RU2428166C2 - Preparation for skin protection against affection by aggressive technical liquids - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to field of medicine, namely to combustiology and toxicology and deals with preparations for protection of open parts of skin against affection by drip-liquid aggressive technical liquids (concentrated nitric acid and sodium hydroxide solution), and can be used in direct work with them. In preparation composition included are highly molecular perfluorpolyether and fluorinated surface-active substance - highly molecular fluortenside in amount, wt %: highly molecular fluortenside- 5-10; highly molecular perfluorpolyether - to 100.

EFFECT: preparation possesses high characteristics of protective and exploitation properties, does not produce irritating impact on skin.

4 ex, 8 tbl, 2 dwg

Description

The invention relates to medicine, namely to combustiology and toxicology, and relates to means for protecting exposed skin from damage by drip-liquid aggressive technical fluids (acids and alkalis), and can be used in direct work with them.

As aggressive technical fluids, concentrated (fuming) nitric acid HNO ₃ (which is a component of rocket fuel) and concentrated sodium hydroxide solution NaOH (used to prepare degassing solution No. 2-bsc) were considered as the most common in practice.

Currently, for the treatment of exposed skin in order to protect them from damage by acids and alkalis, both protective creams and film-forming compositions are used.

Among the first, for example, is a hand protection product including wax, sea buckthorn oil, gelatin, emulsifier, water, vegetable oil and preservative. At least one component or a mixture thereof from the group is used as an emulsifier: lanolin, glycerol monostearate, cosmetic stearin, triethanolamine, quartamine. The components are taken in a specific quantitative content. The cream forms a protective film, provides a nourishing effect and protects from the harmful effects of various solvents, acids, alkalis and other harmful components [1].

However, protective creams of this type have a significant drawback. They are easily erased from the surface of the skin, which requires multiple treatments of the skin of the hands during the working day.

As a film-forming agent for protecting the skin of the hands from alkalis, acids and solvents in the manufacture of building materials, an agent [2] is used containing dry casein glue, distilled water, glycerin, 96% ethyl alcohol and chalk in the following ratio, wt.%:

- casein glue "OB" - 20;

- distilled water - 20;

- glycerin - 33;

- 96% ethyl alcohol - 20;

- chalk powder - 7.

The method of preparation of such a solution consists in the joint mixing of dry casein glue, water, glycerin, alcohol, chalk. A solution of this product, applied to the surface of the skin of the hands, dries quickly and forms a protective "artificial" film.

However, from the point of view of the effectiveness of protecting the skin from lesions by droplet-corrosive technical fluids, the formulation in question has a significant drawback, consisting in its ability to be easily washed off with water.

This formulation is accepted as a prototype as the closest in technical essence (film-forming).

The aim of the invention is to find a means of protection of exposed skin, providing a high level of protective properties in relation to concentrated nitric acid and sodium hydroxide solution that does not irritate the skin and has high performance properties.

Achieving this goal is ensured by creating a formulation that includes perfluoropolyether and fluorinated surfactant - fluorotenside.

In this case, compounds with a molecular weight of 1800-3000 Da of the following chemical formula are used as perfluoropolyether:

, n=10-20.

, n = 10-20.

As the fluorotenside, a compound with the quaternary ammonium base γ- (hydroxyethyl dimethylammonio) propylamide keslot chloride propylamide of the following chemical formula is used:

or a surfactant compound β-hydroxyethylamide perfluoropelargonic acid of the following chemical formula [3]:

C ₈ F ₁₇ COHNH ₂ C ₂ H ₄ OH.

Thus, the composition of the proposed protective agent included the following ingredients in an amount, wt.%:

- fluorotenside - 5-10;

- perfluoropolyether - up to 100.

This composition, when applied to the skin surface, has the properties of not only an inert barrier against concentrated nitric acid and sodium hydroxide solution, but also a medium that effectively prevents the diffusion of molecules of these aggressive technical fluids.

Active active principle of the claimed funds are modified (not fully fluorinated) perfluorocarbons - fluorotensides [3]. When mixed with a perfluoropolyether, they form a heterogeneous medium consisting of a perfluoropolyether containing micelles (fluorosomes) of fluorotenside. Micelles are formed as a result of physicochemical interactions of perfluoropolyether and fluorotenzide molecules, when one part of the molecules of these compounds is tropic to a perfluorocarbon medium, which allows it to dissolve in perfluoropolyether, and the other part to a non-fluorinated part of the fluorotenside molecule. This ensures the formation of supramolecular structures, the distinguishing feature of which is the presence of a center for physicochemical binding of HNO ₃ and NaOH molecules.

The diagram of the supramolecular structure formed by fluorotenzides in the environment of a perfluoropolyether (Fig. 1) shows a perfluoropolyether molecule (1), a fluorotenzide molecule (facing the fluorinated part into a perfluoropolyether medium) (2) and fluorosome (micelle) (3).

The ability to achieve the objectives of the invention is confirmed by the following examples.

Example 1. The protective properties of the claimed funds and funds of the prototype in relation to concentrated nitric acid and sodium hydroxide solution in experiments in vitro.

The setup for in vitro experiments is shown in figure 2.

The essence of in vitro experiments was to determine the amounts of nitric acid and sodium hydroxide passed into distilled water (4) with a pH of 6.4 through a layer of protective agent applied to tracing paper (5). Tracing paper (6) was stretched over the lower narrow opening of the funnel (7) with a radius of 1 cm and was fixed outside with a thin copper wire. A layer of protective agent (of the claimed agent or prototype agent) was applied to the tracing paper from the side of the large opening of the funnel (with a flow rate of 0.25 ml / dm ² ) and was evenly distributed over the surface of the tracing paper for 30 minutes. Then, one flying drop of nitric acid or sodium hydroxide was applied on top of the protective agent layer.

The experiments used nitric acid “ChP” (“Himeks”, St. Petersburg) [4], as well as sodium hydroxide in flakes (chda) (“Neva Reagent”, St. Petersburg) [5], of which prepared a 10% ex tempore aqueous solution. The mass of a drop of nitric acid or sodium hydroxide solution was dosed with a microsyringe and amounted to 10 mg. Immediately after applying the drop, the funnel was closed on top with a sealed rubber membrane and quickly placed in a glass cup (9) with 10 ml of distilled water so that the funnel was fixed at the level of contact of the tracing paper with the surface of the water. From this moment, the time of diffusion of the acid or alkali into the water was counted. A glass container was placed on a magnetic stirrer (10), and throughout the experiment, uniform mixing of the entire volume of water was carried out.

Assessment of the diffusion dynamics of droplets of nitric acid or sodium hydroxide through the protective layer from the inventive means or prototype means was carried out by measuring the pH of water using electrodes of an ionomer universal EV-74 (8). The pH of the water was measured at the following time intervals: first, after 1 min and 5 min from the beginning of the experiment, and then every 10 min until the diffusion process stopped (stabilization of pH values). The amount of nitric acid or sodium hydroxide penetrated into the water was determined by the corresponding calibration curves establishing the relationship between the amount of aggressive liquid in the water and the pH of the water.

The control was a clean tracing paper without a protective layer.

The experimental results are presented in tables 1-2.

When assessing the dynamics of the diffusion of drops of nitric acid and sodium hydroxide, it was found that in the control, that is, without the use of a protective agent, the diffusion of nitric acid through tracing paper occurs quite quickly, and after 20 minutes almost all the amount of acid applied to the tracing paper penetrates into the tracing paper. Diffusion of sodium hydroxide occurs 3 times slower, and all of its amount penetrates only after 60 minutes.

In the case of using the prototype agent, the diffusion of nitric acid under the protective layer begins immediately, and after 70 minutes 9.89 mg of acid from 10.0 mg applied to the treated tracing paper penetrated into the water (98.9%).

A concentrated sodium hydroxide solution begins to penetrate under the protective layer from the prototype also after 1 min after application, and after 80 minutes the amount of alkali that penetrated into the water was 9.88 mg, i.e. 98.8% of the amount applied to the tracing paper.

The use of the claimed means allows you to significantly more effectively inhibit the penetration of both nitric acid and sodium hydroxide, which begins much later, that is, only after 70 minutes and the amount of nitric acid and sodium hydroxide penetrated in this case was 0.01 mg each. 140 minutes after the start of the experiment, the amount of nitric acid and sodium hydroxide penetrated into the water was 3.07 mg and 1.67 mg, respectively, which corresponds to 31.0% and 16.9% of the amount of aggressive fluids applied to the tracing paper.

As can be seen, the data of all in vitro experiments indicate that the protective properties of the claimed funds in relation to concentrated nitric acid and sodium hydroxide solution exceeded the protective properties of the prototype. The protective layer of the claimed means with a minimum flow rate of 0.25 ml / dm ² completely prevented the penetration of the considered aggressive chemical compounds for 60 minutes

Example 2. The protective properties of the claimed funds and funds of the prototype in relation to concentrated nitric acid and sodium hydroxide solution in experiments in vivo.

The protective effectiveness of the claimed means and prototype means was evaluated in in vivo experiments on white outbred female rats weighing 180-220 g with the application of drops of concentrated nitric acid and 10% sodium hydroxide solution weighing 10 mg.

In the experiment, 3 groups of animals were formed, 10 rats each. A day before the experiment, in the back of the rats, a skin area of 10 cm ^{2 was} freed from the hairline with scissors.

In animals of the first group, the skin site was not protected and was used as a control.

On the day of the experiment, one hour before the application of aggressive technical fluid, the prepared area of the skin in animals of the second group was protected with the prototype, and in animals of the third group with the claimed tool. The consumption rate of protective agents was 0.25 ml / dm ² .

Evaluation criteria for the protective effectiveness of the studied drugs were:

- the time of appearance of hyperemia on the skin;

- the diameter of the lesions of the skin;

- maximum severity of skin lesions;

- the healing period of skin lesions.

The severity of local skin lesions was evaluated in points on a five-point system [6].

The results of studies of the protective efficacy of the claimed means and prototype means relative to concentrated nitric acid and 10% sodium hydroxide solution are presented, respectively, in tables 3 and 4.

When a concentrated sodium hydroxide solution was applied to the skin of rats, the following protective efficacy of the studied formulations was revealed. When protecting the skin with the prototype, the diameter of the developed lesions was two times smaller than in the control, and they healed a week earlier. When protected by the claimed means, skin lesions were not observed at all.

When exposed to concentrated rat nitric acid on the skin of rats, the use of the prototype agent does not allow for a reliable reduction of both the diameter of the foci of skin lesions and the reduction in the healing time of skin lesions. The skin lesion in this case corresponded to 4.3 points.

In the case of protecting the skin with the claimed agent, the diameter of the developed lesions compared with the control was 4.1 mm (33.6%) less, the skin lesion did not exceed 2.7 points, and the healing time of the skin lesions decreased by 3 times.

Example 3. Evaluation of the irritating effect of the claimed funds and funds of the prototype on the skin.

The irritant effect of the claimed agent and the prototype agent on the skin was evaluated on female rats weighing 200-220 g. Two groups of animals of 10 rats each participated in the experiment.

On the day of the experiment, the animals were fixed on the machines and scissors were released from the hairline patches of the skin of the back with an area of 10 cm ² . Once a day for three days the animals were applied the claimed tool or tool prototype. The consumption rate of the protective agent was 0.25 ml / dm ² , air temperature - + 16 ° C. After 5 hours of exposure, each time protective agents were washed off the skin with warm water and soap, then simply with warm water and blotted with filter paper.

The irritant effect of the studied agents was evaluated daily visually, as well as by measuring the skin surface temperature and skin fold thickness in comparison with control measurements carried out 30 minutes before the experiment.

The surface temperature of the skin of animals was measured using a Nihon Konden instrument (model MGA-III). The sensor on the skin surface was held for 60 seconds.

The measurement of the thickness of the skin fold was carried out using a MK-50 micrometer. The skin taken from two sides in the fold, and slightly drawn, was introduced between the measuring surfaces of the micrometer. When a third rattle sound appeared, the measurement was considered complete.

During the three-day application of the claimed agent to the skin and subsequent five-day observation of the animals, no signs of skin irritation (hyperemia, edema, infiltration, peeling, etc.) were visually observed. The sites of application of the protective equipment of the animals themselves were not disturbed, their palpation was painless. The surface temperature of the skin in experimental animals remained virtually unchanged, as evidenced by the data presented in table 5.

Measurement of the thickness of the skin fold at the application sites of the claimed agent after one, two, and three times their application showed that in no case does it significantly change (p> 0.05) compared with the initial values. The results of the experiment, presented in table 6, objectively confirm the absence of skin edema, even after repeated application of the claimed funds.

Thus, three times daily application of the inventive product on the skin of rats with a five-hour exposure was not accompanied by an irritating effect on the skin.

In the case of using the prototype means, there is a tendency to increase the thickness of the skin fold and increase the temperature of the skin surface, which is probably due to the mechanical effect of the dry crust of the components of the prototype means.

Example 4. Evaluation of the operational properties of the claimed means and means of the prototype.

Evaluation of the operational properties of the claimed means and prototype means was carried out by studying their runability and abrasion from the surface of the skin of rats. The dynamics of draining funds from the vertical surface of the skin beyond the marked area was recorded for 30 minutes. The abrasion of the protective layer from the studied agents was evaluated after 30 minutes of runoff.

The study of the features of the formation of a protective layer from the studied agents was carried out on the skin of outbred female rats weighing 180-210 g. On the day of the experiment, the animals were fixed in the machine tools, the coat was removed from the skin of the back with scissors, a skin area of 10 cm ^{2 was} noted and the claimed tool or prototype tool. The consumption of protective equipment was 0.25 g / dm ² , the air temperature was + 16 ° C. The studied agents were collected in a glass pipette and weighed on an analytical balance such as VLR-200 with an accuracy of four decimal places. After processing, the pipette was weighed again and the amount of applied agent was determined by the difference in weights.

First, the stackability of protective equipment was determined. In the experiment, it was taken into account that in humans, most of the skin has a vertical surface. For this, the animals immediately after applying the test protective agent together with the machine were fixed in an upright position. The drained product was collected by filter paper, and its amount was determined by weighing. The observation intervals were 2, 5, 10, 15 and 30 minutes after application of the product.

Then, the abrasion of the studied protective agents from the skin surface was determined in the same animals, for which the treated skin patches were blotted three times with pieces of filter paper with an area of 20 cm ² , and then these pieces were weighed. Stackability and abrasionability of the studied funds from the skin surface was expressed as a percentage of their initially applied amount.

The persistence of the agents on the skin of experimental animals was also determined - one of the most important operational properties, representing the ratio of the residual amount of the agent after three times erasure to the total amount applied to the skin surface, expressed as a percentage and determining the duration of the protective effect of the agent.

The results of the study of the formation on the surface of the skin of rats of the protective layer of the claimed means and prototype means, are presented in table 7, showed that the dynamics of the runoff of the claimed means significantly differed from the specified characteristics of the prototype means. So, 2 minutes after applying to the skin of experimental animals of the claimed funds remained 96.5% of the originally applied amount, which is 9.4% more than the prototype. The prototype agent drained faster from the skin, and after 15 minutes the residual amount of the claimed agent on the skin of the experimental animals exceeded the same value for the prototype agent by 18.6%, and after 30 minutes, when the dripping process ended, 86.6 remained on the skin of rats % of the claimed funds, which is 32.8% more than the prototype.

The results of the study of abrasion, presented in table 8, showed that the amount of the claimed funds remaining on the surface of the skin of experimental animals after draining for 30 minutes and subsequent triple erasure was 48.8% of the initial amount, which is 5 times more than that of prototype means in similar conditions. The persistence of the claimed funds is 5 times greater than this characteristic of the prototype.

Thus, the data of the above studies indicate that the inventive tool can be used to protect the skin from concentrated nitric acid and 10% sodium hydroxide solution. The effectiveness and duration of the protective properties of the claimed tool is superior to the prototype tool, as it completely impeded the penetration of the considered aggressive chemical compounds for 60 minutes In addition, it has a higher level of operational properties (the persistence of the claimed funds on the skin is 5 times higher than this characteristic of the prototype). At the same time, the claimed agent does not irritate the skin even after three times application.

The claimed invention satisfies the criterion of "novelty", as the first proposed tool that provides not only mechanical protection of the skin from the effects of aggressive technical fluids, but also actively prevents the diffusion of their molecules due to the formation of fluorotenside micelles.

The claimed invention meets the criterion of "inventive step", since it does not use well-known technical solutions. Of the available sources of information, the observed manifestation of the protective properties of the proposed tool in relation to aggressive fluids was not obvious.

Compliance with the criterion of "suitability for industrial use" is proved by the results of the above studies, which show that the claimed tool can be widely used in practice, since its components are low-toxic compounds produced by the domestic chemical industry. The inventive tool is characterized by high protective effectiveness, the absence of irritating effects on the skin, a high level of operational properties.

A means of protecting the skin from damage by aggressive fluids Table 1 The diffusion dynamics of a drop of nitric acid with a mass of 10 mg through the layer of the claimed funds or funds of the prototype (n = 5) Duration of diffusion, min The amount of nitric acid penetrated through the protective layer (M ± m), mg The control Prototype tool The inventive tool one 4.75 ± 0.27 0.59 ± 0.10 * 0 5 9.98 ± 0.02 2.88 ± 0.21 * 0 10 9.96 ± 0.03 5.45 ± 0.18 * 0 twenty 9.98 ± 0.02 8.56 ± 0.23 * 0 thirty - 9.91 ± 0.04 0 60 - 9.88 ± 0.02 0 70 - 9.89 ± 0.03 0.01 ± 0.01 * 80 - - 0.07 ± 0.03 * 90 - - 0.27 ± 0.06 * 110 - - 0.92 ± 0.11 * 120 - - 1.74 ± 0.14 * 130 - - 2.37 ± 0.16 * 140 - 3.07 ± 0.15 * * - differences are significant (p <0.05)

A means of protecting the skin from damage by aggressive fluids table 2 The dynamics of diffusion of a drop of sodium hydroxide weighing 10 mg through the layer of the claimed funds or funds of the prototype (n = 5) Duration of diffusion, min The amount of sodium hydroxide penetrated through the protective layer (M ± m), mg The control Prototype tool The inventive tool one 0.88 ± 0.12 0.09 ± 0.03 * 0 5 2.82 ± 0.30 0.21 ± 0.18 * 0 10 5.64 ± 0.26 0.59 ± 0.22 * 0 twenty 9.88 ± 0.04 2.88 ± 0.23 * 0 thirty 9.92 ± 0.05 5.50 ± 0.26 * 0 60 9.89 ± 0.04 8.62 ± 0.15 * 0 70 - 9.92 ± 0.06 0.01 ± 0.01 * 80 - 9.88 ± 0.04 0.02 ± 0.01 * 90 - - 0.08 ± 0.04 * 110 - - 0.28 ± 0.09 * 120 - - 0.65 ± 0.11 * 130 - - 0.97 ± 0.13 * 140 - - 1.67 ± 0.12 * * - differences are significant (p <0.05)

A means of protecting the skin from damage by aggressive fluids Table 3 The protective effectiveness of the claimed means and prototype means (flow rate - 0.25 g / dm ² , exposure 1 hour) when applying nitric acid (drop weighing 10 mg) on the skin of rats (M ± m), n = 10) Test Recipe Protective Evaluation Criteria The diameter of the skin lesion, mm Skin lesion score The healing period of skin lesions, days The control 12.2 ± 0.54 5 24 ± 1,2 The inventive tool 8.1 ± 0.22 * 2.7 ± 0.87 * 8 ± 1.8 * Prototype tool 10.3 ± 0.67 4.3 ± 0.17 19 ± 2.2 * - differences are significant (p <0.05) Table 4 The protective effectiveness of the claimed means and prototype means (flow rate - 0.25 g / dm ² , exposure 1 hour) when applying sodium hydroxide (drop of 10 mg) on the skin of rats (M ± m), n = 10) Test Recipe Protective Evaluation Criteria The diameter of the skin lesion, mm Skin lesion score The healing period of skin lesions, days The control 10.2 ± 0.54 5 22 ± 1.0 The inventive tool 0 0 Prototype tool 5.3 ± 0.67 * four 15 ± 0.7 * * - differences are significant (p <0.05)

A means of protecting the skin from damage by aggressive fluids Table 5 The effect of a five-hour exposure of the claimed drug on the skin surface temperature in rats (M ± m), n = 10 Test Protective Skin surface temperature, ° C source after applying the protective agent once twice Three times The inventive tool 32.8 ± 0.40 28.9 ± 1.52 29.4 ± 1.63 29.2 ± 1.42 Prototype tool 32.7 ± 0.45 33.2 ± 1.70 33.5 ± 2.10 34.1 ± 2.20

Table 6 The effect of a five-hour exposure of the claimed drug on the thickness of the skin fold in rats (M ± m), n = 10 Test Protective The thickness of the skin fold, mm source after applying the protective agent once twice Three times The inventive tool 1.54 ± 0.03 1.49 ± 0.040 1.56 ± 0.08 1.53 ± 0.09 Prototype tool 1.56 ± 0.03 1.63 ± 0.035 1.66 ± 0.09 1.70 ± 0.08

A means of protecting the skin from damage by aggressive fluids Table 7 The dynamics of the formation of the protective layer of the claimed means and prototype means on the skin of rats (M ± m), n = 10 Test Protective The residual amount of protective agent (% of the applied amount) after a period of time, min 2 5 10 fifteen thirty The inventive tool 96.5 ± 1.5 94.0 ± 2.2 91.4 ± 2.6 86.1 ± 3.1 86.6 ± 2.7 Prototype tool 88.2 ± 3.3 83.8 ± 4.2 77.9 ± 5.6 72.6 ± 6.0 65.2 ± 5.8

Table 8 The abrasion of the protective layer of the claimed means and prototype means from the skin of rats after 30 minutes of draining (M ± m), n = 10 Test Protective Erasable protective agent,% of the applied amount Left after runoff Erased Remains after three times erasing (persistence) The inventive tool 86.6 ± 2.7 7.8 ± 2.5 48.8 ± 0.8 Prototype tool 65.2 ± 5.8 55.6 ± 5.4 9.6 ± 1.8 *

BIBLIOGRAPHY

1. RU 2286138 C1, 10.27.2006.

2. RU 2118154 C1, 08.27.1998.

3. Maksimov B.N. Industrial organofluorine products: Ref. ed. / B.N. Maksimov [et al.] - Ed. 2nd, per. and add. - St. Petersburg: Chemistry, 1996 .-- 544 p.

4. GOST 4461-77 Reagents. Nitric acid. Technical conditions

5. GOST 4328-77 Reagents. Sodium hydroxide. Technical conditions

6. GOST B 26534-89 Individual anti-chemical package. Technical and biomedical requirements.

Claims (1)

A means of protecting the skin from damage by aggressive technical fluids, characterized in that it includes liquid perfluoropolyether and fluorotenside in the following ingredients, wt.%:
fluorotenside 5-10 perfluoropolyether up to 100,
with the proviso that the fluorotenside is γ- (hydroxyethyl dimethyl ammonium) propyl fluoropelarboxylic acid propylamide chloride of the following chemical formula:

or β-hydroxyethylamide perfluoropelargonic acid of the following chemical formula:

and perfluoropolyether is a perfluoropolyether with a molecular weight of 1800-3000 Yes of the following chemical formula:

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