Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/12—Ketones
  • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• Lung cancers are usually divided into two groups by clinical and biological criteria: (1 ) non-small-cell lung cancer (NSCLC) (Boring et aL. 1994). and (2 ) small-cell lung cancer (SCLC).
• NSCLC non-small-cell lung cancer
• SCLC small-cell lung cancer
• Most small-cell lung cancers are sensitive to chemotherapy, whereas NSCLC usually are refractory to chemotherapy at the time of diagnosis (Minna et ai, 1989). Thus NSCLC are the cause of most lung cancer deaths (Boring, et ai. 1994).
• intensive effort has been made to characterize specific gene alteration in lung cancers and to develop therapies that target those genes.
• neu oncogenes are associated with the proliferative potential.
• new-mediated cancers appear to be resistant to host defense mechanisms.
• overexpression of the neu oncogene in transfected cells results in resistance to tumor necrosis factor, a major effector molecule in macrophage-mediated tumor cell cytotoxicity.
• neu expression has also been detected in ovarian cancer and its overexpression results in poor prognosis.
• the expression of neu oncogenes in human tumor cells induce resistance to several host cytotoxic mechanisms.
• second agents that may be used with emodin or emodin-like tyrosine kinase inhibitor are anti-neoplastic agents.
• examples of these are cisplatin; doxorubicin (Mechetner & Roninson, 1992) and analogues, such as 14-O-hemiesters of doxorubicin; etoposide; vincristine (Shirai et al., 1994; Friche et aL, 1993); vinblastine (Bear, 1994; McKinney & Hosford, 1993); actinomycin D (McKinney & Hosford, 1993); daunomycin (Bear, 1994); daunorubicin (Muller et al., 1994); taxotere (Hunter et al., 1993); taxol (Mechetner & Roninson, 1992); and tamoxifen (Trump et al.. 1992).
• the skilled artisan is directed to "Phy
• Agents that directly cross-link nucleic acids, specifically DNA, are envisaged and are shown herein, to eventuate DNA damage leading to a synergistic antineoplastic combination Agents such as cisplatin. and other DNA alkvlating agents may be used.
• emodin as an exemplary emodm-like inhibitor to synergistically enhance the antineoplastic effects of the doxorubicin in the treatment of cancers.
• Those of skill in the art will be able to use the invention as exemplified potentiate the effects of doxorubicin in a range of different new-mediated cancers.
• Vincristine has been effective in Hodgkin's disease and other lymphomas. Although it appears to be somewhat less beneficial than vinblastine when used alone in Hodgkin's disease, when used with mechlorethamine, prednisone. and procarbazme (the so-called MOPP regimen), it is the preferred treatment for the advanced stages (DI and IV) of this disease. In non-Hodgkin's lymphomas, vincristine is an important agent, particularly when used with cyclophosphamide, bleomycin, doxorubicin. and prednisone. Vincristine is more useful than vinblastine in lymphocytic leukemia.
• Vinblastine is metabolized in the liver to biologically activate denvative desacetylvinblasune Approximately 15% of an administered dose is detected intact in the u ⁇ ne, and about 10% is recovered in the feces after biliary excretion Doses should be reduced in patients with hepatic dysfunction At least a 50% reduction in dosage is indicated if the concentration of bilirubm m plasma is greater than 3 mg dl (about 50 mM).
• the active compounds of the present invention will often be formulated for parenteral administration, e g , formulated for injection via the intravenous, intramuscular, sub-cutaneous, or even intraperitoneal routes
• parenteral administration e g
• aqueous composition that contains emodin or emodm-like compounds alone or in combination with a second agent as active ingredients
• Such compositions can be prepared as mjectables. either as liquid solutions or suspensions, solid forms suitable for using to prepare solutions or suspensions upon the addition of a liquid pnor to injection can also be prepared; and the preparations can also be emulsified.
• Example 2 The results from Example 2 show that phosphotyrosme level of pl85 ⁇ "' is repressed by emodin. To examine whether this reduction m tyrosine phosphorylation affects the tyrosine kinase activity of pl85 n ' M . the immuno-complex kinase assay was used.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 1997
  • 1997-01-31 JP JP9527880A patent/JP2000504020A/ja active Pending
  • 1997-01-31 EP EP97904188A patent/EP0877608A1/en not_active Withdrawn
  • 1997-01-31 CA CA002245165A patent/CA2245165A1/en not_active Abandoned
  • 1997-01-31 AU AU18545/97A patent/AU1854597A/en not_active Abandoned
  • 1997-01-31 WO PCT/US1997/001686 patent/WO1997027848A1/en not_active Ceased

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