The present application provides a colloid drug aggregate composition and methods of use and manufacture thereof. While the formation of colloidal aggregates leads to artifacts in early drug discovery, their composition makes them attractive as nanoparticle formulations for targeted drug delivery. The present application provides an acid-responsive composition comprising: a colloidal aggregate of one or more drugs and a stabilizing agent, wherein the colloidal aggregate disrupts, dissolves or disassembles when the acid-responsive composition is in an acid environment having a pH of less than 7.4. The colloidal aggregate of the composition will disassemble upon contact with acid or upon introduction to an acidic environment, such as is found in the endosomes of cells. This approach makes this composition an attractive vehicle for drug delivery to a target site in a subject or to cells.

Oral administration of a solid dosage form of the present invention comprising an effective amount of rifabutin, an effective amount of clarithromycin, an effective amount of clofazimine, and an effective amount of an absorption enhancer, is used to treat a subject suffering from, or susceptible to, Mycobacterium avium subspecies paratuberculosis infection. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in the increased metabolism of clarithromycin caused by rifabutin. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in the metabolism of rifabutin caused by clarithromycin. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in risk of a subject developing leucopenia or uveitis as a result of rifabutin.

Provided herein are methods for the treatment of disease with monoacylglycerol lipase (MAGL) inhibitors.

Provided herein are methods for the treatment of disease with monoacylglycerol lipase (MAGL) inhibitors.

The present invention is directed to various 3′,4′-dihydro-2′H-spiro[indoline-3:1′-isoquinolin]-2-one compounds and methods for treating disease states and/or conditions which are mediated through sphingosine-1-phosphate receptor(s). The present invention is also directed to the use of these compounds as anticancer agents and as modulators of sphingosine-1-phosphate receptor function in the treatment of disease states and/or conditions which are mediated through these receptors. In addition, the invention relates to pharmaceutical compositions comprising one or more of these compounds alone or in combination with other therapeutic agents. The invention is also directed to methods of treatment of cancer and/or conditions that may respond to the modulation of sphingosine-1-phosphate receptor function and which employ compounds of the present invention or pharmaceutical compositions comprising one or more of the compounds of this invention.

The present invention is directed to various 3′,4′-dihydro-2′H-spiro[indoline-3:1′-isoquinolin]-2-one compounds and methods for treating disease states and/or conditions which are mediated through sphingosine-1-phosphate receptor(s). The present invention is also directed to the use of these compounds as anticancer agents and as modulators of sphingosine-1-phosphate receptor function in the treatment of disease states and/or conditions which are mediated through these receptors. In addition, the invention relates to pharmaceutical compositions comprising one or more of these compounds alone or in combination with other therapeutic agents. The invention is also directed to methods of treatment of cancer and/or conditions that may respond to the modulation of sphingosine-1-phosphate receptor function and which employ compounds of the present invention or pharmaceutical compositions comprising one or more of the compounds of this invention.

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:

X-A-Y-Z-R  (I)

which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:

X-A-Y-Z-R  (I)

which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.