RU2469714C1 - Emulsion of perfluoroorganic compounds with gas transport properties - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to fine stable emulsions of perfluoroorganic compounds (PFOC) which may be used as a base for preparing blood substitutes with gas transport function, as well as radiopaque contrast agents and mediums for organ preservation. The emulsion contains PFOC in the amount of 8÷80.0 wt %, an emulsifying and stabilising additive in the amount of 0.25÷8.0 wt % and a physiologically acceptable solution - the rest. The emulsifying and stabilising additive of the emulsion is presented by a non-ionic surfactant presenting mixed block copolymers of ethylene oxide and/or propylene oxide and/or polyalkylene glycol esters of tocopherol with polyglycidyl esters of fluorinated alcohols in relation 2:1 to 0.5:1, or the anionic surfactant presenting a monoester salt of dicarboxylic acid with aliphatic and/or pxyalkylated aliphatic and/or perfluorinated alcohols, or mixed said non-ionic and anionic surfactants in relation 39:1 to 1:39.

EFFECT: emulsion under the invention is aggregation- and sedimentation-stable; average particle size is no more than 200 nm; it is stored for a long period of time at room and high temperature with no substantial change in emulsion particle size.

11 cl, 24 tbl, 23 ex

Description

The invention relates to medicine and colloid chemistry, in particular to highly dispersed stable emulsions based on organofluorine compounds (PFOS), which are capable of transporting oxygen, carbon dioxide, nitrogen and other gases and can serve as the basis for creating perfusion environments, in particular blood substitutes with gas transport function, as well as radiopaque agents and organ preservation media. In addition, the inventive emulsions can be used in the pharmaceutical industry and cosmetics for the preparation of components of medicinal and cosmetic ointments, gels, creams.

The limited ability to obtain donor erythrocyte-containing media (blood products), associated with a continuous decrease in the number of blood donors worldwide, as well as the problem of their storage makes the search for alternative drugs that can perform the main blood function: oxygen transport from the lungs to tissues and carbon dioxide from tissues into the lungs.

The need to create gas-carrying blood substitutes is also due to the need for blood substitutes, which have the ability that red blood cells lack: to penetrate into the plasma and spasmodic capillaries of ischemic organs.

Currently, the development of blood substitutes with a gas transport function is carried out in two directions:

- obtaining oxygen-transporting blood substitutes based on free hemoglobin modified with water-soluble polymers;

- creation of oxygen-transporting blood substitutes based on emulsified PFOS.

To create oxygen-carrying blood substitutes based on modified hemoglobin, hemoglobin of donor and bovine blood is used, as well as recombinant and transgenic hemoglobin. The main problems in the creation of such blood substitutes is the difficulty in obtaining a polymer compound with hemoglobin, which can circulate in the blood for a long time, has a good ability to give oxygen to tissues, and at the same time does not adversely affect systemic hemodynamics. In addition, the disadvantages of blood substitutes based on modified hemoglobin are the temporary occurrence of pulmonary and general hypertension, which is especially pronounced with fast-paced infusions, an increase in blood viscosity, and a decrease in cardiac output, which, combined with a high cost, limits the widespread use of such drugs.

The most promising direction turned out to be the development of oxygen-carrying blood substitutes based on PFOS, which dissolve any gases (oxygen, carbon dioxide, nitrogen, etc.) without forming any chemical compounds with them. Moreover, the dissolution of gases occurs according to Henry's law, that is, linearly, directly proportional to the partial pressure of the gas and its solubility coefficient.

The dissolution of gases in PFOS and their release upon changes in the partial pressure of gases occurs almost instantly. This is one of the most valuable characteristics of drugs in this group. It was established that the dissolution or evolution of oxygen in PFOS occurs in 14-26 ms, while in the hemoglobin-oxyhemoglobin system this time is 200-250 ms.

PFOS is chemically and metabolically inert, does not have any toxic activity. There are no biochemical systems in the body that can destroy PFOS.

A feature of PFOS is their high hydrophobicity, that is, they do not dissolve in water and they can be injected into a vein only in the form of finely dispersed emulsions with a certain particle size of PFOS coated with a layer of emulsifier, which can be used surfactants.

Therefore, the most important characteristics of PFOS-based blood substitutes are the concentration of the emulsion, the size and particle size distribution of the emulsion, and the particular emulsifier used.

In this case, the smaller the particle size of the emulsion, the better, since the emulsion is administered intravenously and with large particle sizes can cause embolism (blockage) of blood vessels. In addition, the presence of large particles larger than 200-300 im (see Mitsuno Toka, Kokuritsu Kobe, Medical Institute, Japan, “The Practical Use of Artificial Blood”, Shizen, 1981, 36 (9), pp. 62-69), is cause reactogenicity and toxicity of emulsions.

An important indicator is also the stability of emulsions based on PFOS, which depends mainly on the properties of the PFOS and emulsifying agents (surfactants) used.

Thus, PFOS emulsions are complex colloidal systems consisting of a dispersion medium — an emulsifier solution (SAS) in a solution physiologically acceptable for a living organism and a dispersed phase — PFOS or a mixture of several PFOS.

Particles of PFOS emulsions are phagocytosed by cells of the reticuloendothelial system and accumulate in various organs. The half-life of PFOS from the body is one of the indicators of the quality of PFOS emulsions. The amount of PFOS accumulated in the body depends on the properties of PFOS (for example, vapor pressure, solubility in lipids, etc.) and the magnitude of the administered dose.

To obtain PFOS emulsions, as a rule, two types of PFOS are used simultaneously, as a rule. One of them is selected from the group (C ₈ -C ₁₀ ) containing PFOS, for example, perfluorodecalin (PFD) or perfluorooctyl bromide (PFOB), the second from the group (C ₁₁ -C ₁₂ ) of nitrogen-containing PFOS, for example, perfluorotripropylamine (PFTPA), perfluoromethyl β-cyclohexylpiperidine (PFMCP) or perfluorotributylamine (PFBA).

Compounds of the first type are rapidly eliminated from the body (within a month), but do not provide sufficient stability for their emulsions, while compounds of the second type, on the contrary, give the emulsion high stability, allowing them to be stored without freezing, but they are not excreted for several years.

As emulsifiers and stabilizers, non-toxic high-molecular substances are used, in particular proxanols (foreign analogues - pluronics) and phospholipids. Their amount in PFOS emulsions is, whenever possible, minimal and necessary only for the purpose of dispersing and stabilizing PFOS.

The effect of PFOS emulsions on the body, on the one hand, is mediated through the physicochemical effect of the emulsifier on body cells. On the other hand, the emulsion as a dispersed system also affects the whole organism.

Toxicity, reactogenicity, average particle diameter of PFOS emulsions and storage stability are important indicators of the quality of PFOS emulsions. The toxicity of PPS emulsions is evaluated by LD ₅₀ , which represents the dose of emulsion administered in ml per kg of animal body weight at which 50% of the animals survive. PFOS emulsions should have a long shelf life, and storage conditions should be simple. An indicator of PFOS emulsions is a change in the average particle diameter during storage for 1-2 years.

The dispersion and stability of PFOS emulsions depends on both the properties of the emulsifier (SAS) and the affinity of PFOS for the emulsifier (SAS). For example, when using phospholipids as an emulsifier, the dissolution temperature of PFOS in hexane is important, which serves as a measure of the lipophilicity of PFOS.

Thus, the following indicators can be used to characterize PFOS emulsions:

- the average particle diameter of the emulsion;

- change in the average particle diameter of the emulsion during sterilization by autoclaving;

- change in the average particle diameter of the emulsion over 12 months at a constant storage temperature in the range from + 4 ° C to + 30 ° C;

- viscosity of the emulsion;

- toxicity, the measure of which is the value of LD ₅₀ ;

- the half-life of PFOS from the body;

- oxygen capacity of the emulsion.

Based on these indicators, it is possible to determine the advantage of one PFOS emulsion over another.

Currently known emulsions PFOS "first" and "second" generations. The “first” generation PFOS emulsions with a PFOS concentration of not more than 20 vol.% Were developed on the basis of nonionic surfactants or on the basis of nonionic surfactants with small additions of phospholipids and had an oxygen capacity of not more than 12 vol.%. Since an increase in the concentration of PFOS in emulsions of the "first" generation leads to a sharp increase in viscosity, in clinical practice only emulsions of the "first" generation with a concentration of PFOS of not more than 10 vol.% Have been used.

An example of an “first” generation emulsion is the Perftoran preparation (RF patent No. 2070033, A61K 9/10, 12/10/1996), which contains two PFOS-PFD and PFMTSP in the ratio of PFD: PFMTSP = 2: 1 at a total concentration of the PFOS mixture in finished product 10 vol.%. As a stabilizer, the emulsion contains 4 wt.% Non-ionic surfactants: proxanol-268. The composition of "Perftoran" also includes a set of salts and an oncotic component.

The Perftoran emulsion immediately after manufacture, according to the manufacturers, has an average particle diameter of 60-110 nm and a particle diameter range of 100 to 300 nm, which differs significantly from the particle sizes measured by photon correlation spectroscopy, which we use to estimate the particle sizes of the emulsions created PFOS (the average particle size of the Perftoran emulsion after thawing, measured by this method, is 200-300 nm, and the range of particle diameters is from 150 to 700 nm). The content of fluorine ions in the emulsion is 10 ^-5 mol / L.

Emulsion "Perftoran" has the following disadvantages:

- low oxygen capacity of the emulsion, which is due to the low content of PFOS in the emulsion (not more than 20 wt.%);

- long-term storage of the emulsion is possible only in frozen form at a temperature of no higher than -18 ° C, and at a temperature of + 4 ° C the emulsion delaminates after a few days;

- the use of an emulsion requires compliance with a strictly defined and complex defrosting procedure;

- the impossibility of sterilization by autoclaving;

- is reactogenic.

In order for “Perftoran” to retain its properties for a long time, after manufacture it is stored frozen at a temperature of -18 ÷ -4 ° C, and before use it is thawed, moving from a refrigerator compartment with a temperature of 0 ÷ + 4 ° C, using special heating mode to prevent separation of the emulsion. Such a complex application technology, permissible for planned treatment, greatly complicates its use and does not allow emergency use in case of urgent need.

The "second" generation emulsions are based on phospholipid surfactants and have a PFOS concentration of up to 50 vol.%, While they have a fairly low viscosity, and the oxygen capacity of such emulsions can reach 26 vol.%.

The “second” generation emulsions include PFOS emulsion containing PFD or perfluorooctyl bromide (PFOB) in an amount of 40-50 vol.% And PFMTSP in an amount of 1-10 vol.% And is stabilized by phospholipids in an amount of 2-6 vol.% [RF patent No. 2088217, cl. A61, K9 / 10]. The average particle diameter of the PFOS emulsion is 232 nm. After 11 months of storage in a refrigerator at a temperature of + 4 ° C, the average particle diameter of this emulsion increases by 23%, i.e., the stability index is 1.23. The emulsion has an oxygen capacity of up to 22 vol.%.

The emulsion has the following disadvantages:

- large average particle diameter;

- high content of large particles (14.9% of the particles have a diameter of more than 400 nm);

- insufficiently high storage stability.

Closest to the claimed emulsion PFOS, is an emulsion [RF patent No. 2240108, A61K 9/107, 2004 - prototype], which as an emulsifier (surfactant) contains phospholipids of egg yolk or soy, and as a stabilizing additive - C ₁₀ fatty carboxylic acids -C ₂₂ , their salts and triglycerides.

As PFOS, the emulsion contains PFD in an amount of 40-66% wt.% (20-50 vol.%), PFMTSP in an amount of 1.2-40 wt.%. (0.6-20 vol.%); phospholipids in an amount of 2-10 wt.%; a stabilizing additive selected from the group of C ₁₀ -C ₂₂ fatty acids and / or their salts in an amount of 0.05-0.25 wt.% and triglycerides in an amount of 0-1 wt.%. The composition of the emulsion also includes an antioxidant - tocopherol in an amount of 0.001-0.05 wt.%. The ratio of PFMTSP to PFD is from 1: 2 to 1:10. Additionally, the emulsion may contain glucose - 2 g / l, and salts: sodium chloride - 6 g / l; potassium chloride - 0.39 g / l; magnesium chloride - 0.19 g / l; sodium bicarbonate - 0.65 g / l; sodium hydrogen phosphate - 0.2 g / l.

The average particle diameter of this emulsion is 185-221 nm.

The emulsion has the following disadvantages:

- the particle diameter distribution is bimodal in nature, the distribution curve has a second maximum in the region of 400 nm, apparently related to the distribution in the emulsion of particles of poorly water-soluble fatty acids, triglycerides and phospholipids used as emulsion stabilizers in large amount - up to 10 wt.%;

- phospholipids used as an emulsifier have a number of significant drawbacks, for example, as the majority of objects obtained from biological material, they are pyrogenic and reactogenic, therefore, with insufficient purification, they can cause allergic reactions, especially when used in such high concentrations (up to 10% ) [S.I. Vorobyov. Infusion solutions with oxygen-transporting properties // Russian Journal of Anesthesiology and Intensive Care, 1999, No. 2, pp. 18-24.];

- egg yolk or soybean phospholipids used as an emulsion stabilizer contain polyunsaturated fatty acid residues that can be oxidized by oxygen present in dissolved form in the perfluorocarbon component of the emulsion, with the formation of toxic peroxide and epoxy compounds, as well as polymers, therefore their use as an emulsifier requires the introduction of an antioxidant in a much larger amount than used in the prototype (tocopherol - 0.001-0.05 wt.%);

- egg yolk or soybean phospholipids used as emulsion stabilizer in high concentration sharply increase the production cost of this emulsion, especially when using foreign highly purified phospholipids.

In addition, a significant drawback of almost all known PFOS emulsions, including the prototype, is the need to use high pressure homogenizers from 100 to 1200 atm, and the perfluorocarbon mixture must be passed through the slot of the homogenizer up to 12 times (cycles) under alternating pressure by increasing the pressure in the homogenizer in 1.1-1.2 times in the homogenization process [RF patent No. 2088217, class. A61, K9 / 10].

The present invention is the creation of aggregatively and sedimentation-stable emulsions based on PFOS, with an average particle size of not more than 200 nm and capable of being stored for a long time (at least 1 year) not only in the refrigerator, but also at room and elevated temperature without significant change particle size of the emulsion and for the preparation of which simple and affordable dispersants can be used without the use of sophisticated equipment based on high pressure homogenizers (up to 1200 atm).

The problem is solved in that a composition is proposed, which is an emulsion containing PFOS, an emulsifying and stabilizing additive and a physiologically acceptable solution for the body, and characterized in that it contains a nonionic surfactant (nonionic surfactant) as an emulsifying and stabilizing additive, which is a mixture block copolymers of ethylene oxide and propylene oxide and / or polyalkylene glycol esters of tocopherol of the formula:

where n + p = 30-150, m = 2-50

with polyglycidyl ethers of fluorinated alcohols and / or perfluorinated alcohols in a ratio of 2: 1 to 0.5: 1, or an anionic surfactant (APA), which is a salt of a monoester of dibasic carboxylic acid with aliphatic and / or hydroxyalkylated aliphatic and / or perfluorinated alcohols, or a mixture of these nonionic surfactants and anionic surfactants (with a ratio of nonionic surfactants and anionic surfactants from 39: 1 to 1:39) in the following ratio of components (wt.%)

- PFOS - 8 ÷ 80.0; - emulsifying and stabilizing additive - 0.25 ÷ 8.0 - physiologically acceptable solution for the body - the rest.

As a block copolymer of ethylene oxide and propylene oxide, the inventive emulsion may contain block copolymers of ethylene oxide and propylene oxide with a molecular weight of 6000-13000, in which the content of ethylene oxide can vary from 60 to 80%, for example emuxol-268 (proxanol-268), or analogues: lutrol F127, proxanol 168, pluronic PE 6800.

Along with derivatives of block copolymers of ethylene oxide and propylene oxide, nonionic surfactants contain polyglycidyl ethers of perfluorinated C ₆ -C ₁₆ alcohols, for example, of the general formula (2):

(2) n = 6-16, m = 4-20

and / or fluorinated alcohols C ₆ -C ₁₆ , for example, of the general formula (3):

(3) x + y = 2n + 1, n = 6-16, m = 4-20

The ratio of the derived block copolymer of ethylene oxide and propylene and polyglycidyl ether of fluorinated and / or perfluorinated alcohols can vary from 2: 1 to 1: 2.

Sodium and / or potassium and / or ammonium or substituted ammonium salts of monoesters of malonic and / or maleic and / or fumaric and / or succinic and / or glutaric and / or adipic acids and C ₈ aliphatic alcohols can be used as ACAS in the claimed composition. -C ₂₂ , and / or C ₈ -C ₂₂ hydroxyalkylated aliphatic alcohols and / or C ₈ -C ₁₂ perfluorinated alcohols, for example, low toxicity (LD ₅₀ > 10 g / kg), a surfactant of general formula (4):

where, R ₁ is alkyl with C ₈ -C ₂₂ , R ₂ - (CH ₂ ) _2-4 -, -CH = CH-, m - 0-10, n - 0-20, Kat ⁺ - Na ⁺ , K ⁺ , NH4 ⁺ , NR ' ₃ H ⁺

The combined use of nonionic surfactants and anionic surfactants also ensures the achievement of a technical result: obtaining aggregatively and sedimentation-stable PFOS emulsions having an average particle size of not more than 200 nm and capable of being stored for a long time (at least 1 year) without a significant change in the particle diameter of the emulsion.

The use of ACAS provides a stable emulsion of PFOS at very low concentrations of emulsifying and stabilizing additives up to 0.25%. The decrease in the concentration of surfactants below the specified value does not allow to obtain a stable emulsion of PFOS.

When using nonionic surfactants as an emulsifying and stabilizing additive or a mixture thereof with a surfactant, the amount of surfactant increases and in the case of using only a nonionic surfactant mixture, it can reach 8%. With an increase in the amount of surfactants of more than 8%, the properties of PFOS practically do not change, and in some cases worsen.

The use of the proposed nonionic surfactants and anionic surfactants as emulsifying and stabilizing additives makes it possible to obtain stable emulsions using various PFOS, in particular, the claimed composition may contain:

- only rapidly derived (C ₈ -C ₁₀ ) PFOS;

- or a mixture of two PFOS: rapidly excreted (C ₈ -C ₁₀ ) PFOS and slowly excreted (C ₁₁ -C ₁₂ ) PFOS in a ratio of 2/1 to 10/1, respectively;

- or a mixture of three PFOS: two rapidly discharged (C ₈ -C ₁₀ ) PFOS and one slowly discharged (C ₁₁ -C ₁₂ ) PFOS in a ratio of 1/1/1 to 5/5/1, respectively, or a mixture of one rapidly discharged ( C ₈ -C ₁₀ ) PFOS and two slowly output (C ₁₁ -C ₁₂ ) PFOS in a ratio of 4/1/1 to 20/1/1, respectively;

- or a mixture of four PFOS: two fast-releasing (C ₈ -C ₁₀ ) PFOS and two slowly-releasing (C ₁₁ -C ₁₂ ) PFOS in a ratio of 2/2/1/1 to 10/10/1/1, respectively.

As rapidly excreting PFOS, perfluorodecalin (PFD) or perfluorooctyl bromide (PFOB) can be used, for example, and nitrogen-containing PFOS, for example perfluorotripropylamine (PFTPA), perfluoromethylcyclohexylpiperibidine (PFMPTPTl) or perfluorooctylamine (PFMPTF).

The rapidly eliminating PFOS is the basis of the perfluorocarbon phase, and due to it, the bulk of the dissolved gases are transferred. Slowly excreted nitrogen-containing (C ₁₁ -C ₁₂ ) PFOS is used both as a gas carrier and as an additional emulsion stabilizer that creates active adsorption centers on the surface of emulsion droplets.

A distinctive feature of the claimed composition from the majority of organofluorine emulsions known so far is the possibility of obtaining a stable emulsion based on only rapidly eliminating PFOS.

A significant difference of the claimed composition is also the possibility of obtaining stable emulsions with a high concentration of PFOS, which can reach 80 wt.%, Which provides a high oxygen capacity of up to 30 vol.%.

As a physiologically acceptable solution for the body, the claimed composition may contain physiological or isotonic solution. In particular, a solution containing glucose - 2 g / l, and salts can be used: sodium chloride - 6 g / l; potassium chloride - 0.39 g / l; magnesium chloride - 0.19 g / l; sodium bicarbonate - 0.65 g / l; sodium hydrogen phosphate - 0.2 g / l.

As an additional stabilizing additive, the claimed composition may contain C ₁₀ -C ₂₂ fatty acids and / or their salts in an amount of up to 0.15 wt.%, And / or triglycerides in an amount of up to 1 wt.%. In addition, along with emulsifiers and stabilizers, the claimed composition may additionally contain up to 0.5 wt.% Antioxidant, which can be used, for example, alpha-tocopherol.

The proposed composition allows to obtain a stable emulsion of PFOS, having an average particle size of 100-200 nm with a range of particle diameters from 90 to 500 nm, a significant difference of which is its high stability during prolonged storage, including at room temperature. So after 12 months of storage at a temperature of + 15- + 25 ° С, the average particle diameter of this emulsion increases only by 15%, that is, the stability index is 1.15.

Therefore, for the inventive emulsion does not require freezing during prolonged storage. The guaranteed shelf life of such an emulsion at a temperature of +4 to + 30 ° C is at least one year, while the average particle diameter of the emulsion at the end of the storage period does not exceed 250 nm, which approximately corresponds to the particle diameter of the freshly thawed industrial product "Perftoran".

The high aggregative stability of the claimed composition allows its sterilization not only by autoclaving, for example, in the temperature range from 100 to 120 ° C, but also by sterilization filtration of the emulsion obtained through a pore diameter of 200 nm to obtain the finished dosage form of a submicron perfluorocarbon emulsion with an average particle size of 100-200 nm Therefore, the production of the inventive emulsion (of the claimed composition) does not require aseptic production conditions and special sterilization methods.

A significant difference of the claimed composition is also the possibility of its use without any preliminary operations of defrosting and heating, which is of great importance when using the drug in emergency cases.

The determination of acute toxicity (LD ₅₀ ) showed that the claimed emulsion is characterized by low toxicity - LD _{50 is} not less than 140 ml / kg.

The fundamental difference between the claimed emulsion from the prototype and other known drugs is a very simple technology for its manufacture, which does not require the use of sophisticated equipment based on high pressure homogenizers (up to 1200 atm). To obtain the inventive composition, you can use a conventional dispersant, in particular a publicly available ultrasonic dispersant.

The manufacturing process of the inventive emulsion includes the following stages:

- first prepare a mixture of PFOS (component 1),

- then the emulsifier is dissolved in physiological or other isotonic solution (component 2).

- The resulting emulsifier solution (component 2) is loaded into a glass of an ultrasonic dispersant, the ultrasonic dispersant is turned on, and PFOS (component 1) is added over 3-15 minutes.

- After adding the entire amount of component 1, the emulsion is dispersed for another 20-60 minutes until the PFOS completely transitions to a highly dispersed state. The emulsification time is determined by the type and nature of the used surfactants and the parameters of the dispersing equipment.

Example 1 (prototype). The emulsion, the composition is completely similar to the emulsion of the prototype, obtained using an ultrasonic dispersant.

Component 1: - 25 ml of a mixture consisting of 40 g PFD and 10 g PFMTSP. The ratio of PFD: PFMTSP = 4: 1.

Component 2: emulsifiers - stabilizers: egg yolk phospholipids in an amount of 2 wt.%, And sodium palmitate in an amount of 0.05 wt.%, Dissolved in 77.95 ml of physiological saline.

Component 2 is loaded into a glass of an ultrasonic dispersant, the dispersant is turned on, and Component 1 is pinned with stirring for 5 minutes, after the entire amount of Component 1 has been added, the emulsion is dispersed for another 30 minutes, taking samples every 5 minutes to measure the particle size distribution of the emulsion.

Dispersion is stopped after the average particle diameter in two consecutive samples is no longer different.

The final formulation of the organofluorine emulsion has the following composition: PFD - 40 wt.%, PFMTSP - 10 wt.%, (Ratio PFD / PFMCP = 4/1), the total content of PFOS - 50 wt.% (25 vol.%), Egg lecithin yolk - 2%, palmitic acid - 0.05 wt.%, physiological saline - 47.95 wt.%.

The indicators of the obtained emulsion and their changes after 1 year of storage are shown in table 1.

Table 1 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 221 265 2 Viscosity, cP 7.5 9 3 The annual stability index for the arithmetic mean particle diameter. - 1,2 four LD50 for mice, ml / kg 158 148

Example 2

Component 1:10 ml of a mixture consisting of 13.3 g PFD and 6.7 g PFMTSP (ratio PFD / PFMTSP = 2/1).

Component 2: emulsifier - sodium monododecyl succinate (AAS) - 1.0 g dissolved in 79.0 g of standard saline.

Component 2 is loaded into a glass of an ultrasonic dispersant, the dispersant is turned on, and Component 1 is pinned for 5 minutes with stirring, after the total amount of Component 1 has been added, the emulsion is dispersed for another 20 minutes. Receive 100 g (90 ml) of an emulsion of the following composition: PFD 13.4 wt.% - PFMTSP 6.6 wt.% (Ratio 2/1) the total content of PFOS 20 wt.% (11 vol.%), Sodium monododecyl succinate (APAW) ) - 1 wt.%, Physiological saline - 79 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 2.

table 2 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 130 156 2 Viscosity, cP 1.10 1.15 3 Arithmetic average particle diameter annual stability index - 1,2 four LD50 for mice, ml / kg 150 145

Example 3. Analogously to example 2, using as a component 1-10 ml of a mixture consisting of 13.3 g of PFOB and 6.7 g of PFMTSP (ratio PFOB / PFMTSP = 2/1), and components 2 - a mixture of 3.9 g emulsifier (5, APAW):

and 0.1 g of α-tocopherol polyalkylene glycol ester with a molecular weight of 2670 containing 66% ethylene oxide dissolved in 76.0 g of standard physiological saline, 100 g (90 ml) of an emulsion of the following composition are obtained: PFOB 13.4 wt.% - PFMTSP 6.6 wt.% (Ratio 2/1), the total content of PFOS - 20 wt.% (Or 11 vol.%), Emulsifiers - 4 wt.%, Including ACAS - 3.9 wt.%, Nonionic surfactants - 0.1 wt.%, Physiological saline - 76 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 3.

Table 3 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 135 150 2 Viscosity, cP 1.15 1,2 3 Arithmetic average particle diameter annual stability index - 1,11 four LD50 for mice, ml / kg 155 152

Example 4. Analogously to example 2, using as a component 1-10 ml of a mixture consisting of 8.0 g PFOB, 8.0 g PFD 2.0 g PFMTSP, 2.0 g PFTPA (ratio of components PFOB / PFD / PFMTSP / PFTPA = 4: 4: 1: 1), and components 2, which is a mixture of 1.0 g of an emulsifier of the formula (6, APAW):

0.05 g glycidol ether of perfluorinated telomere alcohol (4F / 20G) with a molecular weight of 1912 and containing 20 glycidol fragments in the molecule and 0.05 g of a block copolymer of ethylene oxide and propylene oxide (emuxole 268) with a molecular weight of 13612 dissolved in 78 , 8 g of standard saline solution, 100 g (90 ml) of an emulsion of the following composition are obtained: PFOB 6.7 wt.%, PFD 6.7% wt., PFMTSP 3.3 wt.%, PFTPA 3.3 wt.% ( ratio 4/4/1/1), the total content of PFOS - 20 wt.% (or 11 vol.%), emulsifiers - 1.1 wt.%, including ACAS - 1.0 wt.%, Nonionic surfactants - 0.1 wt.%, Physiological saline - 78.8 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 4.

Table 4 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 142 163 2 Viscosity, cP 1,1 1,2 3 Arithmetic average particle diameter annual stability index - 1.15 four LD50 for mice, ml / kg 160 155

Example 5. Analogously to example 2, using as a component 1-30 ml of a mixture consisting of 45 g of PFD and 15 g of PFTPA, and component 2, which is a mixture of 1.95 g of potassium monodecyl succinate (AAS) and 0.05 g of emuxol 268 as well as 0.5 g of tripalmitin dissolved in 37.5 g of standard saline solution, 100 g (67 ml) of the emulsion are obtained, which has the following composition: PFD - 45 wt.%, PFTPA - 15 wt.% (ratio 3 / 1), the total content of PFOS is 60 wt.% (Or 45 vol.%), Potassium monodecyl succinate (APA) - 1.95 wt.%; emuxol 268 (nonionic surfactant) - 0.05 wt.%, physiological saline - 37.5 wt.%.

The indicators of the obtained emulsion and their changes after 1 year of storage are shown in table 5.

Table 5 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 130 155 2 Viscosity at a temperature of 25 ° C, cPz 11.3 11.1 3 Arithmetic average particle diameter annual stability index - 1.19 four LD50 for mice, ml / kg 138 136

Example 6. Analogously to example 2, using as a component 1-40 ml of a mixture consisting of 57 g of PFD and 23 g of PFMTSP, and component 2, consisting of a mixture of 3.5 g of potassium monononyl succinate (AAS) and 0.35 g of fluorine-containing nonionic surfactant (7) of the following structure:

where n = 6, m = 6

dissolved in 16.15 g of standard saline, 100 g (56 ml) of an organofluid emulsion having the following composition are obtained: PFD - 57 wt.%, PFMTSP - 23 wt.% (ratio 2.5 / 1), total PFOS content - 80 wt.%, (Or 67 vol.%), Potassium monodecyl succinate (APA) - 3.5 wt.%, Nonionic fluorine-containing surfactant - 0.35 wt.%, Physiological saline - 16.15 wt.%.

The performance of the emulsion and their changes after 1 year of storage are shown in table 6.

Table 6 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 167 195 2 Viscosity, cP 31 35 3 Arithmetic average particle diameter annual stability index - 1.17 four LD50 for mice, ml / kg 150 145

Example 7. Analogously to example 2, using as a component 1-4 ml of a mixture consisting of 6.4 g of PFD and 1.6 g of PFMCP, and component 2, which is a mixture of 0.25 g of triethanolammonium monotetradecyl glutarate (AAS) and 0 02 g of polyalkylene-glycol ether of α-tocopherol with a molecular weight of 2786, containing 63% ethylene oxide (nonionic surfactant), dissolved in 91.65 g of standard physiological saline, 100 g (96 ml) of an organofluid emulsion having the following composition are obtained: PFD - 6.4 wt.%, PFMTSP - 1.6 wt.% (Ratio 4/1), the total content of PFOS - 8 wt.%, (Or 6 about b.%), potassium monotetradecyl succinate (AAS) - 0.25% wt.%, α-tocopherol polyalkylene glycol ether (nonionic surfactant) - 0.02 wt.%, physiological saline - 91.73 wt.%.

The performance of the emulsion and their changes after 1 year of storage are shown in table 7.

Table 7 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 125 150 2 Viscosity, cP one one 3 The annual stability index for the arithmetic mean particle diameter - 1,2 four LD50 for mice, ml / kg 175 172

Example 8. Analogously to example 2, using as a component 1-40 ml of a mixture consisting of 72.7 g of PFOB and 7.3 g of PFPA, and component 2, which is 4 g of sodium monooctyl succinate (APA), as well as 0.15 g of myristic acid and 0.2 g of trimyristin in 16.0 g of standard saline solution, 100 g (60 ml) of an organofluorine emulsion having the following composition are obtained: PFOB - 72.7 wt.%, PFTPA - 7.3 wt.% ( ratio 10/1), the total content of PFOS is 80 wt.% (or 66.7 vol.%), sodium mono-octyl succinate (APA) - 4 wt.%, myristic acid - 0.15%, trimyristin - 0.2 % physiologist solution cal -. 15.65 wt%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 8.

Table 8 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 130 150 2 Viscosity, cP 35 37 3 The annual stability index for the arithmetic mean particle diameter - 1.15 four LD50 for mice, ml / kg 136 132

Example 9. Analogously to example 2, using as component 1 - 30 ml of a mixture consisting of 50 g of PFD and 10 g of PFMTSP (ratio of PFD / PFMTSP = 5: 1), components 2-3.0 g of APAA formula (8):

and 0.05 g of sodium stearate dissolved in 36.95 g of a standard polyelectrolyte isotonic solution (Ringer's solution: sodium chloride - 6 g / l; potassium chloride - 0.39 g / l; magnesium chloride - 0.19 g / l; sodium bicarbonate - 0.65 g / l; sodium hydrogen phosphate - 0.2 g / l and glucose - 2 g / l), 100 g (67 ml) of an organofluorine emulsion having the following composition are obtained: PFD - 50 wt.%, PFMTSP - 10 wt.% (Ratio 5/1), the total content of PFOS - 60 wt.%, (Or 45 vol.%), Emulsifier (8) - 3 wt.%, Sodium stearate - 0.05%, isotonic Ringer's solution - 36.95 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 9.

Table 9 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 145 170 2 Viscosity, cP 11.5 12,2 3 The annual stability index for the arithmetic mean particle diameter - 1.17 four LD50 for mice, ml / kg 140 138

Example 10. Analogously to example 2, using as a component 1-30 ml of a mixture of PFOS consisting of 25 g PFD 20 g PFOB and 15 g PFMTSP (ratio PFD / PFOB / PFMTSP = 5/4/3), and component 2, consisting from a mixture of 1 g of potassium monononyl succinate and 2 g of ACAS of the formula:

in 37 g of a standard saline solution, 100 g (67 ml) of an emulsion of the following composition are obtained: PFD - 25 wt.%, PFOB - 20 wt.%, PFMTSP - 15 wt.% (5/4/3 ratio), total PFOS content - 60 wt.% (Or 45 vol.%), Emulsifiers (mixture of ACS) - 3 wt.%, Saline - 37 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 10.

Table 10 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 130 155 2 Viscosity, cP 10.5 11,2 3 The annual stability index for the arithmetic mean particle diameter - 1.19 four LD50 for mice, ml / kg 140 142

Example 11. Analogously to example 2, using as a component 1-10 ml of a mixture consisting of 13.3 g of PFD and 6.7 g of PFMCP (ratio of PF, D / PFMCP = 2/1), and component 2, which is a mixture 4.0 g of emuxol 268 and 4.0 g of perfluorinated nonionic surfactant of the formula (7), in 72 g of standard saline, 100 g (90 ml) of an emulsion of the following composition are obtained: PFD - 13.3 wt.%, PFMTSP - 6.7 wt.% (ratio 2/1), the total content of PFOS - 20 wt.% (or 10 vol.%), emulsifiers (mixture of nonionic surfactants) - 8 wt.%, saline - 72 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 11.

Table 11 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 180 200 2 Viscosity, cP 1.3 1.4 3 The annual stability index for the arithmetic mean particle diameter - 1,11 four LD50 for mice, ml / kg 136 139

Example 12. Analogously to example 2, using as a component 1-15 ml of a mixture consisting of 20.0 g of PFOB and 10.0 g of PFBA (ratio of components PFOB / PFBA = 2: 1), and component 2, which is a mixture of 3 , 0 g of a block copolymer of ethylene oxide and propylene oxide with a molecular weight of 12,600 and an ethylene oxide content of 72% and 5.0 g of glycidol ether of perfluorinated telomere alcohol (4F / 20G) with a molecular weight of 1912 and containing 20 glycidol fragments in the molecule, dissolved in 62.0 g of standard saline, 100 g (85 ml) of emulsion are obtained after composition: PFOB 20 wt.%, PFBA 10 wt.% (ratio 2/1), the total content of PFOS - 30 wt.% (or 17.6 vol.%), emulsifiers (nonionic surfactants) - 8 wt.% and physiological solution - 62 wt.%.

The performance of the original emulsion and their changes after 1 year of storage are shown in table 12.

Table 12 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 165 188 2 Viscosity, cP 2.0 2.1 3 The annual stability index for the arithmetic mean particle diameter - 1.14 four LD50 for mice, ml / kg 160 155

Example 13. Analogously to example 2, using as a component 1-10 ml of a mixture consisting of 8.0 g of PFOB, 8.0 g of PFD, 2.0 g of PFMCP, 2.0 g of PFTA (ratio of components PFOB / PFD / PFMCP / PFTBA = 4: 4: 1: 1), and components, which is a mixture of 3.8 g of α-tocopherol polyalkylene glycol ether with a molecular weight of 2786, containing 63% ethylene oxide, 4.0 g of perfluorinated telomeric alcohol glycidol ether (4F / 20G) with a molecular weight of 1912 and containing 20 glycidol fragments in the molecule and 0.2 g of the sodium salt of lauryl alcohol succinate, dissolved in 72.0 g s standard saline solution, 100 g (90 ml) of an emulsion of the following composition are obtained: PFOB 6.7 wt.%, PFD 6.7 wt.%, PFMTSP 3.3 wt.%, PFBA 3.3 wt.% (ratio 4 / 4/1/1), the total content of PFOS is 20 wt.% (Or 11 wt.%), Emulsifiers (nonionic surfactants) - 8.0 wt.%, Physiological saline - 78.8 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 13.

Table 13 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 142 170 2 Viscosity, cP 1,1 1,2 3 The annual stability index for the arithmetic mean particle diameter - 1,2 four LD50 for mice, ml / kg 160 155

Example 14. Analogously to example 2, using as a component 1-20 ml of a mixture consisting of 26.6 g of PFD and 13.4 g of PFMCP (ratio PFD / PFMCP = 2/1), and component 2, which is a mixture of 3, 0 g of potassium monodecyl succinate and 1.0 g of potassium heptafluorooctyl succinate, as well as 0.15 g of lauric acid in 55.85 g of standard saline, receive 100 g (80 ml) of an emulsion of the following composition: PFD - 13.3 wt.%, PFMTSP - 6.7 wt.% (Ratio 2/1), the total content of PFOS - 40 wt.% (Or 10 vol.%), The total emulsifier (mixture of APS) - 4 wt.%, Saline - 55.85 wt. %

The performance of the emulsion and their changes after 1 year of storage are shown in table 14.

Table 14 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 170 198 2 Viscosity, cP 2.5 2.5 3 The annual stability index for the arithmetic mean particle diameter - 1.16 four LD50 for mice, ml / kg 136 139

Example 15. Analogously to example 2, using as a component 1-30 ml of a mixture consisting of 40 g of PFD and 20 g of PFTA, and component 2, which is a mixture of 1.8 g of potassium monodecyl succinate (AAS), 0.05 g of emuxol 268 and 0.15 g of perfluorinated nonionic surfactants (7) dissolved in 37 g of standard saline solution, 100 g (67 ml) of an emulsion are obtained, which has the following composition: PFD - 40 wt.%, PFBA - 20 wt.% (ratio 2 / 1), the total content of PFOS is 60 wt.% (Or 45 vol.%), Potassium monodecyl succinate (APA) - 1.8 wt.%; Nonionic surfactants: nonionic surfactants - 0.2 wt.%, Physiological saline - 38 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 15.

Table 15 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 165 184 2 Viscosity at a temperature of 25 ° C, cPz 11.0 13.1 3 The annual stability index for the arithmetic mean particle diameter - 1.12 four LD50 for mice, ml / kg 140 141

Example 16. Analogously to example 2, using as a component 1-10 ml of a mixture consisting of 13.3 g of PFOB and 6.7 g of PFMCP (ratio PFOB / PFMCP = 2/1), and components 2: a mixture of 3.5 g AASA of formula (5) with a nonionic surfactant, which is a mixture of 0.1 g of α-tocopherol polyalkylene glycol ether with a molecular weight of 2670, containing 66% ethylene oxide with 0.4 g of perfluorinated surfactant of the formula (7) dissolved in 76.0 g of standard physiological solution, 100 g (90 ml) of an emulsion of the following composition are obtained: PFOB 13.4 wt.% - PFMTSP 6.6 wt.% (ratio 2/1), the total content of PFOS - 20 wt.% (silt 11 vol%), emulsifiers -. 4 wt%, including. ACAS - 3.5 wt.%, Nonionic surfactants - 0.5 wt.%, Physiological saline - 76 wt.%.

The performance of the resulting emulsion and their changes after 1 year of storage are shown in table 16.

Table 16 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 145 165 2 Viscosity, cP 1.15 1,2 3 The annual stability index for the arithmetic mean particle diameter - 1.14 four LD50 for mice, ml / kg 155 152

Example 17. Analogously to example 2, using as a component 1-40 ml of a mixture consisting of 70 g of PFOB and 10 g of PFTA, and component 2 (AAS), which is a mixture of 3 g of sodium monooctyl succinate and an emulsifier of formula (6), in 16 , 0 g of standard saline solution, 100 g (60 ml) of an organofluorine emulsion are obtained having the following composition: PFOB - 70 wt.%, PFBA - 10 wt.% (Ratio 7/1), the total content of PFOS - 80 wt.% ( or 66.7 vol.%), APAW - 4 wt.%, physiological saline - 16 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 17.

Table 17 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 170 190 2 Viscosity, cP 35 40 3 The annual stability index for the arithmetic mean particle diameter - 1.12 four LD50 for mice, ml / kg 136 132

Example 18. Analogously to example 2, using as a component 1-10 ml of a mixture consisting of 6.7 g of PFD and 3.3 g of PFMTSP (ratio PFD / PFMTSP = 2/1), and component 2 (nonionic surfactant), which is a mixture of 3.0 g of lutrol F127 and 3.0 g of perfluorinated surfactant of the formula (7), as well as 0.5 g of α-tocopherol in 83.5 g of standard saline solution, 100 g (90 ml) of an emulsion of the following composition are obtained: PFD - 6.7 wt.%, PFMTSP - 3.3 wt.% (Ratio 2/1), the total content of PFOS - 10 wt.% (Or 10 vol.%), Emulsifiers (mixture of nonionic surfactants) - 6 wt.%, Physiological solution - 83.5 wt.%.

The performance of the emulsion and their changes after 1 year of storage are shown in table 18.

Table 18 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 155 182 2 Viscosity, cP 1.3 1.4 3 The annual stability index for the arithmetic mean particle diameter - 1.17 four LD50 for mice, ml / kg 136 139

Example 19. Analogously to example 2, using as a component 1-4 ml of a mixture consisting of 6.4 g of PFD and 1.6 g of PFMCP, and component 2, which is a mixture of 0.25 g of lithium salt monotetradecylglutarate (AAS) and nonionic surfactants (a mixture of 0.02 g of α-tocopherol polyalkylene glycol ether with a molecular weight of 2786 containing 63% ethylene oxide with 0.01 g of pluronic PE 6800 dissolved in 91.65 g of standard saline solution, 100 g (96 ml) of organofluorine emulsion are obtained, having the following composition: PFD - 6.4 wt.%, PFMTSP - 1.6 wt.% (ratio 4/1), the total content of PF C - 8 wt.%, (Or 6 vol.%), Potassium monotetradecyl succinate (APA) - 0.25% wt., Α-tocopherol polyalkylene glycol ether (nonionic surfactant) - 0.03 wt.%, Physiological saline - 91.72 wt. .%.

The performance of the emulsion and their changes after 1 year of storage are shown in table 19.

Table 19 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 190 200 2 Viscosity, cP one one 3 The annual stability index for the arithmetic mean particle diameter - 1.05 four LD50 for mice, ml / kg 175 172

Example 20. Analogously to example 2, using as a component 1-20 g of PFD and component 2, which is a solution of 1.5 g of sodium monododecyl succinate (ACAS), and 0.1 g of palmitic acid sodium salt in 78.4 g of standard saline 100 g (96 ml) of an organofluorine emulsion are obtained having the following composition: PFD - 20 wt.%, sodium monotetradedecyl succinate (APAW) - 1.5% wt.%, sodium salt of palmitic acid - 0.1%, physiological saline - 78 , 4 wt.%.

The performance of the emulsion and their changes after 1 year of storage are shown in table 20.

Table 20 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 175 195 2 Viscosity, cP 1.13 1.17 3 The annual stability index for the arithmetic mean particle diameter - 1,11 four LD50 for mice, ml / kg 148 150

Example 21. Analogously to example 2, using as a component 1-25 g of PFOB, 2.5 g of component 2, which is potassium monononyl succinate (AAS), 0.05 g of stearic acid, 0.5 g of trioctanoin in 71.95 g of standard physiological saline, 100 g (96 ml) of an organofluorine emulsion are obtained having the following composition: PFOB — 25 wt.%, sodium monotetradedecyl succinate (APA) — 2.5 wt.%, saline — 71.95 wt.%.

The indicators of the emulsion obtained and their changes after 1 year of storage are shown in table 21.

Table 21 No. The name of indicators Emulsion Storage Time 0 after 1 year one Arithmetic average particle diameter, nm 185 200 2 Viscosity, cP 2.45 2.7 3 The annual stability index for the arithmetic mean particle diameter - 1,08 four LD50 for mice, ml / kg 148 150

Example 22

To 25 g of an emulsion with a PFOS content of 80 wt.%, Obtained according to example 6, 75 g of an infusion solution are diluted with stirring. Get 100 g of an emulsion with a PFOS content of 20 wt.%.

The emulsion indicators before and after dilution are shown in table 22.

Table 22 No. The name of indicators Before dilution After dilution one Arithmetic average particle diameter, nm 160 140 2 Viscosity, cP 31 1,5 3 The content of PFOS, wt.% 80 twenty

Example 23

To 25 g of an emulsion with a PFOS content of 60 wt.%, Obtained according to example 15, 75 g of an infusion solution are diluted with stirring. Get 100 g of an emulsion with a PFOS content of 15 wt.%.

The performance of the emulsion before and after dilution are shown in table 23.

Table 23 No. The name of indicators Before dilution After dilution one Arithmetic average particle diameter, nm 145 175 2 Viscosity, cP 11.0 1,2 3 The content of PFOS, wt.% 60 fifteen

The listed examples are merely illustrative and do not limit the possibility of using other combinations of the claimed emulsion.

To compare the physico-chemical properties of the claimed PFOS emulsion with the physico-chemical properties of the industrial product Perftorana, PFOS emulsion from the prototype and PFOS emulsion according to the composition of the prototype, but obtained using an ultrasonic disperser, table 24 shows the particle sizes and stability indices of the above emulsions PFOS when stored indoors.

Table 24 Emulsion PFOS The content of PFOS, wt.% Particle sizes, microns Stability index D sr-arithm. D min D max Perftoran twenty 0.20 0.13 0.70 1.40 An emulsion made according to the composition of the prototype fifty 0.17 0.10 0.55 1.20 The emulsion according to the invention (Example 5) 60 0.14 0.09 0.44 1.19

As can be seen from the above tables and examples, the proposed emulsion with gas transport properties has the following advantages compared to "Perftoran" and an emulsion made according to the composition of the prototype, but according to the method of the claimed composition:

- smaller average particle diameter;

- higher stability during storage;

- low toxicity;

- does not require special equipment for long-term storage;

- low cost (no special expensive equipment is required; affordable PFOS and surfactants are used).

Claims (11)

1. An emulsion of perfluororganic compounds with gas transport properties, containing a perfluororganic compound (PFOS), an emulsifying and stabilizing additive, characterized in that as an emulsifying and stabilizing additive contains a nonionic surfactant (NSAID), which is a mixture of ethylene oxide block copolymers and propylene oxide and / or polyalkylene glycol esters of tocopherol of the formula:

where n + p = 30-150, m = 2-50 with polyglycidyl ethers of fluorinated alcohols and / or perfluorinated alcohols in a ratio of 2: 1 to 0.5: 1, or an anionic surfactant (APA), which is a salt a monoester of a dibasic carboxylic acid with aliphatic and / or oxyalkylated aliphatic and / or perfluorinated alcohols, or a mixture of these nonionic surfactants and anionic surfactants (with a ratio of nonionic surfactants and anionic surfactants from 39: 1 to 1:39) with the following ratio of components wt.%:
PFOS 8 ÷ 80.0 emulsifying and stabilizing additive 0.25 ÷ 8.0 physiologically acceptable solution for the body rest 2. The emulsion according to claim 1, characterized in that as PFOS contains a mixture of two PFOS: rapidly derived (C ₈ -C ₁₀ ) PFOS and slowly derived (C ₁₁ -C ₁₂ ) PFOS in a ratio of 2: 1 to 10: 1 respectively. 3. The emulsion according to claim 1, characterized in that as PFOS contains a mixture of three PFOS: two rapidly derived (C ₈ -C ₁₀ ) PFOS and one slowly derived (C ₁₁ -C ₁₂ ) PFOS in a ratio of 1: 1: 1 to 5: 5: 1, respectively, or a mixture of one rapidly removing (C ₈ -C ₁₀ ) PFOS and two slowly removing (C ₁₁ -C ₁₂ ) PFOS in a ratio of 4: 1: 1 to 20: 1: 1, respectively. 4. The emulsion according to claim 1, characterized in that as PFOS contains a mixture of four PFOS: two rapidly derived (C ₈ -C ₁₀ ) PFOS and two slowly removed (C ₁₁ -C ₁₂ ) PFOS in a ratio of 2: 2 : 1: 1 to 10: 10: 1: 1, respectively. 5. An emulsion according to any one of claims 2 to 4, characterized in that, as rapidly excreted PFOS, contains perfluorodecalin and / or perfluorooctyl bromide. 6. The emulsion according to any one of claims 2 to 4, characterized in that, as slowly discharged PFOS, contains nitrogen-containing PFOS - perfluorotripropylamine, or perfluoromethylcyclohexylpiperidine, or perfluorotributylamine, or mixtures thereof. 7. The emulsion according to claim 1, characterized in that the ASA contains salts of monoesters of malonic, or maleic, or fumaric, or succinic, or glutaric, or adipic acid with aliphatic and / or hydroxyalkylated aliphatic and / or perfluorinated alcohols or their mixture. 8. The emulsion according to claim 1, characterized in that the ASAS contains sodium, or potassium, or ammonium, or substituted ammonium salts of dicarboxylic acid monoesters with hydroxyalkylated aliphatic and / or perfluorinated alcohols, or mixtures thereof. 9. The emulsion according to claim 1, characterized in that it further comprises C ₁₀ -C ₂₂ fatty acids or their salts in an amount of up to 0.15 wt.% Or triglycerides in an amount of up to 0.5 wt.% Or a mixture thereof. 10. The emulsion according to claim 1, characterized in that it further comprises an antioxidant in an amount up to 0.5 wt.%. 11. The emulsion according to claim 1, characterized in that as a physiologically acceptable solution for the body contains a physiological or other isotonic solution.