RU2726001C1 - Aquaplant biologically active composition - Google Patents

Abstract

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a biologically active composition for treating and correcting immune status. Biologically active composition for treating and correcting the immune status, consisting of preserved donor connective tissue with eliminated cell elements, wherein 80–90 % of chemical bonds of proteoglycans and glycoproteins are unlocked, and the composition is lyophilizate for oral administration and contains: hydrolysed collagen, chondroitin sulphate, elastin taken in certain proportions.

EFFECT: composition described above enables higher therapeutic effectiveness of the biologically active composition due to high content of hydrolysed collagen, which provides structuring of water.

3 cl, 2 tbl, 2 ex

Description

The invention relates to medicine, in particular to immunopharmacology and can be used as a biologically active pharmaceutical preparation for the treatment and correction of immune status.

Any pathological processes, including the stress response of the body, are accompanied by the development of an immunodeficiency state of one degree or another severity, activation of lipid peroxidation; the development of intoxication processes and dictate the need for an integrated therapeutic approach. Therefore, the development of effective and safe agents with high therapeutic activity, including indirectly through the correction of immune status and the regulation of free radical mechanisms, remains an urgent task.

It is known to use for treatment and correction of the immune status of biologically active complexes based on products of animal origin - pantocrine, royal jelly, bear bile, mummy extract, extracts of holothuria, etc.

Known biologically active complex "Arctic +" (RF patent No. 23234489, IPC A61K 35/60, A61K 38/02, A61P 25/24, published 01.03.2006), made on the basis of the secret of the renal tubules of the spawning male three-spined stickleback and the secret of Atlantic gills salmon activated for extended life by the symbiotic larvae of the pearl mollusk. This complex is used mainly as an antitumor agent, and as a solvent and preservative it contains five-year-old cognac, which limits the scope of its use by patients for health reasons, as well as for religious reasons.

Known drug "Pantocrine", used as a restorative and tonic; its use is limited by contraindications and the possible development of allergic reactions.

Known drugs made on the basis of chondroitin sulfate and used to stimulate metabolic processes in cartilage with joint damage. Both injection forms for local administration (alflutop, chondrolone) and oral preparations (Arthra, Teraflex, chondroitin-glucosamine complex) are used. Information on the use of glucosamine-chondroitin complexes as an immunostimulating and normalizing metabolic agent in the prior art was not found.

The well-known Alloplant biomaterial for regenerative surgery, consisting of canned donor human connective tissue with eliminated cellular elements, in which the chemical bonds of propioglycans and glycoproteins structured in bundles of collagen fibers and are partially eliminated from bundles of glycosaminoglycan fibers to residual, is unlocked by 80-90% content greater than or equal to 50%. In particular, it can be presented in dispersed form as a lyophilizate (RF patent No. 2189257, IPC A61L 27/00, A01N 1/00, published September 20, 2002). This material has extremely low antigenic properties. It is adopted as a prototype of the claimed invention.

The study of the properties of Alloplant biomaterial revealed its stimulating effect on the state of local and general immunity when injected into biologically active points (RF patent No. 2238076, IPC AH 39/08, A61K 35/12, published October 20, 2004).

The well-known Alloplant biomaterial is used exclusively in a parenteral manner, which limits its use.

The objective of the invention is the creation of a new biologically active composition for oral administration.

The technical result of the invention is to increase the therapeutic effectiveness of the biologically active composition due to the increased content of hydrolyzed collagen, which provides the structuring of water.

The technical result is achieved by a biologically active composition consisting of canned donor connective tissue with eliminated cellular elements, in which the chemical bonds of proteoglycans and glycoproteins are unblocked by 80-90%, which, in contrast to the prototype, is a lyophilisate for oral use and contains, by weight. %:

hydrolyzed collagen 80-85, chondroitin sulfate 12-17, elastin 2-7.

According to the invention, the biologically active composition may be an aqueous solution of lyophilisate with a concentration of 5-10 mg per 1 liter. water.

According to the invention, the biologically active composition may be water soluble effervescent tablets having, by weight. %:

lyophilisate 0.5-0.6 sodium bicarbonate 11-13, lemon acid 11-13, dextrates up to 100.

To prepare the biologically active composition of Aquaplant, donor tissues (fascia, calcaneal aponeurosis) are freed from muscle fibers, crushed and subjected to freezing to -20 ° C twice to mechanically destroy cellular elements, and then membranolysis of the tissue is carried out using a 3% trypsin solution heated to 40 ° C with constant stirring for 3 hours. In this case, the chemical bonds of collagen are unblocked with proteoglycans and glycoproteins, which, as is known from the selected prototype (RU 2189257), provides biomaterial with a significant decrease in antigenic properties. Subsequent treatment of the material with a composition comprising diethyl ether and ethyl alcohol for 60 minutes allows the elimination of adipose tissue. Wash the tissue from the reagents in running water for 12 hours and then in distilled water for 30 minutes, dry it in a lyophilizer and grind it in a rotary mill. The result is an amorphous powder - lyophilisate, containing at least 80% hydrolyzed collagen, from 12 to 17% chondroitin sulfate and from 2 to 7% elastin - Aquaplant. After lyophilization, the biomaterial is packaged in a double plastic bag and sterilized by a stream of fast electrons, the radiation dose is 20-25 kGy, which makes the Aquaplant sterile from bacterial and fungal infections.

To achieve a therapeutic effect, Aquaplant is dissolved in water at a rate of 5 to 15 mg per 1 liter of water, the prepared solution is stored at a temperature of +4 to + 6 ° C.

The created Aquaplant composition contains biologically active compounds that, when dissolved in water, form molecular clusters. When using the Aquaplant solution inside, there is almost instant assimilation of active structures that trigger oxidation-reduction processes at the mitochondrial level of body cells. The normalization of cellular metabolism is accompanied by the activation of intracellular antioxidant enzymes - superoxide dismutase, glutathione peroxidase and catalase, which starts the process of utilization of free radicals and is an important mechanism of protection against lipid peroxidation products. At the same time, at the level of the immune system, the monocytic-macrophage link is activated, including that regulating autophagy processes. Thus, the mechanisms of protecting the body from the damaging effect of free radicals and its consequences are activated.

The optimal concentration was selected based on the results of a study of the effect of oral administration of Aquaplant on the activity of antioxidant defense enzymes in 29 healthy volunteers. Volunteers were divided into groups comparable by gender and age: group 1 (n equals 5 people) - control - received clean water, the remaining groups received Aquaplant solution in various concentrations: group 2 (n = 6) 5 mg / l, group 3 (n = 6) 10 mg / l, group 4 (n = 6) 15 mg / l and group 5 (n = 6) 20 mg / l.

The change in the activity level of antioxidant defense enzymes in healthy volunteers is shown in Table 1.

As can be seen from table 1, the use of Aquaplant solution was accompanied by an increase in the activity of antioxidant defense enzymes, not exceeding the reference values. An increase in the dosage of the drug above 10 mg / l was safe, but was not accompanied by a significant increase in the therapeutic effect.

For ease of use and transportation, Aquaplant can be produced in the form of soluble effervescent tablets containing various excipients (table 2).

Tablets are made by compression with a force of 18 kN, a tablet diameter of 25 mm, a dissolution time of 120 s.

Example 1

A double-blind, randomized study of palliative care patients was conducted (38 people, 10 men and 18 women). 20 people every day 3 times a day received 1 glass of Aquaplant (10 mg per 1 liter of water), the control group - 18 people - 3 times a day drank water. The analysis of the psychological and physical condition of the patients was carried out according to the visual analogue scale (VAS), SAN test and general clinical blood test (OAK).

After 10 days, patients of the main group showed a significant subjective decrease in pain according to YOUR from 7.4 points to 5.3 points, while the control group remained almost unchanged. The increase in all indicators of the SAN test in patients of the main group was 19.6% higher than in the control group. A significant increase in hemoglobin level by 7.6% compared with the control group was observed in the KLA in patients taking Aquaplant. Thus, the use of Aquaplant contributed to an increase in activity, improving the mood and well-being of patients.

Example 2

A blind randomized study of 27 patients with irritable bowel syndrome was conducted. Against the background of the diet and the basic treatment of the disease, 15 patients (the main group) received Aquaplant solution 100 ml 2 times a day, 12 patients (control group) received pure water 100 ml 2 times a day for 14 days. In all patients, improvement was observed during treatment. At the same time, on the 14th day of the study, in the main group, the pain symptom according to YOUR was 1.7 points less than in the control group. Analysis of the activity of antioxidant enzymes showed that in patients receiving Aquaplant, the level of glutathione peroxidase increased by 19.1% (p - less than 0.01), and the level of catalase by 24.2% (p - less than 0.01), whereas in patients of the control group, these indicators increased by 15.4% (p - less than 0.01) and 18.6% (p - less than 0.01), respectively. The analysis of the immunogram showed in patients of the main group an increase in the absolute number of monocytes by 6.72% and the phagocytic index by 12.4%, which indicated the activation of a non-specific immune response. The study showed that the use of Aquaplant solution in patients with irritable bowel syndrome contributed to a more pronounced decrease in pain, slowdown of free-radical oxidation due to the activation of antioxidant defense enzymes, and also relief of the symptoms of the disease due to the mild immunostimulating effect on the macrophage link of the immune system.

Thus, the proposed biologically active composition Aquaplant has an immunostimulating, antioxidant, tonic and trophostimulating effect.

Claims (5)

1. A biologically active composition for the treatment and correction of the immune status, consisting of canned donor connective tissue with eliminated cellular elements, in which the chemical bonds of proteoglycans and glycoproteins are unlocked by 80-90%, characterized in that it is a lyophilisate for oral use and contains wt. %: hydrolyzed collagen 80-85 chondroitin sulfate 12-17 elastin 2-7 2. The biologically active composition according to claim 1, characterized in that it can be made in the form of an aqueous solution of lyophilisate with a concentration of the latter 5-10 mg per 1 liter of water. 3. The biologically active composition according to p. 1, characterized in that it can be made in the form of water-soluble effervescent tablets having, in the composition, wt. %: lyophilisate 0.5-0.6 sodium bicarbonate 11-13 lemon acid 11-13 dextrans up to 100