RU2071778C1 - Method of preparing agent showing antitumor activity - Google Patents

Abstract

FIELD: medicine, oncology, pharmacy. SUBSTANCE: method involves preliminary separate dissolving mercuric chloride and bee honey in 96 degrees ethanol. Both spirituous solutions were mixed for 15-20 min and the formed mixture is kept in dark place at 18-22 C for 2-3 days. Then spirituous solution containing mercuric chloride and bee honey is added to the softened base that is animal fat or fat mixture followed by the repeated mass keeping in dark place at 18-22 C for 3-6 days. Agent shows antitumor and antiviral activity. EFFECT: improved method of agent preparing. 1 tbl

Description

 The invention relates to medicine, in particular to the technology of medicines, and can be used in the pharmaceutical industry for the production of mercury-containing preparations intended for the treatment of tumors of both benign and malignant nature, viral diseases, herpes, tick-borne encephalitis, etc. and also as a general strengthening agent.

 Various mercury-containing compositions having an antitumor effect and methods for their preparation are known.

 The patent literature describes a method for preparing a mercury-containing composition with antitumor activity. The method of preparing the composition is quite complex and painstaking. It is based on the sublimation of its five mercury-containing ingredients: mercuric chloride, mercury chloride (calomel), mercury sulfide (cinnabar), mercury oxide and mercury sulfate. The final powder product is intended for internal use in the treatment of soft tissue cancer.

It should be noted that upon receipt of the known composition by sublimation, three mercury-containing compounds mercury oxide, mercury chloride and mercury sulfate decompose to metallic mercury (Hg ^o ), which is fusible and volatile. In this regard, the composition is not clear at the final stage of preparation. In the patent there is no analytical characteristic of the obtained drug.

 In folk medicine, a method is described for preparing an antitumor agent containing mercury dichloride (mercuric chloride) in its composition. The method consists in dissolving mercury dichloride (mercuric chloride) in water, followed by maintaining the solution for 6 hours. Obtained by this method, the tool is an aqueous solution.

 The known method has the following disadvantages.

 1. Since water, which is used as a solvent in this composition, by its physicochemical properties does not protect mercury ions from their toxic effects on the body, the preparation obtained from this recipe has toxicity.

 2. If stored improperly, especially in the light and in contact with air, the main active component of mercury dichloride (mercuric chloride) in an aqueous solution is constantly decomposed and, as a result, pharmacological activity is lost.

 The closest analogue of the proposed method is a method of preparing a drug with antitumor activity, known in traditional medicine [1]. The method consists in preparing two solutions. At the beginning, N1 solution is prepared. To do this, 0.5 kg of honey is dissolved in 3 liters of boiled and chilled water, then 7 8 ml of concentrated sulfuric acid is added.

 Preparation of solution N2: 1.0 g of mercury dichloride (mercuric chloride) is dissolved in 250 ml of ethyl alcohol.

 Obtained, as described above, solutions of NN1 and 2 are not further mixed. Patients in the treatment according to a certain scheme use a separate solution of N1 separately, drop by drop, during the 1st, 3rd and 5th months; during the 2nd and 4th months, N2 solution.

 It should be noted the following disadvantages of this method.

 1.Because two separate solutions (NN1, 2) are being prepared separately, which subsequently do not mix, the N1 solution cannot neutralize or at least partially reduce the toxicity of the N2 solution.

2. Ethyl alcohol, which is used in the preparation of N2 solution, acts as a solvent for the main active component of mercury dichloride (mercuric chloride). It is known that this solvent, by its chemical nature, does not enter into a coordination bond with mercury ions (Hg ²⁺ ), as a result of which N2 solution is toxic.

 3. The danger in the preparation of solution N1 is the work with the initial concentrated sulfuric acid and the fact of storage of this acid.

 The objective of the invention was the development of an original, scientifically-based method for producing a composition, which is a highly active, non-toxic agent that exhibits antitumor activity, as well as an antiviral and general strengthening effect on the body.

To solve this problem, a method for producing a mercury-containing composition having the following composition has been developed:
mercury dichloride (0.02 0.5%) 0.15 3.75 g
natural bee honey 230 280 g
animal fat 230 280 g
ethyl alcohol 96 ^o up to 550 ml.

 In the preparation of the proposed tool, you can use either a mixture of animal fats: a mixture of pork fat and cattle fat, or separately pig fat, badger fat, etc. The resulting composition can be used in medicine as an antitumor and antiviral agent either internally or externally .

 The choice of auxiliary components in favor of the above was made on the basis that the above components belong to high-quality food products, which due to their valuable chemical composition (the presence of enzymes, sterols, vitamins, minerals, etc.) increase the body's resistance to various infections, contribute to treatment of such serious diseases as pulmonary tuberculosis, pneumonia, chronic inflammatory diseases of the upper respiratory tract, etc.

The rich chemical composition of auxiliary components, as well as their protective effect on the main active ingredient of the mercury dichloride (mercuric chloride) composition, allows using the proposed method to eliminate the toxic properties of divalent mercury ions (Hg ²⁺ ).

 Characterization of the starting components.

 Honey bee is a natural biologically active product produced by bees from nectar of flowering plants, but different in physical and chemical properties from nectar.

 Bee honey is not only a high-calorie food product, but also an effective therapeutic agent.

 The quality of natural bee honey is regulated by the State Standard and the Rules of Veterinary Sanitary Expertise. On the international market, the quality of natural bee honey is regulated by the CMEA standard.

The main components of honey: amino acids, carbohydrates, enzymes, vitamins, hormones, organic acids, bactericides and many others, by their chemical nature, are ligands with respect to divalent mercury ions (Hg ²⁺ ), which in free form are toxic to a living organism.

The ligand molecules of honey also contain such reactive groups as OH ^- , NH ₂ ^+, and others. Under certain conditions, they interact with divalent mercury ions (Hg ²⁺ ) through its free coordination bonds. Ultimately, this interaction leads to a non-toxic mercury-containing drug.

In this regard, fermentation is included in the preparation technology of the preparation, the purpose of which is the protective protection of mercury ions (Hg ²⁺ ), which is carried out as a result of the complexation process with honey ligands.

 Carbohydrates, in particular fructose and glucose, are actively involved in this process. These components of inverted sugar determine the dietary properties of bee honey. In the gastrointestinal tract, their rapid, almost 100% absorption and assimilation occurs. Therefore, bee honey, as a valuable dietary product, is recommended for people who are sick, weakened, in need of enhanced nutrition, as well as athletes, pilots, etc. to restore strength, because when taking honey, an increase in muscle performance is noted. A possible mechanism of this process is the accumulation in the muscles of glycogen and trace elements, in particular zinc.

 As a result, tonic activity of the central and endocrine systems in the human body is observed, leading to a general strengthening effect.

It should be noted that simple carbohydrates of honey (glucose, fructose, sucrose, etc.) protect divalent mercury ions (Hg ²⁺ ) from toxic effects on a living organism due to free hydroxyl groups that act as donors, participating in the process of complexation with ions divalent mercury (Hg ²⁺ ).

 The physiological effect of bee honey is largely dependent on the enzymes it contains. Honey contains bee: inhibin, glucose oxidase, invertase, amylase (diastase), catalase, peroxidase, inulase, phosphatosis, etc. These enzymes cause the breakdown of complex carbohydrates to simpler ones, the latter also take part in the protection of mercury ions due to those released during the reaction hydroxyl groups.

Entering into the chemical interaction, enzymes significantly accelerate the complex formation of divalent mercury ions (Hg ²⁺ ) with the ligand components of bee honey.

 So, the invertase enzyme is involved in the breakdown of ordinary sucrose sugar into easily absorbed carbohydrates by the body: glucose and fructose.

 The enzyme amylase (diastase) breaks down the complex carbohydrate starch to the less complex carbohydrate maltose, etc.

 An antitoxic effect was noted for the honey catalase enzyme, which neutralizes hydrogen peroxide. The latter is formed in the human body as a result of the influence of many adverse factors of various diseases, overwork, stressful situations. Hydrogen peroxide, lingering in liver cells and red blood cells, violates their vital functions.

It is interesting to note that during the complexation of divalent mercury ions (Hg ²⁺ ) with honey ligands, nitrogen atoms contained in such components of honey as acetylcholine and histamine take an active part. These compounds are physiologically active substances.

 Regular intake of bee honey, which contains acetylcholine, as it compensates for the lack of this humoral substance in the elderly, which has a positive effect on their vital activity, this is especially important in case of heart rhythm disturbance, with heartbeat.

 The histamine contained in honey compensates for the histamine-forming function of the body, which is significantly reduced in a sick person.

 As a result, the secretory function of the stomach and intestinal motility are stimulated, appetite is excited, the assimilation of food is improved, and thereby conditions are created for a faster recovery of forces.

Bee honey ligands include organic acids and vitamins. They, as well as other compounds containing honey, take part in the protective protection of divalent mercury ions (Hg ²⁺ ), participating in the complexation process.

Vitamins of honey are mainly represented by B vitamins (B ₁ , B ₂ , B ₆ and B ₃ ).

 Vitamins PP, K, E, carotene (provitamins A) are present in bees in honey in an insignificant amount, and their content in honey is variable.

 Bee honey is enriched with vitamins and protein substances, mainly due to pollen, which is a natural admixture of honey.

It consists of: 21 amino acids, peptides, enzymes, coenzymes, all known vitamins, except B ₁₂ , deoxyribose, reducing and non-reducing sugars, fats, lecithin and other biological factors.

 None of the biochemical and physiological processes in the body take place without the participation of trace elements, the latter can be activators of the action of enzymes or their inhibitors. They participate in metabolic (protein, fat, carbohydrate), hormonal, vitamin and other processes, protein synthesis, heat transfer, hematopoiesis, bone formation, reproduction, immunobiological reactions, have gerontological properties.

 Bee honey contains various mineral salts: macrocells (salts of Na, K, Ca, Mg, P, etc.), and about 30 trace elements (salts of Cu, Mn, I, Zn, Al, Co, Ni, etc. )

 It is extremely important that many trace elements are in honey in the same concentration and in the same proportion to each other as in human blood.

 The common chemical composition of honey and blood determines the nutritional, dietary, biological and therapeutic properties of bee honey. The intake of severely deficient microelements with honey in the body eliminates their lack in everyday food products, which helps to restore health.

 The choice in favor of the second auxiliary component of pork fat (or a mixture of pork fat and cattle fat, or badger fat, or bear fat and other animal fats) was made because fats in the body act as a source of energetic nutritional material.

Fat characteristic:
Refined pork fat is one of the best bases for ointments, it perfectly covers the skin (it is easily smeared, fresh does not irritate it at all, it perceives the vast majority of medicines, it is well absorbed by the skin and is easily washed off with soap (emulsified with soapy water).

Physiochemical properties:
white homogeneous mass of soft consistency, a weak peculiar non-rancid odor and taste. Melting point 34 36 ^o C. The refractive index at 50 ^o C 1,456 1,460. Acid number no more than 2, iodine number 46 66.

 According to its fatty acid composition, pork fat is characterized by a high content of unsaturated fatty acids, such as: oleic, linoleic, linolenic, arachidonic. Saturated fatty acids contain: palmitic, stearic, myristic. The quality of pork fat is regulated by the State Pharmacopoeia, as well as GOST.

 The biological activity of pork fat (in IE / 1 g) is high, significantly higher compared to other fats; for example, summer butter has 1.1; beef fat 1.5; cocoa butter 3.8; pork fat 6.9.

 A positive property of pork fat is the fact that with environmental radiation damage, radionuclides do not accumulate in it and pork fat is considered to be absolutely “pure” in comparison with other fats.

 Pork fat is absorbed better than beef and mutton fats. The coefficient of its digestibility is 96, the highest indicator of digestibility.

Bovine Fat
It is obtained by reheating fat covering the organs of cattle. Melting point 42 50 ^o C.

Composition:
contains 55% tripalmitic, tristearic and up to 45% trioleic acids. The sum of specific mono-, di- and trisaturated acids, such as eicosenoic, erucic, in beef and pork fats is 0.2 0.5 and 2.5 - 3.3%, respectively.

 As an ointment base, beef fat is significantly inferior to porcine fat due to melting at a higher temperature and, therefore, a worse skin cover.

 In addition, animal fats contain such valuable substances for a living organism as vitamins, phospholipids, stearins. Fat contains fat-soluble vitamins: A, E, D, K.

 Vitamins A and E are antioxidants and protect fats from oxidation.

 In this regard, pork fat (as well as other fats) due to the vitamins oxidation inhibitors contained in it: A, E protect the main component of mercury dichloride (mercuric chloride) from oxidation that occurs when the drug is stored incorrectly under the influence of atmospheric oxygen, etc. d.

 In the body of a sick person, these vitamins inhibit radical oxidation reactions, participate in protein biosynthesis, tissue respiration and other major processes of cellular metabolism, thereby exerting a general strengthening effect.

 Vitamin K.

 The main physiological significance lies in its participation in the blood coagulation mechanism.

 Fat phospholipids.

 They include compounds such as lipoic, arachidonic acid, choline, etc. which are biologically active substances. Their combined presence in a complex complex of phospholipids significantly enhances their physiological effect on the body.

 Phospholipids form the basis of cell membranes that exchange cells with the environment for substances and energy, and determine the internal architecture of the cell.

 The content of lecithin in phospholipids is especially high.

Thus, the lecithin content in pork fat is 0.03%. Lecithin is a surface-active compound and takes part in complex formation, enhancing the protective protection of the main active component of Vituride K mercury dichloride (HgCl ₂ ) from its toxic effect on a living organism.

Due to the phospholipids contained in fats and, in particular, lecithin, the preparation obtained by the proposed method has high permeability through cell membranes, thereby providing a more effective entry of the main active component of mercury dichloride (mercuric chloride HgCl ₂ ) into the body of a sick person.

In the proposed production method, the physicochemical properties of auxiliary components, in particular bee honey, were taken into account. It is known that bee honey cannot be heated, because at a temperature of 37 ^o C it loses its antimicrobial properties. At temperatures above 40 ^o C, honey quickly loses bactericidal properties, at 60 ^o C enzymes are destroyed, at 80 ^o C - sugar, and a significant amount of hydroxymethyl furfural is formed.

In this regard, the technological mode of the process of obtaining funds is defined in the range of 18 22 ^o C.

Based on the foregoing, the preparation method of the product is as follows: first, in half the amount of 96 ^o ethyl alcohol according to the recipe indicated on p.4, bee honey (solution N1) is dissolved. Then prepare a solution of N2. To obtain it, mercury dichloride (mercuric chloride) is dissolved in the remaining amount of ethyl alcohol. The resulting N2 solution is added with stirring to the N1 solution. The mixture is thoroughly stirred for 15 to 20 minutes and maintained with periodic stirring in a dark place at a temperature of 18 20 ^o C for 2 to 3 days. After the specified time has elapsed, a second auxiliary component, softened animal fat or a mixture of fats, is added to the resulting mixture of alcoholic solutions of mercury dichloride (mercuric chloride) and bee honey. The mass is thoroughly mixed and again kept in a dark place at a temperature of 18 20 ^o C for 3 to 6 days.

During this time, a fermentation process is carried out and at the same time the complexation of mercury ions (Hg ²⁺ ) with ligand compounds and surfactants contained in bee honey and natural fat is carried out. The chemical reaction is carried out due to active hydroxyl (OH), cartoxyl (C $\genfrac{}{}{0ex}{}{\text{O}}{\text{OH}}$ ) ,, amino (LN ₂ ), quaternary ammonium bases, double carbon bonds, and other functional groups of ligand molecules for coordination bonds of divalent mercury ions (Hg ²⁺ ).

 As a result of this interaction, mercury-containing complexes are formed that make up the active principle of the drug.

 Obtained according to the proposed technological method, the composition does not have toxicity.

In the body, mercury-containing complexes undergo ligand exchange. Mercury ions (Hg ²⁺ ) released during the decomposition of the complexes react again with sulfhydryl groups of protein molecules (it is known that many forms of tumors are accompanied by impaired production of enzymes, proteins, hormones), block their action, create the desired antitumor effect, and then the decay products are excreted from the body through the kidneys, saliva, skin with sweating.

 Antitumor and antiviral activity was noted for the agent. In addition, the tool has a positive effect on the general well-being of patients, improves their mental and physical performance, as a result of treatment with this drug, the overall vitality increases.

 The invention is illustrated by the following examples.

 Example 1

To 125.0 ml of ethyl alcohol 96 ^o add 1.0 g of mercury dichloride (mercuric chloride), the mixture is stirred.

To 125 ml of ethyl alcohol 96 ^o add 250 g of honey bee, the mixture is stirred until a homogeneous mass (N ₂ ).

Then a solution of mercury dichloride (mercuric chloride) in ethyl alcohol N1 is added carefully, stirring for 20 minutes, to bee honey in ethyl alcohol (N2). The resulting mass is thoroughly mixed and maintained with periodic stirring at a temperature of 18 ^o C for 3 days.

After the specified time has elapsed, 250 g of softened pork fat is added in portions to the resulting mass, the mixture is thoroughly mixed and kept at a temperature of 18 ^o C for 4 days.

Storage. List A. At a temperature of 5 to 10 ^o C in a dark place.

 Physico-chemical characteristics of the drug are given in the table.

 Example 2

The process is carried out similarly to that described in example 1 with the difference that 0.15 g of mercuric chloride is dissolved in the preparation of the preparation, and instead of pork fat, a softened mixture of pork fat and cattle fat, taken in equal amounts, is used, and the second exposure to the resulting mass is carried out at a temperature 20 ^o C for 6 days.

 Physico-chemical characteristics of the drug are given in the table.

 Example 3

The method is carried out as described in example 1, with the difference that when preparing the preparation 3.75 g of mercuric chloride is taken, and badger fat is used instead of pork fat, and the second exposure to the resulting mass is carried out at a temperature of 22 ^o C for 3 days.

 Physico-chemical characteristics of the drug are given in the table.

The study of antiviral activity of the drug on a model of genital herpes in male guinea pigs
Based on studies conducted at the Research Institute of Virology, Russian Academy of Medical Sciences, it was found that the drug in various modifications and with different application regimens does not have a visible toxic effect on guinea pigs.

 On the model of genital herpes in male guinea pigs, it was found that the drug has a pronounced antiherpetic activity against herpes simplex virus (HSV) of the 2nd antigenic type, strain HV, the weight of male guinea pigs taken in the experiment, 200 250 g, they contain standard vivarium conditions.

 Virus-containing fluid was applied to penis (a) pre-scarified skin, and scarification was performed using surgical tweezers. Treatment was started 48 hours after infection according to the treatment regimen 2 times a day for 10 days.

 In groups of animals treated locally with the obtained agent and received it per os, the characteristic symptoms of herpes infection developed on the 3rd day, on the 5th day there was a sharp decrease in the severity of symptoms, its complete disappearance was noted on the 15th day of observation. Survival of guinea pigs in this group was 100% of the generalization of GI was not observed.

 We give examples illustrating the antitumor activity of the drug.

 Example 1

 An extract from an outpatient card for a patient N., 58 years old.

 10.10.1994, the Patient asked about recurrent leukoplakia of the cervix, which was confirmed by a biopsy performed on 09/28/1994

 Histology: cervical leukoplakia with the phenomenon of acanthosis.

 From the anamnesis: menopause of 7 years, suffered from severe postmenopausal syndrome for 2 3 years. In 1992, a microstroke, a complete restoration of functions. Since 1989, leukoplakia observation has been diagnosed. In 1993, electroconization histology leukoplakia. Medical treatment. In 1994, leukoplakia was again diagnosed and confirmed by histological examination. On examination (smears taken for cytology). RU. The vagina is free, pink mucosa, prolapse of the anterior wall. The neck is sharply shortened, the external pharynx is retracted. On the back lip, an extensive area of leukoplakia, partially rising above the surface of the neck, leukoplakia reaches the arches without passing to the vagina. Appendages are not determined. Parametries are free. With colposcopy: the entire posterior lip of the cervix is whitish in color with plaques rising above the surface. Lugol's solution is not stained. On the front lip of the uterus, cords and uneven coloration are visible (the result of electroconization). Cytology: a large number of scales in smears, cells with hyperchromic nuclei, dyskariosis, and single “bare” nuclei are found. Flat squamous cells, in the form of clusters, white blood cells, single red blood cells.

 Diagnosis: leukoplakia with atypia of individual cells.

 Recommended treatment: tampons with ointment "Viturid K-2" for 6 hours, followed by douching with chamomile, a succession.

 10/10/1994 was introduced a swab with ointment K-2. The vagina is smeared with petroleum jelly (I).

 10/14/1994 g. Local reaction: mild hyperemia, mucous discharge. A swab with K-2 ointment was introduced for 6 hours (after douching) (I).

 10.17.1994, sharp hyperemia of the mucous membrane of the cervix and vagina, profuse mucous discharge, a feeling of "burning" and a slight itch. After treatment, a swab with K-2 ointment was introduced for 4 hours (III). After extraction - douching, rest 4 days.

 10/21/1994, hyperemia and a small swelling of the neck is maintained, the discharge decreased. A tampon was introduced for 6 hours (IV). After extraction, douching with infusion of chamomile, a series, lubrication with ointments.

 Inspection after 2 weeks.

 November 4, 1994; 14 days have passed since the end of treatment.

 R. U. The vagina is free, the mucous membrane of the neck and vagina is hyperemic. The discharge is moderate, mucous. On the back lip, the leukoplastic plaques almost disappeared, in their place there was a bright red surface, not bleeding. From the periphery, immature epithelium “flows” onto the “erosion”. The mucous membrane is faint, in places more intense.

 Continued douching, lubrication with ointments 2 times a week, vitamin balls are recommended.

 Inspection after 1 month.

 12/14/1994, 40 days have passed since the treatment of leukoplakia with atypia of individual cells with K-2 ointment, a total of 4 applications of 6 hours each.

 At home, the patient treated the vagina with infusion of chamomile, soda.

 RU. The walls of the vagina are pink, the discharge is scarce, mucous. The cervix is sharply shortened, the surface is covered with a slightly reddish epithelium, some areas are more initiated, and leukoplakia is not visually detected. However, the neck is slightly stained with Lugol's solution. The external pharynx is slightly gaping. The palpation of the neck is firm. Cytology: a large number of leukocytes, squamous cells are hyperchromic, but their sizes are not increased. There are scales, parabasal cells, metaplasized epithelium. According to the clinic and cytology, a significant improvement (the disappearance of leukoplakia, epithelization).

 Recommended: treatment of the vagina and the introduction of vitamin balls.

 Inspection after 2 months.

 Example 2

 Extract from the outpatient card patient N, a 44 years old.

 12/26/1994, the Patient asked about the "erosion" of the cervix, increasing in recent years, serous-turbid discharge from the vagina.

 From the anamnesis: pregnancies 5, childbirth 2nd. Since 1978, cervical erosion was treated with tampons, diathermocoagulation was performed twice. The positive effect was not observed for long, so the treatment was repeated periodically. In 1990, she again felt deterioration.

 On examination. The patient suffers from hypertension II tbsp. RU. The vagina is free (smears taken for cytology), the neck is somewhat hypertrophied, its surface is "mottled", does not bleed. Left postpartum scar. Around the external pharynx is a fine-grained area. Colposcopy reveals whitish “strands”: areas of metaplasized epithelium, transformation zone for 9–11 hours. When stained with Lugol's solution, the front lip is sometimes iodinegative, the back lip is colored, but slightly.

 Cytology: among cells of squamous and cylindrical epithelium, there are cells with hyperchromia of nuclei, dyskariosis, basal cells with proliferation and metaplasized cells.

 Diagnosis: dysplasia I II art. Treatment with ointment Viturid K-2 (honey, alcohol, fat, vituride).

 12/26/1994, a tampon with K-2 ointment for 6 hours. The vagina is lubricated with liquid paraffin oil.

 12/29/1994, a slight hyperemia of the neck, an increase in mucous secretions. Tampon with ointment K-2 (II).

 01/03/1995, hyperemia of the neck and walls of the vagina, complaints of "burning", which disappears after lubrication with flucinar. Tampon with ointment K-2 (III).

 01/06/1995, the Neck and walls of the vagina are somewhat swollen, hyperemia is pronounced (local reaction). The discharge is abundant, liquid, mucous-turbid.

 Recommended baths and douching with chamomile. The tampon was not introduced.

 01/17/1995, the swelling decreased. Hyperemia of the neck and walls of the vagina somewhat decreased. Tampon with ointment K-29 (IV).

 01/13/1995. Complaints of a slight itching and moderate "burning" in the vagina. The discharge is abundant, mucous-turbid. Swab with ointment K-2 (V).

 January 17, 1995 The complaints are the same. Hyperemia of the neck and vagina is significantly pronounced, the discharge is plentiful. Tampon with ointment K-2 (VI).

 Recommended: douching with infusion of chamomile, succession, lubrication with ointments (flucinar, celestoderm, oxycorit) every other day. Inspection in 10 days.

 01/30/1995, it took 10 days after treatment.

 R. U. The vagina is free, its walls are slightly hyperemic. The neck is bright red in color, as if "cleansed", the surface is smooth, does not bleed. Colposcopy shows an abundance of blood vessels, open glands. After lubrication with a 3% solution of vinegar, the vessels contracted, the "tongues" of the immature epithelium were clearly visible.

 Continued vaginal douching and lubrication 2 times a week are recommended.

 Inspection after 3 weeks.

 02.24.1995, 37 days have passed since the treatment (dysplasia I II) with tampons with Viturid K-2 ointment. The patient, after removing the tampon, independently made baths, douching with chamomile, and a series of baths with baths with the addition of manganese solution. R.U. The vagina is free, its walls are pink, folding is well defined. The cervix is somewhat hypertrophied, on the left are traces of the postpartum rupture. The surface of the neck is smooth. The body of the uterus is slightly enlarged, the appendages are not detected, the arches are deep. Parametries are free. Colposcopy revealed many open glands, tongues of immature epithelium from the periphery. Around the glands sections of keratinizing epithelium (epidermis). When staining with Lugol's solution, the neck is "mottled", but large areas are colored evenly. Active cervical epithelization continues.

 According to the clinic and cytology, a positive effect was noted.

 Douching is recommended once a week, the introduction of vaginal balls.

 Inspection after 1 month.

 Example 3

 Extract from the outpatient card for patient S-th, 64 years old.

 01/20/1995, the Patient asked about a disease of the cervix. During the last 2 months atypical cells were found in smears.

 01/14/1995 cervical biopsy, histology: dysplasia III, two areas without underlying tissue, suspicious for intraepithelial cancer. Concomitant diseases: diabetes, hypertension, coronary heart disease. From the anamnesis: menopause 10 years. Pregnancy 6, childbirth 2. I did not contact a gynecologist for 7 years. At the end of 1994, pain appeared, the gynecologist discovered colitis, was treated on an outpatient basis. In smears of dysplasia.

 On examination, R.U. The vagina is narrow, the mucous membrane is atrophic, the neck is small, shortened. Around the external pharynx small papillary growths. With colposcopy: atrophic squamous epithelium, the entire neck is iodinegative. Cytology: cells of the deep layers, many parabasal. Individual cells with violations of the nuclear cytoplasm, hyperchromic ratios, pycnosis of nuclei. Single cells are polymorphic, many white blood cells and bacteria. There are mitoses.

 Dysplasia III.

 Treatment: swab with K-2 ointment (for 4-6 hours, followed by vaginal treatment).

 01/20/1995, a tampon with K-2 ointment was introduced for 4 hours, the walls of the vagina were treated with flucinar (I).

 01/23/1995, the local reaction is weakly expressed. Mild hyperemia, significant discharge. A tampon with K-2 ointment was introduced for 6 hours, the vagina was treated with flucinar (II).

 01/26/1995, the local reaction is moderate, heavy discharge, itching, a feeling of "heat" in the vagina. A tampon with K-2 ointment was introduced for 6 hours, the vagina was treated with flucinar (III).

 01/30/1995, the patient held the swab for only 4 hours, there was a "burning" in the vagina, up to pain. On examination, severe hyperemia, swelling of the vaginal mucosa, copious discharge, mucous-turbid. After processing the vagina, the swab was not inserted.

 02/03/1995 the local reaction subsided. A swab with K-2 was introduced for 4 hours (IV). The patient is invited to the clinic for treatment.

 02/08/1995, the local reaction is moderate. A swab with K-2 was introduced for 4 hours (V).

 02/20/1995, 12 days after local treatment with ointment K-2. Complaints of itching in the vagina. R. U. The mucous membrane of the vagina and cervix is slightly hyperemic, the discharge is mucous, odorless. Around the external pharynx there is a bright red mucous membrane, with touching the flowery discharge. With colposcopy of the phenomenon of inflammation, the mucous membrane is weakly stained.

 It is recommended to continue processing the vagina.

 Inspection after 1 month.

 March 24, 1995 Two months have passed since the treatment of dysplasia III. (5 applications). R.U. The walls of the vagina are pale, the discharge is scarce, the neck is small, covered with pale epithelium, a pink border around the pharynx. Lugol's solution is slightly colored. Cytology: basal squamous cells, parabasal sizes, there is a hyperchromia of the nuclei, a lot of white blood cells. Discariosis in individual cells. According to the examination and cytology, positive dynamics were noted.

 Vaginal and douching treatment recommended.

 Inspection after 6 weeks.

 Example 4

 Patient N. at the All-Russian Scientific Research Center of RAMS on 04/07/93 for cervical cancer underwent advanced removal of the uterus with the right appendages and the left fallopian tube, transplantation of the left ovary to the level of the n / end of the kidney (T, Mo). In the postoperative period, which was uneventful, a combination of radiation therapy was performed (remote pelvis; intracavitary SOD 66 Gy).

 Subsequently, during 1993 and 1994. received treatment with vituride (local treatment in the form of tampons) 3 courses on 1 ring, which she tolerated well, without complications.

 During follow-up examinations and dynamic observation in October 1993, an uneven thickening of the vaginal dome and thickening of its walls was revealed, which was regarded as a relapse of the tumor in the postoperative zone (stump).

 Continued local treatment with vituride, was under dynamic observation. During examination and examination in December 1994 (after 3 courses of treatment with vituride), data for tumor recurrence were not obtained (cytological examination, ultrasound data, normal blood and urine tests, etc.). No complaints at this time.

 Feeling good, active, good nutrition. Skin, mucous membrane - normal color, peripheral l / nodes, accessible palpation, not enlarged. Locally only cicatricial changes.

Claims (3)

1. The method of obtaining funds with antitumor activity, including separate dissolution of mercuric chloride in 96 ^o ethanol and natural bee honey in a solvent, characterized in that 96 ^o ethanol is used as a solvent for natural bee honey, after dissolution both of them obtained alcohol is mixed under stirring for 15 20 minutes and the mixture was allowed to stand in a dark place at a temperature of 18 22 ^o C for 2 to 3 days, and then enter it with stirring into the fat base and re-soak the resulting mixture was dissolved in a dark place at 18 22 ^o C for 3 to 6 days, with the ingredients taken in the following amounts, g:
Sublimate 0.15 3.75
Natural bee honey 230 280
Fat base 230 280
Ethyl alcohol 96 ^o Up to 750 ml
2. The method according to p. 1, characterized in that the fat base is animal fat.  3. The method according to PP. 1 and 2, characterized in that the fat base consists of a mixture of fats taken in various ratios.  4. The method according to p. 1, characterized in that the fat base is pre-softened.

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