RU2694835C1 - Agent increasing body post-hypothermal resistance - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is presented is application of a combination of pyrogenal in dose of 12.5 mcg/kg intramuscularly 1 hour before immersion and Relanium 5 mg/kg with sodium oxybutyrate in dose of 500 mg/kg intragastric 30 minutes before immersion in cold water as an agent, reducing lethality and accelerating recovery of body temperature after termination of cooling in water.

EFFECT: persons who carry out labour activity in emergency situations associated with acute overcooling in cold water, as well as groups of population in conditions of similar emergency situations, may be provided with sets of means.

1 cl, 1 tbl

Description

The present invention relates to the field of medicine and can be used to increase the body's resistance in the post-hypothermic period after a general acute hypothermia.

Hypothermia (hypothermia) is a condition that occurs when the temperature of a person’s body and warm-blooded animals drops below their normal values. General hypothermia is caused by exposure to cold and is characterized by general and local reactions of the body. At the same time, cold refers to the thermodynamic state of the environment, in which conditions are created to exceed the body's heat loss over its heat production, resulting in a transition to a new level of functioning aimed at preserving viability in changing environmental conditions.

The most common cause of acute hypothermia is a person being at a low temperature for a long time, especially if the air humidity is high. The hypothermia promotes the development of a fixed position of a person on a cold surface with high thermal conductivity. Very quickly hypothermia occurs when a person is immersed in cold water.

According to statistics, from 10 to 15% of people who died during long transitions in the cold period of the year were victims of hypothermia [1, 2].

Unsatisfactory results of treatment of victims in the posthypothermic period are stated in 15-50% of clinical observations [3, 4, 5]. In Russia, up to 11 thousand hospitalizations due to cold injuries and up to 4 thousand deaths from hypothermia per year are recorded [6, 7].

After completion of treatment, 59% of workers who suffered from severe cold injury retain occupational performance on average. After completing treatment, victims of frostbite do not return to labor activity more often than in 59% of cases [8].

 The chances for the rapid provision of specialized assistance in conditions of accidents, including in marine disasters, are extremely small. In this regard, the creation of conditions during the cooling period for the subsequent effective self-heating and restoration of vital functions is of particular importance. The best approach to solving this problem is the introduction into the body at the initial stage of cooling or in advance (for example, one hour before the hypothermia is expected) of such a pharmacological agent that would increase the body’s resistance during the cooling period and help restore the body temperature and normalize vital functions. after cooling (post-hypothermic period).

A known agent that increases the body's resistance to hypothermia (RF Patent No. 2010569), containing 10 mg of a drug belonging to the benzodiazepine group and 2 g of sodium hydroxybutyrate. These doses are intended for people injured during accidents. The authors of this tool offer several developments based on this combination.

As a prototype, a tool is taken according to the patent of the Russian Federation No. 2268049, which increases the body’s resistance in the post-hypothermic period. This invention lies in the fact that the proposed use of a combination of Relanium at a dose of 5 mg / kg with sodium hydroxybutyrate 500 mg / kg (ROH). The tool reduces the mortality rate in the experiment and accelerates the recovery of body temperature after the termination of cooling in water. But, despite a certain efficiency of using the means proposed in the prototype, during the first hour of self-heating the percentage of mortality of rats who received RON is still quite high (25%).

The problem to which the present invention is directed, is the development of a more effective means that increases the body's resistance and significantly reduces the risk of death in the posthypothermic period.

This is achieved by the fact that as a means of increasing the body’s resistance in the post-hypothermic period, it is proposed to use a pyrogenal combination in a dose of 12.5 µg / kg when administered intramuscularly 1 hour before cooling in water and RHE (Relanium 5 mg / kg with sodium hydroxybutyrate 500 mg / kg, see prototype) 30 minutes before immersion intragastrically.

Pyrogenal as a highly active non-specific immunomodulator of a broad spectrum of action, is not a narcotic and is available for the population. In accordance with the essence of the invention, appropriate pharmacoanalogs can be used in the composition of the agent. Doses of the components of the formulation can vary in the therapeutic range.

Examples of the invention in comparison with the control group of animals, while the experimental conditions, including the temperature and duration of cooling, the order of introduction of RON were identical to those used in the prototype:

White Wtar rats weighing 180 ± 12 g were used as experimental animals. Each group consisted of 8 clinically healthy animals. Before the start of the experiment, the animals were kept for at least 7 days in vivarium conditions on a standard diet. 12 hours before the start of the experiment, the rats were deprived of food, water was given without restrictions.

Rats were immobilized on a metal frame of 3 rats (one from each group), experimental animals were fixed on the frame using hemp twine, while the electrothermometer sensor was inserted into the intestine to a depth of 2.5-3 cm. The rectal temperature (RT) was recorded at Iso-Thermex v.4. (Columbus Instruments) with an accuracy of 0.1 ° C.

Cooling was performed in a 50 l metal bath. Before the start of the experiment, the bath was filled with tap water with a temperature of + 7 ° C. After filling the bath with water, the frame with rats immobilized on it was lowered along the vertical guides until the water level reached the lower border of the animal's neck.

Experimental groups (8 animals per group):

1) Control (without pharmacological load, water prepared);

2) Group 1 (pyrogenal 0.1 ml per individual, i.e. 2.5 μg on average, 200 grams, dose 2.5 / 2 = 1.25 μg / 100 grams, ie 12.5, respectively µg / kg) intramuscularly 1 hour before the dive and Relanium 5 mg / kg + sodium hydroxybutyrate 500 mg / kg 30 minutes before the immersion intragastrically).

Before immersion in animals, the initial rectal temperature was measured.

Next, the immobilized rats were cooled in water with a temperature of + 7 ° C for 15 minutes, the PT was measured automatically every 30 s for the entire period of immersion. Then the rats were removed from the bath, the animals' hair was wiped dry with a rag and placed in individual cages. During the entire posthypothermic period, the ambient air temperature was in the range of 20-22 ° C at a relative humidity of 60-70%. When observing recorded changes in the behavior of animals, mortality, recorded RT every hour.

The results of the experiments are presented in table 1.

Table 1. The effect of the test means on rectal temperature and mortality of experimental animals in the posthypothermic period.

Group Rectal temperature, ° C Duration of the self-heating period background after the dive 1 hour 2 hours 3 hours day PL * CPT ** Submarine CPT Submarine CPT Submarine CPT Control 37.8 ± 0.3 17.2 ± 0.3 62.5% 21.8 ± 0.3 62.5% 30.3 ± 0.4 62.5% 36.2 ± 0.6 62.5% 38.1 ± 0.7 Group 1 37.8 ± 0.2 19.4 ± 0.6 0 25.9 ± 1.2 0 34.1 ± 0.8 0 38.3 ± 0.3 0 38.5 ± 0.3 RON (prototype) 36.9 ± 0.2 15.0 ± 0.4 25.0 20.1 25.0 25.5 25.0 29.2 - - Note - PL * - The percentage of mortality; CPT ** - Average rectal temperature, ° С

It was established that when cooled for 15 min, the average rectal temperature in animals of all groups decreased to a level of 17.2-19.4 ° C. The main manifestations of the clinical picture of acute hypothermia in animals at the time of completion of cooling were different: control animals with severe cyanosis and typical symptoms of "cold" anesthesia with a lateral position and loss of pain sensitivity. Animals treated with pharmacological stress had a less cyanotic skin tone and maintained a response to painful stimuli, while maintaining a lateral position.

During the first hour of self-warming, the lethality among the control animals (with water) reached 62.5%, and in rats that received a pharmacological load in the form of the proposed agent — 0%. In the future, the death of animals within 1.5 days is not marked.

The most intense self-warming was observed in rats that were under the action of RON in combination with pyrogenal: already 3-4 hours after the end of cooling, their RT actually reached the initial level. The rate of recovery of body temperature in the "control" rats was significantly lower.

After the recovery of body temperature, the rats of both groups did not differ in appearance and behavior from each other and did not differ from intact animals.

Thus, the prophylactic administration of the agent proposed in the present invention, prior to the start of cooling, excluded lethality (unlike the prototype, where the lethality reached 25%) and accelerated the recovery of body temperature in the posthypothermic period.

The sets (sets) of funds can be provided to persons who work in emergency situations associated with acute overcooling in cold water, as well as groups of the population in similar emergency situations.

Bibliographic references:

1. Kuznetsova N.L., Savkin A.N. Comprehensive survey and treatment options for victims with cold trauma of the upper extremity // Mat. I Intern. Congress "Modern technologies of diagnosis, treatment and rehabilitation for injuries and diseases of the upper limb." Moscow, 2007. P.56-57.

2. Risk factors. Survival School. // Electronic resource. http://www.e-reading.club/chapter.php/24168/2/Il'in__Shkola_vyzhivaniya_v_prirodnyh_usloviyah.html.

3. Vikhriev B.S., Kichemasov S.Kh., Skvortsov Yu.R. Local lesions cold. L .: Medicine, 1991. 188 p.

4. Kichemasov S.Kh., Burmistrov V.M., Vikhriev B.S., Skvortsov Yu.R. Frostbite as a problem of skin plastic surgery // Herald of Surgery im. I.I. Grekova, 1998. №5. Pp. 97-99.

5. Ingram B.J., Raymond T.J. Recognition and treatment of freezing and nonfreezing cold injuries. // Curr Sports Med Rep. 2013 Mar-Apr; 12 (2): 125-30.

6. Chashchin V.P., Dedenko I.I. Labor and human health in the North. Murmansk Prince. Publ. 1990. 104 p.

7. Chashchin V.P. Anfalova G.L., Nikanov A.N. , Chernev A.V. Safety rules in the organization and production of work in open areas, territories and inside unheated premises in the cold season. Approved Resolution of the Governor of the Murmansk region 07.06.99 №242-PG. National Research Center "Pazori" - Murmansk, 1999. 22 p.

8. Azhayev A.N., Berzin I.A., Deeva S.A. Physiological and hygienic aspects of the effect of low temperatures on the human body. - M .: Medicine, 2008. 120 p.

Claims (1)

The use of pyrogenic combination at a dose of 12.5 µg / kg intramuscularly 1 hour before the dive and Relanium at a dose of 5 mg / kg with sodium hydroxybutyrate at a dose of 500 mg / kg intragastrically 30 minutes before immersion in cold water as a means of reducing mortality and accelerating the recovery of body temperature in the post-hypothermic period.