Contipro A.s.

Contipro Biotech S.r.o.

Kristina Nesporova

Vladimir Velebny

Gloria Huerta-Angeles

Radovan Buffa

Ivana Basarabova

Petra Sedova

Daniela Smejkalova

Klara Slezingrova

Romana Sulakova

Lucie Wolfova

Josef Chmelar

Jaromir Kulhanek

Martina Hermannova

Jaroslav Novotny

Miroslava Nemcova

Pavel Klein

Robert Pospisil

Martina Hasova

Martina Tepla

Tereza Ehlova

Ondrej Kotland

Leos Hromek

Jakub Syrovatka

Martin Bobek

Martina Pospisilova

Lucie Vistejnova

Antonin Minarik

Vit Matuska

Eva Prikopova

Jan Kucera

Daniel Jirak

Sergej Karel

Jiri Mrazek

Marcela Dusankova

Dagmar Cozikova

Andrea Galisova

Jana Sogorkova

Martina Moravcova

Klara Slesingrova

Tereza Silova

Klara Slezingerova

The invention relates to a self-supporting, biodegradable film comprising a C-C-acylated derivative of hyaluronic acid according to the general formula (I), where R is Hor Na, and where Ris H or &#x2014;C(&#x2550;O)CH, where x is an integer within the range from 9 to 21 and y is an integer within the range from 11 to 43 and CHis a linear or branched, saturated or unsaturated C-Cchain, wherein in at least one repeating unit one or more of Ris &#x2014;C(&#x2550;O)CHand where n is within the range from 12 to 4000; a method of preparation thereof and use thereof. 

Self-supporting, biodegradable film based on hydrophobized hyaluronic acid, method of preparation and use thereof

The invention relates to an antitumor composition based on hydrophobized hyaluronan and inorganic nanoparticles stabilized by oleic acid. The hydrophobized hyaluronan in the form of an acylated hyaluronan serves in the composition as a carrier of inorganic nanoparticles. Out of the group of inorganic nanoparticles, the composition may comprise superparamagnetic nanoparticles, nanoparticles of ZnO and moreover, upconversion nanoparticles. Said composition is selectively cytotoxic with respect to both suspension and adherent tumor cell lines, especially with respect to tumor cell lines of colorectum carcinoma and adenocarcinoma, lung carcinoma, hepatocellular carcinoma and breast adenocarcinoma. The highest cytotoxic effects were observed in case of the composition based on an oleyl derivative of hyaluronan with SPIONs. The composition of acylated hyaluronan with SPIONs may also be advantageously used for an in vivo detection of accumulation of the composition in the body, preferably in a tumor or in liver. Said composition is sterilizable in the final package.

Antitumor composition based on hyaluronic acid and inorganic nanoparticles, method of preparation thereof and use thereof

The invention relates to conjugates of hyaluronic acid oligomer according to the general formulae I, II III or IV, or a salt thereof, the method of preparation thereof and use thereof, where the oligomer is bonded to the respective substrate by its ending anomeric center via a bi-functional amino linker by means of an amino or imino bond. This type of conjugates allows releasing oligomers in their native form. The prepared systems exhibited an enhanced biological activity against selected lines of cancer cells. 

Conjugates of oligomer of hyaluronic acid or of a salt thereof, method of preparation thereof and use thereof

The invention relates to a method of preparation hydrophobized hyaluronic acid (Formula I) and further to a method of encapsulating biologically active substances into the nanomicelles of hydrophobized hyaluronan serving as carriers of biologically active hydrophobic substances. The hydrophobization of hyaluronan is carried out through an esterification reaction of hyaluronan with long-chain carboxylic acids, the latter being activated by a halogenide derivative of 2,4,6-trichlorobenzoic acid or by another organic chloride. In an aqueous environment, water-soluble hydrophobized derivatives can form nanomicelles in which nonpolar substances can be bound by means of non-covalent physical interactions. The core of a nanomicelle is formed by hydrophobic acyl functional groups while the shell of a nanomicelle is formed by hyaluronic acid. The encapsulation of the substances into nanomicelles can be performed by means of the solvent exchange method or by means of sonication. Hyaluronic nanomicelles support the penetration of bound substances in topical applications and enable the bound substances to be transferred into the individual cells. The nanomicelles obtained from hydrophobized hyaluronan derivatives are usable in cosmetic and pharmaceutical applications. 

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The invention relates to the preparation and use of &#x3b1;,&#x3b2;-unsaturated aldehyde of hyaluronan having a double bond in the positions 4 and 5 and an aldehydic group in the position 6 of the glucosamine part of the polysaccharide. The method of preparation is based on dehydration of hyaluronan having an aldehydic group in the position 6 of the glucosamine part of the polysaccharide. Two methods have been described, which are dehydration in a solution or heating in solid state in absence of solvents, bases or other additives. This derivative allows stabilization of conjugates of hyaluronan with amino compounds by means of a multiple bond from the aldehyde side, and therefore, it is possible to effectively immobilize practically any compound containing an amino group to such modified hyaluronan in physiological conditions. In case of using a diamine or compounds or polymers containing three or more amino groups, it is possible to prepare crosslinked hyaluronan derivatives. The described solution brings along a significant advantage not only in the field of carriers of biologically active substances, but also in tissue engineering where crosslinking with biologically acceptable amino compounds in physiological conditions is very much demanded. 

Hyaluronic acid derivative, method of preparation thereof, method of modification thereof and use thereof

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Brno, Czechia

Kristina Nesporova