JPWO2019226685A5 - - Google Patents

Claims (32)

A composition for treating pulmonary hypertension in an individual comprising nanoparticles comprising an mTOR inhibitor and a carrier protein, the composition comprising a step of administering the composition to the individual. The composition, wherein the dose of the mTOR inhibitor is about 10 mg / m ² or less. The composition according to claim 1, wherein the dose of the mTOR inhibitor in the composition is about 0.1 mg / m ² or more. The composition according to claim 2, wherein the dose of the mTOR inhibitor in the composition is about 5 mg / m ² or more. The composition according to claim 1 or 2, wherein the dose of the mTOR inhibitor in the composition is about 5 mg / m ² or less. The composition according to claim 4, wherein the dose of the mTOR inhibitor in the composition is about 5 mg / m ² . The composition according to any one of claims 1 to 5, wherein the concentration of the mTOR inhibitor in blood is at least about 2 ng / ml 5 days after administration of the nanoparticle composition. The composition according to any one of claims 1 to 6, wherein the concentration of the mTOR inhibitor in blood is about 20 ng / ml or less 7 days after administration of the nanoparticle composition. The composition according to any one of claims 1 to 7, wherein the nanoparticle composition is administered at least once a week. The composition according to any one of claims 1 to 7, wherein the nanoparticle composition is administered at least once a week. The composition according to claim 9, wherein the nanoparticle composition is administered once a week. The composition according to claim 9, wherein the nanoparticle composition is administered once every two weeks for two out of three weeks or three out of four weeks. The composition according to any one of claims 1 to 11, wherein the nanoparticle composition is administered for at least about 4 weeks. The composition according to any one of claims 1 to 12, wherein the pulmonary hypertension is pulmonary arterial hypertension. The pulmonary hypertension is idiopathic pulmonary arterial hypertension (IPAH), hereditary pulmonary arterial hypertension (HPAH), drug and toxin-induced PAH, PAH associated with connective tissue disease, and PAH associated with congenital cardiac defects. The composition according to any one of claims 1 to 13, which is selected from the group consisting of. 13. The composition of claim 13, wherein the individual has WHO functional classification class III or IV pulmonary arterial hypertension. The composition according to any one of claims 1 to 15, wherein the mTOR inhibitor is the only pharmaceutically active agent administered to the individual that is useful in the treatment of pulmonary hypertension. The composition according to any one of claims 1 to 16, wherein the composition comprises more than about 50% of the mTOR inhibitor in the form of nanoparticles. The composition according to any one of claims 1 to 17, wherein the nanoparticle composition is administered parenterally. The composition according to claim 18, wherein the nanoparticle composition is administered intravenously. The composition according to claim 18, wherein the nanoparticle composition is subcutaneously administered. The composition according to any one of claims 1 to 20, wherein the mTOR inhibitor is rapamycin. The composition according to any one of claims 1 to 21, wherein the individual has received at least one previous treatment for pulmonary hypertension. 22. The composition of claim 22, wherein the individual has received at least two previous treatments for pulmonary hypertension. The previous treatment comprises administration of a drug selected from the group consisting of prostacycline analogs, endothelin-1 receptor antagonists, phosphodiesterase 5 (PDE-5) inhibitors and soluble guanylate cyclase (sGC) stimulators. 22 or the composition according to claim 23. The composition according to any one of claims 22 to 24, wherein the individual has progressed during the previous treatment. The composition according to any one of claims 1 to 25, wherein the carrier protein is albumin. 26. The composition of claim 26, wherein the albumin is human serum albumin. The composition according to any one of claims 1 to 27, wherein the nanoparticles in the composition have an average diameter of about 200 nm or less. The composition according to any one of claims 1 to 28, wherein the carrier protein in the nanoparticles has a weight ratio of less than about 18: 1 to the mTOR inhibitor. The composition according to any one of claims 1 to 29, wherein the individual is a human. Nanoparticles comprising (a) mTOR inhibitor and carrier protein, wherein the dose of said mTOR inhibitor in the composition is about 10 mg / m ² or less, and (b) pharmaceutically acceptable. A unit dosage form for the treatment of pulmonary hypertension, including with carriers. The kit is a nanoparticle comprising (a) an mTOR inhibitor and a carrier protein, wherein the dose of the mTOR inhibitor in the kit is about 10 mg / m ² or less, and (b) pulmonary hypertension. A kit comprising instructions for using the kit in the treatment of the disease.