Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – X-ray contrast imaging agent
Reexamination Certificate
2001-01-10
2002-07-02
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
X-ray contrast imaging agent
C540S145000
Reexamination Certificate
active
06413495
ABSTRACT:
TECHNICAL FIELD
This invention relates to a novel, X-ray-intercepting metal complex of a chlorin e6 derivative which is useful for detection, diagnosis and/or therapy of tumor or solid cancer or lesions of arteriosclerosis by X-ray radiography or X-ray irradiation. More specifically, this invention relates to a novel X-ray-intercepting gold complex or platinum complex of mono-L-aspartyl chlorin e6 or mono-L-glutamyl chlorin e6, which is capable of administering to a host mammal for the purposes of conducting detection, diagnosis and/or therapy by X-ray radiography or X-ray irradiation of tumor or solid cancer or lesions of arteriosclerosis (for example, atherosclerosis layer in an inner wall of artery) formed in the host mammal, and which is able to accumulate and distribute preferentially within the tumor, solid cancer or the lesions of arteriosclerosis and can act not only as a contrast medium capable of affording sharp X-ray image of the tumor, solid cancer and lesions of arteriosclerosis, but also is effective in therapeutic treatment of the tumor, solid cancer or the lesions of arteriosclerosis.
This invention also relates to a pharmaceutical composition comprising as an active ingredient the above-mentioned novel X-ray-intercepting gold complex or platinum complex of the chlorin e6 derivative. This invention further includes methods for the detection, diagnosis and/or therapy of tumor, solid cancer or lesions of arteriosclerosis formed in the host mammal, by using the novel X-ray-intercepting gold complex or platinum complex of the chlorin e6 derivative as above-mentioned.
BACKGROUND ART
Photochemotherapy or photodynamic therapy so called is a method for the therapeutic treatment of cancer or tumor and arteriosclerosis or other diseases, which comprises administration of a photosensitive substance capable of being excited by irradiation of ultraviolet ray or laser light. That is, it is the chemotherapy wherein ultraviolet ray or laser light is irradiated to the tissue of cancer or tumor or to lesions of arteriosclerosis in which the photosensitive substance pre-administered has been present and accumulated, or ultraviolet ray or laser light is irradiated to a bloodstream extracorporeally circulated of blood containing the photosensitive substance, so that the photosensitive substance can be excited to effect the therapeutic treatment as intended.
As the photosensitive substances to be used in such photochemotherapy or photodynamic therapy, there are known hematoporphyrin derivatives and chlorin derivatives (refer, for example, to Japanese Patent Application Publication Kokai Hei 2-138280 (patented under Japanese Patent No. 2520735), the corresponding European Patent Application Publication No. 350948 Al and Japanese Patent Publications Hei 6-88902 and Hei 6-89000, as well as U.S. Pat. Nos. 4,656,186, 4,675,338, 4,693,885 and 4,997,639 specifications). Further, one article reports a result of clinical study on photochemotherapy applied to superficial early stage cancers where a hematoporphyrin derivative is administered (refer to the Journal of the Society of Cancer Therapy of Japan, Vol. 29, pp. 1757-1766 (1994)). In particular, Japanese Patent Publications Hei 6-88902 and Hei 6-89000 and U.S. Pat. Nos. 4,656,186, 4,675,338 and 4,693,885 specifications mentioned above disclose the use, as a photochemotherapeutic agent in the diagnosis and therapeutic treatment of tumor or solid cancer, of an appropriate chlorin derivative, particularly of mono-L-aspartyl chlorin e6 and mono-L-glutamyl chlorin e6, which is represented by the following general formula (A)
wherein n stands for an integer of 1 or 2, or a salt thereof. The literatures further disclose that mono-L-aspartyl chlorin e6 or mono-L-glutamyl chlorin e6 or a salt thereof is preferentially up-taken within the tissue of tumor or solid cancer and is accumulated therein.
U.S. Pat. No. 4,997,639 specification discloses that mono-L-aspartyl chlorin e6 or other suitable chlorin derivative or a salt thereof, if administered to a host mammal, can preferentially be up-taken in such a part or parts of the host body where cholesterol has deposited therein and has been accumulated, and thus it is effective to detect the cholesterol-accumulated part by such photodynamic diagnosis method. Further, Japanese Patent Application Publication Kokai Hei 4-330013 and U.S. Pat. No. 5,308,861 specification disclose that mono-L-aspartyl chlorin e6 or other suitable chlorin derivative or a salt thereof may preferentially be accumulated in the lesions of arteriosclerosis as formed in the inner wall of artery which are accompanying with coronary arteriosclerosis inductive of cardiac infarct or angina pectoris; arteriosclerosis obliterans as induced in limb peripheral artery or aorta abdominalis; and cerebral arteriosclerosis inductive of transient cerebral ischemia or cerebral infarct, and that they may be useful for diagnosis of such lesions of arteriosclerosis by a photodynamic diagnosis method, and also that the irradiation of laser light to such lesions containing the chlorin derivative so accumulated can bring about some remedying and curing effects on the lesions of arteriosclerosis. Japanese Patent Application Publication Kokai Hei 4-330013 and U.S. Pat. No. 5,308,861 specification further report that the chlorin derivative is superior to the hematoporphyrin derivative in respect of the accumulating ability and in respect of the curative effect on the lesions of arteriosclerosis, as viewed from the results of tests of the chlorin derivative in comparison with the hematoporphyrin derivative.
Furthermore, Japanese Patent Publications Hei 6-88902 and Hei 6-89000 and U.S. Pat. Nos. 4,675,338 and 4,693,885 mentioned above disclose that the chlorin derivative described therein can form a metal complex with magnesium, iron, zinc, nickel, cobalt or copper. Further, Japanese Patent specification No. 2520735 (issued on Jul. 31, 1996) and European Patent Application Publication No. 350948A mentioned above disclose that metal porphyrins containing zinc, iron, copper, manganese, potassium, indium or other metals as the coordinating metal are useful in the photodynamic diagnosis or photodynamic therapy of cancers or tumors.
Further, a Japanese journal, YAKUGAKU ZASSHI Vol. 84, No. 12, pp. 1152-1157 (1964) reports that chlorophyllin as derived from chlorophyll can form a metal chelate compound with magnesium, cobalt, manganese, vanadium, silver or gold.
As far as the inventors of this invention have been aware of, however, there is known no metal complex of mono-L-aspartyl chlorin e6 or mono-L-glutamyl chlorin e6 with gold or platinum, up to date.
On the other hand, in the photochemotherapy and photodynamic diagnosis with using the hematoporphyrin derivatives or chlorin derivatives as a photosensitive substance, there has been used, in most cases, ultraviolet ray or laser light of a wavelength in a range of 300-800 nm as the radiation for exciting said photosensitive substance to emit the fluorescence therefrom.
However, the depth to which a laser light is capable of transmitting in the internal tissues of the host body is 5 mm-8 mm under the operating conditions used in the usual photochemotherapy and is 10 mm-20 mm at most even in such cases where a peak output of the laser light is elevated much (refer to Biotherapy, Vol. 7, pp. 673-680 (1993)). In such photochemotherapy as targetted on tissues of cancer or tumors which are existing in deep parts of the host body, it is necessary to conduct a surgical invasion with a danger or risk for patients, for example, a surgical operation for incision to reach the cancer or tumor, pouring of a photosensitive substance into the region of such cancer or tumor tissue or surgical insertion of a laser irradiation device into the body, and the like. In such cases where the photochemotherapy is directed to treatment of the arteriosclerosis, it becomes necessary to perform a special and troublesome surgical invasion, such as an insertion of a laser irradiation device into the blood vessels. Since, however, such a su
Aizawa Katsuo
Aman Noriaki
Gomi Shuichi
Sumi Shinjiro
Takahashi Hirotada
Habte Kahsay
Larson & Taylor PLC
Meiji Seika Kaisha Ltd.
Raymond Richard L.
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