Contipro Biotech S.r.o.

Contipro A.s.

Lucie Wolfova

Vladimir Velebny

Radovan Buffa

Ivana Basarabova

Kristina Nesporova

Romana Sulakova

Pavlina Prochazkova

Tomas Bobula

Hana Vagnerova

Petra Sedova

Klara Slezingrova

Miroslava Nemcova

Pavel Klein

Robert Pospisil

Martina Hasova

Martin Pravda

Marcela Foglarova

Krzysztof Niedoba

Lenka Kohutova

Veronika Moravcova

Ondrej Zidek

Martin Bobek

Lenka Kovarova

Jiri Betak

Martina Moravcova

Jolana Scudlova

Ilona Matejkova

Tomas Pitucha

Krzystof Niedoba

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 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

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Opava, Czechia

Lucie Wolfova