HUP0501127A2 - Pharmaceutical and food compositions for influencing expression of genes, and process for producing them - Google Patents

Abstract

A therapeutic product comprises water and/or organic compound with deuterium content of 0.01-5000 parts per million. ACTIVITY : None given. MECHANISM OF ACTION : None given.

Description

Pharmaceutical and food preparations influencing gene expression and process for their production

Inventor: Gábor Somlyai

Date of announcement: November 30, 2005.

Applicant: HYD Research and Development Ltd.

1215 Budapest, Deák F. u. 51 /a

The subject of the invention is pharmaceutical and food preparations influencing the expression of various genes, which are suitable for influencing and curing the course of various types of diseases, and a method for their production.

The general principle of drug development in recent decades has been to try to produce molecules that act by influencing a given chemical process, either synthetically or by isolating them from plants or animal organs. The defining principle was that, during the testing of tens of thousands of molecules, they tried to "fish out" those molecules that proved to be effective in certain test systems. A significant advance in drug development was that biochemical and genetic research made it possible to identify and isolate proteins that play a key role in a given process. The development of computer technology and structural research made it possible to design those molecules that, based on the knowledge of the structure of the target proteins, were assumed to be able to bind to a given point of the protein and thereby influence its function. This direction of development has resulted in our understanding of the molecular mechanisms of many processes, the structure and function of proteins, and this has given us the opportunity to search for molecules that influence the function of enzymes, which, after a long period of development, can be used as drugs to treat a given disease.

The human genetic project promises a major breakthrough, during which the sequence of approximately 3 billion base pairs of the human genome will be determined. The work done so far has already made it possible to identify numerous genes, opening up the possibility of identifying genes that play a key role in the development of a given disease. Progress in this area is particularly significant in relation to cancer. In recent years, numerous oncogenes, tumor suppressor genes and other genes that play a role in the regulation of cell division have been identified. These results have also given new impetus to the development of anti-cancer drugs, since with knowledge of genes, it is relatively easy to identify the structure and function of proteins and, based on this knowledge, it is possible to design a potential inhibitor. A common feature of these developments is that the target is the product of the gene, the protein (enzyme).

The invention is based on the recognition that changing the D concentration in the water space of cells, which can mean lowering it below or raising it above the natural concentration value (150 ppm), can influence the expression of certain specific genes and thus offers the possibility of inhibiting or stimulating the function of genes that are key to a given disease by changing the D concentration, depending on which process serves the patient's recovery.

The invention is further based on the recognition that, in addition to the use of water with a reduced deuterium content, it is possible to further enhance the specific effect on different genes by "labeling" certain organic molecules with hydrogen or deuterium. This offers the possibility of intervening in pathological processes at the level of gene activation in a wide range of diseases and influencing them in a healthy direction in order to heal the patient.

In recent years, scientific publications (FEBS Lett. 1993; 317: 1-4, Natural Medicine 1996; 10: 29-32, Pet Medicine 1996; 3:114-5,

Erfahrungsheilkunde 1997; 7: 381-88, J. R. Heys and D. G. Melillo (eds) 1997 Synthesis and Applications of Isotopically Labelled Compounds. John Wiley and Sons Ltd. pp. 137-141, Z. Onkol/J. of Oncol. 1998; 30: 91-94) and Hungarian patents were issued (Registration numbers: 208084, 209787, 214.824) from the recognition that deuterium present in nature plays an important role in the regulation of cell division. In addition to the animal experiments described in the patents, the antitumor effect of water with a reduced deuterium content (Dd-water) has since been confirmed in human studies. In a nearly two-year human phase II, double-blind clinical trial (where neither the treating physician nor the patient knows which of the patients being followed is receiving the active substance or the placebo), we found significant differences between the treated and control groups of prostate cancer patients. This study clearly confirmed the results of previous animal and human studies.

Over the past twelve years, a total of 500-600 tons of Dd-water have been used in nearly 3,000 patients. During the follow-up of patients consuming Dd-water, it was evident that tumor cells react sensitively to deuterium withdrawal and in the overwhelming majority of cases (70-80%) are unable to adapt to the change even with an adequate dose, which results in a decrease in tumor volume and complete regression of the tumor. When examining the survival data of patients with the same tumor type in a larger patient population (50,200 patients), we found that the life expectancy or the proportion of those alive increased 2-4 times in patients consuming Dd-water compared to patients receiving conventional treatment alone. Apart from the macroscopically observable phenomena, no observations were available on the changes occurring at the molecular level. While continuing basic research, we made the unexpected observation that changes in D concentration affected the activity of certain genes.

In accordance with the above, the aim of the invention is to develop a preparation with reduced or increased deuterium content, sometimes supplemented with organic molecules specially "labeled" with hydrogen or deuterium, which is suitable for modifying the activity (inhibition or induction) of key genes in a given disease in a direction beneficial to the disease and thus promoting healing.

The invention is further based on the recognition that during the consumption of water, aqueous solutions containing less or more D than natural, or carbohydrates, amino acids, lipids and other nature-identical molecules containing less or more deuterium than natural in organic bonds, the activity of several genes is influenced by the change in the D content of the patient's body, so that the activity of certain genes is enhanced, while at the same time the activity of other genes is inhibited, and thus the processes taking place in the patient are modified towards a healthy state, which can lead to recovery.

Based on the above, the method of the invention is suitable for the treatment of various diseases, for the preparation of pharmaceutical preparations containing water containing 0.01-5000 ppm deuterium and/or carbohydrates, amino acids, lipids and other nature-identical molecules containing less or more deuterium than natural (0.01-5000 ppm). According to the invention, we proceed by producing water containing 0.01-5000 ppm D by electrolysis and/or distillation or in another way. The water containing 0.015000 ppm D is used to produce carbohydrates, amino acids, lipids and other nature-identical molecules with reduced or increased deuterium content, and the water with different D contents thus obtained and the carbohydrates, amino acids, lipids and other nature-identical molecules produced using it are mixed with conventional carriers and/or excipients in pharmaceutical preparation and converted into pharmaceutical preparations in a conventional manner in pharmaceutical preparation.

Among the production options for water with reduced or increased deuterium content, we highlight two: electrolysis and distillation, which can produce large quantities of water with a D content different from the natural one at a relatively low specific cost.

a) A 15-20% aqueous KOH solution is electrolyzed at a voltage of 2-5 V with direct current, separating the cathode from the anode. The hydrogen with a reduced D content that is released at the cathode is burned, the resulting water vapor is condensed through a distillation system and collected separately. The D concentration in the resulting water is 30-40 ppm. (Separation of Hydrogen Isotopes Eds.:Howard K. Rae, American Chemical Society Symposium Series 68, Washington D.C. 1978; Isotope Separation Eds.:Stelio Villani, American Nuclear Society 1983). The D content of the water thus obtained can be further reduced by repeated electrolysis. Water with a higher than natural D content can be obtained from the solution remaining during electrolysis by simple distillation.

b) The distilled water is boiled in a distillation tower suitable for fractional distillation with 50-150 plates at a pressure of 50-60 mbar at 45-50°C. During the distillation, the reflux value is 12-13, and the distillation in the still is 10 times. The D-concentration of the overhead product when using such parameters ranges between 0.1 and 30 ppm. (Separation of Hydrogen Isotopes, Eds.:Howard K. Rae, American Chemical Society Symposium Series 68, Washington D.C. 1978; Isotope Separation Eds.:Stelio Villani, American

Nuclear Society 1983). By changing the parameters during the operation of the column, e.g. by significantly increasing the column load, it is possible to produce water with a D content higher than 30 ppm in large quantities. Another possibility is to subject the reduced D-content water obtained from the column to further fractional distillation in a connected, similar column (or columns) to further deplete the D-content of the water. During the production of water with an increased D-content, the water in the kettle is not continuously diluted with normal water in the above apparatus, which allows the withdrawal of water with a higher D-content than the natural one after a sufficient time.

The compositions of the invention can be used in medicine in the form of the active ingredient and inert, non-toxic carriers. The active ingredient is converted into preparations suitable for oral (e.g. solution, emulsion, suspension, etc.) or parenteral (e.g. infusion solution) administration.

Pharmaceutical preparations are produced using methods known per se in pharmaceutical production, by mixing the active ingredient and inert inorganic or organic carriers, and then bringing the mixture into galenic form.

Water or ethanol can be conveniently used as a carrier.

The pharmaceutical preparations may also contain additional excipients customary in the pharmaceutical industry (e.g. wetting, sweetening and flavoring agents, buffer solution, etc.).

The daily dose of the pharmaceutical compositions according to the invention can be varied within wide limits and depends on several factors, such as the D concentration of the water, the weight of the patient, the age of the patient, the type and severity of the disease, etc. The orally administered daily dose for a patient weighing 70 kg may be 0.01-2 liters of modified D-containing water (MDW), the D concentration of which may vary between 0.01 and 5000 ppm. Partly for the enjoyment value, partly in order to increase the effect, the MDW may contain e.g. 20-30 grams of carbohydrates with reduced or increased deuterium content, or certain amino acids with reduced or increased deuterium content, or other flavoring and aroma substances.

The main advantages of the composition and method of the invention are as follows:

a) Its application opens up the possibility of interfering with the previously unknown regulatory system of the cell.

b) It allows us to restore the state characteristic of healthy processes by intervening not at the level of proteins, but at the level of gene expression.

c) With its use, the use of currently used medications can be reduced or, in some cases, eliminated.

d) Only nature-identical molecules are used during the treatment, therefore no harmful side effects are expected.

e) The compounds used in the process have no toxic or immunogenic effects.

f) The preparations are simple to produce and do not produce environmentally hazardous waste.

g) The products can be produced more cheaply than current medicines.

The method according to the invention is described in the following examples without limiting the scope of the invention.

Example 1

Production of drinking water with a favorable salt composition

We mix the water with reduced D content and a mineral water with a known salt composition (Csillaghegyi, Balti) in the following proportions:

a) 0.25 volume parts water containing 90 ppm D + 0.75 volume parts mineral water (final concentration of D is 135 ppm)

b) 0.5 volume part water containing 90 ppm D + 0.5 volume part mineral water (final concentration of D is 120 ppm)

c) 0.75 volume parts water containing 90 ppm D + 0.25 volume parts mineral water (final concentration of D is 105 ppm)

d) 0.25 volume parts of water containing 60 ppm D + 0.75 volume parts of mineral water (final concentration of D is 127.5 ppm)

e) 0.5 volume of water containing 60 ppm D + 0.5 volume of mineral water (final concentration of D is 105 ppm)

f) 0.75 volume parts water containing 60 ppm D + 0.25 volume parts mineral water (final concentration of D 82.5 ppm)

Example 2

The cation and anion concentrations of the reduced D-content water are adjusted with an artificially prepared concentrate with a preferred salt composition.

One possible composition of the stock solution is as follows:

KCl 5.7 g

MgCl2 x θ H2O 199.65 g

CaCl2 x 6 H2O 236.25 g

The stock solution thus prepared is added to 1000 liters of Dd-water to obtain the following final concentration: 23.8 mg/l Mg ²⁺ , 64.1 mg/l Ca ²⁺ , 3 mg/l K ⁺ , 192 mg/l Cl'.

Example 3

Production of modified D-containing food preparations

Using water with a modified D content of 0.01-5000 ppm, we grow peppers, tomatoes, peas, green beans, etc. in a manner known in plant production. The plants are transformed into food products in a manner customary in the food industry.

Example 4

Production of modified D-containing organic molecules

From plants grown according to example 3, using the D-containing water used during cultivation, we isolate a type of molecule, which can be a carbohydrate, protein, etc. The material thus obtained is used in purified form to treat a given group of diseases.

Claims (3)

I Patent claims 1. Pharmaceutical preparations that influence the activity of gene expression and are thus suitable for the treatment and cure of various diseases, characterized in that they contain water with a D-concentration of 0.01-5000 ppm. 2. Pharmaceutical and food preparations that influence the activity of gene expression and are thus suitable for the treatment and cure of various diseases, characterized in that the medicine or food contains carbohydrates, proteins, lipids and other nature-identical molecules with a D-concentration of 0.01-5000 ppm. 3. The composition according to claim 2, characterized in that in the cultivation or breeding of plants and animals intended for pharmaceutical and food industry use, water containing 0.01-5000 ppm deuterium is used, or purified molecules are adjusted to the desired D-concentration by isotope exchange.