Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Attached to antibody or antibody fragment or immunoglobulin;...
Patent
1979-02-12
1982-04-27
Nucker, Christine M.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Attached to antibody or antibody fragment or immunoglobulin;...
128659, 424 9, A61K 4900, A61K 4300
Patent
active
043270743
ABSTRACT:
Hyperacidified tumors having high .beta.-glucuronidase activity can be treated with glucuronides with aglycones toxic to the tumor cells with great safety toward the rest of the body by first administering an alkalinizing agent in an amount sufficient to maintain the pH level of non-tumor tissues at approximately 7.4 during the glucuronide treatment. This will cause inactivation of .beta.-glucuronidase activity in the rest of the body. Novel glucuronides are disclosed the aglycones of which exert a higher toxic effect in an acid environment or is water-soluble only in an alkaline environment. Such compounds have particular utility with the above process. By substituting radioisotopes into the aglycone, diagnosis and in situ radiation therapy may be accomplished. Bacterial cells having .beta.-glucuronidase activity may also be diagnosed and treated in accordance with the present invention. A urine test is disclosed to determine the amount of free glucuronic acid in the urine which is an indication of the presence of a tumor in the body having high .beta.-glucuronidase activity.
REFERENCES:
patent: Re29465 (1977-11-01), Johnson
patent: 3758455 (1973-09-01), Arita
patent: 3880995 (1975-04-01), Jones
patent: 3959253 (1976-05-01), Jones
Von Ardenne, M. et al, "Anti-Cancer Agents with Activation in Strongly Hyperacidified Tumor Tissue: CMT-Selectines" Agressologie, 1976, 17, 5,261-264.
Von Ardenne, M. et al, "Tumor pH and pH-dependent Increases in the Toxicity of Anti-Neoplastic Drugs", Pharmazie 32, (2): 74-75, 1977.
Bicker, U., "Application of .beta.-D-Glucuronides and Glucose Together Suggests a New Direction for Cancer Chemotherapy Nature, 252, Dec. 20-27, 174, pp. 726-727.
Sweeney, M. J., et al, "Possible In Situ Activation of Mycophenolic Acid by .beta.-Glucuronidase", Cancer Research 31, pp. 477-478, Apr. 1971.
Kaneko, M., et al., "Synthesis of D-Glucuronic Acid Derivatives of 5-Fluorouracil Having O-Glycosidic Linkage" Chem. Phar. Bull., 25 (9), pp. 2458-2460, (1977).
Baba, T., et al, "5-Fluorouracil-O-.beta.-Glucuronide as a Newly Synthesized Chemically Modified, Non-Toxic Anticancer Drug", Gann, 69, pp. 283, 284, Apr. 1978.
Connors, T. A., "Cure of Mice Bearing Advanced Plasma Cell Tumors With Aniline Mustard: The Relationship Between Glucuronidase Activity and Tumor Sensitivity, Nature, Lond., 210, pp. 866-867, 1966.
Bukhari, M. A., et al., "Aryl-2-halogenoalkylamines XXVI-Glucuronic, Sulfuric and Phosphoric Esters of p-di-2-chloroethylaminophenol", Biochem. Pharm., 21, pp. 963-967, (1972).
Ball, C. R., et al, "Enzyme-Activated Anti-Tumor Agents-Conjugates of p-hydroxyaniline Mustard as Substrates for Hydrolytic Enzymes", Biochem. Pharm., 23, pp. 3171-3177, (1974).
Watabe, T. et al., "The Effect of Various Substituents on the Hydrolysis of Mono-substituted Phenol-.beta.-D-Glucuronic Acids by .beta.-Glucuronidase", Chem. Pharm. Bull. 18(2) pp. 414-415 (1970).
Fenselau, C. "Mandelonitrile Beta-Glucuronidase: Synthesis and Characterization", Science , 198 (4317) pp. 625-627, 1977.
Anghileri, L. J. et al "Beta-Gucuronide Activity in Tumors: Accumulation of Radioiodinated Phenolphthalein", Oncology 25:pp. 19-32 (1971).
Mitchell, J. S., "Attempts to Develop Radioactive Drugs in the Treatment of Cancer", Radiotracer Tech. Appl. vol. 2, 1977, pp. 1081-1110.
Gullino, T. M., et al, "Modifications of the Acid-Base Status of the Internal Milieu of Tumors", Journal of the National Cancer Institute, 34, 6, pp. 857-869, (1965).
Levij, I. S., et al "Inhibition by 2,4-Dinitrophenol of 9,10-Dimethyl--1,2-Benzanthracene Carcinogenesis in the Hamster Cheek Pouch", Oncology, 31, pp. 334-337 (1975).
Merck Index, 9th edition, 7325 "Podophyllotoxin". _
Nucker Christine M.
Schwartz Erwin S.
Schwimmer Adolf W.
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