Heumann Pharma Gmbh

U.S. Bioscience, Inc.

Medimmune Oncology, Inc.

U.S. Bioscience Inc. and Individuals

Ingomar Grafe

Johann Peter Morsdorf

Martin Stogniew

Paul Edwin Kennedy

Kurt-Henning Ahrens

Johann M&ouml;rsdorf

Johann P Morsdorf

The present invention provides for thermally stable forms of 2,4-diamino-5-methyl-6-&lsqb;(3,4,5-trimethoxyanilino)methyl&rsqb; quinazoline, or trimetrexate. A crystalline 2,4-diamino-5-methyl-6-&lsqb;(3,4,5-trimethoxyanilino)methyl&rsqb; quinazoline monohydrate, or trimetrexate monohydrate, belonging to the space group P{overscore (1)}(&num;2) and having a triclinic cell with dimensions of about a&equals;7.699 &angst;, b&equals;9.606 &angst; and c&equals;13.012 &angst; is disclosed. A novel Schiff base compound, 2,4-diamino-5-methyl-6-&lsqb;(3,4,5-trimethoxyphenylimino)-methinyl&rsqb;quinazoline, is also disclosed. The present invention further provides novel methods of producing stable trimetrexate free base compounds, including crystalline trimetrexate monohydrate. The crystalline monohydrate form provides increased stability over the anhydrous form.

Thermally stable trimetrexates and processes for producing the same

A new crystalline and anhydrous form of doxazosin mesylate is described. The new form is crystalline and anhydrous and is characterized in its X-ray spectrum by the following reflex positions of high and medium intensity: 8.49.degree., 11.72.degree., 16.03.degree., 18.29.degree., 21.03.degree., 22.87.degree. and 25.02.degree.. Owing to its crystalline properties, the new form of doxazosin mesylate according to the invention has surprising advantages both with regard to its synthesis and for pharmaceutical processing into solid dosage forms. A process for preparing the new form of doxazosin mesylate and pharmaceutical compositions comprising the new form of doxazosin mesylate are also described.

Polymorphic form of doxazosin mesylate (form III)

A new crystalline and anhydrous form of doxazosin mesylate is described. The new form is crystalline and anhydrous and is characterized in its X-ray spectrum by the following reflex positions of high and medium intensity: 10.68.degree., 14.45.degree., 17.37.degree., 23.45.degree., 23.82.degree. and 24.30 .degree.. Owing to its crystalline properties, the new form of doxazosin mesylate according to the invention has surprising advantages both with regard to its synthesis and for pharmaceutical processing into solid dosage forms. A process for preparing the new form of doxazosin mesylate and pharmaceutical compositions comprising the new form of doxazosin mesylate are also described.

Polymorphic form of doxazosin mesylate (form II)

A new crystalline and anhydrous form of doxazosin mesylate is described. The new form is crystalline and anhydrous and is characterized in its X-ray spectrum by the following reflex positions of high and medium intensity: 15.40.degree., 16.85.degree., 18.06.degree., 24.15.degree. and 25.81.degree.. Owing to its crystalline properties, the new form of doxazosin mesylate according to the invention has surprising advantages both with regard to its synthesis and for pharmaceutical processing into solid dosage forms. A process for preparing the new form of doxazosin mesylate and pharmaceutical compositions comprising the new form of doxazosin mesylate are also described.

Polymorphic form of doxazosin mesylate (Form I)

The present invention provides for a crystalline form of trimetrexate either as a glucuronate, acetate, hydrochloride, methanosulfonate or lactate salt, which can be processed galenically as a stable, well-defined solid substance and processes for producing the crystalline forms. Such crystalline forms allow for prolonged stability in storage and for oral and intravenous administration of the drug.

Crystalline trimetrexate salts and the process for making the same

The present invention provides for thermally stable forms of 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline, or trimetrexate. A crystalline 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline monohydrate, or trimetrexate monohydrate, belonging to the space group P1(#2) and having a triclinic cell with dimensions of about a=7.699 .ANG., b=9.606 .ANG. and c=13.012 .ANG. is disclosed. A novel Schiff base compound, 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyphenylimino)-methinyl]quinazoline , is also disclosed. The present invention further provides novel methods of producing stable trimetrexate free base compounds, including crystalline trimetrexate monohydrate. The crystalline monohydrate form provides increased stability over the anhydrous form.

Growing community of inventors

Nurnberg, Germany

Ingomar Grafe