RU2788332C1 - Ointment for the treatment of traumatic damage to the skin - Google Patents

Abstract

FIELD: pharmacology and medicine.

SUBSTANCE: invention relates to the field of pharmacology and medicine. Claimed is an ointment for external application to skin tissues, useful in the treatment of accidental traumatic skin injuries, containing petrolatum, triethylene glycol, vaseline oil, lanthanum complex or lanthanum nitrate, lanolin, cetearyl alcohol, allantoin, preservatives and water.

EFFECT: development of a composition of a wound healing, anti-inflammatory and regenerating agent for external use, effective, having increased efficiency at an early stage in order to ensure wound healing by primary intention.

1 cl, 4 tbl, 3 ex

Description

The field of technology to which the invention belongs

The invention relates to the field of pharmacology and medicine. More specifically, it provides an ointment useful in the treatment of accidental traumatic skin injuries (abrasions, cuts and puncture wounds) and burns (thermal, chemical and combined), exhibiting complex antibacterial and regenerative effects when applied directly to the wound area.

State of the art

The resistance of microorganisms to most modern means of treating injuries of the skin causes an urgent need to create drugs with maximum efficiency and a wide range of biocidal action. It is also desirable that the drug be effective at all stages of therapy, namely in the healing of the injury wound and in restoring the skin to its pre-injury state. This can be achieved by means of multi-component action.

Various compositions are known from the prior art with the main active ingredients - a lanthanum complex or lanthanum nitrate, which has an antimicrobial effect and is also involved in the process of skin tissue regeneration, and allantoin, which stimulates reparative processes in skin tissues.

The lanthanum complex is a complex compound of triethylene glycol with lanthanum nitrate hexahydrate and has the following formula:

glycerol 30.0 - 63.0 polyethylene glycol-155 2.0 - 15.0 triethylene glycol 10.0 - 37.8 ethanol 5.8 - 16.2 sodium or potassium hydroxide 0.7 - 1.3 nitrate or hydrochloride salt of lanthanum, or cerium, or praseodymium, or neodymium 1.8 - 2.2 water rest

It is a white crystalline powder, odorless, hygroscopic.

From the prior art (RU 2038072, publ. 06/27/1995) a cream is known for protecting the skin from chemicals containing glycerin, ethyl alcohol and water, characterized in that it additionally contains polyethylene glycol 155, triethylene glycol, sodium or potassium hydroxide, nitrate or hydrochloric acid salt lanthanum, or cerium, or praseodymium, or neodymium in the following ratio, wt. %:

As follows from the description of the invention, the proposed cream can be useful as a cosmetic product for skin care of hands, face, neck, etc. and can be used to protect the skin from the harmful effects of pesticides in agriculture, the chemical industry, and everyday life, such as organophosphorus pesticides during their skin-resorptive penetration.

An agent of similar purpose based on lanthanum salts is proposed in the description of the invention to patent RU 2159105 (published on November 20, 2000). The composition has the following composition, wt.%:

glycerol 30 - 60 polyethylene oxide (M. m. 3000 - 6500) 12 - 15 triethylene glycol 10 - 35 ethanol 5 - 15 potassium or sodium hydroxide 0.5 - 1.5 lanthanum (III) in the form of hydrochloric acid or nitrate salt 1.5 - 2 succinic acid 0.2 - 2 hyaluronic acid 0.05 - 0.5 distilled water up to 100

In the composition, triethylene glycol and polyoxaalkylene act as promoters, and glycerol is a softener.

To obtain the composition, a solution of a lanthanum salt in aqueous triethylene glycol, an alkali solution in ethyl alcohol and a mixture of glycerin, triethylene glycol and polyoxaalkylene are prepared separately, combined at elevated temperature and stirring, succinic acid is added, cooled to room temperature, and hyaluronic acid is added at room temperature before packaging and homogenized by stirring at low shear forces.

In the description of the invention to patent RU 2124357 (publ. 01/10/1999) a method for treating wound surfaces is disclosed, including washing, irrigation and dressing, characterized in that at the stage of inflammation, the Eplan liniment is used with the following composition, wt.%:

lanthanum nitrate hexahydrate in terms of lanthanum 2.2 - 2.8 triethylene glycol 60 - 64 ethyl carbitol 23 - 27 glycerol 1.8 - 2.2 sodium hydroxide 0.7 - 0.9 water rest

and at the stage of reparation, the Eplan-M ointment of the following composition is applied to the wound surface, wt.%:

Liniment "Eplan" 80 - 85 Polyethylene glycol (PEG-115) 10 - 20

The disadvantage of the known solution is the alkaline environment created on the skin, which in the case of complicated injuries can cause damage to the deeper layers of the skin, leading to the formation of coarse scar tissue. In addition, an alkaline environment promotes a partial transition of lanthanum nitrate to the form of an oxocation, which reduces the equilibrium concentration of bactericidal effective adducts of lanthanum with polyhydroxyalkyl compounds (triethylene glycol, glycerin).

As a further development of the technical solution known from RU 2124357, we can consider a pharmaceutical composition in accordance with the patent RU 2203035 (publ. 04/27/2003), which has disinfectant, sporocidal and wound healing properties, which includes the chemotherapeutic agent "Eplan", and surface-active a substance which is used as a quaternary ammonium compound of the general formula

[RR ₁ N ⁺ R ₂ R ₃ ]X-,

where R, R ₁ , R ₂ , R ₃ are substituents selected from the group consisting mainly of hydrogen, alkyl, highly fluorinated alkyl, cycloalkyl, aryl, phenyl, phenylalkyl and pyridine,

X - OH, halogen or alkyl phosphite, while the quaternary ammonium compound is preferably cetyltrimethylammonium chloride of the formula [CH ₃ (CH ₂ ) ₁₄ CH ₂ N ⁺ (CH ₃ ) ₃ ]·Cl-, and the content of surfactant in the composition is from 0.01 to 5 wt.%, which has the same disadvantage, which consists in a sufficiently high content of alkali.

Also known are other compositions and methods of their use for the treatment of wound surfaces, which contain a salt of rare earth metals. In particular, patent RU 2144816 (publ. 27.01.2000) proposes a wound healing composition containing an active principle, a fatty base containing glycerin, and excipients, characterized in that it contains soluble lanthanide salts as an active principle, such as nitrate or lanthanum hydrochloride, "Olifen" (sodium poly-(2,5-dihydroxyphenylene)-4-thiosulfonate), as part of the fatty base - triethylene glycol and polyethylene glycol-115, as excipients - alkali, fragrance and alcohol-containing solvent (20 - 50% th aqueous solution of ethyl alcohol) in the following ratio of ingredients, wt.%:

lanthanide salts 0.5 - 1.0 "Olifen" 0.3 - 2.0 dioxidine 0.2 - 1.0 triethylene glycol 12.0 - 60.0 glycerol 2.0 - 30.0 polyethylene glycol-115 20.0 - 35.0 fragrance 0.01 - 1.5 alkali 0.7 - 1.5 solvent rest

In accordance with patent RU 2210356 (publ. 20.08.2003) a therapeutic and prophylactic cream for protecting any skin type is proposed, containing triethylene glycol, nitrate or hydrochloric acid salt of lanthanum or cerium, glycerin, polyethylene glycol-115, ethyl alcohol, potassium hydroxide and distilled water, characterized in that it additionally contains ethylene glycol, pine nut oil and/or milk thistle, vitamins A, E, C, F in the following ratio, wt. %:

triethylene glycol 30.0-45.0 nitrate or hydrochloride salt of lanthanum or cerium 0.4-0.8 glycerol 10.0-25.0 polyethylene glycol-115 10.0-20.0 ethylene glycol 10.0-16.0 ethanol 8.0-12.0 potassium hydroxide 0.3-0.7 pine nut and/or milk thistle oil 0.3-0.7 vitamins: AND 0.04-0.08 E, F 0.7-1.3 FROM 4-12 analgin 0.3-0.6 distilled water rest

Patent RU 2675764 (published on December 24, 2018) discloses a pharmaceutical composition for a similar purpose, which has the composition (wt.%):

triethylene glycol 35.0-50.0 nitrate or hydrochloride salt of lanthanum or cerium 0.4-0.8 glycerol 6.0-10.0 polyethylene glycol-115 10.0-20.0 propylene glycol 1.0-4.0 ethanol 3.0-6.0 potassium hydroxide 0.3-0.5 pine nut or milk thistle oil 0.3-0.7 hyaluronic acid 2.0-4.0 diazolin 4.0-5.0 glycyram 1.0-4.0 vitamins: AND 0.04-0.08 E, F 0.7-1.3 FROM 0.3-0.6 analgin 0.3-0.6 distilled water rest

The disadvantage of these inventions is the presence of alcohol, which can dry and irritate the skin, disrupt its protective function and worsen its condition.

In the description of the invention to the patent RU 2381801 (publ. 20.02.2010) a method for obtaining a drug for external use is disclosed, including the following steps:

a) obtaining an aqueous solution of lanthanum nitrate hexahydrate by reacting lanthanum oxide and nitric acid at a molar ratio of lanthanum oxide and nitric acid 1: (5-6) at a temperature of from about 60 ° C to about 80 ° C with exposure of the reaction mass for 2- 3 h;

b) dissolution of the obtained product in triethylene glycol at a molar ratio of these components 1:(22-25) with exposure at a temperature of 35-45°C for 1-2 hours;

c) adding glycerin to the solution from stage b) in a molar ratio of glycerol: lanthanum nitrate 1: (1.3-1.5) and the simultaneous addition of ethyl alcohol in a molar ratio of lanthanum nitrate: ethyl alcohol 1: (1.5-1, 7);

d) preparation of an alkaline solution of ethyl carbitol (2-(2-ethoxy) ethanol by adding a 40-45% aqueous solution of sodium hydroxide or potassium hydroxide to pH 6.5-7.4 at a temperature of 18-32 ° C with keeping the reaction mass for 0 ,5-1.5 h, ethyl carbitol is taken in a molar ratio of 1: (9-11);

e) portionwise addition of an alkaline solution of ethyl carbitol to the product prepared in step c) for 2-2.5 hours and exposure at a temperature of 20-32°C for 14-16 hours to obtain the target drug.

An ointment containing 15% polyethylene glycol PEG-115 can be prepared from the obtained medicinal product, which is added for 1-2 hours at a temperature of 45-68°C and intensive stirring, after which the ointment is kept at a temperature of 40-65°C until a constant viscosity and packaged at a temperature of 45-65°C.

Patent RU 2275184 (published on April 27, 2006) discloses an agent that can be used to protect the skin from the harmful effects of the external environment, incl. from the harmful effects of production factors, for the prevention of skin diseases, protection of the skin from pathogenic microorganisms, dangerous and especially dangerous infections, for healing skin lesions, as a regenerating agent containing polyethylene glycol with a high degree of polymerization, glycerin, lanthanum nitrate, sodium hydroxide and water, characterized in that it additionally contains the substance "Panavir" (polysaccharides of Solanum tuberosum shoots), polyethylene glycol with a degree of polymerization n=4-8, and as polyethylene glycol with a high degree of polymerization it contains polyethylene glycol with a degree of polymerization n=32-800 in the following ratio of components, wt.%:

glycerol 15.0-30.0 polyethylene glycol (n = 32-800) 10.0-25.0 polyethylene glycol (n = 4-8) 20.0-40.0 sodium or potassium hydroxide 0.1-0.7 lanthanum nitrate 1.8-2.2 "Panavir" 0.0001-0.0003 water rest

which may additionally contain ethyl or isopropyl alcohol in an amount of 0.1-1.5 wt.%.

Compositions of a wound healing gel are known, which contain allantoin. So, in patent RU 2603459 (publ. 11/27/2016) a wound healing gel for external use of the following composition is proposed, wt. %:

sodium alginate 2.0-5.0; taurine 4.0; allantoin 0.5; glycerol 6.5; nipagin 0.1; purified water up to 100.0

On a mouse model of experimental skin injury (male adult outbred mice weighing 18-25 g, a round skin flap of 60 mm ² was removed on the back in the neck, an open wound), the half-healing time of the wound was found to be about 7 days. Complete healing occurred in 12-13 days. Healing was not accompanied by inflammation and necrosis of the skin.

Another wound healing gel for external use, disclosed in the description of the invention to patent RU 2611400 (publ. 21.02.2017), contains the following amounts of components, wt.%:

aurine 4.0; chitosan 1.0-4.0; allantoin 0.5; acetic acid up to a pH value of 3.6-6.0; purified water rest

Chitosan forms a bacteriostatic film over the wound surface, which reduces the likelihood of inflammatory complications. However, for the dissolution of chitosan and subsequent gelation, an acidic environment is required, which causes some difficulty in working with chitosan and a lower pH value of the composition compared to the pH of healthy skin. A common disadvantage of gel forms is their significant absorption by the skin. For this reason, they are less effective than creams and ointments that form a denser layer.

Patent BY 14418 (publ. 30.08.2009) discloses a preparation of antimicrobial and wound healing action, including lanthanum nitrate in the following ratio, wt. %:

lanthanum nitrate 1.0-15.0; polyethylene glycol-400 53.0-85.0; solvent 3.0-7.5; aerosil-300 8.5-17.0; purified water rest

To obtain the drug, lanthanum nitrate is dissolved in a polyethylene glycol-400 medium at 15-25°C in the presence of a mixture of purified water and at least one solvent selected from the group including ethyl alcohol, ethyl carbitol and isopropanol, Aerosil-300 is introduced into the resulting solution and mix until gelatinous. Aerosil, used in a sufficiently large amount as a thickener, additionally prevents the formation of a strong film, which does not help to isolate the wound from contamination by pathogenic microorganisms.

As the closest analogues, the authors selected compositions disclosed in the description of the invention to patent RU 2124357, namely, a composition for treating wound and burn surfaces containing lanthanum nitrate hexahydrate, and a wound healing gel disclosed in RU 2603459, which contains allantoin.

From the prior art, various types of action of allantoin on damaged tissues of the skin and subcutaneous layers are known. So, in the publication of Paller A., Nardi R., Do H., Reha A., Viereck C., Castelli J. An investigation into multifaceted mechanisms of action of allantoin in wound healing / J. Am. Acad. Derm . Vol. 76. Iss. 6. Suppl. 1 (201 7 ). P. AB40, allantoin has been shown to have a variety of properties and effects that facilitate the transition of a wound from an inflammatory to a proliferative state, including antioxidant and anti-inflammatory properties, direct antimicrobial activity, and keratolytic activity that promotes wound healing. Allantoin has been found to promote healthy tissue proliferation by stimulating cell proliferation and extracellular matrix synthesis. Allantoin may also play a role in tissue formation and differentiation, in particular in stimulating the development of granulation tissue and epithelialization. Allantoin may also reduce scarring by preventing epidural fibrosis, as tested in a rat model.

Araujo LU, Grabe-Guimaraes A., Mosqueira VC, Carneiro CM, Silva-Barcellos NM Profile of wound healing process induced by allantoin / Acta Cir. Bras . 2010 Oct. 25(5). pp. 460-466 for three random samples of female Wistar rats (n = 20 for each sample), the profiles of the wound healing process induced by allantoin included in a lotion containing an oil-water 5% allantoin emulsion were characterized in the control group (without treatment ) and with topical application for 14 days of a lotion containing only excipients. The area of the wound was assessed planimetrically, and qualitative and quantitative histological analyzes were also performed. The obtained results indicate that the mechanism of wound healing induced by allantoin includes regulation of the inflammatory response and stimulation of fibroblast proliferation and extracellular matrix synthesis, which improves wound healing and accelerates skin recovery to its original state.

According to the authors of the claimed invention, the average specialist in this field is not able to come to the proposed technical solution, based solely on the well-known disinfectant, sporicidal, bactericidal and anti-inflammatory effects of lanthanum (III) salts in combination with aliphatic polyhydroxy compounds, as well as the listed types of activity of allantoin, known from the prior art, as well as on the totality of the general knowledge available to him.

Disclosure of the essence of the invention

According to the information given in the review by V.I. Evdokimov, A.S. Kourov. Genesis of scientific research on burn injury (analysis of domestic journal articles in 2005-2017) / Medico - biological and socio - psychological problems of safety in emergency situations . 2018. No. 4. P. 108-109 in 2005, there were 255 patients with thermal and chemical burns per 100 thousand people of the Russian population. In 2015, they decreased by 25.4% to 190 per 100 thousand of the population. The share of burns in the structure of all injuries is at the level of 2 - 3%.

In the Sen C.K. Human Wounds and Its Burden: An Updated Compendium of Estimates / Adv. Wound Care (2019).8(2). R. 42 reports that in 2014, acute injuries in the United States resulted in 17.2 million clinic visits. Statistics on acute and chronic wounds provided by Wounds UK (UK) show that the annual prevalence of wounds increased by 71% between 2012/2013 and 2017/2018. The cost of treating patients increased by 48% in real terms. The National Health Society, according to its own data, reports 3.8 million patients with various types of wounds.

Thus, given the widespread occurrence of accidental traumatic skin injuries, the problems of their sanitation and treatment are relevant all over the world, especially in geriatric and pediatric practice, as well as in cases of reduced immunity that impede wound healing.

The technical objective of the invention is to develop a composition of a wound healing, anti-inflammatory and regenerating agent for external use, effective, having increased efficiency at an early stage in order to ensure wound healing by primary intention.

The technical result is the expansion of the arsenal of agents for the treatment and treatment of skin injuries, which accelerate the processes of wound healing due to the synergistic effect of a salt or a complex of lanthanum (III) and allantoin.

In accordance with the claimed invention, an ointment for external application to skin tissues damaged due to injuries, such as abrasions, cut and puncture wounds, as well as thermal, chemical and combined burns, containing, in mass. %:

petrolatum 50-60 triethylene glycol 10-15; Vaseline oil 6-8 lanthanum complex or lanthanum nitrate 4-7 lanolin 4-5 cetearyl alcohol 2-3 allantoin 0.2-0.5 preservative 0.05-0.2 water up to 100

Implementation of the invention

The invention will be further illustrated by examples of its implementation in the form of variants of the composition of the claimed ointment for external application, confirming its industrial applicability with the achievement of the claimed technical result, as well as studies of the effectiveness of the ointment for wound healing on experimental models of excisional and burn wounds. During the study, it was found that the proposed ointment has a particularly beneficial effect on the reparative process of both excisional and burn wounds in the early stages, which is important for reducing the likelihood of complications caused by contamination and reproduction of pathogenic microorganisms in the wound.

Example 1 Preparation of an ointment according to the invention

To prepare the fatty phase, weighed portions of vaseline, vaseline oil, lanolin, cetearyl alcohol, taken in accordance with each of the options for ointment 1-3, are added to a melting vessel placed in a heated water bath and melted at a temperature of 85°C. After melting all the components, the mixture is continuously stirred.

Allantoin is dissolved in water at 45°C. Separately dissolve the lanthanum complex or lanthanum nitrate in triethylene glycol with stirring at a temperature of 60°C. The resulting solution of the lanthanum complex or lanthanum nitrate is introduced into the fat phase with vigorous stirring. Then a pre-prepared preservative solution (propylparaben, methylparaben or a mixture thereof) in triethylene glycol is added. The allantoin solution is introduced into the system after it has been cooled to 45°C with vigorous stirring.

In accordance with the invention, variants of the proposed ointment are prepared with the ratios of components (wt.%):

Component Option 1 Option 2 Option 3 Petrolatum 50.8 56.2 58.5 Vaseline oil 6.5 7.8 8.0 Lanolin 4.2 4.8 5.0 Cetearyl alcohol 2.3 2.6 2.9 Allantoin 0.2 0.3 0.5 Lanthanum complex or lanthanum nitrate 4.2 5.1 6.8 triethylene glycol 10.6 12.9 14.5 Methylparaben 0.05 absent absent Propylparaben absent 0.1 absent Methylparaben + propylparaben absent absent 0.1+0.1 Water up to 100 up to 100 up to 100

Example 2 Excision Wound Healing Study

The study is carried out on mature female outbred rats. An excisional wound with an area of approximately 3.8 cm ² is created by circular excision of a skin flap with a radius of 1.0±0.1 cm along with subcutaneous fat. After creating experimental wounds, the preparations are applied 3 times a day for 27 days. The research results are presented in Table 1, and the numerical data for their comparative analysis are given in Table 2.

From the data in Table 2, it is obvious that the ointments according to the invention have the most pronounced effect at the stage of wound healing up to day 6 of the study, while their effectiveness is approximately 120-220% in relation to the control group and 190-360% in relation to the group mice treated with Eplan. In the future, the relative effectiveness of the proposed compositions of the ointment is reduced compared with the control by day 9, and compared with the group receiving "Eplan", by day 20, exceeding the reference values by 5-15%. In the second half of the study (days 13-27), the proposed variants of ointment 1-3, as well as the drug "Eplan" do not accelerate tissue regeneration.

Example 3. Study of the healing of thermal burn wounds

The study is carried out on mature female outbred rats. A thermal burn is caused by applying a PS2-12×100 glass test tube (manufactured by MiniMed LLP, RF) filled with boiling water (temperature ~100°C) to the skin of the back, holding it for 45 seconds. After creating experimental wounds with an area of approximately 3.0 cm ² drugs are applied 3 times a day for 27 days. The research results are presented in Table 3, and the numerical data for their comparative analysis are given in Table 4.

From the data of Table 4 it follows that the ointments in accordance with the invention are most effective at the stage of wound healing: the maximum efficiency by day 9 of the study is approximately 170-230% in relation to the control group and 400-570% in relation to the group of mice treated with the drug "Eplan". In the future, the relative effectiveness of the proposed compositions of the ointment decreases, reaching levels that are not statistically significantly different from all three comparison groups.

In terms of efficiency relative to the group of mice treated with the drug "D-Panthenol" (manufactured by Ozon LLC, RF) of the composition:

D-panthenol 5.00 g petrolatum 27.00 g liquid paraffin 10.00 g lanolin 17.00 g cholesterol 0.50 g isopropyl myristate 3.00 g methyl parahydroxybenzoate 0.07 g propyl parahydroxybenzoate 0.03 g water 37.40 g

ointments in accordance with the invention do not show statistically significant differences during the entire time of the study.

Table 1. Healing Efficiency Experimental of excisional wounds with the declared ointment in comparison with the control group and the drug "Eplan" Day Group 21. Control Group 22. "Eplan" Group 23. Ointment. Option 1 Group 24. Ointment. Option 2 Group 25. Ointment. Option 3 S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % 6 3.27 14.0 3.47 8.7 3.17 16.6 2.62 31.1 2.69 29.2 nine 1.13 70.3 1.90 50.0 1.09 71.3 0.94 75.3 0.98 74.2 13 0.64 83.2 0.89 76.6 0.62 83.7 0.58 84.7 0.60 84.2 sixteen 0.36 90.5 0.82 78.4 0.47 87.6 0.40 89.5 0.43 88.7 20 0.20 94.7 0.70 81.6 0.25 93.4 0.23 94.0 0.24 93.7 23 0.07 98.2 0.26 93.2 0.19 95.0 0.13 96.6 0.15 96.0 27 0.06 98.4 0.08 97.9 0.08 97.9 0.03 99.2 0.03 99.2 Table 2. The effectiveness of the claimed ointment in comparison with the control group and the drug "Eplan" in the healing of excisional wounds Day Efficiency (%): compared to Group 21 compared to Group 22 "Eplan" Ointment. Option 1 Ointment. Option 2 Ointment. Option 3 Ointment. Option 1 Ointment. Option 2 Ointment. Option 3 6 62 119 222 209 191 357 336 nine 71 101 107 105 143 151 148 13 92 101 102 101 109 111 110 sixteen 87 97 99 98 112 114 113 20 86 99 99 99 114 115 115 23 95 97 98 98 102 104 103 27 99 99 101 101 one hundred 101 101

Table 3. Efficiency of healing of experimental burns with the claimed ointment in comparison with the control group, Eplan and D-panthenol Day Group 31. Control Group 32. "Eplan" Group 33.
D-Panthenol Group 34.
Ointment. Option 1 Group 35.
Ointment. Option 2 Group 36
Ointment. Option 3 S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % S _R , cm ² S _W / S _R , % 6 4.61±0.31 121.3 4.86±0.27 127.9 3.99±0.24 105.0 4.19±0.32 110.3 4.13±0.36 108.7 4.12±0.28 108.4 nine 3.41±0.10 10.3 3.64±0.14 4.2 2.87±0.25 24.5 3.15±0.20 17.1 2.90±0.16 23.7 2.89±0.19 23.9 13 1.90±0.25 50.0 3.09±0.12 18.7 1.71±0.36 55.0 1.98±0.23 47.9 1.92±0.22 49.5 1.95±0.30 48.7 sixteen 1.57±0.16 58.7 1.57±0.30 58.7 1.12±0.36 70.5 1.48±0.35 61.0 1.34±0.39 64.7 1.30±0.27 65.8 20 0.78±0.10 79.5 0.91±0.19 76.1 0.63±0.25 81.4 0.90±0.12 76.3 0.85±0.10 77.6 0.84±0.14 77.9 23 0.48±0.08 87.4 0.45±0.07 88.2 0.33±0.15 91.3 0.62±0.17 83.7 0.60±0.15 84.2 0.62±0.10 83.7 27 0.28±0.02 92.6 0.29±0.10 92.4 0.20±0.08 94.8 0.31±0.06 91.8 0.18±0.09 95.3 0.21±0.07 94.5

Table 4. The effectiveness of the claimed ointment in comparison with the control group, the drug "Eplan" and D-panthenol in the healing of burns Day Efficiency (%): compared to Group 31 compared to Group 32 compared to Group 33 eplan D-Panthenol Ointment. Option 1 Ointment. Option 2 Ointment. Option 3 D-Panthenol Ointment. Option 1 Ointment. Option 2 Ointment. Option 3 Ointment. Option 1 Ointment. Option 2 Ointment. Option 3 6 105 87 91 90 89 82 86 85 85 105 104 103 nine 41 238 166 230 232 583 407 564 569 70 97 98 13 37 110 96 99 97 294 256 265 260 87 90 89 sixteen one hundred 120 104 110 112 120 104 110 112 87 92 93 20 96 102 96 98 98 107 one hundred 102 102 94 95 96 23 101 104 96 96 96 104 95 95 95 92 92 92 27 one hundred 102 99 103 102 103 99 103 102 97 101 one hundred

Claims (2)

Ointment for external application to skin tissues damaged due to injuries, such as abrasions, cut and stab wounds, as well as thermal, chemical and combined burns, containing, in mass. %: Petrolatum 50-60 triethylene glycol 10-15 Vaseline oil 6-8 Lanthanum complex or lanthanum nitrate 4-7 Lanolin 4-5 Cetearyl alcohol 2-3 Allantoin 0.2-0.5 preservative 0.05-0.2 Water up to 100