The way to promote adaptation to extreme and stress factors

 

(57) Abstract:

Usage: the invention relates to methods for increasing the body's resistance to extreme influences with the use of biologically active substances. The solution can be used in medicine and veterinary medicine in the treatment of acute hypoxic conditions, ischemia of the brain, heart, shock, stress, as well as analgesic and antidepressant funds. Goal: create a physiological means of promoting adaptation to the adverse effects of extreme factors using low-toxic biologically active substances. The essence of the invention: a method of protecting the body from extreme and stressful influences by intramuscular or intragastric administration in subconsiously doses (1 to 300 mg/kg) of aqueous solutions of the composition containing fine metal silver and poly-N-vinyl pyrrolidone (PVP) with MM (6 - 40) 103when the ratio of ingredients, wt.h.:

PVP - 1

Silver - 0,01 - 2,33

Positive effect: after intragastric administration of these compositions in the body achieves high efficiency protection against hypoxia, shock, pain, depression and stress, from the Xia to the means of promoting adaptation to extreme and stressful effects of biologically active water-soluble polymer compositions containing fine metal silver, stabilized poly-N - vinyl pyrrolidone; with adaptogenic properties.

The invention may find wide use in medicine and veterinary medicine as potential drugs with antihypoxic, anti-shock, analgesic, antidepressant and antistress activity.

The terms used in the description and clarification.

Colloid-commercial drug product, including colloidal metallic silver (70%) and the products of hydrolysis of casein. Used as an antimicrobial agent /TSB, 3rd ed., so 12, M.: Izd. SCS, 1973/.

PVP - poly-N-vinyl pyrrolidone - synthetic water-soluble polymer of General formula

.

Used in medicine as a blood plasma substitute and detoxifier. Produced for medical purposes with different molecular masses (mol.m. 12600 2700 - plasma substitute "Gemodez", mol.m. 8000 2000 - plasma substitute "Gemodez-H", mol.m. 35000 5000 for coating tablets and as a binder in the finished dosage forms.

ATP - adenosine-5' -triphosphate dinarama salt, hydrate /99%, they say.m. 551,15, so pl. 176oC, one hundred is the known analogs of the proposed method are ways to stimulate adaptation to extreme and stress factors using as the active principle of natural adaptogens, first of all adenosine and its derivatives.

The described method with the introduction intramuscularly (I/m) or intraperitoneally (br) ATP doses of 10 - 50 mg/kg /I/, to ensure adaptation to extreme factors, such as lack of oxygen, shock, pain, stress. Oral or intragastric (W/W) introduction to the same doses of adenosine and its derivatives ineffective as adaptogens.

The main disadvantage of this method is that in these therapeutic doses of ATP and adenosine have adverse physiological effect: significantly reduce blood pressure, inhibit cardiac activity, and at doses above 50 mg/kg inhibit the function of the Central nervous system and cause severe cardiovascular and respiratory insufficiency /3/.

The objective of the invention was to overcome the disadvantages of the known solutions, i.e. the creation of means of promoting adaptation to extreme and stress factors using as the active agent of low funds with minimum side effects.

This problem was solved stated by way of introduction as the active agent a water-soluble polymer in a ratio of components, wt.h.:

PVP mol.m. (6 - 40)103- 1

Fine metal silver - 0,01 - 2,33

This composition is injected intragastrically (W/W) or intramuscularly (I/m) at doses of 1.0 to 300 mg/kg of body weight.

Analysis of the known level of science and technology did not reveal any information about the ways in which active early would be a silver-containing composition with adaptogenic properties. The closest analogue of the active agent in the composition is a drug colloid, is only used as an antibacterial and antiviral agent.

So acting, the claimed solution to meet the requirement of "novelty."

The inventive method is based on the first detected property of the polymeric composition containing fine metal silver, to stimulate the body's adaptation to extreme and stressful factors in b/W or/m injected into the body in subconsiously doses.

Finding non-obvious dependencies between the structure and properties of silver-containing composition suggests the invention according to the requirement of "inventive step".

Adaptogenic properties of the claimed compositions were evaluated by a number of special tests:

1. the th and tissue himicheskoi hypoxia in rats caused by injection of sodium nitrite.

2. Antishock effect of the composition was evaluated in a model of severe insulin shock, called in/m introduction of a double fatal dose of insulin.

3. Analgesic effect of substances were evaluated on their ability to lengthen the duration of the latent period otdergivanija tail of rats when it is immersed in hot water (56oC).

4. Antidepressant effect of the substances was evaluated in the swimming test Porsolt on white mice by duration of immobilization of animals.

5. Antistress effect of the substances was evaluated on the model vodoemulsionnaja stress on rats in comparison with the reference drug sodium oxybutyrate, and recorded the number and size of erosions in the gastric mucosa, resulting from stress.

Example 1. In the dark glass reactor, equipped with stirrer, addition funnel and a bubbler for blowing an inert gas (nitrogen, argon), download 1172,6 ml of distilled water, 100 g of ethyl alcohol and 200 g of PVP mol. m 126000 2700. The solution is heated under stirring for 10 min to 75oC and at this temperature, add to it 27,39 g of silver nitrate (HTA, stirred at the same temperature until complete exhaustion of ionic silver (the control sample with a 1% aqueous solution of sodium chloride). Received a bluish-green solution is dried in the spray dryer and get the target water-soluble composition of the fine metal silver and PVP in the form of a powder greenish-gray color. The yield of the target product 217,2 g (99,9%); the content of the metal 7,94%.

Conditions for obtaining compositions of other compositions according to examples NN2-5 are given in table.1. Also there are indicators of acute toxicity of compositions intraperitoneal injection white mice.

Example 6 (control - canned hypoxia in mice).

Mice (n=20) weighing 20 g was introduced in/W using a metal probe 0.3 ml of distilled water and after 30 min, animals were placed in a closed airtight jar for up to 100 cm3. Through 11,3 1,6 min, all animals died from oxygen starvation.

Example 7. In the conditions of example 6 for 30 min before hypoxia mice (n=20) instead of distilled water were introduced in a/W 0.3 ml of 1% aqueous solution of the composition of the composition specified in example 1, which corresponded to a dose of 100 mg/kg of body weight. Through 18,2 1,8 min, all animals died from oxygen starvation, the 8 (control - Himicheskaya hypoxia in rats).

White outbred rats (n=100) weighing 160-200 g were injected intragastrically 0.3-0.5 ml of distilled water and after 30 min did intramuscular injection of sodium nitrate at a dose of 85 mg/kg of body weight. Through 1,37 0,16 o'clock on the background of pronounced hypoxia killed 92 8% of the animals.

Example 9. In the conditions of example 8 for 30 minutes before injection of sodium nitrite to rats (n=100) were injected intramuscularly with 0.1% aqueous solution of the composition obtained in the conditions of example 2. The dose of the composition was 10 mg/kg of body weight. A day after hypoxia died 37,5 7,5% of the animals.

Example 10 (control - deadly insulin shock in rats).

White outbred rats (n=100) weighing 170-190 g were injected I/m double a lethal dose of insulin (2.5 IU of insulin per 100 g rat). After 3-4 hours of severe hypoglycemic shock caused the death of 100% of the animals.

Example 11. In the conditions of example 10 for 30 min before insulin injections, the animals were injected intramuscularly in 0.01% aqueous solution of the composition obtained in the conditions of example 3. Within 8 hours after the shock death of rats from the shock was not observed. One day after injection of insulin killed 38 7% of the animals.

Example 12 (control - analgesic effect, as measured by the or/W 0.3 ml of distilled water and after 30 min was recorded latent period of reflex otdergivanija tail of rats during its immersion in hot water with a temperature of 56oC, which was 3,50,42 C.

Example 13. In the conditions of example 12 intragastric administration of a composition obtained in the conditions of example 4, at a dose of 300 mg/kg of body, completely inhibited the reflex otdergivanija tail in rats when it is overheating (the latent period of reflex more than 40), and the analgesic effect was maintained within 3-8 hours

Example 14 (control - depression mice in the Porsolt test).

White mice-males (n= 20) weighing 18-20 g, starving 12 hours or more before the experience, was introduced in/W 0.2 ml of distilled water and after 30 min, the mice were lowered to swim in a glass jar with a diameter of 40 mm and a height of 700 mm in water with a temperature of 28-30oC. was Detected in mice duration of all stops in swimming (immobilization) during the observation period for 5 min (1st to 6th minute after immersion), which was 110,030,9 C.

Example 15. Intramuscular injection of mice aqueous composition obtained in the conditions of example 1 at a dose of 15 mg/kg 60 min before the test according to example 14, evoked in animals two opposite physiological effect depending on the innate ability of animals to swim. 80% good floating individuals showed a strong antidepressant effect, as is their immobilization in the Porsolt test was increased to 155,010,0 C.

Example 16 (control - vodoemulsionnye stress in rats)

Outbred rats-males (n=20) weighing 210-260 g was introduced in/W 0,8 - 1,2 distilled water and after 30 min, animals were placed in close cases. Animals were fixed in an untenable position: they could not turn on his side and turn around. Canisters with animals were placed with a temperature of 21-24oC. water Level corresponded to the xiphoid process of the rat. The duration of stay in the water was 7 o'clock In animals recorded the number and size of erosions in the gastric mucosa, resulting from stress. The average number of erosions was 12,03,2, and their area of 15.6 4.6 mm2.

Example 17. In the conditions of example 16 as an antistress drug compare the use of the sodium salt of 4-hydroxybutiric acid /Aldrich, 1992/93, S. 695, the cost of 100 g 75,85 dollars. USA/, which was administered to rats in a dose of 300 mg/kg body weight 30 min before stress. The average number of erosions in animals amounted to 8,6 6,1 size and 8,25,2 mm2, i.e. 2 times less than in control.

Example 18. In the conditions of example 16 for 30 min prior to stress to the animals instead of water was injected into/W 0,1% aqueous solution of the composition obtained in the conditions of example 1. The dose was 4 the above than in the control.

Adaptogenic properties of silver-containing compositions of different composition when they are in the/f and/m injected into the body, as well as some natural adaptogens are given in table. 2-6.

Analysis of these data shows that the claimed means of promoting adaptation to extreme impacts on its effectiveness is comparable to or exceeds the effectiveness of the known methods and more physiological, because the positive effect is not only systemic, but also intragastric administration of the active agent.

The way to promote adaptation to extreme and stress factors by introducing an aqueous solution of the active principle, characterized in that the active agent using a composition containing fine metal silver and poly-N-vinyl pyrrolidone in a ratio of components, wt.h.:

Poly-N-vinyl pyrrolidone - 1

Silver - 0,01 - 2,33

this poly-N-vinyl pyrrolidone take MM from 6000 to 40000, the active principle is administered intragastrically or intramuscularly in doses of from 1 to 300 mg/kg of body weight.

 

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1 cl, 3 ex, 1 tbl

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