Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-09-15
2003-03-25
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S456000
Reexamination Certificate
active
06538023
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to the therapeutic efficacy of green tea polyphenols for patients of sickle cell anemia (SCA). SCA is a serious disease generally found in a specific ethnic group, namely, African Americans and inhabitants of the African continent and nearby countries. In America, 1 out of every 500 of African descents suffers, but in Africa, the ratio is ten times higher. Approximate patient numbers are around 100,000 in the United States, but several millions in Africa. When sickle cell crisis occurs, the patients experience severe pain which is caused by the occlusion of blood vessels jammed with red blood cells. Since the average life span of their red blood cells is only about two weeks as opposed to about 120 days for normal subjects, the patients suffer from chronic anemia. Frequently observed symptoms are: acute chest syndromes, splenic infarction; cardiomegaly; neurological disorders such as hemiplegia, convulsions, coma and stupor; pathologic bone abnormalities such as marrow expansion, avascular necrosis, and osteomyelitis; and leg ulceration. In Africa, SCA causes high mortality in infants and children. Their survival rate to adulthood in Africa is less than 50%. Even though the patients' survival to adulthood is not uncommon in the United States, SCA is a disastrous disease.
Considering the demographics of SCA, the best hope for the majority of patients would be a low cost self-administered oral therapy. Currently, one such hope for these patients is oral administration of hydroxyurea. This is designed to increase the level of fetal hemoglobin which does not polymerize under deoxygenation. Hydroxyurea therapy has been shown to have beneficial effects, but it is still not free of side effects including bone marrow suppression. If the suppression develops, the patients have to stop the medication until the bone marrow could recover. Since SCA is a genetic disease, any drugs would have to be taken for life-long. There is no guarantee that the prolonged administration of hydroxyurea might cause undesirable side effects. Therefore, a safer method is urgently needed.
SUMMARY OF THE INVENTION
The inventor found from in vitro experiments that green tea polyphenols could inhibit dense cell formation by inhibiting K-Cl cotransport phenomenon across the sickle red blood cell membrane. This K-Cl cotransport is the major mechanism by which sickle cells are dehydrated in the circulation. It has been shown that the formation of dense cells is the triggering cause for sickle cell crisis (Ballas, S. K. and Smith, E. D. Blood 79:2154-2163, 1992; Fabrey, M. E., Benjamin, L., Lawrence, C. and Nagel, R. L. Blood 64:559-563, 1984).
Therefore, the prevention of dense cell formation would solve many of the problems from which the patients are suffering. Here, we propose a new therapy of SCA by oral administration of green tea polyphenols, such as Polyphenon™ E or its purified components, at the dosage of 200 mg to 1,000 mg/50 kg body weight of the patients/day. A preferred dosage is 600 mg/50 kg body weight of the patients/day. Green tea polyphenols are known to be safe. For example, the acute oral toxicity (LD
50
) of Polyphenon™ E, in which Epigallocathechin gallate (EGCg) is the major component as shown in Table 1, is 1.5 gram/kg body weight in mice.
Many attendant features of this invention will become readily appreciated as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings:
REFERENCES:
patent: 5273992 (1993-12-01), Brugnara et al.
Grinberg L. N. et al., Abstract to “Protective effects of tea polyphenols against oxidative damage ot red blood cells”, Biochem. Pharmacol. 54, No. 9, pp. 973-978, 1997.*
Zhang, A. et al., Abstract to “Inhibitory effects of jasmine green tea epicatechin isomers on free readical-induced lysis of red blood cells.”, Life Sci. 61, No. 4, 383-394, 1997.*
Olivieri, O. et al., “Activation of K+/Cl-cotransport in human erythrocytes exposed to oxidative agents”, Biochim Biophys Acta, Mar. 10, 1993, pp. 1176(1-2):34-42 [PubMed abstract].
Agil, A. et al., “Hydroxy-urea protects erythrocytes against oxidative damage”, Redox Rep. 2000, 5(1), pp. 29-34 [PubMed abstract].
Iyamu, E.W., et al., “Hydroxyurea-induced oxidative damage of normal and sickle cell hemoglobins in vitro: amelioration by radical scavengers”, J. Clin Lab Anal. 2000, 15(1):1-7 [PubMed abstract].
Caesar Rivise Bernstein Cohen & Pokotilow Ltd.
Jones Dwayne C.
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