Contipro A.s.

Contipro Pharma A.s.

Contipro Biotech S.r.o.

Radovan Buffa

Vladimir Velebny

Ivana Basarabova

Tomas Bobula

Pavlina Prochazkova

Hana Vagnerova

Petra Sedova

Kristina Nesporova

Jaromir Kulhanek

Lucie Wolfova

Josef Chmelar

Katerina Knotkova

Helena Krejci

Lubos Sobotka

Sofiane Kettou

Lucie Pospisilova

Drahomira Chladkova

Romana Sulakova

Gloria Huerta-Angeles

Martina Hermannova

Klara Slezingrova

Jaroslav Novotny

Veronika Stepankova

Ondrej Zidek

Lucie Marholdova

Michaela Moravkova

Kristyna Lipenska

Ondrej Kotland

Stanislav Pepeliaev

Vit Svozil

Veronika Moravcova

Tereza Ehlova

Leos Hromek

Tomás Pitucha

Martin Sojka

Martin Bobek

Iva Doleckova

Pavel Klein

Robert Pospisil

Sona Moravcikova

Martina Hasova

Lenka Kohutova

Miroslava Berkova

Lenka Kovarova

Tomas Pitucha

Jiri Betak

Martina Moravcova

Jolana Scudlova

Ilona Matejkova

Tereza Silova

Simunkova Lucie

CHLÁDKOVÁ Drahomira

Lucie PospisilovÁ

Miroslava NÉMCOVÂ

Vladimir VelebnÝ

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

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 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 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 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

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Humenne, Slovakia

Radovan Buffa