Gel composition of wide spectrum of biological action

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents a gel biologically active composition for topical application containing chitosan hydrochloride in an amount of 10-20 wt %, an organic acid in an amount of 1-10 wt %, distilled water - the rest. The above organic acid is specified in acetic, ascorbic, glycolic, lactic, citric or succinic acids.

EFFECT: providing a lower toxicity and a wider spectrum of biological action of the composition ensured by the synergetic effect of a reaction of chitosan hydrochloride and the organic acid.

11 ex, 11 tbl, 2 dwg

 

The invention relates to biologically active drugs and can be used in medicine, namely in dentistry, gynecology and laryngology, as well as in the pharmaceutical, food industry, veterinary medicine, cosmetics and biotechnology.

It is known that chitosan - derived biopolymer chitin - possesses a valuable combination of physico-chemical and biological properties. Non-toxicity, especially its chemical structure (presence of elementary units of the macromolecule groups-OH, -NH2and-NHCOCH3), the variation of the content of the amino groups and the degree of protonation, a wide range of molecular weight() and others provide a wide range of samples of chitosan and materials based on it to solve a number of problems in different spheres of life [Chitosan/Ed. by R. A. A., Muzzarelli. TRANS. from English. HP Paczkowski. N. Novgorod: Publishing house "Vector-Tis". 2001. 372 S.; galbraikh HP Chitin and chitosan: structure, properties, applications //Morozovsk.Both educational. Journe. 2001. So 7. No. 1. S. 51-56; Chitin and chitosan: synthesis, properties and applications /Ed. by K. G. Skryabin, G. A. Vikhoreva, B. N. Varlamov. M.: Nauka. 2002. 368 S.; Germans S. C. Complex technology of chitin and chitosan from crustacean shell. M.: Publishing house of the Institute. 2006. 134 C.].Among many varieties of drugs chitosan-based gels and gel forms them is have a number of advantages. They have a viscous consistency, provide greater bioavailability, have a moisturizing effect on the skin and compared with ointments is better absorbed. Their pharmacological action extended and more pronounced. In addition, unlike ointments in the event of contact with skin or clothing, they are easily washed off with water, leaving no trace.

A method of obtaining biologically active complex on the basis of chitosan lactate (ecogel) and composition of biologically active complex for the protection of agricultural plants [see RF patent №2316963, IPC A01N59/00, A01N25/04, A61K31/722, A01N37/02]. Active complex on the basis of chitosan lactate receive dissolving the chitosan in an aqueous solution of lactic acid in the reagent ratio 1:1, a temperature of 65-75°C. and a fixed pH (6.5-7.0) with constant stirring with a vortex motion of the mass flow at saturation mass of silver ions with subsequent magnetic treatment. You get the gel, past the magnetic treatment and containing in g/l: chitosan with DM=75-88 mole.% -1.0-50.0 (0.1-5.0 wt.%), lactic acid is 1.0-50.0 (0.1-5.0 wt.%), silver ions - 7.5-10.0 mg/l and water - the rest.

The disadvantage of this active complex on the basis of chitosan lactate is the complexity, the multi-stage receiving, strict control of temperature and pH, the use of expensive drug ion is in silver, as well as additional equipment for magnetic treatment. It is hard to imagine based on the above data that the authors are dealing with the "gel" because they do not use a crosslinking agent. Furthermore, it is known that the effect of activation after treatment in a magnetic field is maintained for a short period of time (up to one day) [Sokolsky Y. M. Manicina water: truth and fiction. L.: Chemistry. 1990. 144 C.].

The famous "gel" for skin care and treatment of its diseases and composition to obtain [see RF patent №2085187, IPC A61K7/48]. The song in addition to chitosan, vitamin mixture and distilled water additionally contains antiseptic and anesthetic.

The disadvantage of this gel is the difficulty of obtaining and the content of toxic substances (antiseptic and anesthetic), which can cause allergic reactions, reduce the immune status, etc.,

Closest to the claimed invention in its technical essence is a gel composition based on chitosan, wound healing, burns, anti-inflammatory, hepatoprotective, antidiabetic and anticancer activity [see RF patent №2366408, IPC A61K9/00, A61K31/519, A61K31/722, A61P1/16, A61P3/10, A61P17/02, A61P29/00, A61P35/00]. The claimed composition in addition to chitosan 15-25 g/l (1.5-2.5 wt.%) and distilled water contains tripcentral 1.5-2.5 g/l (0.15-0.25 wt.%.

The disadvantage of the gel composition is complexity, the multistage obtain, the use of such organic solvents as acetic acid and dimethylsulfoxide (these components are not shown in the composition of the gel composition in the claims). To enhance the biological activity of the composition required to enter additional component - alkaloid triplatin, the effect of which on human cells to date poorly understood. Tripcentral poorly soluble in water, for its introduction in the gel composition use solution of the alkaloid in dimethyl sulfoxide. Dimethyl sulfoxide is contraindicated in certain diseases of the liver, kidneys, strokes, cataracts, glaucoma, pregnancy, etc.

The objective of the invention is the creation of a gel-like composition based on low molecular weight (=38 kDa) chitosan hydrochloride wide spectrum of biological actions: antibacterial, anti-inflammatory, wound healing and beauty.

Technical result provided by the invention, is to reduce the toxicity and the expansion of the spectrum of biological action of the composition due to the synergistic effect of the interaction of chitosan hydrochloride and pharmacopoeial organic acid selected from the series: acetic, ascorbic, glycolic, lactic, lemon is Aya and amber.

The problem is solved in that the gel-like composition containing activetestsuite substance and distilled water, according to the decision as activitiesthese substance containing chitosan hydrochloride, the composition further comprises an organic acid selected from the series: acetic, ascorbic, glycolic, lactic, citric, succinic; in the following ratio of initial components, wt.%:

the chitosan hydrochloride10-20
organic acid1-10
distilled waterrest

The invention is illustrated by drawings.

In Fig. 1 shows the structural formula of the polymer composition.

In Fig. 2 shows the dynamics of the process of wound healing in laboratory animals.

It was established experimentally that the concentration of polymer (Cp) chitosan hydrochloride, less than 10 wt.% not sufficient to obtain a gel-like consistency, and more than 20 wt.% in the accepted conditions of dissolution does not lead to the full participation of the polymer in the formation of a gel-like composition that pharmacological and economic point of view is inappropriate.

Concentrateorgano acid (C to) in the composition was determined empirically on the pH value to 3 depending on the type of biological activity (for example, the state standard of the Russian Federation on "cosmetic Gels").

Comparing the experimental data of elemental analysis of the original sample and potentiometric titration of water, aqueous acid (0.1 NHCl) solutions of the original sample and the composition of chitosan hydrochloride in aqueous solution of organic acid (for example, ascorbic) we can conclude that in the gel composition is formed of a double salt of chitosan, which in addition to the groups hydrochloride includes at least one group ascorbate chitosan part of a macromolecule (or counterion other acid).

The estimated structural formula of the polymer compositions is shown in Fig. 1, where x is the number of monomer units of chitosan ascorbate, y chitosan hydrochloride, z-N-acetyl-D-glucosamine.

Studies have shown an increase in biological activity and expansion of the spectrum of biological action of the inventive gel compositions.

The inventive gel composition was prepared as follows.

Use the industrial design of chitosan hydrochloride (=CD, SD=80±2 mole.%), produced by CJSC "Bioprogress". A portion of the hydrochloride of the chitosan is dissolved in an aqueous solution of acetic or ascorbic or glycolic acid, or lactic, or what imoney, or succinic acid fixed concentration with continuous stirring for 3 hours at a temperature of 20-22°C. the Obtained gel-like (viscous) system is kept in a static condition during one day. Then the composition was filtered through a fabric filter and packaged in sterile containers. All operations is carried out with the observance of sanitary-epidemiological requirements. The gel composition is to be stored in the refrigerator at a temperature of +4°to+6°C.

To evaluate the cytotoxicity and mutagenic effect used microkernel test (TWO test) and rapid method for evaluation of General toxic and skin-irritating action on a culture of motile cells (Methodical recommendations. Mr No. FT/394 the Ministry of health of Russia. M., 2002).

Antibacterial activity was studied on the example of the test strains Escherichiacoli 113-13, or Staphylococcusaureus 209 P, or Bacilluscereus 8035 using sterile liquid nutrient medium - meat-peptone broth (BCH) and solid nutrient medium - meat-peptone agar (MPA).

Anti-inflammatory effect was evaluated on the models in vitro (cell culture) and in vivo (in clinical practice).

Wound-healing activity of the samples was conducted invivo animal models (white mice-males and outbred rats-females). When working with experimental animals are guided by the order of Ministry of health of the USSR №755 from 12.08.177, and the requirements of the European Convention for the protection of laboratory animals. All manipulations with animals were performed under ether anesthesia.

Cosmetic effect was evaluated in models of in vivo - the volunteers will use questionnaires.

All methods of testing and tests are given in the specific examples.

The applicability of the proposed solutions are illustrated by the following examples.

Example 1. Evaluation of cytotoxicity and mutagenic effect.

Evaluation of cytotoxicity and mutagenic effect on the example of a gel-like composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid. The gel composition is subjected to pre-clinical Toxicological studies using micro-test (TWO test) and the rapid assessment method General toxic and skin-irritating action on a culture of motile cells (Methodical recommendations. Mr No. FT/394 the Ministry of health of Russia. M., 2002). The results are shown in tables 1 and 2.

Table 1

The results of determination of the acute toxicity of the sample gel composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid in the culture of motile cells in vitro

The test-objectDilutionIndec is the toxicity of It, %Evaluation of the test sampleND on MIMHazard class ER50
Bostaurustaurus175.4Has no toxic actionMr 2.1.7.2279-07<5
class 4 a Little dangerous
0.181.4Has no toxic action
0.0196.5Has no toxic action
0.001100.2Has no toxic action

Table 2

The results of determination of the acute toxicity of the sample gel composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid ME-method

The duration of incubation of cell cultures with medicationThe concentration of aqueous extract of 1 g in 10 ml waterThe results of the analysisEvaluation of the test sample ND on MIM
24 hours1000.51±0.05%
Control
0.48±0.01%
No mutagenic effectNo. 224.01.17.066/2009

As you can see from the data presented in tables 1 and 2, the degree of impact on human health, the sample gel composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid belongs to the 4th class of hazard (low hazard, GOST 12.1.007-76) and has no mutagenic effect on human cells.

Example 2. Antibacterial action.

In a separate tube containing sterile meat-peptone broth (BCH) is added to the sample gel composition based on chitosan hydrochloride and an aqueous solution of organic acids (acetic, ascorbic, glycolic, lactic, citric, succinic) in a volume ratio of 1:1 and mixed thoroughly. Then each of the resulting stock solutions of the samples of the composition of salts of chitosan is added 0.1 ml of the cell suspension (105CFU/ml) of the test strains Escherichiacoli 113-13 or Staphylococcusaureus 209 P or Bacilluscereus 8035. The tubes are placed in a thermostatted rocking chair and cultivated for three days at 37°C. as control are taken in the same concentrations suspension test-stammo is in the BCH without adding the samples of a gel-like composition. Antibacterial activity is measured after 24, 48 and 72 hours visually for turbidity of the solution and by seeding the contents of the test tubes (0.1 ml) on meat-peptone agar (MPA). The results are shown in table 3.

Table 3

Physico-chemical characterization and antimicrobial activity of samples of gel-like compositions based on complex salts of chitosan

The characteristic gel-like compositionCharacteristic of the system BCH + gel composition + microorganisms*
The original polymerSolventpHTurbidity
after 24 h
The growth of culture after seeding on MPA through t h
Functional groupWithP, wt.%NameWithTo, %244872
BCH + microorganisms7.2Muddy+/td> ++
ChitosanWater-7.5Opalescent-++
-NH24
The chitosan hydrochlorideWater-5.9Opalescent-++
-NH3+Cl-4
15Acetic acid23.5Transparent---
15Ascorbic acid93.1 Transparent---
15Lactic acid13.1Transparent---
15Glycolic acid53.0Transparent---
15Citric acid23.1Transparent---
15Succinic acid23.4Transparent---

*Microorganisms: E. coli 113-13, S. aureus 209 P, B. cereus 8035;

"-" the lack of growth of strains of microorganisms;

"+" the growth of microorganisms.

From the party of regions is presented in table 3 data shows, that gel-like composition on the basis of chitosan hydrochloride and an aqueous solution of organic acids (acetic, ascorbic, glycolic, lactic, citric, succinic) shows prolonged antibacterial activity compared to the aqueous solution of the original polymer chitosan regardless of the chemical form it is in, i.e., in the form of policeware (-NH2) or in the form of polysol (-NH3+Cl-). This experimentally determined that the maximum soluble concentration of the original polymer is 4 wt.%. Most concentration as chitosan and chitosan hydrochloride leads to swelling of the polymer.

The group of examples 3-8. Anti-inflammatory effect.

Anti-inflammatory effect on the example of a gel-like composition of chitosan hydrochloride in an aqueous solution of ascorbic acid. The tests are done on the models in vitro (cell culture) and in vivo (in clinical practice).

Example 3. As test models used in vitro culture of epithelial cells MA-104 (Institute of Cytology RAS, St. Petersburg). Cells are grown in an atmosphere of 5% CO2when 37º in a nutrient medium, DMEM with the addition of 10% fetal calf serum (Gibco, USA) without antibiotics. Cells that have reached the monolayer, are subjected to enzymatic disaggregation, laundered f is sfinno-buffered saline (PBS; Sigma, USA), resuspended in fresh medium and added to the Petri dishes to a final concentration of 130-150 thousand cells in 1 ml medium DMEM not containing (negative control) or containing a sterile sample of a gel-like composition (7 µl per 1 ml of medium). Monitoring changes in the concentration of cytokines IL-1β, IL-8 and TNF-α in the growth media by enzyme-linked immunosorbent assay according to the instructions supplied with the kits produced by JSC "Vector-best" (Novosibirsk, Russia).

The results of determination of cytokine production in culture MA-104 in response to contact with a gel-like composition is shown in table 4.

Table 4

Cytokine production in culture of epithelial cells MA-104 in the growth environment of DMEM with or without the addition of a gel-like composition

TNF-α
CytokineThe concentration of cytokine in the growth environment, PG/ml
Without adding songs
through t, d
To add a song
through t, d
0.5120.512
4.12.82.32.100
IL-806.0636.0028.0702.0
IL-1β5.2139.512.414.8189.926.8

From table 4 it is seen that the gel composition on the 1st day decreases in 2 times, and on the 2nd day completely suppresses the secretion of the cytokine TNF-α, which is the major mediator of the inflammatory response; enhances the production of the cytokine IL-8, causing the migration of cells of innate immunity in inflammation; increases the production of the cytokine IL-1β, stimulating the phagocytic activity of micro - and macrophages. Thus, in vitro model of culture of epithelial cells MA-104 detected anti-inflammatory gel composition by suppressing the production of anti-inflammatory cytokine TNF-α and stimulation of effector cells of innate immunity

Example 4. In clinical practice, 15 patients suffering from chronic periodontitis mild severity, conducted a 10-day traditional combination therapy together with the application of a gel-like composition on the area of the papilla and marginal gingiva with capture 1-2 cm of the mucous membrane of the alveolar process and instillation in periodontal pockets. Daily treatments of 15 minutes. The comparison group consists of 15 patients receiving traditional complex therapy without the use of a gel-like composition. The clinical condition of periodontal tissues was estimated using indexes: hygiene (IG), periodontal (PI), papillary-marginal-alveolar (RMA). Bone health interdental septa is estimated according to intraoral radiography. Anti-inflammatory effect is defined as the reduction of the index of the RMA by the formula:

PE=100 × [PMA(1) - PMA(2)] /PMA(1), (%),

where PE - anti-inflammatory effect; indices PMA(1) and (2) are assessed before and after therapy.

The results are shown in table 5.

Table 5

Index assessment of periodontal tissues in patients with chronic mild periodontitis before and after traditional therapy with and without the use of a gel-like composition

IndicatorsThe study groupThe comparison group
Before therapyAfter therapyBefore therapyAfter therapy
PMA (%)44.35±2.156.37±0.6447.40±2.4620.15±1.37
IG (points)2.26±0.501.18±0.302.37±0.401.20±0.02
PI (points)3.57±0.102.53±0.153.60±0.432.95±0.30
Effect (%)85.657.5

From table 5 it is seen that in the treatment of patients with chronic periodontitis mild anti-inflammatory effect is 1.5 times higher in the case of traditional therapy in combination with daily applications of a gel-like composition.

Example 5. Same as in example 4, but in the treatment of patients with chronic periodontitis among whom her severity.

Table 6

Index assessment of periodontal tissues in patients with chronic periodontitis moderate before and after traditional therapy with and without the use of a gel-like composition

IndicatorsThe study groupThe comparison group
Before therapyAfter therapyBefore therapyAfter therapy
PMA (%)58.60±4.298.40±1.1560.30±4.1924.70±2.02
IG (points)2.54±0.401.24±0.242.45±0.451.20±0.45
PI (points)4.73±0.203.63±0.254.66±0.453.61±0.35
Effect (%)85.759.0

From the data of table 6 shows that treatment of patients with chronic paro is anticom moderate anti-inflammatory effect was to 1.45 times higher in the case of traditional therapy in combination with daily applications of a gel-like composition.

Example 6. Same as in example 4, but in the treatment of patients with chronic catarrhal gingivitis.

Table 7

Index assessment of periodontal tissues in patients with chronic catarrhal gingivitis before and after traditional therapy with and without the use of a gel-like composition

IndicatorsThe study groupThe comparison group
Before therapyAfter therapyBefore therapyAfter therapy
PMA (%)28.30±0.955.25±0.0927.70±0.8910.43±0.25
IG (points)2.15±0.451.16±0.102.10±0.401.17±0.23
PI (points)2.05±0.201.98±0.172.14±0.352.10±0.20
Effect (%)81.4 62.3

From the data in table 7 shows that in the treatment of patients with chronic catarrhal gingivitis anti-inflammatory effect was 1.3 times higher in the case of traditional therapy in combination with daily applications of a gel-like composition.

Example 7. The group of patients with exacerbation of chronic hypertrophic pharyngitis (10 people) is a traditional therapy - double searing lymphoid granules oropharyngeal 10% silver nitrate solution (silver nitrate) with an interval of one day. In the second (experimental) group of patients with chronic hypertrophic pharyngitis (10 people) for 4 days in addition to traditional therapy daily treatment of throat gel composition (morning and evening) for 30-60 seconds. Hyperemia and the degree of infiltration of granules lymphoid tissue of the oropharynx is assessed by the visual analogue scale (VAS) scores from 0 to 5. The severity of pain in the throat (pain, feeling sore, dryness, feeling of a foreign body in the throat) is assessed by YOUR (0-10 points). Thus for 0 there is no sign, and 5 and 10 (respectively) is the maximum intensity. The results of applying the gel compositions are presented in tables 8 and 9.

Table 8

Dynamics of change of intensity of pain in the throat during therapy of chronic hypertro the practical pharyngitis without and with application of a gel-like composition

TherapyThe intensity of pain in the throat (on YOUR 0-10 points)
Before therapyThrough t, d
123
Traditional8.1±1.76.0±0.85.2±1.41.7±1.5
Traditional+treatment gel composition8.3±1.51.9±1.700

Table 9

Dynamics of changes in the severity of hyperemia granules lymphoid tissue of the pharynx in the treatment of chronic hypertrophic pharyngitis without and with application of a gel-like composition

TherapyThe severity of hyperemia granules lymphoid tissue of the pharynx
(on YOUR 0-5 points)
Before the treatmentthrough t, d
1 3
Traditional4.5±0.74.0±1.22.4±0.5
Traditional+treatment gel composition4.7±0.81.9±0.71.0±0.1

On the basis of data given in tables 8 and 9, it can be argued that the use of a gel-like composition in combination with traditional therapy of chronic hypertrophic pharyngitis provides significantly higher analgesic effect and a more pronounced regression of the symptoms of inflammation.

Example 8. 15 women suffering from vaginal dysbiosis, is a traditional therapy (metronidazole 500 mg orally 2 times a day for 7 days.) in conjunction with the processing of the mucous membrane of the vagina gel composition in an amount of 1 ml of 1 every 2 days for 10 days. The comparison group consists of 15 women also suffering from vaginal dysbiosis and receiving traditional treatment, but without the use of a gel-like composition. The effectiveness of anti-inflammatory action is estimated by the complaints of the patients and the clinical picture. The results are shown in table 10.

Table 10

The dynamics of the relief of symptoms of vaginal dysbiosis during the performance of the traditional therapy with and without the use of a gel-like composition

SymptomsThe studied group,
day
The comparison group,
day
1251012510
Itching and burning++++++
The discharge (leucorrhoea)++++++
Hyperemia of the mucous membrane+++

Rez is litty, presented in table 10, indicate a high efficiency of application of the gel composition based on chitosan hydrochloride and a solution of ascorbic as anti-inflammatory agents in combination with traditional therapy vaginal dysbiosis.

The group of examples 9-10. Wound healing effect.

Testing wound healing actions of samples of a gel-like composition is carried out in vivo in animal models. When working with experimental animals are guided by the order of Ministry of health of the USSR №755 from 12.08.1977, and the requirements of the European Convention for the protection of laboratory animals. All manipulations with animals held under ether anesthesia.

Example 9. The study of wound healing actions of a gel-like composition based on chitosan hydrochloride and ascorbic acid is conducted on the model of adult outbred white mice-males with an average weight of 18-20 g Standard wound artificially modeled on nepilirovanny back surface by resection of the area of the dermal layer of the skin area of 1 cm2. In the experimental group of animals (10 PCs) gel composition is evenly applied to bare the wound surface. In the control group (10 PCs) wound healing is a primary tension without causing gel-like composition. About the course of the wound process judged odynamic reducing the area of the wound and in her condition.

In Fig. 2 shows the dynamics of the process of wound healing in laboratory animals (white mice) when using the gel composition based on chitosan hydrochloride and ascorbic acid (a-b) and control (g-e): svezhesvarennaya wound (a, g), the condition of the wound on 3-and (b, d) and 14 days (b, e) experiment. Found that when using the gel composition of wound healing occurs in an average of 1.7-2 times faster than in the control.

Example 10. The study of wound healing actions of a gel-like composition based on chitosan hydrochloride and acetic acid is carried out on the model, Mature mongrel female rats with an average weight of 300, Thermal burns IIIB degree with an average area of 9.8 mm2modeled in the interscapular area. Formed on the 3rd day the scab and diseased tissues are removed by the method of sharp how agressively to debride. The control animal group (15 rats) left untreated, the rest (15 rats) exposed wound surface is covered with a gel-like composition.

Found that when using the gel composition based on chitosan hydrochloride in an aqueous solution of acetic acid is observed acceleration of the healing process of burn wound IIIB degree on average 1.6 times.

Example 11. Cosmetic effect.

On cleansed face, neck and hands light KRU the new movements caused a small amount of gel composition on the basis of chitosan hydrochloride and mortar breast, glycolic or citric acid. After 3-5 minutes, the composition is washed off with plenty of warm water. The procedure is repeated no more than 1-2 times a week. Cosmetic effects observed when using a gel-like compositions based on salts of chitosan, is reflected in table 11.

Table 11

Cosmetic effect of gel composition on the basis of the hydrochloride of chitosan and organic acids

Thus, the use of low molecular weight salt of chitosan - chitosan hydrochloride in combination with various organic Pharmacopoeia acids allows to expand the range of biological activity and to obtain a composition, which, depending on the selected acid also shows antibacterial activity, anti-inflammatory, wound healing and beauty. Thus obtained composition is non-toxic, easy to obtain, low cost and accessible to a wide range of consumers.

Gel bioactive composition for application to the skin containing activetestsuite substance hydrochloride, chitosan and distilled water, wherein the composition further comprises an organic acid selected from the series: acetic, ascorbic, glycol, lactic, citric, succinic; in the following ratio of initial components, wt.%:

TrackCosmetic effect
PolymerSolvent
The chitosan hydrochlorideLactic acidExfoliating
Lightening
Disinfectant
The lifting effect
Keratoplasticheskie
Glycolic acidExfoliating
Disinfectant
Keratoplasticheskie
Citric acidLightening
Astringent
Refreshing
Keratoplasticheskie
Disinfectant
Succinic acidKeratoplasticheskie
Protective
Refreshing
Disinfectant
the chitosan hydrochloride10-20
organic acid1-10
distilled waterrest



 

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22 cl, 18 dwg, 1 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I: cis-COOR-XCH-(CH2)a-CH=CH-(CH2)b-CH3, wherein (a) and (b) can take any value from 0 to 14, (X) is specified in: OH, NH2, CH3, F, F3C, HS, O-CH3, PO4(CH2-CH3)2 and CH3COO, and (R) represents sodium (Na) applicable for preventing and/or treating obesity, hypertension and/or cancer. Also, the invention refers to using the compounds of formula I for preparing a pharmaceutical and/or nutrient composition, to the pharmaceutical and/or nutrient composition based on the compounds of formula I, to a cosmetic, non-therapeutic method for improving skin manifestations and to a method for preventing and/or treating the diseases in humans and animals with using the compounds of formula I.

EFFECT: preparing the new compounds.

18 cl, 22 dwg, 5 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is a group of inventions containing a combination of the avermectine compound specified in ivermectine, invermectine, avermectine, abamectine, doramectine, eprinomectine and selamectine, aversectine B, AB or C, emamectine B1a, emamectine B1b and their derivatives, or latidectine, and the alpha-2 adrenergic receptors agonist compound specified in apraclonidine, brimonidine, clonidine, dexmedetomidine, guanabenze acetate, lidamidine, lofexidine, methyldopa, rilmenidine, talipexole, tiamenidine, tizanidine, tolonidine or salts thereof, to be used as a therapeutic agent in treating and/or preventing rosacea, including eye rosacea, using the above combination for preparing the therapeutic agent applicable for treating and/or preventing rosacea, a product in the form of a kit and a pharmaceutical composition of the same formulation and application both, using the above product for preparing the therapeutic agent for treating and/or preventing rosacea.

EFFECT: what is shown is the synergetic effect of the combination in treating rosacea and eliminating the withdrawal effect usually observed at the end of treatment with alpha-2 adrenergic receptor agonists.

20 cl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a water-soluble complex of β-cyclodextrine-histochrome initiation with a molar ratio of the said components from 1:1 to 3:1. To obtain an initiation complex at the first stage performed are: mixing of dry β-cyclodextrine with bidistilled water (DDH2O), shaking the solution at a temperature of 55-65°C until total dissolution, after which cooling of the solution to 37-45°C is realised, at the second stage a 1% solution of histochrome in a volume, necessary for obtaining the necessary concentration is added to the obtained solution, after which the solution is subjected to shaking at 25-45°C for 1.5-2 hours.

EFFECT: prolonged antioxidant action.

2 cl, 4 dwg, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention represents method of preparing viscoelastic protector of corneal endothelium, including dissolution of initial therapeutic component with excessive viscosity in phosphate buffer, filtration and sterilisation until required viscosity value is obtained, characterized by the fact that as initial therapeutic component used is 3% solution of native hyaluronic acid, after dissolution 1% peptide complex, consisting of amino acid desmosine and following short-chained peptides-oligopeptides: GlyTrpIle; IleAspIle; PheArgPro; GlnHisHis; ProHisTyr; ThrTrpTrp; LysPheThr; LysArgMet; PheCysMet; IleIle; AspLysLys; TrpPro; GluThr, is introduced, and sterilisation is carried out by ionizing radiation in the range of radioactive radiation from 78×107 Mrad to 11×108 Mrad.

EFFECT: recovery of biochemical processes in endothelial layer of cornea with constant eye cornea moistening and increase of biocompatibility, which contributes to fast rehabilitation after traumas or surgery.

2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a composition, adapted for intravenous introduction, intended for the treatment or prevention of pathological processes of crystallisation or calcification in a person, subjected to dialysis. The composition contains inositol phosphate and/or its pharmaceutically acceptable salt, with a dose of inositol phosphate and/or its salt constituting from 1 nmol/kg to 0.1 mil/kg. The invention also relates to a combined method of treatment, including the intravenous introduction of the said composition of the dialysis liquid simultaneously.

EFFECT: method is intended for the treatment or prevention of pathological processes, associated with an impairment of the regulation of physiologically adequate levels of inositol phosphate in blood plasma of the person, subjected to dialysis.

10 cl, 4 dwg, 1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an antibacterial composition and is intended for the oral cavity care. The antibacterial composition contains an antibacterial system, including a 4-isopropyl-3-methylphenol (IPMP) source of zinc ions and alkali metal C8-18 alkylsulphate and a perorally acceptable carrier or an excipient. The composition Ph constitutes from 5.5 to 7.5.

EFFECT: application of the invention provides the antimicrobial activity.

9 cl, 4 dwg, 3 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and represents a local pharmaceutical composition for treating rosacea containing at least 0.02% berberine or a biologically equivalent berberine analogue, such as palmatine, and an ingredient specified in a group consisting of water, methanol, ethanol and dimethylsulphoxide, wherein berberine or the biologically equivalent berberine analogue represents the major pharmaceutically active ingredient.

EFFECT: invention provides extending the range of products for treating rosacea.

4 cl, 6 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: invention represents eye drops containing a pharmaceutically acceptable additive acid salt and methylethylpyridinole, taurine and a composition of group B vitamins.

EFFECT: creating the combined preparation for treating traumatic and dystrophic eye injuries causing no irritant action and possessing improved pharmacological properties.

5 cl, 6 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: what is declared is an infusion solution for filling the deficiency and meeting the physiological needs for water and basic electrolytes, which contains the following ingredients: sodium (Na+) - 27.72-28.28 mmole/l; fumarate(H2C4O42-) - 13.86-14.14 mmole/l; potassium (K+) - 18.61-18.99 mmole/l; calcium (Ca2+) - 3.56-3.64 mmole/l; magnesium (Mg2+) - 2.18-2.22 mmole/l; chlorine (Cl-) - 30.0-30.6 mmole/l; glucose (C6H12O6) - 189.1-192.9 mmole/l, water for injections.

EFFECT: solution contains the basic electrolyte concentration balanced for meeting the physiological needs; it is safe for the clinical application and can be used in diseases of various aetiology for patients of any age.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents an injectable form of 5α-androstane-3β,5,6β-triol containing a liquid injectable form, containing a solvent, or a solid injectable form containing at least one soluble additive with the above at least one soluble additive containing hydroxypropyl-β-cyclodextrine.

EFFECT: invention provides preparing the stable injectable form of 5α-androstane-3β,5,6β-triol.

10 cl, 7 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to an injection medical composition for local application in treatment of haemorrhoid, which contains hydroxychloroquine. In particular, the composition contains hydroxychloroquine in a physiological solution for injection with a local anaesthetic and an antioxidant.

EFFECT: injection composition by the invention ensures strengthening of haemorrhoid tissue for blocking metabolism in the haemorrhoid tissue, and as a result -necrosis of the haemorrhoid tissue.

5 cl, 8 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: storage-stable pharmaceutical composition represents a liquid formulation containing bortezomib and a system of anhydrous solvents and applicable for injection. A primary ingredient of the system of anhydrous solvents is propylene glycol. Bortezomib is found in the concentration of at least 1 mg/ml. The pharmaceutical composition contains a total amount of aqueous buffer of 10 vol. % or more.

EFFECT: stable pharmaceutical composition according to invention maintains bortezomib degradation at the level of not less than 10 wt % when keeping the liquid formulation for at least three months in the ambient environment.

9 cl, 10 tbl

FIELD: medicine.

SUBSTANCE: invention represents an irrigation solution containing sodium chloride, mono- and dibasic sodium phosphate, glycosaminoglycans, glucose or its derivatives, water-soluble cellulose or its derivatives, neuraminic acid, an antihypertensive agent and water.

EFFECT: irrigation solution is balanced; it possesses the anti-inflammatory, anti-oedemic and antihypertensive properties.

3 ex

FIELD: chemistry.

SUBSTANCE: stabiliser includes modified chitosan which is obtained by modifying chitosan particles located in an emulsion of an organic solvent - water, with pH 6.0-6.5, by first reacting a mixture consisting of a carboxylic acid in an organic solvent and a condensing agent, and then with an organic base, wherein the carboxylic acid used is either palmitic acid or stearic acid or dodecanoic acid, the condensing agent used is a mixture of hydroxysuccinimide and an aliphatic carbodiimide or formaldehyde and an aliphatic isocyanide, and the organic base used is triethylamine.

EFFECT: effective liposome composition stabiliser which can be obtained using a simple method.

8 cl, 3 tbl, 5 ex, 7 dwg

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