RU2461383C2 - Plasma-substitute preparation with rheological and hemodynamic properties and agent for treating - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention refers to chemical-pharmaceutical industry, and concerns a plasma-substitute compound with the rheological and hemodynamic properties on the basis of a block copolymer of ethylene oxide and propylene oxide, and hydroxyethylstarch, and using it in medicine and cosmetology.

EFFECT: preparing the plasma-substitute compound with the improved rheological and hemodynamic properties of mixed two active ingredients: the surfactant proxanol - the block copolymer of ethylene oxide and propylene oxide of molecular weight 1 to 20 kDa and the hemodynamic agent hydroxyethylstarch of molecular weight 40 to 200 kDa in the ratio of 1/1 to 10/10 respectively with an acceptable electrolyte solution.

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Description

The invention relates to the biomedical industry and relates to a plasma substitution composition based on a surfactant and a hemodynamic agent and its use as a rheological and hemodynamic agent intended for use in blood loss and treatment of various diseases.

Currently, they have found very widespread use in everyday life, in pharmacy and medicine, various surface-active substances (surfactants). Among them, nonionic surfactants (nonionic surfactants) stand out for their potential for promising use in medicine, since they have the lowest toxicity among surfactants. Of greatest interest is the use of nonionic surfactants for medical purposes. Among nonionic surfactants, proxanol is of particular interest, and among them proxanol-268.

As you know, proxanols are a synthetic compound. It is a block copolymer of ethylene oxide and propylene oxide. The properties of proxanols are described in sufficient detail in the literature [Schenfeld N., 1982]. Nonionic surfactants have low toxicity. Therefore, in medicine, they first found application as stabilizers for emulsions of biomedical use. It was found that with a certain pier. the mass and the ratio of hydrophilic and hydrophobic blocks equal to 20/80, proxanols dissolve well in water and perfectly stabilize various emulsions.

The choice of proxanols for intravenous administration and, in particular, as part of perfluorocarbon emulsions is described in [E.F. Illarionov, E.I. Mayevsky, Yu.E. Kirsh and others. Sb-k: Fluorocarbon gas-transporting media. Pushchino, 1984, pp. 73-78]. The use of proxanol in the composition of perfluorocarbon emulsions is well known, described in numerous publications and may be the subject of a separate study.

Foreign analog of proxanols is Pluronic F-68 (Pluronic F-68).

The use of Pluronic F-68 for the treatment of fat embolism is well known [Adams J.E., Owens G. et al. Surg. Forum - 1959. - Vol. 10. - p.585]. A solution of Pluronic F-68 when administered intravenously reduces the surface tension of blood plasma, improves microcirculation, increases blood pressure and diuresis. Interacting with cell membranes, Pluronic F-68 prevented the aggregation of blood cells [Hymes A.C., Safavian M.H., Gunter T.J. surg. Res. - 1971. - Vol. 11. - p. 191-197]. Interacting with cell membranes, Pluronic F-68 increased the osmotic resistance of red blood cells [Janoff A.S., Mazovon D.L. et al. Amer.J. Hemat. - 1981. - Vol. 10. - p. 171-179]. Pluronic F-68 supports slightly oncotic blood plasma pressure [Hymes A.C., Safavian M.H. et al. J. thorac. cardiovasc. Surg. - 1968. - Vol. 56. - p.16-22]. A solution of Pluronic F-68 when administered intravenously significantly reduces blood viscosity without changing the hematocrit, improves microcirculation. Also described is the use of Pluronic F-68 as an additive in the composition of perfusion media, where surfactants significantly extended the time for successful perfusion of isolated organs. Interacting with cell membranes, Pluronic F-68 prevented the aggregation of blood cells [Paton B.S., Grover F.L. et al. Organ Perfusion and Preservation. Ed. J.C. Norman. - New York, 1968]. Protective anti-hemolytic properties of the water-structured membrane space: with an increase in the amount of adsorbed proxanol and, therefore, an increase in the structural barrier preventing the penetration of hemolytic, the protective effect increases, thus reducing the breakdown of red blood cells. At high concentrations of proxanol and in the case of multilayer adsorption, polyoxyethylene chains begin to intertwine with each other and, according to the data provided by K.Tringer, squeeze out bound water, thereby significantly reducing the hydration of the adsorbed layer and isolating cells from external influences [K. Tringer . The state and role of water in biological objects. M., 1967, p.143-150]. For the first time, the possibility of using nonionic surfactants and proxanols, in particular for wound healing, was reported by M. Mudarov [Mudarov M. S. Stimulation of the healing of aseptic postoperative wounds. Abstract of diss. M., 1976].

The use of nonionic surfactants for medical and cosmetic purposes

Patents of the Russian Federation are known in which proxanol is used as a means of stimulating reparative processes, and as a biologically active component for cosmetology, stimulating metabolic processes in integumentary tissues. This is a patent of the Russian Federation No. 2026072, MKI AK61K 31/745, priority dated January 31, 1992, “Means for stimulating reparative processes” (Oksinoid O.E., Sidlyarov D.P., Zakharov V.V., Nikolaev A.V. , Akhsyanov U.U., Litvinenko Yu.A., Krasnopolsky Yu.M., Temirov Yu.P.), applicant and patent holder of Nizar JSC, publ. 01/10/95, bull. No. 1. The aim of the invention is the acceleration of reparative processes in the wound. The goal is achieved by using a block copolymer of ethylene oxide and propylene oxide. The presented results show that a 20% aqueous solution of the block copolymer has the most pronounced effect stimulating repair processes, and a decrease or increase in the concentration of the block copolymer is accompanied by a decrease in this effect. In the case of using 10-30% solutions, the processes of cleansing wounds, the formation of granulation tissues, and the appearance of marginal epithelization proceeded more actively than in the control, without pronounced inflammatory reactions of suppuration. The block copolymer of ethylene oxide and propylene oxide proposed as a stimulant is not an individual substance and is a mixture of polymers of different molecular weights, which depends on the polymerization conditions. However, subject to standard polymerization conditions, reproducible product characteristics are achieved. It is practically most convenient to use a block copolymer having a molecular weight of 3-25 kDa and a weight ratio of oxypropylene and oxyethylene parts of 20/80, i.e. with the characteristics that meet this product manufactured by the industry.

As a result of a patent search, a patent of the Russian Federation No. 2063223, MKI AK61K 31/075, 31/23, "Method of immunostimulation in an experiment", publ. 07/10/96, bull. No. 19. The invention relates to medicine, namely immunology. The proposed means STEAROX-920 and OS-20 (nonionic surfactants) can stimulate the immune system suppressed by snake venoms or other zootoxins. This allows us to recommend them as a means to correct indicators of the immune status of individuals who have undergone snake bites, karakurt, scorpion, etc. The above nonionic surfactants are not proxanols (STEAROX-920 is polyethylene glycol monostearate, and OS-20 is monoalkyl ether of polyethylene glycol), however, it is known that proxanols also affect the immune system. Therefore, the possibility of their use as immunostimulants in the immune system suppressed by snake venoms and other zootoxins cannot be ruled out.

In the patent of the Russian Federation No. 2033789, MKI A61K 7/00, 31/765, priority dated July 20, 1992, “Biologically active substance of cosmetics, stimulating metabolic processes in integumentary tissues” (Oksinoyd O.E., Sidlyarov D.P. , Zakharov V.V.), applicant and patent holder of JSC "Nizar", publ. 04/30/95, bull. No. 12, it is proposed to use proxanols for use in cosmetology, with the goal of stimulating metabolic processes in integumentary tissues.

The possibility and feasibility of using a block copolymer of ethylene oxide and propylene oxide in cosmetics is based, in particular, on its ability to improve the processes of blood microcirculation in the subcutaneous tissue and positively affect the metabolic processes in it, which, in particular, is confirmed by experimental information cited in the patent. Experimental data show that the effect of the block copolymer of ethylene oxide and propylene oxide on the course of reparative processes is more favorable than the effect of sea buckthorn oil: the copolymer stimulates the synthesis of hydroxyproline, a collagen precursor, to a greater extent and practically does not differ from sea buckthorn oil in its effect on the biosynthesis of nucleic acids . The block copolymer of ethylene oxide and propylene oxide showed a higher wound healing activity than methyluracil, solcoseryl, collagen sponge, sea buckthorn oil. In addition, this compound promotes the regeneration of not only deeply affected tissues (traumatic wounds, burns, etc.), but also prevents the development of necrotic processes. In the preparation of water-based cosmetics, the amount of block copolymer sufficient for the manifestation of its biological activity is 10-20%, and for the manifestation of biological activity in fat-based cosmetics is 20-30%. It is known, for example, that the oxypolypropylene part imparts hydrophobic properties to the block copolymer, and such copolymers are preferable to be used in fat-based cosmetics, and the oxypolyethylene part gives hydrophilic properties to the block copolymer, and it is preferable to use such copolymers in water-based cosmetic preparations.

In the patent of the Russian Federation No. 2033163, MKI AK61K 33/16, 7/00, priority dated 07/20/92, "Means that stimulate wound healing and / or improve metabolism in integumentary tissues" (Oksinoyd O.E., Sidlyarov D.P. , Zakharov V.V.), applicant and patent holder of JSC "Nizar", publ. 04/20/95, bull. No. 11, proxanol is used in conjunction with perfluorocarbons (PPS), where it also plays the role of a stabilizer of the PFS emulsion. The invention relates to medicine and cosmetology. The purpose of the invention is to expand the range of medicines and cosmetics with wound healing and metabolic properties. The block copolymer of ethylene oxide and propylene oxide has a wound healing effect in the first phase of the wound process due to a local improvement in microcirculation in the tissues adjacent to the lesion, as well as due to direct biostimulation of activity that enhances tissue regeneration.

Also known is a patent of the Russian Federation No. 2020934, MKI AK61K 31/18, 31/045, 31/425, priority dated 01.03.91, "Means for the treatment of infected wounds" (Lyapunov N.A., Kalinichenko N.F., Blatun L .A., Bashura G.S., Malyakova N.F., Osolodchenko T.P., Georgievsky V.P., Khovanskaya N.P., Pavlova V.V., Koshelev Yu.A., Fadeykina A.G. ., Starobinets Z.G.), publ. 10/15/94, bull. No. 19. The invention relates to medicine, in particular to surgery. To increase antibacterial activity and expand the spectrum of antibacterial action, the antibacterial agent contains streptocide and nitazole, a condensation product of propylene and ethylene oxides mol. m. 13000 (proxanol-268), 1,2-propylene glycol (PEO-400) in the following ratio of components, wt.%: streptocid 2-6; nitazole 1-3; proxanol-268, 20-30; 1,2-propylene glycol 37.5-42.7; PEO-400 18.0-37.5.

This group also includes patent EP No. 0431884, MKI A61K 31/77 dated 06/12/91, Bull.91 / 24, "Non-toxic wound cleansing compositions", which describes aqueous disinfectants wounds of a composition containing at least one nonionic ethylene oxide / propylene oxide block copolymer and at least one electrolyte, and their use for disinfecting and / or treating wounds in a non-toxic manner. In the examples, Pluronic F-68, Pluronic 104, Pluronic L-64, Pluracare 10R-5, Tetronic 304, Tetronic 904, Tetronic 59R-4, etc. were used.

We find very interesting patent EP No. 0305470, MKI A61K 31/77 dated 11.11.92, Bull.92 / 46, "Anti-infective compounds and method of use (" Anti-infective compounds and method of use "), in which it is proposed to use nonionic block copolymers for the manufacture of pharmaceutical compositions that are introduced into the body to kill and inhibit the growth of bacteria and viruses caused by infection.

PCT Patent WO 93/03738, MKI A61K 31/745, 31/08, 03/04/93, "Method for treating vascular obstructions caused by abnormal cells" describes a method that provides treatment of ischemia resulting from the microvascular risk caused by abnormal cells in the bloodstream, which are often the result of complications of malaria and leukemia. The method is especially useful in the treatment of cerebral malaria. The method consists in administering to a animal or human with a microvascular risk a therapeutically effective amount of a surface-active copolymer.

PCT Patent WO 92/19250, MKI A61K 31/745, 11/12/92, Method for treating hypothermia, describes a method that provides treatment for hypothermia and protects a person or animal from hypothermia. This invention relates to methods for protecting a person or animal from damage during hypothermia, similar to that which occurs during bypass surgery. The surface active copolymer may be a condensation product of ethylene oxide and propylene oxide.

Very interesting and important is the article by SMMoghini, ISMuir, L. Illum, SSDavis and V. Kolb-Bachofen "Coating particles with a block co-polymer (poloxamine-908) suppresses opsonization but permits the activity of dysopsonins in the serum" , Biochimica et Biophysica Acta, 1179 (1993) 157-165. This article describes the interaction of microspheres, uncoated and coated with a Poloxamine-908 block copolymer, with the immune system. The surfaces of polystyrene microspheres (60 nm in diameter) and colloidal gold particles (17 nm in diameter) were coated with a block copolymer of polyoxyethylene (POE) and polyoxypropylene (POP) - poloxamine-908. The polymer was adsorbed to the microspheres strictly through its hydrophobic POP segments. This left the POE chains in a mobile state, since they are directed outward from the surface and, thus, ensure the stability of the suspension of particles from compression aggregation. A comparative assessment of blood purification and biodistribution of uncoated and coated with poloxamine-908 polystyrene labeled microspheres 1 hour after intravenous administration to rats was performed. Poloxamine coating significantly reduced the accumulation of microspheres by the liver and kept them in the systemic circulation. This observation was then confirmed by electron microscopy, demonstrating that Kupffer cells were weighed with uncoated latex, but only a few particles coated with poloxamine-908 were absorbed. The interaction of gold particles coated and uncovered with poloxamine with freshly isolated sinusoidal cells of rat liver was studied using an electron microscope. The accumulation of gold particles in Kupffer cells after opsonization using (autologous) plasma was in accordance with the previous observation, where the dominant opsonization activator was identified as fibronectin. In contrast, the coating of gold particles with poloxamine-908 prior to plasma opsonization prevented the absorption of fibronectin on their surface. Thus, it was demonstrated that organ-specific receptors, active opsonins and plasma desopsonins regulate the in vivo removal of certain materials from circulation. Poloxamine-908 coating modulates particle withdrawal, effectively blocking opsonization, but still allowing disopsonization.

In connection with the question of the interaction of proxanols on the immune system, Dale E. Hammerschmidt, Gregory M. Vercellotti "Limitation of Complement Activation by Perfluorocarbon Emulsions: superiority of Lecithin-Emulsified Preparations" Biomat., Art. Cells, Art. Org., 16 (1-3), 431-438 (1988), in which it is shown that the introduction of PPS emulsions stabilized with proxanol (Pluronic F-68) causes complement activation. Perfluoroadamantane emulsions made with highly purified lecithin as an emulsifier caused significantly less complement activation than the corresponding emulsions made with Pluronic F-68 as an emulsifier. Emulsification technology does not seem to play a role. The perfluoroadamantane emulsion made with Pluronic F-68 as an emulsifier activates the complement system three times higher than the same emulsion made with lecithin. It was also found that when combined with the use of a mixture of Pluronic F-68 and lecithin as an emulsifier, the latter does not protect against complement activation, regardless of the sequence in which the emulsion was introduced into the composition.

Thus, the following areas of proxanol use for medical purposes were identified:

- to prevent and treat fat embolism;

- to improve microcirculation (decrease in blood viscosity without changing hematocrit, lowering the surface tension of blood plasma);

- to prevent blood cell aggregation (platelet aggregation, erythrocyte hemolysis);

- to increase the osmotic resistance of red blood cells;

- to increase blood pressure and urine output;

- for transplantation as an additive in the composition of perfusion media to extend the time for successful perfusion of isolated organs;

- for treatment in brain traumatology as an additive in the composition of perfusion media;

- to stimulate the healing of aseptic postoperative wounds;

- to stimulate metabolic processes in integumentary tissues (stimulation of reparative processes);

- as a biologically active substance in cosmetics, stimulating the processes of metabolism in integumentary tissues (improvement of blood microcirculation in subcutaneous tissue and a positive effect on metabolic processes in it);

- as the basis of an antibacterial substance;

- for the treatment of vascular obstruction caused by pathological cells in the bloodstream;

- to protect and treat damage during hypothermia;

- as agents affecting the immune system;

- as an anti-infectious composition, introduced into the body to destroy and suppress the growth of bacteria and viruses caused by infection;

- as a non-toxic disinfecting wound of the composition;

- established the antitumor properties of proxanols;

- thrombolytic properties of proxanols have been established;

- as an emulsifier to stabilize fat and perfluorocarbon emulsions;

- as a biologically active component of perfluorocarbon emulsions (blood substituting, perfusion and cardioplegic compositions).

Closest to the proposed patent is EP No. 0498470, MKI A61K 31/77, 37/54, 08/12/92, Bull.92 / 33. "An inject able pharmaceutical composition for the protection of tissue damaged by ischemia", which describes the use of surface-active copolymers as the main component of the drug to create a pharmaceutical composition, administered intravenously into the body to protect tissues from damage caused by ischemia.

However, the main disadvantage of the prototype is the impossibility of introducing into the bloodstream a large amount of water-soluble surfactant, due to the absence in its composition of a hemodynamic agent that holds water in the bloodstream and prevents tissue edema. Such substances as albumin, plasma, dextrans can act as a hemodynamic agent. This serious drawback reduces the effectiveness of the use of the prototype, due to the development of edema and the subsequent severe complication, especially with large blood loss and a correspondingly high need for the administration of a proxanol preparation.

The aim of the present invention is to provide a plasma-replacing agent based on a surfactant - a block copolymer of ethylene oxide and propylene, which has rheological and hemodynamic effects and exhibits a complex of beneficial effects characteristic of proxanols, which can be administered intravenously in a large volume and not have any negative effects. action.

The goal is achieved in that the plasma substitute for biomedical purposes, including a surfactant, according to the invention contains: a mixture based on a block copolymer of ethylene oxide and propylene and the hemodynamic agent of hydroxyethyl starch in a ratio of from 1/1 to 10/10, respectively, and physiologically acceptable electrolyte solution.

The composition of the plasma substituting agent, characterized in that the content of the block copolymer of ethylene oxide and propylene is from 0.1% to 40%.

The composition of the plasma substituting agent, characterized in that the content of hydroxyethyl starch is from 1% to 20%.

The composition of the plasma substituting agent, characterized in that a block copolymer of ethylene oxide and propylene with a molecular weight of 1-20 kD is used as a surfactant.

The composition of the plasma substituting agent, characterized in that hydroxyethyl starch with a molecular weight of 40-200 kD is used as a hemodynamic agent.

The composition of the plasma-replacing agent, characterized in that the following solutions are used as a physiologically acceptable electrolyte solution: sodium chloride, potassium chloride, sodium phosphate, sodium bicarbonate.

The composition of the plasma-replacing agent, characterized in that the electrolyte solution contains: sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The composition of the plasma-substituting agent, characterized in that the preferred first embodiment contains: 4% block copolymer of ethylene oxide and propylene with a molecular weight of 13 kD, 6% hydroxyethyl starch with a molecular weight of 200 kD, sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

A tool based on the composition of a block copolymer of ethylene oxide and propylene and hydroxyethyl starch with a physiologically acceptable electrolyte solution, characterized in that it is intended for use as a synthetic plasma substitute with rheological and hemodynamic effects, as an infusion, perfusion, disinfection, parenteral, immunotropic cardioprotective and cosmetic agents and agents for treating various diseases, can also be used as an external Means for cosmetic and therapeutic ointments or creams for wounds, ulcers, and other external diseases.

A product based on the composition of a block copolymer of ethylene oxide and propylene and hydroxyethyl starch with a physiologically acceptable electrolyte solution, characterized in that it can be used for intravenous, intraarterial, oral, intracavitary use and can be diluted with any compatible solution or composition that is also compatible with antiviral, before use antibacterial, antifungal composition or colloidal silver, or other medium.

The proposed composition of a plasma-substituting agent based on a block copolymer of ethylene oxide and propylene and hydroxyethyl starch has a wide range of different physicochemical and biomedical properties due to the active components included in the composition.

Hydroxyethyl starch (hydroxyethyl starch) is a colloidal solution that has a high colloidal osmotic pressure and is able to bind and retain water. Hydroxyethylated starch is a high molecular weight compound consisting of polymerized glucose residues. The source of HES is native starch (aminopectin), which is cleaved to obtain molecules with a specific molecular weight, as well as hydroxyethylation, in which free hydroxyl groups of glucose residues are replaced by hydroxyethyl groups. Due to the ability to bind and retain water, hydroxyethyl starch has the ability to increase the volume of circulating blood by 85-100% of the injected volume (the plasma-replacing effect stably persists for 4-6 hours). Hydroxyethyl starch restores impaired hemodynamics, improves microcirculation, rheological properties of blood (by reducing the hematocrit), reduces the viscosity of the plasma, reduces platelet aggregation and prevents the aggregation of red blood cells. The similarity of the structure of hydroxyethyl starch with the structure of glycogen explains the high level of tolerance and the practical absence of adverse reactions.

The proposed composition of a plasma-replacing agent based on a block copolymer of ethylene oxide and propylene and hydroxyethyl starch can be used as synthetic plasma-replacing agents with enhanced rheological and hemodynamic properties and is introduced in large volumes without complications associated with edema of tissues and organs.

The proposed composition of a plasma-replacing agent based on a block copolymer of ethylene oxide and propylene and hydroxyethyl starch can be used as a drug that improves microcirculation, restores impaired hemodynamics, reduces plasma viscosity, reduces platelet aggregation and prevents red blood cell aggregation.

The proposed composition of a plasma-replacing agent based on a block copolymer of ethylene oxide and propylene and hydroxyethyl starch can be used as synthetic plasma-replacing agents: to prevent and treat fat embolism; to stimulate the healing of aseptic postoperative wounds and stimulate reparative processes; for the treatment of vascular pathologies; as a compound affecting the immune system.

The proposed composition of a plasma-replacing agent based on a block copolymer of ethylene oxide and propylene and hydroxyethyl starch can be used as synthetic plasma-replacing agents with antitumor and thrombolytic properties.

The proposed composition of the plasma substituting agent can be used as a synthetic perfusion disinfection, parenteral, immunotropic, cardioprotective agent.

The proposed composition of the plasma-replacing agent can be used for external use as the basis of water-soluble therapeutic ointments or creams for applying, irrigation, soaking long non-healing wounds, ulcers, and other external diseases.

The proposed composition of the plasma-substituting agent can be used for external use as the basis of cosmetic water-soluble ointments or creams for skin care.

Thus, all the presented positive factors of a plasma-replacing agent based on a block copolymer of ethylene oxide and propylene and hydroxyethyl starch contribute to a more efficient and safe use of proxanol preparations and expand their field of application.

DETAILED DESCRIPTION OF THE INVENTION

Getting composition

Example 1. Obtaining a plasma-replacing composition of 1% block copolymer of ethylene oxide and propylene and 1% hydroxyethyl starch.

2 grams of a block copolymer of ethylene oxide and propylene and 2 grams of hydroxyethyl starch are dissolved in 100 ml of pyrogen-free water. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma substitute preparation had the following composition: 1% block copolymer of ethylene oxide and propylene; 1% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used as a plasma substitute with rheological and hemodynamic properties for intravenous and intraarterial administration, for oral, intracavitary, internal and external use.

Example 2. Obtaining a plasma-replacing composition of 2% block copolymer of ethylene oxide and propylene and 2% hydroxyethyl starch.

4 grams of a block copolymer of ethylene oxide and propylene and 4 grams of hydroxyethyl starch are dissolved in 100 ml of pyrogen-free water. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma-replacing drug had the following composition: 2% block copolymer of ethylene oxide and propylene; 2% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used as a plasma substitute with rheological and hemodynamic properties for intravenous and intraarterial administration, for oral, intracavitary, internal and external use.

Example 3. Obtaining a plasma-replacing composition of 4% block copolymer of ethylene oxide and propylene and 4% hydroxyethyl starch.

In 100 ml of pyrogen-free water, 8 grams of a block copolymer of ethylene oxide and propylene and 8 grams of hydroxyethyl starch are dissolved. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma substitute preparation had the following composition: 4% block copolymer of ethylene oxide and propylene; 4% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used as a plasma substitute with rheological and hemodynamic properties for intravenous and intraarterial administration, for oral, intracavitary, internal and external use.

Example 4. Obtaining a plasma-replacing composition of 4% block copolymer of ethylene oxide and propylene and 6% hydroxyethyl starch.

In 100 ml of pyrogen-free water, 8 grams of a block copolymer of ethylene oxide and propylene and 12 grams of hydroxyethyl starch are dissolved. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma substitute preparation had the following composition: 4% block copolymer of ethylene oxide and propylene; 6% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used as a plasma substitute with rheological and hemodynamic properties for intravenous and intraarterial administration, for oral, intracavitary, internal and external use.

Example 5. Obtaining a plasma-replacing composition of 10% block copolymer of ethylene oxide and propylene and 10% hydroxyethyl starch.

In 100 ml of pyrogen-free water, 20 grams of a block copolymer of ethylene oxide and propylene and 20 grams of hydroxyethyl starch are dissolved. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma substitute preparation had the following composition: 10% block copolymer of ethylene oxide and propylene; 10% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used as perfusion, disinfection, parenteral, immunotropic, cardioprotective agents.

Example 6. Obtaining a plasma-replacing composition of 14% block copolymer of ethylene oxide and propylene and 12% hydroxyethyl starch.

In 100 ml of pyrogen-free water, 28 grams of a block copolymer of ethylene oxide and propylene and 24 grams of hydroxyethyl starch are dissolved. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma substitute preparation had the following composition: 14% block copolymer of ethylene oxide and propylene; 12% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used for external use as the basis of water-soluble therapeutic ointments or creams for applying, irrigation, soaking long non-healing wounds, ulcers, and other external diseases.

Example 7. Obtaining a plasma-replacing composition of 18% block copolymer of ethylene oxide and propylene and 16% hydroxyethyl starch.

In 100 ml of pyrogen-free water, 36 grams of a block copolymer of ethylene oxide and propylene and 32 grams of hydroxyethyl starch are dissolved. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma-replacing drug had the following composition: 18% block copolymer of ethylene oxide and propylene; 16% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used for external use as the basis of cosmetic water-soluble ointments or creams for skin care.

Example 8. Obtaining a plasma-replacing composition of a 20% block copolymer of ethylene oxide and propylene and 20% hydroxyethyl starch.

40 grams of a block copolymer of ethylene oxide and propylene and 40 grams of hydroxyethyl starch are dissolved in 100 ml of pyrogen-free water. After that, a twice concentrated electrolyte solution is added to the resulting concentrated solution of active ingredients.

The final formulation (dosage form) of the plasma substitute preparation had the following composition: 20% block copolymer of ethylene oxide and propylene; 20% hydroxyethyl starch; sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l.

The resulting composition can be used for external use as the basis of water-soluble therapeutic ointments or creams for applying, irrigation, soaking long-healing wounds, ulcers, and other external diseases.

Claims (10)

1. The composition of the plasma-substituting agent for biomedical purposes, including the surfactant according to the invention contains: a mixture based on a block copolymer of ethylene oxide and propylene and a hemodynamic agent of hydroxyethyl starch in a ratio of 1/1 to 10/10, respectively, and a physiologically acceptable electrolyte solution. 2. The composition of the plasma-replacing agent according to claim 1, characterized in that the content of the block copolymer of ethylene oxide and propylene is from 0.1% to 40%. 3. The composition of the plasma-replacing agent according to claim 1, characterized in that the content of hydroxyethyl starch is from 1% to 20%. 4. The composition of the plasma substituting agent according to claim 1, characterized in that a block copolymer of ethylene oxide and propylene with a molecular weight of 1-20 kD is used as a surfactant. 5. The composition of the plasma-replacing agent according to claim 1, characterized in that hydroxyethyl starch with a molecular weight of 40-200 kD is used as a hemodynamic agent. 6. The composition of the plasma-replacing agent according to claim 1, characterized in that the following are used as the physiologically acceptable electrolyte solution: sodium chloride, potassium chloride, sodium phosphate, sodium bicarbonate. 7. The composition of the plasma-replacing agent according to claim 1, characterized in that the electrolyte solution contains: sodium chloride - 5.0-9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l. 8. The composition of the plasma-replacing agent according to claim 1, characterized in that the preferred first embodiment contains: 4% block copolymer of ethylene oxide and propylene with a molecular weight of 13 kD, 6% hydroxyethyl starch with a molecular weight of 200 kD, sodium chloride - 5.0 -9.5 g / l; potassium chloride - 0.35-0.45 g / l; sodium phosphate - 0.20-0.60 g / l; sodium bicarbonate - 0.35-0.70 g / l. 9. The tool based on the composition according to claim 1 of a block copolymer of ethylene oxide and propylene and hydroxyethyl starch with a physiologically acceptable electrolyte solution, characterized in that it is intended for use as a synthetic plasma substitute with rheological and hemodynamic effects, as an infusion, perfusion, disinfectant, parenteral, immunotropic, cardioprotective and cosmetic agents and agents for treating various diseases, can also be used as naru a topical product for cosmetic and therapeutic ointments or creams for wounds, ulcers, and other external diseases. 10. The tool based on the composition according to claim 1 from a block copolymer of ethylene oxide and propylene and hydroxyethyl starch with a physiologically acceptable electrolyte solution according to claim 9, characterized in that it can be used for intravenous, intraarterial, oral, intracavitary use and can be diluted before use any compatible solution or composition also compatible with an antiviral, antibacterial, antifungal, or colloidal silver, or other medium.