Contipro A.s.

Contipro Pharma A.s.

Gloria Huerta-Angeles

Vladimir Velebny

Kristina Nesporova

Daniela Smejkalova

Klara Slezingrova

Radovan Buffa

Romana Sulakova

Josef Chmelar

Jaromir Kulhanek

Martina Hermannova

Jaroslav Novotny

Miroslava Nemcova

Sofiane Kettou

Lucie Pospisilova

Drahomira Chladkova

Daniel Jirak

Martin Bobek

Lucie Vistejnova

Antonin Minarik

Martina Tepla

Eva Prikopova

Jakub Syrovatka

Dagmar Cozikova

Martina Pospisilova

Jana Sogorkova

Jan Kucera

Vit Matuska

Pavel Klein

Jiri Mrazek

Marcela Dusankova

Sergej Karel

Andrea Galisova

Martina Brandejsova

Eva Achbergerova

Karel Soucek

Zuzana Jouklova

Klara Slesingrova

Klara Slezingerova

Martina Moravcova

Jana Ruzickova

Simunkova Lucie

CHLÁDKOVÁ Drahomira

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 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 a new method of preparation of a hyaluronan derivative with an aldehydic group in the position (6) of the polysaccharide glucosamine part. The hyaluronic acid oxidation can be performed by means of TEMPO/NaCIO or TEMPO/TCC systems in a protic environment with or without the presence of anorganic salts. Thus prepared aldehyde can be used for binding amines, diamines, amino acids, peptides and other compounds containing an amino group, e.g. by means of the reductive amination with NaBHCN in water or in a water-organic solvent system. When a diamine or compounds containing three or more amino groups are used, cross-linked hyaluronan derivatives can be prepared. Cross-linked derivatives can be also prepared by a reaction of the aldehyde with a hyaluronan substituted by an amino-alkyl group HA-alkyl-NH.

Method of preparation of an oxidized derivative of hyaluronic acid and a method of modification thereof

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Gloria Huerta-Angeles