RU2316333C1 - Biologically active additive to agent for cosmetic healthy bath based on unossified antlers and magnesium and agent for cosmetic healthy bath based on the same - Google Patents

Abstract

FIELD: medicine, balneology.

SUBSTANCE: claimed additive contains mixture of dehydrated crystalline bischofite and ultradisperse powder from unossified antlers of elk, or reindeer, or Siberian stag in ratio from 1:1 to 3:1. Claimed agent contains abovementioned additive and water.

EFFECT: agent of increased therapeutic effect.

4 cl, 9 ex, 1 tbl

Description

The invention relates to medicine, namely to balneology and physiotherapy, and can be used for prophylactic and therapeutic effects on both the skin of a person and his internal organs in the treatment of concomitant diseases.

Known biologically active additive for baths, which use hyaluronic acid (0.5-1.0 g per bath) (Japanese application No. 2134315, IPC A61K 7/50, publ. 05.23.1990). Hyaluronic acid (HA) is a high molecular weight water-soluble polysaccharide that forms viscous solutions or gels with water. Due to HA, this composition provides increased blood circulation in the capillaries of the skin, accelerates the reparative processes in soft tissues.

However, this biologically active bath additive has a limited range of biologically active components - only hyaluronic acid, which reduces its therapeutic and prophylactic properties. In addition, the HA in the bath composition is contained in a significant amount, which increases the cost of one bath to $ 100.

It is known to use the natural bischofite mineral as a biologically active additive for a balneological medicine (Mashkovsky M.D. Medicines (a manual for doctors), part 1, - M .: Medicine, 1993, p. 1220). The main component of bischofite is magnesium chloride hexahydrate MgCl ₂ * 6H ₂ O. It is obtained in the form of brine when drilling wells. Bischofite has a moderately anti-inflammatory and analgesic effect in chronic inflammatory diseases.

However, with daily use of bischofite brine for quite a long time, tissue irritation and skin allergic reactions are possible, which are explained by the acid reaction of bischofite solution (pH 5.2). Another disadvantage of the known agent is that the concentration of bischofite brine used in medical practice is low, and even more so, the concentrations of essential trace elements contained in bischofite are insignificant, which generally reduces the biological activity and therapeutic effectiveness of the agent.

Known balneological product containing mineralized salts (bischofite) and additionally an organic solvent dimexide and a base - synthetic high and low molecular weight polyethylene oxides with a ratio of components, wt.%: Bischofite (mineralized saline solution) - 30-50; dimexide - 5-15; polyethylene oxide 2000-6000-20-30, polyethylene oxide mol.m. 200-400 - up to 100. Technical result: the product has a high penetrating ability, providing a uniform effect of salt ingredients (RF patent No. 2138249, IPC A61K 7/50, publ. 09/27/1999). The tool is used for diseases: musculoskeletal system, peripheral nervous system, surgical.

A disadvantage of the known agent is the limited scope of its application: the agent cannot be used in the form of baths due to the insolubility of high molecular weight polyethylene oxides in water. In addition, despite the fact that dimexide is approved for use in medicine, it is often poorly tolerated by patients, reduces tissue oxygenation, and has a sharp unpleasant odor.

Known balneological therapeutic and prophylactic agent based on bischofite, including a penetrating agent, which contains crystalline dehydrated bischofite as a base, and as an penetrating agent, an aquacomplex of titanium glycerol solvate (Tizol), and additionally contains sodium chloride, aerosil, and CO ₂ extracts of medicinal plants in the following ratio of components (RF patent No. 2221551, IPC A61K 7/50, publ. 20.01.2004), wt.%:

crystalline dehydrated bischofite 30.0-85.0 titanium glycerosolvate aquacomplex (Tizol) 1.0-15.0 aerosil 0.2-0.8 CO ₂ -extracts of medicinal plants 0.05-0.30 sodium chloride rest

A known composition for therapeutic baths, including cooking water of antlers of deer with the following concentration of substances (mg / l):

organic matter 298.0-330.0 nitrogen 15,5-23,2 lipids 24.9-30.1

(ed. certificate of the USSR No. 1819606, IPC A61H 33/00, publ. 06/07/93), which is used to treat radicular and reflex syndromes of lumbar osteochondrosis. The temperature of the cooking water during use is 38.0-39.0 ° C, and the duration of the bath is 15 minutes.

However, cooking water is obtained by processing whole raw materials from deer antlers, which, on the one hand, is a cheap production waste, and on the other hand, contains an insufficient spectrum of useful biologically active substances and their quantitative content in the composition, compared with extracts obtained from antler powder, which reduces the therapeutic and prophylactic properties of this bath composition.

Known solution of antlers for physiotherapy (balneotherapy), including extract from crushed antlers and water (RF patent No. 2111003, IPC A61K 35/52, publ. 05.20.1998).

However, the antler solution for balneotherapy has an insufficient content of useful biologically active substances, which are extracted from large antler particles of 4-7 mm in size.

The closest analogue (prototype) of a biologically active additive for therapeutic baths is a mixture of powder from deer antlers, reindeer or Manchurian deer, zeolite and salt additives (patent application No. 2004126286, IPC A 61 K 7/50, publ. 10.02. 06) with the following content of components, wt.%:

zeolite 5.0-15.0 salt components 15.0-35.0 ultrafine antler powder the rest is up to 100%

The closest analogue (prototype) of the composition for baths is a means (elixir) for balneotherapy (patent application No. 2004126286, IPC A61K 7/50, publ. 10.02.06), including an aqueous-alcoholic extract of a biologically active additive containing a mixture of ultrafine powder from antlers, zeolite and salt components in the following components, wt.%:

ultrafine powder mixture from antlers, zeolite and salt components 1.0-10.0 alcohol 35.0-45.0 water the rest is up to 100%

The disadvantage of this biologically active additive and composition for baths is the use as salt components mainly of sodium and potassium salts, which reduces the biological activity of balneological agents.

The technical result of the proposed biologically active additives and bath products based on it is to expand the range of biologically active substances used in balneology and increase the therapeutic properties.

The specified technical result is achieved by using a mixture of crystalline dehydrated bischofite and ultrafine powder from deer antlers, or reindeer, or Manchurian deer as a biologically active additive to the remedy for health-improving cosmetic panto-magnesium baths. The ratio of crystalline dehydrated bischofite and ultrafine antler powder is from 1: 1 to 3: 1. In this interval, the ratio of the components of a biologically active additive provides the most optimal manifestation of the therapeutic properties of its components. When the ratio of components is less than 1: 1, for example 1: 2, the content of magnesium ions in the final balneological solution is significantly reduced and, accordingly, the biological activity of the bath is significantly reduced. When the ratio of components is more than 3: 1, the content of the extract from deer antlers or reindeer is significantly reduced, which also significantly reduces the therapeutic and prophylactic properties of the bath.

The specified technical result is also achieved by the fact that in the tool for health-improving cosmetic panto-magnesium baths, including ultrafine powder from deer antlers or reindeer or Manchurian deer, alcohol and a base, according to the invention, it additionally contains crystalline dehydrated bischofite mixed with ultrafine powder from antlers in a ratio of 1: 1 to 3: 1 with the following content of components, wt.%:

a mixture of crystalline dehydrated bischofite and ultrafine powder from antlers in the ratio from 1: 1 to 3: 1 0.5-7.0 alcohol 30.0-40.0 the basis the rest is up to 100%

As a basis, the product contains water or a gelling component.

As a gelling component, the agent may comprise a polyethylene oxide gel with a molecular weight of 1500.

The water-alcohol extract of antler powder contains a significant amount of proteins (albumin, globulins), vitamins (A, E, D and C), steroid substances, including growth hormones, somatostatin, insulin, testosterone, estradiol.

Bischofite is a natural mineral, in composition it is a magnesium chloride solution containing other salts (magnesium bromide, calcium sulfate, calcium chloride, etc.), as well as more than 30 trace elements, which gives it therapeutic and prophylactic properties (anti-inflammatory and analgesic effect).

Magnesium ions stimulate the formation of substances that regulate the transport of ions in tissues. When taking magnesium mineral baths, the deficiency of magnesium ions is restored, which develops in diseases accompanied by decreased secretion of the stomach, the exchange of sugars and proteins. Magnesium ions play an important role in maintaining potassium and calcium homeostasis, possesses calcium channel blocker properties, and is involved in many enzymatic reactions, protein and carbohydrate metabolism.

The gel of polyethylene oxide (VFS 42-3017-97 dated 03/31/1998) gives the product a gel-like state, has a stabilizing effect on the biologically active substances included in the cosmetic product and increases the usability of this product. In addition, the gel of polyethylene oxide is well soluble in water, by itself softens and moisturizes the skin, promotes better penetration of nutrients and enzymes through the skin barrier, pH 6.5-7.0.

With the combined use of bischofite and antler extract, an increase in their therapeutic and prophylactic effect was found in comparison with the individual action of these components, which allowed to reduce their quantitative content in the balneological product.

In accordance with the above, the set of essential features of the proposed biologically active additives from a mixture of bischofite and powder from antlers, as well as the means based on it, compares with the criteria of "novelty" and "inventive step" in comparison with the set of essential features of known technical solutions-analogues.

The following are examples of the compositions of a biologically active additive to the agent for panto-magnesium baths (examples 1-3), wt.%:

Example 1. The ratio of the components 1: 1

crystalline dehydrated bischofite 50,0 ultrafine antler powder 50,0

Example 2. The ratio of the components 1: 2

crystalline dehydrated bischofite 33.3 ultrafine antler powder 66.7

Example 3. The ratio of the components 1: 3

crystalline dehydrated bischofite 25.0 ultrafine antler powder 75.0

The following are examples of the compositions of the means for panto-magnesium baths (examples 4-9), wt.%):

Example 4. Agent for water-based panto-magnesium baths

a mixture of crystalline dehydrated bischofite and ultrafine powder from antlers in the ratio 1: 1 0.5 alcohol 30,0 water the rest is up to 100%

Example 5. The agent for panto-magnesium baths on a gel basis

a mixture of crystalline dehydrated bischofite and ultrafine powder from antlers in the ratio 3: 1 7.0 alcohol 40,0 polyethylene oxide gel the rest is up to 100%

Example 6. The technology of preparation of funds for health-improving panto-magnesium baths

In the manufacture of the drug, simple technological equipment is used, equipped with a reactor with a stirrer.

To prepare the product, a gel base or water is loaded into a stirred reactor at a temperature of + (18-20) ° С and the components are added with stirring according to the formulation given in examples 4 and 5. The components are mixed for 20-30 minutes and the pH of the mixture is measured. If the pH of the mixture is below 7.2, then a phosphate-salt additive (Na ₂ HPO ₄ × 12H ₂ O) is added to the composition in an amount sufficient to maintain a pH of 7.2. Then the mixture is homogenized again in the reactor for 20-30 minutes, the finished product is packaged in a container and stored at a temperature of + 7 ° C. The cold method of preparing the product allows you to maximize the activity of its constituent components.

Example 7. The method of taking panto-magnesium baths using the inventive means

The bath is filled (100-150 liters) with warm water, t = 36-38 degrees Celsius. Take the product for the panto-magnesium baths, packed in a bottle and shake the contents several times. The contents are poured from the vial into the bath, the water is gently stirred. A thick part of the product may remain in the bottle. It is recommended that you fill the vial with the solution from the bath and pour the contents back into the bath. The composition of the bath corresponds to examples 4 or 5 of the present description. Immerse yourself in the bath for 10-15 minutes. If you wish, you can wet your hair or briefly immerse yourself in the bath with your head, eyes closed. If the solution gets into the eyes, it is recommended to rinse them with clean, warm water. After the procedure is completed, the body is not rinsed, but only blotted with a sheet or towel, and the hair is dried with a towel. It is advisable to take water procedures no earlier than 2 hours after taking a bath. After the bath, they rest for 30-40 minutes with calm, relaxing music. A recovery course using the proposed tool consists of ten such daily procedures.

The frequency of the recovery course is determined by the general condition of the patient’s body, but should not be more often than once every six months. It is recommended to store the product at room temperature in a dark place.

Example 8. Data from the study of the action of funds for cosmetic panto-magnesium baths on the functional activity of macrophages of peritoneal exudate

A technique was used to determine the functional activity of peritoneal macrophages using the NBT test, which reflects the level of redox metabolism of cells.

The production of reactive oxygen species (superoxide anion radical, singlet oxygen, hydrogen peroxide, etc.) accompanies activation of phagocytosis, increased bactericidal potentials of macrophages and reflects the level of redox metabolism of phagocytes. Since the process of reduction of nitro-blue tetrazolium to diformazan correlates with the formation of reactive oxygen species, the basis for assessing the functional state of macrophages is the reduction reaction of a colorless solution of nitro-blue tetrazolium reagent to dark blue diformosan.

Peritoneal cells were added to the wells of a 96-well plate (1 × 10 ⁶ cells / well) in RPMI medium with 5% cattle serum (cattle). Cultures were carried out for 2 hours in a CO ₂ incubator at 37 ° C. Then, the cells were washed with Hanks solution and 100 μl of nitro-blue tetrazolium at a concentration of 1 mg / ml and 50 μl of a 1% suspension of opsonized ram erythrocytes (EB) were added to each well. After incubation for 1 hour, the cells were washed with Hanks solution and fixed with 10% formalin solution. Next, the macrophage monolayer was washed with distilled water and dried. After that, 60 μl of 2M KOH and 70 μl of dimethyl sulfoxide were added to each well. The level of functional activity was evaluated by the change in optical density (OD) of the solution, which was measured at a wavelength of 620 nm on a Multiscan device. Indicators of functional activity of macrophages were expressed in units of OD × 100.

The experimental data were statistically processed using the Statgrapfics 5.0 software package. Student's t-test was chosen as a reliability criterion.

The table below shows the functional activity of resident peritoneal macrophages of Wistar rats 3 days, 7 days and 21 days after the application of various preparations for balneotherapy.

Based on these data, we can conclude about the ability of the claimed means for panto-magnesium baths to modulate the redox metabolism of rat peritoneal macrophages.

Data on the applicative application of drugs to the skin of rats to determine the functional activity of macrophages No. gr. A drug Indicators (average in the group) of the functional activity of macrophages (restoration of HCT)) of rats after application of drugs through 3 days 7 days 21 days one. Intact - 28.58 ± 13.96 48.01 ± 5.38 2. water 26.86 ± 11.97 35.26 ± 5.55 55.50 ± 11.42 3. an aqueous solution of the agent according to example 4 (0.01 wt.%) 42.50 ± 23.26 53.69 ± 1.36 108.73 ± 7.60 four. an aqueous solution of the agent according to example 5 (0.0001 wt.%) 41.87 ± 4.42 49.62 ± 2.79 81.87 ± 3.74

Example 9. Determination of immunomodulating properties of the agent for panto-magnesium baths

Description of the experiment. The experiments were performed on sexually mature female Wistar rats. In accordance with the tasks, animals were divided into the following groups. Group 1 - intact rats. Group 2 - rats that have their hair cut with 5% of the total skin surface in the interscapular region. This area was washed daily with tap water, and then dried with a towel. Group 3 - rats that have their hair cut with 5% of the total skin surface in the interscapular region. An aqueous solution of the inventive agent having a quantitative content of components in accordance with Example 4 was applied to this area (agent content in an aqueous solution of 0.001 wt.%). Exposure time is 20 minutes. Group 4 - rats, which were cut hair with 5% of the total surface of the skin in the interscapular region. The claimed agent having a quantitative content of the components in accordance with Example 5 (the content of the agent in an aqueous solution of 0.001 wt.%) Was applied to this section. Exposure time is 20 minutes.

Results.

After 14 and 21 days from the start of the experiment, measurements were made of the thickness of the skin fold at the site of application according to the standard method. A statistically significant thickening of the skin fold was found in rats using zeolite-containing compositions. In particular, in rats of group 3, the thickness of the skin fold varies within 2.40 mm, in rats of group 4 2.49 mm, in the control of 2.30 mm. At the end of the experiment on day 22, rats were decapitated and axillary lymph nodes were removed and phagocytic cells adhered to the glass were isolated. It was established that viable dendritic cells, as well as macrophages, are sown from lymph nodes of rats of the experimental groups in comparison with the control in a significantly larger amount. In the cytoplasm of some macrophages, crystalline particles with a diameter of 1-5 microns are determined.

Thus, under the influence of the claimed agent for panto-magnesium baths, nonspecific activation of the macrophage link of the immune system of the skin occurs. The positive effect of the application of the claimed means: increased drainage function of the lymphatic vessels of the skin, decreased interstitial edema of the skin, strengthened the walls of blood and lymphatic capillaries of the skin, improved the appearance of the skin and its mechanical properties, non-specific activation of the macrophage link of the skin’s immune system.

A study of the toxicity of the claimed aqueous solution of the claimed drug was carried out in accordance with the requirements and instructions of the Pharmacological Committee of the Ministry of Health of the Russian Federation (V.P. Fisenko et al., 2001). The study of the local irritating effect on the skin was carried out in accordance with the “Methodological recommendations for identifying experimentally skin hypersensitivity to substances in solution” and “Methodological guidelines for the formulation of studies on the study of irritating properties ...”.

The results of the studies were subjected to statistical processing, the significance of differences was evaluated using Student's criterion (Microsoft Excel).

The study of acute and chronic toxicity.

The inventive tool for panto-magnesium baths when administered orally, can be classified as moderately toxic substances. The acute toxicity of the agent for male rats is 15.54 g / kg, and for female rats - 15.69 g / kg.

Local-irritant action of an aqueous solution of the drug (according to examples 4 and 5) with a single application on the skin of guinea pigs was not detected. When irritating properties were detected with multiple applications of guinea pigs on the skin, functional disorders of the skin, characterized by the appearance of varying degrees of erythema, edema, cracks, ulcerations, changes in skin temperature, they were not noted, which indicates the absence of non-allergic contact dermatitis when using an aqueous solution of the drug.

Based on the studies, it was found that the product based on a mixture of bischofite and antler powder showed optimal biopharmaceutical parameters, such as the degree of magnesium release and osmotic activity. When studying the anti-inflammatory properties, an aqueous solution of the agent showed the maximum anti-inflammatory effect. On models of carrageenin, histamine and serotonin edema, an aqueous solution of the drug showed a pronounced antiflogistic effect. Reduced joint inflammation in adjuvant rheumatoid arthritis. An aqueous solution of the agent accelerated the processes of epithelization of skin damage during ultraviolet burns, cryotrauma, increased the rate of contraction of the wound area and its cleansing from bacterial contamination. Influenced the formation of scar tissue of an infected and uninfected wound, increasing the strength of the formed scar. Reduced the development of puffiness and erythema of the affected area of the skin, accelerated the discharge of necrotic crusts in experimental contact dermatitis. An aqueous solution of the agent increased the bactericidal properties of the skin and reduced the permeability of blood vessels, stimulated phagocytosis, improved tissue regeneration, and had a slight local analgesic effect.

With the combined use of bischofite and antler extract, an increase in their therapeutic and prophylactic effect was found in comparison with the individual action of these components, which allowed to reduce their quantitative content in the balneological product compared to the prototype.

Claims (4)

1. The use of a mixture of crystalline dehydrated bischofite and ultrafine powder from deer antlers or reindeer or Manchurian deer in a ratio of 1: 1 to 3: 1 for the preparation of products for recreational cosmetic baths. 2. Means for health-improving cosmetic baths, including ultrafine powder from deer antlers or reindeer or deer, alcohol and a base, characterized in that it additionally contains crystalline dehydrated bischofite mixed with ultrafine powder from antlers in a ratio of 1: 1 to 3: 1 with the following content of components, wt.%: a mixture of crystalline dehydrated bischofite and ultrafine powder from antlers in the ratio from 1: 1 to 3: 1 0.5-7.0 alcohol 30.0-40.0 the basis the rest is up to 100% 3. The tool for health-improving cosmetic baths according to claim 2, characterized in that as a basis it contains water or a gelling component. 4. The tool for health-improving cosmetic baths according to claim 3, characterized in that as a gel-forming component it contains a polyethylene oxide gel with a molecular weight of 1500.