Active oxygen scavenger and cancer chemopreventer from Grifola

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Reexamination Certificate

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C424S725000

Reexamination Certificate

active

06616928

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an active oxygen scavenging agent and a cancer chemopreventing agent both which can prevent biological damage in living bodies caused by excess active oxygen and can also prevent the development of cancer, and also relates to a food or animal feed comprising the active oxygen scavenging agent and/or the cancer chemopreventing agent.
2. Description of the Prior Art
Oxygen is essential for most of the animals and plants on the earth to live. However, excess oxygen exerts a harmful action called “oxygen toxicity”, which is likely to damage a living body, and therefore upon recently has been focused on as a causative substance of the acceleration of aging and various diseases or disorders specific to adult people, including cancer.
Oxygen found in the atmosphere normally takes the form of a stable, so-called “triplet oxygen”. Upon taking up into a living body, the oxygen is partially converted into a highly reactive substance called “active oxygen”. Active oxygen is necessary for killing pathogenic viruses or bacteria invading into a living body, and plays an extremely important role in biophylaxis. However, it has become evident that excess active oxygen in a living body adversely acts on proteins, lipids and even nucleic acids to cause various kinds of damage in the living body, and therefore is a cause of the acceleration of aging and the development of various diseases, such as arteriosclerosis, diabetes, Alzheimer's disease and Crohn's disease.
The active oxygen species produced in a living body include: in a narrow sense, superoxide anion radical (O
2

), hydrogen peroxide (H
2
O
2
), hydroxyl radical (.OH) and singlet oxygen (
1
O
2
); and in an broad sense, in addition to the above four species, alkoxy radical (LO.), lipid peroxy radical (LOO.), nitric oxide (NO) and peroxy nitrite (ONOO

) which is a reaction product of nitrogen oxide and a superoxide.
As the scavengers for these active oxygen species, the following substances are known:
(1) superoxide dismutase (SOD)—for superoxide anion radicals;
(2) catalase, glutathione peroxidase, ascorbate peroxidase, and the like—for hydrogen peroxide;
(3) carotenoids, tocopherol and the like—for singlet oxide; and
(4) tocopherol, flavonoids, ascorbic acid, glutathione, carotenoids and the like—for alkoxy radicals and lipid peroxy radicals.
These scavengers, however, have disadvantages. For example, superoxide dismutase (SOD) is difficult to be applied to experiments that use cells, animals and plants, because it is a protein. Other enzymatic scavengers, such as catalase for hydrogen peroxide, are also difficult to handle for the same reason as mentioned for SOD. Carotenoids, tocopherol and the like for singlet oxide have poor selective activity.
With respect to hydroxyl radicals (.OH), no specific scavenger is found, because hydroxyl radicals can react with various biocomponents in a diffusion-dependent mode. Mannitol, dimethyl sulfoxide (DMSO), ethanol, thiourea and the like are known to be scavengers for hydroxyl radicals. However, these substances are insufficient for scavenging hydroxyl radicals when used singly, and therefore the use of these substances in combination must be considered. Thus, up to now, no satisfactory scavenger has been developed.
On the other hand, a number of new methods for the diagnosis and treatment of cancer have been developed. Nevertheless, the number of deaths caused by cancer tends to increase on a worldwide basis. Therefore, in parallel to the extensive studies on cancer eradication, value is increasingly being placed upon studies on the prevention of cancer. The methodologies for the prevention of cancer are as follows:
(i) Identification and removal of carcinogenic substances; and
(ii) Screening and active intake of cancer preventing substances.
Since there are innumerable chemical substances in the surroundings, it will take enormous labor and cost to identify and screen carcinogenic substances. Even if identified, it is probably impossible to eliminate the carcinogenic substances from the environment. Therefore, although it is still necessary to avoid the substances which are clearly shown to be involved in cancer development, it has been considered that the active intake of cancer preventing substances is very effective for cancer prevention.
Actually, the researchers of the National Cancer Institute of U.S.A. established a category “cancer chemoprevention”, which is defined as an approach to inhibit the development and growth of cancer through administration of a certain substance. This approach has recently been studied intensively in most countries of the world including the U.S.A. However, as yet, no effective approach for the prevention of cancer has been found, and such an approach is demanded.
SUMMARY OF THE INVENTION
Under these circumstances, the present inventors have extensively screened the daily foods that have the scavenging activity against active oxygen species, particularly hydroxyl radicals. As a result, the inventors have found that Maitake and related mushrooms and derivatives thereof have an effective hydroxyl radical scavenging activity, as well as a superoxide anion radical scavenging activity and a superoxide dismutase (SOD)-like activity. This finding leads the accomplishment of the invention.
In addition to the active oxygen scavenging activity, the inventors have also examined daily foods on the cancer chemopreventing activity.
The research on the cancer chemopreventing activity takes more labor and cost compared to a tumor-growth inhibition test that is usually performed for the development of a anticancer agent or the like. This is because such a research requires a far longer period of time for the administration of test substances into test animals and for the observation of the pathologic process, and had to be performed under tightly controlled conditions for the test animals. Nevertheless, through such a research, the inventors have found that Maitake and related mushrooms and derivatives thereof have a cancer chemopreventing activity. This finding leads the accomplishment of the invention.


REFERENCES:
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patent: 5854404 (1998-12-01), Nanba et al.
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Garuda International Web Site: http://www.cowcium.com/dmaiext.htm, Oct. 1998.*
Gura, T. Systems for Identifying New Drugs are Often Faulty; Science, vol. 278, 1997 pp. 1041-1042.*
Kelloff, G. J., Boone, C. W., Malone, W. F., Steele, V. E., Recent results in preclinical and clinical drug development of chemopreventive agents at the National Cancer Institute, inCancer Chemoprevention, pp. 41-55, CRC Press (1992).
Nanba, H., Maitake Mushroom immune therapy to prevent from cancer growth and metastasis,Explore! Vol 6 No. 1, pp. 16-18, 1995.
Benner, S. E., Pastorino, U., Lippman, S. M., Hong, W. K., Second international cancer chemoprevention conference,Cancer ResearchVol 54, pp. 854-856, 1994.
McNamee, D., New society focuses on cancer chemoprevention,The Lancet, Vol 346, p. 1222, 1995.

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