The present invention relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one lipid lowering agent (e.g., PPAR-alpha agonist, PPAR-delta agonist, PPAR-alpha and delta dual agonist, and/or statin). Also disclosed is use of the combination for the treatment or prevention of a FXR mediated disease or condition, such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), portal hypertension, bile acid diarrhea, NAFLD (nonalcoholic fatty liver disease), NASH (non-alcohol-induced steatohepatitis), and other chronic liver diseases. The combination of the present invention is useful for the treatment or prevention of conditions related to elevated lipid and liver enzyme levels. The present invention also relates to packs or kits including the pharmaceutical combination.

The present invention relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one lipid lowering agent (e.g., PPAR-alpha agonist, PPAR-delta agonist, PPAR-alpha and delta dual agonist, and/or statin). Also disclosed is use of the combination for the treatment or prevention of a FXR mediated disease or condition, such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), portal hypertension, bile acid diarrhea, NAFLD (nonalcoholic fatty liver disease), NASH (non-alcohol-induced steatohepatitis), and other chronic liver diseases. The combination of the present invention is useful for the treatment or prevention of conditions related to elevated lipid and liver enzyme levels. The present invention also relates to packs or kits including the pharmaceutical combination.

A composition for treating multiple disease causes including a glycocalyx restoring and maintaining compound. A method of treating multiple disease causes, by administering a glycocalyx restoring and maintaining compound to an individual, restoring the glycocalyx, reversing inflammation, and reversing oxidative damage. A method of treating cardiovascular disease. A method of restoring the glycocalyx. A method of reversing inflammation. A method of reversing oxidative damage. A method of treating any disease involving a membrane that has a glycocalyx. A method of treating multiple disease causes. A method of restoring the structural and functional integrity of receptors in the glycocalyx. A method of restoring the glycocalyx and receptors therein and potentiating drug response. A composition for treating disease including the glycocalyx restoring and maintaining compound and an antibody. A composition for treating cardiovascular disease including the glycocalyx restoring and maintaining compound and a MAb anti-PCSK9.

A composition for treating multiple disease causes including a glycocalyx restoring and maintaining compound. A method of treating multiple disease causes, by administering a glycocalyx restoring and maintaining compound to an individual, restoring the glycocalyx, reversing inflammation, and reversing oxidative damage. A method of treating cardiovascular disease. A method of restoring the glycocalyx. A method of reversing inflammation. A method of reversing oxidative damage. A method of treating any disease involving a membrane that has a glycocalyx. A method of treating multiple disease causes. A method of restoring the structural and functional integrity of receptors in the glycocalyx. A method of restoring the glycocalyx and receptors therein and potentiating drug response. A composition for treating disease including the glycocalyx restoring and maintaining compound and an antibody. A composition for treating cardiovascular disease including the glycocalyx restoring and maintaining compound and a MAb anti-PCSK9.

A composition for treating multiple disease causes including a glycocalyx restoring and maintaining compound. A method of treating multiple disease causes, by administering a glycocalyx restoring and maintaining compound to an individual, restoring the glycocalyx, reversing inflammation, and reversing oxidative damage. A method of treating cardiovascular disease. A method of restoring the glycocalyx. A method of reversing inflammation. A method of reversing oxidative damage. A method of treating any disease involving a membrane that has a glycocalyx. A method of treating multiple disease causes. A method of restoring the structural and functional integrity of receptors in the glycocalyx. A method of restoring the glycocalyx and receptors therein and potentiating drug response. A composition for treating disease including the glycocalyx restoring and maintaining compound and an antibody. A composition for treating cardiovascular disease including the glycocalyx restoring and maintaining compound and a MAb anti-PCSK9.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (I): ##STR00001##
including stereoisomers and pharmaceutically acceptable salts thereof, wherein Z, L, R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (I): ##STR00001##
including stereoisomers and pharmaceutically acceptable salts thereof, wherein Z, L, R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.

The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.

The disclosure provides methods for treating estrogen receptor positive (ER.sup.+) cancer in women with an effective amount of lasofoxifene, a pharmaceutically acceptable salt thereof, or a prodrug thereof. The disclosure also includes the detection of the Estrogen Receptor 1 (ESR1) gene mutations that lead to endocrine resistance and treatment of endocrine resistant ER.sup.+ cancers.