Combined sirolimus and nintedanib therapy for vascular lesions and hereditary hemorrhagic telangiectasia
View Patent ↗Methods and pharmaceutical compositions comprising one or more mTOR inhibitors such as sirolimus and one or more receptor tyrosine kinase inhibitors such as nintedanib are disclosed for treating vascular lesions and hereditary hemorrhagic telangiectasia.
1. A method of treating one or more of an arteriovenous malformation, a vascular lesion and bleeding in a subject who has hereditary hemorrhagic telangiectasia (HHT) comprising administering to the subject sirolimus and nintedanib in therapeutically effective amounts to treat an arteriovenous malformation, a vascular lesion and/or bleeding in the subject, wherein sirolimus and nintedanib are the only therapeutic agents administered to the subject.
2. A method of treating hereditary hemorrhagic telangiectasia (HHT) in a subject in need thereof comprising administering to the HHT subject sirolimus and nintedanib in therapeutically effective amounts to treat abnormal blood vessel formation in the subject, wherein sirolimus and nintedanib are the only therapeutic agents administered to the subject.
3. The method of claim 1 , wherein sirolimus and nintedanib are co-administered to the subject.
4. The method of claim 3 , wherein sirolimus and nintedanib are co-administered in the same formulation.
5. The method of claim 1 , wherein sirolimus and nintedanib are administered sequentially.
6. The method of claim 5 , wherein sirolimus and nintedanib are administered within 24 hours of each other.
7. The method of claim 1 , wherein tacrolimus is administered to the subject in a therapeutically effective amount prior to administration of sirolimus and nintedanib.
8. The method of claim 1 , wherein administration is by oral administration, by nasal administration, by rectal administration or transdermally.
9. The method of claim 1 , wherein the subject is a human.
10. The method of claim 1 , wherein sirolimus is administered in a dose of 0.03-1 mg/kg body weight/day.
11. The method of claim 10 , wherein sirolimus is administered in a dose of 0.04 mg/kg body weight/day.
12. The method of claim 1 , wherein nintedanib is administered in a dose of 0.02-5 mg/kg body weight/day.
13. The method of claim 12 , wherein nintedanib is administered in a dose of 0.5 mg/kg body weight/day.
14. The method of claim 7 , wherein tacrolimus is administered in a dose of 0.03-1 mg/kg body weight/day.
15. The method of claim 1 , wherein bleeding occurs in the nose, oral mucosa, lung, liver, gastrointestinal tract, brain and/or retina.
16. The method of claim 2 , wherein sirolimus and nintedanib are co-administered to the subject.
17. The method of claim 16 , wherein sirolimus and nintedanib are co-administered in the same formulation.
18. The method of claim 2 , wherein sirolimus and nintedanib are administered sequentially.
19. The method of claim 18 , wherein sirolimus and nintedanib are administered within 24 hours of each other.
20. The method of claim 2 , wherein tacrolimus is administered to the subject in a therapeutically effective amount prior to administration of sirolimus and nintedanib.
21. The method of claim 2 , wherein the subject is a human.
22. The method of claim 2 , wherein sirolimus is administered in a dose of 0.03-1 mg/kg body weight/day.
23. The method of claim 2 , wherein nintedanib is administered in a dose of 0.02-5 mg/kg body weight/day.
24. The method of claim 20 , wherein tacrolimus is administered in a dose of 0.03-1 mg/kg body weight/day.