaaza macrocyclic ring complexes possessing oral bioavailability
View Patent ↗Aspects of the present disclosure relate to compounds which have enhanced oral bioavailability. A transition metal complex includes a transition metal coordinated by a macrocycle comprising the pentaaza 15-membered macrocyclic ring corresponding to Formula A and two axial ligands having the formula —OC(O)X 1 . each of the two axial ligands has the formula —OC(═O)X 1 wherein each X 1 is independently substituted or unsubstituted phenyl or —C(—X 2 )(—X 3 )(—X 4 ); each X 2 is independently substituted or unsubstituted phenyl, or substituted or unsubstituted alkyl; each X 3 is independently hydrogen, hydroxyl, alkyl, amino, —X 5 C(═O)R 13 where X 5 is NH or O, and R 13 is C 1 -C 18 alkyl, substituted or unsubstituted aryl or C 1 -C 18 aralkyl, or —OR 14 , where R 14 is C 1 -C 18 alkyl, substituted or unsubstituted aryl or C 1 -C 18 aralkyl, or together with X 4 is (═O); and each X 4 is independently hydrogen or together with X 3 is (═O).
1. A pentaaza macrocyclic ring complex corresponding to the following formula:
2. A pharmaceutical composition comprising the pentaaza macrocyclic ring complex of claim 1 and a pharmaceutically acceptable excipient.
3. The pharmaceutical composition of claim 2 wherein the composition comprises at least one of mono/diglyceride and triglycerides of caprylic/capric acids.
4. The pharmaceutical composition of claim 3 , wherein the composition comprises a mixture of caprylic/capric acid triglycerides.
5. The pharmaceutical composition of claim 2 wherein the pharmaceutical composition is suitable for oral administration to a human subject.
6. The pharmaceutical composition of claim 2 wherein the pharmaceutical composition is in a solid or semi-solid dosage form.
7. The pharmaceutical composition of claim 2 wherein the pharmaceutical composition is in the form of at least one selected from the group consisting of a tablet, gelatin capsule, HPMC capsule, gel and suspension suitable for oral administration.
8. The pharmaceutical composition of claim 2 wherein the pharmaceutical composition comprises an enteric coating layer.
9. A pharmaceutical composition for oral administration comprising:
a pentaaza macrocyclic ring complex corresponding to the following formula:
a pharmaceutically acceptable excipient comprising a mixture of caprylic/capric acid triglycerides; and
an enteric coated capsule comprising hydroxypropylmethylcellulose (HPMC),
wherein the capsule comprises the pentaaza macrocyclic ring complex and pharmaceutically acceptable excipient contained therein.