Ceskoslovenska Akademie Ved

Carlton Medical Products Limited

Jindrich Kopecek

Jiri Vacik

Pavla Rejmanova

Drahoslav Lim

Jaroslav Kalal

Jaroslav Drobnik

Karel Ulbrich

Ladislav Sprincl

Jiri Labsky

Vladimir Chytry

Josef Exner

Jiri Strohalm

Blanka Rihova

John B Lloyd

Ruth Duncan

Hedvika Bazilova Nee Sverinova

A polymeric drug comprising an inert synthetic polymeric carrier combined through aminoacid or peptide spacers with a bioactive molecule, a targeting moiety, and an optional cross-linkage, comprises:

Synthetic polymeric drugs

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

There is disclosed a hydrophilic gel suitable for exposure to repeated long-term contact with live tissues or mucous membranes and consisting of macromolecules obtained by polymerizing a mixture of at least two copolymerizable units and a crosslinking agent. The mixture consists of from 52 to 99.5 parts by weight of N,N-diethylacrylamide, 43 to 0.1 parts by weight of a member selected from the group consisting of N,N-dialkyl acrylamide, N-alkyl methacrylamide, nitriles of acrylic and methacrylic acids and from 5 to 0.4 parts by of a divinylic monomer selected from the group consisting of diesters of acrylic acid and methacrylic acid, and methylene or ethylene-bis-methacrylamide or acrylamide.

Hydrophilic N,N-diethyl acrylamide copolymers

Surgical infusion solutions, useful particularly as blood plasma substitutes, comprising physiological solution of polymers or copolymers formed from ethyleneglycol acrylates and methacrylates, acrylamide, methacrylamide and acrylamides and methacrylamides substituted on the nitrogen atom with either one or two lower alkyl radicals and/or one or two hydroxyalkyl or dihydroxyalkyl radicals containing 1 to 6 carbon atoms and mixtures of these polymeric materials dissolved in a physiological solvent therefor. The polymerization or copolymerization is carried out by solution polymerization methods and the polymeric material is precipitated by mixing it in a suitable non-solvent therefor, but which is miscible with the polymerization solvent.

Infusion solutions and method of manufacturing same

A composition of matter with improved mechanical properties which contain 2 - 50 mol. percent of methacrylonitrile or acrylonitrile and 50 - 98 mol. percent of glycol monoesters of acrylic or methacrylic acid, where the glycol is selected from the group comprising ethylene glycol, diethylene glycol, triethylene glycol and their mixtures. 0.1 - 30 mol. percent of the glycol monoesters may be substituted by a crosslinking agent selected from the group comprising 1,4-cyclohexanedimethyl dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, 1,6-hexamethylene-bis-acrylamide, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, methylene-bis-acrylamide, ethylene-bis-acrylamide. Also hydrogen catalysts of compositions bonded to platinum, palladium or rhodium metal. A process for producing the matter, wherein glycol esters of acrylic or methacrylic acid are copolymerized with methacrylonitrile or acrylonitrile, if desired in the presence of a crosslinking agent.

Hydrophilic nitrite copolymers

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Prague, Czechia

Jindrich Kopecek