Ceskoslovenska Akademie Ved

Other

Boehringer Mannheim Gmbh

Tschechoslowakische Academie Der Wissenschaften

Czechoslovenska Akademie Ved of Praha

Jaroslav Kalal

Frantisek Svec

Jaroslav Drobnik

Miroslav Stol

Pavel Cefelin

Karel Bouchal

Jiri Labsky

Marie Tlustakova

Milan Adam

Miroslav Tolar

Eva Zurkova

Hans-Georg Batz

Jiri Coupek

Artur Stoy

Jiri Vacik

Vladimir Stoy

Manfred Baier

Miroslav Bleha

Jindrich Kopecek

Zdenek Plichta

Jiri Zima

Karel Ulbrich

Jinrich Kopecek

Vladimir Saudek

Svatopluk Pokorny

Paul Tanswell

Josef Exner

Pavla Rejmanova

Arnold Aramovich Adamian

Marie Metalova

Jiri Strohalm

Vladimir Chytry

Eva Votavova

Jaromir Lukas

Michail I Kuzin

Daniel Horak

Klara Z Gumargalieva

Jurij V Moiseiev

Jiri Kulisek

Josef Vavrouch

Jiri Horak

Bohumil Bednar

Jaromir Zachoval

Jiri Petr

Zdenek Pelcbauer

The invention pertains to the method for producing a biocompatible layer on the surface of particles of porous synthetic sorbents. An object of the invention consists in the method for producing a biocompatible layer on the surface of particles of porous synthetic sorbents by action of a solution of biocompatible polymer of acrylate or methacrylate type, or of its monomer in the presence of polymerization initiators, on a suspension of sorbent, which is agitated with steam. The method according to the invention renders a material, the sorption capacity of which is entirely retained. This is due to water, which remains enclosed in the pores of sorbent and enables the sorption of toxins also inside the gel particles. In addition, steam can be prepared completely apyrogenic and thus to secure that the sorbents remain clean inside. Clinical tests reveal that the sorbents coated by the method according to the invention have an excellent hemocompatibility.

Method for producing a biocompatible layer on the surface of particles

The invention pertains to X-ray contrast spherical hydrogel particles based on polymers and copolymers of acrylates and methacrylates and to a method of their preparation. The subject of this invention are X-ray contrast spherical hydrogel particles based on polymers and copolymers of acrylates and methacrylates characterized by the particles of spherical form with diameter 0.2 to 2 mm, which strongly swell in water and contain a derivative of amino-triiodobenzoic acid of general formula I, ##STR1## where R.sup.1,R.sup.2 is hydrogen, acyl group with 1 to 3 carbon atoms or alkyl with 1 to 10 carbon atoms and X is halogen, --OH or --NH(CH.sub.2).sub.n NH.sub.2, where n=1-6, covalently bonded to the polymer skeleton. A method for preparation of X-ray contrast hydrogel particles according to the invention in which hydrogel particles, containing hydroxyl or epoxide groups localized on side chains of the polymer skeleton, are allowed to swell in an excess of a solvent chosen from the group comprising dioxane, dimethylacetamide, dimethylformamide, tetrahydrofuran and dimethylsulfoxide, which contains the dissolved derivative of amino-triiodobenzoic acid of the general formula I, optionally together with a compound reacting with hydrogen halogenide formed, which is selected, for example, from the group comprising tertiary amines, the dispersion is heated to 100.degree. C. at utmost and allowed to react for 150 hours at utmost, the solid phase is separated and freed of soluble substances by washing. The procedure according to the invention provides spherical hydrogels with X-ray contrast properties without changing their other properties substantial for application in medical practice.

X-ray contrast spherical hydrogel particles based on polymer and

The invention relates to a composite polymeric material suitable for biological and medical applications and to the method for preparation thereof. The composite material consists of 1-99 wt. % of hydrophilic polymer or copolymer based on methacrylic or acrylic esters, 1-99 wt. % of fibrillar collagen, and up to 2.5 wt. % of a crosslinking agent, based on both polymeric components. The composite material may further comprise biologically active compounds and other auxiliary materials, as fillers and/or plasticizers. The composite material is prepared by dispersing the fibrillar collagen in a solution or a highly swollen dispersion of the synthetic hydrophilic polymer or copolymer in a lytropic agent and the subsequent removal of the lyotropic agent, thus forming a matrix of the synthetic polymer or copolymer penetrated by fibrillar collagen or vice versa. The composite material may be applied on a solid support or reinforced with glass, plastics, cellulose, or metallic materials.

Composite polymeric material for biological and medical application and

The invention relates to a composite polymeric material suitable for biological and medical applications and to the method for preparation thereof. The composite material consists of 1-99 wt. % of hydrophilic polymer or copolymer based on methacrylic or acrylic esters, 1-99 wt. % of fibrillar collagen, and up to 2.5 wt. % of a crosslinking agent, based on both polymeric components. The composite material may further comprise biologically active compounds and other auxiliary materials, as fillers and/or plasticizers. The composite material is prepared by dispersing the fibrillar collagen in a solution or a highly swollen dispersion of the synthetic hydrophilic polymer or copolymer in a lyotropic agent and the subsequent removal of the lyotropic agent, thus forming a matrix of the synthetic polymer or copolymer penetrated by fibrillar collagen or vice versa. The composite material may be applied on a solid support or reinforced with glass, plastics, cellulose, or metallic materials. A method for the preparation of the composite material consists in dispersing of fibrillar collagen in a solution or a highly swollen dispersion of the synthetic hydrophilic polymer or copolymer in a lyotropic agent, e.g. in water diluted carboxylic acids, strongly acidified aqueous mixtures of ethanol and methanol, high-concentrated aqueous solutions of lyotropic salts, and high-concentrated aqueous solutions of urea or guanidinium chloride, at temperature not exceeding 37.degree. C., and the subsequent removing of the lyotropic agent from the viscous dispersion at temperature not exceeding 37.degree. C. using the known methods. The crosslinking agent, e.g. trimethylolurea, formaldehyde, acetaldehyde, glutaraldehyde, starch dialdehyde, glyoxal, or Cr(III) salts, may be added in the course of preparation of the dispersion or after removal of the lyotropic agent.

Composite polymeric material for biological and medical applications and

Hydrophilic latex particles consisting of a homo- or co-polymer of monomers which are sparingly soluble in water, which hydrophilic latex particles can be prepared by emulsion polymerization in the presence of a water-soluble, radical-forming initiator but without an addition of an emulsifier, stabilizer or wetting agent. A process for the preparation of these hydrophilic latex particles, wherein a monomer which is sparingly soluble in water or several monomers which are sparingly soluble in water are dispersed in water and, with the exclusion of oxygen, for example in an inert atmosphere, are homo- or co-polymerized by emulsion polymerization in the presence of a water-soluble, radical-forming initiator but without any addition of an emulsifier, stabilizer or wetting agent. A diagnostic agent containing these hydrophilic latex particles as carrier and biologically and/or immunologically active substances covalently bound to this carrier either directly or via a coupling agent as a bridge.

Hydrophilic latex particles and use thereof

The invention relates to the polar polymeric sorbent applicable in gas and liquid chromatography, which is based on glycidyl esters. The sorbent is formed by the macroporous copolymer containing 3-70% of polymerized monomeric units with epoxy groups, e.g. glycidyl methacrylate or glycidyl acrylate units, and 97-30% of a crosslinking agent, e.g. alkylene dimethacrylate, alkylene diacrylate, hydroxyalkylene dimethacrylate, hydroxyalkylene diacrylate (alkylene containing 1-6 C atoms), or divinylbenzene. The sorbent may further contain up to 30% of polymerized monomeric units containing nitrile groups, e.g. acrylonitrile and methacrylonitrile units. The polarity of sorbent can be further modified, according to the invention, by the reaction with various nucleophilic agents, e.g. water, alcohols, carboxylic acids and their derivatives, ammonia, amines, thioalcohols, acrylonitrile. The sorbent is thermally and mechanically stable and was used for the gas-chromatographic and liquid-chromatographic separation of complex mixtures of compounds. Its polarity was expressed in terms of modified Rohrschneider indices.

Polar polymeric sorbent based on glycidyl esters for gas and liquid

The invention relates to three-dimensional carriers consisting of inorganic porous material and 0.001-95% of unextractably sorbed reactive polymer of the general formula I: ##STR1## where R.sub.1, R.sub.2, R.sub.4 respectively are hydrogen atom, alkyl with 1-5 carbon atoms, or aryl, and R.sub.3 is the group --COO--(CH.sub.2).sub.n --, and to a method for its preparation. The three-dimensional carriers may be prepared by coating the inorganic porous material with a monomer, which is left to polymerize under the conditions of solution polymerization, while the soluble polymer, which is not bound on the surface of the inorganic material, is removed by extraction. The three-dimensional carrier may also be prepared by depositing a solution of a polymer of general formula I and with a degree of polymerization lower than 10.sup.3 on the inorganic porous material, leaving the two materials in contact with each other, and separating the unbound polymer by extraction. The carriers of inorganic porous material-reactive polymer combine good properties of the inorganic material with the high reactivity of the polymeric coating. An advantage of the carrier is not only the combining of inorganic porous materials with a polymer containing epoxy groups, but also an ample opportunity of modifying the carrier by chemical reactions of the epoxy group. This opportunity may be employed in bonding biologically active compounds, dyes, complex-forming compounds and other low-molecular and high-molecular weight compounds to the carrier.

Three-dimensional carrier of inorganic porous material-reactive polymer

The invention relates to a negative electron resist for application in electron lithography. It consists of an organic copolymer formed by copolymerization of butadiene or isoprene with glycidyl acrylate or glycidyl methacrylate. The resist exhibits the high sensitivity to irradiation by electrons and, at the same time, a good adhesion to the base and a resistance towards common etching agents. The copolymer is advantageously prepared by radical polymerization and a high purity of the product does not require further purification. The electron resist manufactured in this way has the long-term workability.

Electron resist

The invention relates to a solid insoluble carrier which is activated for bonding of nucleophilic groups and to a method of its preparation. The carrier contains active groups --O.CO.O.R, where R is the residue selected from the group comprising nitrophenyl, dinitrophenyl, trichlorophenyl, pentachlorophenyl, N-succinimidyl, N-phthalimidyl, and 8-quinolinyl. Active groups are bonded to polysaccharides, phenol-formaldehyde resins, polyacrylates, or polyacrylamides. The invention further relates to a method for preparation of the polymeric carrier, which consists in treatment of polymers carrying hydroxyl functions and selected from the group comprising polysaccharides, phenol-formaldehyde resins, polyacrylates, and polyacrylamides, with esters of chloroformic acid which contain the above mentioned active groups.

Activated solid carrier and a method of its preparation

The invention relates to a method of manufacturing shaped articles from crystalline or quasi-crystalline acrylonitrile polymers and copolymers, said method consisting in cooling down a solution of said polymer or copolymer in a mixture containing from 50 to 99.5% by weight of a solvent and from 0.5 to 50% by weight of a precipitant to a temperature below the gelation point of the solution until the same gelatinizes, without changing its composition, to the desired shape, whereafter the solvent is removed from the shaped thermoreversible gel thus obtained at temperatures lower than the gelation point of the solution, preferably using a liquid precipitant of polyacrylonitrile miscible with the solvent. It is advantageous to remove the solvent at a temperature which is at least 10.degree. C. lower than the gelation temperature of the polymer solution used. The shaping can be carried out in any convenient way, e.g. using a stationary or rotating mold. Beads, spheres, filaments and foils can be shaped without any mold in the usual way. The method is also suitable for coating surfaces.

Method of manufacturing shaped articles from crystalline acrylonitrile

Polymeric color pH indicators are prepared which are insoluble in the measured aqueous medium and show a certain range of color change. These polymeric indicators are the product of copolymerization of a hydrophilic comonomer, selected from esters, amides and N-substituted amides of acrylic and methacrylic acid, with 0.1- 30 wt.% of a comonomer. The comonomer forms the pH-indicating color center by a subsequent coupling with a suitable diazonium salt or a passive component. Vinylic monomers comprising an aromatic system in the molecule are suitable as the functional comonomers. The indicators are prepared by radical copolymerization of the comonomers either in a suspension or in a solution, followed by the subsequent coupling with a diazonium compound, or diazotizing and coupling with a passive component, to obtain the pH-indicating sites of polymer. The product is in the form of small spherical macroporous particles suitable for pH indication in flow-through column processes, in small volumes, or on a microscope stage, or in the form of a solution applicable as a paint and indicating the pH of vessels, reactors, etc. coated therewith, or useful for application to inert carriers.

Polymeric color indicators and a method of their preparation

Polymeric form of a biologically active compound containing at least one -NH.sub.2 group in its molecule, adapted for the protracted release of said biologically active compound by enzymatic cleavage of the polymer in vivo in the organism. The active compound is bonded by its -NH.sub.2 group to the carboxylic group of an L-amino acid as for instance, .beta.-phenylalanine, tyrosine, tryptophane, lysine, arginine, glycine, alanine, leucine, citruline or ornithine, which latter is in twin bonded by its amino group to the terminal carboxylic group of the side chain of a substituted amide or ester of acrylic or methacrylic acid, said side chain constituting a linear moiety containing at least 3 carbon atoms. The latter compound or monomer is copolymerized with a hydrophilic monomer such as, N-alkylmethacrylamide, N-alkylacrylamide, N,N-dialkylacrylamide, wherein alkyl has 1-6 carbon atoms and may contain 1 to 3 OH groups, or glycol acrylate or methacrylate alone or in admixture, and which copolymer may contain further monomeric components, for example, cross-linking agents. It is the copolymer which constitutes the subject matter of the invention, i.e., the biologically active substance bearing -NH.sub.2 groups in a form releasable by enzymatic cleavage. The copolymer can also be prepared using as the monomer a compound containing the bonded L-amino acid and in which the terminal carboxylic group has been converted to the reactive ester. The active compound is then bonded to the thusly prepared reactive polymer. The enzymatic release of the active compound bearing -NH.sub.2 groups can be controlled, i.e., regulated by the size of the side chain carrying the L-amino acid.

Preparation of biogically active substances bearing -NH.sub.2 groups in

Three-dimensional polymeric material in the form of spherical particles of diameter .ltoreq.3 mm and containing up to 40% of free aldehyde groups which exhibits a measurable specific surface area is prepared by copolymerization of an aldehyde monomer R.sub.1 CH.dbd.C(CH.dbd.O)R.sub.2, where R.sub.1 is H, C.sub.1-5 alkyl, aryl or furyl and R.sub.2 is H, C.sub.1-5 alkyl, halogen, CN, phenyl or furyl, with a crosslinking agent in the aqueous dispersion phase. The dispersion contains 1 - 25% of a component reducing the monomer solubility in water, which is either an inorganic salt of alkali metal or alkaline earth metal or a water-soluble alcohol. The crosslinking agent used as comonomer is divinylbenzene, diester CH.sub.2 .dbd.C(R.sub.1)COOR.sub.2 OCOC(R.sub.1).dbd.CH.sub.2 (R.sub.1 .dbd. H, C.sub.1-10 alkyl or halogen; R.sub.2 .dbd. C.sub.1-10 alkylene or hydroxyalkylene), or diamide CH.sub.2 .dbd.C(R.sub.1)CONHR.sub.2 NHCOC(R.sub.1).dbd.CH.sub.2 (R.sub.1 .dbd. H, C.sub.1-10 alkyl or halogen; R.sub.2 .dbd. C.sub.1-10 alkylene or phenylene). The material may be used in continuous column processes, e.g. in catalysis of organic syntheses, separation of amines, and immobilization of compounds which contain primary amino groups.

Polymeric material containing aldehyde groups and the method of its

The invention relates to polymeric materials containing variable amounts of aldehyde groups and comprising the chain units ##STR1## where R.sup.1, R.sup.2 and R.sup.3 are H, C.sub.1 - C.sub.5 alkyl, aryl, furyl, halogen, nitrile group or hydroxyl and R.sup.4 is C.sub.1 - C.sub.20 alkylene, arylene, --COO(CH.sub.2).sub.n --, --O--(CH.sub.2).sub.n --, --COO(CH.sub.2).sub.n CH(OH)CH.sub.2 OCO(CH.sub.2).sub.m -- or --(CH.sub.2).sub.n OCOR.sup.5 COO(CH.sub.2).sub.m -- (n and m are integers 0 - 20 and R.sup.5 is the single bond, C.sub.1 - C.sub.20 alkylene or hydroxyalkylene or arylene). The material may be in the form of globules with a measurable specific surface area and is suitable for bonding of biologically active compounds containing primary amino groups or other amines to produce polymeric chelating agents. The invention further relates to the method for preparation the above materials which consists in treatment of the polymeric materials comprising units of the general formula ##STR2## where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the aforesaid meaning and R.sup.6 is H, C.sub.1 - C.sub.20 alkyl or aryl, with the aqueous solution of periodic acid at 0.degree. - 200.degree. C and the pressure 1 Pa to 20 MPa.

Aldehyde polymers from periodic acid treatment of epoxide polymers

The invention relates to copolymers based on N-substituted acrylamides, N-substituted methacrylamides and N,N-disubstituted acrylamides and to a method for their manufacturing, which copolymers are prepared under conditions when the phase separation takes place. The resulting copolymer contains reactive groups and serves as the intermediate for preparation of biologically active compounds (enzymes, hormones, drugs, etc.) bonded to the polymer. The procedure according to the invention enables to prepare porous polymers suitable as separation barriers (membranes) or column packings for gel or affinity chromatography, if the polymerization is carried out in the presence of a divinyl component.

Copolymers based on N-substituted acrylamides, N-substituted

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Prague, Czechia

Jaroslav Kalal