Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1998-02-17
1999-11-16
Geist, Gary
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514546, 514548, 514567, 560130, 560142, 560143, 560144, 560146, 562453, 562472, 562475, 568771, A01N 3710, A01N 3712, C07C 6501, C07C22960
Patent
active
059859270
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to novel medicinal substances which selectively control tumor tissue, while healthy tissue is virtually not attacked. The novel medicinal substances are therefore outstandingly suitable for cancer therapy.
2. Background Art
Prior art medicines used in chemotherapy are, as a rule, only partly successful, i.e. they do not result in a definitive cure. In addition, the substances used in the prior art frequently act only on a particular category of tumors. Another disadvantage of the chemotherapeutic agents currently known are their frequently harmful side effects, because chemotherapeutic agents are generally able to have cytostatic effects on proliferating tissue. The known chemotherapeutic agents are also unsatisfactory in controlling metastasis formation, and this is one of the main reasons which has prevented decisive success in cancer therapy to date.
It is known that tumor tissue has, in the extracellular media, a reduced average pH of about 6.5 to 7.0, and the pH on the surface of cancer cells may even fall to 5, whereas the pH in normal tissue and in blood is about 7.2 to 7.5, and this is described, for example, in DE-A 44 07 484 and in Tumor Biol., 1994, 15: 304-310. These publications disclose that the natural immune defenses are blocked by the reduction in the pH range in tumor cells, because the body's own defense cells react with full cytotoxicity for cancer target cells only in the slightly basic media of more than 7. DE-A 44 07 484 therefore proposes bringing the acidic external media of cancer cells to the normal physiological pH level of 7 to 7.5 and thus controlling the cancer cells by the body's own immune defenses. To this end, the acidic external media of cancer cells is brought to a physiological pH of 7 to 7.5 either by artificial alkalinization measures or by preventing the acidification process itself.
Although the medicinal products described in DE-A 44 07 484 represent an advance in cancer therapy, it would be desirable to have available medicinal products which, besides the body's own immune defenses, selectively control tumor cells and thus can be used as chemotherapeutic agents with relatively few side effects.
OBJECT OF THE INVENTION
It is therefore an object of the present invention to provide medicinal substances which have a strong cytotoxic effect substantially selectively on tumor tissue. This object is achieved by the subject-matter of the claims.
Whereas in DE-A 44 07 484 it was attempted to increase the extracellular pH of tumor tissue and thus to destroy the tumor tissue by means of the body's own defensive substances, a different route is followed in the present instance. The intention is precisely not to alter the extracellular media in the tumor tissue in respect of the pH; on the contrary, the intention is for the reduced pH in the extracellular tumor tissue to serve as target area for substances which are pH-sensitive, i.e. either for substances which are protonated in the acidic media and act to destroy cells exclusively in this protonated state, or for substance complexes which decompose in the acidic media and thereby release a substance which acts to destroy cells. Such substances and substance complexes are activated, by reason of their pH-sensitivity, only in cancerous tumors and areas of metastasis and therefore represent an ideal cancer therapeutic agent. It should also be particularly emphasized that this novel cancer therapeutic agent acts generally on all tumor types, irrespective of the specific type of cancer.
Preferred compounds according to the invention are those which, after they have been protonated, act to destroy cells. The invention is described further on the basis of such compounds, but the following description also applies analogously to compound complexes which decompose in the acidic media of the tumor cell tissue and thereby release a substance which destroys cells.
SUMMARY OF THE INVENTION
The invention relates to a medicinal product for the selective con
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Davis Brian J.
Geist Gary
Lieberstein Eugene
Meller Michael N.
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