RU1805961C - Substance with antiburn activity - Google Patents

Abstract

The invention relates to medicine, in particular to the pharmacotherapy of burn injuries. To do this, a mixture of poly.enoic fatty acids omega-3 series is applied to the affected surface as an anti-burn agent. 2 ill., 2 tablets

Description

The invention relates to pharmaceutical preparations containing organic active ingredients. namely higher fatty acids.

 In order to expand the arsenal of means of acting on a living organism, omega-3 acids are used as an anti-burn agent in the present invention.

The use of omega-3 acids from marine raw materials during a burn gave an unexpected result in qualitative and quantitative characteristics, superior to the use of the commercial anti-burn preparation 1 Linetol of the same nature (a preparation based on flaxseed oil fatty acids).

A mixture of omega-3 acids or their derivatives (e.g. ethyl esters of omega-3 acids) is a light yellow to slightly brown oily mobile liquid with a specific fishy odor. The mixture does not lose its liquid consistency even at -30 ° C. The mixture is not combustible and does not contain any solvents. Hereinafter, the omega-3 acid mixture will be referred to as the omega-3 acid preparation. .

The content of an effective start in the preparation, eicosapentaenoic and docosahexaenoic acids, can vary from 5 to 100%. The lower limit is determined on the basis that the decrease in the total content of these acids below 5% significantly or completely reduces the effectiveness of the drug due to the high ballast content of other fatty acids that do not have such an effect. The upper boundary corresponds to the moment when the preparation contains only two acids - eicosapentaenoic and docosahexaenoic. Such a drug will be most effective. However, in practice, the methods for preparing such a preparation are rather laborious, therefore, as mentioned earlier, for use in medicine, these acids are usually concentrated in the preparations to. 30-75%.

The basis of the diagnostic signs, which monitored the evolution of the bjogbwa wound, were macroscopically determined circulatory disorders caused by a burn. At the same time, we proceeded from the fact that the structure of the skin of rats is basically similar to that of humans and also

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about

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about

with

is a three-component system formed by the epidermis, dermis and subcutaneous fat, most pronounced in the back. In places where the skin is covered with hair, the epidermis in animals is less complex and consists of only three layers: basal, prickly and horny. As a result, the morphology of the burn wound of rats is different from that in humans. So, with second-degree burns, rats do not form bubbles. In addition, the Wistar rats used in our experiments are albinos in which the specific function of melanocytes located in the basal layer of the epidermis is impaired and they are not able to synthesize melanin pigment.

Typical microcirculatory disorders during thermal injury to the skin are primarily: biphasic vessel. one hundred reaction (short-term narrowing and long-term expansion) of the microvessels in the affected area; a significant increase in the permeability of the wall of postcapillary venules, a significant slowdown in blood flow (up to its complete stop - stasis). The presence of vascular stasis is an indicator of deep tissue damage.

From erythrocytes that have left the bloodstream to the surrounding tissue, hemoglobin is cleaved, i.e. hemolysis, which is very typical for burns. Subsequently, hemoglobin breaks down into a number of products, and in small accumulations of blood, when red blood cells exit the vessels by diapedesis, only hemosiderin is detected. It forms during the first 24 hours from the moment of hemorrhage, which gives the tissue in places a rusty brown color. On the surface of the skin, this appears as a secondary pathological element such as spot.

Pronounced stasis develops only towards the end of the first day after a burn. The presence of vascular stasis is an indicator of deep tissue damage. Often, stasis is combined with impaired trophic tissue. If a similar phenomenon is observed in the skin, then local necrosis develops, which is defined as a necrotic scab. The elasticity of the scab of the skin of albino rats, as well as its color (from light brown to red and dark brown), corresponds to the depth of the lesion, one stage or another of the evolution of the wound process, and, as far as we can extrapolate, one of the degrees of burns, adopted for humans at the XXVII All-Union Congress of Surgeons in 1960

Based on the foregoing, we grouped daily revealed pathological signs of the affected skin surface into four main groups (according to the stages of the evolution of a burn wound):

I) the entire thickness of the skin is elastic, there are stains due to hemolysis and the formation of hemosiderin;

Ii) the entire thickness of the skin is elastic with the soft light brown scab present on its surface;

Iii) the entire thickness of the skin is elastic with the soft red-brown scab present on its surface;

Iv) a dense, coin-like, dark brown scab, often with a different pattern of dilated blood vessels in a stasis state.

Note: -:

1. In no case in our experiments with the use of the above preparations did the scab not solder with the underlying muscles, did not melt, and, when the animals were opened, the depth of the pathological process did not go beyond subcutaneous fat.

2. After measuring the area occupied by the pathological element, the percentage of this area to the entire area of the skin surface that was in contact with the heated part of the metal object was calculated.

3. The animals having one stage or another were divided into four groups

the evolution of a burn wound according to the above signs, separately for the tested drugs. For each day, rat distribution histograms were constructed. Statistical processing was performed

in comparison of each experimental group (linoleum or omega-3 acid preparation) with the control (petrolatum) according to the formula:

X2

1

(fi P2 - T2 P1 y

45Sh P2.-G. fi + f2

where X is the compliance criterion (agreement criterion);

fi and fa are the frequencies of the classes of the first and second series;

gn and P2 - the number of individuals in each of them.

Differences at P 0.05 were considered statistically significant.

PRI me R 1. The use of omega-3 acids as an anti-burn agent.

In the experiment, 63 female Wistar rats (from the nursery of the USSR Academy of Medical Sciences Stolbov) were used weighing 130-150 grams, which were divided into 3 groups of 21 animals each. Rats of all groups were in cells of 7 animals. Animals all period

kept on a standard diet adopted in the nursery, water ad libitum,

Group I served as a control; rats of this group were treated with vaseline after a burn.

Group II was treated with a commercial anti-burn drug Lynetol.

Group III was treated with a test preparation of omega-3 acids (in the form of ethyl esters of these acids), which was, as mentioned earlier in the description, an oily liquid of light yellow color. The total content of eicosapentaenoic and docosahexaenoic acids is 65.8% (eicosapentaenoic - 33.0%, docosahexaenoic, 8%). The remaining fatty acids, as minor components, totaled 34.2%.

Before the experiment, under light ether anesthesia, the hair was carefully plucked from a skin area measuring 25 x 25 mm in the middle third of the back. The burn was caused by applying a massive metal object to the exposed skin, which had a smooth round protrusion of 20 mm in diameter at the contact site. The temperature of the metal object was constantly maintained by controlled heating. In order to obtain a superficial thermal injury immediately before annealing with a syringe, up to 3 cm of air was injected under the skin to form an air cushion at the contact point. The temperature exposure lasted 3 seconds, after which test preparations of room temperature (20 ° -22 ° C) were applied to the affected skin surface in an amount of 150 mg per animal. The rats were kept separate from each other until the preparation was completely dry. The experiment was carried out from 9 to 12 hours, the preparations were repeated at 18-19 hours. All subsequent days, the treatment time remained the same. On the next day and then every day from 9 to 10 hours, individual pathological elements resulting from the evolution of the burn wound were examined and measured, as well as their description according to the method proposed earlier.

The survey results are given in table. 1, For the sake of clarity and convenience, the same table is presented in the form of histograms in Figs. 1 and 2, 4 stages are highlighted in red, as the most unfavorable, in which the surface is a dense dark brown scab.

As can be seen from figure 1, a day after a superficial burn of the skin of rats with a metal object with a temperature of 80 ° C

for 3 seconds, more than half lively. Then treated with vaseline, they had macroscopically well-defined hyperpigmentation (as a result of the breakdown of 5 hemosiderin) and elastic skin at the site of thermal injury (contact). .

0 necrosis and the formation of hard, dark red scabs, containing in their brightly expressed dilated thrombosed blood vessels, treatment of rats with lynetol restrained

5 development of the pathological picture with the exception of the seventh of animals (Pi-2 0.25, see tzbl, 1) ..

Treatment with the omega-3 acid preparation stabilized at this stage the pathological processes at the stage of spotting (hyperpigmentation) (PI-S 0.01).

The second and third days of the burn wound in all groups continued to evolve, but after treatment with omea 5 ha-3 acids, it was statistically

significant slowdown in the development of pathological elements: respectively by 2 and

3 days in relation to the control PI-Z 0,05

. and PI-Z 0.025. Treatment with linoleum gives

0 while Pi-2 0.50 and Pi-2 0.75 (see tab. 1) ..

On the fifth day, in rats treated with the omega-3 acid preparation, only one specimen showed a solid dark red

5 scabs, against almost half of those in the control and a third when treated with linoleum. . At the same time, the beginning of exfoliation of scabs in all groups occurs, and when processing omega-3 acids, this process

0. Passes quickly and, apparently, less painfully, since most of the animals in this group have a soft and thin scab, the skin is elastic to the entire thickness at the site of injury PI-Z 0.025, for linetol Pi-2 0.90

5 in relation to control (table. 1).

On the seventh day, statistically significant differences in the benefits of treating lesions with omega-3 acids were already, 01, for linetol Pi-2 0.50

0 (table. 1).

On the ninth day, the scab in all groups significantly departs from the surface of the skin, connecting with it only on an extremely limited area in the center, and with

5 treated with omega-3 acids, the skin under the scabs is elastic and has a pale pink tint, slightly different from non-burned skin, while when treated with petrolatum and linetolomone, it is reddish, sometimes with secondary

necrosis, i.e. the formation of secondary scabs, to the touch is thickened and slightly elastic, with the effects of fusion with the underlying tissues, which indicates a deepening of burns.

PRI me R 2. The use of the drug omega-3 acids as an anti-burn agent,

To confirm the results obtained in the first experiment (example 1), a second experiment was carried out, but without linoleum, because this drug is already sufficiently tested.

In the experiment, 42 female Wistar rats (from the nursery of the USSR Academy of Medical Sciences Stolbov) were used weighing 120-130 grams, which were divided into two groups of 21 animals each. Rats of both groups were in cells of 7 individuals. The animals were kept for the entire period on a standard diet adopted in the nursery, water ad libitum,.

Group I - served as a control, rats of this group after a burn were treated with petrolatum.

Group II - was treated with an omega-3 acid preparation (in the form of their ethyl esters), which was a light yellow oily liquid. The total content of eicosapentaenoic and docosahexaenoic acids is 60.0% (eicosapentaenoic - 33.4%, docosahexanoic - 26.6%). The remaining fatty acids as minor components were 40.0%.

The application of thermal injury, as well as the removal of diagnostic signs with their subsequent statistical processing, was carried out as in example 1,

As can be seen from Fig. 2, the histogram of the distribution of animals treated with petroleum jelly over the stages of evolution of the burn wound was repeated as in the first experiment. However, later on the 2nd, 3rd, 5th day, this group of rats transferred a little harder than in the first experiment, but practically this difference was expressed in units of individuals.

A similar situation was observed when treating animals with an omega-3 acid preparation (Fig. 2). Statistically nonetheless

a significant difference (Pi-2 0.05) per day in the positive effect of the drug omega-3 acids does not allow to doubt its effectiveness (reliability of the results

X see table. 2).

Thus, the described observations, their grouping according to the stages of evolution of the burn wound followed by statistical processing. Using the chi-square (X2) criteria, we conclude that treatment with omega-3 acids immediately after thermal damage (hereinafter daily) to rat skin sharply delays the development of pathological elements in the burn wound, maintains skin elasticity, reduces necrotic processes, which is ultimately less traumatic for the injured (affected) and provides a faster e

and high-quality healing of burn wounds, eliminates secondary necrosis and deepening of burns.

The advantages of omega-3 acids include their availability, as

Methods for producing omega-3 acids are well developed, harmless in combination with high biological potential for burns.

In the USSR, especially with a deficiency of this kind of drugs, the use of omega-3 acid preparations would significantly increase the effectiveness of the treatment of burn injuries and, perhaps, to some extent, satisfy

requirements for such preparations. 1 The Union has a wide raw material base for the preparation of preparations. These are mainly fish fats and sea animals, for which the issue of disposal has not yet been resolved. In addition, omega-3 acid production technologies have been developed which make it possible to produce such preparations in good yield and at low cost.

Claims (1)

Gain Formula Use of a omega-3 series polyene fatty acid mixture as an anti-burn agent.