The remedy for the prevention and treatment of ketosis

 

(57) Abstract:

The invention relates to the field of medicine and biology and relates to drugs that regulate metabolism. The invention lies in the fact that the proposed tool consists of the sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonic introduced in an aqueous solution of glycerol, which contains magnesium as pharmacologically active substances and excipients, the concentration of glycerol in aqueous solution is 50-200 g/l, sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonic of 0.2-2.0 g/l, and magnesium 0.2 to 2.2 g/l Magnesium is introduced in the form of water-soluble monooly or their compositions. The invention provides a more pronounced ability to prevent the development of ketosis. 1 C.p. f-crystals, 2 tab.

The invention relates to the field of medicine and biology and relates to drugs, regulating metabolic processes.

The proposed tool can be used in medical practice for the prevention and treatment of ketosis.

Ketosis denote a phenomenon caused by increased production and accumulation in the body of excess ketone bodies are acetone, acetoacetate and beta occiput is, gives accompanied by the accumulation in the blood of acetone, acetoacetate and -oxybutyrate, there is a lack of homeostasis and disorder functions of the various organs and systems. Ketone bodies have a depressive effect on the Central nervous system, causing disruption of acid-base balance and water-electrolyte balance. Ketone bodies have the ability to cause depression of myocardial contractility. Hypoxic effect when ketosis is associated with a significant increase in the content in erythrocytes glucolysed hemoglobin, reducing the content of 2,3-diphosphoglycerate and the shift of the dissociation curve of hemoglobin to the right. The extreme degree of disability due to ketone bodies is the result of severe acidosis - ketoaldehydes coma.

Ketosis may develop diabetes, pregnancy, starvation, alcohol intoxication, when postintoksikatinom alcohol syndrome and treatment of alcohol teturamom.

In diabetes mellitus type I ketosis is a common metabolic disorder that causes severe, sometimes fatal, disorders. Alcohol abuse, his moderate and even episodic the tx2">

During pregnancy ketosis develops as a result of increased utilization of fatty acids, glucose and amino acids fruit, and compensatory hyperproduction of ketone bodies in the liver of the mother. Ketone bodies, freely cross the placenta, have toxic effects on the Central nervous system of the fetus, which increases the risk of fetal death and postnatal period has a negative impact on the mental development of the child. The most difficult ketosis occurs during pregnancy in women with diabetes mellitus.

When alcohol intoxication ketosis develops as a result of activation of lipolysis in adipose tissue by catecholamines, inhibition of beta-oxidation of fatty acids in liver acetaldehyde and higher recovery acetoacetate in beta-oxybutyrate.

When postintoksikatinom alcohol syndrome causes of ketosis are the same as with alcohol intoxication.

All pathological conditions associated with risk of developing ketosis, characterized by the presence of acidosis, energy shortages and decreased activity of antioxidant systems with the development of oxidative stress and dehydration.

Methods medical, Pato is by therapy of the underlying disease (for example, insulin therapy in diabetes), applying methods of diet, as well as ways symptomatic therapy effects of ketosis (for example, normalization of acid-base balance, water balance etc).

Diet therapy when threatened and developed ketosis is traditionally based on the following elements: exclusion from the diet of glucose, sucrose, fat and protein, the purpose of food products containing other digestible carbohydrates (fructose, honey, jam, juice, mousses, semolina), plenty of fluids (up to 1.5-3.0 liters per day), alkaline mineral water, sweeteners (sorbitol, and xylitol), with antiketogenic effect.

It is established that in addition to xylitol and sorbitol ability to provide antiketogenic effect has glycerin. However, this goal is rarely used. Glycerin has an unpleasant, sickly sweet taste. When used it in pure form or in the form of aqueous solutions, it causes many people nausea and even vomiting. The latter is due to its high osmolarity and the ability to cause irritation of receptors of the stomach.

Known soft drink "Amethyst" [1] containing liquid basis, istochniki adverse consequences of drinking, but it does not provide effective prevention and treatment of ketosis.

Also known preparative form of the sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonic containing a mixture of monomers comprising 50-70% of dimeric compounds affecting cell metabolism [2] and soft drink [3] , including the sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonate, has a tonic effect.

Based on the known properties of the sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonic its applicability for potentiation useful (antiketogenic) effect of glycerol was not obvious and well-known tools [2, 3] does not have a pronounced therapeutic effect in the prevention and treatment of ketosis.

However, it is also known the use of magnesium salts in the form of plain products or the inclusion of multi-component medicines for different purposes [4].

On the basis of known properties and applications of magnesium was effective to eliminate the side effects of glycerol was not obvious.

The closest analogue of the proposition is a well-known tool [5] DL start - sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonate - effective amount and a pharmaceutically acceptable excipient.

Sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonic used as a remedy for the correction of pathological conditions associated with metabolic processes.

However, in the known tool is not provided by components that enhance therapeutic effect for profilaktiki and treatment of ketosis.

therapeutic result is a more pronounced ability to prevent the development of ketosis is achieved in the proposed tool, consisting of a sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonate and additional pharmacologically active substances and excipients, in that it contains as an additional pharmacologically active substances and excipients aqueous solution of glycerin and magnesium salts, in an aqueous solution of glycerol concentration of 50-200 g/l entered sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonic with a concentration of 0.2-2.0 g/l and magnesium concentrations of 0.2-2.2 g/L.

Magnesium is introduced in the form of water-soluble monooly or their combinations (sulfate, Oia is the following.

In the proposed tool antiketogenic effect of glycerol increases with sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonate, representing a mixture of monomers (from dimer to hexamer), but a side effect that occurs when the enteral intake of glycerol (nausea, vomiting), is eliminated by using magnesium ions.

Magnesium ions are used, inter alia, to compensate for the deficiency of magnesium in the body and eliminate associated with magnesium deficiency of disability (a state of hyperexcitability, convulsive States, eclampsia, cardiac arrhythmias, cerebral blood flow, hypertension, disorders of gastric digestion, sleep disorders, intoxication with salts of heavy metals and others).

The expediency of application of glycerol in combination with magnesium salts is determined by the fact that magnesium ions have the ability to reduce the reflex excitability of the neurons and smooth muscle of the stomach and slow neuromuscular transmission. The introduction of magnesium salts in the glycerin solution eliminates the ability of the latter to cause nausea and vomiting, thus preventing a side effect that does not allow the use of glycerol in medical practice.

The procedure for making the sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonate and magnesium in a solution of glycerin does not matter.

When using this drug combination is amplified positive antiketogenic effect of glycerol and eliminates its negative side effects (nausea, vomiting).

The proposal to use an aqueous solution of glycerin in the above concentrations is due to the fact that the more concentrated its solutions have extremely low organoleptic properties and cause nausea and vomiting even in the presence in solution of magnesium salts. The maximum content of glycerol in the solution (200 g/l) determined based on the above considerations. The minimum concentration of glycerol (50 g/l) is minimally effective. When using such a solution in 250 ml single dose of glycerol is about 0.2 g/kg In smaller doses as observed antiketogenic effect of glycerol is poorly defined.

We offer a range of concentrations of sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonate in solution due to the following reasons. The upper bound concentration of this compound (2.0 g/l) determined on the basis of its average (0.5 g) and maximum (1.0 g) a single dose. When using a solution in a dose of 250 ml in the human organism 0.5 g of sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonate. In case of the use solution in the amount of 0.5 l dose of sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonic increases to a maximum value of 1.0,

Concentration made in the glycerin solution of magnesium determined by experiment. Minimum dose of magnesium (0.2 g/l) matched by observations on the people-volunteers, indicating that at lower concentration of magnesium ions in a solution of glycerin beneficial effect of magnesium is not shown. The maximum concentration (2.2 g/l) corresponds to the maximum content of magnesium in food products, in particular in watermelon.

The effectiveness of drug combinations against vasodilate by depriving rats of access to food for 4 days (fasting) and the introduction into the stomach of the hungry rats ketogenic Caprylic acid at a dose of 2.5 mm/kg twice a day for 4 days. For control were rats treated with standard balanced feed without limitations.

On the third and fourth day of the experiment the animals in the experimental groups were administered intragastric aqueous solution of glycerol at a concentration of 100 g/l in 15 ml/kg or equiano number of similar glycerin solution, which was made sodium salt of [poly-(2,5-dihydroxyphenyl)]-4-thiosulfonic at a concentration of 0.5 g/l and magnesium sulfate at a concentration of 2.5 g/l as the control solution used water that was injected according to the same scheme in the amount of 15 ml/kg

At the end of the experiment (the fifth day from the start of the experiment) in the blood of rats investigated the total content of ketone bodies.

The results are presented in table. 1 and 2.

Sources of information

1. RF patent 2005391, M CL A 23 L 2/00, 1994

2. RF patent 2123333, M. class. And 61 To 31/185, 1998

3. RF patent 2116735, M CL A 23 L 2/00, 1998

4. The Handbook. Vidal. Medicines in Russia. - 2000

5. RF patent 2124888, M. class. And 61 To 31/185, 1999

1. The remedy for the prevention and treatment of ketosis, containing the sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonate and additional farmacologicas is Rina and magnesium salts, moreover, the concentration of an aqueous solution of glycerol is 50-200 g/l, sodium salt of [poly-(2,5-dihydroxyphenyl)] -4-thiosulfonic of 0.2-2.0 g/l, and magnesium salts of 0.2-2.2 g/L.

2. Means under item 1, characterized in that the magnesium is present in the form of water-soluble monooly or their combinations - sulfate, salicylate, stearate, lactate, ascorbate, citrate, carbonate, chloride, Asparaginate.

 

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