UA139685U - ANTI-INFLAMMATOR IN THE FORM OF GEL WITH SAPROPEL EXTRACT - Google Patents

Abstract

Anti-inflammatory agent in the form of a gel with sapropel extract contains the active substance from natural mineral ingredients, excipients and purified water. Aqueous sapropel extract is used as an active ingredient from natural mineral ingredients, and Upolrez 10 carbopol and potassium sorbate preservative are used as excipients.

Description

The utility model belongs to the pharmaceutical industry and medicine, in particular to dermatotropic soft drugs for cutaneous use for the treatment of wounds and burns.

The well-known gel for udders and teats "Nizhnodiy" (manufactured by "Brofarma", Ukraine), containing needle extract - 5 mg and auxiliary substances - corn oil, pumpkin seed oil, glycerin, Tween-80, emulsifier T-2, water. The action of the drug is due to the peculiarities of the interaction of substances of natural origin.

But a product with a pronounced needle smell is not always appropriate to use for regular care of the skin of the udder of dairy animals.

There is a cream with sapropel extract to protect sensitive skin (patent SM Me 101732212,

AbIK 8/98), which contains the following components: alkanolamine salts of alkyl phosphate esters, lanolin, isomeric aliphatic esters, ethylene glycol monostearate, petroleum jelly, liquid lanolin, lanolin alcohol, sodium salt of 4-hydroxybenzoic acid, fragrance, sapropel extract from ZO to 40 95 and purified water.

Offered to protect sensitive skin.

A well-known cosmetic sapropel mask (patent OA Mo 114262, AbIK 8/92, 10.05.2017, Bull. Mo 9), which contains a base of natural mineral ingredients, additives of chemical origin and water, as a base of natural mineral origin, sapropast obtained by the cavitation method is used from sapropel with moisture content from 50 to 90 95, and used as preservatives

Euxyl K 100 and Nizin.

But this tool is used only in cosmetology, that is, this mask has a narrow spectrum of action.

The well-known ointment "Vulnuzan" (borpapta, VO), in which a solution of stabilized Black Sea alkali "Solilug" is used as an active ingredient, which is a mineral solution (300-350 g/l) with macrocomponents (including magnesium salts up to 295 g/l l), microcomponents, microalgae and biologically active substances of the Pomorie and Burgas salt lakes. It has a strong anti-inflammatory and antibacterial effect, strengthens the protective and regenerating properties of the skin.

There is a wound-healing agent in the form of an ointment (patent VO Mo 2003337, Ab1IKZ35/16| in the composition of the ointment base of the m/w emulsion type (lanolin 30.0, olive oil 30.0, TWIN-80 2.5, water

Distilled 37.5) inject peat in injection form (a product of peat distillation) in a ratio of 97.

The famous sapropel liniment (patent KO Me 2320320, Ab1KZ5/16)| containing insecticide, xeroform, aerosol, castor oil, as insecticide containing sapropel tar.

Well-known "Elton" ointments containing oil extract of sapropel from the sulfide lake "Elton"

Volgograd region of the Russian Federation, auxiliary substances and "Elton" ointment based on PEO, containing an oil solution of sapropel from Lake Elton 10.0 and PZO-1500, P3O-400.

The disadvantages of the well-known ointment are the insufficient spectrum of therapeutic action and the presence of scarcely available components in the formulation.

The basis of a useful model is the task of creating an effective anti-inflammatory agent used for the treatment of wounds and burns.

The task is solved by the fact that the anti-inflammatory agent in the form of a gel with sapropel extract, which contains an active substance from natural mineral ingredients, a preservative and purified water, according to a useful model, as an active substance from natural mineral ingredients, aqueous sapropel extract is used, and as auxiliary - carbopol brand Cze 10 and preservative potassium sorbate, with the following ratio of components, wt. 9o: aqueous extract of sapropel 10.0-20.0 (1710) carbopol brand She 10 0.8-1.5 potassium sorbate 0.2-0.8 purified water the rest.

According to a useful model, sapropel extract from the Prybych lake deposit in the Volyn region (Ukraine) is used to develop the composition of the gel.

Example 1. Gel production technology.

The main stages of the technological process are: dissolution of potassium sorbate, swelling of carbomer, addition of sapropel extract. Preparation of gel. Packing the gel into tubes.

Packing tubes in bundles

The technological process of gel production is carried out in compliance with the necessary sanitary rules and norms. In order to prevent microbial contamination of gels, preventive measures are carried out, which include technological and sanitary work on the preparation of premises, technological equipment, technological clothing and personnel.

ShGge 10 carbopol and potassium sorbate are weighed on a scale. Purified water is measured in a measuring cup accordingly. Purified water is poured from the gauge into the reactor. Add pre-weighed potassium sorbate, stir until dissolved (visual control). Pre-weighed OPGE 10 carbomer is added. Leave to swell for 30-60 minutes. During swelling, periodically turn on the mixer and stir at a speed of 60-90 rpm. There should be no lumps of non-swollen carbomer in the sample (visual control). Sapropel extract is gradually added with constant stirring at a speed of 60-90 rpm. In the sample, the gel should be homogeneous (visual control). If the mass is homogeneous, the technological process is continued. In case of inhomogeneity, homogenization is continued for 5-10 minutes.

At the end of the gel homogenization period, the mixer is turned off and a sample is taken for analysis for compliance with the requirements of regulatory documentation.

After receiving positive results of the analysis, the gel is submitted to the "Packing of the gel" stage.

Example 2. Anti-inflammatory activity of a gel with sapropel extract.

Anti-inflammatory activity of samples of gels with sapropel extract was studied on the model of UV erythema in rats.

Acute photodynamic skin injury in rats was induced using the "EARTH Ray" irradiator with a DRT 125-1 mercury-quartz lamp (range of ultraviolet radiation 230-400 nm).

The research was conducted on clinically healthy white outbred rats aged 3-4 months (females), weighing 180-220 g, which were kept in standard vivarium conditions on a generally accepted diet.

Experimental animals were divided into four groups, 6 animals in each (n-6):

I - control pathology (CP) - untreated animals with UV erythema;

II - the comparison group - animals with UV erythema, which were treated with the comparison drug - "Panthenol" ointment (Hemopharm AD, Serbia).

And - animals with UV erythema, which were treated with a drug - sample Mo 1 (gel with sapropel extract 10 9b);

IM - animals with UV erythema, which were treated with a drug - sample Mo 2 (gel with

With sapropel extract 15 9b).

One day before the experiment, the fur on the left side of the animals was removed. Before irradiation, the animals were anesthetized with barbamil (0.8 ml of a 195 aqueous solution of barbamil per 100 g of the animal's weight, the depilated skin area was covered with a wide patch with a 1 cm hole.

The irradiator was placed at a distance of 10 cm from the animal, the exposure time was 60 seconds.

Gels with sapropel extract were applied to the surface of the skin in a conditionally therapeutic dose of 25 mg/cm immediately after irradiation, and then daily, from the 1st to the 7th day of the experiment.

The anti-inflammatory activity of the studied drugs was evaluated for 7 days by the thickness of the skin fold, which was measured with a caliper in mm, and the state of the skin in points (0 - no erythema; 1 - weak erythema (pink tone); 2. - moderately expressed erythema ( pink-red background); small scaly peeling of the skin; C - pronounced erythema (red tone), large scaly peeling of the skin, point hemorrhages; 4 - sharply expressed erythema (bright red tone), focal necrosis and hemorrhages.

According to the obtained data, macroscopic signs of photodynamic inflammation of the skin developed gradually and in the group of control pathology (KP) reached the maximum intensity on the 2nd-3rd day after irradiation (Table 1). Skin inflammation was characterized by tissue swelling, hyperemia, hemorrhages, and the development of hemorrhagic crusts with ulcers. Complete restoration of the skin, according to the indicators of the intensity of the inflammatory reaction and the thickness of the skin fold, was observed in the KP group on the 14th day after irradiation.

Table 1

Intensity of the inflammatory reaction on the skin of rats on the model of acute photodynamic inflammation, points (M x t, p-b)

Grupar--2-- 7-3 CHILDREN'S LACK 2020200 5 A I I

Group 171112 1 3 1 4 | 6 | 7 1 | ptyuozhboo | 3505022 | 3.50:0.22 | 3332021 | 3.0050.00 | 0835017 about | 0.5b0zh022y | 26730217 | 25050227 | 1.83:017" | 1.50х50.227 | 1.3350.21" yo | o6b7zhb2i | T5Ozhb22E| 1itsho tick | okho" | 0.33zhO, g1ilE | 0.000, Ol

Table 1 (continued) tour row 6 i

Notes: " - the differences are significant relative to the values of group I (control pathology), p<0.05;

I - the differences are reliable relative to the values of group I! (comparison group), re0.05

Against the background of treatment with gels with sapropel extract, on the 2nd to 7th day of the experiment, a reliable, relative to KP, decrease in the intensity of photodynamic inflammation of the skin of experimental animals was observed, which was characterized by a decrease in edema and hyperemia, as well as a decrease in the thickness of the skin fold (Table 2).

Table 2

The thickness of the skin fold in rats on the model of acute photodynamic inflammation of the skin, mm (M zh t, p-6) 111 207-006 | 2275006 | 2.75,540.09 | 2.7950.08 | 2.5750.09 | 2,2050,06 o, 2055006 | 2h15:50.05 | 2.4750.067 | 24350.097 | 2,2350,067 | 2,1250.06 yo, 2035006 | 2175004 | 2.3750.087 | 2.28:0.077 | 206 | 2.0850.05

Note: " - the differences are significant relative to the values of group I (control pathology), p<0.05;

I - the differences are reliable relative to the values of group I! (comparison group), p«e0.05;

The decrease in the intensity of the inflammatory reaction that we observed in the Sh and IM groups was accompanied by a significant decrease in the thickness of the skin fold relative to the CP group by 13.8 and 19.3 95, respectively (Table 2d).

On the 6th day after UV irradiation, complete healing of UV erythema was observed in the IM group (Table 1). On the 7th day after UV-irradiation, complete recovery of the skin was recorded in the PI group (Table 1).

Medicinal preparations based on sapropel extract have pronounced anti-inflammatory properties, allow to reduce the intensity of acute photodynamic inflammation and shorten the duration of its treatment.

Example 3. Determination of the acute toxicity of a gel with sapropel extract.

Given that the gel is a means for dermal application, its possible toxic effect at a single dermal application was investigated. The research materials were: gel with sapropel extract from the Prybych deposit, Volyn region (under the conventional name "Saprogel", containing water extract of sapropel, Tse 10 carbopol, potassium sorbate, purified water), gel base (carbopol in the base, which was used in comparative studies of toxicity indicators were neutralized by trometamol) and the reference drug "Nizhnodiy gel" containing pine extract - 5 mg/g (manufactured by "Brovapharma" LLC, Ukraine).

The acute toxicity of the cream was studied in 30 sexually mature clinically healthy male rats (line

Umistag), aged 6-8 months, weighing 200-230 g, with one-time dermal application. From experimental rats, groups of 5 animals each were formed (n--5).

Test samples - gel with sapropel extract ("Saprogel") and a reference drug

Zo ("Gentle" gel) was applied to a pre-cut area of the skin of the back, which was at least 10 95 of the total surface area of the animal. Test samples were applied in a thin layer at a dose of 2810 mg/kg. The way of contact of test samples with the body is chosen in accordance with the expected way of using medicines in clinical practice.

The animals of the negative control groups were applied the gel base accordingly in an equivalent amount. Animals were fasted overnight before sampling.

The animals had free access to water, they were allowed to eat only four hours after applying the objects.

According to the standard procedure, within 14 days after the skin applications of the test samples, the effect of the drug on the survival behavior, appearance and manifestations of violations of the physiological state of the animals was recorded daily. The weight of the animals was determined 3, 7 and 14 days after the start of the experiment. 14 days after application of the test samples, the animals were decapitated under light chloroform anesthesia, dissected and macroscopically examined the internal organs, their mass coefficients (MC) were calculated

The results of the research demonstrated the absence of animal deaths when the experimental samples were applied (Table 3).

Table C

Survival of rats in an experiment to study the acute toxicity of "Saprogel" and the reference drug when applied to the skin

Animals that died/ total

Group of animals treated Sex Dose, mg/kg number of animals 2810 2810 2810

As evidenced by the results of the study of body weight dynamics during the experiment, the animals that received the test sample and the reference sample "Nyzhnody gel" did not differ in these parameters from the group of rats that were applied to the skin with a gel base (Table 4).

Table 4

Dynamics of body weight of white outbred rats (g) after dermal application of "Saprogel" and the reference drug; Mkht, p-5

Experimental group of animals 14 days 218,754.7 220.06 1 220,057.2 225,057.7 220,053.5 228,356.5 236,755.6 236,755.6 212,055.0 219,357.5 221,156.5 2027,Act

During the autopsy and macroscopic examination of the internal organs of rats 14 days after the introduction of the samples, the size, color, consistency, and location of the internal organs of the animals that received the test samples and the reference drug did not exceed the physiological norm. The mass coefficients of the internal organs of animals that were applied the gel or the comparison drug "Nyzhnody gel" did not differ from the group of rats that were applied the gel base and among themselves (Table 5).

Table 5

Mass coefficients of internal organs of rats on the 14th day after a single skin application of "Saprogel" and the reference drug; M zh t, p-5. . Experimental groups of animals

Researched bodies 3075012 3.06:0.09 3.0520.11 0.330.01 0.3350.01 0.3750.02 0.340.01 0.3450.01 0.3450.02 0.330.01 0.310.01 0.360.01 0.60х0.01 0.61х0.02 0.6350.01 0.38х0.02 0.3250.01 0.3450.02 0.026:50.001 0.021-0.002 0.027-0.001 0.134-0.007 0.14350.011 0.113 ,011

Table 5

Mass coefficients of internal organs of rats on the 14th day after a single skin application of "Saprogel" and the reference drug; M zh t, p-5

Researched bodies of the D Id RU t r t- to t

Gel base Saprogel Nizhnodiy gel

Right testicle 0.6750.01 0.7250.02 0.6950.01 0.68х0.01 0.71х0.02 0.66:0.03

Thus, the GVO of the "Saprogel" gel lies outside the limits of the IM toxicity class (GVO" 2810 mg/kg), which allows them to be classified as practically non-toxic substances (M class of toxicity).

No differences between the gel-developed comparative drug were found in the experiment, which allows us to consider the drug "Saprogel" and the reference sample to be equivalent in terms of toxicity when applied to the skin of rats once.

Claims (2)

USEFUL MODEL FORMULA 1. An anti-inflammatory agent in the form of a gel with sapropel extract, which contains an active substance from natural mineral ingredients, auxiliary substances and purified water, which differs in that the active substance from natural mineral ingredients is an aqueous extract of sapropel, and as an auxiliary agent - carbopol brand OPge 10 and preservative potassium sorbate, with the following ratio of components, wt. 9o: aqueous sapropel extract 10.0-200 (1710) I I carbopol grade She 10 0.8-1.5 potassium sorbate 0.2-0.8 purified water the rest. 2. Anti-inflammatory agent according to claim 1, which differs in that sapropel from the Prybych lake deposit in the Volyn region (Ukraine) is used for the aqueous sapropel extract.