RU2760838C1 - Method for treating burns of degree 3a by applying glauconite powder - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine and concerns a method of treating burns of degree 3A by applying glauconite powder topically externally to the surface of a burn wound representing a ready dispersed form.EFFECT: invention provides treatment of burns of degree 3A without causing antibiotic resistance and allergic reactions.1 cl, 1 ex

Description

The invention relates to methods for treating grade 3A burns. It can find application in the treatment of burns by applying to the burned surface a powder made from the natural mineral glauconite, which does not contain antibiotics and allergens.

Burns represent a worldwide health problem in the world. According to the Federal State Statistics Service in Russia in 2015 alone, there were about 300,000 cases of burn injury [Healthcare in Russia. 2015: stat. Sat. Moscow: Rosstat; 2015. 174 s.]. In the structure of burn injury, a special place is occupied by grade A burns (classification of the 27th All-Union Congress of Surgeons). With them, not only the epidermis perishes, but also the dermis partially. Epithelialization of these burns occurs within 3-6 weeks. due to the derivatives of the skin (hair follicles, sebaceous and sweat glands), preserved in the deep layers of the dermis. With an unfavorable course of the wound process, complete regeneration of the skin does not occur (borderline burns), granulation tissue is formed [K.S. Kobelev and V.I. Midlenko. The current state of the problem of local conservative treatment of superficial and borderline burns. // Ulyanovsk medical and biological journal. No. 4. 2017. S. 1-12. DOI 10.23648 / UMBJ.2017.28.8735]. Patients with deep and extensive burns require immediate treatment [Zinatullin P.M. Improving the treatment of patients with thermal burns / P.M. Zinatullin. - Moscow: Medicine, 2010. - 21 p.].

A burn is a type of traumatic injury that develops under the influence of high temperatures, chemicals, radiation energy or electric current.

The most common causes of thermal burns are flames and water. A burn of 1 degree, that is, erythema - redness of the skin, swelling, pain. It usually goes away in 3-5 days, but a trace and slight peeling remains in its place. A burn of 2 degrees, otherwise the formation of blisters - severe pain, intense redness, exfoliation of the epidermis. After about a week, complete scarring occurs. A third degree burn, that is, tissue necrosis is divided into 3A and 3B. Grade 3A burns are characterized by slight skin necrosis, with a rough bottom of the burn with lateral hemorrhage. A grade 3B burn is the necrosis of all layers of the skin. A dense scab is usually black in color. Loss of skin sensitivity is noted.

Burn of 4 degrees, otherwise carbonization of tissues. It occurs with prolonged exposure to very high temperatures. Death of the skin and deep-lying tissues to their entire depth; skin, muscles, and bone tendons are damaged. Deep scab, loss of sensitivity, suppurative process often occurs. Burns 1, 2, 3A degrees refer to minor burns, the dermis can be restored without the help of drugs.

Burns 3B and 4 degrees are very severe, in most cases surgical intervention is required [Burns and frostbite, IV. Mikhin, Yu.V. Kukhtenko, Volgograd State Medical University, Volgograd, 2012].

Ointments are often used to treat thermal burns. For example, Levomekol. Levomekol is an antibacterial combined agent for external use with a pronounced immunostimulating and anti-inflammatory effect. Levomekol does not allow pathogenic microflora to grow, suppresses inflammatory processes, removes purulent discharge, has a wound healing effect and starts the regeneration processes of the epidermis. A similar tandem is provided by two active components in the composition of the ointment - Chloramphenicol (aka Levomycetin) and Methyluracil. Chloramphenicol is a natural antibiotic that actively blocks intestinal, Pseudomonas aeruginosa and staphylococcal bacillus. And methyluracil accelerates the regeneration of the epidermis. The peculiarity of methyluracil is the ability to easily and quickly penetrate the dermis without affecting the membrane membrane of the cells. This process is associated with the removal of excess fluid from the intercellular space, which is usually the cause of edema and bruising [Electronic resource]. - Access mode: https://uteka.ru/articles/lekarstvennye-preparaty/levomekol/ (date of access 12.04.2019)].

Povidone-iodine ointment contains iodine for wound disinfection and an auxiliary component that accelerates the healing of a burn wound. Iodine is contained in the form of a complex of polyvinylpyrrolidone iodine. The concentration of active iodine is 0.1 - 1%. Povidone-iodine ointment has an antiseptic, disinfectant, antifungal and antiprotozoal effect. Blocks amino groups of cellular proteins. Possesses a wide spectrum of antimicrobial action. It is active against bacteria (including Escherichia coli, Staphylococcus aureus), fungi, viruses, protozoa. Polyvinylpyrrolidone iodine belongs to iodophores that bind iodine. Upon contact with the skin and mucous membranes, iodine is gradually and evenly released, exerting a bactericidal effect on microorganisms [Radar Drug Directory [Electronic resource]. - Access mode: https://rlsnet.ru (date of treatment 05/25/2019)].

The "Rescuer" balm, made from natural ingredients without the use of antibacterial agents, has a similar effect. It actively restores the protective properties of damaged skin. The mechanism of the unique action of the balm is based on its ability to restore the protective properties of damaged skin and stimulate regeneration processes [Electronic resource]. - Access mode: https://www.neboleem.net/balzam-spasatel.php (date of access 9.11.2020)].

In addition to ointments, a cream is an effective remedy for burns. As a rule, it is used at the stage of repairing damaged tissue, to prevent the formation of scars and scars. For sunburn and thermal burns, Panthenol aerosol can be used. Its effect is similar to that of an ointment, while the cream, compared to the ointment, has a lighter texture and is more easily absorbed into the skin. In the presence of serious injuries, when contact with the wound causes severe pain, it is recommended to use sprays. They are easily sprayed onto the affected surface, avoiding additional contact with the painful skin area. [Directory of medicines VIDAL [Electronic resource]. - Access mode: https://www.vidal.ru (date of access: 25.05.2019)].

A known method for the treatment of limited burns coated with Silkofix Gel Ag. [A method of treating local burn wounds of II-III A degree. RU 2648869 C1, 28.03.2018]. It is made on the basis of a polyurethane film coated with an acrylate hypoallergenic adhesive, with an atraumatic absorbent rayon pad. The microporous base ensures air and moisture exchange, thus does not cause maceration of the skin. Promotes a welcoming, moist environment, accelerating the wound healing process. An increase in the effectiveness of treatment of patients with local burn wounds of II-III A degree is achieved by the fact that when changing the coating "Silkofix Gel Ag" ultraviolet irradiation of the burn wound is used, daily increasing the duration of the radiation session by 30 seconds until the epithelialization of the wound is completed; sequentially affect the wound with a low-frequency magnetic pulsating field with a frequency of 50 Hz, an induction of 30 mT for 5 minutes, daily increasing the duration of the irradiation session by 1 minute until the epithelialization of the wound is completed. The mechanism of the therapeutic effect of ultraviolet radiation is based on its anti-inflammatory, bactericidal and antiviral effects. The result of treatment is achieved due to wound sanitation, reduction of tissue edema and the stimulating, healing effect of ultraviolet radiation. Magnetotherapy has anesthetic, anti-inflammatory and pronounced anti-edema effect. In this method of treating local burn wounds of II-III A degrees, several approaches are combined (dressing, ultraviolet irradiation and magnetotherapy), which together helps to reduce the time of epithelialization of wounds.

Also, for burn injuries, powders are used. The drug Baneocin contains two antibiotics - neomycin, which is an aminoglycoside that inhibits protein synthesis in bacteria, and bacitracin. The latter is a polypeptide antibiotic that inhibits the synthesis of the bacterial cell wall. It is not assigned systemically. Local application of Baneocin powder significantly reduces the risk of sensitization, which is characteristic of the systemic use of antibiotics. Tissue tolerance Baneocin is regarded as excellent [Blatun L.A. Baneocin - prospects for use in the complex surgical treatment of purulent-necrotic lesions of the lower extremities in patients with diabetic foot syndrome. Blatun // Zhurn. them. prof. B.M. Kostyuchenko. Wounds and wound infections. - 2015. - No. 3. - S. 36-45].

Galmanin powder containing salicylic acid, zinc oxide, which have a drying, antiseptic and anti-inflammatory effect, is applied in a thin layer to the affected skin and clean skin once a day. [Electronic resource]. - Access mode: https://health.mail.ru/drug/galmanin/ (date of access: 09.11.2020)].

Powder Ranavexim is used in powder form for external use. Ranavexim is applied directly to the affected surface; dressings are carried out after 1 - 2 days. Ranavexim contains streptocid sulfanilamide, which inhibits the growth of bacteria and promotes burn healing. [Electronic resource]. - Access mode: https://health.mail.ru/drug/ranaveksim/ (date of access: 09.11.2020)].

Children's powder, containing talc, zinc oxide, potato starch, is widely used to treat wetness and diaper rash, and also has a drying effect. It is applied topically. For the prevention of diaper rash, baby powder is applied in a thin layer to areas of the body. In case of rash and dermatitis, the powder is applied in a thin layer to the affected areas of the skin [VIDAL Medicines Handbook [Electronic resource]. - Access mode: https://ymadam.net/deti/zdorov-e-rebenka/prisypka-detskaja.php (date of access: 9.11.2020)]. Baby powder can cause an allergic reaction due to the presence of zinc oxide in it. Zinc oxide has an antibacterial effect against Escherichia coli and Staphylococcus aureus, [https://ru.essays.club/zhansayaiuytgf.html accessed 16.06.2021]. [Directory of medicines VIDAL [Electronic resource]. - Access mode: https://ymadam.net/deti/zdorov-e-rebenka/prisypka-detskaja.php (date of access: 9.11.2020)].

Powders for external use, that is, powders, have several advantages over other dosage forms for treating wound injuries: the relative simplicity of the production technology and its low cost, stability and long shelf life. The powders are painlessly applied, without causing injury, without putting pressure on the wound or burn, have adsorbent properties, absorbing wound discharge, which helps to cleanse and heal the wound.

Many topical burn powders contain antibiotics that can cause antibiotic resistance [T.V. Svyatenko, M.A. Nikolaychuk, A.A. Frankenberg. Current opportunities and immediate prospects in the treatment of bacterial skin infections. Ukrainian Journal of Dermatology, Venereology, Cosmetology, 2010; 2 (37). S. 23-28].

A relatively small assortment of powders, with their probable presence of allergenicity and the ability to cause antibiotic resistance, suggests the need to search for a dosage form free from these shortcomings, which is glauconite powder for treating burn wounds.

In [A method for increasing the effectiveness of wound healing. (RU 2698298 C1, 26.08.2019] it is proposed to use glauconite powder in the treatment of full-thickness wounds. The authors suggest, without conducting laboratory studies, that glauconite powder can promote wound healing of burn lesions, without indicating what degree of burn damage is in question. At the same time, the effectiveness of wound healing is assessed by the strength of the scar of a full-thickness wound after wound healing, measured using a wound tensiometer, and not by the epithelization of a simulated burn of degree 3 A. Meanwhile, in combustiology there are methods for assessing burn damage of a certain degree, which make it possible to reliably recognize both the degree and the area of the burn lesion, and by the change area of burn injury, dynamics of epithelialization of wounds [Patent 2016147428 of the Russian Federation, Device for modeling experimental thermal burn wounds of various degrees. // Patent of Russia No. 172252: published 03.07.2017. , Buzlama A.V., Patent 114147 of the Russian Federation, IPC G01B 5/26. Palletka for planimetric measurements of objects in biology and medicine / A.V. Buzlama, Yu.N. Chernov, A.I. Slivkin; applicant and patentee FGOU VPO Voronezh State University. - No. 2010135853/28: Appl. 08/26/10; publ. 03/10/12, Bul. No. 7. - 2 p.].

Children's powder (Registration number: P N000921 / 01), which exhibits dermatoprotective properties (manufactured in Russia, JSC Sintez), was selected as a drug prototype. Produced in the form of a powder for external use, 40 g and 50 g in polyethylene cans. Such signs of the prototype - children's powder - as dispersion and finished form, which does not require mixing the components or mixing the composition before applying to the burn surface, coincide with the essential features of the proposed method. Zinc oxide present in the composition has an antibacterial effect against Escherichia coli and Staphylococcus aureus, [https://ru.essays.club/zhansayaiuytgf.html date of access 06/16/2021], but at the same time it can cause an allergic reaction [Directory of medicines means VIDAL [Electronic resource]. - Access mode: https://ymadam.net/deti/zdorov-e-rebenka/prisypka-detskaja.php (date of access: 9.11.2020)].

The technical problem is to develop a method for treating burns by applying on the burn surface a natural glauconite substance that does not contain antibiotics and allergens in the form of a powder. The use of the glauconite substance helps to solve the problem of import substitution, reduce the cost of treatment and care for burns, prevent contact of the burn surface with preparations containing antibiotics and allergens.

This technical problem is solved by comparing the parameters of the healing of thermal burns in outbred conventional rats of the two experimental groups and the control group. The control group of animals was observed without treatment. In one experimental group of animals, a powder of crushed sterile glauconite at a dose of 100 mg was applied to the surface of the burn, in another experimental group - baby powder was applied daily throughout the experiment, for the first time one hour after the application of the burn.

The essence of the method lies in the fact that glauconite immobilizes bactericidal components, and thus plays the role of a means for antibacterial therapy [Some aspects of the use of glauconite in medicine / S.B. Venig, V.G. Sergeant, E.I. Selifonova // Methods of computer diagnostics in biology and medicine: materials of the All-Russian Youth Conference, Saratov, 10-12 Nov. 2015 - Saratov, 2015. - S. 217-220.].

Glauconite from the Bondarskoye deposit in the Tambov region contains: SiO ₂ (66.9 ... 75.81%); MgO (1.02 ... 1.62%), Al ₂ O ₃ (3.1 ... 6.57%), K ₂ O (1.51 ... 2.43%), Fe ₂ O ₃ (6.87 ... 12,0%), Na ₂ O (0,1 ... 0,23%), FeO (0,28%), TiO ₂ (0,12 ... 0,34%), P ₂ O ₅ (0.33 ... 3.38%), MnO (0.012 ... 0.019%), SO ₃ (0.06 ... 0.15%), CaO (1.08 ... 5.14%) [Vigdorovich V.I. Adsorption processes: textbook. manual. for students of chem. specialties of universities / V.I. Vigdorovich, L.E. Tsygankova, N.V. Shel. - Tambov. - 2014. - 150 p.]. Numerous studies [Study of the microbiocenosis of the skin and intestines in patients with atopic dermatitis / O.V. Georgieva [et al.] // Effective pharmacotherapy. - 2012. - № 11. - P. 32-35, Some aspects of the use of glauconite in medicine / S.B. Venig, V.G. Sergeant, E.I. Selifonova // Methods of computer diagnostics in biology and medicine: materials of the All-Russian youth conference, Saratov, 10-12 Nov. 2015 - Saratov, 2015 .-- S. 217-220, Khrebtova O.M. Biotesting of glauconite on infusoria / О.М. Khrebtova // Bulletin of the Baltic Federal University im. I. Kant. - 2016. - No. 2. - P. 73 - 76, Enterosorbent and a method for its production: US Pat. (19) RU (11) 2545711 (13) C1 Rus. Federation: IPC A61K 33/06, A61K 33/26, A61K 9/107, A61R 1/00 / M.Yu. Volkov, A.A. Kalilets. No. 2013151541/15; declared 11/20/2013; publ. 10.04.2015, Bul. No. 10. - P. 2-7] show that glauconite does not have a toxic effect and according to the classification of chemicals according to the degree of hazard in accordance with GOST 12.1.007.76 belongs to class 4 - slightly hazardous substances.

To conduct preclinical studies of the treatment of burns by external application of powder, glauconite from the Bondarskoye deposit, Tambov region, was ground in a mortar to obtain a fine powder consisting of isodiametric particles less than 200 μm in size with rounded edges (microscopic assessment), which indicates its suitability for use as a powder for application to the wound surface. Then the substance of glauconite was sterilized for 60 minutes in an oven at a temperature of 180 ° C. Preclinical studies of the glauconite substance were carried out on 15 outbred female conventional rats weighing 250-290 g, 5 animals in each group. The animals were kept under standard conditions in the vivarium of the pharmaceutical faculty of Voronezh State University, fed with full-feed compound feed, drinking ad libitum through nipple drinkers. During the research, the international principles for the humane treatment of animals were observed [Guidelines for conducting preclinical studies of drugs: 2 hours / ed. A.N. Mironov. - Moscow: Grif and K, 2012. - 944 p.].

Thermal burns of degree 3A were simulated using a patented electric heating device developed by Professor Vladimir Anatolyevich Nikolaevsky. It is a heating metal plate of a given area, the heating temperature is regulated by a dimmer and controlled by an electronic thermometer [Patent 2016147428 Russian Federation, Device for simulating experimental thermal burn wounds of various degrees. // Patent of Russia No. 172252: published on 03.07.2017. declared 2016. / Nikolaevsky V.A., Fedosov P.A., Buzlama A.V.].

Burns were inflicted under conditions of anesthesia caused by intraperitoneal administration of urethane and chloralose. Previously, a day before the start of the experiment, by cutting with the subsequent application of depilatory cream, the hair was removed in the upper outer interscapular region [Simulation of burn injury in an experiment on laboratory animals. [Electronic resource]. - Access mode: http://combustiolog.ru/journal/razdel-7-e-ksperimental-ny-e-issledovaniya. (date of treatment 05/25/2019)].

The control group of animals remained untreated. In one experimental group of animals, a powder of crushed sterile glauconite at a dose of 100 mg was applied to the burn surface, daily throughout the experiment, for the first time one hour after the burn was applied. In another experimental group of animals, a comparison preparation (prototype) was applied for children's powder containing talc, zinc oxide, potato starch and auxiliary components. The comparison drug was used in the same dose according to the same scheme as the glauconite powder [Experimental Pharmacology - principles, models, analysis / A.V. Buzlama [and others]. - Voronezh: Publishing and Printing Center of Voronezh State University, 2013. -363 p.].

Every 5 days, the area of burns was measured using pallets with a scale-coordinate grid, initially and then on the 15th day, the body weight was measured, the general clinical condition of the animals and the appearance of burn wounds were constantly monitored [Patent 114147 of the Russian Federation, IPC G01B 5/26. Pallet for planimetric measurements of objects in biology and medicine. / A.V. Buzlama, Yu.N. Chernov, A.I. Slivkin; applicant and patentee FGOU VPO Voronezh State University. - No. 2010135853/28: app. 08/26/10; publ. 03/10/12. Bul. No. 7. - 2 p.].

It was found that on the 15th day from the beginning of the experiment, the animals of the control and experimental groups showed a decrease in body weight by no more than 5-6% from the initial one. This is naturally associated with the processes of protein breakdown and a decrease in appetite in the first days against the background of thermal burns.

In animals of the control group without treatment, on the 5th day, the degree of healing, calculated as the difference with the initial average for the group, the area of the burn was 19.7%, starting from the 10th day, a significant significant decrease in the area was revealed by 48.4%, on the 15th 62 , 2% and on the 20th day of the experiment 74.3%. At the same time, all animals showed the presence of marginal hyperemia or hemorrhages along the edge of the burn scab and significant retraction of the bottom of the burn wound; starting from the 1st day, no suppuration was detected during the observation period; on the 13th day, the primary scab was gone only in 25% of the animals, on the 16th, in 50% of the animals. At the same time, after necrectomy, a dense secondary scab was formed, which slowed down the wound healing process by primary intention.

The use of the reference drug - children's powder, for the healing of a burn wound of degree 3A causes a decrease in the area of the burn wound on the 5th day by 3.5%, on the 10th day - 24.0%, on the 15th - 67.6%, by 20 On the e day from the beginning of the experiment, 86.18% earlier, compared to how it happened with the animals in the control group. At the same time, no suppuration was revealed during the observation period, on the 13th day the primary scab disappeared in 60% of the animals, on the 16th in all (100%) animals, the wound was dry and clean, which promoted healing by primary intention. Complete healing of the burn occurs on the 25th day. Thus, the prototype - children's powder has anti-burn activity.

The use of the dosage form - glauconite powder for the healing of a 3A burn reduces its area on the 5th day by 17.9%, on the 10th day - 44.6%, on the 15th day - 45.7%, on the 20th day - 67.1% earlier compared to how it happened with the animals in the control group. No suppuration was detected during the observation period, on the 13th day the primary scab remained in all 100% of the animals, on the 16th day the scab was gone in 80% of the animals, the wound was dry and clean, which promoted healing by primary intention [Preclinical studies of medicinal substances: a textbook / A.V. Buzlama [and others]; ed. A.A. Svistunova. - Moscow: GEOTAR-Media, 2017 .-- 384 p .; Sepetliev D.A. Statistical methods in scientific medical research / D.A. Sepetliev. - Moscow: Medicine, 1968. - 420 p.]. Complete healing of the burn occurs on the 28th day. It is shown that the dosage form - glauconite powder when applied topically for the treatment of burn wounds of grade 3A has anti-burn activity, is not significantly inferior in efficiency to the prototype - children's powder.

The proposed method for treating burns through the use of a natural glauconite substance that does not contain antibiotics and allergens, when applied topically in the form of a powder, is expedient, since it has anti-burn activity.

Claims (1)

A method of treating grade 3A burns by applying glauconite powder topically and externally to the surface of a burn wound, which is a finished dispersed form.