Bristol-myers Squibb Compnay

E. R. Squibb Sons, Inc.

Sailesh A Varia

Andrea Panaggio

Krishnaswamy Srinivas Raghavan

Timothy M Malloy

Rebanta Bandyopadhyay

Uwe D Treuner

Joseph E Sundeen

William H Koster

Peter H Ermann

Henner Straub

Michael Fakes

Kent Amsberry

Richard L O'Laughlin

Nemichand B Jain

Sunanda A Ranadive

Abu T Serajuddin

Robert Abramowitz

Marilia M Faustino

Marvin Barry Cohen

A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50% by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg/mL to about 0.9 mg/mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

Parenteral formulation for epothilone analogs

The invention relates to methods of increasing the bioavailability of orally administered epothilones. Epothilones administered by the methods of the invention are sufficiently bioavailable to have a pharmacological effect. The invention further relates to pharmaceutical compositions, pharmaceutical dosage forms, and kits for use in the methods of the invention.

Pharmaceutical compositions, dosage forms and methods for oral administration of epothilones

Methods of administering epothilone analogs for the treatment of cancer

The invention relates to methods of increasing the bioavailability of orally administered epothilones. Epothilones administered by the methods of the invention are sufficiently bioavailable to have a pharmacological effect The invention further relates to pharmaceutical compositions, pharmaceutical dosage forms, and kits for use in the methods of the invention.

A ras-farnesyltransferase inhibitor complex formed of ras-farnesyltransferase inhibitor or a pharmaceutically acceptable salt thereof, of the formula I

Complex of ras-farnesyltransferase inhibitor and sulfobutylether-7-&bgr;-cyclodextrin or 2-hydroxypropyl-&bgr;-cyclodextrin and method

Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring.

Hereroaryl derivatives of monocyclic beta-lactam antibiotics

A three component pharmaceutical formulation of one or more pharmacologically active substances such that greater than 80% of the pharmacologically active substance will be released in the large intestine. The first component comprises the pharmacologically active substance, microcrystalline cellulose, a pH-sensitive polymer, and optionally an osmotic agent. The second component is a delayed release coating, and the third component is an enteric coating.

Colonic drug delivery system

Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring. Also described are various intermediates for the preparation of compounds of formula 1.

Intermediates for the preparation of heteroaryl derivatives of

Heteroaryl derivatives of monocyclic beta-lactam antibiotics

A steroid lotion formulation which has enhanced physical and chemical stability is formed of (11.beta.,17.alpha.)-17-(ethylthio)-9.alpha.-fluoro-11.beta.-hydroxy-17-(m ethylthio)androsta-1,4-diene-3-one (tipredane), and a vehicle containing as major ingredients polyethylene glycol, propylene glycol and water together with a potassium citrate buffer or tromethamine buffer, and sodium metabisulfite and butylated hydroxytoluene as antioxidants.

Steriod lotion formulation

A steroid cream formulation which has enhanced physical and chemical stability is formed of (11.beta.,17.alpha.)-17-(ethylthio)-9.alpha.-fluoro-11.beta.-hydroxy-17-(m ethylthio)androsta-1,4-dien-3-one (tipredane), and a vehicle containing as major ingredients glyceryl monostearate having an acid value of greater than 4, propylene glycol and water together with a sodium citrate or potassium citrate buffer, a non-acidic long chain fatty acid wax to impart proper consistency, and sodium metabisulfite as an antioxidant, together with emulsifiers, skin conditioners, emollients, lubricants and other conventional cream formulation ingredients.

Steroid cream formulation

A steroid ointment formulation which has enhanced physical and chemical stability is formed of 11.beta.,17.alpha.)-17-(ethylthio)-9.alpha.-fluoro-11.beta.-hydroxy-17-(me thylthio)androsta-1,4-dien-3-one (tipredane), and a vehicle containing as major ingredients propylene glycol and water, cetearyl alcohol and ceteareth 20 or other dispersing agent for propylene glycol, together with a sodium or potassium citrate and magnesium hydroxide buffer to impart a neutral or slightly alkaline apparent pH (5 to 9), a non-acidic long chain fatty acid wax to impart proper consistency to the ointment and sodium metabisulfite and butylated hydroxy toluene as antioxidants, together with thickeners, emollients, lubricants and other conventional ointment formulation ingredients.

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Plainsboro, NJ, United States of America

Sailesh A Varia