Contipro A.s.

Contipro Biotech S.r.o.

Contipro Pharma A.s.

Ceske Vysoke Uceni Technicke V Praze, Fakulta Strojni

Ustav Struktury a Mechaniky Hornin Av Cr, V.v.i.

Prospon Spol. S.r.o.

Vladimir Velebny

Tomas Suchy

Radovan Buffa

Kristina Nesporova

Ivana Basarabova

Gloria Huerta-Angeles

Katerina Knotkova

Jaromir Kulhanek

Josef Chmelar

Lucie Wolfova

Petra Sedova

Hana Vagnerova

Pavlina Prochazkova

Tomas Bobula

Romana Sulakova

Helena Krejci

Marek Pokorny

Jaroslav Novotny

Miroslava Nemcova

Martina Hermannova

Klara Slezingrova

Lucie Pospisilova

Drahomira Chladkova

Sofiane Kettou

Lubos Sobotka

Martin Flegel

Daniela Smejkalova

Ondrej Zidek

Michaela Moravkova

Stanislav Pepeliaev

Tomás Pitucha

Martina Tepla

Ondrej Kotland

Martin Sojka

Leos Hromek

Jakub Syrovatka

Martin Bobek

Jan Klemes

Marcela Dusankova

Lucie Vistejnova

Vit Matuska

Eva Prikopova

Adela Kotzianova

Jiri Mrazek

Dagmar Cozikova

Andrea Galisova

Jana Sogorkova

Jan Kucera

Daniel Jirak

Pavel Klein

Robert Pospisil

Martin Fogl

Martina Hasova

Martin Pravda

Antonin Minarik

Marcela Foglarova

Krzysztof Niedoba

Miroslava Berkova

Veronika Moravcova

Iva Doleckova

Marek Pokorný

Kristyna Lipenska

Lada Suková

Tereza Ehlova

Sergej Karel

Sona Moravcikova

Jiri Rebícek

Martina Pospisilova

Vit Svozil

Veronika Stepankova

Lenka Kohutova

Lucie Marholdova

Lenka Kovarova

Julie Bystronova

Martina Brandejsova

Tomas Pitucha

Roman Frycak

Jiri Betak

Vojtech Zapotocky

Jolana Kubickova

Katerina Janouchova

Helena Richtrova

Eva Achbergerova

Karel Soucek

Martina Moravcova

Dzianis Smirnou

Jolana Scudlova

Ilona Matejkova

Jiri Rebicek

Ladislav Burgert

Radim Hrdina

Zuzana Jouklova

Evgeniy Toropisyn

Klara Slesingrova

Kristýna Lipenska

Sarka Kocova

Frantisek Denk

A chlorinated derivative of hyaluronic acid or of a modified hyaluronic acid (chloramide) is provided. The chloramide has an amidic group (&#x2014;NH&#x2014;CO&#x2014;). The hydrogen of the amidic group is substituted by a chlorine atom, according to the structural formula &#x2014;NCl&#x2014;CO&#x2014;. The substitution degree of the hyaluronic acid or of the modified hyaluronic acid by chlorine is in an amount of from 50 to 100 %.

Chlorinated derivative of hyaluronic acid, method of preparation thereof, a composition containing the derivative, and use thereof

An antimicrobial composition is provided. The composition comprises a chloramid of hyaluronic acid or of modified hyaluronic acid. The chloramid has an amidic group (&#x2014;NH&#x2014;CO&#x2014;). The hydrogens of the amidic group are substituted by chlorine atoms according to the structural formula &#x2014;NCl&#x2014;CO&#x2014;. The composition further comprises an iodide. The substitution degree of the hyaluronic acid or of the modified hyaluronic acid by chlorine is in an amount of from 50% to 100%.

Composition comprising an iodide and a derivative of hyaluronic acid with an oxidative effect, method of preparation thereof and use thereof

Device for the production of nanofibrous and/or microfibrous layers having an increased thickness uniformity by spinning a liquid material (), said device comprising: a collecting electrode (), a spinning nozzle () for dispensing the liquid material () to be spun, an assembly for guiding the collecting electrode () and/or for guiding a base strip () along the collecting electrode () or adjacent to it, such that&#x2014;in the area faced by the outlet orifice () of the spinning nozzle ()&#x2014;the collecting electrode () and/or the base strip () move(s) in the direction (MD) spaced from the outlet orifice () of the spinning nozzle (), a power supply for generating a voltage of 10 to 150 kV between the collecting electrode () and the spinning nozzle (), at least one body (), which moves along the liquid surface to destabilize the locations of the points where fibres () are formed on the surface of the liquid material () at the outlet orifice () of the spinning nozzle (). The nanofibrous and/or microfibrous layers having an increased thickness uniformity are produced by spinning a liquid material () in an electrostatic field, wherein a body () is moved along the surface of the spun liquid in order to destabilize positions of locations, where the fibers originate.

Device and method for production of nanofibrous and/or microfibrous layers having an increased thickness uniformity

The invention discloses a method of preparation of crosslinked materials based on polysaccharides using electromagnetic radiation in an aqueous solution containing a polysaccharide with a bound carbamate photoremovable protecting group (PPG with group &#x2014;NH&#x2014;CO&#x2014;O&#x2014;) and a polysaccharide containing an aldehyde group &#x2014;CHO. The crosslinking process itself is carried out by means of a condensation reaction of the photochemically released amino group (&#x2014;NH) with the aldehyde group (&#x2014;CHO) forming a bond of imine type (&#x2014;N&#x2550;CH&#x2014;). Both processes proceed simultaneously and they can be performed under physiological conditions. The advantage of the suggested solution is the temporal and spatial control of crosslinking that allows the preparation of advanced materials for tissue engineering where the crosslink density and thus the mechanical properties in the material structure can be tailored.

Method of crosslinking of polysaccharides using photoremovable protecting groups

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 the preparation of new polysaccharide derivatives comprising a double bond in the positions 4 and 5 of the pyranose cycle. The method of preparation consists in the oxidation of OH group in the position 6 to an aldehyde, followed by the elimination to form a double &#x2014;C&#x2550;C&#x2014; bond in the positions 4 and 5, and the final reduction of the aldehyde group in the position 6 into the original alcohol. The derivatives of polysaccharides prepared according to the invention show an enhanced antioxidant activity and some of them also a selective negative influence on carcinoma cell viability. (formula) where R represents &#x2014;NH&#x2014;CO&#x2014;CHor &#x2014;OH. 

Unsaturated derivatives of polysaccharides, method of preparation thereof and use thereof

The invention relates to the preparation and the use of &#x3b1;,&#x3b2;-unsaturated aldehydes in the structure of sulfated polysaccharides. It concerns the derivatives with a conjugated double bond in the 4th and 5th positions of the galactopyranose part situated in the 6th position with respect to the aldehyde, according to the general structural formula (I) or its hydrated form according to the general structural formula (II). The preparation of these derivatives derives from sulfated polysaccharides containing a galactopyranose ring sulfated in the 4th position that is bound in the polymer chain via &#x3b1;(1&#x2192;3) or &#x3b2;(1&#x2192;3) O-glycosidic bond. In the described solution, the sulfated polysaccharides undergo a regio- and chemoselective oxidation to form C6-saturated aldehyde, which, via a direct elimination of the sulfate group, provides the &#x3b1;,&#x3b2;-unsaturated derivative according to the general formula (I) or (II). The described solution is technically advantageous, because it leads directly to &#x3b1;,&#x3b2;-unsaturated aldehydes, without any elimination agents, higher temperature, or isolation of intermediates during the synthesis. The conjugation in the structure of &#x3b1;,&#x3b2;-unsaturated aldehyde allows, under physiological conditions, to bind a wide variety of biocompatible amines in the structure of the sulfated polysaccharides. The proposed method allows to prepare materials suitable for pH-responsive drug delivery systems, or for the preparation of scaffolds in tissue engineering or regenerative medicine. Formulae for the abstract (I), (II) above, where R is OH, O&#x2014;SO&#x2014;OH, O&#x2014;SO&#x2014;ONa, or NH&#x2014;Ac. 

Derivatives of sulfated polysaccharides, method of preparation, modification 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

The invention related to hyaluronic derivative according to formula (I), methods of preparation thereof and a hydrogel prepared obtained from the derivative and methods of preparation thereof. The hydrogel can be used in tissue engineering, cosmetics, medicine or regenerative medicine such as the forming of scaffolds for the treatment of articular cartilage or bone tissue defects. 

Derivatives of hyaluronic acid capable of forming hydrogels

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

The invention relates to a hyaluronic acid derivative and methods of preparation and modification of a hyaluronan derivative with an aldehydic group in the position (6) of the polysaccharide glucosamine part. The oxidation of the hyaluronic acid can be performed by means of Dess-Martin periodinane (DMP) agent. The prepared aldehyde can be used for binding amine, diamine, amino acid, peptide 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 also be prepared by the reaction of the aldehyde with a hyaluronan substituted by an amino-alkyl group HA-alkyl-NH.

Oxidized derivative of hyaluronic acid, a method of preparation thereof and a method of modification thereof

An apparatus for a production of two-dimensional or three-dimensional fibrous materials of microfibers or nanofibers containing a set of spinning metal nozzles connected to a first potential, a set of electrodes of a collector facing the set of the nozzles, arranged at regular spacing and connected to a second potential, and a collecting plate or a collecting cylinder for collecting microfibers or nanofibers settled between couples of adjacent electrodes of the collector. The substance of the invention is as follows: the set of the electrodes of the collector contains at least two electrodes of the collector arranged in a plane and the collecting plate in line of its intersection or a tangent to the collecting cylinder, that is perpendicular to a contact line with the plane of the electrodes of the collector, form with the plane of the electrodes of the collector an angle &#x3b1;, the size of which ranging between 0&#xb0; and 90&#xb0;, the collecting plate or the collecting cylinder being supported movably in relation to the electrodes of the collector in a direction lying in the plane that is perpendicular to the plane of the electrodes of the collector and in which the axis of the electrode lies, the direction of the collecting plate or the collecting cylinder movement forming with this electrode axis an angle &#x3b2;, the size of which ranging between 0&#xb0; and 90&#xb0;. Such arrangement enables creating of large areal and voluminous objects of ordered nanofibers.

Apparatus for production of two-dimensional or three-dimensional fibrous materials of microfibres and nanofibres

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Zamberk, Czechia

Vladimir Velebny