RU2552790C1 - Burn-treating composition - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: burn-treating composition for local application based on Vaseline lanolin, or carbopol, or hydrogel; as an active substance, the composition contains 5% dry extract of the herbal raw material big-flowered self and self-heal containing 60% rosmarinic acid.

EFFECT: above composition is effective for treating burns; it is non-toxic.

7 tbl, 10 ex, 12 dwg

Description

The invention relates to pharmaceutical production, namely to pharmaceutical compositions for topical use, intended for the treatment of thermal skin burns. Compositions for topical application with anti-inflammatory, wound healing and anti-burn effects are proposed.

Superficial burns account for an average of 70-80% of all burns (Burns. World Health Organization, Fact Sheet No. 365, 2012). Treatment of patients with these burns is carried out conservatively using various medicinal compositions. Currently, many modern medicines are used to treat burns, the effect of which is to prevent the development of wound infection, to regenerate tissues and to reduce inflammatory processes.

Solutions of rivanol, furacilin, dimexide, chlorhexidine abigluconate, ethonia, miramistin, iodine preparations - betadine, iodonol, 1% iodopirone, iodovidone, which have a wide spectrum of antibacterial action, are known in the local treatment of burns of the II and IIIa degrees. Widely used in the treatment of burn wounds, levomekol, levosin, levonorsin, dioxicol, dioxid ointment, depantol, methyluracil. The pronounced antimicrobial, dehydrating, anti-inflammatory, necrolytic and analgesic effect of such ointments makes them the drugs of choice for the treatment of burn wounds, including with border burns of the IIIa degree. Among foreign drugs on a water-soluble basis, solcoseryl, sulfamilon, flamazine, contractubex are widely used. In addition to the advantages, synthetic drugs used in the treatment of superficial burns have disadvantages: they have a sensitizing effect, allergic and irritating effects, affect the reproductive functions of the body (Kuzin M.I., Sologub V.K., Yudenich V.V. Burn disease. M .: Medicine. 1982. 160 s .; www.rlsnet.ru Radar station - an encyclopedia of drugs and pharmaceutical assortment goods; Mashkovsky MD. Medicines: a guide for doctors in 2 volumes, M .: Medicine. 2010. 1216) .

It is known that raw materials of plant origin have efficacy, safety, minimal risk of an allergic effect, practically no side effects, less toxic. Widely used as a medicinal plant material - seed oil of the plant of milk thistle (Lebedev A.A., Simerzina L.V., Lebedev P.A. Means with wound healing and hepatoprotective action // RF Patent 2014840, publ. 30.06.1994) , sea buckthorn oil (Radbil B.A., Kushnir CR, Saratikov A.S., Stolyarets V.I. Medicinal product of wound healing, anti-burn and anti-inflammatory action // RF Patent 2111760, publ. 05.27.1998), burdock root and chamomile flowers (Maleeva G.L. Anti-burn agent and method for its preparation // P patent of the Russian Federation 2159628, publ. 11/27/2000), dandelion oil and chamomile oil (Gaisanova L.I. Gaisanova balm with wound healing, anti-inflammatory and anti-burn effects // Patent of the Russian Federation 2337702, publ. 10.11.2008). However, obtaining oil is a costly and lengthy process.

The closest technical solution to the claimed invention, selected as a prototype, is a tool for treating burns and wounds, including an aqueous solution of Siberian larch containing 0.002% dihydroquercitin (Ripka V.N., Solodovnikova E.S. / RF patent 2470653, publ. 12/27/2012). The choice of dihydroquercetin for the treatment of burns is associated with its antioxidant activity. However, the highest antioxidant activity among natural antioxidants is characteristic of rosmarinic acid (Brewer MS Natural Antioxidants: Sources, Compounds, Mechanisms of Action, and Potential Applications // Comprehensive Reviews in Food Scienceand Food Safety. 2011. V.10. P.221-247 ; Tepe B. Antioxidant potentials and rosmarinic acid levels of the methanolic extracts of Salvia virgata (Jacq), Salvia staminea (Montbret & Aucher ex Bentham) and Salvia verbenaca (L.) from Turkey // Bioresource Technology. 2008. No. 99. 1584. -1588.).

Plants containing rosmarinic acid in their composition are widely used in pharmacology and the pharmaceutical industry. Rosmarinic acid has a high anti-inflammatory (Al-Sereiti MR, Abu-Amer K.M., Sen P. Pharmacology of rosemary (Rosmarinus officinalis Linn.) And its therapeutic potentials. Indian J. Exper. Biol. 1999. No. 37. P. 124-130.), Anti-allergenic (Ito H., Miyazaki T., Ono M., Sakurai H. Antiallergic activities of rabdosiin and its related compounds: chemical and biochemical evaluations. Bioorganic and Medicinal Chemistry. 1998. V.6. No. 7 P.1051-1056.), Antiviral (Dimitrova Z., Dimov B., Manolova N., Pancheva S., Ilieva D., Shishkov S. Antiherpes effect of Melissa officinalis L. extracts. Ada Microbiol Bulg. 1993. V .29. P.65-72.), Antioxidant (Malencic DJ, Gasic O., Popovic M., Boza P. Screening for antioxidant properties of Salvia reflexa Hornem. Phytother. Res. 2000. V.14. P.546- 548.) activity. The high content of rosmarinic acid in plants Prunella grandiflora L. (black-headed large-flowered) and Prunella vulgaris (common black-headed) (Alekseeva L.I., Bolotnik E.V. Rosmarinic acid and antioxidant activity of Prunella grandiflora and Prunella vulgaris (Lamiaceae) // Plant World of Asian Russia, 2013, No. 1, pp. 121-125).

The objective of the present invention is to expand the arsenal of drugs in the treatment of burns.

The technical result of the present invention is the creation of a pharmaceutical composition for topical application with anti-burn effect in the absence of acute and chronic toxicity, the absence of local irritating effects, the absence of sensitizing properties of the compositions, as well as the detection of the property to provide a therapeutic effect with a safe effect on the body.

An anti-burn composition for topical application, based on petrolatum, lanolin, or carbopol, or hydrogel, according to the invention, containing as active substance 5% of dry extract from plant material, black-headed large-flowered and black-headed common with 60% rosmarinic acid.

The invention is illustrated by the following notation and images:

- Anti-burn composition M-1 - a mixture of the required number of components (the composition is shown in table 1 of the description), prepared in a special way on the basis of petrolatum-lanolin.

- Anti-burn composition M-2 - a mixture of the required number of components (the composition is shown in table 2 of the description), prepared in a special way on the basis of carbopol.

- Anti-burn composition M-3 - a mixture of the required number of components (the composition is shown in table 3 of the description), prepared in a special way based on hydrocream (composition is shown in table 4 of the description).

Figure 1-9 shows the results of epithelialization of burn wounds in experimental rats using the compositions (example 9 of the description), in particular:

- in Fig. 1 - a photo is presented a day after a thermal burn;

- in Fig. 2 - a photo is presented on the 15th day after the burn on the background of treatment with the composition M-1;

- in Fig. 3 - a photo is presented on the 21st day after a burn against the background of treatment with the composition M-1;

- in Fig. 4 - the photo is presented on the 15th day after the burn on the background of treatment with the composition M-2;

- in Fig. 5 - a photo is presented on the 21st day after a burn against the background of treatment with the composition M-2;

- in Fig. 6 - a photo is presented on the 15th day after the burn on the background of treatment with the composition M-3;

- in Fig. 7 - a photo is presented on the 21st day after a burn against the background of treatment with the composition M-3;

- in Fig. 8 - a photo is presented on the 15th day after a burn in the control group;

- in Fig. 9 - a photo is presented on the 21st day after a burn in the control group.

Figures 10-12 show the results of epithelialization of burn wounds in experimental rats on the background of using the basis for the composition (example 2-4 of the description), in particular:

- in Fig. 10 - a photo is presented on the 21st day after a burn on the background of treatment with the basis for the composition M-1;

- in Fig. 11 - a photo is presented on the 21st day after a burn on the background of treatment with the basis for composition M-2;

- in Fig. 12 - a photo is presented on the 21st day after a burn on the background of treatment with the basis for composition M-3.

The justification of the properties of the newly developed compositions with anti-inflammatory, wound healing and anti-burn effects and their use is confirmed by the following examples:

Example 1. Preparation of a dry extract of a blackhead large-flowered and common blackhead.

The aerial part of the plants of the black-headed large-flowered and the common black-headed plants was dried at room temperature and ground, extracted with 96% ethanol for 24 hours at room temperature. The extract was filtered through a paper filter and dried on a rotary evaporator. Dry samples (100 mg) were extracted with 10 ml of 96% methanol. HPLC of rosmarinic acid was performed on Knauer equipment: Smartline 1000 pump, UV-VIS Smartline 2500 detector using a Kromasil 100-5C18 250 × 4 mm column (Eka Nobel, Sweden) at an elution rate of 0.7 ml / min at a wavelength of 310 nm s using an eluent of water-acetonitrile-phosphoric acid (85: 15: 0.05, by volume). The amount of rosmarinic acid was calculated by absolute calibration. A dry extract containing 60% rosmarinic acid was added to the petrolatum-lanolin mixture, or carbopol, or hydrogel.

Example 2. Preparation of an anti-burn composition based on petrolatum-lanolin M-1.

The required number of components was weighed. Samples of petrolatum and lanolin were placed in a porcelain cup and heated in a water bath. The molten base was transferred to a warm mortar, stirred until cooling, after which a dry blackhead extract, previously ground in an alcohol-water-glycerin mixture (1: 6: 3), was added. All were thoroughly mixed until smooth. The composition of the components is presented in table 1.

Table 1 The composition of the anti-burn composition M-1 Name of components Mass g Petroleum jelly 85.0 Lanolin 7.0 Water 3.0 Dry Blackhead Extract 5,0 Total weight 100.0

Example 3. Preparation of an anti-burn composition based on carbopol M-2. The required number of components was weighed. Samples of methyl paraben and propyl paraben were dissolved in hot water. Then it was cooled and carbopol was slowly poured on a magnetic stirrer while stirring. Stirring was continued until the lumps disappeared and the polymer completely swelled. Dry blackhead extract was added to the polymer solution and stirring continued. At the same time, a neutralizing solution was prepared: 10% NaOH was dissolved in water. When the extract dissolved, a neutralizing solution was added. The composition of the components is presented in table 2.

table 2 The composition of the anti-burn composition M-2 Name of components Mass g Carbopol 1,50 Methylparaben 0.25 Propylparaben 0.25 10% sodium hydroxide solution 2.00 Water 91.00 Dry Blackhead Extract 5.00 Total weight 100.00

Example 4. Preparation of an anti-burn composition based on M-3 hydrocream.

The required number of components was weighed. Samples of hydrocream and blackhead extract were placed in a mortar, mixed thoroughly until smooth. Samples of the components are presented in table 3. The composition of the hydrocream is presented in table 4.

Table 3 The composition of the anti-burn composition M-3 Name of components Mass g Hydrocream 95.0 Dry Blackhead Extract 5,0 Total weight 100.0

Table 4 The composition of the basis of hydrocream Name of components Mass g Glycerol 2.0 Triethanolamine 0.3 Emulsion Wax 3.0 Corn oil 1,0 Glyceryl stearate 3.0 Mineral oil 5,0 Caprylic and Capric Acid Triglycerides 3.0

Cyclomethicone 2.0 Carbopol 0.25 Cacao butter 3.0 Purified water Up to 100 Total weight one hundred

Example 5. Assessment of acute toxicity of anti-burn compositions. The study of acute toxicity was carried out on outbred white mice weighing 18-24 g. The composition of the dosage forms was administered intragastrically through a probe with a diameter of 2 mm in the form of 50% suspension solutions. The volume of solutions for mice was 0.5 ml / 10 g. After administration of the tested compositions, the animals were monitored on the first day every hour, and once a day on the next 14 days. During the entire observation period, the main criteria for taking into account the behavior of animals were: general condition, behavior, intensity and nature of motor activity, coordination of movements, skeletal muscle tone, presence and nature of seizures, frequency and depth of breathing (table 5).

Table 5 Indicators of acute toxicity of anti-burn compositions Composition Volume ml Quantity in group Died Survived M-1 one 10 - 10 M-2 one 10 - 10 M-3 one 10 - 10

The presented material indicates the absence of acute toxicity of the tested compositions, since we have not recorded fatal outcomes among experimental animals with the indicated maximum injected volumes.

Example 6. Evaluation of the chronic toxicity of anti-burn compositions. Assessment of chronic toxicity in rats was performed on 15 white rats of a subtype of a Wistar population of both sexes of the same age group, 5 rats from each group for 7 days. Test compositions were applied to rats on tails.

Reactions in the form of hyperemia on the part of the skin in animals when using 7 compositions were not observed. Thus, we can conclude that the compositions used do not have an irritating effect.

Example 7. Evaluation of the local irritant effect of anti-burn compositions.

The experiment was carried out on three chinchilla rabbits. When making compositions M-1, M-2, M-3 over the eyelid of the right eye at a dose of 50 mg (the left eye served as a control), no manifestations of hyperemia were observed. The time of manifestation of hyperemia from the mucous membranes of the eyes in rabbits was determined within 30 minutes. The compositions used do not have an irritating effect on the mucous membrane of the eye of rabbits.

Example 8. The study of the sensitizing properties of anti-burn compositions.

In order to assess the sensitizing properties of the compositions, studies were performed on 3 rabbits. On prepared skin areas 4 × 4 cm in size of the right lateral surface of the abdomen, experimental samples of compositions were applied daily. Applications were carried out for 3 days. On the 4th day of the experiment, a resolving test was performed by applying the studied compositions to similar, previously prepared skin areas on the left. Reactions in the form of hyperemia, edema on the part of the skin in animals when using the compositions were not noted, which allowed us to continue the experiment until 28 days. Thus, we can conclude that the compositions used do not have a sensitizing effect and the danger of their use is unlikely.

Example 9. Evaluation of the healing of burn wounds in experimental animals with the use of anti-burn compositions.

The experiment was carried out on 40 white rats of both sexes of the same age group. Experimental animals were divided into four groups of ten animals each. Three groups were experienced and one control. The thermal burn to rats under ether anesthesia was created by a metal plate heated to a temperature of 100-98 ° C. The contact time of the plate with a clipped area of the skin of the animal is 40 seconds. This burn corresponds to the II-IIIa degree of severity. A day after the burn, the rats of the experimental groups were applied to the affected areas of the skin developed compositions. The control group did not receive treatment. The studied compositions for medicinal purposes were applied to burn surfaces once a day at the same time with a glass rod, evenly distributing over the entire surface for 21 days. The results of epithelialization of burn wounds in experimental rats with the use of compositions are presented in dynamics in table 6 and figures 1-9.

Table 6 Epithelialization of burn wounds when using anti-burn compositions Groups of animals (composition) Time, day The formation of a crust (scab) Violation of the integrity of the spine of the crust (scab) Rejection of the crust (scab) Scar formation Wool coating M-1 3 7 9 fourteen 23 M-2 3 6 8 13 21 M-3 3 6 8 12 21 Control group (untreated) four 8 eleven twenty 27

According to the results of the experiments, it was found that in the experimental groups, against the background of application, the compositions showed more active healing of thermal burns, on average 3-7 days earlier in relation to the control untreated group.

Example 10. Evaluation of the healing of burn wounds in experimental animals on the background of the use of the basis for the composition.

The bases for the compositions were prepared as described in Examples 2-4 without using a dry blackhead extract. The assessment of the healing of burn wounds in experimental animals with the use of the base for the composition was carried out as described in example 9. The results of epithelialization of burn wounds in experimental rats with the use of the base for the composition are shown in Figures 10-12 and table 7.

Table 7 Epithelialization of burn wounds using the basis of anti-burn compositions Groups of animals (basis for composition) The time of scar formation, day M-1 twenty M-2 twenty M-3 twenty Control group (untreated) twenty

According to the results of the experiments, it was found that in the experimental groups, against the background of the application of the base for the compositions, the same healing of thermal burns was observed, on average, for 21 days, as in the control untreated group.

Claims (1)

An anti-burn composition for topical application, based on petrolatum, lanolin, or carbopol, or hydrogel, characterized in that the composition contains as active substance 5% of the dry extract from plant material of the black-headed large-flowered and black-headed ordinary with 60% rosmarinic acid.

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