The present invention provides therapeutic agents and compositions comprising elastin-like peptides (ELPs) and therapeutic proteins. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist, insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

A compound having agonist activity at the GLP-1 (glucagon-like-peptide 1) and GLP-2 (glucagon-like peptide 2) receptors, and a pharmaceutical composition containing the compound or a pharmaceutically acceptable salt or solvate thereof in admixture with a pharmaceutically acceptable carrier, an excipient or a vehicle are provided. The compound can be used, inter alia, in the prophylaxis or treatment of intestinal damage and dysfunction, regulation of body weight, and prophylaxis or treatment of metabolic dysfunction.

A compound having agonist activity at the GLP-1 (glucagon-like-peptide 1) and GLP-2 (glucagon-like peptide 2) receptors, and a pharmaceutical composition containing the compound or a pharmaceutically acceptable salt or solvate thereof in admixture with a pharmaceutically acceptable carrier, an excipient or a vehicle are provided. The compound can be used, inter alia, in the prophylaxis or treatment of intestinal damage and dysfunction, regulation of body weight, and prophylaxis or treatment of metabolic dysfunction.

Disclosed in the present application is a crystal polymorph of potassium N-[8-(2-hydroxybenzoyl)amino]octanoate, wherein the crystal polymorph of potassium N-[8-(2-hydroxybenzoyl)amino]octanoate is crystal Form I, and the crystal Form I has at least an X-ray powder diffraction pattern with characteristic peaks represented by 2θ° of 7.83±0.2, 26.64±0.2 and 18.89±0.2. The crystal polymorph of potassium N-[8-(2-hydroxybenzoyl)amino]octanoate provided by the present application has four crystal forms, has high solubility and strong stability, can deliver drugs more effectively, increases the permeability of the delivered drugs in the gastrointestinal tract, and is beneficial to the preparation of oral preparations, such that preventive and/or therapeutic drugs can be better delivered into the body to achieve the effect of improving the bioavailability.

Disclosed in the present application is a crystal polymorph of potassium N-[8-(2-hydroxybenzoyl)amino]octanoate, wherein the crystal polymorph of potassium N-[8-(2-hydroxybenzoyl)amino]octanoate is crystal Form I, and the crystal Form I has at least an X-ray powder diffraction pattern with characteristic peaks represented by 2θ° of 7.83±0.2, 26.64±0.2 and 18.89±0.2. The crystal polymorph of potassium N-[8-(2-hydroxybenzoyl)amino]octanoate provided by the present application has four crystal forms, has high solubility and strong stability, can deliver drugs more effectively, increases the permeability of the delivered drugs in the gastrointestinal tract, and is beneficial to the preparation of oral preparations, such that preventive and/or therapeutic drugs can be better delivered into the body to achieve the effect of improving the bioavailability.

A composition containing a glucagon derivative and a GLP-1 and GIP receptor dual agonist, and uses thereof are disclosed. The glucagon derivative comprises an amino acid sequence of the formula 1: X1-X2-QGTF-X7-SD-X10-S-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-F-X23-X24-WL-X27-X28-X29-X30 (Formula 1). The composition is useful in preventing or treating metabolic syndrome.

A composition containing a glucagon derivative and a GLP-1 and GIP receptor dual agonist, and uses thereof are disclosed. The glucagon derivative comprises an amino acid sequence of the formula 1: X1-X2-QGTF-X7-SD-X10-S-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-F-X23-X24-WL-X27-X28-X29-X30 (Formula 1). The composition is useful in preventing or treating metabolic syndrome.

Provided are therapeutic combinations or formulations of drugs comprising triple monoamine reuptake inhibitors, melanin concentrating hormone receptor 1 (MCHRT) antagonists and diazoxide or its formulations and various combinations thereof, these in combination with other drugs or active agents. Provided are methods for the treatment of various conditions, including genetic confirmed syndromes, and diseases, using therapeutic combinations and formulations of drugs as provided herein. Provided are methods for administering triple monoamine reuptake inhibitors (TRIs), melanin concentrating hormone receptor 1 (MCHRT) antagonists and diazoxide or diazoxide or its formulations, whose dosages are determined using a method as provided herein including empirical methods for safe and predictable titration and to determine the initial therapeutic dose; model-based methods for safe and predictable titration and to determine the initial therapeutic dose and to determine the lowest therapeutic dose or to determine an optimal effective dose, including use of Bayesian pharmacometric models.

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH.sub.2).sub.x—CO—*, and Chem. 2: HOOC—C.sub.6H.sub.4—O—(CH.sub.2).sub.y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH.sub.2).sub.q—CH[(CH.sub.2).sub.w—NR.sub.1R.sub.2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R.sub.1 and R.sub.2 independently represent *—H or *—CH.sub.3, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH.sub.2).sub.x—CO—*, and Chem. 2: HOOC—C.sub.6H.sub.4—O—(CH.sub.2).sub.y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH.sub.2).sub.q—CH[(CH.sub.2).sub.w—NR.sub.1R.sub.2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R.sub.1 and R.sub.2 independently represent *—H or *—CH.sub.3, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.