395 results about "Tacrolimus" patented technology

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

The invention is directed to an injectable nanoparticulate immunosuppressant composition for the formation of a subcutaneous or intramuscular depot. The invention is also directed to an injectable composition of nanoparticulate tacrolimus and / or sirolimus which eliminates the need to use polyoxyl 60 hydrogenated castor oil (HCO-60) and / or polysorbate 80 as a solubilizer. This invention further discloses a method of making an injectable nanoparticulate tacrolimus and / or sirolimus composition and is also directed to methods of treatment using the injectable nanoparticulate formulations comprising tacrolimus, sirolimus, or combination thereof for a subcutaneous or intramuscular depot for the prophylaxis of organ rejection and for the treatment of psoriasis or other immune diseases

It has been discovered that the stimulation of beta -adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta -adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta -adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta -adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

The present invention is directed to nanoparticulate tacrolimus compositions. The composition comprising tacrolimus particles having an effective average particle size of less than about 2000 nm and at least one surface stabilizer.

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

Ocular solutions containing at least one macrolide antibiotic and / or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions. The solution may contain a supratherapeutic concentration of agent(s) so that a therapeutic concentration of a topically administered solution accumulates in a diseased ocular structure sufficient to treat the disease.

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

Containing at least one macrolide antibiotic and / or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial, and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions.

An intravenous pacemaker electrode has an electrode tip designed to release a drug, where the drug contains at least one of the active substances sirolimus, paclitaxel, everolimus, fibrin, rapamycin, and tacrolimus.

The invention teaches derivatives of ascomycin and methods of preparing immunogens and other conjugates useful in immunoassays for quantitatively measuring concentrations of tacrolimus in patient specimens. Antibodies produced from the disclosed immunogens capable of binding to tacrolimus with cross-reactivity of no more than 5% with each of 15-O-demethyl tacrolimus, 31-O-demethyl tacrolimus, and 13,31-O-didemethyl tacrolimus, less than 40% with 13-O-demethyl tacrolimus, and less than 1% with cyclosporin, rapamycin, mycophenolic acid, prednisone, hydrocortisol, and prednisolone are described. Further, immunoassays for measuring the concentration of tacrolimus using such antibodies are taught.

Drug eluting coating compositions are composed of at least one therapeutic agent dispersed in modified, biologically active binders. The therapeutic agents included in the coating composition are paclitaxel, sirolimus, tacrolimus, everolimus, actinomycin-D, dexamethasone, mycophenolic acid, cyclosporins, estradiol, and derivatives and analogs thereof. These therapeutic agents are applied to the surface of the medical device by a modified, biologically active binders. By using these biologically active binders, the therapeutic agents can be applied to at least one surface of a medical implant without using inert polymer carriers.

The present invention is directed to pharmaceutical nanoparticulate compositions of an immunosuppressive agent. The pharmaceutical compositions comprise solid particles of an immunosuppressive agent having an effective average particle size of less than about 2000 nm and one or more surface stabilizers associated with the surface of the immunosuppressive agent particles.

A pharmaceutical composition comprising tacrolimus (FK-506) dissolved and / or dispersed in a hydrophilic or water-miscible vehicle to form a solid dispersion or solid solution at ambient temperature have improved bioavailability.

A pharmaceutical composition comprising tacrolimus (FK-506) dissolved and / or dispersed in a hydrophilic or water-miscible vehicle to form a solid dispersion or solid solution at ambient temperature have improved bioavailability.

The present invention provides methods, diagnostic assays, and diagnostic kits based on said methods, to determine levels of immunosuppressive complexes containing immunosuppressive drugs tacrolimus, sirolimus and cyclosporine A separately and in combination, formed in the blood of a drug-treated patient or in a patient candidate to immunosuppressive drug therapy. These methods, assays and kits are especially useful when using automated systems.

The present invention relates to an injectable nanoparticulate immunosuppressant composition for the formation of a subcutaneous or intramuscular depot. The invention is also directed to an injectable composition of nanoparticulate tacrolimus and / or sirolimus which eliminates the need to use polyoxyl 60 hydrogenated castor oil (HCO-60) and / or polysorbate 80 as a solubilizer. This invention further discloses a method of making an injectable nanoparticulate tacrolimus and / or sirolimus composition and is also directed to methods of treatment using the injectable nanoparticulate formulations comprising tacrolimus, sirolimus, or combination thereof for a subcutaneous or intramuscular depot for the prophylaxis of organ rejection and for the treatment of psoriasis or other immune diseases.

A sustained release pharmaceutical composition for tacrolimus, comprising a solid dispersion containing tacrolimus or a pharmaceutically acceptable salt thereof, and a carrier for a sustained release pharmaceutical composition, wherein a dissolution rate of tacrolimus after 4 hours from the beginning of a dissolution test is less than 35%, is disclosed.