Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1994-03-07
1997-02-25
Nutter, Nathan M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514513, 514515, 514529, 514538, 514563, 514567, A61K 3121, A01N 3700, A01N 4740, A01N 4746
Patent
active
056059302
ABSTRACT:
Compositions and methods of treating anemia, cancer, AIDS, or severe .beta.-chain hemoglobinopathies by administering a therapeutically effective amount of phenylacetate or pharmaceutically acceptable derivatives thereof or derivatives thereof alone or in combination or in conjunction with other therapeutic agents including retinoids, hydroxyurea, and flavonoids. Intravesicle methods of treatment of cancers phenylacetate. Pharmacologically-acceptable salts alone or in combinations and methods of preventing AIDS and malignant conditions, and inducing cell differentiation are also aspects of this invention. A product as a combined preparation of phenylacetate and a retinoid, hydroxyurea, or flavonid (or other mevalonate pathway inhibitor) for simultaneous, separate, or sequential use in treating a neoplastic condition in a subject. Methods of modulating lipid metabolism and/or reducing serum triglycerides in a subject using phenylacetate.
REFERENCES:
patent: 3973022 (1976-08-01), Goschke
patent: 3976673 (1976-08-01), Pifferi
patent: 3998966 (1976-12-01), Fried et al.
patent: 4028404 (1977-06-01), Bays et al.
patent: 4282214 (1981-08-01), Flora et al.
patent: 4457942 (1984-07-01), Brusilow
patent: 4470970 (1984-09-01), Burzynski
patent: 4720506 (1988-01-01), Munakata et al.
patent: 5204367 (1993-04-01), Wright et al.
patent: 5244922 (1993-09-01), Burzynski
Neish et al, "Phenyacetic Acid as a Potential Therapeutic Agent for the Treatment of Human Cancer" Experentia, vol. 27:860-861 (1971).
Smigel, K., Non-toxic drug being tested to treat cancer and anemias [news], J. Natl. Cancer Inst., 84(18):1398 (Sep. 16, 1992).
Ross, Philip D. and Subramanian, S., Inhibition of sickle cell hemoglobin gelation by some aromatic compounds, Biochem. Biophys. Res. Commun., 77:1217-1223 (1977).
Jones, G. L., Anti sickling effects of Betw Di Ethylaminoethylidiphenylpropyl acetate SFK-525-A, Pharmacologist, 20(3):204 (1978).
Erhum, Wilson O., Acetonyl esters of hydroxybenzoic acids as potential antisickling agents, Niger. J. Pharm., 12:285-287 (1981).
Abemayor, E. et al., Effects of retinoic acid on the in vivo growth of human neuroblastoma cells, Cancer Lett. (Netherlands), 55(1):1-5 (Nov. 19, 1990).
Cinatl, J. et al., In vitro differentiation of human neuroblastoma cells induced by sodium phenylacetate, Cancer Lett. (Netherlands), 70(1-2):15-24 (Jun. 15, 1993).
Gorski, G. K. et al., Synergistic inhibition of human rhabdomyosarcoma cells by sodium phenylacetate and tretinoin, In vitro Cell. Dev. Biol., 29A:189-191 (Mar. 1993).
Burzynski, S. R. et al., Preclinical studies on antineoplaston as2-1 and antineoplaston AS2-5, Drugs Exptl. Clin. Res., Supplemental 1, XII:11-16 (1986).
Timothy J. Ley, et al., 5-Azacytidine Selectively Increases .gamma.-globin Synthesis in a Pateint with .beta..sup.+ Thalassemia, New England Journal of Medicine, vol. 307:1469-1475 (Dec. 8, 1982).
Michael B. Sporn, et al., Chemoprevention of Cancer with Retinoids, Federartion Proceedings, vol. 38:2528-2534 (Oct. 1979).
Richard L. Momparler, et al., Clinical Trial on 5-AZA-2'-Deoxycytidine in Patients with Acute Leukemia, Pharmac. Ther., vol. 30:277-286 (1985).
Gary J. Kelloff, et al., Chemoprevention Clinical Trials, Mutation Research, vol. 267:291-295 (1992).
I. Bernard Weinstein, Cancer Prevention: Recent Progress sand Future Opportunities, Cancer Research, vo. 51:5080s-5085s (1991).
Olli Simell, et al., Waste Nitrogen Excretion Via Amino Acylation: Benzoate and Phenylacetate in Lysinuric Protein Intolerance, Pediatr. Res., vol. 20:1117-1121 (1986).
Neish, et al., Phenylacetic Acid as a Potential Therapeutic Agent for the Treatment of Human Cancer, Experentia, vol. 27:860-861 (1971).
J. A. Stamatoyannopoulos, et al., Therapeutic Approaches to Hemoglobin Switching in Treatment of Hemoglobinopathies, Annu. Rev. Med., vol. 43:497-521 (1992).
Marcot et al., Chemical Abstracts, 83, 1975,:53278s (1975).
Leary, Cancer Drug Also Helps in Treating Sickle Cell Anemia, Researchers Say, Atlanta Journal-Constitution, Thursday, Aug. 20, 1992.
Dvorit Samid, et al., Selective Growth Arrest and Phenotypic Reversion of Prostate Cancer Cells In Vitro by NonToxic Pharmacological Concentrations of Phenylacetate, The Journal of Clinical Investigation, vol. 91:2288-2295 (1993).
Dvorit Samid, et al., Induction of Erythroid Differentiation and Fetal Hemoglobin Production in Human Leukemic Cells Treated with Phenylacetate, Journal of the Amercan Society of Hematology, vol. 80:1576-1581 (1992).
Dvorit Samid, et al., Phenylacetate: A Novel Nontoxic Inducter of Tumor Cell Differentiation, Cancer Research, vol. 52:1988-1992 (1992).
George J. Dover, et al., Increased Fetal Hemoglobin in Patients Receiving Sodium 4-Phenylbutyrate, The New England Journal of Medicine, vol. 327:569-570 (1992).
Brusilow, S. W. and Horwich, A. L., Urea cycle Enzymes, in Metabolic Basis of Inherited Diseases 629-633 (C. R. Scriver ed., 1989).
Shecter, Y. et al., Hydroxyphenyl Acetate Derivatives Inhibit Protein Tyrosine Kinase Activity and Proliferation in Nb2 Rat Lymphoma Cells and Insulin-Induced Lipogenesis in Rat Adipocytes, Molecular and Cellular Endocrinology, vol. 80, pp. 183-192 (1991).
Samid, D. et al., Interferon in Combinaton with Antitumourigenic Phenyl Derivatives: Potentiatio of IFN.alpha. Activity In-Vitro, British J. Haematology, vol. 79, Supp. 1, pp. 81-83 (Oct. 10, 1991).
The Merck Index (Susan Budavari, et al. eds., 1989).
Burzynski, S., Preclinical Studies on Antineoplaston AS2-1 and Antineoplaston AS2-5, Drugs Exptl. Clin. Res., 12[Supp. I], pp. 11-16 (1986).
M. A. Smith, et al., Retinoids in Cancer Therapy, Journal of Clinical Oncology, 10:839-864 (1992).
R. L. Stephens, M. D., et al., Adriamycin and Cyclophosophamide Versus Hydroxyurea in Advanced Prostatic Cancer: A Randomized Southwest Oncology Group Study, Cancer 53:406-410 (1984).
Ljeune. F., et al., Disseminated melanoma, preclinicla therapeutic studies, clinical trails and patient treatment, Oncology 5:390-396 (1993).
Wuarin, L., et al., Effects of interferon-gamma and its interaction with retinoic acid on human neuroblastoma differentiation, Int. J. Cancer 48:136-141(1991).
Hendrix, M. J. C., et al., Retinoic acid inhibition of human melanoma cell invastion through a reconstituted basement membrane and its relatiion to decreases in the expression of proteolytic enzymes and motility factor receptor, Cancer Research 50:4121-4130 (1990).
Rudling, M. J., et al., Low density lipoprotein receptor activity in human intracranial tumors and its relation to the cholesterol requirement, Cancer Research 50:483-487 (1990).
Lando, M., et al., Modulation of intracellular cyclic adenosine monophosphate levels and the differentiation response of human neuroblastoma cells, Cancer Research 50:722-727.
Bloedow, C. E., Phase II studies of hydroxyurea (NSC-32065) in adults: miscellaneous tumors, Cancer Chemotherapy Reports No. 40, pp. 39-41 (1964).
Kandutsch, A. A. and Saucier, S. E., Regulation of sterol synthesis in eveloping brains of normal and jimpy mice, Archives of Biochemistry and Biophysics 135:201-208 (1969).
Evans, A. E., et al., A Review of 17 IV-S Neublastoma Patients at the Children's Hospital of Philadelphia, Cancer 45:833-839 (1980).
Thiele, C. J., et al., Decrased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma, Nature 313:404-406 (1985).
Giuffr e, L., et al., Cyclic AMP induces differentiation in vitro of human melanoma cells, Cancer 61:1132-1141 (1988).
Nordenberg, J., et al., Growth inhibition of murine melanoma by butyric acid and dimethylsylfoxide, Experimental Cell Research 162:77-85 (1986).
Sidell, N., et al., Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines, Experimental Cell Research 148:21-30 (1983).
Donehower, R. C., Hydroxyurea, Cancer Chemotherapy, pp. 225-233 1993.
Questionable methods of cancer management: hydrogen peroxide and other `hyperoxygenation` therapies, Questionable Methods 43:47-56 (1993).
Finklestein, J. Z., et al., 13-c9s-retinoic acid (NSC 122758) in the tr
Nutter Nathan M.
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