Merck + Co., Inc.

Other

Dupont Pharmaceuticals Company

Oread Laboratories, Inc.

University of Kansas

Bristol-myers Squibb Pharma Company

Arnold J Repta

Munir A Hussain

Edward M Scolnick

Alfred W Alberts

Takeru Higuchi, Deceased

Larry A Sternson

Pierre M De Montigny

Joseph P Vacca

Douglas G Batt

Bruce D Dorsey

William John Pitts

Takeru Higuchi

Burton H Sage

Prabhakar Kondaji Jadhav

Jose Alexander

Philip G Green

Carl Randolph Bock

John F Stobaugh

By Kenji Higuchi, Co-executor

By Martin Dickinson, Jr, Co-executor

Dilbir Bindra

David W Bourne

Parviz Mojaverian

Kenji W Higuchi, Co-executor

John F Stabaugh

The invention provides a method and device for administering an amine drug, such as &lsqb;S-(R,S)&rsqb;-2-&lsqb;4-&lsqb;&lsqb;(4-methyl)piperazin-1-yl&rsqb;carbonyl&rsqb;phenoxy&rsqb;-3,3-diethyl-N-&lsqb;1-(3,4-methylenedioxyphenyl)butyl&rsqb;-4-oxo-1-azetidinecarboxamide), in a sustained release dosage form. The invention includes a pharmaceutical composition and dosage form containing a polyalkylamine polymer and an amine drug. The polyalkylamine polymer is a hydrogel that forms hydrated particles when exposed to an aqueous environment. When mixed with the amine drug in the core of a coated tablet, the polyalkylamine polymer controls the release of the amine drug into an aqueous environment of use. The hydrated particles of the polymer together with the amine drug are released from the tablet core through plural apertures in the surrounding coat.

Use of polyalkylamine polymers in controlled release devices

This invention relates to novel heterocycles which are useful as antagonists of the &agr;,&bgr;,integrin and related cell surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, to iontophoretic delivery of such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

Integrin inhibitor prodrugs

This invention relates to novel methods and devices for iontophoretically administering therapeutic doses of integrin receptor antagonists in a controlled manner through the skin. Such integrin receptor antagonists include but are not limited to antagonists of the IIb/IIIa and &agr;,&bgr;,integrins and related cell surface adhesive protein receptors. The present invention includes iontophoretic delivery devices comprising integrin inhibitors. Such methods and devices are useful, alone or in combination with other therapeutic agents, for the treatment of thromboembolic disorders, angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

Iontophoretic delivery of integrin inhibitors

This invention relates to novel methods and devices for iontophoretically administering therapeutic doses of cell adhesion receptor antagonists in a controlled manner through the skin. Such antagonist compounds include but are not limited to antagonists of the IIb/IIIa and .alpha..sub.v .beta..sub.3 integrins and related cell surface adhesive protein receptors. The present invention includes iontophoretic delivery devices comprising cell adhesion receptor antagonists. Such methods and devices are useful, alone or in combination with other therapeutic agents, for the treatment of thromboembolic disorders, angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

Iontophoretic delivery of cell adhesion inhibitors

Prodrugs of the HIV protease inhibitor L-735,524 are useful in the inhibition of HIV protease, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating ADS and methods of preventing or treating infection by HIV are also described.

Prodrugs of an inhibitor of HIV protease

The instant invention is directed to a method for enhancing the lowering of plasma cholesterol level in a subject in need thereof which comprises the time-controlled administration of a nontoxic therapeutically effective amount of an HMG-CoA reductase inhibitor to said subject which surprisingly affords an equivalent or improved reduction of plasma cholesterol levels while significantly reducing the amount of HMG-CoA reductase inhibitor circulating in the bloodstream of the subject as compared to the same parameters when the oral administration of a conventional rapid release dosage form is utilized.

Method for enhancing the lowering of plasma-cholesterol levels

Method for enhancing the lowering of plasma cholesterol levels

There is provided a fluorescent adduct which is amenable to detection by fluorometric and electrochemical techniques. The adduct is of the formula: ##STR1## wherein X is a radical derived from a primary amine of the formula X--NH.sub.2 and where R.sub.1 --R.sub.6 are selected from various organic or inorganic substituents.

Polycyclic nitriles

A method of assaying primary amines or cyanide is disclosed. The process is carried out by reacting a substituted or unsubstituted naphthalene-2,3-dicarboxaldehyde or o-phthalaldehyde, reactive with primary amines and cyanide, with cyanide ions and at least one primary amine to form an adduct amenable to fluorometric or electrochemical assaying techniques. The adduct is then fluorometrically or electrochemically assayed. Also disclosed are 1-cyano-benz[f]isoindole adducts.

Assaying method for primary amines using aromatic dialdehydes

A method of parenterally delivering aqueously unstable drugs that includes the aqueous dilution of a stable, anhydrous organic solution having the drug dissolved therein. The resulting organic-aqueous solution is physiologically suitable for parenteral delivery into a warm-blooded mammal and contains the drug in an effective dosage concentration per unit volume.

Method of parenterally delivering drugs and related compositions

Acronycine derivatives having the structural formula: ##SPC1## Wherein R is acyl and A is an anion of a suitably strong acid, stabilized formulations thereof and pharmaceutical compositions comprised of same exhibit broad spectrum antitumor activity, and are especially suited for intravenous administration.

Acronycine derivatives

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Lawrence, KS, United States of America

Arnold J Repta