RU1836138C - Synthetic carbon material of spherical granulation intended for sorption of substances from solution and method - Google Patents

Abstract

Synthetic carbon material of spherical granulation has an increased sorption capacity, selectivity, mechanical strength, and biocompatibility. A method for its preparation includes carbonization of porous organic polymers, heat treatment, activation, followed by modification. Synthetic carbon material is an effective adsorbent for the absorption of substances from solutions, the extraction of heavy metals and radionuclides, the ultrafine purification of substances and the removal of toxic components from biological fluids, for example, for hemosorption of human blood. 26 e. P. f-ly.

Description

The invention relates to processes for the purification of chemical solutions and biological fluids using granular carbon sorbents used to remove heavy and radioactive metals, ultrafine purification of substances and the removal of toxic components from biological fluids, for example, for hemosorption of human blood.

The aim of the invention is to provide a synthetic carbon material of spherical granulation for sorption of substances from solutions and biological fluids, which has at the same time high sorption capacity, selectivity, mechanical strength, high biocompatibility. Another object of the present invention is to provide a method for producing a material with the above properties, which makes it possible to obtain a sorbent with controlled porosity.

This is achieved by synthetic carbon material of spherical granulation for sorption of substances from solutions and biological fluids having a micro-, meso- and macroporous structure, which has the following characteristics:

The volume of micropores. cm3 / g Volume of mesopores, cm3 / g Volume of macropores, cm3 / g Specific pore surface, m2 / g

Mesopore specific surface area, m2 / g Effective half-width of micropores, nm

Effective radius of meso- or macropores, nm

0.2-0.6 0.2-2.1 0.1-0.5

150-2000 20-300 0.2-1.1 3-250

fe

OS l About

(I a

CA

The ratio of the volumes of micro- and mesopores1: 1-3.5

Pellet diameter, mm0.1-2.0

In this case, the synthetic carbon material contains functional protonogenic groups —OH on the surface. -COOH in an amount of 0.5-3.5 meq / g with a ratio of 1: (1.5-2.5).

In addition, the material additionally contains on the surface cations of metals selected from the group: Na +, K +, Ca, or a mixture thereof in an amount of 0.25-3.5 meq / g.

The material also additionally contains biologically active additives on the surface selected from the group: proteins, antigens, amino acids, enzymes. Moreover, the material contains in the pores a magnetic form of iron oxide in an amount of 20-30 wt.%.

The material also contains in the pores and / or on the surface of the granules copper and / or zinc ions in an amount of not more than 0.25 meq / g for copper and not more than 1.5 meq / g for zinc.

The goal is also achieved by a method of producing synthetic carbon material of spherical granulation for sorption of substances from solutions and biological fluids, including carbonization of porous organic polymers of spherical granulation, heat treatment, activation to obtain a carbon carrier and its modification, in which carbonization is carried out by pyrolysis without access to air or with a lack of oxygen when the temperature rises to 500 ° C for 2-24 hours or by liquid-phase oxidation at 130-180 ° C with sulfuric acid or leum, and heat treatment is carried out at 700-800 ° C for 15-30 minutes in an inert gas stream. In this case, porous organic polymers selected from the group are used for carbonization: copolymers of vinyl pyridine or styrene or acrylonitrile with divinylbenzene, polycondensates of phenol or furfural or furan with aldehydes or ion-exchange resins based on them. The carbonizate is heat treated in a stream of inert gas selected from the group: nitrogen, carbon dioxide, argon. Activation is carried out in a stream of water vapor at 700-900 ° C for 1-24 hours. The resulting carbon support is modified by liquid phase oxidation in a solution of 20-30 wt.%. nitric acid at 100 ° C, followed by washing and transferring to the H-form.

Moreover, washing is carried out repeatedly with an alkaline 1-5% sodium hydroxide solution, and transferring to the H-form with a 5-10 wt.% Hydrochloric acid solution, and then with water.

After conversion to H-form, the product is neutralized and dried to obtain an enterosorbent.

In addition, after conversion to H-form, the product is additionally subjected to a solution of metal chlorides and / or hydroxides selected from the group: sodium, potassium, magnesium, calcium, followed by drying of the product to obtain entero0

5

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5

0

5

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5

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sorbent.

The resulting carbon carrier can be subjected to another type of modification, namely that it is demineralized with a 6 M hydrochloric acid solution at 100 ° C for 1-20 hours, followed by neutralization with alkali and drying of the product to obtain an enterosorbent. Magnetic iron oxide is additionally added to this enterosorbent by impregnation with a solution of ferric chloride followed by heat treatment.

After heat treatment, this product is further dedusted by treatment with a solution of biocompatible surfactants and subjected to ion balancing. In this case ft, compounds selected from the group of heparin, reopoliglyukin, hemodez, hydrolysis are used as a surfactant.

In this case, ion balancing is carried out by treatment with a 1% solution of alkali and hydrochloric acid to a solution pH of 4-7, followed by sterilization and hemosorbent.

Ionic balancing is also carried out to a pH of a solution of 8-10, followed by sterilization to obtain hemosorbent. The hemosorbents obtained as a result of ionic balancing are additionally subjected to treatment with a 2-5% solution of hydrogen peroxide in physiological saline to obtain also a hemosorbent.

In addition, the oxidized form of the carbon carrier is treated with a solution of metal chlorides and / or hydroxides selected from the group: sodium, potassium, magnesium, calcium to obtain enterosorbent. The resulting enterosorbent is de-dusted, ion-balanced to a pH of 6.5-7.5 and sterilized to give hemocationionite. This hemocathionite is contacted with a solution of a mixing agent, and then with a solution of a crosslinking agent, and then with a solution of a biologically active substance to obtain an immunosorbent.

The possibility of producing a synthetic carbon material is illustrated by the following specific examples.

EXAMPLE 1.50 kg of a porous copolymer of 2-methyl, 5-vinylpyridine with spherical granulation divinylbenzene with a diameter of granules of 0.5-1.6 mm are carbonized in a static mode in air at a stepwise temperature increase at a speed of 30 ° / h from 180 to 350 ° C, and then subjected to heat treatment at 800 ° C for

10.5 hours in a stream of argon, and then activated in a static mode with water vapor at 850 ° C for 4 hours. The resulting carbon support was placed in a stirred reactor, treated with a 2-fold volume of a 6 M hydrochloric acid solution and boiled t with stirring for 6 hours. The treatment is repeated with a new portion of the solution. Next, the product is neutralized with a solution of caustic soda by heating and stirring the solution to a pH of 5-5.5. The product is separated from the solution and dried to an air-dry state. The result is a carbon material with the following characteristics: Volume of micropores, cm3 / g Volume of mesopores, cm3 / g Volume of macropores, cm3 / g

1110-1180

120-140

0.79-0.81 34-36

0.46-0.49 0.74-0.78 0.21-0.26

 Specific surface j of pores, m2 / g Specific surface j of mesopores, m2 / g | The effective half-width j of micropores, nm | The effective radius of the meso- | or macropores, nm {The ratio of the volumes of micro- and mesopores1: 1.6-1.7

 The diameter of the granule, mmO.Z - b.b

| Sorbtion activity according to methylene blue, mg / g 260-310

 The obtained sorption material is used as an adsorptive preparation - enterosorbent for detoxification of organisms (for various diseases, in particular, for acute and chronic poisoning by industrial and household} heavy metals, including mercury | and lead, radionuclides, fungal toxins, liver and kidney diseases, endogenous intoxication and conditions caused by inflammation or decomposition of tissues. In addition, this material is used in cleaning saline solutions from | microimpurities d -metals and rganicheskih j substances deep water purification, organic solvents, stabilizing lekarst- (governmental funds (blood substitutes), separation and isolation of biological | Sgiach components, such as vitamin Oz adduct thereof with cholesterol and others.

Example 2.1. The carbon carrier obtained in Example 1 is poured with 5 L of a 30% solution of ferric chloride and incubated for 20 hours. Then, concentrated sodium hydroxide solution and 130 g of ammonium nitrate powder were added to the carbon 5 material. The mixture is heated to 90 ° C and maintained at this temperature for 2 hours. The product is washed with distilled water and dried in vacuum at 70 ° C, and then calcined in argon atmosphere at 600 ° C for 2.5 hours.

The result is a carbon material with the following characteristics:

. l ... ......., "" .....-. A.-4 / .. n Af

5 Micropore volume, Mesopore volume, cm3 / g Macropore volume, cm3 / g Specific surface

0.38-0.42 0.69-0.71 0.15-0.18

880-910

60-90

pore, m / g

0 Specific surface area of mesopores, m2 / g Effective half-width of micropores, nm 0.68-0.70

Effective radius of meso-5 or macropores, nm33-35

The ratio of the volumes of micro- and mesopores1: 1.8-1.9

Pellet diameter, mm 0.2-1.6

The content in the pores of magnetic iron oxide,% .21-26

The resulting sorption material is used as an enterosorbent, which is fixed by a magnetic field in certain parts of the gastrointestinal tract during 5 endogenous intoxications, ulcerative manifestations, digestion and metabolism. In addition, this material is used in sorption processes in complex hydrodynamic regimes, for example, in a fluidized or fluidized bed, etc.

Example 3. The chloromethylated copolymer of styrene with divinylbenzene was poured with concentrated sulfuric acid, the mixture was heated and kept at 180 ° С for 3 h. The product is subjected to heat treatment at 750 ° C for 15 minutes in a stream of carbon dioxide, after which they are dynamically activated with water vapor at 870 ° C for 6 hours. The carbon carrier obtained is poured in twice the volume of a 35% solution of nitric acid and boiled for 6 hours. The resulting product 3 times it is washed with a 3% boiling solution of caustic soda until the colored impurities are removed, and then it is converted into the H form with a 10% solution of hydrochloric acid to pH 1 and demineralized water to pH 4.

880-900 75-95

The resulting oxidized carbon carrier is neutralized with a 1% sodium hydroxide solution by heating and stirring to a solution pH of 5-5.5. The product is separated from the solution and dried to an air-dry state,

The result is a carbon material with the following characteristics:

Micropore volume, cm3 / g 0.34-0.37

Mesopore volume, cm3 / g 0.41-0.43

Macropore volume, cm3g0.11-0.13

Specific surface area.

por, m2 / g

Specific surface

mesopore, m2 / g

Half Width Effective

micropores, nm0.56-0.59

The effective radius of the mesoili macropores, nm 12-14

Volume ratio

micro and mesopore1: 1.3-1.4

Pellet diameter, mm 0.31-1.8

The content of the groups is COOH,

meq / g 2.1-2.4

The obtained sorption material is used as an enterosorbent for detoxification of the body, gastrointestinal diseases with metal salts, radionuclides, organic ladies of the main nature, in the treatment of coronary heart disease, acute radiation sickness, complications in chemo and radiation therapy of cancer, disorders of electrolyte protein, enzyme and the lipid state of the body.

The material is also used to obtain highly pure solutions of salts and water, and to remove microimpurities from various technical, including non-aqueous, media.

Example 4.1 kg of the oxidized carbon support obtained in Example 3 is placed in a reactor with a 4 L stirrer of a 6 M hydrochloric acid solution and boiled with stirring for 6 hours. Then the solution is drained, the product is washed with distilled water to remove excess acid (pH 3.5 -4) and dedusted using a dilute heparin solution, pour 6 l of a 1% solution of potassium hydroxide and 1 l of a 6% solution of potassium chloride and stir for 2 hours (pH 8.5-9). Upon reaching the indicated pH, 100 t are added to the solution and stirred for 1 hour (pH 6.5-7). Then the product is separated from the solution, 6 L of isotonic KCI solution (0, 15 N) is poured and O, 15 N are balanced with a KOH solution to a pH of 7.4-7.5. Upon reaching the indicated pH, the solution is changed into a pyrogen-free isotonic solution of potassium chloride and the resulting product is placed in pressurized containers (columns, vials) and sterilized.

The characteristics of the obtained hemosorbent are as follows: Structurally sorption characteristics correspond to the material obtained in example 3 and additionally contains:

Potassium, meq / g 0.65-0.85

Magnesium, meq / g 0.40-0.66

The material is used to purify blood from toxic substances and to correct its biochemical status in the treatment of acute

and chronic poisoning, liver and kidney diseases, crash syndrome, hyper- and hypokalemia burns, sepsis, meningitis, hepatitis, a number of neuropsychiatric diseases, as well as blood diseases and restoration of the properties of donated blood for long periods of storage.

PRI me R 5. 10 g of the carbon hemosorbent obtained in example 4} pour 30 ml of 0.15 n sodium chloride solution containing 2 g of 1-ethyl-3 (3-dimethylaminopropyl) -carbodiimide hydrochloride and potassium dihydrogen phosphate buffer phosphate solution (pH 4) was added. The mixture is stirred, after which the carbon material is washed with 100 ml of the indicated sterile buffer solution. To the washed product was added 1 ml of a house dust dust allergen solution with a concentration of 1 mg%, pre-mixed with 50 ml of sterile buffer. physiological saline with a pH of 7.2 until the optical density is reached. washing solution less than 0.05 at a wavelength of 230 nm (evidence of product purity).

The resulting immunosorbent has the composition, May. %:

Carbon Matrix 99.29

Potassium ions 0.015

Moreover, as a crosslinking agent, a compound selected from the group: carbodiimide is used. g utar aldehyde, tetrachloride titanium. As a biologically active substance, a compound selected from the group is used: protein, antigen, amino acid, enzyme. The resulting enterosorbents, hemosorbents, immunosorbents are additionally treated with zinc and / or copper chloride and applied to

elastic substrate to obtain an application sorbent.

The advantages of the proposed technical solution are that due to the specificity of the selected raw material — organic porous polymer of spherical granulation and the combination of techniques of the proposed technology for producing carbonaceous material, it is possible to obtain strong spherical granules with a smooth surface, chemically pure with high specific indicators of porosity, with a particularly narrow distribution of pore volumes and radii in the region of sorption micro-juices and transport mesoscopic or macropores. (In addition, the transport pores have a bottle-shaped form, where macropores are accessed through narrow channels - mesopores, and thus the principle of molecular sieve action at the stage of transport of molecules to: orbit micropores is realized.

This provides increased absorption and kinetic characteristics: of the orbital material in relation to a wide Class of organic substances when they are absorbed from solutions. Moreover, the selectivity of the sorption process is achieved both by a specific pore structure and by subsequent modification of the material. Modification of the material includes the formation of protonogenic functional groups on the surface by treatment with an oxidizing agent, the introduction of metal cations and ferromagnetic additives, and the immobilization of various biologically active compounds. As a result of a change in the chemical nature of the surface, the carbon material acquires additional properties, such as riosociety and. in particular, hemocompatibility, i.e. lack of an aggressive nature to blood cells, especially to white blood cells and platelets. In addition, the material acquires the ability to absorb | or generate ions of materials, to magnetization, as well as biospecific (certain interactions. The specified set of new properties, “provided by the proposed method allows directionally obtain materials for use in sorption processes for the extraction, concentration, separation and purification of various technological solutions, as well as for detoxification and correction of biochemical parameters of biological fluids. These include blood, its plasma, lymph, etc. i The material obtained according to the proposed method was effectively used in the methods of enterosorption, hemosorption, immunosorption and application sorption for various severe pathologies of the body. These include severe poisoning, including industrial poisoning and household dames, fighting

poisonous substances and radionuclides. Various pathologies of the liver and kidneys, neuropsychiatric pathologies., Including drug addiction and alcohol syndrome. Themes, acute radiation sickness, complications in chemo and radiation therapy of cancer patients, coronary heart disease. Infectious pathologies, including sepsis and burns. In addition, the materials obtained by the proposed method can be effectively used to obtain highly pure water, solutions of salts, organic solvents, as well as for the separation of iodine, mercury, lead, radionuclides and other components from various media.

Sodium ions 0.320

Magnesium ions 0.004

Chlorine ions 0.336

Immobilized Household Dust Allergen

The resulting immunosorbent is used to treat bronchial asthma, allergies.

Similarly, synthesized sorbents are used to bind immunoglobulins, free hemoglobin, circulating immune complexes and the like, which is necessary for effective treatment of autoimmune and skin diseases by the sorption method.

In addition, immunosorbents of this type are used in biotechnology for the implementation of biocatalysis, the isolation of immunoglobulins, liposaccharides and other components of biological systems responsible for the immune status of the body.

Example 6. The south of the enterosorbent or hemosorbent or immunosorbent obtained in examples 1-5, washed with 100 ml of 2.5 N. a solution of copper chloride or 1.5 N. zinc chloride solution for 3 hours, separated from the solution and applied to an elastic gauze bandage or towel in a wet or dry state. The obtained application sorbent is used for topical treatment of difficult to heal wound surfaces, ZE and burns.

Summary of the invention 1. Synthetic carbon material of spherical granulation for sorption of substances from solutions and biological fluids having a micro-, meso-, macroporous structure, characterized in that. in order to increase its sorption capacity, selectivity, mechanical strength, biocompatibility and provide the possibility of obtaining controlled porosity, it has the following characteristics:

11183613812

..

micropore volume 0.2-0.6 cm / g8. The method according to claim 7, about t l and h a

the volume of mesopores. 0.2-2.1 cm / g, 1 using porous organic

macropore volume0.1-0.5 cm3 / g; polymers selected from the group: copolymer surface of vinylpyridine or styrene or acrylopore150-2000 m / g; .5 nitrile with divinylbenzene,

specific surface phenol or furfural polycondensates or

mesopore2 (NYOM2 / g; furan with aldehydes or ion exchange

effective half-resin based on them, on micropores. 0.2-1.1 to them; .- 9. The method according to PP. 7 and 8, due to the effective radius of the meso-10i so that the heat treatment of the carbonizate

or macropores 3-250 nm; carried out in a stream of inert gas, the ratio of the volumes of micro-selected from the group: nitrogen, carbon dioxide,

imesopore 1: 1-3.5; argon,

granule diameter 0.1-2.0 nm, 10. The method according to PP. 7-9, about t and h and yu.shch and 2. Material pop. 1, characterized in that the activation is carried out in a stream of water. that it contains steam func- tionality on the surface at 700–900 ° С for 1-24 hours. The optional protonogenic groups —OH, –11. Capable of PP. 7–10, excellent GOOH in an amount of 0.5–3.5 meq / g, given that the resulting product undergoes a ratio of 1: 1.5–2.5. Modifications by liquid-phase oxide 3. The material of Claim 2, comprising 20 exposure in a solution on May 20-35. % nitric in that it contains on the surface of the cationic acid at 100 ° C, followed by its base metals / selected from the group: Na, K, washing and converting to the H-form to obtain MD2 +, Ca2, or a mixture thereof the amount of 0.25th oxidized carbon form 3.5 meq / g of carrier.

4.Material popp. 2 I.Z. distinguishing yuschi- 25 12. Method nori. 11, excellent and so on. that it additionally contains natami, that biologically active surfaces are washed repeatedly with biologically active surfactants with an additional 1-5% solution of caustic soda, ki selected from the group: proteins, antigens, and transfer to the H form - 5-10 wt .% solution- amino acids, enzymes .rom hydrochloric acid, and then with water,

5. Material pop. 1, excluding 30 13. Method popp. 11 and 12, characterized in that it contains a magnetic form in the pores so that after the iron oxide is converted to the H-form in an amount of 20-30 wt.%, The product is neutralized and dried with

6. Material according to 1-4, distinguished by the production of an enterosorbent.

and with the fact that it additionally contains c.14. Popp method 11 and 12, distinguishing pores and / or on the surface of the granules of ions 35 with the fact that after conversion to the H-form, the product

copper and / or zinc in an amount not more than subjected to processing races, 25 meq / g for copper and not more than 1.5 meq / g. a mixture of metal chloride and / or metal hydroxide zinc, fishing, selected from the group: sodium, potassium,

magnesium, calcium, followed by drying

 7. A method for producing a synthetic ug-40 product to obtain an enterosorbent. spherical granule material -15. Popp method 7-10, distinguishing for the sorption of substances from solutions and the fact that the modification of carbon biological fluids, including carriers, is carried out by demineralization of 6 M carbonization of porous organic by a hydrochloric acid solution at 100 ° C in spherical temperatures granulation, heat treatment for 1–20 h, followed by neutralization, activation with alkali production and drying of the product from a carbon carrier, and its modification, obtaining enterosorbent. about l and ch and yuschi and with the fact that, with a view. increasing its sorption capacity, ce-.16. The method according to claim 15, characterized by leverage, mechanical strength, bio-50, in that the enterosorbent is additionally mixed and provided with the possibility of adding magnetic iron oxide by obtaining controlled porosity, carbo impregnation with an iron chloride solution is carried out using by pyrolysis without heat treatment, air access or with a lack of oxygen when the temperature rises to 500 ° C 55 55 17. The method according to PP. 15 and 16, optionally for 2-24 hours or by means of liquid phase, in that the product is additionally deoxidized at 130-180 ° С with sulfuric acid by treatment with a solution of bios-ip oleum, and heat treatment is carried out surfactant 700-800 ° C for 15-30 minutes in a stream of inert substance and subjected to an ionic balanced gas.

18. Method. 17, characterized by TeV that, as a surfactant, compounds selected from the group are used: heparin, reopoliglyukin, heme 1 dec, hydrosine.

19. The method according to p. 17, with the exception that ion balancing is carried out by treatment with a 1% solution of alkali and hydrochloric acid to a pH of a solution of 4-7, followed by sterilization and obtaining g of sorbent.

20. The method according to claim 17, with the exception that ionic balancing is also carried out 1 to pH 9MO solution followed by el-arylation to obtain hemosorbent.

21. The method according to paragraphs. 17-20, which implies that the product is additionally treated with a 2-5% solution of hydrogen peroxide in physiological saline with the emission of hemosorbent.

22. The method according to paragraphs. 11 and 12, with the exception that the oxidized form of the carbon support is treated with a solution of yu chloride or metal hydroxides selected from the group: sodium, potassium, magnesium, calcium, to obtain enterosorbent.

5

0

5

23. The method according to claim 22, with the fact that the product is dust free, subjected to ion balancing to a pH of 6.5-7.5 and sterilized to produce hematocationite.

24 The method according to p. 23. about t l and ch and y-sch And and With that. that hemocationion is in contact with a solution of a crosslinking agent, and then with a solution of a biologically active substance to obtain an immunosorbent,

25 ,. The method according to p. 24, from l and h and y u and with that. that a compound selected from the group: carbodiimide is used as a crosslinking agent. glutaraldehyde, titanium tetrachloride.

. 26. The method according to PP. 24 and 25, rtl Ichayusch- and with that. that as a biologically active substance, a compound selected from the group is used: protein, antigen, amino acid, enzyme.

27. The method according to PP. 13-16,19-24, with the exception that the product is further treated with zinc and / or copper chloride and applied to an elastic substrate to obtain an application sorbent. ..,. -,