11,7 substituted camptothecin derivatives and formulations of 11

Details 11,7 substituted camptothecin derivatives and formulations of 11 11,7 substituted camptothecin derivatives and formulations of 11

1994-04-19

1995-11-21

Daus, Donald G.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546 48, A61K 31475

Patent

active

054687543

ABSTRACT:
The novel compounds 11-hydroxy-7-ethyl camptothecin and 11-hydroxy-7-methoxy camptothecin (11,7-HECPT and 11,7-HMCPT) are active anticancer compounds which are poorly soluble in water. Because of their novelty, 11,7-HECPT and 11,7-HMCPT derivatives have not been directly administered by parenteral or oral routes to human subjects as an antitumor composition for the purpose of inhibiting the growth of cancer cells. The claimed compositions are useful as compared to the water soluble camptothecin derivatives, such as CPT-11, in clinical trials. The unpredictable interpatient variability in the metabolic production of an active metabolite from CPT-11 limits the utility of CPT-11. This invention overcomes these limitations by claiming novel pharmaceutically acceptable lactone stable formulations of 11,7-HECPT or 11,7-HMCPT, to directly administer to patients. The present invention also claims 11,7-HECPT and 11,7-HMCPT compositions, the synthesis of 11,7-HECPT or 11,7-HMCPT, the methods of formulation of 11,7-HECPT or 11,7-HMCPT, and the methods of use of 11,7-HECPT or 11,7-HMCPT. Additionally, the claimed invention is directed to novel dosages, schedules, and routes of administration for both the 11,7-HECPT or 11,7-HMCPT formulations to humans with various forms of cancer. Other embodiments of this invention include isolation methods and methods of synthesis of certain camptothecin derivatives.

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