RU2686843C1 - Method of treatment of combined radiation-thermal lesions and agent for implementing it - Google Patents

Abstract

FIELD: medicine; veterinary.SUBSTANCE: invention refers to medicine and veterinary science and can be used for treating combined radiation-thermal injuries in rats. That is ensured by introducing a biological preparation of vegetable origin, purified turpentine, into animals. Turpentine is administered subcutaneously in dose of 0.4 ml under the wound surface of the affected area immediately after the radiation-thermal burn, and then 3, 7, 11, 15, 20 and 24 days later.EFFECT: invention provides treating combined radiation-thermal injuries in rats by anti-radiation and anti-burn action of turpentine.1 cl, 7 ex

Description

The invention relates to the field of medicine, veterinary medicine and radiation biology and can be used for the treatment of victims of accidents at nuclear power plants, when it is possible the combined action of ionizing radiation and thermal factors: flame, fire, heated steam, etc .; treatment of the population, animals, military contingents after a nuclear explosion with radiation and thermal damage, treatment of complications observed in combination radiation therapy of cancer patients, the method can also be recommended for use in the treatment of burn disease.

There is a method of treating radiation lesions of the body, involving the introduction of mammalian anti-radiation serum subcutaneously at a dose of 100-125 mg / kg of small body weight and 200-250 mg / kg - for adults during the first 10 days after irradiation, and a method for producing a drug for treating radiation lesions of the body (RU patent No. 2169572, А61К 35/28, published on June 27, 2001).

The disadvantage of this method is the limited use of the drug - it only protects against radiation damage to the body.

There is a method of treating the body for burns by intravenous administration of a 40% hexamethylenetetramine solution, a 10% sodium bromide solution with caffeine and a 10% salicylic ointment applied to the affected area, removal of dead tissues, treatment of granulating defects with Vishnevsky ointment (see the article “Burn.” - Veterinary Encyclopedic Dictionary. - M .: Soviet Encyclopedia. - 1981. - p. 350-351).

The disadvantage of this method is the low therapeutic efficacy of the agents used and the lack of their protection in case of a combined radiation-thermal injury.

There is a method of treatment of combined radiation-thermal lesions of the body by intramuscular injection of anti-inflammatory cytokine-pentoxifylline in a dose of 5 mg / kg and monoclonal antibodies at a rate of 10 μg / mol (see the article by R. Bududov and L. P. Ulyanova “Effects of level modulators of cytokines on the survival of mice and rats with radiation-thermal lesions // Radiation Biology. Radio Ecol. - 2004. - V. 44. - № 4. - P. 302-304).

The disadvantage of the treatment method is that, first, the animals were irradiated at a dose of 7.0 Gy, which is LD ₉₀ , and, second, the simulation of a thermal burn was performed using flashes of light, which simply causes skin erythema without developing necrotic lesions. A natural burn of degree IIIb is accompanied by a severe lesion of the skin with the development of skin inflammation with subsequent demarcation of necrotic tissue, which dictates the need for more radical methods of treating burns and radiation sickness with their combined effect.

It is known that radiation injuries and burn injuries are accompanied by immunity dysfunction on the basis of endogenous intestinal infection with the transformation of the systemic inflammatory response, resulting in radiation-burn sepsis. Burning on the background of radiation damage, due to dysfunction of the immune system, causes an increase in the development of conditionally pathogenic microflora, a significant contribution to which is made by E. coli and enterobacteria (Enterobacter) - the main producers of endo- and exotoxins leading to the development of endogenous enteric infections , and staphylococcus (St. aureus), infected burn (thermotoxins) and microbial toxins (staphylotoxins) are the main contributors to the development of a burn injury at the site of injury. Against this background, the use of antibiotics that have an antimicrobial effect is an effective means of combating the consequences of radiation-thermal damage.

There is a method of treatment for mass radiation lesions, treatment of post-radiation wound infection and sepsis, which consists in the introduction of antibiotics (tetracyclines) together with a sorbent of magnesium oxide (patent RU №2161486 C2. А61К 31/65, published 10.01.2001).

The disadvantage of this method is the use of known antibiotics that do not eliminate all violations of the microbial associations of the body that occur after radiation and thermal effects, no effect on the pathogenetic factors of radiogenic stress and burn disease at the site of the application of the burn injury.

There is also known a method of treating radiation-thermal damage of the body by a single subcutaneous injection of 14 Gy of bifidobacterin irradiated with gamma rays at a dose of 1.43 * 10 ⁶ CFU / kg, followed by applying 10% sealer oil on the burned area, then after 3- 4 days - 10% of ointment of Hypericum (patent RU No. 2549451, А61К 35/66, published 04/27/2015. Bull. No. 12). The disadvantage of this method is weak radioprotective, antitermotoxic activity of the drug and weak antiseptic activity against wound infection of used ointments.

At the same time, it is known that herbal preparations from the class of terpenoids that have a stress-protective effect by inhibiting toxic radicals - lipid peroxidation products (POL) - malondialdehyde, which play a key role in the development of radio-induced toxemia (radiotoxinemia) (see the article by TV Panfilova and etc. “Triterpeinoid meliacin reduces stress-induced POL” // Byul. Ex. Biology and Medetsin - 2004. - T. 141. - № 6. - P. 633-635).

Consequently, drugs of plant origin (herbal remedies) - pine terpenoids have the most important mechanism - a protective effect in stress pathologies by blocking the formation of toxic radicals against the background of effects on the body of stressors (ionizing radiation, pathogenic agents, chemical toxicants, etc.). One of the most important terpenes used in medicine and veterinary medicine is turpentine oil - turpentine, which has a wide spectrum of action: anti-inflammatory, analgesic, antibacterial, antiparasitic, granulation, immuno-hemopoestimulating, neuro-sedative and activating function of the central nervous system, see: M. Mozgov - Pharmacology: A Guide for Veterinarians. - Moscow: State Publishing House of Agricultural Materials - 1954. - P. 207-209). Therefore, this tool (turpentine) has all the properties that can eliminate the pathological processes induced by radiogenic stress and burn injury.

This was the basis for the use of purified turpentine obtained from resin (Gum turpentine, production - OOO Reaktiv, GOST 1571-82) as an anti-radiation and anti-burn agent for a combined radiation-thermal injury.

The objective of the invention is to simplify and reduce the cost of the method with a simultaneous increase in the anti-radiation activity of the drug and the elimination of post-traumatic wound infection after causing burn injury on the background of radiogenic damage to the body.

The task is solved in that for the treatment of combined radiation-thermal lesions of the organism of animals, a biological preparation of plant origin is used - purified turpentine at a dose of 0.4 ml, which is administered to animals once subcutaneously under the wound surface of the affected area during the first 24 hours after radiation-thermal exposure, and then after 3.7, 11, 15, 20 and 24 days.

Examples of the method described in the following examples.

Example 1. The control group of white rats weighing 200-220 g was subjected to total uniform gamma irradiation at a dose of 7.0 Gy (dose rate of 5.49 R / min) on the Puma unit with a source of ¹³⁷ Cs. A few minutes after irradiation by applying a brass heel (d = 25 mm) heated to 180 ° C to the clipped area of the upper thigh of the thigh (d = 25 mm) in the Ricci kiln (Coal Activation Regulator, model TO 10BTQS, oven size 450 × 330 × 350, weight 3 kg).

Two brass patches were used, one was left in the oven at the time of the burn injury to the other animals. According to the degree of damage to the skin and underlying tissues, this burn corresponded to a III-B degree burn with an area of 15% of the skin in the thigh area. All control animals with the specified form of a combined radiation-thermal lesion (CRTD) died within 20 days after a two-factor exposure.

Example 2. To assess the action of the proposed pharmacopoeial drug - purified turpentine used a group of rats similar to the control. Purified turpentine at a dose of 1.0 ml was injected once subcutaneously in the area affected by the burn (directly under the burn surface) of the animal's skin, immediately after the application of the burn, and then after 3, 7, 11, 15, 20 and 24 days. In this group, by 30 days after CRTD, 50 ± 5% of rats survived.

Example 3. After the CRTD described in item 1, the affected turpentine was injected once subcutaneously (under the burn area of the skin) purified turpentine at a dose of 0.6 ml immediately after the application of the burn, and then after 3, 7, 11, 15, 20 and 24 days. By 30 days after the CRTD, 73.3 ± 3.4% of the rats survived.

Example 4. After the CRTD described in item 1, the purified turpentine was administered subcutaneously once a dose of 0.4 ml was applied subcutaneously to the rats immediately after the application of the burn, and then after 3, 7, 11, 15, 20 and 24 days. In this group of rats, by 30 days after two-factor exposure, 100 ± 0% of rats survived.

The introduction of purified turpentine in this dose for two days after CRTD leads to a decrease in bacterial toxemia in affected rats from 82.9 to 21% (P <0.01), the amount of toxic lipoperability products (malondyldehyde - MDA) in serum decreases in two times, the number of radiotoxins and thermotoxins in RBF (reaction of bentonite flocculation with sensitized quinoid radiotoxin and burn toxin sheep erythrocytes) - the test decreases by 1.9 and 2.1 times, respectively.

Example 5. After the CRTD described in item 1, the purified turpentine was administered subcutaneously once in a dose of 0.2 ml immediately after applying the burn, and then after 3, 7, 11, 15, 20 and 24 days. In this group of rats, by 30 days after two-factor exposure, 37 ± 5% of rats survived.

Example 6. After the CRTD described in paragraph 1, the affected rats under the burned area of the skin were injected with purified turpentine at a dose of 0.4 ml after 2, 4, 6, 8, 10 days after irradiation and causing burn injury. By 30 days after a two-factor lesion of administering the test drug, 80% of the rats survived in 2 days, 50% after 4 days, 37.5% after 6 days, 21.3% after 8 days, and 5.1% after 10 days rats.

Example 7. To assess the wound healing (granulation) effectiveness of purified turpentine on the background of a two-factor lesion, the control (1st) and experimental (2nd) groups of rats were subjected to a combined radiation-thermal lesion described in paragraph 1 and treated with purified turpentine according to p 4. Then, in the dynamics of the control and treated animals, observations were made, taking into account the severity of the course, the time of healing and rejection of the scabs from the burn surfaces.

In the control rats subjected to radiation-thermal exposure, suppurations of the affected part of the body were observed, and healing of the burn wound did not occur - the animals died against the background of tissue suppuration of the wounds - wound sepsis. In contrast to the controls, in radiation-affected and burned experimental animals treated with turpentine, the course of radiation and burn disease proceeded according to a modified (lightened) variant. In rats of the 2nd group, which under the wound (burned) surface was injected with purified turpentine at a dose of 0.4 ml, the process of formation of a burn scab began on day 2 versus 6 days in control animals. The appearance of the demarcation line and granulation tissue around the affected areas in animals treated with purified turpentine occurred on the 19th day after the start of treatment versus the 25th day in control animals. Complete healing of burn wounds in animals of the 2nd group, against the background of application of the proposed remedy, occurred on the 35th day after the treatment of burns. In the control animals, the healing of burn wounds did not occur until the end of the observation period and until death. The experiments are repeated several times during 2015-2017.

Thus, the use of purified turpentine (GOST 1571-82) as a biological preparation of plant origin for the treatment of CRTP animals in the body with direct introduction under the burned area of the skin provides a significant increase in the survival rate of affected animals due to accelerated healing (granulation) of the affected tissue, inhibiting the overall intoxication of the body with radiotoxins and thermotoxins, reduction of bacterial toxemia of the body.

Claims (1)

The method of treatment of combined radiation-thermal lesions in rats by administering a biological preparation of plant origin - purified turpentine, which is administered at a dose of 0.4 ml subcutaneously under the wound surface of the affected area immediately after the radiation-thermal burn, and then after 3, 7, 11, 15, 20 and 24 days.