RU2275205C2 - Biologically active phospholipid-comprising complex for treatment of psoriasis and chronic prostatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention proposes the biologically active complex comprising phospholipids and the following biologically active substances - fatty acids, serines, peptides, amino acids, vitamins trace elements and extraction from cattle testicles prepared by successive fractionation with carbon dioxide and ethyl alcohol. The complex provides expanding spectrum of medicinal agents used in dermatological and urological practice and improving quality of the preparation. Invention can be used in treatment of psoriasis, prostatitis caused by prostatitis of sexual disorders.

EFFECT: valuable medicinal properties of complex.

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Description

The invention relates to medicine and can be used to treat psoriasis, prostatitis and prostatitis-related sexual disorders.

A number of complex drugs are known that contain phospholipids as the main active substance together with other ingredients of plant, animal origin or obtained chemically.

These drugs include Lipopharm, Lipostabil, Aminophosphatide (1), as well as Lipofundin (2), Intralipid (3), Essentiale (4).

Common to all these drugs is the presence of phospholipids in them as the main active substance. The presence of phospholipids determines the main focus of the drug - the regulation of intracellular processes at the membrane level. The functional significance of phospholipids is based on their biphasic nature, which makes it possible to regulate the permeability of the lipid layer of biological membranes, restore its physicochemical properties and create more adequate conditions for the functioning of enzymes. Phospholipids have antioxidant properties.

As a prototype, the drug Essentiale, produced in Germany, was selected. Essentiale (Esseutiale) is available in two dosage forms - injection solution and capsules. The preparation contains about 70% of natural phospholipids (the source is not specified) in the form of diglycerin esters of cholinophosphoric acid, an extract from soy beans with a high content of unsaturated fatty acids and is supplemented with components such as solid fat, soybean oil, hydrogenated castor oil, ethanol, ethyl vanillin, 4-methoxyacetophenone, gelatin, dyes E 171 and E 172, DL-a-tocopherol. Indications for use Essentiale are chronic liver disease, fatty degeneration and toxic liver damage, psoriasis, radiation syndrome.

The aim of the invention is to expand the range of drugs in dermatological and urological practice, improving the quality of the drug.

The essence of the invention consists in the use of a new complex preparation containing phospholipids and such biologically active components - fatty acids, sterols, peptides, amino acids, vitamins, trace elements for the treatment of psoriasis, prostatitis and prostatitis-related sexual disorders in men. The entire listed complex of substances in the composition of the drug under the conditional name Stimatex is represented by natural biologically active substances isolated from the testes of cattle. The cattle testis tissue, purified from ballast lipids by extraction with carbon dioxide, is extracted with a solution of ethyl alcohol. The alcohol extract is separated by centrifugation. The centrifuge was evaporated.

The complex contains natural biologically active substances in the following amounts (wt.% Of dry matter):

phospholipids 56.5 ± 4.0 other lipids 17.2 ± 2.5 including loose higher fat acids and sterols nitrogen-containing substances, including 20.0 ± 4.0 peptides and amino acids vitamins, micro and macrocells 6.3

The complex of biologically active substances that make up the drug ensures its high efficiency, since the effect of phospholipids is combined and supplemented by the action of low molecular weight peptides that act as bioregulators. Fatty acids, in particular, arachidonic, linoleic, are biogenic precursors of prostaglandins that are involved in the regulation of cellular metabolism and affect blood circulation, including microcirculation.

The amino acids that make up the complex stimulate metabolic processes, being a plastic material for protein synthesis, and vitamins and trace elements enhance the antioxidant properties of phospholipids and enzyme activity. The synergism of the components of the complex drug Stimatex determines the high effectiveness of its action.

In the pathogenesis of a number of diseases there is a violation of lipid metabolism, and in these cases, drugs that normalize this process are used for treatment, including drugs containing phospholipids. So taken by us for the prototype Essentiale is successfully used to treat psoriasis. The course of complex treatment with this drug is at least 3 months. Essentials are used in two dosage forms. The injection solution is administered 2-4 ampoules per day for 10 days, the contents of the ampoules are diluted with the patient's blood in a ratio of 1: 1. Before intravenous infusion Essentiale is prescribed a two-week course of treatment by taking 2 capsules 3 times a day, and after intravenous infusion continue to take capsules for 2 months. The cost of a course of treatment with the drug is high, and therefore its use in hospitals is very limited. The positive effect of drugs containing phospholipids was also noted in the treatment of prostatitis. Lipids - Neutral fats, phospholipids and cholesterol are an important component of prostate secretion. The main part of phospholipids - phosphatidylcholine (lecithin) - is a constant component of the subcellular structure of membranes, which determines their permeability. A large number of lecithin grains in the secretion of the prostate gland is an indicator of its healthy state (6).

Based on these data, clinical testing of the new drug Stimatex was conducted in two clinics - the Nizhny Novgorod Research Institute of Skin and Venereology in the Department of Chronic Dermatoses and in the regional hospital named after N.A.Semashko. For the clinical study, two dosage forms of the drug were prepared - suppositories and freeze-dried powder. Suppositories were prepared on the basis of Vitepsol N-15 and W-35 according to the technology generally accepted for the manufacture of this dosage form. The mass of the suppository was 2 g, and the content in the suppository of the active substance was (150 ± 10) mg. To prepare the lyophilized form, Stimatex was suspended in water to a concentration of (600 ± 50) mg%, the suspension was poured into vials of 10 and 25 cm ³ and subjected to freeze drying by uniformly applying heat to the shelves of a freeze-drying unit at 5 ° C per hour at a pressure of 0.03 Top and condenser temperature minus (50 ± 2) ° С. The drying time was 22-26 hours, the residual moisture content of the drug did not exceed (3.0 ± 0.5)%.

A significant difference between the complex drug Stimatex from the prototype is as follows:

1) the complex is represented by biologically active components isolated from natural raw materials by the original method;

2) with the exception of phospholipids, all other ingredients do not repeat the composition of Essentiale;

3) Stimatex is used in other dosage forms - suppositories and freeze-dried powder.

The advantage over the prototype is as follows:

1) the dosage form of the drug in the form of suppositories promotes the rapid release of drugs from the base. Due to the high absorption capacity of the rectal mucosa, a high concentration of the drug in the blood is quickly achieved. In connection with the loss of the barrier function of the liver, the duration of the circulation of the drug substance in the bloodstream increases;

2) the suppository form allows you to eliminate the disadvantages of the injection of the drug - the method of administration is painless and does not require qualified medical personnel;

3) there is no possibility of infection of the patient;

4) the absence in the preparation of chemicals, fillers, dyes, stabilizers;

5) a balanced complex of natural substances, providing a synergy of their action, is isolated from one source of raw materials - the testes of cattle;

6) the availability of the drug in connection with its lower cost and domestic production;

and also, as follows from the following clinical testing data,

7) indications for use in prostatitis, absent in the indications for the prototype;

8) a shorter course of treatment.

Prior to testing, the Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology conducted an expert assessment of the toxicity of the new drug. Experimental toxicological studies have shown that the drug in terms of acute toxicity, cumulation coefficient, irritating, sensitizing and general resorption actions meets the safety requirements for pharmacological agents.

The effectiveness of Stimatex in the treatment of psoriasis patients was carried out in the Department of Chronic Dermatoses NIIKVI. The group of patients consisted of 5 women and 7 men aged 18 to 47 years. All patients had common psoriasis in the acute stage of the process. Stimatex was used rectally in the form of suppositories once a day for 15-30 days. Before and after treatment, a general blood test, urinalysis, serum transaminases, serum lipid, phospholipid spectrum and erythrocyte membranes were studied.

Table 1.
List of patients receiving stimatex No. FULL NAME. sick No. of medical history one Simonova N.V. 2121 2 Kadyaev S.F. 2108 3 Pastukhova E.P. 70 four Timachev V.A. 107 5 Zaitseva N.M. 683 6 Kukushkina O.V. 706 7 Strelnikov A.V. 762 8 Mishina E.V. 782 9 Talalushkin L.A. 767 10 Schepalov V.V. 875 eleven Kashtanov A.I. 940 12 Leontiev V.V. 163

All patients tolerated Stimatex well. Complications and side effects were not recorded. In all psoriasis patients who received Stimatex, after 7-10 days, a significant improvement in the clinical picture of the disease was noted in the form of cessation of peeling, a decrease in the brightness of the rashes and a decrease in the infiltration in the foci. In 6 patients, previous exacerbations of psoriasis were stopped only by the use of cytostatics (methotrexate), which have pronounced adverse side effects. The use of Stimatex in this group of patients allowed achieving remission without the use of methotrexate.

In the course of therapy with Stimatex, no adverse shifts were recorded from the general blood test, urinalysis, or serum transaminases. When studying lipid metabolism, it was shown that Stimatex does not significantly affect serum cholesterol. Under the influence of Stimatex, normalization of the level of total lipids and triglycerides was noted. As is known, the biochemical composition of cell membranes reflects the metabolism of the cell as a whole, and therefore its functioning. When studying the phospholipid spectrum and lipid peroxidation of erythrocyte membranes in patients with psoriasis before treatment, an increase in the fraction of phosphatidylcholine (FC) and phosphatidylethanolamine (PEA), as well as a decrease in lysophosphatidylcholine (LPC), was revealed, which indicates a violation of the permeability of erythrocyte membranes. After treatment with Stimatex, a positive dynamics of these indicators was observed. As a result of a clinical study, Stimatex was recommended as a promising drug in the treatment of psoriasis. Stimatex, along with a fairly high efficiency, has good tolerance and safety.

Clinical testing of Stimatex in the urology department of the hospital. N.A.Semashko was preceded by testing patients according to the R. Voll method.

Examination of patients and testing of the drug was carried out on the hardware-software complex "Imedis-Fall" manufactured by the company "Imedis". Two dosage forms of the drug were tested - suppositories and lyophilized powder of Stimatex. The testing method was as follows: the test drug is included in the device-patient circuit through a passive electrode. For testing, BAT (biologically active points) of those meridians that corresponded to the proposed pharmacological spectrum of action of the studied drugs were used.

According to the method of R. Voll, 14 patients of four age groups were examined and conducted drug testing:

30-40 years old - 3 people;

40-50 years old - 3 people;

50-60 years old - 6 people;

60 years - 2 people.

Among the patients, 3 groups were identified:

1. congestive inflammatory diseases of the prostate gland - 6 people,

2. prostate adenoma - 2 people,

3. without organic pathology - 6 people.

Studies were conducted on the following BAT:

1. Hypothalamus (assessment of the effects of acute and chronic intoxication, psycho-organic pathology and radicular cysts).

2. The pineal gland, pituitary gland (indirect assessment of the antigonadotropic function of the pineal gland and gonadotropic function of the pituitary gland).

3. Gonads, adrenal glands.

4. Prostate, seminal tubercle, seminal vesicles, penis.

5. Appendages of the testicles, spermatic cord.

Studies of the above BAT allowed us to determine the effect of drugs at all levels of the pathogenesis of the disease.

Based on the test results, it was possible to conclude that the effect of the test dosage forms should be most pronounced at the following levels:

Hypothalamus, pituitary gland, gonads, adrenal glands, prostate, epididymis.

Stimatex in the studied dosage forms was effective in almost all age categories, but its effect was most pronounced in the age group of 50-60 years. According to the results of the studies, it was possible to predict the following effect of the studied dosage forms of the drug on:

1. Regulation of inflammatory and degenerative processes in the prostate gland.

2. Stimulation of the function of the gonads with hypofunction.

3. Stimulation of spermatogenesis.

4. Inhibition of stagnant inflammatory processes.

5. Absorbable effect on connective tissue, including benign neoplasms, cicatricial changes and structures.

6. Improving the hemodynamics of the genitals.

These studies served as the basis for conducting clinical testing of the drug in a group of patients with chronic prostatitis.

The group of patients consisted of 16 men aged 19 to 50 years.

Stimatex was used rectally in suppositories once a day for two weeks to one month.

The control group received standard therapy - Viprosol in suppositories.

In two patients, chronic prostatitis was combined with benign stage 1 prostate hyperplasia, in two patients it was complicated by urethritis. 10 patients had a history of STIs (chlamydia, ureaplasmosis, gardperellosis), in one patient the right kidney and chronic cystitis were removed.

All patients underwent examination before treatment: ultrasound of the prostate, analysis of prostatic juice, smears from the urethra. Before treatment, as well as during treatment, on the basis of the functional diagnostics department, drug testing was carried out according to the method of R. Voll.

In the course of treatment, 15 of 16 patients showed objective and subjective improvement. Positive dynamics was noted in the reduction or termination of pain, the disappearance of a burning sensation in the urethra, a decrease in the frequency of urination, an improvement in erection, an increase in potency, and the disappearance of pain during coitus. Compared with the control group, with the use of the drug Stimatex positive dynamics was noted at an earlier date - on the fourth or fifth day of use instead of 10 days with standard therapy. Significantly reduced the time to stop the phenomena with exacerbation of chronic cystitis. Persistent improvement occurred on day 14-30, depending on the severity of the disease. List of patients who received Stimatex.

Table 2 No. p / p Surname I.O. sick Age No. of medical history one Klygin I.N. 50 years 107101 2 Pershin A.M. 37 years 106814 3 Kiselev D.Yu. 32 years 342 outpatient card four Shcherbakov D.V. 22 years old 0118133 5 Kargapoltsev S.V. 29 years 100501 6 Smirnov L.G. 41 years old 101277 7 Nurutdinov A.Z. 46 years old 106949 8 Uryadov P.E. 24 years 108721 9 Dubinin Yu.V. 40 years 114044 10 Bychkov V.A. 49 years old 100815 eleven Vorontsov A.A. 29 years 114497 12 Ushakov P.V. 19 years 115083 13 Afanasyev S.V. 28 years 100661 fourteen Zuykov Yu. 46 years old 5071 fifteen Kitaev V.A. 24 years outpatient card 16 Martynov O.A. 27 years 11463

All patients tolerated the drug well, allergies, complications and side effects were not recorded.

As a result of tests, Stimatex is recommended as a promising drug for the treatment of prostatitis.

Information sources

1. V.I. Shvets, Yu.M. Krasnopolsky. Bulletin of the Academy of Medical Sciences of the USSR, No. 6, 1990, pp. 19-27.

2. M.D. Mashkovsky. Medicines, M., Medicine, 1986, v.2.

3. A 61 K 9/14, 31/557 US 6251436 B1.

4.A 61 K 31/685 FR 2556050 A1.

5. A 61 K 35/12, 35/30, 35/48, 35/50 RU 2192871 C2.

6. N.P. Shamshin. Metabolic aspects in dermatology, Sat. scientific Proceedings of KVI, Gorky, 1984, pp. 96-99.

Claims (1)

A biologically active complex for the treatment of psoriasis and chronic prostatitis, characterized in that it is extracted from cattle testicles by sequential fractionation of carbon dioxide and ethyl alcohol and includes phospholipids in an amount of 56.5 ± 4.0%, free higher fatty acids and sterols in an amount 17.2 ± 2.5%, peptides and amino acids in an amount of 20.0 ± 4.0%, as well as vitamins, macro- and microelements in an amount of 6.3%.