A substance having antihypoxic activity

 

(57) Abstract:

The invention relates to medicine, specifically to pharmacology, and relates to the use of previously known antimicrobial colloidal preparations of silver of the protargol and colloid for a new purpose as antihypoxants. The solution can be used in medicine and veterinary medicine in therapy of acute hypoxic conditions, ischemia of organs and tissues. The protargol preparations and colloid are used for protection against hypoxia by intragastric administration in the body in doses of 0.15oC750 mg/kg of body weight in the form of aqueous solutions. table 1.

The invention relates to biologically active protein preparations of silver, or more precisely to the new usage of the previously known silver-containing products "Colloid" and "Protargol".

The claimed technical solution can be widely used in medicine and veterinary medicine in therapy of acute hypoxic conditions, in particular during ischemia of the brain and heart, which significantly extends the use of known Proteinate silver.

Protargol is a colloidal silver oxide, stabilized products hydrolise gelatin, and contains 7,8oC8,3 Masi mucous membranes of the eyes, the upper respiratory tract and genitourinary system. On the world market price is 1000 USD for 1 kg

Colloid is a colloid metal silver, stable products of hydrolysis of casein, and contains 70 wt. metal [1] is Used in medicine for the same purpose as a protargol, however, its value is 3 times higher than that of the protargol.

These known drugs was previously known only antimicrobial and antiviral activity [1]

Known natural antihypoxants, the most important role among them is played by adenosine and its derivatives, which upon intramuscular injection in the body in doses of 10oC50 mg/kg body weight increases the body's resistance to hypoxia (lack of oxygen) [5] the Cost of these antigipoksanta rather high and amounts to adenosine 1,888 million US dollars per 1 kg, and for adenosine-triphosphate (ATP)- 5175 US dollars per 1 kg.

The main disadvantage of natural antihypoxants is that they are already in therapeutic doses exhibit undesirable side effect [2] sharply reduce blood pressure, inhibit cardiac activity and functions of the Central nervous force is the increased resistance to hypoxia, not with adverse pharmacological effects.

This problem was solved by application of known Proteinate silver as antihypoxants. The solution is based on the first detected non-obvious, not derived from prior knowledge about the properties of known Proteinate silver, functions lies in their ability to provide an antihypoxic action of enteric or systemic administration into the body in subconsiously doses.

Determined that intraperitoneal injection to rats, the magnitude of LD50for protargol and colloid respectively 250 mg/kg and 70 mg/kg of body weight, and oral and intragastric introduction of more than 1500 mg/kg

Previously countrymusic and intragastric administration of proteins silver for medicinal purposes has not been used.

Analysis of the known level of science and technology confirmed the absence of any information about the new functions of known proteins of silver. This allows to conclude that the novelty of the proposed solution. The discovery of the new function does not follow clearly from prior knowledge. This confirms the compliance of the claimed invention in the application for a new nasnanlong solutions demand "industrial applicability", and for a better understanding of the invention provide specific examples of its implementation.

To assess antihypoxic action of silver-containing proteins used two independent test: model cupping hypoxia with hypercapnia and model of tissue himicheskoi hypoxia induced by intramuscular injection of sodium. In the first case, antihypoxic activity of the substances was evaluated by their ability to lengthen the lifetime of the mice under conditions of oxygen starvation, and in the second case, the survival rates of white rats (in) a day after hypoxia.

Example 1 (control jar hypoxia with hypercapnia in mice)

White mice (n=20) weighing 18-20 g were injected intragastrically using a rigid metal probe 0.3 ml of distilled water and the animals were placed in a closed airtight jar for up to 100 cm3. Through 11,31,6 min all mice died from lack of oxygen.

Example 2 (control-Himicheskaya hypoxia in rats)

White rats (n= 20) weighing 160-200 g were injected intragastrically using a probe 0.8 ml of distilled water and after 30 min was introduced to them intramuscularly sodium nitrite at a dose of 85 mg/kg of body weight. Through 1,37 0,16 h watched the death of 928% of the animals (survival 8 1%)

Example 4. In the conditions of example 1 for 30 min before hypoxia mice (n=20) instead of water was injected intramuscularly aqueous solution of the colloid at a dose of 30 mg/kg of body weight. The lifespan of mice under conditions of oxygen starvation was 22,82,3 minutes

Example 5. In the conditions of example 2 for 30 min before the injection to rats (n=20) of sodium nitrite, the animals were injected intragastrically aqueous solution of protargol at a dose of 150 mg/kg of body weight. In contrast to the control (example 2) death of animals occurred in the more distant time and a day after hypoxia survived of 56.4

5,9 rats, i.e. 7 times more than in the control.

Example 6. In the conditions of example 5 intramuscular injection to rats (n=20) of an aqueous solution of a colloid in a dose of 5 mg/kg of body weight, instead in/W the introduction of protargol, provided twenty-four hours after injection of sodium nitrite survival rate is 61.8 6.8% of animals. Protective effect cerebrosidase proteins from hypoxia at various doses and routes of administration in the body, as well as standard antihypoxic drug ATP (see table).

The invention is illustrated in the following examples, confirming dostii.

Analysis of the data presented in the table shows that the silver-containing Proteinate more effective as antihypoxants than ATP, and their activity in contrast to ATP is manifested not only in intramuscular, but after intragastric administration in the body.

Antihypoxic effect of silver-containing Proteinate manifests itself in doses much lower than those of their acute toxicity, in contrast to ATP is not accompanied by hypotension, depression of cardiovascular activities and functions of the Central nervous system.

Special studies have established that the basis of antihypoxic action of these substances is as a direct excitation of cholinergic neurons in the intramural plexus of the small intestine, and enhanced activity of endogenous neurotransmitters released during hypoxia.

This solution can be used in medicine and veterinary medicine in therapy of acute hypoxic conditions, ischemia of organs and tissues.

The use of water-soluble silver-containing Proteinate from a number containing protargol and colloid, as compounds having antihypoxic activity.

 

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