From Big Medical Encyclopedia

IONITES (synonym ion exchangers) — the substances capable to enter exchange reactions of ions at contact with solutions of electrolytes. Find broad application in biochemical, researches at fractionation by a chromatography of various low-molecular metabolites and biopolymers. Are used for removal of calcium ions from a blood plasma before its preservation. In a wedge, practice are applied to normalization of electrolytic balance and removal from an organism of some harmful products of exchange or toxic exogenous substances. With the help And. successfully emit valuable medicinal substances and antibiotics, in particular streptomycin. Important range of application And. receiving desalinized water as in laboratory, and commercially, and also sewage treatment is.

Though vast majority And. represents solid matters, almost water-insoluble and organic solvents, are available as well the liquid ionites which are solution of low-molecular ionoobmenivayushchy substances in organic liquids. Special field of chemistry And. creation membrane is I.

Nerastvorimye I. consist of a molecular framework (matrix), on Krom there are ionizable group. As a result of dissociation of such ionizable group the ion pair is formed; at the same time one of ions (see) it is motionless as it is covalently connected with a matrix (the fixed ion), and other ion (antiion) is mobile. The antiion compensates a charge of a motionless ion; it can easily exchange on the ions of electrolyte, of the same name on a charge (see. Ion exchange reactions ). Unlike adsorptions (see), at a cut absorption of one substances does not cause allocations of others, exchange of ions on And. it is carried out stoichiometric, i.e. binding of ions of one look causes release of the corresponding quantity of ions of other look.

Natural And. in the form of silicates were found for the first time in the soil in 1850. Synthetic ion-exchange resins were for the first time received in 1935 by polycondensation of formaldehyde with phenol, and also arylamines. Ion-exchange resins had considerable advantages before known earlier natural And., it was the reason of their broad theoretical and practical studying. Great success in receiving ion-exchange resins was achieved in 1942 when it was shown that it is possible to enter the chemical groups possessing ionizable group into the pitch received earlier. In 1956 in biochemical, to practician entered And. on a cellulose basis.

One of the most important characteristics And. their ion exchange capacity is, edges it is characterized by exchange capacity (the lake e.), i.e. quantity of the exchanging ions in a mass unit dry or unit volume of the bulked-up ionite; lake e. express in mg-ekv/g or mg-ekv/sm3. During the definition static the lake e. hinge plate And. place in solution of the studied electrolyte and after establishment of balance register quantity of the ions absorbed from solution; dynamic lake e. determine by the volume of electrolyte which needs to be passed through a column with an ionite before its saturation, i.e. before emergence of the absorbed ions in a filtrate. Values static and dynamic lake e. depend on the size pH of the environment, concentration of electrolyte and other factors. Full of the lake e. an ionite is determined by curves potentiometric titration (see); it corresponds to total quantity of ionizable group of an ionite, this size is a constant for this sample

of I. I. classify by various signs; one of the most important — a sign of a charge of an antiion; on this sign And. divide into cation exchangers (cation exchangers) and anion exchangers (anion exchangers).

Cation exchangers can be considered as the polyacid capable to exchange of cations, napr, ions of sodium and potassium:

R — SO 3 - Na + +> KCl — R — SO 3 - K + + NaCl,

where R — a matrix And.

Anion exchangers are the polybases capable to exchange of anions, napr, ions of chlorine and nitrate:

R — N + H 3 Cl - + NaNO 3 -> R — N + H 3 NO 3 - + NaCl.

Many properties I. are connected with the chemical nature of their matrix; on this sign And. divide on inorganic and organic. By origin And. divide on natural and synthetic. In size of dissociation of ionizable group among And. allocate strong and weak (highly acid and subacid cation exchangers, strong-basic and weak-basic anion exchangers). On the basis of uniformity or heterogeneity of ionizable group distinguish monofunctional and multifunctional And. Natural mineral cation exchangers are many aluminosilicates (zeolites, clays, glauconites); apatites belong to natural mineral anion exchangers. Aluminosilicate (permutit) is an example of synthetic mineral cation exchanger. Natural organic cation exchangers are humic to - you soils and coals.

Among And. most the synthetic ion-exchange resins representing polymers with a mesh hydrocarbon matrix on a cut are important there are ionizable group; chains of hydrocarbon macromolecules «are sewed» among themselves by cross bonds. Thanks to existence of ionizable group such polymer, keeping generally hydrophobic nature, has a certain hydrophily therefore at contact with solution of electrolyte it bulks up. The size of swelling is defined by structure of ion-exchange resin and, first of all, degree of its «sshitost», character and quantity of ionizable group, composition of solution of electrolyte.

Ion-exchange resins receive generally polycondensation of the connections containing ionizable group (this process proceeds with allocation of water molecules), copolymerization of the vinyl monomers containing ionizable group (monomers connect according to the mechanism of free radical reactions) and, at last, introduction of ionizable group to polymeric molecules (so-called polymeranalogous reactions). In the latter case as a matrix usually use the structured polymers received by copolymerization of styrene and divinyl benzene. Polymeranalogous reactions are the main way of receiving ion-exchange resins in the industry. Ion-exchange resins are used or in the form of the fine particles received as a result of crushing of lumps of pitch or in the form of balls (granules) received during the carrying out polyreaction in water solution in the presence of emulsifiers and at high temperature. Average grains size of ion-exchange resins is from 0,25 to 1,5 mm. Size of the lake e. fluctuates for various ion-exchange resins within 2 — 10 mg-ekv/g.

Some are listed in tab. 1 the domestic and produced abroad ion-exchange resins which found broad application in practice.

Especially pure ion-exchange resins release abroad under brands bio-is glad And (analogs of pitches daueks), bio-reks, CG amberlit.

In biochemistry ion exchangers on a cellulose basis (TsI) are widely used. TsI receive by processing of powdery or fibrous cellulose in alkaline condition halide-derivative connections which part ionizable group are. E.g., at action on cellulose (C — IT) monochloroacetic to - you are formed carboxymethylcellulose: Ts-ON + ClCH 2 COOH —> C — ABOUT — CH 2 COOH + NHCL, and at effect of diethylaminoethyl chloride — diethylaminoethyl cellulose (DEAE-cellulose): C — IT + CClC 2 H 4 N (C 9 H 5 ) 2 -> C — ABOUT — C 2 H 4 — N (C 2 H 5 ) 2 + HCl. Size of the lake e. for TsI it is equal to 0,5 — 1 mg-ekv/of.

Similar drugs I. receive also on the basis of sephadex which represents the gel which is formed as a result of sewing together by means of epichlorohydrin of chains of natural polymer — a dextran (see. Molecular sieves ). Lake e. these drugs makes 3 — 4 mg-ekv/g.

TsI which were widely used in biochemistry are given in tab. 2.

And for fractionation of peptides especially successfully apply ion-exchange resins to the analysis of amino-acid composition of proteins. On a basis And. devices for the automatic analysis of protein hydrolyzates are created (aminoacid analyzers); the integrated analysis of mix of amino acids is carried out in 60 — 90 min., for the analysis it is enough of 10 - 3 mkmolya (1 nmol) each of amino acids. Division of amino acids and oligopeptid is effectively carried out on strongly sewed ion-exchange resins which size of a time of grains is sufficient for penetration of small molecules which can interact, therefore, with ionizable group in grains. For fractionation of larger peptides use less sewed ion-exchange resins.

Ion-exchange resins most often are unsuitable for fractionation of such macromolecules as proteins, nucleinic to - you and polysaccharides. First of all their lake e. concerning macromolecules it is extremely low as ion exchange reaction in this case is limited to the surface of grains of ion-exchange resin. Macromolecules because of the big sizes cannot get into strongly «sewed» grains of ion-exchange resin, and the functional groups located in grains are unavailable to ion exchange. Besides, a matrix of ion-exchange resin, as a rule, strongly a gidrofobna that can cause a denaturation of labile proteins, especially enzymes. At last, linear polymers of the RNA and DNA type with a large number of the dissociating groups contact ion-exchange resins, especially strong and average type, is so strong that are eluated only at extreme pH values in denaturant conditions. Proteins, nucleinic to - you and even viruses are successfully divided and purified on TsI which are deprived of the specified shortcomings. The matrix of TsI has such structure (a big surface and a large time), thanking a cut the most part of ionizable group participates in ion exchange with macromolecules.

Besides, the matrix of TsI is very hydrophilic, it considerably reduces probability of a denaturation of proteins and nucleinic to - t. With the help chromatography (see) on TsI the large number of various individual proteins, first of all enzymes is secreted.

At demineralization of water it is passed via cationite filters therefore calcium ions and magnesium are replaced on ions of sodium. At a consecutive transmission of water through system of cationite and anionite filters or via the filter containing mix of cation exchanger and anion exchanger occurs almost full it demineralization (see).

In laboratory practice by preparation of environments for cellular cultures and microorganisms, and also in pharm. the industries the water purified by means of commercial deionizers of different productivity with success replaces the diart. water.

And. use also in pharm. the industries for removal of salts from solutions of medicinal substances and in the food industry, napr, for release of sugar syrup from undesirable ions. Besides, And. apply to sewage treatment, to concoction of valuable ions, napr, the ions of silver, gold, etc. which are present at drain waters of galvanic workshops for catching and concoction of radioactive ions. In the chemical industry And. use as catalysts.

Use in medicine of ion-exchange resins

Both organic, and inorganic ion-exchange resins (cation exchangers and anion exchangers) find application in pilot studies and in a wedge, practice. For the medical purposes use high cleaning drugs I., exempted from toxic impurity.

During the work with various forms I. it is necessary to consider unequal degree of their affinity to these or those ions, and also a possibility of disturbance of ionic balance of an organism at the expense of the released ions.

There are two main methods of use of ion-exchange resins: introduction of per os or with an enema and use in systems of extracorporal blood circulation (hemoperfusion, hemadsorption, hemosorption) in whom the column filled with the granulated pitch is included p an extracorporal contour. In addition, K. P. Krylov (1972) also use of membrane ionites is offered.

One of the most essential indications to use of cation exchangers is the hyperpotassemia. Depending on features the wedge, pictures in this case can be applied both the ion-exchange resins mentioned a method of use.

As a rule, administration of per os cation exchangers or with an enema, offered for the first time in 1950 by J. R. Elkinton and soavt., it is shown in the conditions of rather slowly developing hyperpotassemia, napr, at hron, to a renal failure. Originally cation exchangers applied in a sodium form. However along with the expressed decrease in content of potassium in blood at the same time the hypernatremia, undesirable to patients, at the expense of the sodium which is released during ion exchange was observed. Attempts to apply a calcic form of cation exchanger led respectively to a hypercalcemia. The possibility of use of an aluminum form of cation exchanger is investigated.

The dosage of ion-exchange resin fluctuates depending on a condition of the patient, use of others to lay down. means, etc. Most often it makes from 8 to 60 g of cation exchanger a day. Duration of treatment — from several days to several months.

More bystry elimination of potassium, need in a cut arises at increase in its concentration in blood to dangerous limits (at bystry rate of increase of content of potassium in blood, emergence a wedge, symptoms of potassium intoxication), can be reached by means of hemoperfusion through the column filled with ion-exchange resin (with use, e.g., domestic KU-2 or KU-3 ion-exchange resins). For prevention of a blood coagulation in an extracorporal contour hemoperfusion is carried out in the conditions of a geparinization. The volume of a column usually makes 100 — 200 ml, duration of hemoperfusion — of 30 min. till 2 — 4 o'clock. As a rule, during this time it is possible significantly (sometimes to norm) to reduce the content of potassium in a blood plasma.

Ability of cation exchangers to actively delete the ammonia collecting in blood at a liver failure was established in an experiment and confirmed at a wedge, use of a method. In certain cases at the same time temporary improvement of a condition of patients was noted. However observations in this area are very limited.

In pilot studies the possibility of use of hemoperfusion and for removal of radioactive materials was shown (e.g., radioactive strontium). Efficiency of a method at the same time approached that at hemodialysis (see).

Hemoperfusion using ion-exchange resins is not deprived also a number of shortcomings, the most essential of which are development of thrombocytopenia and disturbance of electrolytic balance of a blood plasma. For prevention of the last it was offered to use mix of various forms of the cation exchangers which are picked up in the corresponding proportion. For prevention or reduction of falling of number of thrombocytes attempts of use of the encapsulated particles are made And.

As well as cation exchangers, anion exchangers are used both at reception of per os and at hemoperfusion. One of indications to use of anion exchangers is the hypercholesterolemia and a hyperlipemia. Effect of ion-exchange resins in this case is caused by disturbance of a circulation bilious to - t due to their absorption And. Decrease in absorption of cholesterol in intestines and stimulation of transformation of cholesterol in bilious to - you results. Decrease in concentration of cholesterol in a blood plasma is a consequence of it. Decrease in concentration of cholesterol under the influence of anion exchangers fluctuates depending on a number of factors, making, according to various authors, 14 — 20%. Drugs such are effective at the patients suffering from a giperlipoproteinemiya of the II type. Exchange of lipoproteids with decrease in their concentration in blood is at the same time broken. Usually anion exchangers are used by per os in a dose of 15 — 30 g a day. Duration of use — up to two years. Any considerable side effects at prolonged use of anion exchangers were not noted (locks are sometimes observed). At some diseases of a liver administration of anion exchangers led to disappearance of a skin itch, characteristic of this disease.

The available data indicate also a possibility of decrease in concentration of bilirubin in blood serum at administration of anion exchangers. However to delete bilirubin from blood in significant amounts it was possible only at hemoperfusion with use of specially modified ionites.

A number of researches established a possibility of use of hemoperfusion with use of anion exchangers for removal of some toxic agents, and first of all barbiturates. Efficiency of elimination of barbiturates can be significantly increased at rather small increase in a pH value of perfusing blood. More effective in this respect appeared macroreticular not loaded And., used for treatment of some poisonings (e.g., poisonings sekobarbitaly, barbamyl, etc.).

Attempts of turning on of devices are made with And. in a contour of extracorporal circulation at a hemodialysis and peritoneal dialysis for increase in their efficiency. For preparation of the decalcified blood I. apply seldom.

Along with use of organic ionites in medical practice find application and inorganic I. Tak, the cation exchanger containing mix of aluminum hydroxide and magnesium hydroxide (the branded name «Almagelum», NRB) was widely adopted. This drug per os in quality is appointed antiacid means (see) and for binding in went. - kish. a path of phosphates that usually is required for prevention of their excess absorption and accumulation in a blood plasma from patients with hron, a renal failure. In the latter case this drug can be appointed within many months. At reception of Almagelum locks are among by-effects, uncontrolled administration of drug can lead to a hypophosphatemia.

Inorganic And. (a hydroxide of zirconium and phosphate of zirconium) are used also in systems of a hemodialysis and peritoneal dialysis for regeneration of the dialyzing solution.

However use And. it is connected with need of careful medical control and use of the difficult laboratory equipment (control of concentration of electrolytes and the size pH of blood etc.), a possibility of side effects, existence of the special equipment. All this complicates their broader and versatile use in therapeutic practice.



Bibliography: Amflett K. B. Inorganic ionites, the lane with English, M., 1966; Osborn D. G. Synthetic ion exchangers, the lane with English, M., 1964; Riemann W. and Walton. Ion-exchange chromatography in analytical chemistry, the lane with English, M., 1973; Saldadzek. M, Pashkov A. B. and Titov V. S. Ion-exchange high-molecular compounds, M., 1960; Tikhonenko T. I. Methodical fundamentals of biochemistry of viruses, M., 1973; Tremiyon B. Division on ion-exchange resins, the lane with fr., M., 1967; Shimangko I. I., etc. About use of ion-exchange resins at disturbances of electrolytic composition of blood, Surgery, No. 11, page 92, 1971; Lopukhin U. M and. lake of Bilirubin removal by anion-exchange resin, Lancet, v. 2, p. 461, 1975; Sachs B. A. a. Wolfman L. Colestipol therapy of hyperlipidemia in man, Proc. Soc. exp. Biol. (N. Y.), v. 147, p. 694, 1974.

L. M. Ginodman; AA. P. Levitsky, E. B. Gor-bovitsky (vn. Bol.).