Warner-lambert Company

Gerard C Hokanson

James C French

Michael Ray Harris

Josefino B Tunac

John P Schaumberg

Kuchi S Murthy

John H Wilton

Frank Waldman

Mahdi B Fawzi

Jay Weiss

Timothy R Hurley

Richard H Bunge

Robert G Reisch, Jr

Jane Ellen Daniel

Christopher Franklin Bigge

Edward Faith Elslager

Blanche D Graham

Tim A Smitka

Allen I Kay

Alex J Brankiewicz

Marjorie A Underhill

Stephen W Mamber

Robert Reisch

Cynthia A Young

Donald L Kern

The present invention is directed to ACE inhibitor-containing compositions stabilized by the presence of magnesium oxide. Preferably, the ACE inhibitor, quinapril, is protected from certain forms of degradation when prepared in a pharmaceutical composition consisting essentially of magnesium oxide as the stabilizing agent. The presence of magnesium oxide also lends itself to favorable processing conditions during the manufacture of ACE inhibitor-containing compositions, especially processing by wet granulation.

Stabilization of quinapril using magnesium oxide

A purified isolate of an actinomycete identified as ATCC 39366 is capable of producing the anti-microbial compound CL-1957B which also exhibits antitumor properties. The antimicrobial compound CL-1957B is produced by cultivating isolate ATCC 39366 under aerobic conditions in a culture medium containing assimilable sources of carbon and nitrogen until a substantial quantity of the CL-1957B compound is produced, and subsequently isolating the compound. The antibiotic compound CL-1957B, its pharmaceutically acceptable salts, the pharmaceutical compositions comprising this substance together with a pharmaceutically acceptable carrier is also disclosed, as are methods of treating microbial infections and tumors in mammals, employing these pharmaceutical compositions.

CL-1957B antibiotic compound and its production

The oxidation--and color-stability of certain ace inhibitors is optimized when they are formulated with a stabilizer and at least one lubricant and/or excipient.

Drug compositions stabilized against oxidation

The cyclization and hydrolysis of certain ACE inhibitors is minimized when they are formulated with a stabilizer and at least one lubricant and/or excipient.

Stabilized drug compositions

A purified isolate of an actinomycete identified as ATCC 39366 is capable of producing the anti-microbial compound CL-1957A which also exhibits antitumor properties. The antimicrobial compound CL-1957A is produced by cultivating isolate ATCC 39366 under aerobic conditions in a culture medium containing assimilable sources of carbon and nitrogen until a substantial quantity of the CL-1957A compound is produced, and subsequently isolating the CL-1957A compound. The antibiotic compound CL-1957A and pharmaceutical compositions comprising this substance together with a pharmaceutically acceptable carrier is also disclosed, as are methods of treating microbial infections and tumors in mammals, employing these pharmaceutical compositions.

CL-1957A antibiotic compound

The cyclization, hydrolysis, and coloration of certain ACE inhibitors is minimized when they are formulated with a metal-containing stabilizer and a saccharide.

Stabilized compositions

2'-Chloropentostatin is a potent inhibitor of the enzyme adenosine deaminase and possesses utility as an agent for potentiating the activity of antiviral agents for the treatment of DNA viruses which agents contain an adenine moiety, such as 9-(beta-D-arabinosyl)adenine. A pure strain of actinomycete, designated ATCC 39365 which is capable of producing 2'-chloropentostatin, a method of producing 2'-chloropentostatin by aerobic fermentation, and pharmaceutical compositions including 2'-chloropentostatin are also disclosed.

2-chloropentostatin compound having adenosine diaminase inhibitory

The antimicrobial agent CL-1565-A can be effectively stabilized for up to about two years using certain salts or esters of carboxylic acids or their precursors as stabilizing additives.

Novel pyranone compounds and related compounds, methods of preparing the compounds, and their use as cytotoxic and/or antileukemic agents or precursors, are provided.

Antibiotic CL-1565 complex derivatives

CL-1577-B.sub.4 compound is derived by the solvolysis under anhydrous conditions of either CL-1577A compound of CL-1577B compound, obtained from the fermentative action of a purified strain of Actinomycete designated ATCC 39363 under aerobic conditions. CL-1577-B.sub.4 compound is a potent antimicrobial agent, possessing activity against a number of gram-positive and gram-negative bacteria, yeasts, and fungi. In addition, the compound exhibits in vivo activity against the P388 murine leukemia cell line and in vitro activity against the L1210 murine leukemia cell line. A method of making the compound as well as pharmaceutical compositions and methods for their use are also disclosed.

CL-1577-B.sub.4 compound, its production and use

Acids, esters, imine acids, imine esters, and imine amides derived from 6-formyl-4,7,9-trihydroxy-1-phenazinecarboxylic acid, methyl ester and from 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylic acid, methyl ester demonstrate antimicrobial and antineoplastic activity. A purified strain of Streptomyces galanosa, NRRL 15738, is capable of producing 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylic acid, methyl ester in isolable quantities from a fermentation broth containing assimilable sources of carbon and nitrogen.

Antimicrobial and antitumor phenazine carboxaldehydes and derivatives

CL-1577-B.sub.4 compound is derived by the solvolysis under anhydrous conditions of either CL-1577A compound or CL-1577B compound, obtained from the fermentative action of a purified strain of Actinomycete designated ATCC 39363 under aerobic conditions. CL-1577-B.sub.4 compound is a potent antimicrobial agent, possessing activity against a number of gram-positive and gram-negative bacteria, yeasts, and fungi. In addition, the compound exhibits in vivo activity against the P388 murine leukemia cell line and in vitro activity against the L1210 murine leukemia cell line. A method of making the compound as well as pharmaceutical compositions and methods for their use are also disclosed.

A strain of actinomycete, NRRL 15758, is capable of producing the CL-1724 complex of compounds under conditions of aerobic fermentation in the presence of assimilable sources of carbon and nitrogen. The compound CL-1724B-2 exhibiting antimicrobial and antitumor activity, is claimed together with pharmaceutical compositions and methods of treating microbial infections and tumors in mammals employing these pharmaceutical compositions.

CL-1724 Antibiotic compounds, their production and use

A purified isolate of an actinomycete identified as ATCC 39364 is capable of producing the antimicrobial/antitumor compound 2-amino-1,9-dihydro-6H-purine-6-one-7-oxide, commonly known as guanine-N.sup.7 -oxide. Guanine-N.sup.7 -oxide is produced by cultivating isolate ATCC 39364 under aerobic conditions in a culture medium containing assimilable sources of carbon and nitrogen until a substantial amount of the compound is produced and thereafter isolating the compound. The antibiotic/antitumor compound guanine-N.sup.7 -oxide and pharmaceutical compositions comprising this compound or one of its pharmaceutically acceptable salts together with a pharmaceutically acceptable carrier are also disclosed as is a method of treating microbial infections in a mammal or of treating tumors in a mammal.

Growing community of inventors

Ann Arbor, MI, United States of America

Gerard C Hokanson