FIELD: medicine, pharmaceutics.

SUBSTANCE: there is offered the administration of the preparation Histochrome (echinochrome, 2,3,5,6,8-pentahydroxy-7-ethyl-1,4-nahthochine, formerly known as an antioxidant) as a diuretic.

EFFECT: histochrome exhibits an evident diuretic action equal thiazide-type diuretics in intensity, does not cause associated hypokaliemia, has an absolute advantage over thiazide-type diuretics.

2 tbl


The invention relates to medicine, namely to pharmacology, and relates to means having a diuretic effect.

Currently known means, showing diuretic activity: loop diuretics, tiazidove diuretics, carbonic anhydrase inhibitors, potassium-sparing diuretics, spironolactone, diuretics vegetable origin.

Known drug, namely hydrochlorothiazide possessing diuretic effect [Glezer GA Diuretics. - M.: Interbook, 1993. - 352 S.]. Hydrochlorothiazide belongs to a group casinovip diuretics. Diuretic effect due to violations of the reabsorption of sodium ions and, as a consequence of water in the distal tubules of the kidneys. The drug is widely used in the treatment of diseases of the cardiovascular system, as well as other pathologies involving violations of water-electrolyte balance.

Hydrochlorothiazide has some significant drawbacks that limit its application. These include: gipokaliemicakie action diabetogenic effect, disorders of calcium metabolism and other

You know, the drug furosemide, possessing diuretic effect [Bryukhanov V.M., Zverev AF Side effects of modern diuretics. Novosibirsk: "Ceres", 2003. - 224 S.]. Furosemide belongs to the group of loop diuretics. Diuretic on the op perate has a breach reabsorption of sodium ions and as a consequence water in thick ascending Department of Genle loop. The drug is widely used in the treatment of diseases of the cardiovascular system, as well as other pathologies involving violations of water-electrolyte balance.

Furosemide has a number of disadvantages: the rapid weakening of the diuretic effect with repeated introductions, gipokaliemicakie action, the development of pseudohyperparathyroidism etc.

The technical result is an expanding Arsenal of diuretic funds.

The technical result is achieved by using as diuretics drug Histogram®.

Drug Histogram® is a pharmaceutical form of individual substances - natural quinoid pigments of marine invertebrates of echinochrome (2,3,5,6,8-pentahydroxy-7-ethyl-1,4 naphthoquinone, state registration number P No. 002363/01-2003).

Know the use of the drug Histogram® for the treatment of eye diseases (number of state registration of R No. 002363/02-2003) [RF Patent 2134107, A61K 35/56, 1999]. Histogram® is used in cardiology to reduce the size of myocardial infarction and prevention of reperfusion lesions of the myocardium (the state registration number R No. 002363/01-2003) [RF Patent 2137472, A61K 31/05, 1999], for the treatment of hemorrhagic stroke [RF Patent 2266737, A61K 31/05, 2005]. The drug entered in the Register of medicines, resolved to note the wetlands in the Russian Federation [the Big Russian encyclopedia of drugs, M., 2001, "Remedium", volume 2, s]. Pharmacotherapeutic group: anti-oxidant agent. The certificate of trademark registration 183145.

Histogram® is available in two dosage forms "Historom® solution for intravenous 1%" and "Histogram® solution for injection 0,02%"

"Historom® solution for intravenous 1%" prescribed for acute myocardial infarction in combination with thrombolytic drugs to eliminate caused by reperfusion complications. "Historom® solution for injection 0,02%" is used in dystrophic diseases of the retina and cornea, diabetic retinopathy, retinal hemorrhages into the vitreous body, retina, anterior chamber, with dyscirculatory violations in the Central artery and vein of the retina.

The use of the drug Histogram® as diuretics are not described in literature.

Brand new in the alleged invention is that the drug Histogram® can be used as a means of having diuretic activity.

New properties of the drug were found experimentally. The invention will be clear from the following description.

Experiments to study the diuretic properties of the drug Histogram® were carried out at 40 Wistar rats of both sexes weighing 180-220 g throughout the experiment the animals were the individual cells, adapted to collect urine in the conditions of free access to water and food. Under the terms of the experiment, rats were divided into two groups of 20 animals each. In the first (comparison group) for 10 days to rats subcutaneously administered hydrochlorothiazide dose of 20 mg/kg In the second (experimental group) for 10 days subcutaneously administered drug Histogram® at a dose of 10 mg/kg Every 2-3 days measurements were taken of the main indicators of kidney function is the volume of diuresis, urinary excretion of sodium and potassium ions, excretion of urine creatinine.

Statistical processing was performed using the Statistica for Windows 6.0". Expected average value, the standard error for the detection of significant differences used the criterion of student.

The results are shown in examples 1-2.

Example 1. It is established that the dynamics of the diuretic effect of hydrochlorothiazide in the experiment on rats is of the following nature. The level of urination in animals steadily increased, reaching a maximum on day 6 of experiments, when he exceeded targets by more than 4 times (table 1). Then after 10 days of administration of the drug diuretic response was somewhat weakened, still significantly outperforming the baseline - 3.2 times. It is important that the observed increased urination was accompanied by a significant INCR is the increase renal excretion of sodium ions, which is in good agreement with literature data. As can be seen from the experimental results, hydrochlorothiazide had no effect on the process of glomerular filtration, because the amount of excretion with urine creatinine throughout the experience remained unchanged. Thus, hydrochlorothiazide in the experiment on rats had a marked diuretic action, which arose due to violations of the reabsorption of sodium.

Example 2. Animals treated with Histogram®, diuretic effect was developed, starting from the third day, when the urination significantly increased 2.1 times. In the days that followed diuretic effect of the drug is further increased, reaching a maximum on day 7, when it exceeded control values by almost 5 times. Then in the last 10-day administration and even through the day after the drug level of diuresis was still characterized by high values, exceeding the original figures 4.1 and 3.7 times, respectively (table 2).

Against this background, not been a substantial increase in the excretion of urine sodium ions. Significant increased excretion of electrolyte was observed only on the 9th and 11th days of experience. This may mean that unlike hydrochlorothiazide histogram increases urination, not by inhibiting the reabsorption of sodium and due to other reasons. Partly osny diuretic effect of histogram can be explained by increased glomerular filtration, as in the experiment, there was an increase in the excretion of creatinine. Dynamics of increased excretion of creatinine were in the nature comparable to those described for the dynamics of urination: on the 5th day, there was an increase of the described indicator 2.8 times, on the 7th day - to 5.6-fold, 9-th and 11-th day - 3.8 and 3.3 times, respectively. However, a powerful diuretic effect of histogram, comparable in strength to the effects of hydrochlorothiazide, caused not only by increased filtering. Probably histogram exerts an inhibitory effect on the reabsorption of osmotically free water, which requires additional experimental evidence.

No less important is the fact that, as the experiments showed, histogram virtually no effect on the renal excretion of potassium ions. Significant increase in the excretion of urine of this electrolyte was observed only on the 9th and 11th days of experience. However, it is well known that the comparator drug hydrochlorothiazide, like all tiazidove diuretics, has a powerful calibrations action, leading to the development of hypokalemia, which is a very serious side effect [2].

Thus, the drug Histogram® has a strong diuretic effect, by force of which he is not inferior tiazidovy diuretics. Thus Historom® has a unique mechanism of mojego the aqueous actions it is much less effect on the reabsorption of sodium ions and causes only a small increase in the glomerular filtration rate. However, the main components in the mechanism of action require further in-depth study. Importantly, the drug Histogram® does not cause hypokalemia, therefore, has a definite advantage over tiazidnymi diuretics.

Table 1.
The influence of long-term administration of dihlotiazid on excretory kidney function
IndexControl3 dayday 6day 10
Diuresis (ml/day)5,7±0,5123,4±2,16*23,7±2,28*18,2±2,21*
The creatinine excretion (mmol/day)5,0±0,144,6±0,425,0±0,415,3±0,39
Note: *- p<0.05 compared to control.

td align="right" namest="c0" nameend="c7"> Table 2.
The influence of long-term administration of the drug Histogram® excretory kidney function
IndexControl1 day3 days5 days7 days9 days11 days
Diuresis (ml/day)2,9±0,403,2±0,646,1±1,0310,4±1,88*14,1±2,17*12,1±1,57*10,6±1,65*
The sodium excretion (mmol/day)37,7±3,2029,1±4,1031,4±2,9332,7±4,0745,4±4,2757,0±11,7*to 85.5±16,65*
The potassium excretion (mmol/day)496,0±32,1435,0±72,8464,0±65,5492,0±42,8618,0±66,9797,0±59,3*870,0±66,3*
The creatinine excretion (mmol/day)3.3V±0,343,0±0,502,3±0,289,2±1,20*18,6±2,24*12,7±2,71*10,92±1,95*
Note:* - p<0.05 compared to control.

The use of the drug Histogram as diuretics.


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