RU2542454C2 - Method for general controlled hyperthermia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to experimental medicine, and can be used for general controlled hyperthermia. That is ensured by the general warm-up of an experimental animal's body with the preliminary intraperitoneal administration of an animal toxin. The intraperitoneal administration of the animal toxin is preceded by administering protamine sulphate in a dose of 10mg/kg; the animal toxin is bee poison 2.5mg/kg, or cobra poison 0.5mg/kg, or carpet viper poison 1.5mg/kg, or copperhead snake poison 2mg/kg, or scorpion poison 1mg/kg, or lebetina viper poison 2mg/kg.

EFFECT: invention provides the higher survival rate of the animals, particularly 24 hours later, with the low negative effect of the administered animal toxin on the animal's body.

2 tbl, 1 ex

Description

The proposed method relates to medicine, in particular to experimental medicine, and can be used in oncology. A known method of general controlled hyperthermia of the human body, including general heating of the body by immersion in hot water, using fentanyl anesthesia, mechanical ventilation and the introduction of urotropin before heating, at a height and after restoration of normothermia (1).

The disadvantages of this method include: the complexity of the experiment, the use of drugs and muscle relaxants, intubation of the respiratory tract.

It is known to use, under controlled hyperthermia, before general warming up the animal's body for intramuscular administration of the compound: 2-piperazino-1- (thietanyl-3) benzimidazole dihydrochloride. This compound increases the physical performance of animal hyperthermia in the experiment (2).

There is also known a method involving general heating of the body with preliminary intramuscular administration of a substance that increases resistance to hyperthermia, while 3- (2-dimethylaminoethylthio) -8-methyl-1,2,4-triazino dihydrochloride is used as the specified substance [5,6 -b] indole (3).

The disadvantage of this method is the relatively low percentage of animal survival.

The closest in the set of essential features and the achieved technical effect is the known method of controlled hyperthermia, selected by the authors as a prototype (4). This method involves general heating of the body at 50 ° C and 30% humidity with preliminary intraperitoneal administration 10 minutes before heating the substance, which increases resistance to hyperthermia. As the specified substance, zootoxin is used, such as: muzzle poison at a dose of 4 mg / kg, or efa poison at a dose of 3 mg / kg, or cobra venom at a dose of 1 mg / kg, or bee venom at a dose of 5 mg / kg.

Table 1 shows the results of a study of the effect of introduced zootoxins on the survival of animals (150 non-linear male rats weighing 200 + 10 g) under conditions of hyperthermia.

The disadvantages of this method is the high dose of zootoxin administered, which adversely affects the animal organism, and low animal survival after hyperthermia.

The objective of the invention is to develop a method of general controlled hyperthermia, after which there is a high survival rate of animals, in particular after 24 hours, with a low negative effect on the animal's body of introduced zootoxin.

The problem is solved by the proposed method of general controlled hyperthermia, including general heating of the body with preliminary intraperitoneal administration of zootoxin, according to the invention, before administration of zootoxin, protamine sulfate is administered at a dose of 10 mg / kg intraperitoneally, and bee venom, or cobra venom, or efa venom, as zootoxin or muzzle venom, or scorpion venom, or gyurza venom, and their dose is: bee venom 2.5 mg / kg, cobra venom 0.5 mg / kg, efa venom 1.5 mg / kg, muzzle venom 2.0 mg / kg, scorpion venom 1.0 mg / kg, gyurza poison 2.0 mg / kg.

The technical result of the proposed method is to increase the survival time of animals after a general controlled hyperthermia and reduce the dose of zootoxin administered and, as a result, reduce the negative effect of zootoxin on the animal's body. In addition, the proposed method allows to expand the arsenal of used zootoxins.

This technical result is achieved by the fact that before the introduction of zootoxin, protamine sulfate is administered intraperitoneally at a dose of 10 mg / kg, and bee venom, cobra venom, efa venom, thyroid muzzle venom, scorpion venom, gyurza venom are used as zootoxin, while their dose is: bee venom 2.5 mg / kg, cobra venom 0.5 mg / kg, efa venom 1.5 mg / kg, muzzle venom 2.0 mg / kg, scorpion venom 1.0 mg / kg, gyurza venom 2 mg / kg.

This technical result is due to the introduction of protamine sulfate at a dose of 10 mg / kg, which allows to reduce the dose of zootoxin administered.

The proposed method is as follows.

Preliminary, the animal is injected with protamine sulfate at a dose of 10 mg / kg, then after 10 minutes the animal is injected with zootoxin, such as bee venom, or cobra venom, or efa venom, or muzzle scorpion venom, or scorpion venom, or gyurza venom, and the dose zootoxin is: bee venom 2.5 mg / kg, cobra venom 0.5 mg / kg, efa venom 1.5 mg / kg, muzzle venom 2.0 mg / kg, scorpion venom 1.0 mg / kg, gyurza venom 2.0 mg / kg, and 10 minutes after the introduction of zootoxin carry out the general heating of the animal’s body, placing it in a climatic chamber in which the animal is kept for 45 m in at a temperature of 50 ° C and 30% humidity. Survival of animals after hyperthermia is assessed after 1 hour, 6 hours and 24 hours.

Examples of specific uses of the proposed method.

Example 1

The proposed method was implemented general controlled hyperthermia 230 laboratory non-linear male rats weighing 200 ± 10 g. The control group consisted of 20 animals that were injected with saline in the same volume.

The remaining animals were divided into 6 groups of 35 animals each. Each animal in all 6 groups was preliminarily injected with protamine sulfate at a dose of 10 mg / kg, and after 10 minutes the animals were injected with zootoxin:

- 1st group - bee venom in a dose of 2.5 mg / kg;

- to the 2nd group - cobra venom at a dose of 0.5 mg / kg;

- 3rd group - efa poison in a dose of 1.5 mg / kg;

- to the 4th group - muzzle poison at a dose of 2.0 mg / kg;

- to the 5th group - scorpion venom at a dose of 1 mg / kg;

- to the 6th group - gyurza venom at a dose of 2 mg / kg.

Then, 10 minutes after the administration of zootoxin, the body was warmed up for each animal in each group by placing them in a climatic chamber in which the animals were kept for 45 minutes at a temperature of 50 ° C and 30% humidity.

Survival animals were evaluated 1, 6, and 24 hours after hyperthermia.

The results of the general controlled hyperthermia of the proposed method are shown in table 2.

As can be seen from the obtained results, the proposed method of general controlled hyperthermia allows to achieve high survival of animals, in particular after 24 hours, with a low negative effect of the introduced zootoxin on the animal's body.

In addition, the proposed method allows to expand the arsenal of used zootoxins.

Information sources

1. RF patent No. 21266667, application No. 98107893 dated 05/05/1998 "Method of general controlled hyperthermia of the human body."

2. RF patent No. 2210370, application No. 2002125319/14 dated September 16, 2002 for “A substance that enhances physical performance in hyperthermia”.

3. USSR AS No. 1547279, application No. 4467653/04 of July 29, 1988 for 3- (2-Dimethylaminoethylthio) -8-methyl-1,2,4-triazino [5,6-b] indole dihydrochloride, which increases resistance to hyperthermia "

4. The prototype. RF patent No. 2313353, application No. 2006100638/14 dated 01/10/2006 “Method of controlled hyperthermia”.

Claims (1)

A method of general controlled hyperthermia, including general warming of the body with preliminary intraperitoneal administration of zootoxin, characterized in that before the introduction of zootoxin, protamine sulfate is administered at a dose of 10 mg / kg intraperitoneally, and bee venom 2.5 mg / kg or cobra venom 0.5 mg is used as zootoxin / kg, or efa venom 1.5 mg / kg, or muzzle poison 2 mg / kg, or scorpion venom 1 mg / kg, or gyurza venom 2 mg / kg.