Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
2000-08-25
2002-10-15
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C424S464000, C424S451000, C424S489000
Reexamination Certificate
active
06465447
ABSTRACT:
TECHNICAL FIELD
This invention relates to a method for separating an active fraction of Tochukaso (or
Cordyceps sinensis
) having antitumor activity and an active component contained therein, as well as to the chemical structure of the active component. Furthermore, the invention relates to an antitumor agent containing the active fraction or the active component.
BACKGROUND ART
Tochukaso is parasitic on insects or larvae thereof belonging to Lepidoptera (such as butterfly and moth) or Coleoptera to form sclerotium within their bodies; and it is a fruit body formed in summer on the body surfaces of the insects or larvae that are the hosts. Approximately 350 species of Tochukaso(s) are known in the world. It is a material that has traditionally been administered in oral form as a Chinese medicine since it has absolutely no toxicity to humans and exhibits a variety of effects. Today, it is listed in “The Pharmaceutical Sciences of Chinese Plants” and “The Encyclopedia of Chinese Medicines,” which are the text books concerning Chinese medicines; in this country-Japan, it is also described in many Chinese medical references such as “Oriental Drugs, New Edition.”
Pharmacological actions described in the various documents are believed to be such that they are effective for energy buildup, nourishment/robustness and circulatory diseases [The Japanese Journal of Pharmacology, 63, 213 (1995)], diabetes [Biol. Pharm. Bull., 16, 1291-1293 (1993); ibid., 19, 294-296 (1996)], hepatic disorders [Prog. Med., 12, 1172-1174 (1992)] and the like. Furthermore, recent pharmacological studies have demonstrated that the fungi of Tochukaso (
Cordyceps sinensis
) possess a wide variety of activities and pharmacological actions. The antitumor and immunopotentiation activities have also been reported in the Academic Records of the Japanese Society for Immunology, vol. 18, 665 (1988), Japanese Journal of Bacteriology, 45, 763 (1990), and J. Kanazawa Med. Univ. 17, 330-335 (1992).
However, there have been only a few cases where the active component of Tochukaso that had been completely purified was used for research and clinical purposes [J. Am. Pharm. Ass., 46, 114-118 (1957); Japanese Unexamined Patent Publication Hei 8-81386]. This posed the problem that large amounts of the Tochukaso bulk materials or tablets were required when the unpurified extracts were administered and also the problem in the uniformity or reliability of pharmacological action. Moreover, few studies have been done that are related to the classification and identification of active species from Tochukaso, as well as to the mechanism of manifestation of its pharmacological action. In Asian countries, including the People's Republic of China, where the greatest number of Tochukaso species has been found to live, medicinal herbs such as Pueravia Radix extract (Kakkon Tou) are taken brewing up. Thus, at present Tochukaso is being used following the customs and faiths of different regions. It has not yet reached the point where the pharmacological effect of Tochukaso can be maintained securely and stably.
Accordingly, in order to effectively and reliably utilize the pharmacological action of Tochukaso, particularly pharmacological effects such as antitumor activity and immunopotentiation activity, there is a strong need for the development of a method to separate an active component having the activity among the components of Tochukaso.
DISCLOSURE OF THE INVENTION
This invention takes note of an antitumor effect possessed by Tochukaso and aims at providing a separation method by which a compound having said effect can be obtained in a pure state. Further, an object of the invention is to provide a compound having such antitumor effect. Still further, an object of the invention is to provide an antitumor agent containing said compound.
REFERENCES:
patent: 1-296991 (1989-11-01), None
patent: 8-81386 (1996-03-01), None
patent: 9-235293 (1997-09-01), None
Tsunoo et al., ‘Non-Purinergic and Non-Adrengergic Effects of Cordyceps Sinensis (Tochu-Kaso) on Respiratory Tracts and Aortae’, 16018, P2-191, p. 213.
Kiho et al., ‘Polysaccharides in Fungi. XXXII. Hypoglycemic Activity and Chemical Properties of a Polysaccharide from the Cultural Mycelium of Cordyceps Sinensis’, Biol. Pharm. Bull. 16(12) 1291-1293 (1993).
Kiho et al., ‘Polysaccharides in Fungi XXXVI. Hypoglycemic Activity of Polysaccharide (CS-F30) from the Cultural Mycelium of Cordyceps sinensis and Its Effect on Glucose Metabolism in Mouse Liver’, Biol. Pharm. Bull. 19)2) 294-296 (1996).
Yoshida et al., ‘Potentiating Effect of an Extract of Cordyceps sinensis (Berk.) Sacc. on Cytostatic Activity of Mouse Effector Cells Against Tumor Cells’, (J. Kanazawa Med. Univ.) 17:330-335, 1992.
Chatterjee et al., ‘Cordyceps sinenis (Berkeley) Saccardo: Structure of Cordycepic Acid’, Journal of the American Pharm. Assoc., vol. XLVI, No. 2, 114-118, (Feb. 1957).
Japanese Society For Immunology, vol. 18, 665 (1988).
Prog. Med. 12:1172-74 (1992) Japanese Journal of Bacteriiology 45, 763 (1990).
Kuo et al., ‘Growth Inhibitors Against Tumor Cells in Cordyceps Sinensis Other Than Cordycepin and Polysaccharides’, Cancer Investigation, vol. 12, No. 6, 1994, pp. 611-615.
Shiao et al., ‘Natural Products of Cordyceps’, Proceedings In the National Science Council Republic of China Part A, vol. 13, No. 6, 1989, pp. 382-387.
Kadota et al., ‘Steroidal Components of I-Tiam-Hong and Cordyceps-Sinensis Separation and Identification By High-Performance Liquid Chromatography’, Yakugaku Zasshi, vol. 106, No. 12, 1986, pp. 1092-1097.
Chen Chao-Long
Goto Sigeru
Pan Tair-Long
Fitch Even Tabin & Flannery
Hisamitsu Pharmaceuticals Co., Inc.
Nguyen Helen
Webman Edward J.
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