CS206593B1 - Preparation method of haemocompatible sorbents coated with acrylate,or methacrylate polymer - Google Patents

Description

The present invention relates to a process for preparing sorbents coated with an acrylate or methacrylate polymer. The form of the resulting system is entirely dependent on the form of the sample subjected to modification.

Due to its large specific surface area, activated carbon is used as a sorbent, especially for non-polar substances. Due to its properties, it can be used as a sorbent to treat acute poisoning (eg barbiturates). On the surface of sorbents, when placed in the bloodstream, blood cells and platelets also become trapped. This results in blockage of the column and thrombus formation.

This undesirable property of activated carbon is currently suppressed by coating its surface with a biocompatible polymer such as gelatin (Brock A .: Clin. Chem. 19, 140 B, 1973), dextran (Morishita M., Fukushima M., Inaba Y.: Japan Kokai 75, 10 292), albumin (Chang TMS: Can. J. Physiol. Pharmacol. 1969, 1043), cellulose (Adsorba 300 0 from Gambro) or acrylic gel (Kolthammer J .: Pharmac. Pharmacol. 1975, 801; Andrade JD, Kunitomo K., Van Wagenen, R. et al., Trans. Amer. Soe, artif. Int. Org. 17, 222, 1971). The preparation of coatings with these substances is mostly based on the already finished polymer, the solution of which is applied to the surface of activated carbon. The preparation of the polymer on activated carbon based on the monomer was carried out by the authors (Andrade JD, Kunitomo K, Van Wagenen R. et al., Trans. Amer. Soc. Artif. Int.

Org. 17, 222. 1971) by applying an ethanolic monomer solution to a dry sorbent on which the monomer was polymerized at 80 ° C.

The monomer in this preparation process must obviously contain a diester acting as a reinforcing agent, since the pure, uncrosslinked polymer is soluble in ethanol and would therefore be washed off from activated carbon, which was fully confirmed in an attempt to reproduce the process. However, the crosslinked poly (2-hydroxyethyl methacrylate) membrane has a lower permeability for the higher molecular weight substances, despite the fact that when the monomer solution is applied to dry activated carbon, the internal surface of the sorbent particles must be occupied after polymerization. and hence sorption capacity.

SUMMARY OF THE INVENTION The present invention provides a process for the preparation of hemocompatible sorbents coated with an acrylate or methacrylate polymer, characterized in that the sorbent is selected from the group consisting of coconut shell charcoal, activated carbon, sulfonated styrene-divinylbenzene ion exchangers and 2,3-epoxypropyl methacrylate gel The polymer is coated with a polymer precipitant selected from the group consisting of water, hexane, pentane and ether and then radically polymerizes the monomer with the addition of a polymerization initiator at a temperature at which initiator polymerization centers are formed rapidly enough or the sorbent is treated with a oligomer solution that is on the surface of the sorbent are polymerized under the same conditions.

In the process according to the invention, the precipitant must be vacuum-soaked onto the sorbent. The polymerization or dopolymerization of the oligomers must proceed rapidly to ensure the formation of a homogeneous, thin and sufficiently permeable polymer film on the surface of the sorbent particles. It is therefore necessary to use rapidly disintegrating radical polymerization initiators, preferably a redox initiation system capable of initiating radical polymerization even at normal temperature.

Water or solvents such as hexane, pentane or ether are preferably used as polymer precipitants.

An advantage of the process according to the invention is that the inner surface of the sorbent, i.e. the pores of, for example, activated carbon, are filled with water or solvent, so that the water-insoluble polymer formed only envelops the outer surface of the particles. This results in a weak membrane permeable to molecules up to a molecular weight of at least 6,000. At the same time, the polymer membrane is swellable in the aqueous environment in which the polymerization takes place, making it more flexible and thus not so easily abrasive to the sorbent. The inner surface of the sorbent is protected from the polymer in this preparation process and its sorption properties are thus fully maintained. The strength of the polymer film and its adherence to the non-polar sorbent can be increased by adding a small amount of a less polar monomer, such as methyl methacrylate.

The amount of polymer forming the sorbent coating depends only on the particle size of the coated coal and not on the amount of monomer used for polymerization. The polymer content was determined as the weight gain of the sorbent after drying the representative sample to constant weight. The specific surface area of the coated charcoal was reduced by about 200 m ² / g over the surface of the uncoated charcoal, i.e. from 1200 m ² / g to 1000 m ² / g at about 4% by weight polymer on activated carbon.

In addition to activated carbon, coated porous gels, ion exchangers and others can be used as sorbents. For own medical purposes (Horák J .: Hemoperfusion over activated charcoal in acute liver failure in the experiment, candidate dissertation, Prague 1977), the coated charcoal in the capsule is placed in the extracorporeal blood circulation. Animal testing has shown that activated carbon coated in this way has good haemocompatibility.

The invention is described in more detail in the examples without being limited thereto.

Example 1.

A solution of 2.65 g of sodium pyrosulphite in 50 ml of water was poured into 650 g of coconut charcoal activated carbon (Chemviron, SG XII, 4 x 10 mesh particle size) onto which redistilled water was poured in vacuo. After standing for 10 minutes, a solution of 2.65 g of ammonium persulfate in 50 ml of water and 65 g of 2-hydroxyethyl methacrylate containing 0.09% diester was poured onto the carbon. The suspension was allowed to stand at room temperature for 10 hours with occasional shaking under an inert atmosphere. About 10 liters of distilled water were boiled out of the coated coal. The polymer content on carbon is about 3%.

Haematological changes in the dog during perfusion through hemosorb

Hemoglobin (g / 100 ml) Hematocrit

Leukocytes (% of baseline value)

Platelets (% of baseline value)

Plasma protein (g / 100 ml)

Albumin (% plasma. Whites.) • T _o '14.29 1.85 d 41.00 ± 4.70

100.0 '100.0

6.44 - 0.64

50.80 ± 1.90 ^T 30

13.8 ΐ 1.52 ^χ / 38.6 ± 4.80 ^xxx /

37.9 ± 22.80 ^xxx /

69.5 ± 9.60 ^xxx /

5.9 ± 0.63 ^xx /

52.0 - 2.90

Ti

14.17 ± 1.92

39.90 ± 5.10

38.00 ± 26.50 ^xxx /

84.00 ± 24.40

6.04 ± 0.59 ^xx /

50.90 ± 1.90 ^T 4

13.95 ± 2.16

39.70 ± 6.20

82.50 ± 59.30

91.30 ± 29.00

5.84 ± 0.73 ^xx /

50.90 ± 3.80

Explanatory notes:

n = 7, ^x / p <0.05, ^xx / p <0.01, ^xxx / p <0.001

Example 2

A solution of 5 g of sodium metabisulfite in 50 ml of water was poured onto 500 g of coconut shell activated carbon (Chemviron SC XII, 12 x 30 mesh particle size) soaked in redistilled water. After standing for 20 minutes a solution of 5 g of ammonium persulfate in 50 ml of water and 100 g of 2-hydroxyethyl methacrylate was poured on the carbon. After standing for 15 hours at room temperature, the coated coal was boiled about 14 liters of water. The polymer content is about 4.5%.

Example3

A solution of 4 g of sodium pyrosulfite in 150 ml of water was poured onto 200 g of activated carbon.

After 15 minutes of standing, a solution of 2-hydroxyethyl methacrylate oligomer, prepared by polymerizing 30 g of monomer with a solution of 2 g of ammonium persulfate in 20 ml of water, was poured onto the carbon.

After standing at room temperature for 8 hours, the sample was treated as in Example 1. The polymer content was 2.5%.

Example 4

Hexane was soaked in 200 g activated carbon under vacuum, the charcoal was aspirated, washed with ethanol and a mixture of 2 g sodium pyrosulfite and 2 g ammonium persulfate in 60 ml water and 30 ml 2-hydroxyethyl methacrylate was poured onto the activated carbon. After standing at room temperature for 8 hours, a 5% aqueous ethanol solution was poured onto the charcoal, and the coated charcoal was eluted until the hydrocarbon was removed. The coal was then boiled about 15 L of distilled water. The polymer content was 6%. In some experiments, hexane has been replaced by another hydrocarbon (pentane, etc.) or ether. In a similar treatment, the polymer content on activated carbon varied between 6 and 11%.

Example5

241 g of activated carbon soaked in distilled water were poured under vacuum into a solution of 75 g of 2-hydroxyethyl methacrylate, 0.75 g of glycol dimethacrylate and 0.75 g of benzoyl peroxide in 300 ml of ethanol. After standing at room temperature for 10 minutes, the excess solution was discarded and the mixture was polymerized at 80 ° C for 3 hours. After washing with ethanol and water, the polymer content was 15% ·

Example '6

250 g of coconut shell activated carbon (Ghemviron SA, SC XII 12 x 30) were soaked in water under an inert atmosphere with 250 ml of a 20% solution of 2-hydroxyethyl methacrylate in absolute ethanol with 5 ml of 30% hydrogen peroxide. After standing for 15 minutes and pouring off the excess solution, the mixture was polymerized under vacuum at 50 mbar for 3 hours at 80 ° C.

After a thorough washing of about 10 liters of water, the polymer content of activated carbon is about 7%.

Example 7

500 g of coconut shell charcoal (Chemviron SA, SC XII 4x10) were evacuated (6 Pa, 30 minutes) in a vacuum of about 3 l of boiled distilled water. After about 15 minutes of standing, the excess water was discarded and a solution of 15 g of sodium pyrosulfite in 45 ml of water was poured onto the charcoal. After carefully mixing and standing for 5 minutes under an inert atmosphere, a mixture of 150 g of 2-hydroxyethyl methacrylate, 15 g of methyl methacrylate and a solution of 15 g of ammonium persulfate in 45 ml of water was added to the moist charcoal. The suspension was stirred gently for about 30 minutes and then allowed to stand at room temperature for 8 hours. After boiling about 50 L of distilled water, a polymer content of about 3% was found.

Haematological changes in a healthy dog weighing 16 kg, perfused over activated coconut charcoal (200 g), coated with a copolymer of 10% methacrylate

^T o T30 T1 T4 Hemoglobin (g%) 14.4 13.92 14.4 14.4 Hematocrit 39 37.5 37.5 41 Leukocytes 6 600 4 800 4 700 6 500 Platičky 391 000 291 450 498 800 404 800 Plasma. protein (g%) 7.25 6.12 6.31 6.18

Example 8 g of spherical gel particles based on 2,3-epoxypropyl methacrylate-ethylenedimethacrylate copolymer, in which the epoxy group is converted to aldehyde groups, were poured under vacuum with distilled water and allowed to stand at room temperature for about 10 minutes. After pouring off the excess water, the sorbent was poured into a solution of 0.01 g of azobisisobutyronitrile in 2 g of 2-hydroxyethyl acrylate with 0.5 ml of water. The suspension was polymerized after careful mixing at 70 ° C for 60 minutes under an inert atmosphere. After washing with water, a polymer content of 14% was found.

EXAMPLE 9 g of an ion exchanger based on sulfonated styrene-divinylbenzene resin (Ostion KS) soaked in distilled water were poured in an inert atmosphere with a mixture of solutions of 1 g potassium pyrosulfite, 1 g ammonium persulfate in 3 ml water with 5 g 2-hydroxyethyl methacrylate. The stirred suspension was allowed to stand under an inert atmosphere for 5 hours at room temperature. The polymer content is about 9%.

EXAMPLE 10 g of an ether-soaked macroporous 2,3-epoxypropyl methacrylate gel were poured in an inert atmosphere with a solution of 0.5 g of ferrous sulfate in 2 ml of water. After standing for 5 minutes at room temperature, a solution of 9 g of 2-hydroxyethyl acrylate in 20 ml of water mixed with 2 ml of 30% hydrogen peroxide was added to the suspension. After careful mixing, the suspension was polymerized for 2 hours at 50 ° C. The coated sorbent was passed through water and slowly evacuated up to 8 kPa at a temperature of about 30 ° C. After removing the ether and washing the gel with water, the polymer content was found to be 15%.

They did

500 g of activated carbon were poured over with distilled water, evacuated and after pouring off the excess water, a solution of 5 g of ferrous chloride in 10 ml of ice water was poured. A mixture of 10 g of 2-hydroxyethyl methacrylate, 2 g of methyl acrylate with a solution of 5 g of sodium perborate in 100 ml of water was immediately poured in an inert atmosphere. After careful mixing, the suspension was allowed to polymerize at room temperature for 18 hours. After the sorbent was boiled off about 5 L of distilled water, a polymer content of about 5% was found. The same result was obtained by swapping methyl acrylate with acrylonitrile.

Claims (2)

SUBJECT OF THE INVENTION A process for the preparation of hemocompatible sorbents coated with an acrylate or methacrylate polymer, characterized in that a sorbent selected from the group consisting of coconut shell charcoal, activated carbon, sulfonated styrene-divinylbenzene ion-exchangers and 2,3-epoxypropyl methacrylate gel is applied to the sorbent. a polymer precipitant selected from the group consisting of water, hexane, pentane and ether and then radically polymerizes the monomer with the addition of a polymerization initiator at a temperature at which the initiator forms polymerization initiation centers quickly or is treated with a solution of oligomers on the surface sorbent dopolymerized under the same conditions. 2. A process according to claim 1 wherein the precipitant is soaked onto the sorbent by vacuum.