Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing
Patent
1994-06-02
1999-01-05
Burn, Brian M.
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
4235802, 4236477, A61K 908
Patent
active
058559213
DESCRIPTION:
BRIEF SUMMARY
This invention relates to pharmaceutical products for curing tumorous diseases and a process or preparing same.
Nowadays there are a number of methods (surgical intervention, therapy by irradiation, hormonotherapy, applying antitumor agents) for combatting against malignant tumors. All these methods together with the recent results in diagnostics have resulted in major advances in the last decade, but in spite of these results the applied methods have many disadvantages.
The main reason of the problem is that since the molecular mechanism of the cell-proliferation is still not known, the intervention into the course of the disease by the available means is rather difficult. It is therefore that the way of the recovery or at least a delay in the development of the disease involve frequently the removal of some parts of organs or troubles in the blood-forming process when antitumor agents, etc. are used.
The proper answer to this question can be expected only with full knowledge of the (sub) molecular processes playing a key role in initiating the cell proliferation.
By means of the development of the molecular biology, biological science is just before recognizing the decisive regulating processes through which it will be possible to restore patients suffering from tumorous diseases to health.
Taking into consideration the recent results of molecular biology the conclusion can be drawn that a common early response of eukaryotic cells to stimuli which activate the proliferation is an increase in intracellular pH due to an exchange of extracellular Na.sup.+ for (1982)!. The conclusion that the activation of the Na.sup.+ /H.sup.+ exchange system is indispensable to initiate the cell growth has been supported by numerous experimental results.
It was found that specific mutation abolishing Na.sup.+ /H.sup.+ exchange 4833-4837 (1984)!.
Recent evidence suggests that growth factors activate Na.sup.+ /H.sup.+ exchange system suggesting that Na.sup.+ /H.sup.+ exchange may function
The relationship between the activated Na.sup.+ /H.sup.+ exchange system and the tumorous character of cell lines have been proved, too. The pH was found to be increased after transformation of cell line comparing to the correlation was found between the expression of oncogene and the elevated intracellular pH, because injecting the protein encoded by Ha-ras or the expression of V-mos and Ha-ras oncogenes in the cell increased the intracellular pH by activating the Na.sup.+ /H.sup.+ exchange system
Similar changes were found by activating another membrane-bound hydrogen-ion transport system. In this case an ATPase gene was isolated from yeast, and used to transform mouse and monkey cell lines. The gene was expressed and the ATPase, by continually extruding protons, caused a sustained alkalinization of the cytoplasm. The really surprising result of this experiment was that the cells transformed by the gene of ATPase of
This latest experiment proves that the induction of cell proliferation is connected not only with the activation of the Na.sup.+ /H.sup.+ exchange system, but also with the activation of an other proton-extruding system which can serve as a signal to cell proliferation, in general.
A simple explanation for the above phenomenon can be that the cell proliferation is initiated by increase in intracellular pH. This explanation was, however, not confirmed by the experiments in which an artificial increase in cytoplasmic pH has not raised the cell
The above-mentioned molecular processes can be interpreted by investigating the possible role of hydrogen and of deuterium in controlling the above processes.
In nature the ratio of hydrogen to deuterium is about 6000:1. Because of the mass difference of 100% the two isotopes show different behaviour in chemical reactions. It is a generally accepted view that the D-bonds participating in chemical reactions can be split at a lower rate because of the isotope effect, therefore they need an augmented activation energy Reactions. A kemia ujabb eredmenyei (in Hungarian). (Recent Results in Chem
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The Merck Index, 10th Ed (1983) pp. 424-425.
Remingtons Pharmaceutical Sciences, 16.sup.th Ed., Arthur Osol, Editor in Chief (Jan. 1980) pp. 1239-1243.
Internal Medicine, 4.sup.th Ed. Editor-in-Chief Jay Stein, pp. 699-715 (Jan. 1993).
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