Gatt Technologies Bv

Bender Analytical Holding B.v.

Cilag International Gmbh

Echo Pharmaceuticals B.v.

Bender Analytical Holdong B.v.

Ethicon, Gmbh

Johannes Caspar Mathias Elizabeth Bender

Gerard H Llanos

Richard Hoogenboom

Jan Cornelis Maria Van Hest

Hubert Clemens Pellikaan

Pieter Sebastiaan Vermeulen

Marcel Alexander Boerman

Harry Van Goor

Joost Opsteen

Abraham Reinier Keereweer

Geert Feye Woerlee

Rosa Pilar Félix Lanao

María José Sánchez-fernández

Sander Cornelis Gerardus Leeuwenburgh

Patrick Andreas Anton Van Vliet

María José SÁNCHEZ-FERNÁNDEZ

Julius Marcus Van Dijck

Rosa Pilar FÉLIX Lanao

Maryssa Gudrun Ailsa Mann

Michael Kamps

Biocompatible, flexible, haemostatic sheets are provided comprising a water-resistant cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space and fibres comprising a nucleophilic polymer carrying reactive nucleophilic groups; and distributed within the interstitial space throughout the fibrous carrier structure, a plurality of reactive polymer particles comprising a water-soluble electrophilic polymer carrying at least three reactive electrophilic groups that are capable of reacting with both amine groups in tissue and blood and with the reactive nucleophilic groups of the nucleophilic polymer to form covalent bonds, wherein the reactive polymer particles have a diameter between 0.5-100 μm and are present in an amount of at least 3% by weight of the fibrous carrier structure.

Biocompatible, flexible, haemostatic sheet

The invention provides a method for preparing tissue-adhesive sheets that may suitably be applied as an implantable haemostatic or sealing construct during surgical procedures, said method comprising:

Method for preparing a tissue-adhesive sheet

The present disclosure provides polyoxazoline (POx) copolymers which exhibit very high affinity for calcium ions, are capable of forming hydrogels and are bioresorbable. The polyoxazoline copolymers comprise at least 20 oxazoline units, including at least 4 non-terminal oxazoline units that contain a calcium binding group. Methods of making such polyoxazoline copolymers and using them in biomedical applications are also provided.

Polyoxazoline copolymer comprising calcium binding groups

A biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent is disclosed. The EL-POX comprises m electrophilic groups; and the nucleophilic cross-linking agent comprises n nucleophilic groups, wherein the m electrophilic groups are capable of reacting with the n nucleophilic groups to form covalent bonds; wherein m&#x2265;2, n&#x2265;2 and m+n&#x2265;5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m&#x2265;3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. Biocompatible medical products and kits comprising the cross-linked POX-polymers are also disclosed.

Cross-linked polymers and implants derived from electrophilically activated polyoxazoline

A process of preparing an adhesive haemostatic product is provided. The process comprises: (a) coating a porous solid substrate with a coating liquid that comprises an electrophilically activated polyoxazoline (EL-POX) and a solvent to produce a coated substrate; and (b) removing the solvent from the coated substrate. The EL-POX comprises at least 2 reactive electrophilic groups. The process enables the application of an EL-POX coating that leaves the pore structure of the substrate largely intact so that the ability of the porous substrate to absorb body fluids, such as blood, remains essentially unaffected. The EL-POX coated haemostatic product obtained by the present process has excellent adhesive properties due to the presence of electrophilic reactive groups that are capable of reacting with e.g. amine groups that are naturally present in tissue, under the formation of covalent bonds.

Tissue-adhesive porous haemostatic product

A biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-PDX) with a nucleophilic cross-linking agent is disclosed. The EL-PDX comprises m electrophilic groups; and the nucleophilic cross-linking agent comprises n nucleophilic groups, wherein the m electrophilic groups are capable of reacting with the n nucleophilic groups to form covalent bonds; wherein m&#x2265;2, n&#x2265;2 and m+n&#x2265;5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m&#x2265;3; and wherein the EL-PDX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. Biocompatible medical products and kits comprising the cross-linked PDX-polymers are also disclosed.

One aspect of the invention relates to a biocompatible medical product comprising at least 1% by weight of dry matter of a covalently cross-linked polymer that is obtained by reacting a nucleophilically activated polyoxazoline (NU-PDX) with an electrophilic cross-linking agent other than an electrophilically activated polyoxazoline, said NU-PDX comprising m nucleophilic groups; and said electrophilic cross-linking agent comprising n electrophilic groups, wherein the m nucleophilic groups are capable of reaction with the n electrophilic groups to form covalent bonds; wherein m&#x2267;2, n&#x2267;2 and m+n&#x2267;5; and wherein the NU-PDX comprises at least 30 oxazoline units in case the electrophilic cross-linking agent is an isocyanate. Also provided is a kit for producing the aforementioned biocompatible cross-linked polymer. The biocompatible cross-linked polymers according to the invention have excellent implant and/or sealing characteristics.

Cross-linked polymers and medical products derived from nucleophilically activated polyoxazoline

One aspect of the invention relates to a biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent, said electrophilically activated POX comprising m electrophilic groups; and said nucleophilic cross-linking agent comprising n nucleophilic groups, wherein the m electrophilic groups are capable of reaction with the n nucleophilic groups to form covalent bonds; wherein m&#x2267;2, n&#x2267;2 and m+n&#x2267;5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m&#x2267;3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. The invention further relates to biocompatible medical products comprising such a cross-linked POX-polymer. Also provided is a kit for producing a biocompatible, cross-linked POX-polymer. The invention further provides a tissue adhesive medical product comprising at least 1% by weight of dry matter of EL-POX, said EL-POX comprising at least 2 electrophilic groups, including at least one pendant electrophilic group. The polymers according to the invention have excellent implant and/or sealing characteristics.

One aspect of the invention relates to a biocompatible medical product comprising at least 1% by weight of dry matter of a covalently cross-linked polymer that is obtained by reacting a nucleophilically activated polyoxazoline (NU-POX) with an electrophilic cross-linking agent other than an electrophilically activated polyoxazoline, said NU-POX comprising m nucleophilic groups; and said electrophilic cross-linking agent comprising n electrophilic groups, wherein the m nucleophilic groups are capable of reaction with the n electrophilic groups to form covalent bonds; wherein m&#x2267;2, n&#x2267;2 and m+n&#x2267;5; and wherein the NU-POX comprises at least 30 oxazoline units in case the electrophilic cross-linking agent is an isocyanate. Also provided is a kit for producing the aforementioned biocompatible cross-linked polymer. The biocompatible cross-linked polymers according to the invention have excellent implant and/or sealing characteristics.

One aspect of the invention relates to a pharmaceutical dosage unit for sublingual, buccal, pulmonary or oral administration, said dosage unit having a weight of 20-500 mg and comprising 1-80 wt. % of a microgranulate that is distributed throughout a solid hydrophilic matrix; said microgranulate being characterized in that it: has a volume weighted average diameter of 5-100 m; contains at least 0.01 wt. %, preferably at least 0.1 wt. % of one or more water-insoluble pharmaceutically active substances; contains at least 10 wt. %, preferably at least 20 wt. % of an emulsifier component; and is capable of forming a micro-emulsion upon contact with saliva or water. The dosage units of the present invention achieve the inherent benefits of oral delivery while at the same time realizing a high transmucosal absorption rate of the cannabinoids contained therein. Other aspects of the present invention relate to the use of the aforementioned dosage units in the therapeutic or prophylactic treatment and to a process for the manufacture of said dosage units.

Dosage unit for sublingual, buccal or oral administration of water-insoluble pharmaceutically active substances

The present invention relates to ready-to-use sterile, alginate-based, aqueous compositions for medical use. More particularly, the invention relates to an aqueous composition for medical use that has been sterilized by heat sterilization and having a viscosity at 25&#xb0; C. of at least 300 cP) (Helipath&#xae; T F spindle, 100 rpm at 25&#xb0; C.), said composition having a pH in the range of 6.5-7.5; containing 0.5-10 wt. % of an alginate salt; and further containing 10-500 mM of one or more dissolved C-Cmono- or dicarboxylates that are optionally substituted with up to 2 hydroxyl groups. The alginate-based composition of the present invention has excellent storage stability and is easy to manufacture. The alginate-based aqueous compositions of the present invention can advantageously be used, for instance, to prevent adhesions between a healing trauma site and adjacent surrounding tissue. These compositions can further be used in implants or in pharmaceutical preparations for oral administration.

Sterile alginate-based aqueous composition for medical use and process for the preparation thereof

The invention relates to drug delivery systems comprising a water-soluble polymer matrix and a bioactive agent entrained therein, said water soluble polymer matrix containing at least 50 wt. % of polyoxazoline having a molar mass of at least 5 40,000 g/mol. The drug delivery systems of the present invention offer the advantage that the bioactive agent is readily released when the drug delivery system is contacted with water. The drug delivery system can be in the form of a solid dispersion, a mucoadhesive sheet, a tablet, a powder, a capsule.

Drug delivery system comprising polyoxazoline and a bioactive agent

The present invention relates to a method for removing impurities from biopolymer material, e.g. polysaccharides, polypeptides or polynucleotides. More particularly, the present invention provides a method of reducing lipopolysaccharide levels in a lipopolysaccharide containing biopolymer material, comprising the successive steps of: a) providing an aqueous solution containing 0.05-50 wt. % of dissolved lipopolysaccharide-containing biopolymer material; 0.001-10 wt.% of a surfactant; 0.05-15 wt. % of solid adsorbent; and at least 50 wt. % of water; b) allowing the adsorbent to adsorb lipopolysaccharides; c) separating the solid adsorbent containing adsorbed lipopolysaccharides from the remaining aqueous solution; and d) recovering the biopolymer material containing a reduced level of lipopolysaccharide from the separated aqueous solution.

Growing community of inventors

Utrecht, Netherlands

Johannes Caspar Mathias Elizabeth Bender