Antitumor and immunomodulatory means and methods of treatment of cancer patients, skin diseases and ulcers


A61K31/305 -

 

(57) Abstract:

The invention can be used to treat patients with benign and malignant diseases irrespective of their origin and localization immunodeficiency different origin. The essence of the proposal is in use for the treatment of antitumor and immunomodulating agents containing as active principle a sublimate, as well as dry, sweet natural grape wine or whey with 3-4% sugar or honey. Medicinal product according to the invention is used in certain amounts for the treatment of cancer patients inside and in the form of lotions, compresses, douches, individually or in various combinations. In addition applied externally and inside befungin. If the previous patient contact with heavy metals treatment starts with the reception of befangen inside. In addition, drugs used for the treatment of skin diseases and ulcers, both inside and externally. 2 C. and 8 C.p. f-crystals, 1 table.

The invention relates to medicine and can be used to treat patients with benign and slocate, and radiation diseases, as well as for conflict prevention incompatible transplant, for pain relief and wound-healing.

There are various anti-cancer drugs, which are represented by compounds of different chemical structure. Such compounds can be produced either by chemical means or by extraction of biologically active substances from raw materials of vegetable and animal origin. Currently also discovered many natural compounds that have strong antitumor effects in animal experiments. However, the vast majority of these drugs proved to be highly toxic and therefore they have not found application in the clinic.

Widespread as a means of exhibiting antitumor action, got some antibiotics, in particular, semi-synthetic derivatives using nuclei of molecules known antitumor antibiotics [1]

Known drug cicloferon with a broad antitumor spectrum. As active principle the product contains N-bis - (chloroethyl)-N-O-trimetilenovy broadcast diamida phosphoric acid. Apply the product inside SS="ptx2">

Apply cyclophosphamide inside, in/in or/m, often in combination with other drugs to reduce the side effects, while using different regimens [2]

You know the "Adjuvant" exhibiting immunomodulatory action.

Apply the product in 1-2 ml of isotonic/m as immunostimulant and biostimulant diseases, accompanied by a decrease in cellular immunity, including acute and chronic suppurative processes and inflammatory diseases, burn disease, when the depression of the immune and hematopoietic function after radiation or chemotherapy in cancer patients [3]

Known antitumor agent, Kolchanova ointment, 0.5% for external use containing the active components, as well as pharmacologically acceptable excipients emulsifier, alcohol, water [4]

The treatment is carried out, causing the surface of the tumor and surrounding tissue ointment, cover the top with a gauze cloth and stick with adhesive tape.

It is known that for the treatment of various dermatological diseases and tumors using levamisole, appointed inside tablets [5]

Also for the treatment of dermatological diseases prima "Solcoseryl" for the treatment of venous ulcers and gangrene.

Apply the product in the/m or/in, and topically in the form of creams or jellies. Usually spend complex treatment [7]

The objective of the invention is the creation of new high-performance and low-toxic anticancer agents and methods of treatment using them.

The problem is solved by using composition-based dichloride mercury semi-natural grape wine or dairy whey with 3-4% sugar content used orally or topically as anti-tumor and immune-modulating means.

In addition, for the treatment of those diseases in which appointed interior solution of mercuric chloride, are used according to the indications in the form of external application drug, containing in its composition as an active ingredient the sublimate, but in higher concentrations.

As a semi-dry to semi-sweet natural wine, you can use one of the following wines "Motwani", "the pearl of the steppe", "Sauvignon", etc. In the manufacturing technology of these wines is the process of heating up to 60aboutWith necessary to stop the fermentation part of the sugars. When the specified temperature is reversible coagulation of vegetable proteins, small reversibly blocked ions of mercury Hg2+consequently eliminates the toxicity of the solution.

The composition of whey also includes reversible coagulated proteins released with sulfhydryl groups of SH that are reversibly blocked by ions of mercury Hg2+resulting toxicity of the solution is reduced to zero.

For internal use as antitumor and immunomodulating means serves to apply the composition on the basis of mercuric chloride containing pork fat, honey and alcohol 96% taken in certain proportions.

Current top offer three compositions is mercuric chloride HgCl2and sugar constituent of grape wines, whey and honey in certain concentrations.

Reversible blocking of sulfhydryl groups of receptors, growth factors, steroid hormone receptors and adrenergic receptors ions of mercury Hg2+stops tumor growth.

Duplicate antitumor protection break disulfide bonds of growth factors, immunoglobulins and receptors of lymphocytes in the presence of mercury ions.

The basis of the mechanism of action is blockade of biological Timah complexes, characterized nucleophilicity ligands. Installed the inclusion of mercury ions in a molecule of transfer RNA, which plays a Central role in protein biosynthesis. Change under the influence of mercury ions are exposed to the membranes of the endoplasmic reticulum, compacted membranes, decreases their permeability through communication with diligently in a protein component.

In the initial period of exposure to low concentrations of ions of mercury Hg2+there is a significant release of adrenal hormones and the activation of their synthesis. Observed phase changes in the concentration of catecholamines in the adrenal glands. There is increasing monoaminooxidase activity of the mitochondrial fractions of liver.

Biochemical changes are in violation of oxidative fosforilirovanija in the mitochondria of tissues of the kidneys, transamination and balance between the activity of the catalysts resynthesis and breakdown of glycogen. Moreover, it is noted hypocoagulation shifts, reduced fibrinogen level and extent of thrombotest.

The adopted solution inside the amount for six hours at 93% excreted from the body.

The invention is represented by the three compositions used both individually and in co the La intravenous administration under the conditional name "Viturid" contains, wt.

The sublimate of 0.01-0.1

Semi-dry, semi-sweet

natural grape

wine or milk

whey with 3-4%

sugar content of the Rest

Prepare medication as follows: mercuric chloride in an amount of from 0.01 to 0.1 g dissolved in normal conditions in 100 ml of semi-dry or semi-sweet natural grape wine or dairy whey with 3-4% sugar content.

In this way there were obtained the following compounds:

the mercuric chloride 0.01 g; the wine is semi-dry, natural grape 100 ml.

the mercuric chloride 0.06 g; sweet natural wine 100 ml

the mercuric chloride 0.1 g; whey with 4% sugar 100 ml

Apply the product per os in the form of a solution.

"Vita balm" for external use has the following composition, wt.

The sublimate 0,3-1,5

Semi-dry, semi-sweet

natural grape

wine or milk, Siva-

of pigs with 3-4% content

the content of sugar the Rest

The personnel get the usual dissolution of mercuric chloride in grape wine or dairy whey.

In this way we obtained the following compounds:

the mercuric chloride 0.3 g; semi-dry, semi-sweet grape is>Given that mercury compounds easily form an amalgam with the metal, in order to avoid the reduction of the activity of the drug should avoid contact with metals.

The resulting solution was kept for weeks in a cool place at a temperature not exceeding 15aboutIn the dark place.

After manufacturing the drug store in a container in dark glass at a temperature not exceeding 15aboutWith in a dark place.

When storing possible precipitation of compounds of tartaric acid, so before use, the solution should be shaken.

Biological properties of drugs stored for a long time.

Antitumor and immunomodulatory agent used inside under the conditional name "Viturid To" has the following composition, g: Sublimate 0,25-1,0 lard 230-280 Honey 230-280 Alcohol 96% To 750

Get the tool as follows.

The sublimate is dissolved in the required amount of alcohol and mixed with other ingredients of the composition, with a solution of corrosive sublimate in alcohol in small portions, carefully rubbing, making pre-softened and mixed lard and honey.

The specified str>the mercuric chloride 1 g; lard 280; honey 280; alcohol 96% to 750.

the sublimate 0,6; lard 250; honey 250; alcohol 96% to 750.

Studies of antitumor activity of the drug "Viturid" and Balsam conducted on human leukocyte tumor cultures of the line L-41.

The cultivation of crops was performed according to the conventional method. Seeding of cells was 1.105cells in 1 ml of medium. As the nutrient medium used in equal proportions medium 199 and Wednesday Needle with the addition of 10% bovine serum and antibiotics: 100 units of penicillin and 50 units of streptomycin per 1 ml of medium.

Drug Viturid" separately and wine "Hereti" and mercuric chloride diluted in protein-free culture medium and made them in different concentrations of 3-4 culture for contact with the cell monolayer. As the active principle in the preparation "Viturid is mercuric chloride, prior experience to compare found that U/50corrosive sublimate, inhibiting the growth of tumor cultures L-41 is less than 10 mg/ml On the second day after setting experience produced microscopic evaluation of drug action on a four-point system and quantitative determination of the protein content of crops by the percentage inhibition of growth inhibition of protein synthesis. The data are shown in the table.

Studies have shown that ED50preparation "Viturid" is 9.9 g/ml IU50corrosive sublimate is about to 8.0 g/ml of Affinity values U50drugs suggests that the active principle in the preparation "Viturid is mercuric chloride. Wine "Hereti" in the tested concentrations has a slight stimulating effect on culture (10%).

According to existing standard methods selection of anticancer drugs in the USSR and the United States the drug is active, if U50less than or equal to 100 mcg/ml.

Studies have shown that ED50preparation "Viturid is 10 g/ml, which is 10 times higher than the standard and is indicative of his pronounced cytotoxic effect on tumor cultures.

The research material immunomodifying actions served samples of venous blood, which was taken from the cubital vein in the morning.

To evaluate the results of treatment of drugs Viturid" was used generally accepted in modern clinical immunology laboratory methods.

1. Determination of total T-lymphocytes and their subpopulation with you is CLASS="ptx2">

3. The determination of the number of b cells among total lymphocytes.

4. Quantitative determination of immunoglobulins major isotope (G, M, And by radial immunodiffusion.

5. Quantitative determination of circulating immune complexes by precipitation with PEG-6000 and based on the spectrophotometer at a wavelength of 450 nm.

6. Cytochemical characterization of enzyme activity faguoqitirute blood cells nst-test.

7. The activity of the phagocytic reaction using a latex particle, and determining the phagocytic number (the number of cells with the phenomena of capture of particles at different stages of phagocytosis and phagocytic index (number phagocytosing particles in each cell).

After the first course of treatment Vitoria in the immune system has the following changes: the total number of lymphocytes decreased in most patients, some increased; the number of T-lymphocytes decreased in most patients, some patients has increased; the number of T-suppressor lymphocytes cytotoxic T-cells decreased in almost all surveyed; the number of T-lymphocytes helper-inductors in some patients umenshilos the>The level of b-lymphocytes In half of the patients increased, the other decreased and was below the norm.

Changes in the content of immunoglobulins in the immune complexes and serum wore irregular.

Thus, changes in the concentration of immunoglobulins wore izotopicheskii nature, i.e. depending on the isotope of immunoglobulin curve of his changes was different.

The concentration of immunoglobulin isotypes G and decreased, and the levels of immunoglobulin M increased in different degrees of increase.

Initial data show that the activity of the phagocytic reaction and willingness of phagocytes to the functional activity of all patients do not have significant deviations from the norm.

After the first course of treatment may be noted the increase of spontaneous cytochemical activity of neutrophils in all patients on the background of a slight decline induced prodigiozana cytochemical reactions. This activity of phagocytes against cytochemical picture is confirmed by the fact that the number phagocytosing of latex particles (phagocytic index) also increases in all cases on the background of a slight decrease in neutrophilic granulocytes, to who m the survey within the error of the experience.

A survey of patients who received 2-3 courses of the drug after 6 months from the start of treatment.

After 6 months of treatment when comparing the figures it can be stated that the total number of lymphocytes in all patients increased 1.5-2 times and was 1200-1400 cells/ml. Only one patient it does not reach the standards, although increased 2 times from 440 to 854 cells/ml.

Changes in the contents of subpopulations resulted in a drastic change of the ratio of Th:TS. In patients it decreased. The dysregulation of subpopulations as a sign of a compromised immune reactivity of the organism at this stage of the examination takes place, however, it does not affect humoral immunity, and is limited to the relationship of cell populations.

The number of b-lymphocytes increased slightly in some patients and at the same time in other patients it decreased.

The most distinctive and positive feature of a change in the level of immunoglobulins was that after 2-3 courses of treatment increases the concentration of IgG in the 1.5-3.5 times the concentration of IgA 1.2-2.1 times.

The level of IgM in all patients declined from 0.55 to 0.76 g/l, slightly lower than the average physiological norm.

init, as a positive indication of immunological reactivity.

Phagocytic reaction: spontaneous cytochemical activity slightly (within error experience) declined amid a growth-induced prodigiozana cytochemical activity.

Phagocytic index in all cases increased 1.5-1.8 times against the background of larger or smaller increase in phagocytic activity of neutrophils. In two cases the phagocytic activity as the number of cells that engulfed the latex particles decreased from 84% to 51% and from 76% to 55%

Immunological evaluation of patients treated with the proposed remedy, gives grounds to conclude that immunomodulating effect of the drug "Viturid".

Currently recognized and leading methods of treatment of cancer patients is surgical, chemotherapy and radiotherapy, alone or in various combinations.

Despite the progress made in this area, the problem remains unresolved and up to date, which involves finding new ways of approach to the understanding of the pathogenesis and principles of treatment of cancer patients.

Since 1976, Farmkomiteta MOH MOP the population cobalt salts. The drug is recommended as symptomatic means improving in some cases the health of patients with tumors of different localization. The drug is prescribed inside 3 tsp. of extract injected into 150 ml of water and take 1 tablespoon 3 times a day for half an hour before meals.

The preparation according to the Pharmacopoeia has a toning and soothing properties, improves the tone of the autonomic nervous system. As a matter of fact antitumor agent externally befungin was not used. Observations have made it possible to successfully use it in treatment of cancer patients.

Befungin contains chromogenic, polyvinylcarbazole complex, agaricales acid, flavonoids, ash, rich in manganese, resin.

One of the targets of action of the dipole compounds included in the composition of the chromogenic polyvinylcarbazole complex befangen (more precisely, reversible their oxidized forms) are solarthermie group of proteins. When blocking surgically groups of receptors of growth factors disappears linking their ability, stops the growth of malignant tumors.

Phenolic compounds included in the composition of the complex (hpcf) block also sulfhydryl group of receptors with is allowed to use befungin for the treatment of patients with cancer in combination with drugs of mercury Vitoria, balm Vita.

Befungin applied inside featured in the Pharmacopoeia doses, with the same solution spend douching and moisten the outer or vaginal swabs.

The drug is contraindicated in rapidly decaying tumors, i.e., the resulting inflammation is not able to be blocked, the system of glucocorticoids, which in turn blocked phenolic compounds present in bertina.

The method of treatment can be applied at any age, it is easy to transfer patients, is associated with a small number of restrictions and complications, does not impair the ability to work sick.

A similar effect has the above drugs on the basis of mercury, while they are more powerful effect, because only the presence of mercury ions causes rupture of disulfide bonds of growth factors, immunoglobulins receptors of lymphocytes, erythrocytes, and all of cytokines.

Were developed approaches and methods of treatment of patients with various forms of cancer. In the treatment process used befungin, Viturid and Viturid To the inside, externally in the form of lotions, douches, enemas are the same medications as well as balsam Vita".

the th body choice and duration of use of a drug may vary, at the same time, you should follow certain principles of treatment. For example, rather should strictly adhere to the dietary restrictions with the exception of such foods as meat, fish, eggs, as in the treatment of beforeno and preparations of mercury are blocked sulfhydryl groups in the system of proteolytic enzymes, i.e., decreases the body's ability to digest protein foods.

Often the treatment begins with a reception of Viturid inside the first three days of 5 ml 3 times a day, then 10 ml 3 times a day for months with subsequent transition optionally befungin in traditional breeding also 5-10 ml inside a month. Provided the previous treatment of patient contact with heavy metals (e.g., manufacturing) the treatment begins with the ingestion of Befangen. Parallel to the medication inside or independently perform local effect Vitoria, balsam Vita or beforeno in the form of lotions, tampons, douches and enemas. Depending on the localization process, the selection of areas of influence varies on the coccyx, inguinal lymph nodes, axillary region, spine, joints, localized education cover or bone-sustituted or befangen inside you can use the local fancy features as well as vaginal tampons and douches. In the treatment of gastric lesions on a background of reception of Viturid inside wrap with Vita balm on the axillary region and coccyx, enemas with beforeno. With the defeat of the prostate Viturid inside, lotions balm on the coccyx, inguinal and axillary lymph nodes, befungin in the form of enemas. When myeloid leukemia of Viturid inside, wrap with balm on the coccyx, chest, inguinal and axillary lymph nodes, spine, joints. With the defeat of soft tissue and osteogenic sarcomas of Viturid inside and lotions with the balm on the coccyx, inguinal and axillary region, the spine, and the affected area. In the treatment of patients with advanced forms of the disease, and malignant lesions of the lung, best results are obtained when applied to the inside of Viturid K.

When treating patients with any localization process should appoint tampons, douching with Vitoria go by beforeno when vaginal secretions.

During treatment, the possible appearance of lesions, including pustular skin, especially in the affected area.

Possible rises in temperature, the latest cropped daily jet on/in the introduction of 40% glucose solution. In the case of nevoso the>When in the process of treatment of headaches, they can be cut short by dropping of Viturid in the nose.

A drug with a high concentration of mercury Viturid It is used in the treatment of malignant diseases of the lungs, in the presence of pus and blood in the sputum, in the treatment of concomitant lesions in severe cases.

Preparations on the basis of mercury are proven in the treatment of skin diseases such as psoriasis and atopic dermatitis. This is due, apparently, with immunomodulatory properties of drugs, which when applied externally also exhibit anti-inflammatory and reparative properties.

It is known that drugs similar actions are widely used for indoor and outdoor use in treatment of skin diseases.

Good results are achieved when combined admission of Viturid inside and exterior use Viturid and balm.

Attempts to use drugs on the basis of mercury in the treatment of trophic ulcers of the lower extremities showed their success in the appointment of Viturid inside of the General scheme and externally in the form of lotions.

The data show that the drug "Viturid provides wyrazisci "Viturid" and is approximately 8 g/ml Wine "Hereti" in the investigated concentration has on the culture of a slight stimulating effect in the range of 4.2 to 8.8%

1. Antitumor and immunomodulatory agent containing the active principle and excipients, characterized in that the active principle tool contains mercuric chloride and the active medium is in the form of semi-dry or semi-sweet natural grape wine or whey with 3 to 4% sugar content in the following ratio, wt.

The sublimate 0,01 0,1

Semi-dry or semi-sweet natural grape wine or whey with 3 to 4% sugar content of the Rest

2. Antitumor and immunomodulatory tool for internal use containing the active principle and excipients, characterized in that the active principle tool contains mercuric chloride, as well as auxiliary substances lard, honey and alcohol 96% in the following ratio of components, g:

The sublimate 0,25 1,0

Lard 230 280

Honey 230 280

Alcohol 96% To 750

3. Antitumor and immunomodulatory agent for external use containing the active principle and spamoed in the form of semi-dry or semi-sweet natural grape wine or whey with 3 to 4% sugar content in the following ratio of components, wt.

The sublimate 0,3 1,5

Semi-dry or semi-sweet natural grape wine or whey with 3 to 4% sugar content of the Rest

4. The method of treatment of cancer patients, including the use of medicinal substances, characterized in that the quality of medicines used tool on p. 1 inside for 5 to 10 ml per reception 3 times a day, under item 2 on the inside and on the PP. 1 and 3 externally in the form of lotions, compresses, douches, individually or in various combinations.

5. The method according to p. 4, characterized in that it further apply befungin inside and externally in traditional dilutions.

6. The method according to PP. 4 and 5, characterized in that the ingestion of Vitoria and befangen alternate month.

7. The method according to PP. 4,5 and 6, characterized in that during the previous patient contact with heavy metals treatment starts with the reception of befangen inside.

8. The method according to PP. 4 to 7, characterized in that when the temperature in the treatment process performed on the background of the sugar load, such as honey, orally, or intravenously injected daily 40% glucose solution.

9. The method according to PP. 4 to 8, characterized in that when the occurrence of headaches drug under item 1 priklauso internal and external application of medicines, characterized in that the quality of medicines use of the drug under item 1 inside for 5 to 10 ml per reception 3 times a day and externally and the drug under item 3 externally.

 

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