The present invention pertains to inter alia methods for purifying extracellular vesicles including exposing a sample comprising at least one extracellular vesicle to ultrafiltration; and exposing the sample following the ultrafiltration in step (i) to size exclusion liquid chromatography.

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Provided herein are Diaminopyrimidine Compounds having the following structures:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidine Compound, and methods for treating or preventing liver fibrotic disorders or a condition treatable or preventable by inhibition of a JNK pathway.

The present invention relates to a granular pharmaceutical composition obtained by coating a nucleus with: (1) a layer containing a material having a damp-proofing function, and (2) a drug layer containing linaclotide, a pharmaceutically acceptable salt, or a hydrate thereof, and (3) a layer containing a material having a damp-proofing function. Also, the present invention relates to a method for manufacturing the granular pharmaceutical composition obtained by coating the nucleus with (1) the layer containing the material having a damp-proofing function, (2) the drug layer containing the linaclotide, the pharmaceutically acceptable salt, or the hydrate thereof, and (3) the layer containing the material having a damp-proofing function.

Provided herein is a method of treating or alleviating one or more symptoms of a disorder, disease, or condition mediated by a dopamine D.sub.2 or D.sub.3 receptor with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof. Also provided herein is a method of increasing the serum prolactin level with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof.

Provided herein is a method of treating or alleviating one or more symptoms of a disorder, disease, or condition mediated by a dopamine D.sub.2 or D.sub.3 receptor with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof. Also provided herein is a method of increasing the serum prolactin level with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof.

A method of diagnosis and treatment of primary biliary cholangitis is provided. Additionally, a pharmaceutical composition and a solid dosage form for the treatment of primary biliary cholangitis, containing ursodeoxycholic and obeticholic acids, are provided. The technical contribution resides in obtaining a new all-purpose pharmaceutical composition and solid dosage form for the treatment of PBC, which includes both ursodeoxycholic and obeticholic acids, which is effective in use at all stages of PBC and has a complex mechanism of action. In particular, simultaneous blockage of the transport and synthesis of bile acids is achieved.

A method of diagnosis and treatment of primary biliary cholangitis is provided. Additionally, a pharmaceutical composition and a solid dosage form for the treatment of primary biliary cholangitis, containing ursodeoxycholic and obeticholic acids, are provided. The technical contribution resides in obtaining a new all-purpose pharmaceutical composition and solid dosage form for the treatment of PBC, which includes both ursodeoxycholic and obeticholic acids, which is effective in use at all stages of PBC and has a complex mechanism of action. In particular, simultaneous blockage of the transport and synthesis of bile acids is achieved.

The present disclosure relates to a method of modulating the half-life of a binding domain specific to a serum carrier protein by mutating the sequence and a modulated binding domain specific to a serum carrier protein.

The present invention concerns a method to modulate the level of or to modify a target molecule in a subject or an environment, said method comprising: administering in said subject or providing to said environment an engineered bacterial strain comprising (i) a heterologous or engineered nucleic acid involved in the expression of a molecule of interest, wherein the expression of said molecule of interest modulates directly or indirectly the level of or modify the target molecule in said subject or environment and (ii) an autologous gene or gene set involved in the import and/or metabolism of a milk oligosaccharide; and further administering to said subject, or providing to said environment, said milk oligosaccharide; whereby the level of the target molecule in said subject or environment is modulated or the target molecule is modified in said subject or environment.