75 results about "Treprostinil" patented technology

The present invention describes novel methods for using Treprostinil or its derivative, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of ischemic lesions, such as digital ulcers, in subjects with scleroderma (including systemic sclerosis), Buerger's disease, Raynaud's disease, Raynaud's phenomenon and/or other conditions that cause such lesions. The invention also relates to kits for treatment and/or prevention of ischemic lesions, comprising an effective amount of Treprostinil or its derivative, or a pharmaceutically acceptable salt thereof.

Treprostinil can be administered using a metered dose inhaler. Such administration provides a greater degree of autonomy to patients. Also disclosed are kits that include a metered dose inhaler containing a pharmaceutical formulation containing treprostinil.

This invention pertains generally to prostacyclin analogs and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. Generally, the compounds and methods of the present invention increase the oral bioavailability and circulating concentrations of treprostinil when administered orally. Compounds of the present invention have the following formula:

The present invention is directed to compositions and methods for pain management, and for treating inflammation or an inflammation-associated disorder in a subject comprising administering to the subject a therapeutically effective amount of a COX-2 inhibitor and a therapeutically effective amount of a prostacyclin analog, such as treprostinil, a pharmaceutically acceptable salt thereof, or a treprostinil derivative described herein.

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

The present invention describes novel methods for using 9-deoxy-2′,9-α-methano-3-oxa-4,5,6-trinor-3,7-(1′,3′-interphenylene)-13,14-dihydro-prostaglandin F₁ (also known as Treprostinil) or its derivative, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of foot ulcers in subjects with diabetic neuropathy. The invention also relates to kits for treatment and/or prevention of foot ulcers, comprising an effective amount of Treprostinil or its derivative, or a pharmaceutically acceptable salt thereof.

Treprostinil is prepared by a process which involves Pauson-Khan cyclization of an an alkene-substituted, alkyne-substituted benzene corresponding to formula: (I) where PMB represents para-methoxy benzyl protecting group and R₁ and R₂ are alcohol protecting groups. Following cyclization, the resulting compound can be subjected to several chemical trans-formations followed by alkylation, hydrolysis and salt formation to yield treprostinil sodium. The use of para-methoxybenzyl group as the phenolic protecting group confers several process advantages that result in simplified purification of the final product and improved yields.

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C₂-C₁₈ alkyl, branched C₃-C₁₈ alkyl, linear C₂-C₁₈ alkenyl, branched C₃-C₁₈ alkenyl, aryl, aryl-C₁-C₁₈ alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described, for example, for administration via subcutaneous or intravenous infusion to a patient in need of pulmonary hypertension treatment. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom.

The present invention relates to prodrugs or a pharmaceutically acceptable salt thereof comprising a covalent treprostinil carrier conjugate as well as pharmaceutical composition comprising said compounds. The compounds may be used as medicaments, especially for diseases or disorders which can be treated by treprostinil, such as pulmonary arterial hypertension (PAH).

Administration of aerosolized Treprostinil formulations may provide a more homogeneous lung deposition of treprostinil, whereby making deep lung delivery possible.

Oral pharmaceutical compositions of treprostinil, a prodrug, or a pharmaceutically acceptable salt thereof are provided. The compositions possess absolute oral bioavailability of greater than 10% and achieve circulating concentrations when administered orally. Methods of treating prostacyclin responsive conditions including pulmonary arterial hypertension (PAH) by administering such compositions also are provided.

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

A method is disclosed for preparing a synthetic intermediate for treprostinil via a stereoselective alkyne addition reaction using a chiral inducing agent. Also described are methods of preparing treprostinil or a pharmaceutically acceptable salt thereof comprising the alkyne addition reaction as well as novel intermediates useful for synthesis prostacyclin derivatives. A functional alcohol protecting group protects the alcohol group from participating in reactions that are occurring in other parts of the molecule. The intermediate is later deprotected prior to conversion and hydrolyzing to obtain the final treprostinil product.

Methods for making prodrugs of trepreostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C₅-C₁₈ alkyl, branched C₅-C₁₈ alkyl, linear C₂-C₁₈ alkenyl, branched C₃-C₁₈ alkenyl, aryl, aryl-C₁-C₁₈ alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

A para-methoxy protected benzaldehyde useful in preparation of treprostinil, and of formula: (Formula (1)) is prepared by subjecting to Claisen re-arrangement a substituted benzaldehyde of formula (1a): (Formula (Ia)) to form the m-hydroxy-substituted benzaldehyde of formula (1b): (Formula (Ib)) and then reacting compound (1b) with a p-methoxybenzyl (PMB) compound to form a PMB-substituted benzaldehyde of formula (1).

The present disclosure provides a dry powder composition of treprostinil prodrugs and a method of treating pulmonary hypertension (e.g., pulmonary arterial hypertension), portopulmonary hypertension, or pulmonary fibrosis in a patient in need thereof. The dry powder composition includes (a) from about 0.1 wt % to about 3 wt % of a compound of Formula (I):

or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof, (b) from about 0.01 wt % to about 3 wt % of DSPE-PEG2000, (c) from about 10 wt % to about 50 wt % of leucine, and the balance being (d) a sugar selected from the group consisting of trehalose and mannitol. The entirety of (a), (b), (c), and (d) is 100 wt %, and R¹ is tetradecyl, pentadecyl, hexadecyl, heptadecyl, or octadecyl. The method includes administering an effective amount of the dry powder composition to the lungs of the patient by inhalation via a dry powder inhaler. In certain compositions and methods provided herein, R¹ is hexadecyl, e.g., linear hexadecyl.

The present disclosure provides methods, compositions, devices and systems for dermal and transdermal administration of treprostinil or salts thereof, and optionally an additional therapeutic agent. Treprostinil and salts thereof can be dermally or transdermally administered to treat any medical conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.