The invention provides topical compositions and methods for using the compositions. The compositions can be used for the treatment of fibrotic or connective tissue disorders involving scarring, sub-dermal plaque accumulations, or fibrosis of muscle tissue. The disorders can be painlessly treated by the topical application of a composition described herein. One or more calcium channel blocker agents can serve as an active ingredient of the compositions, optionally in combination with, for example, one or more of emu oil and superoxide dismutase. The composition can further include pharmaceutically acceptable carriers that can facilitate the non-invasive transdermal delivery of the active(s) to subdermal sites.

The invention provides topical compositions and methods for using the compositions. The compositions can be used for the treatment of fibrotic or connective tissue disorders involving scarring, sub-dermal plaque accumulations, or fibrosis of muscle tissue. The disorders can be painlessly treated by the topical application of a composition described herein. One or more calcium channel blocker agents can serve as an active ingredient of the compositions, optionally in combination with, for example, one or more of emu oil and superoxide dismutase. The composition can further include pharmaceutically acceptable carriers that can facilitate the non-invasive transdermal delivery of the active(s) to subdermal sites.

Provided herein is a pharmaceutical composition comprising two or more compounds, wherein each compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium channel blocker, a histamine H.sub.1-receptor agonist, a histamine H.sub.2-receptor agonist, a histamine H.sub.3-receptor antagonist, or a β.sub.2-adrenoreceptor agonist. Also provided herein is a method of treating, preventing, or ameliorating a cardiovascular disease in a subject, comprising administering to the subject in need thereof two or more compounds, wherein each compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium channel blocker, a histamine H.sub.1-receptor agonist, a histamine H.sub.2-receptor agonist, a histamine H.sub.3-receptor antagonist, or a β.sub.2-adrenoreceptor agonist.

Provided herein is a pharmaceutical composition comprising two or more compounds, wherein each compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium channel blocker, a histamine H.sub.1-receptor agonist, a histamine H.sub.2-receptor agonist, a histamine H.sub.3-receptor antagonist, or a β.sub.2-adrenoreceptor agonist. Also provided herein is a method of treating, preventing, or ameliorating a cardiovascular disease in a subject, comprising administering to the subject in need thereof two or more compounds, wherein each compound is independently a phosphodiesterase inhibitor, an adenosine receptor antagonist, a calcium channel blocker, a histamine H.sub.1-receptor agonist, a histamine H.sub.2-receptor agonist, a histamine H.sub.3-receptor antagonist, or a β.sub.2-adrenoreceptor agonist.

Provided herein is a pharmaceutical composition comprising (i) a phosphodiesterase inhibitor or an adenosine receptor antagonist, (ii) a calcium channel blocker, (iii) a histamine H.sub.1-receptor agonist, a histamine H.sub.2-receptor agonist, or a histamine H.sub.3-receptor antagonist, and (iv) a β.sub.2-adrenoreceptor agonist; wherein at least one of two or more active pharmaceutical compounds is deuterium enriched. Also provided herein is a pharmaceutical composition comprising at least one of two or more deuterated compounds which increase pharmacokinetic half-life (increasing the duration of action) and reduce side effects by allowing for reduction of the dose levels. A method of use thereof pharmaceutical composition for treating, preventing, or ameliorating a cardiovascular disease.

Provided herein is a pharmaceutical composition comprising (i) a phosphodiesterase inhibitor or an adenosine receptor antagonist, (ii) a calcium channel blocker, (iii) a histamine H.sub.1-receptor agonist, a histamine H.sub.2-receptor agonist, or a histamine H.sub.3-receptor antagonist, and (iv) a β.sub.2-adrenoreceptor agonist; wherein at least one of two or more active pharmaceutical compounds is deuterium enriched. Also provided herein is a pharmaceutical composition comprising at least one of two or more deuterated compounds which increase pharmacokinetic half-life (increasing the duration of action) and reduce side effects by allowing for reduction of the dose levels. A method of use thereof pharmaceutical composition for treating, preventing, or ameliorating a cardiovascular disease.

The present invention relates to methods for lowering stroke damages and/or lowering blood pressure in a subject with a stroke in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a short acting dihydropyridine compound, preferably clevidipine or a pharmaceutically acceptable salt or ester thereof. Also provided are related medicaments, pharmaceutical compositions, and methods for preparing the medicaments.

The present invention relates to methods for lowering stroke damages and/or lowering blood pressure in a subject with a stroke in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a short acting dihydropyridine compound, preferably clevidipine or a pharmaceutically acceptable salt or ester thereof. Also provided are related medicaments, pharmaceutical compositions, and methods for preparing the medicaments.

The present invention relates to a dosage form for transdermal administration of at least one active pharmaceutical ingredient with a logP≥3, comprising at least one penetration accelerator, wherein the at least one penetration accelerator comprises dimethylethylene urea, the use of such a dosage form as a medicament, and the use of dimethylethylene urea as penetration accelerator to increase the skin penetration of active pharmaceutical ingredients with a logP≥3.

Provided is a pharmaceutical composition comprising clevidipine in a sterile, ready to use, physically stable, aqueous dispersion of nanoparticles that stabilizes clevidipine against formation of impurities and is suitable for parenteral administration.