RU2376978C2 - Complex api preparation in form of suppositories for treatment of andrological diseases and method of obtaining it - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to pharmaceutical industry, medicine and concerns composition, obtaining and application of original complex API preparation in form of rectal suppository. Claimed is complex natural preparation in form of suppository for treatment of andrologic diseases which contains ambrosia or bee-bread, cocoa butter or other fat base, preparation additionally contains homogenised larvae of queen bee with native royal jelly or lyophilised powder from homogenised drone larvae and drone jelly. Claimed is method of obtaining suppository including homogenisation of queen bee larvae and native royal jelly preliminarily frozen at temperature -21°C, and further unfrozen at +5-8°C and extracted from ovaries or lyophilisation of homogenised drone larvae and drone jelly, addition to obtained mass of crushed bee-bread or ambrosia, step-by-step mixing of said fractions with cocoa butter or other fat base until hoimogeneous suppository mass is obtained, formation of suppositories with 3.0 g weight, cooling, packing, marking. Claimed is method of treating patients with andrologic diseases by means of suppositories.

EFFECT: invention ensures expanding pharmacologic activity of suppository for treatment of andrologic diseases by ensuring increase of spermatogenesis and erectile function.

3 cl, 2 ex, 4 tbl

Description

The invention relates to the pharmaceutical industry, medicine, and relates to a composition, a method for producing and using an original complex apipreparation in the form of a rectal suppository having an expanded spectrum of pharmacological activity used for the treatment of andrological diseases.

The inventive preparation is created on the basis of bee products, represents rectal suppositories and includes homogenized native queen bee larvae with royal jelly or lyophilized powder from drone larvae and drone milk homogenate, bee pollen or flower pollen, cocoa butter or other fatty base.

All the components that make up the suppositories have a rich chemical composition (Table 1), have hepatoprotective, anabolic, anti-inflammatory and antioxidant effects, normalize metabolic processes in tissues at the ultrastructural level, improve their trophism, stimulate a number of biological processes, including immune and endocrine systems that regulate the level of genital and other hormones.

There are several types of nutritious milk produced by bees: uterine, bee and drone.

By the origin and chemical composition, the milk that feeds the larvae of working bees and drones is somewhat different from the milk that bees lay in mother liquors to feed the queen bee.

Royal jelly is a mixture of the secretion of the pharyngeal and maxillary glands of the working bee, which they use to feed uterine larvae.

Bee or drone milk is a substrate produced exclusively by the pharyngeal glands of working bees and intended to feed only the larvae of working bees or drones.

The lipid composition of royal jelly has no analogues - 80-90% of fatty acids of milk contains special short-chain (8-10 carbon atoms) hydroxy and dicarboxylic fatty acids. It contains various unsaturated acids. The main place among them is occupied by palmitic, oleic, linoleic, lipoic. These acids are the precursors of prostaglandins, thromboxanes and leukotrienes, perform a plastic function and play a significant role in the restoration of vascular endothelium. Unsaturated fatty acids, which are part of royal jelly, are embedded in biological membranes, change their properties and activity of membrane-bound proteins themselves, disconnecting the processes of oxidation and phosphorylation [15].

Table 1
The composition of some beekeeping products (μg per 1 g) (cited by A. Kayyasu, 1968; Iliyesh N.V., 1983; Shkenderova S. et al., 1985; Shemetkova M. et al., 1987; Pavlyuk R.Yu. ., 2003; Vakhonina T.V., 2000; 2006; Khismatullina N.Z., 2005; A. Tikhonova et al., 2006) Content Royal jelly Bee larvae Lyophilized drone larvae powder pollen Honey Structure, % Protein 18.0-45.0 17.0 41.6-51.2 7.0-40.0 0.5 Fats 7.0-19.0 2,8 4.8 1,0-20,0 0.2 Carbohydrates 15.8-52.0 0.8 30.0-41.7 20,0-40,0 76.0 Vitamins In ₁ 1,2-18,0 5.74 23,2 15.0 0.1 In ₂ 5.3-20.4 10.92 38,2 2200 0.6 B _c 0.16-0.5 2,56 7.0 0.13 At ₅ 38-250.0 28.89 134.0 20.0-51.0 1.3 At ₆ 2.0-44.2 0.56 2.2 9.0 3.2 B ₁₂ 0.05-0.14 N 1,5-5,0 6.0 0.001 Carotenoids 0.8 9,4 2125.0 FROM 3.0-5.0 122.0 2053.0 35.0-550.0 PP 190.0 210.0 3.6 E 1.73 15.9 3.0-1700.0 Trace elements Potassium 1600,0 5,0 5560,0 4000,0 470.0 Sodium 2100.0 380.0 9004,0 270,0 100.0 Phosphorus 1990.0 180.0 Calcium 280,0 140.0 1264.0 1400.0 140.0 Copper 8.0 20,0 24.0 20,0 0.59 Iron 32,0 200,0 8.0 Zinc 19.0 55.0 52.0 11.0 0.94 Magnesium 1420.0 20,0 4240.0 500,0 30,0 Manganese 1,0 44.0 4.0 0.34 Recommended Dosage 250 mg 250 mg 30.0 g 100.0 g

Another part of royal jelly lipids is phospholipids (lecithin, sphingomyelins, cephalin and sterols). These compounds are the main components of plasma membranes and plasma lipoproteins that perform both structural and metabolic functions [8, 9].

When examining the blood plasma of patients with high cholesterol, high and low density lipoproteins, triglycerides, it was found that a decrease in royal jelly was observed. Restoring normal levels of blood lipoproteins has a positive effect on the microcirculation of various organs and tissues [15].

Amylase, invertase, gluoxidase, acid phosphate, which are part of the royal jelly, possessing enzymatic activity, catalyze the hydrolytic cleavage of sucrose, starch, esters, choline and other compounds. Exogenous choline contained in milk improves impulse conduction along the nerve fiber, and γ-aminobutyric acid, which is part of it, is involved in the transmission of nerve impulses and improves metabolic processes in the brain, thereby reducing asthenovegetative and neurological disorders in patients with various somatic diseases.

Royal jelly and drone milk have an ambiguous effect on vascular tone. Their intake stimulates the sympathetic and parasympathetic departments of the autonomic nervous system, and helps to normalize blood pressure in hyper- and hypotensive patients. These features of royal jelly and drone milk allow us to recommend them not only for treating patients with unstable hemodynamics, but also to use them in the treatment of the angiogenic variant of erectile dysfunction.

Royal jelly and drone milk increase the body's resistance to hypoxia, improving the processes of tissue respiration and their oxygen consumption [7]. These beekeeping products have a pronounced effect on the cellular and humoral parts of the immune system, which allows us to consider them as promising immunomodulators in the treatment of many chronic diseases, including and chronic prostatitis [6].

It has been established that royal jelly and drone milk contain phytohormones, which are involved in spermatozoa and oocytogenesis, and according to the feedback principle, in the mechanisms of regulating the level of sex hormones [11, 14].

An active role in maintaining metabolism is played by a number of vitamins and minerals. With erectile dysfunction, the body's need for these substances increases and is not compensated by the usual diet. Reception of uterine and drone milk in this disease allows you to compensate for the increased needs of the body in these vital compounds.

The larvae of the queen bee and drones in their chemical composition resemble royal and drone milk. Larvae serve as a source of development for the bee family. However, the life span of the queen bee is 10 times that of working bees, and the mass of eggs laid by it per day exceeds its body weight by several times. Against the background of feeding with royal jelly for 5-6 days, the larvae increase their mass by 1.5-3 thousand times. This fact has no analogues of a similar growth of living organisms in nature and indirectly indicates the anabolic properties of royal jelly.

Perga is a mixture of flower pollen and honey, processed by enzymes, placed and rammed by bees in cells of cells, where its lactic acid fermentation takes place.

Flower pollen is the male reproductive cells of plants located on the tips of the stamens in the form of small pollen grains that bees collect for their nutrition.

Honey is a viscous, sweet-tasting substance formed as a result of processing by bees of flower nectar - the juice produced by the nectaries of flowering plants and consisting largely of carbohydrates and water.

Perga is a product rich in proteins, fats, vitamins, mineral salts and other biologically active substances. It has a versatile positive effect on the body, while exhibiting stimulating, anabolic, hepatoprotective and other properties [12].

Cocoa butter (or another fatty base) make up the suppository base.

On the basis of royal jelly, the domestic industry produces tablets, suppositories, powder, ointment 3%, cream 6% and eye films of the Apilak drug. It has proved itself to be well-developed by Comilfo together with the Scientific Research Institute of Beekeeping and introduced into practical use a new drug based on royal jelly AP-ITON-25 [1].

Imported royal jelly preparations are presented on the market in the following dosage forms - dragee with royal jelly (Vitadion), royal jelly in ampoules for oral administration, Melkaltsin granules, eye drops Kolgel (2% aqueous solution of royal jelly) (Romania), “ Apisperum ”,“ Apifortil ”,“ Super Strange Royal Jelly ”,“ Ultravital ”,“ Hamus irradiad ”,“ Royal jelly for injections ”.

Outside Russia, for the treatment of urological diseases (acute and chronic prostatitis, benign prostatic hypertrophy), Mipronol rectal suppositories (Romania) have been created, tested and applied. Suppositories of the drug consist of polyfler honey (0.4 g), propolis extract (thick extract) (0.25 g), pollen (0.15 g), royal jelly (0.15) and cocoa butter.

In the Russian Federation, rectal suppositories "Prostopin" {prototype} have been created and are used on the basis of beekeeping products to treat these diseases. The use of Prostopin suppositories is effective for the treatment of acute and chronic prostatitis, benign prostatic hypertrophy, and unlike Mipronol, it is used in the treatment of hemorrhoids, anal fissure and infectious diseases of the genitourinary system. Suppositories "Prostopin" are the closest in composition and pharmacological action to the claimed drug "Apipollar". The composition of Prostopin suppositories includes: polyfler honey (0.12 g), propolis (native or concentrate) (0.31 g), dried bee bread (0.15 g), flower pollen (0.08 g), royal jelly bee (0.10 g) or royal jelly freeze-dried milk (0.033 g), beeswax (0.06 g), anhydrous lanolin (sheep fat) (0.12 g) and cocoa butter (1.97 g) or others of the listed bases - solid fat, supporin-M, massupol, vitepsol.

The goal is to expand the pharmacological activity of the suppository for the treatment of andrological diseases by providing increased spermatogenesis, erectile function.

The inventive suppository differs from the "Prostopin" (prototype) suppositories in its qualitative and quantitative composition, has expanded indications for use.

The effectiveness of the proposed suppositories was evaluated by the example of patients with diseases of the urogenital system of men.

The common clinical signs of the proposed suppositories and prototype is a positive effect in the treatment of diseases of the genitourinary system - benign prostatic hyperplasia and chronic prostatitis. Like suppositories "Prostopin", the claimed suppositories contain dried pollen or flower pollen, royal jelly or royal jelly lyophilized, cocoa butter or other fatty base.

Distinctive features of the proposed suppositories from the prototype is that:

a) as an additional source of vitamins, proteins, fatty acids, enzymes and microelements, native homogenized bee uterus larvae or lyophilized powder from drone larvae and drone milk homogenate are used;

b) bee uterus larvae and royal jelly are stored in a natural biological environment - mother liquors until the preparation of the suppository (Patent No. 2306698 from 2007.09.27);

c) the suppository does not contain honey, propolis and wax. Studies conducted by Fesenko L.M. and Aripov O.A. (2007) showed that plant flavonoids, which are part of propolis, reduce the level of blood nitric oxide [13]. It is known that nitric oxide acts as an erection neurotransmitter, as it causes relaxation of smooth muscles and arterioles of the cavernous bodies of the penis. Therefore, the use of suppositories containing propolis for the treatment of patients with erectile dysfunction is ineffective;

d) royal jelly is used in the recommended daily doses indicated in the "List of scientific and technical documentation for beekeeping products and their compositions" (2001) by the Institute of Nutrition of the Academy of Medical Sciences, Acad. Ryazan Medical University. I.P. Pavlova [11];

e) are used to treat male infertility and erectile dysfunction.

The technological process consists of three main stages:

1) preparation of the starting components;

2) preparation of a mixture of starting components with a suppository base;

3) preparation of suppository mass, molding and packaging of suppositories, packaging and labeling.

For the preparation of the claimed suppositories, raw materials are used in the sequence indicated in the temporary technical conditions (VTU) for this type of product.

1. The technological scheme and description of the manufacturing process of suppositories containing:

a) bee uterus larvae:

Example I. Preparation of suppositories containing native bee uterus larvae and royal jelly:

1.1. Defrosting and extracting royal jelly with queen bee larva from mother liquors. Royal jelly with bee uterus larva, stored in mother liquors at a temperature of -21 ° C, is thawed at a temperature of + 5- + 8 ° C for 5-10 minutes and is removed from them with a glass spatula.

1.2. Preparation of a homogenate from bee uterus larvae and native royal jelly.

Thawed royal jelly with queen bee larvae thawed and extracted from the mother liquors is homogenized in a tissue-grinding plant of the MIM-300 or MPW type.

1.3. Preparation of powder from bee bread or pollen.

Pre-ground bee bread or pollen are homogenized in a C50.0 mixer (“Drunk Barrel”) for 5 minutes.

2.1. Preparation of a mixture of homogenized larvae of queen bees and native royal jelly and suppository base.

The homogenised larvae and queen bees native royal jelly mass of 0.5 g is added with constant stirring to a _^half portion of suppository base, heated to a temperature of 26 + ... + 30 ° C.

2.2. Preparation of a mixture of bee bread or pollen with a suppository base. Pregrinding pollen or pollen weighing 0.5 g is added with constant stirring to a _^half portion of suppository base, heated to a temperature of 26 + ... + 30 ° C.

3.1. Mixing the components of suppository mass.

All components of the suppository mass (paragraphs 2.1 and 2.2) must have a temperature of not higher than + 40 ° C before mixing. The order of their mixing does not matter. The resulting suppository mass is mixed until a homogeneous mass.

3.2 Formation of rectal suppositories 3.0.

3.3. When molding suppositories in a manual way, the molten suppository mass is cooled to a temperature of + 26 ... + 30 ° C and poured into demountable molds. Pre-empty molds are lubricated with an alcoholic solution of calcium stearate, cooled using a refrigeration device (automatic mode) or a freezer for 10-20 minutes. The filled forms are placed in the freezer for 30-40 minutes. After hardening, the suppository is removed and transferred to a pallet covered with parchment paper. Finished suppositories are rejected in appearance and subjected to analysis.

3.4. The suppositories are poured on machines with separate casting and packaging operations (Franco-Crespi, Italy), or on a fully automated line (Hefliger and Karg Servac200S, Germany), or other similar machines.

Example II Preparation of suppositories containing lyophilized powder from drone larvae and drone milk homogenate:

1.1. Preparation of lyophilized powder from drone larvae and drone milk homogenate.

Drone milk and drone larvae of 7–9 days old with a total mass of 417.0 g are subjected to coarse grinding in a tissue grinding machine of the MIM-300 or MPW type.

To obtain 95.0 g of powder, the resulting biomass was poured into trays, frozen at a temperature of -20 ° C, subjected to freeze-drying in a SU-3.0 type apparatus, and dried at a temperature not exceeding + 40 ° C to a residual moisture content of not more than 5% .

1.2. Preparation of bee pollen (or pollen) powder.

Pre-ground bee bread or pollen are homogenized in a C50.0 mixer (“Drunk Barrel”) for 5 minutes.

2.1. Preparation of a mixture of lyophilized powder from a homogenate of drone larvae and drone milk with a suppository base.

The lyophilized powder from the homogenate drone larvae of the drone and jelly 0.5 g is added with constant stirring to a _^half portion of suppository base, heated to a temperature of 26 + ... + 30 ° C.

2.2. Preparation of a mixture of bee bread (pollen) with a suppository base.

Pregrinding pollen or pollen 0.5 g is added with constant stirring to a _^half portion of suppository base, heated to a temperature of 26 + ... + 30 ° C.

3.1. Mixing the components of suppository mass.

All components of the suppository mass (paragraphs 2.1 and 2.2) must have a temperature of not higher than + 40 ° C before mixing. The order of their mixing does not matter. The resulting suppository mass is mixed until a homogeneous mass.

3.2. Formation of rectal suppositories 3.0.

Subsequent preparation of suppositories is carried out in accordance with paragraphs 3.3 and 3.4 of Example I.

A study of the clinical efficacy of the claimed suppositories was conducted in patients with erectile dysfunction, impaired spermatogenesis, benign prostatic hyperplasia and chronic prostatitis.

All patients, taking into account the type of urological (andrological) pathology, were divided into two groups: the 1st group included 11 patients with impaired spermatogenesis (oligozoospermia and teratozoospermia of the 2nd to 3rd degree), the 2nd group included 12 patients with erectile dysfunction (ED) ) Of 12 patients of the 2nd group, 4 patients had chronic prostatitis and 3 had benign prostatic hyperplasia. The age of patients with impaired spermatogenesis was 33 ± 5 years, patients with ED - 41 ± 7 years. The main criteria for violation of the qualitative composition of sperm are: sperm concentration, characteristics of the motility of these cells (fast linear, slow linear or nonlinear progressive types of movement, as well as the number of locally moving and immobile sperm) and the concentration of pathological forms of spermatozoa and spermatogenesis cells.

All patients with impaired spermatogenesis within 24 days underwent a course of treatment, which included the use of the claimed suppositories containing native homogenized uterine larvae or lyophilized powder from homogenate of drone larvae and drone milk. Suppositories were administered 1 time per day, alternately, after preliminary bowel movement. For even numbers, suppositories containing bee uterus larva and royal jelly were used; for odd numbers, suppositories with lyophilized powder from drone larvae and drone milk homogenate were used. As a result of treatment in patients with oligozoospermia, an increase in ejaculate volume by 1.5-2 times and restoration of normal sperm color was noted. In patients with teratozooospermia, the number of motile sperm cells increased by a factor of 2–3, while the concentration of immobile sperm cells decreased by 20–40% (see the appendix: an example of treatment of a patient). Against the background of the therapy, the number of pathological forms of spermatozoa decreased by 16-30%, and the pool of immature spermatogenesis cells increased by 2 times (on average up to 8%).

In patients with ED, treatment was carried out in 3 courses lasting 24 days with an interval between them of 7-10 days. Suppositories were administered 1 time per day, alternately, after preliminary bowel movement. For even numbers, suppositories containing bee uterus larva and royal jelly were used; for odd numbers, suppositories with lyophilized powder from drone larvae and drone milk homogenate were used. In patients with ED, vasculogenic and hormonal changes were mandatory studied. Particular importance was given to such risk factors for ED as hypertension, coronary heart disease, diabetes mellitus, a long history of smoking and psychogenic disorders.

Against the background of the treatment, 85% of patients of the 2nd group noted an improvement in erection. In addition, upon completion of the course of treatment, all patients with chronic prostatitis significantly reduced pain, dysuria stopped, urine and prostate secretion tests returned to normal: the absence or decrease in the content of leukocytes was detected (no more than 1100-1700 in 1 mm ³ ).

According to the ultrasound research method, in 2 patients with ED and benign prostatic hypertrophy, the volume and echo structure of the gland after courses of therapy approached normal values. At the same time, a significant decrease in the volume of residual urine was noted (on average by 40%). After the course of treatment, patients with benign prostatic hypertrophy noted a decrease in the intensity of irritative symptoms and pain in the perineum, as well as an improvement in the psychosomatic component.

In gynecological practice, treatment was applied to 63 patients aged 38 ± 11 years. All of them were divided into three groups. The first group consisted of 28 patients who had a pronounced clinical picture of menopausal syndrome. The second group included 16 women with high follicle-stimulating, low luteinizing hormones and estrogens. The third group consisted of 19 patients with cervical erosion.

Apipollar suppositories with homogenized bee uterus larvae were administered intravaginally daily, one at night for 24 days. The course of treatment was 2-3 times with an interval of 7-10 days. As a result of treatment, 25 patients of the first group showed a decrease in asthenovegetative disorders in the form of irritability, hot flashes, blood to the face, and “interruptions” in the region of the heart. Their blood pressure and general clinical blood and urine tests returned to normal.

Treatment was effective in 13 of 16 patients of the 2nd group with hormonal dysfunction. Their estrogen, follicle-stimulating and luteinizing hormones returned to normal. In some patients, menstruation recovered, and during the ultrasound examination, follicles in the ovaries were visualized.

In 17 of 19 patients of the third group with cervical erosion during the control colposcopy, epithelization of erosion was noted after 2 courses of treatment.

The anabolic, hepatoprotective (including antioxidant and immunomodulating) properties of Apipollar suppositories were evaluated according to the results of observation and treatment of 103 burned patients. All patients were daily injected with one suppository containing homogenized uterine and lyophilized drone larvae in the morning and night in the rectum after preliminary bowel movement for 24 days. After 7-10 days, the course of treatment was repeated again.

In the blood of 30 burnt patients with hypoproteinemia, in a laboratory assessment of the level of total protein receiving the proposed suppositories, there was a clear tendency to a lower severity of protein deficiency, the total protein content exceeded the same value in the group that did not receive them, on average, by 4-12 g / l ( p> 0.05) (Table 2).

The use of Apipollar suppositories for toxic hepatitis in 28 victims of burns contributed to a pronounced positive dynamics in their clinical condition and laboratory parameters. Patients noted an improvement in overall health, a decrease in pain in the right hypochondrium. Alanine aminotransferase and aspartate aminotransferase indices returned to normal within 6 ± 2 days. The decrease in the level of molecules of average mass occurred 2 times faster than the initial one (255 ± 15 conv. Units). Moreover, by 33 days, not only the activity of catalase (502 ± 99 conventional units) increased, but also the color index (0.60 ± 0.08 conventional units). These changes indicated a decrease in the severity of toxicosis and the manifestation of the hepatoprotective properties of the suppositories used.

table 2
The dynamics of the severity of hypoproteinemia in patients with reduced body weight when using suppositories and control groups (M ± m) Observation groups The total plasma protein content (g / l) upon enrolment after 14 days after 21 days after 28 days after 35 days Control group 60 ± 5 51 ± 4 55 ± 6 57 ± 6 59 ± 4 Apipollar Suppository Group 61 ± 3 54 ± 3 58 ± 4 62 ± 5 66 ± 5

In 18 patients who received suppositories on the first day after thermal injury, venous blood luminescence parameters were studied to evaluate hepatoprotective and antioxidant properties.

Already 2 days after the start of the administration of suppositories, the content of reactive oxygen species and lipid peroxidation products in the blood of the victims, as well as blood luminescence indices, decreased significantly, and after 4 days the luminescence indices decreased almost 2 times compared to the control group (Table 3) .

Table 3
Venous blood luminescence indices (mV, M ± m) in patients on the first day after thermal trauma with the use of suppositories and control group Observation groups Average luminescence upon enrolment after 48 hours after 72 hours after 96 hours Control group
Apipollar Suppository Group 8.2 ± 0.5 16.6 ± 1.0 14.7 ± 1.5 22.2 ± 2.3 8.1 ± 0.6 8 ± 0.7 10.3 ± 0.5 12.6 ± 0.7 * - the differences are significant (p <0.05) compared with the group not receiving suppositories

In the blood of patients receiving Apipollar suppositories, there was a decrease in the level of malondialdehyde and diene conjugates with a relatively stable level of the antioxidant activity index of the blood and a slight increase in the activity of catalase and superoxide dismutase.

In the group of patients who suffered a burn injury, pronounced immunosuppression, characterized by a decrease in the total number of lymphocytes: T-lymphocytes - up to 40% and their subpopulations - T-helpers - up to 24% and T-killers up to 14%, natural killers - up to 6% relative norms, developed before treatment in all victims by 5-10 days of illness. A low ability of lymphocytes to develop inhibitory factors of leukocyte migration (FTML) in response to phytohemagglutinin (PHA) and conkovalin A (ConA), as well as an increase in the production of circulating immune complexes (CIC), were noted. When treating with Apipollar suppositories, already after 10 days a decrease in the number of leukocytes, an increase in the level of T-lymphocytes from 1.0 × 109 / L ± 0.1 to 1.8 × 109 / L ± 0.1 (p <0 , 05), Ig A from 2.9 ± 0.7 g / L to 3.1 ± 0.4 g / L, Ig M from 1.4 ± 0.5 g / L to 2.4 ± 0.6 g / l, Ig G from 12.9 ± 1.9 g / l to 13.1 ± 0.6 g / l. When assessing FTML with PHA and ConA, as well as the level of the CEC, their decrease was noted by 15-20% (p <0.05) (Table 4).

Table 4
Indicators of immune status in burnt patients with the use of Apipollar suppositories and control group (M ± m) Indicators The value of indicators control group (donors) before introduction 10 days after administration White blood cells 10 ⁹ / l 5.3-8.1 16.2 ± 1.5 9.4 ± 1.5 * Lymphocytes 10 ⁹ / l 1.7-2.1 2.9 ± 0.5 2.8 ± 0.6 % 28-39 19.1 ± 3.2 27.9 ± 2.1 * T lymphocytes 10 ⁹ / l 0.68-1.26 1.0 ± 0.1 1.8 ± 0.1 * T-helpers 10 ⁹ / l 0.34-0.6 0.9 ± 0.3 1.0 ± 0.3 T suppressors 10 ⁹ / l 0.22-0.44 0.6 ± 0.1 0.6 ± 0.2 Natural killer cells ^× 10 ⁹ / l 0.15-0.4 0.5 ± 0.1 0.5 ± 0.1 B lymphocytes ^× 10 ⁹ / l 0.15-0.52 0.5 ± 0.1 0.5 ± 0.2 Ig A g / l 1.4-4.2 2.9 ± 0.7 3.1 ± 0.4 Ig M g / l 0.5-1.9 1.4 ± 0.5 2.4 ± 0.6 Ig G g / l 8-16 12.9 ± 1.9 13.1 ± 0.6 RTML with PHA % 20-60 98 ± 11 61 ± 4 * RTML with KonA % 40-75 90 ± 8.3 60 ± 6.0 * CEC Units 20-60 101 ± 8.6 89 ± 9.0 * * - the differences are significant (p <0.05) compared with the period before the introduction of suppositories

None of the patients receiving suppositories had an allergic reaction.

Thus, the studies confirm the effectiveness of the proposed suppositories in the treatment of a number of gastroenterological, andrological and gynecological diseases. The use of suppositories in patients with oligospermia leads to a pronounced clinical effect and helps to improve the performance of spermograms. The high biological activity of suppositories allows their use in infertility, erectile and hormonal dysfunctions, pathology of the prostate gland, menopause, as well as in the treatment of diseases of the digestive system as anabolic, hepatoprotective, immunomodulating and antioxidant agents.

Literature

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Claims (3)

1. A complex natural preparation in the form of a suppository for the treatment of andrological diseases, containing flower pollen or bee bread, cocoa butter or other fatty base, characterized in that it further comprises homogenized bee uterus larvae with native royal jelly or lyophilized powder from homogenized drone larvae and drone milk in the following ratio of components per 1 suppository weighing 3.0 g, g:
a) homogenized bee uterus larvae with native royal jelly or lyophilized powder from a homogenate of drone larvae and drone milk 0.5,
b) bee bread or pollen 0.5,
c) cocoa butter or other fatty base else. 2. A method for producing a suppository according to claim 1, including the homogenization of queen bee larvae and native royal jelly, previously frozen at -21 ° C, and subsequently thawed at 5-8 ° C and extracted from the queen cells, or lyophilization of homogenized drone larvae and drone milk, adding to the resulting mass of ground beef or pollen, stepwise mixing these fractions with cocoa butter or another fat base until a homogeneous suppository mass is formed, forming suppositories m assoy 3.0 g, cooling, packaging, labeling. 3. The method of treating patients with andrological diseases with suppositories according to claim 1, which consists in the administration of rectally suppositories in a dose of 3.0 g per day for 24 days, followed by a repeat of the course 1-3 times with intervals of 7-10 days between courses.