Ceskoslovenska Akademie Ved

Jaroslav Drobnik

Jaroslav Kalal

Frantisek Rypacek

Vladimir Saudek

Frantisek Svec

Jiri Labsky

Marie Metalova

Jiri Vacik

Jindrich Kopecek

Karel Ulbrich

Jinrich Kopecek

Josef Exner

Jiri Strohalm

Pavla Rejmanova

Arnold Aramovich Adamian

Vladimir Chytry

Daniel Horak

Klara Z Gumargalieva

Jurij V Moiseiev

Helena Stepankova

Dagmar Noskova

Jan Uher

Michail I Kuzin

The present invention pertains to a preparation for diagnosing the transport function of the fallopian tube and to a method for making such a preparation. The diagnostic preparation for investigation of the transport function of female fallopian tube, comprises a suspension of a biocompatible, biodegradable, and, if desired, labelled particles, in a vehicle commonly used for parenteral applications wherein the particles have a spherical shape with diameters in the region 10 to 600 um, which are formed from a soft hydrophilic gel based on a polymer selected from the group comprising additionally crosslinked water-soluble nontoxic and biodegradable inert polysaccharides and physiologically inert water-soluble and biodegradable poly(amino acids), polypeptides, and their derivatives, which may contain physiologically active substances. The particles retain their shape and size in the environment of peritoneal cavity and uterotubal tract for at least 80 hours with the subsequent degradation to nontoxic product within 5 to 60 days. A method for preparation of the diagnostic preparation comprises dispersing an aqueous solution of physilogically inert, biodegradable polymer selected from the group of polysaccharides, poly(amino acids), polypeptides, and their derivatives, in a medium of nonpolar water-immiscible solvent, to 10 wt. % of the polymer having a degree of polymerization of 50 to 500, said suspension containing of 80 to 100 mol. % of .gamma.-alkyl-L-glutamate units and 0 to 20 mol. % units of L-glutamic acid, units as a suspension stabilizer, with mixing sufficient to form polymeric spherical particles with diameter 100 to 600 um, which are transferred into the gel state with bifunctional crosslinking agents. The particles are washed and then dispersed in an aqueous solution. The resulting suspension is then sterilized by heat.

Composition for diagnosing the transport function of the fallopian tube

The invention pertains to copolymers activated for bonding of biologically active compounds and to a method for preparation thereof. Soluble and biodegradable copolymers activated for bonding of biologically active compounds which have their main chain formed from units of aspartic acid or glutamic acid, or both, or also from units of other amino acids, according to the general formula I ##STR1## where n is 1 or 2, m is 1 or 2, a+b+c is 100, a is 0.5 to 100, b is 0 to 99.5, c is 0 to 80; the substituent R.sup.1 is --NH--NH.sub.2, --N.tbd.N or ##STR2## where x is 2 to 6, R.sup.2 is --NH(CH.sub.2).sub.x OH where x=2 to 6; and R.sup.3 is methyl, 2-propyl, 2-methylpropyl, butyl, 2-butyl, benzyl or 4-hydroxybenzyl, and the molecular weight is 5,000 to 1,000,000.

Soluble and biodegradable polyamino acid activated for bonding of

A macromolecular compound with antitumor activity in which hydroxy groups in side chains of a polymer have the character of primary, secondary or tertiary alcohols and are completely or in part esterified with carboxyl in the position C4 of 1,2,4-tricarboxybenzene, whereas the carboxyls in positions C1 and C2 bind an atom of platinum with coordination bonded amino ligands. A method for producing the macromolecular compound consists in acylation of the polymer carrying alcohol groups with chloride anhydride of trimellitic acid of the formula II, ##STR1## hydrolyzing the anhydride in the subsequent step, and bonding an atom of bivalent platinum carrying an amino ligand to the formed vicinal carboxylic groups.

Macromolecular coordination compound containing platinum with antitumor

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 pertains to a biodegradable implant formed from a gel completely decomposable in body, which contains the antitumour medical - diamminedichloroplatinum addition compound (cisplatin) and to a method for preparation of this implant. An object of the invention is a biodegradable implant, wherein a matrix of the said implant is formed by a starch gel containing 0.2 to 2 wt. % NaCl, plasticized by addition of 1 to 30 wt. % of glycerol, suitably shaped, and contains the homogeneously dispersed microcrystalline cisplatin in the amount of 1 to 15 wt. %. A method for preparation the implant according to the invention consists in a homogeneous mixing of 1 wt. part of a viscous aqueous solution, obtained by dissolution of 0.4 to 4 wt. % NaCl and conversion of 1 to 6 wt. % of starch to a paste by boiling, with 0.1 to 0.8 wt. parts of glycerol, 0.5 to 1 wt. part of starch, and the required amount of microcrystalline cisplatin, deaeration of the mixture, conversion to a gel in a mould determining the final shape of implant by heating in a boiling-water bath, and, eventually, in hardening by soaking in a water-miscible solvent, advantageously in acetone or ethanol. An advantage of the implant according to the invention consists in a relatively fast release of cisplatin into surroundings, which is desirable with respect to the mechanism of cisplatin action. Another advantage is the degradability of implant to products natural for body, which have not toxicologic nor immunologic importance.

Biodegradable implant and a method for preparation thereof

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

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

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 Drobnik