RU2309750C2 - Therapeutic and cosmetic agent and preparation for therapy of damaged external tissues - Google Patents

Abstract

FIELD: cosmetology, medicines.

SUBSTANCE: claimed agent represents composition containing mixture of 4-hydroxyphenylene-2,4-dioxybemzene or 2-(1-oxy-4-hydroxyphenylene)-benzoquinone with hydroquinone in ratio from 99:1 to 1:99. Preparation for treatment of body external tissues contains said agent in amount of 0.5-10 g in daily dose. Composition of present invention are useful in treatment of wound, burn, in surgery, stomatology, etc.

EFFECT: agent of increased effectiveness.

3 cl, 4 tbl, 11 ex

Description

The invention relates to medicine, namely to new compositions used to treat wounds, burns and other injuries of the skin, restore optimal functioning of the tissues of the mouth and other body cavities, and can be used in surgery, dentistry, cosmetology and other related fields.

Known for the treatment of damage to the external tissues of the body, in particular the skin, preparations based on antibiotics, sulfa drugs, ointments containing vitamins, enzymes, alcohols, natural biologically active substances (propolis, mummy, honey), etc. (DE 3800972, CL A61K 31/59, 1989).

The disadvantages of most biologically active substances are a narrow spectrum of action, the possibility of complications, and relatively low efficiency.

The closest to the claimed group of inventions in terms of structure and spectrum of action is the drug Olifen (RU 2104009, class А61К 31/765, 1998), which is a sodium salt of polyoxyphenylene thiosulfuric acid, which is able to activate the energy-producing capabilities of cells and thereby stimulate the course of repair processes in damaged cells, restoring their functional activity. Such properties are determined by the structural feature of polyoxyphenylenes, which are characterized by a high degree of conjugation of molecules, which, when introduced into the body, makes it possible to actively influence bioenergetic processes in cells, trap and "quench" free radicals, and influence blood rheology.

A disadvantage of compounds of this type is the production of a mixture of oligomers during the reaction, which leads to poor standardization of the drug, poor solubility of the compounds in water, the presence of an unpleasant aftertaste, the presence of complications (especially when administered intravenously), insufficiently high efficiency, stimulating the growth of microorganisms (SU 820195 ), which is a negative factor during prolonged storage of compositions based on them: ointments, shampoos, etc.

Currently, for the treatment of the skin using drugs in various dosage forms: capsules for oral administration (tribenoside, vinisol, eskusan); in the form of tampons and napkins impregnated with solutions of olosol, estericide, carolitin, sea buckthorn oil; in the form of ointments and powders containing, in particular, antibiotics, etc. (Remezova O.V. et al. International Medical Reviews, 1993. Vol. 1, No. 4, p. 324-327).

The disadvantages of drugs for internal use are limited use, the presence of contraindications, as well as lack of effectiveness, which allows them to be used mainly only as an element in complex therapy. The disadvantages of the external forms are the high consumption of medicines, the limited use for pathologies requiring long-term treatment and complicated by purulent discharge.

Various creams are widely used to treat skin lesions, containing active principles - vitamins, herbal extracts, etc., fat base - petrolatum, glycerin, polyethylene oxide, etc., auxiliary additives - perfumes, preservatives, etc. (VFS No. 42-2821-96; SU 1178446, 1985).

In particular, a composition is known (WO 88/03020) that stimulates the regeneration of the epithelium, which consists of the active principle - vitamins of groups A, E, D (0.5-2%), fat base - petrolatum (7-10%) and glycerin (10%) and auxiliary additives - antioxidant (0.2%), emulsifier (7-10%). However, this cream is also not effective for significant lesions of the skin, in particular, due to the relatively low effectiveness of the active principle, due to the low biocidal and repair properties.

The closest in technical essence to the claimed therapeutic and cosmetic product is the wound healing composition “Lesta” developed by the author (RU 2144816, class A61K 9/00, 1997), which includes: lanthanide salts, dioxidine and the drug OLIFEN, as as a fat base: a mixture of triethylene glycol, polyethylene glycol-115 (according to TU 6-14-826-78) and glycerol, as service additives - perfumes, and also a solvent - water-alcohol mixture in the following ratio of ingredients (wt.%): salt lanthanides 0.5-1.0; drug OLIFEN - 0.3-2.0; dioxidine 0.2-1.0; triethylene glycol 12.0-60.0; polyethylene glycol-115 20.0-35.0; glycerin 2-30; perfume 0.01-1.5; alkali 0.7-1.5; solvent rest. As salts of lanthanides, as a rule, lanthanum nitrate or hydrochloride is used. The disadvantage of “Lesta” is a rather limited range of its application.

At the same time, Olifen, which is included in it, along with the use of ointment as a part of the ointment, has shown promise for use as part of preparations that optimize the condition of soft tissues of the oral cavity, improve skin and hair, and improve the quality of hair in animals and feathers in birds. The indicated use of Olifen as a substance that stimulates the functional activity of the external tissues of the body (RU 2104009, 1994, class A61K 31/765) is the closest to the claimed preparation by its technical nature and the achieved effect.

The disadvantage of using Olifen is the lack of effectiveness, instability of the composition, a stimulating effect on the growth of microorganisms located on the human or animal body.

The problem solved by the author is to create a composition with higher efficiency and combining the positive properties of Oliphene (antioxidant and antihypoxic activity) with antibacterial action.

The technical result was achieved by using a composition containing a mixture of polyoxyarylene ethers (POAE) with hydroquinone in a weight ratio of from 99: 1 to 1:99. In this case, both 4-hydroxyphenylene-2,4-dioxibenzene (HFB), obtained in accordance with RU 2224737, and 2- (1-hydroxy-4-hydroxyphenylene) benzoquinone (GC), obtained in accordance with RU 2230467, can be used as POAE.

The appearance of new properties of the composition is apparently due to the interaction between polarized POAE molecules, which are characterized by conjugated structures of molecular orbitals, and polarized hydroquinone (GC) molecules, which, upon interaction, allow one to obtain superconjugated complexes both in solution and in the solid phase as a result contact between the molecules of the ingredients.

As shown by experiments, the appearance of such complexes significantly increases the antioxidant, antihypoxic and other characteristics of POAE, allowing either to increase these parameters of the drug or to reduce the concentration of POAE in the final product by replacing them with hydroquinone (GC).

The introduction of POAE into the composition at a dose of less than 1% practically does not affect the properties of GC, and at a dose of more than 99% it does not give significant differences from the use of pure POAE.

A new composition is obtained by mixing ingredients or mixtures containing these products and mixing or grinding the mixture until a homogeneous product with stable characteristics is obtained, after which ointment forms or other preparations are obtained on its basis using standard technologies.

The composition, depending on the composition, has an LD ₅₀ of 800 to 5000 mg / kg weight; LD ₁₆ from 300 to 1500 mg / kg of body weight, LD ₈₄ from 3000 to 6500 mg / kg of body weight with a single dose of not more than 5 mg / kg of body weight. Compared with Oliphene, the composition is about 3-5 times less toxic. In terms of acute lethal toxicity and morphological data, it can be attributed to class IV low-hazard substances (GOST 12.1.007-76.SSBT. "Harmful substances. Classification and general safety requirements"). Toxicometry data, observations of experimental animals for 14 days after acute administration, as well as necropsy data make it a class IV low-toxic drug (H. Hodge et all. Clinical Toxilogy of Commercial Products / Acute Poisoining. Ed. IV, Baltimore 1975, 427 p.). Currently, permission has been obtained for its use as a food additive. Further tests are being conducted to study the properties of the composition and its mechanism of action.

In order to normalize the surface tissues of the body, the drug is used either orally in the form of a powder, capsules, tablets or drinks containing it, or externally in the form of shampoos, bath additives or ointments, into which, depending on the composition, the composition is administered from 0.005% to 20% wt. .

The final composition is determined by the nature of the surface being treated: clean skin, damaged skin, wound surface, burn, scalp with hair follicles, gums, etc.

The daily dose of introducing the composition into the body is, as a rule, depending on the administration technology used, from 0.5 to 10 g. Although it is possible to use larger or lower doses depending on the disease.

As the tests showed, the introduction of mixtures of POAE with hydroquinone in standard ointment, emulsion, gel, etc. compounds dramatically increases their effectiveness.

The essence and advantages of the claimed group of inventions are illustrated by the following examples.

Example 1. Samples of hydroquinone and 4-hydroxyphenylene-2,4-dioxibenzene (HFB), obtained according to the technology of RU 2224737, were weighed and mixed in a predetermined ratio, and then passed through a ball mill until a homogeneous mass. The composition of the compositions is given in table 1.

Table 1.
The composition of the compositions based on HFB Composition number Composition,% wt. Hydroquinone HSE Composition 1 99 one Composition 2 95 5 Composition 3 90 10 Composition 4 66 34 Composition 5 34 66 Composition 6 10 90 Composition 7 one 99

Weighed portions of hydroquinone and 2- (1-hydroxy-4-hydroxyphenylene) benzoquinone (OX), obtained according to RU 2230467, were weighed and mixed in a predetermined ratio, and passed through a ball mill. The composition of the compositions is given in table 2.

Table 2.
The composition of the compositions based on OGH Composition number Composition,% wt. Hydroquinone OGH Composition 8 99 one Composition 9 95 5 Composition 10 90 10 Composition 11 70 thirty Composition 12 34 66 Composition 13 10 90 Composition 14 one 99

All compositions were tested for the possibility of negative effects on the skin. The effect on the skin and the skin-resorptive effect of substances was studied on white rats in accordance with the guidelines (Assessment of the effects of harmful chemical compounds on the skin and justification of the maximum permissible levels of skin contamination (guidelines) No. 2162-79. M., 1980, 23 s )

For this, after placing the animals in special houses, their tails were placed 2/3 in pulp, which was obtained by mixing the powders of substances with cold water in the ratio of 90% powder, 10% water for 4 hours. After 1 and 16 hours after the end of a single application, erythema or edema of the skin of the tails was not observed (the edema was measured by measuring the thickness of the tails in the middle part using a thickness gauge of the type TR-1-10). A 20-fold application did not cause the death of experimental animals and did not reveal an irritating effect on the skin during the 5-day follow-up period.

Morphologically, the skin of the tails at the place of application of the powders of substances did not represent changes. The epidermis and appendages of the skin are unchanged. The layers of the epidermis are distinct, the basement membrane is preserved. Epithelial cells of the external and internal root vaginas of the hair follicles and connective tissue bag are well defined.

Macroscopic and microscopic changes in the internal organs of animals were absent. The study of morphological, biochemical, hematological and physiological parameters of experimental white rats did not reveal significant differences from the control group (animal tails were placed in water).

Therefore, the tested compositions do not have an irritating effect on the skin and a skin-resorptive effect, i.e. non-toxic in contact with skin or in contact with it.

For further research, mainly preparations containing

- 17% wt. GC and 83% wt. HFB (Epofen preparation);

- 5% wt. OGH and 95% wt. GC (Epohin drug);

after processing them in a ball mill for 10 minutes

Epofen was a black single-crystal powder. pH of a 1% solution of 8.0-8.2, LD ₅₀ (male rats) = 6420 ± 180 mg / kg.

Epochin was a monocrystalline powder of a dark gray color. pH of a 1% solution of 7.6-7.8, LD ₅₀ (male rats) = 3820 ± 120 mg / kg.

Example 2. The effect of the composition on microorganisms. In the course of the study, the effect of the composition on the culture of microorganisms was studied. Test cultures were selected according to the principle of their different sensitivity to adverse environmental influences, including to chemicals due to

- the type of structure of the cell wall (gracilicut, pharmacic, yeast);

- the presence on the cell wall of additional surface layers;

- the origin of the strain (museum or clinical isolate);

- individual characteristics of the microorganism;

- the density of the population of microorganisms experiencing the "pressure" of an unfavorable factor.

As an additional indicator, the affiliation of the test culture to normal (NM) or conditionally pathogenic (UPM) microflora was taken into account. The list and characteristics of test cultures are given in table.3

Table 3.
Characterization of the used test cultures. Test culture Type of cell wall structure Representative of NM or UPM Museum strain or clinical isolate Resistance to adverse effects Escherichia coli M-17 Gracilicut NM Museum Moderate Klebsiella pneumonia Gracilicut UPM Clinical isolate High (capsules) Salmonella enteritidis Gracilicut UPM Museum Weak Staphylococcus aureus 209 Firmikutny UPM Museum Moderate Lactobacillus acidophilus D76 Firmikutny NM Museum Moderate Candida albicans Yeast UPM Clinical isolate High

Research Methods.

Test cultures were grown in appropriate culture media (Lactobacillus acidophilus in MPC-1; Escherichia coli M-17, Klebsiella pneumonia, Salmonella enteritidis, Staphylococcus aureus 209 in nutrient broth; Candida albicans in maltose broth) for 24 hours at 37 ° C. From liquid cultures, standard suspensions with a density of 10 ³ -10 CFU / ml were prepared and 100 μ1 were applied to the surface of similar agar media containing 0.025-0.5% of the studied preparations. Crops were incubated at 37 ° C for 5 days, scanning daily, after which colonies were counted. The results were expressed in lgKOE / ml (see table 4).

Note. In cases of lack of colony growth, it was believed that the _100 μ1 sample contains less than 1 colony, i.e. less than 10 colonies in 1 ml. Accordingly, lgKOE / ml = 1 is correctly represented as lgKOE / ml <1.

Table 4.
The survival of microorganisms in the presence of the drug Epohin, depending on the concentration of the drug and the density of the microbial population. Test culture The control Epochin,% 0.025 0.05 0.1 0.25 0.5 Escherichia coli M-17 8 8 8 8 8 8 7 7 7 7 7 7 6 6 6 6 6 5 5 5 5 5 5 four four four four four four 3 3 3 3 3 3 3 Klebsiella pneumonia 8 8 8 2 one one 7 7 7 2 one one 6 6 5 one one one 5 5 four one one one four four 3 one one one 3 3 2 one one one Salmonella enteritidis 8 8 8 8 8 5 6 6 6 6 6 one four four four four four one Staphylococcus aureus 209 8 8 8 8 four 3 7 7 7 7 3 one 6 6 6 6 one one 5 5 5 5 one one four four four four one one 3 3 3 3 one one Lactobacillus acidophilus D-76 8 8 four 3 one one 7 7 3 2 one one 6 6 one one one one 5 5 one one one one four four one one one one 3 3 one one one one Candida albicans 8 8 8 8 7 7 7 7 7 7 6 6 6 6 6 6 5 5 5 5 5 5 four four four four four four 3 3 3 3 3 3 2 2

Example 3. According to the technology for producing the wound healing composition “Lesta”, the preparation “Lesta-E” was prepared containing the composition No. 6 as an active principle obtained by the method of Example 1. To do this, 0 was dissolved in 50 l of a 50% aqueous-alcohol solution , 5 kg of lanthanum nitrate and 0.5 kg of composition No. 6. Then, 0.5 kg of dioxidine, 20 kg of polyethylene glycol-115, 25 kg of triethylene glycol, 10 kg of glycerin and 0.01 kg of coniferous fragrance were added. The composition was thoroughly mixed, adjusted with a solution of sodium hydroxide to pH 7.3 and packaged. The final product contained 0.5% lanthanum salts, 0.05% hydroquinone, 0.45% HFB, 0.5% dioxidine, 20% polyethylene glycol, 25% triethylene glycol, 10% glycerol, 0.01% perfume, 20% ethanol, 23, 5% water.

The drug was tested in the form of applications containing 5 g of ointment, carried out once a day for 60 minutes, in order to establish its effect on the epithelization of the skin in rabbits. The wound was applied with a scalpel to the shaved surface of the skin of the rabbit. With a wound length of 2.5 mm, a depth of 0.7 mm, a scab formed at the beginning of the second day, healing (the wound is covered, the edges converged completely) at the end of the third day, full restoration of skin elasticity - for 10-11 days. In the control group, using the standard Lesta ointment, where Olifen was used as the active principle in the same dose, healing was observed on days 12–13, and restoration of elasticity on days 40–45.

Example 4. 100 ml of a 20% aqueous solution of composition No. 1 was dissolved in a hot water bath. The content of composition No. 1 in water was 0.005%. After 20 minutes of lying in the bath, tingling of the skin surface, a surge of vigor, a feeling of increased purity were noted. It was noted that this composition cleanses the skin well, prevents pore asphyxiation, improves peripheral blood circulation.

Example 5. Composition No. 7 was dissolved in warm water and the horses were soldered on the basis of a dose of 10 g of the drug per day. After 10 days of admission, the animals were feeling well and in good mood. The skin, mane and tail acquired an improved shine, existing minor skin defects (wounds, cuts) disappeared.

Example 6. In LLP "Nagornoye" of the Leningrad region, tests of composition No. 14 were carried out to preserve the number of birds.

The drug was added to water at a dose of 0.001% when fattening meat chickens from ISA cross on cellular equipment until 25 days of age of the bird. In the experiment and control using an equivalent dose of Olifen, 10 thousand animals were involved. The average weight of the chicken at 40 days in the experiment was 2110 g, in the control - 2050. The safety of chickens in the experiment was 94%, in the control - 86%. Improved bird feather quality was observed compared to the control group.

Example 7. A 5% emulsion of composition No. 7 in sea buckthorn oil was applied in the form of masks once a day for 1 month. in the cosmetic room of Nora LLC, St. Petersburg, in patients with various dermatoses and clinical skin defects: acne vulgaris - 17 people, atony of the skin of the face, neck; wrinkles - 32 people; dermatitis of various etiologies - 12 people. A positive result was achieved after 4-5 masks (appearance, infiltration improved, rashes with acne disappeared, acne elimination, seborrhea).

Example 8. Clinical trials of dietary supplement EPOFEN were conducted in the purulent surgery department of the Central Clinical Hospital named after ON. Semashko of the Ministry of Railways of the Russian Federation on the basis of the Department of Surgical Diseases and New Endosurgical Technologies of the Moscow State Medical-Dental University for patients with long-term non-healing wounds, suffering from chronic venous insufficiency.

Upon admission, all patients underwent examination according to the generally accepted scheme, assessed the degree of compensation of venous blood flow, the state of microcirculation in the tissues (laser Doppler fluometry), prescribed complex treatment aimed at compensating for venous outflow from tissues of the lower extremities, resolving perifocal inflammatory changes in the tissues, and cleansing of the ulcer ( wounds) and its healing.

The treatment was carried out in combination with the already proven methods - surface treatment of ulcers (wounds) with low-frequency ultrasound, vacuum, stepwise mechanical necrectomy and treatment of wounds and surrounding tissues with infrared laser radiation. Epofen was used topically as a 20% polyethylene oxide ointment. In this case, a comparative study of the effectiveness of epophene was carried out according to the results of treatment of representative groups of patients according to the area and depth of ulcers (wounds), the severity of perifocal inflammation, the severity of microcirculation disorders. Epofen was used in the treatment of 39 patients. The comparison group consisted of 40 patients.

To assess the effectiveness of the complex therapy, clinical, cytological, histological studies were performed, as well as an assessment of microcirculation in the tissues. The results of the study showed that, with traditional treatment, the healing of trophic ulcers and long-term non-healing wounds is characterized by the formation of defective granulation tissue with microcirculatory disorders, edema, chronic inflammatory infiltration and purulent-necrotic tissue changes, wound infection, inhibition of fibroblast and epithelial proliferation.

The use of epofen in the form of an ointment stimulated a macrophage reaction, enhanced the proliferation of fibroblasts and epithelium, and reduced infection of the wound (ulcer).

Cleansing of ulcers (wounds) was achieved on average by 5.6 days from the start of treatment (in the comparison group - by 13.6 days), granulation by 8.7 days (in the comparison group - by 14.3 days), the appearance of epithelization - to 7.2 days (in the comparison group - to 12.2 days) and the final healing of ulcers (wounds) - to 14.3 days (in the comparison group - to 19.4 days) from the start of treatment.

Allergic reactions of a general and local nature when using EPOFEN ointment were not noted. There are no contraindications to the use of the drug.

Example 9. Tests of the drug Epokhin were carried out in the purulent surgery department of the Central Clinical Hospital. ON. Semashko for the treatment of patients with frostbite.

Upon admission to all patients, an examination was performed according to the generally accepted scheme, the degree of compensation of venous blood flow, the state of microcirculation in the tissues (laser Doppler fluometry) were evaluated, complex treatment was prescribed, resolution of perifocal inflammatory changes in the tissues, wound cleansing and its healing. The treatment was carried out in conjunction with the already proven methods - surface treatment of wounds with low-frequency ultrasound, vacuum, staged mechanical necrectomy and treatment of wounds and surrounding tissues with infrared laser radiation.

Epohin was used topically in the form of a 10% ointment based on polyethylene oxide. In this case, a comparative study of the effectiveness of the epoch compared with the effectiveness of the treatment of representative groups of patients in terms of area and depth of frostbite was carried out.

Epohin was used in the treatment of 12 patients with frostbite of the fingers of the lower and upper extremities. Of these, 4 patients had frostbite of the 2nd degree, 8 patients had frostbite of the 3-4th degree. The comparison group consisted of 20 patients.

To assess the effectiveness of the complex therapy, clinical, cytological, histological studies were performed, as well as an assessment of microcirculation in the tissues. The results of the study showed that with traditional treatment, the healing of long-healing wounds is characterized by the formation of inferior granulation tissue with microcirculation disorders, edema, chronic inflammatory infiltration and purulent-necrotic tissue changes, wound infection, inhibition of fibroblast and epithelial proliferation.

The use of epochin in the form of an ointment stimulated a macrophage reaction, enhanced the proliferation of fibroblasts and epithelium, and reduced wound infection.

Wound cleansing (necrosis rejection, the formation of clear demarcation) was achieved on average by 15.8 days from the start of treatment (in the comparison group - to 21.3 days), granulation by 19.4 days (in the comparison group - to 26.5 days), the appearance of epithelization - by 14.8 days (in the comparison group - by 19.2 days) and the final healing of wounds - by 23.7 days (in the comparison group - by 29.8 days) from the start of treatment, which allowed to reduce the length of stay of patients in a hospital bed from 27.3 to 19.2 days.

The early formation of the demarcation barrier made it possible to perform finger amputations on average 13.4 days from the start of treatment (in the comparison group - 19.1 days). In all cases, after applying the epochin in the form of a 10% ointment before surgery, the postoperative stumps healed by first intention without any signs of purulent inflammation.

Allergic reactions of a general and local nature when using 10% EPOCHIN ointment were not noted. There are no contraindications to the use of the drug.

As a result, it was found that the local use of epochin in the form of a 10% ointment in the treatment of patients with cold injury (frostbite) stimulates a macrophage reaction, improves trophism of damaged tissues, reduces wound infection, accelerates its cleaning, stimulates reparative processes in the treatment of patients with superficial (2 tbsp) frostbite allows you to reduce the healing time of wounds by an average of 6.1 days, while treating patients with deep (3-4 tbsp.) Frostbite allows you to reduce the time of preoperative preparation in an average of 5.7 days, and when combined with ingestion of 0.5 g 3 times a day (in the form of a powder dissolved in water or other liquids) - for 6.4 days.

Example 10. Clinical trials of dietary supplement “EPOFEN” for patients with purulent surgical infection were carried out in the purulent surgery department of the Central Clinical Hospital named after ON. Semashko Ministry of Railways of the Russian Federation on the basis of the Department of Surgical Diseases and New Endosurgical Technologies of the Moscow State Medical and Dental University. Epofen was used in the form of a powder of 0.5 g for oral administration. The course of treatment was 10 days.

Upon admission, all patients underwent examination according to the generally accepted scheme, complex treatment was prescribed aimed at normalizing metabolic processes and homeostasis, correcting the immune status, resolving perifocal inflammatory changes in the tissues, cleansing the wound and its healing. The treatment was carried out in combination with the already proven methods - surface treatment of ulcers (wounds) with low-frequency ultrasound, vacuum, stepwise mechanical necrectomy and treatment of wounds and surrounding tissues with infrared laser radiation. At the same time, a comparative study of the effectiveness of epofen was carried out according to the results of treatment of representative groups of patients according to the area and depth of ulcers (wounds), the severity of perifocal inflammation and the severity of microcirculation disorders. Epofen was used in the treatment of 67 patients aged 22 to 85 years, including 39 women and 28 men, who made up the main group. The comparison group consisted of 70 patients whose treatment was carried out by traditional methods.

51 (76.1%) patients on the day of admission or after a brief preoperative preparation underwent surgical treatment of a purulent-necrotic focus. Subsequently, staged necrectomy was performed in 10 patients. Local treatment was carried out using a combination of immobilized enzymes and 0.5% sodium hypochlorite solution, wound treatment with low-frequency ultrasound, and low-frequency laser radiation.

Analysis of objective data in the studied groups showed the following. In the main group, intoxication symptoms stopped on 2.1-1.3 days (comparison group - on 4.1 ± 1.4 days), the temperature gradient normalized on 4.4 ± 1.5 days (comparison group - on 5, 5 ± 2.1 days), wound cleansing - on 8.9 ± 1.7 days (comparison group - on 12.6 ± 1.8 days), discharge home - on 12.3 ± 1.3 days (comparison group - on 16.4 ± 1.2 days).

A study of laboratory blood parameters before and after prescribing the drug revealed an increase in hemoglobin level by 11 ± 0.8 g / l in 52 (77.6%) patients in the main group. In the comparison group, a decrease in hemoglobin level by an average of 6 ± 1.3 g / l was noted in 28 (40%) patients.

The cancellation of antibacterial drugs in the main group was carried out on 5.1 ± 1.3 days, while in the control group on 8.3 ± 1.1 days.

The study of the immune status revealed that on the 10th day of treatment the number of T-lymphocytes in patients of the main group reached the norm (64.1 ± 1.1%), an increase in the number of T-helpers (57.5 ± 1.1%) and a decrease level of T-suppressors (7.2 ± 1.5%). In patients of the control group, the number of T-lymphocytes was lower (56.4 ± 1.7%), the number of T-helpers was 53.4 ± 1.4, and the number of T-suppressors was 9.9 ± 1.8%.

Thus, according to the immunological examination of patients revealed a pronounced immunomodulating effect after treatment with epophene in patients of the main group compared with the control group.

Assessment of the degree of toxemia was carried out according to the leukocyte intoxication index using the formula Ya.Ya. Kalf-Kallifa. Assessing the degree of toxemia revealed a complete normalization of the leukocyte intoxication index in 58 (86.6%) patients of the main subgroup (1.00 conventional units), while remaining on average at 1.42 ± 0.21 standard. units the index of leukocyte intoxication index in the comparison group in 64 (91.4%) testified to the preservation of endogenous intoxication syndrome.

Allergic reactions, side effects of epophen during the study were not identified. There are no contraindications to the use of the drug.

The inclusion of epofen in the complex therapy of patients with abscesses and phlegmons of various localization, infected wounds provides an impact on the main mechanisms of the development of the disease and has a positive effect on humoral and cellular immunity, increased nonspecific resistance, and the course of reparative processes. Combined therapy with epofen allows reducing the duration of the course of antibacterial therapy by 3.2 days and, thus, the consumption of expensive antibacterial drugs, and the duration of inpatient treatment - by 4.1 days.

Example 11. The effect of the composition of Epofen on the tissues of the oral cavity was studied in the framework of clinical trials conducted at the outpatient base of MSMSU. The treatment was carried out on 57 patients of both sexes. The control group consisted of 20 patients.

Of the 57 patients: 17 - with periodontal diseases, 8 - with gingivitis, 5 - with bleeding after tooth extraction, 5 - with alveolitis (inflammation of the socket after complex removal), 15 - with pulpitis and periodontitis, 7 - other diseases of the oral mucosa .

The treatment of this group was carried out only by the drug according to the following method. After sanitation, the generally accepted method was rinsed with a 3% aqueous solution of the oral preparation. After that, turundas, tampons or applications were applied to the affected areas with 6% emulsion of the Epofen preparation and 0.5 g of the powder of the Epofen-A preparation inside as a solution of the Zevita drink containing 5% solution of the composition or the Extreme chocolate bar containing 0.15% Epochin.

Treatment continued depending on the diagnosis and severity of the disease. A positive effect was observed within 1-2 days after the start of treatment. The drug was well tolerated by patients, there were no side effects. Burning, itching, pain, bleeding, suppuration from the gums stopped during the day, swelling was eliminated. The general condition of patients improved, the temperature returned to normal on the second day, immunological parameters showed a tendency to normalize.

Compared with the control group, the treatment time was reduced by 2 times.

It was shown that the drug practically replaces complex drug treatment, replaces antibacterial, anti-inflammatory and etiotropic therapy, and also has a hemostatic, wound healing effect, is an immunomodulator and improves the general condition, and increases working capacity.

Tests have shown that the claimed composition is promising as a means of restoring the activity of the skin due to wounds, diseases, aging, to improve the quality of healthy skin. Its use is promising for improving the functioning of the gums, provides the normalization of the barrier and metabolic function of the skin in mammals, including humans, and birds.

Claims (3)

1. Therapeutic cosmetic product based on polyoxyphenylenes, characterized in that as polyoxyphenylenes it contains 2- (1-hydroxy-4-hydroxyphenylene) benzoquinone or 4-hydroxyphenylene-2,4-dioxo-benzene and additionally hydroquinone in a weight ratio of 2 - (1-hydroxy-4-hydroxyphenylene) benzoquinone or 4-hydroxyphenylene-2,4-dioxo-benzene: hydroquinone from 99: 1 to 1:99. 2. The drug for the treatment of damage to the external tissues of the body, including the cosmetic cosmetic product according to claim 1 in a daily dose of from 0.5 to 10 g. 3. The drug according to claim 2, characterized in that it is used in the form of a 0.05-20% solution or emulsion.