This invention relates to drug delivery and in particular to the delivery of biologically active agents in the form of dry powders for inhalation. The invention also relates to methods for preparing such dry powder formulations and methods for their use.

This invention relates to drug delivery and in particular to the delivery of biologically active agents in the form of dry powders for inhalation. The invention also relates to methods for preparing such dry powder formulations and methods for their use.

The present invention provides cyclic oligopeptides and methods for using the same. The cyclic oligopeptides of the invention are analogues of oxytocin wherein the disulfide linkage between Cys.sup.1 and Cys.sup.2 are replaced with a more stable amide bond. The cyclic oligopeptides of the invention can also include a glycoside to increase blood-brain barrier penetration. In particular, the cyclic oligopeptide of the invention is of the formula: (A) (SEQ ID NO:2) where one of AA.sup.1 or AA.sup.6 is an amino acid having a carboxylic acid side-chain and the other is a carboxylic acid having an amine functional group on the side-chain such that X.sup.1 and X.sup.2 together form an amide bond; and each of AA.sup.2-AA.sup.5 and AA.sup.7-AA.sup.11 is independently natural or unnatural amino acids with at least one, typically at least two, often at least three, more often at least four, and most often at least five of which is an amino acid that is present in the corresponding position of oxytocin.

The present invention provides cyclic oligopeptides and methods for using the same. The cyclic oligopeptides of the invention are analogues of oxytocin wherein the disulfide linkage between Cys.sup.1 and Cys.sup.2 are replaced with a more stable amide bond. The cyclic oligopeptides of the invention can also include a glycoside to increase blood-brain barrier penetration. In particular, the cyclic oligopeptide of the invention is of the formula: (A) (SEQ ID NO:2) where one of AA.sup.1 or AA.sup.6 is an amino acid having a carboxylic acid side-chain and the other is a carboxylic acid having an amine functional group on the side-chain such that X.sup.1 and X.sup.2 together form an amide bond; and each of AA.sup.2-AA.sup.5 and AA.sup.7-AA.sup.11 is independently natural or unnatural amino acids with at least one, typically at least two, often at least three, more often at least four, and most often at least five of which is an amino acid that is present in the corresponding position of oxytocin.

The present disclosure provides novel V1a partial agonists for partially activating a V1a receptor. The partial V1a agonist has a therapeutic index of at least 20 (e.g., at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100). Also provided are method of treating liver fibrosis, cirrhosis, portal hypertension, ascites, esophageal varices, fundal varices, bleeding, arterial hypotension, and/or hepatorenal syndrome, including administering to a subject in need thereof a therapeutically effective dose of a composition including the V1a partial agonist(s) of the present disclosure, optionally in combination with a V2 antagonist.

A recombinant protein comprising multiple multi-peptide sets includes first through fifth sequencing primers and first through fourth multi-peptide regions. The first multi-peptide region is between the first and the second sequencing primers. The second multi-peptide region is between the second and the third sequencing primers. The third multi-peptide region is between the third and the fourth sequencing primers. The fourth multi-peptide region is between the fourth and the fifth sequencing primers. In each of the multi-peptide regions, multiple functional peptides can be inserted, and manufacturing thereof can be done through expression of the recombinant protein, thereby significantly enhancing the concentrations of the functional peptides. With the combination of peptide having different functions, the recombinant protein product can provide more complete and more comprehensive functionality. This application also discloses a pharmaceutical composition comprising the recombinant protein and a method for preparing the recombinant protein.

A recombinant protein comprising multiple multi-peptide sets includes first through fifth sequencing primers and first through fourth multi-peptide regions. The first multi-peptide region is between the first and the second sequencing primers. The second multi-peptide region is between the second and the third sequencing primers. The third multi-peptide region is between the third and the fourth sequencing primers. The fourth multi-peptide region is between the fourth and the fifth sequencing primers. In each of the multi-peptide regions, multiple functional peptides can be inserted, and manufacturing thereof can be done through expression of the recombinant protein, thereby significantly enhancing the concentrations of the functional peptides. With the combination of peptide having different functions, the recombinant protein product can provide more complete and more comprehensive functionality. This application also discloses a pharmaceutical composition comprising the recombinant protein and a method for preparing the recombinant protein.

The present invention relates to crystalline forms of carbetocin, a method of their manufacture, and pharmaceutical compositions thereof.

The present invention relates to crystalline forms of carbetocin, a method of their manufacture, and pharmaceutical compositions thereof.

A recombinant protein comprising multiple multi-peptide sets includes first through fifth sequencing primers and first through fourth multi-peptide regions. The first multi-peptide region is between the first and the second sequencing primers. The second multi-peptide region is between the second and the third sequencing primers. The third multi-peptide region is between the third and the fourth sequencing primers. The fourth multi-peptide region is between the fourth and the fifth sequencing primers. In each of the multi-peptide regions, multiple functional peptides can be inserted, and manufacturing thereof can be done through expression of the recombinant protein, thereby significantly enhancing the concentrations of the functional peptides. With the combination of peptide having different functions, the recombinant protein product can provide more complete and more comprehensive functionality. This application also discloses a pharmaceutical composition comprising the recombinant protein and a method for preparing the recombinant protein.