A pharmaceutical composition capable of forming free burst release effect in-situ forming implant useful for injection inside bone injuries without surgery is provided. This pharmaceutical composition includes; biodegradable polymer, selective estrogen receptor modulator, organic solvent and liquid lipid, solidifies upon contacting with the surrounding medium and form solid implant with compact framework by in-situ phase separation method to deliver the selective estrogen receptor modulator. This compact framework restores the porous structure of the implant by time which is essential in promoting bone healing.

The present invention relates to the use of a 2,3,5-substituted thiophene compound for the prevention, amelioration or treatment of mastocytosis. The 2,3,5-substituted thiophene compound has excellent inhibitory activity against the growth of mastocytosis cells and against an inflammatory response caused by mastocytosis, and thus may be effectively used for the prevention, amelioration or treatment of mastocytosis.

The present invention relates to the use of a 2,3,5-substituted thiophene compound for the prevention, amelioration or treatment of mastocytosis. The 2,3,5-substituted thiophene compound has excellent inhibitory activity against the growth of mastocytosis cells and against an inflammatory response caused by mastocytosis, and thus may be effectively used for the prevention, amelioration or treatment of mastocytosis.

Provided herein are methods of using a compound provided herein (e.g., Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, or Compound 7, or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof), in combination with a second) active agent for treating cancer. The second active agent is one or more of a PLK1 inhibitor, a BRD4 inhibitor, a BET inhibitor, an NEK2 inhibitor, an AURKB inhibitor, an MEK inhibitor, a PHF19 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BIRCS inhibitor, or a DNA methyltransferase inhibitor.

Provided herein are methods of using a compound provided herein (e.g., Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, or Compound 7, or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof), in combination with a second) active agent for treating cancer. The second active agent is one or more of a PLK1 inhibitor, a BRD4 inhibitor, a BET inhibitor, an NEK2 inhibitor, an AURKB inhibitor, an MEK inhibitor, a PHF19 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BIRCS inhibitor, or a DNA methyltransferase inhibitor.

The present invention relates to treatment of coronavirus-induced disease, specifically COVID-19 disease, wherein the disease is characterized by mast cell degranulation, acute inflammation, pulmonary and/or vascular pathologies. The treatment comprises administering to a subject a composition comprising a mast cell stabilizer and/or inhibitor of mast cell products, such as TY-51469, nafamostat mesylate, cromolyn, or ketotifen. The invention also provides a method of diagnosing a subject as having SARS-CoV-2, the method comprising determining the level and/or activity of a mast cell protease such as chymase or tryptase in the serum from a subject.

The present invention relates to treatment of coronavirus-induced disease, specifically COVID-19 disease, wherein the disease is characterized by mast cell degranulation, acute inflammation, pulmonary and/or vascular pathologies. The treatment comprises administering to a subject a composition comprising a mast cell stabilizer and/or inhibitor of mast cell products, such as TY-51469, nafamostat mesylate, cromolyn, or ketotifen. The invention also provides a method of diagnosing a subject as having SARS-CoV-2, the method comprising determining the level and/or activity of a mast cell protease such as chymase or tryptase in the serum from a subject.

An abuse deterrent and misuse deterrent transdermal patch comprising aversive agents incorporated in the backing layer of the patch. The aversive agents can exhibit biphasic or sustained kinetics of release with an immediate portion released rapidly and an extended portion released in a prolonged manner when exposed to a dissolution medium. The prolonged aversive agent release provides deterrence against extraction of drug from fresh and used patches and serves to prevent accidental misuse of used patches by children. The abuse deterrent and misuse deterrent patch systems can be used for transdermal delivery of therapeutically active agents and particularly those drugs that are highly prone to abuse such as opiate and opioid analgesics and stimulants.

An abuse deterrent and misuse deterrent transdermal patch comprising aversive agents incorporated in the backing layer of the patch. The aversive agents can exhibit biphasic or sustained kinetics of release with an immediate portion released rapidly and an extended portion released in a prolonged manner when exposed to a dissolution medium. The prolonged aversive agent release provides deterrence against extraction of drug from fresh and used patches and serves to prevent accidental misuse of used patches by children. The abuse deterrent and misuse deterrent patch systems can be used for transdermal delivery of therapeutically active agents and particularly those drugs that are highly prone to abuse such as opiate and opioid analgesics and stimulants.

This invention relates to methods of preparing nanotherapeutic compounds and compositions comprising nanotherapeutic compounds. The nanotherapeutic compounds prepared according to the methods provided herein are useful for the treatment of disease, for example, cancer, in a subject in need thereof.