CS217253B1 - Haemocompatible sorbent and method of preparation thereof - Google Patents

Abstract

The subject of the invention is hemocompatible sorbent, consisting of its own synthetic % resin and 0.1 to 20 wt. % hemocompatible polymer coating of acrylate or methacrylate type. The method of preparing this sorbent rests in that it is applied to the resin a suitable polymer precipitant, and thereafter a polymer solution is applied to the resin; on the resin-coated surface by means of a precipitating agent polymerizes the monomer radically or oligomers thereof. An advantage of the material prepared by the process according to the invention, it is excellent hemocompatibility and thus the possibility to use it for Own medical purposes.

Description

The present invention relates to a hemecempatile serbent and to a method of manufacture.

There are a number of situations in internal medicine where it is necessary to eliminate textual substances from the blood, whether by usex or endegenníhe fasting. A very simple methedeu for these purposes is hemeperusion, in which the patient's blood passes through a selectively serbent.

In the current debate, the use of activated charcoal is the main cause of haemeperfusion, which is pushed down by various hemekempatable pelymers that suppress the aeration of the perfused blood elements, particularly platelets (Walker J.M., DEnti E., Van Wagenen R., Andřade J.D .:

Kidney lntern.10, 320, 19761. However, in the last debut, synthetic resins which do not cause embellisations in the edd of coal are not used to fill hemeperfusion calenders (Reeenbaum JL, Winsten S., US Kramer, Merta J., Raja R. : Trans.Amer.Sec.Artif.

Int.Organa 1970, 134). Among the non-inert resins, in particular, Amberlite XAD-2 and XAD-4 are used, which are good aerbevat substances such as barbiturates, salicylants, tricyclic antidepressants, etc. Lewex 1 was used from these resins. However, their active substance is not covered by a hemekeepatile polymer layer, but at most is treated with albumin. However, when the kelene blood is leaked, 90% of the blood platelets and more than 70% of the leukecytes are breathed to the eerbentus (Reeenbaum JL, Kramer KS, Raja R., Winsten S., Dalal F .: Kidney Itera.10, 341, 1976) $ Willsem RA, Hefmann AF, Kuster G.

G.R .: Gastreenterelegy 66, 9 $, 1974). Some authors have observed the declines of pressure in the calonium and the formation of blood clots (Oeeney, D.O., Infanteline W., " -ane R .; Qiemat., Med.Dev. Let.Org. 1979, 443). With such significant decreases in the fermal blood elements that the organism has to cope with, it is not possible to treat chronic conditions with epakeval perfusions and in hemeperfusion acute there is a significant risk of bleeding campuses.

The subject of the invention is a hemi-permeable serbent consisting of a synthetic resin proper and 0.1 to 20 tactiles. % of the hemecepatable polymer coating of acrylate or methacrylate type.

The method for preparing this serbet is characterized in that a suitable polymeric precipitant is applied to the resin and a polymer restex is applied to the resin, or the monomer or its eligemers are radially polymerized on the resin-coated resin.

The monomer Pelymerizame must pass rapidly to ensure the formation of a homogeneous, thin and sufficiently permeable polymer membrane on the serbet particles. It is desirable to use rapidly resolving polymerization initiators, and to provide a redex initiator system capable of initiating radical palymerization even at nermal temperature.

Of the synthetic resins, styrene-divinylbenzene-like polymers of varying porosity (Amberlite XAD-2 and XAD-4, Servachr XAD-2 and XAD-4, Ostien SP-1, apo ') may be used with acrylic or methacrylic esters of divinylbenzene ( Amberlite XAD-7 XAD-8, Servachr XAD-7 and XAD-8, or others). Of the ion exchange materials, styrene-divinylbenzene cepelyomers substituted with, for example, quaternary amine groups and varying degrees of crosslinking, and in various farms, CDewex 1X4, Domex 1, etc., styrene-divinylbenzene (Ostien app, Ostien ADP, Ostien app, Ostien ADP) ), acrylic or methacrylic acid cepelyomers with divinylbenzene (Ostien KM, Amberlite IRC, or others).

Which polymeric precipitants can be used with preference for carbonaceous solvents

-2aliphatic such as pentane, hexane, etc., as well as aromatic character such as benzene, taluene, xylenes, etc., as well as acetone, diethyl ether or water.

The advantage of the material prepared by the process according to the invention is its excellent haemocompatibility. In addition, the described sorbent preparation method is very versatile, since by selecting a suitable polymer precipitant, pelymer coatings can be prepared on a variety of synthetic resins with suitable particle sizes.

The amount of polymer forming the sorbet coating depends only on the particle size of the resin. The amount of polymer to be present on the resin surface must be such that it forms a thin, completely continuous layer as can be seen from electron scanning microscope images.

The amount of polymer in the sorbent was determined as the weight gain of the resin after drying the heat presentation sample to constant weight.

For medical purposes, the coated sorbent was placed in a suitable shape polypropylene column into the extracorporeal blood stream. Tests have shown that sorbents coated by the method of the invention have excellent haemocompatibility. At the end of the four-hour plasmaperfusion, the number of white blood cells averaged 94.1 and 18.1%, and the platelet count was 95.2 - 21.3% of baseline (n - 10). For hemoperfusion, the corresponding numbers were 67.6 - 25.2% for leukocytes and 103.1 - 12.7% for thromboocytes (n = 1Q3. Blood pressure never changed more than 10 torres (1.33kPa) during perfusion, ,, No clinical complications of the procedure occurred and subjectively the perfusion was tolerated very well in all cases.The surface of the sorbent was free of blood clots or trapped blood elements after dismantling the column.

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

Example 1

Sufficient pentane was poured onto 100 g of Amberlite XAD-2 resin having a particle size of about 0.3 mm to completely cover the resin with solvent. After the excess pentane was cast, a mixture of 10 g of 2-hydroxyethyl methacrylate with a solution of 1 g of ammonium persulfate and 1 g of sodium pyrosulfite was poured onto the resin. The suspension was thoroughly shaken. After standing for about 8 hours, water was poured on the sorbent and the suspension was purged with water until the pentane residue was ejected. the sorbent was thoroughly extracted with water. The polymer content was about

%.

Example .2

100 g of Servachrome XAD-2 having a particle size of 0.4 to 1.0 mm was poured in water and after excess water dripped, a solution of 1 g of pollen (2-hydroxyethyl methacrylate), in methanol-science, was poured onto Servachr XAD-2. After shaking, the coated sorbent was repeatedly extracted with boiling water. The amount of polymer in the sorbent is roughly 1% · »

Example 3

100 g of SP-1 with a particle size of 1.5 to 3.substituted with benzene was then poured into a solution of 1 g of 2-hydroxyethyl methacrylate, 0.1 g of ammonium persulfate and 0.1 g of sodium pyrosulfite in science. After standing at room temperature for 10 hours, benzene was removed from the sorbent by steam. After repeated extraction of the sorbent with water, the polymer content was 0.2

3 '

EXAMPLE 4 da 100 g of ftmberlite Xe.D.-4 f-1 mm particle size, a defect in the flowing medium was soaked in vacuo to completely cover the resin. By dissolving excess science, a residue of 1 g of (2-hydroxyethyl methacrylate) pollen in ethanol was poured onto the serbent. After shaking, the sorbent was left with 12 hedges per laberaterial jaws and then extracted by epakevani by heating. The amount of polymer in the serbent was 1%.

Example 5

50 g of SP-1 screen of 0.2 mm particle size was vacuum soaked in toluene, and a mixture of 10 g of 2-hydroxyethyl methacrylate, 0.1 g of hydrogen peroxide, 0.2 g of sodium pyrosulphite and water was poured into the resin. The suspension was heated to 50 ° C under an inert atmosphere with stirring for 8 hours. The teluen was then removed by bubbling the suspension with vapor. The polymer content was about $ 10.

Example 6

200 g of Servachrome XAD-4 and valikedti particles of 0.3 to 1 mm were vacuum soaked in water and poured into a solution of 4 g of pollen (2-hydroxyethyl methacrylate) in ethanol-science mixture and the suspension was allowed to stand for 4 hours. Repeated extraction by heat recovery yielded a serbent with approximately 2% polymer.

Example 7

4 and 50 g ugtiene KM was poured distilled acetone and then reztek? g of 2-hydroxyethyl methacrylate, °, 1 g of hydrogen peroxide and 0.01 g of iron (II) sulfate in science. The suspension was allowed to stand for 24 hours after shaking. Acetone was removed from the serbent by repeated extraction of the vede. The amount of polymer in the serbent was about 18 µb,

The same result was obtained using ether as the polymer precipitant.

Example 8 g of Servachram XAD-7 resin was defective in vacuum. For the casting of the excess defect, a mixture of 2 g of N -hydroxyethyl acrylate, 0.1 g of methyl methacrylate, 0.05 g of ammonium persulfate, 0.05 g of potassium pyrosulphite and water was taught on the resin. Upon careful mixing, the suspension was polymerized at an ambient temperature for 18 hours under an inert atmosphere. Polymer content of about 5% was found after boiling up the serbent in science.

Example 9

159 g of styrene-ethylenedimethacrylate in kepelymer were poured over with a sufficient amount of hot water to completely cover the resin. Then, 0.15 g of ammonium pyresulphate in science was added under argon. After standing for about 10 minutes, a mixture of 0.15 g of ammonium perchlorate and 15 g of 4-hydroxyethyl methacrylate with 0.2% ethyl dimethacrylate was added.

The mixture was stirred for 20 minutes and then plated to stand at room temperature for 7 hedes. For washing, the sorbent contained 5 hmet. % polymer.

-4Example 10

400 g of acrylenitrile-divinylbenzene resin are vacuum soaked with water. After pouring off the excess water, a solution of 4 g of poly (2-hydroxy ethyl methacrylate) was poured into the resin in an ethanol-water mixture. To wash excess pelymer, the resin contained 2.5% polymer.

EXAMPLE 11 g of acrylonitrile-ethylenedimethacrylate copolymer was poured over the defect and then a solution of 2 g of 2-hydroxy-ethyl acrylate and 0.2 g of phenetic acid in water was poured onto the cepelymer. ΓΌ washing of the coated sorbent revealed the presence of 4% pelymer.

Example 12

500 g of 2,3-epoxyprepyl methacrylate kepelymer with ethylenedimethyl acrylate were poured over with diethyl ether and then with a solution of 5 g of pollen (2-hydroxyethyl methacrylate) in methanol. The suspension was shaken for 20 minutes and then boiled with deatilevane with water. The pelymer content was 1% "

Claims (5)

SUBJECT OF THE INVENTION CLAIMS 1. A hemocempatibile sorbent, characterized in that it consists of a synthetic resin and from 0.1 to 20% by weight of a hemecempatable pelymer of the methacrylate or acrylate type. 2. A process for the preparation of a haemocompatible serbent according to the process of claim 1, characterized in that a pelymer is precipitated onto the resin and then polymerized monemer or oligomers thereof by radical polymerization. 3. A process for the preparation of a haemcompatible sorbent according to claim 1, characterized in that a polymeric precipitant is applied to the resin and thereafter a solution of a hemecompatible pelymer. 4. Process according to claim 2, characterized in that it is precipitated onto the resin by soaking in a vacuum. 5. A process according to claim 2, wherein the polymer is precipitated with aliphatic or aromatic hydrocarbons, acetone or diethyl ether.