The disclosure describes nanocarried and/or microcarried jasmonate compounds and their pharmaceutical compositions, as well as use thereof for treating or preventing angiogenesis-related or NF-κB-related disorders. Also disclosed are methods of making the nanocarried and/or microcarried compounds and their compositions.

The disclosure describes nanocarried and/or microcarried jasmonate compounds and their pharmaceutical compositions, as well as use thereof for treating or preventing angiogenesis-related or NF-κB-related disorders. Also disclosed are methods of making the nanocarried and/or microcarried compounds and their compositions.

The present invention relates to high doses of macitentan (INN), i.e. propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof for use in the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients. Moreover, the present invention relates to the use of high doses of macitentan for the manufacture of a medicament as well as to a method for the treatment of said diseases. Further, the present invention relates to a dosage regimen as well as to a combination of macitentan with one or more phosphodiesterase type 5 (PDE5) inhibitors, prostacyclin analogues, prostacyclin receptor agonists or soluble guanylate cyclase stimulators. Besides, the present invention relates to a pharmaceutical composition for the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients comprising a high dose of macitentan. Moreover, the present invention relates to the use of high doses aprocitentan for the same purpose.

The present invention relates to high doses of macitentan (INN), i.e. propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof for use in the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients. Moreover, the present invention relates to the use of high doses of macitentan for the manufacture of a medicament as well as to a method for the treatment of said diseases. Further, the present invention relates to a dosage regimen as well as to a combination of macitentan with one or more phosphodiesterase type 5 (PDE5) inhibitors, prostacyclin analogues, prostacyclin receptor agonists or soluble guanylate cyclase stimulators. Besides, the present invention relates to a pharmaceutical composition for the treatment of pulmonary vascular disease and/or cardiac dysfunction in functional single ventricular heart disease patients, especially in Fontan-palliated patients comprising a high dose of macitentan. Moreover, the present invention relates to the use of high doses aprocitentan for the same purpose.

A pharmaceutical composition comprises an effective amount of an insulin analogue comprising modified A-chain and B-chain polypeptides. The modified A chain comprises one or more substitutions relative to wild-type human insulin A-chain selected from a Gln, His or Glu substitution at position A8, a Glu or Ala substitution at position A14, and an Ala, Gln, Gly, or Thr substitution at position A21. The modified B-chain polypeptide comprises one or more modifications relative to wild-type human insulin B-chain selected from a deletion of the amino acid or amino acids at position B1, B1 and B2, or B1-B3, an Ala or Glu substitution at position B2, a Glu or Ala substitution at position B3, an Ala substitution at position B4; and a Glu or Lys substitution at position B29. The composition comprises one or more of iloprost, citrate, EDTA and a polyphosphate compound. The composition may be used to treat diabetes.

A pharmaceutical composition comprises an effective amount of an insulin analogue comprising modified A-chain and B-chain polypeptides. The modified A chain comprises one or more substitutions relative to wild-type human insulin A-chain selected from a Gln, His or Glu substitution at position A8, a Glu or Ala substitution at position A14, and an Ala, Gln, Gly, or Thr substitution at position A21. The modified B-chain polypeptide comprises one or more modifications relative to wild-type human insulin B-chain selected from a deletion of the amino acid or amino acids at position B1, B1 and B2, or B1-B3, an Ala or Glu substitution at position B2, a Glu or Ala substitution at position B3, an Ala substitution at position B4; and a Glu or Lys substitution at position B29. The composition comprises one or more of iloprost, citrate, EDTA and a polyphosphate compound. The composition may be used to treat diabetes.

The invention relates to ophthalmic compositions comprising a nitric oxide releasing phosphodiesterase type 5 inhibitor (NO-PDE5 inhibitor) and a prostaglandin analog, and to the use of these ophthalmic compositions for the treatment of all forms of glaucoma or ocular hypertension as well as eyes diseases or conditions associated with elevated intraocular pressure. The NO-PDE5 inhibitor is selected from the following compounds: [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy) hexanoate (Compound (1)), [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 3-[(2S)-2,3-bis(nitrooxy)propoxy]propanoate (Compound (1A)) or 2-{4-[3-(5-Ethyl-4-oxo-7-propyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)-4-propoxybenzene-1-sulfonyl]piperazin-1-yl}ethyl 3-[(2S)-2,3-bis(nitrooxy) propoxy]propanoate (Compound (2)). The prostaglandin analog is selected from latanoprost, bimatoprost, travoprost or tafluprost.

The invention relates to ophthalmic compositions comprising a nitric oxide releasing phosphodiesterase type 5 inhibitor (NO-PDE5 inhibitor) and a prostaglandin analog, and to the use of these ophthalmic compositions for the treatment of all forms of glaucoma or ocular hypertension as well as eyes diseases or conditions associated with elevated intraocular pressure. The NO-PDE5 inhibitor is selected from the following compounds: [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy) hexanoate (Compound (1)), [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 3-[(2S)-2,3-bis(nitrooxy)propoxy]propanoate (Compound (1A)) or 2-{4-[3-(5-Ethyl-4-oxo-7-propyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)-4-propoxybenzene-1-sulfonyl]piperazin-1-yl}ethyl 3-[(2S)-2,3-bis(nitrooxy) propoxy]propanoate (Compound (2)). The prostaglandin analog is selected from latanoprost, bimatoprost, travoprost or tafluprost.

The present disclosure relates to compositions and combinations comprising one or more insulin(s) and one or more vasoactive agent(s), and use thereof for increasing subcutaneous insulin absorption and/or treating diabetes and/or treating or preventing hyperglycemia or complications in a patient in need thereof.

The present disclosure relates to compositions and combinations comprising one or more insulin(s) and one or more vasoactive agent(s), and use thereof for increasing subcutaneous insulin absorption and/or treating diabetes and/or treating or preventing hyperglycemia or complications in a patient in need thereof.